IntroductionSelective reporting bias occurs when chance or selective outcome reporting rather than the intervention contributes to group differences. The prevailing concern about selective reporting bias is the possibility of results being modified towards specific conclusions. In this study, we evaluate randomized controlled trials (RCTs) published in hematology journals, a group in which selective outcome reporting has not yet been explored.MethodsOur primary goal was to examine discrepancies between the reported primary and secondary outcomes in registered and published RCTs concerning hematological malignancies reported in hematology journals with a high impact factor. The secondary goals were to address whether outcome reporting discrepancies favored statistically significant outcomes, whether a pattern existed between the funding source and likelihood of outcome reporting bias, and whether temporal trends were present in outcome reporting bias. For trials with major outcome discrepancies, we contacted trialists to determine reasons for these discrepancies. Trials published between January 1, 2010 and December 31, 2015 in Blood; British Journal of Haematology; American Journal of Hematology; Leukemia; and Haematologica were included.ResultsOf 499 RCTs screened, 109 RCTs were included. Our analysis revealed 118 major discrepancies and 629 total discrepancies. Among the 118 discrepancies, 30 (25.4%) primary outcomes were demoted, 47 (39.8%) primary outcomes were omitted, and 30 (25.4%) primary outcomes were added. Three (2.5%) secondary outcomes were upgraded to a primary outcome. The timing of assessment for a primary outcome changed eight (6.8%) times. Thirty-one major discrepancies were published with a P-value and twenty-five (80.6%) favored statistical significance. A majority of authors whom we contacted cited a pre-planned subgroup analysis as a reason for outcome changes.ConclusionOur results suggest that outcome changes occur frequently in hematology trials. Because RCTs ultimately underpin clinical judgment and guide policy implementation, selective reporting could pose a threat to medical decision making.

BackgroundSelective outcome reporting is a significant methodological concern. Comparisons between the outcomes reported in clinical trial registrations and those later published allow investigators to understand the extent of selection bias among trialists. We examined the possibility of selective outcome reporting in randomized controlled trials (RCTs) published in neurology journals.MethodsWe searched PubMed for randomized controlled trials from Jan 1, 2010 –Dec 31, 2015 published in the top 3 impact factor neurology journals. These articles were screened according to specific inclusion criteria. Each author individually extracted data from trials following a standardized protocol. A second author verified each extracted element and discrepancies were resolved. Consistency between registered and published outcomes was evaluated and correlations between discrepancies and funding, journal, and temporal trends were examined.Results180 trials were included for analysis. 10 (6%) primary outcomes were demoted, 38 (21%) primary outcomes were omitted from the publication, and 61 (34%) unregistered primary outcomes were added to the published report. There were 18 (10%) cases of secondary outcomes being upgraded to primary outcomes in the publication, and there were 53 (29%) changes in timing of assessment. Of 82 (46%) major discrepancies with reported p-values, 54 (66.0%) favored publication of statistically significant results.ConclusionAcross trials, we found 180 major discrepancies. 66% of major discrepancies with a reported p-value (n = 82) favored statistically significant results. These results suggest a need within neurology to provide more consistent and timely registration of outcomes.

Selective outcome reporting is a form of bias resulting from discrepancies between outcomes presented in a trial's registration and the published report. We investigate this selective bias in obesity clinical trials. A PubMed search was conducted to identify randomized controlled trials (RCTs) published in four obesity journals from 2013 to 2015. Primary, secondary and tertiary outcomes were recorded for each trial and compared to pre-specified outcomes in each trial's registration. Of the 392 identified articles, 142 were included in the final analysis; 22 (15%) RCTs demonstrated major outcome discrepancies between registration and publication: No primary outcomes were demoted to a secondary or tertiary outcome; 14 (36.84%) primary outcomes were omitted; 14 (36.84%) primary outcomes were added: 5 (13.16%) secondary outcomes were upgraded to primary outcomes; and timing of assessment for a primary outcome changed 5 (13.16%) times. Out of the 63 prospectively registered studies, 53 had no discrepancies. A total of 76 of the studies (29.80%) were unregistered or did not have an associated registration number. Our results suggest that selective outcome reporting may be a concern in obesity clinical trials. As selective outcome reporting may distort clinical findings and limit outcomes in systematic reviews, we encourage trialists and journal editors to work towards solutions to mitigate this issue.

Langerhans cell histiocytosis (LCH) is a rare histiocytic neoplasm. To date, there is a lack of U.S. Food and Drug Administrationapproved treatments in adult LCH to establish optimal first-line therapy. We conducted a retrospective, single-center case series evaluating the use of BRAF inhibitors in adult patients with BRAF V600E-LCH proven by biopsy. Our case series is the first to report the use of BRAF inhibitors as first-line therapy in adults with LCH. We also report the efficacy with single-agent dabrafenib in adult LCH. All but one of our patients had favorable response to targeted therapy.

