Mental Health

From the Milwaukee County Behavioral Health Division, Milwaukee, WI.

Abstract

Objective: Implementation of the Quadruple Aim of health care must begin with a clearly articulated set of concepts, or core domains (CDs), that comprise each aim. These CDs can then be operationalized with existing or new measures. If aligned to the organization’s mission and strategic goals, these CDs have the potential to focus quality improvement activities and reduce measurement burden. This article represents the efforts of a publicly funded behavioral health system to operationalize the Quadruple Aim through the development of CDs.

Methods: Various stakeholders across the organization were consulted on their perceptions of the Quadruple Aim and the CDs they believed should support it. Then, a review of existing literature on core metrics for health care and population health was completed, summarized, and integrated with the stakeholder feedback.

Results: These efforts led to the development and adoption of 15 CDs, with an accompanying literature review and set of recommendations of new and existing measures for each domain.

Conclusions: It is possible to create a comprehensive yet economical set of CDs and attendant measures that can be implemented in a staged, scalable, enterprise manner. It is hoped that the process articulated here, and the accompanying literature review, may be of some benefit to other public or government-run health systems in their own quality improvement journey to operationalize the Quadruple Aim by developing a set of CDs.

Keywords: quality measures; quality improvement; adult behavioral health.

First articulated in 2008, the Triple Aim proposes that health care systems should simultaneously seek to improve the patient’s experience of care, improve the health of populations, and reduce the per capita costs of care for populations.¹ More recently, some have argued that health care provider burnout can deleteriously impact the attainment of the Triple Aim and have therefore advocated for an expanded focus to include a fourth Aim, the work life quality of the staff.² Milwaukee County Behavioral Health Division (BHD), a publicly funded, county-based behavioral health care system in Milwaukee, Wisconsin, recently adopted the Quadruple Aim as the framework by which it will organize its quality activities.

Although originally developed for medical organizations, BHD believes that the Quadruple Aim has strong applicability to county-level behavioral health services. Many county-based behavioral health divisions provide a variety of programs to large segments of the county based on financial eligibility and/or clinical need, and thus often have responsibilities to populations or subpopulations, rather than programs. County health divisions, such as Milwaukee County’s Department of Health and Human Services, are often asked to improve outcomes and client experience of care with neutral growth budgets and less reliance on taxes to fund programs, while simultaneously attracting and retaining competent staff.

Crucial to the effective implementation of the Quadruple Aim, however, is a clear set of population- level measures that help organizations assess their progress.³ Unfortunately, as some authors have noted, evaluation of the Quadruple Aim remains a challenge because the “concepts of (population) health, quality of care and costs are not unanimously defined and measures for these concepts are under construction.”⁴ Several authors have provided some guidance to assist in the development of a set of measures that effectively capture the elements of the Quadruple Aim.^5,6 However, the recent rapid proliferation of quality measures in health care^7,8 has been both burdensome and costly for providers.^9,10 Any measures adopted should not only be as meaningful as possible with regards to assessing progress towards the basic aims of health care, but should also be parsimonious, to limit measurement burden for providers (and patients) and focus attention on important issues.^11,12

To select the most effective, parsimonious set of measures possible, one must first select a set of key foci from among the many possible areas of focus that the core measure is intended to represent. The core domains (CDs), if appropriately consistent with the strategic goals of the organization, provide a mechanism to orient the efforts of the organization at every level and help every staff member of the organization understand how his or her work impacts the progress towards these goals.¹¹ The CDs, therefore, represent the opportunity to affect a greater integration of efforts across the organization toward these shared aims, creating uniformity of purpose at every level. Further, increasing organizational attention on the CDs can also help to reduce measurement burden by streamlining and focusing the data capture processes on the most valuable elements of quality and health, and discarding other extraneous measures (albeit not at the expense of other reporting requirements).¹¹ The remainder of this article describes the CDs selected by BHD to assess its progress toward implementation of the Quadruple Aim and are organized by the Aim which they best represent.

Methods

To effectively implement the Quadruple Aim at BHD, it was necessary to clearly define the subpopulation of focus for our efforts.⁶ In this case, the subpopulation of interest was defined as all adult clients (18 years and older) who received at least 1 service encounter within a specified time frame from a program that BHD either operated or contracted with to provide care. Services provided by the BHD network include everything from psychiatric inpatient services to mental health and addiction treatment and care management. A limited array of social services, including housing and employment services, is also available to eligible consumers. BHD is the county-run behavioral health provider for individuals who are uninsured or underinsured in Milwaukee County, a demographically diverse, primarily urban county of approximately 950,000 people located in Wisconsin. Approximately 15,000 adults receive services at BHD each year.

This work began by obtaining executive sponsorship for the project, in this case from the Chief Operations Officer and Executive Medical Director of BHD. With their backing, an initial review of the literature produced a preliminary set of possible domains, for which we created working definitions. We then made a list of key stakeholders throughout BHD to whom we needed to present the idea of the Quadruple Aim, and the CDs under each Aim, to secure their support. These stakeholders, which included individuals involved in quality activities, program managers, and executive leadership, were strategically selected based on their relative influence within the organization. A set of brief presentations and handouts explaining the project were then developed and shared at different focus groups with these stakeholders over the course of 6 months. These focus groups served to not only educate the organization about the Quadruple Aim and the CDs but afforded participants an opportunity to provide feedback as well.

During the focus groups, we asked participants which domains they believed were most important (were “core”) when operationalizing the Quadruple Aim. The focus groups provided feedback on the domain definitions, feedback that was used to develop uniform, mutually agreed upon definitions for the CDs that were generalizable to all departments at BHD, regardless of the focus of their services within the continuum of care or the continuum of age. This was a crucial step, as it will eventually enable BHD to aggregate data across departments, even if there are minor discrepancies in the specific items they use to assess the CDs. Comments from the focus groups ultimately resulted in a truncated list of domains and definitions, which, coupled with the literature review, resulted in our final set of CDs.

During our review of the literature, we also looked for items that we felt could best represent each CD in the briefest, most meaningful way. (These items were not meant to supersede existing data, but to provide examples that could be implemented with existing data or recommendations that could be utilized in the absence of existing data.) During this process, we made every effort to make use of existing data-reporting requirements. For example, if we had a state mandate to collect data on housing status, we attempted to leverage this required data point to represent the CD related to housing. In other cases, we attempted to utilize claims or other administrative data to operationalize the CD, such as in the cost-of-care metric articulated in the section the Third Aim. For CDs for which no data existed or were insufficient, we emphasized the use of single- versus multi-item scales. For example, if we found a single-item global assessment of quality of life that had good psychometric properties relative to its longer parent scale, we selected the single item. This approach to item selection allowed us to create the most efficient, parsimonious set of measures possible, which we believed would enable us to comprehensively assess all the CDs with the least amount of burden to staff and clients. These items were presented at stakeholder focus groups, during which we asked for comments on the existing measures in their program or department and gave them the opportunity to comment on the new recommended measures.

A working definition is provided for each CD, followed by a brief review of the research base supporting its inclusion in the final list. The item(s) selected by BHD to represent each CD and the source of the item(s) are then supplied. These items were based either on measures currently collected because of existing reporting mandates or, in the case where extant measures were not available, on new items that demonstrated acceptable psychometric properties in the research literature. The CDs and items are organized by the Aim they best represent. A full list of the CDs by Quadruple Aim and items by CD is provided in the Appendix of the online version of this article. This article concludes with a brief summary of this effort and a discussion of how staff will utilize these items at different levels throughout the BHD system.

The First Aim: Population Health

Health Outcomes

Deaths. This can be defined as the cause of death, as determined by the medical examiner’s office (where appropriate) or as the age at time of death. This CD can also be reported as proportion of deaths considered premature (eg, before age 75) or calculated as total years of potential life lost.

Brief review and suggested item(s). Rates and causes of premature mortality are critical foci for the County Health Rankings & Roadmaps,¹³ the Institute for Healthcare Improvement’s “Guide to Measuring the Triple Aim,”⁶ the Centers for Disease Control and Prevention’s “Community Health Assessment for Population Health Improvement,”¹⁴ and the Institute of Medicine’s (IOM) “Vital Signs: Core Metrics for Health and Health Care Progress.”¹¹ There is ample evidence that individuals with serious mental illness are at increased risk of early mortality relative to the general population,^15-18 and this risk applies to those with substance use disorders as well.^15,19-20 BHD tracks all deaths that occur while patients are receiving BHD-funded, community-based services.

Self-Reported Health and Well-Being. This CD asks patients to rate their current physical and mental health status, as well as their overall quality of life.

Brief review and suggested item(s): Self-rated physical health. Premature mortality among individuals with behavioral health issues appears to be due, in large part, to their increased vulnerability to the development of medical comorbidities.^16,21 A single self-rating question has demonstrated considerable sensitivity to premature mortality,^22,23 with predictive properties up to a decade prior to death.^24,25 Further, self-rated health has been associated with subsequent functional decline,^26,27 acute service utilization,^28,29 and overall health care costs.²⁸

Brief review and suggested item(s): Self-rated mental health. Mental health disorders are associated with significant disability worldwide,³⁰ and comorbid mental health issues can exacerbate the course of other medical problems. For example, depression is associated with increased rates of mortality among individuals with diabetes and³¹ cardiovascular disease,³² as well as with rates of overall mortality,³³ and psychiatric comorbidity is associated with longer lengths of stay and higher costs among patients hospitalized for medical problems.³⁴ Research has found that a single-item measure of self-rated mental health is associated with the presence of psychiatric diagnoses, psychiatric symptoms, and subsequent depression and serious mental illness up to 1 year post-assessment.^35,36 There is even evidence that self-rated mental health may be more strongly associated with self-ratings of overall health than self-ratings of physical health.³⁷

Brief review and suggested item(s): Self-rated quality of life. Quality of life is a critical component of the recovery journey and overall health.³⁸ For example, the County Health Rankings & Roadmaps lists “quality of life” as 1 of its key “health outcomes” in its County Health Rankings.¹³ As some authors have noted, quality of life is often inferred from other “objective” recovery domains, such as employment, health status, or housing status. However, there is evidence that these objective domains are functionally distinct from the inherently subjective construct of quality of life.³⁹ This has led other authors to conclude that these domains should be assessed separately when evaluating outcomes.⁴⁰ Single-item quality of life assessments have been used in research with individuals with cancer,⁴¹ adults with disabilities,⁴² patients with cystic fibrosis,⁴³ and children with epilepsy.⁴⁴ For this effort, BHD selected the first global quality of life item from the World Health Organization’s WHOQOL-BREF quality of life assessment,⁴⁵ an item used in other quality of life research.⁴⁶

Health Factors

Substance Use. This CD is a composite of 4 different types of substance use, any recent heavy alcohol use (defined as 5 or more drinks in one sitting), any recent drug use, any recent prescription drug abuse, and any recent tobacco use.

Brief review and suggested item(s). As noted, substance use disorders confer an increased risk for early mortality^15,19 and are significantly implicated in disease disability burden worldwide.³⁰ Substance use has also been associated with both the onset^47,48 and exacerbation of mental health diagnoses.^49-51 Further, substance use appears to heighten the risk of violence in the general population⁵² and especially among those with a co-occurring mental illness.^53,54 The County Health Rankings & Roadmaps list alcohol and drug use as key behaviors to address to improve the overall health of a given county,¹³ and the Centers for Medicare & Medicaid Services (CMS) has endorsed initiation and engagement in addiction treatment as one of the measures in its Adult Core Set.⁵⁵

Tobacco use continues to be one of the most significant risk factors for early mortality worldwide, and evidence indicates that it is associated with a lower life expectancy of nearly 10 years.⁵⁶ Unfortunately, rates of tobacco use are even higher among those with severe mental illness relative to the general population, and their rates of smoking cessation are lower.^57,58 Tobacco use is a significant risk factor for the high rates of early mortality in individuals with severe mental illness.¹⁸ Further, a recent meta-analysis noted that, relative to those who continued to smoke, those who ceased smoking had reduced rates of psychological distress and increased quality of life rankings.⁵⁹ Reducing tobacco use is one of the key components of the County Health Rankings & Roadmaps, and medication assistance with smoking and tobacco use cessation is also listed in the CMS Adult Core Set.^13,55

An accumulating body of evidence suggests that single-item measures can adequately detect alcohol^60-62 and drug use disorders.^60-64 McNeely and colleagues recently developed and tested a brief 4-item screen, the Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS) tool.^65,66 Preliminary evidence suggests that the TAPS tool can effectively identify the presence of problematic and disordered use of tobacco, alcohol, prescription medications, and other drugs.^65-67 BHD will use the 4 items from the TAPS tool to represent its substance use CD.

Education/Employment Status. This CD assesses the proportion of BHD members who have completed high school, who are in some type of educational or training program, or who are engaged in some type of employment activity (defined as full-time, part-time, supported, sheltered workshop, or as a full-time homemaker).

Brief review and suggested item(s). Research indicates that unemployment is a risk factor for mortality, even after controlling for other risk factors (eg, age, sex, socioeconomic status [SES], health).⁶⁸ Unemployment is associated with poorer physical and mental health in the general population and among those with disabilities.^69-71 Promisingly, evidence suggests that gaining employment or re-employment is associated with better health,⁷² even for individuals with substance use disorders⁷³ or moderate⁷⁴ to severe mental health disorders.^75-78 Some authors have even proposed that, above and beyond the associated health benefits, employment may also help to realize a modest cost savings due to reduced service utilization and disability.^79,80 Employment is a core tenet in the Substance Abuse and Mental Health Services Administration’s (SAMHSA’s) model of recovery,⁸¹ and is also listed as an important recovery goal for individuals with behavioral health issues.⁸² BHD collects data on employment status on all the patients it serves as part of its state-mandated reporting requirements and will use this item in the CD data set.⁸³

Living Situation. This is measured as the proportion of people who live in permanent, supportive, stable housing; it may also be measured as the percentage of the population living with severe housing problems or who are homeless.

Brief review and suggested item(s). Housing problems can be conceptualized as 3 inter-related components: conditions within the home, neighborhood conditions, and housing affordability, each of which can contribute uniquely to poorer physical and mental health of individuals and families⁸⁴ and to educational outcomes for children.^85,86 Further, individuals who are homeless have a standardized mortality ratio 2 to 5 times that of the general population,^87-89 even after controlling for low income status,⁹⁰ and some evidence suggests these rates are even higher among unsheltered versus sheltered homeless individuals.⁹¹ Interventions to improve the condition of housing have demonstrated positive impacts on both physical and mental health,⁹² and a recent study found that individuals receiving housing assistance in the form of public housing or multifamily housing from the Department of Housing and Urban Development had better self-rated physical and mental health relative to individuals on the wait list for housing assistance.⁹³ Moreover, the provision of housing has been shown to promote reductions in substance use and health service utilization among homeless individuals with substance use disorders.⁹⁴ Rog and colleagues reviewed the literature on permanent supportive housing for individuals with substance use or mental health disorders who were homeless or disabled, and found that provision of housing led to reduced rates of homelessness, emergency department (ED) and inpatient utilization and increased consumer satisfaction.⁹⁵

Importantly, evidence suggests that housing is viewed as facilitative of recovery. For example, in a recent qualitative study of homeless individuals with mental illness, housing was seen as a critical first step in recovery, providing a sense of security, increasing feelings of personal independence and autonomy, improving perceptions of health and well-being, and affording a stable environment to rebuild relationships with important others.⁹⁶ BHD collects data on housing status on all the patients it serves as part of its state-mandated reporting requirements and will utilize this item in the CD data set.⁸³

Social Relationships. This is defined as recent interactions with family, supportive networks (formal and informal), and other recovery services.

Brief review and suggested item(s). Research has long established that social relationships have a significant impact on health, including rates of mortality as well as physical and mental health morbidity.^97-99 Social connectedness is another of the pillars supporting an individual’s recovery in SAMHSA’s formulation. Several reviews of the recovery literature^38,82 support its importance to the recovery process and inclusion in any assessment of holistic recovery. Social support has been shown to promote recovery among individuals with severe mental illness^100-102 and substance use disorders,¹⁰³ and may mitigate the progression of chronic, life-threatening physical illnesses.⁹⁷ For the purposes of BHD’s CD data set, the social support question from the “100 Million Healthier Lives Common Questionnaire for Adults” will be used to assess individuals’ perceived adequacy of social support.¹⁰⁴

Legal Involvement. Defined as involvement with the civil or criminal justice system, including arrests, imprisonment, or detainment.

Brief review and suggested item(s). Involvement in the criminal justice system is both disruptive for the individual in recovery and expensive to the larger health care system.¹⁰⁵ Individuals with substance use¹⁰⁶ and severe mental health disorders¹⁰⁷ are over-represented in the prison system, and evidence suggests that general physical and mental health declines while individuals are in prison.^108,109 Perhaps even more concerning, numerous studies have demonstrated an increase in mortality rates for individuals recently released from prison relative to the general population, particularly during the period immediately following release.^108-110 This relationship may even persist long term.¹¹¹ Further, research indicates that individuals recently released from prison have increased emergency care and hospital utilization.^112,113

Incarceration can have significant impacts on the health of the broader community as well. For example, research has found an association between parental incarceration to rates of infant mortality,¹¹⁴ increased behavioral and developmental problems of children of incarcerated parents,^115,116 lower rates of child support payments,¹¹⁷ and poorer cardiovascular health of female partners of incarcerated individuals.¹¹⁸ Formerly incarcerated individuals experience slower wage growth as well.¹¹⁹ However, evidence also indicates that engagement in mental health¹²⁰ and substance abuse¹²¹ treatment can reduce the likelihood of subsequent recidivism. As part of its state-mandated reporting, BHD is required to provide information on the criminal justice system involvement of its clients in the previous 6 months, including whether they have been jailed or imprisoned,⁸³ and this will function as its measure of legal involvement in its CD data set.

Socioeconomic Status. Socioeconomic status is the social standing or class of an individual or group. It is often measured as a combination of education, income, and occupation. It can also be defined subjectively, such as one’s evaluation of status relative to similar others or based on an individual’s interpretation of her or his financial needs.

Brief review and suggested item(s). A large body of evidence supports the existence of a robust relationship between lower SES and poor health, including mortality and chronic medical diseases,^122-124 as well as mental illness.^125-127 Although previous research has examined this relationship using objective indicators of SES (eg, income, education level, occupation), there has recently been an increased interest in exploring the relationship of subjective SES with health indices. Subjective SES is generally assessed by asking individuals to rate themselves relative to others in the society in which they live, in terms of wealth, occupation, educational level, or other indicators of social status. Evidence suggests that subjective SES is associated with objective measures of SES,^128-130 and relates to measures of physical and mental health as well, even after controlling for objective SES.^130-135 BHD will be using a modified version of the Subject SES Scale,^131,135 which is deployed in the “100 Million Healthier Lives Common Questionnaire for Adults.”¹⁰⁴

Acute Service Use. This is defined as an admission to a medical or psychiatric emergency room or to a medical or psychiatric hospital or to a detoxification facility.

Brief review and suggested item(s). The CMS Adult Core Set includes “plan all cause readmissions” as a key quality metric.⁵⁵ Hospital readmissions are also endorsed by the National Committee on Quality Assurance as one of its Health Effectiveness Data and Information Set (HEDIS) measures and by the National Quality Forum. Readmissions, despite their widespread endorsement, are a somewhat controversial measure. Although readmissions are costly to the health care system,¹³⁶ the relationship between readmissions and quality is inconsistent. For example, Krumholz and colleagues¹³⁷ found differential rates of readmission for the same patient discharged from 2 different hospitals, which were categorized based on previous readmission rates, suggesting that hospitals do have different levels of performance even when treating the same patient. However, other data indicate that 30-day, all-cause, risk-standardized readmission rates are not associated with hospital 30-day, all-cause, risk-standardized mortality rates.¹³⁸

Chin and colleague found that readmissions to the hospital that occurred more than 7 days post-discharge were likely due to community- and household-related factors, rather than hospital-related quality factors.¹³⁹ Transitional care interventions that have successfully reduced 30-day readmission rates are most often multicomponent and focus not just on hospital-based interventions (eg, discharge planning, education) but on follow-up care in the community by formal supports (eg, in-home visits, telephone calls, outpatient clinic appointments, case management) and informal supports (eg, family and friends).^140-143 Further, qualitative evidence suggests that some individuals perceive psychiatric hospitalizations to be the result of insufficient resources or unsuccessful attempts to maintain their stability in the community.¹⁴⁴ Thus, unplanned or avoidable hospital readmissions may represent a failure of the continuum of care not only from the perspective of the health care system, but from the patient perspective as well.

Frequent or nonurgent use of EDs is conceptually similar to excessive or avoidable inpatient utilization in several ways. For example, overuse of EDs is costly, with some estimates suggesting that it is responsible for up to $38 billion in wasteful spending each year.¹⁴⁵ Individuals with frequent ED visits have a greater disease burden¹⁴⁶ and an increased risk of mortality compared to nonfrequent users.¹⁴⁷ Research suggests that individuals who visit the ED for non-urgent issues do so because of perceived difficulties associated with accessing primary care, and the convenience of EDs relative to primary care.^148-150 Moreover, similar to the hospital readmission literature discussed earlier, successful strategies to reduce high rates of ED utilization generally focus on continuum of care interventions, such as provision of case management services.^151-155

This evidence implies that frequent ED utilization and hospital readmissions may not be a fundamental issue of quality (or lack thereof) in hospitals or EDs but rather a lack of, or ineffectual, transitional and continuum of care strategies and services. To underscore this point, some authors have argued that a system that is excessively crisis-oriented hinders recovery because it is reactive rather than proactive, predicated on the notion that one’s condition must deteriorate to receive care.¹⁵⁶

Although some organizations may have access to claims data or may function as self-contained health systems (eg, the Veterans Health Administration [VHA] ), others may not have access to such data. In the absence of claims data, patient self-report of service utilization has been used as a proxy for actual agency records.¹⁵⁷ Although concordance between medical and/or agency records and patient self-report has been variable,¹⁵⁷ evidence generally suggests that rates of agreement are higher the shorter the recall time interval.^158,159 BHD does not have access to comprehensive claims data and has therefore chosen to use 5 dichotomously scored (yes/no) questions—related to medical inpatient, medical ED, psychiatric inpatient, psychiatric ED, and detoxification use in the last 30 days—to represent the CD of acute service utilization.

The Second Aim: Quality of Care

Safety

Safety is defined as avoiding injuries to patients from the care that is intended to help them.

Brief review and suggested item(s). As noted in “Crossing the Quality Chasm,” the IOM’s seminal document, “the health care environment should be safe for all patients, in all of its processes, all the time.”¹⁶⁰ The landmark Harvard Medical Practice Study in 1991 found that adverse events occurred in nearly 4% of all hospital admissions and, among these, over a quarter were due to negligence.¹⁶¹ Other estimates of adverse events range as high as 17%.¹⁶² Indeed, a recent article by Makary and Daniel estimated that medical errors may be the third leading cause of death in the United States.¹⁶³ Unfortunately, research on safety in the mental health field has lagged behind that of physical health,¹⁶⁴ with evidence indicating that research in nonhospital settings in mental health care may be particularly scarce.¹⁶⁵ In a study of adverse events that occurred in psychiatric inpatient units in the VHA system between 2015 and 2016, Mills and colleagues found that of the 87 root cause analysis reports, suicide attempts were the most frequent, and, among safety events, falls were the most frequently reported, followed by medication events.¹⁶⁶ Another report on data collected from psychiatric inpatient units in the VHA revealed that nearly one-fifth of patients experienced a safety event, over half of which were deemed preventable.¹⁶⁷ These numbers likely represent an underestimation of the true volume of safety events, as another study by the same research group found that less than 40% of safety events described in patient medical records were documented in the incident reporting system.¹⁶⁸ BHD will utilize the total number of complaints and incident reports submitted within a given time frame as its “safety” metric in the CD data set.

Wait Time for Service

The CD is defined as the length of time between the date a patient first contacted BHD for services and the date of their first clinical service.

Brief review and suggested item(s). “Timeliness” was listed among the 6 aims for improvement in “Crossing the Quality Chasm” in 2001, and it remains no less relevant today.¹⁶⁰ For example, evidence indicates that access to primary care is inversely related to avoidable hospitalizations.¹⁶⁹ One study found that, of patients hospitalized for cardiovascular problems, those who had difficulty accessing routine care post discharge had higher 30-day readmission rates.¹⁷⁰ Among VHA patients, longer wait times are associated with more avoidable hospitalizations and higher rates of mortality.¹⁷¹ Longer wait times appear to decrease the likelihood of attending a first appointment for individuals with substance use^172,173 and mental health disorders.¹⁷⁴ Importantly, longer wait times are associated with lower ratings of the patient experience of care, including perceptions of the quality of and satisfaction with care,¹⁷⁵ and may be associated with worse outcomes for individuals in early intervention for psychosis treatment.¹⁷⁶ For the purposes of the CD data set, BHD will monitor the length of time between the date a patient first contacted BHD for services and the date of their first clinical service.

 

 

Patient Satisfaction

Patient satisfaction is defined as the degree of patients’ satisfaction with the care they have received.

Brief review and suggested item(s). Research has consistently demonstrated the relationship of the patient’s experience of care to a variety of safety and clinical effectiveness measures in medical health care,¹⁷⁷ and the therapeutic alliance is one of the most consistent predictors of outcomes in behavioral health, regardless of therapeutic modality.¹⁷⁸ Patient satisfaction is a commonly assessed aspect of the patient experience of care. Patient satisfaction scores have been correlated with patient adherence to recommended treatment regimens, care quality, and health outcomes.¹⁷⁹ For example, Aiken et al found that patient satisfaction with hospital care was associated with higher ratings of the quality and safety of nursing care in these hospitals.¹⁸⁰ Increased satisfaction with inpatient care has been associated with lower 30-day readmission rates for patients with acute myocardial infarction, heart failure, and pneumonia,¹⁸¹ and patients with schizophrenia who reported higher treatment satisfaction also reported better quality of life.^182,183 Many satisfaction survey options exist to evaluate this CD, including the Consumer Assessment of Healthcare Providers and Systems and the Client Satisfaction Questionnaire; BHD will utilize an outpatient behavioral health survey from a third-party vendor.

The Third Aim: Cost of Care

Cost of Care

This can be defined as the average cost to provide care per patient per month.

Brief review and suggested item(s). Per capita cost, or rather, the total cost of providing care to a circumscribed population divided by the total population, has been espoused as an important metric for the Triple Aim and the County Health Rankings.^6,13 Indeed, between 1960 and 2016, per capita expenditures for health care have grown 70-fold, and the percent of the national gross domestic product accounted for by health expenditures has more than tripled (5.0% to 17.9%).¹⁸⁴ One of the more common metrics deployed for assessing health care cost is the per capita per month cost, or rather, the per member per month cost of the predefined population for a given health care system.^6,185,186 In fact, some authors have proposed that cost of care can be used not only to track efficient resource allocation, but can also be a proxy for a healthier population as well (ie, as health improves, individuals use fewer and less-expensive services, thus costing the system less).¹⁸⁷ To assess this metric, BHD will calculate the total amount billed for patient care provided within BHD’s health network each month (irrespective of funding source) and then divide this sum by the number of members served each month. Although this measure does not account for care received at other health care facilities outside BHD’s provider network, nor does it include all the overhead costs associated with the care provided by BHD itself, it is consistent with the claims-based approach used or recommended by other authors.^6,188

The Fourth Aim: Staff Well-being

Staff Quality of Work Life

This can be defined as the quality of the work life of health care clinicians and staff.

Brief review and suggested item(s). Some authors have suggested that the Triple Aim framework is incomplete and have proffered compelling arguments that provider well-being and the quality of work life constitutes a fourth aim.² Provider burnout is prevalent in both medical^2,189 and behavioral health care.^190,191 Burnout among health care professionals has been associated with higher rates of perceived medical errors,¹⁹² lower patient satisfaction scores,^189,193 lower rates of provider empathy,¹⁹⁴ more negative attitudes towards patients,¹⁹⁵ and poorer staff mental and physical health.¹⁹¹

Burnout is also associated with higher rates of absenteeism, turnover intentions, and turnover.^{190,191,196,197} However, burnout is not the only predictor of staff turnover; for example, turnover rates are a useful proxy for staff quality of work life for several reasons.¹⁹⁸ First, turnover is associated with substantial direct and indirect costs, including lost productivity, increased errors, and lost revenue and recruitment costs, with some turnover cost estimates as high as $17 billion for physicians and $14 billion for nurses annually.^199-201 Second, research indicates that staff turnover can have a deleterious impact on implementation of evidence-based interventions.^202-205 Finally, consistent with the philosophy of utilizing existing data sources for the CD measures, turnover can be relatively easily extracted from administrative data for operated or contracted programs, and its collection does not place any additional burden on staff. As a large behavioral health system that is both a provider and payer of care, BHD will therefore examine the turnover rates of its internal administrative and clinical staff as well as the turnover of staff in its contracted provider network as its measures for the Staff Quality of Work Life CD.

Clinical Implications

These metrics can be deployed at any level of the organization. Clinicians may use 1 or more of the measures to track the recovery of individual clients, or in aggregate for their entire caseload. Similarly, managers can use these measures to assess the overall effectiveness of the programs for which they are responsible. Executive leaders can evaluate the impact of several programs or the system of care on the health of a subpopulation of clients with a specific condition, or for all their enrolled members. Further, not all measures need be utilized for every dashboard or evaluative effort. The benefit of a comprehensive set of measures lies in their flexibility—1 or more of the measures may be selected depending on the project being implemented or the interests of the stakeholder.

It is important to note that many of the CDs (and their accompanying measures) are aligned to/consistent with social determinants of health.^206,207 Evidence suggests that social determinants make substantial contributions to the overall health of individuals and populations and may even account for a greater proportion of variance in health outcomes than health care itself.²⁰⁸ The measures articulated here, therefore, can be used to assess whether and how effectively care provision has addressed these social determinants, as well as the relative impact their resolution may have on other health outcomes (eg, mortality, self-rated health).

These measures can also be used to stratify clients by clinical severity or degree of socioeconomic deprivation. The ability to adjust for risk has many applications in health care, particularly when organizations are attempting to implement value-based purchasing models, such as pay-for-performance contracts or other alternative payment models (population health-based payment models).²⁰⁹ Indeed, once fully implemented, the CDs and measures will enable BHD to more effectively build and execute different conceptual models of “value” (see references 210 and 211 for examples). We will be able to assess the progress our clients have made in care, the cost associated with that degree of improvement, the experience of those clients receiving that care, and the clinical and social variables that may influence the relative degree of improvement (or lack thereof). Thus, the CDs provide a conceptual and data-driven foundation for the Quadruple Aim and any quality initiatives that either catalyze or augment its implementation.

 

 

Conclusion

This article provides an overview of the CDs selected by BHD to help organize, focus, advance, and track its quality efforts within the framework of the Quadruple Aim. Although items aligned to each of these CDs are offered, the CDs themselves have been broadly conceptualized such that they can flexibly admit a variety of possible items and/or assessments to operationalize each CD and thus have potential applicability to other behavioral health systems, particularly public systems that have state-mandated and other data reporting requirements.

Bearing in mind the burden that growing data collection requirements can have on the provision of quality care and staff work satisfaction and burnout,^10,212 the CDs (and the items selected to represent each) are designed with “strategic parsimony” in mind. Although the CDs are inclusive in that they cover care quality, cost of care, staff quality of life, and general population health, only CDs and items undergirded by a solid evidence base and high value with regards to BHD’s mission and values, as determined by key stakeholders, were selected. Moreover, BHD attempted to make use of existing data collection and reporting mandates when selecting the final pool of items to reduce the measurement burden on staff and clients. Thus, the final set of CDs and items are designed to be comprehensive yet economical.

The CDs are deeply interrelated. Although each CD may be individually viewed as a valuable metric, improvements in any 1 CD will impact the others (eg, increasing care quality should impact population health, increasing staff quality of life should impact the quality of care). Moreover, this idea of interrelatedness acknowledges the need to view health systems and the populations they serve holistically, in that improvement is not simply the degree of change in any given metric (whether individually or collectively), but rather something more entirely. The concepts of value, quality, and health are complex, multidimensional, and dynamic, and the CDs that comprise these concepts should not be considered independently from one another. The CDs (and items) offered in this article are scalable in that they can be used at different levels of an organization depending on the question or stakeholder, and can be used individually or in combination with one another. Moreover, they are adaptable to a variety of risk-adjusted program, population health, and value-based evaluation models. It is hoped that the process articulated here, and the accompanying literature review, may benefit other public or government-run health systems in their own quality journey to operationalize the Quadruple Aim by developing a set of CDs.

Corresponding author: Walter Matthew Drymalski, PhD; walter.drymalski@milwaukeecountywi.gov.

Financial disclosures: None.

From the Milwaukee County Behavioral Health Division, Milwaukee, WI.

Abstract

Objective: Implementation of the Quadruple Aim of health care must begin with a clearly articulated set of concepts, or core domains (CDs), that comprise each aim. These CDs can then be operationalized with existing or new measures. If aligned to the organization’s mission and strategic goals, these CDs have the potential to focus quality improvement activities and reduce measurement burden. This article represents the efforts of a publicly funded behavioral health system to operationalize the Quadruple Aim through the development of CDs.

Methods: Various stakeholders across the organization were consulted on their perceptions of the Quadruple Aim and the CDs they believed should support it. Then, a review of existing literature on core metrics for health care and population health was completed, summarized, and integrated with the stakeholder feedback.

Results: These efforts led to the development and adoption of 15 CDs, with an accompanying literature review and set of recommendations of new and existing measures for each domain.

Conclusions: It is possible to create a comprehensive yet economical set of CDs and attendant measures that can be implemented in a staged, scalable, enterprise manner. It is hoped that the process articulated here, and the accompanying literature review, may be of some benefit to other public or government-run health systems in their own quality improvement journey to operationalize the Quadruple Aim by developing a set of CDs.

Keywords: quality measures; quality improvement; adult behavioral health.

First articulated in 2008, the Triple Aim proposes that health care systems should simultaneously seek to improve the patient’s experience of care, improve the health of populations, and reduce the per capita costs of care for populations.¹ More recently, some have argued that health care provider burnout can deleteriously impact the attainment of the Triple Aim and have therefore advocated for an expanded focus to include a fourth Aim, the work life quality of the staff.² Milwaukee County Behavioral Health Division (BHD), a publicly funded, county-based behavioral health care system in Milwaukee, Wisconsin, recently adopted the Quadruple Aim as the framework by which it will organize its quality activities.

Although originally developed for medical organizations, BHD believes that the Quadruple Aim has strong applicability to county-level behavioral health services. Many county-based behavioral health divisions provide a variety of programs to large segments of the county based on financial eligibility and/or clinical need, and thus often have responsibilities to populations or subpopulations, rather than programs. County health divisions, such as Milwaukee County’s Department of Health and Human Services, are often asked to improve outcomes and client experience of care with neutral growth budgets and less reliance on taxes to fund programs, while simultaneously attracting and retaining competent staff.

Crucial to the effective implementation of the Quadruple Aim, however, is a clear set of population- level measures that help organizations assess their progress.³ Unfortunately, as some authors have noted, evaluation of the Quadruple Aim remains a challenge because the “concepts of (population) health, quality of care and costs are not unanimously defined and measures for these concepts are under construction.”⁴ Several authors have provided some guidance to assist in the development of a set of measures that effectively capture the elements of the Quadruple Aim.^5,6 However, the recent rapid proliferation of quality measures in health care^7,8 has been both burdensome and costly for providers.^9,10 Any measures adopted should not only be as meaningful as possible with regards to assessing progress towards the basic aims of health care, but should also be parsimonious, to limit measurement burden for providers (and patients) and focus attention on important issues.^11,12

To select the most effective, parsimonious set of measures possible, one must first select a set of key foci from among the many possible areas of focus that the core measure is intended to represent. The core domains (CDs), if appropriately consistent with the strategic goals of the organization, provide a mechanism to orient the efforts of the organization at every level and help every staff member of the organization understand how his or her work impacts the progress towards these goals.¹¹ The CDs, therefore, represent the opportunity to affect a greater integration of efforts across the organization toward these shared aims, creating uniformity of purpose at every level. Further, increasing organizational attention on the CDs can also help to reduce measurement burden by streamlining and focusing the data capture processes on the most valuable elements of quality and health, and discarding other extraneous measures (albeit not at the expense of other reporting requirements).¹¹ The remainder of this article describes the CDs selected by BHD to assess its progress toward implementation of the Quadruple Aim and are organized by the Aim which they best represent.

