Advanced Search

Completed Systematic Reviews




The Use of Chloroquine and Hydroxychloroquine for Prophylaxis and Treatment of COVID-19


Public Project Complete

Statistics: 24 Studies, 1 Key Question, 1 Extraction Form,
Date Published: May 29, 2020 06:30PM
Description: The purpose of this review is to determine if hydroxychloroquine or chloroquine is effective and safe when used alone or when combined with azithromycin for the prophylaxis and treatment of COVID-19.
Contributor(s): Adrian V. Hernandez, MD, PhD; Yuani M. Roman, MD, MPH; Vinay Pasupuleti, MD, MS, PhD; Joshuan J. Barboza, MSc; C. Michael White, PharmD.
DOI: DOI pending.
Funding Source: Prepared by the University of Connecticut Evidence-based Practice Center under Contract No. HHSA290-2015-00012I | Task Order 1
Methodology Description: On May 8, 2020, we comprehensively searched: PubMed-Medline, EMBASE-OVID, Scopus, Web of Science, the Cochrane Library, pre-prints and pre-proofs from the following web pages: http://eppi.ioe.ac.uk/COVID19_MAP/covid_map_v3.html, https://connect.biorxiv.org/relate/content/181, https://www.preprints.org/, and Trial registry websites of the WHO, USA, and China: https://www.who.int/ictrp/en/, www.clinicaltrials.gov, and http://www.chictr.org.cn/. The searches were very broad containing the agents under investigation “hydroxychloroquine or chloroquine” and the virus or disease state “SARS-CoV-2 or COVID-19”. As such, it would capture efficacy and harm outcome studies as well as active treatment and prophylaxis studies. We did not predefine outcomes to allow the broadest assessment of the literature base available. Three investigators independently selected studies, and disagreements were resolved by discussion. We used a pre-defined extraction sheet that was modified dynamically as new outcomes were identified in the studies. Extractions were performed independently by two authors and revised by two other authors. Discrepancies in extractions were resolved by discussion. Risk of bias assessments were performed independently by two investigators in comparative studies using the ROBINS-I tool for non-randomized studies of interventions and the Cochrane risk of bias 2.0 tool for randomized controlled trials. Discrepancies in risk of bias assessments were resolved by discussion. We only performed random effects meta-analyses of two RCTs for dichotomous outcomes. The inverse variance method was used, and effects were described as relative risks (RR) and their 95% confidence intervals. Heterogeneity of effects between RCTs were described with the I2 statistic, being a value >60% considered high heterogeneity. The certainty or quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach (27). GRADE profile v2 tables were developed in GRADEpro Guideline Development Tool.

Zoom Preview | Show Downloadable Content

Interventions for Substance Use Disorders in Adolescents: A Systematic Review


Public Project Complete

Statistics: 118 Studies, 1 Key Question, 1 Extraction Form,
Date Published: May 19, 2020 09:56PM
Description: The review aims to inform health care providers, policymakers, and a clinical practice guideline update from the American Academy of Child and Adolescent Psychiatry (AACAP) about the currently available evidence on interventions for adolescents to reduce or cease substance use. The review addresses both behavioral and pharmacological interventions used for adolescents or young adults with problematic substance use or a diagnosis of a substance use disorder (SUD), excluding tobacco.
Contributor(s): Dale W. Steele, Sara J. Becker, Kristin J. Danko, Ethan M. Balk, Ian J. Saldanha, Gaelen P. Adam, Sarah M. Bagley, Catherine Friedman. Anthony Spirito, Kelli Scott, Evangelia E. Ntzani, Iman Saeed, Bryant Smith, Jonah Popp, Thomas A. Trikalinos
DOI: DOI pending.
Funding Source: HHSA 290-2015-00002-I
Methodology Description: We conducted literature searches in MEDLINE, the Cochrane CENTRAL Trials Registry, Embase, CINAHL, and PsycINFO databases (all from inception) to identify primary studies meeting our criteria through April 11, 2019. As a part of an independent methods project, an interim search of MEDLINE was undertaken using text mining tools on October 30, 2018. A separate search for SRs of interventions for alcohol disorders/problematic alcohol use in the college setting was conducted in MEDLINE, Cochrane Database of Systematic Reviews, and Epistemonikos also through April 11, 2019; after discussion with the Technical Expert Panel (TEP), it was decided to restrict the review of this topic to existing SRs because the literature is vast and has been extensively reviewed. The literature search yielded 33,272 citations. We found 118 randomized controlled trials that evaluated treatment of adolescents or young adults with problematic substance use or substance use disorders.

