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Protein proves essential for hematopoietic recovery
in the bone marrow
New research suggests the cell survival protein MCL-1, a target for a number of new anticancer agents, is essential for hematopoietic recovery.
Investigators found that reducing MCL-1 levels hindered hematopoietic recovery after chemotherapy and radiotherapy caused extensive destruction of mature blood cells.
Reducing MCL-1 also impaired reconstitution of the bone marrow after hematopoietic stem cell transplant (HSCT).
“Our previous research has shown that targeting MCL-1 could be used with great success for treating certain blood cancers,” said Alex Delbridge, PhD, of the Walter and Eliza Hall Institute of Medical Research in Melbourne, Victoria, Australia.
“However, we have now shown that MCL-1 is also critical for emergency recovery of the blood cell system after cancer therapy-induced blood cell loss.”
Dr Delbridge and his colleagues reported these findings in Blood.
Experiments in mice revealed that loss of a single MCL-1 allele, which reduced MCL-1 protein levels, greatly compromised the immune system and hindered red blood cell recovery after treatment with 5-fluorouracil, γ-irradiation, or HSCT.
Further investigation showed that the pro-apoptotic gene PUMA plays a key role in this phenomenon, as MCL-1 inhibits PUMA. In mice, knocking out PUMA alleviated—but did not eliminate—the HSC survival defect caused by deletion of both MCL-1 alleles.
“This exquisite dependency on MCL-1 for emergency blood cell production has important implications for potential cancer treatments involving MCL-1 inhibitors,” Dr Delbridge said.
“If MCL-1 inhibitors are to be used in combination with other cancer therapies, careful monitoring of the blood cell system will be needed,” added Stephanie Grabow, PhD, also of the Walter and Eliza Hall Institute.
“Our institute colleagues are working to evaluate a potential new drug to treat blood cancers by targeting MCL-1. Our findings suggest that MCL-1 inhibitors and chemotherapeutic drugs should not be used simultaneously.”
Dr Delbridge said this research also offers insights that could help improve HSCT.
“Stem cell transplants can be dangerous because, until the blood cell system is functionally restored, patients are vulnerable to infection,” he said. “Our research suggests that increasing levels of MCL-1 or decreasing the activity of opposing proteins could be a viable strategy for speeding up the regeneration process and reducing the risk of infection after stem cell transplantation.” 
in the bone marrow
New research suggests the cell survival protein MCL-1, a target for a number of new anticancer agents, is essential for hematopoietic recovery.
Investigators found that reducing MCL-1 levels hindered hematopoietic recovery after chemotherapy and radiotherapy caused extensive destruction of mature blood cells.
Reducing MCL-1 also impaired reconstitution of the bone marrow after hematopoietic stem cell transplant (HSCT).
“Our previous research has shown that targeting MCL-1 could be used with great success for treating certain blood cancers,” said Alex Delbridge, PhD, of the Walter and Eliza Hall Institute of Medical Research in Melbourne, Victoria, Australia.
“However, we have now shown that MCL-1 is also critical for emergency recovery of the blood cell system after cancer therapy-induced blood cell loss.”
Dr Delbridge and his colleagues reported these findings in Blood.
Experiments in mice revealed that loss of a single MCL-1 allele, which reduced MCL-1 protein levels, greatly compromised the immune system and hindered red blood cell recovery after treatment with 5-fluorouracil, γ-irradiation, or HSCT.
Further investigation showed that the pro-apoptotic gene PUMA plays a key role in this phenomenon, as MCL-1 inhibits PUMA. In mice, knocking out PUMA alleviated—but did not eliminate—the HSC survival defect caused by deletion of both MCL-1 alleles.
“This exquisite dependency on MCL-1 for emergency blood cell production has important implications for potential cancer treatments involving MCL-1 inhibitors,” Dr Delbridge said.
“If MCL-1 inhibitors are to be used in combination with other cancer therapies, careful monitoring of the blood cell system will be needed,” added Stephanie Grabow, PhD, also of the Walter and Eliza Hall Institute.
“Our institute colleagues are working to evaluate a potential new drug to treat blood cancers by targeting MCL-1. Our findings suggest that MCL-1 inhibitors and chemotherapeutic drugs should not be used simultaneously.”
Dr Delbridge said this research also offers insights that could help improve HSCT.
“Stem cell transplants can be dangerous because, until the blood cell system is functionally restored, patients are vulnerable to infection,” he said. “Our research suggests that increasing levels of MCL-1 or decreasing the activity of opposing proteins could be a viable strategy for speeding up the regeneration process and reducing the risk of infection after stem cell transplantation.”
in the bone marrow
New research suggests the cell survival protein MCL-1, a target for a number of new anticancer agents, is essential for hematopoietic recovery.
Investigators found that reducing MCL-1 levels hindered hematopoietic recovery after chemotherapy and radiotherapy caused extensive destruction of mature blood cells.
Reducing MCL-1 also impaired reconstitution of the bone marrow after hematopoietic stem cell transplant (HSCT).
“Our previous research has shown that targeting MCL-1 could be used with great success for treating certain blood cancers,” said Alex Delbridge, PhD, of the Walter and Eliza Hall Institute of Medical Research in Melbourne, Victoria, Australia.
“However, we have now shown that MCL-1 is also critical for emergency recovery of the blood cell system after cancer therapy-induced blood cell loss.”
Dr Delbridge and his colleagues reported these findings in Blood.
Experiments in mice revealed that loss of a single MCL-1 allele, which reduced MCL-1 protein levels, greatly compromised the immune system and hindered red blood cell recovery after treatment with 5-fluorouracil, γ-irradiation, or HSCT.
Further investigation showed that the pro-apoptotic gene PUMA plays a key role in this phenomenon, as MCL-1 inhibits PUMA. In mice, knocking out PUMA alleviated—but did not eliminate—the HSC survival defect caused by deletion of both MCL-1 alleles.
“This exquisite dependency on MCL-1 for emergency blood cell production has important implications for potential cancer treatments involving MCL-1 inhibitors,” Dr Delbridge said.
“If MCL-1 inhibitors are to be used in combination with other cancer therapies, careful monitoring of the blood cell system will be needed,” added Stephanie Grabow, PhD, also of the Walter and Eliza Hall Institute.
“Our institute colleagues are working to evaluate a potential new drug to treat blood cancers by targeting MCL-1. Our findings suggest that MCL-1 inhibitors and chemotherapeutic drugs should not be used simultaneously.”
Dr Delbridge said this research also offers insights that could help improve HSCT.
“Stem cell transplants can be dangerous because, until the blood cell system is functionally restored, patients are vulnerable to infection,” he said. “Our research suggests that increasing levels of MCL-1 or decreasing the activity of opposing proteins could be a viable strategy for speeding up the regeneration process and reducing the risk of infection after stem cell transplantation.”
Inconsistent Code Status Documentation
For hospitalized patients, providers should ideally establish advanced directives for cardiopulmonary resuscitation, commonly referred to as a patient's code status. Having an end‐of‐life plan is important and is associated with better quality of life for patients.[1, 2, 3, 4, 5] Advanced directive discussions and documentation are key quality measures to improve end‐of‐life care for vulnerable elders.[6, 7, 8]
Clear and consistent code status documentation is a prerequisite to providing care that respects hospitalized patients' preferences. Code status documentation only occurs in a minority of hospitalized patients, ranging from 25% of patients on a general medical ward to 36% of patients on elderly‐care wards.[9] Even in high‐risk patients, such as patients with metastatic cancer, providers only documented code status 20% of the time.[10] Even when code status documentation occurs, the amount of detail regarding patient goals and values, prognosis, and treatment options is generally poor.[11, 12] There are also concerns about the accuracy of code status documentation.[13, 14, 15, 16, 17, 18, 19] For example, a recent study found that for patients who had discussed their code status during their hospitalization, only 30% had documentation of their preferences in their chart that accurately reflected what was discussed.[20]
Further complicating matters is the fact that providers document key patient information, such as a patient's code status, in multiple places (eg, progress notes, physician orders). As a result, an additional documentation problem of inconsistency can arise for 2 reasons. First, code status documentation can be inconsistent because of incomplete documentation. Incomplete documentation is primarily a problem in patients who do not want to be resuscitated (ie, do not resuscitate [DNR]), because the absence of code status documentation leads front‐line staff to assume that the patient wants to be resuscitated (ie, full code). Second, inconsistent documentation can occur because of conflicting documentation (eg, a patient has a different code status documented in 2 or more places).
Together, these documentation problems have the potential to lead healthcare providers to resuscitate patients who do not wish to be resuscitated, or for patients who wish to be resuscitated to have delays in their resuscitation efforts. This study will extend the knowledge from the previous literature by exploring how the complexity and redundancy of clinical documentation practices affect the quality of code status documentation. To our knowledge, there are no prior studies that focus specifically on the frequency and clinical relevance of inconsistent code status documentation for inpatients across multiple documentation sources.
METHODS
Study Context
This is a point‐prevalence study conducted at 3 academic medical centers (AMCs) affiliated with the University of Toronto. At all 3 AMCs, the majority of general internal medicine (GIM) patients are admitted to 1 of 4 clinical teaching units (CTUs). The physician team on each CTU consists of 1 attending staff, 1 senior resident (second or third year resident), 2 to 3 first‐year residents, and 2 to 3 medical students. CTUs typically care for between 15 and 25 patients. The research ethics boards at each of the AMCs approved this study.
Existing Code Status Documentation Processes
At all 3 AMCs, providers document patient code status in 5 different places: (1) progress notes (admission and daily progress notes in the paper chart), (2) physician orders (computerized orders at 1 site, paper orders at the other 2 sites), (3) electronic sign‐out lists (Web‐based tools used by residents to support patient handover), (4) nursing‐care plan (used by nurses to document care plans for their assigned patients), and (5) DNR sheet (a cover sheet placed at the front of the paper chart in patients who have a DNR order) (see Supporting Information, Appendix, in the online version of this article). None of these documentation sources link automatically to one another. Once a physician establishes a patient's code status, it should be documented in the progress notes. The same physician should also write the code status as a physician order and update the patient's code status in the Web‐based electronic sign‐out list. The nurse responsible for the patient transcribes the code status order in the nursing‐care plan. For DNR patients, nurses or physicians (depending on the AMC) also place the DNR sheet in the front of the chart.
At our 3 AMCs, in the event of a cardiac arrest, resident physicians and nurses are typically the first responders. To quickly determine a patient's code status nurses and resident physicians look for the presence or absence of a DNR sheet. In addition, nurses rely on their nursing‐care plan and resident physicians rely on their electronic sign‐out list.
Eligibility Criteria and Sampling Strategy
Our study included GIM patients admitted to a CTU at 1 of 3 AMCs, and excluded admitted GIM patients who remained in the emergency department (due to differences in code status documentation processes). Data collection took place between September 2010 and September 2011 on days when the principal author (A.S.W.) was available to collect the data.
We collected data for all patients from a single GIM CTU on the same day to minimize the chance that a team updates or changes a patient's code status during data collection. We included each of the 4 CTUs at the 3 study sites once during the study period (ie, 12 full days of data collection).
Study Measures and Data Collection
One study author (A.S.W.) screened the 5 code status documentation sources listed above for each patient and recorded the documented code status as full code, DNR, or blank (if there was nothing entered) in a database. We also collected patient demographic data, admitting diagnosis, length of stay, admission to home ward (ie, the medicine ward affiliated with the CTU team that admitted the patient), free‐text code status documentation, transfer to the intensive care unit during their hospitalization, and whether the patient is receiving comfort measures, up to the time of data collection. Because the study investigators were not members of the team providing care to patients included in the study, we could not directly elicit the patient's actual code status.
The primary study outcome measures were the completeness and consistency of code status documentation across the 5 documentation sources. For completeness, we included data relating to 4 documentation sources only, excluding the DNR sheet because it is only relevant for DNR patients. We defined inconsistent code status documentation a priori as (1) the code status is conflicting in at least 2 documentation sources (eg, full code in 1 source and DNR in another) or (2) the code status is documented in 1 or more documentation source and not documented in at least 1 documentation source (eg, full code in 1 source and blank in another).
We then subdivided code status documentation inconsistencies into nonclinically relevant and clinically relevant subcategories. For example, a nonclinically relevant inconsistency would be if a physician documented full code in the physician orders, but a nurse did not document anything in the nursing‐care plan, because most providers would assume a preference for resuscitation in the absence of code status documentation in the nursing‐care plan.
We defined clinically relevant inconsistencies as those that would reasonably lead healthcare providers referring to different documentation sources to respond differently in the event of a cardiac arrest (eg, the physician orders show DNR whereas the nursing‐care plan is blanka provider who refers to the physician orders would not resuscitate the patient, but another provider who refers to the blank nursing‐care plan would resuscitate the patient).
We determined the proportion of patients with inconsistent code status documentation by listing the 31 different permutations of code status documentation in our data (Figure 1). Using the prespecified definition of inconsistent code status documentation, 3 study authors (I.A.D., B.M.W., R.C.W.) independently determined whether each permutation met the criteria for inconsistent code status documentation, and judged the clinical relevance of each documentation inconsistency. We resolved disagreements by consensus.
Statistical Analysis
We calculated descriptive statistics for all variables, summarizing continuous measures using means and standard deviations, and categorical measures using counts, percentages, and their associated 95% confidence intervals. Logistic regression analyses adjusting for the correlation among observations taken from the same team were carried out. Each of the 4 variables of interest (patient age, length of stay, receiving comfort measures, free text code status documentation) was run in a bivariate model to obtain unadjusted estimates as well as the final multivariable model. All estimates were displayed as odds ratios (ORs) and their associated 95% confidence intervals (CIs). A P value <0.05 was used to denote statistical significance. We also carried out a kappa analysis to assess inter‐rater agreement when judging whether inconsistent documentation is clinically relevant. All analyses were carried out using SAS version 9.3 (SAS Institute, Cary, NC).
RESULTS
There were 194 patients potentially eligible for inclusion. Seven admitted GIM patients who had not been transferred from the emergency department were excluded, leaving 187 patients in the study. The mean patient age was 70 years; 83 (44%) were female. The median length of stay up to the time of data collection was 6 days, with the majority (156 [83%]) of patients admitted to their home ward. Ten (5%) patients were receiving comfort measures.
Completeness of Code Status Documentation
Thirty‐eight (20%; 95% CI, 14%‐26%) patients had complete and consistent code status documentation across all documentation sources, whereas 27 (14%; 95% CI, 9%‐19%) patients had no code status documented in any documentation source. By documentation source, providers documented code status in the progress notes for 89 patients (48%; 95% CI, 40%‐55%), the physician orders for 107 patients (57%; 95% CI, 50%‐64%), the nursing‐care plan for 110 patients (59%; 95% CI, 51%‐66%), and the electronic sign‐out list for 129 patients (69%; 95% CI, 62%‐76%).
Consistency of Code Status Documentation
The remaining 122 patients (65%; 95% CI, 58%‐72%) had at least 1 code status documentation inconsistency. Of these, 38 patients (20%; 95% CI, 14%‐26%) had a clinically relevant code status documentation inconsistency. Code status documentation inconsistency differed by site; the 2 hospitals with paper‐based physician orders had fewer patients with complete and consistent code status documentation compared to the hospital where physician orders are electronic (15% vs 42%, respectively, P<0.001) (Table 1).
| Physician Code Status Order | Sites 1 & 2: Paper‐Based, N=108 | Site 3: Electronic, N=52 | P Value |
|---|---|---|---|
| Consistent code status documentation | 16 (15%) | 22 (42%) | |
| Inconsistent code status documentation, nonclinically relevant | 60 (56%) | 30 (58%) | <0.0001 |
| Inconsistent code status documentation, clinically relevant | 32 (30%) | 6 (12%) |
The permutations of clinically relevant and nonclinically relevant inconsistencies are summarized in Figure 1. We achieved high inter‐rater reliability among the 3 independent reviewers with respect to rating the clinical relevance of documentation inconsistencies (=0.86 [95% CI, 0.76‐0.95]).
