Open Access: Opening or Closing Doors for Junior Faculty?

The Open Access movement has transformed the landscape of medical publishing. Federal regulations regarding Open Access have expanded in the USA, and journals have adapted by offering a variety of Open Access models that range widely in cost and accessibility. For junior faculty with little to no funding, navigating this ever-changing landscape while simultaneously balancing the pressures of publication and promotion may present a particular challenge. Open Access provides the opportunity to amplify the reach and impact of scientific research, yet it often comes at a cost that may not be universally affordable. In this perspective, we discuss the impact of Open Access through the lens of junior faculty in general internal medicine. We describe the potential benefits and pitfalls of Open Access on junior faculty with a focus on research dissemination and cost. Finally, we propose sustainable solutions at the individual and systems-level to help navigate the world of Open Access to promote career growth and development.

Public Health Crisis in Gaza-The Responsibility of US-Based Academic Medical Journals.

In this Viewpoint, the authors write that US-based medical journals have an obligation to create space for discourse about the human costs of war and other political drivers of health.

Prevalence and Tolerance of Prognostic Uncertainty Among Thoracic Oncologists.

We undertook a cross-sectional survey of a random sample of thoracic oncologists from the American Society of Clinical Oncology clinical directory to characterize whether prognostic uncertainty has increased and if tolerance of uncertainty is associated with prognostic discussion practices. We also assessed the Physicians' Reactions to Uncertainty Scale and presented a vignette about an incurable patient with uncertain life expectancy. One hundred and ninety-two of 438 surveys (43.8%) were received. Of the respondents, 52.1% agreed "there is more prognostic uncertainty in the management of lung cancer now than 10 years ago," and 37.4% noted difficulty "staying up-to-date." In multivariable analyses, physician-reported anxiety about uncertainty (p = .05) and reluctance to disclose uncertainty (p = .04) were inversely associated with reporting having prognostic discussions with most patients. For the vignette, 92.1% reported they would discuss incurability, but only 76.3% said they would discuss the patient's life expectancy. Our data suggest prognostic uncertainty has increased in thoracic oncology and oncologists' tolerance of uncertainty may affect discussion practices.

Fit older adults with advanced myelodysplastic syndromes: who is most likely to benefit from transplant?

We conducted a prospective observational study of fit adults aged 60-75 with advanced MDS, enrolled hierarchically for adverse MDS risk (intermediate-2 or high-risk international prognostic score [IPSS], low or intermediate-1 IPSS with poor-risk cytogenetics, or therapy-related MDS) or standard risk with severe cytopenia. A total of 290 patients enrolled at two centers: 175 for adverse risk and 115 for standard risk with severe cytopenia. 113 underwent HCT after a median of 5 months; median follow-up for all was 39.5 months. In univariable analyses, the hazard ratio (HR) for death comparing HCT with no HCT was 0.84 (p = 0.30). The HR for death was 0.64 (p = 0.04) for HCT ≤ 5 months after enrollment and 1.20 (p = 0.39) for HCT > 5 months. In multivariable analyses controlling for age, gender, ECOG performance status, cytogenetic risk, and IPSS risk group, HR for death was 0.75 (p = 0.13) for HCT compared to no HCT, 0.57 (p = 0.01) for adverse MDS risk and 1.33 (p = 0.36) for standard risk with severe cytopenia. In this large, prospective cohort of fit older adults with advanced MDS, we found that survival was significantly improved if HCT was performed early or for adverse risk disease but not for standard risk disease with severe cytopenia.

How Do Blood Cancer Doctors Discuss Prognosis? Findings from a National Survey of Hematologic Oncologists.

Background: Although blood cancers are accompanied by a high level of prognostic uncertainty, little is known about when and how hematologic oncologists discuss prognosis. Objectives: Characterize reported practices and predictors of prognostic discussions for a cohort of hematologic oncologists. Design: Cross-sectional mailed survey in 2015. Setting/Subjects: U.S.-based hematologic oncologists providing clinical care for adult patients with blood cancers. Measurements: We conducted univariable and multivariable analyses assessing the association of clinician characteristics with reported frequency of initiation of prognostic discussions, type of terminology used, and whether prognosis is readdressed. Results: We received 349 surveys (response rate = 57.3%). The majority of respondents (60.3%) reported conducting prognostic discussions with "most" (>95%) of their patients. More than half (56.8%) preferred general/qualitative rather than specific/numeric terms when discussing prognosis. Although 91.3% reported that they typically first initiate prognostic discussions at diagnosis, 17.7% reported routinely never readdressing prognosis or waiting until death is imminent to revisit the topic. Hematologic oncologists with ≤15 years since medical school graduation (odds ratio [OR] 0.51; confidence interval (95% CI) 0.30-0.88) and those who considered prognostic uncertainty a barrier to quality end-of-life care (OR 0.57; 95% CI 0.35-0.90) had significantly lower odds of discussing prognosis with "most" patients. Conclusions: Although the majority of hematologic oncologists reported discussing prognosis with their patients, most prefer general/qualitative terms. Moreover, even though prognosis evolves during the disease course, nearly one in five reported never readdressing prognosis or only doing so near death. These findings suggest the need for structured interventions to improve prognostic communication for patients with blood cancers.