Methods

To effectively implement the Quadruple Aim at BHD, it was necessary to clearly define the subpopulation of focus for our efforts.⁶ In this case, the subpopulation of interest was defined as all adult clients (18 years and older) who received at least 1 service encounter within a specified time frame from a program that BHD either operated or contracted with to provide care. Services provided by the BHD network include everything from psychiatric inpatient services to mental health and addiction treatment and care management. A limited array of social services, including housing and employment services, is also available to eligible consumers. BHD is the county-run behavioral health provider for individuals who are uninsured or underinsured in Milwaukee County, a demographically diverse, primarily urban county of approximately 950,000 people located in Wisconsin. Approximately 15,000 adults receive services at BHD each year.

This work began by obtaining executive sponsorship for the project, in this case from the Chief Operations Officer and Executive Medical Director of BHD. With their backing, an initial review of the literature produced a preliminary set of possible domains, for which we created working definitions. We then made a list of key stakeholders throughout BHD to whom we needed to present the idea of the Quadruple Aim, and the CDs under each Aim, to secure their support. These stakeholders, which included individuals involved in quality activities, program managers, and executive leadership, were strategically selected based on their relative influence within the organization. A set of brief presentations and handouts explaining the project were then developed and shared at different focus groups with these stakeholders over the course of 6 months. These focus groups served to not only educate the organization about the Quadruple Aim and the CDs but afforded participants an opportunity to provide feedback as well.

During the focus groups, we asked participants which domains they believed were most important (were “core”) when operationalizing the Quadruple Aim. The focus groups provided feedback on the domain definitions, feedback that was used to develop uniform, mutually agreed upon definitions for the CDs that were generalizable to all departments at BHD, regardless of the focus of their services within the continuum of care or the continuum of age. This was a crucial step, as it will eventually enable BHD to aggregate data across departments, even if there are minor discrepancies in the specific items they use to assess the CDs. Comments from the focus groups ultimately resulted in a truncated list of domains and definitions, which, coupled with the literature review, resulted in our final set of CDs.

During our review of the literature, we also looked for items that we felt could best represent each CD in the briefest, most meaningful way. (These items were not meant to supersede existing data, but to provide examples that could be implemented with existing data or recommendations that could be utilized in the absence of existing data.) During this process, we made every effort to make use of existing data-reporting requirements. For example, if we had a state mandate to collect data on housing status, we attempted to leverage this required data point to represent the CD related to housing. In other cases, we attempted to utilize claims or other administrative data to operationalize the CD, such as in the cost-of-care metric articulated in the section the Third Aim. For CDs for which no data existed or were insufficient, we emphasized the use of single- versus multi-item scales. For example, if we found a single-item global assessment of quality of life that had good psychometric properties relative to its longer parent scale, we selected the single item. This approach to item selection allowed us to create the most efficient, parsimonious set of measures possible, which we believed would enable us to comprehensively assess all the CDs with the least amount of burden to staff and clients. These items were presented at stakeholder focus groups, during which we asked for comments on the existing measures in their program or department and gave them the opportunity to comment on the new recommended measures.

A working definition is provided for each CD, followed by a brief review of the research base supporting its inclusion in the final list. The item(s) selected by BHD to represent each CD and the source of the item(s) are then supplied. These items were based either on measures currently collected because of existing reporting mandates or, in the case where extant measures were not available, on new items that demonstrated acceptable psychometric properties in the research literature. The CDs and items are organized by the Aim they best represent. A full list of the CDs by Quadruple Aim and items by CD is provided in the Appendix of the online version of this article. This article concludes with a brief summary of this effort and a discussion of how staff will utilize these items at different levels throughout the BHD system.

The First Aim: Population Health

Health Outcomes

Deaths. This can be defined as the cause of death, as determined by the medical examiner’s office (where appropriate) or as the age at time of death. This CD can also be reported as proportion of deaths considered premature (eg, before age 75) or calculated as total years of potential life lost.

Brief review and suggested item(s). Rates and causes of premature mortality are critical foci for the County Health Rankings & Roadmaps,¹³ the Institute for Healthcare Improvement’s “Guide to Measuring the Triple Aim,”⁶ the Centers for Disease Control and Prevention’s “Community Health Assessment for Population Health Improvement,”¹⁴ and the Institute of Medicine’s (IOM) “Vital Signs: Core Metrics for Health and Health Care Progress.”¹¹ There is ample evidence that individuals with serious mental illness are at increased risk of early mortality relative to the general population,^15-18 and this risk applies to those with substance use disorders as well.^15,19-20 BHD tracks all deaths that occur while patients are receiving BHD-funded, community-based services.

Self-Reported Health and Well-Being. This CD asks patients to rate their current physical and mental health status, as well as their overall quality of life.

Brief review and suggested item(s): Self-rated physical health. Premature mortality among individuals with behavioral health issues appears to be due, in large part, to their increased vulnerability to the development of medical comorbidities.^16,21 A single self-rating question has demonstrated considerable sensitivity to premature mortality,^22,23 with predictive properties up to a decade prior to death.^24,25 Further, self-rated health has been associated with subsequent functional decline,^26,27 acute service utilization,^28,29 and overall health care costs.²⁸

Brief review and suggested item(s): Self-rated mental health. Mental health disorders are associated with significant disability worldwide,³⁰ and comorbid mental health issues can exacerbate the course of other medical problems. For example, depression is associated with increased rates of mortality among individuals with diabetes and³¹ cardiovascular disease,³² as well as with rates of overall mortality,³³ and psychiatric comorbidity is associated with longer lengths of stay and higher costs among patients hospitalized for medical problems.³⁴ Research has found that a single-item measure of self-rated mental health is associated with the presence of psychiatric diagnoses, psychiatric symptoms, and subsequent depression and serious mental illness up to 1 year post-assessment.^35,36 There is even evidence that self-rated mental health may be more strongly associated with self-ratings of overall health than self-ratings of physical health.³⁷

Brief review and suggested item(s): Self-rated quality of life. Quality of life is a critical component of the recovery journey and overall health.³⁸ For example, the County Health Rankings & Roadmaps lists “quality of life” as 1 of its key “health outcomes” in its County Health Rankings.¹³ As some authors have noted, quality of life is often inferred from other “objective” recovery domains, such as employment, health status, or housing status. However, there is evidence that these objective domains are functionally distinct from the inherently subjective construct of quality of life.³⁹ This has led other authors to conclude that these domains should be assessed separately when evaluating outcomes.⁴⁰ Single-item quality of life assessments have been used in research with individuals with cancer,⁴¹ adults with disabilities,⁴² patients with cystic fibrosis,⁴³ and children with epilepsy.⁴⁴ For this effort, BHD selected the first global quality of life item from the World Health Organization’s WHOQOL-BREF quality of life assessment,⁴⁵ an item used in other quality of life research.⁴⁶

Health Factors

Substance Use. This CD is a composite of 4 different types of substance use, any recent heavy alcohol use (defined as 5 or more drinks in one sitting), any recent drug use, any recent prescription drug abuse, and any recent tobacco use.

Brief review and suggested item(s). As noted, substance use disorders confer an increased risk for early mortality^15,19 and are significantly implicated in disease disability burden worldwide.³⁰ Substance use has also been associated with both the onset^47,48 and exacerbation of mental health diagnoses.^49-51 Further, substance use appears to heighten the risk of violence in the general population⁵² and especially among those with a co-occurring mental illness.^53,54 The County Health Rankings & Roadmaps list alcohol and drug use as key behaviors to address to improve the overall health of a given county,¹³ and the Centers for Medicare & Medicaid Services (CMS) has endorsed initiation and engagement in addiction treatment as one of the measures in its Adult Core Set.⁵⁵

Tobacco use continues to be one of the most significant risk factors for early mortality worldwide, and evidence indicates that it is associated with a lower life expectancy of nearly 10 years.⁵⁶ Unfortunately, rates of tobacco use are even higher among those with severe mental illness relative to the general population, and their rates of smoking cessation are lower.^57,58 Tobacco use is a significant risk factor for the high rates of early mortality in individuals with severe mental illness.¹⁸ Further, a recent meta-analysis noted that, relative to those who continued to smoke, those who ceased smoking had reduced rates of psychological distress and increased quality of life rankings.⁵⁹ Reducing tobacco use is one of the key components of the County Health Rankings & Roadmaps, and medication assistance with smoking and tobacco use cessation is also listed in the CMS Adult Core Set.^13,55

An accumulating body of evidence suggests that single-item measures can adequately detect alcohol^60-62 and drug use disorders.^60-64 McNeely and colleagues recently developed and tested a brief 4-item screen, the Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS) tool.^65,66 Preliminary evidence suggests that the TAPS tool can effectively identify the presence of problematic and disordered use of tobacco, alcohol, prescription medications, and other drugs.^65-67 BHD will use the 4 items from the TAPS tool to represent its substance use CD.

Education/Employment Status. This CD assesses the proportion of BHD members who have completed high school, who are in some type of educational or training program, or who are engaged in some type of employment activity (defined as full-time, part-time, supported, sheltered workshop, or as a full-time homemaker).

Brief review and suggested item(s). Research indicates that unemployment is a risk factor for mortality, even after controlling for other risk factors (eg, age, sex, socioeconomic status [SES], health).⁶⁸ Unemployment is associated with poorer physical and mental health in the general population and among those with disabilities.^69-71 Promisingly, evidence suggests that gaining employment or re-employment is associated with better health,⁷² even for individuals with substance use disorders⁷³ or moderate⁷⁴ to severe mental health disorders.^75-78 Some authors have even proposed that, above and beyond the associated health benefits, employment may also help to realize a modest cost savings due to reduced service utilization and disability.^79,80 Employment is a core tenet in the Substance Abuse and Mental Health Services Administration’s (SAMHSA’s) model of recovery,⁸¹ and is also listed as an important recovery goal for individuals with behavioral health issues.⁸² BHD collects data on employment status on all the patients it serves as part of its state-mandated reporting requirements and will use this item in the CD data set.⁸³

Living Situation. This is measured as the proportion of people who live in permanent, supportive, stable housing; it may also be measured as the percentage of the population living with severe housing problems or who are homeless.

Brief review and suggested item(s). Housing problems can be conceptualized as 3 inter-related components: conditions within the home, neighborhood conditions, and housing affordability, each of which can contribute uniquely to poorer physical and mental health of individuals and families⁸⁴ and to educational outcomes for children.^85,86 Further, individuals who are homeless have a standardized mortality ratio 2 to 5 times that of the general population,^87-89 even after controlling for low income status,⁹⁰ and some evidence suggests these rates are even higher among unsheltered versus sheltered homeless individuals.⁹¹ Interventions to improve the condition of housing have demonstrated positive impacts on both physical and mental health,⁹² and a recent study found that individuals receiving housing assistance in the form of public housing or multifamily housing from the Department of Housing and Urban Development had better self-rated physical and mental health relative to individuals on the wait list for housing assistance.⁹³ Moreover, the provision of housing has been shown to promote reductions in substance use and health service utilization among homeless individuals with substance use disorders.⁹⁴ Rog and colleagues reviewed the literature on permanent supportive housing for individuals with substance use or mental health disorders who were homeless or disabled, and found that provision of housing led to reduced rates of homelessness, emergency department (ED) and inpatient utilization and increased consumer satisfaction.⁹⁵

Importantly, evidence suggests that housing is viewed as facilitative of recovery. For example, in a recent qualitative study of homeless individuals with mental illness, housing was seen as a critical first step in recovery, providing a sense of security, increasing feelings of personal independence and autonomy, improving perceptions of health and well-being, and affording a stable environment to rebuild relationships with important others.⁹⁶ BHD collects data on housing status on all the patients it serves as part of its state-mandated reporting requirements and will utilize this item in the CD data set.⁸³

Social Relationships. This is defined as recent interactions with family, supportive networks (formal and informal), and other recovery services.

Brief review and suggested item(s). Research has long established that social relationships have a significant impact on health, including rates of mortality as well as physical and mental health morbidity.^97-99 Social connectedness is another of the pillars supporting an individual’s recovery in SAMHSA’s formulation. Several reviews of the recovery literature^38,82 support its importance to the recovery process and inclusion in any assessment of holistic recovery. Social support has been shown to promote recovery among individuals with severe mental illness^100-102 and substance use disorders,¹⁰³ and may mitigate the progression of chronic, life-threatening physical illnesses.⁹⁷ For the purposes of BHD’s CD data set, the social support question from the “100 Million Healthier Lives Common Questionnaire for Adults” will be used to assess individuals’ perceived adequacy of social support.¹⁰⁴

Legal Involvement. Defined as involvement with the civil or criminal justice system, including arrests, imprisonment, or detainment.

Brief review and suggested item(s). Involvement in the criminal justice system is both disruptive for the individual in recovery and expensive to the larger health care system.¹⁰⁵ Individuals with substance use¹⁰⁶ and severe mental health disorders¹⁰⁷ are over-represented in the prison system, and evidence suggests that general physical and mental health declines while individuals are in prison.^108,109 Perhaps even more concerning, numerous studies have demonstrated an increase in mortality rates for individuals recently released from prison relative to the general population, particularly during the period immediately following release.^108-110 This relationship may even persist long term.¹¹¹ Further, research indicates that individuals recently released from prison have increased emergency care and hospital utilization.^112,113

Incarceration can have significant impacts on the health of the broader community as well. For example, research has found an association between parental incarceration to rates of infant mortality,¹¹⁴ increased behavioral and developmental problems of children of incarcerated parents,^115,116 lower rates of child support payments,¹¹⁷ and poorer cardiovascular health of female partners of incarcerated individuals.¹¹⁸ Formerly incarcerated individuals experience slower wage growth as well.¹¹⁹ However, evidence also indicates that engagement in mental health¹²⁰ and substance abuse¹²¹ treatment can reduce the likelihood of subsequent recidivism. As part of its state-mandated reporting, BHD is required to provide information on the criminal justice system involvement of its clients in the previous 6 months, including whether they have been jailed or imprisoned,⁸³ and this will function as its measure of legal involvement in its CD data set.

Socioeconomic Status. Socioeconomic status is the social standing or class of an individual or group. It is often measured as a combination of education, income, and occupation. It can also be defined subjectively, such as one’s evaluation of status relative to similar others or based on an individual’s interpretation of her or his financial needs.

Brief review and suggested item(s). A large body of evidence supports the existence of a robust relationship between lower SES and poor health, including mortality and chronic medical diseases,^122-124 as well as mental illness.^125-127 Although previous research has examined this relationship using objective indicators of SES (eg, income, education level, occupation), there has recently been an increased interest in exploring the relationship of subjective SES with health indices. Subjective SES is generally assessed by asking individuals to rate themselves relative to others in the society in which they live, in terms of wealth, occupation, educational level, or other indicators of social status. Evidence suggests that subjective SES is associated with objective measures of SES,^128-130 and relates to measures of physical and mental health as well, even after controlling for objective SES.^130-135 BHD will be using a modified version of the Subject SES Scale,^131,135 which is deployed in the “100 Million Healthier Lives Common Questionnaire for Adults.”¹⁰⁴

Acute Service Use. This is defined as an admission to a medical or psychiatric emergency room or to a medical or psychiatric hospital or to a detoxification facility.

Brief review and suggested item(s). The CMS Adult Core Set includes “plan all cause readmissions” as a key quality metric.⁵⁵ Hospital readmissions are also endorsed by the National Committee on Quality Assurance as one of its Health Effectiveness Data and Information Set (HEDIS) measures and by the National Quality Forum. Readmissions, despite their widespread endorsement, are a somewhat controversial measure. Although readmissions are costly to the health care system,¹³⁶ the relationship between readmissions and quality is inconsistent. For example, Krumholz and colleagues¹³⁷ found differential rates of readmission for the same patient discharged from 2 different hospitals, which were categorized based on previous readmission rates, suggesting that hospitals do have different levels of performance even when treating the same patient. However, other data indicate that 30-day, all-cause, risk-standardized readmission rates are not associated with hospital 30-day, all-cause, risk-standardized mortality rates.¹³⁸

Chin and colleague found that readmissions to the hospital that occurred more than 7 days post-discharge were likely due to community- and household-related factors, rather than hospital-related quality factors.¹³⁹ Transitional care interventions that have successfully reduced 30-day readmission rates are most often multicomponent and focus not just on hospital-based interventions (eg, discharge planning, education) but on follow-up care in the community by formal supports (eg, in-home visits, telephone calls, outpatient clinic appointments, case management) and informal supports (eg, family and friends).^140-143 Further, qualitative evidence suggests that some individuals perceive psychiatric hospitalizations to be the result of insufficient resources or unsuccessful attempts to maintain their stability in the community.¹⁴⁴ Thus, unplanned or avoidable hospital readmissions may represent a failure of the continuum of care not only from the perspective of the health care system, but from the patient perspective as well.

Frequent or nonurgent use of EDs is conceptually similar to excessive or avoidable inpatient utilization in several ways. For example, overuse of EDs is costly, with some estimates suggesting that it is responsible for up to $38 billion in wasteful spending each year.¹⁴⁵ Individuals with frequent ED visits have a greater disease burden¹⁴⁶ and an increased risk of mortality compared to nonfrequent users.¹⁴⁷ Research suggests that individuals who visit the ED for non-urgent issues do so because of perceived difficulties associated with accessing primary care, and the convenience of EDs relative to primary care.^148-150 Moreover, similar to the hospital readmission literature discussed earlier, successful strategies to reduce high rates of ED utilization generally focus on continuum of care interventions, such as provision of case management services.^151-155

This evidence implies that frequent ED utilization and hospital readmissions may not be a fundamental issue of quality (or lack thereof) in hospitals or EDs but rather a lack of, or ineffectual, transitional and continuum of care strategies and services. To underscore this point, some authors have argued that a system that is excessively crisis-oriented hinders recovery because it is reactive rather than proactive, predicated on the notion that one’s condition must deteriorate to receive care.¹⁵⁶

Although some organizations may have access to claims data or may function as self-contained health systems (eg, the Veterans Health Administration [VHA] ), others may not have access to such data. In the absence of claims data, patient self-report of service utilization has been used as a proxy for actual agency records.¹⁵⁷ Although concordance between medical and/or agency records and patient self-report has been variable,¹⁵⁷ evidence generally suggests that rates of agreement are higher the shorter the recall time interval.^158,159 BHD does not have access to comprehensive claims data and has therefore chosen to use 5 dichotomously scored (yes/no) questions—related to medical inpatient, medical ED, psychiatric inpatient, psychiatric ED, and detoxification use in the last 30 days—to represent the CD of acute service utilization.

The Second Aim: Quality of Care

Safety

Safety is defined as avoiding injuries to patients from the care that is intended to help them.

Brief review and suggested item(s). As noted in “Crossing the Quality Chasm,” the IOM’s seminal document, “the health care environment should be safe for all patients, in all of its processes, all the time.”¹⁶⁰ The landmark Harvard Medical Practice Study in 1991 found that adverse events occurred in nearly 4% of all hospital admissions and, among these, over a quarter were due to negligence.¹⁶¹ Other estimates of adverse events range as high as 17%.¹⁶² Indeed, a recent article by Makary and Daniel estimated that medical errors may be the third leading cause of death in the United States.¹⁶³ Unfortunately, research on safety in the mental health field has lagged behind that of physical health,¹⁶⁴ with evidence indicating that research in nonhospital settings in mental health care may be particularly scarce.¹⁶⁵ In a study of adverse events that occurred in psychiatric inpatient units in the VHA system between 2015 and 2016, Mills and colleagues found that of the 87 root cause analysis reports, suicide attempts were the most frequent, and, among safety events, falls were the most frequently reported, followed by medication events.¹⁶⁶ Another report on data collected from psychiatric inpatient units in the VHA revealed that nearly one-fifth of patients experienced a safety event, over half of which were deemed preventable.¹⁶⁷ These numbers likely represent an underestimation of the true volume of safety events, as another study by the same research group found that less than 40% of safety events described in patient medical records were documented in the incident reporting system.¹⁶⁸ BHD will utilize the total number of complaints and incident reports submitted within a given time frame as its “safety” metric in the CD data set.

Wait Time for Service

The CD is defined as the length of time between the date a patient first contacted BHD for services and the date of their first clinical service.

Brief review and suggested item(s). “Timeliness” was listed among the 6 aims for improvement in “Crossing the Quality Chasm” in 2001, and it remains no less relevant today.¹⁶⁰ For example, evidence indicates that access to primary care is inversely related to avoidable hospitalizations.¹⁶⁹ One study found that, of patients hospitalized for cardiovascular problems, those who had difficulty accessing routine care post discharge had higher 30-day readmission rates.¹⁷⁰ Among VHA patients, longer wait times are associated with more avoidable hospitalizations and higher rates of mortality.¹⁷¹ Longer wait times appear to decrease the likelihood of attending a first appointment for individuals with substance use^172,173 and mental health disorders.¹⁷⁴ Importantly, longer wait times are associated with lower ratings of the patient experience of care, including perceptions of the quality of and satisfaction with care,¹⁷⁵ and may be associated with worse outcomes for individuals in early intervention for psychosis treatment.¹⁷⁶ For the purposes of the CD data set, BHD will monitor the length of time between the date a patient first contacted BHD for services and the date of their first clinical service.

 

 

Patient Satisfaction

Patient satisfaction is defined as the degree of patients’ satisfaction with the care they have received.

Brief review and suggested item(s). Research has consistently demonstrated the relationship of the patient’s experience of care to a variety of safety and clinical effectiveness measures in medical health care,¹⁷⁷ and the therapeutic alliance is one of the most consistent predictors of outcomes in behavioral health, regardless of therapeutic modality.¹⁷⁸ Patient satisfaction is a commonly assessed aspect of the patient experience of care. Patient satisfaction scores have been correlated with patient adherence to recommended treatment regimens, care quality, and health outcomes.¹⁷⁹ For example, Aiken et al found that patient satisfaction with hospital care was associated with higher ratings of the quality and safety of nursing care in these hospitals.¹⁸⁰ Increased satisfaction with inpatient care has been associated with lower 30-day readmission rates for patients with acute myocardial infarction, heart failure, and pneumonia,¹⁸¹ and patients with schizophrenia who reported higher treatment satisfaction also reported better quality of life.^182,183 Many satisfaction survey options exist to evaluate this CD, including the Consumer Assessment of Healthcare Providers and Systems and the Client Satisfaction Questionnaire; BHD will utilize an outpatient behavioral health survey from a third-party vendor.

The Third Aim: Cost of Care

Cost of Care

This can be defined as the average cost to provide care per patient per month.

Brief review and suggested item(s). Per capita cost, or rather, the total cost of providing care to a circumscribed population divided by the total population, has been espoused as an important metric for the Triple Aim and the County Health Rankings.^6,13 Indeed, between 1960 and 2016, per capita expenditures for health care have grown 70-fold, and the percent of the national gross domestic product accounted for by health expenditures has more than tripled (5.0% to 17.9%).¹⁸⁴ One of the more common metrics deployed for assessing health care cost is the per capita per month cost, or rather, the per member per month cost of the predefined population for a given health care system.^6,185,186 In fact, some authors have proposed that cost of care can be used not only to track efficient resource allocation, but can also be a proxy for a healthier population as well (ie, as health improves, individuals use fewer and less-expensive services, thus costing the system less).¹⁸⁷ To assess this metric, BHD will calculate the total amount billed for patient care provided within BHD’s health network each month (irrespective of funding source) and then divide this sum by the number of members served each month. Although this measure does not account for care received at other health care facilities outside BHD’s provider network, nor does it include all the overhead costs associated with the care provided by BHD itself, it is consistent with the claims-based approach used or recommended by other authors.^6,188

The Fourth Aim: Staff Well-being

Staff Quality of Work Life

This can be defined as the quality of the work life of health care clinicians and staff.

Brief review and suggested item(s). Some authors have suggested that the Triple Aim framework is incomplete and have proffered compelling arguments that provider well-being and the quality of work life constitutes a fourth aim.² Provider burnout is prevalent in both medical^2,189 and behavioral health care.^190,191 Burnout among health care professionals has been associated with higher rates of perceived medical errors,¹⁹² lower patient satisfaction scores,^189,193 lower rates of provider empathy,¹⁹⁴ more negative attitudes towards patients,¹⁹⁵ and poorer staff mental and physical health.¹⁹¹

Burnout is also associated with higher rates of absenteeism, turnover intentions, and turnover.^{190,191,196,197} However, burnout is not the only predictor of staff turnover; for example, turnover rates are a useful proxy for staff quality of work life for several reasons.¹⁹⁸ First, turnover is associated with substantial direct and indirect costs, including lost productivity, increased errors, and lost revenue and recruitment costs, with some turnover cost estimates as high as $17 billion for physicians and $14 billion for nurses annually.^199-201 Second, research indicates that staff turnover can have a deleterious impact on implementation of evidence-based interventions.^202-205 Finally, consistent with the philosophy of utilizing existing data sources for the CD measures, turnover can be relatively easily extracted from administrative data for operated or contracted programs, and its collection does not place any additional burden on staff. As a large behavioral health system that is both a provider and payer of care, BHD will therefore examine the turnover rates of its internal administrative and clinical staff as well as the turnover of staff in its contracted provider network as its measures for the Staff Quality of Work Life CD.

Clinical Implications

These metrics can be deployed at any level of the organization. Clinicians may use 1 or more of the measures to track the recovery of individual clients, or in aggregate for their entire caseload. Similarly, managers can use these measures to assess the overall effectiveness of the programs for which they are responsible. Executive leaders can evaluate the impact of several programs or the system of care on the health of a subpopulation of clients with a specific condition, or for all their enrolled members. Further, not all measures need be utilized for every dashboard or evaluative effort. The benefit of a comprehensive set of measures lies in their flexibility—1 or more of the measures may be selected depending on the project being implemented or the interests of the stakeholder.

It is important to note that many of the CDs (and their accompanying measures) are aligned to/consistent with social determinants of health.^206,207 Evidence suggests that social determinants make substantial contributions to the overall health of individuals and populations and may even account for a greater proportion of variance in health outcomes than health care itself.²⁰⁸ The measures articulated here, therefore, can be used to assess whether and how effectively care provision has addressed these social determinants, as well as the relative impact their resolution may have on other health outcomes (eg, mortality, self-rated health).

These measures can also be used to stratify clients by clinical severity or degree of socioeconomic deprivation. The ability to adjust for risk has many applications in health care, particularly when organizations are attempting to implement value-based purchasing models, such as pay-for-performance contracts or other alternative payment models (population health-based payment models).²⁰⁹ Indeed, once fully implemented, the CDs and measures will enable BHD to more effectively build and execute different conceptual models of “value” (see references 210 and 211 for examples). We will be able to assess the progress our clients have made in care, the cost associated with that degree of improvement, the experience of those clients receiving that care, and the clinical and social variables that may influence the relative degree of improvement (or lack thereof). Thus, the CDs provide a conceptual and data-driven foundation for the Quadruple Aim and any quality initiatives that either catalyze or augment its implementation.

 

 

Conclusion

This article provides an overview of the CDs selected by BHD to help organize, focus, advance, and track its quality efforts within the framework of the Quadruple Aim. Although items aligned to each of these CDs are offered, the CDs themselves have been broadly conceptualized such that they can flexibly admit a variety of possible items and/or assessments to operationalize each CD and thus have potential applicability to other behavioral health systems, particularly public systems that have state-mandated and other data reporting requirements.

Bearing in mind the burden that growing data collection requirements can have on the provision of quality care and staff work satisfaction and burnout,^10,212 the CDs (and the items selected to represent each) are designed with “strategic parsimony” in mind. Although the CDs are inclusive in that they cover care quality, cost of care, staff quality of life, and general population health, only CDs and items undergirded by a solid evidence base and high value with regards to BHD’s mission and values, as determined by key stakeholders, were selected. Moreover, BHD attempted to make use of existing data collection and reporting mandates when selecting the final pool of items to reduce the measurement burden on staff and clients. Thus, the final set of CDs and items are designed to be comprehensive yet economical.

The CDs are deeply interrelated. Although each CD may be individually viewed as a valuable metric, improvements in any 1 CD will impact the others (eg, increasing care quality should impact population health, increasing staff quality of life should impact the quality of care). Moreover, this idea of interrelatedness acknowledges the need to view health systems and the populations they serve holistically, in that improvement is not simply the degree of change in any given metric (whether individually or collectively), but rather something more entirely. The concepts of value, quality, and health are complex, multidimensional, and dynamic, and the CDs that comprise these concepts should not be considered independently from one another. The CDs (and items) offered in this article are scalable in that they can be used at different levels of an organization depending on the question or stakeholder, and can be used individually or in combination with one another. Moreover, they are adaptable to a variety of risk-adjusted program, population health, and value-based evaluation models. It is hoped that the process articulated here, and the accompanying literature review, may benefit other public or government-run health systems in their own quality journey to operationalize the Quadruple Aim by developing a set of CDs.

Corresponding author: Walter Matthew Drymalski, PhD; walter.drymalski@milwaukeecountywi.gov.

Financial disclosures: None.

From the Milwaukee County Behavioral Health Division, Milwaukee, WI.

Abstract

Objective: Implementation of the Quadruple Aim of health care must begin with a clearly articulated set of concepts, or core domains (CDs), that comprise each aim. These CDs can then be operationalized with existing or new measures. If aligned to the organization’s mission and strategic goals, these CDs have the potential to focus quality improvement activities and reduce measurement burden. This article represents the efforts of a publicly funded behavioral health system to operationalize the Quadruple Aim through the development of CDs.

Methods: Various stakeholders across the organization were consulted on their perceptions of the Quadruple Aim and the CDs they believed should support it. Then, a review of existing literature on core metrics for health care and population health was completed, summarized, and integrated with the stakeholder feedback.

Results: These efforts led to the development and adoption of 15 CDs, with an accompanying literature review and set of recommendations of new and existing measures for each domain.

Conclusions: It is possible to create a comprehensive yet economical set of CDs and attendant measures that can be implemented in a staged, scalable, enterprise manner. It is hoped that the process articulated here, and the accompanying literature review, may be of some benefit to other public or government-run health systems in their own quality improvement journey to operationalize the Quadruple Aim by developing a set of CDs.

Keywords: quality measures; quality improvement; adult behavioral health.

First articulated in 2008, the Triple Aim proposes that health care systems should simultaneously seek to improve the patient’s experience of care, improve the health of populations, and reduce the per capita costs of care for populations.¹ More recently, some have argued that health care provider burnout can deleteriously impact the attainment of the Triple Aim and have therefore advocated for an expanded focus to include a fourth Aim, the work life quality of the staff.² Milwaukee County Behavioral Health Division (BHD), a publicly funded, county-based behavioral health care system in Milwaukee, Wisconsin, recently adopted the Quadruple Aim as the framework by which it will organize its quality activities.

Although originally developed for medical organizations, BHD believes that the Quadruple Aim has strong applicability to county-level behavioral health services. Many county-based behavioral health divisions provide a variety of programs to large segments of the county based on financial eligibility and/or clinical need, and thus often have responsibilities to populations or subpopulations, rather than programs. County health divisions, such as Milwaukee County’s Department of Health and Human Services, are often asked to improve outcomes and client experience of care with neutral growth budgets and less reliance on taxes to fund programs, while simultaneously attracting and retaining competent staff.

Crucial to the effective implementation of the Quadruple Aim, however, is a clear set of population- level measures that help organizations assess their progress.³ Unfortunately, as some authors have noted, evaluation of the Quadruple Aim remains a challenge because the “concepts of (population) health, quality of care and costs are not unanimously defined and measures for these concepts are under construction.”⁴ Several authors have provided some guidance to assist in the development of a set of measures that effectively capture the elements of the Quadruple Aim.^5,6 However, the recent rapid proliferation of quality measures in health care^7,8 has been both burdensome and costly for providers.^9,10 Any measures adopted should not only be as meaningful as possible with regards to assessing progress towards the basic aims of health care, but should also be parsimonious, to limit measurement burden for providers (and patients) and focus attention on important issues.^11,12

To select the most effective, parsimonious set of measures possible, one must first select a set of key foci from among the many possible areas of focus that the core measure is intended to represent. The core domains (CDs), if appropriately consistent with the strategic goals of the organization, provide a mechanism to orient the efforts of the organization at every level and help every staff member of the organization understand how his or her work impacts the progress towards these goals.¹¹ The CDs, therefore, represent the opportunity to affect a greater integration of efforts across the organization toward these shared aims, creating uniformity of purpose at every level. Further, increasing organizational attention on the CDs can also help to reduce measurement burden by streamlining and focusing the data capture processes on the most valuable elements of quality and health, and discarding other extraneous measures (albeit not at the expense of other reporting requirements).¹¹ The remainder of this article describes the CDs selected by BHD to assess its progress toward implementation of the Quadruple Aim and are organized by the Aim which they best represent.

Methods

To effectively implement the Quadruple Aim at BHD, it was necessary to clearly define the subpopulation of focus for our efforts.⁶ In this case, the subpopulation of interest was defined as all adult clients (18 years and older) who received at least 1 service encounter within a specified time frame from a program that BHD either operated or contracted with to provide care. Services provided by the BHD network include everything from psychiatric inpatient services to mental health and addiction treatment and care management. A limited array of social services, including housing and employment services, is also available to eligible consumers. BHD is the county-run behavioral health provider for individuals who are uninsured or underinsured in Milwaukee County, a demographically diverse, primarily urban county of approximately 950,000 people located in Wisconsin. Approximately 15,000 adults receive services at BHD each year.

This work began by obtaining executive sponsorship for the project, in this case from the Chief Operations Officer and Executive Medical Director of BHD. With their backing, an initial review of the literature produced a preliminary set of possible domains, for which we created working definitions. We then made a list of key stakeholders throughout BHD to whom we needed to present the idea of the Quadruple Aim, and the CDs under each Aim, to secure their support. These stakeholders, which included individuals involved in quality activities, program managers, and executive leadership, were strategically selected based on their relative influence within the organization. A set of brief presentations and handouts explaining the project were then developed and shared at different focus groups with these stakeholders over the course of 6 months. These focus groups served to not only educate the organization about the Quadruple Aim and the CDs but afforded participants an opportunity to provide feedback as well.

During the focus groups, we asked participants which domains they believed were most important (were “core”) when operationalizing the Quadruple Aim. The focus groups provided feedback on the domain definitions, feedback that was used to develop uniform, mutually agreed upon definitions for the CDs that were generalizable to all departments at BHD, regardless of the focus of their services within the continuum of care or the continuum of age. This was a crucial step, as it will eventually enable BHD to aggregate data across departments, even if there are minor discrepancies in the specific items they use to assess the CDs. Comments from the focus groups ultimately resulted in a truncated list of domains and definitions, which, coupled with the literature review, resulted in our final set of CDs.

During our review of the literature, we also looked for items that we felt could best represent each CD in the briefest, most meaningful way. (These items were not meant to supersede existing data, but to provide examples that could be implemented with existing data or recommendations that could be utilized in the absence of existing data.) During this process, we made every effort to make use of existing data-reporting requirements. For example, if we had a state mandate to collect data on housing status, we attempted to leverage this required data point to represent the CD related to housing. In other cases, we attempted to utilize claims or other administrative data to operationalize the CD, such as in the cost-of-care metric articulated in the section the Third Aim. For CDs for which no data existed or were insufficient, we emphasized the use of single- versus multi-item scales. For example, if we found a single-item global assessment of quality of life that had good psychometric properties relative to its longer parent scale, we selected the single item. This approach to item selection allowed us to create the most efficient, parsimonious set of measures possible, which we believed would enable us to comprehensively assess all the CDs with the least amount of burden to staff and clients. These items were presented at stakeholder focus groups, during which we asked for comments on the existing measures in their program or department and gave them the opportunity to comment on the new recommended measures.