To identify correlates of clinically relevant code status documentation inconsistencies, we included 4 variables of interest (patient age, length of stay, receiving comfort measures, and free text code status documentation) in a logistic regression analysis. Bivariate analyses demonstrated that increased age (OR =1.07 [95% CI, 1.05‐1.10] for every 1‐year increase in age, P<0.001) and receiving comfort measures (OR= 10.98 [95% CI, 1.94‐62.12], P=0.007) were associated with a clinically relevant code status documentation inconsistency. Using these 4 variables in a multivariable analysis clustering for physician team, increased age (OR=1.07 [95% CI, 1.04‐1.10] for every 1‐year increase in age, P<0.0001) and receiving comfort measures (OR=9.39 [95% CI, 1.3565.19], P=0.02) remained as independent positive correlates of having a clinically relevant code status documentation inconsistency (Table 2).
| Clinically Relevant Inconsistencies, N=38 | No Inconsistencies and Nonclinically Relevant Inconsistencies, N=149 | P Value | |
|---|---|---|---|
| |||
| Age, y, mean (SD) | 83 (10) | 67 (19) | <0.0001* |
| Length of stay, d, median (IQR) | 6.5 (310) | 6 (219) | 0.39 |
| Receiving comfort measures, n (%) | 7 (18%) | 3 (2%) | <0.0001* |
| Free‐text code status documentation, n (%) | 18 (47%) | 58 (39%) | 0.34 |
DISCUSSION
We found that 2 out of 3 patients had at least 1 inconsistency in code status documentation, and that 1 in 5 patients had at least 1 clinically relevant code status documentation inconsistency. The majority of clinically relevant inconsistencies occurred because there was a DNR order written in some sources of code status documentation, and no orders in other documentation sources. However, there were 4 striking examples where DNR was written in some sources of code status documentation and full code was written in other documentation sources (Figure 1).
Older patients and patients receiving comfort measures were more likely to have a clinically relevant inconsistency in code status documentation. This is particularly concerning, because they are among the most vulnerable patients at highest risk for having an in‐hospital cardiac arrest.
Our study extends the findings of prior studies that identified gaps in completeness and accuracy of code status documentation and describes another important gap in the quality and consistency of code status documentation.[20] This becomes particularly important because efforts aimed at increasing documentation of patients' code status without ensuring consistency across documentation sources may still result in patients being resuscitated or not resuscitated inappropriately.
This issue of poorly integrated health records is relevant for many other aspects of patient care. For example, 1 study found significant discrepancies in patient medication allergy documentation across multiple health records.[21] This fragmentation of documentation of the same patient information in multiple health records requires attention and should be the focus of institutional quality improvement efforts.
There are several potential ways to improve the code status documentation process. First, the use of standard fields or standardized orders can increase the completeness and improve the clarity of code status documentation.[22, 23] For institutions with an electronic medical record, forcing functions may further increase code status documentation. One study found that the implementation of an electronic medical record increased code status documentation from 4% to 63%.[24] We found similarly that the site with electronic physician orders had higher rates of complete and consistent code status documentation.
A second approach is to minimize the number of different sources for code status documentation. Institutions should critically examine each place where providers could document code status and decide whether this information adds value, and create policies to restrict unnecessary duplicate documentation and ensure accurate documentation of code status in several key, centralized locations.[25] A third option would be to automatically synchronize all code status documentation sources.[25] This final approach requires a fully integrated electronic health record.
Our study has several limitations. Although we report a large number of code status documentation inconsistencies, we do not know how many of these lead to incorrect resuscitative measures, so the actual impact on patient care is unknown. Also, because we were focusing on inconsistencies among sources of code status documentation, and not on accurate documentation of a patients' code status, the patients' actual preferences were not elicited and are not known. Finally, we carried out our study in 3 AMCs with residents that rotate from 1 site to another. The transient nature of resident work may increase the likelihood of documentation inconsistencies, because trainees may be less aware of local processes. In addition, the way front‐line staff uses clinical documentation sources to determine a patient's code status may differ at other institutions. Therefore, our estimate of clinical relevance may not be generalizable to other institutions with different front‐line processes or with healthcare teams that are more stable and aware of local documentation processes.
In summary, our study uncovered significant gaps in the quality of code status documentation that span 3 different AMCs. Having multiple, poorly integrated sources for code status documentation leads to a significant number of concerning inconsistencies that create opportunities for healthcare providers to inappropriately deliver or withhold resuscitative measures that conflict with patients' expressed wishes. Institutions need to be aware of this potential documentation hazard and take steps to minimize code status documentation inconsistencies. Even though cardiac arrests occur infrequently, if healthcare teams take inappropriate action because of these code status documentation inconsistencies, the consequences can be devastating.
Disclosure
Nothing to report.
- , , , et al. Advance directives for medical care—a case for greater use. N Engl J Med. 1991;324(13):889–895.
- , , , et al; Canadian Researchers at the End of Life Network (CARENET). What matters most in end‐of‐life care: perceptions of seriously ill patients and their family memebrs. CMAJ. 2006;174(5):627–633.
- , , . Advance directives and outcomes of surrogate decision making before death. N Eng J Med. 2010;362(13):1211–1218.
- , , , et al. Associations between end‐of‐life discussions, patient mental health, medical care near death, and caregiver bereavement adjustment. JAMA. 2008;300(14):1665–1673.
- , , , . The impact of advance care planning on end of life care in elderly patients: randomized controlled trial. BMJ. 2010;340:c1345.
- , . Quality indicators for end‐of‐life care in vulnerable elders. Ann Intern Med. 2001;135(8):667–685.
- , , , . Assessing care of vulnerable elders: methods for developing quality indicators. Ann Intern Med. 2001;135:647–652.
- , , , et al. Perceptions by family members of the dying experience of older and seriously ill patients. Ann Intern Med. 1997;126(2):97–106.
- , . Cardiopulmonary resuscitation: capacity, discussion and documentation. Q J Med. 2006;99(10):683–690.
- , , , et al. Code status documentation in the outpatient electronic medical records or patients with metastatic cancer. J Gen Intern Med. 2009;25(2):150–153.
- , , , et al. Factors associated with discussion of care plans and code status at the time of hospital admission: results from the multicenter hospitalist study. J Hosp Med. 2008;3(6):437–445.
- , , , . Documentation quality of inpatient code status discussions. J Pain Symptom Manage. 2014;48(4):632–638.
- , , , . The use of life‐sustaining treatments in hospitalized persons aged 80 and older. J Am Geriatr Soc. 2002;50(5):930–934.
- The SUPPORT Principal Investigators. A controlled trial to improve care for seriously ill hospitalized patients: the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT). JAMA. 1995;274(20):1591–1598.
- , , . Some treatment‐withholding implications of no‐code orders in an academic hospital. Crit Care Med. 1984;12(10):879–881.
- . A prospective study of patients with DNR orders in a teaching hospital. Arch Intern Med. 1998;148(10):2193–2198.
- , . Compliance with do‐not‐resuscitate orders for hospitalized patient transported to radiology department. Ann Int Med. 1998;129(10):801–805.
- , . Identification of inpatient DNR status: a safety hazard begging for standardization. J Hosp Med. 2007;2(6):366–371.
- . Controlling death: the false promise of advance directives. Ann Int Med. 2007;147(1):51–57.
- , , , et al. Failure to engage hospitalized elderly patients and their families in advance care planning. JAMA Intern Med. 2013;173(9):778–787.
- , , , et al. The recording of drug sensitivities for older people living in care homes. Br J Clin Pharmacol. 2010;69(5):553–557.
- , , , , , . A comparison of methods to communicate treatment preferences in nursing facilities: traditional practices versus the physician orders for life‐sustaining treatment program. J Am Geriatr Soc. 2010;58(7):1241–1248.
- , , , et al. Evaluation of a treatment limitation policy with a specific treatment‐limiting order page. Arch Intern Med. 1994;154(4):425–432.
- , , , et al. An electronic medical record intervention increased nursing home advance directive orders and documentation. J Am Geriatr Soc. 2007;55(7):1001–1006.
- , , , et al. Honouring patient's resuscitation wishes: a multiphased effort to improve identification and documentation. BMJ Quality Safety. 2013;22(1):85–92.
For hospitalized patients, providers should ideally establish advanced directives for cardiopulmonary resuscitation, commonly referred to as a patient's code status. Having an end‐of‐life plan is important and is associated with better quality of life for patients.[1, 2, 3, 4, 5] Advanced directive discussions and documentation are key quality measures to improve end‐of‐life care for vulnerable elders.[6, 7, 8]
Clear and consistent code status documentation is a prerequisite to providing care that respects hospitalized patients' preferences. Code status documentation only occurs in a minority of hospitalized patients, ranging from 25% of patients on a general medical ward to 36% of patients on elderly‐care wards.[9] Even in high‐risk patients, such as patients with metastatic cancer, providers only documented code status 20% of the time.[10] Even when code status documentation occurs, the amount of detail regarding patient goals and values, prognosis, and treatment options is generally poor.[11, 12] There are also concerns about the accuracy of code status documentation.[13, 14, 15, 16, 17, 18, 19] For example, a recent study found that for patients who had discussed their code status during their hospitalization, only 30% had documentation of their preferences in their chart that accurately reflected what was discussed.[20]
Further complicating matters is the fact that providers document key patient information, such as a patient's code status, in multiple places (eg, progress notes, physician orders). As a result, an additional documentation problem of inconsistency can arise for 2 reasons. First, code status documentation can be inconsistent because of incomplete documentation. Incomplete documentation is primarily a problem in patients who do not want to be resuscitated (ie, do not resuscitate [DNR]), because the absence of code status documentation leads front‐line staff to assume that the patient wants to be resuscitated (ie, full code). Second, inconsistent documentation can occur because of conflicting documentation (eg, a patient has a different code status documented in 2 or more places).
Together, these documentation problems have the potential to lead healthcare providers to resuscitate patients who do not wish to be resuscitated, or for patients who wish to be resuscitated to have delays in their resuscitation efforts. This study will extend the knowledge from the previous literature by exploring how the complexity and redundancy of clinical documentation practices affect the quality of code status documentation. To our knowledge, there are no prior studies that focus specifically on the frequency and clinical relevance of inconsistent code status documentation for inpatients across multiple documentation sources.
METHODS
Study Context
This is a point‐prevalence study conducted at 3 academic medical centers (AMCs) affiliated with the University of Toronto. At all 3 AMCs, the majority of general internal medicine (GIM) patients are admitted to 1 of 4 clinical teaching units (CTUs). The physician team on each CTU consists of 1 attending staff, 1 senior resident (second or third year resident), 2 to 3 first‐year residents, and 2 to 3 medical students. CTUs typically care for between 15 and 25 patients. The research ethics boards at each of the AMCs approved this study.
Existing Code Status Documentation Processes
At all 3 AMCs, providers document patient code status in 5 different places: (1) progress notes (admission and daily progress notes in the paper chart), (2) physician orders (computerized orders at 1 site, paper orders at the other 2 sites), (3) electronic sign‐out lists (Web‐based tools used by residents to support patient handover), (4) nursing‐care plan (used by nurses to document care plans for their assigned patients), and (5) DNR sheet (a cover sheet placed at the front of the paper chart in patients who have a DNR order) (see Supporting Information, Appendix, in the online version of this article). None of these documentation sources link automatically to one another. Once a physician establishes a patient's code status, it should be documented in the progress notes. The same physician should also write the code status as a physician order and update the patient's code status in the Web‐based electronic sign‐out list. The nurse responsible for the patient transcribes the code status order in the nursing‐care plan. For DNR patients, nurses or physicians (depending on the AMC) also place the DNR sheet in the front of the chart.
At our 3 AMCs, in the event of a cardiac arrest, resident physicians and nurses are typically the first responders. To quickly determine a patient's code status nurses and resident physicians look for the presence or absence of a DNR sheet. In addition, nurses rely on their nursing‐care plan and resident physicians rely on their electronic sign‐out list.
Eligibility Criteria and Sampling Strategy
Our study included GIM patients admitted to a CTU at 1 of 3 AMCs, and excluded admitted GIM patients who remained in the emergency department (due to differences in code status documentation processes). Data collection took place between September 2010 and September 2011 on days when the principal author (A.S.W.) was available to collect the data.
We collected data for all patients from a single GIM CTU on the same day to minimize the chance that a team updates or changes a patient's code status during data collection. We included each of the 4 CTUs at the 3 study sites once during the study period (ie, 12 full days of data collection).
Study Measures and Data Collection
One study author (A.S.W.) screened the 5 code status documentation sources listed above for each patient and recorded the documented code status as full code, DNR, or blank (if there was nothing entered) in a database. We also collected patient demographic data, admitting diagnosis, length of stay, admission to home ward (ie, the medicine ward affiliated with the CTU team that admitted the patient), free‐text code status documentation, transfer to the intensive care unit during their hospitalization, and whether the patient is receiving comfort measures, up to the time of data collection. Because the study investigators were not members of the team providing care to patients included in the study, we could not directly elicit the patient's actual code status.
The primary study outcome measures were the completeness and consistency of code status documentation across the 5 documentation sources. For completeness, we included data relating to 4 documentation sources only, excluding the DNR sheet because it is only relevant for DNR patients. We defined inconsistent code status documentation a priori as (1) the code status is conflicting in at least 2 documentation sources (eg, full code in 1 source and DNR in another) or (2) the code status is documented in 1 or more documentation source and not documented in at least 1 documentation source (eg, full code in 1 source and blank in another).
We then subdivided code status documentation inconsistencies into nonclinically relevant and clinically relevant subcategories. For example, a nonclinically relevant inconsistency would be if a physician documented full code in the physician orders, but a nurse did not document anything in the nursing‐care plan, because most providers would assume a preference for resuscitation in the absence of code status documentation in the nursing‐care plan.
We defined clinically relevant inconsistencies as those that would reasonably lead healthcare providers referring to different documentation sources to respond differently in the event of a cardiac arrest (eg, the physician orders show DNR whereas the nursing‐care plan is blanka provider who refers to the physician orders would not resuscitate the patient, but another provider who refers to the blank nursing‐care plan would resuscitate the patient).
We determined the proportion of patients with inconsistent code status documentation by listing the 31 different permutations of code status documentation in our data (Figure 1). Using the prespecified definition of inconsistent code status documentation, 3 study authors (I.A.D., B.M.W., R.C.W.) independently determined whether each permutation met the criteria for inconsistent code status documentation, and judged the clinical relevance of each documentation inconsistency. We resolved disagreements by consensus.
Statistical Analysis
We calculated descriptive statistics for all variables, summarizing continuous measures using means and standard deviations, and categorical measures using counts, percentages, and their associated 95% confidence intervals. Logistic regression analyses adjusting for the correlation among observations taken from the same team were carried out. Each of the 4 variables of interest (patient age, length of stay, receiving comfort measures, free text code status documentation) was run in a bivariate model to obtain unadjusted estimates as well as the final multivariable model. All estimates were displayed as odds ratios (ORs) and their associated 95% confidence intervals (CIs). A P value <0.05 was used to denote statistical significance. We also carried out a kappa analysis to assess inter‐rater agreement when judging whether inconsistent documentation is clinically relevant. All analyses were carried out using SAS version 9.3 (SAS Institute, Cary, NC).
