Faculty Bibliography

Context:Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine, usually benign, tumors. Currently, the only reliable criterion of malignancy is the presence of metastases. Objective:The aim of this study was to identify genes associated with malignancy in PPGLs. Design:Transcriptomic profiling was performed on 40 benign and 11 malignant PPGLs. Genes showing a significantly different expression between benign and malignant PPGLs with a ratio ≥4 were confirmed and tested in an independent series by quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemistry was performed for the validated genes on 109 benign and 32 malignant PPGLs. Functional assays were performed with hPheo1 cells. Setting:This study was conducted at the Department of Pathology of the Erasmus MC University Medical Center Rotterdam Human Molecular Genetics laboratory of the de Duve Institute, University of Louvain. Patients:PPGL samples from 179 patients, diagnosed between 1972 and 2015, were included. Main outcome measures:Associations between gene expression and malignancy were tested using supervised clustering approaches. Results:Ten differentially expressed genes were selected based on messenger RNA (mRNA) expression array data. Contactin 4 (CNTN4) was overexpressed in malignant vs benign tumors [4.62-fold; false discovery rate (FDR), 0.001]. Overexpression at the mRNA level was confirmed using qRT-PCR (2.90-fold, P = 0.02; validation set: 4.26-fold, P = 0.005). Consistent findings were obtained in The Cancer Genome Atlas cohort (2.7-fold; FDR, 0.02). CNTN4 protein was more frequently expressed in malignant than in benign PPGLs by immunohistochemistry (58% vs 17%; P = 0.002). Survival after 7 days of culture under starvation conditions was significantly enhanced in hPheo1 cells transfected with CNTN4 complementary DNA. Conclusion:CNTN4 expression is consistently associated with malignant behavior in PPGLs.

Although blood transfusion is a lifesaving therapy for some patients, transfusion has been named 1 of the top 5 overused procedures in US hospitals. As unnecessary transfusions only increase risk and cost without providing benefit, improving transfusion practice is an effective way of promoting high-value care. Most high-quality clinical trials supporting a restrictive transfusion strategy have been published in the past 5 to 10 years, so the value of a successful patient blood management program has only recently been recognized. We review the most recent transfusion practice guidelines and the evidence supporting these guidelines. We also discuss several medical societies' Choosing Wisely campaigns to reduce or eliminate overuse of transfusions. A blueprint is presented for developing a patient blood management program, which includes discussion of specific methods for optimizing transfusion practice.

Colchicine is an ancient medication that is currently approved for the treatment of gout and FMF. However, colchicine has a wide range of anti-inflammatory activities, and studies indicate that it may be beneficial in a variety of other conditions. This paper reviews the evidence for the well-established use of colchicine in gout, as well as several other rheumatic diseases. In addition, we highlight the potential benefit of colchicine in cardiac disease, including coronary artery disease in patients both with and without gout.

As part of the Choosing Wisely® campaign, the Society of Hospital Medicine recommends against performing "repetitive complete blood count chemistry testing in the face of clinical and lab stability." With this recommendation as a framework, we targeted 2 hospitalist-run inpatient medicine units that employed bedside, scripted, interdisciplinary rounds. Our multifaceted intervention included prompting the hospitalist to identify clinically stable patients for next-day discharge and to discontinue labs when appropriate. It was coupled with the education of the clinicians and a regular data review for the hospitalists and unit staff. Among 2877 discharges included in a 1-year period, there was a significantly decreasing trend after the intervention in the percentage of patients getting labs in the 24, 48, and 72 hours before discharge (-1.87%, -1.47%, and -0.74% decrease per month, respectively; P < 0.05). Our structured, multifaceted approach effectively reduced daily lab testing in the 24 to 48 hours prior to discharge.

BACKGROUND: Migraine is one of the top 10 most disabling conditions among adults worldwide. Most migraine research is quantitative and indicates concerns about medication adherence, stigma, and more. Qualitative studies might reveal an improved understanding of migraine patients' perspectives regarding migraine treatment. OBJECTIVE: The aim of this study was to synthesize the qualitative research on migraine patients' perspectives regarding migraine treatment to (a) identify common patterns across various types of migraine treatment studies and (b) inform future research. METHODS: A systematic search for qualitative studies in the HA (HA) literature was conducted in Medline (PubMed), PsycINFO, EMBASE, CINAHL, Web of Science, Joanna Briggs Institute EBP Database, and The Cochrane Library. Search terms (subject headings and keywords) were HA, HA disorders, migraine, qualitative studies, and qualitative research. Qualitative studies were systematically identified by using published qualitative search filters recommended by The InterTASC Information Specialists' Sub-Group (ISSG). The search was limited to English only, peer reviewed publications, and studies published between 1996 and 2016. For screening, additional inclusion criteria were (1) adult migraine patients; (2) must mention treatment in the title or study design of the abstract. Ten studies met the inclusion criteria. The Critical Appraisal Skills Program tool was applied to appraise study quality. Thematic analysis produced the codes and themes. Two authors read articles separately and individually created codes. Code lists were synthesized and themes emerged iteratively from the process. RESULTS: Study sample sizes ranged from 10 to 33 participants, with our findings representing 161 participants. Data were collected either using interviews or focus groups. The more common methodologies were grounded theory and phenomenology. Few (3) studies described the number of headache (HA) days for inclusion in the study. Eight out of 10 used International Classification of Headache Disorders (ICHD) criteria. Our synthesis produced five major themes. The first theme was "Migraine patients' difficulties with health care utilization," and it included issues surrounding the cost of migraine treatment (seeing providers and prescription medications). The second theme was "Migraine patients' perceived relationships with their providers," which included the role and relationship with the provider, as well as trust in the provider and the providers' knowledge in managing HAs. The third theme was "Thoughts about the various migraine treatments." It was based on patients' comments indicating an aversion to prescription medications, the use of non-pharmacological interventions for treatment, behavioral modification as a form of treatment, and the need for additional treatment options. The fourth and fifth themes were "Understanding diagnosis/triggers" and "Societal implications," respectively. The latter theme included feelings of not being taken seriously and issues surrounding quality of life. DISCUSSION: The metasynthesis revealed several key commonalities regarding patients' perspectives on migraine treatment and identified new areas for research using a qualitative approach. Researchers conducting qualitative research with patients experiencing migraines might consider using and reporting more of the inclusion and exclusion criteria commonly used in migraine research, for example, reporting whether the ICHD criteria were used and the number of HA days for patients to be in a study. Future studies might be done to determine how the role of allied health care providers, for example, pharmacists, physical therapists, and psychologists, might be expanded to help with migraine treatment and ultimately to improve patient outcomes.