A working definition is provided for each CD, followed by a brief review of the research base supporting its inclusion in the final list. The item(s) selected by BHD to represent each CD and the source of the item(s) are then supplied. These items were based either on measures currently collected because of existing reporting mandates or, in the case where extant measures were not available, on new items that demonstrated acceptable psychometric properties in the research literature. The CDs and items are organized by the Aim they best represent. A full list of the CDs by Quadruple Aim and items by CD is provided in the Appendix of the online version of this article. This article concludes with a brief summary of this effort and a discussion of how staff will utilize these items at different levels throughout the BHD system.

The First Aim: Population Health

Health Outcomes

Deaths. This can be defined as the cause of death, as determined by the medical examiner’s office (where appropriate) or as the age at time of death. This CD can also be reported as proportion of deaths considered premature (eg, before age 75) or calculated as total years of potential life lost.

Brief review and suggested item(s). Rates and causes of premature mortality are critical foci for the County Health Rankings & Roadmaps,¹³ the Institute for Healthcare Improvement’s “Guide to Measuring the Triple Aim,”⁶ the Centers for Disease Control and Prevention’s “Community Health Assessment for Population Health Improvement,”¹⁴ and the Institute of Medicine’s (IOM) “Vital Signs: Core Metrics for Health and Health Care Progress.”¹¹ There is ample evidence that individuals with serious mental illness are at increased risk of early mortality relative to the general population,^15-18 and this risk applies to those with substance use disorders as well.^15,19-20 BHD tracks all deaths that occur while patients are receiving BHD-funded, community-based services.

Self-Reported Health and Well-Being. This CD asks patients to rate their current physical and mental health status, as well as their overall quality of life.

Brief review and suggested item(s): Self-rated physical health. Premature mortality among individuals with behavioral health issues appears to be due, in large part, to their increased vulnerability to the development of medical comorbidities.^16,21 A single self-rating question has demonstrated considerable sensitivity to premature mortality,^22,23 with predictive properties up to a decade prior to death.^24,25 Further, self-rated health has been associated with subsequent functional decline,^26,27 acute service utilization,^28,29 and overall health care costs.²⁸

Brief review and suggested item(s): Self-rated mental health. Mental health disorders are associated with significant disability worldwide,³⁰ and comorbid mental health issues can exacerbate the course of other medical problems. For example, depression is associated with increased rates of mortality among individuals with diabetes and³¹ cardiovascular disease,³² as well as with rates of overall mortality,³³ and psychiatric comorbidity is associated with longer lengths of stay and higher costs among patients hospitalized for medical problems.³⁴ Research has found that a single-item measure of self-rated mental health is associated with the presence of psychiatric diagnoses, psychiatric symptoms, and subsequent depression and serious mental illness up to 1 year post-assessment.^35,36 There is even evidence that self-rated mental health may be more strongly associated with self-ratings of overall health than self-ratings of physical health.³⁷

Brief review and suggested item(s): Self-rated quality of life. Quality of life is a critical component of the recovery journey and overall health.³⁸ For example, the County Health Rankings & Roadmaps lists “quality of life” as 1 of its key “health outcomes” in its County Health Rankings.¹³ As some authors have noted, quality of life is often inferred from other “objective” recovery domains, such as employment, health status, or housing status. However, there is evidence that these objective domains are functionally distinct from the inherently subjective construct of quality of life.³⁹ This has led other authors to conclude that these domains should be assessed separately when evaluating outcomes.⁴⁰ Single-item quality of life assessments have been used in research with individuals with cancer,⁴¹ adults with disabilities,⁴² patients with cystic fibrosis,⁴³ and children with epilepsy.⁴⁴ For this effort, BHD selected the first global quality of life item from the World Health Organization’s WHOQOL-BREF quality of life assessment,⁴⁵ an item used in other quality of life research.⁴⁶

Health Factors

Substance Use. This CD is a composite of 4 different types of substance use, any recent heavy alcohol use (defined as 5 or more drinks in one sitting), any recent drug use, any recent prescription drug abuse, and any recent tobacco use.

Brief review and suggested item(s). As noted, substance use disorders confer an increased risk for early mortality^15,19 and are significantly implicated in disease disability burden worldwide.³⁰ Substance use has also been associated with both the onset^47,48 and exacerbation of mental health diagnoses.^49-51 Further, substance use appears to heighten the risk of violence in the general population⁵² and especially among those with a co-occurring mental illness.^53,54 The County Health Rankings & Roadmaps list alcohol and drug use as key behaviors to address to improve the overall health of a given county,¹³ and the Centers for Medicare & Medicaid Services (CMS) has endorsed initiation and engagement in addiction treatment as one of the measures in its Adult Core Set.⁵⁵

Tobacco use continues to be one of the most significant risk factors for early mortality worldwide, and evidence indicates that it is associated with a lower life expectancy of nearly 10 years.⁵⁶ Unfortunately, rates of tobacco use are even higher among those with severe mental illness relative to the general population, and their rates of smoking cessation are lower.^57,58 Tobacco use is a significant risk factor for the high rates of early mortality in individuals with severe mental illness.¹⁸ Further, a recent meta-analysis noted that, relative to those who continued to smoke, those who ceased smoking had reduced rates of psychological distress and increased quality of life rankings.⁵⁹ Reducing tobacco use is one of the key components of the County Health Rankings & Roadmaps, and medication assistance with smoking and tobacco use cessation is also listed in the CMS Adult Core Set.^13,55

An accumulating body of evidence suggests that single-item measures can adequately detect alcohol^60-62 and drug use disorders.^60-64 McNeely and colleagues recently developed and tested a brief 4-item screen, the Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS) tool.^65,66 Preliminary evidence suggests that the TAPS tool can effectively identify the presence of problematic and disordered use of tobacco, alcohol, prescription medications, and other drugs.^65-67 BHD will use the 4 items from the TAPS tool to represent its substance use CD.

Education/Employment Status. This CD assesses the proportion of BHD members who have completed high school, who are in some type of educational or training program, or who are engaged in some type of employment activity (defined as full-time, part-time, supported, sheltered workshop, or as a full-time homemaker).

Brief review and suggested item(s). Research indicates that unemployment is a risk factor for mortality, even after controlling for other risk factors (eg, age, sex, socioeconomic status [SES], health).⁶⁸ Unemployment is associated with poorer physical and mental health in the general population and among those with disabilities.^69-71 Promisingly, evidence suggests that gaining employment or re-employment is associated with better health,⁷² even for individuals with substance use disorders⁷³ or moderate⁷⁴ to severe mental health disorders.^75-78 Some authors have even proposed that, above and beyond the associated health benefits, employment may also help to realize a modest cost savings due to reduced service utilization and disability.^79,80 Employment is a core tenet in the Substance Abuse and Mental Health Services Administration’s (SAMHSA’s) model of recovery,⁸¹ and is also listed as an important recovery goal for individuals with behavioral health issues.⁸² BHD collects data on employment status on all the patients it serves as part of its state-mandated reporting requirements and will use this item in the CD data set.⁸³

Living Situation. This is measured as the proportion of people who live in permanent, supportive, stable housing; it may also be measured as the percentage of the population living with severe housing problems or who are homeless.

Brief review and suggested item(s). Housing problems can be conceptualized as 3 inter-related components: conditions within the home, neighborhood conditions, and housing affordability, each of which can contribute uniquely to poorer physical and mental health of individuals and families⁸⁴ and to educational outcomes for children.^85,86 Further, individuals who are homeless have a standardized mortality ratio 2 to 5 times that of the general population,^87-89 even after controlling for low income status,⁹⁰ and some evidence suggests these rates are even higher among unsheltered versus sheltered homeless individuals.⁹¹ Interventions to improve the condition of housing have demonstrated positive impacts on both physical and mental health,⁹² and a recent study found that individuals receiving housing assistance in the form of public housing or multifamily housing from the Department of Housing and Urban Development had better self-rated physical and mental health relative to individuals on the wait list for housing assistance.⁹³ Moreover, the provision of housing has been shown to promote reductions in substance use and health service utilization among homeless individuals with substance use disorders.⁹⁴ Rog and colleagues reviewed the literature on permanent supportive housing for individuals with substance use or mental health disorders who were homeless or disabled, and found that provision of housing led to reduced rates of homelessness, emergency department (ED) and inpatient utilization and increased consumer satisfaction.⁹⁵

Importantly, evidence suggests that housing is viewed as facilitative of recovery. For example, in a recent qualitative study of homeless individuals with mental illness, housing was seen as a critical first step in recovery, providing a sense of security, increasing feelings of personal independence and autonomy, improving perceptions of health and well-being, and affording a stable environment to rebuild relationships with important others.⁹⁶ BHD collects data on housing status on all the patients it serves as part of its state-mandated reporting requirements and will utilize this item in the CD data set.⁸³

Social Relationships. This is defined as recent interactions with family, supportive networks (formal and informal), and other recovery services.

Brief review and suggested item(s). Research has long established that social relationships have a significant impact on health, including rates of mortality as well as physical and mental health morbidity.^97-99 Social connectedness is another of the pillars supporting an individual’s recovery in SAMHSA’s formulation. Several reviews of the recovery literature^38,82 support its importance to the recovery process and inclusion in any assessment of holistic recovery. Social support has been shown to promote recovery among individuals with severe mental illness^100-102 and substance use disorders,¹⁰³ and may mitigate the progression of chronic, life-threatening physical illnesses.⁹⁷ For the purposes of BHD’s CD data set, the social support question from the “100 Million Healthier Lives Common Questionnaire for Adults” will be used to assess individuals’ perceived adequacy of social support.¹⁰⁴

Legal Involvement. Defined as involvement with the civil or criminal justice system, including arrests, imprisonment, or detainment.

Brief review and suggested item(s). Involvement in the criminal justice system is both disruptive for the individual in recovery and expensive to the larger health care system.¹⁰⁵ Individuals with substance use¹⁰⁶ and severe mental health disorders¹⁰⁷ are over-represented in the prison system, and evidence suggests that general physical and mental health declines while individuals are in prison.^108,109 Perhaps even more concerning, numerous studies have demonstrated an increase in mortality rates for individuals recently released from prison relative to the general population, particularly during the period immediately following release.^108-110 This relationship may even persist long term.¹¹¹ Further, research indicates that individuals recently released from prison have increased emergency care and hospital utilization.^112,113

Incarceration can have significant impacts on the health of the broader community as well. For example, research has found an association between parental incarceration to rates of infant mortality,¹¹⁴ increased behavioral and developmental problems of children of incarcerated parents,^115,116 lower rates of child support payments,¹¹⁷ and poorer cardiovascular health of female partners of incarcerated individuals.¹¹⁸ Formerly incarcerated individuals experience slower wage growth as well.¹¹⁹ However, evidence also indicates that engagement in mental health¹²⁰ and substance abuse¹²¹ treatment can reduce the likelihood of subsequent recidivism. As part of its state-mandated reporting, BHD is required to provide information on the criminal justice system involvement of its clients in the previous 6 months, including whether they have been jailed or imprisoned,⁸³ and this will function as its measure of legal involvement in its CD data set.

Socioeconomic Status. Socioeconomic status is the social standing or class of an individual or group. It is often measured as a combination of education, income, and occupation. It can also be defined subjectively, such as one’s evaluation of status relative to similar others or based on an individual’s interpretation of her or his financial needs.

Brief review and suggested item(s). A large body of evidence supports the existence of a robust relationship between lower SES and poor health, including mortality and chronic medical diseases,^122-124 as well as mental illness.^125-127 Although previous research has examined this relationship using objective indicators of SES (eg, income, education level, occupation), there has recently been an increased interest in exploring the relationship of subjective SES with health indices. Subjective SES is generally assessed by asking individuals to rate themselves relative to others in the society in which they live, in terms of wealth, occupation, educational level, or other indicators of social status. Evidence suggests that subjective SES is associated with objective measures of SES,^128-130 and relates to measures of physical and mental health as well, even after controlling for objective SES.^130-135 BHD will be using a modified version of the Subject SES Scale,^131,135 which is deployed in the “100 Million Healthier Lives Common Questionnaire for Adults.”¹⁰⁴

Acute Service Use. This is defined as an admission to a medical or psychiatric emergency room or to a medical or psychiatric hospital or to a detoxification facility.

Brief review and suggested item(s). The CMS Adult Core Set includes “plan all cause readmissions” as a key quality metric.⁵⁵ Hospital readmissions are also endorsed by the National Committee on Quality Assurance as one of its Health Effectiveness Data and Information Set (HEDIS) measures and by the National Quality Forum. Readmissions, despite their widespread endorsement, are a somewhat controversial measure. Although readmissions are costly to the health care system,¹³⁶ the relationship between readmissions and quality is inconsistent. For example, Krumholz and colleagues¹³⁷ found differential rates of readmission for the same patient discharged from 2 different hospitals, which were categorized based on previous readmission rates, suggesting that hospitals do have different levels of performance even when treating the same patient. However, other data indicate that 30-day, all-cause, risk-standardized readmission rates are not associated with hospital 30-day, all-cause, risk-standardized mortality rates.¹³⁸

Chin and colleague found that readmissions to the hospital that occurred more than 7 days post-discharge were likely due to community- and household-related factors, rather than hospital-related quality factors.¹³⁹ Transitional care interventions that have successfully reduced 30-day readmission rates are most often multicomponent and focus not just on hospital-based interventions (eg, discharge planning, education) but on follow-up care in the community by formal supports (eg, in-home visits, telephone calls, outpatient clinic appointments, case management) and informal supports (eg, family and friends).^140-143 Further, qualitative evidence suggests that some individuals perceive psychiatric hospitalizations to be the result of insufficient resources or unsuccessful attempts to maintain their stability in the community.¹⁴⁴ Thus, unplanned or avoidable hospital readmissions may represent a failure of the continuum of care not only from the perspective of the health care system, but from the patient perspective as well.

Frequent or nonurgent use of EDs is conceptually similar to excessive or avoidable inpatient utilization in several ways. For example, overuse of EDs is costly, with some estimates suggesting that it is responsible for up to $38 billion in wasteful spending each year.¹⁴⁵ Individuals with frequent ED visits have a greater disease burden¹⁴⁶ and an increased risk of mortality compared to nonfrequent users.¹⁴⁷ Research suggests that individuals who visit the ED for non-urgent issues do so because of perceived difficulties associated with accessing primary care, and the convenience of EDs relative to primary care.^148-150 Moreover, similar to the hospital readmission literature discussed earlier, successful strategies to reduce high rates of ED utilization generally focus on continuum of care interventions, such as provision of case management services.^151-155

This evidence implies that frequent ED utilization and hospital readmissions may not be a fundamental issue of quality (or lack thereof) in hospitals or EDs but rather a lack of, or ineffectual, transitional and continuum of care strategies and services. To underscore this point, some authors have argued that a system that is excessively crisis-oriented hinders recovery because it is reactive rather than proactive, predicated on the notion that one’s condition must deteriorate to receive care.¹⁵⁶

Although some organizations may have access to claims data or may function as self-contained health systems (eg, the Veterans Health Administration [VHA] ), others may not have access to such data. In the absence of claims data, patient self-report of service utilization has been used as a proxy for actual agency records.¹⁵⁷ Although concordance between medical and/or agency records and patient self-report has been variable,¹⁵⁷ evidence generally suggests that rates of agreement are higher the shorter the recall time interval.^158,159 BHD does not have access to comprehensive claims data and has therefore chosen to use 5 dichotomously scored (yes/no) questions—related to medical inpatient, medical ED, psychiatric inpatient, psychiatric ED, and detoxification use in the last 30 days—to represent the CD of acute service utilization.

The Second Aim: Quality of Care

Safety

Safety is defined as avoiding injuries to patients from the care that is intended to help them.

Brief review and suggested item(s). As noted in “Crossing the Quality Chasm,” the IOM’s seminal document, “the health care environment should be safe for all patients, in all of its processes, all the time.”¹⁶⁰ The landmark Harvard Medical Practice Study in 1991 found that adverse events occurred in nearly 4% of all hospital admissions and, among these, over a quarter were due to negligence.¹⁶¹ Other estimates of adverse events range as high as 17%.¹⁶² Indeed, a recent article by Makary and Daniel estimated that medical errors may be the third leading cause of death in the United States.¹⁶³ Unfortunately, research on safety in the mental health field has lagged behind that of physical health,¹⁶⁴ with evidence indicating that research in nonhospital settings in mental health care may be particularly scarce.¹⁶⁵ In a study of adverse events that occurred in psychiatric inpatient units in the VHA system between 2015 and 2016, Mills and colleagues found that of the 87 root cause analysis reports, suicide attempts were the most frequent, and, among safety events, falls were the most frequently reported, followed by medication events.¹⁶⁶ Another report on data collected from psychiatric inpatient units in the VHA revealed that nearly one-fifth of patients experienced a safety event, over half of which were deemed preventable.¹⁶⁷ These numbers likely represent an underestimation of the true volume of safety events, as another study by the same research group found that less than 40% of safety events described in patient medical records were documented in the incident reporting system.¹⁶⁸ BHD will utilize the total number of complaints and incident reports submitted within a given time frame as its “safety” metric in the CD data set.

Wait Time for Service

The CD is defined as the length of time between the date a patient first contacted BHD for services and the date of their first clinical service.

Brief review and suggested item(s). “Timeliness” was listed among the 6 aims for improvement in “Crossing the Quality Chasm” in 2001, and it remains no less relevant today.¹⁶⁰ For example, evidence indicates that access to primary care is inversely related to avoidable hospitalizations.¹⁶⁹ One study found that, of patients hospitalized for cardiovascular problems, those who had difficulty accessing routine care post discharge had higher 30-day readmission rates.¹⁷⁰ Among VHA patients, longer wait times are associated with more avoidable hospitalizations and higher rates of mortality.¹⁷¹ Longer wait times appear to decrease the likelihood of attending a first appointment for individuals with substance use^172,173 and mental health disorders.¹⁷⁴ Importantly, longer wait times are associated with lower ratings of the patient experience of care, including perceptions of the quality of and satisfaction with care,¹⁷⁵ and may be associated with worse outcomes for individuals in early intervention for psychosis treatment.¹⁷⁶ For the purposes of the CD data set, BHD will monitor the length of time between the date a patient first contacted BHD for services and the date of their first clinical service.

 

 

Patient Satisfaction

Patient satisfaction is defined as the degree of patients’ satisfaction with the care they have received.

Brief review and suggested item(s). Research has consistently demonstrated the relationship of the patient’s experience of care to a variety of safety and clinical effectiveness measures in medical health care,¹⁷⁷ and the therapeutic alliance is one of the most consistent predictors of outcomes in behavioral health, regardless of therapeutic modality.¹⁷⁸ Patient satisfaction is a commonly assessed aspect of the patient experience of care. Patient satisfaction scores have been correlated with patient adherence to recommended treatment regimens, care quality, and health outcomes.¹⁷⁹ For example, Aiken et al found that patient satisfaction with hospital care was associated with higher ratings of the quality and safety of nursing care in these hospitals.¹⁸⁰ Increased satisfaction with inpatient care has been associated with lower 30-day readmission rates for patients with acute myocardial infarction, heart failure, and pneumonia,¹⁸¹ and patients with schizophrenia who reported higher treatment satisfaction also reported better quality of life.^182,183 Many satisfaction survey options exist to evaluate this CD, including the Consumer Assessment of Healthcare Providers and Systems and the Client Satisfaction Questionnaire; BHD will utilize an outpatient behavioral health survey from a third-party vendor.

The Third Aim: Cost of Care

Cost of Care

This can be defined as the average cost to provide care per patient per month.

Brief review and suggested item(s). Per capita cost, or rather, the total cost of providing care to a circumscribed population divided by the total population, has been espoused as an important metric for the Triple Aim and the County Health Rankings.^6,13 Indeed, between 1960 and 2016, per capita expenditures for health care have grown 70-fold, and the percent of the national gross domestic product accounted for by health expenditures has more than tripled (5.0% to 17.9%).¹⁸⁴ One of the more common metrics deployed for assessing health care cost is the per capita per month cost, or rather, the per member per month cost of the predefined population for a given health care system.^6,185,186 In fact, some authors have proposed that cost of care can be used not only to track efficient resource allocation, but can also be a proxy for a healthier population as well (ie, as health improves, individuals use fewer and less-expensive services, thus costing the system less).¹⁸⁷ To assess this metric, BHD will calculate the total amount billed for patient care provided within BHD’s health network each month (irrespective of funding source) and then divide this sum by the number of members served each month. Although this measure does not account for care received at other health care facilities outside BHD’s provider network, nor does it include all the overhead costs associated with the care provided by BHD itself, it is consistent with the claims-based approach used or recommended by other authors.^6,188

The Fourth Aim: Staff Well-being

Staff Quality of Work Life

This can be defined as the quality of the work life of health care clinicians and staff.

Brief review and suggested item(s). Some authors have suggested that the Triple Aim framework is incomplete and have proffered compelling arguments that provider well-being and the quality of work life constitutes a fourth aim.² Provider burnout is prevalent in both medical^2,189 and behavioral health care.^190,191 Burnout among health care professionals has been associated with higher rates of perceived medical errors,¹⁹² lower patient satisfaction scores,^189,193 lower rates of provider empathy,¹⁹⁴ more negative attitudes towards patients,¹⁹⁵ and poorer staff mental and physical health.¹⁹¹

Burnout is also associated with higher rates of absenteeism, turnover intentions, and turnover.^{190,191,196,197} However, burnout is not the only predictor of staff turnover; for example, turnover rates are a useful proxy for staff quality of work life for several reasons.¹⁹⁸ First, turnover is associated with substantial direct and indirect costs, including lost productivity, increased errors, and lost revenue and recruitment costs, with some turnover cost estimates as high as $17 billion for physicians and $14 billion for nurses annually.^199-201 Second, research indicates that staff turnover can have a deleterious impact on implementation of evidence-based interventions.^202-205 Finally, consistent with the philosophy of utilizing existing data sources for the CD measures, turnover can be relatively easily extracted from administrative data for operated or contracted programs, and its collection does not place any additional burden on staff. As a large behavioral health system that is both a provider and payer of care, BHD will therefore examine the turnover rates of its internal administrative and clinical staff as well as the turnover of staff in its contracted provider network as its measures for the Staff Quality of Work Life CD.

Clinical Implications

These metrics can be deployed at any level of the organization. Clinicians may use 1 or more of the measures to track the recovery of individual clients, or in aggregate for their entire caseload. Similarly, managers can use these measures to assess the overall effectiveness of the programs for which they are responsible. Executive leaders can evaluate the impact of several programs or the system of care on the health of a subpopulation of clients with a specific condition, or for all their enrolled members. Further, not all measures need be utilized for every dashboard or evaluative effort. The benefit of a comprehensive set of measures lies in their flexibility—1 or more of the measures may be selected depending on the project being implemented or the interests of the stakeholder.

It is important to note that many of the CDs (and their accompanying measures) are aligned to/consistent with social determinants of health.^206,207 Evidence suggests that social determinants make substantial contributions to the overall health of individuals and populations and may even account for a greater proportion of variance in health outcomes than health care itself.²⁰⁸ The measures articulated here, therefore, can be used to assess whether and how effectively care provision has addressed these social determinants, as well as the relative impact their resolution may have on other health outcomes (eg, mortality, self-rated health).

These measures can also be used to stratify clients by clinical severity or degree of socioeconomic deprivation. The ability to adjust for risk has many applications in health care, particularly when organizations are attempting to implement value-based purchasing models, such as pay-for-performance contracts or other alternative payment models (population health-based payment models).²⁰⁹ Indeed, once fully implemented, the CDs and measures will enable BHD to more effectively build and execute different conceptual models of “value” (see references 210 and 211 for examples). We will be able to assess the progress our clients have made in care, the cost associated with that degree of improvement, the experience of those clients receiving that care, and the clinical and social variables that may influence the relative degree of improvement (or lack thereof). Thus, the CDs provide a conceptual and data-driven foundation for the Quadruple Aim and any quality initiatives that either catalyze or augment its implementation.

 

 

Conclusion

This article provides an overview of the CDs selected by BHD to help organize, focus, advance, and track its quality efforts within the framework of the Quadruple Aim. Although items aligned to each of these CDs are offered, the CDs themselves have been broadly conceptualized such that they can flexibly admit a variety of possible items and/or assessments to operationalize each CD and thus have potential applicability to other behavioral health systems, particularly public systems that have state-mandated and other data reporting requirements.

Bearing in mind the burden that growing data collection requirements can have on the provision of quality care and staff work satisfaction and burnout,^10,212 the CDs (and the items selected to represent each) are designed with “strategic parsimony” in mind. Although the CDs are inclusive in that they cover care quality, cost of care, staff quality of life, and general population health, only CDs and items undergirded by a solid evidence base and high value with regards to BHD’s mission and values, as determined by key stakeholders, were selected. Moreover, BHD attempted to make use of existing data collection and reporting mandates when selecting the final pool of items to reduce the measurement burden on staff and clients. Thus, the final set of CDs and items are designed to be comprehensive yet economical.

The CDs are deeply interrelated. Although each CD may be individually viewed as a valuable metric, improvements in any 1 CD will impact the others (eg, increasing care quality should impact population health, increasing staff quality of life should impact the quality of care). Moreover, this idea of interrelatedness acknowledges the need to view health systems and the populations they serve holistically, in that improvement is not simply the degree of change in any given metric (whether individually or collectively), but rather something more entirely. The concepts of value, quality, and health are complex, multidimensional, and dynamic, and the CDs that comprise these concepts should not be considered independently from one another. The CDs (and items) offered in this article are scalable in that they can be used at different levels of an organization depending on the question or stakeholder, and can be used individually or in combination with one another. Moreover, they are adaptable to a variety of risk-adjusted program, population health, and value-based evaluation models. It is hoped that the process articulated here, and the accompanying literature review, may benefit other public or government-run health systems in their own quality journey to operationalize the Quadruple Aim by developing a set of CDs.

Corresponding author: Walter Matthew Drymalski, PhD; walter.drymalski@milwaukeecountywi.gov.

Financial disclosures: None.

About 60% of children taking antipsychotic medication do not receive recommended metabolic monitoring, according to an analysis of Medicaid data from two states.

The number and types of providers involved in a child’s care are associated with the likelihood that the child will receive metabolic monitoring, according to the study, which was published in Pediatrics.

The results suggest that primary care providers and mental health providers should collaborate to monitor children taking antipsychotics, the researchers said.

“Shared care arrangements between primary care physicians and mental health specialists significantly increased the chances that metabolic monitoring would be done, compared with care delivered by one provider,” reported Elizabeth A. Shenkman, PhD, chair of the department of health outcomes and biomedical informatics at the University of Florida, Gainesville, and colleagues. “The results of our study point to the importance of state Medicaid agencies and Medicaid managed care plans in identifying all providers caring for the children taking antipsychotic medication and using this information to engage the providers in quality improvement efforts to improve metabolic monitoring rates.”


 

Comparing specialties

Children who take antipsychotic medication are at risk for obesity, impaired glucose metabolism, and hyperlipidemia, but less than 40% receive recommended metabolic monitoring with glucose and cholesterol tests.

To examine how health care provider specialty influences the receipt of metabolic monitoring, Dr. Shenkman and colleagues analyzed Medicaid enrollment and health care and pharmacy claims data from Florida and Texas.

They focused on 41,078 children who had an antipsychotic medication dispensed at least twice in 2017 and were eligible for inclusion in the Centers for Medicare & Medicaid Services metabolic monitoring measure. The Metabolic Monitoring for Children and Adolescents on Antipsychotics measure is a “priority nationally and is currently on the CMS Child Core Set, which is used to annually assess state-specific performance on pediatric quality measures,” the authors wrote.

About 65% were boys, and the children had an average age of 12 years. The researchers compared metabolic monitoring rates when children received outpatient care from a primary care provider, a mental health provider with prescribing privileges, or both.

Less than 40% of the children received metabolic monitoring, that is, at least one diabetes test and at least one cholesterol test, during the year.

Most of the children (61%) saw both primary care providers and mental health providers. Approximately one-third had a primary care provider prescribe antipsychotic medication the majority of the time, and 60% had a mental health provider prescribe antipsychotic medication the majority of the time.

Patients who saw both types of providers were significantly more likely to receive metabolic monitoring, relative to those who saw primary care providers only (adjusted odds ratio, 1.42). Those seeing a mental health provider alone had adjusted odds of metabolic monitoring that were 23% lower than those seeing a primary care provider alone.

Children who had a mental health provider prescribe the medication the majority of the time were 25% more likely to receive metabolic monitoring, compared with those who had a primary care provider prescribing the medication the majority of the time.
 

Slipping through the cracks

Child psychiatrist Fred Volkmar, MD, commented that the results are “sadly” unsurprising and reflect issues that pertain to other psychotropic drugs as well as antipsychotics and to adults as well as children.

The researchers “are quite right to point to it,” and “we really do need to develop better plans for improving” monitoring, said Dr. Volkmar, the Irving B. Harris Professor in the Child Study Center and professor of psychology at Yale University, New Haven, Conn.

“Increasingly we are asking primary care providers ... to take care of folks who have important either developmental or mental health problems,” Dr. Volkmar said. While they can do a good job, they increasingly are underpaid. Monitoring patients takes work, and they may be less familiar with the medications. “Either they prescribe these medications or they are asked to monitor them in place of the specialist provider who may have started them or suggested them,” he said. Metabolic monitoring may not be prioritized and can easily “slip through the cracks.” At the same time, doctors need to be aware of the risk of serious side effects of antipsychotic medications, such as malignant hyperthermia.

These medications can be overused and inappropriately used, which is a further complication. And when patients are taking multiple medications, there may be a need for additional monitoring and awareness of drug interactions.

“These medications are very complicated to use,” and there needs to be a way to connect primary care providers with child psychiatrists who are best trained in their use, said Dr. Volkmar.

A system with reminders can facilitate effective metabolic monitoring, he suggested. Dr. Volkmar has established a routine while providing care for a group home of adults with autism. Every 3 months, he reviews lab results. “You just have to force yourself to do it.”

Shared care arrangements may be another way to promote metabolic monitoring, Dr. Shenkman and colleagues said.

“Attributing care back to the multiple providers is important for care coordination and development of strategies to ensure that the evidence-based care is delivered and there is appropriate follow-up with the family and child to be sure care is received,” the study authors wrote. “Formalized shared care arrangements and adaptation of existing care delivery models to support integrated care, which can vary in degree from external coordination to on-site intervention and collaboration, are effective methods to promote partnership between primary and mental health providers.”

It is possible that clinicians in the study ordered metabolic monitoring but families did not take the children for testing, the investigators noted. In addition, it is not clear how much information providers have about other providers their patients are seeing.

The study authors and Dr. Volkmar had no disclosures.

jremaly@mdedge.com

About 60% of children taking antipsychotic medication do not receive recommended metabolic monitoring, according to an analysis of Medicaid data from two states.

The number and types of providers involved in a child’s care are associated with the likelihood that the child will receive metabolic monitoring, according to the study, which was published in Pediatrics.

The results suggest that primary care providers and mental health providers should collaborate to monitor children taking antipsychotics, the researchers said.

“Shared care arrangements between primary care physicians and mental health specialists significantly increased the chances that metabolic monitoring would be done, compared with care delivered by one provider,” reported Elizabeth A. Shenkman, PhD, chair of the department of health outcomes and biomedical informatics at the University of Florida, Gainesville, and colleagues. “The results of our study point to the importance of state Medicaid agencies and Medicaid managed care plans in identifying all providers caring for the children taking antipsychotic medication and using this information to engage the providers in quality improvement efforts to improve metabolic monitoring rates.”


 

Comparing specialties

Children who take antipsychotic medication are at risk for obesity, impaired glucose metabolism, and hyperlipidemia, but less than 40% receive recommended metabolic monitoring with glucose and cholesterol tests.

To examine how health care provider specialty influences the receipt of metabolic monitoring, Dr. Shenkman and colleagues analyzed Medicaid enrollment and health care and pharmacy claims data from Florida and Texas.

They focused on 41,078 children who had an antipsychotic medication dispensed at least twice in 2017 and were eligible for inclusion in the Centers for Medicare & Medicaid Services metabolic monitoring measure. The Metabolic Monitoring for Children and Adolescents on Antipsychotics measure is a “priority nationally and is currently on the CMS Child Core Set, which is used to annually assess state-specific performance on pediatric quality measures,” the authors wrote.

About 65% were boys, and the children had an average age of 12 years. The researchers compared metabolic monitoring rates when children received outpatient care from a primary care provider, a mental health provider with prescribing privileges, or both.

Less than 40% of the children received metabolic monitoring, that is, at least one diabetes test and at least one cholesterol test, during the year.

Most of the children (61%) saw both primary care providers and mental health providers. Approximately one-third had a primary care provider prescribe antipsychotic medication the majority of the time, and 60% had a mental health provider prescribe antipsychotic medication the majority of the time.

Patients who saw both types of providers were significantly more likely to receive metabolic monitoring, relative to those who saw primary care providers only (adjusted odds ratio, 1.42). Those seeing a mental health provider alone had adjusted odds of metabolic monitoring that were 23% lower than those seeing a primary care provider alone.

Children who had a mental health provider prescribe the medication the majority of the time were 25% more likely to receive metabolic monitoring, compared with those who had a primary care provider prescribing the medication the majority of the time.
 

Slipping through the cracks

Child psychiatrist Fred Volkmar, MD, commented that the results are “sadly” unsurprising and reflect issues that pertain to other psychotropic drugs as well as antipsychotics and to adults as well as children.

The researchers “are quite right to point to it,” and “we really do need to develop better plans for improving” monitoring, said Dr. Volkmar, the Irving B. Harris Professor in the Child Study Center and professor of psychology at Yale University, New Haven, Conn.

“Increasingly we are asking primary care providers ... to take care of folks who have important either developmental or mental health problems,” Dr. Volkmar said. While they can do a good job, they increasingly are underpaid. Monitoring patients takes work, and they may be less familiar with the medications. “Either they prescribe these medications or they are asked to monitor them in place of the specialist provider who may have started them or suggested them,” he said. Metabolic monitoring may not be prioritized and can easily “slip through the cracks.” At the same time, doctors need to be aware of the risk of serious side effects of antipsychotic medications, such as malignant hyperthermia.

These medications can be overused and inappropriately used, which is a further complication. And when patients are taking multiple medications, there may be a need for additional monitoring and awareness of drug interactions.

“These medications are very complicated to use,” and there needs to be a way to connect primary care providers with child psychiatrists who are best trained in their use, said Dr. Volkmar.

A system with reminders can facilitate effective metabolic monitoring, he suggested. Dr. Volkmar has established a routine while providing care for a group home of adults with autism. Every 3 months, he reviews lab results. “You just have to force yourself to do it.”

Shared care arrangements may be another way to promote metabolic monitoring, Dr. Shenkman and colleagues said.

“Attributing care back to the multiple providers is important for care coordination and development of strategies to ensure that the evidence-based care is delivered and there is appropriate follow-up with the family and child to be sure care is received,” the study authors wrote. “Formalized shared care arrangements and adaptation of existing care delivery models to support integrated care, which can vary in degree from external coordination to on-site intervention and collaboration, are effective methods to promote partnership between primary and mental health providers.”

It is possible that clinicians in the study ordered metabolic monitoring but families did not take the children for testing, the investigators noted. In addition, it is not clear how much information providers have about other providers their patients are seeing.

The study authors and Dr. Volkmar had no disclosures.

jremaly@mdedge.com

About 60% of children taking antipsychotic medication do not receive recommended metabolic monitoring, according to an analysis of Medicaid data from two states.

The number and types of providers involved in a child’s care are associated with the likelihood that the child will receive metabolic monitoring, according to the study, which was published in Pediatrics.

