Drug-induced orthostatic hypotension: A systematic review and meta-analysis of randomised controlled trials

Background Drug-induced orthostatic hypotension (OH) is common, and its resulting cerebral hypoperfusion is linked to adverse outcomes including falls, strokes, cognitive impairment, and increased mortality. The extent to which specific medications are associated with OH remains unclear. Methods and findings We conducted a systematic review and meta-analysis to evaluate the extent to which specific drug groups are associated with OH. EMBASE, MEDLINE, and Web of Science databases were searched from inception through 23 November 2020. Placebo-controlled randomised controlled trials (RCTs) on any drug reporting on OH as an adverse effect in adults (≥18 years) were eligible. Three authors extracted data on the drug, OH, dose, participant characteristics, and study setting. The revised Cochrane risk-of-bias tool for randomised trials (RoB 2) was used to appraise evidence. Summary odds ratios (ORs) were estimated for OH using fixed effects Mantel–Haenszel statistics. We conducted subgroup analysis on validity of OH measurement, drug dose, risk of bias, age, and comorbidity. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool was used to summarise the certainty of evidence. Of 36,940 citations, 69 eligible RCTs were included in the meta-analysis comprising 27,079 participants. Compared with placebo, beta-blockers and tricyclic antidepressants were associated with increased odds of OH (OR 7.76 [95% CI 2.51, 24.03]; OR 6.30 [95% CI 2.86, 13.91]). Alpha-blockers, antipsychotics, and SGLT-2 inhibitors were associated with up to 2-fold increased odds of OH, compared to placebo. There was no statistically significant difference in odds of OH with vasodilators (CCBs, ACE inhibitors/ARBs, SSRIs), compared to placebo. Limitations of this study are as follows: data limited to placebo-controlled studies, (excluding head-to-head trials), many RCTs excluded older participants; therefore results may be amplified in older patients in the clinical setting. The study protocol is publicly available on PROSPERO (CRD42020168697). Conclusions Medications prescribed for common conditions (including depression, diabetes, and lower urinary tract symptoms) were associated with significantly increased odds of OH. Drugs causing sympathetic inhibition were associated with significantly increased odds of OH, while most vasodilators were associated with small nonsignificant differences in odds of OH, compared to placebo. Drugs targeting multiple parts of the orthostatic blood pressure (BP) reflex pathway (e.g. sympathetic inhibition, vasodilation, cardio-inhibitory effects) may carry cumulative risk, suggesting that individuals with polypharmacy could benefit from postural BP monitoring.

Humanitarian Evidence Summary No.20

This is the 20th monthly Humanitarian Evidence Summary (HUMES) to signpost FCDO and other UK government departments to the latest relevant evidence and discourse on humanitarian action to inform and support their response. It is the result of 1 day of work per month and is not intended to be a comprehensive summary of available evidence on humanitarian action but aims to make original documents easily accessible to decision-makers that, if relevant to them, they could refer to before making decisions.

Nudges as Behavior Change Interventions to Improve Health and Well-Being. Protocol for a scoping review (Preprint)

UNSTRUCTURED Objective Our objective is to map and summarize the evidence on nudges that assess behavior change interventions to improve health and well-being. Design This is the protocol for a scoping review Data source A comprehensive search will be conducted on Cochrane database of systematic reviews (CDSR); Database of Abstracts of Reviews of Effectiveness (DARE); HTA Database; PubMed; LILACS; CINAHL; PsyclNFO; EMBASE; EPPI-Centre Evidence Library; WHO institutional Repository for information Sharing; NICE public health guidelines and systematic reviews; through an advanced search in the Epistemonikos platform. The search will cover the period until the day before this protocol is submitted to a journal. Eligibility criteria for study selection and methods Only systematic reviews (SR) will be included, which are operationally defined as any secondary research that includes only primary clinical studies, with the above search strategy applied in at least two databases that have assessed the use of nudges related to health, including SR of broader scope. Primary studies, clinical practice guides, abstracts and other evidence summary designs will be excluded. The electronic search results will be added according to the inclusion criteria. This manuscript will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) [10] Ethics and Dissemination Ethical approval is deemed unnecessary. The results of this review will be widely disseminated through peer reviewed publications, social networks and traditional media.