Background: Germ cell tumors (GCTs) with malignant somatic transformation (MST) represent an uncommon variant of what is typically a curable malignancy. There is a paucity of data on time of somatic transformation, response to conventional therapy, and survival outcomes of different somatic subtypes. Methods: After obtaining institutional review board (IRB) approval, we searched our institutional database from 1982 to 2017 and identified patients with GCTs with MST. Patient characteristics, pathologic description, treatment, and clinical outcomes were extracted from the medical records. Results: We identified 24 cases of GCTs with MST; the MST was adenocarcinoma in 50% and sarcoma in 50%. Median age at diagnosis was 27. Alpha-fetoprotein and beta-human chorionic gonadotropin were undetectable in 44%, both were elevated in 54%. The majority were advanced stage (71% stage III), and International Germ Cell Cancer Collaborative Group (IGCCCG) risk was classified as ‘good' in 60%. Median follow-up was 41 months (range 10-346 months). Median progression-free survival was 84 months (95% confidence interval (CI) 56-232), and median overall survival was 219 months (95% CI 165-not reported). Conclusion: Patients with GCTs with an MST appear to have poor responses to cisplatin-based chemotherapy, suggesting that somatic component-driven therapies should be considered. Furthermore, resection of residual disease when feasible is an essential component of management.

Langerhans cell histiocytosis (LCH) is a histiocytic neoplasm that can involve the lungs as single system (LCH-SSL) or multisystem disease (LCH-MSL). The role of fullbody radiographic staging to determine whether patients have LCH-SSL or LCH-MSL is unclear. Long-term outcomes of LCH-SSL versus LCH-MSL and multisystem without lung involvement (LCH-MSNL) are unknown. A retrospective study of adult LCH patients seen at our center from January 2000 to 2020 was performed. In Part 1, we addressed utility of whole-body staging imaging among those presenting with isolated pulmonary signs or symptoms. Staging was defined as fluorodeoxyglucose positron emission tomography-computed tomography (CT) or whole-body CT obtained within 3 months of diagnosis. In Part 2, we examined the frequency of developing extra-pulmonary disease over time and mortality in patients with LCH-SSL. In Part 3, we compared the overall survival of LCH-SSL, LCH-MSL, and LCH-MSNL. Part 1: 240 patients with LCH were identified. A total of 112 (47%) had pulmonary signs or symptoms at presentation. Thirty-four (30%) underwent radiographic staging and only one showed evidence of extra-pulmonary disease. Part 2: 108 (45%) were LCH-SSL. Median follow-up duration of 4.5 years (95% confidence interval [

Context Access to primary care (PC) improves health outcomes and decreases health care costs. The shortage of PC physicians and shifting physician workforce makes this an ongoing concern. Osteopathic medical schools are making strides to fill this void. Considering the critical need for PC physicians in the United States, this study aims to identify factors related to choosing a PC specialty. Objective To understand possible motivations of osteopathic medical students pursuing a career in PC specialties by examining the role of sex and the influence of 5 key factors in this decision. Methods Responses from the annual American Association of Colleges of Osteopathic Medicine graduate survey (2007-2016) were analyzed. Self-reported practice decision considerations of 5 key factors, including (1) intellectual and technical content, (2) debt level, (3) lifestyle, (4) prestige/income level, and (5) personal experience and abilities were summarized, and their subjective value was contrasted between osteopathic medicine graduates pursuing PC specialties vs those pursuing non-PC specialties. Results The mean percentage of graduates pursuing PC and non-PC specialties from 2007 to 2016 was 31.3% and 68.7%, respectively. Women were 1.75 times more likely to choose PC than men (95% CI, 1.62-1.89). Regardless of specialty choice, lifestyle was the most important factor each year (1027 for PC [75.3%] vs 320 for non-PC [63.3%] in 2016; P<.0001). Students entering PC were more likely to report prestige and income level to be “no or minor influence” compared with students entering non-PC specialties (P<.0001). Debt level was more likely to be a “major influence” to students choosing to enter non-PC specialties than to those entering PC (P<.0001), and the percentage of non-PC students has grown from 383 in 2007 (22.9%) to 833 in 2016 (30.6%). Conclusion Sex was found to significantly influence a graduate's choice of specialty, and female graduates were more likely to enter practice in PC. Each of the 5 survey factors analyzed was significantly different between students entering PC and students entering non-PC specialties. Lifestyle was deemed a major influencing factor, and responses suggested that debt level is a strong influencing factor among students pursuing non-PC specialties.

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