The results suggest that primary care providers and mental health providers should collaborate to monitor children taking antipsychotics, the researchers said.

“Shared care arrangements between primary care physicians and mental health specialists significantly increased the chances that metabolic monitoring would be done, compared with care delivered by one provider,” reported Elizabeth A. Shenkman, PhD, chair of the department of health outcomes and biomedical informatics at the University of Florida, Gainesville, and colleagues. “The results of our study point to the importance of state Medicaid agencies and Medicaid managed care plans in identifying all providers caring for the children taking antipsychotic medication and using this information to engage the providers in quality improvement efforts to improve metabolic monitoring rates.”


 

Comparing specialties

Children who take antipsychotic medication are at risk for obesity, impaired glucose metabolism, and hyperlipidemia, but less than 40% receive recommended metabolic monitoring with glucose and cholesterol tests.

To examine how health care provider specialty influences the receipt of metabolic monitoring, Dr. Shenkman and colleagues analyzed Medicaid enrollment and health care and pharmacy claims data from Florida and Texas.

They focused on 41,078 children who had an antipsychotic medication dispensed at least twice in 2017 and were eligible for inclusion in the Centers for Medicare & Medicaid Services metabolic monitoring measure. The Metabolic Monitoring for Children and Adolescents on Antipsychotics measure is a “priority nationally and is currently on the CMS Child Core Set, which is used to annually assess state-specific performance on pediatric quality measures,” the authors wrote.

About 65% were boys, and the children had an average age of 12 years. The researchers compared metabolic monitoring rates when children received outpatient care from a primary care provider, a mental health provider with prescribing privileges, or both.

Less than 40% of the children received metabolic monitoring, that is, at least one diabetes test and at least one cholesterol test, during the year.

Most of the children (61%) saw both primary care providers and mental health providers. Approximately one-third had a primary care provider prescribe antipsychotic medication the majority of the time, and 60% had a mental health provider prescribe antipsychotic medication the majority of the time.

Patients who saw both types of providers were significantly more likely to receive metabolic monitoring, relative to those who saw primary care providers only (adjusted odds ratio, 1.42). Those seeing a mental health provider alone had adjusted odds of metabolic monitoring that were 23% lower than those seeing a primary care provider alone.

Children who had a mental health provider prescribe the medication the majority of the time were 25% more likely to receive metabolic monitoring, compared with those who had a primary care provider prescribing the medication the majority of the time.
 

Slipping through the cracks

Child psychiatrist Fred Volkmar, MD, commented that the results are “sadly” unsurprising and reflect issues that pertain to other psychotropic drugs as well as antipsychotics and to adults as well as children.

The researchers “are quite right to point to it,” and “we really do need to develop better plans for improving” monitoring, said Dr. Volkmar, the Irving B. Harris Professor in the Child Study Center and professor of psychology at Yale University, New Haven, Conn.

“Increasingly we are asking primary care providers ... to take care of folks who have important either developmental or mental health problems,” Dr. Volkmar said. While they can do a good job, they increasingly are underpaid. Monitoring patients takes work, and they may be less familiar with the medications. “Either they prescribe these medications or they are asked to monitor them in place of the specialist provider who may have started them or suggested them,” he said. Metabolic monitoring may not be prioritized and can easily “slip through the cracks.” At the same time, doctors need to be aware of the risk of serious side effects of antipsychotic medications, such as malignant hyperthermia.

These medications can be overused and inappropriately used, which is a further complication. And when patients are taking multiple medications, there may be a need for additional monitoring and awareness of drug interactions.

“These medications are very complicated to use,” and there needs to be a way to connect primary care providers with child psychiatrists who are best trained in their use, said Dr. Volkmar.

A system with reminders can facilitate effective metabolic monitoring, he suggested. Dr. Volkmar has established a routine while providing care for a group home of adults with autism. Every 3 months, he reviews lab results. “You just have to force yourself to do it.”

Shared care arrangements may be another way to promote metabolic monitoring, Dr. Shenkman and colleagues said.

“Attributing care back to the multiple providers is important for care coordination and development of strategies to ensure that the evidence-based care is delivered and there is appropriate follow-up with the family and child to be sure care is received,” the study authors wrote. “Formalized shared care arrangements and adaptation of existing care delivery models to support integrated care, which can vary in degree from external coordination to on-site intervention and collaboration, are effective methods to promote partnership between primary and mental health providers.”

It is possible that clinicians in the study ordered metabolic monitoring but families did not take the children for testing, the investigators noted. In addition, it is not clear how much information providers have about other providers their patients are seeing.

The study authors and Dr. Volkmar had no disclosures.

jremaly@mdedge.com

The national rate of methamphetamine overdose deaths shot up significantly between 2011 and 2018, particularly among non-Hispanic American Indian and Alaska Native communities, new research shows.

Rates rose for both men and women but more so among men, the study found. The spike in these deaths underscores the need for culturally tailored prevention and treatment strategies, the study authors said.

“While much attention is focused on the opioid crisis, a methamphetamine crisis has been quietly, but actively, gaining steam – particularly among American Indians and Alaska Natives, who are disproportionately affected by a number of health conditions,” senior investigator Nora D. Volkow, MD, director of the National Institute on Drug Abuse, said in a press release.

The study was published online Jan. 20 in JAMA Psychiatry.
 

Highly toxic

Methamphetamine is highly toxic. Its use is associated with pulmonary and cardiovascular pathology and frequently co-occurs with other substance use and mental disorders.

In addition, there are currently no Food and Drug Administration–approved medications to reverse methamphetamine overdose or treat methamphetamine use disorder.

However, behavioral therapies can be effective in reducing the harm associated with methamphetamine use. In addition, a recent clinical trial reported significant therapeutic benefits with the combination of naltrexone with bupropion in patients with methamphetamine use disorder.

For the study, the investigators used deidentified public health surveillance data from the Centers for Disease Control and Prevention’s National Vital Statistics System files for multiple causes of death.

The researchers used the psychostimulant category to estimate death rates from methamphetamine. The authors noted that up to 90% of psychostimulant-involved death certificates mentioned methamphetamine.

Researchers stratified age-adjusted overdose death rates during 2011-2018 by sex and race/ethnicity and limited the analysis to those aged 25-54 years. Approximately 80% of methamphetamine users are between the ages of 25 and 54 years.

During the study period, rates for methamphetamine-involved deaths increased from 1.8 to 10.1 per 100,000 among men (average annual percentage change, 29.1; 95% confidence interval, 25.5-32.8; P < .001) and from 0.8 to 4.5 per 100,000 among women (AAPC, 28.1; 95% CI, 25.1-31.2; P < .001).
 

Need for tailored interventions

For both men and women, those in non-Hispanic American Indian or Alaska Native communities had the highest rates. These increased from 5.6 to 26.4 per 100,000 among men and from 3.6 to 15.6 per 100,000 among women.

While American Indian and Alaska Native individuals experience sociostructural disadvantages, their cultural strengths “can be leveraged to improve addiction outcomes,” the investigators wrote.

Non-Hispanic Whites had the second highest rates. These rose from 2.2 to 12.6 per 100,000 among men (AAPC, 29.8; 95% CI, 24.3-35.4; P < .001) and from 1.1 to 6.2 per 100,000 among women (AAPC, 29.1; 95% CI, 25.2-33.2; P < .001).

Rates among Hispanic individuals increased from 1.4 to 6.6 per 100,000 for men and from 0.5 to 2.0 per 100,000 for women. Among non-Hispanic Asian individuals, rates increased to 3.4 per 100,000 for men and to 1.1 per 100,000 for women. Non-Hispanic Black individuals had low rates. Within each racial/ethnic group, rates were higher among men versus women.

Methamphetamine death rates may be underestimated because some overdose death certificates do not report specific drugs involved, the authors noted.

Identifying populations that have a higher rate of methamphetamine overdose is a crucial step toward curbing the underlying methamphetamine crisis,” study author Beth Han, MD, PhD, of NIDA, said in a press release.

“By focusing on the unique needs of individuals and developing culturally tailored interventions, we can begin to move away from one-size-fits-all approaches and toward more effective, tailored interventions,” she said.

The study was sponsored by NIDA.

A version of this article first appeared on Medscape.com.

The national rate of methamphetamine overdose deaths shot up significantly between 2011 and 2018, particularly among non-Hispanic American Indian and Alaska Native communities, new research shows.

Rates rose for both men and women but more so among men, the study found. The spike in these deaths underscores the need for culturally tailored prevention and treatment strategies, the study authors said.

“While much attention is focused on the opioid crisis, a methamphetamine crisis has been quietly, but actively, gaining steam – particularly among American Indians and Alaska Natives, who are disproportionately affected by a number of health conditions,” senior investigator Nora D. Volkow, MD, director of the National Institute on Drug Abuse, said in a press release.

The study was published online Jan. 20 in JAMA Psychiatry.
 

Highly toxic

Methamphetamine is highly toxic. Its use is associated with pulmonary and cardiovascular pathology and frequently co-occurs with other substance use and mental disorders.

In addition, there are currently no Food and Drug Administration–approved medications to reverse methamphetamine overdose or treat methamphetamine use disorder.

However, behavioral therapies can be effective in reducing the harm associated with methamphetamine use. In addition, a recent clinical trial reported significant therapeutic benefits with the combination of naltrexone with bupropion in patients with methamphetamine use disorder.

For the study, the investigators used deidentified public health surveillance data from the Centers for Disease Control and Prevention’s National Vital Statistics System files for multiple causes of death.

The researchers used the psychostimulant category to estimate death rates from methamphetamine. The authors noted that up to 90% of psychostimulant-involved death certificates mentioned methamphetamine.

Researchers stratified age-adjusted overdose death rates during 2011-2018 by sex and race/ethnicity and limited the analysis to those aged 25-54 years. Approximately 80% of methamphetamine users are between the ages of 25 and 54 years.

During the study period, rates for methamphetamine-involved deaths increased from 1.8 to 10.1 per 100,000 among men (average annual percentage change, 29.1; 95% confidence interval, 25.5-32.8; P < .001) and from 0.8 to 4.5 per 100,000 among women (AAPC, 28.1; 95% CI, 25.1-31.2; P < .001).
 

Need for tailored interventions

For both men and women, those in non-Hispanic American Indian or Alaska Native communities had the highest rates. These increased from 5.6 to 26.4 per 100,000 among men and from 3.6 to 15.6 per 100,000 among women.

While American Indian and Alaska Native individuals experience sociostructural disadvantages, their cultural strengths “can be leveraged to improve addiction outcomes,” the investigators wrote.

Non-Hispanic Whites had the second highest rates. These rose from 2.2 to 12.6 per 100,000 among men (AAPC, 29.8; 95% CI, 24.3-35.4; P < .001) and from 1.1 to 6.2 per 100,000 among women (AAPC, 29.1; 95% CI, 25.2-33.2; P < .001).

Rates among Hispanic individuals increased from 1.4 to 6.6 per 100,000 for men and from 0.5 to 2.0 per 100,000 for women. Among non-Hispanic Asian individuals, rates increased to 3.4 per 100,000 for men and to 1.1 per 100,000 for women. Non-Hispanic Black individuals had low rates. Within each racial/ethnic group, rates were higher among men versus women.

Methamphetamine death rates may be underestimated because some overdose death certificates do not report specific drugs involved, the authors noted.

Identifying populations that have a higher rate of methamphetamine overdose is a crucial step toward curbing the underlying methamphetamine crisis,” study author Beth Han, MD, PhD, of NIDA, said in a press release.

“By focusing on the unique needs of individuals and developing culturally tailored interventions, we can begin to move away from one-size-fits-all approaches and toward more effective, tailored interventions,” she said.

The study was sponsored by NIDA.

A version of this article first appeared on Medscape.com.

The national rate of methamphetamine overdose deaths shot up significantly between 2011 and 2018, particularly among non-Hispanic American Indian and Alaska Native communities, new research shows.

Rates rose for both men and women but more so among men, the study found. The spike in these deaths underscores the need for culturally tailored prevention and treatment strategies, the study authors said.

“While much attention is focused on the opioid crisis, a methamphetamine crisis has been quietly, but actively, gaining steam – particularly among American Indians and Alaska Natives, who are disproportionately affected by a number of health conditions,” senior investigator Nora D. Volkow, MD, director of the National Institute on Drug Abuse, said in a press release.

The study was published online Jan. 20 in JAMA Psychiatry.
 

Highly toxic

Methamphetamine is highly toxic. Its use is associated with pulmonary and cardiovascular pathology and frequently co-occurs with other substance use and mental disorders.

In addition, there are currently no Food and Drug Administration–approved medications to reverse methamphetamine overdose or treat methamphetamine use disorder.

However, behavioral therapies can be effective in reducing the harm associated with methamphetamine use. In addition, a recent clinical trial reported significant therapeutic benefits with the combination of naltrexone with bupropion in patients with methamphetamine use disorder.

For the study, the investigators used deidentified public health surveillance data from the Centers for Disease Control and Prevention’s National Vital Statistics System files for multiple causes of death.

The researchers used the psychostimulant category to estimate death rates from methamphetamine. The authors noted that up to 90% of psychostimulant-involved death certificates mentioned methamphetamine.

Researchers stratified age-adjusted overdose death rates during 2011-2018 by sex and race/ethnicity and limited the analysis to those aged 25-54 years. Approximately 80% of methamphetamine users are between the ages of 25 and 54 years.

During the study period, rates for methamphetamine-involved deaths increased from 1.8 to 10.1 per 100,000 among men (average annual percentage change, 29.1; 95% confidence interval, 25.5-32.8; P < .001) and from 0.8 to 4.5 per 100,000 among women (AAPC, 28.1; 95% CI, 25.1-31.2; P < .001).
 

Need for tailored interventions

For both men and women, those in non-Hispanic American Indian or Alaska Native communities had the highest rates. These increased from 5.6 to 26.4 per 100,000 among men and from 3.6 to 15.6 per 100,000 among women.

While American Indian and Alaska Native individuals experience sociostructural disadvantages, their cultural strengths “can be leveraged to improve addiction outcomes,” the investigators wrote.

Non-Hispanic Whites had the second highest rates. These rose from 2.2 to 12.6 per 100,000 among men (AAPC, 29.8; 95% CI, 24.3-35.4; P < .001) and from 1.1 to 6.2 per 100,000 among women (AAPC, 29.1; 95% CI, 25.2-33.2; P < .001).

Rates among Hispanic individuals increased from 1.4 to 6.6 per 100,000 for men and from 0.5 to 2.0 per 100,000 for women. Among non-Hispanic Asian individuals, rates increased to 3.4 per 100,000 for men and to 1.1 per 100,000 for women. Non-Hispanic Black individuals had low rates. Within each racial/ethnic group, rates were higher among men versus women.

Methamphetamine death rates may be underestimated because some overdose death certificates do not report specific drugs involved, the authors noted.

Identifying populations that have a higher rate of methamphetamine overdose is a crucial step toward curbing the underlying methamphetamine crisis,” study author Beth Han, MD, PhD, of NIDA, said in a press release.

“By focusing on the unique needs of individuals and developing culturally tailored interventions, we can begin to move away from one-size-fits-all approaches and toward more effective, tailored interventions,” she said.

The study was sponsored by NIDA.

A version of this article first appeared on Medscape.com.

A 62-year-old man presented to our skin clinic with multiple pruritic, tense, bullous lesions that manifested on his arms, abdomen, back, and upper thighs over a 1-month period. There were no lesions in his oral cavity or around his eyes, nose, or penile region. He denied dysphagia.

The patient had multiple comorbidities, including diabetes, hypertension, recent stroke, and end-stage renal disease. He was being prepared for dialysis. His medications included torsemide, warfarin, amiodarone, metoprolol, pantoprozole, atorvastatin, and nifedipine. About 3 months prior to this presentation, he was started on oral linaglipton 5 mg/d, an oral antihyperglycemic medication. He had no history of skin disease or cancer, and his family history was not significant.

Physical examination showed multiple 5-mm to 2-cm blisters and bullae on the flexural surface of both of his arms (FIGURE), back, lower abdomen, and upper thighs. His palms and soles were not involved. The lesions were nontender, tense, and filled with clear fluid. Some were intact and others were rupturing. There was no mucocutaneous involvement. Nikolsky sign was negative. There were no signs of bleeding.

The family physician (FP) obtained a 4-mm punch biopsy at the edge of a 6-mm blister for light microscopy and a 3-mm perilesional punch biopsy for direct immunofluorescence (DIF) microscopy.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Dx: Bullous pemphigoid secondary to linagliptin use

DIF of the biopsy sample demonstrated linear deposition of complement 3 (C3) and immunoglobulin (Ig) G along the basement membrane zone. Indirect immunofluorescence on salt-split skin demonstrated linear deposition of IgG and C3 on both the roof and floor of the induced blisters. These findings and the patient’s clinical presentation met the criteria for bullous pemphigoid (BP), which is the most common autoimmune skin-blistering disease.¹

FPs are increasingly using DPP-4 inhibitors as oral antihyperglycemic agents for type 2 diabetes mellitus. Therefore, it’s important to recognize this medication class’s association with BP

BP is associated with subepidermal blistering, which can occur in reaction to a variety of triggers. Pathogenesis of this condition involves IgG anti-basement membrane autoantibody complex formation with the hemidesmosomal antigens BP230 and BP180—a process that activates C3 and the release of proteases that can be destructive to tissue along the dermo-epidermal junction.¹

Growing incidence. BP usually occurs in patients > 60 years, with no racial or gender preference.¹ The incidence rate of BP ranges from 2.4 to 21.7 new cases per 1 million individuals among various worldwide populations.² The incidence appears to have increased 1.9- to 4.3-fold over the past 2 decades.²

What you’ll see, who’s at risk

Symptoms of BP include localized areas of erythema or pruritic urticarial plaques that gradually become more extensive. A patient may have pruritis alone for an extended period prior to developing blisters and bullae. The bullae are tense and normally 1 to 7 cm in size.¹ Eruption is generalized, mostly affecting the lower abdomen, as well as the flexural parts of the extremities. The palms and soles also can be affected.

FPs should be aware of the atypical clinical variants of BP. In a review by Kridin and Ludwig, variants can be prurigo-like, eczema-like, urticaria-like, dyshidrosiform type, erosive type, and erythema annulare centrifugum–like type.² At-risk populations, such as elderly patients (> 70 years), whose pruritis manifests with or without bullous formation, should be screened for BP.^3,4

Continue to: Risk factors for BP

Risk factors for BP. Certain conditions linked to developing BP include neurologic disorders (dementia and Parkinson disease) and psychiatric disorders (unipolar and bipolar disorder).⁴ Further, it is important to note any medications that could be the cause of a patient’s BP, including dipeptidyl peptidase-4 (DPP-4) inhibitors, psychotropic medications, spironolactone, furosemide, beta-blockers, and antibiotics.³ This patient was taking a beta-blocker (metoprolol) and a DPP-4 inhibitor (linagliptin). Because he was most recently started on linagliptin, we suspected it may have had a causal role in the development of BP.

The association of DPP-4 inhibitors and BP

FPs are increasingly using DPP-4 inhibitors—including sitagliptin, vildagliptin, and linagliptin—as oral antihyperglycemic agents for type 2 diabetes mellitus. Therefore, it’s important to recognize this medication class’s association with BP.⁵ In a case-control study of 165 patients with BP, Benzaquen et al reported that 28 patients who were taking DPP-4 inhibitors had an associated increased risk for BP (adjusted odds ratio = 2.64; 95% confidence interval [CI], 1.19-5.85).³

The pathophysiology of BP associated with DPP-4 inhibitors remains unclear, but mechanisms have been proposed. The DPP-4 enzyme is expressed on many cells, including keratinocytes, T cells, and endothelial cells.³ It is possible that DPP-4 inhibition at these cells could stimulate activity of inflammatory cytokines, which can lead to enhanced local eosinophil activation and trigger bullous formation. DPP-4 enzymes are also involved in forming plasmin, which is a protease that cleaves BP180.³ Inhibition of this process can affect proper cleavage of BP180, impacting its function and antigenicity.^3,6

Other conditions that also exhibit blisters

There are some skin conditions with similar presentations that need to be ruled out in the work-up.

Bullous diabeticorum is a rare, spontaneous, noninflammatory condition found in patients with diabetes.¹ Blisters usually manifest as large, tense, asymmetrical, mildly tender lesions that commonly affect the feet and lower legs but can involve the trunk. These usually develop overnight without preceding trauma. Biopsy would show both intra-­epidermal and subepidermal bulla with normal DIF findings.¹ This condition usually has an excellent prognosis.

Continue to: Pemphigus vulgaris

Pemphigus vulgaris is characterized by nonpruritic, flaccid, painful blisters. This condition usually begins with manifestation of painful oral lesions that evolve into skin blisters. Some patients can develop mucocutaneous lesions.¹ Nikolsky sign is positive in these cases. Light microscopy would show intra-­epidermal bullae.

Dermatitis herpetiformis. This condition—usually affecting middle-age patients—is associated with severe pruritis and burning. It may start with a few pruritic papules or vesicles that later evolve into urticarial papules, vesicles, or bullae. Dermatitis herpetiformis can resemble herpes simplex virus. It can also be associated with gluten-sensitive enteropathy and small bowel lymphoma.¹ DIF of a biopsy sample would show granular deposition of IgA within the tips of the dermal papillae and along the basement membrane of perilesional skin.¹

Epidermolysis bullosa acquisita is a rare, severe, chronic condition with subepidermal mucocutaneous blistering.¹ It is associated with skin fragility and spontaneous trauma-induced blisters that heal with scar formation and milia. IgG autoantibodies reacting to proteins in the basement membrane zone can cause the disease. It is also associated with Crohn disease.¹ DIF findings are similar in BP, but they are differentiated by location of IgG deposits; they can be found on the dermal side of separation in epidermolysis bullosa acquisita, as compared with the epidermal side in BP.¹

How to make the Dx in 3 steps

To effectively diagnose and classify BP, use the following 3-step method:

1. Establish the presence of 3 of 4 ­clinical characteristics: patient’s age > 60 years, absence of atrophic scars, absence of mucosal involvement, and absence of bullous lesions on the head and neck.
2. Order light microscopy. Findings should be consistent with eosinophils and neutrophils containing subepidermal bullae.
3. Order a punch biopsy to obtain a perilesional specimen. DIF of the biopsy findings should feature linear deposits of IgG with or without C3 along the dermo-epidermal junction. This step is essential for an accurate diagnosis.

Depending on the severity of disease, treatment can include the use of potent topical corticosteroids alone or in combination with systemic corticosteroids and antiinflammatory antibiotics.

There also is benefit in ordering supplemental studies, such as an enzyme-linked immunosorbent assay for the detection of anti-BP180 or anti-BP230 IgG autoantibodies.⁷ However, for this patient, we did not order this study.

Continue to: Management focuses on steroids

Management focuses on steroids

The offending agent should be discontinued immediately. Depending on the severity of disease, treatment can include the use of potent topical corticosteroids alone or in combination with systemic corticosteroids and anti-inflammatory antibiotics (eg, doxycycline, minocycline, erythromycin).^1,7 For patients with resistant or refractory disease, consider azathioprine, methotrexate, dapsone, and chlorambucil.^1,7 Exceptional cases may benefit from the use of mycophenolate mofetil, intravenous immunoglobulin, or plasmapheresis.^1,7

For this patient, initial treatment included discontinuation of linagliption and introduction of topical clobetasol 0.05% and oral prednisone 40 mg/d for 7 days, followed by prednisone 20 mg for 7 days. He was also started on oral doxycycline 100 mg bid and oral nicotinamide 500 mg bid.

A 62-year-old man presented to our skin clinic with multiple pruritic, tense, bullous lesions that manifested on his arms, abdomen, back, and upper thighs over a 1-month period. There were no lesions in his oral cavity or around his eyes, nose, or penile region. He denied dysphagia.

The patient had multiple comorbidities, including diabetes, hypertension, recent stroke, and end-stage renal disease. He was being prepared for dialysis. His medications included torsemide, warfarin, amiodarone, metoprolol, pantoprozole, atorvastatin, and nifedipine. About 3 months prior to this presentation, he was started on oral linaglipton 5 mg/d, an oral antihyperglycemic medication. He had no history of skin disease or cancer, and his family history was not significant.

Physical examination showed multiple 5-mm to 2-cm blisters and bullae on the flexural surface of both of his arms (FIGURE), back, lower abdomen, and upper thighs. His palms and soles were not involved. The lesions were nontender, tense, and filled with clear fluid. Some were intact and others were rupturing. There was no mucocutaneous involvement. Nikolsky sign was negative. There were no signs of bleeding.

The family physician (FP) obtained a 4-mm punch biopsy at the edge of a 6-mm blister for light microscopy and a 3-mm perilesional punch biopsy for direct immunofluorescence (DIF) microscopy.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Dx: Bullous pemphigoid secondary to linagliptin use

DIF of the biopsy sample demonstrated linear deposition of complement 3 (C3) and immunoglobulin (Ig) G along the basement membrane zone. Indirect immunofluorescence on salt-split skin demonstrated linear deposition of IgG and C3 on both the roof and floor of the induced blisters. These findings and the patient’s clinical presentation met the criteria for bullous pemphigoid (BP), which is the most common autoimmune skin-blistering disease.¹

FPs are increasingly using DPP-4 inhibitors as oral antihyperglycemic agents for type 2 diabetes mellitus. Therefore, it’s important to recognize this medication class’s association with BP

BP is associated with subepidermal blistering, which can occur in reaction to a variety of triggers. Pathogenesis of this condition involves IgG anti-basement membrane autoantibody complex formation with the hemidesmosomal antigens BP230 and BP180—a process that activates C3 and the release of proteases that can be destructive to tissue along the dermo-epidermal junction.¹

Growing incidence. BP usually occurs in patients > 60 years, with no racial or gender preference.¹ The incidence rate of BP ranges from 2.4 to 21.7 new cases per 1 million individuals among various worldwide populations.² The incidence appears to have increased 1.9- to 4.3-fold over the past 2 decades.²

What you’ll see, who’s at risk

Symptoms of BP include localized areas of erythema or pruritic urticarial plaques that gradually become more extensive. A patient may have pruritis alone for an extended period prior to developing blisters and bullae. The bullae are tense and normally 1 to 7 cm in size.¹ Eruption is generalized, mostly affecting the lower abdomen, as well as the flexural parts of the extremities. The palms and soles also can be affected.

FPs should be aware of the atypical clinical variants of BP. In a review by Kridin and Ludwig, variants can be prurigo-like, eczema-like, urticaria-like, dyshidrosiform type, erosive type, and erythema annulare centrifugum–like type.² At-risk populations, such as elderly patients (> 70 years), whose pruritis manifests with or without bullous formation, should be screened for BP.^3,4

Continue to: Risk factors for BP

Risk factors for BP. Certain conditions linked to developing BP include neurologic disorders (dementia and Parkinson disease) and psychiatric disorders (unipolar and bipolar disorder).⁴ Further, it is important to note any medications that could be the cause of a patient’s BP, including dipeptidyl peptidase-4 (DPP-4) inhibitors, psychotropic medications, spironolactone, furosemide, beta-blockers, and antibiotics.³ This patient was taking a beta-blocker (metoprolol) and a DPP-4 inhibitor (linagliptin). Because he was most recently started on linagliptin, we suspected it may have had a causal role in the development of BP.

The association of DPP-4 inhibitors and BP

FPs are increasingly using DPP-4 inhibitors—including sitagliptin, vildagliptin, and linagliptin—as oral antihyperglycemic agents for type 2 diabetes mellitus. Therefore, it’s important to recognize this medication class’s association with BP.⁵ In a case-control study of 165 patients with BP, Benzaquen et al reported that 28 patients who were taking DPP-4 inhibitors had an associated increased risk for BP (adjusted odds ratio = 2.64; 95% confidence interval [CI], 1.19-5.85).³

The pathophysiology of BP associated with DPP-4 inhibitors remains unclear, but mechanisms have been proposed. The DPP-4 enzyme is expressed on many cells, including keratinocytes, T cells, and endothelial cells.³ It is possible that DPP-4 inhibition at these cells could stimulate activity of inflammatory cytokines, which can lead to enhanced local eosinophil activation and trigger bullous formation. DPP-4 enzymes are also involved in forming plasmin, which is a protease that cleaves BP180.³ Inhibition of this process can affect proper cleavage of BP180, impacting its function and antigenicity.^3,6

Other conditions that also exhibit blisters

There are some skin conditions with similar presentations that need to be ruled out in the work-up.

Bullous diabeticorum is a rare, spontaneous, noninflammatory condition found in patients with diabetes.¹ Blisters usually manifest as large, tense, asymmetrical, mildly tender lesions that commonly affect the feet and lower legs but can involve the trunk. These usually develop overnight without preceding trauma. Biopsy would show both intra-­epidermal and subepidermal bulla with normal DIF findings.¹ This condition usually has an excellent prognosis.

Continue to: Pemphigus vulgaris

Pemphigus vulgaris is characterized by nonpruritic, flaccid, painful blisters. This condition usually begins with manifestation of painful oral lesions that evolve into skin blisters. Some patients can develop mucocutaneous lesions.¹ Nikolsky sign is positive in these cases. Light microscopy would show intra-­epidermal bullae.

Dermatitis herpetiformis. This condition—usually affecting middle-age patients—is associated with severe pruritis and burning. It may start with a few pruritic papules or vesicles that later evolve into urticarial papules, vesicles, or bullae. Dermatitis herpetiformis can resemble herpes simplex virus. It can also be associated with gluten-sensitive enteropathy and small bowel lymphoma.¹ DIF of a biopsy sample would show granular deposition of IgA within the tips of the dermal papillae and along the basement membrane of perilesional skin.¹

Epidermolysis bullosa acquisita is a rare, severe, chronic condition with subepidermal mucocutaneous blistering.¹ It is associated with skin fragility and spontaneous trauma-induced blisters that heal with scar formation and milia. IgG autoantibodies reacting to proteins in the basement membrane zone can cause the disease. It is also associated with Crohn disease.¹ DIF findings are similar in BP, but they are differentiated by location of IgG deposits; they can be found on the dermal side of separation in epidermolysis bullosa acquisita, as compared with the epidermal side in BP.¹

How to make the Dx in 3 steps

To effectively diagnose and classify BP, use the following 3-step method:

1. Establish the presence of 3 of 4 ­clinical characteristics: patient’s age > 60 years, absence of atrophic scars, absence of mucosal involvement, and absence of bullous lesions on the head and neck.
2. Order light microscopy. Findings should be consistent with eosinophils and neutrophils containing subepidermal bullae.
3. Order a punch biopsy to obtain a perilesional specimen. DIF of the biopsy findings should feature linear deposits of IgG with or without C3 along the dermo-epidermal junction. This step is essential for an accurate diagnosis.

Depending on the severity of disease, treatment can include the use of potent topical corticosteroids alone or in combination with systemic corticosteroids and antiinflammatory antibiotics.

There also is benefit in ordering supplemental studies, such as an enzyme-linked immunosorbent assay for the detection of anti-BP180 or anti-BP230 IgG autoantibodies.⁷ However, for this patient, we did not order this study.

Continue to: Management focuses on steroids

Management focuses on steroids

The offending agent should be discontinued immediately. Depending on the severity of disease, treatment can include the use of potent topical corticosteroids alone or in combination with systemic corticosteroids and anti-inflammatory antibiotics (eg, doxycycline, minocycline, erythromycin).^1,7 For patients with resistant or refractory disease, consider azathioprine, methotrexate, dapsone, and chlorambucil.^1,7 Exceptional cases may benefit from the use of mycophenolate mofetil, intravenous immunoglobulin, or plasmapheresis.^1,7

For this patient, initial treatment included discontinuation of linagliption and introduction of topical clobetasol 0.05% and oral prednisone 40 mg/d for 7 days, followed by prednisone 20 mg for 7 days. He was also started on oral doxycycline 100 mg bid and oral nicotinamide 500 mg bid.

A 62-year-old man presented to our skin clinic with multiple pruritic, tense, bullous lesions that manifested on his arms, abdomen, back, and upper thighs over a 1-month period. There were no lesions in his oral cavity or around his eyes, nose, or penile region. He denied dysphagia.

The patient had multiple comorbidities, including diabetes, hypertension, recent stroke, and end-stage renal disease. He was being prepared for dialysis. His medications included torsemide, warfarin, amiodarone, metoprolol, pantoprozole, atorvastatin, and nifedipine. About 3 months prior to this presentation, he was started on oral linaglipton 5 mg/d, an oral antihyperglycemic medication. He had no history of skin disease or cancer, and his family history was not significant.

Physical examination showed multiple 5-mm to 2-cm blisters and bullae on the flexural surface of both of his arms (FIGURE), back, lower abdomen, and upper thighs. His palms and soles were not involved. The lesions were nontender, tense, and filled with clear fluid. Some were intact and others were rupturing. There was no mucocutaneous involvement. Nikolsky sign was negative. There were no signs of bleeding.

The family physician (FP) obtained a 4-mm punch biopsy at the edge of a 6-mm blister for light microscopy and a 3-mm perilesional punch biopsy for direct immunofluorescence (DIF) microscopy.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Dx: Bullous pemphigoid secondary to linagliptin use

DIF of the biopsy sample demonstrated linear deposition of complement 3 (C3) and immunoglobulin (Ig) G along the basement membrane zone. Indirect immunofluorescence on salt-split skin demonstrated linear deposition of IgG and C3 on both the roof and floor of the induced blisters. These findings and the patient’s clinical presentation met the criteria for bullous pemphigoid (BP), which is the most common autoimmune skin-blistering disease.¹

FPs are increasingly using DPP-4 inhibitors as oral antihyperglycemic agents for type 2 diabetes mellitus. Therefore, it’s important to recognize this medication class’s association with BP

BP is associated with subepidermal blistering, which can occur in reaction to a variety of triggers. Pathogenesis of this condition involves IgG anti-basement membrane autoantibody complex formation with the hemidesmosomal antigens BP230 and BP180—a process that activates C3 and the release of proteases that can be destructive to tissue along the dermo-epidermal junction.¹

Growing incidence. BP usually occurs in patients > 60 years, with no racial or gender preference.¹ The incidence rate of BP ranges from 2.4 to 21.7 new cases per 1 million individuals among various worldwide populations.² The incidence appears to have increased 1.9- to 4.3-fold over the past 2 decades.²

What you’ll see, who’s at risk

Symptoms of BP include localized areas of erythema or pruritic urticarial plaques that gradually become more extensive. A patient may have pruritis alone for an extended period prior to developing blisters and bullae. The bullae are tense and normally 1 to 7 cm in size.¹ Eruption is generalized, mostly affecting the lower abdomen, as well as the flexural parts of the extremities. The palms and soles also can be affected.

FPs should be aware of the atypical clinical variants of BP. In a review by Kridin and Ludwig, variants can be prurigo-like, eczema-like, urticaria-like, dyshidrosiform type, erosive type, and erythema annulare centrifugum–like type.² At-risk populations, such as elderly patients (> 70 years), whose pruritis manifests with or without bullous formation, should be screened for BP.^3,4

Continue to: Risk factors for BP

Risk factors for BP. Certain conditions linked to developing BP include neurologic disorders (dementia and Parkinson disease) and psychiatric disorders (unipolar and bipolar disorder).⁴ Further, it is important to note any medications that could be the cause of a patient’s BP, including dipeptidyl peptidase-4 (DPP-4) inhibitors, psychotropic medications, spironolactone, furosemide, beta-blockers, and antibiotics.³ This patient was taking a beta-blocker (metoprolol) and a DPP-4 inhibitor (linagliptin). Because he was most recently started on linagliptin, we suspected it may have had a causal role in the development of BP.

