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Completed Systematic Reviews




Interventions for Drug Use – Supplemental Report: A Systematic Review for the U.S. Preventive Services Task Force [Entered Retrospectively]


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Statistics: 91 Studies, 6 Key Questions, 1 Extraction Form,
Date Published: Jan 20, 2021 09:44PM
Description: Background: A U.S. Preventive Services Task Force (USPSTF) report found no consistent evidence that counseling interventions are effective at reducing drug use or improving other health outcomes in populations whose drug use was identified through primary care-based screening with questions about drug use or drug-related risks (i.e., “screen-detected populations”). Evidence from studies of persons seeking or referred for treatment for substance use or with clinical signs or symptoms of substance use (i.e., “treatment-seeking populations”) might also be useful for informing assessments regarding screening in primary care settings. Purpose: This report updates a 2008 USPSTF report on screening for illicit drug use and supplements an updated USPSTF report on screening for any drug use, focusing on the benefits and harms of pharmacotherapy and psychosocial interventions for persons whose drug use was identified when seeking substance use treatment, when presenting with signs or symptoms of drug use, when screened for drug use in primary care or other settings with questions about drug use or drug-related risks, or other means. Data Sources: The Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Ovid MEDLINE, Embase, and PsycINFO from inception to September 2018; surveillance for new literature was conducted through November 22, 2019. Study Selection: We included trials of Food and Drug Administration (FDA)-approved pharmacotherapies for opioid use disorder (methadone, buprenorphine, and naltrexone) and trials of psychosocial interventions for persons engaging in opioid, stimulant, cannabis, and mixed drug or polysubstance use. We also included trials of preemptive prescribing of naloxone in primary care settings as a rescue medication for opioid-related overdose. Trials compared included interventions against placebo, a minimal intervention, waitlist control, or usual care, and evaluated outcomes at >3 months for drug use or other risky behaviors; health, social, and legal consequences of drug use; or harms of treatment. 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): We included a total of 71 trials, with 19 trials of pharmacotherapies and 52 trials of psychosocial interventions. All trials of pharmacotherapies and 25 trials of psychosocial interventions were conducted in treatment-seeking populations. Psychosocial interventions commonly incorporated cognitive-behavioral or motivational interventions and ranged from brief interventions consisting of one or two sessions of no more than one hour to multiple treatment sessions over weeks or months. In most pharmacotherapy trials, drug use counseling was provided to all patients. No study evaluated benefits or harms of preemptive naloxone prescribed in primary care settings versus placebo or no naloxone as a rescue medication for opioid-related overdose. In treatment-seeking populations with opioid use disorder, naltrexone (12 trials; relative risk [RR] 0.73, 95% confidence interval [CI] 0.62 to 0.85; number needed to treat [NNT] 5.3) and opioid agonist therapy with methadone or buprenorphine (4 trials; RR 0.75, 95% CI 0.59 to 0.82; NNT 2.9) were associated with decreased risk of drug use relapse compared with placebo or no pharmacotherapy. Naltrexone and methadone/buprenorphine therapy were also associated with increased likelihood of retention in substance use treatment (9 trials; RR 1.71, 95% CI 1.13 to 2.49; NNT 6.7 and 7 trials; RR 2.58, 95% CI 1.78 to 4.59; NNT 2.6; respectively). Evidence on harms of pharmacotherapies was limited, but indicated no increased risk of serious adverse events. Psychosocial interventions were associated with increased likelihood of abstinence from drug use versus control conditions at 3 to 4 months (15 trials, RR 1.60, 95% CI 1.24 to 2.13; NNT 11) and at 6 to 12 months (14 trials; RR 1.25, 95% CI 1.11 to 1.52; NNT 17), based on trials primarily conducted in treatment-seeking populations. Psychosocial interventions were also associated with a greater decrease versus control conditions in the number of drug use days (19 trials; mean difference -0.49 day in the last 7 days, 95% CI -0.85 to -0.13) and a small but statistically significant greater decrease in drug use severity (16 trials; standard mean difference -0.18, 95% CI -0.32 to -0.05) at 3- to 4-month followup. There was no difference between psychosocial interventions versus controls on drug use days or severity at longer (6 to 12 month) followup. Effects of psychosocial interventions were generally stronger in trials of treatment-seeking than screen-detected populations, trials that evaluated cannabis use than other types of drug use, and trials of more intensive than brief interventions. Few trials evaluated effects of psychosocial interventions for opioid or stimulant use, and estimates were imprecise. Limitations: Limitations included restriction to English-language articles, statistical heterogeneity in pooled analyses, and little evidence on drug-related health, social, or legal outcomes; most trials had methodological limitations. Evidence was lacking on effectiveness of treatments for opioid use disorder related to prescription drug use or stimulant use and evidence was limited for adolescents or pregnant persons. Conclusions: Pharmacotherapy and psychosocial interventions are effective at improving drug use outcomes, but evidence of effectiveness remains primarily derived from trials conducted in treatment-seeking populations. Although the applicability of data from such trials to persons whose drug use is identified through primary care-based screening is uncertain, intervention trials that enrolled patients based on screening identified a spectrum of drug use, ranging from mild drug use to more severe, untreated disease. The applicability of current evidence on drug use interventions to screening might be greater for the subset of patients screened in primary care settings with severe, untreated drug use who could utilize pharmacotherapies or more intensive psychosocial interventions.