RESULTS
There were 194 patients potentially eligible for inclusion. Seven admitted GIM patients who had not been transferred from the emergency department were excluded, leaving 187 patients in the study. The mean patient age was 70 years; 83 (44%) were female. The median length of stay up to the time of data collection was 6 days, with the majority (156 [83%]) of patients admitted to their home ward. Ten (5%) patients were receiving comfort measures.
Completeness of Code Status Documentation
Thirty‐eight (20%; 95% CI, 14%‐26%) patients had complete and consistent code status documentation across all documentation sources, whereas 27 (14%; 95% CI, 9%‐19%) patients had no code status documented in any documentation source. By documentation source, providers documented code status in the progress notes for 89 patients (48%; 95% CI, 40%‐55%), the physician orders for 107 patients (57%; 95% CI, 50%‐64%), the nursing‐care plan for 110 patients (59%; 95% CI, 51%‐66%), and the electronic sign‐out list for 129 patients (69%; 95% CI, 62%‐76%).
Consistency of Code Status Documentation
The remaining 122 patients (65%; 95% CI, 58%‐72%) had at least 1 code status documentation inconsistency. Of these, 38 patients (20%; 95% CI, 14%‐26%) had a clinically relevant code status documentation inconsistency. Code status documentation inconsistency differed by site; the 2 hospitals with paper‐based physician orders had fewer patients with complete and consistent code status documentation compared to the hospital where physician orders are electronic (15% vs 42%, respectively, P<0.001) (Table 1).
| Physician Code Status Order | Sites 1 & 2: Paper‐Based, N=108 | Site 3: Electronic, N=52 | P Value |
|---|---|---|---|
| Consistent code status documentation | 16 (15%) | 22 (42%) | |
| Inconsistent code status documentation, nonclinically relevant | 60 (56%) | 30 (58%) | <0.0001 |
| Inconsistent code status documentation, clinically relevant | 32 (30%) | 6 (12%) |
The permutations of clinically relevant and nonclinically relevant inconsistencies are summarized in Figure 1. We achieved high inter‐rater reliability among the 3 independent reviewers with respect to rating the clinical relevance of documentation inconsistencies (=0.86 [95% CI, 0.76‐0.95]).
To identify correlates of clinically relevant code status documentation inconsistencies, we included 4 variables of interest (patient age, length of stay, receiving comfort measures, and free text code status documentation) in a logistic regression analysis. Bivariate analyses demonstrated that increased age (OR =1.07 [95% CI, 1.05‐1.10] for every 1‐year increase in age, P<0.001) and receiving comfort measures (OR= 10.98 [95% CI, 1.94‐62.12], P=0.007) were associated with a clinically relevant code status documentation inconsistency. Using these 4 variables in a multivariable analysis clustering for physician team, increased age (OR=1.07 [95% CI, 1.04‐1.10] for every 1‐year increase in age, P<0.0001) and receiving comfort measures (OR=9.39 [95% CI, 1.3565.19], P=0.02) remained as independent positive correlates of having a clinically relevant code status documentation inconsistency (Table 2).
| Clinically Relevant Inconsistencies, N=38 | No Inconsistencies and Nonclinically Relevant Inconsistencies, N=149 | P Value | |
|---|---|---|---|
| |||
| Age, y, mean (SD) | 83 (10) | 67 (19) | <0.0001* |
| Length of stay, d, median (IQR) | 6.5 (310) | 6 (219) | 0.39 |
| Receiving comfort measures, n (%) | 7 (18%) | 3 (2%) | <0.0001* |
| Free‐text code status documentation, n (%) | 18 (47%) | 58 (39%) | 0.34 |
DISCUSSION
We found that 2 out of 3 patients had at least 1 inconsistency in code status documentation, and that 1 in 5 patients had at least 1 clinically relevant code status documentation inconsistency. The majority of clinically relevant inconsistencies occurred because there was a DNR order written in some sources of code status documentation, and no orders in other documentation sources. However, there were 4 striking examples where DNR was written in some sources of code status documentation and full code was written in other documentation sources (Figure 1).
Older patients and patients receiving comfort measures were more likely to have a clinically relevant inconsistency in code status documentation. This is particularly concerning, because they are among the most vulnerable patients at highest risk for having an in‐hospital cardiac arrest.
Our study extends the findings of prior studies that identified gaps in completeness and accuracy of code status documentation and describes another important gap in the quality and consistency of code status documentation.[20] This becomes particularly important because efforts aimed at increasing documentation of patients' code status without ensuring consistency across documentation sources may still result in patients being resuscitated or not resuscitated inappropriately.
This issue of poorly integrated health records is relevant for many other aspects of patient care. For example, 1 study found significant discrepancies in patient medication allergy documentation across multiple health records.[21] This fragmentation of documentation of the same patient information in multiple health records requires attention and should be the focus of institutional quality improvement efforts.
There are several potential ways to improve the code status documentation process. First, the use of standard fields or standardized orders can increase the completeness and improve the clarity of code status documentation.[22, 23] For institutions with an electronic medical record, forcing functions may further increase code status documentation. One study found that the implementation of an electronic medical record increased code status documentation from 4% to 63%.[24] We found similarly that the site with electronic physician orders had higher rates of complete and consistent code status documentation.
A second approach is to minimize the number of different sources for code status documentation. Institutions should critically examine each place where providers could document code status and decide whether this information adds value, and create policies to restrict unnecessary duplicate documentation and ensure accurate documentation of code status in several key, centralized locations.[25] A third option would be to automatically synchronize all code status documentation sources.[25] This final approach requires a fully integrated electronic health record.
Our study has several limitations. Although we report a large number of code status documentation inconsistencies, we do not know how many of these lead to incorrect resuscitative measures, so the actual impact on patient care is unknown. Also, because we were focusing on inconsistencies among sources of code status documentation, and not on accurate documentation of a patients' code status, the patients' actual preferences were not elicited and are not known. Finally, we carried out our study in 3 AMCs with residents that rotate from 1 site to another. The transient nature of resident work may increase the likelihood of documentation inconsistencies, because trainees may be less aware of local processes. In addition, the way front‐line staff uses clinical documentation sources to determine a patient's code status may differ at other institutions. Therefore, our estimate of clinical relevance may not be generalizable to other institutions with different front‐line processes or with healthcare teams that are more stable and aware of local documentation processes.
In summary, our study uncovered significant gaps in the quality of code status documentation that span 3 different AMCs. Having multiple, poorly integrated sources for code status documentation leads to a significant number of concerning inconsistencies that create opportunities for healthcare providers to inappropriately deliver or withhold resuscitative measures that conflict with patients' expressed wishes. Institutions need to be aware of this potential documentation hazard and take steps to minimize code status documentation inconsistencies. Even though cardiac arrests occur infrequently, if healthcare teams take inappropriate action because of these code status documentation inconsistencies, the consequences can be devastating.
Disclosure
Nothing to report.
For hospitalized patients, providers should ideally establish advanced directives for cardiopulmonary resuscitation, commonly referred to as a patient's code status. Having an end‐of‐life plan is important and is associated with better quality of life for patients.[1, 2, 3, 4, 5] Advanced directive discussions and documentation are key quality measures to improve end‐of‐life care for vulnerable elders.[6, 7, 8]
Clear and consistent code status documentation is a prerequisite to providing care that respects hospitalized patients' preferences. Code status documentation only occurs in a minority of hospitalized patients, ranging from 25% of patients on a general medical ward to 36% of patients on elderly‐care wards.[9] Even in high‐risk patients, such as patients with metastatic cancer, providers only documented code status 20% of the time.[10] Even when code status documentation occurs, the amount of detail regarding patient goals and values, prognosis, and treatment options is generally poor.[11, 12] There are also concerns about the accuracy of code status documentation.[13, 14, 15, 16, 17, 18, 19] For example, a recent study found that for patients who had discussed their code status during their hospitalization, only 30% had documentation of their preferences in their chart that accurately reflected what was discussed.[20]
Further complicating matters is the fact that providers document key patient information, such as a patient's code status, in multiple places (eg, progress notes, physician orders). As a result, an additional documentation problem of inconsistency can arise for 2 reasons. First, code status documentation can be inconsistent because of incomplete documentation. Incomplete documentation is primarily a problem in patients who do not want to be resuscitated (ie, do not resuscitate [DNR]), because the absence of code status documentation leads front‐line staff to assume that the patient wants to be resuscitated (ie, full code). Second, inconsistent documentation can occur because of conflicting documentation (eg, a patient has a different code status documented in 2 or more places).
Together, these documentation problems have the potential to lead healthcare providers to resuscitate patients who do not wish to be resuscitated, or for patients who wish to be resuscitated to have delays in their resuscitation efforts. This study will extend the knowledge from the previous literature by exploring how the complexity and redundancy of clinical documentation practices affect the quality of code status documentation. To our knowledge, there are no prior studies that focus specifically on the frequency and clinical relevance of inconsistent code status documentation for inpatients across multiple documentation sources.
METHODS
Study Context
This is a point‐prevalence study conducted at 3 academic medical centers (AMCs) affiliated with the University of Toronto. At all 3 AMCs, the majority of general internal medicine (GIM) patients are admitted to 1 of 4 clinical teaching units (CTUs). The physician team on each CTU consists of 1 attending staff, 1 senior resident (second or third year resident), 2 to 3 first‐year residents, and 2 to 3 medical students. CTUs typically care for between 15 and 25 patients. The research ethics boards at each of the AMCs approved this study.
Existing Code Status Documentation Processes
At all 3 AMCs, providers document patient code status in 5 different places: (1) progress notes (admission and daily progress notes in the paper chart), (2) physician orders (computerized orders at 1 site, paper orders at the other 2 sites), (3) electronic sign‐out lists (Web‐based tools used by residents to support patient handover), (4) nursing‐care plan (used by nurses to document care plans for their assigned patients), and (5) DNR sheet (a cover sheet placed at the front of the paper chart in patients who have a DNR order) (see Supporting Information, Appendix, in the online version of this article). None of these documentation sources link automatically to one another. Once a physician establishes a patient's code status, it should be documented in the progress notes. The same physician should also write the code status as a physician order and update the patient's code status in the Web‐based electronic sign‐out list. The nurse responsible for the patient transcribes the code status order in the nursing‐care plan. For DNR patients, nurses or physicians (depending on the AMC) also place the DNR sheet in the front of the chart.
At our 3 AMCs, in the event of a cardiac arrest, resident physicians and nurses are typically the first responders. To quickly determine a patient's code status nurses and resident physicians look for the presence or absence of a DNR sheet. In addition, nurses rely on their nursing‐care plan and resident physicians rely on their electronic sign‐out list.
Eligibility Criteria and Sampling Strategy
Our study included GIM patients admitted to a CTU at 1 of 3 AMCs, and excluded admitted GIM patients who remained in the emergency department (due to differences in code status documentation processes). Data collection took place between September 2010 and September 2011 on days when the principal author (A.S.W.) was available to collect the data.
We collected data for all patients from a single GIM CTU on the same day to minimize the chance that a team updates or changes a patient's code status during data collection. We included each of the 4 CTUs at the 3 study sites once during the study period (ie, 12 full days of data collection).
Study Measures and Data Collection
One study author (A.S.W.) screened the 5 code status documentation sources listed above for each patient and recorded the documented code status as full code, DNR, or blank (if there was nothing entered) in a database. We also collected patient demographic data, admitting diagnosis, length of stay, admission to home ward (ie, the medicine ward affiliated with the CTU team that admitted the patient), free‐text code status documentation, transfer to the intensive care unit during their hospitalization, and whether the patient is receiving comfort measures, up to the time of data collection. Because the study investigators were not members of the team providing care to patients included in the study, we could not directly elicit the patient's actual code status.
The primary study outcome measures were the completeness and consistency of code status documentation across the 5 documentation sources. For completeness, we included data relating to 4 documentation sources only, excluding the DNR sheet because it is only relevant for DNR patients. We defined inconsistent code status documentation a priori as (1) the code status is conflicting in at least 2 documentation sources (eg, full code in 1 source and DNR in another) or (2) the code status is documented in 1 or more documentation source and not documented in at least 1 documentation source (eg, full code in 1 source and blank in another).
We then subdivided code status documentation inconsistencies into nonclinically relevant and clinically relevant subcategories. For example, a nonclinically relevant inconsistency would be if a physician documented full code in the physician orders, but a nurse did not document anything in the nursing‐care plan, because most providers would assume a preference for resuscitation in the absence of code status documentation in the nursing‐care plan.
We defined clinically relevant inconsistencies as those that would reasonably lead healthcare providers referring to different documentation sources to respond differently in the event of a cardiac arrest (eg, the physician orders show DNR whereas the nursing‐care plan is blanka provider who refers to the physician orders would not resuscitate the patient, but another provider who refers to the blank nursing‐care plan would resuscitate the patient).
We determined the proportion of patients with inconsistent code status documentation by listing the 31 different permutations of code status documentation in our data (Figure 1). Using the prespecified definition of inconsistent code status documentation, 3 study authors (I.A.D., B.M.W., R.C.W.) independently determined whether each permutation met the criteria for inconsistent code status documentation, and judged the clinical relevance of each documentation inconsistency. We resolved disagreements by consensus.
Statistical Analysis
We calculated descriptive statistics for all variables, summarizing continuous measures using means and standard deviations, and categorical measures using counts, percentages, and their associated 95% confidence intervals. Logistic regression analyses adjusting for the correlation among observations taken from the same team were carried out. Each of the 4 variables of interest (patient age, length of stay, receiving comfort measures, free text code status documentation) was run in a bivariate model to obtain unadjusted estimates as well as the final multivariable model. All estimates were displayed as odds ratios (ORs) and their associated 95% confidence intervals (CIs). A P value <0.05 was used to denote statistical significance. We also carried out a kappa analysis to assess inter‐rater agreement when judging whether inconsistent documentation is clinically relevant. All analyses were carried out using SAS version 9.3 (SAS Institute, Cary, NC).
RESULTS
There were 194 patients potentially eligible for inclusion. Seven admitted GIM patients who had not been transferred from the emergency department were excluded, leaving 187 patients in the study. The mean patient age was 70 years; 83 (44%) were female. The median length of stay up to the time of data collection was 6 days, with the majority (156 [83%]) of patients admitted to their home ward. Ten (5%) patients were receiving comfort measures.
Completeness of Code Status Documentation
Thirty‐eight (20%; 95% CI, 14%‐26%) patients had complete and consistent code status documentation across all documentation sources, whereas 27 (14%; 95% CI, 9%‐19%) patients had no code status documented in any documentation source. By documentation source, providers documented code status in the progress notes for 89 patients (48%; 95% CI, 40%‐55%), the physician orders for 107 patients (57%; 95% CI, 50%‐64%), the nursing‐care plan for 110 patients (59%; 95% CI, 51%‐66%), and the electronic sign‐out list for 129 patients (69%; 95% CI, 62%‐76%).