Zoom Preview | Show Downloadable Content

Primary Care Relevant Interventions for Tobacco and Nicotine Use Prevention and Cessation in Children and Adolescents: A Systematic Review for the U.S. Preventive Services Task Force


Public Project Complete

Statistics: 26 Studies, 3 Key Questions, 1 Extraction Form,
Date Published: May 19, 2020 04:57PM
Description: Structured Abstract Background: Interventions to discourage use of tobacco products among children and adolescents may help decrease tobacco-related illness. Tobacco products for this review include electronic nicotine delivery systems, often referred to as e-cigarettes. Purpose: To systematically update the 2013 U.S. Preventive Services Task Force (USPSTF) review on primary care relevant interventions for tobacco use prevention and cessation in children and adolescents. Data Sources: We searched the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews, MEDLINE, PsycINFO, and EMBASE (September 1, 2012 to June 25, 2019) with surveillance through February 7, 2020. Study Selection: We selected primary care relevant studies based on inclusion and exclusion criteria developed for each key question. We included randomized and nonrandomized controlled trials of children and adolescents up to 18 years of age for cessation and 25 years of age for prevention. Trials that compared behavioral or pharmacological interventions with a no or minimal smoking intervention control group (e.g., usual care, attention control, wait list) were included. Data Extraction: One investigator abstracted data and a second investigator checked data abstraction for accuracy. Two investigators independently assessed study quality using methods developed by the USPSTF. Data Synthesis (Results): Twenty-six trials met inclusion criteria. Behavioral interventions were associated with decreased likelihood of smoking initiation compared with control interventions (k=13, n=21,700; 7.4% vs. 9.2%; relative risk [RR] 0.82, 95% confidence interval [CI] 0.73 to 0.92). In trials restricted to smokers, behavioral interventions had no effect on smoking prevalence (k=9, n=2,516, 80.7% vs. 84.1% continued smoking, RR 0.97, 95% CI, 0.93 to 1.01). Behavioral interventions were more effective than control interventions at decreasing smoking prevalence in trials of smokers and nonsmokers (k=7, n=10,533; 16.8% vs. 20.1%; RR 0.91, 95% CI, 0.83 to 0.995). However, these results were sensitive to inclusion of two trials of very intensive interventions. Two trials of bupropion and one trial of nicotine replacement therapy found no significant benefits of medication on likelihood of smoking cessation. One trial each found no evidence for a beneficial intervention effect on health outcomes or on adult smoking. Limitations: Few trials addressed the prevention or cessation of tobacco products other than cigarettes; no trials evaluated effects of interventions on e-cigarette use. Trials of pharmacotherapy were few and had small sample sizes. Conclusions: Behavioral interventions can reduce the likelihood of smoking initiation in nonsmoking youth and young adults. Research is needed to identify effective behavioral interventions for youth who smoke or who use other tobacco products and to understand the effectiveness of pharmacotherapy on cessation. Due to the rapid escalation of e-cigarette use among youth, both prevention and cessation trials that target and/or include e-cigarettes are imminently needed.
Contributor(s): Shelley Selph, MD, MPH Carrie D. Patnode, PhD, MPH Steffani R. Bailey, PhD Miranda Pappas, MA Ryan Stoner, PhD Erica Hart, MST Roger Chou, MD
DOI: DOI pending.
Funding Source: Agency for Healthcare Research and Quality
Methodology Description: Data Sources: We searched the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews, MEDLINE, PsycINFO, and EMBASE (September 1, 2012 to June 25, 2019) with surveillance through February 7, 2020. Study Selection: We selected primary care relevant studies based on inclusion and exclusion criteria developed for each key question. We included randomized and nonrandomized controlled trials of children and adolescents up to 18 years of age for cessation and 25 years of age for prevention. Trials that compared behavioral or pharmacological interventions with a no or minimal smoking intervention control group (e.g., usual care, attention control, wait list) were included. Data Extraction: One investigator abstracted data and a second investigator checked data abstraction for accuracy. Two investigators independently assessed study quality using methods developed by the USPSTF.

Zoom Preview | Show Downloadable Content

Pharmacologic and Nonpharmacologic Treatments for Posttraumatic Stress Disorder: Groundwork for a Publicly Available Repository of Randomized Controlled Trial Data


