Assessing fragility of statistically significant findings from randomized controlled trials assessing pharmacological therapies for opioid use disorders: a systematic review.

BACKGROUND: The fragility index is a statistical measure of the robustness or "stability" of a statistically significant result. It has been adapted to assess the robustness of statistically significant outcomes from randomized controlled trials. By hypothetically switching some non-responders to responders, for instance, this metric measures how many individuals would need to have responded for a statistically significant finding to become non-statistically significant. The purpose of this study is to assess the fragility index of randomized controlled trials evaluating opioid substitution and antagonist therapies for opioid use disorder. This will provide an indication as to the robustness of trials in the field and the confidence that should be placed in the trials' outcomes, potentially identifying ways to improve clinical research in the field. This is especially important as opioid use disorder has become a global epidemic, and the incidence of opioid related fatalities have climbed 500% in the past two decades. METHODS: Six databases were searched from inception to September 25, 2021, for randomized controlled trials evaluating opioid substitution and antagonist therapies for opioid use disorder, and meeting the necessary requirements for fragility index calculation. Specifically, we included all parallel arm or two-by-two factorial design RCTs that assessed the effectiveness of any opioid substitution and antagonist therapies using a binary primary outcome and reported a statistically significant result. The fragility index of each study was calculated using methods described by Walsh and colleagues. The risk of bias of included studies was assessed using the Revised Cochrane Risk of Bias tool for randomized trials. RESULTS: Ten studies with a median sample size of 82.5 (interquartile range (IQR) 58, 179, range 52-226) were eligible for inclusion. Overall risk of bias was deemed to be low in seven studies, have some concerns in two studies, and be high in one study. The median fragility index was 7.5 (IQR 4, 12, range 1-26). CONCLUSIONS: Our results suggest that approximately eight participants are needed to overturn the conclusions of the majority of trials in opioid use disorder. Future work should focus on maximizing transparency in reporting of study results, by reporting confidence intervals, fragility indexes, and emphasizing the clinical relevance of findings. TRIAL REGISTRATION: PROSPERO CRD42013006507. Registered on November 25, 2013.

Pre- and post-COVID-19 gender trends in authorship for paediatric radiology articles worldwide: a systematic review.

BACKGROUND: Gender inequalities in academic medicine persist despite progress over the past decade. Evidence-based targeted interventions are needed to reduce gender inequalities. OBJECTIVE: This systematic review aimed to investigate the impact of COVID-19 on gender trends in authorship of paediatric radiology research worldwide. MATERIALS AND METHODS: This prospectively registered, PRISMA-compliant systematic review searched the following databases: PubMed, MEDLINE, Web of Science, and Scopus from January 1, 2018, to May 29, 2023, with no restrictions on country of origin. Screening and data extraction occurred independently and in duplicate. Gender of first, last, and corresponding authors were determined using an artificial intelligence-powered, validated, multinational database ( www.genderize.io ). Two time periods were categorised according to the Johns Hopkins Center for Systems Science and Engineering: pre-COVID (prior to March 2020) and peak and post-COVID (March 2020 onwards). One-sample binomial testing was used to analyse proportion of authorship based on gender. Categorical variables were described as frequencies and percentages, and compared using testing chi-square or Fisher exact testing, with a threshold of P<0.05 representing statistical significance. RESULTS: In total, 922 articles were included with 39 countries represented. A statistically significant difference in authorship based on gender persisted during the peak and post-COVID time period (March 2020 onwards) where women represented a statistically significant lower proportion of last (35.5%) and corresponding (42.7%) authors (P<0.001, P=0.001, respectively). Statistically significant differences for first authors were not found in either period (P=0.08 and P=0.48). CONCLUSION: This study identifies differences in gender trends for authorship in paediatric radiology research worldwide. Future efforts to increase authorship by women are needed.

Implementation of Patient-Reported Outcome Measures for Gender-Affirming Care Worldwide: A Systematic Review.

Importance: Gender-affirming care is a key clinical area that can benefit from implementation of patient-reported outcome measures (PROMs). Identifying barriers to and enablers of PROM implementation is needed to develop an evidence-based implementation strategy. Objective: To identify (1) PROMs previously implemented for gender-affirming care and constructs measured, (2) how patients completed PROMs and how results were reported and used, and (3) barriers to and enablers of PROM implementation. Evidence Review: In this systematic review, PubMed, Embase, MEDLINE, PsycINFO, CINAHL, and Web of Science were searched from inception to October 25, 2021, and updated on December 16, 2022. Gray literature was searched through gray literature database, online search engine, and targeted website searching. Inclusion criteria were (1) original articles of (2) a formally developed PROM or ad hoc instrument administered for gender-affirming care to (3) patients accessing gender-affirming care. The Critical Appraisal Skills Programme tool was used to evaluate quality of included studies. This review was registered on PROSPERO (CRD42021233080). Findings: In total, 286 studies were included, representing 85 395 transgender and nonbinary patients from more than 30 countries. A total of 205 different PROMs were used in gender-affirming care. No studies described using an implementation science theory, model, or framework to support PROM deployment. Key barriers to PROM implementation included issues with evidence strength and quality of the PROM, engaging participants, and PROM complexity. Key enablers of PROM implementation included using PROMs validated for gender-affirming care, implementing PROMs able to be deployed online or in person, implementing PROMs that are shorter and reduce patient burden, engaging key stakeholders and participants as part of developing an implementation plan, and organizational climate. Conclusions and Relevance: In this systematic review of barriers to and enablers of PROM implementation in gender-affirming care, PROM implementation was inconsistent and did not follow evidence-based approaches in implementation science. There was also a lack of patient input in creating implementation strategies, suggesting a need for patient-centered approaches to PROM implementation. Frameworks created from these results can be used to develop evidence-based PROM implementation initiatives for gender-affirming care and have potential generalizability for other clinical areas interested in implementing PROMs.

Delirium and other neuropsychiatric manifestations of COVID-19 infection in people with preexisting psychiatric disorders: a systematic review.

BACKGROUND: Psychiatric disorders increase risk of neuropsychiatric disease and poor outcomes, yet little is known about the neuropsychiatric manifestations of COVID-19 in the psychiatric population. The primary objective is to synthesize neuropsychiatric outcomes of COVID-19 in people with preexisting psychiatric disorders. METHODS: Data were collected during an ongoing review of the impact of pandemics on people with existing psychiatric disorders. All study designs and gray literature were included. Medline, PsychInfo, CINAHL, EMBASE, and MedRx were searched from inception to September 1 2020. Risk of bias was assessed using a published tool that can accommodate all study types. Two independent authors screened the studies and extracted data. Data were narratively synthesized, as there were insufficient data to meta-analyze. Evidence was appraised according to GRADE. RESULTS: Four case reports were included, comprising 13 participants from three countries. Many large-sample, relevant papers were omitted for not reporting psychiatric history, despite reporting other comorbidities. Included participants (n = 13) were hospitalized with COVID-19 and appeared to meet criteria for delirium. Myoclonus, rigidity, and alogia were also reported. The most commonly reported preexisting psychiatric diagnoses were mood disorders, schizophrenia, and alcohol use disorder. CONCLUSIONS: People with preexisting psychiatric disorders may experience delirium, rigidity, myoclonus, and alogia during COVID-19 infection; although higher quality and longitudinal data are needed to better understand these phenomena. Relevant COVID-19 literature does not always report psychiatric history, despite heightened neuropsychiatric vulnerability within this population. TRIAL REGISTRATION:  PROSPERO (CRD42020179611).