Sepsis is the number one killer in U.S. hospitals. About one in three patient deaths in a hospital are attributable to sepsis, according to the Centers for Disease Control and Prevention, and it is the leading cause of readmission for U.S. hospitals as well.

Patricia Kritek MD, EdM, of the division of pulmonary, critical care, and sleep medicine at the University of Washington, Seattle, hopes to bring attendees up to speed on sepsis with her presentation, “Put SIRS on the SOFA and Let’s get Septic! Update in Sepsis” at HM20 Virtual.

Each year, approximately 1.7 million American adults develop sepsis, and nearly 270,000 Americans will die from sepsis annually. Although sepsis disproportionately affects young children, older adults, patients with chronic diseases, and those with a weak immune system, the disease can affect anyone.

With that reputation, sepsis is on the forefront of hospitalists’ minds. Hospitalists are traditionally well versed in current sepsis guidelines, but time to treatment is paramount, and it can be difficult to stay up to date on the latest studies in the field. In addition, some newer, controversial treatments have emerged recently, and there is currently a debate regarding the efficacy of these treatments in the care of patients with sepsis.

The title of Dr. Kritek’s presentation hints at the theme: Hospitalists may have learned the systemic inflammatory response syndrome (SIRS) criteria for diagnosing sepsis, but the Sequential Organ Failure Assessment (SOFA) Score developed by the Third International Consensus Definitions for Sepsis and Septic Shock – previously known as the sepsis-related organ failure assessment score – has been the new method since 2016 to assess the clinical outcomes of patients with sepsis.

The quick SOFA score (qSOFA), developed by the Society of Critical Care and European Society of Intensive Care Medicine in 2016 guidelines, further helps hospitalists and other hospital physicians identify those patients at highest risk of mortality from sepsis outside an intensive care unit setting.

Dr. Kritek, who is a board-certified critical care medicine physician, has previously presented this talk at the Society for Hospital Medicine Annual Conference in the past. This year the presentation will include a number of studies that examine what role vitamin C, thiamine, and glucocorticoids have in treating patients with sepsis, she said. For example, it is thought that parenteral administration of vitamin C could raise plasma levels and reduce multiorgan failure. Thiamine could be useful in sepsis treatment because of its role in glucose metabolism and lactate production, while glucocorticoids could help improve the mortality rate of patients with sepsis.

While Dr. Kritek said she is not going to be advocating for the benefit of vitamin C and thiamine during the session, “this is an area of ongoing debate, and we will walk through the most recent data to try to make sense of it,” she said.

Dr. Kritek noted that the role of balanced crystalloids in resuscitation will be discussed versus when to use saline, as well as the potential of new vasopressors for the treatment of septic shock.

“Our goal will be to integrate the most recent literature into day-to-day practice,” Dr. Kritek said.Dr. Kritek reports no conflicts of interest.

“Put SIRS on the SOFA and Let’s get Septic! Update in Sepsis”

Sepsis is the number one killer in U.S. hospitals. About one in three patient deaths in a hospital are attributable to sepsis, according to the Centers for Disease Control and Prevention, and it is the leading cause of readmission for U.S. hospitals as well.

Patricia Kritek MD, EdM, of the division of pulmonary, critical care, and sleep medicine at the University of Washington, Seattle, hopes to bring attendees up to speed on sepsis with her presentation, “Put SIRS on the SOFA and Let’s get Septic! Update in Sepsis” at HM20 Virtual.

Each year, approximately 1.7 million American adults develop sepsis, and nearly 270,000 Americans will die from sepsis annually. Although sepsis disproportionately affects young children, older adults, patients with chronic diseases, and those with a weak immune system, the disease can affect anyone.

With that reputation, sepsis is on the forefront of hospitalists’ minds. Hospitalists are traditionally well versed in current sepsis guidelines, but time to treatment is paramount, and it can be difficult to stay up to date on the latest studies in the field. In addition, some newer, controversial treatments have emerged recently, and there is currently a debate regarding the efficacy of these treatments in the care of patients with sepsis.

The title of Dr. Kritek’s presentation hints at the theme: Hospitalists may have learned the systemic inflammatory response syndrome (SIRS) criteria for diagnosing sepsis, but the Sequential Organ Failure Assessment (SOFA) Score developed by the Third International Consensus Definitions for Sepsis and Septic Shock – previously known as the sepsis-related organ failure assessment score – has been the new method since 2016 to assess the clinical outcomes of patients with sepsis.

The quick SOFA score (qSOFA), developed by the Society of Critical Care and European Society of Intensive Care Medicine in 2016 guidelines, further helps hospitalists and other hospital physicians identify those patients at highest risk of mortality from sepsis outside an intensive care unit setting.

Dr. Kritek, who is a board-certified critical care medicine physician, has previously presented this talk at the Society for Hospital Medicine Annual Conference in the past. This year the presentation will include a number of studies that examine what role vitamin C, thiamine, and glucocorticoids have in treating patients with sepsis, she said. For example, it is thought that parenteral administration of vitamin C could raise plasma levels and reduce multiorgan failure. Thiamine could be useful in sepsis treatment because of its role in glucose metabolism and lactate production, while glucocorticoids could help improve the mortality rate of patients with sepsis.

While Dr. Kritek said she is not going to be advocating for the benefit of vitamin C and thiamine during the session, “this is an area of ongoing debate, and we will walk through the most recent data to try to make sense of it,” she said.

Dr. Kritek noted that the role of balanced crystalloids in resuscitation will be discussed versus when to use saline, as well as the potential of new vasopressors for the treatment of septic shock.

“Our goal will be to integrate the most recent literature into day-to-day practice,” Dr. Kritek said.Dr. Kritek reports no conflicts of interest.

“Put SIRS on the SOFA and Let’s get Septic! Update in Sepsis”

Sepsis is the number one killer in U.S. hospitals. About one in three patient deaths in a hospital are attributable to sepsis, according to the Centers for Disease Control and Prevention, and it is the leading cause of readmission for U.S. hospitals as well.

Patricia Kritek MD, EdM, of the division of pulmonary, critical care, and sleep medicine at the University of Washington, Seattle, hopes to bring attendees up to speed on sepsis with her presentation, “Put SIRS on the SOFA and Let’s get Septic! Update in Sepsis” at HM20 Virtual.

Each year, approximately 1.7 million American adults develop sepsis, and nearly 270,000 Americans will die from sepsis annually. Although sepsis disproportionately affects young children, older adults, patients with chronic diseases, and those with a weak immune system, the disease can affect anyone.

With that reputation, sepsis is on the forefront of hospitalists’ minds. Hospitalists are traditionally well versed in current sepsis guidelines, but time to treatment is paramount, and it can be difficult to stay up to date on the latest studies in the field. In addition, some newer, controversial treatments have emerged recently, and there is currently a debate regarding the efficacy of these treatments in the care of patients with sepsis.

The title of Dr. Kritek’s presentation hints at the theme: Hospitalists may have learned the systemic inflammatory response syndrome (SIRS) criteria for diagnosing sepsis, but the Sequential Organ Failure Assessment (SOFA) Score developed by the Third International Consensus Definitions for Sepsis and Septic Shock – previously known as the sepsis-related organ failure assessment score – has been the new method since 2016 to assess the clinical outcomes of patients with sepsis.

The quick SOFA score (qSOFA), developed by the Society of Critical Care and European Society of Intensive Care Medicine in 2016 guidelines, further helps hospitalists and other hospital physicians identify those patients at highest risk of mortality from sepsis outside an intensive care unit setting.

Dr. Kritek, who is a board-certified critical care medicine physician, has previously presented this talk at the Society for Hospital Medicine Annual Conference in the past. This year the presentation will include a number of studies that examine what role vitamin C, thiamine, and glucocorticoids have in treating patients with sepsis, she said. For example, it is thought that parenteral administration of vitamin C could raise plasma levels and reduce multiorgan failure. Thiamine could be useful in sepsis treatment because of its role in glucose metabolism and lactate production, while glucocorticoids could help improve the mortality rate of patients with sepsis.

While Dr. Kritek said she is not going to be advocating for the benefit of vitamin C and thiamine during the session, “this is an area of ongoing debate, and we will walk through the most recent data to try to make sense of it,” she said.

Dr. Kritek noted that the role of balanced crystalloids in resuscitation will be discussed versus when to use saline, as well as the potential of new vasopressors for the treatment of septic shock.

“Our goal will be to integrate the most recent literature into day-to-day practice,” Dr. Kritek said.Dr. Kritek reports no conflicts of interest.

“Put SIRS on the SOFA and Let’s get Septic! Update in Sepsis”

If US pharmacies were permitted to dispense methadone for opioid use disorder (OUD) it would improve national access to treatment and save costs, new research suggests.

Under current federal regulations, only opioid treatment programs (OTPs) are permitted to dispense methadone maintenance treatment. This stands in sharp contrast to how methadone is dispensed in Canada, Australia, and the United Kingdom, where patients can obtain daily doses of methadone maintenance from community pharmacies.

“It’s challenging for patients in many parts of the US to access methadone treatment,” Robert Kleinman, MD, of Stanford University School of Medicine, Stanford, California, said in a JAMA Psychiatry podcast.

“It’s important for policymakers to consider strategies that enhance access to methadone maintenance treatment, in that it’s associated with large reductions in mortality from opioid use disorder. One possibility is to use pharmacies as dispensing sites,” said Kleinman.

The study was published online July 15 in JAMA Psychiatry.

An Hour vs 10 Minutes

Kleinman examined how pharmacy-based dispensing would affect drive times to the nearest OTP for the general US population. The analysis included all 1682 OTP locations, 69,475 unique pharmacy locations, and 72,443 census tracts.

The average drive time to OTPs in the US is 20.4 minutes vs a drive time of 4.5 minutes to pharmacies.

Driving times to OTPs are particularly long in nonmetropolitan counties while pharmacies remain “relatively easily accessible” in nonmetropolitan counties, he said.

In “micropolitan” counties, for example, the drive time to OTPs was 48.4 minutes vs 7 minutes to pharmacies. In the most rural counties, the drive time to OTPs is 60.9 minutes vs 9.1 minutes to pharmacies.

“This suggests that pharmacy-based dispensing has the potential to reduce urban or rural inequities, and access to methadone treatment,” Kleinman said.

In a mileage cost analysis, Kleinman determined that the average cost of one-way trip to an OTP in the US is $3.12 compared with 45 cents to a pharmacy. In the most rural counties, the average cost one-way is $11.10 vs $1.27 to a pharmacy.

Kleinman says decreasing drive times, distance, and costs for patients seeking methadone treatment by allowing pharmacies to dispense the medication may help achieve several public health goals.

“Patients dissuaded from obtaining treatment because of extended travel, particularly patients with disabilities, unreliable access to transportation, or from rural regions, would have reduced barriers to care. Quality of life may be increased for the more than 380,000 individuals currently receiving methadone treatment if less time is spent commuting,” he writes.

Time for Change

The authors of an accompanying editorial, say the “regulatory burden” on methadone provision in the US “effectively prohibits the integration of methadone prescribing into primary care, even in rural communities where there may exist no specialty substance use treatment options.”

However, federal and state agencies are starting to take action to expand geographic access to methadone treatment, note Paul Joudrey, MD, MPH, and coauthors from Yale School of Medicine, New Haven, Connecticut.

The US Drug Enforcement Administration has proposed allowing mobile methadone units, and Ohio and Kentucky have passed laws to allow greater use of federally qualified health centers and other facilities for methadone dispensing.

“While these policies are welcomed, the results here by Kleinman and others suggest they fall short of needed expansion if patients’ rights to evidence-based care for OUD are to be ensured. Importantly, even with broad adoption of mobile or pharmacy-based dispensing, patients would still face a long drive time to a central OTP before starting methadone,” Joudrey and colleagues write.

In their view, the only way to address this barrier is to modify federal law, and this “should be urgently pursued in the context of the ongoing overdose epidemic. It is time for policies that truly support methadone treatment for OUD as opposed to focusing on diversion.”

This article first appeared on Medscape.com.

If US pharmacies were permitted to dispense methadone for opioid use disorder (OUD) it would improve national access to treatment and save costs, new research suggests.

Under current federal regulations, only opioid treatment programs (OTPs) are permitted to dispense methadone maintenance treatment. This stands in sharp contrast to how methadone is dispensed in Canada, Australia, and the United Kingdom, where patients can obtain daily doses of methadone maintenance from community pharmacies.

“It’s challenging for patients in many parts of the US to access methadone treatment,” Robert Kleinman, MD, of Stanford University School of Medicine, Stanford, California, said in a JAMA Psychiatry podcast.

“It’s important for policymakers to consider strategies that enhance access to methadone maintenance treatment, in that it’s associated with large reductions in mortality from opioid use disorder. One possibility is to use pharmacies as dispensing sites,” said Kleinman.

The study was published online July 15 in JAMA Psychiatry.

An Hour vs 10 Minutes

Kleinman examined how pharmacy-based dispensing would affect drive times to the nearest OTP for the general US population. The analysis included all 1682 OTP locations, 69,475 unique pharmacy locations, and 72,443 census tracts.

The average drive time to OTPs in the US is 20.4 minutes vs a drive time of 4.5 minutes to pharmacies.

Driving times to OTPs are particularly long in nonmetropolitan counties while pharmacies remain “relatively easily accessible” in nonmetropolitan counties, he said.

In “micropolitan” counties, for example, the drive time to OTPs was 48.4 minutes vs 7 minutes to pharmacies. In the most rural counties, the drive time to OTPs is 60.9 minutes vs 9.1 minutes to pharmacies.

“This suggests that pharmacy-based dispensing has the potential to reduce urban or rural inequities, and access to methadone treatment,” Kleinman said.

In a mileage cost analysis, Kleinman determined that the average cost of one-way trip to an OTP in the US is $3.12 compared with 45 cents to a pharmacy. In the most rural counties, the average cost one-way is $11.10 vs $1.27 to a pharmacy.

Kleinman says decreasing drive times, distance, and costs for patients seeking methadone treatment by allowing pharmacies to dispense the medication may help achieve several public health goals.

“Patients dissuaded from obtaining treatment because of extended travel, particularly patients with disabilities, unreliable access to transportation, or from rural regions, would have reduced barriers to care. Quality of life may be increased for the more than 380,000 individuals currently receiving methadone treatment if less time is spent commuting,” he writes.

Time for Change

The authors of an accompanying editorial, say the “regulatory burden” on methadone provision in the US “effectively prohibits the integration of methadone prescribing into primary care, even in rural communities where there may exist no specialty substance use treatment options.”

However, federal and state agencies are starting to take action to expand geographic access to methadone treatment, note Paul Joudrey, MD, MPH, and coauthors from Yale School of Medicine, New Haven, Connecticut.

The US Drug Enforcement Administration has proposed allowing mobile methadone units, and Ohio and Kentucky have passed laws to allow greater use of federally qualified health centers and other facilities for methadone dispensing.

“While these policies are welcomed, the results here by Kleinman and others suggest they fall short of needed expansion if patients’ rights to evidence-based care for OUD are to be ensured. Importantly, even with broad adoption of mobile or pharmacy-based dispensing, patients would still face a long drive time to a central OTP before starting methadone,” Joudrey and colleagues write.

In their view, the only way to address this barrier is to modify federal law, and this “should be urgently pursued in the context of the ongoing overdose epidemic. It is time for policies that truly support methadone treatment for OUD as opposed to focusing on diversion.”

This article first appeared on Medscape.com.

If US pharmacies were permitted to dispense methadone for opioid use disorder (OUD) it would improve national access to treatment and save costs, new research suggests.

Under current federal regulations, only opioid treatment programs (OTPs) are permitted to dispense methadone maintenance treatment. This stands in sharp contrast to how methadone is dispensed in Canada, Australia, and the United Kingdom, where patients can obtain daily doses of methadone maintenance from community pharmacies.

“It’s challenging for patients in many parts of the US to access methadone treatment,” Robert Kleinman, MD, of Stanford University School of Medicine, Stanford, California, said in a JAMA Psychiatry podcast.

“It’s important for policymakers to consider strategies that enhance access to methadone maintenance treatment, in that it’s associated with large reductions in mortality from opioid use disorder. One possibility is to use pharmacies as dispensing sites,” said Kleinman.

The study was published online July 15 in JAMA Psychiatry.

An Hour vs 10 Minutes

Kleinman examined how pharmacy-based dispensing would affect drive times to the nearest OTP for the general US population. The analysis included all 1682 OTP locations, 69,475 unique pharmacy locations, and 72,443 census tracts.

The average drive time to OTPs in the US is 20.4 minutes vs a drive time of 4.5 minutes to pharmacies.

Driving times to OTPs are particularly long in nonmetropolitan counties while pharmacies remain “relatively easily accessible” in nonmetropolitan counties, he said.

In “micropolitan” counties, for example, the drive time to OTPs was 48.4 minutes vs 7 minutes to pharmacies. In the most rural counties, the drive time to OTPs is 60.9 minutes vs 9.1 minutes to pharmacies.

“This suggests that pharmacy-based dispensing has the potential to reduce urban or rural inequities, and access to methadone treatment,” Kleinman said.

In a mileage cost analysis, Kleinman determined that the average cost of one-way trip to an OTP in the US is $3.12 compared with 45 cents to a pharmacy. In the most rural counties, the average cost one-way is $11.10 vs $1.27 to a pharmacy.

Kleinman says decreasing drive times, distance, and costs for patients seeking methadone treatment by allowing pharmacies to dispense the medication may help achieve several public health goals.

“Patients dissuaded from obtaining treatment because of extended travel, particularly patients with disabilities, unreliable access to transportation, or from rural regions, would have reduced barriers to care. Quality of life may be increased for the more than 380,000 individuals currently receiving methadone treatment if less time is spent commuting,” he writes.

Time for Change

The authors of an accompanying editorial, say the “regulatory burden” on methadone provision in the US “effectively prohibits the integration of methadone prescribing into primary care, even in rural communities where there may exist no specialty substance use treatment options.”

However, federal and state agencies are starting to take action to expand geographic access to methadone treatment, note Paul Joudrey, MD, MPH, and coauthors from Yale School of Medicine, New Haven, Connecticut.

The US Drug Enforcement Administration has proposed allowing mobile methadone units, and Ohio and Kentucky have passed laws to allow greater use of federally qualified health centers and other facilities for methadone dispensing.

“While these policies are welcomed, the results here by Kleinman and others suggest they fall short of needed expansion if patients’ rights to evidence-based care for OUD are to be ensured. Importantly, even with broad adoption of mobile or pharmacy-based dispensing, patients would still face a long drive time to a central OTP before starting methadone,” Joudrey and colleagues write.

In their view, the only way to address this barrier is to modify federal law, and this “should be urgently pursued in the context of the ongoing overdose epidemic. It is time for policies that truly support methadone treatment for OUD as opposed to focusing on diversion.”

This article first appeared on Medscape.com.

CASE

Marcelo G* is a 46-year-old man who presented to our family medicine clinic with a complex medical history including end-stage renal disease (ESRD) and hemodialysis, chronic anemia, peripheral vascular disease, venous thromboembolism and anticoagulation, major depressive disorder, osteoarthritis, and lumbosacral radiculopathy. His current medications included vitamin B complex, cholecalciferol, atorvastatin, warfarin, acetaminophen, diclofenac gel, and capsaicin cream. Mr. G reported bothersome bilateral knee and back pain despite physical therapy and consistent use of his current medications in addition to occasional intra-articular glucocorticoid injections. He mentioned that he had benefited in the past from intermittent opioid use.

How would you manage this patient’s care?

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

In 2013, an estimated 191 million prescriptions for ­opioids were written by health care providers, which is the equivalent of all adults living in the United States having their own opioid prescription.¹ This large expansion in opioid prescribing and use has also led to a rise in opioid overdose deaths, whether from prescribed or illicit use.¹ The Centers for Disease Control and Prevention (CDC) points out that each day, approximately 128 Americans die from an opioid overdose.¹ Deaths that occur from opioid overdose often involve the prescribed opioids methadone, oxycodone, and hydrocodone, the illicit opioid heroin, and, of particular concern, prescription and illicit fentanyl.¹

IMAGE: © JOE GORMAN

Family physicians write more opioid prescriptions than any other specialty, and they are therefore uniquely positioned to protect patients, improve the quality of their care, and ultimately produce a meaningful public health impact.

The extent of this problem has sparked the development of health safety initiatives and research efforts. Through production quotas, the US Drug Enforcement Administration (DEA) reduced the number of opioids produced across all schedule I and schedule II lists in 2017 by as much as 25%.² The DEA again reduced the amounts produced in 2018.³ For 2020, the DEA has determined that the production quotas and assessment of annual needs are sufficient.⁴

The CDC has also promoted access to naloxone and prevention initiatives; pharmacies in some states have standing orders for naloxone, and medical personnel and law enforcement now carry it.^1,5 Finally, new research has identified risk factors that influence one’s potential for addiction, such as mental illness, history of substance and alcohol abuse, and a low income.⁶ Interestingly, while numerous initiatives and strategies have been implemented across health systems, there is little evidence that demonstrates how implementation of safe prescribing strategies has affected overall patient safety and avoidance of opioid-related harms.

Nevertheless, concerns related to ­opioids are especially important for primary care ­providers, who manage many patients with acute and chronic diseases and disorders that require pain control.⁷ Family physicians write more opioid prescriptions than any ­other specialty,⁸ and they are therefore uniquely positioned to protect patients, improve the quality of their care, and ultimately produce a meaningful public health impact. This article provides a guide to safe opioid prescribing.

Continue to: Use the patient interview to ensure that Tx aligns with patient goals

 

 

Use the patient interview to ensure that Tx aligns with patient goals

For patients presenting with chronic pain, conduct a complete general history and physical examination that includes a review of available records; a medical, surgical, social, family, medication, and allergy history; a review of systems; and documentation of any psychiatric comorbidities (ie, depression, anxiety, psychiatric disorders, personality traits). Inquiries about social history and current medications should explore the possibility of previous and current substance use and misuse.

While causes of pain can be assessed through physical examination and diagnostic tests, the patient interview is an invaluable source of information. No single means of assessment has consistently demonstrated superiority over another in measuring pain, and numerous standard assessment tools are available (TABLE 1^9-13).¹⁴ Unidimensional tools are often easy and quick ways to assess pain intensity. Multidimensional tools, although more time intensive, are designed to gather more subjective information about the patient’s pain. Finally, use an instrument such as the 9-item Patient Health Questionnaire (PHQ-9) to screen patients for psychological distress.^15,16

Use state prescription drug monitoring programs and urine drug testing to confirm patient compliance.

Provide an environment for patients to openly discuss their experiences, expectations, preferences, fears, and coping efforts, as well as the impact that pain has had on their lives.^17,18 Without this foundational understanding, medical treatment may work against the patient’s goals. An empathic approach allows for effective communication, shared decision making, and ultimately, an avenue for individualized therapy.

