BACKGROUND Neurotrophins of the nerve growth factor family are soluble polypeptides that are best known for their role in nerve growth, survival and differentiation in the central nervous system. A growing body of literature shows that neurotrophins and their receptors are also expressed throughout the reproductive tract. OBJECTIVE AND RATIONALE Neurotrophins are key regulatory proteins in reproductive physiology during development and throughout adult life. Of the neurotrophins, the literature describing the expression and function of brain-derived neurotrophic factor (BDNF) and its high-affinity receptor, neurotrophin receptor kinase-2 (NTRK2), has been expanding rapidly. We therefore conducted a systematic inductive qualitative review of the literature to better define the role of the BDNF in the reproductive tract. We postulate that BDNF and NTRK2 are central regulatory proteins throughout the reproductive system. SEARCH METHODS An electronic search of Medline (PubMed) and Web of Science for articles relating to BDNF and the reproductive system was carried out between January 2018 and February 2019. OUTCOMES In the ovary, BDNF expression and levels have been linked with follicle organisation during ovarian development, follicle recruitment and growth and oocyte maturation. In the endometrium, BDNF is involved in cell proliferation and neurogenesis. In contrast, literature describing the role of BDNF in other reproductive tissues is sparse and BDNF-NTRK2 signalling in the male reproductive tract has been largely overlooked. Whilst estradiol appears to be the primary regulator of BDNF expression, we also identified reports describing binding sites for glucocorticoid and myocyte enhancer factor-2, a calcium-response element through activation of an N-methyl-D-aspartate (NMDA) receptor, and aryl hydrocarbon receptor nuclear transporter protein-4 (ARNT) response elements in promoter regions of the BDNF gene. Expression is also regulated by multiple microRNAs and post-translational processing of precursor proteins and intracellular shuttling. BDNF-NTRK2 signalling is modulated through tissue specific receptor expression of either the full-length or truncated NTRK2 receptor; however, the functional importance remains to be elucidated. Dysregulation of BDNF expression and circulating concentrations have been implicated in several reproductive disorders including premature ovarian failure, endometriosis, pre-eclampsia, intra-uterine growth restriction (IUGR) and several reproductive cancers. WIDER IMPLICATIONS We conclude that BDNF and its receptors are key regulatory proteins central to gonadal development, ovarian regulation and uterine physiology, as well as embryo and placenta development. Furthermore, dysregulation of BDNF-NTRK2 in reproductive diseases suggests their potential role as candidate clinical markers of disease and potential therapeutic targets.
Background Postpartum depression (PPD) is a highly prevalent mental health problem that affects parental health with implications for child health in infancy, childhood, adolescence and beyond. The primary aim of this study was to critically appraise available systematic reviews describing interventions for PPD. The secondary aim was to evaluate the methodological quality of the included systematic reviews and their conclusions. Methods An electronic database search of MEDLINE, Embase, and the Cochrane Library from 2000 to 2020 was conducted to identify systematic reviews that examined an intervention for PPD. A Measurement Tool to Assess Systematic Reviews was utilized to independently score each included systematic review which was then critically appraised to better define the most effective therapeutic options for PPD. Results Of the 842 studies identified, 83 met the a priori criteria for inclusion. Based on the systematic reviews with the highest methodological quality, we found that use of antidepressants and telemedicine were the most effective treatments for PPD. Symptoms of PPD were also improved by traditional herbal medicine and aromatherapy. Current evidence for physical exercise and cognitive behavioural therapy in treating PPD remains equivocal. A significant, but weak relationship between AMSTAR score and journal impact factor was observed (p = 0.03, r = 0.24; 95% CI, 0.02 to 0.43) whilst no relationship was found between the number of total citations (p = 0.27, r = 0.12; 95% CI, − 0.09 to 0.34), or source of funding (p = 0.19). Conclusion Overall the systematic reviews on interventions for PPD are of low-moderate quality and are not improving over time. Antidepressants and telemedicine were the most effective therapeutic interventions for PPD treatment.