Consistency of Code Status Documentation
The remaining 122 patients (65%; 95% CI, 58%‐72%) had at least 1 code status documentation inconsistency. Of these, 38 patients (20%; 95% CI, 14%‐26%) had a clinically relevant code status documentation inconsistency. Code status documentation inconsistency differed by site; the 2 hospitals with paper‐based physician orders had fewer patients with complete and consistent code status documentation compared to the hospital where physician orders are electronic (15% vs 42%, respectively, P<0.001) (Table 1).
| Physician Code Status Order | Sites 1 & 2: Paper‐Based, N=108 | Site 3: Electronic, N=52 | P Value |
|---|---|---|---|
| Consistent code status documentation | 16 (15%) | 22 (42%) | |
| Inconsistent code status documentation, nonclinically relevant | 60 (56%) | 30 (58%) | <0.0001 |
| Inconsistent code status documentation, clinically relevant | 32 (30%) | 6 (12%) |
The permutations of clinically relevant and nonclinically relevant inconsistencies are summarized in Figure 1. We achieved high inter‐rater reliability among the 3 independent reviewers with respect to rating the clinical relevance of documentation inconsistencies (=0.86 [95% CI, 0.76‐0.95]).
To identify correlates of clinically relevant code status documentation inconsistencies, we included 4 variables of interest (patient age, length of stay, receiving comfort measures, and free text code status documentation) in a logistic regression analysis. Bivariate analyses demonstrated that increased age (OR =1.07 [95% CI, 1.05‐1.10] for every 1‐year increase in age, P<0.001) and receiving comfort measures (OR= 10.98 [95% CI, 1.94‐62.12], P=0.007) were associated with a clinically relevant code status documentation inconsistency. Using these 4 variables in a multivariable analysis clustering for physician team, increased age (OR=1.07 [95% CI, 1.04‐1.10] for every 1‐year increase in age, P<0.0001) and receiving comfort measures (OR=9.39 [95% CI, 1.3565.19], P=0.02) remained as independent positive correlates of having a clinically relevant code status documentation inconsistency (Table 2).
| Clinically Relevant Inconsistencies, N=38 | No Inconsistencies and Nonclinically Relevant Inconsistencies, N=149 | P Value | |
|---|---|---|---|
| |||
| Age, y, mean (SD) | 83 (10) | 67 (19) | <0.0001* |
| Length of stay, d, median (IQR) | 6.5 (310) | 6 (219) | 0.39 |
| Receiving comfort measures, n (%) | 7 (18%) | 3 (2%) | <0.0001* |
| Free‐text code status documentation, n (%) | 18 (47%) | 58 (39%) | 0.34 |
DISCUSSION
We found that 2 out of 3 patients had at least 1 inconsistency in code status documentation, and that 1 in 5 patients had at least 1 clinically relevant code status documentation inconsistency. The majority of clinically relevant inconsistencies occurred because there was a DNR order written in some sources of code status documentation, and no orders in other documentation sources. However, there were 4 striking examples where DNR was written in some sources of code status documentation and full code was written in other documentation sources (Figure 1).
Older patients and patients receiving comfort measures were more likely to have a clinically relevant inconsistency in code status documentation. This is particularly concerning, because they are among the most vulnerable patients at highest risk for having an in‐hospital cardiac arrest.
Our study extends the findings of prior studies that identified gaps in completeness and accuracy of code status documentation and describes another important gap in the quality and consistency of code status documentation.[20] This becomes particularly important because efforts aimed at increasing documentation of patients' code status without ensuring consistency across documentation sources may still result in patients being resuscitated or not resuscitated inappropriately.
This issue of poorly integrated health records is relevant for many other aspects of patient care. For example, 1 study found significant discrepancies in patient medication allergy documentation across multiple health records.[21] This fragmentation of documentation of the same patient information in multiple health records requires attention and should be the focus of institutional quality improvement efforts.
There are several potential ways to improve the code status documentation process. First, the use of standard fields or standardized orders can increase the completeness and improve the clarity of code status documentation.[22, 23] For institutions with an electronic medical record, forcing functions may further increase code status documentation. One study found that the implementation of an electronic medical record increased code status documentation from 4% to 63%.[24] We found similarly that the site with electronic physician orders had higher rates of complete and consistent code status documentation.
A second approach is to minimize the number of different sources for code status documentation. Institutions should critically examine each place where providers could document code status and decide whether this information adds value, and create policies to restrict unnecessary duplicate documentation and ensure accurate documentation of code status in several key, centralized locations.[25] A third option would be to automatically synchronize all code status documentation sources.[25] This final approach requires a fully integrated electronic health record.
Our study has several limitations. Although we report a large number of code status documentation inconsistencies, we do not know how many of these lead to incorrect resuscitative measures, so the actual impact on patient care is unknown. Also, because we were focusing on inconsistencies among sources of code status documentation, and not on accurate documentation of a patients' code status, the patients' actual preferences were not elicited and are not known. Finally, we carried out our study in 3 AMCs with residents that rotate from 1 site to another. The transient nature of resident work may increase the likelihood of documentation inconsistencies, because trainees may be less aware of local processes. In addition, the way front‐line staff uses clinical documentation sources to determine a patient's code status may differ at other institutions. Therefore, our estimate of clinical relevance may not be generalizable to other institutions with different front‐line processes or with healthcare teams that are more stable and aware of local documentation processes.
In summary, our study uncovered significant gaps in the quality of code status documentation that span 3 different AMCs. Having multiple, poorly integrated sources for code status documentation leads to a significant number of concerning inconsistencies that create opportunities for healthcare providers to inappropriately deliver or withhold resuscitative measures that conflict with patients' expressed wishes. Institutions need to be aware of this potential documentation hazard and take steps to minimize code status documentation inconsistencies. Even though cardiac arrests occur infrequently, if healthcare teams take inappropriate action because of these code status documentation inconsistencies, the consequences can be devastating.
Disclosure
Nothing to report.
- , , , et al. Advance directives for medical care—a case for greater use. N Engl J Med. 1991;324(13):889–895.
- , , , et al; Canadian Researchers at the End of Life Network (CARENET). What matters most in end‐of‐life care: perceptions of seriously ill patients and their family memebrs. CMAJ. 2006;174(5):627–633.
- , , . Advance directives and outcomes of surrogate decision making before death. N Eng J Med. 2010;362(13):1211–1218.
- , , , et al. Associations between end‐of‐life discussions, patient mental health, medical care near death, and caregiver bereavement adjustment. JAMA. 2008;300(14):1665–1673.
- , , , . The impact of advance care planning on end of life care in elderly patients: randomized controlled trial. BMJ. 2010;340:c1345.
- , . Quality indicators for end‐of‐life care in vulnerable elders. Ann Intern Med. 2001;135(8):667–685.
- , , , . Assessing care of vulnerable elders: methods for developing quality indicators. Ann Intern Med. 2001;135:647–652.
- , , , et al. Perceptions by family members of the dying experience of older and seriously ill patients. Ann Intern Med. 1997;126(2):97–106.
- , . Cardiopulmonary resuscitation: capacity, discussion and documentation. Q J Med. 2006;99(10):683–690.
- , , , et al. Code status documentation in the outpatient electronic medical records or patients with metastatic cancer. J Gen Intern Med. 2009;25(2):150–153.
- , , , et al. Factors associated with discussion of care plans and code status at the time of hospital admission: results from the multicenter hospitalist study. J Hosp Med. 2008;3(6):437–445.
- , , , . Documentation quality of inpatient code status discussions. J Pain Symptom Manage. 2014;48(4):632–638.
- , , , . The use of life‐sustaining treatments in hospitalized persons aged 80 and older. J Am Geriatr Soc. 2002;50(5):930–934.
- The SUPPORT Principal Investigators. A controlled trial to improve care for seriously ill hospitalized patients: the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT). JAMA. 1995;274(20):1591–1598.
- , , . Some treatment‐withholding implications of no‐code orders in an academic hospital. Crit Care Med. 1984;12(10):879–881.
- . A prospective study of patients with DNR orders in a teaching hospital. Arch Intern Med. 1998;148(10):2193–2198.
- , . Compliance with do‐not‐resuscitate orders for hospitalized patient transported to radiology department. Ann Int Med. 1998;129(10):801–805.
- , . Identification of inpatient DNR status: a safety hazard begging for standardization. J Hosp Med. 2007;2(6):366–371.
- . Controlling death: the false promise of advance directives. Ann Int Med. 2007;147(1):51–57.
- , , , et al. Failure to engage hospitalized elderly patients and their families in advance care planning. JAMA Intern Med. 2013;173(9):778–787.
- , , , et al. The recording of drug sensitivities for older people living in care homes. Br J Clin Pharmacol. 2010;69(5):553–557.
- , , , , , . A comparison of methods to communicate treatment preferences in nursing facilities: traditional practices versus the physician orders for life‐sustaining treatment program. J Am Geriatr Soc. 2010;58(7):1241–1248.
- , , , et al. Evaluation of a treatment limitation policy with a specific treatment‐limiting order page. Arch Intern Med. 1994;154(4):425–432.
- , , , et al. An electronic medical record intervention increased nursing home advance directive orders and documentation. J Am Geriatr Soc. 2007;55(7):1001–1006.
- , , , et al. Honouring patient's resuscitation wishes: a multiphased effort to improve identification and documentation. BMJ Quality Safety. 2013;22(1):85–92.
- , , , et al. Advance directives for medical care—a case for greater use. N Engl J Med. 1991;324(13):889–895.
- , , , et al; Canadian Researchers at the End of Life Network (CARENET). What matters most in end‐of‐life care: perceptions of seriously ill patients and their family memebrs. CMAJ. 2006;174(5):627–633.
- , , . Advance directives and outcomes of surrogate decision making before death. N Eng J Med. 2010;362(13):1211–1218.
- , , , et al. Associations between end‐of‐life discussions, patient mental health, medical care near death, and caregiver bereavement adjustment. JAMA. 2008;300(14):1665–1673.
- , , , . The impact of advance care planning on end of life care in elderly patients: randomized controlled trial. BMJ. 2010;340:c1345.
- , . Quality indicators for end‐of‐life care in vulnerable elders. Ann Intern Med. 2001;135(8):667–685.
- , , , . Assessing care of vulnerable elders: methods for developing quality indicators. Ann Intern Med. 2001;135:647–652.
- , , , et al. Perceptions by family members of the dying experience of older and seriously ill patients. Ann Intern Med. 1997;126(2):97–106.
- , . Cardiopulmonary resuscitation: capacity, discussion and documentation. Q J Med. 2006;99(10):683–690.
- , , , et al. Code status documentation in the outpatient electronic medical records or patients with metastatic cancer. J Gen Intern Med. 2009;25(2):150–153.
- , , , et al. Factors associated with discussion of care plans and code status at the time of hospital admission: results from the multicenter hospitalist study. J Hosp Med. 2008;3(6):437–445.
- , , , . Documentation quality of inpatient code status discussions. J Pain Symptom Manage. 2014;48(4):632–638.
- , , , . The use of life‐sustaining treatments in hospitalized persons aged 80 and older. J Am Geriatr Soc. 2002;50(5):930–934.
- The SUPPORT Principal Investigators. A controlled trial to improve care for seriously ill hospitalized patients: the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT). JAMA. 1995;274(20):1591–1598.
- , , . Some treatment‐withholding implications of no‐code orders in an academic hospital. Crit Care Med. 1984;12(10):879–881.
- . A prospective study of patients with DNR orders in a teaching hospital. Arch Intern Med. 1998;148(10):2193–2198.
- , . Compliance with do‐not‐resuscitate orders for hospitalized patient transported to radiology department. Ann Int Med. 1998;129(10):801–805.
- , . Identification of inpatient DNR status: a safety hazard begging for standardization. J Hosp Med. 2007;2(6):366–371.
- . Controlling death: the false promise of advance directives. Ann Int Med. 2007;147(1):51–57.
- , , , et al. Failure to engage hospitalized elderly patients and their families in advance care planning. JAMA Intern Med. 2013;173(9):778–787.
- , , , et al. The recording of drug sensitivities for older people living in care homes. Br J Clin Pharmacol. 2010;69(5):553–557.
- , , , , , . A comparison of methods to communicate treatment preferences in nursing facilities: traditional practices versus the physician orders for life‐sustaining treatment program. J Am Geriatr Soc. 2010;58(7):1241–1248.
- , , , et al. Evaluation of a treatment limitation policy with a specific treatment‐limiting order page. Arch Intern Med. 1994;154(4):425–432.
- , , , et al. An electronic medical record intervention increased nursing home advance directive orders and documentation. J Am Geriatr Soc. 2007;55(7):1001–1006.
- , , , et al. Honouring patient's resuscitation wishes: a multiphased effort to improve identification and documentation. BMJ Quality Safety. 2013;22(1):85–92.
© 2015 Society of Hospital Medicine
Chronic lymphocytic leukemia prognosis relatively good after transplantation failure
Unlike for those with acute leukemia, patients with chronic lymphocytic leukemia who had disease progression after undergoing transplantation had a relatively good prognosis, with 2- and 5-year overall survival rates of 67% and 38%, investigators reported online April 6 in the Journal of Clinical Oncology.*
Patients with chronic lymphocytic leukemia (CLL) who experienced acute or chronic graft-versus-host disease (GVHD) had significantly longer overall survival (OS) than those who did not have GVHD (P = .04 and P = .05, respectively). “Nearly half our patients with active CLL after transplantation had chronic GVHD, and the association of chronic GVHD with achieving cure and its power to predict OS among patients for whom transplantation failed suggests that the GVL (graft-versus-leukemia) effect contributes to prolonged survival even in patients with a high burden of disease,” wrote Dr. Uri Rozovski and associates at the University of Texas MD Anderson Cancer Center, Houston (J. Clin. Oncol. 2015 Apr. 6 [doi:10.1200/JCO.2014.58.6750]).
A matched-pair analysis showed that patients who underwent allogeneic stem cell transplant (SCT) about the same time and did not relapse also had higher rates of acute and chronic GVHD (P = .004 and P = .011, respectively).
The retrospective review of the Bone Marrow Transplantation Program database identified 358 patients with CLL or RT who underwent SCT from 1998 to 2011. The study evaluated 72 patients who had disease progression at a median 74 months after SCT, most of whom received one to eight lines of treatment after relapse and had a median OS of almost 3 years from the time of progression. Multivariate analysis showed that low hemoglobin levels and the presence of Richter’s transformation (RT) were associated with shorter OS; chronic GVHD and response to the first post-SCT treatment predicted longer OS.
Patients with RT had a worse prognosis, with a median OS of 15 months (95% confidence interval, 2-28 months) and 2- and 5-year survival rates of 36% and 0%. Transplantation carried a significant risk for transformation: 16 (30%) patients with CLL developed RT after allogeneic SCT. Conversely, four patients with RT developed CLL after transplantation.
The authors note that even in patients who did not maintain a durable response, SCT was beneficial. The study cohort received a variety of salvage treatments, and patients who received ibrutinib responded well. “Because of the favorable outcomes with ibrutinib in relapsed/refractory CLL, we believe that ibrutinib might have a role in the treatment of disease progression following transplantation failure,” they wrote.
*Correction, 4/8/2015: A previous version of this article misstated the type of leukemia referenced in the study.
Unlike for those with acute leukemia, patients with chronic lymphocytic leukemia who had disease progression after undergoing transplantation had a relatively good prognosis, with 2- and 5-year overall survival rates of 67% and 38%, investigators reported online April 6 in the Journal of Clinical Oncology.*
Patients with chronic lymphocytic leukemia (CLL) who experienced acute or chronic graft-versus-host disease (GVHD) had significantly longer overall survival (OS) than those who did not have GVHD (P = .04 and P = .05, respectively). “Nearly half our patients with active CLL after transplantation had chronic GVHD, and the association of chronic GVHD with achieving cure and its power to predict OS among patients for whom transplantation failed suggests that the GVL (graft-versus-leukemia) effect contributes to prolonged survival even in patients with a high burden of disease,” wrote Dr. Uri Rozovski and associates at the University of Texas MD Anderson Cancer Center, Houston (J. Clin. Oncol. 2015 Apr. 6 [doi:10.1200/JCO.2014.58.6750]).