Balancing treatment with risk mitigation

The challenge of managing chronic pain is to balance treating the patient with the basic principle of nonmaleficence (primum non nocere: “first, do no harm”). The literature has shown that risk factors such as a family history of substance abuse or sexual abuse, younger age, and psychological disease may be linked to greater risk for opioid misuse.^19,20 However, despite the many risk-screening tools available, no single instrument has reliably and accurately predicted those at higher propensity for prescription addiction. In fact, risk-screening tools as a whole remain unregulated by the US Food and Drug Administration (FDA) and other authorities.²¹ Still, screening tools provide useful information as one component of the risk-mitigation process.

Screening tools. The tools most commonly used clinically to stratify risk prior to prescribing opioids are the 5-item Opioid Risk Tool (ORT),²² the revised 24-item Screener and Opioid Assessment for Patients with Pain (SOAPP-R),²³ which are patient self-administered assessments, and the 7-item clinician-administered DIRE (Diagnosis, Intractability, Risk, Efficacy).²⁴ Given the subtle differences in criteria and the time required for each of these risk assessments, we recommend choosing one based on site-specific resources and overall clinician comfort.²⁵ Risk stratification helps to determine the optimal frequency and intensity of monitoring, not necessarily to deny care to “high-risk” patients.

Continue to: In fact, just as the "universal precautions"...

In fact, just as the “universal precautions” approach has been applied to infection control, many have suggested using a similar approach to pain management. Risk screening should never be misunderstood as an attempt to diminish or undermine the patient’s burden of pain. By routinely conducting thorough and respectful inquiries of risk factors for all patients, clinicians can reduce stigma, improve care, and contain overall risk.^26,27

Monitoring programs and patient agreements. In addition to risk-screening tools, the CDC recommends using state prescription drug monitoring programs (PDMP) and urine drug testing (UDT) data to confirm the use of prescribed and illicit substances.²⁸ All 50 states have implemented PDMPs.²⁹ Consider incorporating these components into controlled-substance agreements, which ultimately aim to promote safety and trust between patients and providers. Of course, such agreements do not eliminate all risks associated with opioid prescribing, nor do they guarantee the absence of adverse outcomes. However, when used correctly, they can provide safeguards to reduce misuse and abuse. They also have the potential to preserve the patient-provider relationship, as opposed to providers cursorily refusing to prescribe opioids altogether. The term “controlled-substance agreement” is preferable to “pain contract” or “narcotic contract” as the latter 2 terms may feel stigmatizing and threatening.³⁰

Risk evaluation and mitigation strategy (REMS). In an effort to ensure that benefits of opioid analgesics continue to outweigh the risks, the FDA approved the extended-release (ER)/long-acting (LA) opioid analgesics shared system REMS. Under this REMS, a consortium of ER/LA opioid manufacturers is mandated to provide prescriber education in the form of accredited continuing education and patient educational materials, available at https://opioidanalgesicrems.com/RpcUI/home.u.

CASE

After reviewing Mr. G’s chart and conducting a history, we learned that his bilateral knee osteoarthritis was atraumatic and likely due to overuse—although possibly affected by major trauma in a motor vehicle accident 5 years earlier. Imaging also revealed multilevel disc degeneration contributing to his radicular back pain, which seemed to be worse on days after working as a caterer. Poor lifting form at work may have contributed to his pain. Nevertheless, he had been consistent with medical follow-up and denied current or past use of illicit substances. Per the numeric rating scale (NRS), he reported 8 out of 10 pain in his knees and 6 out of 10 in his back. In addition to obtaining a PHQ-9 score of 4, we conducted a DIRE assessment and obtained a score of 19 out of a possible 21, indicating that he may be a good candidate for long-term opioid analgesia.

Criteria for prescribing opioids and for guiding treatment goals

Prescribing an opioid requires establishing a medical necessity based on 3 criteria:³¹

• pain of moderate-to-severe degree
• a physical diagnosis or suspected organic problem
• documented treatment failure of a noncontrolled substance, adjuvant agents, physician-ordered physical therapy, structured exercise program, and interventional techniques.

Continue to: Treatment goals should be established...

Treatment goals should be established and understood by the prescriber and patient prior to initiation of opioids.²⁸ Overarching treatment goals for all opioids prescribed are pain relief (but not necessarily a focus on pain scores), improvement in functional activity, and minimization of adverse effects, with the latter 2 goals taking precedence.³¹ To assess outcomes, formally measure progress toward goals from baseline evaluations. This can be achieved through repeated use of validated tools such as those mentioned earlier, or may be more broadly considered as progress toward employment status or increasing participation in activities.³¹ All pain management plans involving opioids should include continued efforts with nonpharmacologic therapy (eg, exercise therapy, weight loss, behavioral training) and nonopioid pharmacologic therapy (eg, nonsteroidal anti-­inflammatory drugs, tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, anticonvulsants).²⁸

Have an “exit strategy.” As part of goal setting, also consider how therapy will be discontinued if benefits do not outweigh the risks of harm.²⁸ Weigh functional status gains against adverse opioid consequences using the PEG scale (pain, enjoyment of life, and general activity) (TABLE 2³²).³³ Improvements of 30% from baseline have been deemed clinically meaningful by some,³² but not all benefits will be easy to quantify. At the start of treatment dialogue, use the term “therapeutic trial” instead of ”treatment plan” to more effectively convey that opioids will be continued only if safe and effective, and will be prescribed at the lowest effective dose as one component of the multimodal approach to pain.³⁰

Initiation of treatment: Opioid selection and dosing

When initiating opioid therapy, prescribe an immediate-release, short-acting agent instead of an ER/LA formulation.²⁸

For moderate pain, first consider tramadol, codeine, tapentadol, or hydrocodone.³¹ Second-line agents for moderate pain are hydrocodone or oxycodone.³¹

For severe pain, first-line agents include hydrocodone, oxycodone, hydromorphone, or morphine.³¹ Second-line agents for severe pain are fentanyl and, with careful supervision or referral to a pain specialist, methadone or buprenorphine.³¹

Continue to: Of special note...

Of special note, methadone should not be the first choice for ER/LA opioid due to its unique long half-life and ability to prolong the QT interval.³⁴ Only clinicians familiar with its use should prescribe methadone, while referring to the drug’s clinical practice guideline for further advice.

At the start, prescribe the lowest effective dosage (referring to the product labeling for guidance) and calculate total daily dose in terms of morphine milligram equivalents (MME) (TABLE 3^35-37).²⁸ Exercise caution when considering opioids for patients with respiratory sleep disorders and for patients ≥ 65 years due to altered pharmacokinetics in the elderly population.³⁸ Also make dose adjustments for renal and hepatic insufficiency (TABLE 4³⁵).

All pain management involving opioids should include nonpharmacologic components, such as exercise and weight loss.

Doses between 20 to 50 MME/d are considered relatively low dosages.²⁸ Be cautious when prescribing an opioid at any dosage, and reassess evidence of individual benefits and risks before increasing the dosage to ≥ 50 MME/d.²⁸ Regard a dosage of 90 MME/d as maximal.²⁸ While there is no analgesic ceiling, doses greater than 90 MME/d are associated with risk for overdose and should prompt referral to a pain specialist.³¹ Veterans Administration guidelines cite strong evidence that risk for overdose and death significantly increases at a range of 20 to 50 MME/d.³³ Daily doses exceeding 90 MME/d should be documented with rational justification.²⁸

CASE

Noncontrolled medications are preferred in the treatment of chronic pain. However, the utility of adjuvant options such as NSAIDs, duloxetine, or gabapentin were limited in Mr. G’s case due to his ESRD. Calcium channel α2-δ ligands may have been effective in reducing symptoms of neuropathic pain but would have had limited efficacy against osteoarthritis. Based on his low risk for opioid misuse, we decided to start Mr. G on oxycodone 2.5 mg PO, every 6 hours as needed for moderate-to-severe pain, and to follow up in 1 month. We also explained proper lifting form to him and encouraged him to continue with physical therapy.

Deciding to continue therapy with opioids

There is a lack of convincing evidence that opioid use beyond 6 months improves quality of life; patients do not report a significant reduction in pain beyond this time.²⁸ Thus, a repeat evaluation of continued medical necessity is essential before deciding in favor of ongoing, long-term treatment with opioids. Continue prescribing opioids only if there is meaningful pain relief and improved function that outweighs the harms that may be expected for a given patient.³¹ With all patients, consider prescribing naloxone to accompany dispensed opioid prescriptions.²⁸ This is particularly important for those at risk for misuse (history of overdose, history of substance use disorder, dosages ≥ 50 MME/d, or concurrent benzodiazepine use). Resources for prescribing naloxone in primary care settings can be found through Prescribe to Prevent at http://prescribetoprevent.org. Due to the established risk of overdose, avoid, if possible, concomitant prescriptions of benzodiazepines and opioids.³¹

Continue to: Follow-up and monitoring

 

 

Follow-up and monitoring

Responsiveness to opioids varies greatly among individuals.^38,39 An opioid that leads to a therapeutic analgesic effect in one patient may cause adverse events or toxicity in another. Periodically reassess the appropriateness of chronic opioid therapy and modify treatment based on its ability to meet therapeutic goals. While practice behaviors and clinic policies vary across institutions, risk stratification can provide guidance on the frequency and intensity of follow-up and monitoring. Kaye et al²¹ describe a triage system in which low-risk patients may be managed by a primary care provider with routine follow-up and reassessment every 3 months.²¹ Moderate-risk patients may warrant additional management by specialists and a monthly follow-up. High-risk patients may need referrals to interdisciplinary pain centers or addiction specialists.²¹

Along these lines, the CDC recommends conducting a PDMP review and UDT before initiating therapy, followed by a periodic PDMP (every 1-3 months) and a UDT at least annually. Keep in mind, providers should follow their state-specific regulations, as monitoring requirements may vary. In addition, clinicians should always be alert to adverse reactions (TABLE 4³⁵) and sudden behavior changes such as respiratory depression, nausea, constipation, pruritus, cognitive impairment, falls, motor vehicle accidents, and aberrant behaviors. Under these circumstances, consider a dose reduction and, in certain cases, discontinuation.

Additionally, in cases of pain unresponsive to escalating opioid doses, include opioid-induced hyperalgesia (OIH) in the differential. Dose reductions, opioid rotations, and office-based detoxifications are all options for the treatment of OIH.⁴⁰ Assessment of pain and function can be accomplished using the PEG scale (TABLE 2).³²

CASE

Two weeks into Mr. G’s initial regimen, he called to report no change in pain or functional status. We increased his dose to 5 mg PO every 6 hours as needed. At his 1-month follow-up appointment, he reported his pain as 6/10 and no adverse effects. We again increased his dose to 10 mg PO every 6 hours as needed, with follow-up in another month.

Discontinuation and tapering of opioids

Indications for discontinuing opioids are patient request, resolution of pain, doses ≥ 90 MME/d (in which case a pain specialist should be consulted), inadequate response, untoward adverse effects, and abuse and misuse.^1,31,41 However, providers may also face the challenge of working with patients for whom the benefit of opioid therapy is uncertain but who do not have an absolute contraindication. Guidance on this matter may be found in a 2017 systematic review of studies on reducing or discontinuing long-term opioid therapy.⁴² Although evidence on the whole was low quality, it showed that tapering or discontinuing opioids may actually reduce pain and improve function and quality of life.

Continue to: When working with a patient to taper treatment

When working with a patient to taper treatment, consider using a multidisciplinary approach. Also, assess the patient’s pain level and perception of needs for opioids, make clear the substantial effort that will be asked of the patient, and agree on coping strategies the patient can use to manage the taper.^31,43 While the evidence does not appear to support one tapering regimen over another, we can offer some recommendations on ways to individualize a tapering regimen (TABLE 5).^{1,31,41,43,44}

General recommendations. Gradually reduce the original MME dose by 5% to 10% every week to every 4 weeks, with frequent follow-up and adjustments as needed based on the individual’s response.^1,31,41,43 In the event that the patient does not tolerate this dose-reduction schedule, tapering can be slowed further.³¹ Avoid abrupt discontinuation.³³ Opioid abstinence syndrome, a myriad of symptoms caused by deprivation of opioids in physiologically dependent individuals, ­although rare, can occur during tapering and can be managed with clonidine 0.1 to 0.2 mg orally every 6 hours or transdermal clonidine patch 0.1 mg/24 hours weekly during the taper.³¹

Methadone should not be the first choice for an extended-release/long-acting opioid due to its long half-life and ability to prolong the QT interval.

Tapering of long-term opioid treatment is not without risk. Immediate risks include withdrawal syndrome, hyperalgesia, and dropout, while ongoing issues are potential relapse, problems in increasing and maintaining function, and medicolegal implications.⁴³ Withdrawal symptoms begin 2 to 3 half-lives after the last dose of opioid, and resolution varies depending on the duration of use, the most recent dose, and speed of tapering.⁴³ In general, a patient needs 20% to 25% of the previous day’s dose to prevent withdrawal symptoms.³¹ Increased pain appears to be a brief, time-limited occurance.⁴³ Dropout and relapse tend to be attributed to patient factors such as depressive symptoms and higher pain scores at initiation of the taper.⁴³ Low pain at the end of tapering has been shown to predict long-term abstinence from opioids.⁴³

CASE

Two months into his oxycodone regimen, Mr. G reported improved functional status at his catering job and overall improved quality of life. He had improved his lifting form and was attending biweekly physical therapy sessions. His pain score was 3/10. He expressed a desire to “not get hooked on opioids,” and mentioned he had “tried stopping the medicine last week” but experienced withdrawal symptoms. We discussed and prescribed the following 5-week taper plan: 2.5 mg reduction of oxycodone per dose, every 2 weeks x 2. Then 2.5 mg PO every 6 hours as needed x 1 week before stopping.

Organizing your approach

As part of goal setting, consider how therapy will be discontinued if benefits do not outweigh the risks of harm.

To optimize the chance for success in opioid treatment and to heighten vigilance and minimize harm to patients, we believe an organized approach is key (TABLE 6^{14,22-24,28,30-32}), particularly since this class of medication lacks strong evidence to support its long-term use.

CORRESPONDENCE 
Tracy Mahvan, PharmD, BCGP, University of Wyoming, School of Pharmacy, 1000 East University Avenue, Laramie, WY 82071; tbaher@uwyo.edu.

CASE

Marcelo G* is a 46-year-old man who presented to our family medicine clinic with a complex medical history including end-stage renal disease (ESRD) and hemodialysis, chronic anemia, peripheral vascular disease, venous thromboembolism and anticoagulation, major depressive disorder, osteoarthritis, and lumbosacral radiculopathy. His current medications included vitamin B complex, cholecalciferol, atorvastatin, warfarin, acetaminophen, diclofenac gel, and capsaicin cream. Mr. G reported bothersome bilateral knee and back pain despite physical therapy and consistent use of his current medications in addition to occasional intra-articular glucocorticoid injections. He mentioned that he had benefited in the past from intermittent opioid use.

How would you manage this patient’s care?

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

In 2013, an estimated 191 million prescriptions for ­opioids were written by health care providers, which is the equivalent of all adults living in the United States having their own opioid prescription.¹ This large expansion in opioid prescribing and use has also led to a rise in opioid overdose deaths, whether from prescribed or illicit use.¹ The Centers for Disease Control and Prevention (CDC) points out that each day, approximately 128 Americans die from an opioid overdose.¹ Deaths that occur from opioid overdose often involve the prescribed opioids methadone, oxycodone, and hydrocodone, the illicit opioid heroin, and, of particular concern, prescription and illicit fentanyl.¹

IMAGE: © JOE GORMAN

Family physicians write more opioid prescriptions than any other specialty, and they are therefore uniquely positioned to protect patients, improve the quality of their care, and ultimately produce a meaningful public health impact.

The extent of this problem has sparked the development of health safety initiatives and research efforts. Through production quotas, the US Drug Enforcement Administration (DEA) reduced the number of opioids produced across all schedule I and schedule II lists in 2017 by as much as 25%.² The DEA again reduced the amounts produced in 2018.³ For 2020, the DEA has determined that the production quotas and assessment of annual needs are sufficient.⁴

The CDC has also promoted access to naloxone and prevention initiatives; pharmacies in some states have standing orders for naloxone, and medical personnel and law enforcement now carry it.^1,5 Finally, new research has identified risk factors that influence one’s potential for addiction, such as mental illness, history of substance and alcohol abuse, and a low income.⁶ Interestingly, while numerous initiatives and strategies have been implemented across health systems, there is little evidence that demonstrates how implementation of safe prescribing strategies has affected overall patient safety and avoidance of opioid-related harms.

Nevertheless, concerns related to ­opioids are especially important for primary care ­providers, who manage many patients with acute and chronic diseases and disorders that require pain control.⁷ Family physicians write more opioid prescriptions than any ­other specialty,⁸ and they are therefore uniquely positioned to protect patients, improve the quality of their care, and ultimately produce a meaningful public health impact. This article provides a guide to safe opioid prescribing.

Continue to: Use the patient interview to ensure that Tx aligns with patient goals

 

 

Use the patient interview to ensure that Tx aligns with patient goals

For patients presenting with chronic pain, conduct a complete general history and physical examination that includes a review of available records; a medical, surgical, social, family, medication, and allergy history; a review of systems; and documentation of any psychiatric comorbidities (ie, depression, anxiety, psychiatric disorders, personality traits). Inquiries about social history and current medications should explore the possibility of previous and current substance use and misuse.

While causes of pain can be assessed through physical examination and diagnostic tests, the patient interview is an invaluable source of information. No single means of assessment has consistently demonstrated superiority over another in measuring pain, and numerous standard assessment tools are available (TABLE 1^9-13).¹⁴ Unidimensional tools are often easy and quick ways to assess pain intensity. Multidimensional tools, although more time intensive, are designed to gather more subjective information about the patient’s pain. Finally, use an instrument such as the 9-item Patient Health Questionnaire (PHQ-9) to screen patients for psychological distress.^15,16

Use state prescription drug monitoring programs and urine drug testing to confirm patient compliance.

Provide an environment for patients to openly discuss their experiences, expectations, preferences, fears, and coping efforts, as well as the impact that pain has had on their lives.^17,18 Without this foundational understanding, medical treatment may work against the patient’s goals. An empathic approach allows for effective communication, shared decision making, and ultimately, an avenue for individualized therapy.

Balancing treatment with risk mitigation

The challenge of managing chronic pain is to balance treating the patient with the basic principle of nonmaleficence (primum non nocere: “first, do no harm”). The literature has shown that risk factors such as a family history of substance abuse or sexual abuse, younger age, and psychological disease may be linked to greater risk for opioid misuse.^19,20 However, despite the many risk-screening tools available, no single instrument has reliably and accurately predicted those at higher propensity for prescription addiction. In fact, risk-screening tools as a whole remain unregulated by the US Food and Drug Administration (FDA) and other authorities.²¹ Still, screening tools provide useful information as one component of the risk-mitigation process.

Screening tools. The tools most commonly used clinically to stratify risk prior to prescribing opioids are the 5-item Opioid Risk Tool (ORT),²² the revised 24-item Screener and Opioid Assessment for Patients with Pain (SOAPP-R),²³ which are patient self-administered assessments, and the 7-item clinician-administered DIRE (Diagnosis, Intractability, Risk, Efficacy).²⁴ Given the subtle differences in criteria and the time required for each of these risk assessments, we recommend choosing one based on site-specific resources and overall clinician comfort.²⁵ Risk stratification helps to determine the optimal frequency and intensity of monitoring, not necessarily to deny care to “high-risk” patients.

Continue to: In fact, just as the "universal precautions"...

In fact, just as the “universal precautions” approach has been applied to infection control, many have suggested using a similar approach to pain management. Risk screening should never be misunderstood as an attempt to diminish or undermine the patient’s burden of pain. By routinely conducting thorough and respectful inquiries of risk factors for all patients, clinicians can reduce stigma, improve care, and contain overall risk.^26,27

Monitoring programs and patient agreements. In addition to risk-screening tools, the CDC recommends using state prescription drug monitoring programs (PDMP) and urine drug testing (UDT) data to confirm the use of prescribed and illicit substances.²⁸ All 50 states have implemented PDMPs.²⁹ Consider incorporating these components into controlled-substance agreements, which ultimately aim to promote safety and trust between patients and providers. Of course, such agreements do not eliminate all risks associated with opioid prescribing, nor do they guarantee the absence of adverse outcomes. However, when used correctly, they can provide safeguards to reduce misuse and abuse. They also have the potential to preserve the patient-provider relationship, as opposed to providers cursorily refusing to prescribe opioids altogether. The term “controlled-substance agreement” is preferable to “pain contract” or “narcotic contract” as the latter 2 terms may feel stigmatizing and threatening.³⁰

Risk evaluation and mitigation strategy (REMS). In an effort to ensure that benefits of opioid analgesics continue to outweigh the risks, the FDA approved the extended-release (ER)/long-acting (LA) opioid analgesics shared system REMS. Under this REMS, a consortium of ER/LA opioid manufacturers is mandated to provide prescriber education in the form of accredited continuing education and patient educational materials, available at https://opioidanalgesicrems.com/RpcUI/home.u.

CASE

After reviewing Mr. G’s chart and conducting a history, we learned that his bilateral knee osteoarthritis was atraumatic and likely due to overuse—although possibly affected by major trauma in a motor vehicle accident 5 years earlier. Imaging also revealed multilevel disc degeneration contributing to his radicular back pain, which seemed to be worse on days after working as a caterer. Poor lifting form at work may have contributed to his pain. Nevertheless, he had been consistent with medical follow-up and denied current or past use of illicit substances. Per the numeric rating scale (NRS), he reported 8 out of 10 pain in his knees and 6 out of 10 in his back. In addition to obtaining a PHQ-9 score of 4, we conducted a DIRE assessment and obtained a score of 19 out of a possible 21, indicating that he may be a good candidate for long-term opioid analgesia.

Criteria for prescribing opioids and for guiding treatment goals

Prescribing an opioid requires establishing a medical necessity based on 3 criteria:³¹

• pain of moderate-to-severe degree
• a physical diagnosis or suspected organic problem
• documented treatment failure of a noncontrolled substance, adjuvant agents, physician-ordered physical therapy, structured exercise program, and interventional techniques.

Continue to: Treatment goals should be established...