Impact of lenalidomide use among non-transfusion dependent patients with myelodysplastic syndromes.

Chemotherapies approved for defined subgroups promise personalized oncologic care, but their off-label impact is unclear. Lenalidomide is approved for lower-risk, transfusion-dependent (TD) myelodysplastic syndromes (MDS) with del(5q), but frequently used in MDS outside this indication. We characterized lenalidomide use and outcomes among non-TD patients with MDS. Patients 65 or older diagnosed with MDS between 2007 and 2013 were identified using SEER; linked Medicare claims were evaluated for transfusions, lenalidomide use, and incident toxicities. TD was ≥2 transfusion episodes within an 8-week period; responses were transfusion independence (TI) and ≥50% transfusion reduction (minor response). We compared overall survival for non-TD patients receiving lenalidomide versus those not receiving lenalidomide, matched on disease and patient characteristics. We identified 676 patients who had received lenalidomide, including 275 (40.7%) TD and 401 (59.3%) non-TD; 18.5% (125/676) had zero claims for RBC transfusion prior to receiving lenalidomide. Incident toxicities among patients prescribed lenalidomide were similar in TD and non-TD groups, except incident thromboembolic events were higher among non-TD patients (10.8% vs. 6.0%, P = .04). Comparing 191 non-TD patients receiving lenalidomide within 6 months of MDS diagnosis to risk-matched MDS controls, lenalidomide was not associated with improved OS (P = .78). Among TD patients (n = 275), 31% achieved TI, and 30% achieved minor hematologic response, with a median time to TI of 4.1 weeks. In conclusion, we confirmed the benefit of lenalidomide among TD patients with MDS; however, many non-TD patients also received lenalidomide. These patients experienced accompanying toxicity without evidence of benefit in terms of transfusion needs or overall survival.

Treating Childhood Malnutrition in Rural Haiti: Program Outcomes and Obstacles.

BACKGROUND: Haiti has the worst malnutrition rate in the Western hemisphere. In October 2010, a cholera epidemic erupted and spread rapidly throughout the country, straining Haiti's already fragile health infrastructure across all levels of care. This study reviews data from an outpatient therapeutic feeding program (OTP) for acute childhood malnutrition at a clinic in rural Haiti with a focus on the effect of the 2010 cholera epidemic on program operations. METHODS: A retrospective chart review was conducted for the complete set of patients who were enrolled in the OTP from its inception in March 2009 through January 2014. FINDINGS: A total of 187 charts were retrieved representing 176 unique patients, of whom 5 were currently enrolled in care. At admission, 96 (51.3%) met criteria for severe acute malnutrition, 88 (47.1%) met criteria for moderate acute malnutrition, and 3 (1.6%) did not meet criteria for acute malnutrition. Of the 182 completed charts, 119 (65.4%) reached their target weight (≥-1 weight-for-height z-score) by discharge (ie, were "cured"), 43 (23.6%) defaulted, 11 (6.0%) were discharged prematurely, 8 (4.4%) died, and 1 (0.5%) was hospitalized. A total of 11 patients (6.3%) who were initially admitted relapsed after discharge and were later readmitted. Data from 170 complete records (93.4%) were included in a multivariate logistic regression. Severe (vs moderate) acute malnutrition was negatively associated with likelihood of being cured when controlling for other patient- and care-related factors (OR = 0.261, P = .002). Average cholera burden was negatively correlated with likelihood of OTP treatment cure when controlling for patient- and care-related variables (OR = 0.859, P = .002) but was insignificant when controlling for year. CONCLUSIONS: Results from the study have been used to inform a restructuring of the clinic's acute malnutrition program toward a more community-centered model of management, the context and implications of which are discussed in relation to the existing literature.

The sigma(E) stress response is required for stress-induced mutation and amplification in Escherichia coli.

Pathways of mutagenesis are induced in microbes under adverse conditions controlled by stress responses. Control of mutagenesis by stress responses may accelerate evolution specifically when cells are maladapted to their environments, i.e. are stressed. Stress-induced mutagenesis in the Escherichia coli Lac assay occurs either by 'point' mutation or gene amplification. Point mutagenesis is associated with DNA double-strand-break (DSB) repair and requires DinB error-prone DNA polymerase and the SOS DNA-damage- and RpoS general-stress responses. We report that the RpoE envelope-protein-stress response is also required. In a screen for mutagenesis-defective mutants, we isolated a transposon insertion in the rpoE P2 promoter. The insertion prevents rpoE induction during stress, but leaves constitutive expression intact, and allows cell viability. rpoE insertion and suppressed null mutants display reduced point mutagenesis and maintenance of amplified DNA. Furthermore, sigma(E) acts independently of stress responses previously implicated: SOS/DinB and RpoS, and of sigma(32), which was postulated to affect mutagenesis. I-SceI-induced DSBs alleviated much of the rpoE phenotype, implying that sigma(E) promoted DSB formation. Thus, a third stress response and stress input regulate DSB-repair-associated stress-induced mutagenesis. This provides the first report of mutagenesis promoted by sigma(E), and implies that extracytoplasmic stressors may affect genome integrity and, potentially, the ability to evolve.