Lisa S. Rotenstein

Prevalence of Depression, Depressive Symptoms, and Suicidal Ideation Among Medical Students: A Systematic Review and Meta-Analysis

Importance Medical students are at high risk for depression and suicidal ideation. However, the prevalence estimates of these disorders vary between studies. Objective To estimate the prevalence of depression, depressive symptoms, and suicidal ideation in medical students. Data Sources and Study Selection Systematic search of EMBASE, ERIC, MEDLINE, psycARTICLES, and psycINFO without language restriction for studies on the prevalence of depression, depressive symptoms, or suicidal ideation in medical students published before September 17, 2016. Studies that were published in the peer-reviewed literature and used validated assessment methods were included. Data Extraction and Synthesis Information on study characteristics; prevalence of depression or depressive symptoms and suicidal ideation; and whether students who screened positive for depression sought treatment was extracted independently by 3 investigators. Estimates were pooled using random-effects meta-analysis. Differences by study-level characteristics were estimated using stratified meta-analysis and meta-regression. Main Outcomes and Measures Point or period prevalence of depression, depressive symptoms, or suicidal ideation as assessed by validated questionnaire or structured interview. Results Depression or depressive symptom prevalence data were extracted from 167 cross-sectional studies (n = 116 628) and 16 longitudinal studies (n = 5728) from 43 countries. All but 1 study used self-report instruments. The overall pooled crude prevalence of depression or depressive symptoms was 27.2% (37 933/122 356 individuals; 95% CI, 24.7% to 29.9%, I2 = 98.9%). Summary prevalence estimates ranged across assessment modalities from 9.3% to 55.9%. Depressive symptom prevalence remained relatively constant over the period studied (baseline survey year range of 1982-2015; slope, 0.2% increase per year [95% CI, -0.2% to 0.7%]). In the 9 longitudinal studies that assessed depressive symptoms before and during medical school (n = 2432), the median absolute increase in symptoms was 13.5% (range, 0.6% to 35.3%). Prevalence estimates did not significantly differ between studies of only preclinical students and studies of only clinical students (23.7% [95% CI, 19.5% to 28.5%] vs 22.4% [95% CI, 17.6% to 28.2%]; P = .72). The percentage of medical students screening positive for depression who sought psychiatric treatment was 15.7% (110/954 individuals; 95% CI, 10.2% to 23.4%, I2 = 70.1%). Suicidal ideation prevalence data were extracted from 24 cross-sectional studies (n = 21 002) from 15 countries. All but 1 study used self-report instruments. The overall pooled crude prevalence of suicidal ideation was 11.1% (2043/21 002 individuals; 95% CI, 9.0% to 13.7%, I2 = 95.8%). Summary prevalence estimates ranged across assessment modalities from 7.4% to 24.2%. Conclusions and Relevance In this systematic review, the summary estimate of the prevalence of depression or depressive symptoms among medical students was 27.2% and that of suicidal ideation was 11.1%. Further research is needed to identify strategies for preventing and treating these disorders in this population.

Opportunities and Challenges for Biosimilars: What's on the Horizon in the Global Insulin Market?

IN BRIEF Biosimilar insulins are likely to enter the insulin landscape as patents for major branded insulin products start to expire in the next few years. Biosimilar insulins have the potential to reduce diabetes treatment costs, increase the accessibility of insulin treatment, and expand the number of insulin brands available for those with diabetes. However, they will have to overcome numerous regulatory hurdles, meet a variety of commercial demands, and effectively confront competition from both established and next-generation branded insulin products before they can succeed on the global market.

Making Patients and Doctors Happier — The Potential of Patient-Reported Outcomes

Interviews with providers suggest that incorporating collection of patient-reported outcomes into routine care can improve physician satisfaction, enhance physician–patient relationships, increase workflow efficiency, and enable crucial conversations.

The Ideal Diabetes Therapy: What Will It Look Like? How Close Are We?

IN BRIEF Although the number of diabetes treatments has substantially increased in the past two decades, todays therapies are considered far from ideal. Yet, what constitutes an ideal therapy is not readily clear, as diabetes drug therapies are regularly judged both by their effects on glycemia and by a wide variety of nonglycemic metrics. This review describes the characteristics of an ideal diabetes therapy from the perspective of patients, physicians, payors, and financial analysts and examines how well currently available therapies and several late-stage candidates meet these guideposts.

Dual functionalized PVA hydrogels that adhere endothelial cells synergistically.

Cell adhesion molecules govern leukocyte-endothelial cell (EC) interactions that are essential in regulating leukocyte recruitment, adhesion, and transmigration in areas of inflammation. In this paper, we synthesized hydrogel matrices modified with antibodies against vascular cell adhesion molecule-1 (VCAM1) and endothelial leukocyte adhesion molecule-1 (E-Selectin) to mimic leukocyte-EC interactions. Adhesion of human umbilical vein ECs to polyvinyl alcohol (PVA) hydrogels was examined as a function of the relative antibody ratio (anti-VCAM1:anti-E-Selectin) and substrate elasticity. Variation of PVA backbone methacrylation was used to affect hydrogel matrix stiffness, ranging from 130 to 720 kPa. Greater EC adhesion was observed on hydrogels presenting 1:1 anti-VCAM1:anti-E-Selectin than on gels presenting either arginine-glycine-asparagine (RGD) peptide, anti-VCAM1, or anti-E-Selectin alone. Engineered cell adhesion - based on complementing the EC surface presentation - may be used to increase the strength of EC-matrix interactions. Hydrogels with tunable and synergistic adhesion may be useful in vascular remodeling.