Treatment goals should be established and understood by the prescriber and patient prior to initiation of opioids.²⁸ Overarching treatment goals for all opioids prescribed are pain relief (but not necessarily a focus on pain scores), improvement in functional activity, and minimization of adverse effects, with the latter 2 goals taking precedence.³¹ To assess outcomes, formally measure progress toward goals from baseline evaluations. This can be achieved through repeated use of validated tools such as those mentioned earlier, or may be more broadly considered as progress toward employment status or increasing participation in activities.³¹ All pain management plans involving opioids should include continued efforts with nonpharmacologic therapy (eg, exercise therapy, weight loss, behavioral training) and nonopioid pharmacologic therapy (eg, nonsteroidal anti-­inflammatory drugs, tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, anticonvulsants).²⁸

Have an “exit strategy.” As part of goal setting, also consider how therapy will be discontinued if benefits do not outweigh the risks of harm.²⁸ Weigh functional status gains against adverse opioid consequences using the PEG scale (pain, enjoyment of life, and general activity) (TABLE 2³²).³³ Improvements of 30% from baseline have been deemed clinically meaningful by some,³² but not all benefits will be easy to quantify. At the start of treatment dialogue, use the term “therapeutic trial” instead of ”treatment plan” to more effectively convey that opioids will be continued only if safe and effective, and will be prescribed at the lowest effective dose as one component of the multimodal approach to pain.³⁰

Initiation of treatment: Opioid selection and dosing

When initiating opioid therapy, prescribe an immediate-release, short-acting agent instead of an ER/LA formulation.²⁸

For moderate pain, first consider tramadol, codeine, tapentadol, or hydrocodone.³¹ Second-line agents for moderate pain are hydrocodone or oxycodone.³¹

For severe pain, first-line agents include hydrocodone, oxycodone, hydromorphone, or morphine.³¹ Second-line agents for severe pain are fentanyl and, with careful supervision or referral to a pain specialist, methadone or buprenorphine.³¹

Continue to: Of special note...

Of special note, methadone should not be the first choice for ER/LA opioid due to its unique long half-life and ability to prolong the QT interval.³⁴ Only clinicians familiar with its use should prescribe methadone, while referring to the drug’s clinical practice guideline for further advice.

At the start, prescribe the lowest effective dosage (referring to the product labeling for guidance) and calculate total daily dose in terms of morphine milligram equivalents (MME) (TABLE 3^35-37).²⁸ Exercise caution when considering opioids for patients with respiratory sleep disorders and for patients ≥ 65 years due to altered pharmacokinetics in the elderly population.³⁸ Also make dose adjustments for renal and hepatic insufficiency (TABLE 4³⁵).

All pain management involving opioids should include nonpharmacologic components, such as exercise and weight loss.

Doses between 20 to 50 MME/d are considered relatively low dosages.²⁸ Be cautious when prescribing an opioid at any dosage, and reassess evidence of individual benefits and risks before increasing the dosage to ≥ 50 MME/d.²⁸ Regard a dosage of 90 MME/d as maximal.²⁸ While there is no analgesic ceiling, doses greater than 90 MME/d are associated with risk for overdose and should prompt referral to a pain specialist.³¹ Veterans Administration guidelines cite strong evidence that risk for overdose and death significantly increases at a range of 20 to 50 MME/d.³³ Daily doses exceeding 90 MME/d should be documented with rational justification.²⁸

CASE

Noncontrolled medications are preferred in the treatment of chronic pain. However, the utility of adjuvant options such as NSAIDs, duloxetine, or gabapentin were limited in Mr. G’s case due to his ESRD. Calcium channel α2-δ ligands may have been effective in reducing symptoms of neuropathic pain but would have had limited efficacy against osteoarthritis. Based on his low risk for opioid misuse, we decided to start Mr. G on oxycodone 2.5 mg PO, every 6 hours as needed for moderate-to-severe pain, and to follow up in 1 month. We also explained proper lifting form to him and encouraged him to continue with physical therapy.

Deciding to continue therapy with opioids

There is a lack of convincing evidence that opioid use beyond 6 months improves quality of life; patients do not report a significant reduction in pain beyond this time.²⁸ Thus, a repeat evaluation of continued medical necessity is essential before deciding in favor of ongoing, long-term treatment with opioids. Continue prescribing opioids only if there is meaningful pain relief and improved function that outweighs the harms that may be expected for a given patient.³¹ With all patients, consider prescribing naloxone to accompany dispensed opioid prescriptions.²⁸ This is particularly important for those at risk for misuse (history of overdose, history of substance use disorder, dosages ≥ 50 MME/d, or concurrent benzodiazepine use). Resources for prescribing naloxone in primary care settings can be found through Prescribe to Prevent at http://prescribetoprevent.org. Due to the established risk of overdose, avoid, if possible, concomitant prescriptions of benzodiazepines and opioids.³¹

Continue to: Follow-up and monitoring

 

 

Follow-up and monitoring

Responsiveness to opioids varies greatly among individuals.^38,39 An opioid that leads to a therapeutic analgesic effect in one patient may cause adverse events or toxicity in another. Periodically reassess the appropriateness of chronic opioid therapy and modify treatment based on its ability to meet therapeutic goals. While practice behaviors and clinic policies vary across institutions, risk stratification can provide guidance on the frequency and intensity of follow-up and monitoring. Kaye et al²¹ describe a triage system in which low-risk patients may be managed by a primary care provider with routine follow-up and reassessment every 3 months.²¹ Moderate-risk patients may warrant additional management by specialists and a monthly follow-up. High-risk patients may need referrals to interdisciplinary pain centers or addiction specialists.²¹

Along these lines, the CDC recommends conducting a PDMP review and UDT before initiating therapy, followed by a periodic PDMP (every 1-3 months) and a UDT at least annually. Keep in mind, providers should follow their state-specific regulations, as monitoring requirements may vary. In addition, clinicians should always be alert to adverse reactions (TABLE 4³⁵) and sudden behavior changes such as respiratory depression, nausea, constipation, pruritus, cognitive impairment, falls, motor vehicle accidents, and aberrant behaviors. Under these circumstances, consider a dose reduction and, in certain cases, discontinuation.

Additionally, in cases of pain unresponsive to escalating opioid doses, include opioid-induced hyperalgesia (OIH) in the differential. Dose reductions, opioid rotations, and office-based detoxifications are all options for the treatment of OIH.⁴⁰ Assessment of pain and function can be accomplished using the PEG scale (TABLE 2).³²

CASE

Two weeks into Mr. G’s initial regimen, he called to report no change in pain or functional status. We increased his dose to 5 mg PO every 6 hours as needed. At his 1-month follow-up appointment, he reported his pain as 6/10 and no adverse effects. We again increased his dose to 10 mg PO every 6 hours as needed, with follow-up in another month.

Discontinuation and tapering of opioids

Indications for discontinuing opioids are patient request, resolution of pain, doses ≥ 90 MME/d (in which case a pain specialist should be consulted), inadequate response, untoward adverse effects, and abuse and misuse.^1,31,41 However, providers may also face the challenge of working with patients for whom the benefit of opioid therapy is uncertain but who do not have an absolute contraindication. Guidance on this matter may be found in a 2017 systematic review of studies on reducing or discontinuing long-term opioid therapy.⁴² Although evidence on the whole was low quality, it showed that tapering or discontinuing opioids may actually reduce pain and improve function and quality of life.

Continue to: When working with a patient to taper treatment

When working with a patient to taper treatment, consider using a multidisciplinary approach. Also, assess the patient’s pain level and perception of needs for opioids, make clear the substantial effort that will be asked of the patient, and agree on coping strategies the patient can use to manage the taper.^31,43 While the evidence does not appear to support one tapering regimen over another, we can offer some recommendations on ways to individualize a tapering regimen (TABLE 5).^{1,31,41,43,44}

General recommendations. Gradually reduce the original MME dose by 5% to 10% every week to every 4 weeks, with frequent follow-up and adjustments as needed based on the individual’s response.^1,31,41,43 In the event that the patient does not tolerate this dose-reduction schedule, tapering can be slowed further.³¹ Avoid abrupt discontinuation.³³ Opioid abstinence syndrome, a myriad of symptoms caused by deprivation of opioids in physiologically dependent individuals, ­although rare, can occur during tapering and can be managed with clonidine 0.1 to 0.2 mg orally every 6 hours or transdermal clonidine patch 0.1 mg/24 hours weekly during the taper.³¹

Methadone should not be the first choice for an extended-release/long-acting opioid due to its long half-life and ability to prolong the QT interval.

Tapering of long-term opioid treatment is not without risk. Immediate risks include withdrawal syndrome, hyperalgesia, and dropout, while ongoing issues are potential relapse, problems in increasing and maintaining function, and medicolegal implications.⁴³ Withdrawal symptoms begin 2 to 3 half-lives after the last dose of opioid, and resolution varies depending on the duration of use, the most recent dose, and speed of tapering.⁴³ In general, a patient needs 20% to 25% of the previous day’s dose to prevent withdrawal symptoms.³¹ Increased pain appears to be a brief, time-limited occurance.⁴³ Dropout and relapse tend to be attributed to patient factors such as depressive symptoms and higher pain scores at initiation of the taper.⁴³ Low pain at the end of tapering has been shown to predict long-term abstinence from opioids.⁴³

CASE

Two months into his oxycodone regimen, Mr. G reported improved functional status at his catering job and overall improved quality of life. He had improved his lifting form and was attending biweekly physical therapy sessions. His pain score was 3/10. He expressed a desire to “not get hooked on opioids,” and mentioned he had “tried stopping the medicine last week” but experienced withdrawal symptoms. We discussed and prescribed the following 5-week taper plan: 2.5 mg reduction of oxycodone per dose, every 2 weeks x 2. Then 2.5 mg PO every 6 hours as needed x 1 week before stopping.

Organizing your approach

As part of goal setting, consider how therapy will be discontinued if benefits do not outweigh the risks of harm.

To optimize the chance for success in opioid treatment and to heighten vigilance and minimize harm to patients, we believe an organized approach is key (TABLE 6^{14,22-24,28,30-32}), particularly since this class of medication lacks strong evidence to support its long-term use.

CORRESPONDENCE 
Tracy Mahvan, PharmD, BCGP, University of Wyoming, School of Pharmacy, 1000 East University Avenue, Laramie, WY 82071; tbaher@uwyo.edu.

CASE

Marcelo G* is a 46-year-old man who presented to our family medicine clinic with a complex medical history including end-stage renal disease (ESRD) and hemodialysis, chronic anemia, peripheral vascular disease, venous thromboembolism and anticoagulation, major depressive disorder, osteoarthritis, and lumbosacral radiculopathy. His current medications included vitamin B complex, cholecalciferol, atorvastatin, warfarin, acetaminophen, diclofenac gel, and capsaicin cream. Mr. G reported bothersome bilateral knee and back pain despite physical therapy and consistent use of his current medications in addition to occasional intra-articular glucocorticoid injections. He mentioned that he had benefited in the past from intermittent opioid use.

How would you manage this patient’s care?

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

In 2013, an estimated 191 million prescriptions for ­opioids were written by health care providers, which is the equivalent of all adults living in the United States having their own opioid prescription.¹ This large expansion in opioid prescribing and use has also led to a rise in opioid overdose deaths, whether from prescribed or illicit use.¹ The Centers for Disease Control and Prevention (CDC) points out that each day, approximately 128 Americans die from an opioid overdose.¹ Deaths that occur from opioid overdose often involve the prescribed opioids methadone, oxycodone, and hydrocodone, the illicit opioid heroin, and, of particular concern, prescription and illicit fentanyl.¹

IMAGE: © JOE GORMAN

Family physicians write more opioid prescriptions than any other specialty, and they are therefore uniquely positioned to protect patients, improve the quality of their care, and ultimately produce a meaningful public health impact.

The extent of this problem has sparked the development of health safety initiatives and research efforts. Through production quotas, the US Drug Enforcement Administration (DEA) reduced the number of opioids produced across all schedule I and schedule II lists in 2017 by as much as 25%.² The DEA again reduced the amounts produced in 2018.³ For 2020, the DEA has determined that the production quotas and assessment of annual needs are sufficient.⁴

The CDC has also promoted access to naloxone and prevention initiatives; pharmacies in some states have standing orders for naloxone, and medical personnel and law enforcement now carry it.^1,5 Finally, new research has identified risk factors that influence one’s potential for addiction, such as mental illness, history of substance and alcohol abuse, and a low income.⁶ Interestingly, while numerous initiatives and strategies have been implemented across health systems, there is little evidence that demonstrates how implementation of safe prescribing strategies has affected overall patient safety and avoidance of opioid-related harms.

Nevertheless, concerns related to ­opioids are especially important for primary care ­providers, who manage many patients with acute and chronic diseases and disorders that require pain control.⁷ Family physicians write more opioid prescriptions than any ­other specialty,⁸ and they are therefore uniquely positioned to protect patients, improve the quality of their care, and ultimately produce a meaningful public health impact. This article provides a guide to safe opioid prescribing.

Continue to: Use the patient interview to ensure that Tx aligns with patient goals

 

 

Use the patient interview to ensure that Tx aligns with patient goals

For patients presenting with chronic pain, conduct a complete general history and physical examination that includes a review of available records; a medical, surgical, social, family, medication, and allergy history; a review of systems; and documentation of any psychiatric comorbidities (ie, depression, anxiety, psychiatric disorders, personality traits). Inquiries about social history and current medications should explore the possibility of previous and current substance use and misuse.

While causes of pain can be assessed through physical examination and diagnostic tests, the patient interview is an invaluable source of information. No single means of assessment has consistently demonstrated superiority over another in measuring pain, and numerous standard assessment tools are available (TABLE 1^9-13).¹⁴ Unidimensional tools are often easy and quick ways to assess pain intensity. Multidimensional tools, although more time intensive, are designed to gather more subjective information about the patient’s pain. Finally, use an instrument such as the 9-item Patient Health Questionnaire (PHQ-9) to screen patients for psychological distress.^15,16

Use state prescription drug monitoring programs and urine drug testing to confirm patient compliance.

Provide an environment for patients to openly discuss their experiences, expectations, preferences, fears, and coping efforts, as well as the impact that pain has had on their lives.^17,18 Without this foundational understanding, medical treatment may work against the patient’s goals. An empathic approach allows for effective communication, shared decision making, and ultimately, an avenue for individualized therapy.

Balancing treatment with risk mitigation

The challenge of managing chronic pain is to balance treating the patient with the basic principle of nonmaleficence (primum non nocere: “first, do no harm”). The literature has shown that risk factors such as a family history of substance abuse or sexual abuse, younger age, and psychological disease may be linked to greater risk for opioid misuse.^19,20 However, despite the many risk-screening tools available, no single instrument has reliably and accurately predicted those at higher propensity for prescription addiction. In fact, risk-screening tools as a whole remain unregulated by the US Food and Drug Administration (FDA) and other authorities.²¹ Still, screening tools provide useful information as one component of the risk-mitigation process.

Screening tools. The tools most commonly used clinically to stratify risk prior to prescribing opioids are the 5-item Opioid Risk Tool (ORT),²² the revised 24-item Screener and Opioid Assessment for Patients with Pain (SOAPP-R),²³ which are patient self-administered assessments, and the 7-item clinician-administered DIRE (Diagnosis, Intractability, Risk, Efficacy).²⁴ Given the subtle differences in criteria and the time required for each of these risk assessments, we recommend choosing one based on site-specific resources and overall clinician comfort.²⁵ Risk stratification helps to determine the optimal frequency and intensity of monitoring, not necessarily to deny care to “high-risk” patients.

Continue to: In fact, just as the "universal precautions"...

In fact, just as the “universal precautions” approach has been applied to infection control, many have suggested using a similar approach to pain management. Risk screening should never be misunderstood as an attempt to diminish or undermine the patient’s burden of pain. By routinely conducting thorough and respectful inquiries of risk factors for all patients, clinicians can reduce stigma, improve care, and contain overall risk.^26,27

Monitoring programs and patient agreements. In addition to risk-screening tools, the CDC recommends using state prescription drug monitoring programs (PDMP) and urine drug testing (UDT) data to confirm the use of prescribed and illicit substances.²⁸ All 50 states have implemented PDMPs.²⁹ Consider incorporating these components into controlled-substance agreements, which ultimately aim to promote safety and trust between patients and providers. Of course, such agreements do not eliminate all risks associated with opioid prescribing, nor do they guarantee the absence of adverse outcomes. However, when used correctly, they can provide safeguards to reduce misuse and abuse. They also have the potential to preserve the patient-provider relationship, as opposed to providers cursorily refusing to prescribe opioids altogether. The term “controlled-substance agreement” is preferable to “pain contract” or “narcotic contract” as the latter 2 terms may feel stigmatizing and threatening.³⁰

Risk evaluation and mitigation strategy (REMS). In an effort to ensure that benefits of opioid analgesics continue to outweigh the risks, the FDA approved the extended-release (ER)/long-acting (LA) opioid analgesics shared system REMS. Under this REMS, a consortium of ER/LA opioid manufacturers is mandated to provide prescriber education in the form of accredited continuing education and patient educational materials, available at https://opioidanalgesicrems.com/RpcUI/home.u.

CASE

After reviewing Mr. G’s chart and conducting a history, we learned that his bilateral knee osteoarthritis was atraumatic and likely due to overuse—although possibly affected by major trauma in a motor vehicle accident 5 years earlier. Imaging also revealed multilevel disc degeneration contributing to his radicular back pain, which seemed to be worse on days after working as a caterer. Poor lifting form at work may have contributed to his pain. Nevertheless, he had been consistent with medical follow-up and denied current or past use of illicit substances. Per the numeric rating scale (NRS), he reported 8 out of 10 pain in his knees and 6 out of 10 in his back. In addition to obtaining a PHQ-9 score of 4, we conducted a DIRE assessment and obtained a score of 19 out of a possible 21, indicating that he may be a good candidate for long-term opioid analgesia.

Criteria for prescribing opioids and for guiding treatment goals

Prescribing an opioid requires establishing a medical necessity based on 3 criteria:³¹

• pain of moderate-to-severe degree
• a physical diagnosis or suspected organic problem
• documented treatment failure of a noncontrolled substance, adjuvant agents, physician-ordered physical therapy, structured exercise program, and interventional techniques.

Continue to: Treatment goals should be established...

Treatment goals should be established and understood by the prescriber and patient prior to initiation of opioids.²⁸ Overarching treatment goals for all opioids prescribed are pain relief (but not necessarily a focus on pain scores), improvement in functional activity, and minimization of adverse effects, with the latter 2 goals taking precedence.³¹ To assess outcomes, formally measure progress toward goals from baseline evaluations. This can be achieved through repeated use of validated tools such as those mentioned earlier, or may be more broadly considered as progress toward employment status or increasing participation in activities.³¹ All pain management plans involving opioids should include continued efforts with nonpharmacologic therapy (eg, exercise therapy, weight loss, behavioral training) and nonopioid pharmacologic therapy (eg, nonsteroidal anti-­inflammatory drugs, tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, anticonvulsants).²⁸

Have an “exit strategy.” As part of goal setting, also consider how therapy will be discontinued if benefits do not outweigh the risks of harm.²⁸ Weigh functional status gains against adverse opioid consequences using the PEG scale (pain, enjoyment of life, and general activity) (TABLE 2³²).³³ Improvements of 30% from baseline have been deemed clinically meaningful by some,³² but not all benefits will be easy to quantify. At the start of treatment dialogue, use the term “therapeutic trial” instead of ”treatment plan” to more effectively convey that opioids will be continued only if safe and effective, and will be prescribed at the lowest effective dose as one component of the multimodal approach to pain.³⁰

Initiation of treatment: Opioid selection and dosing

When initiating opioid therapy, prescribe an immediate-release, short-acting agent instead of an ER/LA formulation.²⁸

For moderate pain, first consider tramadol, codeine, tapentadol, or hydrocodone.³¹ Second-line agents for moderate pain are hydrocodone or oxycodone.³¹

For severe pain, first-line agents include hydrocodone, oxycodone, hydromorphone, or morphine.³¹ Second-line agents for severe pain are fentanyl and, with careful supervision or referral to a pain specialist, methadone or buprenorphine.³¹

Continue to: Of special note...

Of special note, methadone should not be the first choice for ER/LA opioid due to its unique long half-life and ability to prolong the QT interval.³⁴ Only clinicians familiar with its use should prescribe methadone, while referring to the drug’s clinical practice guideline for further advice.

At the start, prescribe the lowest effective dosage (referring to the product labeling for guidance) and calculate total daily dose in terms of morphine milligram equivalents (MME) (TABLE 3^35-37).²⁸ Exercise caution when considering opioids for patients with respiratory sleep disorders and for patients ≥ 65 years due to altered pharmacokinetics in the elderly population.³⁸ Also make dose adjustments for renal and hepatic insufficiency (TABLE 4³⁵).

All pain management involving opioids should include nonpharmacologic components, such as exercise and weight loss.

Doses between 20 to 50 MME/d are considered relatively low dosages.²⁸ Be cautious when prescribing an opioid at any dosage, and reassess evidence of individual benefits and risks before increasing the dosage to ≥ 50 MME/d.²⁸ Regard a dosage of 90 MME/d as maximal.²⁸ While there is no analgesic ceiling, doses greater than 90 MME/d are associated with risk for overdose and should prompt referral to a pain specialist.³¹ Veterans Administration guidelines cite strong evidence that risk for overdose and death significantly increases at a range of 20 to 50 MME/d.³³ Daily doses exceeding 90 MME/d should be documented with rational justification.²⁸

CASE

Noncontrolled medications are preferred in the treatment of chronic pain. However, the utility of adjuvant options such as NSAIDs, duloxetine, or gabapentin were limited in Mr. G’s case due to his ESRD. Calcium channel α2-δ ligands may have been effective in reducing symptoms of neuropathic pain but would have had limited efficacy against osteoarthritis. Based on his low risk for opioid misuse, we decided to start Mr. G on oxycodone 2.5 mg PO, every 6 hours as needed for moderate-to-severe pain, and to follow up in 1 month. We also explained proper lifting form to him and encouraged him to continue with physical therapy.

Deciding to continue therapy with opioids

There is a lack of convincing evidence that opioid use beyond 6 months improves quality of life; patients do not report a significant reduction in pain beyond this time.²⁸ Thus, a repeat evaluation of continued medical necessity is essential before deciding in favor of ongoing, long-term treatment with opioids. Continue prescribing opioids only if there is meaningful pain relief and improved function that outweighs the harms that may be expected for a given patient.³¹ With all patients, consider prescribing naloxone to accompany dispensed opioid prescriptions.²⁸ This is particularly important for those at risk for misuse (history of overdose, history of substance use disorder, dosages ≥ 50 MME/d, or concurrent benzodiazepine use). Resources for prescribing naloxone in primary care settings can be found through Prescribe to Prevent at http://prescribetoprevent.org. Due to the established risk of overdose, avoid, if possible, concomitant prescriptions of benzodiazepines and opioids.³¹

Continue to: Follow-up and monitoring

 

 

Follow-up and monitoring

Responsiveness to opioids varies greatly among individuals.^38,39 An opioid that leads to a therapeutic analgesic effect in one patient may cause adverse events or toxicity in another. Periodically reassess the appropriateness of chronic opioid therapy and modify treatment based on its ability to meet therapeutic goals. While practice behaviors and clinic policies vary across institutions, risk stratification can provide guidance on the frequency and intensity of follow-up and monitoring. Kaye et al²¹ describe a triage system in which low-risk patients may be managed by a primary care provider with routine follow-up and reassessment every 3 months.²¹ Moderate-risk patients may warrant additional management by specialists and a monthly follow-up. High-risk patients may need referrals to interdisciplinary pain centers or addiction specialists.²¹

Along these lines, the CDC recommends conducting a PDMP review and UDT before initiating therapy, followed by a periodic PDMP (every 1-3 months) and a UDT at least annually. Keep in mind, providers should follow their state-specific regulations, as monitoring requirements may vary. In addition, clinicians should always be alert to adverse reactions (TABLE 4³⁵) and sudden behavior changes such as respiratory depression, nausea, constipation, pruritus, cognitive impairment, falls, motor vehicle accidents, and aberrant behaviors. Under these circumstances, consider a dose reduction and, in certain cases, discontinuation.

