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.

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.

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.

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.

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).

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.

Perceptions of shared decision making and decision aids among rural primary care clinicians.

BACKGROUND: Shared decision making (SDM) and decision aids (DAs) increase patients' involvement in health care decisions and enhance satisfaction with their choices. Studies of SDM and DAs have primarily occurred in academic centers and large health systems, but most primary care is delivered in smaller practices, and over 20% of Americans live in rural areas, where poverty, disease prevalence, and limited access to care may increase the need for SDM and DAs. OBJECTIVE: To explore perceptions and practices of rural primary care clinicians regarding SDM and DAs. DESIGN: Cross-sectional survey. Setting and Participants Primary care clinicians affiliated with the Oregon Rural Practice-based Research Network. RESULTS: Surveys were returned by 181 of 231 eligible participants (78%); 174 could be analyzed. Two-thirds of participants were physicians, 84% practiced family medicine, and 55% were male. Sixty-five percent of respondents were unfamiliar with the term shared decision making, but following definition, 97% reported that they found the approach useful for conditions with multiple treatment options. Over 90% of clinicians perceived helping patients make decisions regarding chronic pain and health behavior change as moderate/hard in difficulty. Although 69% of respondents preferred that patients play an equal role in making decisions, they estimate that this happens only 35% of the time. Time was reported as the largest barrier to engaging in SDM (63%). Respondents were receptive to using DAs to facilitate SDM in print- (95%) or web-based formats (72%), and topic preference varied by clinician specialty and decision difficulty. CONCLUSIONS: Rural clinicians recognized the value of SDM and were receptive to using DAs in multiple formats. Integration of DAs to facilitate SDM in routine patient care may require addressing practice operation and reimbursement.

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.

Change in Oregon maternity care workforce after malpractice premium subsidy implementation.

OBJECTIVES: (1) To determine the proportion of maternity care providers who continue to deliver babies in Oregon; (2) to determine the important factors relating to the decision to discontinue maternity care services; and (3) to examine how the rural liability subsidy is affecting rural maternity care providers' ability to provide maternity care services. STUDY DESIGN: We surveyed all obstetrical care providers in Oregon in 2002 and 2006. Survey data, supplemented with state administrative data, were analyzed for changes in provision of maternity care, reasons for stopping maternity care, and effect of the malpractice premium subsidy on practice. PRINCIPAL FINDINGS: Only 36.6% of responding clinicians qualified to deliver babies were actually providing maternity care in Oregon in 2006, significantly lower than the proportion (47.8%) found in 2002. Cost of malpractice premiums remains the most frequently cited reason for stopping maternity care, followed by lifestyle issues. Receipt of the malpractice subsidy was not associated with continuing any maternity services. CONCLUSIONS: Oregon continues to lose maternity care providers. A state program subsidizing the liability premiums of rural maternity care providers does not appear effective at keeping rural providers delivering babies. Other policies to encourage continuation of maternity care need to be considered.

Cervical cancer screening and updated Pap guidelines.

Cervical cancer and its dysplasia precursors account for significant morbidity and mortality in women worldwide. Human papillomavirus infection is common, preventable, and now widely accepted as the causative agent with oncogenic potential in the development of cervical cancer. Screening via Papanicolaou testing is critical, and interpretation of test results with knowledge of patient risk factors is imperative. Many evidence-based guidelines for screening, interpretation, and management have been developed and are widely available for use.

Venous thromboembolism during pregnancy.

Venous thromboembolism is the leading cause of maternal death in the United States. Pregnancy is a risk factor for deep venous thrombosis, and risk is further increased with a personal or family history of thrombosis or thrombophilia. Screening for thrombophilia is not recommended for the general population; however, testing for inherited or acquired thrombophilic conditions is recommended when personal or family history suggests increased risk. Factor V Leiden and prothrombin G20210A mutation are the most common inherited thrombophilias, and antiphospholipid antibody syndrome is the most important acquired defect. Clinical symptoms of deep venous thrombosis may be subtle and difficult to distinguish from gestational edema. Venous compression (Doppler) ultrasonography is the diagnostic test of choice. Pulmonary embolism typically presents postpartum with dyspnea and tachypnea. Multidetector-row (spiral) computed tomography is the test of choice for pulmonary embolism. Warfarin is contraindicated during pregnancy, but is safe to use postpartum and is compatible with breastfeeding. Low-molecular-weight heparin has largely replaced unfractionated heparin for prophylaxis and treatment in pregnancy.