A matched-pair analysis showed that patients who underwent allogeneic stem cell transplant (SCT) about the same time and did not relapse also had higher rates of acute and chronic GVHD (P = .004 and P = .011, respectively).
The retrospective review of the Bone Marrow Transplantation Program database identified 358 patients with CLL or RT who underwent SCT from 1998 to 2011. The study evaluated 72 patients who had disease progression at a median 74 months after SCT, most of whom received one to eight lines of treatment after relapse and had a median OS of almost 3 years from the time of progression. Multivariate analysis showed that low hemoglobin levels and the presence of Richter’s transformation (RT) were associated with shorter OS; chronic GVHD and response to the first post-SCT treatment predicted longer OS.
Patients with RT had a worse prognosis, with a median OS of 15 months (95% confidence interval, 2-28 months) and 2- and 5-year survival rates of 36% and 0%. Transplantation carried a significant risk for transformation: 16 (30%) patients with CLL developed RT after allogeneic SCT. Conversely, four patients with RT developed CLL after transplantation.
The authors note that even in patients who did not maintain a durable response, SCT was beneficial. The study cohort received a variety of salvage treatments, and patients who received ibrutinib responded well. “Because of the favorable outcomes with ibrutinib in relapsed/refractory CLL, we believe that ibrutinib might have a role in the treatment of disease progression following transplantation failure,” they wrote.
*Correction, 4/8/2015: A previous version of this article misstated the type of leukemia referenced in the study.
Unlike for those with acute leukemia, patients with chronic lymphocytic leukemia who had disease progression after undergoing transplantation had a relatively good prognosis, with 2- and 5-year overall survival rates of 67% and 38%, investigators reported online April 6 in the Journal of Clinical Oncology.*
Patients with chronic lymphocytic leukemia (CLL) who experienced acute or chronic graft-versus-host disease (GVHD) had significantly longer overall survival (OS) than those who did not have GVHD (P = .04 and P = .05, respectively). “Nearly half our patients with active CLL after transplantation had chronic GVHD, and the association of chronic GVHD with achieving cure and its power to predict OS among patients for whom transplantation failed suggests that the GVL (graft-versus-leukemia) effect contributes to prolonged survival even in patients with a high burden of disease,” wrote Dr. Uri Rozovski and associates at the University of Texas MD Anderson Cancer Center, Houston (J. Clin. Oncol. 2015 Apr. 6 [doi:10.1200/JCO.2014.58.6750]).
A matched-pair analysis showed that patients who underwent allogeneic stem cell transplant (SCT) about the same time and did not relapse also had higher rates of acute and chronic GVHD (P = .004 and P = .011, respectively).
The retrospective review of the Bone Marrow Transplantation Program database identified 358 patients with CLL or RT who underwent SCT from 1998 to 2011. The study evaluated 72 patients who had disease progression at a median 74 months after SCT, most of whom received one to eight lines of treatment after relapse and had a median OS of almost 3 years from the time of progression. Multivariate analysis showed that low hemoglobin levels and the presence of Richter’s transformation (RT) were associated with shorter OS; chronic GVHD and response to the first post-SCT treatment predicted longer OS.
Patients with RT had a worse prognosis, with a median OS of 15 months (95% confidence interval, 2-28 months) and 2- and 5-year survival rates of 36% and 0%. Transplantation carried a significant risk for transformation: 16 (30%) patients with CLL developed RT after allogeneic SCT. Conversely, four patients with RT developed CLL after transplantation.
The authors note that even in patients who did not maintain a durable response, SCT was beneficial. The study cohort received a variety of salvage treatments, and patients who received ibrutinib responded well. “Because of the favorable outcomes with ibrutinib in relapsed/refractory CLL, we believe that ibrutinib might have a role in the treatment of disease progression following transplantation failure,” they wrote.
*Correction, 4/8/2015: A previous version of this article misstated the type of leukemia referenced in the study.
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: The prognosis for patients with chronic lymphocytic* leukemia who have undergone failed stem cell transplantation (SCT) is relatively good.
Major finding: From the time of progression after SCT, median OS was 36 months (95% CI, 24-48) for patients with CLL, and 38% survived 5 or more years.
Data source: The retrospective database review identified 72 patients with CLL or Richter’s transformation who underwent allogenic SCT from 1998 to 2011 and progressed after transplantation.
Disclosures: Dr. Rozovski reported having no disclosures. Two of the coauthors reported ties to several industry sources.
Avoid voriconazole in transplant patients at risk for skin cancer
SAN FRANCISCO – Voriconazole increased the risk of squamous cell carcinoma by 73% in a review of 455 lung transplant patients at the University of California, San Francisco.
The increase was for any exposure to the drug after transplant (adjusted hazard ratio, 1.73; P = .03). The investigators also found that each additional 30-day exposure at 200 mg of voriconazole twice daily increased the risk of squamous cell carcinoma (SCC) by 3.0% (HR, 1.03; P < .001). The results were adjusted for age at transplant, sex, and race. Overall, SCC risk was highest among white men aged 50 years or older at the time of transplant.
Although voriconazole did protect against posttransplant Aspergillus colonization (aHR, 0.50; P < .001), it did not reduce the risk of invasive aspergillosis. The drug reduced all-cause mortality only among colonized subjects (aHR, 0.34; P = .03), and offered no mortality benefit among those who were not colonized.
There was no difference in all-cause mortality between patients who had any exposure to voriconazole and those who did not, “but we actually found a 2% increased risk of death for each 1 month on the medication. Patients who weren’t colonized were the ones contributing to this increased risk of death,” said lead investigator Matthew Mansh, now a medical student at Stanford (Calif.) University.
There was no increased risk of SCC with alternative antifungals, including inhaled amphotericin and posaconazole. These alternatives should be considered instead of voriconazole in people at higher risk for skin cancer after lung transplants, according to the study, Mr. Mansh noted.
Voriconazole, which is widely used for antifungal prophylaxis after solid organ transplants, has been linked to skin cancer. The reason for the carcinogenic effect is not known; researchers are working to unravel the molecular mechanisms.
“Physicians should be cautious when using voriconazole in the care of transplant recipients. If you see a patient who is developing phototoxicity” with voriconazole, “and if they don’t have evidence of Aspergillus colonization, you may want to limit exposure to high doses of this drug or suggest an alternative,” Mr. Mansh said.
“We have now demonstrated that the alternatives “don’t carry this increased risk of cutaneous SCC,” Mr. Mansh said at the American Academy of Dermatology annual meeting.
The mean age of the study patients at transplant was 52 years, and the majority of patients were white; slightly more than half were men. Most had bilateral lung transplants, with pulmonary fibrosis at the leading indication.
Voriconazole was used in 85% of the patients for an average of 10 months. A quarter of voriconazole patients developed SCC within 5 years of transplant, and 43% within 10 years. Among patients who did not receive the drug, 15% developed SCC within 5 years of transplant, and 28% developed SCC within 10 years of transplant.
“The benefit of voriconazole in terms of death was limited to patients with evidence of Aspergillus colonization, and it wasn’t dose dependent. Patients who had a higher cumulative exposure did not get more benefit,” Mr. Mansh said.
Mr. Mansh had no relevant disclosures.
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Dr. Paul T. Nghiem |
This is a carefully done study with a practical message: voriconazole patients are at a prolonged increased risk for squamous cell carcinoma. If patients develop phototoxicity or are fair-skinned, have sun damage, a history of squamous cell carcinoma or other risk factors, I think it’s highly appropriate to suggest an alternative. The alternatives are not at all associated with phototoxicity or squamous cell carcinoma.
Dr. Paul T. Nghiem moderated the late-breaker presentation in which the study was presented and is a professor of dermatology at the University of Washington, Seattle. Dr. Nghiem had no disclosures related to the study.
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Dr. Paul T. Nghiem |
This is a carefully done study with a practical message: voriconazole patients are at a prolonged increased risk for squamous cell carcinoma. If patients develop phototoxicity or are fair-skinned, have sun damage, a history of squamous cell carcinoma or other risk factors, I think it’s highly appropriate to suggest an alternative. The alternatives are not at all associated with phototoxicity or squamous cell carcinoma.
Dr. Paul T. Nghiem moderated the late-breaker presentation in which the study was presented and is a professor of dermatology at the University of Washington, Seattle. Dr. Nghiem had no disclosures related to the study.
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|
Dr. Paul T. Nghiem |
This is a carefully done study with a practical message: voriconazole patients are at a prolonged increased risk for squamous cell carcinoma. If patients develop phototoxicity or are fair-skinned, have sun damage, a history of squamous cell carcinoma or other risk factors, I think it’s highly appropriate to suggest an alternative. The alternatives are not at all associated with phototoxicity or squamous cell carcinoma.
Dr. Paul T. Nghiem moderated the late-breaker presentation in which the study was presented and is a professor of dermatology at the University of Washington, Seattle. Dr. Nghiem had no disclosures related to the study.
SAN FRANCISCO – Voriconazole increased the risk of squamous cell carcinoma by 73% in a review of 455 lung transplant patients at the University of California, San Francisco.
The increase was for any exposure to the drug after transplant (adjusted hazard ratio, 1.73; P = .03). The investigators also found that each additional 30-day exposure at 200 mg of voriconazole twice daily increased the risk of squamous cell carcinoma (SCC) by 3.0% (HR, 1.03; P < .001). The results were adjusted for age at transplant, sex, and race. Overall, SCC risk was highest among white men aged 50 years or older at the time of transplant.
Although voriconazole did protect against posttransplant Aspergillus colonization (aHR, 0.50; P < .001), it did not reduce the risk of invasive aspergillosis. The drug reduced all-cause mortality only among colonized subjects (aHR, 0.34; P = .03), and offered no mortality benefit among those who were not colonized.
There was no difference in all-cause mortality between patients who had any exposure to voriconazole and those who did not, “but we actually found a 2% increased risk of death for each 1 month on the medication. Patients who weren’t colonized were the ones contributing to this increased risk of death,” said lead investigator Matthew Mansh, now a medical student at Stanford (Calif.) University.
There was no increased risk of SCC with alternative antifungals, including inhaled amphotericin and posaconazole. These alternatives should be considered instead of voriconazole in people at higher risk for skin cancer after lung transplants, according to the study, Mr. Mansh noted.
Voriconazole, which is widely used for antifungal prophylaxis after solid organ transplants, has been linked to skin cancer. The reason for the carcinogenic effect is not known; researchers are working to unravel the molecular mechanisms.
“Physicians should be cautious when using voriconazole in the care of transplant recipients. If you see a patient who is developing phototoxicity” with voriconazole, “and if they don’t have evidence of Aspergillus colonization, you may want to limit exposure to high doses of this drug or suggest an alternative,” Mr. Mansh said.
“We have now demonstrated that the alternatives “don’t carry this increased risk of cutaneous SCC,” Mr. Mansh said at the American Academy of Dermatology annual meeting.
The mean age of the study patients at transplant was 52 years, and the majority of patients were white; slightly more than half were men. Most had bilateral lung transplants, with pulmonary fibrosis at the leading indication.
Voriconazole was used in 85% of the patients for an average of 10 months. A quarter of voriconazole patients developed SCC within 5 years of transplant, and 43% within 10 years. Among patients who did not receive the drug, 15% developed SCC within 5 years of transplant, and 28% developed SCC within 10 years of transplant.
“The benefit of voriconazole in terms of death was limited to patients with evidence of Aspergillus colonization, and it wasn’t dose dependent. Patients who had a higher cumulative exposure did not get more benefit,” Mr. Mansh said.
Mr. Mansh had no relevant disclosures.
SAN FRANCISCO – Voriconazole increased the risk of squamous cell carcinoma by 73% in a review of 455 lung transplant patients at the University of California, San Francisco.
The increase was for any exposure to the drug after transplant (adjusted hazard ratio, 1.73; P = .03). The investigators also found that each additional 30-day exposure at 200 mg of voriconazole twice daily increased the risk of squamous cell carcinoma (SCC) by 3.0% (HR, 1.03; P < .001). The results were adjusted for age at transplant, sex, and race. Overall, SCC risk was highest among white men aged 50 years or older at the time of transplant.
Although voriconazole did protect against posttransplant Aspergillus colonization (aHR, 0.50; P < .001), it did not reduce the risk of invasive aspergillosis. The drug reduced all-cause mortality only among colonized subjects (aHR, 0.34; P = .03), and offered no mortality benefit among those who were not colonized.
There was no difference in all-cause mortality between patients who had any exposure to voriconazole and those who did not, “but we actually found a 2% increased risk of death for each 1 month on the medication. Patients who weren’t colonized were the ones contributing to this increased risk of death,” said lead investigator Matthew Mansh, now a medical student at Stanford (Calif.) University.
There was no increased risk of SCC with alternative antifungals, including inhaled amphotericin and posaconazole. These alternatives should be considered instead of voriconazole in people at higher risk for skin cancer after lung transplants, according to the study, Mr. Mansh noted.
Voriconazole, which is widely used for antifungal prophylaxis after solid organ transplants, has been linked to skin cancer. The reason for the carcinogenic effect is not known; researchers are working to unravel the molecular mechanisms.
“Physicians should be cautious when using voriconazole in the care of transplant recipients. If you see a patient who is developing phototoxicity” with voriconazole, “and if they don’t have evidence of Aspergillus colonization, you may want to limit exposure to high doses of this drug or suggest an alternative,” Mr. Mansh said.
“We have now demonstrated that the alternatives “don’t carry this increased risk of cutaneous SCC,” Mr. Mansh said at the American Academy of Dermatology annual meeting.
The mean age of the study patients at transplant was 52 years, and the majority of patients were white; slightly more than half were men. Most had bilateral lung transplants, with pulmonary fibrosis at the leading indication.
Voriconazole was used in 85% of the patients for an average of 10 months. A quarter of voriconazole patients developed SCC within 5 years of transplant, and 43% within 10 years. Among patients who did not receive the drug, 15% developed SCC within 5 years of transplant, and 28% developed SCC within 10 years of transplant.
“The benefit of voriconazole in terms of death was limited to patients with evidence of Aspergillus colonization, and it wasn’t dose dependent. Patients who had a higher cumulative exposure did not get more benefit,” Mr. Mansh said.
Mr. Mansh had no relevant disclosures.
AT AAD 2015
Key clinical point: Use an alternative antifungal after lung transplant in white men aged 50 years and older.
Major finding: Exposure to voriconazole increased the risk of squamous cell carcinoma by 73% after lung transplant (aHR, 1.73; P = .03); each additional 30‐day exposure at 200 mg twice daily increased the risk by 3.0% (HR 1.03; P < .001).
Data source: Retrospective cohort study of 455 lung transplant patients
Disclosures: The lead investigator had no relevant disclosures.
Dermoscopical screening surpasses app for melanoma diagnosis
A smartphone application was less effective at correctly diagnosing malignant melanoma than clinical diagnosis by dermatologists, based on data from a study evaluating 195 melanocytic lesions.
The app, which used fractal image analysis, was 73% specific and 83% sensitive, whereas the dermatologists’ clinical examinations were 88% sensitive and 97% specific.
Both diagnostic methods’ results were compared to histopathologic analyses of the nevi. The histopathologic analyses found 40 melanomas, 42 dysplastic nevi, and 113 benign nevi.