Additionally, in cases of pain unresponsive to escalating opioid doses, include opioid-induced hyperalgesia (OIH) in the differential. Dose reductions, opioid rotations, and office-based detoxifications are all options for the treatment of OIH.⁴⁰ Assessment of pain and function can be accomplished using the PEG scale (TABLE 2).³²

CASE

Two weeks into Mr. G’s initial regimen, he called to report no change in pain or functional status. We increased his dose to 5 mg PO every 6 hours as needed. At his 1-month follow-up appointment, he reported his pain as 6/10 and no adverse effects. We again increased his dose to 10 mg PO every 6 hours as needed, with follow-up in another month.

Discontinuation and tapering of opioids

Indications for discontinuing opioids are patient request, resolution of pain, doses ≥ 90 MME/d (in which case a pain specialist should be consulted), inadequate response, untoward adverse effects, and abuse and misuse.^1,31,41 However, providers may also face the challenge of working with patients for whom the benefit of opioid therapy is uncertain but who do not have an absolute contraindication. Guidance on this matter may be found in a 2017 systematic review of studies on reducing or discontinuing long-term opioid therapy.⁴² Although evidence on the whole was low quality, it showed that tapering or discontinuing opioids may actually reduce pain and improve function and quality of life.

Continue to: When working with a patient to taper treatment

When working with a patient to taper treatment, consider using a multidisciplinary approach. Also, assess the patient’s pain level and perception of needs for opioids, make clear the substantial effort that will be asked of the patient, and agree on coping strategies the patient can use to manage the taper.^31,43 While the evidence does not appear to support one tapering regimen over another, we can offer some recommendations on ways to individualize a tapering regimen (TABLE 5).^{1,31,41,43,44}

General recommendations. Gradually reduce the original MME dose by 5% to 10% every week to every 4 weeks, with frequent follow-up and adjustments as needed based on the individual’s response.^1,31,41,43 In the event that the patient does not tolerate this dose-reduction schedule, tapering can be slowed further.³¹ Avoid abrupt discontinuation.³³ Opioid abstinence syndrome, a myriad of symptoms caused by deprivation of opioids in physiologically dependent individuals, ­although rare, can occur during tapering and can be managed with clonidine 0.1 to 0.2 mg orally every 6 hours or transdermal clonidine patch 0.1 mg/24 hours weekly during the taper.³¹

Methadone should not be the first choice for an extended-release/long-acting opioid due to its long half-life and ability to prolong the QT interval.

Tapering of long-term opioid treatment is not without risk. Immediate risks include withdrawal syndrome, hyperalgesia, and dropout, while ongoing issues are potential relapse, problems in increasing and maintaining function, and medicolegal implications.⁴³ Withdrawal symptoms begin 2 to 3 half-lives after the last dose of opioid, and resolution varies depending on the duration of use, the most recent dose, and speed of tapering.⁴³ In general, a patient needs 20% to 25% of the previous day’s dose to prevent withdrawal symptoms.³¹ Increased pain appears to be a brief, time-limited occurance.⁴³ Dropout and relapse tend to be attributed to patient factors such as depressive symptoms and higher pain scores at initiation of the taper.⁴³ Low pain at the end of tapering has been shown to predict long-term abstinence from opioids.⁴³

CASE

Two months into his oxycodone regimen, Mr. G reported improved functional status at his catering job and overall improved quality of life. He had improved his lifting form and was attending biweekly physical therapy sessions. His pain score was 3/10. He expressed a desire to “not get hooked on opioids,” and mentioned he had “tried stopping the medicine last week” but experienced withdrawal symptoms. We discussed and prescribed the following 5-week taper plan: 2.5 mg reduction of oxycodone per dose, every 2 weeks x 2. Then 2.5 mg PO every 6 hours as needed x 1 week before stopping.

Organizing your approach

As part of goal setting, consider how therapy will be discontinued if benefits do not outweigh the risks of harm.

To optimize the chance for success in opioid treatment and to heighten vigilance and minimize harm to patients, we believe an organized approach is key (TABLE 6^{14,22-24,28,30-32}), particularly since this class of medication lacks strong evidence to support its long-term use.

CORRESPONDENCE 
Tracy Mahvan, PharmD, BCGP, University of Wyoming, School of Pharmacy, 1000 East University Avenue, Laramie, WY 82071; tbaher@uwyo.edu.

Given an opportunity to see physicians’ notes about their visits, patients mostly understand and agree with them, a survey shows.

Overall, 93% of respondents said the notes accurately described the visit; only 6% reported that something important was missing, write Suzanne G. Leveille, RN, PhD, of the University of Massachusetts, Boston, and colleagues in the Journal of General Internal Medicine.

“I think it’s wonderful news,” commented Howard Levy, MD, PhD, who spearheaded the implementation of open notes at Johns Hopkins University, Baltimore. “I’m thrilled with this report.”

Currently, 50 million Americans have access to their notes, the researchers report. Starting Nov. 2, 2020, the 21st Century Cures Act will require all US physicians to provide this access.

The regulation follows a movement to involve patients more actively in their care. Previous research has shown that access to visit notes improves patients’ feelings of control, helps them adhere to their medication regimens, and enables them to better understand their care plans.

Although physicians often feel that giving patients access to notes will lead to unnecessary conversations that will waste their time, previous studies have not borne that out. “Most clinical providers don’t notice a thing,” Levy told Medscape Medical News. “There was no change in the volume of work.”

Leveille and colleagues wanted to know how patients viewed the clarity, accuracy, and completeness of the notes they were reading and whether they had suggestions for improvements.

They surveyed all 136,815 adult outpatients affiliated with Beth Israel Deaconess Medical Center in Boston, Massachusetts; the University of Washington Medicine, in Seattle; and the Geisinger Health System, based in Danville, Pennsylvania. These systems all offer patients access to physicians’ notes.

The researchers asked the patients to recall one note written by a doctor, nurse practitioner, physician assistant, or mental health professional.

They received responses from 21,664 patients who had read at least one note. Of these, two thirds were women, three quarters were aged 45 years or older, and 85% were White.

Seventy-two percent had completed college. Although 85% reported being in good or excellent health, more of the respondents than nonrespondents had chronic health problems.

Ninety-seven percent of those with college educations understood their notes, compared with 92% of those who had not completed college, a finding that conflicted with the researchers’ expectations. “Good gracious, that’s wonderful,” Levy said. “In medicine we almost never get a 92% success rate in anything we do.”

Of the patients in fair or poor health, 88.6% said the note was accurate, compared with 94.4% of those in better health. Those in worse health were also more likely to say something important was missing.

When patients didn’t understand something, 35% searched the Internet, 27% asked a clinician, 7% asked a friend or family member, and 27% didn’t get help. (The researchers did not account for the other 4%.)

Of those patients whose note was written by a physician, 95% reported that the note accurately described the visit, compared with 92% of those whose note was written by a nurse practitioner and 90% of those whose note was written by a physician assistant.

Of patients reporting on a primary care note, 97% understood the note, compared with 94% of those reporting on a note from a visit to a specialist.

Ninety-three percent of those who understood their note were likely to recommend their clinician, compared with 77% of those who didn’t completely understand their note.

Asked how the notes could be improved, 3,812 people responded with comments of at least five words. These responses were included in the analysis.

Most commonly, patients wanted new information to be prominently featured at the top of the note, with clear instructions about next steps, referrals, and explanations of test results.

Often, they complained of old information or templates that felt impersonal. They stumbled over medical jargon and suggested links to glossaries. They bristled at such terms as “obese” and “patient denies.” Some wanted a way to comment on the notes.

Regarding the portals in which the notes were found, some patients said the notes were sometimes hard to find. Some said the notes were not posted quickly enough after the visits.

Levy said physicians should learn to write notes more succinctly, and he expects new regulations from the Centers for Medicare & Medicaid Services to encourage that. Previous regulations may have given physicians the impression that longer notes would allow them to bill at higher rates, he said. “The change in billing requirements will make it easier for healthcare providers to feel comfortable that they don’t have to restate information that had already been stated,” he said.

On the other hand, physicians should continue to use medical terminology, he said. “At times we use jargon, because it conveys rich, dense information in a few words,” he said. “That’s something that we should not have to give up.” Patients can research terms they don’t understand, he said.

Family physician Doug Iliff, MD, thinks it’s about time that his colleagues share their notes. He’s been doing it since he opened his solo practice in Topeka, Kansas, in 1984.

He still does it the way he always did, with carbonless copy paper. After each visit, he simply tears off the copy and hands it to the patient.

“It makes them know we’re on the same page,” he told Medscape Medical News. “It gives them confidence that I’m telling them what I really think.”

He has one comment on the work of Leveille and her colleagues. “Why are they studying this? Isn’t it obvious that it’s a good thing?”

The study was funded by the Robert Wood Johnson Foundation, the Gordon and Betty Moore Foundation, the Peterson Center on Healthcare, and the Cambia Health Foundation. The study authors, Iliff, and Levy have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Given an opportunity to see physicians’ notes about their visits, patients mostly understand and agree with them, a survey shows.

Overall, 93% of respondents said the notes accurately described the visit; only 6% reported that something important was missing, write Suzanne G. Leveille, RN, PhD, of the University of Massachusetts, Boston, and colleagues in the Journal of General Internal Medicine.

“I think it’s wonderful news,” commented Howard Levy, MD, PhD, who spearheaded the implementation of open notes at Johns Hopkins University, Baltimore. “I’m thrilled with this report.”

Currently, 50 million Americans have access to their notes, the researchers report. Starting Nov. 2, 2020, the 21st Century Cures Act will require all US physicians to provide this access.

The regulation follows a movement to involve patients more actively in their care. Previous research has shown that access to visit notes improves patients’ feelings of control, helps them adhere to their medication regimens, and enables them to better understand their care plans.

Although physicians often feel that giving patients access to notes will lead to unnecessary conversations that will waste their time, previous studies have not borne that out. “Most clinical providers don’t notice a thing,” Levy told Medscape Medical News. “There was no change in the volume of work.”

Leveille and colleagues wanted to know how patients viewed the clarity, accuracy, and completeness of the notes they were reading and whether they had suggestions for improvements.

They surveyed all 136,815 adult outpatients affiliated with Beth Israel Deaconess Medical Center in Boston, Massachusetts; the University of Washington Medicine, in Seattle; and the Geisinger Health System, based in Danville, Pennsylvania. These systems all offer patients access to physicians’ notes.

The researchers asked the patients to recall one note written by a doctor, nurse practitioner, physician assistant, or mental health professional.

They received responses from 21,664 patients who had read at least one note. Of these, two thirds were women, three quarters were aged 45 years or older, and 85% were White.

Seventy-two percent had completed college. Although 85% reported being in good or excellent health, more of the respondents than nonrespondents had chronic health problems.

Ninety-seven percent of those with college educations understood their notes, compared with 92% of those who had not completed college, a finding that conflicted with the researchers’ expectations. “Good gracious, that’s wonderful,” Levy said. “In medicine we almost never get a 92% success rate in anything we do.”

Of the patients in fair or poor health, 88.6% said the note was accurate, compared with 94.4% of those in better health. Those in worse health were also more likely to say something important was missing.

When patients didn’t understand something, 35% searched the Internet, 27% asked a clinician, 7% asked a friend or family member, and 27% didn’t get help. (The researchers did not account for the other 4%.)

Of those patients whose note was written by a physician, 95% reported that the note accurately described the visit, compared with 92% of those whose note was written by a nurse practitioner and 90% of those whose note was written by a physician assistant.

Of patients reporting on a primary care note, 97% understood the note, compared with 94% of those reporting on a note from a visit to a specialist.

Ninety-three percent of those who understood their note were likely to recommend their clinician, compared with 77% of those who didn’t completely understand their note.

Asked how the notes could be improved, 3,812 people responded with comments of at least five words. These responses were included in the analysis.

Most commonly, patients wanted new information to be prominently featured at the top of the note, with clear instructions about next steps, referrals, and explanations of test results.

Often, they complained of old information or templates that felt impersonal. They stumbled over medical jargon and suggested links to glossaries. They bristled at such terms as “obese” and “patient denies.” Some wanted a way to comment on the notes.

Regarding the portals in which the notes were found, some patients said the notes were sometimes hard to find. Some said the notes were not posted quickly enough after the visits.

Levy said physicians should learn to write notes more succinctly, and he expects new regulations from the Centers for Medicare & Medicaid Services to encourage that. Previous regulations may have given physicians the impression that longer notes would allow them to bill at higher rates, he said. “The change in billing requirements will make it easier for healthcare providers to feel comfortable that they don’t have to restate information that had already been stated,” he said.

On the other hand, physicians should continue to use medical terminology, he said. “At times we use jargon, because it conveys rich, dense information in a few words,” he said. “That’s something that we should not have to give up.” Patients can research terms they don’t understand, he said.

Family physician Doug Iliff, MD, thinks it’s about time that his colleagues share their notes. He’s been doing it since he opened his solo practice in Topeka, Kansas, in 1984.

He still does it the way he always did, with carbonless copy paper. After each visit, he simply tears off the copy and hands it to the patient.

“It makes them know we’re on the same page,” he told Medscape Medical News. “It gives them confidence that I’m telling them what I really think.”

He has one comment on the work of Leveille and her colleagues. “Why are they studying this? Isn’t it obvious that it’s a good thing?”

The study was funded by the Robert Wood Johnson Foundation, the Gordon and Betty Moore Foundation, the Peterson Center on Healthcare, and the Cambia Health Foundation. The study authors, Iliff, and Levy have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Given an opportunity to see physicians’ notes about their visits, patients mostly understand and agree with them, a survey shows.

Overall, 93% of respondents said the notes accurately described the visit; only 6% reported that something important was missing, write Suzanne G. Leveille, RN, PhD, of the University of Massachusetts, Boston, and colleagues in the Journal of General Internal Medicine.

“I think it’s wonderful news,” commented Howard Levy, MD, PhD, who spearheaded the implementation of open notes at Johns Hopkins University, Baltimore. “I’m thrilled with this report.”

Currently, 50 million Americans have access to their notes, the researchers report. Starting Nov. 2, 2020, the 21st Century Cures Act will require all US physicians to provide this access.

The regulation follows a movement to involve patients more actively in their care. Previous research has shown that access to visit notes improves patients’ feelings of control, helps them adhere to their medication regimens, and enables them to better understand their care plans.

Although physicians often feel that giving patients access to notes will lead to unnecessary conversations that will waste their time, previous studies have not borne that out. “Most clinical providers don’t notice a thing,” Levy told Medscape Medical News. “There was no change in the volume of work.”

Leveille and colleagues wanted to know how patients viewed the clarity, accuracy, and completeness of the notes they were reading and whether they had suggestions for improvements.

They surveyed all 136,815 adult outpatients affiliated with Beth Israel Deaconess Medical Center in Boston, Massachusetts; the University of Washington Medicine, in Seattle; and the Geisinger Health System, based in Danville, Pennsylvania. These systems all offer patients access to physicians’ notes.

The researchers asked the patients to recall one note written by a doctor, nurse practitioner, physician assistant, or mental health professional.

They received responses from 21,664 patients who had read at least one note. Of these, two thirds were women, three quarters were aged 45 years or older, and 85% were White.

Seventy-two percent had completed college. Although 85% reported being in good or excellent health, more of the respondents than nonrespondents had chronic health problems.

Ninety-seven percent of those with college educations understood their notes, compared with 92% of those who had not completed college, a finding that conflicted with the researchers’ expectations. “Good gracious, that’s wonderful,” Levy said. “In medicine we almost never get a 92% success rate in anything we do.”

Of the patients in fair or poor health, 88.6% said the note was accurate, compared with 94.4% of those in better health. Those in worse health were also more likely to say something important was missing.

When patients didn’t understand something, 35% searched the Internet, 27% asked a clinician, 7% asked a friend or family member, and 27% didn’t get help. (The researchers did not account for the other 4%.)

Of those patients whose note was written by a physician, 95% reported that the note accurately described the visit, compared with 92% of those whose note was written by a nurse practitioner and 90% of those whose note was written by a physician assistant.

Of patients reporting on a primary care note, 97% understood the note, compared with 94% of those reporting on a note from a visit to a specialist.

Ninety-three percent of those who understood their note were likely to recommend their clinician, compared with 77% of those who didn’t completely understand their note.

Asked how the notes could be improved, 3,812 people responded with comments of at least five words. These responses were included in the analysis.

Most commonly, patients wanted new information to be prominently featured at the top of the note, with clear instructions about next steps, referrals, and explanations of test results.

Often, they complained of old information or templates that felt impersonal. They stumbled over medical jargon and suggested links to glossaries. They bristled at such terms as “obese” and “patient denies.” Some wanted a way to comment on the notes.

Regarding the portals in which the notes were found, some patients said the notes were sometimes hard to find. Some said the notes were not posted quickly enough after the visits.

Levy said physicians should learn to write notes more succinctly, and he expects new regulations from the Centers for Medicare & Medicaid Services to encourage that. Previous regulations may have given physicians the impression that longer notes would allow them to bill at higher rates, he said. “The change in billing requirements will make it easier for healthcare providers to feel comfortable that they don’t have to restate information that had already been stated,” he said.

On the other hand, physicians should continue to use medical terminology, he said. “At times we use jargon, because it conveys rich, dense information in a few words,” he said. “That’s something that we should not have to give up.” Patients can research terms they don’t understand, he said.

Family physician Doug Iliff, MD, thinks it’s about time that his colleagues share their notes. He’s been doing it since he opened his solo practice in Topeka, Kansas, in 1984.

He still does it the way he always did, with carbonless copy paper. After each visit, he simply tears off the copy and hands it to the patient.

“It makes them know we’re on the same page,” he told Medscape Medical News. “It gives them confidence that I’m telling them what I really think.”

He has one comment on the work of Leveille and her colleagues. “Why are they studying this? Isn’t it obvious that it’s a good thing?”

The study was funded by the Robert Wood Johnson Foundation, the Gordon and Betty Moore Foundation, the Peterson Center on Healthcare, and the Cambia Health Foundation. The study authors, Iliff, and Levy have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

EVIDENCE SUMMARY

A double-blind, double-dummy, placebo-controlled RCT comparing a combination of clopidogrel, aspirin, and omeprazole with clopidogrel, aspirin, and placebo found no increase in composite CV outcomes with the PPI (TABLE).¹ Using a PPI did, however, significantly reduce gastrointestinal (GI) bleeding (hazard ratio [HR] = 0.13; 95% confidence interval [CI], 0.03-0.56).Although several meta-analyses have been conducted, they all rely on this single RCT that directly addresses the question, plus post-hoc analyses of other RCTs.

Four of 5 analyses find little or no difference in CV outcomes with a PPI

Four of 5 posthoc analyses (which weren’t themselves randomized) of RCTs found unclear or no differences in composite CV outcomes with concurrent use of a PPI and antiplatelet therapy, after multivariate adjustment for differences in populations taking or not taking a PPI.

Posthoc analysis of the largest study found worse CV outcomes for both clopidogrel and ticagrelor with concomitant PPI use.² However, patients on any GI drugs (PPI or non-PPI) had composite outcomes similar to patients on a PPI (PPI vs non-PPI GI treatment: HR = 0.98; 95% CI, 0.79-1.23), and patients not taking GI drugs had fewer composite outcomes compared with patients on a PPI (clopidogrel vs no GI therapy: HR = 1.29; 95% CI, 1.12-1.49; ticagrelor vs no GI therapy: HR = 1.30; 95% CI, 1.14-1.49). Researchers postulated that because the rate of composite outcomes increased equally for patients on any GI drug, the higher rate of CV adverse events with a PPI might have been related to GI disease rather than PPI use.

A similar posthoc analysis found no differences with or without PPI use among patients with ACS undergoing planned percutaneous coronary intervention (PCI) and assigned to clopidogrel or prasugrel.³ Researchers performed multivariate adjustment for differences in age, gender, ethnicity, and initial presence of unstable angina/non-ST-elevation MI.

A smaller study also found no significant differences in composite CV outcomes in patients using PPIs.⁴ Patients did have higher rates of MI (HR = 0.62; 95% CI, 0.42-0.91), but they were more likely to be older and have a previous diagnosis of non-ST-elevation MI, higher incidence of previous coronary artery bypass graft surgery, and history of peptic ulcer disease.

The fourth posthoc analysis of an RCT found that concomitant PPI use (91% of patients on lansoprazole) didn’t alter outcomes among patients undergoing PCI and receiving dual antiplatelet therapy with clopidogrel and aspirin.⁵ Researchers used a multivariate adjustment for differences in age, gender, and renal function and found no difference in outcomes during the 6-month or 24-month period. PPI prescription was at physician discretion. Researchers didn’t assess for dose-dependent effects of PPI.

A fifth, flawed study finds more adverse events with PPIs

A posthoc analysis of a smaller, open-label trial found increased major adverse cardiac events with PPI use among patients taking clopidogrel after PCI.⁶ Researchers didn’t adjust for differences in populations at baseline, however, and patients taking PPIs were more likely to be female or older and have diabetes, GI disease, or higher serum creatinine levels.

Continue to: Editor's takeaway

 

 

Editor’s takeaway

The best evidence (a large RCT) found that adding a PPI to antiplatelet therapy didn’t alter CV outcomes in patients with ACS, but it did reduce GI bleeds. Hopefully this will give providers the confidence to use PPIs, if clinically indicated, in patients taking antiplatelet therapy with clopidogrel or prasugrel.

EVIDENCE SUMMARY

A double-blind, double-dummy, placebo-controlled RCT comparing a combination of clopidogrel, aspirin, and omeprazole with clopidogrel, aspirin, and placebo found no increase in composite CV outcomes with the PPI (TABLE).¹ Using a PPI did, however, significantly reduce gastrointestinal (GI) bleeding (hazard ratio [HR] = 0.13; 95% confidence interval [CI], 0.03-0.56).Although several meta-analyses have been conducted, they all rely on this single RCT that directly addresses the question, plus post-hoc analyses of other RCTs.

Four of 5 analyses find little or no difference in CV outcomes with a PPI

Four of 5 posthoc analyses (which weren’t themselves randomized) of RCTs found unclear or no differences in composite CV outcomes with concurrent use of a PPI and antiplatelet therapy, after multivariate adjustment for differences in populations taking or not taking a PPI.

Posthoc analysis of the largest study found worse CV outcomes for both clopidogrel and ticagrelor with concomitant PPI use.² However, patients on any GI drugs (PPI or non-PPI) had composite outcomes similar to patients on a PPI (PPI vs non-PPI GI treatment: HR = 0.98; 95% CI, 0.79-1.23), and patients not taking GI drugs had fewer composite outcomes compared with patients on a PPI (clopidogrel vs no GI therapy: HR = 1.29; 95% CI, 1.12-1.49; ticagrelor vs no GI therapy: HR = 1.30; 95% CI, 1.14-1.49). Researchers postulated that because the rate of composite outcomes increased equally for patients on any GI drug, the higher rate of CV adverse events with a PPI might have been related to GI disease rather than PPI use.