Engineered endothelial cell adhesion via VCAM1 and E-Selectin antibody-presenting alginate hydrogels

Materials that adhere to the endothelial cell (EC) lining of blood vessels may be useful for treating vascular injury. Cell adhesion molecules (CAMs), such as endothelial leukocyte adhesion molecule-1 (E-selectin) and vascular cell adhesion molecule-1 (VCAM1), modulate EC-leukocyte interactions. In this study, we mimicked cell-cell interactions by seeding cells on alginate hydrogels modified with antibodies against E-selectin and VCAM1, which are upregulated during inflammation. ECs were activated with interleukin-1α to increase CAM expression and subsequently seeded onto hydrogels. The strength of cell adhesion onto gels was assessed via a centrifugation assay. Strong, cooperative EC adhesion was observed on hydrogels presenting a 1:1 ratio of anti-VCAM1:anti-E-selectin. Cell adhesion was stronger on dual functionalized gels than on gels modified with anti-VCAM1, anti-E-selectin or the arginine-glycine-aspartic acid (RGD) peptide alone. Anti-VCAM1:anti-E-selectin-modified hydrogels may be engineered to adhere the endothelium cooperatively.

Characterization of the shark myelin Po protein.

Myelin, the insulating sheath made by extensive plasma membrane wrapping, is dependent on the presence of highly adhesive molecules that keep the two sides of the membrane in tight contact. The Po glycoprotein (Po) is the major component of the peripheral nervous system (PNS) myelin of mammals. The exact role that Po protein has played in the evolution of myelin is still unclear, but several phylogenetic observations suggest that it is a crucial component in the development of myelin as a multi-lamellar membrane structure. Sharks, which appeared in the fossil record about 400 million years ago, are the first fully myelinated organisms. In this study we investigated the expression pattern of shark myelin Po to suggest a way it might have played a role in the evolution of myelin in the central nervous system. We found that sharks have more than two isoforms (32, 28 and 25 kD), and that some of these might not be fully functional because they lack the domains known for Po homophilic adhesion.

Embryonic development of glial cells and myelin in the shark, Chiloscyllium punctatum

Glial cells are responsible for a wide range of functions in the nervous system of vertebrates. The myelinated nervous systems of extant elasmobranchs have the longest independent history of all gnathostomes. Much is known about the development of glia in other jawed vertebrates, but research in elasmobranchs is just beginning to reveal the mechanisms guiding neurodevelopment. This study examines the development of glial cells in the bamboo shark, Chiloscyllium punctatum, by identifying the expression pattern of several classic glial and myelin proteins. We show for the first time that glial development in the bamboo shark (C. punctamum) embryo follows closely the one observed in other vertebrates and that neural development seems to proceed at a faster rate in the PNS than in the CNS. In addition, we observed more myelinated tracts in the PNS than in the CNS, and as early as stage 32, suggesting that the ontogeny of myelin in sharks is closer to osteichthyans than agnathans.

Characterization of the trunk neural crest in the bamboo shark, Chiloscyllium punctatum

The neural crest is a population of mesenchymal cells that after migrating from the neural tube gives rise to structure and cell types: the jaw, part of the peripheral ganglia, and melanocytes. Although much is known about neural crest development in jawed vertebrates, a clear picture of trunk neural crest development for elasmobranchs is yet to be developed. Here we present a detailed study of trunk neural crest development in the bamboo shark, Chiloscyllium punctatum. Vital labeling with dioctadecyl tetramethylindocarbocyanine perchlorate (DiI) and in situ hybridization using cloned Sox8 and Sox9 probes demonstrated that trunk neural crest cells follow a pattern similar to the migratory paths already described in zebrafish and amphibians. We found shark trunk neural crest along the rostral side of the somites, the ventromedial pathway, the branchial arches, the gut, the sensory ganglia, and the nerves. Interestingly, C. punctatum Sox8 and Sox9 sequences aligned with vertebrate SoxE genes, but appeared to be more ancient than the corresponding vertebrate paralogs. The expression of these two SoxE genes in trunk neural crest cells, especially Sox9, matched the Sox10 migratory patterns observed in teleosts. Also of interest, we observed DiI cells and Sox9 labeling along the lateral line, suggesting that in C. punctatum, glial cells in the lateral line are likely of neural crest origin. Although this has been observed in other vertebrates, we are the first to show that the pattern is present in cartilaginous fishes. These findings demonstrate that trunk neural crest cell development in C. punctatum follows the same highly conserved migratory pattern observed in jawed vertebrates. J. Comp. Neurol. 521:3303–3320, 2013.

Implementing patient-reported outcome surveys as part of routine care: lessons from an academic radiation oncology department

Patient reported outcomes (PROs) are reports of health conditions that come directly from patients. Use of PROs has been associated with improved patient outcomes, enhanced quality of life, and reduced end-of-life spending. Yet there are still outstanding questions regarding the process of implementing PRO collection in routine practice. In this article, we describe the experience of selecting and implementing PROs in a multisite, multidisease academic medical center-based radiation oncology practice and demonstrate that such large-scale rollout is feasible. We establish that PROs can be implemented with minimal to no workflow delays, are generally seen as valuable by clinicians, and can enhance patient-doctor communication. We additionally detail the challenges involved in selecting clinically relevant PRO questionnaires and the centrality of physician buy-in, easy data access, and clear workflows to successful implementation.