“The smartphone application ... might be a promising tool in the pre-evaluation of pigmented moles by laypersons,” although the current technology falls short, compared with clinical diagnosis by a dermatologist, according to the study’s researchers.
Find the full study in Journal of the European Academy of Dermatology and Venereology (doi:10.1111/jdv.12648).
A smartphone application was less effective at correctly diagnosing malignant melanoma than clinical diagnosis by dermatologists, based on data from a study evaluating 195 melanocytic lesions.
The app, which used fractal image analysis, was 73% specific and 83% sensitive, whereas the dermatologists’ clinical examinations were 88% sensitive and 97% specific.
Both diagnostic methods’ results were compared to histopathologic analyses of the nevi. The histopathologic analyses found 40 melanomas, 42 dysplastic nevi, and 113 benign nevi.
“The smartphone application ... might be a promising tool in the pre-evaluation of pigmented moles by laypersons,” although the current technology falls short, compared with clinical diagnosis by a dermatologist, according to the study’s researchers.
Find the full study in Journal of the European Academy of Dermatology and Venereology (doi:10.1111/jdv.12648).
A smartphone application was less effective at correctly diagnosing malignant melanoma than clinical diagnosis by dermatologists, based on data from a study evaluating 195 melanocytic lesions.
The app, which used fractal image analysis, was 73% specific and 83% sensitive, whereas the dermatologists’ clinical examinations were 88% sensitive and 97% specific.
Both diagnostic methods’ results were compared to histopathologic analyses of the nevi. The histopathologic analyses found 40 melanomas, 42 dysplastic nevi, and 113 benign nevi.
“The smartphone application ... might be a promising tool in the pre-evaluation of pigmented moles by laypersons,” although the current technology falls short, compared with clinical diagnosis by a dermatologist, according to the study’s researchers.
Find the full study in Journal of the European Academy of Dermatology and Venereology (doi:10.1111/jdv.12648).
Nursing home residents have poor outcomes after lower-extremity revascularization
A substantial number of nursing home residents undergo lower-extremity revascularization each year, but very few of them gain any function and approximately half die within the year, according to a report published online April 6 in JAMA Internal Medicine.
In a population-based analysis of Medicare claims and a database that tracks virtually all U.S. nursing homes, 82% of residents who underwent the procedure during a 3-year period had either died or were unable to walk a year afterward. Most showed a clinically significant decline in function within 3 months of having the procedure, said Dr. Lawrence Oresanya of the department of surgery, University of California, San Francisco, and his associates.
“Our findings can inform conversations between physicians, patients, and families about the risks and expected outcomes of surgery and whether the surgery is likely to be worthwhile. Our findings also highlight the importance of carefully considering a prognosis independent of vascular disease and assessing the goals of care. Ambulatory function … may be impossible to attain,” they wrote.
Lower-extremity revascularization is usually performed to maintain elderly patients’ functional independence by preserving their limbs. But a closer examination of these procedures is warranted in the nursing home population “because nursing home residents, in general, have high levels of functional dependence unrelated to peripheral arterial disease, and higher rates of mortality after most invasive procedures,” the investigators said.
Dr. Oresanya and his colleagues identified 10,784 nursing home residents across the country who underwent lower-extremity revascularization. The procedure was elective in 67% of cases and emergent or urgent in 33%. An endovascular approach was used in 56%, and an open approach in the remainder, with the endovacular approach being more associated with clinical success than open surgery.
The mean patient age was 82 years, and serious comorbidities were very common: 60% had cognitive impairment, 57% had heart failure, and 29% had renal failure. Three-fourths of the patients were nonambulatory at the time of surgery.
The investigators assumed that most patients in this setting had critical limb ischemia rather than claudication. They did not have information about the severity of the lower-extremity ischemia, or about the prevalence or duration of nonhealing wounds or gangrene.
One year after lower-extremity revascularization, mortality was 51% among ambulatory patients and 53% among nonambulatory patients. Only 13% of the entire cohort were able to walk, and only 18% had maintained or improved their presurgical functional status. “Revascularization rarely allowed a nonambulatory resident to become ambulatory,” Dr. Oresanya and his associates wrote (JAMA Intern. Med. 2015 April 6 [doi:10.1001/jamainternmed.2015.0486]).
The researchers were unable to determine whether these poor outcomes resulted from the surgery itself or were due to these patients’ “insufficient physiologic reserve.”
They also cautioned that they confined their study strictly to functional outcomes of lower-extremity revascularization, namely ambulation and mortality. Some patients may have derived other benefits from the procedure, such as relief of pain, healing of wounds, and avoidance of major amputation.
The authors reported having no relevant financial disclosures.
The findings of Oresanya et al. are balanced and valuable, even though the data didn’t give them specific clinical information such as the indications for revascularization and were insensitive to subtle issues such as patient and family wishes for level of care. Such studies point the way to a more rational clinical approach to the care of frail elders with a limited life span but with the prospect of constant pain and discomfort.
But it is important to note that most of the procedures in this study likely were performed to relieve symptoms of ischemic leg pain, nonhealing wounds, or worsening gangrene. In this setting, the surgery should be viewed as a palliative measure rather than as a definitive therapeutic procedure to extend ambulatory function.
William J. Hall, M.D., is at the University of Rochester, New York. He reported having no relevant financial disclosures. Dr. Hall made these remarks in an invited commentary accompanying Dr. Oresanya’s report (JAMA Intern. Med. 2015 April 6 [doi:10.1001/jamainternmed.2015.32]).
The findings of Oresanya et al. are balanced and valuable, even though the data didn’t give them specific clinical information such as the indications for revascularization and were insensitive to subtle issues such as patient and family wishes for level of care. Such studies point the way to a more rational clinical approach to the care of frail elders with a limited life span but with the prospect of constant pain and discomfort.
But it is important to note that most of the procedures in this study likely were performed to relieve symptoms of ischemic leg pain, nonhealing wounds, or worsening gangrene. In this setting, the surgery should be viewed as a palliative measure rather than as a definitive therapeutic procedure to extend ambulatory function.
William J. Hall, M.D., is at the University of Rochester, New York. He reported having no relevant financial disclosures. Dr. Hall made these remarks in an invited commentary accompanying Dr. Oresanya’s report (JAMA Intern. Med. 2015 April 6 [doi:10.1001/jamainternmed.2015.32]).
The findings of Oresanya et al. are balanced and valuable, even though the data didn’t give them specific clinical information such as the indications for revascularization and were insensitive to subtle issues such as patient and family wishes for level of care. Such studies point the way to a more rational clinical approach to the care of frail elders with a limited life span but with the prospect of constant pain and discomfort.
But it is important to note that most of the procedures in this study likely were performed to relieve symptoms of ischemic leg pain, nonhealing wounds, or worsening gangrene. In this setting, the surgery should be viewed as a palliative measure rather than as a definitive therapeutic procedure to extend ambulatory function.
William J. Hall, M.D., is at the University of Rochester, New York. He reported having no relevant financial disclosures. Dr. Hall made these remarks in an invited commentary accompanying Dr. Oresanya’s report (JAMA Intern. Med. 2015 April 6 [doi:10.1001/jamainternmed.2015.32]).
A substantial number of nursing home residents undergo lower-extremity revascularization each year, but very few of them gain any function and approximately half die within the year, according to a report published online April 6 in JAMA Internal Medicine.
In a population-based analysis of Medicare claims and a database that tracks virtually all U.S. nursing homes, 82% of residents who underwent the procedure during a 3-year period had either died or were unable to walk a year afterward. Most showed a clinically significant decline in function within 3 months of having the procedure, said Dr. Lawrence Oresanya of the department of surgery, University of California, San Francisco, and his associates.
“Our findings can inform conversations between physicians, patients, and families about the risks and expected outcomes of surgery and whether the surgery is likely to be worthwhile. Our findings also highlight the importance of carefully considering a prognosis independent of vascular disease and assessing the goals of care. Ambulatory function … may be impossible to attain,” they wrote.
Lower-extremity revascularization is usually performed to maintain elderly patients’ functional independence by preserving their limbs. But a closer examination of these procedures is warranted in the nursing home population “because nursing home residents, in general, have high levels of functional dependence unrelated to peripheral arterial disease, and higher rates of mortality after most invasive procedures,” the investigators said.
Dr. Oresanya and his colleagues identified 10,784 nursing home residents across the country who underwent lower-extremity revascularization. The procedure was elective in 67% of cases and emergent or urgent in 33%. An endovascular approach was used in 56%, and an open approach in the remainder, with the endovacular approach being more associated with clinical success than open surgery.
The mean patient age was 82 years, and serious comorbidities were very common: 60% had cognitive impairment, 57% had heart failure, and 29% had renal failure. Three-fourths of the patients were nonambulatory at the time of surgery.
The investigators assumed that most patients in this setting had critical limb ischemia rather than claudication. They did not have information about the severity of the lower-extremity ischemia, or about the prevalence or duration of nonhealing wounds or gangrene.
One year after lower-extremity revascularization, mortality was 51% among ambulatory patients and 53% among nonambulatory patients. Only 13% of the entire cohort were able to walk, and only 18% had maintained or improved their presurgical functional status. “Revascularization rarely allowed a nonambulatory resident to become ambulatory,” Dr. Oresanya and his associates wrote (JAMA Intern. Med. 2015 April 6 [doi:10.1001/jamainternmed.2015.0486]).
The researchers were unable to determine whether these poor outcomes resulted from the surgery itself or were due to these patients’ “insufficient physiologic reserve.”
They also cautioned that they confined their study strictly to functional outcomes of lower-extremity revascularization, namely ambulation and mortality. Some patients may have derived other benefits from the procedure, such as relief of pain, healing of wounds, and avoidance of major amputation.
The authors reported having no relevant financial disclosures.
A substantial number of nursing home residents undergo lower-extremity revascularization each year, but very few of them gain any function and approximately half die within the year, according to a report published online April 6 in JAMA Internal Medicine.
In a population-based analysis of Medicare claims and a database that tracks virtually all U.S. nursing homes, 82% of residents who underwent the procedure during a 3-year period had either died or were unable to walk a year afterward. Most showed a clinically significant decline in function within 3 months of having the procedure, said Dr. Lawrence Oresanya of the department of surgery, University of California, San Francisco, and his associates.
“Our findings can inform conversations between physicians, patients, and families about the risks and expected outcomes of surgery and whether the surgery is likely to be worthwhile. Our findings also highlight the importance of carefully considering a prognosis independent of vascular disease and assessing the goals of care. Ambulatory function … may be impossible to attain,” they wrote.
Lower-extremity revascularization is usually performed to maintain elderly patients’ functional independence by preserving their limbs. But a closer examination of these procedures is warranted in the nursing home population “because nursing home residents, in general, have high levels of functional dependence unrelated to peripheral arterial disease, and higher rates of mortality after most invasive procedures,” the investigators said.
Dr. Oresanya and his colleagues identified 10,784 nursing home residents across the country who underwent lower-extremity revascularization. The procedure was elective in 67% of cases and emergent or urgent in 33%. An endovascular approach was used in 56%, and an open approach in the remainder, with the endovacular approach being more associated with clinical success than open surgery.
The mean patient age was 82 years, and serious comorbidities were very common: 60% had cognitive impairment, 57% had heart failure, and 29% had renal failure. Three-fourths of the patients were nonambulatory at the time of surgery.
The investigators assumed that most patients in this setting had critical limb ischemia rather than claudication. They did not have information about the severity of the lower-extremity ischemia, or about the prevalence or duration of nonhealing wounds or gangrene.
One year after lower-extremity revascularization, mortality was 51% among ambulatory patients and 53% among nonambulatory patients. Only 13% of the entire cohort were able to walk, and only 18% had maintained or improved their presurgical functional status. “Revascularization rarely allowed a nonambulatory resident to become ambulatory,” Dr. Oresanya and his associates wrote (JAMA Intern. Med. 2015 April 6 [doi:10.1001/jamainternmed.2015.0486]).
The researchers were unable to determine whether these poor outcomes resulted from the surgery itself or were due to these patients’ “insufficient physiologic reserve.”
They also cautioned that they confined their study strictly to functional outcomes of lower-extremity revascularization, namely ambulation and mortality. Some patients may have derived other benefits from the procedure, such as relief of pain, healing of wounds, and avoidance of major amputation.
The authors reported having no relevant financial disclosures.
FROM JAMA INTERNAL MEDICINE
Key clinical point: Many nursing home residents undergo lower-extremity revascularization every year, but few survive and are ambulatory 1 year later.
Major finding: One year after lower-extremity revascularization, mortality was approximately 50%, only 13% of the entire cohort were able to walk, and only 18% had maintained or improved their presurgical functional status.
Data source: A population-based cohort study involving almost all (10,784) U.S. nursing home residents who had lower-extremity revascularization in 2005-2008 and were followed for 1 year.
Disclosures: This study was supported in part by the National Institute on Aging and the University of California, San Francisco, Claude D. Pepper Older Americans Independence Center. Dr. Oresanya and his associates reported having no relevant financial disclosures.
Few PE patients treated with catheter-directed interventions had complications
A review of research suggests that catheter-directed interventions (CDIs) have fewer complications but are not necessarily better at preventing mortality than are standard treatments for pulmonary embolisms, according to Dr. Efthymios D. Avgerinos and Dr. Rabih A. Chaer of the University of Pittsburgh.
Of 594 patients with massive pulmonary embolisms (PEs) who received various forms of CDI, 86.5% survived (range, 40%-100%), according to a systematic review of 35 noncontrolled studies.
“In 95% of these patients, CDIs were initiated without prior intravenous thrombolysis,” while 60%-67% of the patients also received a thrombolytic agent during the procedure, they wrote. The patient survival rate was 91.2% in studies that provided at least 80% of their patients with local thrombolytic therapy during a CDI, compared with 82.8% in studies in which less than 80% of participants received thrombolytic therapy.
Not all findings, however, suggested that it was more favorable for the patients to receive the thrombolytic therapy, Overall, the pooled rates of major and minor complications were 7.9% and 2.4%, respectively. The 25 major complications reported included bleeding complications requiring transfusion, renal failure requiring hemodialysis, cardiopulmonary events, cerebrovascular events, and death.
Other research on CDIs found that right ventricle dilation was reversed in patients with submassive PEs who received fixed-dose, ultrasound-assisted, catheter-directed thrombosis combined with anticoagulation. According to the recently published randomized controlled trial, which compared the effects of fixed-dose, ultrasound-assisted, catheter-directed thrombosis and anticoagulation to anticoagulation alone, the mean right-to-left-ventricle ratio was reduced for patients in the CDI group after 1 day. Such a change did not occur in the control group, but at 90 days, the average ratio “became comparable between the two groups … with a trend in favor of the [CDI],” according to Dr. Avgerinos and Dr. Chaer. None of this study’s participants suffered from major bleeding complications.
“There is increasing evidence that percutaneous CDIs are an essential, effective and safe alternative to systemic thrombolysis or anticoagulation in the contemporary management of massive and submassive PE,” the reviewers noted. More research is needed to confirm the differences in the outcomes between using systemic thrombolysis and catheter-based techniques for treating PEs, as no clinical trial comparing CDIs with systemic thrombolysis for PE has been done, they added.
Read the full review of research in the Journal of Vascular Surgery (doi:10.1016/j.jvs.2014.10.036).
A review of research suggests that catheter-directed interventions (CDIs) have fewer complications but are not necessarily better at preventing mortality than are standard treatments for pulmonary embolisms, according to Dr. Efthymios D. Avgerinos and Dr. Rabih A. Chaer of the University of Pittsburgh.
