Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in Adults: A Living Systematic Review.

BACKGROUND: The role of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) in coronavirus disease 2019 (COVID-19) susceptibility, severity, and treatment is unclear. PURPOSE: To evaluate, on an ongoing basis, whether use of ACEIs or ARBs either increases risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or is associated with worse COVID-19 disease outcomes, and to assess the efficacy of these medications for COVID-19 treatment. DATA SOURCES: MEDLINE (Ovid) and Cochrane Database of Systematic Reviews from 2003 to 4 May 2020, with planned ongoing surveillance for 1 year; the World Health Organization database of COVID-19 publications and medRxiv.org through 17 April 2020; and ClinicalTrials.gov to 24 April 2020, with planned ongoing surveillance. STUDY SELECTION: Observational studies and trials in adults that examined associations and effects of ACEIs or ARBs on risk for SARS-CoV-2 infection and COVID-19 disease severity and mortality. DATA EXTRACTION: Single-reviewer abstraction confirmed by another reviewer, independent evaluation by 2 reviewers of study quality, and collective assessment of certainty of evidence. DATA SYNTHESIS: Two retrospective cohort studies found that ACEI and ARB use was not associated with a higher likelihood of receiving a positive SARS-CoV-2 test result, and 1 case-control study found no association with COVID-19 illness in a large community (moderate-certainty evidence). Fourteen observational studies, involving a total of 23 565 adults with COVID-19, showed consistent evidence that neither medication was associated with more severe COVID-19 illness (high-certainty evidence). Four registered randomized trials plan to evaluate ACEIs and ARBs for treatment of COVID-19. LIMITATION: Half the studies were small and did not adjust for important confounding variables. CONCLUSION: High-certainty evidence suggests that ACEI or ARB use is not associated with more severe COVID-19 disease, and moderate-certainty evidence suggests no association between use of these medications and positive SARS-CoV-2 test results among symptomatic patients. Whether these medications increase the risk for mild or asymptomatic disease or are beneficial in COVID-19 treatment remains uncertain. PRIMARY FUNDING SOURCE: None. (PROSPERO: registration number pending).

Rapid Reviews Methods Series: Involving patient and public partners, healthcare providers and policymakers as knowledge users.

Rapid reviews (RRs) are a helpful evidence synthesis tool to support urgent and emergent decision-making in healthcare. RRs involve abbreviating systematic review methods and are conducted in a condensed timeline to meet the decision-making needs of organisations or groups that commission them. Knowledge users (KUs) are those individuals, typically patient and public partners, healthcare providers, and policy-makers, who are likely to use evidence from research, including RRs, to make informed decisions about health policies, programmes or practices. However, research suggests that KU involvement in RRs is often limited or overlooked, and few RRs include patients as KUs. Existing RR methods guidance advocates involving KUs but lacks detailed steps on how and when to do so. This paper discusses the importance of involving KUs in RRs, including patient and public involvement to ensure RRs are fit for purpose and relevant for decision-making. Opportunities to involve KUs in planning, conduct and knowledge translation of RRs are outlined. Further, this paper describes various modes of engaging KUs during the review lifecycle; key considerations researchers should be mindful of when involving distinct KU groups; and an exemplar case study demonstrating substantive involvement of patient partners and the public in developing RRs. Although involving KUs requires time, resources and expertise, researchers should strive to balance 'rapid' with meaningful KU involvement in RRs. This paper is the first in a series led by the Cochrane Rapid Reviews Methods Group to further guide general RR methods.

Rapid reviews methods series: Guidance on assessing the certainty of evidence.

This paper is part of a series of methodological guidance from the Cochrane Rapid Reviews Methods Group. Rapid reviews (RRs) use modified systematic review methods to accelerate the review process while maintaining systematic, transparent and reproducible methods. This paper addresses considerations for rating the certainty of evidence (COE) in RRs. We recommend the full implementation of GRADE (Grading of Recommendations, Assessment, Development and Evaluation) for Cochrane RRs if time and resources allow.If time or other resources do not permit the full implementation of GRADE, the following recommendations can be considered: (1) limit rating COE to the main intervention and comparator and limit the number of outcomes to critical benefits and harms; (2) if a literature review or a Delphi approach to rate the importance of outcomes is not feasible, rely on informal judgements of knowledge users, topic experts or team members; (3) replace independent rating of the COE by two reviewers with single-reviewer rating and verification by a second reviewer and (4) if effect estimates of a well-conducted systematic review are incorporated into an RR, use existing COE grades from such a review. We advise against changing the definition of COE or the domains considered part of the GRADE approach for RRs.

Electromyography tests in patients with implanted cardiac devices are safe regardless of magnet placement.