Public Project Complete

Statistics: 318 Studies, 2 Key Questions, 1 Extraction Form,
Date Published: May 19, 2020 04:57PM
Description: Background. Posttraumatic stress disorder (PTSD) reduces quality of life and functioning. People with PTSD have symptoms such as intrusive thoughts, nightmares, flashbacks, avoidance of trauma-related stimuli, negative beliefs about oneself and/or others, and hypervigilance. The symptoms may be due to direct or indirect exposure to trauma, such as witnessing actual or threatened death, injury, or violence including sexual violence and threats of harm. Although recent clinical practice guidelines and reviews exist, providing a single, updatable source of PTSD treatment trials would be useful for clinicians, researchers, and policymakers. Purpose. To provide detailed information on PTSD treatment research, we systematically abstracted data from randomized controlled trials (RCTs) of PTSD interventions. The National Center for Posttraumatic Stress Disorder (NCPTSD) intends to use the data to develop a publicly available data repository. The NCPTSD is part of the U.S. Department of Veterans Affairs. Data Sources. We searched PTSDpubs (formerly PILOTS), Ovid® MEDLINE®, Cochrane CENTRAL, PsycINFO®, Embase®, CINAHL®, and Scopus® for eligible RCTs and reviewed reference lists of selected systematic reviews and clinical practice guidelines. Methods. In consultation with NCPTSD, we established inclusion criteria for RCTs and specific data elements to be abstracted. We dually reviewed citations from the literature search, and then the full text of potentially includable articles for eligibility, resolving any disagreements using consensus. One team member abstracted data from included RCTs into evidence tables, and a second reviewer checked abstracted data for accuracy and completeness. The primary publication for each RCT was abstracted; data and citations from any secondary publications (i.e., companion papers) appear in the same record. Findings. We identified 318 RCTs of PTSD interventions for abstraction (106 pharmacologic studies and 212 nonpharmacologic studies) published from 1988 to 2018, with a peak number of publications (31) in 2015. Psychotherapeutic interventions were the most commonly studied (55%), whereas 30 percent evaluated pharmacologic interventions. Most studies were conducted in the United States (61%), and most had sample sizes in the range of 25 to 100 participants (60% of studies) with a relatively small number of studies enrolling fewer than 25 participants (18%). More studies enrolled participants from a community population (57%) than from a military, veteran or other population, and the majority of studies were conducted in the outpatient setting (67%). Studies most often enrolled participants with a mix of trauma types (51%), followed by studies of participants with combat-related trauma (20%). Although there was wide variation, the most commonly used PTSD assessment methods were the Clinician-Administered PTSD Scale (CAPS) and the Structured Clinical Interview for DSM (SCID). Less than half of the studies reported loss of PTSD diagnosis or clinically meaningful response/remission of symptoms. Several other data elements were infrequently reported, including the number of participants with a history of traumatic brain injuries and the number of trauma types. Conclusions. The data abstracted from 318 RCTs of treatments for PTSD can be used to create a publicly available data repository. By identifying important gaps in the research, such a data repository can inform future study design and conduct.
Contributor(s): Maya O’Neil, Ph.D. Marian McDonagh, Pharm.D. Frances Hsu, M.S. Tamara Cheney, M.D. Kathleen Carlson, Ph.D., M.S. Rebecca Holmes, M.D., M.S. Shaun Ramirez, M.P.H. Erica Hart, M.S.T. Katrina Murphy, B.S. Elaine Graham, M.L.S. Roger Chou, M.D.
DOI: DOI pending.
Funding Source: Agency for Healthcare Research and Quality (AHRQ)
Methodology Description: Methods. In consultation with NCPTSD, we established inclusion criteria for RCTs and specific data elements to be abstracted. We dually reviewed citations from the literature search, and then the full text of potentially includable articles for eligibility, resolving any disagreements using consensus. One team member abstracted data from included RCTs into evidence tables, and a second reviewer checked abstracted data for accuracy and completeness. The primary publication for each RCT was abstracted; data and citations from any secondary publications (i.e., companion papers) appear in the same record.

Zoom Preview | Show Downloadable Content

Noninvasive Testing for Coronary Artery Disease [Entered Retrospectively]