Contributor(s): Roger Chou, MD Tracy Dana, MLS Ian Blazina, MPH Sara Grusing, BA Rongwei Fu, PhD Christina Bougatsos, MPH
DOI: DOI pending.
Funding Source: This report is based on research conducted by the Pacific Northwest Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. HHSA-290-2015-00007-I, Task Order No. 4)
Methodology Description: Study Selection: We included trials of Food and Drug Administration (FDA)-approved pharmacotherapies for opioid use disorder (methadone, buprenorphine, and naltrexone) and trials of psychosocial interventions for persons engaging in opioid, stimulant, cannabis, and mixed drug or polysubstance use. We also included trials of preemptive prescribing of naloxone in primary care settings as a rescue medication for opioid-related overdose. Trials compared included interventions against placebo, a minimal intervention, waitlist control, or usual care, and evaluated outcomes at >3 months for drug use or other risky behaviors; health, social, and legal consequences of drug use; or harms of treatment. 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): We included a total of 71 trials, with 19 trials of pharmacotherapies and 52 trials of psychosocial interventions. All trials of pharmacotherapies and 25 trials of psychosocial interventions were conducted in treatment-seeking populations. Psychosocial interventions commonly incorporated cognitive-behavioral or motivational interventions and ranged from brief interventions consisting of one or two sessions of no more than one hour to multiple treatment sessions over weeks or months. In most pharmacotherapy trials, drug use counseling was provided to all patients. No study evaluated benefits or harms of preemptive naloxone prescribed in primary care settings versus placebo or no naloxone as a rescue medication for opioid-related overdose. In treatment-seeking populations with opioid use disorder, naltrexone (12 trials; relative risk [RR] 0.73, 95% confidence interval [CI] 0.62 to 0.85; number needed to treat [NNT] 5.3) and opioid agonist therapy with methadone or buprenorphine (4 trials; RR 0.75, 95% CI 0.59 to 0.82; NNT 2.9) were associated with decreased risk of drug use relapse compared with placebo or no pharmacotherapy. Naltrexone and methadone/buprenorphine therapy were also associated with increased likelihood of retention in substance use treatment (9 trials; RR 1.71, 95% CI 1.13 to 2.49; NNT 6.7 and 7 trials; RR 2.58, 95% CI 1.78 to 4.59; NNT 2.6; respectively). Evidence on harms of pharmacotherapies was limited, but indicated no increased risk of serious adverse events. Psychosocial interventions were associated with increased likelihood of abstinence from drug use versus control conditions at 3 to 4 months (15 trials, RR 1.60, 95% CI 1.24 to 2.13; NNT 11) and at 6 to 12 months (14 trials; RR 1.25, 95% CI 1.11 to 1.52; NNT 17), based on trials primarily conducted in treatment-seeking populations. Psychosocial interventions were also associated with a greater decrease versus control conditions in the number of drug use days (19 trials; mean difference -0.49 day in the last 7 days, 95% CI -0.85 to -0.13) and a small but statistically significant greater decrease in drug use severity (16 trials; standard mean difference -0.18, 95% CI -0.32 to -0.05) at 3- to 4-month followup. There was no difference between psychosocial interventions versus controls on drug use days or severity at longer (6 to 12 month) followup. Effects of psychosocial interventions were generally stronger in trials of treatment-seeking than screen-detected populations, trials that evaluated cannabis use than other types of drug use, and trials of more intensive than brief interventions. Few trials evaluated effects of psychosocial interventions for opioid or stimulant use, and estimates were imprecise.