The association of DPP-4 inhibitors and BP

FPs are increasingly using DPP-4 inhibitors—including sitagliptin, vildagliptin, and linagliptin—as oral antihyperglycemic agents for type 2 diabetes mellitus. Therefore, it’s important to recognize this medication class’s association with BP.⁵ In a case-control study of 165 patients with BP, Benzaquen et al reported that 28 patients who were taking DPP-4 inhibitors had an associated increased risk for BP (adjusted odds ratio = 2.64; 95% confidence interval [CI], 1.19-5.85).³

The pathophysiology of BP associated with DPP-4 inhibitors remains unclear, but mechanisms have been proposed. The DPP-4 enzyme is expressed on many cells, including keratinocytes, T cells, and endothelial cells.³ It is possible that DPP-4 inhibition at these cells could stimulate activity of inflammatory cytokines, which can lead to enhanced local eosinophil activation and trigger bullous formation. DPP-4 enzymes are also involved in forming plasmin, which is a protease that cleaves BP180.³ Inhibition of this process can affect proper cleavage of BP180, impacting its function and antigenicity.^3,6

Other conditions that also exhibit blisters

There are some skin conditions with similar presentations that need to be ruled out in the work-up.

Bullous diabeticorum is a rare, spontaneous, noninflammatory condition found in patients with diabetes.¹ Blisters usually manifest as large, tense, asymmetrical, mildly tender lesions that commonly affect the feet and lower legs but can involve the trunk. These usually develop overnight without preceding trauma. Biopsy would show both intra-­epidermal and subepidermal bulla with normal DIF findings.¹ This condition usually has an excellent prognosis.

Continue to: Pemphigus vulgaris

Pemphigus vulgaris is characterized by nonpruritic, flaccid, painful blisters. This condition usually begins with manifestation of painful oral lesions that evolve into skin blisters. Some patients can develop mucocutaneous lesions.¹ Nikolsky sign is positive in these cases. Light microscopy would show intra-­epidermal bullae.

Dermatitis herpetiformis. This condition—usually affecting middle-age patients—is associated with severe pruritis and burning. It may start with a few pruritic papules or vesicles that later evolve into urticarial papules, vesicles, or bullae. Dermatitis herpetiformis can resemble herpes simplex virus. It can also be associated with gluten-sensitive enteropathy and small bowel lymphoma.¹ DIF of a biopsy sample would show granular deposition of IgA within the tips of the dermal papillae and along the basement membrane of perilesional skin.¹

Epidermolysis bullosa acquisita is a rare, severe, chronic condition with subepidermal mucocutaneous blistering.¹ It is associated with skin fragility and spontaneous trauma-induced blisters that heal with scar formation and milia. IgG autoantibodies reacting to proteins in the basement membrane zone can cause the disease. It is also associated with Crohn disease.¹ DIF findings are similar in BP, but they are differentiated by location of IgG deposits; they can be found on the dermal side of separation in epidermolysis bullosa acquisita, as compared with the epidermal side in BP.¹

How to make the Dx in 3 steps

To effectively diagnose and classify BP, use the following 3-step method:

1. Establish the presence of 3 of 4 ­clinical characteristics: patient’s age > 60 years, absence of atrophic scars, absence of mucosal involvement, and absence of bullous lesions on the head and neck.
2. Order light microscopy. Findings should be consistent with eosinophils and neutrophils containing subepidermal bullae.
3. Order a punch biopsy to obtain a perilesional specimen. DIF of the biopsy findings should feature linear deposits of IgG with or without C3 along the dermo-epidermal junction. This step is essential for an accurate diagnosis.

Depending on the severity of disease, treatment can include the use of potent topical corticosteroids alone or in combination with systemic corticosteroids and antiinflammatory antibiotics.

There also is benefit in ordering supplemental studies, such as an enzyme-linked immunosorbent assay for the detection of anti-BP180 or anti-BP230 IgG autoantibodies.⁷ However, for this patient, we did not order this study.

Continue to: Management focuses on steroids

Management focuses on steroids

The offending agent should be discontinued immediately. Depending on the severity of disease, treatment can include the use of potent topical corticosteroids alone or in combination with systemic corticosteroids and anti-inflammatory antibiotics (eg, doxycycline, minocycline, erythromycin).^1,7 For patients with resistant or refractory disease, consider azathioprine, methotrexate, dapsone, and chlorambucil.^1,7 Exceptional cases may benefit from the use of mycophenolate mofetil, intravenous immunoglobulin, or plasmapheresis.^1,7

For this patient, initial treatment included discontinuation of linagliption and introduction of topical clobetasol 0.05% and oral prednisone 40 mg/d for 7 days, followed by prednisone 20 mg for 7 days. He was also started on oral doxycycline 100 mg bid and oral nicotinamide 500 mg bid.

THE CASE

Emily T.* is a 15-year-old, cisgender, homeless runaway. While on the streets, she was lured to a hotel where a “pimp” informed her she was going to work for him. She repeatedly tried to leave, but he would strike her, so she eventually succumbed. She was forced to have sex with several men and rarely allowed to use condoms.

On 1 occasion, when she went to a hospital with her pimp to visit a patient, her aunt (a nurse on duty at that facility) saw Ms. T and called the police. The pimp was arrested. Ms. T was interviewed by the police and gave a statement but refused a forensic exam.

Because of her involvement with the pimp, she was incarcerated. In prison, she was seen by a physician. On evaluation, she reported difficulty sleeping, flashbacks, and feelings of shame and guilt.¹

● How would you proceed with this patient?

* The patient’s name has been changed to protect her identity.

Child and adolescent sex trafficking is defined as the sexual exploitation of minors through force, fraud, or coercion. Specifically, it includes the recruitment, harboring, transportation, or advertising of a minor, and includes the exchange of anything of value in return for sexual activity. Commercial sexual exploitation and sex trafficking against minors include crimes such as prostitution; survival sex (exchanging sex/sexual acts for money or something of value, such as shelter, food, or drugs); pornography; sex tourism, mail-order-bride trade, and early marriage; or sexual performances (peep shows or strip clubs).²

Providing optimal care for children and adolescents exploited by sex trafficking depends on knowing risk factors, having an awareness of recommended screening and assessment tools, and employing a trauma-­informed approach to interviews, examination, and support.²

Continue to: Recognize clues to trafficking

 

 

Recognize clues to trafficking

The Centers for Disease Control and Prevention (CDC) offers a framework for trafficking prevention. Health care providers are encouraged to use the CDC Social-Ecological Model which describes targeted prevention strategies at the individual, relationship, community, and societal levels.³

Risk factors for entering trafficking. Younger age increases a child’s vulnerability to exploitation, due to a lack of maturity, limited cognitive development, and ease of deception. The mean age of trafficking survivors is 15 years.⁴ History of child abuse and other traumatic experiences can lead children to run away from home. It is estimated that, once on the streets, most teens will be recruited by a trafficker within 48 hours.⁵ Poor self-esteem, depression, substance abuse, history of truancy, and early sexual maturation also increase the risk of becoming involved in trafficking (TABLE 1).^2,6-8

Clinical findings suggestive of trafficking. Many physicians grasp the critical role they play in confronting trafficking, but they lack specific training, experience, and assessment tools.³ Notably, in 1 retrospective study, 46% of victims had been seen by a provider within the previous 2 months.⁶ One of the major challenges to identifying survivors of trafficking is to recognize critical signs, of which there are many (TABLE 1^2,6-8). Often these include a history of sexual assault, multiple pregnancies, requests for contraception at an early age, or evidence of physical injury.

Screen to identify trafficking

Universal, validated screening tools to accurately identify trafficked youth is an area of growing research. Some tools have been validated, but only for specific populations such as homeless or incarcerated youth or in emergency department (ED) patients. Tools for sex trafficking identification that may be useful in primary care include the Child Sex Trafficking (CST) screen validated in ED settings (TABLE 2),⁹ the Commercial Sexual Exploitation-Identification Tool (CSE-IT) in multiple settings (TABLE 3),^10,11 and the Quick Youth Indicators for Trafficking (QYIT) in homeless youth (TABLE 4).¹¹ The QYIT is the first validated labor and sex trafficking screening tool in homeless young adults. Children who screen positive for sex trafficking should be further assessed using a comprehensive tool.

Barriers to effective recognition of trafficked individuals. Financial factors limit access to health care. Also, survivors have cited multiple barriers for health professionals that prevent identification of survivors’ trafficked status.^12,13 Once in the medical setting, disclosure is impacted by time constraints, fear of judgment by clinicians, and the risk of re-traumatization. Survivors have also cited lack of privacy, control strategies by their traffickers, lack of provider empathy, and fear of police as barriers to disclosure.¹⁴

Continue to: The medical impact of trafficking

The medical impact of trafficking

Sexual exploitation is a traumatic experience that is known to cause harm across multiple domains including serious physical injuries related to violence, as well as reproductive and mental health consequences.^15,16

Acute and chronic illnesses. In an initial evaluation, assess the survivor’s acute medical conditions (TABLE 5).^15,16 Common acute issues include physical injuries due to assault, infections, and reproductive complications.¹⁷ Health concerns can also result from stressors such as deprivation of food and sleep, hazardous living conditions, and limited access to care.¹⁷

Suspect possible sex trafficking when a patient has a history of sexual assault and multiple pregnancies, requests contraception at an early age, and/or has evidence of physical injury.

As part of caring for sex-trafficking survivors, assess for, and treat, chronic health issues such as pain, gastrointestinal complaints, poor dental care, malnutrition, and fatigue.^16,18 Substance use, as well as chronic mental health concerns (eg, anxiety, depression, posttraumatic stress disorder [PTSD]) may also influence the clinical presentation.

Physical injuries. A cross-sectional study of female survivors of sex trafficking in the United States found that 89% sustained physical injury resulting from violence, including fractures, open wounds, head injury, dental problems, burns, and anogenital trauma.^16,17 In many cases, acute injury may not be present in the clinical setting since care is often delayed, but a full examination can reveal signs of prior trauma.¹⁶

Reproductive health concerns. Significant, long-term impact on reproductive health can result due to forced penetration by multiple perpetrators, sodomy, and sex without protection or lubricants. Survivors are therefore at high risk for unplanned and unwanted pregnancies, sexually transmitted infections (STIs), pelvic pain, and infertility.¹⁶

Continue to: Psychological effects and trauma exposure

Psychological effects and trauma exposure. Survivors often have experienced abuse and neglect prior to commercial exploitation, and they may exhibit long-term sequelae. Survivors may present with major depression, anxiety, panic attacks, suicidality, addiction, PTSD, or aggression.¹⁶ Long-term sequelae for patients can include dysfunctional relationships due to an inability to trust, self-destructive behaviors, and significant shame.^2,18

Care and treatment of trafficked youth

Initial presentation may occur in a variety of health care settings. Use a trauma-informed approach emphasizing physical and emotional safety and positive relationships, to reduce risk to the survivor, staff, and providers.¹⁹ Establishing trust and rapport may provide better short-term safety, as well as help build stronger long-term relationships that can lead to better health outcomes.

Clinical examination. Provide traumatized patients with a sense of safety, control, and autonomy in the health care setting. During the physical exam, be aware of the impact of re-traumatization as patients are asked to undress, endure sensitive examinations, and undergo invasive procedures. Explain the examination, ask for permission at each step, and use slow movements. Allow the patient to guide certain sensitive exams.¹⁵ Adopt an approach that recognizes the impact of trauma, avoids revictimization, and acknowledges the resilience of survivors.²⁰

Treatment plan. After the initial exam, treat acute physical injuries and determine if any further testing is needed. Offer emergency contraception, STI prophylaxis, pre-exposure prophylaxis, and vaccines.¹⁵ After assessing patient readiness, offer local resources, identify safe methods for communication, identify individuals who could intervene in a crisis, and consider a safety plan (TABLE 6).

Coordination of care. Consider referrals to behavioral health services, substance recovery centers, food programs, housing resources, and a primary care clinic.¹⁵ ED clinicians may be asked to complete a sexual or physical assault forensic examination. After obtaining informed consent, one needs to¹⁹

• document skin signs such as scars, bites, strangulation marks, and tattoos. Note the size, shape, color, location, and other characteristics of each lesion.
• perform an oral, genital, and rectal examination and use a sexual assault evidence kit as indicated.
• use body diagrams and take photographs of all injuries/physical findings.
• order diagnostic testing as appropriate (eg, imaging to assess fractures).

Continue to: THE CASE

THE CASE

During Ms. T’s incarceration, she was tested for STIs and treated for gonorrhea, trichomonas, and bacterial vaginosis. She was educated about sexual health, was counseled on contraception, and accepted condoms. She was referred to a therapist and given information on additional community resources she could contact upon her release.

During a physical examination, explain the process, ask for permission at each step, use slow movements, and allow the patient to guide certain sensitive exams.

A year after her release, she was incarcerated again. She also had an unplanned pregnancy. With the support she received from community programs, social workers, and her primary care provider, she moved in with her family, where she is currently living. She denies any ongoing trafficking activity.

CORRESPONDENCE
Piali Basu, DO, MPH, UCSF Primary Care, 185 Berry Street, Lobby 1, Suite 1000, San Francisco, CA 94107; piali.basu@ucsf.edu

THE CASE

Emily T.* is a 15-year-old, cisgender, homeless runaway. While on the streets, she was lured to a hotel where a “pimp” informed her she was going to work for him. She repeatedly tried to leave, but he would strike her, so she eventually succumbed. She was forced to have sex with several men and rarely allowed to use condoms.

On 1 occasion, when she went to a hospital with her pimp to visit a patient, her aunt (a nurse on duty at that facility) saw Ms. T and called the police. The pimp was arrested. Ms. T was interviewed by the police and gave a statement but refused a forensic exam.

Because of her involvement with the pimp, she was incarcerated. In prison, she was seen by a physician. On evaluation, she reported difficulty sleeping, flashbacks, and feelings of shame and guilt.¹

● How would you proceed with this patient?

* The patient’s name has been changed to protect her identity.

Child and adolescent sex trafficking is defined as the sexual exploitation of minors through force, fraud, or coercion. Specifically, it includes the recruitment, harboring, transportation, or advertising of a minor, and includes the exchange of anything of value in return for sexual activity. Commercial sexual exploitation and sex trafficking against minors include crimes such as prostitution; survival sex (exchanging sex/sexual acts for money or something of value, such as shelter, food, or drugs); pornography; sex tourism, mail-order-bride trade, and early marriage; or sexual performances (peep shows or strip clubs).²

Providing optimal care for children and adolescents exploited by sex trafficking depends on knowing risk factors, having an awareness of recommended screening and assessment tools, and employing a trauma-­informed approach to interviews, examination, and support.²

Continue to: Recognize clues to trafficking

 

 

Recognize clues to trafficking

The Centers for Disease Control and Prevention (CDC) offers a framework for trafficking prevention. Health care providers are encouraged to use the CDC Social-Ecological Model which describes targeted prevention strategies at the individual, relationship, community, and societal levels.³

Risk factors for entering trafficking. Younger age increases a child’s vulnerability to exploitation, due to a lack of maturity, limited cognitive development, and ease of deception. The mean age of trafficking survivors is 15 years.⁴ History of child abuse and other traumatic experiences can lead children to run away from home. It is estimated that, once on the streets, most teens will be recruited by a trafficker within 48 hours.⁵ Poor self-esteem, depression, substance abuse, history of truancy, and early sexual maturation also increase the risk of becoming involved in trafficking (TABLE 1).^2,6-8

Clinical findings suggestive of trafficking. Many physicians grasp the critical role they play in confronting trafficking, but they lack specific training, experience, and assessment tools.³ Notably, in 1 retrospective study, 46% of victims had been seen by a provider within the previous 2 months.⁶ One of the major challenges to identifying survivors of trafficking is to recognize critical signs, of which there are many (TABLE 1^2,6-8). Often these include a history of sexual assault, multiple pregnancies, requests for contraception at an early age, or evidence of physical injury.

Screen to identify trafficking

Universal, validated screening tools to accurately identify trafficked youth is an area of growing research. Some tools have been validated, but only for specific populations such as homeless or incarcerated youth or in emergency department (ED) patients. Tools for sex trafficking identification that may be useful in primary care include the Child Sex Trafficking (CST) screen validated in ED settings (TABLE 2),⁹ the Commercial Sexual Exploitation-Identification Tool (CSE-IT) in multiple settings (TABLE 3),^10,11 and the Quick Youth Indicators for Trafficking (QYIT) in homeless youth (TABLE 4).¹¹ The QYIT is the first validated labor and sex trafficking screening tool in homeless young adults. Children who screen positive for sex trafficking should be further assessed using a comprehensive tool.

Barriers to effective recognition of trafficked individuals. Financial factors limit access to health care. Also, survivors have cited multiple barriers for health professionals that prevent identification of survivors’ trafficked status.^12,13 Once in the medical setting, disclosure is impacted by time constraints, fear of judgment by clinicians, and the risk of re-traumatization. Survivors have also cited lack of privacy, control strategies by their traffickers, lack of provider empathy, and fear of police as barriers to disclosure.¹⁴

Continue to: The medical impact of trafficking

The medical impact of trafficking

Sexual exploitation is a traumatic experience that is known to cause harm across multiple domains including serious physical injuries related to violence, as well as reproductive and mental health consequences.^15,16

Acute and chronic illnesses. In an initial evaluation, assess the survivor’s acute medical conditions (TABLE 5).^15,16 Common acute issues include physical injuries due to assault, infections, and reproductive complications.¹⁷ Health concerns can also result from stressors such as deprivation of food and sleep, hazardous living conditions, and limited access to care.¹⁷

Suspect possible sex trafficking when a patient has a history of sexual assault and multiple pregnancies, requests contraception at an early age, and/or has evidence of physical injury.

As part of caring for sex-trafficking survivors, assess for, and treat, chronic health issues such as pain, gastrointestinal complaints, poor dental care, malnutrition, and fatigue.^16,18 Substance use, as well as chronic mental health concerns (eg, anxiety, depression, posttraumatic stress disorder [PTSD]) may also influence the clinical presentation.

Physical injuries. A cross-sectional study of female survivors of sex trafficking in the United States found that 89% sustained physical injury resulting from violence, including fractures, open wounds, head injury, dental problems, burns, and anogenital trauma.^16,17 In many cases, acute injury may not be present in the clinical setting since care is often delayed, but a full examination can reveal signs of prior trauma.¹⁶

Reproductive health concerns. Significant, long-term impact on reproductive health can result due to forced penetration by multiple perpetrators, sodomy, and sex without protection or lubricants. Survivors are therefore at high risk for unplanned and unwanted pregnancies, sexually transmitted infections (STIs), pelvic pain, and infertility.¹⁶

Continue to: Psychological effects and trauma exposure

Psychological effects and trauma exposure. Survivors often have experienced abuse and neglect prior to commercial exploitation, and they may exhibit long-term sequelae. Survivors may present with major depression, anxiety, panic attacks, suicidality, addiction, PTSD, or aggression.¹⁶ Long-term sequelae for patients can include dysfunctional relationships due to an inability to trust, self-destructive behaviors, and significant shame.^2,18

Care and treatment of trafficked youth

Initial presentation may occur in a variety of health care settings. Use a trauma-informed approach emphasizing physical and emotional safety and positive relationships, to reduce risk to the survivor, staff, and providers.¹⁹ Establishing trust and rapport may provide better short-term safety, as well as help build stronger long-term relationships that can lead to better health outcomes.

Clinical examination. Provide traumatized patients with a sense of safety, control, and autonomy in the health care setting. During the physical exam, be aware of the impact of re-traumatization as patients are asked to undress, endure sensitive examinations, and undergo invasive procedures. Explain the examination, ask for permission at each step, and use slow movements. Allow the patient to guide certain sensitive exams.¹⁵ Adopt an approach that recognizes the impact of trauma, avoids revictimization, and acknowledges the resilience of survivors.²⁰

Treatment plan. After the initial exam, treat acute physical injuries and determine if any further testing is needed. Offer emergency contraception, STI prophylaxis, pre-exposure prophylaxis, and vaccines.¹⁵ After assessing patient readiness, offer local resources, identify safe methods for communication, identify individuals who could intervene in a crisis, and consider a safety plan (TABLE 6).

Coordination of care. Consider referrals to behavioral health services, substance recovery centers, food programs, housing resources, and a primary care clinic.¹⁵ ED clinicians may be asked to complete a sexual or physical assault forensic examination. After obtaining informed consent, one needs to¹⁹

• document skin signs such as scars, bites, strangulation marks, and tattoos. Note the size, shape, color, location, and other characteristics of each lesion.
• perform an oral, genital, and rectal examination and use a sexual assault evidence kit as indicated.
• use body diagrams and take photographs of all injuries/physical findings.
• order diagnostic testing as appropriate (eg, imaging to assess fractures).

Continue to: THE CASE

THE CASE

During Ms. T’s incarceration, she was tested for STIs and treated for gonorrhea, trichomonas, and bacterial vaginosis. She was educated about sexual health, was counseled on contraception, and accepted condoms. She was referred to a therapist and given information on additional community resources she could contact upon her release.

During a physical examination, explain the process, ask for permission at each step, use slow movements, and allow the patient to guide certain sensitive exams.

A year after her release, she was incarcerated again. She also had an unplanned pregnancy. With the support she received from community programs, social workers, and her primary care provider, she moved in with her family, where she is currently living. She denies any ongoing trafficking activity.

CORRESPONDENCE
Piali Basu, DO, MPH, UCSF Primary Care, 185 Berry Street, Lobby 1, Suite 1000, San Francisco, CA 94107; piali.basu@ucsf.edu

THE CASE

Emily T.* is a 15-year-old, cisgender, homeless runaway. While on the streets, she was lured to a hotel where a “pimp” informed her she was going to work for him. She repeatedly tried to leave, but he would strike her, so she eventually succumbed. She was forced to have sex with several men and rarely allowed to use condoms.

On 1 occasion, when she went to a hospital with her pimp to visit a patient, her aunt (a nurse on duty at that facility) saw Ms. T and called the police. The pimp was arrested. Ms. T was interviewed by the police and gave a statement but refused a forensic exam.

Because of her involvement with the pimp, she was incarcerated. In prison, she was seen by a physician. On evaluation, she reported difficulty sleeping, flashbacks, and feelings of shame and guilt.¹

● How would you proceed with this patient?

* The patient’s name has been changed to protect her identity.

Child and adolescent sex trafficking is defined as the sexual exploitation of minors through force, fraud, or coercion. Specifically, it includes the recruitment, harboring, transportation, or advertising of a minor, and includes the exchange of anything of value in return for sexual activity. Commercial sexual exploitation and sex trafficking against minors include crimes such as prostitution; survival sex (exchanging sex/sexual acts for money or something of value, such as shelter, food, or drugs); pornography; sex tourism, mail-order-bride trade, and early marriage; or sexual performances (peep shows or strip clubs).²

Providing optimal care for children and adolescents exploited by sex trafficking depends on knowing risk factors, having an awareness of recommended screening and assessment tools, and employing a trauma-­informed approach to interviews, examination, and support.²

Continue to: Recognize clues to trafficking

 

 

Recognize clues to trafficking

The Centers for Disease Control and Prevention (CDC) offers a framework for trafficking prevention. Health care providers are encouraged to use the CDC Social-Ecological Model which describes targeted prevention strategies at the individual, relationship, community, and societal levels.³

Risk factors for entering trafficking. Younger age increases a child’s vulnerability to exploitation, due to a lack of maturity, limited cognitive development, and ease of deception. The mean age of trafficking survivors is 15 years.⁴ History of child abuse and other traumatic experiences can lead children to run away from home. It is estimated that, once on the streets, most teens will be recruited by a trafficker within 48 hours.⁵ Poor self-esteem, depression, substance abuse, history of truancy, and early sexual maturation also increase the risk of becoming involved in trafficking (TABLE 1).^2,6-8

Clinical findings suggestive of trafficking. Many physicians grasp the critical role they play in confronting trafficking, but they lack specific training, experience, and assessment tools.³ Notably, in 1 retrospective study, 46% of victims had been seen by a provider within the previous 2 months.⁶ One of the major challenges to identifying survivors of trafficking is to recognize critical signs, of which there are many (TABLE 1^2,6-8). Often these include a history of sexual assault, multiple pregnancies, requests for contraception at an early age, or evidence of physical injury.

Screen to identify trafficking

Universal, validated screening tools to accurately identify trafficked youth is an area of growing research. Some tools have been validated, but only for specific populations such as homeless or incarcerated youth or in emergency department (ED) patients. Tools for sex trafficking identification that may be useful in primary care include the Child Sex Trafficking (CST) screen validated in ED settings (TABLE 2),⁹ the Commercial Sexual Exploitation-Identification Tool (CSE-IT) in multiple settings (TABLE 3),^10,11 and the Quick Youth Indicators for Trafficking (QYIT) in homeless youth (TABLE 4).¹¹ The QYIT is the first validated labor and sex trafficking screening tool in homeless young adults. Children who screen positive for sex trafficking should be further assessed using a comprehensive tool.

Barriers to effective recognition of trafficked individuals. Financial factors limit access to health care. Also, survivors have cited multiple barriers for health professionals that prevent identification of survivors’ trafficked status.^12,13 Once in the medical setting, disclosure is impacted by time constraints, fear of judgment by clinicians, and the risk of re-traumatization. Survivors have also cited lack of privacy, control strategies by their traffickers, lack of provider empathy, and fear of police as barriers to disclosure.¹⁴

Continue to: The medical impact of trafficking

The medical impact of trafficking

Sexual exploitation is a traumatic experience that is known to cause harm across multiple domains including serious physical injuries related to violence, as well as reproductive and mental health consequences.^15,16

Acute and chronic illnesses. In an initial evaluation, assess the survivor’s acute medical conditions (TABLE 5).^15,16 Common acute issues include physical injuries due to assault, infections, and reproductive complications.¹⁷ Health concerns can also result from stressors such as deprivation of food and sleep, hazardous living conditions, and limited access to care.¹⁷

Suspect possible sex trafficking when a patient has a history of sexual assault and multiple pregnancies, requests contraception at an early age, and/or has evidence of physical injury.

As part of caring for sex-trafficking survivors, assess for, and treat, chronic health issues such as pain, gastrointestinal complaints, poor dental care, malnutrition, and fatigue.^16,18 Substance use, as well as chronic mental health concerns (eg, anxiety, depression, posttraumatic stress disorder [PTSD]) may also influence the clinical presentation.

Physical injuries. A cross-sectional study of female survivors of sex trafficking in the United States found that 89% sustained physical injury resulting from violence, including fractures, open wounds, head injury, dental problems, burns, and anogenital trauma.^16,17 In many cases, acute injury may not be present in the clinical setting since care is often delayed, but a full examination can reveal signs of prior trauma.¹⁶

Reproductive health concerns. Significant, long-term impact on reproductive health can result due to forced penetration by multiple perpetrators, sodomy, and sex without protection or lubricants. Survivors are therefore at high risk for unplanned and unwanted pregnancies, sexually transmitted infections (STIs), pelvic pain, and infertility.¹⁶

Continue to: Psychological effects and trauma exposure

Psychological effects and trauma exposure. Survivors often have experienced abuse and neglect prior to commercial exploitation, and they may exhibit long-term sequelae. Survivors may present with major depression, anxiety, panic attacks, suicidality, addiction, PTSD, or aggression.¹⁶ Long-term sequelae for patients can include dysfunctional relationships due to an inability to trust, self-destructive behaviors, and significant shame.^2,18

Care and treatment of trafficked youth

Initial presentation may occur in a variety of health care settings. Use a trauma-informed approach emphasizing physical and emotional safety and positive relationships, to reduce risk to the survivor, staff, and providers.¹⁹ Establishing trust and rapport may provide better short-term safety, as well as help build stronger long-term relationships that can lead to better health outcomes.

Clinical examination. Provide traumatized patients with a sense of safety, control, and autonomy in the health care setting. During the physical exam, be aware of the impact of re-traumatization as patients are asked to undress, endure sensitive examinations, and undergo invasive procedures. Explain the examination, ask for permission at each step, and use slow movements. Allow the patient to guide certain sensitive exams.¹⁵ Adopt an approach that recognizes the impact of trauma, avoids revictimization, and acknowledges the resilience of survivors.²⁰

Treatment plan. After the initial exam, treat acute physical injuries and determine if any further testing is needed. Offer emergency contraception, STI prophylaxis, pre-exposure prophylaxis, and vaccines.¹⁵ After assessing patient readiness, offer local resources, identify safe methods for communication, identify individuals who could intervene in a crisis, and consider a safety plan (TABLE 6).

Coordination of care. Consider referrals to behavioral health services, substance recovery centers, food programs, housing resources, and a primary care clinic.¹⁵ ED clinicians may be asked to complete a sexual or physical assault forensic examination. After obtaining informed consent, one needs to¹⁹

• document skin signs such as scars, bites, strangulation marks, and tattoos. Note the size, shape, color, location, and other characteristics of each lesion.
• perform an oral, genital, and rectal examination and use a sexual assault evidence kit as indicated.
• use body diagrams and take photographs of all injuries/physical findings.
• order diagnostic testing as appropriate (eg, imaging to assess fractures).

Continue to: THE CASE

THE CASE

During Ms. T’s incarceration, she was tested for STIs and treated for gonorrhea, trichomonas, and bacterial vaginosis. She was educated about sexual health, was counseled on contraception, and accepted condoms. She was referred to a therapist and given information on additional community resources she could contact upon her release.

During a physical examination, explain the process, ask for permission at each step, use slow movements, and allow the patient to guide certain sensitive exams.

A year after her release, she was incarcerated again. She also had an unplanned pregnancy. With the support she received from community programs, social workers, and her primary care provider, she moved in with her family, where she is currently living. She denies any ongoing trafficking activity.

CORRESPONDENCE
Piali Basu, DO, MPH, UCSF Primary Care, 185 Berry Street, Lobby 1, Suite 1000, San Francisco, CA 94107; piali.basu@ucsf.edu

Atopic dermatitis (AD), also known as eczema, is a chronic inflammatory skin condition that is well known for its relapsing, pruritic rash in children and adults. Less recognized are its associated conditions—allergic rhinitis, asthma, food allergies, attention-deficit/hyperactivity disorder (ADHD), depression, and anxiety—and its burden on patients and their families. In fact, families that have children with AD report lower overall quality of life than those with otherwise healthy children.¹ Given AD’s prevalence across age groups and its effect on the family, family physicians are uniquely positioned to diagnose, care for, and counsel patients with AD and its associated maladies.

The prevalence and pathogenesis of AD

AD affects up to 20% of children and 5% of adults in the United States.² AD typically manifests before a child reaches age 5 (often in the first 6 months of life), and it is slightly more common in females (1.3:1). A family history of atopy (eczema, asthma, allergic rhinitis) is common. In fact, children with one atopic parent have a 2- to 3-fold increased risk of atopic dermatitis; those with 2 atopic parents have a 3- to 5-fold increased risk.³

The pathophysiology of AD is complex, culminating in impaired barrier function of the skin and transepidermal water loss resulting in dry and inflamed skin. Additionally, alterations in a cell-mediated immune response leading to an immunoglobulin (Ig) E-mediated hypersensitivity is also theorized to play a role in the development of AD.

Signs and symptoms

Signs at birth. Physical signs of atopic dermatitis typically appear between birth and 6 months. In infancy, lesions generally occur on the scalp, face (FIGURES 1A and 1B), neck, and extensor surfaces of the extremities. Lesions are typically papules and vesicles, sometimes accompanied by serous exudate and crusting. Eczematous lesions typically spare the groin and diaper area, and their presence in this area should raise suspicion for an alternative diagnosis.

Beginning at age 2 years, eczematous lesions are more commonly limited to the folds of the flexor surfaces. Instead of the weeping and crusting lesions seen in infancy, eczema in older children manifests as dry, lichenified papules and plaques in areas that are typically affected in adults: the wrist, hands, ankles, and popliteal and antecubital fossa.²

Although lesions in adults are similar to those of childhood, they may manifest in a more localized area (hand or eyelid, for example). As is the case in childhood, the lesions are dry, sometimes lichenified, and found on the flexural surfaces (FIGURES 2A and 2B).²

Symptom triggers are unproven

While anecdotal reports cite various triggers for AD flares, a systematic review found little scientific evidence to substantiate identifiable triggers.⁴ Triggers often cited and studied are foods, dust mite exposure, airborne allergens, detergents, sunlight, fabrics, bacterial infections, and stress. While as many as one-third of people with AD who also have confirmed dust mite allergy report worsening of symptoms when exposed to dust, a Cochrane review of 7 randomized controlled trials totaling 324 adults and children with eczema found that efforts at dust mite mitigation (laundering of bed covers, increased vacuuming, spraying for mites) were not effective in reducing symptoms.⁵

Continue to: How quality of life diminishes with AD

How quality of life diminishes with AD

AD substantially lessens quality of life. For children, the most distressing physical symptoms include itching that inhibits sleep and provokes scratching, pain, and bleeding. Emotional distress can cause irritability, crying, and uncooperativeness with treatments. Parents also report that they frequently restrict their children from activities, such as playing in the heat or swimming, that may lead to worsening of their eczema.⁶

The loss of sleep associated with AD is not completely understood but is likely multifactorial. Pruritus and scratching leading to sleeplessness is the most obvious culprit, but an altered circadian rhythm, immune system response, and changes in skin physiology are also likely factors.⁷ Whatever the cause, sleep disturbance is reported in as many as 60% of patients with AD, and the degree of sleep disturbance is proportional to increases in disease severity and worsening of quality-of-life scores.⁸ Lost sleep is not limited to patients; parents of children with AD also report significant loss of sleep and subsequent decreased work productivity and quality of life.⁹

Children with AD are often the target of bullying.¹⁰ A 2015 survey by the National Eczema Association indicates that 1 in 5 children reported being bullied due to their AD.¹¹

Associated conditions and comorbidities

AD increases patients’ risks for other illnesses, due either to their underlying atopy or to the effects of AD symptoms (TABLE^12-17).

Atopic march

Atopic march—the clinical succession of AD, allergic rhinitis, and asthma—is a well-­established clinical progression. The presence of all 3 conditions appears to be more common in children diagnosed with AD before 2 years of age.¹² Typically, allergic rhinitis manifests at around age 4, and asthma develops between ages 6 and 8. The severity of AD predicts progression. Compared with an 8% chance of asthma developing among the general population, children with mild AD have a 20% to 30% chance of developing asthma, and those with severe AD have about a 70% chance.¹²

Continue to: Food allergies

 

 

Food allergies

Patients with AD are at higher risk for food-induced anaphylaxis, with up to one-third of AD patients having an IgE-mediated food allergy.¹³ While it is theorized that the impaired skin barrier of an atopic child may allow for early sensitization and allergy development, a landmark 2015 study demonstrated that early allergen introduction (specifically, peanuts) may serve as a preventive strategy in those at high risk of food allergies.¹⁴ Current guidelines recommend that physicians be aware of the increased possibility of food allergies in those with AD, and consider evaluating a child for milk, egg, peanut, wheat, and soy allergy if the child is younger than 5 years and has eczema that does not resolve with treatment, or has eczema and a history of an allergic reaction to a specific food.¹⁵

Interestingly, despite the strong association between AD and food allergies, it is not clear that food allergies trigger atopic flares; as such, elimination diets are not universally recommended in those without a proven food allergy.

Psychiatric diagnoses

Children with AD have an increased prevalence of several psychiatric conditions, including ADHD, depression, anxiety, conduct disorder, and autism when compared with peers who do not have AD, and the probability correlates with the severity of AD.¹⁶ While there is a clear link—secondary to nocturnal pruritis—between AD and sleep deprivation, it is not clear whether the sleep deprivation leads to an increase in these psychiatric conditions or if AD is an independent risk factor.

Consider recommending bleach baths in cases of moderate-to-severe atopic dermatitis with frequent bacterial infections.

