Trends of sources of clinical research funding from 1990 to 2020: a meta-epidemiological study.

Evidence has raised concerns regarding the association between funding sources and doubtful data. Our main outcome was to analyze trends on funding sources in articles published from 1990 to 2020 in the more influential journals of internal and general medicine. In this meta-epidemiological study, we included peer-reviewed studies from the 10 highest impact journals in general and internal medicine published between January 1990 and February 2020 based on published original research according to the 2018 InCites Journal of Citation Reports, these consisted of the following: The New England Journal of Medicine, The Lancet, JAMA, BMJ, JAMA Internal Medicine, Annals of Internal Medicine, PLOS Medicine, Cachexia, BMC Medicine, and Mayo Clinic Proceedings Two reviewers working in duplicate extracted data regarding year of publication, study design, and sources of funding. In total, 496 articles were found; of these, 311 (62.7%) were observational studies, 167 (33.7%) were experimental, and 16 (3.2%) were secondary analyses. Percentages of grant sources through the years were predominantly from government (60%), industry (23.83%), and non-governmental (16.06%) organizations. The percentage of industry subsidies tended to decrease, but this was not significant in a linear regression model (r=0.02, p≥0.05). Government and non-government funding sources showed a trend to decrease in the same univariate analysis with both significant associations (r=0.21, p≤0.001 and r=0.10, p≤0.001, respectively). The main funding source in medical research has consistently been government aid. Despite previous reported data, no association was found between the source of funding and statistically significant results favoring study authors' hypothesis.

The Effect of Post warming Culture Period Between Thawing and Transfer of Cryopreserved Embryos on Reproductive Outcomes After In Vitro Fertilization (IVF): A Systematic Review and Meta-analysis.

BACKGROUND: The purpose of this study was to evaluate the effect of post warming culture period between thawing and transfer of cryopreserved embryos on reproductive outcomes after in vitro fertilization (IVF). METHODS: An extensive literature search was performed using PubMed, EmBase, and the Cochrane library from January 2000 to August 2019. A systematic review and meta-analysis of clinical trials was performed in this manuscript. The trials represented patients with embryo transfers of at least one previously cryopreserved good quality embryo. Main outcome measures of the study included clinical pregnancy rate, live birth rate, miscarriage rate, and ectopic pregnancy rate. RESULTS: A total of 5338 trial/abstracts were identified through a literature search. Totally, five studies were included in the systematic review, and three in the final meta-analysis. The studies included 1717 embryo transfers, 605 after short culture, and 1112 after long culture. The clinical pregnancy rate (CPR) was the most consistent outcome reported. The CPR was slightly better after short time culture with a RR of 1.09 (0.95-1.26, 95%CI) but this difference was not statistically significant. The great heterogenicity in the results reported in the included studies made it impossible to compare all planned outcomes. CONCLUSION: There are no differences in reproductive outcomes if cryopreserved embryos are transferred after overnight culture or after two hours of culture following thawing. Due to small number and the poor quality of trials reported on this topic, the results of this review should be treated with caution.

Preliminary efficacy and tolerability profiles of first versus second-generation Long-Acting Injectable Antipsychotics in schizophrenia: A systematic review and meta-analysis.

We performed a systematic review and meta-analysis of the efficacy and safety of second generation (SG) long-acting antipsychotics (LAIAs) versus first generation (FG) LAIAs in schizophrenia. We conducted a comprehensive search in PubMed, MEDLINE, EMBASE and PsycINFO until May 2019. Inclusion criteria for randomized trials included: (1) patients ≥18 years with schizophrenia, (2) efficacy evaluated through the Positive and Negative Syndrome Scale (PANSS), (3) safety assessment through clinimetry, laboratory analysis, somatometry or adverse events, and (4) treatment duration ≥12 weeks. Data was synthesized using mean differences (MD) for continuous outcomes and risk ratios (RR) for dichotomous outcomes using a random-effect model. Of 1872 citations, 17 trials were included, and direct comparisons of SG vs FG-LAIAs were observed in 3 (n = 459). SG and FG-LAIAs had similar effects on PANSS scores (MD -1.35; 95% CI -8.33-5.64), tardive dyskinesia (RR 0.99; 95% CI, 0.47-2.07), all-cause discontinuation (RR 1.01; 95% CI 0.75-1.36), discontinuation due to inadequate efficacy (RR 1.13; 95% CI 0.81-1.59) or adverse events (RR 1.08; 95% CI 0.55-2.11). SG-LAIAs reduced the risk of using antiparkinsonian drugs (RR 0.54; 95% CI 0.54-0.76) but significantly increased serum prolactin, weight and BMI. For long-term management, depot preparations of paliperidone, haloperidol, risperidone and fluphenazine were equally effective at symptom control and adherence, with significant differences in their safety profiles. These results however are considerably limited due to the small number of included studies and are therefore preliminary, not generalizable. More clinical trials are required to obtain a broader perspective of SG-LAIAs compared to FG-LAIAs.