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Screening for Hepatitis B Virus Infection in Nonpregnant Adolescents and Adults: A Systematic Review for the U.S. Preventive Services Task Force [Entered Retrospectively]


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Statistics: 52 Studies, 7 Key Questions, 1 Extraction Form,
Date Published: Jan 20, 2021 09:43PM
Description: Background: A 2014 review for the US Preventive Services Task Force (USPSTF) found antiviral therapy for hepatitis B virus (HBV) infection associated with improved intermediate outcomes, although evidence on clinical outcomes was limited. Purpose: To update the 2014 HBV screening review in nonpregnant adolescents and adults to inform the USPSTF. Data Sources: We utilized the 2014 review, searched the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Ovid MEDLINE (2014 to August 2019); with surveillance through July 24, 2020. Study Selection: Eligible studies included randomized controlled trials (RCTs) and cohort studies on the benefits and harms of screening versus no screening, and the yield of alternative screening strategies; RCTs on the effects of antiviral therapy versus placebo or no therapy and preferred versus nonpreferred therapies on intermediate outcomes, clinical outcomes, and harms; and cohort studies on clinical outcomes and on the association between intermediate outcomes following antiviral therapy and clinical outcomes. 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): Fifty total studies (30 trials and 20 cohort studies) with a total of 94,168 participants were included; of these, 22 were added for this update. No study directly evaluated the effects of screening for HBV infection versus no screening on clinical outcomes, such as mortality, hepatocellular carcinoma, or cirrhosis. Screening strategies that focused on risk factors such as ever having immigrated from high prevalence countries plus demographic and behavioral risk factors would identify nearly all HBV infection cases. In one study (N=21,008), only screening immigrants from high HBV prevalence countries would miss approximately two-thirds of infected persons. Based on 18 trials (N=2,972), antiviral therapy was associated with greater likelihood than placebo or no treatment for achieving intermediate outcomes, such as virologic suppression and hepatitis B e antigen or hepatitis B surface antigen loss or seroconversion; the numbers needed to treat ranged from 2.6 for virological suppression to 17 for hepatitis B e antigen seroconversion. Based on 12 trials (N=4,127), preferred (first-line) antiviral therapies were at least as likely as nonpreferred therapies to achieve intermediate outcomes. Based on 16 trials (N=4,809), antiviral therapy might be associated with improved clinical outcomes, but data were sparse and imprecise. Nine cohort studies (N=3,893) indicated an association between achieving an intermediate outcome following antiviral therapy and improved clinical outcomes, but were heterogeneous (hazards ratios ranged from 0.07 to 0.87). Antiviral therapy was associated with higher risk of withdrawal due to adverse events versus placebo or no antiviral therapy. Limitations: Only English-language articles were included, clinical outcome data for antiviral therapies were limited, observational studies were included on effects of antiviral therapy on long-term clinical outcomes and the association between intermediate and clinical outcomes, and some studies were conducted in countries where the prevalence and natural history of HBV infection are different from the United States. Conclusions: There was no direct evidence for the clinical benefits and harms of HBV screening versus no screening. Antiviral therapy for HBV infection was associated with improved intermediate outcomes and may improve clinical outcomes. Research is needed to clarify effects of screening and subsequent interventions on clinical outcomes and to identify optimal screening strategies.
Contributor(s): Roger Chou, MD Ian Blazina, MPH Christina Bougatsos, MPH Rebecca Holmes, MD, MS Shelley Selph, MD, MPH Sara Grusing, BA Janice Jou, MD, MHS
DOI: DOI pending.
Funding Source: This report is based on research conducted by the Pacific Northwest Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. HHSA290201500009-I, Task Order No. 14)
Methodology Description: Data Sources: We utilized the 2014 review, searched the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Ovid MEDLINE (2014 to August 2019); with surveillance through July 24, 2020. Study Selection: Eligible studies included randomized controlled trials (RCTs) and cohort studies on the benefits and harms of screening versus no screening, and the yield of alternative screening strategies; RCTs on the effects of antiviral therapy versus placebo or no therapy and preferred versus nonpreferred therapies on intermediate outcomes, clinical outcomes, and harms; and cohort studies on clinical outcomes and on the association between intermediate outcomes following antiviral therapy and clinical outcomes. 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.