A similar posthoc analysis found no differences with or without PPI use among patients with ACS undergoing planned percutaneous coronary intervention (PCI) and assigned to clopidogrel or prasugrel.³ Researchers performed multivariate adjustment for differences in age, gender, ethnicity, and initial presence of unstable angina/non-ST-elevation MI.

A smaller study also found no significant differences in composite CV outcomes in patients using PPIs.⁴ Patients did have higher rates of MI (HR = 0.62; 95% CI, 0.42-0.91), but they were more likely to be older and have a previous diagnosis of non-ST-elevation MI, higher incidence of previous coronary artery bypass graft surgery, and history of peptic ulcer disease.

The fourth posthoc analysis of an RCT found that concomitant PPI use (91% of patients on lansoprazole) didn’t alter outcomes among patients undergoing PCI and receiving dual antiplatelet therapy with clopidogrel and aspirin.⁵ Researchers used a multivariate adjustment for differences in age, gender, and renal function and found no difference in outcomes during the 6-month or 24-month period. PPI prescription was at physician discretion. Researchers didn’t assess for dose-dependent effects of PPI.

A fifth, flawed study finds more adverse events with PPIs

A posthoc analysis of a smaller, open-label trial found increased major adverse cardiac events with PPI use among patients taking clopidogrel after PCI.⁶ Researchers didn’t adjust for differences in populations at baseline, however, and patients taking PPIs were more likely to be female or older and have diabetes, GI disease, or higher serum creatinine levels.

Continue to: Editor's takeaway

 

 

Editor’s takeaway

The best evidence (a large RCT) found that adding a PPI to antiplatelet therapy didn’t alter CV outcomes in patients with ACS, but it did reduce GI bleeds. Hopefully this will give providers the confidence to use PPIs, if clinically indicated, in patients taking antiplatelet therapy with clopidogrel or prasugrel.

EVIDENCE SUMMARY

A double-blind, double-dummy, placebo-controlled RCT comparing a combination of clopidogrel, aspirin, and omeprazole with clopidogrel, aspirin, and placebo found no increase in composite CV outcomes with the PPI (TABLE).¹ Using a PPI did, however, significantly reduce gastrointestinal (GI) bleeding (hazard ratio [HR] = 0.13; 95% confidence interval [CI], 0.03-0.56).Although several meta-analyses have been conducted, they all rely on this single RCT that directly addresses the question, plus post-hoc analyses of other RCTs.

Four of 5 analyses find little or no difference in CV outcomes with a PPI

Four of 5 posthoc analyses (which weren’t themselves randomized) of RCTs found unclear or no differences in composite CV outcomes with concurrent use of a PPI and antiplatelet therapy, after multivariate adjustment for differences in populations taking or not taking a PPI.

Posthoc analysis of the largest study found worse CV outcomes for both clopidogrel and ticagrelor with concomitant PPI use.² However, patients on any GI drugs (PPI or non-PPI) had composite outcomes similar to patients on a PPI (PPI vs non-PPI GI treatment: HR = 0.98; 95% CI, 0.79-1.23), and patients not taking GI drugs had fewer composite outcomes compared with patients on a PPI (clopidogrel vs no GI therapy: HR = 1.29; 95% CI, 1.12-1.49; ticagrelor vs no GI therapy: HR = 1.30; 95% CI, 1.14-1.49). Researchers postulated that because the rate of composite outcomes increased equally for patients on any GI drug, the higher rate of CV adverse events with a PPI might have been related to GI disease rather than PPI use.

A similar posthoc analysis found no differences with or without PPI use among patients with ACS undergoing planned percutaneous coronary intervention (PCI) and assigned to clopidogrel or prasugrel.³ Researchers performed multivariate adjustment for differences in age, gender, ethnicity, and initial presence of unstable angina/non-ST-elevation MI.

A smaller study also found no significant differences in composite CV outcomes in patients using PPIs.⁴ Patients did have higher rates of MI (HR = 0.62; 95% CI, 0.42-0.91), but they were more likely to be older and have a previous diagnosis of non-ST-elevation MI, higher incidence of previous coronary artery bypass graft surgery, and history of peptic ulcer disease.

The fourth posthoc analysis of an RCT found that concomitant PPI use (91% of patients on lansoprazole) didn’t alter outcomes among patients undergoing PCI and receiving dual antiplatelet therapy with clopidogrel and aspirin.⁵ Researchers used a multivariate adjustment for differences in age, gender, and renal function and found no difference in outcomes during the 6-month or 24-month period. PPI prescription was at physician discretion. Researchers didn’t assess for dose-dependent effects of PPI.

A fifth, flawed study finds more adverse events with PPIs

A posthoc analysis of a smaller, open-label trial found increased major adverse cardiac events with PPI use among patients taking clopidogrel after PCI.⁶ Researchers didn’t adjust for differences in populations at baseline, however, and patients taking PPIs were more likely to be female or older and have diabetes, GI disease, or higher serum creatinine levels.

Continue to: Editor's takeaway

 

 

Editor’s takeaway

The best evidence (a large RCT) found that adding a PPI to antiplatelet therapy didn’t alter CV outcomes in patients with ACS, but it did reduce GI bleeds. Hopefully this will give providers the confidence to use PPIs, if clinically indicated, in patients taking antiplatelet therapy with clopidogrel or prasugrel.

CASE Woman with vulvar itch and white vaginal discharge

A 26-year-old sexually active nulligravid woman requests evaluation for moderately intense “itching in the vagina and on the vulva.” She uses combination oral contraceptives and has 2 current sexual partners. On physical examination, you note a thick, white, curd-like discharge that is adherent to the vaginal epithelium. The vulva is erythematous, and small “satellite lesions” are evident in the intertriginous folds.

• What is the most likely diagnosis?
• How should you treat this patient?

Approximately 75% of all women will have at least 1 episode of vulvovaginal candidiasis (VVC) in their lifetime.¹ Candida albicans, the most commonly identified organism in these infections, colonizes the vagina of many individuals commensally; higher rates of colonization occur in women with diabetes, obesity, recent use of broad-spectrum antibiotics, steroid use and immunosuppression, and in women who are pregnant. Of special interest, pregnant women have an increased risk of symptomatic infection, and they respond less favorably to conventional treatment regimens.¹

Deconstructing C albicans and other species

Historically, in more than 90% of cases, C albicans is the principal cause of VVC. While it remains the most prevalent Candida species in the United States, over the last 15 years studies have demonstrated that in some countries, such as India and Nigeria, C albicans constitutes less than half of the cultured species in women with VVC. This observation may be due to the widespread availability and use of common antifungal medications, which leads to resistance and selection for resistant species.^1,2

In asymptomatic women, vaginal colonies of C albicans grow in the yeast form. This condition is usually well tolerated by the host and does not cause a major immune response. In periods of stress for the host micro- and mycobiomes, however (dysbiosis, immune suppression, trauma), C albicans is induced into morphogenesis, proliferating and forming hyphae that are thought to activate the host immune response. The vaginal epithelium becomes sensitized to the presence of C albicans and recruits large numbers of neutrophils that, in turn, drive the pathophysiology of VVC.³

There is a theory that the separation of the urethra and anus by the vagina has exerted evolutionary pressure to maintain the presence of commensal C albicans yeast colonies in the vagina. C albicans exerts an antagonistic effect on many bacteria and, therefore, may act as a “microbiologic barrier” between the anus and the urethra to prevent urinary tract infections that, before the modern antibiotic era, may have caused serious morbidity and even mortality.³

Other organisms that cause VVC include C glabrata, C parapsilosis, and C tropicalis. Ex vivo experiments have shown that co-infection of C albicans with C glabrata enhances the ability of C glabrata to invade tissue.² C glabrata is more frequently resistant to commonly used antifungal compounds than C albicans,^2,4 which suggests that identifying the specific fungal pathogen is becoming increasingly important in planning targeted therapy.

Continue to: A common infection...

A common infection

While three-quarters of women will experience VVC at least once in their lifetime, between 40% and 45% will experience it more than once, and 5% to 8% will develop recurrent VVC. Among pregnant women, 15% will develop symptomatic VVC.^1,2

However, because VVC is not a reportable disease and antifungal medication is available over the counter without physician consultation, these numbers likely underestimate the true incidence of the infection.⁴

Complications in pregnancy

Vaginal infections, including VVC, bacterial vaginosis (BV), and trichomoniasis, may be associated with 40% of preterm deliveries.⁵ The high concentrations of estrogen and progesterone during pregnancy create a uniquely glycogen-rich vaginal environment in which Candida species can flourish.^2,4 Even asymptomatic colonization of the vagina with Candida species has been associated with preterm labor, preterm birth, and low birth weight.^1,6 This association appears to have more severe consequences if VVC occurs in the second trimester compared with the first trimester.⁶

Additionally, congenital candidiasis of the newborn may result from intrauterine Candida infection or heavy maternal vaginal colonization at delivery, and the infection is evident within 24 hours of birth. It presents typically as oropharyngeal candidiasis (thrush) of the newborn.¹

Clinical manifestations of infection

The classic manifestations of Candida infection are similar in both the pregnant and nonpregnant patient: acute vaginal and vulvar pruritus and thick, white, malodorous “cottage cheese” vaginal discharge.^1,4 Exercise caution, however, in treating presumptively based on these symptoms alone, especially in pregnancy, because they are not specific to candidiasis.⁴ Vaginal discharge is not always present, and it may vary in appearance and odor. Pruritus is the most specific symptom of Candida infection, but studies show that it is an accurate predictor in only 38% of cases.⁷

Other common signs and symptoms include the sensation of burning, dysuria, dyspareunia, fissures, excoriations, and pruritus ani. Physical examination demonstrates erythema and swelling of labial, vulvar, and vaginal structures, with a normal cervix and an adherent white or off-white discharge. When the discharge is removed from the vaginal wall, small bleeding points may appear.^1,4

Making the diagnosis

As mentioned, history alone is not sufficient to make a definitive diagnosis of candidiasis. The diagnosis should be made by examining vaginal secretions under a microscope or by culture.⁴ A wet mount and KOH (potassium hydroxide) prep help differentiate VVC, BV, and trichomoniasis. Culture is particularly valuable in identifying less common fungal organisms, such as C glabrata and C tropicalis.

Vaginal pH testing is not conclusive for Candida because vaginal pH is normal in VVC. However, pH assessment can rule in other causative organisms if the value is abnormal (that is, elevated pH of 4.5 or greater with BV and trichomoniasis).¹

Treatment options

Acute infection. A pregnant woman who tests positive for VVC may safely be treated in any trimester with a 7-day course of a topical azole.⁸ If the patient prefers the convenience of oral therapy, after the first trimester, oral fluconazole, 150 mg on day 1 and day 3, may be used for treatment. Note that fluconazole has been associated with an increased risk of spontaneous abortion and cardiac septal defects when used in the first trimester.¹

The Centers for Disease Control and Prevention recommends a number of topical treatments for VVC (TABLE).⁸ Several of these drugs are available over the counter without a prescription. Topical azoles are more effective than nystatin in treating VVC, and posttreatment cultures are negative in up to 90% of treated patients.⁸

Recurrent infections. Recurrent VVC is defined as 4 or more episodes of symptomatic VVC within 12 months.⁸ Typical first-line treatment of recurrent infections in nonpregnant patients is a 6-month course of fluconazole, 150 mg weekly.^9,10 As noted, however, fluconazole should not be used in the first trimester of pregnancy. It is acceptable therapy thereafter for patients who have troublesome recurrent or persistent infections.

Continue to: Strategies for preventing recurrence...

Strategies for preventing recurrence

While it is logical to consider antimycotic prophylaxis in women with a history of recurring VVC and/or a significant number of known risk factors, data suggest that extended prophylaxis with an azole does not consistently achieve long-term elimination of vaginal Candida organisms after cessation of the azole.⁹

At-risk women should be counseled to make lifestyle adjustments, such as wearing breathable cotton clothing, particularly undergarments; promptly changing out of damp clothing; and forgoing the use of commercial intravaginal feminine hygiene products.

Recent research has shown that the use of Saccharomyces cerevisiae–based probiotics has promise for controlling the burden of C albicans in women receiving antifungal drugs for VVC and also for preventing recurrence; however, this approach has undergone limited testing in humans, and its efficacy and safety in pregnancy is unknown.¹¹ ●

CASE Woman with vulvar itch and white vaginal discharge

A 26-year-old sexually active nulligravid woman requests evaluation for moderately intense “itching in the vagina and on the vulva.” She uses combination oral contraceptives and has 2 current sexual partners. On physical examination, you note a thick, white, curd-like discharge that is adherent to the vaginal epithelium. The vulva is erythematous, and small “satellite lesions” are evident in the intertriginous folds.

• What is the most likely diagnosis?
• How should you treat this patient?

Approximately 75% of all women will have at least 1 episode of vulvovaginal candidiasis (VVC) in their lifetime.¹ Candida albicans, the most commonly identified organism in these infections, colonizes the vagina of many individuals commensally; higher rates of colonization occur in women with diabetes, obesity, recent use of broad-spectrum antibiotics, steroid use and immunosuppression, and in women who are pregnant. Of special interest, pregnant women have an increased risk of symptomatic infection, and they respond less favorably to conventional treatment regimens.¹

Deconstructing C albicans and other species

Historically, in more than 90% of cases, C albicans is the principal cause of VVC. While it remains the most prevalent Candida species in the United States, over the last 15 years studies have demonstrated that in some countries, such as India and Nigeria, C albicans constitutes less than half of the cultured species in women with VVC. This observation may be due to the widespread availability and use of common antifungal medications, which leads to resistance and selection for resistant species.^1,2

In asymptomatic women, vaginal colonies of C albicans grow in the yeast form. This condition is usually well tolerated by the host and does not cause a major immune response. In periods of stress for the host micro- and mycobiomes, however (dysbiosis, immune suppression, trauma), C albicans is induced into morphogenesis, proliferating and forming hyphae that are thought to activate the host immune response. The vaginal epithelium becomes sensitized to the presence of C albicans and recruits large numbers of neutrophils that, in turn, drive the pathophysiology of VVC.³

There is a theory that the separation of the urethra and anus by the vagina has exerted evolutionary pressure to maintain the presence of commensal C albicans yeast colonies in the vagina. C albicans exerts an antagonistic effect on many bacteria and, therefore, may act as a “microbiologic barrier” between the anus and the urethra to prevent urinary tract infections that, before the modern antibiotic era, may have caused serious morbidity and even mortality.³

Other organisms that cause VVC include C glabrata, C parapsilosis, and C tropicalis. Ex vivo experiments have shown that co-infection of C albicans with C glabrata enhances the ability of C glabrata to invade tissue.² C glabrata is more frequently resistant to commonly used antifungal compounds than C albicans,^2,4 which suggests that identifying the specific fungal pathogen is becoming increasingly important in planning targeted therapy.

Continue to: A common infection...

A common infection

While three-quarters of women will experience VVC at least once in their lifetime, between 40% and 45% will experience it more than once, and 5% to 8% will develop recurrent VVC. Among pregnant women, 15% will develop symptomatic VVC.^1,2

However, because VVC is not a reportable disease and antifungal medication is available over the counter without physician consultation, these numbers likely underestimate the true incidence of the infection.⁴

Complications in pregnancy

Vaginal infections, including VVC, bacterial vaginosis (BV), and trichomoniasis, may be associated with 40% of preterm deliveries.⁵ The high concentrations of estrogen and progesterone during pregnancy create a uniquely glycogen-rich vaginal environment in which Candida species can flourish.^2,4 Even asymptomatic colonization of the vagina with Candida species has been associated with preterm labor, preterm birth, and low birth weight.^1,6 This association appears to have more severe consequences if VVC occurs in the second trimester compared with the first trimester.⁶

Additionally, congenital candidiasis of the newborn may result from intrauterine Candida infection or heavy maternal vaginal colonization at delivery, and the infection is evident within 24 hours of birth. It presents typically as oropharyngeal candidiasis (thrush) of the newborn.¹

Clinical manifestations of infection

The classic manifestations of Candida infection are similar in both the pregnant and nonpregnant patient: acute vaginal and vulvar pruritus and thick, white, malodorous “cottage cheese” vaginal discharge.^1,4 Exercise caution, however, in treating presumptively based on these symptoms alone, especially in pregnancy, because they are not specific to candidiasis.⁴ Vaginal discharge is not always present, and it may vary in appearance and odor. Pruritus is the most specific symptom of Candida infection, but studies show that it is an accurate predictor in only 38% of cases.⁷

Other common signs and symptoms include the sensation of burning, dysuria, dyspareunia, fissures, excoriations, and pruritus ani. Physical examination demonstrates erythema and swelling of labial, vulvar, and vaginal structures, with a normal cervix and an adherent white or off-white discharge. When the discharge is removed from the vaginal wall, small bleeding points may appear.^1,4

Making the diagnosis

As mentioned, history alone is not sufficient to make a definitive diagnosis of candidiasis. The diagnosis should be made by examining vaginal secretions under a microscope or by culture.⁴ A wet mount and KOH (potassium hydroxide) prep help differentiate VVC, BV, and trichomoniasis. Culture is particularly valuable in identifying less common fungal organisms, such as C glabrata and C tropicalis.

Vaginal pH testing is not conclusive for Candida because vaginal pH is normal in VVC. However, pH assessment can rule in other causative organisms if the value is abnormal (that is, elevated pH of 4.5 or greater with BV and trichomoniasis).¹

Treatment options

Acute infection. A pregnant woman who tests positive for VVC may safely be treated in any trimester with a 7-day course of a topical azole.⁸ If the patient prefers the convenience of oral therapy, after the first trimester, oral fluconazole, 150 mg on day 1 and day 3, may be used for treatment. Note that fluconazole has been associated with an increased risk of spontaneous abortion and cardiac septal defects when used in the first trimester.¹

The Centers for Disease Control and Prevention recommends a number of topical treatments for VVC (TABLE).⁸ Several of these drugs are available over the counter without a prescription. Topical azoles are more effective than nystatin in treating VVC, and posttreatment cultures are negative in up to 90% of treated patients.⁸

Recurrent infections. Recurrent VVC is defined as 4 or more episodes of symptomatic VVC within 12 months.⁸ Typical first-line treatment of recurrent infections in nonpregnant patients is a 6-month course of fluconazole, 150 mg weekly.^9,10 As noted, however, fluconazole should not be used in the first trimester of pregnancy. It is acceptable therapy thereafter for patients who have troublesome recurrent or persistent infections.

Continue to: Strategies for preventing recurrence...

Strategies for preventing recurrence

While it is logical to consider antimycotic prophylaxis in women with a history of recurring VVC and/or a significant number of known risk factors, data suggest that extended prophylaxis with an azole does not consistently achieve long-term elimination of vaginal Candida organisms after cessation of the azole.⁹

At-risk women should be counseled to make lifestyle adjustments, such as wearing breathable cotton clothing, particularly undergarments; promptly changing out of damp clothing; and forgoing the use of commercial intravaginal feminine hygiene products.

Recent research has shown that the use of Saccharomyces cerevisiae–based probiotics has promise for controlling the burden of C albicans in women receiving antifungal drugs for VVC and also for preventing recurrence; however, this approach has undergone limited testing in humans, and its efficacy and safety in pregnancy is unknown.¹¹ ●

CASE Woman with vulvar itch and white vaginal discharge

A 26-year-old sexually active nulligravid woman requests evaluation for moderately intense “itching in the vagina and on the vulva.” She uses combination oral contraceptives and has 2 current sexual partners. On physical examination, you note a thick, white, curd-like discharge that is adherent to the vaginal epithelium. The vulva is erythematous, and small “satellite lesions” are evident in the intertriginous folds.

• What is the most likely diagnosis?
• How should you treat this patient?

Approximately 75% of all women will have at least 1 episode of vulvovaginal candidiasis (VVC) in their lifetime.¹ Candida albicans, the most commonly identified organism in these infections, colonizes the vagina of many individuals commensally; higher rates of colonization occur in women with diabetes, obesity, recent use of broad-spectrum antibiotics, steroid use and immunosuppression, and in women who are pregnant. Of special interest, pregnant women have an increased risk of symptomatic infection, and they respond less favorably to conventional treatment regimens.¹

Deconstructing C albicans and other species

Historically, in more than 90% of cases, C albicans is the principal cause of VVC. While it remains the most prevalent Candida species in the United States, over the last 15 years studies have demonstrated that in some countries, such as India and Nigeria, C albicans constitutes less than half of the cultured species in women with VVC. This observation may be due to the widespread availability and use of common antifungal medications, which leads to resistance and selection for resistant species.^1,2

In asymptomatic women, vaginal colonies of C albicans grow in the yeast form. This condition is usually well tolerated by the host and does not cause a major immune response. In periods of stress for the host micro- and mycobiomes, however (dysbiosis, immune suppression, trauma), C albicans is induced into morphogenesis, proliferating and forming hyphae that are thought to activate the host immune response. The vaginal epithelium becomes sensitized to the presence of C albicans and recruits large numbers of neutrophils that, in turn, drive the pathophysiology of VVC.³

There is a theory that the separation of the urethra and anus by the vagina has exerted evolutionary pressure to maintain the presence of commensal C albicans yeast colonies in the vagina. C albicans exerts an antagonistic effect on many bacteria and, therefore, may act as a “microbiologic barrier” between the anus and the urethra to prevent urinary tract infections that, before the modern antibiotic era, may have caused serious morbidity and even mortality.³

Other organisms that cause VVC include C glabrata, C parapsilosis, and C tropicalis. Ex vivo experiments have shown that co-infection of C albicans with C glabrata enhances the ability of C glabrata to invade tissue.² C glabrata is more frequently resistant to commonly used antifungal compounds than C albicans,^2,4 which suggests that identifying the specific fungal pathogen is becoming increasingly important in planning targeted therapy.

Continue to: A common infection...

