Mitchell R. Lunn

Randomized clinical trial to evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome

There is no known treatment for chronic fatigue syndrome (CFS). Little is known about its pathogenesis. Human herpesvirus 6 (HHV‐6) and Epstein–Barr virus (EBV) have been proposed as infectious triggers. Thirty CFS patients with elevated IgG antibody titers against HHV‐6 and EBV were randomized 2:1 to receive valganciclovir (VGCV) or placebo for 6 months in a double‐blind, placebo‐controlled trial. Clinical endpoints aimed at measuring physical and mental fatigue included the Multidimensional Fatigue Inventory (MFI‐20) and Fatigue Severity Scale (FSS) scores, self‐reported cognitive function, and physician‐determined responder status. Biological endpoints included monocyte and neutrophil counts and cytokine levels. VGCV patients experienced a greater improvement by MFI‐20 at 9 months from baseline compared to placebo patients but this difference was not statistically significant. However, statistically significant differences in trajectories between groups were observed in MFI‐20 mental fatigue subscore (P = 0.039), FSS score (P = 0.006), and cognitive function (P = 0.025). VGCV patients experienced these improvements within the first 3 months and maintained that benefit over the remaining 9 months. Patients in the VGCV arm were 7.4 times more likely to be classified as responders (P = 0.029). In the VGCV arm, monocyte counts decreased (P < 0.001), neutrophil counts increased (P = 0.037) and cytokines were more likely to evolve towards a Th1‐profile (P < 0.001). Viral IgG antibody titers did not differ between arms. VGCV may have clinical benefit in a subset of CFS patients independent of placebo effect, possibly mediated by immunomodulation and/or antiviral effect. Further investigation with longer treatment duration and a larger sample size is warranted. J. Med. Virol. 85:2101–2109, 2013.

Prioritizing health disparities in medical education to improve care

Despite yearly advances in life‐saving and preventive medicine, as well as strategic approaches by governmental and social agencies and groups, significant disparities remain in health, health quality, and access to health care within the United States. The determinants of these disparities include baseline health status, race and ethnicity, culture, gender identity and expression, socioeconomic status, region or geography, sexual orientation, and age. In order to renew the commitment of the medical community to address health disparities, particularly at the medical school level, we must remind ourselves of the roles of doctors and medical schools as the gatekeepers and the value setters for medicine. Within those roles are responsibilities toward the social mission of working to eliminate health disparities. This effort will require partnerships with communities as well as with academic centers to actively develop and to implement diversity and inclusion strategies. Besides improving the diversity of trainees in the pipeline, access to health care can be improved, and awareness can be raised regarding population‐based health inequalities.

Response to valganciclovir in chronic fatigue syndrome patients with human herpesvirus 6 and Epstein–Barr virus IgG antibody titers

Valganciclovir has been reported to improve physical and cognitive symptoms in patients with chronic fatigue syndrome (CFS) with elevated human herpesvirus 6 (HHV‐6) and Epstein–Barr virus (EBV) IgG antibody titers. This study investigated whether antibody titers against HHV‐6 and EBV were associated with clinical response to valganciclovir in a subset of CFS patients. An uncontrolled, unblinded retrospective chart review was performed on 61 CFS patients treated with 900 mg valganciclovir daily (55 of whom took an induction dose of 1,800 mg daily for the first 3 weeks). Antibody titers were considered high if HHV‐6 IgG ≥1:320, EBV viral capsid antigen (VCA) IgG ≥1:640, and EBV early antigen (EA) IgG ≥1:160. Patients self‐rated physical and cognitive functioning as a percentage of their functioning prior to illness. Patients were categorized as responders if they experienced at least 30% improvement in physical and/or cognitive functioning. Thirty‐two patients (52%) were categorized as responders. Among these, 19 patients (59%) responded physically and 26 patients (81%) responded cognitively. Baseline antibody titers showed no significant association with response. After treatment, the average change in physical and cognitive functioning levels for all patients was +19% and +23%, respectively (P < 0.0001). Longer treatment was associated with improved response (P = 0.0002). No significant difference was found between responders and non‐responders among other variables analyzed. Valganciclovir treatment, independent of the baseline antibody titers, was associated with self‐rated improvement in physical and cognitive functioning for CFS patients who had positive HHV‐6 and/or EBV serologies. Longer valganciclovir treatment correlated with an improved response. J. Med. Virol. 84:1967–1974, 2012.

Sexual and gender minority identity disclosure during undergraduate medical education: "in the closet" in medical school.

Purpose To assess identity disclosure among sexual and gender minority (SGM) students pursuing undergraduate medical training in the United States and Canada. Method From 2009 to 2010, a survey was made available to all medical students enrolled in the 176 MD- and DO-granting medical schools in the United States and Canada. Respondents were asked about their sexual and gender identity, whether they were “out” (i.e., had publicly disclosed their identity), and, if they were not, their reasons for concealing their identity. The authors used a mixed-methods approach and analyzed quantitative and qualitative survey data. Results Of 5,812 completed responses (of 101,473 eligible respondents; response rate 5.7%), 920 (15.8%) students from 152 (of 176; 86.4%) institutions identified as SGMs. Of the 912 sexual minorities, 269 (29.5%) concealed their sexual identity in medical school. Factors associated with sexual identity concealment included sexual minority identity other than lesbian or gay, male gender, East Asian race, and medical school enrollment in the South or Central regions of North America. The most common reasons for concealing one’s sexual identity were “nobody’s business“ (165/269; 61.3%), fear of discrimination in medical school (117/269; 43.5%), and social or cultural norms (110/269; 40.9%). Of the 35 gender minorities, 21 (60.0%) concealed their gender identity, citing fear of discrimination in medical school (9/21; 42.9%) and lack of support (9/21; 42.9%). Conclusions SGM students continue to conceal their identity during undergraduate medical training. Medical institutions should adopt targeted policies and programs to better support these individuals.