METHODS: We compared the problems or complications associated with electrodiagnostic testing in 77 patients with implanted cardiac devices. Thirty tests were performed after magnet placement, and 47 were performed without magnet application. RESULTS: All electrodiagnostic tests were performed safely in all patients without any serious effect on the implanted cardiac devices with or without magnet placement. A significantly higher number of patient symptoms and procedure changes were reported in the magnet group (P < 0.013). No statistical difference was found in the testing difficulty or ECG changes. CONCLUSION: The magnet group patients had an approximately 11-fold greater risk of symptoms than those in the control group. Our data do not support a recommendation that magnet placement is necessary for routine electrodiagnostic testing in patients with implanted cardiac devices, as long as our general and specific guidelines are followed.

Paper 2: Performing rapid reviews.

BACKGROUND: Health policy-makers must often make decisions in compressed time frames and with limited resources. Hence, rapid reviews have become a pragmatic alternative to comprehensive systematic reviews. However, it is important that rapid review methods remain rigorous to support good policy development and decisions. There is currently little evidence about which streamlined steps in a rapid review are less likely to introduce unacceptable levels of uncertainty while still producing a product that remains useful to policy-makers. METHODS: This paper summarizes current research describing commonly used methods and practices that are used to conduct rapid reviews and presents key considerations and options to guide methodological choices for a rapid review. RESULTS: The most important step for a rapid review is for an experienced research team to have early and ongoing engagement with the people who have requested the review. A clear research protocol, derived from a needs assessment conducted with the requester, serves to focus the review, defines the scope of the rapid review, and guides all subsequent steps. Common recommendations for rapid review methods include tailoring the literature search in terms of databases, dates, and languages. Researchers can consider using a staged search to locate high-quality systematic reviews and then subsequently published primary studies. The approaches used for study screening and selection, data extraction, and risk-of-bias assessment should be tailored to the topic, researcher experience, and available resources. Many rapid reviews use a single reviewer for study selection, risk-of-bias assessment, or data abstraction, sometimes with partial or full verification by a second reviewer. Rapid reviews usually use a descriptive synthesis method rather than quantitative meta-analysis. Use of brief report templates and standardized production methods helps to speed final report publication. CONCLUSIONS: Researchers conducting rapid reviews need to make transparent methodological choices, informed by stakeholder input, to ensure that rapid reviews meet their intended purpose. Transparency is critical because it is unclear how or how much streamlined methods can bias the conclusions of reviews. There are not yet internationally accepted standards for conducting or reporting rapid reviews. Thus, this article proposes interim guidance for researchers who are increasingly employing these methods.

Methods of induction of labour: a systematic review.

BACKGROUND: Rates of labour induction are increasing. We conducted this systematic review to assess the evidence supporting use of each method of labour induction. METHODS: We listed methods of labour induction then reviewed the evidence supporting each. We searched MEDLINE and the Cochrane Library between 1980 and November 2010 using multiple terms and combinations, including labor, induced/or induction of labor, prostaglandin or prostaglandins, misoprostol, Cytotec, 16,16,-dimethylprostaglandin E2 or E2, dinoprostone; Prepidil, Cervidil, Dinoprost, Carboprost or hemabate; prostin, oxytocin, misoprostol, membrane sweeping or membrane stripping, amniotomy, balloon catheter or Foley catheter, hygroscopic dilators, laminaria, dilapan, saline injection, nipple stimulation, intercourse, acupuncture, castor oil, herbs. We performed a best evidence review of the literature supporting each method. We identified 2048 abstracts and reviewed 283 full text articles. We preferentially included high quality systematic reviews or large randomised trials. Where no such studies existed, we included the best evidence available from smaller randomised or quasi-randomised trials. RESULTS: We included 46 full text articles. We assigned a quality rating to each included article and a strength of evidence rating to each body of literature. Prostaglandin E2 (PGE2) and vaginal misoprostol were more effective than oxytocin in bringing about vaginal delivery within 24 hours but were associated with more uterine hyperstimulation. Mechanical methods reduced uterine hyperstimulation compared with PGE2 and misoprostol, but increased maternal and neonatal infectious morbidity compared with other methods. Membrane sweeping reduced post-term gestations. Most included studies were too small to evaluate risk for rare adverse outcomes. CONCLUSIONS: Research is needed to determine benefits and harms of many induction methods.

Maternity Care Tracks at US Family Medicine Residency Programs.