A common infection

While three-quarters of women will experience VVC at least once in their lifetime, between 40% and 45% will experience it more than once, and 5% to 8% will develop recurrent VVC. Among pregnant women, 15% will develop symptomatic VVC.^1,2

However, because VVC is not a reportable disease and antifungal medication is available over the counter without physician consultation, these numbers likely underestimate the true incidence of the infection.⁴

Complications in pregnancy

Vaginal infections, including VVC, bacterial vaginosis (BV), and trichomoniasis, may be associated with 40% of preterm deliveries.⁵ The high concentrations of estrogen and progesterone during pregnancy create a uniquely glycogen-rich vaginal environment in which Candida species can flourish.^2,4 Even asymptomatic colonization of the vagina with Candida species has been associated with preterm labor, preterm birth, and low birth weight.^1,6 This association appears to have more severe consequences if VVC occurs in the second trimester compared with the first trimester.⁶

Additionally, congenital candidiasis of the newborn may result from intrauterine Candida infection or heavy maternal vaginal colonization at delivery, and the infection is evident within 24 hours of birth. It presents typically as oropharyngeal candidiasis (thrush) of the newborn.¹

Clinical manifestations of infection

The classic manifestations of Candida infection are similar in both the pregnant and nonpregnant patient: acute vaginal and vulvar pruritus and thick, white, malodorous “cottage cheese” vaginal discharge.^1,4 Exercise caution, however, in treating presumptively based on these symptoms alone, especially in pregnancy, because they are not specific to candidiasis.⁴ Vaginal discharge is not always present, and it may vary in appearance and odor. Pruritus is the most specific symptom of Candida infection, but studies show that it is an accurate predictor in only 38% of cases.⁷

Other common signs and symptoms include the sensation of burning, dysuria, dyspareunia, fissures, excoriations, and pruritus ani. Physical examination demonstrates erythema and swelling of labial, vulvar, and vaginal structures, with a normal cervix and an adherent white or off-white discharge. When the discharge is removed from the vaginal wall, small bleeding points may appear.^1,4

Making the diagnosis

As mentioned, history alone is not sufficient to make a definitive diagnosis of candidiasis. The diagnosis should be made by examining vaginal secretions under a microscope or by culture.⁴ A wet mount and KOH (potassium hydroxide) prep help differentiate VVC, BV, and trichomoniasis. Culture is particularly valuable in identifying less common fungal organisms, such as C glabrata and C tropicalis.

Vaginal pH testing is not conclusive for Candida because vaginal pH is normal in VVC. However, pH assessment can rule in other causative organisms if the value is abnormal (that is, elevated pH of 4.5 or greater with BV and trichomoniasis).¹

Treatment options

Acute infection. A pregnant woman who tests positive for VVC may safely be treated in any trimester with a 7-day course of a topical azole.⁸ If the patient prefers the convenience of oral therapy, after the first trimester, oral fluconazole, 150 mg on day 1 and day 3, may be used for treatment. Note that fluconazole has been associated with an increased risk of spontaneous abortion and cardiac septal defects when used in the first trimester.¹

The Centers for Disease Control and Prevention recommends a number of topical treatments for VVC (TABLE).⁸ Several of these drugs are available over the counter without a prescription. Topical azoles are more effective than nystatin in treating VVC, and posttreatment cultures are negative in up to 90% of treated patients.⁸

Recurrent infections. Recurrent VVC is defined as 4 or more episodes of symptomatic VVC within 12 months.⁸ Typical first-line treatment of recurrent infections in nonpregnant patients is a 6-month course of fluconazole, 150 mg weekly.^9,10 As noted, however, fluconazole should not be used in the first trimester of pregnancy. It is acceptable therapy thereafter for patients who have troublesome recurrent or persistent infections.

Continue to: Strategies for preventing recurrence...

Strategies for preventing recurrence

While it is logical to consider antimycotic prophylaxis in women with a history of recurring VVC and/or a significant number of known risk factors, data suggest that extended prophylaxis with an azole does not consistently achieve long-term elimination of vaginal Candida organisms after cessation of the azole.⁹

At-risk women should be counseled to make lifestyle adjustments, such as wearing breathable cotton clothing, particularly undergarments; promptly changing out of damp clothing; and forgoing the use of commercial intravaginal feminine hygiene products.

Recent research has shown that the use of Saccharomyces cerevisiae–based probiotics has promise for controlling the burden of C albicans in women receiving antifungal drugs for VVC and also for preventing recurrence; however, this approach has undergone limited testing in humans, and its efficacy and safety in pregnancy is unknown.¹¹ ●

Patients with psoriatic disease are known to be at increased risk of heart failure. A new cohort study suggests that part of the risk may be attributable to the disease itself, not just traditional cardiovascular risk factors like obesity and metabolic abnormalities that are common comorbidities in psoriatic disease. There may also be differences in the risk profiles of patients with ischemic and nonischemic heart failure.

Courtesy Dr. Sahil Koppikar

Previous studies have shown that heart failure risk in patients with psoriatic arthritis is 32% higher than in the general population, and with psoriasis, it is 22%-53% higher. However, those studies were based on administrative databases with no clinical information to back up the accuracy of diagnoses, Sahil Koppikar, MD, from the University of Toronto, said during a presentation of the research at the virtual annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).

The finding that psoriatic disease inflammation may be a direct risk factor for heart failure might be good news for patients. “By controlling inflammation, we may be able to reduce the risk of heart failure in these patients,” Dr. Koppikar said.

During a question and answer session, discussant Deepak Jadon, MBChB, PhD, director of the rheumatology research unit and lead for psoriatic arthritis at Addenbrooke’s Hospital, Cambridge (England), noted that patients with conditions like lupus and systemic sclerosis may undergo regular echocardiograms, chest CTs, or other surveillance, and asked if Dr. Koppikar could recommend a framework for similar surveillance in psoriatic arthritis.

“With the current data we have, I don’t know if we can make recommendations. What we learned from our study is that patients that have elevated inflammatory disease, with elevated inflammatory markers for a prolonged period of time, were at higher risk than [if they had elevated markers only] just before the event. So poorly controlled patients might be something you should be more aware of, and maybe get cardiology involved. But I don’t think it’s something we should be doing right now for all patients,” Dr. Koppikar said.

The researchers analyzed data from a psoriasis cohort at the University of Toronto that began in 2006. Every 6-12 months, they were assessed by a rheumatologist and underwent imaging assessment and laboratory tests. The primary outcome of the study was the first heart failure event, which the researchers identified by linking the cohort database with provincial hospitalization and mortality databases. They verified all events by examining medical records. They also assessed the association between heart failure and disease activity over time rather than just before the event.

The analysis included 1,994 patients. A total of 64 new heart failure events occurred during a mean follow-up of 11.3 years (2.85 per 1,000 person-years), including 38 ischemic and 26 nonischemic events. A multivariate analysis found that heart failure was associated with adjusted mean (AM) tender joint count (hazard ratio, 1.51; P = .02), AM swollen joint count (HR, 1.82; P = .04), AM erythrocyte sedimentation rate (HR, 1.26; P = .009), AM C-reactive protein (HR, 1.27; P = .001), Health Assessment Questionnaire (HR, 1.95; P = .001), and minimum disease activity state (HR, 0.40; P = .04). The multivariate analysis was adjusted for sex, hypertension, diabetes mellitus, body mass index, ischemic heart disease, lipids, and smoking status.

When the researchers separated the analysis into ischemic and nonischemic heart failure, some interesting associations popped out. Nonischemic heart failure was associated with AM tender joint count (HR, 1.83; P = .004), but ischemic heart failure was not. Other factors associated with nonischemic but not ischemic heart failure included AM swollen joint count (HR, 3.56; P = .0003), damaged joint count (HR, 1.29; P = .04), and pain score (HR, 1.22; P = .047). Minimum disease activity had the opposite result: It was associated with only ischemic heart failure (HR, 0.40; P = .04).

The study cohort more closely resembles a rheumatology cohort than a dermatology cohort, and it suggests that patients with psoriatic arthritis have different cardiovascular comorbidities than those with pure psoriasis, according to Diamant Thaçi, MD, PhD, professor and chairman of the department of dermatology at the University of Lübeck (Germany). “It shows how it important it is to look for comorbidity in the rheumatologic setting,” Dr. Thaçi said in an interview.

The study was supported by the Arthritis Society. Dr. Koppikar and Dr. Thaçi have no relevant financial disclosures.

SOURCE: Koppikar S et al. GRAPPA 2020 Virtual Annual Meeting.

Patients with psoriatic disease are known to be at increased risk of heart failure. A new cohort study suggests that part of the risk may be attributable to the disease itself, not just traditional cardiovascular risk factors like obesity and metabolic abnormalities that are common comorbidities in psoriatic disease. There may also be differences in the risk profiles of patients with ischemic and nonischemic heart failure.

Courtesy Dr. Sahil Koppikar

Previous studies have shown that heart failure risk in patients with psoriatic arthritis is 32% higher than in the general population, and with psoriasis, it is 22%-53% higher. However, those studies were based on administrative databases with no clinical information to back up the accuracy of diagnoses, Sahil Koppikar, MD, from the University of Toronto, said during a presentation of the research at the virtual annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).

The finding that psoriatic disease inflammation may be a direct risk factor for heart failure might be good news for patients. “By controlling inflammation, we may be able to reduce the risk of heart failure in these patients,” Dr. Koppikar said.

During a question and answer session, discussant Deepak Jadon, MBChB, PhD, director of the rheumatology research unit and lead for psoriatic arthritis at Addenbrooke’s Hospital, Cambridge (England), noted that patients with conditions like lupus and systemic sclerosis may undergo regular echocardiograms, chest CTs, or other surveillance, and asked if Dr. Koppikar could recommend a framework for similar surveillance in psoriatic arthritis.

“With the current data we have, I don’t know if we can make recommendations. What we learned from our study is that patients that have elevated inflammatory disease, with elevated inflammatory markers for a prolonged period of time, were at higher risk than [if they had elevated markers only] just before the event. So poorly controlled patients might be something you should be more aware of, and maybe get cardiology involved. But I don’t think it’s something we should be doing right now for all patients,” Dr. Koppikar said.

The researchers analyzed data from a psoriasis cohort at the University of Toronto that began in 2006. Every 6-12 months, they were assessed by a rheumatologist and underwent imaging assessment and laboratory tests. The primary outcome of the study was the first heart failure event, which the researchers identified by linking the cohort database with provincial hospitalization and mortality databases. They verified all events by examining medical records. They also assessed the association between heart failure and disease activity over time rather than just before the event.

The analysis included 1,994 patients. A total of 64 new heart failure events occurred during a mean follow-up of 11.3 years (2.85 per 1,000 person-years), including 38 ischemic and 26 nonischemic events. A multivariate analysis found that heart failure was associated with adjusted mean (AM) tender joint count (hazard ratio, 1.51; P = .02), AM swollen joint count (HR, 1.82; P = .04), AM erythrocyte sedimentation rate (HR, 1.26; P = .009), AM C-reactive protein (HR, 1.27; P = .001), Health Assessment Questionnaire (HR, 1.95; P = .001), and minimum disease activity state (HR, 0.40; P = .04). The multivariate analysis was adjusted for sex, hypertension, diabetes mellitus, body mass index, ischemic heart disease, lipids, and smoking status.

When the researchers separated the analysis into ischemic and nonischemic heart failure, some interesting associations popped out. Nonischemic heart failure was associated with AM tender joint count (HR, 1.83; P = .004), but ischemic heart failure was not. Other factors associated with nonischemic but not ischemic heart failure included AM swollen joint count (HR, 3.56; P = .0003), damaged joint count (HR, 1.29; P = .04), and pain score (HR, 1.22; P = .047). Minimum disease activity had the opposite result: It was associated with only ischemic heart failure (HR, 0.40; P = .04).

The study cohort more closely resembles a rheumatology cohort than a dermatology cohort, and it suggests that patients with psoriatic arthritis have different cardiovascular comorbidities than those with pure psoriasis, according to Diamant Thaçi, MD, PhD, professor and chairman of the department of dermatology at the University of Lübeck (Germany). “It shows how it important it is to look for comorbidity in the rheumatologic setting,” Dr. Thaçi said in an interview.

The study was supported by the Arthritis Society. Dr. Koppikar and Dr. Thaçi have no relevant financial disclosures.

SOURCE: Koppikar S et al. GRAPPA 2020 Virtual Annual Meeting.

Patients with psoriatic disease are known to be at increased risk of heart failure. A new cohort study suggests that part of the risk may be attributable to the disease itself, not just traditional cardiovascular risk factors like obesity and metabolic abnormalities that are common comorbidities in psoriatic disease. There may also be differences in the risk profiles of patients with ischemic and nonischemic heart failure.

Courtesy Dr. Sahil Koppikar

Previous studies have shown that heart failure risk in patients with psoriatic arthritis is 32% higher than in the general population, and with psoriasis, it is 22%-53% higher. However, those studies were based on administrative databases with no clinical information to back up the accuracy of diagnoses, Sahil Koppikar, MD, from the University of Toronto, said during a presentation of the research at the virtual annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).

The finding that psoriatic disease inflammation may be a direct risk factor for heart failure might be good news for patients. “By controlling inflammation, we may be able to reduce the risk of heart failure in these patients,” Dr. Koppikar said.

During a question and answer session, discussant Deepak Jadon, MBChB, PhD, director of the rheumatology research unit and lead for psoriatic arthritis at Addenbrooke’s Hospital, Cambridge (England), noted that patients with conditions like lupus and systemic sclerosis may undergo regular echocardiograms, chest CTs, or other surveillance, and asked if Dr. Koppikar could recommend a framework for similar surveillance in psoriatic arthritis.

“With the current data we have, I don’t know if we can make recommendations. What we learned from our study is that patients that have elevated inflammatory disease, with elevated inflammatory markers for a prolonged period of time, were at higher risk than [if they had elevated markers only] just before the event. So poorly controlled patients might be something you should be more aware of, and maybe get cardiology involved. But I don’t think it’s something we should be doing right now for all patients,” Dr. Koppikar said.

The researchers analyzed data from a psoriasis cohort at the University of Toronto that began in 2006. Every 6-12 months, they were assessed by a rheumatologist and underwent imaging assessment and laboratory tests. The primary outcome of the study was the first heart failure event, which the researchers identified by linking the cohort database with provincial hospitalization and mortality databases. They verified all events by examining medical records. They also assessed the association between heart failure and disease activity over time rather than just before the event.

The analysis included 1,994 patients. A total of 64 new heart failure events occurred during a mean follow-up of 11.3 years (2.85 per 1,000 person-years), including 38 ischemic and 26 nonischemic events. A multivariate analysis found that heart failure was associated with adjusted mean (AM) tender joint count (hazard ratio, 1.51; P = .02), AM swollen joint count (HR, 1.82; P = .04), AM erythrocyte sedimentation rate (HR, 1.26; P = .009), AM C-reactive protein (HR, 1.27; P = .001), Health Assessment Questionnaire (HR, 1.95; P = .001), and minimum disease activity state (HR, 0.40; P = .04). The multivariate analysis was adjusted for sex, hypertension, diabetes mellitus, body mass index, ischemic heart disease, lipids, and smoking status.

When the researchers separated the analysis into ischemic and nonischemic heart failure, some interesting associations popped out. Nonischemic heart failure was associated with AM tender joint count (HR, 1.83; P = .004), but ischemic heart failure was not. Other factors associated with nonischemic but not ischemic heart failure included AM swollen joint count (HR, 3.56; P = .0003), damaged joint count (HR, 1.29; P = .04), and pain score (HR, 1.22; P = .047). Minimum disease activity had the opposite result: It was associated with only ischemic heart failure (HR, 0.40; P = .04).

The study cohort more closely resembles a rheumatology cohort than a dermatology cohort, and it suggests that patients with psoriatic arthritis have different cardiovascular comorbidities than those with pure psoriasis, according to Diamant Thaçi, MD, PhD, professor and chairman of the department of dermatology at the University of Lübeck (Germany). “It shows how it important it is to look for comorbidity in the rheumatologic setting,” Dr. Thaçi said in an interview.

The study was supported by the Arthritis Society. Dr. Koppikar and Dr. Thaçi have no relevant financial disclosures.

SOURCE: Koppikar S et al. GRAPPA 2020 Virtual Annual Meeting.

Empagliflozin showed favorable effects on diuretic use and congestion symptoms in patients with heart failure with reduced ejection fraction (HFrEF), but the oral sodium glucose cotransporter 2 (SGLT2) inhibitor did not improve the primary endpoint of improved exercise capacity in the EMPERIAL-Reduced trial, investigators reported at the European Society of Cardiology Heart Failure Discoveries virtual meeting.

In the matching EMPERIAL-Preserved trial, conducted in patients with heart failure with preserved ejection fraction (HFpEF), empagliflozin (Jardiance) produced modest improvements in diuretic use, as well as a reduction in unscheduled outpatient visits, compared with placebo-treated controls, although these trends failed to achieve statistical significance. And as in the EMPERIAL-Reduced trial, the SGLT2 inhibitor didn’t move the needle at all on the primary endpoint of improved exercise capacity as measured by 6-minute hall walk distance.

EMPERIAL-Reduced and -Preserved were identically designed, concurrent, phase 3, double-blind, 12-week randomized trials of empagliflozin versus placebo in 312 patients with HFrEF and 315 with HFpEF, defined in EMPERIAL-preserved as a left ventricular ejection fraction above 40%. The majority of participants had type 2 diabetes.

From a baseline median 6-minute walk distance of about 300 meters, the 6-minute walk distance at week 12 was actually 4.0 meters worse in the empagliflozin-treated HFrEF patients than it was in controls and a mere 4.0 meters better than with placebo in empagliflozin-treated patients with HFpEF, reported William T. Abraham, MD, professor of medicine, director of the division of cardiovascular medicine, and associate dean at Ohio State University, Columbus.

He indicated that the audience shouldn’t make too much of the failure to achieve the primary endpoint in the two trials in light of the studies’ major limitations: namely, their relatively small size for purposes of evaluating clinical outcomes and the relatively short 12-week duration.

“In many ways, I would say it’s remarkable that we can observe a positive signal, a favorable signal, in outcomes around congestion. In the case of HFrEF it’s statistically significant, and in HFpEF it’s a trend towards improvement. Of course, there are larger trials ongoing that may confirm these observations. Hopefully the EMPERIAL trials predict a good outcome for those ongoing trials,” Dr. Abraham said.

Piotr Ponikowski, MD, presented the study results for the secondary outcomes of congestion symptoms, diuretic use, and utilization of health care resources. In EMPERIAL-Reduced, intensification of diuretic therapy – often a prelude to acute decompensation and a trip to the hospital – occurred at a rate of 4.5% with empagliflozin and 16.1% with placebo, for a highly significant 73% relative risk reduction. Intensification of loop diuretics occurred in 2.6% of the empagliflozin group and 14.2% of controls, for a 82% risk reduction.

“That’s a pretty significant effect,” observed Dr. Ponikowski, professor of cardiology and head of the department of heart diseases at the Medical University of Wroclaw (Poland).

Moreover, a congestion symptoms score comprising a summary of orthopnea, jugular veinous distention, and edema improved by 47% after 12 weeks on empagliflozin, a statistically significant and clinically meaningful improvement that grew in magnitude over time and at 12 weeks was twice as large, compared with the reduction in placebo group, he added.

There was a trend for fewer unscheduled outpatient visits in the empagliflozin arm of EMPERIAL-Reduced with a rate of 10.4%, compared with 25.8% in controls; however, this 26% reduction in relative risk did not achieve statistical significance.

Intensification of loop diuretics occurred in 9% of EMPERIAL-Preserved participants on empagliflozin and 13.5% on placebo, but this 34% reduction in risk didn’t reach significance.

Adverse events in the EMPERIAL trials were similar across the active treatment and placebo arms. The benign safety profile was similar to what was seen in the earlier major clinical trials of empagliflozin for treatment of type 2 diabetes.

Session chair Stephane Heymans, MD, PhD, of the University of Maastricht (the Netherlands) noted that a substantial minority of patients in EMPERIAL-Reduced were on the combined neprilysin inhibitor sacubitril and the angiotensin receptor blocker valsartan (Entresto), whereas far fewer were in EMPERIAL-Preserved. He wondered if this greater use of background sacubitril/valsartan could explain empagliflozin’s greater efficacy in EMPERIAL-Reduced.

Highly unlikely, according to the investigators.

“It looks like, as is the case with most of our heart failure therapies, that we do see incremental value here. If you met the criteria for these trials, it appears you derived benefit from empagliflozin regardless of whether you were on an angiotensin receptor neprilysin inhibitor or not. I think that speaks to the incremental benefit of SGLT2 inhibitors on top of current guideline-directed medical therapy,” Dr. Abraham said.

Dr. Ponikowski observed that the same point was underscored in the DAPA-HF trial of the SGLT2 inhibitor dapagliflozin (Farxiga) in patients with heart failure (DAPA-HF: N Engl J Med. 2019 Nov 21;381[21]:1995-2008).

“You’ll see that the mortality and morbidity and quality-of-life benefit is in those treated with dapagliflozin with or without angiotensin receptor neprilysin inhibition; so, regardless of background therapy. And the effect is especially clear in patients on both therapies,” the cardiologist said.

The EMPERIAL trials were sponsored by Boehringer Ingelheim. Dr. Abraham and Dr. Ponikowksi reported receiving consultant fees from the company for serving on the trials’ executive committee.

bjancin@mdedge.com

Empagliflozin showed favorable effects on diuretic use and congestion symptoms in patients with heart failure with reduced ejection fraction (HFrEF), but the oral sodium glucose cotransporter 2 (SGLT2) inhibitor did not improve the primary endpoint of improved exercise capacity in the EMPERIAL-Reduced trial, investigators reported at the European Society of Cardiology Heart Failure Discoveries virtual meeting.

In the matching EMPERIAL-Preserved trial, conducted in patients with heart failure with preserved ejection fraction (HFpEF), empagliflozin (Jardiance) produced modest improvements in diuretic use, as well as a reduction in unscheduled outpatient visits, compared with placebo-treated controls, although these trends failed to achieve statistical significance. And as in the EMPERIAL-Reduced trial, the SGLT2 inhibitor didn’t move the needle at all on the primary endpoint of improved exercise capacity as measured by 6-minute hall walk distance.

EMPERIAL-Reduced and -Preserved were identically designed, concurrent, phase 3, double-blind, 12-week randomized trials of empagliflozin versus placebo in 312 patients with HFrEF and 315 with HFpEF, defined in EMPERIAL-preserved as a left ventricular ejection fraction above 40%. The majority of participants had type 2 diabetes.

From a baseline median 6-minute walk distance of about 300 meters, the 6-minute walk distance at week 12 was actually 4.0 meters worse in the empagliflozin-treated HFrEF patients than it was in controls and a mere 4.0 meters better than with placebo in empagliflozin-treated patients with HFpEF, reported William T. Abraham, MD, professor of medicine, director of the division of cardiovascular medicine, and associate dean at Ohio State University, Columbus.

He indicated that the audience shouldn’t make too much of the failure to achieve the primary endpoint in the two trials in light of the studies’ major limitations: namely, their relatively small size for purposes of evaluating clinical outcomes and the relatively short 12-week duration.

“In many ways, I would say it’s remarkable that we can observe a positive signal, a favorable signal, in outcomes around congestion. In the case of HFrEF it’s statistically significant, and in HFpEF it’s a trend towards improvement. Of course, there are larger trials ongoing that may confirm these observations. Hopefully the EMPERIAL trials predict a good outcome for those ongoing trials,” Dr. Abraham said.

Piotr Ponikowski, MD, presented the study results for the secondary outcomes of congestion symptoms, diuretic use, and utilization of health care resources. In EMPERIAL-Reduced, intensification of diuretic therapy – often a prelude to acute decompensation and a trip to the hospital – occurred at a rate of 4.5% with empagliflozin and 16.1% with placebo, for a highly significant 73% relative risk reduction. Intensification of loop diuretics occurred in 2.6% of the empagliflozin group and 14.2% of controls, for a 82% risk reduction.