Changing policies on vaginal birth after cesarean: impact on access.

BACKGROUND: The issue of vaginal birth after cesarean (VBAC) has become highly visible and contentious. In 1999, the American College of Obstetricians and Gynecologists advocated a policy that surgical capability be "immediately available" for women in labor attempting VBAC. METHODS: Every hospital in Colorado, Montana, Oregon, and Wisconsin was contacted by telephone at least once during the period 2003 to 2005. Using a semistructured interview, respondent hospitals were asked whether and when their policies for VBAC had changed and what was the availability of VBAC services before and after the 1999 policy was issued. RESULTS: Of 314 hospitals contacted, 312 responded to the survey (response rate 99.4%). Babies were delivered at 230 (74%) respondent hospitals. Almost one-third, 68 of 222 (30.6%), of responding delivery hospitals that previously offered VBAC services had stopped doing so; seven hospitals had never allowed VBAC. Of the hospitals that still allowed VBAC, 68 percent had changed their VBAC policies since 1999, with the most frequent changes requiring the in-house presence of surgery (53%) and anesthesia (44%) personnel when women desiring VBAC presented in labor. Compared with hospitals that stopped allowing VBAC, those that currently permit VBAC were larger (156.6 vs 58.1 beds, t = 7.02, p < 0.001), closer to other delivery hospitals (20.9 vs 39.2 miles, t = 4.33, p < 0.001), annually delivered more babies (1009.9 vs 458.3, t = 4.41, p < 0.001), and annually had more cesarean deliveries (226.7 vs 105.7, t = 3.91, p < 0.001). CONCLUSIONS: In the years following advocacy of the 1999 policy, the availability of VBAC services significantly decreased, especially among smaller or more isolated hospitals.

Diagnosis and testing in bronchiolitis: a systematic review.

BACKGROUND: The diagnosis of bronchiolitis is based on typical history and results of a physical examination. The indications for and utility of diagnostic and supportive laboratory testing (eg, chest x-ray films, complete blood cell counts, and respiratory syncytial virus testing) are unclear. OBJECTIVES: To review systematically the data on diagnostic and supportive testing in the management of bronchiolitis and to assess the utility of such testing. DESIGN: In conjunction with an expert panel, we generated admissibility criteria and derived relevant terms to search the literature published from 1980 to November 2002 in MEDLINE and the Cochrane Collaboration Database of Controlled Clinical Trials. Trained abstractors completed detailed data collection forms for each article. We summarized the data in tables after performing data integrity checks. RESULTS: Of the 797 abstracts identified, we present evidence from 82 trials that met our inclusion criteria (17 are primary articles on diagnosis of bronchiolitis and 65are reports of treatment or prevention trials). Numerous studies demonstrate that rapid respiratory syncytial virus tests have acceptable sensitivity and specificity, but no data show that respiratory syncytial virus testing affects clinical outcomes in typical cases of the disease. Seventeen studies presented chest x-ray film data. Abnormalities on chest x-ray films ranged from 20% to 96%. Insufficient data exist to show that chest x-ray films reliably distinguish between viral and bacterial disease or predict severity of disease. Ten studies included complete blood cell counts, but most did not present specific results. In one study, white blood cell counts correlated with radiologically defined disease categories of bronchiolitis. CONCLUSIONS: A large number of studies include diagnostic and supportive testing data. However, these studies do not define clear indications for such testing or the impact of testing on relevant patient outcomes. Given the high prevalence of this disease, prospective studies of the utility of such testing are needed and feasible.