What we do know is that one of the strongest associations between AD and a psychiatric condition is with ADHD, with a recent pooled meta-analysis showing a 46% increase in risk.¹⁷ The incidence of depression among children with AD appears to correlate with the severity of AD symptoms: estimated at 5% with mild AD, 7% with moderate disease, and 14% with severe disease (compared with 3% without AD). Similar incremental increases are seen when correlating AD and anxiety.¹⁶

Nonpharmacologic care

Bathing

Bathing habits are critical to controlling AD. While bathing serves to both hydrate the skin and remove allergens, the water’s evaporation off the skin surface can lead to increased transepidermal water loss. Combining bathing and immediate application of a moisturizer improves skin hydration in patients with AD vs bathing alone.¹⁸ Thus, consensus guidelines recommend once-daily bathing (bath or shower) to remove scale and crust, followed by immediate application of a moisturizing emollient.¹⁹

Continue to: Emollients

 

 

Emollients

Application of moisturizing emollients is the mainstay of nonpharmacologic care of AD, and there is strong evidence that their regimented use reduces disease burden and the need for prescription treatment.¹⁹ Emollient creams and ointments help retain moisture and improve the skin’s barrier. While ointments may provide a better barrier, patients tend to prefer creams as they are less greasy than ointments.

Emollient therapy may also help prevent development of AD, especially in those infants thought to be at high risk with a family history of atopy. In a multinational randomized controlled trial, infants who received daily full-body application of emollient beginning at 3 weeks of life were significantly less likely than controls to develop AD by 6 months.²⁰ While the mechanism of action is not clearly understood, it is believed that early emollient use prevents skin dehydration and maintains the skin’s barrier integrity, thus decreasing allergen epidermal penetration and subsequent inflammation.

Bleach bath

A bleach bath, prepared by adding 1/2 cup of unconcentrated bleach (5.25% sodium hypochlorite) to a standard 40-gallon bathtub, produces a chlorine mixture equivalent to an average swimming pool. Soaking in a bleach bath for 10 minutes once or twice weekly is thought to reduce inflammation and bacteria on the skin, but studies of its efficacy in improving atopic symptoms are mixed.

In a pooled analysis of 5 studies evaluating bleach baths vs standard baths, there was no significant difference in disease severity at 4 weeks.²¹ Thus, while bleach baths were effective in decreasing disease severity, they appeared to be no more effective than a standard water bath.²¹ Bleach baths may be helpful, however, in cases of moderate-to-severe disease with frequent bacterial infections.¹⁹

Pharmacologic therapy

Steroids

For symptoms refractory to nonpharmacologic skin care, topical steroids are the initial pharmacologic treatment for AD.19 Choose steroid potency based on symptom severity and disease location. Low- to medium-potency is appropriate for mild disease, and medium- to high-potency is useful for ­moderate-to-severe symptoms. High-­potency steroids are generally avoided on the face and skin folds; however, they can be used for short periods in these areas to induce remission. They must then be quickly tapered and discontinued.

Continue to: Frequency

Frequency. Topical corticosteroids are typically applied twice daily, although recent studies indicate that once-daily application is just as efficacious.²² In addition to treatment of an acute flare, topical steroids are useful as maintenance therapy for patients with recurrent outbreaks in the same anatomical site. Guidelines suggest once- or twice-weekly application of a medium-potency steroid to prolong time between flares.¹⁹

For children, a practical guide is for caregivers to apply the amount of steroid covering 1 adult fingertip to an area of the child’s skin equal to that of 2 adult palms.²³ Topical steroids are generally well tolerated and have a good safety profile. Adverse effects are proportional to the amount and duration of use and include purpura, telangiectasias, striae, and skin atrophy. The risk of skin atrophy increases with higher potency steroids, occlusion (covering affected area after steroid application), use on thin-skinned areas, and older patient age.²⁴

A Cochrane review found that efforts at dust mite mitigation (laundering of bed covers, increased vacuuming, spraying for mites) were not effective in reducing symptoms of atopic dermatitis.

Reassure patients/parents about the safety of topical steroids, as fears regarding the potential adverse effects can limit compliance. In one study of 200 patients with AD, 72.5% of respondents expressed fear of using steroids on their own skin or that of their child, and 24% admitted being noncompliant with therapy based on these concerns.²⁵

Treating flares. Oral steroids are sometimes needed to abort or control an AD flare in older children and adults. A tapering course of prednisone over 5 to 7 days, transitioning to medium- to high-dose topical steroids, may be needed to achieve symptom control.

Topical calcineurin inhibitors

Topical calcineurin inhibitors, including tacrolimus and pimecrolimus, are generally second-line therapy to topical corticosteroids. However, as nonsteroidal agents, topical calcineurin inhibitors do not cause skin atrophy and can be a first-line option in areas where atrophy is more common (face, eyelids, neck, and skin folds).²⁶

Continue to: A Cochrane review found...

Interestingly, despite the strong association between atopic dermatitis and food allergies, it is not clear that food allergies trigger atopic flares.

A Cochrane review found tacrolimus 0.1% to be better than low‐potency topical corticosteroids on the face and neck areas, while results were equivocal when compared with moderate‐potency topical corticosteroids on the trunk and extremities (no difference based on physician assessment, but marginal benefit favoring tacrolimus based on participant scoring).²⁷ When compared head-to-head, tacrolimus was more effective than pimecrolimus, although tacrolimus has a higher rate of local irritation. The most common adverse effects are stinging and burning at the application site, although these adverse effects generally improve with repeated application.

There have been long-term safety concerns with topical calcineurin inhibitors—chiefly a 2006 Food and Drug Administration (FDA) black box warning regarding a possible link between topical calcineurin inhibitors and cancer. However, while there may be a slight increased risk of lymphoma in AD patients, a recent meta-analysis did not find an association between topical calcineurin inhibitors use and lymphoma.²⁸ Given the initial concern—and pending additional data—the FDA currently recommends reserving topical calcineurin inhibitors for second-line therapy and only for the minimum amount of time to induce improvement. It also recommends avoiding their use in patients younger than 2 years and in those with compromised immune systems.

Cisaborole

Cisaborole, a topical phosphodiesterase 4 (PDE4) inhibitor, received FDA approval in 2016 for mild-to-moderate AD. By inhibiting PDE4, the drug limits inflammation. In a multicenter randomized trial, patients applying cisaborole 2% twice a day noted reductions in pruritus, inflammation, excoriation, and lichenification.²⁹ Adverse effects are minimal and limited to application site irritation.

Systemic treatments

While beyond the care of a family physician, symptoms refractory to conservative, nonpharmacologic measures and combinations of topical pharmaceuticals can be treated with systemic immunomodulators such as cyclosporine, azathioprine, and methotrexate. Phototherapy is also effective in patients with more widespread skin involvement. Dupilumab, an injectable monoclonal antibody that binds to interleukin-4 receptor and inhibits inflammation, is approved to treat moderate-to-severe AD in adults.³⁰

Ineffective therapies: Oral montelukast and probiotics

While oral antihistamines are frequently prescribed and used, there are no studies evaluating the use of antihistamines (H1) as monotherapy for AD.³¹ Nonetheless, while not altering the disease process, the sedative effect of antihistamines may palliate the nocturnal pruritus frequently associated with AD. Although nonsedating antihistamines may still have a role for atopic patients with concurrent seasonal and environmental allergies, there is no evidence to support their use in the treatment of AD.

Continue to: Data are limited...

Data are limited on the effectiveness of leukotriene receptor antagonists for AD, and all studies meeting inclusion for a Cochrane review assessed oral montelukast. The review found no benefit with the use of montelukast 10 mg in terms of severity of disease, pruritus, or need for topical steroids.³²

A practical guide is for caregivers to apply the amount of steroid covering 1 adult fingertip to an area of the child’s skin equal to that of 2 adult palms.

A systematic review investigating the benefit of probiotics for the treatment of AD found no improvement in patient-rated eczema scores for quality of life.³³ Additionally, a review of 11 randomized controlled trials including 596 participants found no evidence to suggest efficacy of fish oil, zinc, selenium, vitamin D, vitamin E, pyridoxine, sea buckthorn oil, hempseed oil, or sunflower oil in the treatment of AD.³⁴

Education can reduce AD severity

Family physicians can be a source of education and support for patients and families of patients with AD. Support programs for adults with AD—including education, relaxation techniques, and cognitive behavioral therapy—have been shown to decrease disease severity.³⁵ Comparable improvement in disease severity has been demonstrated in children with AD when similar education is provided to them and their families.

CORRESPONDENCE
Franklin Berkey, DO, Penn State Health, 1850 East Park Avenue, Suite 207, State College, PA 16803; fberkey@ pennstatehealth.psu.edu.

Atopic dermatitis (AD), also known as eczema, is a chronic inflammatory skin condition that is well known for its relapsing, pruritic rash in children and adults. Less recognized are its associated conditions—allergic rhinitis, asthma, food allergies, attention-deficit/hyperactivity disorder (ADHD), depression, and anxiety—and its burden on patients and their families. In fact, families that have children with AD report lower overall quality of life than those with otherwise healthy children.¹ Given AD’s prevalence across age groups and its effect on the family, family physicians are uniquely positioned to diagnose, care for, and counsel patients with AD and its associated maladies.

The prevalence and pathogenesis of AD

AD affects up to 20% of children and 5% of adults in the United States.² AD typically manifests before a child reaches age 5 (often in the first 6 months of life), and it is slightly more common in females (1.3:1). A family history of atopy (eczema, asthma, allergic rhinitis) is common. In fact, children with one atopic parent have a 2- to 3-fold increased risk of atopic dermatitis; those with 2 atopic parents have a 3- to 5-fold increased risk.³

The pathophysiology of AD is complex, culminating in impaired barrier function of the skin and transepidermal water loss resulting in dry and inflamed skin. Additionally, alterations in a cell-mediated immune response leading to an immunoglobulin (Ig) E-mediated hypersensitivity is also theorized to play a role in the development of AD.

Signs and symptoms

Signs at birth. Physical signs of atopic dermatitis typically appear between birth and 6 months. In infancy, lesions generally occur on the scalp, face (FIGURES 1A and 1B), neck, and extensor surfaces of the extremities. Lesions are typically papules and vesicles, sometimes accompanied by serous exudate and crusting. Eczematous lesions typically spare the groin and diaper area, and their presence in this area should raise suspicion for an alternative diagnosis.

Beginning at age 2 years, eczematous lesions are more commonly limited to the folds of the flexor surfaces. Instead of the weeping and crusting lesions seen in infancy, eczema in older children manifests as dry, lichenified papules and plaques in areas that are typically affected in adults: the wrist, hands, ankles, and popliteal and antecubital fossa.²

Although lesions in adults are similar to those of childhood, they may manifest in a more localized area (hand or eyelid, for example). As is the case in childhood, the lesions are dry, sometimes lichenified, and found on the flexural surfaces (FIGURES 2A and 2B).²

Symptom triggers are unproven

While anecdotal reports cite various triggers for AD flares, a systematic review found little scientific evidence to substantiate identifiable triggers.⁴ Triggers often cited and studied are foods, dust mite exposure, airborne allergens, detergents, sunlight, fabrics, bacterial infections, and stress. While as many as one-third of people with AD who also have confirmed dust mite allergy report worsening of symptoms when exposed to dust, a Cochrane review of 7 randomized controlled trials totaling 324 adults and children with eczema found that efforts at dust mite mitigation (laundering of bed covers, increased vacuuming, spraying for mites) were not effective in reducing symptoms.⁵

Continue to: How quality of life diminishes with AD

How quality of life diminishes with AD

AD substantially lessens quality of life. For children, the most distressing physical symptoms include itching that inhibits sleep and provokes scratching, pain, and bleeding. Emotional distress can cause irritability, crying, and uncooperativeness with treatments. Parents also report that they frequently restrict their children from activities, such as playing in the heat or swimming, that may lead to worsening of their eczema.⁶

The loss of sleep associated with AD is not completely understood but is likely multifactorial. Pruritus and scratching leading to sleeplessness is the most obvious culprit, but an altered circadian rhythm, immune system response, and changes in skin physiology are also likely factors.⁷ Whatever the cause, sleep disturbance is reported in as many as 60% of patients with AD, and the degree of sleep disturbance is proportional to increases in disease severity and worsening of quality-of-life scores.⁸ Lost sleep is not limited to patients; parents of children with AD also report significant loss of sleep and subsequent decreased work productivity and quality of life.⁹

Children with AD are often the target of bullying.¹⁰ A 2015 survey by the National Eczema Association indicates that 1 in 5 children reported being bullied due to their AD.¹¹

Associated conditions and comorbidities

AD increases patients’ risks for other illnesses, due either to their underlying atopy or to the effects of AD symptoms (TABLE^12-17).

Atopic march

Atopic march—the clinical succession of AD, allergic rhinitis, and asthma—is a well-­established clinical progression. The presence of all 3 conditions appears to be more common in children diagnosed with AD before 2 years of age.¹² Typically, allergic rhinitis manifests at around age 4, and asthma develops between ages 6 and 8. The severity of AD predicts progression. Compared with an 8% chance of asthma developing among the general population, children with mild AD have a 20% to 30% chance of developing asthma, and those with severe AD have about a 70% chance.¹²

Continue to: Food allergies

 

 

Food allergies

Patients with AD are at higher risk for food-induced anaphylaxis, with up to one-third of AD patients having an IgE-mediated food allergy.¹³ While it is theorized that the impaired skin barrier of an atopic child may allow for early sensitization and allergy development, a landmark 2015 study demonstrated that early allergen introduction (specifically, peanuts) may serve as a preventive strategy in those at high risk of food allergies.¹⁴ Current guidelines recommend that physicians be aware of the increased possibility of food allergies in those with AD, and consider evaluating a child for milk, egg, peanut, wheat, and soy allergy if the child is younger than 5 years and has eczema that does not resolve with treatment, or has eczema and a history of an allergic reaction to a specific food.¹⁵

Interestingly, despite the strong association between AD and food allergies, it is not clear that food allergies trigger atopic flares; as such, elimination diets are not universally recommended in those without a proven food allergy.

Psychiatric diagnoses

Children with AD have an increased prevalence of several psychiatric conditions, including ADHD, depression, anxiety, conduct disorder, and autism when compared with peers who do not have AD, and the probability correlates with the severity of AD.¹⁶ While there is a clear link—secondary to nocturnal pruritis—between AD and sleep deprivation, it is not clear whether the sleep deprivation leads to an increase in these psychiatric conditions or if AD is an independent risk factor.

Consider recommending bleach baths in cases of moderate-to-severe atopic dermatitis with frequent bacterial infections.

What we do know is that one of the strongest associations between AD and a psychiatric condition is with ADHD, with a recent pooled meta-analysis showing a 46% increase in risk.¹⁷ The incidence of depression among children with AD appears to correlate with the severity of AD symptoms: estimated at 5% with mild AD, 7% with moderate disease, and 14% with severe disease (compared with 3% without AD). Similar incremental increases are seen when correlating AD and anxiety.¹⁶

Nonpharmacologic care

Bathing

Bathing habits are critical to controlling AD. While bathing serves to both hydrate the skin and remove allergens, the water’s evaporation off the skin surface can lead to increased transepidermal water loss. Combining bathing and immediate application of a moisturizer improves skin hydration in patients with AD vs bathing alone.¹⁸ Thus, consensus guidelines recommend once-daily bathing (bath or shower) to remove scale and crust, followed by immediate application of a moisturizing emollient.¹⁹

Continue to: Emollients

 

 

Emollients

Application of moisturizing emollients is the mainstay of nonpharmacologic care of AD, and there is strong evidence that their regimented use reduces disease burden and the need for prescription treatment.¹⁹ Emollient creams and ointments help retain moisture and improve the skin’s barrier. While ointments may provide a better barrier, patients tend to prefer creams as they are less greasy than ointments.

Emollient therapy may also help prevent development of AD, especially in those infants thought to be at high risk with a family history of atopy. In a multinational randomized controlled trial, infants who received daily full-body application of emollient beginning at 3 weeks of life were significantly less likely than controls to develop AD by 6 months.²⁰ While the mechanism of action is not clearly understood, it is believed that early emollient use prevents skin dehydration and maintains the skin’s barrier integrity, thus decreasing allergen epidermal penetration and subsequent inflammation.

Bleach bath

A bleach bath, prepared by adding 1/2 cup of unconcentrated bleach (5.25% sodium hypochlorite) to a standard 40-gallon bathtub, produces a chlorine mixture equivalent to an average swimming pool. Soaking in a bleach bath for 10 minutes once or twice weekly is thought to reduce inflammation and bacteria on the skin, but studies of its efficacy in improving atopic symptoms are mixed.

In a pooled analysis of 5 studies evaluating bleach baths vs standard baths, there was no significant difference in disease severity at 4 weeks.²¹ Thus, while bleach baths were effective in decreasing disease severity, they appeared to be no more effective than a standard water bath.²¹ Bleach baths may be helpful, however, in cases of moderate-to-severe disease with frequent bacterial infections.¹⁹

Pharmacologic therapy

Steroids

For symptoms refractory to nonpharmacologic skin care, topical steroids are the initial pharmacologic treatment for AD.19 Choose steroid potency based on symptom severity and disease location. Low- to medium-potency is appropriate for mild disease, and medium- to high-potency is useful for ­moderate-to-severe symptoms. High-­potency steroids are generally avoided on the face and skin folds; however, they can be used for short periods in these areas to induce remission. They must then be quickly tapered and discontinued.

Continue to: Frequency

Frequency. Topical corticosteroids are typically applied twice daily, although recent studies indicate that once-daily application is just as efficacious.²² In addition to treatment of an acute flare, topical steroids are useful as maintenance therapy for patients with recurrent outbreaks in the same anatomical site. Guidelines suggest once- or twice-weekly application of a medium-potency steroid to prolong time between flares.¹⁹

For children, a practical guide is for caregivers to apply the amount of steroid covering 1 adult fingertip to an area of the child’s skin equal to that of 2 adult palms.²³ Topical steroids are generally well tolerated and have a good safety profile. Adverse effects are proportional to the amount and duration of use and include purpura, telangiectasias, striae, and skin atrophy. The risk of skin atrophy increases with higher potency steroids, occlusion (covering affected area after steroid application), use on thin-skinned areas, and older patient age.²⁴

A Cochrane review found that efforts at dust mite mitigation (laundering of bed covers, increased vacuuming, spraying for mites) were not effective in reducing symptoms of atopic dermatitis.

Reassure patients/parents about the safety of topical steroids, as fears regarding the potential adverse effects can limit compliance. In one study of 200 patients with AD, 72.5% of respondents expressed fear of using steroids on their own skin or that of their child, and 24% admitted being noncompliant with therapy based on these concerns.²⁵

Treating flares. Oral steroids are sometimes needed to abort or control an AD flare in older children and adults. A tapering course of prednisone over 5 to 7 days, transitioning to medium- to high-dose topical steroids, may be needed to achieve symptom control.

Topical calcineurin inhibitors

Topical calcineurin inhibitors, including tacrolimus and pimecrolimus, are generally second-line therapy to topical corticosteroids. However, as nonsteroidal agents, topical calcineurin inhibitors do not cause skin atrophy and can be a first-line option in areas where atrophy is more common (face, eyelids, neck, and skin folds).²⁶

Continue to: A Cochrane review found...

Interestingly, despite the strong association between atopic dermatitis and food allergies, it is not clear that food allergies trigger atopic flares.

A Cochrane review found tacrolimus 0.1% to be better than low‐potency topical corticosteroids on the face and neck areas, while results were equivocal when compared with moderate‐potency topical corticosteroids on the trunk and extremities (no difference based on physician assessment, but marginal benefit favoring tacrolimus based on participant scoring).²⁷ When compared head-to-head, tacrolimus was more effective than pimecrolimus, although tacrolimus has a higher rate of local irritation. The most common adverse effects are stinging and burning at the application site, although these adverse effects generally improve with repeated application.

There have been long-term safety concerns with topical calcineurin inhibitors—chiefly a 2006 Food and Drug Administration (FDA) black box warning regarding a possible link between topical calcineurin inhibitors and cancer. However, while there may be a slight increased risk of lymphoma in AD patients, a recent meta-analysis did not find an association between topical calcineurin inhibitors use and lymphoma.²⁸ Given the initial concern—and pending additional data—the FDA currently recommends reserving topical calcineurin inhibitors for second-line therapy and only for the minimum amount of time to induce improvement. It also recommends avoiding their use in patients younger than 2 years and in those with compromised immune systems.

Cisaborole

Cisaborole, a topical phosphodiesterase 4 (PDE4) inhibitor, received FDA approval in 2016 for mild-to-moderate AD. By inhibiting PDE4, the drug limits inflammation. In a multicenter randomized trial, patients applying cisaborole 2% twice a day noted reductions in pruritus, inflammation, excoriation, and lichenification.²⁹ Adverse effects are minimal and limited to application site irritation.

Systemic treatments

While beyond the care of a family physician, symptoms refractory to conservative, nonpharmacologic measures and combinations of topical pharmaceuticals can be treated with systemic immunomodulators such as cyclosporine, azathioprine, and methotrexate. Phototherapy is also effective in patients with more widespread skin involvement. Dupilumab, an injectable monoclonal antibody that binds to interleukin-4 receptor and inhibits inflammation, is approved to treat moderate-to-severe AD in adults.³⁰

Ineffective therapies: Oral montelukast and probiotics

While oral antihistamines are frequently prescribed and used, there are no studies evaluating the use of antihistamines (H1) as monotherapy for AD.³¹ Nonetheless, while not altering the disease process, the sedative effect of antihistamines may palliate the nocturnal pruritus frequently associated with AD. Although nonsedating antihistamines may still have a role for atopic patients with concurrent seasonal and environmental allergies, there is no evidence to support their use in the treatment of AD.

Continue to: Data are limited...

Data are limited on the effectiveness of leukotriene receptor antagonists for AD, and all studies meeting inclusion for a Cochrane review assessed oral montelukast. The review found no benefit with the use of montelukast 10 mg in terms of severity of disease, pruritus, or need for topical steroids.³²

A practical guide is for caregivers to apply the amount of steroid covering 1 adult fingertip to an area of the child’s skin equal to that of 2 adult palms.

A systematic review investigating the benefit of probiotics for the treatment of AD found no improvement in patient-rated eczema scores for quality of life.³³ Additionally, a review of 11 randomized controlled trials including 596 participants found no evidence to suggest efficacy of fish oil, zinc, selenium, vitamin D, vitamin E, pyridoxine, sea buckthorn oil, hempseed oil, or sunflower oil in the treatment of AD.³⁴

Education can reduce AD severity

Family physicians can be a source of education and support for patients and families of patients with AD. Support programs for adults with AD—including education, relaxation techniques, and cognitive behavioral therapy—have been shown to decrease disease severity.³⁵ Comparable improvement in disease severity has been demonstrated in children with AD when similar education is provided to them and their families.

CORRESPONDENCE
Franklin Berkey, DO, Penn State Health, 1850 East Park Avenue, Suite 207, State College, PA 16803; fberkey@ pennstatehealth.psu.edu.

Atopic dermatitis (AD), also known as eczema, is a chronic inflammatory skin condition that is well known for its relapsing, pruritic rash in children and adults. Less recognized are its associated conditions—allergic rhinitis, asthma, food allergies, attention-deficit/hyperactivity disorder (ADHD), depression, and anxiety—and its burden on patients and their families. In fact, families that have children with AD report lower overall quality of life than those with otherwise healthy children.¹ Given AD’s prevalence across age groups and its effect on the family, family physicians are uniquely positioned to diagnose, care for, and counsel patients with AD and its associated maladies.

The prevalence and pathogenesis of AD

AD affects up to 20% of children and 5% of adults in the United States.² AD typically manifests before a child reaches age 5 (often in the first 6 months of life), and it is slightly more common in females (1.3:1). A family history of atopy (eczema, asthma, allergic rhinitis) is common. In fact, children with one atopic parent have a 2- to 3-fold increased risk of atopic dermatitis; those with 2 atopic parents have a 3- to 5-fold increased risk.³

The pathophysiology of AD is complex, culminating in impaired barrier function of the skin and transepidermal water loss resulting in dry and inflamed skin. Additionally, alterations in a cell-mediated immune response leading to an immunoglobulin (Ig) E-mediated hypersensitivity is also theorized to play a role in the development of AD.

Signs and symptoms

Signs at birth. Physical signs of atopic dermatitis typically appear between birth and 6 months. In infancy, lesions generally occur on the scalp, face (FIGURES 1A and 1B), neck, and extensor surfaces of the extremities. Lesions are typically papules and vesicles, sometimes accompanied by serous exudate and crusting. Eczematous lesions typically spare the groin and diaper area, and their presence in this area should raise suspicion for an alternative diagnosis.

Beginning at age 2 years, eczematous lesions are more commonly limited to the folds of the flexor surfaces. Instead of the weeping and crusting lesions seen in infancy, eczema in older children manifests as dry, lichenified papules and plaques in areas that are typically affected in adults: the wrist, hands, ankles, and popliteal and antecubital fossa.²

Although lesions in adults are similar to those of childhood, they may manifest in a more localized area (hand or eyelid, for example). As is the case in childhood, the lesions are dry, sometimes lichenified, and found on the flexural surfaces (FIGURES 2A and 2B).²

Symptom triggers are unproven

While anecdotal reports cite various triggers for AD flares, a systematic review found little scientific evidence to substantiate identifiable triggers.⁴ Triggers often cited and studied are foods, dust mite exposure, airborne allergens, detergents, sunlight, fabrics, bacterial infections, and stress. While as many as one-third of people with AD who also have confirmed dust mite allergy report worsening of symptoms when exposed to dust, a Cochrane review of 7 randomized controlled trials totaling 324 adults and children with eczema found that efforts at dust mite mitigation (laundering of bed covers, increased vacuuming, spraying for mites) were not effective in reducing symptoms.⁵

Continue to: How quality of life diminishes with AD

How quality of life diminishes with AD

AD substantially lessens quality of life. For children, the most distressing physical symptoms include itching that inhibits sleep and provokes scratching, pain, and bleeding. Emotional distress can cause irritability, crying, and uncooperativeness with treatments. Parents also report that they frequently restrict their children from activities, such as playing in the heat or swimming, that may lead to worsening of their eczema.⁶

The loss of sleep associated with AD is not completely understood but is likely multifactorial. Pruritus and scratching leading to sleeplessness is the most obvious culprit, but an altered circadian rhythm, immune system response, and changes in skin physiology are also likely factors.⁷ Whatever the cause, sleep disturbance is reported in as many as 60% of patients with AD, and the degree of sleep disturbance is proportional to increases in disease severity and worsening of quality-of-life scores.⁸ Lost sleep is not limited to patients; parents of children with AD also report significant loss of sleep and subsequent decreased work productivity and quality of life.⁹

Children with AD are often the target of bullying.¹⁰ A 2015 survey by the National Eczema Association indicates that 1 in 5 children reported being bullied due to their AD.¹¹

Associated conditions and comorbidities

AD increases patients’ risks for other illnesses, due either to their underlying atopy or to the effects of AD symptoms (TABLE^12-17).

Atopic march

Atopic march—the clinical succession of AD, allergic rhinitis, and asthma—is a well-­established clinical progression. The presence of all 3 conditions appears to be more common in children diagnosed with AD before 2 years of age.¹² Typically, allergic rhinitis manifests at around age 4, and asthma develops between ages 6 and 8. The severity of AD predicts progression. Compared with an 8% chance of asthma developing among the general population, children with mild AD have a 20% to 30% chance of developing asthma, and those with severe AD have about a 70% chance.¹²

Continue to: Food allergies

 

 

Food allergies

Patients with AD are at higher risk for food-induced anaphylaxis, with up to one-third of AD patients having an IgE-mediated food allergy.¹³ While it is theorized that the impaired skin barrier of an atopic child may allow for early sensitization and allergy development, a landmark 2015 study demonstrated that early allergen introduction (specifically, peanuts) may serve as a preventive strategy in those at high risk of food allergies.¹⁴ Current guidelines recommend that physicians be aware of the increased possibility of food allergies in those with AD, and consider evaluating a child for milk, egg, peanut, wheat, and soy allergy if the child is younger than 5 years and has eczema that does not resolve with treatment, or has eczema and a history of an allergic reaction to a specific food.¹⁵

Interestingly, despite the strong association between AD and food allergies, it is not clear that food allergies trigger atopic flares; as such, elimination diets are not universally recommended in those without a proven food allergy.

Psychiatric diagnoses

Children with AD have an increased prevalence of several psychiatric conditions, including ADHD, depression, anxiety, conduct disorder, and autism when compared with peers who do not have AD, and the probability correlates with the severity of AD.¹⁶ While there is a clear link—secondary to nocturnal pruritis—between AD and sleep deprivation, it is not clear whether the sleep deprivation leads to an increase in these psychiatric conditions or if AD is an independent risk factor.

Consider recommending bleach baths in cases of moderate-to-severe atopic dermatitis with frequent bacterial infections.

What we do know is that one of the strongest associations between AD and a psychiatric condition is with ADHD, with a recent pooled meta-analysis showing a 46% increase in risk.¹⁷ The incidence of depression among children with AD appears to correlate with the severity of AD symptoms: estimated at 5% with mild AD, 7% with moderate disease, and 14% with severe disease (compared with 3% without AD). Similar incremental increases are seen when correlating AD and anxiety.¹⁶

Nonpharmacologic care

Bathing

Bathing habits are critical to controlling AD. While bathing serves to both hydrate the skin and remove allergens, the water’s evaporation off the skin surface can lead to increased transepidermal water loss. Combining bathing and immediate application of a moisturizer improves skin hydration in patients with AD vs bathing alone.¹⁸ Thus, consensus guidelines recommend once-daily bathing (bath or shower) to remove scale and crust, followed by immediate application of a moisturizing emollient.¹⁹

Continue to: Emollients

 

 

Emollients

Application of moisturizing emollients is the mainstay of nonpharmacologic care of AD, and there is strong evidence that their regimented use reduces disease burden and the need for prescription treatment.¹⁹ Emollient creams and ointments help retain moisture and improve the skin’s barrier. While ointments may provide a better barrier, patients tend to prefer creams as they are less greasy than ointments.

Emollient therapy may also help prevent development of AD, especially in those infants thought to be at high risk with a family history of atopy. In a multinational randomized controlled trial, infants who received daily full-body application of emollient beginning at 3 weeks of life were significantly less likely than controls to develop AD by 6 months.²⁰ While the mechanism of action is not clearly understood, it is believed that early emollient use prevents skin dehydration and maintains the skin’s barrier integrity, thus decreasing allergen epidermal penetration and subsequent inflammation.

Bleach bath

A bleach bath, prepared by adding 1/2 cup of unconcentrated bleach (5.25% sodium hypochlorite) to a standard 40-gallon bathtub, produces a chlorine mixture equivalent to an average swimming pool. Soaking in a bleach bath for 10 minutes once or twice weekly is thought to reduce inflammation and bacteria on the skin, but studies of its efficacy in improving atopic symptoms are mixed.

In a pooled analysis of 5 studies evaluating bleach baths vs standard baths, there was no significant difference in disease severity at 4 weeks.²¹ Thus, while bleach baths were effective in decreasing disease severity, they appeared to be no more effective than a standard water bath.²¹ Bleach baths may be helpful, however, in cases of moderate-to-severe disease with frequent bacterial infections.¹⁹

Pharmacologic therapy

Steroids

For symptoms refractory to nonpharmacologic skin care, topical steroids are the initial pharmacologic treatment for AD.19 Choose steroid potency based on symptom severity and disease location. Low- to medium-potency is appropriate for mild disease, and medium- to high-potency is useful for ­moderate-to-severe symptoms. High-­potency steroids are generally avoided on the face and skin folds; however, they can be used for short periods in these areas to induce remission. They must then be quickly tapered and discontinued.

Continue to: Frequency

Frequency. Topical corticosteroids are typically applied twice daily, although recent studies indicate that once-daily application is just as efficacious.²² In addition to treatment of an acute flare, topical steroids are useful as maintenance therapy for patients with recurrent outbreaks in the same anatomical site. Guidelines suggest once- or twice-weekly application of a medium-potency steroid to prolong time between flares.¹⁹

For children, a practical guide is for caregivers to apply the amount of steroid covering 1 adult fingertip to an area of the child’s skin equal to that of 2 adult palms.²³ Topical steroids are generally well tolerated and have a good safety profile. Adverse effects are proportional to the amount and duration of use and include purpura, telangiectasias, striae, and skin atrophy. The risk of skin atrophy increases with higher potency steroids, occlusion (covering affected area after steroid application), use on thin-skinned areas, and older patient age.²⁴

A Cochrane review found that efforts at dust mite mitigation (laundering of bed covers, increased vacuuming, spraying for mites) were not effective in reducing symptoms of atopic dermatitis.

Reassure patients/parents about the safety of topical steroids, as fears regarding the potential adverse effects can limit compliance. In one study of 200 patients with AD, 72.5% of respondents expressed fear of using steroids on their own skin or that of their child, and 24% admitted being noncompliant with therapy based on these concerns.²⁵

Treating flares. Oral steroids are sometimes needed to abort or control an AD flare in older children and adults. A tapering course of prednisone over 5 to 7 days, transitioning to medium- to high-dose topical steroids, may be needed to achieve symptom control.

Topical calcineurin inhibitors

Topical calcineurin inhibitors, including tacrolimus and pimecrolimus, are generally second-line therapy to topical corticosteroids. However, as nonsteroidal agents, topical calcineurin inhibitors do not cause skin atrophy and can be a first-line option in areas where atrophy is more common (face, eyelids, neck, and skin folds).²⁶

Continue to: A Cochrane review found...

Interestingly, despite the strong association between atopic dermatitis and food allergies, it is not clear that food allergies trigger atopic flares.

A Cochrane review found tacrolimus 0.1% to be better than low‐potency topical corticosteroids on the face and neck areas, while results were equivocal when compared with moderate‐potency topical corticosteroids on the trunk and extremities (no difference based on physician assessment, but marginal benefit favoring tacrolimus based on participant scoring).²⁷ When compared head-to-head, tacrolimus was more effective than pimecrolimus, although tacrolimus has a higher rate of local irritation. The most common adverse effects are stinging and burning at the application site, although these adverse effects generally improve with repeated application.

There have been long-term safety concerns with topical calcineurin inhibitors—chiefly a 2006 Food and Drug Administration (FDA) black box warning regarding a possible link between topical calcineurin inhibitors and cancer. However, while there may be a slight increased risk of lymphoma in AD patients, a recent meta-analysis did not find an association between topical calcineurin inhibitors use and lymphoma.²⁸ Given the initial concern—and pending additional data—the FDA currently recommends reserving topical calcineurin inhibitors for second-line therapy and only for the minimum amount of time to induce improvement. It also recommends avoiding their use in patients younger than 2 years and in those with compromised immune systems.

Cisaborole

Cisaborole, a topical phosphodiesterase 4 (PDE4) inhibitor, received FDA approval in 2016 for mild-to-moderate AD. By inhibiting PDE4, the drug limits inflammation. In a multicenter randomized trial, patients applying cisaborole 2% twice a day noted reductions in pruritus, inflammation, excoriation, and lichenification.²⁹ Adverse effects are minimal and limited to application site irritation.

Systemic treatments

While beyond the care of a family physician, symptoms refractory to conservative, nonpharmacologic measures and combinations of topical pharmaceuticals can be treated with systemic immunomodulators such as cyclosporine, azathioprine, and methotrexate. Phototherapy is also effective in patients with more widespread skin involvement. Dupilumab, an injectable monoclonal antibody that binds to interleukin-4 receptor and inhibits inflammation, is approved to treat moderate-to-severe AD in adults.³⁰

Ineffective therapies: Oral montelukast and probiotics

While oral antihistamines are frequently prescribed and used, there are no studies evaluating the use of antihistamines (H1) as monotherapy for AD.³¹ Nonetheless, while not altering the disease process, the sedative effect of antihistamines may palliate the nocturnal pruritus frequently associated with AD. Although nonsedating antihistamines may still have a role for atopic patients with concurrent seasonal and environmental allergies, there is no evidence to support their use in the treatment of AD.

Continue to: Data are limited...

Data are limited on the effectiveness of leukotriene receptor antagonists for AD, and all studies meeting inclusion for a Cochrane review assessed oral montelukast. The review found no benefit with the use of montelukast 10 mg in terms of severity of disease, pruritus, or need for topical steroids.³²

A practical guide is for caregivers to apply the amount of steroid covering 1 adult fingertip to an area of the child’s skin equal to that of 2 adult palms.