Endorsement of reporting guidelines and study registration by endocrine and internal medicine journals: meta-epidemiological study.

OBJECTIVES: To improve the trustworthiness of evidence, studies should be prospectively registered and research reports should adhere to existing standards. We aimed to systematically assess the degree to which endocrinology and internal medicine journals endorse study registration and reporting standards for randomised controlled trials (RCTs), systematic reviews (SRs) and observational studies (ObS). Additionally, we evaluated characteristics that predict endorsement of reporting or registration mechanism by these journals. DESIGN: Meta-epidemiological study. SETTING: Journals included in the 'Endocrinology and Metabolism' and 'General and Internal Medicine' 2017 Journal Citation Reports. PARTICIPANTS: Journals with an impact factor of ≥1.0, focused on clinical medicine, and those who publish RCTs, SRs and ObS were included. PRIMARY OUTCOMES: Requirement of adherence to reporting guideline and study registration as determined from the journals' author instructions. RESULTS: Of the 170 (82 endocrinology and 88 internal medicine) eligible journals, endorsing of reporting standards was the highest for RCTs, with 35 (43%) of endocrine journals and 55 (63%) of internal medicine journals followed by SRs, with 21 (26%) and 48 (55%), respectively, and lastly, by ObS with 41 (50%) of endocrine journals and 21 (24%) of internal medicine journals. In 78 (46%) journals RCTs were required to be registered and published in adherence to the Consolidated Standards of Reporting Trials statement. Only 11 (6%) journals required registration of SRs. Internal medicine journals were more likely to endorse reporting guidelines than endocrine journals except for Strengthening the Reporting of Observational Studies in Epidemiology. No other journal characteristic proved to be an independent predictor of reporting standard endorsement for RCTs besides trial registration. CONCLUSION: Our results highlight that study registration requirement and reporting guideline endorsement are suboptimal in internal medicine and endocrine journals. This malpractice may be further enhanced since endorsement does not imply enforcement, impairing the practice of evidence-based medicine.

Menopausal Hormone Therapy and Mortality: A Systematic Review and Meta-Analysis.

OBJECTIVES: The objective was to assess the effect of menopausal hormonal therapy (MHT) on all-cause and cause-specific mortality. METHODS: We conducted a comprehensive search of several databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, and Scopus) from inception until August 2013. We included randomized controlled trials (RCTs) of more than 6 months of duration comparing MHT with no treatment. Pairs of independent reviewers selected trials, assessed risk of bias and extracted data. We estimated risk ratios (RRs) and 95% confidence intervals (CIs) using the random-effects model. RESULTS: We included 43 RCTs at moderate risk of bias. Meta-analysis showed no effect on mortality (RR 0.99 [95% CI, 0.94-1.05]), regardless of MHT type or history of preexisting heart disease. No association was found between MHT and cardiac death (RR 1.04 [95% CI 0.87-1.23]) or stroke (RR 1.49 [95% CI 0.95-2.31]). Estrogen plus progesterone use was associated with a likely increase in breast cancer mortality (RR 1.96 [95% CI 0.98-3.94]), whereas estrogen use was not. MHT use was not associated with mortality of other types of cancer. In 5 trials, MHT was likely started at a younger age: 2 RCTs with mean age less than 60 and 3 RCTs with MHT started less than 10 years after menopause. Meta-analysis of these 5 RCTs showed a reduction of mortality with MHT (RR 0.70 [95% CI 0.52-0.95]). CONCLUSION: The current evidence suggests that MHT does not affect the risk of death from all causes, cardiac death and death from stroke or cancer. These data may be used to support clinical and policy deliberations about the role of MHT in the care of symptomatic postmenopausal women.