BACKGROUND AND OBJECTIVES: The number of family physicians providing maternity care continues to decline, jeopardizing access to needed care for underserved populations. Accreditation changes in 2014 provided an opportunity to create family medicine residency maternity care tracks, providing comprehensive maternity care training only for interested residents. We examined the relationship between maternity care tracks and residents' educational experiences and postgraduate practice. METHODS: We included questions on maternity care tracks in an omnibus survey of family medicine residency program directors (PDs). We divided respondent programs into three categories: "Track," "No Track Needed," and "No Track." We compared these program types by their characteristics, number of resident deliveries, and number of graduates practicing maternity care. RESULTS: The survey response rate was 40%. Of the responding PDs, 79 (32%) represented Track programs, 55 (22%) No Track Needed programs, and 94 (38%) No Track programs. Residents in a track attended more deliveries than those not in a track (at Track programs) and those at No Track Needed and No Track programs. No Track Needed programs reported the highest proportion of graduates accepting positions providing inpatient maternity care in 2019 (21%), followed by Track programs (17%) and No Track programs (5%; P<.001). CONCLUSIONS: Where universal robust maternity care education is not feasible, maternity care tracks are an excellent alternative to provide maternity care training and produce graduates who will practice maternity care. Programs that cannot offer adequate experience to achieve competence in inpatient maternity care may consider instituting a maternity care track.

Cochrane Rapid Reviews Methods Group offers evidence-informed guidance to conduct rapid reviews.

OBJECTIVES: To develop methods guidance to support the conduct of rapid reviews (RRs) produced within Cochrane and beyond, in response to requests for timely evidence syntheses for decision-making purposes including urgent health issues of high priority. STUDY DESIGN AND SETTING: Interim recommendations were informed by a scoping review of the underlying evidence, primary methods studies conducted, and a survey sent to 119 representatives from 20 Cochrane entities, who were asked to rate and rank RR methods across stages of review conduct. Discussions among those with expertise in RR methods further informed the list of recommendations with accompanying rationales provided. RESULTS: Based on survey results from 63 respondents (53% response rate), 26 RR methods recommendations are presented for which there was a high or moderate level of agreement or scored highest in the absence of such agreement. Where possible, how recommendations align with Cochrane methods guidance for systematic reviews is highlighted. CONCLUSION: The Cochrane Rapid Reviews Methods Group offers new, interim guidance to support the conduct of RRs. Because best practice is limited by the lack of currently available evidence for some RR methods shortcuts taken, this guidance will need to be updated as additional abbreviated methods are evaluated.

Developing trustworthy recommendations as part of an urgent response (1-2 weeks): a GRADE concept paper.

OBJECTIVES: The aim of this study is to propose an approach for developing trustworthy recommendations as part of urgent responses (1-2 week) in the clinical, public health, and health systems fields. STUDY DESIGN AND SETTING: We conducted a review of the literature, outlined a draft approach, refined the concept through iterative discussions, a workshop by the Grading of Recommendations Assessment, Development and Evaluation Rapid Guidelines project group, and obtained feedback from the larger Grading of Recommendations Assessment, Development and Evaluation working group. RESULTS: A request for developing recommendations within 2 week is the usual trigger for an urgent response. Although the approach builds on the general principles of trustworthy guideline development, we highlight the following steps: (1) assess the level of urgency; (2) assess feasibility; (3) set up the organizational logistics; (4) specify the question(s); (5) collect the information needed; (6) assess the adequacy of identified information; (7) develop the recommendations using one of the 4 potential approaches: adopt existing recommendations, adapt existing recommendations, develop new recommendations using existing adequate systematic review, or develop new recommendations using expert panel input; and (8) consider an updating plan. CONCLUSION: An urgent response for developing recommendations requires building a cohesive, skilled, and highly motivated multidisciplinary team with the necessary clinical, scientific, and methodological expertise; adapting to shifting needs; complying with the principles of transparency; and properly managing conflicts of interest.

Accelerated Approval of 17α-Hydroxyprogesterone Caproate: A Cautionary Tale.

Before 2011, 17α-hydroxyprogesterone caproate (17P) was used to prevent recurrent preterm birth in women with singleton pregnancies and was compounded at a low cost (∼$15 per injection). In 2011, the U.S. Food and Drug Administration (FDA) approved a commercial version of 17P (trade name "Makena") through their Accelerated Approval Program, and the price of 17P subsequently increased by nearly 100-fold. This approval was largely based on a methodologically limited, placebo-controlled trial, which found that although 17P significantly reduced preterm births, the placebo group had significantly more participants with a history of preterm birth, potentially confounding the results. The FDA required a confirmatory trial for continued approval that demonstrated clinical benefit. Eight years after accelerated approval, the confirmatory trial, PROLONG (Progestin's Role in Optimizing Neonatal Gestation), found no evidence of an effect of Makena for reducing recurrent preterm birth or perinatal mortality. Trial completion triggered an automatic review of Makena by an advisory committee, which voted 9-7 to recommend revoking approval of Makena for preterm birth. Although the FDA created the Accelerated Approval Program to introduce therapies for serious conditions that lacked treatment options, Makena is an example of the limitations of this program. We encourage the FDA to re-evaluate their program and consider improvements, such as shorter timeframes to complete confirmatory trials, potentially revoking approval if the studies are not completed within a predefined timeframe, and to hold manufacturers responsible, in part, for the costs of therapy if they cannot prove a clinical benefit.