Background: Adherence to study registration and reporting best practices are vital to foster evidence-based medicine. Poor adherence to these standards in clinical trials conducted in Canada would be detrimental to patients, researchers, and the public alike. Methods: All registered clinical trials on ClinicalTrials.gov conducted in Canada as of 2009 and completed by 2019 were identified. A cross-sectional analysis of those trials assessed prospective registration, subsequent result reporting in the registry, and subsequent publication of study findings. The lead sponsor, phase of study, clinical trial site location, total patient enrollment, number of arms, type of masking, type of allocation, year of completion, and patient demographics were examined as potential effect modifiers to these best practices. Results: A total of 6,720 trials met the inclusion criteria. From 2009-2019, 59% (n=3,967) of them were registered prospectively and 39% (n=2,642) reported their results in the registry. Of the trials registered between 2009-2014, 55% (n=1,482) were subsequently published in an academic journal. Of the 3,763 trials conducted exclusively in Canada, 3% (n=123) met all 3 criteria of: prospective registration, reporting in the registry, and publishing findings. In contrast, of the remaining 2,957 trials with both Canadian and international sites, 41% (n=1,238) had an overall compliance to these three criteria. Overall, the odds of having adherence to all three practices concurrently in Canadian trials decreases by 95% when compared to international trials (OR = 0.05; 95CI: 0.04 – 0.06). Conclusion: Canadian clinical trials substantially lacked adherence to study registration and reporting best practices. Knowledge of this widespread non-compliance should motivate stakeholders in the Canadian clinical trials ecosystem to address and continue to monitor this problem. The data presented provides a baseline against which to compare any improvement in the registration and reporting of clinical trials in Canada.
Objectives: The objective of this study was to evaluate the extent, type, and severity of spin in randomized controlled trials (RCTs) in obstetrics and gynecology. Data Sources: The top five highest impact journals in obstetrics and gynecology were systematically searched for RCTs with non-significant primary outcomes published between January 1, 2019, and December 31, 2020. Methods: Study selection and data extraction assessment were conducted independently and in duplicate. The extent, type, and severity of spin was identified and reported with previously established methodology, and risk of bias was assessed with the Cochrane Risk-of-Bias 2 Tool independently and in duplicate. Fisher's exact tests were used to evaluate the association between study characteristics, risk of bias, and spin. Results: We identified 1475 publications, of which 59 met our inclusion criteria. Articles evaluated interventions in obstetrics ( n = 37, 63%) and gynecology ( n = 22, 37%). Spin was not detected in 28 (47%) of the articles: Three (5%) had one, 10 (17%) had two, and 18 (31%) had greater than two occurrences of spin. Compared with articles where no spin was detected, spin was associated with the Cochrane Risk-of-Bias domain pertaining to missing data ( p < 0.05). No association was observed with the journal, funding source, number of authors, types of interventions, and whether the study involved gynecology or obstetrics. Conclusions: Spin was detected in nearly half of 1:1 parallel two-arm RCTs in obstetrics and gynecology, highlighting the need for caution in the interpretation of RCT findings, particularly when the primary outcome is nonsignificant.
Background Peer review is an integral part of maintaining the current standard of scientific publishing. Despite this, there is no training standard for peer reviewers and review guidelines tend to vary between journals. The purpose of this study was to conduct a systematic review of all openly available online training in scholarly peer review and to analyze their characteristics. Methods MEDLINE, PsycINFO, Embase, ERIC, and Web of Science were systematically searched. Additional grey literature searches were conducted on Google, YouTube, university library websites, publisher websites and peer review related events and groups. All English or French training material in scholarly manuscript peer review of biomedical manuscripts openly accessible online on the search date (September 12, 2021) were included. Sources created prior to 2012 were excluded. Screening was conducted in duplicate in two separate phases: title and abstract followed by full text. Data extraction was conducted by one reviewer and verified by a second. Conflicts were resolved by third-party at both stages. Characteristics were reported using frequencies and percentages. A direct content analysis was preformed using pre-defined topics of interest based on existing checklists for peer reviewers. A risk of bias tool was purpose-built for this study to evaluate the included training material as evidence-based. The tool was used in duplicate with conflicts resolved through discussion between the two reviewers. Results After screening 1244 records, there were 45 sources that met the inclusion criteria; however, 23 of 45 (51%) were not able to be fully accessed for data extraction. The most common barriers to access were membership requirements (n = 11 of 23, 48%), availability for a limited time (n = 8, 35%), and paywalls with an average cost of $99 USD (n = 7, 30%). The remaining 22 documents were included in the data analysis. All documents were published in English. Most documents either did not report publication date (n = 10, 45%) or were created in the last five years (n = 10, 45%). The most common training format was an online module (n = 12, 57%) with an estimated completion time of less than one hour (n = 15, 68%). The most frequently covered topics included how to write a peer review report (n = 20, 91%), critical appraisal of data and results (n = 18, 82%), and a definition of peer review (n = 18, 82%). Critical appraisal of reporting guidelines (n = 9, 41%), clinical trials (n = 4, 18%), and statistical analysis (n = 4, 18%) were less commonly covered. Using our ad-hoc risk of bias tool, four documents (18%) met our criteria for evidence-based. Conclusion Our comprehensive search of the literature identified twenty-two openly accessible online training materials in manuscript peer review. For such a crucial step in the dissemination of literature, a lack of training could potentially explain disparities in the quality of scholarly publishing. Future efforts should be focused on creating a more unified openly accessible online manuscript peer review training program.
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