Public Project Complete

Statistics: 46 Studies, 6 Key Questions, 1 Extraction Form,
Date Published: May 18, 2020 06:44PM
Description: Structured Abstract Objectives. This report evaluates the current state of evidence regarding effectiveness and harms of noninvasive technologies for the diagnosis of coronary artery disease (CAD) or dysfunction that results in symptoms attributable to myocardial ischemia in stable symptomatic patients who have no known history of CAD. Data sources. Systematic searches of the following databases were conducted through July 2015: Ovid MEDLINE®, Cochrane CENTRAL, Cochrane Database of Systematic Reviews, and Evidence-Based Medicine Reviews–Health Technology Assessment. Bibliographies of relevant articles were also reviewed. Review methods. Using predefined criteria, randomized controlled trials (RCTs) and observational studies comparing the effectiveness or safety of noninvasive cardiac testing—stress electrocardiography (ECG), stress echocardiography, single-photon emission computed tomography (SPECT), positron emission tomography, coronary computed tomography angiography (CCTA), and calcium scoring via computed tomography—with other noninvasive tests, usual care, or no testing were included. Analyses were stratified by pretest risk of CAD as reported by the authors. The quality of included studies was assessed, data extracted, and results summarized qualitatively and using meta-analysis where feasible. The strength of the evidence was assessed for primary outcomes to reflect the confidence in effect estimates: high strength of evidence (greatest confidence), moderate (moderate confidence), low (low confidence), and insufficient (no evidence or no confidence in the estimate). Results. From 17,146 citations identified, 46 studies were included. Definition of pretest risk across studies varied. There was no clear difference in myocardial infarction (MI) or in all-cause mortality between different testing strategies across settings or pretest risk groups that included patients with intermediate pretest risk, based on low- to moderate-strength evidence from nine trials. Across studies, the frequency was low for all-cause mortality (0%–1.5% in outpatient settings, 0%–1.1% in emergency department [ED] settings past the initial visit) and for MI (0%–0.8% in outpatients, 0%–3% in ED settings). Invasive coronary angiography (ICA) was more common following CCTA than following various functional tests, with a large trial of CCTA versus functional testing providing high-strength evidence. Revascularization referral was more common following CCTA versus functional testing in general (high strength of evidence) and versus exercise ECG (low strength of evidence) but was similar compared with SPECT and usual care (low strength of evidence). In ED settings, additional testing was more common following CCTA than following SPECT (high strength of evidence) but less common versus usual care (moderate strength of evidence). Hospitalization was less common following CCTA than following usual care at the initial ED visit (moderate evidence for intermediate pretest risk; low evidence for low to intermediate pretest risk), but similar for CCTA and functional testing in outpatient settings (moderate strength of evidence). Few studies compared functional tests, and findings were inconsistent for ICA and revascularization referral; however, additional noninvasive testing was less common with SPECT than with exercise ECG (low strength of evidence for all outcomes). The impact of testing on post-test probability of CAD and subsequent clinical decisions regarding treatment or further testing was not described in RCTs. Harms were rarely reported, and limited information regarding radiation exposure was provided. Conclusions. A review of current studies found no clear differences between testing strategies across settings with regard to clinical or management outcomes on which to base recommendations for one strategy over another for any given pretest risk group that included patients with intermediate pretest risk. No conclusions regarding low-risk patients or high-risk patients without ACS are possible. Limited evidence from RCTs found no clear differences between CCTA and other strategies in clinical outcomes across risk groups, although anatomic testing may result in a higher frequency of referral for ICA and revascularization. The frequency of all-cause mortality and MI was low across studies in all settings. The absence of information on post-test risk stratification and subsequent decisionmaking precluded evaluation of the impact of testing on patient management or outcomes. Testing strategies vary in radiation exposure; there is inadequate comparative evidence to make judgments regarding exposure for the initial test or downstream testing. Assessment of harms was limited. Future research using more refined evidence-based definitions of pretest risk, coupled with information on post-test risk stratification, its impact on clinical management (treatment and referral for additional testing), and longer term followup to assess clinical outcomes, are needed to determine optimal testing strategies and roles of tests in different pretest risk groups.
Contributor(s): Andrea C. Skelly, Ph.D., M.P.H. Robin Hashimoto, Ph.D. David I. Buckley, M.D., M.P.H. Erika D. Brodt, B.S. North Noelck, M.D., Ph.D. Annette M. Totten, Ph.D. Jonathan R. Lindner, M.D. Rongwei Fu, Ph.D. Marian McDonagh, Pharm.D.
Funding Source: Prepared by The Pacific Northwest Evidence-based Practice Center, Oregon Health & Science University for: Agency for Healthcare Research and Quality U.S. Department of Health and Human Services 5600 Fishers Lane Rockville, MD 20857 www.ahrq.gov Contract: HHSA 290201200014I.
Methodology Description: Review methods. Using predefined criteria, randomized controlled trials (RCTs) and observational studies comparing the effectiveness or safety of noninvasive cardiac testing—stress electrocardiography (ECG), stress echocardiography, single-photon emission computed tomography (SPECT), positron emission tomography, coronary computed tomography angiography (CCTA), and calcium scoring via computed tomography—with other noninvasive tests, usual care, or no testing were included. Analyses were stratified by pretest risk of CAD as reported by the authors. The quality of included studies was assessed, data extracted, and results summarized qualitatively and using meta-analysis where feasible. The strength of the evidence was assessed for primary outcomes to reflect the confidence in effect estimates: high strength of evidence (greatest confidence), moderate (moderate confidence), low (low confidence), and insufficient (no evidence or no confidence in the estimate).

Zoom Preview | Show Downloadable Content