A systematic review investigating the benefit of probiotics for the treatment of AD found no improvement in patient-rated eczema scores for quality of life.³³ Additionally, a review of 11 randomized controlled trials including 596 participants found no evidence to suggest efficacy of fish oil, zinc, selenium, vitamin D, vitamin E, pyridoxine, sea buckthorn oil, hempseed oil, or sunflower oil in the treatment of AD.³⁴

Education can reduce AD severity

Family physicians can be a source of education and support for patients and families of patients with AD. Support programs for adults with AD—including education, relaxation techniques, and cognitive behavioral therapy—have been shown to decrease disease severity.³⁵ Comparable improvement in disease severity has been demonstrated in children with AD when similar education is provided to them and their families.

CORRESPONDENCE
Franklin Berkey, DO, Penn State Health, 1850 East Park Avenue, Suite 207, State College, PA 16803; fberkey@ pennstatehealth.psu.edu.

Repeated intravenous infusions of ketamine provide rapid relief for patients with posttraumatic stress disorder, new research suggests.

In what investigators are calling the first randomized controlled trial of repeated ketamine administration for chronic PTSD, 30 patients received six infusions of ketamine or midazolam (used as a psychoactive placebo) over 2 consecutive weeks. 

Between baseline and week 2, those receiving ketamine showed significantly greater improvement than those receiving midazolam. Total scores on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) for the first group were almost 12 points lower than the latter group at week 2, meeting the study’s primary outcome measure.

In addition, 67% vs. 20% of the patients, respectively, were considered to be treatment responders; time to loss of response for those in the ketamine group was 28 days.

Although the overall findings were as expected, “what was surprising was how robust the results were,” lead author Adriana Feder, MD, associate professor of psychiatry, Icahn School of Medicine, Mount Sinai, New York, told this news organization.

It was also a bit surprising that, in a study of just 30 participants, “we were able to show such a clear difference” between the two treatment groups, said Dr. Feder, who is also a coinventor on issued patents for the use of ketamine as therapy for PTSD, and codirector of the Ehrenkranz Lab for the Study of Human Resilience at Mount Sinai.

The findings were published online Jan. 5 in the American Journal of Psychiatry.
 

Unmet need

Ketamine is a glutamate N-methyl-D-aspartate (NMDA) receptor antagonist that was first approved by the U.S. Food and Drug Administration for anesthetic use in 1970. It has also been shown to be effective for treatment-resistant depression.

PTSD has a lifetime prevalence of about 6% in the United States. “While trauma-focused psychotherapies have the most empirical support, they are limited by significant rates of nonresponse, partial response, and treatment dropout,” the investigators write. Also, there are “few available pharmacotherapies for PTSD, and their efficacy is insufficient,” they add.  

“There’s a real need for new treatment interventions that are effective for PTSD and also work rapidly, because it can take weeks to months for currently available treatments to work for PTSD,” Dr. Feder said.

The researchers previously conducted a “proof-of-concept” randomized controlled trial of single infusions of ketamine for chronic PTSD. Results published in 2014 in JAMA Psychiatry showed significant reduction in PTSD symptoms 24 hours after infusion.

For the current study, the investigative team wanted to assess whether ketamine was viable as a longer-term treatment.

“We were encouraged by our initial promising findings” of the earlier trial, Dr. Feder said. “We wanted to do the second study to see if ketamine really works for PTSD, to see if we could replicate the rapid improvement and also examine whether a course of six infusions over 2 weeks could maintain the improvement.”

Thirty patients (aged 18-70; mean age, 39 years) with chronic PTSD from civilian or military trauma were enrolled (mean PTSD duration, 15 years).

The most cited primary trauma was sexual assault or molestation (n = 13), followed by physical assault or abuse (n = 8), witnessing a violent assault or death (n = 4), witnessing the 9/11 attacks (n = 3), and combat exposure (n = 2).

During the 2-week treatment phase, half of the patients were randomly assigned to receive six infusions of ketamine hydrochloride at a dose of 0.5 mg/kg (86.7% women; mean CAPS-5 score, 42), while the other half received six infusions of midazolam at a dose of 0.045 mg/kg (66.7% women; mean CAPS-5 score, 40).

In addition to the primary outcome measure of 2-week changes on the CAPS-5, secondary outcomes included score changes on the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Impact of Event Scale-Revised (IES-R).

Treatment response was defined as a 30% or more improvement in symptoms on the CAPS-5. A number of measures were also used to assess potential treatment-related adverse events (AEs).
 

Safe, effective

Results showed significantly lower total CAPS-5 scores for the ketamine group vs. the midazolam group at week 1 (score difference, 8.8 points; P = .03) and at week 2 (score difference, 11.88 points; P = .004).

Those receiving ketamine also showed improvements in three of the four PTSD symptom clusters on the CAPS-5: avoidance (P < .0001), negative mood and cognitions (P = .02), and intrusions (P = .03). The fourth symptom cluster – arousal and reactivity – did not show a significant improvement.

In addition, the ketamine group showed significantly greater improvement scores on the MADRS at both week 1 and week 2.

Treatment response at 2 weeks was achieved by 10 members of the ketamine group and by three members of the midazolam group (P = .03).

Secondary analyses showed rapid improvement in the treatment responders within the ketamine group, with a mean change of 26 points on the total IES-R score between baseline and 24 hours after their first infusion, and a mean change of 13.4 points on the MADRS total past-24-hour score, a 53% improvement on average.

“A response at 2 weeks is very rapid but they got better sometimes within the first day,” Dr. Feder noted.

There were no serious AEs reported. Although some dissociative symptoms occurred during ketamine infusions, with the highest levels reported at the end of the infusion, these symptoms had resolved by the next assessment, conducted 2 hours after infusion.

The most frequently reported AE in the ketamine group, compared with midazolam, after the start of infusions was blurred vision (53% vs. 0%), followed by dizziness (33% vs. 13%), fatigue (33% vs. 87%), headache (27% vs. 13%), and nausea or vomiting (20% vs. 7%).
 

‘Large-magnitude improvement’

The overall findings show that, in this patient population, “repeated intravenous ketamine infusions administered over 2 weeks were associated with a large-magnitude, clinically significant improvement in PTSD symptoms,” the investigators write.

The results “were very satisfying,” added Dr. Feder. “It was heartening also to hear what some of the participants would say. Some told us about how their symptoms and feelings had changed during the course of treatment with ketamine, where they felt stronger and better able to cope with their trauma and memories.”

She noted, however, that this was not a study designed to specifically assess ketamine in treatment-resistant PTSD. “Some patients had had multiple treatments before that hadn’t worked, while others had not received treatment before. Efficacy for treatment-resistant PTSD is an important question for future research,” Dr. Feder said.

Other areas worth future exploration include treatment efficacy in patients with different types of trauma and whether outcomes can last longer in patients receiving ketamine plus psychotherapy treatment, she noted.

“I don’t want to ignore the fact that currently available treatments work for a number of people with chronic PTSD. But because there are many more for whom [the treatments] don’t work, or they’re insufficiently helped by those treatments, this is certainly one potentially very promising approach that can be added” to a clinician’s toolbox, Dr. Feder said.
 

Speaks to clinical utility

Commenting for this news organization, Gerard Sanacora, MD, PhD, professor of psychiatry at Yale University, New Haven, Connecticut, called this a “very solid and well-designed” study.

“It definitely builds on what’s been found in the past, but it’s a critical piece of information speaking to the clinical utility of this treatment for PTSD,” said Dr. Sanacora, who is also director of the Yale Depression Research Program and was not involved with the current research.

He agreed with the investigators that PTSD has long been a condition that is difficult to treat.

“It’s an area that has a great unmet need for treatment options. Beyond that, as ketamine is becoming more widely used, there’s increasing demand for off-label uses. This [study] actually provides some evidence that there may be efficacy there,” Dr. Sanacora said.

Although he cautioned that this was a small study, and thus further research with a larger patient population will be needed, it provides a compelling foundation to build upon.

“This study provides clear evidence to support a larger study to really give a definitive statement on the efficacy and safety of its use for PTSD. I don’t think this is the study that provides that definitive evidence, but it is a very strong indication, and it very strongly supports the initiation of a large study to address that,” said Dr. Sanacora.

He noted that, although he’s used the term “cautious optimism” for studies in the past, he has “real optimism” that ketamine will be effective for PTSD based on the results of this current study.

“We still need some more data to really convince us of that before we can say with any clear statement that it is effective and safe, but I’m very optimistic,” Dr. Sanacora concluded. “I think the data are very strong.”

The study was funded by the Brain and Behavior Research Foundation, Mount Sinai Innovation Partners and the Mount Sinai i3 Accelerator, Gerald and Glenda Greenwald, and the Ehrenkranz Laboratory for Human Resilience. Dr. Feder is a coinventor on issued patents for the use of ketamine as therapy for PTSD. A list of all disclosures for the other study authors are listed in the original article.

A version of this article first appeared on Medscape.com.

Repeated intravenous infusions of ketamine provide rapid relief for patients with posttraumatic stress disorder, new research suggests.

In what investigators are calling the first randomized controlled trial of repeated ketamine administration for chronic PTSD, 30 patients received six infusions of ketamine or midazolam (used as a psychoactive placebo) over 2 consecutive weeks. 

Between baseline and week 2, those receiving ketamine showed significantly greater improvement than those receiving midazolam. Total scores on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) for the first group were almost 12 points lower than the latter group at week 2, meeting the study’s primary outcome measure.

In addition, 67% vs. 20% of the patients, respectively, were considered to be treatment responders; time to loss of response for those in the ketamine group was 28 days.

Although the overall findings were as expected, “what was surprising was how robust the results were,” lead author Adriana Feder, MD, associate professor of psychiatry, Icahn School of Medicine, Mount Sinai, New York, told this news organization.

It was also a bit surprising that, in a study of just 30 participants, “we were able to show such a clear difference” between the two treatment groups, said Dr. Feder, who is also a coinventor on issued patents for the use of ketamine as therapy for PTSD, and codirector of the Ehrenkranz Lab for the Study of Human Resilience at Mount Sinai.

The findings were published online Jan. 5 in the American Journal of Psychiatry.
 

Unmet need

Ketamine is a glutamate N-methyl-D-aspartate (NMDA) receptor antagonist that was first approved by the U.S. Food and Drug Administration for anesthetic use in 1970. It has also been shown to be effective for treatment-resistant depression.

PTSD has a lifetime prevalence of about 6% in the United States. “While trauma-focused psychotherapies have the most empirical support, they are limited by significant rates of nonresponse, partial response, and treatment dropout,” the investigators write. Also, there are “few available pharmacotherapies for PTSD, and their efficacy is insufficient,” they add.  

“There’s a real need for new treatment interventions that are effective for PTSD and also work rapidly, because it can take weeks to months for currently available treatments to work for PTSD,” Dr. Feder said.

The researchers previously conducted a “proof-of-concept” randomized controlled trial of single infusions of ketamine for chronic PTSD. Results published in 2014 in JAMA Psychiatry showed significant reduction in PTSD symptoms 24 hours after infusion.

For the current study, the investigative team wanted to assess whether ketamine was viable as a longer-term treatment.

“We were encouraged by our initial promising findings” of the earlier trial, Dr. Feder said. “We wanted to do the second study to see if ketamine really works for PTSD, to see if we could replicate the rapid improvement and also examine whether a course of six infusions over 2 weeks could maintain the improvement.”

Thirty patients (aged 18-70; mean age, 39 years) with chronic PTSD from civilian or military trauma were enrolled (mean PTSD duration, 15 years).

The most cited primary trauma was sexual assault or molestation (n = 13), followed by physical assault or abuse (n = 8), witnessing a violent assault or death (n = 4), witnessing the 9/11 attacks (n = 3), and combat exposure (n = 2).

During the 2-week treatment phase, half of the patients were randomly assigned to receive six infusions of ketamine hydrochloride at a dose of 0.5 mg/kg (86.7% women; mean CAPS-5 score, 42), while the other half received six infusions of midazolam at a dose of 0.045 mg/kg (66.7% women; mean CAPS-5 score, 40).

In addition to the primary outcome measure of 2-week changes on the CAPS-5, secondary outcomes included score changes on the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Impact of Event Scale-Revised (IES-R).

Treatment response was defined as a 30% or more improvement in symptoms on the CAPS-5. A number of measures were also used to assess potential treatment-related adverse events (AEs).
 

Safe, effective

Results showed significantly lower total CAPS-5 scores for the ketamine group vs. the midazolam group at week 1 (score difference, 8.8 points; P = .03) and at week 2 (score difference, 11.88 points; P = .004).

Those receiving ketamine also showed improvements in three of the four PTSD symptom clusters on the CAPS-5: avoidance (P < .0001), negative mood and cognitions (P = .02), and intrusions (P = .03). The fourth symptom cluster – arousal and reactivity – did not show a significant improvement.

In addition, the ketamine group showed significantly greater improvement scores on the MADRS at both week 1 and week 2.

Treatment response at 2 weeks was achieved by 10 members of the ketamine group and by three members of the midazolam group (P = .03).

Secondary analyses showed rapid improvement in the treatment responders within the ketamine group, with a mean change of 26 points on the total IES-R score between baseline and 24 hours after their first infusion, and a mean change of 13.4 points on the MADRS total past-24-hour score, a 53% improvement on average.

“A response at 2 weeks is very rapid but they got better sometimes within the first day,” Dr. Feder noted.

There were no serious AEs reported. Although some dissociative symptoms occurred during ketamine infusions, with the highest levels reported at the end of the infusion, these symptoms had resolved by the next assessment, conducted 2 hours after infusion.

The most frequently reported AE in the ketamine group, compared with midazolam, after the start of infusions was blurred vision (53% vs. 0%), followed by dizziness (33% vs. 13%), fatigue (33% vs. 87%), headache (27% vs. 13%), and nausea or vomiting (20% vs. 7%).
 

‘Large-magnitude improvement’

The overall findings show that, in this patient population, “repeated intravenous ketamine infusions administered over 2 weeks were associated with a large-magnitude, clinically significant improvement in PTSD symptoms,” the investigators write.

The results “were very satisfying,” added Dr. Feder. “It was heartening also to hear what some of the participants would say. Some told us about how their symptoms and feelings had changed during the course of treatment with ketamine, where they felt stronger and better able to cope with their trauma and memories.”

She noted, however, that this was not a study designed to specifically assess ketamine in treatment-resistant PTSD. “Some patients had had multiple treatments before that hadn’t worked, while others had not received treatment before. Efficacy for treatment-resistant PTSD is an important question for future research,” Dr. Feder said.

Other areas worth future exploration include treatment efficacy in patients with different types of trauma and whether outcomes can last longer in patients receiving ketamine plus psychotherapy treatment, she noted.

“I don’t want to ignore the fact that currently available treatments work for a number of people with chronic PTSD. But because there are many more for whom [the treatments] don’t work, or they’re insufficiently helped by those treatments, this is certainly one potentially very promising approach that can be added” to a clinician’s toolbox, Dr. Feder said.
 

Speaks to clinical utility

Commenting for this news organization, Gerard Sanacora, MD, PhD, professor of psychiatry at Yale University, New Haven, Connecticut, called this a “very solid and well-designed” study.

“It definitely builds on what’s been found in the past, but it’s a critical piece of information speaking to the clinical utility of this treatment for PTSD,” said Dr. Sanacora, who is also director of the Yale Depression Research Program and was not involved with the current research.

He agreed with the investigators that PTSD has long been a condition that is difficult to treat.

“It’s an area that has a great unmet need for treatment options. Beyond that, as ketamine is becoming more widely used, there’s increasing demand for off-label uses. This [study] actually provides some evidence that there may be efficacy there,” Dr. Sanacora said.

Although he cautioned that this was a small study, and thus further research with a larger patient population will be needed, it provides a compelling foundation to build upon.

“This study provides clear evidence to support a larger study to really give a definitive statement on the efficacy and safety of its use for PTSD. I don’t think this is the study that provides that definitive evidence, but it is a very strong indication, and it very strongly supports the initiation of a large study to address that,” said Dr. Sanacora.

He noted that, although he’s used the term “cautious optimism” for studies in the past, he has “real optimism” that ketamine will be effective for PTSD based on the results of this current study.

“We still need some more data to really convince us of that before we can say with any clear statement that it is effective and safe, but I’m very optimistic,” Dr. Sanacora concluded. “I think the data are very strong.”

The study was funded by the Brain and Behavior Research Foundation, Mount Sinai Innovation Partners and the Mount Sinai i3 Accelerator, Gerald and Glenda Greenwald, and the Ehrenkranz Laboratory for Human Resilience. Dr. Feder is a coinventor on issued patents for the use of ketamine as therapy for PTSD. A list of all disclosures for the other study authors are listed in the original article.

A version of this article first appeared on Medscape.com.

Repeated intravenous infusions of ketamine provide rapid relief for patients with posttraumatic stress disorder, new research suggests.

In what investigators are calling the first randomized controlled trial of repeated ketamine administration for chronic PTSD, 30 patients received six infusions of ketamine or midazolam (used as a psychoactive placebo) over 2 consecutive weeks. 

Between baseline and week 2, those receiving ketamine showed significantly greater improvement than those receiving midazolam. Total scores on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) for the first group were almost 12 points lower than the latter group at week 2, meeting the study’s primary outcome measure.

In addition, 67% vs. 20% of the patients, respectively, were considered to be treatment responders; time to loss of response for those in the ketamine group was 28 days.

Although the overall findings were as expected, “what was surprising was how robust the results were,” lead author Adriana Feder, MD, associate professor of psychiatry, Icahn School of Medicine, Mount Sinai, New York, told this news organization.

It was also a bit surprising that, in a study of just 30 participants, “we were able to show such a clear difference” between the two treatment groups, said Dr. Feder, who is also a coinventor on issued patents for the use of ketamine as therapy for PTSD, and codirector of the Ehrenkranz Lab for the Study of Human Resilience at Mount Sinai.

The findings were published online Jan. 5 in the American Journal of Psychiatry.
 

Unmet need

Ketamine is a glutamate N-methyl-D-aspartate (NMDA) receptor antagonist that was first approved by the U.S. Food and Drug Administration for anesthetic use in 1970. It has also been shown to be effective for treatment-resistant depression.

PTSD has a lifetime prevalence of about 6% in the United States. “While trauma-focused psychotherapies have the most empirical support, they are limited by significant rates of nonresponse, partial response, and treatment dropout,” the investigators write. Also, there are “few available pharmacotherapies for PTSD, and their efficacy is insufficient,” they add.  

“There’s a real need for new treatment interventions that are effective for PTSD and also work rapidly, because it can take weeks to months for currently available treatments to work for PTSD,” Dr. Feder said.

The researchers previously conducted a “proof-of-concept” randomized controlled trial of single infusions of ketamine for chronic PTSD. Results published in 2014 in JAMA Psychiatry showed significant reduction in PTSD symptoms 24 hours after infusion.

For the current study, the investigative team wanted to assess whether ketamine was viable as a longer-term treatment.

“We were encouraged by our initial promising findings” of the earlier trial, Dr. Feder said. “We wanted to do the second study to see if ketamine really works for PTSD, to see if we could replicate the rapid improvement and also examine whether a course of six infusions over 2 weeks could maintain the improvement.”

Thirty patients (aged 18-70; mean age, 39 years) with chronic PTSD from civilian or military trauma were enrolled (mean PTSD duration, 15 years).

The most cited primary trauma was sexual assault or molestation (n = 13), followed by physical assault or abuse (n = 8), witnessing a violent assault or death (n = 4), witnessing the 9/11 attacks (n = 3), and combat exposure (n = 2).

During the 2-week treatment phase, half of the patients were randomly assigned to receive six infusions of ketamine hydrochloride at a dose of 0.5 mg/kg (86.7% women; mean CAPS-5 score, 42), while the other half received six infusions of midazolam at a dose of 0.045 mg/kg (66.7% women; mean CAPS-5 score, 40).

In addition to the primary outcome measure of 2-week changes on the CAPS-5, secondary outcomes included score changes on the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Impact of Event Scale-Revised (IES-R).

Treatment response was defined as a 30% or more improvement in symptoms on the CAPS-5. A number of measures were also used to assess potential treatment-related adverse events (AEs).
 

Safe, effective

Results showed significantly lower total CAPS-5 scores for the ketamine group vs. the midazolam group at week 1 (score difference, 8.8 points; P = .03) and at week 2 (score difference, 11.88 points; P = .004).

Those receiving ketamine also showed improvements in three of the four PTSD symptom clusters on the CAPS-5: avoidance (P < .0001), negative mood and cognitions (P = .02), and intrusions (P = .03). The fourth symptom cluster – arousal and reactivity – did not show a significant improvement.

In addition, the ketamine group showed significantly greater improvement scores on the MADRS at both week 1 and week 2.

Treatment response at 2 weeks was achieved by 10 members of the ketamine group and by three members of the midazolam group (P = .03).

Secondary analyses showed rapid improvement in the treatment responders within the ketamine group, with a mean change of 26 points on the total IES-R score between baseline and 24 hours after their first infusion, and a mean change of 13.4 points on the MADRS total past-24-hour score, a 53% improvement on average.

“A response at 2 weeks is very rapid but they got better sometimes within the first day,” Dr. Feder noted.

There were no serious AEs reported. Although some dissociative symptoms occurred during ketamine infusions, with the highest levels reported at the end of the infusion, these symptoms had resolved by the next assessment, conducted 2 hours after infusion.

The most frequently reported AE in the ketamine group, compared with midazolam, after the start of infusions was blurred vision (53% vs. 0%), followed by dizziness (33% vs. 13%), fatigue (33% vs. 87%), headache (27% vs. 13%), and nausea or vomiting (20% vs. 7%).
 

‘Large-magnitude improvement’

The overall findings show that, in this patient population, “repeated intravenous ketamine infusions administered over 2 weeks were associated with a large-magnitude, clinically significant improvement in PTSD symptoms,” the investigators write.

The results “were very satisfying,” added Dr. Feder. “It was heartening also to hear what some of the participants would say. Some told us about how their symptoms and feelings had changed during the course of treatment with ketamine, where they felt stronger and better able to cope with their trauma and memories.”

She noted, however, that this was not a study designed to specifically assess ketamine in treatment-resistant PTSD. “Some patients had had multiple treatments before that hadn’t worked, while others had not received treatment before. Efficacy for treatment-resistant PTSD is an important question for future research,” Dr. Feder said.

Other areas worth future exploration include treatment efficacy in patients with different types of trauma and whether outcomes can last longer in patients receiving ketamine plus psychotherapy treatment, she noted.

“I don’t want to ignore the fact that currently available treatments work for a number of people with chronic PTSD. But because there are many more for whom [the treatments] don’t work, or they’re insufficiently helped by those treatments, this is certainly one potentially very promising approach that can be added” to a clinician’s toolbox, Dr. Feder said.
 

Speaks to clinical utility

Commenting for this news organization, Gerard Sanacora, MD, PhD, professor of psychiatry at Yale University, New Haven, Connecticut, called this a “very solid and well-designed” study.

“It definitely builds on what’s been found in the past, but it’s a critical piece of information speaking to the clinical utility of this treatment for PTSD,” said Dr. Sanacora, who is also director of the Yale Depression Research Program and was not involved with the current research.

He agreed with the investigators that PTSD has long been a condition that is difficult to treat.

“It’s an area that has a great unmet need for treatment options. Beyond that, as ketamine is becoming more widely used, there’s increasing demand for off-label uses. This [study] actually provides some evidence that there may be efficacy there,” Dr. Sanacora said.

Although he cautioned that this was a small study, and thus further research with a larger patient population will be needed, it provides a compelling foundation to build upon.

“This study provides clear evidence to support a larger study to really give a definitive statement on the efficacy and safety of its use for PTSD. I don’t think this is the study that provides that definitive evidence, but it is a very strong indication, and it very strongly supports the initiation of a large study to address that,” said Dr. Sanacora.

He noted that, although he’s used the term “cautious optimism” for studies in the past, he has “real optimism” that ketamine will be effective for PTSD based on the results of this current study.

“We still need some more data to really convince us of that before we can say with any clear statement that it is effective and safe, but I’m very optimistic,” Dr. Sanacora concluded. “I think the data are very strong.”

The study was funded by the Brain and Behavior Research Foundation, Mount Sinai Innovation Partners and the Mount Sinai i3 Accelerator, Gerald and Glenda Greenwald, and the Ehrenkranz Laboratory for Human Resilience. Dr. Feder is a coinventor on issued patents for the use of ketamine as therapy for PTSD. A list of all disclosures for the other study authors are listed in the original article.

A version of this article first appeared on Medscape.com.

Chronic kidney disease (CKD) is a significant comorbidity of diabetes mellitus. The Kidney Disease Outcomes Quality Initiative (KDOQI) of the National Kidney Foundation defines CKD as the presence of kidney damage or decreased kidney function for ≥ 3 months. CKD caused by diabetes is called diabetic kidney disease (DKD), which is 1 of 3 principal microvascular complications of diabetes. DKD can progress to end-stage renal disease (ESRD), requiring kidney replacement therapy, and is the leading cause of CKD and ESRD in the United States.^1-3 Studies have also shown that, particularly in patients with diabetes, CKD considerably increases the risk of cardiovascular events, which often occur prior to ESRD.^1,4

This article provides the latest recommendations for evaluating and managing DKD to help you prevent or slow its progression.

Defining and categorizing diabetic kidney disease

CKD is defined as persistently elevated excretion of urinary albumin (albuminuria) and decreased estimated glomerular filtration rate (eGFR), or as the presence of signs of progressive kidney damage.^5,6 DKD, also known as diabetic nephropathy, is CKD attributed to long-term diabetes. A patient’s eGFR is the established basis for assignment to a stage (1, 2, 3a, 3b, 4, or 5) of CKD (TABLE 1⁷) and, along with the category of albuminuria (A1, A2, or A3), can indicate prognosis.

Taking its toll in diabetes

As many as 40% of patients with diabetes develop DKD.^8-10 Most studies of DKD have been conducted in patients with type 1 diabetes (T1D), because the time of clinical onset is typically known.

Type 1 diabetes. DKD usually occurs 10 to 15 years, or later, after the onset of diabetes.⁶ As many as 30% of people with T1D have albuminuria approximately 15 years after onset of diabetes; almost one-half of those develop DKD.^5,11 After approximately 22.5 years without albuminuria, patients with T1D have approximately a 1% annual risk of DKD.¹²

Type 2 diabetes (T2D). DKD is often present at diagnosis, likely due to a delay in diagnosis and briefer clinical exposure, compared to T1D. Albuminuria has been reported in as many as 40% of patients with T2D approximately 10 years after onset of diabetes.^12,13

Multiple risk factors with no standout “predictor”

Genetic susceptibility, ethnicity, glycemic control, smoking, blood pressure (BP), and the eGFR have been identified as risk factors for renal involvement in diabetes; obesity, oral contraceptives, and age can also contribute. Although each risk factor increases the risk of DKD, no single factor is adequately predictive. Moderately increased albuminuria, the earliest sign of DKD, is associated with progressive nephropathy.¹²

Continue to: How great is the risk?

How great is the risk? From disease onset to proteinuria and from proteinuria to ESRD, the risk of DKD in T1D and T2D is similar. With appropriate treatment, albuminuria can regress, and the risk of ESRD can be < 20% at 10 years in T1D.¹² As in T1D, good glycemic control might result in regression of albuminuria in T2D.¹⁴

As many as 30% of people with T1D have albuminuria approximately 15 years after onset of diabetes; almost one-half of those develop DKD.

For unknown reasons, the degree of albuminuria can exist independent of the progression of DKD. Factors responsible for a progressive decline in eGFR in DKD without albuminuria are unknown.^12,15

Patient evaluation with an eye toward comorbidities

A comprehensive initial medical evaluation for DKD includes a review of microvascular complications; visits to specialists; lifestyle and behavior patterns (eg, diet, sleep, substance use, and social support); and medication adherence, adverse drug effects, and alternative medicines. Although DKD is often a clinical diagnosis, it can be ruled in by persistent albuminuria or decreased eGFR, or both, in established diabetes or diabetic retinopathy when other causes are unlikely (see “Recommended DKD screening protocol,” below).

Screening for mental health conditions and barriers to self-management is also key.⁶

Comorbidities, of course, can complicate disease management in patients with diabetes.^16-20 Providers and patients therefore need to be aware of potential diabetic comorbidities. For example, DKD and even moderately increased albuminuria significantly increase the risk of cardiovascular disease (CVD).¹² Other possible comorbidities include (but are not limited to) nonalcoholic steatohepatitis, fracture, hearing impairment, cancer (eg, liver, pancreas, endometrium, colon, rectum, breast, and bladder), pancreatitis, hypogonadism, obstructive sleep apnea, periodontal disease, anxiety, depression, and eating disorders.⁶

Continue to: Recommended DKD screening protocol

 

 

Recommended DKD screening protocol

In all cases of T2D, in cases of T1D of ≥ 5 years’ duration, and in patients with diabetes and comorbid hypertension, perform annual screening for albuminuria, an elevated creatinine level, and a decline in eGFR.

Screen for potential comorbidities of DKD: For example, the risk of cardiovascular disease is significantly elevated in even moderately increased albuminuria.

To confirm the diagnosis of DKD, at least 2 of 3 urine specimens must demonstrate an elevated urinary albumin:creatinine ratio (UACR) over a 3- to 6-month period.²¹ Apart from renal damage, exercise within 24 hours before specimen collection, infection, fever, congestive heart failure, hyperglycemia, menstruation, and hypertension can elevate the UACR.⁶

Levels of the UACR are established as follows²²:

• Normal UACR is defined as < 30 milligrams of albumin per gram of creatinine (expressed as “mg/g”).
• Increased urinary albumin excretion is defined as ≥ 30 mg/g.
• Moderately increased albuminuria, a predictor of potential nephropathy, is the excretion of 30 to 300 mg/g.
• Severely increased albuminuria is excretion > 300 mg/g; it is often followed by a gradual decline in eGFR that, without treatment, eventually leads to ESRD.

The rate of decline in eGFR once albuminuria is severely increased is equivalent in T1D and T2D.¹² Without intervention, the time from severely increased albuminuria to ESRD in T1D and T2D averages approximately 6 or 7 years.

Clinical features

DKD is typically a clinical diagnosis seen in patients with longstanding diabetes, albuminuria, retinopathy, or a reduced eGFR in the absence of another primary cause of kidney damage. In patients with T1D and DKD, signs of retinopathy and neuropathy are almost always present at diagnosis, unless a diagnosis is made early in the course of diabetes.¹² Therefore, the presence of retinopathy suggests that diabetes is the likely cause of CKD.

Continue to: The presence of microvascular disease...

The presence of microvascular disease in patients with T2D and DKD is less predictable.¹² In T2D patients who do not have retinopathy, consider causes of CKD other than DKD. Features suggesting that the cause of CKD is an underlying condition other than diabetes are rapidly increasing albuminuria or decreasing eGFR; urinary sediment comprising red blood cells or white blood cells; and nephrotic syndrome.⁶

As the prevalence of diabetes increases, it has become more common to diagnose DKD by eGFR without albuminuria—underscoring the importance of routine monitoring of eGFR in patients with diabetes.⁶

Sources of expert guidance. The Chronic Kidney Disease Epidemiology Collaboration equation²³ is preferred for calculating eGFR from serum creatinine: An eGFR < 60 mL/min/1.73 m² is considered abnormal.^3,12 At these rates, the prevalence of complications related to CKD rises and screening for complications becomes necessary.

A more comprehensive classification of the stages of CKD, incorporating albuminuria and progression of CKD, has been recommended by Kidney Disease: Improving Global Outcomes (KDIGO).⁷ Because eGFR and excretion of albumin vary, abnormal test results need to be verified over time to stage the degree of CKD.^3,12 Kidney damage often manifests as albuminuria, but also as hematuria, other types of abnormal urinary sediment, radiographic abnormalities, and other abnormal presentations.

Management

Nutritional factors

Excessive protein intake has been shown to increase albuminuria, worsen renal function, and increase CVD mortality in DKD.^24-26 Therefore, daily dietary protein intake of 0.8 g/kg body weight is recommended for patients who are not on dialysis.³ Patients on dialysis might require higher protein intake to preserve muscle mass caused by protein-energy wasting, which is common in dialysis patients.⁶

Continue to: Low sodium intake

Low sodium intake in CKD patients has been shown to decrease BP and thus slow the progression of renal disease and lower the risk of CVD. The recommended dietary sodium intake in CKD patients is 1500-3000 mg/d.³

Low potassium intake. Hyperkalemia is a serious complication of CKD. A low-potassium diet is recommended in ESRD patients who have a potassium level > 5.5 mEq/L.⁶

Blood pressure

Preventing and treating hypertension is critical to slowing the progression of CKD and reducing cardiovascular risk. BP should be measured at every clinic visit. Aside from lifestyle changes, medication might be needed to reach target BP.

The American Diabetes Association recommends a BP goal of ≤ 140/90 mm Hg for hypertensive patients with diabetes, although they do state that a lower BP target (≤ 130/80 mm Hg) might be more appropriate for patients with DKD.²⁷

The American College of Cardiology recommends that hypertensive patients with CKD have a BP target of ≤ 130/80 mm Hg.²⁸

Continue to: ACE inhibitors and ARBs

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) have renoprotective benefits. These agents are recommended as first-line medications for patients with diabetes, hypertension, and an eGFR < 60 mL/min/1.73 m² and a UACR > 300 mg/g.^29-31 Evidence also supports their use when the UACR is 30 to 299 mg/g.

Studies have shown that, in patients with DKD, ACE inhibitors and ARBs can slow the progression of renal disease.^29,30,32 There is no difference between ACE inhibitors and ARBs in their effectiveness for preventing progression of DKD.⁶ There is no added benefit in combining an ACE inhibitor and an ARB³³; notably, combination ACE inhibitor and ARB therapy can increase the risk of adverse events, such as hyperkalemia and acute kidney injury, especially in patients with DKD.³³

There is no evidence for starting an ACE inhibitor or ARB to prevent CKD in patients with diabetes who are not hypertensive.⁵

ACE inhibitors and ARBs should be used with caution in women of childbearing age, who should use a reliable form of contraception if taking one of these drugs.

Diuretics. Thiazide-type and loop diuretics might potentiate the positive effects of ACE inhibitors and ARBs. KDOQI guidelines recommend that, in patients who require a second agent to control BP, a diuretic should be considered in combination with an ACE inhibitor or an ARB.²⁰ A loop diuretic is preferred if the eGFR is < 30 mL/min/1.73 m².

Continue to: Nondihydropyridine calcium-channel blockers

Nondihydropyridine calcium-channel blockers (CCBs), such as diltiazem and verapamil, have been shown to be more effective then dihydrophyridine CCBs, such as amlodipine and nifedipine, in slowing the progression of renal disease because of their antiproteinuric effects. However, the antiproteinuric effects of nondihydropyridine CCBs are not as strong as those of ACE inhibitors or ARBs, and these drugs do not appear to potentiate the effects of an ACE inhibitor or ARB when used in combination.²⁰

Confirmation of suspected DKD requires an elevated albumin:creatinine ratio in at least 2 of 3 urine specimens over a 3- to 6-month period.

Nondihydropyridine CCBs might be a reasonable alternative in patients who cannot tolerate an ACE inhibitor or an ARB.

Mineralocorticoid receptor antagonists in combination with an ACE inhibitor or ARB have been demonstrated to reduce albuminuria in short-term studies.^34,35

Glycemic levels

Studies conducted in patients with T1D, and others in patients with T2D, have shown that tight glycemic control can delay the onset and slow the progression of albuminuria and a decline in the eGFR.^10,36-39 The target glycated hemoglobin (A1C) should be < 7% to prevent or slow progression of DKD.⁴⁰ However, patients with DKD have an increased risk of hypoglycemic events and increased mortality with more intensive glycemic control.^40,41 Given those findings, some patients with DKD and significant comorbidities, ESRD, or limited life expectancy might need to have an A1C target set at 8%.^6,42

Adjustments to antidiabetes medications in DKD

In patients with stages 3 to 5 DKD, several common antidiabetic medications might need to be adjusted or discontinued because they decrease creatinine clearance.