From patients to providers: changing the culture in medicine toward sexual and gender minorities

Equality for sexual and gender minorities (SGMs)-including members of the lesbian, gay, bisexual, and transgender communities-has become an integral part of the national conversation in the United States. Although SGM civil rights have expanded in recent years, these populations continue to experience unique health and health care disparities, including poor access to health care, stigmatization, and discrimination. SGM trainees and physicians also face challenges, including derogatory comments, humiliation, harassment, fear of being ostracized, and residency/job placement discrimination. These inequities are not mutually exclusive to either patients or providers; instead, they are intertwined parts of a persistent, negative culture in medicine toward SGM individuals.In this Perspective, the authors argue that SGM physicians must lead this charge for equality by fostering diversity and inclusion in medicine. They posit that academic medicine can accomplish this goal by (1) modernizing research on the physician workforce, (2) implementing new policies and programs to promote safe and supportive training and practice environments, and (3) developing recruitment practices to ensure a diverse, competent physician workforce that includes SGM individuals.These efforts will have an immediate impact by identifying and empowering new leaders to address SGM health care reform, creating diverse training environments that promote cultural competency, and aligning medicine with other professional fields (e.g., business, law) that already are working toward these goals. By tackling the inequities that SGM providers face, academic medicine can normalize sexual and gender identity disclosure and promote a welcoming, supportive environment for everyone in medicine, including patients.

What makes a top research medical school? A call for a new model to evaluate academic physicians and medical school performance.

Since the publication of the Flexner Report in 1910, the medical education enterprise has undergone many changes to ensure that medical schools meet a minimum standard for the curricula and clinical training they offer students. Although the efforts of the licensing and accrediting bodies have raised the quality of medical education, the educational processes that produce the physicians who provide the best patient care and conduct the best biomedical research have not been identified. Comparative analyses are powerful tools to understand the differences between institutions, but they are challenging to carry out. As a result, the analysis performed by U.S. News & World Report (USN&WR) has become the default tool to compare U.S. medical schools. Medical educators must explore more rigorous and equitable approaches to analyze and understand the performance of medical schools. In particular, a better understanding and more thorough evaluation of the most successful institutions in producing academic physicians with biomedical research careers are needed. In this Perspective, the authors present a new model to evaluate medical schools’ production of academic physicians who advance medicine through basic, clinical, translational, and implementation science research. This model is based on relevant and accessible objective criteria that should replace the subjective criteria used in the current USN&WR rankings system. By fostering a national discussion about the most meaningful criteria that should be measured and reported, the authors hope to increase transparency of assessment standards and ultimately improve educational quality.

Prioritizing health disparities in medical education to improve care.

Health and health care disparities exist for specific populations worldwide. These populations—defined by race/ethnicity, socioeconomic status, gender identity, and sexual orientation, among other attributes—are the human capital with whom institutions must partner to achieve educational, clinical, and research excellence in health disparities. Partnerships that foster shared leadership will enable academic health centers (AHCs) to be at the vanguard of providing quality, population-based health care and in addressing disparities. We propose the development of heightened partnerships between underserved communities, institutions of higher learning, AHCs, and federal agencies to tackle health disparities through institutional and community commitment and accountability, new governmental incentives and regulation, and an enhanced physician workforce.

Small Molecule Screen Reveals Regulation of Survival Motor Neuron Protein Abundance by Ras Proteins

Small molecule modulators of protein activity have proven invaluable in the study of protein function and regulation. While inhibitors of protein activity are relatively common, small molecules that can increase protein abundance are rare. Small molecule protein upregulators with targeted activities would be of value in the study of the mechanisms underlying loss-of-function diseases. We developed a high-throughput screening approach to identify small molecule upregulators of the Survival of Motor Neuron protein (SMN), whose decreased levels cause the neurodegenerative disease spinal muscular atrophy (SMA). We screened 69,189 compounds for SMN upregulators and performed mechanistic studies on the most active compound, a bromobenzophenone analogue designated cuspin-1. Mechanistic studies of cuspin-1 revealed that increasing Ras signaling upregulates SMN protein abundance via an increase in translation rate. These findings suggest that controlled modulation of the Ras signaling pathway may benefit patients with SMA.

First Annual LGBT Health Workforce Conference: Empowering Our Health Workforce to Better Serve LGBT Communities

The Institute of Medicine has identified significant health disparities and barriers to health care experienced by lesbian, gay, bisexual, and transgender (LGBT) populations. By lowering financial barriers to care, recent legislation and judicial decisions have created a remarkable opportunity for reducing disparities by making health care available to those who previously lacked access. However, the current health-care workforce lacks sufficient training on LGBT-specific health-care issues and delivery of culturally competent care to sexual orientation and gender identity minorities. The LGBT Healthcare Workforce Conference was developed to provide a yearly forum to address these deficiencies through the sharing of best practices in LGBT health-care delivery, creating LGBT-inclusive institutional environments, supporting LGBT personal and professional development, and peer-to-peer mentoring, with an emphasis on students and early career professionals in the health-care fields. This report summarizes the findings of the first annual LGBT Health Workforce Conference.

The new era of precision population health: insights for the All of Us Research Program and beyond

Although precision medicine has made advances in individualized patient treatments, there needs to be continued attention on tailored population health and prevention strategies (often termed “precision population health”). As we continue to link datasets and use “big data” approaches in medicine, inclusion of diverse populations and a focus on disparities reduction are key components within a precision population health framework. Specific recommendations from the All of Us Research Program and the Precision Public Health Summit provide examples for moving this field forward.