94 Short-term use of therapeutic opioids for children and future opioid use disorders: A systematic review and qualitative study of decision-maker information needs

Primary Subject area Emergency Medicine - Paediatric Background Healthcare visits, hospitalizations, and deaths due to opioid-related harms continue to rise for children, despite an overall decline in opioid prescriptions. Decision-makers (including patients and families, clinicians, and policy-makers) require high quality syntheses to inform decisions regarding opioid use. Previous research has found that how systematic review (SR) results are presented may influence uptake by decision-makers. Evidence summaries are appealing to decision-makers as they provide key messages in a succinct manner. Objectives 1) To conduct an SR examining the association between short-term therapeutic exposure to opioids in children and development of opioid use disorder, and 2) To gain perspectives from policy decision-makers on the usability and presentation of results through the form of an evidence summary. Design/Methods We conducted an SR following methods recommended by Cochrane. A medical librarian conducted a comprehensive search and two authors were involved in study selection, data extraction and quality assessment. Studies were eligible if they reported primary research in English or French, and study participants had therapeutic exposure to opioids before age 18 years. Results were described narratively. Decision makers were recruited through purposive and snowball sampling methods, and they participated in interviews to discuss an evidence summary based on the SR. Interviews were transcribed and data were analyzed using content analysis. Ethics approval was obtained for the qualitative study. Results Nineteen American studies involving 47,191,990 participants were included. One study demonstrated that short-term therapeutic exposure may be associated with opioid abuse. Four others showed an association without specifying duration of exposure. Fourteen studies provided information on prevalence or incidence of opioid misuse following therapeutic exposure, median 27.8% [interquartile range 21.4% – 30.7%]; notably, 12 of them did not specify duration of therapeutic exposure. Identified risk factors were contradictory and remain unclear. Decision makers had mixed preferences for the presentation of evidence, depending on their degree of involvement in research versus practice. A majority preferred having methods and key characteristics of studies included in the first page of the evidence summary. They noted that the summary should not be text-heavy and details should be appended. Conclusion A number of studies suggest there is an association between lifetime therapeutic opioid use (unknown duration) and future nonmedical opioid use; however, there is limited evidence to determine whether short-term exposure is specifically associated with these outcomes. Policy and decision-makers prefer a succinct evidence summary for this SR, with study-specific details provided as an appendix. PROSPERO Registration: 122681.

Humanitarian Evidence Summary No.18

This is the 18th monthly Humanitarian Evidence Summary (HUMES) to signpost FCDO and other UK government departments to the latest relevant evidence and discourse on humanitarian action to inform and support their response. It is the result of 1 day of work per month and is not intended to be a comprehensive summary of available evidence on humanitarian action but aims to make original documents easily accessible to decision-makers that, if relevant to them, they could refer to before making decisions.

Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults

This clinical practice guideline is a focused update on management of Clostridioides difficile infection (CDI) in adults specifically addressing the use of fidaxomicin and bezlotoxumab for the treatment of CDI. This guideline was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA). This guideline is intended for use by healthcare professionals who care for adults with CDI, including specialists in infectious diseases, gastroenterologists, hospitalists, pharmacists, and any clinicians and healthcare providers caring for these patients. The panel’s recommendations for the management CDI are based upon evidence derived from topic-specific systematic literature reviews. Summarized below are the recommendations for the management of CDI in adults. The panel followed a systematic process which included a standardized methodology for rating the certainty of the evidence and strength of recommendation using the GRADE approach (Grading of Recommendations Assessment, Development, and Evaluation). A detailed description of background, methods, evidence summary and rationale that support each recommendation, and knowledge gaps can be found online in the full text.

Humanitarian Evidence Summary No.17

This is the 17th monthly Humanitarian Evidence Summary (HUMES) to signpost FCDO and other UK government departments to the latest relevant evidence and discourse on humanitarian action to inform and support their response. It is the result of 1 day of work per month and is not intended to be a comprehensive summary of available evidence on humanitarian action but aims to make original documents easily accessible to decision-makers that, if relevant to them, they could refer to before making decisions.