Continue to: First-generation sulfonylureas

First-generation sulfonylureas should be avoided in DKD. Glipizide and gliclazide are preferred among second-generation sulfonylureas because they do not increase the risk of hypoglycemia in DKD patients, although patients taking these medications still require close monitoring of their blood glucose level.²⁰

Metformin. In 2016, recommendations changed for the use of metformin in patients with DKD: The eGFR, not the serum creatinine level, should guide treatment.⁴³ Metformin can be used safely in patients with (1) an eGFR of < 60 mL/min/1.73 m² and (2) an eGFR of 30 mL/min/1.73 m² with close monitoring. Metformin should not be initiated if the eGFR is < 45 mL/min/1.73 m².⁴³ 

Antidiabetes medications with direct effect on the kidney

Several antidiabetes medications have a direct effect on the kidney apart from their effect on the blood glucose level.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to reduce albuminuria and slow the decrease of eGFR independent of glycemic control. In addition, SGLT2 inhibitors have also been shown to have cardiovascular benefits in patients with DKD.^44,45 

Glucagon-like peptide 1 (GLP-1) receptor agonists have been shown to delay and decrease the progression of DKD.^46-48 Also, similar to what is seen with SGLT2 inhibitors, GLP-1 agonists have demonstrable cardiovascular benefit in patients with DKD.^46,48

Continue to: Dyslipidemia and DKD

 

 

Dyslipidemia and DKD

Because the risk of CVD is increased in patients with DKD, addressing other modifiable risk factors, including dyslipidemia, is recommended in these patients. Patients with diabetes and stages 1 to 4 DKD should be treated with a high-intensity statin or a combination of a statin and ezetimibe.^49,50

Tight glycemic control in T1D and T2D can delay the onset, and slow the progression, of albuminuria and a decline in the eGFR.

If a patient is taking a statin and starting dialysis, it’s important to discuss with him or her whether to continue the statin, based on perceived benefits and risks. It is not recommended that statins be initiated in patients on dialysis unless there is a specific cardiovascular indication for doing so. Risk reduction with a statin has been shown to be significantly less in dialysis patients than in patients who are not being treated with dialysis.⁴⁹

Complications of CKD

Anemia is a common complication of CKD. KDIGO recommends measuring the ­hemoglobin concentration annually in DKD stage 3 patients without anemia; at least every 6 months in stage 4 patients; and at least every 3 months in stage 5. DKD patients with anemia should have additional laboratory testing: the absolute reticulocyte count, serum ferritin, serum transferrin saturation, vitamin B12, and folate.⁵¹

Mineral and bone disorder should be screened for in patients with DKD. TABLE 2⁵² outlines when clinical laboratory tests should be ordered to assess for mineral bone disease.

When to refer to a nephrologist

Refer patients with stage 4 or 5 CKD (eGFR, ≤ 30 mL/min/1.73 m²) to a nephrologist for discussion of kidney replacement therapy.⁶ Patients with stage 3a CKD and severely increased albuminuria or with stage 3b CKD and moderately or severely increased albuminuria should also be referred to a nephrologist for intervention to delay disease progression.

Continue to: Identifying the need for early referral...

Nutritional control is important in DKD: A lowsodium diet can slow progression of DKD, and a low-potassium diet can prevent hyperkalemia in end-stage renal disease.

Identifying the need for early referral to a nephrologist has been shown to reduce the cost, and improve the quality, of care.⁵³ Other indications for earlier referral include uncertainty about the etiology of renal disease, persistent or severe albuminuria, persistent hematuria, a rapid decline in eGFR, and acute kidney injury. Additionally, referral at an earlier stage of DKD might be needed to assist with complications associated with DKD, such as anemia, secondary hyperparathyroidism, mineral and bone disorder, resistant hypertension, fluid overload, and electrolyte disturbances.⁶

ACKNOWLEDGEMENT
The authors thank Colleen Colbert, PhD, and Iqbal Ahmad, PhD, for their review and critique of the manuscript of this article. They also thank Christopher Babiuch, MD, for his guidance in the preparation of the manuscript.

CORRESPONDENCE
Faraz Ahmad, MD, MPH, Care Point East Family Medicine, 543 Taylor Avenue, 2nd floor, Columbus, OH 43203; faraz. ahmad@osumc.edu.

Chronic kidney disease (CKD) is a significant comorbidity of diabetes mellitus. The Kidney Disease Outcomes Quality Initiative (KDOQI) of the National Kidney Foundation defines CKD as the presence of kidney damage or decreased kidney function for ≥ 3 months. CKD caused by diabetes is called diabetic kidney disease (DKD), which is 1 of 3 principal microvascular complications of diabetes. DKD can progress to end-stage renal disease (ESRD), requiring kidney replacement therapy, and is the leading cause of CKD and ESRD in the United States.^1-3 Studies have also shown that, particularly in patients with diabetes, CKD considerably increases the risk of cardiovascular events, which often occur prior to ESRD.^1,4

This article provides the latest recommendations for evaluating and managing DKD to help you prevent or slow its progression.

Defining and categorizing diabetic kidney disease

CKD is defined as persistently elevated excretion of urinary albumin (albuminuria) and decreased estimated glomerular filtration rate (eGFR), or as the presence of signs of progressive kidney damage.^5,6 DKD, also known as diabetic nephropathy, is CKD attributed to long-term diabetes. A patient’s eGFR is the established basis for assignment to a stage (1, 2, 3a, 3b, 4, or 5) of CKD (TABLE 1⁷) and, along with the category of albuminuria (A1, A2, or A3), can indicate prognosis.

Taking its toll in diabetes

As many as 40% of patients with diabetes develop DKD.^8-10 Most studies of DKD have been conducted in patients with type 1 diabetes (T1D), because the time of clinical onset is typically known.

Type 1 diabetes. DKD usually occurs 10 to 15 years, or later, after the onset of diabetes.⁶ As many as 30% of people with T1D have albuminuria approximately 15 years after onset of diabetes; almost one-half of those develop DKD.^5,11 After approximately 22.5 years without albuminuria, patients with T1D have approximately a 1% annual risk of DKD.¹²

Type 2 diabetes (T2D). DKD is often present at diagnosis, likely due to a delay in diagnosis and briefer clinical exposure, compared to T1D. Albuminuria has been reported in as many as 40% of patients with T2D approximately 10 years after onset of diabetes.^12,13

Multiple risk factors with no standout “predictor”

Genetic susceptibility, ethnicity, glycemic control, smoking, blood pressure (BP), and the eGFR have been identified as risk factors for renal involvement in diabetes; obesity, oral contraceptives, and age can also contribute. Although each risk factor increases the risk of DKD, no single factor is adequately predictive. Moderately increased albuminuria, the earliest sign of DKD, is associated with progressive nephropathy.¹²

Continue to: How great is the risk?

How great is the risk? From disease onset to proteinuria and from proteinuria to ESRD, the risk of DKD in T1D and T2D is similar. With appropriate treatment, albuminuria can regress, and the risk of ESRD can be < 20% at 10 years in T1D.¹² As in T1D, good glycemic control might result in regression of albuminuria in T2D.¹⁴

As many as 30% of people with T1D have albuminuria approximately 15 years after onset of diabetes; almost one-half of those develop DKD.

For unknown reasons, the degree of albuminuria can exist independent of the progression of DKD. Factors responsible for a progressive decline in eGFR in DKD without albuminuria are unknown.^12,15

Patient evaluation with an eye toward comorbidities

A comprehensive initial medical evaluation for DKD includes a review of microvascular complications; visits to specialists; lifestyle and behavior patterns (eg, diet, sleep, substance use, and social support); and medication adherence, adverse drug effects, and alternative medicines. Although DKD is often a clinical diagnosis, it can be ruled in by persistent albuminuria or decreased eGFR, or both, in established diabetes or diabetic retinopathy when other causes are unlikely (see “Recommended DKD screening protocol,” below).

Screening for mental health conditions and barriers to self-management is also key.⁶

Comorbidities, of course, can complicate disease management in patients with diabetes.^16-20 Providers and patients therefore need to be aware of potential diabetic comorbidities. For example, DKD and even moderately increased albuminuria significantly increase the risk of cardiovascular disease (CVD).¹² Other possible comorbidities include (but are not limited to) nonalcoholic steatohepatitis, fracture, hearing impairment, cancer (eg, liver, pancreas, endometrium, colon, rectum, breast, and bladder), pancreatitis, hypogonadism, obstructive sleep apnea, periodontal disease, anxiety, depression, and eating disorders.⁶

Continue to: Recommended DKD screening protocol

 

 

Recommended DKD screening protocol

In all cases of T2D, in cases of T1D of ≥ 5 years’ duration, and in patients with diabetes and comorbid hypertension, perform annual screening for albuminuria, an elevated creatinine level, and a decline in eGFR.

Screen for potential comorbidities of DKD: For example, the risk of cardiovascular disease is significantly elevated in even moderately increased albuminuria.

To confirm the diagnosis of DKD, at least 2 of 3 urine specimens must demonstrate an elevated urinary albumin:creatinine ratio (UACR) over a 3- to 6-month period.²¹ Apart from renal damage, exercise within 24 hours before specimen collection, infection, fever, congestive heart failure, hyperglycemia, menstruation, and hypertension can elevate the UACR.⁶

Levels of the UACR are established as follows²²:

• Normal UACR is defined as < 30 milligrams of albumin per gram of creatinine (expressed as “mg/g”).
• Increased urinary albumin excretion is defined as ≥ 30 mg/g.
• Moderately increased albuminuria, a predictor of potential nephropathy, is the excretion of 30 to 300 mg/g.
• Severely increased albuminuria is excretion > 300 mg/g; it is often followed by a gradual decline in eGFR that, without treatment, eventually leads to ESRD.

The rate of decline in eGFR once albuminuria is severely increased is equivalent in T1D and T2D.¹² Without intervention, the time from severely increased albuminuria to ESRD in T1D and T2D averages approximately 6 or 7 years.

Clinical features

DKD is typically a clinical diagnosis seen in patients with longstanding diabetes, albuminuria, retinopathy, or a reduced eGFR in the absence of another primary cause of kidney damage. In patients with T1D and DKD, signs of retinopathy and neuropathy are almost always present at diagnosis, unless a diagnosis is made early in the course of diabetes.¹² Therefore, the presence of retinopathy suggests that diabetes is the likely cause of CKD.

Continue to: The presence of microvascular disease...

The presence of microvascular disease in patients with T2D and DKD is less predictable.¹² In T2D patients who do not have retinopathy, consider causes of CKD other than DKD. Features suggesting that the cause of CKD is an underlying condition other than diabetes are rapidly increasing albuminuria or decreasing eGFR; urinary sediment comprising red blood cells or white blood cells; and nephrotic syndrome.⁶

As the prevalence of diabetes increases, it has become more common to diagnose DKD by eGFR without albuminuria—underscoring the importance of routine monitoring of eGFR in patients with diabetes.⁶

Sources of expert guidance. The Chronic Kidney Disease Epidemiology Collaboration equation²³ is preferred for calculating eGFR from serum creatinine: An eGFR < 60 mL/min/1.73 m² is considered abnormal.^3,12 At these rates, the prevalence of complications related to CKD rises and screening for complications becomes necessary.

A more comprehensive classification of the stages of CKD, incorporating albuminuria and progression of CKD, has been recommended by Kidney Disease: Improving Global Outcomes (KDIGO).⁷ Because eGFR and excretion of albumin vary, abnormal test results need to be verified over time to stage the degree of CKD.^3,12 Kidney damage often manifests as albuminuria, but also as hematuria, other types of abnormal urinary sediment, radiographic abnormalities, and other abnormal presentations.

Management

Nutritional factors

Excessive protein intake has been shown to increase albuminuria, worsen renal function, and increase CVD mortality in DKD.^24-26 Therefore, daily dietary protein intake of 0.8 g/kg body weight is recommended for patients who are not on dialysis.³ Patients on dialysis might require higher protein intake to preserve muscle mass caused by protein-energy wasting, which is common in dialysis patients.⁶

Continue to: Low sodium intake

Low sodium intake in CKD patients has been shown to decrease BP and thus slow the progression of renal disease and lower the risk of CVD. The recommended dietary sodium intake in CKD patients is 1500-3000 mg/d.³

Low potassium intake. Hyperkalemia is a serious complication of CKD. A low-potassium diet is recommended in ESRD patients who have a potassium level > 5.5 mEq/L.⁶

Blood pressure

Preventing and treating hypertension is critical to slowing the progression of CKD and reducing cardiovascular risk. BP should be measured at every clinic visit. Aside from lifestyle changes, medication might be needed to reach target BP.

The American Diabetes Association recommends a BP goal of ≤ 140/90 mm Hg for hypertensive patients with diabetes, although they do state that a lower BP target (≤ 130/80 mm Hg) might be more appropriate for patients with DKD.²⁷

The American College of Cardiology recommends that hypertensive patients with CKD have a BP target of ≤ 130/80 mm Hg.²⁸

Continue to: ACE inhibitors and ARBs

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) have renoprotective benefits. These agents are recommended as first-line medications for patients with diabetes, hypertension, and an eGFR < 60 mL/min/1.73 m² and a UACR > 300 mg/g.^29-31 Evidence also supports their use when the UACR is 30 to 299 mg/g.

Studies have shown that, in patients with DKD, ACE inhibitors and ARBs can slow the progression of renal disease.^29,30,32 There is no difference between ACE inhibitors and ARBs in their effectiveness for preventing progression of DKD.⁶ There is no added benefit in combining an ACE inhibitor and an ARB³³; notably, combination ACE inhibitor and ARB therapy can increase the risk of adverse events, such as hyperkalemia and acute kidney injury, especially in patients with DKD.³³

There is no evidence for starting an ACE inhibitor or ARB to prevent CKD in patients with diabetes who are not hypertensive.⁵

ACE inhibitors and ARBs should be used with caution in women of childbearing age, who should use a reliable form of contraception if taking one of these drugs.

Diuretics. Thiazide-type and loop diuretics might potentiate the positive effects of ACE inhibitors and ARBs. KDOQI guidelines recommend that, in patients who require a second agent to control BP, a diuretic should be considered in combination with an ACE inhibitor or an ARB.²⁰ A loop diuretic is preferred if the eGFR is < 30 mL/min/1.73 m².

Continue to: Nondihydropyridine calcium-channel blockers

Nondihydropyridine calcium-channel blockers (CCBs), such as diltiazem and verapamil, have been shown to be more effective then dihydrophyridine CCBs, such as amlodipine and nifedipine, in slowing the progression of renal disease because of their antiproteinuric effects. However, the antiproteinuric effects of nondihydropyridine CCBs are not as strong as those of ACE inhibitors or ARBs, and these drugs do not appear to potentiate the effects of an ACE inhibitor or ARB when used in combination.²⁰

Confirmation of suspected DKD requires an elevated albumin:creatinine ratio in at least 2 of 3 urine specimens over a 3- to 6-month period.

Nondihydropyridine CCBs might be a reasonable alternative in patients who cannot tolerate an ACE inhibitor or an ARB.

Mineralocorticoid receptor antagonists in combination with an ACE inhibitor or ARB have been demonstrated to reduce albuminuria in short-term studies.^34,35

Glycemic levels

Studies conducted in patients with T1D, and others in patients with T2D, have shown that tight glycemic control can delay the onset and slow the progression of albuminuria and a decline in the eGFR.^10,36-39 The target glycated hemoglobin (A1C) should be < 7% to prevent or slow progression of DKD.⁴⁰ However, patients with DKD have an increased risk of hypoglycemic events and increased mortality with more intensive glycemic control.^40,41 Given those findings, some patients with DKD and significant comorbidities, ESRD, or limited life expectancy might need to have an A1C target set at 8%.^6,42

Adjustments to antidiabetes medications in DKD

In patients with stages 3 to 5 DKD, several common antidiabetic medications might need to be adjusted or discontinued because they decrease creatinine clearance.

Continue to: First-generation sulfonylureas

First-generation sulfonylureas should be avoided in DKD. Glipizide and gliclazide are preferred among second-generation sulfonylureas because they do not increase the risk of hypoglycemia in DKD patients, although patients taking these medications still require close monitoring of their blood glucose level.²⁰

Metformin. In 2016, recommendations changed for the use of metformin in patients with DKD: The eGFR, not the serum creatinine level, should guide treatment.⁴³ Metformin can be used safely in patients with (1) an eGFR of < 60 mL/min/1.73 m² and (2) an eGFR of 30 mL/min/1.73 m² with close monitoring. Metformin should not be initiated if the eGFR is < 45 mL/min/1.73 m².⁴³ 

Antidiabetes medications with direct effect on the kidney

Several antidiabetes medications have a direct effect on the kidney apart from their effect on the blood glucose level.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to reduce albuminuria and slow the decrease of eGFR independent of glycemic control. In addition, SGLT2 inhibitors have also been shown to have cardiovascular benefits in patients with DKD.^44,45 

Glucagon-like peptide 1 (GLP-1) receptor agonists have been shown to delay and decrease the progression of DKD.^46-48 Also, similar to what is seen with SGLT2 inhibitors, GLP-1 agonists have demonstrable cardiovascular benefit in patients with DKD.^46,48

Continue to: Dyslipidemia and DKD

 

 

Dyslipidemia and DKD

Because the risk of CVD is increased in patients with DKD, addressing other modifiable risk factors, including dyslipidemia, is recommended in these patients. Patients with diabetes and stages 1 to 4 DKD should be treated with a high-intensity statin or a combination of a statin and ezetimibe.^49,50

Tight glycemic control in T1D and T2D can delay the onset, and slow the progression, of albuminuria and a decline in the eGFR.

If a patient is taking a statin and starting dialysis, it’s important to discuss with him or her whether to continue the statin, based on perceived benefits and risks. It is not recommended that statins be initiated in patients on dialysis unless there is a specific cardiovascular indication for doing so. Risk reduction with a statin has been shown to be significantly less in dialysis patients than in patients who are not being treated with dialysis.⁴⁹

Complications of CKD

Anemia is a common complication of CKD. KDIGO recommends measuring the ­hemoglobin concentration annually in DKD stage 3 patients without anemia; at least every 6 months in stage 4 patients; and at least every 3 months in stage 5. DKD patients with anemia should have additional laboratory testing: the absolute reticulocyte count, serum ferritin, serum transferrin saturation, vitamin B12, and folate.⁵¹

Mineral and bone disorder should be screened for in patients with DKD. TABLE 2⁵² outlines when clinical laboratory tests should be ordered to assess for mineral bone disease.

When to refer to a nephrologist

Refer patients with stage 4 or 5 CKD (eGFR, ≤ 30 mL/min/1.73 m²) to a nephrologist for discussion of kidney replacement therapy.⁶ Patients with stage 3a CKD and severely increased albuminuria or with stage 3b CKD and moderately or severely increased albuminuria should also be referred to a nephrologist for intervention to delay disease progression.

Continue to: Identifying the need for early referral...

Nutritional control is important in DKD: A lowsodium diet can slow progression of DKD, and a low-potassium diet can prevent hyperkalemia in end-stage renal disease.

Identifying the need for early referral to a nephrologist has been shown to reduce the cost, and improve the quality, of care.⁵³ Other indications for earlier referral include uncertainty about the etiology of renal disease, persistent or severe albuminuria, persistent hematuria, a rapid decline in eGFR, and acute kidney injury. Additionally, referral at an earlier stage of DKD might be needed to assist with complications associated with DKD, such as anemia, secondary hyperparathyroidism, mineral and bone disorder, resistant hypertension, fluid overload, and electrolyte disturbances.⁶

ACKNOWLEDGEMENT
The authors thank Colleen Colbert, PhD, and Iqbal Ahmad, PhD, for their review and critique of the manuscript of this article. They also thank Christopher Babiuch, MD, for his guidance in the preparation of the manuscript.

CORRESPONDENCE
Faraz Ahmad, MD, MPH, Care Point East Family Medicine, 543 Taylor Avenue, 2nd floor, Columbus, OH 43203; faraz. ahmad@osumc.edu.

Chronic kidney disease (CKD) is a significant comorbidity of diabetes mellitus. The Kidney Disease Outcomes Quality Initiative (KDOQI) of the National Kidney Foundation defines CKD as the presence of kidney damage or decreased kidney function for ≥ 3 months. CKD caused by diabetes is called diabetic kidney disease (DKD), which is 1 of 3 principal microvascular complications of diabetes. DKD can progress to end-stage renal disease (ESRD), requiring kidney replacement therapy, and is the leading cause of CKD and ESRD in the United States.^1-3 Studies have also shown that, particularly in patients with diabetes, CKD considerably increases the risk of cardiovascular events, which often occur prior to ESRD.^1,4

This article provides the latest recommendations for evaluating and managing DKD to help you prevent or slow its progression.

Defining and categorizing diabetic kidney disease

CKD is defined as persistently elevated excretion of urinary albumin (albuminuria) and decreased estimated glomerular filtration rate (eGFR), or as the presence of signs of progressive kidney damage.^5,6 DKD, also known as diabetic nephropathy, is CKD attributed to long-term diabetes. A patient’s eGFR is the established basis for assignment to a stage (1, 2, 3a, 3b, 4, or 5) of CKD (TABLE 1⁷) and, along with the category of albuminuria (A1, A2, or A3), can indicate prognosis.

Taking its toll in diabetes

As many as 40% of patients with diabetes develop DKD.^8-10 Most studies of DKD have been conducted in patients with type 1 diabetes (T1D), because the time of clinical onset is typically known.

Type 1 diabetes. DKD usually occurs 10 to 15 years, or later, after the onset of diabetes.⁶ As many as 30% of people with T1D have albuminuria approximately 15 years after onset of diabetes; almost one-half of those develop DKD.^5,11 After approximately 22.5 years without albuminuria, patients with T1D have approximately a 1% annual risk of DKD.¹²

Type 2 diabetes (T2D). DKD is often present at diagnosis, likely due to a delay in diagnosis and briefer clinical exposure, compared to T1D. Albuminuria has been reported in as many as 40% of patients with T2D approximately 10 years after onset of diabetes.^12,13

Multiple risk factors with no standout “predictor”

Genetic susceptibility, ethnicity, glycemic control, smoking, blood pressure (BP), and the eGFR have been identified as risk factors for renal involvement in diabetes; obesity, oral contraceptives, and age can also contribute. Although each risk factor increases the risk of DKD, no single factor is adequately predictive. Moderately increased albuminuria, the earliest sign of DKD, is associated with progressive nephropathy.¹²

Continue to: How great is the risk?

How great is the risk? From disease onset to proteinuria and from proteinuria to ESRD, the risk of DKD in T1D and T2D is similar. With appropriate treatment, albuminuria can regress, and the risk of ESRD can be < 20% at 10 years in T1D.¹² As in T1D, good glycemic control might result in regression of albuminuria in T2D.¹⁴

As many as 30% of people with T1D have albuminuria approximately 15 years after onset of diabetes; almost one-half of those develop DKD.

For unknown reasons, the degree of albuminuria can exist independent of the progression of DKD. Factors responsible for a progressive decline in eGFR in DKD without albuminuria are unknown.^12,15

Patient evaluation with an eye toward comorbidities

A comprehensive initial medical evaluation for DKD includes a review of microvascular complications; visits to specialists; lifestyle and behavior patterns (eg, diet, sleep, substance use, and social support); and medication adherence, adverse drug effects, and alternative medicines. Although DKD is often a clinical diagnosis, it can be ruled in by persistent albuminuria or decreased eGFR, or both, in established diabetes or diabetic retinopathy when other causes are unlikely (see “Recommended DKD screening protocol,” below).

Screening for mental health conditions and barriers to self-management is also key.⁶

Comorbidities, of course, can complicate disease management in patients with diabetes.^16-20 Providers and patients therefore need to be aware of potential diabetic comorbidities. For example, DKD and even moderately increased albuminuria significantly increase the risk of cardiovascular disease (CVD).¹² Other possible comorbidities include (but are not limited to) nonalcoholic steatohepatitis, fracture, hearing impairment, cancer (eg, liver, pancreas, endometrium, colon, rectum, breast, and bladder), pancreatitis, hypogonadism, obstructive sleep apnea, periodontal disease, anxiety, depression, and eating disorders.⁶

Continue to: Recommended DKD screening protocol

 

 

Recommended DKD screening protocol

In all cases of T2D, in cases of T1D of ≥ 5 years’ duration, and in patients with diabetes and comorbid hypertension, perform annual screening for albuminuria, an elevated creatinine level, and a decline in eGFR.

Screen for potential comorbidities of DKD: For example, the risk of cardiovascular disease is significantly elevated in even moderately increased albuminuria.

To confirm the diagnosis of DKD, at least 2 of 3 urine specimens must demonstrate an elevated urinary albumin:creatinine ratio (UACR) over a 3- to 6-month period.²¹ Apart from renal damage, exercise within 24 hours before specimen collection, infection, fever, congestive heart failure, hyperglycemia, menstruation, and hypertension can elevate the UACR.⁶

Levels of the UACR are established as follows²²:

• Normal UACR is defined as < 30 milligrams of albumin per gram of creatinine (expressed as “mg/g”).
• Increased urinary albumin excretion is defined as ≥ 30 mg/g.
• Moderately increased albuminuria, a predictor of potential nephropathy, is the excretion of 30 to 300 mg/g.
• Severely increased albuminuria is excretion > 300 mg/g; it is often followed by a gradual decline in eGFR that, without treatment, eventually leads to ESRD.

The rate of decline in eGFR once albuminuria is severely increased is equivalent in T1D and T2D.¹² Without intervention, the time from severely increased albuminuria to ESRD in T1D and T2D averages approximately 6 or 7 years.

Clinical features

DKD is typically a clinical diagnosis seen in patients with longstanding diabetes, albuminuria, retinopathy, or a reduced eGFR in the absence of another primary cause of kidney damage. In patients with T1D and DKD, signs of retinopathy and neuropathy are almost always present at diagnosis, unless a diagnosis is made early in the course of diabetes.¹² Therefore, the presence of retinopathy suggests that diabetes is the likely cause of CKD.

Continue to: The presence of microvascular disease...

The presence of microvascular disease in patients with T2D and DKD is less predictable.¹² In T2D patients who do not have retinopathy, consider causes of CKD other than DKD. Features suggesting that the cause of CKD is an underlying condition other than diabetes are rapidly increasing albuminuria or decreasing eGFR; urinary sediment comprising red blood cells or white blood cells; and nephrotic syndrome.⁶

As the prevalence of diabetes increases, it has become more common to diagnose DKD by eGFR without albuminuria—underscoring the importance of routine monitoring of eGFR in patients with diabetes.⁶

Sources of expert guidance. The Chronic Kidney Disease Epidemiology Collaboration equation²³ is preferred for calculating eGFR from serum creatinine: An eGFR < 60 mL/min/1.73 m² is considered abnormal.^3,12 At these rates, the prevalence of complications related to CKD rises and screening for complications becomes necessary.

A more comprehensive classification of the stages of CKD, incorporating albuminuria and progression of CKD, has been recommended by Kidney Disease: Improving Global Outcomes (KDIGO).⁷ Because eGFR and excretion of albumin vary, abnormal test results need to be verified over time to stage the degree of CKD.^3,12 Kidney damage often manifests as albuminuria, but also as hematuria, other types of abnormal urinary sediment, radiographic abnormalities, and other abnormal presentations.

Management

Nutritional factors

Excessive protein intake has been shown to increase albuminuria, worsen renal function, and increase CVD mortality in DKD.^24-26 Therefore, daily dietary protein intake of 0.8 g/kg body weight is recommended for patients who are not on dialysis.³ Patients on dialysis might require higher protein intake to preserve muscle mass caused by protein-energy wasting, which is common in dialysis patients.⁶

Continue to: Low sodium intake

Low sodium intake in CKD patients has been shown to decrease BP and thus slow the progression of renal disease and lower the risk of CVD. The recommended dietary sodium intake in CKD patients is 1500-3000 mg/d.³

Low potassium intake. Hyperkalemia is a serious complication of CKD. A low-potassium diet is recommended in ESRD patients who have a potassium level > 5.5 mEq/L.⁶

Blood pressure

Preventing and treating hypertension is critical to slowing the progression of CKD and reducing cardiovascular risk. BP should be measured at every clinic visit. Aside from lifestyle changes, medication might be needed to reach target BP.

The American Diabetes Association recommends a BP goal of ≤ 140/90 mm Hg for hypertensive patients with diabetes, although they do state that a lower BP target (≤ 130/80 mm Hg) might be more appropriate for patients with DKD.²⁷

The American College of Cardiology recommends that hypertensive patients with CKD have a BP target of ≤ 130/80 mm Hg.²⁸

Continue to: ACE inhibitors and ARBs

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) have renoprotective benefits. These agents are recommended as first-line medications for patients with diabetes, hypertension, and an eGFR < 60 mL/min/1.73 m² and a UACR > 300 mg/g.^29-31 Evidence also supports their use when the UACR is 30 to 299 mg/g.

Studies have shown that, in patients with DKD, ACE inhibitors and ARBs can slow the progression of renal disease.^29,30,32 There is no difference between ACE inhibitors and ARBs in their effectiveness for preventing progression of DKD.⁶ There is no added benefit in combining an ACE inhibitor and an ARB³³; notably, combination ACE inhibitor and ARB therapy can increase the risk of adverse events, such as hyperkalemia and acute kidney injury, especially in patients with DKD.³³

There is no evidence for starting an ACE inhibitor or ARB to prevent CKD in patients with diabetes who are not hypertensive.⁵

ACE inhibitors and ARBs should be used with caution in women of childbearing age, who should use a reliable form of contraception if taking one of these drugs.

Diuretics. Thiazide-type and loop diuretics might potentiate the positive effects of ACE inhibitors and ARBs. KDOQI guidelines recommend that, in patients who require a second agent to control BP, a diuretic should be considered in combination with an ACE inhibitor or an ARB.²⁰ A loop diuretic is preferred if the eGFR is < 30 mL/min/1.73 m².

Continue to: Nondihydropyridine calcium-channel blockers

Nondihydropyridine calcium-channel blockers (CCBs), such as diltiazem and verapamil, have been shown to be more effective then dihydrophyridine CCBs, such as amlodipine and nifedipine, in slowing the progression of renal disease because of their antiproteinuric effects. However, the antiproteinuric effects of nondihydropyridine CCBs are not as strong as those of ACE inhibitors or ARBs, and these drugs do not appear to potentiate the effects of an ACE inhibitor or ARB when used in combination.²⁰

Confirmation of suspected DKD requires an elevated albumin:creatinine ratio in at least 2 of 3 urine specimens over a 3- to 6-month period.

Nondihydropyridine CCBs might be a reasonable alternative in patients who cannot tolerate an ACE inhibitor or an ARB.

Mineralocorticoid receptor antagonists in combination with an ACE inhibitor or ARB have been demonstrated to reduce albuminuria in short-term studies.^34,35

Glycemic levels

Studies conducted in patients with T1D, and others in patients with T2D, have shown that tight glycemic control can delay the onset and slow the progression of albuminuria and a decline in the eGFR.^10,36-39 The target glycated hemoglobin (A1C) should be < 7% to prevent or slow progression of DKD.⁴⁰ However, patients with DKD have an increased risk of hypoglycemic events and increased mortality with more intensive glycemic control.^40,41 Given those findings, some patients with DKD and significant comorbidities, ESRD, or limited life expectancy might need to have an A1C target set at 8%.^6,42

Adjustments to antidiabetes medications in DKD

In patients with stages 3 to 5 DKD, several common antidiabetic medications might need to be adjusted or discontinued because they decrease creatinine clearance.

Continue to: First-generation sulfonylureas

First-generation sulfonylureas should be avoided in DKD. Glipizide and gliclazide are preferred among second-generation sulfonylureas because they do not increase the risk of hypoglycemia in DKD patients, although patients taking these medications still require close monitoring of their blood glucose level.²⁰

Metformin. In 2016, recommendations changed for the use of metformin in patients with DKD: The eGFR, not the serum creatinine level, should guide treatment.⁴³ Metformin can be used safely in patients with (1) an eGFR of < 60 mL/min/1.73 m² and (2) an eGFR of 30 mL/min/1.73 m² with close monitoring. Metformin should not be initiated if the eGFR is < 45 mL/min/1.73 m².⁴³ 

Antidiabetes medications with direct effect on the kidney

Several antidiabetes medications have a direct effect on the kidney apart from their effect on the blood glucose level.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to reduce albuminuria and slow the decrease of eGFR independent of glycemic control. In addition, SGLT2 inhibitors have also been shown to have cardiovascular benefits in patients with DKD.^44,45 

Glucagon-like peptide 1 (GLP-1) receptor agonists have been shown to delay and decrease the progression of DKD.^46-48 Also, similar to what is seen with SGLT2 inhibitors, GLP-1 agonists have demonstrable cardiovascular benefit in patients with DKD.^46,48

Continue to: Dyslipidemia and DKD

 

 

Dyslipidemia and DKD

Because the risk of CVD is increased in patients with DKD, addressing other modifiable risk factors, including dyslipidemia, is recommended in these patients. Patients with diabetes and stages 1 to 4 DKD should be treated with a high-intensity statin or a combination of a statin and ezetimibe.^49,50

Tight glycemic control in T1D and T2D can delay the onset, and slow the progression, of albuminuria and a decline in the eGFR.

If a patient is taking a statin and starting dialysis, it’s important to discuss with him or her whether to continue the statin, based on perceived benefits and risks. It is not recommended that statins be initiated in patients on dialysis unless there is a specific cardiovascular indication for doing so. Risk reduction with a statin has been shown to be significantly less in dialysis patients than in patients who are not being treated with dialysis.⁴⁹

Complications of CKD

Anemia is a common complication of CKD. KDIGO recommends measuring the ­hemoglobin concentration annually in DKD stage 3 patients without anemia; at least every 6 months in stage 4 patients; and at least every 3 months in stage 5. DKD patients with anemia should have additional laboratory testing: the absolute reticulocyte count, serum ferritin, serum transferrin saturation, vitamin B12, and folate.⁵¹

Mineral and bone disorder should be screened for in patients with DKD. TABLE 2⁵² outlines when clinical laboratory tests should be ordered to assess for mineral bone disease.

When to refer to a nephrologist

Refer patients with stage 4 or 5 CKD (eGFR, ≤ 30 mL/min/1.73 m²) to a nephrologist for discussion of kidney replacement therapy.⁶ Patients with stage 3a CKD and severely increased albuminuria or with stage 3b CKD and moderately or severely increased albuminuria should also be referred to a nephrologist for intervention to delay disease progression.

Continue to: Identifying the need for early referral...

Nutritional control is important in DKD: A lowsodium diet can slow progression of DKD, and a low-potassium diet can prevent hyperkalemia in end-stage renal disease.

Identifying the need for early referral to a nephrologist has been shown to reduce the cost, and improve the quality, of care.⁵³ Other indications for earlier referral include uncertainty about the etiology of renal disease, persistent or severe albuminuria, persistent hematuria, a rapid decline in eGFR, and acute kidney injury. Additionally, referral at an earlier stage of DKD might be needed to assist with complications associated with DKD, such as anemia, secondary hyperparathyroidism, mineral and bone disorder, resistant hypertension, fluid overload, and electrolyte disturbances.⁶

ACKNOWLEDGEMENT
The authors thank Colleen Colbert, PhD, and Iqbal Ahmad, PhD, for their review and critique of the manuscript of this article. They also thank Christopher Babiuch, MD, for his guidance in the preparation of the manuscript.

CORRESPONDENCE
Faraz Ahmad, MD, MPH, Care Point East Family Medicine, 543 Taylor Avenue, 2nd floor, Columbus, OH 43203; faraz. ahmad@osumc.edu.