Of 594 patients with massive pulmonary embolisms (PEs) who received various forms of CDI, 86.5% survived (range, 40%-100%), according to a systematic review of 35 noncontrolled studies.
“In 95% of these patients, CDIs were initiated without prior intravenous thrombolysis,” while 60%-67% of the patients also received a thrombolytic agent during the procedure, they wrote. The patient survival rate was 91.2% in studies that provided at least 80% of their patients with local thrombolytic therapy during a CDI, compared with 82.8% in studies in which less than 80% of participants received thrombolytic therapy.
Not all findings, however, suggested that it was more favorable for the patients to receive the thrombolytic therapy, Overall, the pooled rates of major and minor complications were 7.9% and 2.4%, respectively. The 25 major complications reported included bleeding complications requiring transfusion, renal failure requiring hemodialysis, cardiopulmonary events, cerebrovascular events, and death.
Other research on CDIs found that right ventricle dilation was reversed in patients with submassive PEs who received fixed-dose, ultrasound-assisted, catheter-directed thrombosis combined with anticoagulation. According to the recently published randomized controlled trial, which compared the effects of fixed-dose, ultrasound-assisted, catheter-directed thrombosis and anticoagulation to anticoagulation alone, the mean right-to-left-ventricle ratio was reduced for patients in the CDI group after 1 day. Such a change did not occur in the control group, but at 90 days, the average ratio “became comparable between the two groups … with a trend in favor of the [CDI],” according to Dr. Avgerinos and Dr. Chaer. None of this study’s participants suffered from major bleeding complications.
“There is increasing evidence that percutaneous CDIs are an essential, effective and safe alternative to systemic thrombolysis or anticoagulation in the contemporary management of massive and submassive PE,” the reviewers noted. More research is needed to confirm the differences in the outcomes between using systemic thrombolysis and catheter-based techniques for treating PEs, as no clinical trial comparing CDIs with systemic thrombolysis for PE has been done, they added.
Read the full review of research in the Journal of Vascular Surgery (doi:10.1016/j.jvs.2014.10.036).
A review of research suggests that catheter-directed interventions (CDIs) have fewer complications but are not necessarily better at preventing mortality than are standard treatments for pulmonary embolisms, according to Dr. Efthymios D. Avgerinos and Dr. Rabih A. Chaer of the University of Pittsburgh.
Of 594 patients with massive pulmonary embolisms (PEs) who received various forms of CDI, 86.5% survived (range, 40%-100%), according to a systematic review of 35 noncontrolled studies.
“In 95% of these patients, CDIs were initiated without prior intravenous thrombolysis,” while 60%-67% of the patients also received a thrombolytic agent during the procedure, they wrote. The patient survival rate was 91.2% in studies that provided at least 80% of their patients with local thrombolytic therapy during a CDI, compared with 82.8% in studies in which less than 80% of participants received thrombolytic therapy.
Not all findings, however, suggested that it was more favorable for the patients to receive the thrombolytic therapy, Overall, the pooled rates of major and minor complications were 7.9% and 2.4%, respectively. The 25 major complications reported included bleeding complications requiring transfusion, renal failure requiring hemodialysis, cardiopulmonary events, cerebrovascular events, and death.
Other research on CDIs found that right ventricle dilation was reversed in patients with submassive PEs who received fixed-dose, ultrasound-assisted, catheter-directed thrombosis combined with anticoagulation. According to the recently published randomized controlled trial, which compared the effects of fixed-dose, ultrasound-assisted, catheter-directed thrombosis and anticoagulation to anticoagulation alone, the mean right-to-left-ventricle ratio was reduced for patients in the CDI group after 1 day. Such a change did not occur in the control group, but at 90 days, the average ratio “became comparable between the two groups … with a trend in favor of the [CDI],” according to Dr. Avgerinos and Dr. Chaer. None of this study’s participants suffered from major bleeding complications.
“There is increasing evidence that percutaneous CDIs are an essential, effective and safe alternative to systemic thrombolysis or anticoagulation in the contemporary management of massive and submassive PE,” the reviewers noted. More research is needed to confirm the differences in the outcomes between using systemic thrombolysis and catheter-based techniques for treating PEs, as no clinical trial comparing CDIs with systemic thrombolysis for PE has been done, they added.
Read the full review of research in the Journal of Vascular Surgery (doi:10.1016/j.jvs.2014.10.036).
Low doses of imatinib promote hematopoiesis
Image by Volker Brinkmann
Low doses of the tyrosine kinase inhibitor imatinib can promote hematopoiesis, according to research published in PLOS Pathogens.
Preclinical experiments revealed that the drug can induce differentiation in hematopoietic stem cells (HSCs) and progenitors in the bone marrow,
augment myelopoiesis, and increase the number of myeloid cells in the blood and spleen.
Researchers said these findings suggest imatinib or related drugs could be used to treat infections.
“We think that low doses of imatinib are mimicking ‘emergency hematopoiesis,’ a normal early response to infection,” said study author Daniel Kalman, PhD, of the Emory University School of Medicine in Atlanta, Georgia.
“This was surprising because there are reports that imatinib can be immunosuppressive in some patients. Our data suggest that, at subclinical doses, imatinib can stimulate bone marrow stem cells to produce several types of myeloid cells, such as neutrophils and macrophages, and trigger their exodus from the bone marrow. However, higher doses appear to inhibit this process.”
Dr Kalman and his colleagues observed a 4-fold increase of neutrophils and a 3-fold increase of monocytes in the bone marrow of imatinib-treated mice. However, these mice did not see a significant change in the number of mature B cells, T cells, dendritic cells, eosinophils, or natural killer cells.
Imatinib did not induce the accumulation of HSCs, but it did regulate the accumulation of multipotent progenitors. The drug also reduced the accumulation of HSCs upon infection, which suggests it may increase the flux of HSCs to progenitors.
Imatinib did not increase the number of transplantable HSCs, but it did induce an irreversible commitment of HSCs into progenitors that could differentiate into myeloid cells ex vivo.
Imatinib induced an irreversible differentiation of HSCs or progenitors into myeloid cells in a dose-dependent manner. The drug facilitated the exodus of myeloid cells from the bone marrow only at lower doses. It inhibited this same process at higher doses.
Despite increasing the number of neutrophils, low doses of imatinib did not activate neutrophils. However, the cells retained the capacity to activate upon infection.
In fact, an increase in the number of neutrophils was sufficient to reduce Mycobacterium marinum bacterial load. And imatinib reduced the bacterial load in mice infected with pathogenic Francisella species.
The researchers said these results suggest low doses of imatinib could potentially be used to treat a variety of infections and might prove particularly useful in immunocompromised patients.
Image by Volker Brinkmann
Low doses of the tyrosine kinase inhibitor imatinib can promote hematopoiesis, according to research published in PLOS Pathogens.
Preclinical experiments revealed that the drug can induce differentiation in hematopoietic stem cells (HSCs) and progenitors in the bone marrow,
augment myelopoiesis, and increase the number of myeloid cells in the blood and spleen.
Researchers said these findings suggest imatinib or related drugs could be used to treat infections.
“We think that low doses of imatinib are mimicking ‘emergency hematopoiesis,’ a normal early response to infection,” said study author Daniel Kalman, PhD, of the Emory University School of Medicine in Atlanta, Georgia.
“This was surprising because there are reports that imatinib can be immunosuppressive in some patients. Our data suggest that, at subclinical doses, imatinib can stimulate bone marrow stem cells to produce several types of myeloid cells, such as neutrophils and macrophages, and trigger their exodus from the bone marrow. However, higher doses appear to inhibit this process.”
Dr Kalman and his colleagues observed a 4-fold increase of neutrophils and a 3-fold increase of monocytes in the bone marrow of imatinib-treated mice. However, these mice did not see a significant change in the number of mature B cells, T cells, dendritic cells, eosinophils, or natural killer cells.
Imatinib did not induce the accumulation of HSCs, but it did regulate the accumulation of multipotent progenitors. The drug also reduced the accumulation of HSCs upon infection, which suggests it may increase the flux of HSCs to progenitors.
Imatinib did not increase the number of transplantable HSCs, but it did induce an irreversible commitment of HSCs into progenitors that could differentiate into myeloid cells ex vivo.
Imatinib induced an irreversible differentiation of HSCs or progenitors into myeloid cells in a dose-dependent manner. The drug facilitated the exodus of myeloid cells from the bone marrow only at lower doses. It inhibited this same process at higher doses.
Despite increasing the number of neutrophils, low doses of imatinib did not activate neutrophils. However, the cells retained the capacity to activate upon infection.
In fact, an increase in the number of neutrophils was sufficient to reduce Mycobacterium marinum bacterial load. And imatinib reduced the bacterial load in mice infected with pathogenic Francisella species.
The researchers said these results suggest low doses of imatinib could potentially be used to treat a variety of infections and might prove particularly useful in immunocompromised patients.
Image by Volker Brinkmann
Low doses of the tyrosine kinase inhibitor imatinib can promote hematopoiesis, according to research published in PLOS Pathogens.
Preclinical experiments revealed that the drug can induce differentiation in hematopoietic stem cells (HSCs) and progenitors in the bone marrow,
augment myelopoiesis, and increase the number of myeloid cells in the blood and spleen.
Researchers said these findings suggest imatinib or related drugs could be used to treat infections.
“We think that low doses of imatinib are mimicking ‘emergency hematopoiesis,’ a normal early response to infection,” said study author Daniel Kalman, PhD, of the Emory University School of Medicine in Atlanta, Georgia.
“This was surprising because there are reports that imatinib can be immunosuppressive in some patients. Our data suggest that, at subclinical doses, imatinib can stimulate bone marrow stem cells to produce several types of myeloid cells, such as neutrophils and macrophages, and trigger their exodus from the bone marrow. However, higher doses appear to inhibit this process.”
Dr Kalman and his colleagues observed a 4-fold increase of neutrophils and a 3-fold increase of monocytes in the bone marrow of imatinib-treated mice. However, these mice did not see a significant change in the number of mature B cells, T cells, dendritic cells, eosinophils, or natural killer cells.
Imatinib did not induce the accumulation of HSCs, but it did regulate the accumulation of multipotent progenitors. The drug also reduced the accumulation of HSCs upon infection, which suggests it may increase the flux of HSCs to progenitors.
Imatinib did not increase the number of transplantable HSCs, but it did induce an irreversible commitment of HSCs into progenitors that could differentiate into myeloid cells ex vivo.
Imatinib induced an irreversible differentiation of HSCs or progenitors into myeloid cells in a dose-dependent manner. The drug facilitated the exodus of myeloid cells from the bone marrow only at lower doses. It inhibited this same process at higher doses.
Despite increasing the number of neutrophils, low doses of imatinib did not activate neutrophils. However, the cells retained the capacity to activate upon infection.
In fact, an increase in the number of neutrophils was sufficient to reduce Mycobacterium marinum bacterial load. And imatinib reduced the bacterial load in mice infected with pathogenic Francisella species.
The researchers said these results suggest low doses of imatinib could potentially be used to treat a variety of infections and might prove particularly useful in immunocompromised patients.
Collaboration may help prevent CLABSIs
Collaborative relationships between nurses and physicians may help reduce the rates of healthcare-associated infections in critical care, according to research published in Critical Care Nurse.
Study investigators found lower rates of central line-associated bloodstream infections (CLABSIs) and ventilator-associated pneumonia (VAP) in critical care units in which nurses reported a more favorable perception of nurse-physician collaboration.
“Our findings suggest that raising the quality of collaboration and communication among nurses and physicians has the potential to improve patient safety,” said study author Christine Boev, RN, PhD, CCRN, of Wegmans School of Nursing at St John Fisher College in Rochester, New York.
Dr Boev and her colleagues analyzed 5 years of data from 671 surveys of nurses in 4 specialized intensive care units (ICUs) at a 750-bed New York hospital.
The investigators also collected patient outcome data from those units for the same period, focusing on patients with CLABSIs or VAP. And the team analyzed unit-level variables such as nurses’ skill mix, nursing hours per patient day, and voluntary turnover.
Results revealed a significant association between nurse-physician collaboration and both CLABSIs and VAP. For every 0.5 unit increase in collaboration, the rate of CLABSIs decreased by 2.98 (P=0.005), and the rate of VAP decreased by 1.13 (P=0.005).
In addition, ICUs with a higher proportion of certified nurses had significantly lower incidences of both CLABSIs and VAP—0.43 (P=0.02) and 0.17 (P=0.01), respectively. And ICUs with higher numbers of nursing hours per patient day had significantly lower rates of CLABSIs—0.42 (P=0.05).
However, there was no significant difference in VAP rates according to nursing hours. And there was no significant difference in the rate of either type of infection according to nurses’ skill mix or voluntary turnover.
Dr Boev said these results suggest that efforts to prevent healthcare-associated infections should include interventions to improve nurse-physician collaboration. Such interventions might include multidisciplinary daily patient rounds and interprofessional educational programs, such as shared simulation training.
Collaborative relationships between nurses and physicians may help reduce the rates of healthcare-associated infections in critical care, according to research published in Critical Care Nurse.
Study investigators found lower rates of central line-associated bloodstream infections (CLABSIs) and ventilator-associated pneumonia (VAP) in critical care units in which nurses reported a more favorable perception of nurse-physician collaboration.
“Our findings suggest that raising the quality of collaboration and communication among nurses and physicians has the potential to improve patient safety,” said study author Christine Boev, RN, PhD, CCRN, of Wegmans School of Nursing at St John Fisher College in Rochester, New York.
Dr Boev and her colleagues analyzed 5 years of data from 671 surveys of nurses in 4 specialized intensive care units (ICUs) at a 750-bed New York hospital.
The investigators also collected patient outcome data from those units for the same period, focusing on patients with CLABSIs or VAP. And the team analyzed unit-level variables such as nurses’ skill mix, nursing hours per patient day, and voluntary turnover.
Results revealed a significant association between nurse-physician collaboration and both CLABSIs and VAP. For every 0.5 unit increase in collaboration, the rate of CLABSIs decreased by 2.98 (P=0.005), and the rate of VAP decreased by 1.13 (P=0.005).
In addition, ICUs with a higher proportion of certified nurses had significantly lower incidences of both CLABSIs and VAP—0.43 (P=0.02) and 0.17 (P=0.01), respectively. And ICUs with higher numbers of nursing hours per patient day had significantly lower rates of CLABSIs—0.42 (P=0.05).
However, there was no significant difference in VAP rates according to nursing hours. And there was no significant difference in the rate of either type of infection according to nurses’ skill mix or voluntary turnover.
Dr Boev said these results suggest that efforts to prevent healthcare-associated infections should include interventions to improve nurse-physician collaboration. Such interventions might include multidisciplinary daily patient rounds and interprofessional educational programs, such as shared simulation training.
Collaborative relationships between nurses and physicians may help reduce the rates of healthcare-associated infections in critical care, according to research published in Critical Care Nurse.
Study investigators found lower rates of central line-associated bloodstream infections (CLABSIs) and ventilator-associated pneumonia (VAP) in critical care units in which nurses reported a more favorable perception of nurse-physician collaboration.
“Our findings suggest that raising the quality of collaboration and communication among nurses and physicians has the potential to improve patient safety,” said study author Christine Boev, RN, PhD, CCRN, of Wegmans School of Nursing at St John Fisher College in Rochester, New York.
Dr Boev and her colleagues analyzed 5 years of data from 671 surveys of nurses in 4 specialized intensive care units (ICUs) at a 750-bed New York hospital.