“That’s a pretty significant effect,” observed Dr. Ponikowski, professor of cardiology and head of the department of heart diseases at the Medical University of Wroclaw (Poland).

Moreover, a congestion symptoms score comprising a summary of orthopnea, jugular veinous distention, and edema improved by 47% after 12 weeks on empagliflozin, a statistically significant and clinically meaningful improvement that grew in magnitude over time and at 12 weeks was twice as large, compared with the reduction in placebo group, he added.

There was a trend for fewer unscheduled outpatient visits in the empagliflozin arm of EMPERIAL-Reduced with a rate of 10.4%, compared with 25.8% in controls; however, this 26% reduction in relative risk did not achieve statistical significance.

Intensification of loop diuretics occurred in 9% of EMPERIAL-Preserved participants on empagliflozin and 13.5% on placebo, but this 34% reduction in risk didn’t reach significance.

Adverse events in the EMPERIAL trials were similar across the active treatment and placebo arms. The benign safety profile was similar to what was seen in the earlier major clinical trials of empagliflozin for treatment of type 2 diabetes.

Session chair Stephane Heymans, MD, PhD, of the University of Maastricht (the Netherlands) noted that a substantial minority of patients in EMPERIAL-Reduced were on the combined neprilysin inhibitor sacubitril and the angiotensin receptor blocker valsartan (Entresto), whereas far fewer were in EMPERIAL-Preserved. He wondered if this greater use of background sacubitril/valsartan could explain empagliflozin’s greater efficacy in EMPERIAL-Reduced.

Highly unlikely, according to the investigators.

“It looks like, as is the case with most of our heart failure therapies, that we do see incremental value here. If you met the criteria for these trials, it appears you derived benefit from empagliflozin regardless of whether you were on an angiotensin receptor neprilysin inhibitor or not. I think that speaks to the incremental benefit of SGLT2 inhibitors on top of current guideline-directed medical therapy,” Dr. Abraham said.

Dr. Ponikowski observed that the same point was underscored in the DAPA-HF trial of the SGLT2 inhibitor dapagliflozin (Farxiga) in patients with heart failure (DAPA-HF: N Engl J Med. 2019 Nov 21;381[21]:1995-2008).

“You’ll see that the mortality and morbidity and quality-of-life benefit is in those treated with dapagliflozin with or without angiotensin receptor neprilysin inhibition; so, regardless of background therapy. And the effect is especially clear in patients on both therapies,” the cardiologist said.

The EMPERIAL trials were sponsored by Boehringer Ingelheim. Dr. Abraham and Dr. Ponikowksi reported receiving consultant fees from the company for serving on the trials’ executive committee.

bjancin@mdedge.com

Empagliflozin showed favorable effects on diuretic use and congestion symptoms in patients with heart failure with reduced ejection fraction (HFrEF), but the oral sodium glucose cotransporter 2 (SGLT2) inhibitor did not improve the primary endpoint of improved exercise capacity in the EMPERIAL-Reduced trial, investigators reported at the European Society of Cardiology Heart Failure Discoveries virtual meeting.

In the matching EMPERIAL-Preserved trial, conducted in patients with heart failure with preserved ejection fraction (HFpEF), empagliflozin (Jardiance) produced modest improvements in diuretic use, as well as a reduction in unscheduled outpatient visits, compared with placebo-treated controls, although these trends failed to achieve statistical significance. And as in the EMPERIAL-Reduced trial, the SGLT2 inhibitor didn’t move the needle at all on the primary endpoint of improved exercise capacity as measured by 6-minute hall walk distance.

EMPERIAL-Reduced and -Preserved were identically designed, concurrent, phase 3, double-blind, 12-week randomized trials of empagliflozin versus placebo in 312 patients with HFrEF and 315 with HFpEF, defined in EMPERIAL-preserved as a left ventricular ejection fraction above 40%. The majority of participants had type 2 diabetes.

From a baseline median 6-minute walk distance of about 300 meters, the 6-minute walk distance at week 12 was actually 4.0 meters worse in the empagliflozin-treated HFrEF patients than it was in controls and a mere 4.0 meters better than with placebo in empagliflozin-treated patients with HFpEF, reported William T. Abraham, MD, professor of medicine, director of the division of cardiovascular medicine, and associate dean at Ohio State University, Columbus.

He indicated that the audience shouldn’t make too much of the failure to achieve the primary endpoint in the two trials in light of the studies’ major limitations: namely, their relatively small size for purposes of evaluating clinical outcomes and the relatively short 12-week duration.

“In many ways, I would say it’s remarkable that we can observe a positive signal, a favorable signal, in outcomes around congestion. In the case of HFrEF it’s statistically significant, and in HFpEF it’s a trend towards improvement. Of course, there are larger trials ongoing that may confirm these observations. Hopefully the EMPERIAL trials predict a good outcome for those ongoing trials,” Dr. Abraham said.

Piotr Ponikowski, MD, presented the study results for the secondary outcomes of congestion symptoms, diuretic use, and utilization of health care resources. In EMPERIAL-Reduced, intensification of diuretic therapy – often a prelude to acute decompensation and a trip to the hospital – occurred at a rate of 4.5% with empagliflozin and 16.1% with placebo, for a highly significant 73% relative risk reduction. Intensification of loop diuretics occurred in 2.6% of the empagliflozin group and 14.2% of controls, for a 82% risk reduction.

“That’s a pretty significant effect,” observed Dr. Ponikowski, professor of cardiology and head of the department of heart diseases at the Medical University of Wroclaw (Poland).

Moreover, a congestion symptoms score comprising a summary of orthopnea, jugular veinous distention, and edema improved by 47% after 12 weeks on empagliflozin, a statistically significant and clinically meaningful improvement that grew in magnitude over time and at 12 weeks was twice as large, compared with the reduction in placebo group, he added.

There was a trend for fewer unscheduled outpatient visits in the empagliflozin arm of EMPERIAL-Reduced with a rate of 10.4%, compared with 25.8% in controls; however, this 26% reduction in relative risk did not achieve statistical significance.

Intensification of loop diuretics occurred in 9% of EMPERIAL-Preserved participants on empagliflozin and 13.5% on placebo, but this 34% reduction in risk didn’t reach significance.

Adverse events in the EMPERIAL trials were similar across the active treatment and placebo arms. The benign safety profile was similar to what was seen in the earlier major clinical trials of empagliflozin for treatment of type 2 diabetes.

Session chair Stephane Heymans, MD, PhD, of the University of Maastricht (the Netherlands) noted that a substantial minority of patients in EMPERIAL-Reduced were on the combined neprilysin inhibitor sacubitril and the angiotensin receptor blocker valsartan (Entresto), whereas far fewer were in EMPERIAL-Preserved. He wondered if this greater use of background sacubitril/valsartan could explain empagliflozin’s greater efficacy in EMPERIAL-Reduced.

Highly unlikely, according to the investigators.

“It looks like, as is the case with most of our heart failure therapies, that we do see incremental value here. If you met the criteria for these trials, it appears you derived benefit from empagliflozin regardless of whether you were on an angiotensin receptor neprilysin inhibitor or not. I think that speaks to the incremental benefit of SGLT2 inhibitors on top of current guideline-directed medical therapy,” Dr. Abraham said.

Dr. Ponikowski observed that the same point was underscored in the DAPA-HF trial of the SGLT2 inhibitor dapagliflozin (Farxiga) in patients with heart failure (DAPA-HF: N Engl J Med. 2019 Nov 21;381[21]:1995-2008).

“You’ll see that the mortality and morbidity and quality-of-life benefit is in those treated with dapagliflozin with or without angiotensin receptor neprilysin inhibition; so, regardless of background therapy. And the effect is especially clear in patients on both therapies,” the cardiologist said.

The EMPERIAL trials were sponsored by Boehringer Ingelheim. Dr. Abraham and Dr. Ponikowksi reported receiving consultant fees from the company for serving on the trials’ executive committee.

bjancin@mdedge.com

A former nursing assistant and Army veteran pleaded guilty to federal murder charges this week in connection with the 2017-2018 deaths of seven patients in a West Virginia veteran’s hospital, according to news reports.

Prosecutors said in court documents filed on July 13 that Reta Mays, 46, injected lethal doses of insulin into seven veterans at the Louis A. Johnson VA Medical Center (VAMC) in rural Clarksburg, W.Va.

Their blood glucose levels plummeted, and each died shortly after their injections, according to the Tennessean.

An eighth patient, a 92-year-old man whom Mays is accused of assaulting with an insulin injection, initially survived after staff were able to stabilize him but died 2 weeks later at a nursing home, NPR reports.

According to NPR, US Attorney Jarod Douglas told the court Tuesday that the medical investigator could not determine whether the insulin contributed to the man’s death but that it was Mays’ intention to kill him.

“No one watched while she injected them with lethal doses of insulin during an 11-month killing rampage,” the Washington Post reported.
 

No motive offered

The Post article said no motive has been established, but after a 2-year investigation into a pattern of suspicious deaths that took the hospital almost a year to detect, Mays, who had denied any wrongdoing in multiple interviews with investigators, told a federal judge she preyed on some of the country›s most vulnerable service members.

An attorney for Mays, Brian Kornbrath, contacted by Medscape Medical News, said: “The defense team decided that we would have no public comment at this time.”

According to court documents from the Northern District of West Virginia, Mays was charged with seven counts of second-degree murder and one count of assault with intent to commit murder in connection with the patient who died later.

Mays was hired at the VAMC in Clarksburg in June 2015. She worked from 7:30 PM to 8:00 AM in the medical surgical unit, court documents say.

According to the documents, “VAMC Clarksburg did not require a nursing assistant to have a certification or licensure for initial appointment or as a condition of continuing employment.”

The documents indicate that in June 2018, a hospitalist employed by VAMC Clarksburg reported concern about several deaths from unexplained hypoglycemic events in the same ward and noted that many of the affected patients did not have diabetes.

By that time, according to the Tennessean, “at least eight patients had died under suspicious circumstances. Several had been embalmed and buried, destroying potential evidence. One veteran had been cremated.”

An internal investigation began, followed by a criminal investigation, and in July 2018, Mays was removed from patient care.
 

Mays fired in 2019 because of lies on resume; claims suffers from PTSD

The Post reports that Mays was fired from the hospital in 2019, 7 months after she was banned from patient care, «after it was discovered she had lied about her qualifications on her resume.»

Court documents indicate that her duties included acting as a sitter for patients, checking vital signs, intake and output, and testing blood glucose levels, but she was not qualified to administer medications, including insulin.

Similarities in the deaths were evident, the Post reported. Citing sources familiar with the case, the report said, “elderly patients in private rooms were injected in their abdomen and limbs with insulin the hospital had not ordered.”

The Post reported that Mays sobbed by the end of the hearing on Tuesday.

The article notes that Mays has three sons and served in the Army National Guard from November 2000 to April 2001 and again from February 2003 to May 2004, when she was deployed to Iraq and Kuwait. She told the judge she was taking medication for posttraumatic stress disorder.

By pleading guilty, she waived her right to have the case presented to a grand jury. A sentencing hearing has not been scheduled, the Post reports.

NPR notes that prosecutors have requested that Mays serve seven consecutive life sentences and an additional 20 years in prison.
 

“Our hearts go out to those affected by these tragic deaths”

A spokesman for VAMC Clarksburg said in a statement to Medscape Medical News: “Our hearts go out to those affected by these tragic deaths. Clarksburg VA Medical Center discovered these allegations and reported them to VA›s independent inspector general more than 2 years ago. Clarksburg VA Medical Center also fired the individual at the center of the allegations.

“We’re glad the Department of Justice stepped in to push this investigation across the finish line and hopeful our court system will deliver the justice Clarksburg-area Veterans and families deserve.”

According to the Tennessean, Michael Missal, inspector general for the Department of Veteran Affairs, said the agency is investigating the hospital’s practices, “including medication management and communications among staffers.”

This article first appeared on Medscape.com.

A former nursing assistant and Army veteran pleaded guilty to federal murder charges this week in connection with the 2017-2018 deaths of seven patients in a West Virginia veteran’s hospital, according to news reports.

Prosecutors said in court documents filed on July 13 that Reta Mays, 46, injected lethal doses of insulin into seven veterans at the Louis A. Johnson VA Medical Center (VAMC) in rural Clarksburg, W.Va.

Their blood glucose levels plummeted, and each died shortly after their injections, according to the Tennessean.

An eighth patient, a 92-year-old man whom Mays is accused of assaulting with an insulin injection, initially survived after staff were able to stabilize him but died 2 weeks later at a nursing home, NPR reports.

According to NPR, US Attorney Jarod Douglas told the court Tuesday that the medical investigator could not determine whether the insulin contributed to the man’s death but that it was Mays’ intention to kill him.

“No one watched while she injected them with lethal doses of insulin during an 11-month killing rampage,” the Washington Post reported.
 

No motive offered

The Post article said no motive has been established, but after a 2-year investigation into a pattern of suspicious deaths that took the hospital almost a year to detect, Mays, who had denied any wrongdoing in multiple interviews with investigators, told a federal judge she preyed on some of the country›s most vulnerable service members.

An attorney for Mays, Brian Kornbrath, contacted by Medscape Medical News, said: “The defense team decided that we would have no public comment at this time.”

According to court documents from the Northern District of West Virginia, Mays was charged with seven counts of second-degree murder and one count of assault with intent to commit murder in connection with the patient who died later.

Mays was hired at the VAMC in Clarksburg in June 2015. She worked from 7:30 PM to 8:00 AM in the medical surgical unit, court documents say.

According to the documents, “VAMC Clarksburg did not require a nursing assistant to have a certification or licensure for initial appointment or as a condition of continuing employment.”

The documents indicate that in June 2018, a hospitalist employed by VAMC Clarksburg reported concern about several deaths from unexplained hypoglycemic events in the same ward and noted that many of the affected patients did not have diabetes.

By that time, according to the Tennessean, “at least eight patients had died under suspicious circumstances. Several had been embalmed and buried, destroying potential evidence. One veteran had been cremated.”

An internal investigation began, followed by a criminal investigation, and in July 2018, Mays was removed from patient care.
 

Mays fired in 2019 because of lies on resume; claims suffers from PTSD

The Post reports that Mays was fired from the hospital in 2019, 7 months after she was banned from patient care, «after it was discovered she had lied about her qualifications on her resume.»

Court documents indicate that her duties included acting as a sitter for patients, checking vital signs, intake and output, and testing blood glucose levels, but she was not qualified to administer medications, including insulin.

Similarities in the deaths were evident, the Post reported. Citing sources familiar with the case, the report said, “elderly patients in private rooms were injected in their abdomen and limbs with insulin the hospital had not ordered.”

The Post reported that Mays sobbed by the end of the hearing on Tuesday.

The article notes that Mays has three sons and served in the Army National Guard from November 2000 to April 2001 and again from February 2003 to May 2004, when she was deployed to Iraq and Kuwait. She told the judge she was taking medication for posttraumatic stress disorder.

By pleading guilty, she waived her right to have the case presented to a grand jury. A sentencing hearing has not been scheduled, the Post reports.

NPR notes that prosecutors have requested that Mays serve seven consecutive life sentences and an additional 20 years in prison.
 

“Our hearts go out to those affected by these tragic deaths”

A spokesman for VAMC Clarksburg said in a statement to Medscape Medical News: “Our hearts go out to those affected by these tragic deaths. Clarksburg VA Medical Center discovered these allegations and reported them to VA›s independent inspector general more than 2 years ago. Clarksburg VA Medical Center also fired the individual at the center of the allegations.

“We’re glad the Department of Justice stepped in to push this investigation across the finish line and hopeful our court system will deliver the justice Clarksburg-area Veterans and families deserve.”

According to the Tennessean, Michael Missal, inspector general for the Department of Veteran Affairs, said the agency is investigating the hospital’s practices, “including medication management and communications among staffers.”

This article first appeared on Medscape.com.

A former nursing assistant and Army veteran pleaded guilty to federal murder charges this week in connection with the 2017-2018 deaths of seven patients in a West Virginia veteran’s hospital, according to news reports.

Prosecutors said in court documents filed on July 13 that Reta Mays, 46, injected lethal doses of insulin into seven veterans at the Louis A. Johnson VA Medical Center (VAMC) in rural Clarksburg, W.Va.

Their blood glucose levels plummeted, and each died shortly after their injections, according to the Tennessean.

An eighth patient, a 92-year-old man whom Mays is accused of assaulting with an insulin injection, initially survived after staff were able to stabilize him but died 2 weeks later at a nursing home, NPR reports.

According to NPR, US Attorney Jarod Douglas told the court Tuesday that the medical investigator could not determine whether the insulin contributed to the man’s death but that it was Mays’ intention to kill him.

“No one watched while she injected them with lethal doses of insulin during an 11-month killing rampage,” the Washington Post reported.
 

No motive offered

The Post article said no motive has been established, but after a 2-year investigation into a pattern of suspicious deaths that took the hospital almost a year to detect, Mays, who had denied any wrongdoing in multiple interviews with investigators, told a federal judge she preyed on some of the country›s most vulnerable service members.

An attorney for Mays, Brian Kornbrath, contacted by Medscape Medical News, said: “The defense team decided that we would have no public comment at this time.”

According to court documents from the Northern District of West Virginia, Mays was charged with seven counts of second-degree murder and one count of assault with intent to commit murder in connection with the patient who died later.

Mays was hired at the VAMC in Clarksburg in June 2015. She worked from 7:30 PM to 8:00 AM in the medical surgical unit, court documents say.

According to the documents, “VAMC Clarksburg did not require a nursing assistant to have a certification or licensure for initial appointment or as a condition of continuing employment.”

The documents indicate that in June 2018, a hospitalist employed by VAMC Clarksburg reported concern about several deaths from unexplained hypoglycemic events in the same ward and noted that many of the affected patients did not have diabetes.

By that time, according to the Tennessean, “at least eight patients had died under suspicious circumstances. Several had been embalmed and buried, destroying potential evidence. One veteran had been cremated.”

An internal investigation began, followed by a criminal investigation, and in July 2018, Mays was removed from patient care.
 

Mays fired in 2019 because of lies on resume; claims suffers from PTSD

The Post reports that Mays was fired from the hospital in 2019, 7 months after she was banned from patient care, «after it was discovered she had lied about her qualifications on her resume.»

Court documents indicate that her duties included acting as a sitter for patients, checking vital signs, intake and output, and testing blood glucose levels, but she was not qualified to administer medications, including insulin.

Similarities in the deaths were evident, the Post reported. Citing sources familiar with the case, the report said, “elderly patients in private rooms were injected in their abdomen and limbs with insulin the hospital had not ordered.”

The Post reported that Mays sobbed by the end of the hearing on Tuesday.

The article notes that Mays has three sons and served in the Army National Guard from November 2000 to April 2001 and again from February 2003 to May 2004, when she was deployed to Iraq and Kuwait. She told the judge she was taking medication for posttraumatic stress disorder.

By pleading guilty, she waived her right to have the case presented to a grand jury. A sentencing hearing has not been scheduled, the Post reports.

NPR notes that prosecutors have requested that Mays serve seven consecutive life sentences and an additional 20 years in prison.
 

“Our hearts go out to those affected by these tragic deaths”

A spokesman for VAMC Clarksburg said in a statement to Medscape Medical News: “Our hearts go out to those affected by these tragic deaths. Clarksburg VA Medical Center discovered these allegations and reported them to VA›s independent inspector general more than 2 years ago. Clarksburg VA Medical Center also fired the individual at the center of the allegations.

“We’re glad the Department of Justice stepped in to push this investigation across the finish line and hopeful our court system will deliver the justice Clarksburg-area Veterans and families deserve.”

According to the Tennessean, Michael Missal, inspector general for the Department of Veteran Affairs, said the agency is investigating the hospital’s practices, “including medication management and communications among staffers.”

This article first appeared on Medscape.com.

Chester Good, MD, MPH, is professor of medicine and pharmacy, University of Pittsburgh School of Medicine and School of Pharmacy. He is also the senior medical director, UPMC Health Plan Insurance Division, as well as the director for the Center for Value-Based Pharmacy Initiatives.
 

What are the potential benefits of value-based contracting for patients with multiple sclerosis, as well as for health systems and payers?

CHESTER GOOD, MD, MPH: I think for all 3, value-based contracting really is about moving from volume to value. And in doing so, what we're trying to do is recognize the value of pharmaceuticals perhaps in ways that we previously have not.

Patients with conditions such as multiple sclerosis (MS) want to be able to live their lives where they can continue to work, maintain their activities of daily living, and maintain their quality of life. Value-based contracting ideally recognizes those patient values and leverages contracting of pharmaceuticals that have been shown to help maintain those qualities in patients. For health systems, our greatest duty is to our patients in terms of maintaining their quality of life, maintaining their health, and preventing disease progression. By developing value-based contracts in which we recognize these measurable outcomes, we're showing a commitment to our patients and trying to hopefully establish the value of our pharmacy benefit.

For most health plans and payers, MS especially has become an increasingly expensive disease, with MS-related medications representing a significant cost burden. It's no secret that MS drugs have gone up significantly in recent years.

In a paper published in JAMA Neurology,¹ we looked at the costs of these self-administered disease-modifying therapies for MS. From 2006 to 2016, the costs more than quadrupled, from a mean of $18,660 a year to more than $75,000, which means they increased at an annual rate of almost 13%. For payers, pharmaceutical spending per 1000 beneficiaries increased tenfold; and out-of-pocket expenses to our patients also increased significantly.

So, that's the reality. But the other reality is that there have been significant advancements in the treatment of MS using pharmaceuticals. And some of these newer treatments are more effective. Moreover, some are easier to take than some of the older therapies, and some are better tolerated from a patient perspective.

As a result of dramatic increase in costs of MS drugs, payers are asking about what they are getting in return for all these dramatic increases in costs. One of the ways to demonstrate that value is to link paying for these drugs with a value-based contract.

Why is a disease such as MS a good fit for value-based contracting?

CHESTER GOOD, MD, MPH: MS is a fairly prevalent disease. Fortunately, pharmacotherapy has gotten better over the years, to the point where it's clear that the pharmacotherapy of MS has really changed the course of the disease for our patients, allowing them to maintain their quality of life and functional abilities.

On a personal level, I had a family member growing up who had MS. And she did not have the benefits of the newer drugs. And through my childhood and early adulthood, I watched as she went from a very productive working person to someone who could no longer work, was unable to take care of her children, and was institutionalized and eventually died from complications of MS. That would be unusual today.

In a value-based contract, what MS outcomes are linked to reimbursement, and how are they measured?

CHESTER GOOD, MD, MPH: Traditionally, outcomes-based agreements focused on things that would be easily measured through administrative data. These are things that either a drug manufacturer or insurer, or both, have identified as being what they think are important outcomes for that disease state, but also things that they think they would be able to measure. Oftentimes, these were intermediate outcomes. Did the patient remain on a drug? Were they adherent? What was the impact on hemoglobin A1c in patients with diabetes? Although these outcomes may be important, they  may not be as important to our patients.