Colorectal Cancer Screening: An Educational Intervention for Nurse Practitioners to Increase Screening Awareness and Participation
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Colorectal cancer screening aims to detect colorectal cancer at an early stage, when treatment is more likely to be curative. Lack of participation in such screening is a major issue in primary care practices, where nurse practitioners (NPs) often provide care. This study aimed to determine whether an educational intervention for NPs would increase their awareness of, and increase patients' participation in, colorectal cancer screening. 
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Cochrane Rapid Reviews Methods Group to play a leading role in guiding the production of informed high-quality, timely research evidence syntheses.

BACKGROUND: Policymakers and healthcare stakeholders are increasingly seeking evidence to inform the policymaking process, and often use existing or commissioned systematic reviews to inform decisions. However, the methodologies that make systematic reviews authoritative take time, typically 1 to 2 years to complete. Outside the traditional SR timeline, "rapid reviews" have emerged as an efficient tool to get evidence to decision-makers more quickly. However, the use of rapid reviews does present challenges. To date, there has been limited published empirical information about this approach to compiling evidence. Thus, it remains a poorly understood and ill-defined set of diverse methodologies with various labels. In recent years, the need to further explore rapid review methods, characteristics, and their use has been recognized by a growing network of healthcare researchers, policymakers, and organizations, several with ties to Cochrane, which is recognized as representing an international gold standard for high-quality, systematic reviews. PURPOSE: In this commentary, we introduce the newly established Cochrane Rapid Reviews Methods Group developed to play a leading role in guiding the production of rapid reviews given they are increasingly employed as a research synthesis tool to support timely evidence-informed decision-making. We discuss how the group was formed and outline the group's structure and remit. We also discuss the need to establish a more robust evidence base for rapid reviews in the published literature, and the importance of promoting registration of rapid review protocols in an effort to promote efficiency and transparency in research. CONCLUSION: As with standard systematic reviews, the core principles of evidence-based synthesis should apply to rapid reviews in order to minimize bias to the extent possible. The Cochrane Rapid Reviews Methods Group will serve to establish a network of rapid review stakeholders and provide a forum for discussion and training. By facilitating exchange, the group will strive to conduct research to advance the methods of rapid reviews.

Ethnicity and prenatal depression: women's experiences and perspectives on communicating about their emotions and feelings during pregnancy.

The purpose of the study was to examine the relationship between ethnicity, the presence of moderate to severe symptoms of depression, and communication about emotions and feelings during prenatal visits. The purpose was also to describe women's perceptions of the barriers to communicating with providers, family, and friends about their emotions or feelings and how to overcome these barriers. Seventy-three women were recruited and interviewed by a bilingual research assistant between June and September 2002 after a prenatal visit occurring between 12- and 32-week gestation. Nineteen percent of women screened as having moderate to severe symptoms of depression. Quality of social relationships had a significant negative relationship with whether women had moderate to severe symptoms of depression. Almost 29% of women reported discussing their emotions or feelings with their providers and this did not differ significantly by ethnicity. Women who discussed their emotions or feelings with their providers did have significantly higher scores on the Beck Depression Inventory-II (BDI-II) than those who did not. Thirty-four percent of women stated that there were barriers to expectant or new mothers communicating with their providers. Women who felt that there were barriers to expectant or new mothers discussing their emotions with their providers did have significantly higher BDI-II scores than those women who did not. Thirty-seven percent of women believed that there were barriers to expectant or new mothers communicating with their family about their emotions. Women felt that providers and families could try to develop trust with them and try to make them feel more comfortable discussing their feelings.

Ethnicity and depression treatment preferences of pregnant women.

African American, Hispanic, and White women between 12 and 32 weeks gestation were recruited to examine their depression treatment preferences. The 73 women who participated were interviewed after their prenatal visit. Nineteen percent of women had symptoms of moderate or severe depression. Women with moderate or severe symptoms of depression were more likely to believe that antidepressants were an acceptable treatment than those without symptoms or with only minor depression symptoms. There were only small differences among the three ethnic groups for antidepressant use preference but most women found them to be unacceptable. In contrast, approximately half of the White women felt that herbal medicines were acceptable compared with 16 and 22 percent for African Americans and Hispanics, respectively. Only 44 percent of African American women felt that counseling from a mental health professional was an acceptable treatment for depression compared to 68 percent for White and 61 percent for Hispanic women. Similarly, African American women were less likely to believe that waiting and getting over depression symptoms naturally was acceptable compared to Hispanic and White women.