The investigators also collected patient outcome data from those units for the same period, focusing on patients with CLABSIs or VAP. And the team analyzed unit-level variables such as nurses’ skill mix, nursing hours per patient day, and voluntary turnover.
Results revealed a significant association between nurse-physician collaboration and both CLABSIs and VAP. For every 0.5 unit increase in collaboration, the rate of CLABSIs decreased by 2.98 (P=0.005), and the rate of VAP decreased by 1.13 (P=0.005).
In addition, ICUs with a higher proportion of certified nurses had significantly lower incidences of both CLABSIs and VAP—0.43 (P=0.02) and 0.17 (P=0.01), respectively. And ICUs with higher numbers of nursing hours per patient day had significantly lower rates of CLABSIs—0.42 (P=0.05).
However, there was no significant difference in VAP rates according to nursing hours. And there was no significant difference in the rate of either type of infection according to nurses’ skill mix or voluntary turnover.
Dr Boev said these results suggest that efforts to prevent healthcare-associated infections should include interventions to improve nurse-physician collaboration. Such interventions might include multidisciplinary daily patient rounds and interprofessional educational programs, such as shared simulation training.
Mindfulness Meditation for Sleep Problems
Study Overview
Objective. To test the treatment effect of a structured mindfulness meditation program versus sleep hygiene education for improving sleep quality.
Study design. Single-site, parallel-group randomized clinical trial.
Setting and participants. Adults aged 55 years and older were recruited from the urban Los Angeles community through a newspaper advertisement and flyers posted in community centers. Participants had to agree to be randomized and have a Pittsburgh Sleep Quality Index (PSQI) score [1] exceeding 5 at screening. Exclusion criteria were current smoking, substance dependence, inability to speak English, depression, cognitive impairment, current daily meditation, and obesity. Also excluded were those who reported a current inflammatory disorder, sleep apnea, restless legs syndrome, illness, or infection.
Intervention. Participants were randomized into 2 standardized treatment conditions: the Mindful Awareness Practices program (MAPs) and sleep hygiene education (SHE). Each treatment consisted of weekly 2-hour group-based classes over the course of the 6-week intervention. The comparison sleep hygiene program matched the MAPs condition for time, attention, group interaction, and expectancy of benefit effects. Eight visits to the study site were requested, including 1 pretreatment assessment visit, 6 intervention sessions, and 1 posttreatment assessment visit. Participants were compensated up to $50 in gift cards and received parking vouchers for visits.
Main outcome measure. The primary outcome measure was the PSQI, a commonly used and validated 19-item self-rated questionnaire that assesses sleep quality and disturbances over a 1-month time interval. A global score greater than 5 yields a diagnostic sensitivity of 89.6% and specificity of 86.5% in distinguishing good and poor sleepers [1]. Secondary outcomes included scores on instruments that measured depression, anxiety, stress, and fatigue.
Results. After screening for eligibility, 49 adults were randomized, 24 to MAPS and 25 to SHE. Session attendance was similar across the groups. Mean (± SD) age of participants was 66.3 (7.4) years and 67% were female. Mean PSQI was 10.2 at baseline and 7.4 postintervention for MAPs, and 10.2 at baseline and 9.1 postintervention for SHE. In the intention-to-treat analyses, PSQI improved by 2.8 in MAPS vs. 1.1 in SHE (between-group mean difference, 1.8; 95% confidence interval, 0.6–2.9) with an effect size of 0.89. Relative improvements in depression scores and daytime fatigue were also noted.
Conclusion. The program improved sleep quality relative to SHE. Mindfulness meditation appears to have a role in addressing the burden of sleep problems in older adults.
Commentary
Older adults commonly report disturbed sleep, and an expanding literature suggests that poor sleep increases the risk of adverse health outcomes, including frailty and lower cognitive function. Current nonpharmacologic treatments for disturbed sleep include sleep hygiene education and cognitive behavioral therapy (CBT), which have been shown to be effective. However, as the current study’s authors point out, clinical interventions like CBT are intensive, require administration by highly trained therapists, and are intended for patients with insomnia [2].
These researchers investigated an alternative intervention consisting of mindfulness meditation. Mindfulness has been defined as being intentionally aware of internal and external experiences that occur at the present moment, without judgment. Mindfulness-based interventions are increasingly being studied for a wide array of health conditions, and courses in the community and online are frequently available.
The results of the current study, which applied mindfulness meditation to the problem of sleep disturbance in older adults, are compelling. The effect size of 0.89 was large and of clinical relevance: as the authors point out, in a meta-analysis of behavioral interventions for insomnia, the average effect size for improvement in subjective sleep outcomes among older adults was 0.76 [3]. It is noteworthy that the authors of the current study recruited patients on the basis of PSQI score and did not require a diagnosis of insomnia. The use of the PSQI means that the sample consisted of patients with self-rated poor sleep quality, and epidemiologic evidence suggests that a PSQI score greater than 5 identifies older persons at risk for adverse health outcomes [4]. Thus, this is a logical group to target. In addition, the sample may have included those with undiagnosed insomnia and other sleep disturbances; this fact makes the findings even more impressive [4].
The use of validated measures are a strength of the study. Limitations include lack of postintervention assessment data for 12% of participants and a preponderance of female and highly educated participants.
Applications for Clinical Practice
Standardized mindfulness programs are becoming more widely available, both online and in the community, and can be be introduced to older adults to help them with moderate sleep disturbances.
1. Buysse DJ, Reynolds CF 3rd, Monk TH, et al. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 1989;28:193–213.
2. Morin CM, Bootzin RR, Buysse DJ, Edinger JD, Espie CA, Lichstein KL. Psychological and behavioral treatment of insomnia: update of the recent evidence (1998-2004). Sleep 2006;29:1398–414.
3. Irwin MR, Cole JC, Nicassio PM. Comparative meta-analysis of behavioral interventions for insomnia and their efficacy in middle-aged adults and in older adults 55+ years of age. Health Psychol 2006;25:3–14.
4. Spira AP. Being mindful of later-life sleep quality and its potential role in prevention. JAMA Intern Med. Published online 16 Feb 2015.
Study Overview
Objective. To test the treatment effect of a structured mindfulness meditation program versus sleep hygiene education for improving sleep quality.
Study design. Single-site, parallel-group randomized clinical trial.
Setting and participants. Adults aged 55 years and older were recruited from the urban Los Angeles community through a newspaper advertisement and flyers posted in community centers. Participants had to agree to be randomized and have a Pittsburgh Sleep Quality Index (PSQI) score [1] exceeding 5 at screening. Exclusion criteria were current smoking, substance dependence, inability to speak English, depression, cognitive impairment, current daily meditation, and obesity. Also excluded were those who reported a current inflammatory disorder, sleep apnea, restless legs syndrome, illness, or infection.
Intervention. Participants were randomized into 2 standardized treatment conditions: the Mindful Awareness Practices program (MAPs) and sleep hygiene education (SHE). Each treatment consisted of weekly 2-hour group-based classes over the course of the 6-week intervention. The comparison sleep hygiene program matched the MAPs condition for time, attention, group interaction, and expectancy of benefit effects. Eight visits to the study site were requested, including 1 pretreatment assessment visit, 6 intervention sessions, and 1 posttreatment assessment visit. Participants were compensated up to $50 in gift cards and received parking vouchers for visits.
Main outcome measure. The primary outcome measure was the PSQI, a commonly used and validated 19-item self-rated questionnaire that assesses sleep quality and disturbances over a 1-month time interval. A global score greater than 5 yields a diagnostic sensitivity of 89.6% and specificity of 86.5% in distinguishing good and poor sleepers [1]. Secondary outcomes included scores on instruments that measured depression, anxiety, stress, and fatigue.
Results. After screening for eligibility, 49 adults were randomized, 24 to MAPS and 25 to SHE. Session attendance was similar across the groups. Mean (± SD) age of participants was 66.3 (7.4) years and 67% were female. Mean PSQI was 10.2 at baseline and 7.4 postintervention for MAPs, and 10.2 at baseline and 9.1 postintervention for SHE. In the intention-to-treat analyses, PSQI improved by 2.8 in MAPS vs. 1.1 in SHE (between-group mean difference, 1.8; 95% confidence interval, 0.6–2.9) with an effect size of 0.89. Relative improvements in depression scores and daytime fatigue were also noted.
Conclusion. The program improved sleep quality relative to SHE. Mindfulness meditation appears to have a role in addressing the burden of sleep problems in older adults.
Commentary
Older adults commonly report disturbed sleep, and an expanding literature suggests that poor sleep increases the risk of adverse health outcomes, including frailty and lower cognitive function. Current nonpharmacologic treatments for disturbed sleep include sleep hygiene education and cognitive behavioral therapy (CBT), which have been shown to be effective. However, as the current study’s authors point out, clinical interventions like CBT are intensive, require administration by highly trained therapists, and are intended for patients with insomnia [2].
These researchers investigated an alternative intervention consisting of mindfulness meditation. Mindfulness has been defined as being intentionally aware of internal and external experiences that occur at the present moment, without judgment. Mindfulness-based interventions are increasingly being studied for a wide array of health conditions, and courses in the community and online are frequently available.
The results of the current study, which applied mindfulness meditation to the problem of sleep disturbance in older adults, are compelling. The effect size of 0.89 was large and of clinical relevance: as the authors point out, in a meta-analysis of behavioral interventions for insomnia, the average effect size for improvement in subjective sleep outcomes among older adults was 0.76 [3]. It is noteworthy that the authors of the current study recruited patients on the basis of PSQI score and did not require a diagnosis of insomnia. The use of the PSQI means that the sample consisted of patients with self-rated poor sleep quality, and epidemiologic evidence suggests that a PSQI score greater than 5 identifies older persons at risk for adverse health outcomes [4]. Thus, this is a logical group to target. In addition, the sample may have included those with undiagnosed insomnia and other sleep disturbances; this fact makes the findings even more impressive [4].
The use of validated measures are a strength of the study. Limitations include lack of postintervention assessment data for 12% of participants and a preponderance of female and highly educated participants.
Applications for Clinical Practice
Standardized mindfulness programs are becoming more widely available, both online and in the community, and can be be introduced to older adults to help them with moderate sleep disturbances.
Study Overview
Objective. To test the treatment effect of a structured mindfulness meditation program versus sleep hygiene education for improving sleep quality.
Study design. Single-site, parallel-group randomized clinical trial.
Setting and participants. Adults aged 55 years and older were recruited from the urban Los Angeles community through a newspaper advertisement and flyers posted in community centers. Participants had to agree to be randomized and have a Pittsburgh Sleep Quality Index (PSQI) score [1] exceeding 5 at screening. Exclusion criteria were current smoking, substance dependence, inability to speak English, depression, cognitive impairment, current daily meditation, and obesity. Also excluded were those who reported a current inflammatory disorder, sleep apnea, restless legs syndrome, illness, or infection.
Intervention. Participants were randomized into 2 standardized treatment conditions: the Mindful Awareness Practices program (MAPs) and sleep hygiene education (SHE). Each treatment consisted of weekly 2-hour group-based classes over the course of the 6-week intervention. The comparison sleep hygiene program matched the MAPs condition for time, attention, group interaction, and expectancy of benefit effects. Eight visits to the study site were requested, including 1 pretreatment assessment visit, 6 intervention sessions, and 1 posttreatment assessment visit. Participants were compensated up to $50 in gift cards and received parking vouchers for visits.
Main outcome measure. The primary outcome measure was the PSQI, a commonly used and validated 19-item self-rated questionnaire that assesses sleep quality and disturbances over a 1-month time interval. A global score greater than 5 yields a diagnostic sensitivity of 89.6% and specificity of 86.5% in distinguishing good and poor sleepers [1]. Secondary outcomes included scores on instruments that measured depression, anxiety, stress, and fatigue.
Results. After screening for eligibility, 49 adults were randomized, 24 to MAPS and 25 to SHE. Session attendance was similar across the groups. Mean (± SD) age of participants was 66.3 (7.4) years and 67% were female. Mean PSQI was 10.2 at baseline and 7.4 postintervention for MAPs, and 10.2 at baseline and 9.1 postintervention for SHE. In the intention-to-treat analyses, PSQI improved by 2.8 in MAPS vs. 1.1 in SHE (between-group mean difference, 1.8; 95% confidence interval, 0.6–2.9) with an effect size of 0.89. Relative improvements in depression scores and daytime fatigue were also noted.
Conclusion. The program improved sleep quality relative to SHE. Mindfulness meditation appears to have a role in addressing the burden of sleep problems in older adults.
Commentary
Older adults commonly report disturbed sleep, and an expanding literature suggests that poor sleep increases the risk of adverse health outcomes, including frailty and lower cognitive function. Current nonpharmacologic treatments for disturbed sleep include sleep hygiene education and cognitive behavioral therapy (CBT), which have been shown to be effective. However, as the current study’s authors point out, clinical interventions like CBT are intensive, require administration by highly trained therapists, and are intended for patients with insomnia [2].
These researchers investigated an alternative intervention consisting of mindfulness meditation. Mindfulness has been defined as being intentionally aware of internal and external experiences that occur at the present moment, without judgment. Mindfulness-based interventions are increasingly being studied for a wide array of health conditions, and courses in the community and online are frequently available.
The results of the current study, which applied mindfulness meditation to the problem of sleep disturbance in older adults, are compelling. The effect size of 0.89 was large and of clinical relevance: as the authors point out, in a meta-analysis of behavioral interventions for insomnia, the average effect size for improvement in subjective sleep outcomes among older adults was 0.76 [3]. It is noteworthy that the authors of the current study recruited patients on the basis of PSQI score and did not require a diagnosis of insomnia. The use of the PSQI means that the sample consisted of patients with self-rated poor sleep quality, and epidemiologic evidence suggests that a PSQI score greater than 5 identifies older persons at risk for adverse health outcomes [4]. Thus, this is a logical group to target. In addition, the sample may have included those with undiagnosed insomnia and other sleep disturbances; this fact makes the findings even more impressive [4].
The use of validated measures are a strength of the study. Limitations include lack of postintervention assessment data for 12% of participants and a preponderance of female and highly educated participants.
Applications for Clinical Practice
Standardized mindfulness programs are becoming more widely available, both online and in the community, and can be be introduced to older adults to help them with moderate sleep disturbances.
1. Buysse DJ, Reynolds CF 3rd, Monk TH, et al. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 1989;28:193–213.
2. Morin CM, Bootzin RR, Buysse DJ, Edinger JD, Espie CA, Lichstein KL. Psychological and behavioral treatment of insomnia: update of the recent evidence (1998-2004). Sleep 2006;29:1398–414.
3. Irwin MR, Cole JC, Nicassio PM. Comparative meta-analysis of behavioral interventions for insomnia and their efficacy in middle-aged adults and in older adults 55+ years of age. Health Psychol 2006;25:3–14.
4. Spira AP. Being mindful of later-life sleep quality and its potential role in prevention. JAMA Intern Med. Published online 16 Feb 2015.
1. Buysse DJ, Reynolds CF 3rd, Monk TH, et al. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 1989;28:193–213.
2. Morin CM, Bootzin RR, Buysse DJ, Edinger JD, Espie CA, Lichstein KL. Psychological and behavioral treatment of insomnia: update of the recent evidence (1998-2004). Sleep 2006;29:1398–414.
3. Irwin MR, Cole JC, Nicassio PM. Comparative meta-analysis of behavioral interventions for insomnia and their efficacy in middle-aged adults and in older adults 55+ years of age. Health Psychol 2006;25:3–14.
4. Spira AP. Being mindful of later-life sleep quality and its potential role in prevention. JAMA Intern Med. Published online 16 Feb 2015.