So for MS, I would argue that it's really important to try to expand on this idea of which MS-specific outcomes are meaningful to our patients, and then try to link them to reimbursement. One of the things that we do at the University of Pittsburgh Medical Center (UPMC) is survey our stakeholders, and we ask what outcomes are important, using the Delphi method. Our most important stakeholder, of course, is our patient. But we also survey the physicians who care for these patients, other clinicians who care for these patients, our pharmacists, pharmacy benefit managers, our industry partners, and sometimes other stakeholders such as employers.

Sometimes, the things that are important to the patients are easily measured. It may be that patients with heart disease don't want to have another heart attack, and typically with a heart attack you end up going into the hospital. In the case of other disease states, however, it may be that what's most important to our patients differs from what we think is most important. We don't make any assumptions. We measure what our patients tell us.

In the case of MS, before we entered into a value-based contract, we did a Delphi survey including patients, physicians, industry partners, payers, and our pharmacy benefits manager.² We did several rounds of surveys, and in the second round we had our stakeholders rank outcomes. What we found was that the most important outcome was “worsening physical disability.” One hundred percent of our stakeholders—not just our patients, but everyone—ranked worsening physical disability as important.

I would've thought that patients would've said, “Well, I don't want an MS flare.” And we could argue that MS flares may result in worsening physical disability, but not always. When we asked what would be the easiest thing to measure, of course MS flares are the easiest thing, because they require an emergency department visit or use of corticosteroids or hospitalization.

Based on our survey, we picked disability progression as our outcome of interest and the basis for our value-based contract. We entered into a contract with Biogen for a couple of their drugs, dimethyl fumarate (Tecfidera) and interferon beta-1a (Avonex), 2 very important MS drugs. This is a classic patient-reported outcome, and of course that poses a lot of interesting challenges about how you actually measure it. So, we had to work with our subject matter experts in the clinics to identify and externally validate a patient-reported outcome that measured disability progression. We worked very hard so that we’re able to collect that in a way that doesn’t inconvenience our physicians or our patients.

There are other tools that can be used, one of which is the PROMIS tool developed through the National Institutes of Health (NIH). That's a way to quantify changes in patient-reported outcomes. The interesting thing is NIH specifically developed this tool with certain disease states in mind, one of which was MS. So, some of the PROMIS domains include pain, fatigue, physical functioning, emotional distress, cognitive functioning, and social functioning. And all these things could be very important to our MS patients.

We actually do use PROMIS measures and PROMIS questionnaires routinely with our patients who come to our neurology clinic. It's not part of our value-based contracts at this point, but it's something that is a potentially interesting way to measure patient-reported outcomes.

What are the key challenges to implementing a value-based contract?

CHESTER GOOD, MD, MPH: Value-based contracting has been far more laborious than I ever imagined. These are legal documents that are very long and complex, and quite daunting. We've tried our best to incorporate figures and diagrams to simplify issues and ensure that we all are understanding things similarly. But at the end of the day, despite our best efforts, these contracts remain very complex, and questions and unexpected situations develop as we implement them. So, that's been one of the challenges.

The pandemic has also posed some challenges. It has affected everything. That includes fewer patient clinic encounters, which is a challenge when some of our value-based contracts require vital signs, lab work, or other things dependent on patient visits. There are also fewer patients presenting with disease states. It’s been well documented that hospitalizations and patient visits to the emergency departments for various conditions have really plummeted in the face of the coronavirus. So, the pandemic is a clear confounder as we try to identify the value of these pharmaceuticals and how they've impacted care. That's been a huge challenge for us.

Another thing to mention is that we’ve tried to be very innovative in our value-based outcomes. But it's been very challenging to do the analyses. What seems to be clear in a contract may not be clear once you start to analyze things, as there are all sorts of scenarios that one cannot anticipate. That has required going back and forth with our industry partners. Fortunately, we have good working relationships with them, and we've been able to work out those wrinkles; but that's been a challenge.

I mentioned the importance of patient-reported outcomes, but they are a challenge to measure. How do you collect patient-reported outcomes in a way that does not pose a burden on our patients or clinicians?

Finally, a significant challenge for health care organizations and insurers that hope to do value-based contracting is that drug companies do not typically  place a lot of risk on the table. While we've been very pleased with our value-based contracts thus far, in the future we hope to see greater risk in these contracts, especially for areas such as gene therapy.

What are the next steps in value-based contracting for MS?

CHESTER GOOD, MD, MPH: Multiple sclerosis can be a progressive disease, and it's over a lifetime. It can affect people's quality of life. It can affect their ability to work. It can affect the quality of their work and what sort of things that they can do.

Because MS can affect every aspect of life, it's not enough to simply measure things like disease flares or MRI lesions. Rather, we need to figure out ways to understand how these drugs impact our patients’ day-to-day lives, the quality of their lives, and their ability to function as normally as possible. I think these other patient-reported outcomes would represent important next steps in MS outcomes measurement. Our current value-based contract has 1 simple, albeit very important, outcome that we're looking at, but are there other ways to measure patients’ quality of life? Perhaps this will involve using PROMIS measures or  other innovative ways to measure patient outcomes. We’ve discussed with some patient interest groups how to incorporate other measures that are very important to our patients.

From a payer perspective, it may not show up in terms of impacting total cost of care. Depending on the disease states, oftentimes if things progress slowly over years, it is difficult to demonstrate an impact. But it's not all only about decreasing our costs because we decrease hospitalizations; it’s also about improving the quality of our patients’ lives.

The next step for us at UPMC is to continue to gather our data and to analyze our outcomes. And based on that, we're hoping to expand our portfolio of drugs for the MS disease state and expand outcomes that we're measuring.

Chester Good, MD, MPH, is professor of medicine and pharmacy, University of Pittsburgh School of Medicine and School of Pharmacy. He is also the senior medical director, UPMC Health Plan Insurance Division, as well as the director for the Center for Value-Based Pharmacy Initiatives.
 

What are the potential benefits of value-based contracting for patients with multiple sclerosis, as well as for health systems and payers?

CHESTER GOOD, MD, MPH: I think for all 3, value-based contracting really is about moving from volume to value. And in doing so, what we're trying to do is recognize the value of pharmaceuticals perhaps in ways that we previously have not.

Patients with conditions such as multiple sclerosis (MS) want to be able to live their lives where they can continue to work, maintain their activities of daily living, and maintain their quality of life. Value-based contracting ideally recognizes those patient values and leverages contracting of pharmaceuticals that have been shown to help maintain those qualities in patients. For health systems, our greatest duty is to our patients in terms of maintaining their quality of life, maintaining their health, and preventing disease progression. By developing value-based contracts in which we recognize these measurable outcomes, we're showing a commitment to our patients and trying to hopefully establish the value of our pharmacy benefit.

For most health plans and payers, MS especially has become an increasingly expensive disease, with MS-related medications representing a significant cost burden. It's no secret that MS drugs have gone up significantly in recent years.

In a paper published in JAMA Neurology,¹ we looked at the costs of these self-administered disease-modifying therapies for MS. From 2006 to 2016, the costs more than quadrupled, from a mean of $18,660 a year to more than $75,000, which means they increased at an annual rate of almost 13%. For payers, pharmaceutical spending per 1000 beneficiaries increased tenfold; and out-of-pocket expenses to our patients also increased significantly.

So, that's the reality. But the other reality is that there have been significant advancements in the treatment of MS using pharmaceuticals. And some of these newer treatments are more effective. Moreover, some are easier to take than some of the older therapies, and some are better tolerated from a patient perspective.

As a result of dramatic increase in costs of MS drugs, payers are asking about what they are getting in return for all these dramatic increases in costs. One of the ways to demonstrate that value is to link paying for these drugs with a value-based contract.

Why is a disease such as MS a good fit for value-based contracting?

CHESTER GOOD, MD, MPH: MS is a fairly prevalent disease. Fortunately, pharmacotherapy has gotten better over the years, to the point where it's clear that the pharmacotherapy of MS has really changed the course of the disease for our patients, allowing them to maintain their quality of life and functional abilities.

On a personal level, I had a family member growing up who had MS. And she did not have the benefits of the newer drugs. And through my childhood and early adulthood, I watched as she went from a very productive working person to someone who could no longer work, was unable to take care of her children, and was institutionalized and eventually died from complications of MS. That would be unusual today.

In a value-based contract, what MS outcomes are linked to reimbursement, and how are they measured?

CHESTER GOOD, MD, MPH: Traditionally, outcomes-based agreements focused on things that would be easily measured through administrative data. These are things that either a drug manufacturer or insurer, or both, have identified as being what they think are important outcomes for that disease state, but also things that they think they would be able to measure. Oftentimes, these were intermediate outcomes. Did the patient remain on a drug? Were they adherent? What was the impact on hemoglobin A1c in patients with diabetes? Although these outcomes may be important, they  may not be as important to our patients.

So for MS, I would argue that it's really important to try to expand on this idea of which MS-specific outcomes are meaningful to our patients, and then try to link them to reimbursement. One of the things that we do at the University of Pittsburgh Medical Center (UPMC) is survey our stakeholders, and we ask what outcomes are important, using the Delphi method. Our most important stakeholder, of course, is our patient. But we also survey the physicians who care for these patients, other clinicians who care for these patients, our pharmacists, pharmacy benefit managers, our industry partners, and sometimes other stakeholders such as employers.

Sometimes, the things that are important to the patients are easily measured. It may be that patients with heart disease don't want to have another heart attack, and typically with a heart attack you end up going into the hospital. In the case of other disease states, however, it may be that what's most important to our patients differs from what we think is most important. We don't make any assumptions. We measure what our patients tell us.

In the case of MS, before we entered into a value-based contract, we did a Delphi survey including patients, physicians, industry partners, payers, and our pharmacy benefits manager.² We did several rounds of surveys, and in the second round we had our stakeholders rank outcomes. What we found was that the most important outcome was “worsening physical disability.” One hundred percent of our stakeholders—not just our patients, but everyone—ranked worsening physical disability as important.

I would've thought that patients would've said, “Well, I don't want an MS flare.” And we could argue that MS flares may result in worsening physical disability, but not always. When we asked what would be the easiest thing to measure, of course MS flares are the easiest thing, because they require an emergency department visit or use of corticosteroids or hospitalization.

Based on our survey, we picked disability progression as our outcome of interest and the basis for our value-based contract. We entered into a contract with Biogen for a couple of their drugs, dimethyl fumarate (Tecfidera) and interferon beta-1a (Avonex), 2 very important MS drugs. This is a classic patient-reported outcome, and of course that poses a lot of interesting challenges about how you actually measure it. So, we had to work with our subject matter experts in the clinics to identify and externally validate a patient-reported outcome that measured disability progression. We worked very hard so that we’re able to collect that in a way that doesn’t inconvenience our physicians or our patients.

There are other tools that can be used, one of which is the PROMIS tool developed through the National Institutes of Health (NIH). That's a way to quantify changes in patient-reported outcomes. The interesting thing is NIH specifically developed this tool with certain disease states in mind, one of which was MS. So, some of the PROMIS domains include pain, fatigue, physical functioning, emotional distress, cognitive functioning, and social functioning. And all these things could be very important to our MS patients.

We actually do use PROMIS measures and PROMIS questionnaires routinely with our patients who come to our neurology clinic. It's not part of our value-based contracts at this point, but it's something that is a potentially interesting way to measure patient-reported outcomes.

What are the key challenges to implementing a value-based contract?

CHESTER GOOD, MD, MPH: Value-based contracting has been far more laborious than I ever imagined. These are legal documents that are very long and complex, and quite daunting. We've tried our best to incorporate figures and diagrams to simplify issues and ensure that we all are understanding things similarly. But at the end of the day, despite our best efforts, these contracts remain very complex, and questions and unexpected situations develop as we implement them. So, that's been one of the challenges.

The pandemic has also posed some challenges. It has affected everything. That includes fewer patient clinic encounters, which is a challenge when some of our value-based contracts require vital signs, lab work, or other things dependent on patient visits. There are also fewer patients presenting with disease states. It’s been well documented that hospitalizations and patient visits to the emergency departments for various conditions have really plummeted in the face of the coronavirus. So, the pandemic is a clear confounder as we try to identify the value of these pharmaceuticals and how they've impacted care. That's been a huge challenge for us.

Another thing to mention is that we’ve tried to be very innovative in our value-based outcomes. But it's been very challenging to do the analyses. What seems to be clear in a contract may not be clear once you start to analyze things, as there are all sorts of scenarios that one cannot anticipate. That has required going back and forth with our industry partners. Fortunately, we have good working relationships with them, and we've been able to work out those wrinkles; but that's been a challenge.

I mentioned the importance of patient-reported outcomes, but they are a challenge to measure. How do you collect patient-reported outcomes in a way that does not pose a burden on our patients or clinicians?

Finally, a significant challenge for health care organizations and insurers that hope to do value-based contracting is that drug companies do not typically  place a lot of risk on the table. While we've been very pleased with our value-based contracts thus far, in the future we hope to see greater risk in these contracts, especially for areas such as gene therapy.

What are the next steps in value-based contracting for MS?

CHESTER GOOD, MD, MPH: Multiple sclerosis can be a progressive disease, and it's over a lifetime. It can affect people's quality of life. It can affect their ability to work. It can affect the quality of their work and what sort of things that they can do.

Because MS can affect every aspect of life, it's not enough to simply measure things like disease flares or MRI lesions. Rather, we need to figure out ways to understand how these drugs impact our patients’ day-to-day lives, the quality of their lives, and their ability to function as normally as possible. I think these other patient-reported outcomes would represent important next steps in MS outcomes measurement. Our current value-based contract has 1 simple, albeit very important, outcome that we're looking at, but are there other ways to measure patients’ quality of life? Perhaps this will involve using PROMIS measures or  other innovative ways to measure patient outcomes. We’ve discussed with some patient interest groups how to incorporate other measures that are very important to our patients.

From a payer perspective, it may not show up in terms of impacting total cost of care. Depending on the disease states, oftentimes if things progress slowly over years, it is difficult to demonstrate an impact. But it's not all only about decreasing our costs because we decrease hospitalizations; it’s also about improving the quality of our patients’ lives.

The next step for us at UPMC is to continue to gather our data and to analyze our outcomes. And based on that, we're hoping to expand our portfolio of drugs for the MS disease state and expand outcomes that we're measuring.

Chester Good, MD, MPH, is professor of medicine and pharmacy, University of Pittsburgh School of Medicine and School of Pharmacy. He is also the senior medical director, UPMC Health Plan Insurance Division, as well as the director for the Center for Value-Based Pharmacy Initiatives.
 

What are the potential benefits of value-based contracting for patients with multiple sclerosis, as well as for health systems and payers?

CHESTER GOOD, MD, MPH: I think for all 3, value-based contracting really is about moving from volume to value. And in doing so, what we're trying to do is recognize the value of pharmaceuticals perhaps in ways that we previously have not.

Patients with conditions such as multiple sclerosis (MS) want to be able to live their lives where they can continue to work, maintain their activities of daily living, and maintain their quality of life. Value-based contracting ideally recognizes those patient values and leverages contracting of pharmaceuticals that have been shown to help maintain those qualities in patients. For health systems, our greatest duty is to our patients in terms of maintaining their quality of life, maintaining their health, and preventing disease progression. By developing value-based contracts in which we recognize these measurable outcomes, we're showing a commitment to our patients and trying to hopefully establish the value of our pharmacy benefit.

For most health plans and payers, MS especially has become an increasingly expensive disease, with MS-related medications representing a significant cost burden. It's no secret that MS drugs have gone up significantly in recent years.

In a paper published in JAMA Neurology,¹ we looked at the costs of these self-administered disease-modifying therapies for MS. From 2006 to 2016, the costs more than quadrupled, from a mean of $18,660 a year to more than $75,000, which means they increased at an annual rate of almost 13%. For payers, pharmaceutical spending per 1000 beneficiaries increased tenfold; and out-of-pocket expenses to our patients also increased significantly.

So, that's the reality. But the other reality is that there have been significant advancements in the treatment of MS using pharmaceuticals. And some of these newer treatments are more effective. Moreover, some are easier to take than some of the older therapies, and some are better tolerated from a patient perspective.

As a result of dramatic increase in costs of MS drugs, payers are asking about what they are getting in return for all these dramatic increases in costs. One of the ways to demonstrate that value is to link paying for these drugs with a value-based contract.

Why is a disease such as MS a good fit for value-based contracting?

CHESTER GOOD, MD, MPH: MS is a fairly prevalent disease. Fortunately, pharmacotherapy has gotten better over the years, to the point where it's clear that the pharmacotherapy of MS has really changed the course of the disease for our patients, allowing them to maintain their quality of life and functional abilities.

On a personal level, I had a family member growing up who had MS. And she did not have the benefits of the newer drugs. And through my childhood and early adulthood, I watched as she went from a very productive working person to someone who could no longer work, was unable to take care of her children, and was institutionalized and eventually died from complications of MS. That would be unusual today.

In a value-based contract, what MS outcomes are linked to reimbursement, and how are they measured?

CHESTER GOOD, MD, MPH: Traditionally, outcomes-based agreements focused on things that would be easily measured through administrative data. These are things that either a drug manufacturer or insurer, or both, have identified as being what they think are important outcomes for that disease state, but also things that they think they would be able to measure. Oftentimes, these were intermediate outcomes. Did the patient remain on a drug? Were they adherent? What was the impact on hemoglobin A1c in patients with diabetes? Although these outcomes may be important, they  may not be as important to our patients.

So for MS, I would argue that it's really important to try to expand on this idea of which MS-specific outcomes are meaningful to our patients, and then try to link them to reimbursement. One of the things that we do at the University of Pittsburgh Medical Center (UPMC) is survey our stakeholders, and we ask what outcomes are important, using the Delphi method. Our most important stakeholder, of course, is our patient. But we also survey the physicians who care for these patients, other clinicians who care for these patients, our pharmacists, pharmacy benefit managers, our industry partners, and sometimes other stakeholders such as employers.

Sometimes, the things that are important to the patients are easily measured. It may be that patients with heart disease don't want to have another heart attack, and typically with a heart attack you end up going into the hospital. In the case of other disease states, however, it may be that what's most important to our patients differs from what we think is most important. We don't make any assumptions. We measure what our patients tell us.

In the case of MS, before we entered into a value-based contract, we did a Delphi survey including patients, physicians, industry partners, payers, and our pharmacy benefits manager.² We did several rounds of surveys, and in the second round we had our stakeholders rank outcomes. What we found was that the most important outcome was “worsening physical disability.” One hundred percent of our stakeholders—not just our patients, but everyone—ranked worsening physical disability as important.

I would've thought that patients would've said, “Well, I don't want an MS flare.” And we could argue that MS flares may result in worsening physical disability, but not always. When we asked what would be the easiest thing to measure, of course MS flares are the easiest thing, because they require an emergency department visit or use of corticosteroids or hospitalization.

Based on our survey, we picked disability progression as our outcome of interest and the basis for our value-based contract. We entered into a contract with Biogen for a couple of their drugs, dimethyl fumarate (Tecfidera) and interferon beta-1a (Avonex), 2 very important MS drugs. This is a classic patient-reported outcome, and of course that poses a lot of interesting challenges about how you actually measure it. So, we had to work with our subject matter experts in the clinics to identify and externally validate a patient-reported outcome that measured disability progression. We worked very hard so that we’re able to collect that in a way that doesn’t inconvenience our physicians or our patients.

There are other tools that can be used, one of which is the PROMIS tool developed through the National Institutes of Health (NIH). That's a way to quantify changes in patient-reported outcomes. The interesting thing is NIH specifically developed this tool with certain disease states in mind, one of which was MS. So, some of the PROMIS domains include pain, fatigue, physical functioning, emotional distress, cognitive functioning, and social functioning. And all these things could be very important to our MS patients.

We actually do use PROMIS measures and PROMIS questionnaires routinely with our patients who come to our neurology clinic. It's not part of our value-based contracts at this point, but it's something that is a potentially interesting way to measure patient-reported outcomes.

What are the key challenges to implementing a value-based contract?

CHESTER GOOD, MD, MPH: Value-based contracting has been far more laborious than I ever imagined. These are legal documents that are very long and complex, and quite daunting. We've tried our best to incorporate figures and diagrams to simplify issues and ensure that we all are understanding things similarly. But at the end of the day, despite our best efforts, these contracts remain very complex, and questions and unexpected situations develop as we implement them. So, that's been one of the challenges.

The pandemic has also posed some challenges. It has affected everything. That includes fewer patient clinic encounters, which is a challenge when some of our value-based contracts require vital signs, lab work, or other things dependent on patient visits. There are also fewer patients presenting with disease states. It’s been well documented that hospitalizations and patient visits to the emergency departments for various conditions have really plummeted in the face of the coronavirus. So, the pandemic is a clear confounder as we try to identify the value of these pharmaceuticals and how they've impacted care. That's been a huge challenge for us.

Another thing to mention is that we’ve tried to be very innovative in our value-based outcomes. But it's been very challenging to do the analyses. What seems to be clear in a contract may not be clear once you start to analyze things, as there are all sorts of scenarios that one cannot anticipate. That has required going back and forth with our industry partners. Fortunately, we have good working relationships with them, and we've been able to work out those wrinkles; but that's been a challenge.

I mentioned the importance of patient-reported outcomes, but they are a challenge to measure. How do you collect patient-reported outcomes in a way that does not pose a burden on our patients or clinicians?

Finally, a significant challenge for health care organizations and insurers that hope to do value-based contracting is that drug companies do not typically  place a lot of risk on the table. While we've been very pleased with our value-based contracts thus far, in the future we hope to see greater risk in these contracts, especially for areas such as gene therapy.

What are the next steps in value-based contracting for MS?

CHESTER GOOD, MD, MPH: Multiple sclerosis can be a progressive disease, and it's over a lifetime. It can affect people's quality of life. It can affect their ability to work. It can affect the quality of their work and what sort of things that they can do.

Because MS can affect every aspect of life, it's not enough to simply measure things like disease flares or MRI lesions. Rather, we need to figure out ways to understand how these drugs impact our patients’ day-to-day lives, the quality of their lives, and their ability to function as normally as possible. I think these other patient-reported outcomes would represent important next steps in MS outcomes measurement. Our current value-based contract has 1 simple, albeit very important, outcome that we're looking at, but are there other ways to measure patients’ quality of life? Perhaps this will involve using PROMIS measures or  other innovative ways to measure patient outcomes. We’ve discussed with some patient interest groups how to incorporate other measures that are very important to our patients.

From a payer perspective, it may not show up in terms of impacting total cost of care. Depending on the disease states, oftentimes if things progress slowly over years, it is difficult to demonstrate an impact. But it's not all only about decreasing our costs because we decrease hospitalizations; it’s also about improving the quality of our patients’ lives.

The next step for us at UPMC is to continue to gather our data and to analyze our outcomes. And based on that, we're hoping to expand our portfolio of drugs for the MS disease state and expand outcomes that we're measuring.