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Acute Treatments for Episodic Migraine in Adults: A Systematic Review and Meta-Analysis


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Statistics: 156 Studies, 3 Key Questions, 3 Extraction Forms,
Date Published: Jan 11, 2021 02:30PM
Description: Objectives. To evaluate the effectiveness and comparative effectiveness of pharmacologic and non-pharmacologic therapies for the acute treatment of episodic migraine in adults. Data source. MEDLINE, Embase, Cochrane Central Registrar of Controlled Trials, Cochrane Database of Systematic Reviews, PsycINFO, Scopus and various grey literature sources from database inception to April 24, 2020. Comparative effectiveness evidence about triptans and nonsteroidal anti-inflammatory drugs (NSAIDs) were extracted from existing systematic reviews. Review methods. We included randomized controlled trials (RCTs) and comparative observational studies that enrolled adults who received an intervention to acutely treat episodic migraine. Pairs of independent reviewers selected and appraised studies. Results. Data on triptans were derived from 186 RCTs summarized in 9 systematic reviews (101,276 patients, most studied was sumatriptan, followed by zolmitriptan, eletriptan, naratriptan, almotriptan, rizatriptan, and frovatriptan). Compared with placebo, triptans resolved pain at 2 hours and 1 day, and increased the risk of mild and transient adverse events (high strength of the body of evidence [SOE]). Data on NSAIDs were derived from 5 systematic reviews (13,214 patients, most studied was ibuprofen, followed by diclofenac and ketorolac). Compared with placebo, NSAIDs probably resolved pain at 2 hours and 1 day, and increased the risk of mild and transient adverse events (moderate SOE). For other interventions, we included 135 RCTs and 6 comparative observational studies (37,653patients). Compared with placebo, antiemetics (low SOE), dihydroergotamine (moderate to high SOE), ergotamine plus caffeine (moderate SOE) and acetaminophen (moderate SOE) reduced acute pain. Opioids were evaluated in 15 studies (2,208 patients). Tramadol in combination with acetaminophen, butorphanol, meperidine, morphine and hydromorphone may reduce pain at 2 hours and 1 day, compared with placebo (low SOE). Some opioids may be less effective than some antiemetics or dexamethasone (low SOE). No studies evaluated instruments for predicting risk of opioid misuse, opioid use disorder or overdose, or evaluated risk mitigation strategies to be used when prescribing opioids for the acute treatment of episodic migraine. Calcitonin gene-related peptide (CGRP) receptor antagonists improved headache relief at 2 hours and increased the likelihood of being headache-free at 2 hours, at 1 day, and at 1 week (low to high SOE). Lasmiditan (the first approved 5-HT1F receptor agonist) restored function at 2 hours and resolved pain at 2 hours, 1 day, and 1 week (moderate to high SOE). Sparse and low SOE suggested possible effectiveness of dexamethasone, dipyrone, flunarazine, magnesium sulfate, octreotide, tezampanel, and tonabersat. Compared with placebo, several non-pharmacologic treatments may improve various measures of pain, including remote electrical neuromodulation (moderate SOE), magnetic stimulation (low SOE), acupuncture (low SOE), chamomile oil (low SOE), external trigeminal nerve stimulation (low SOE), and eye movement desensitization re-processing (low SOE). However, these interventions, including the noninvasive neuromodulation devices, have only been evaluated by single or very few trials. Conclusions. A number of acute treatments for episodic migraine exist with varying degrees of evidence for effectiveness and harms. Use of triptans, NSAIDs, antiemetics, dihydroergotamine, CGRP antagonists, and lasmiditan is associated with improved pain and function. The evidence base for many other interventions for acute treatment, including opioids, remains limited.
Contributor(s): Juliana VanderPluym, MD, Rashmi Halker Singh, MD, Allison S. Morrow, BA, Meritxell Urtecho, MD, Tarek Nayfeh, MD, Victor D. Torres Roldan, MD, Magdoleen H. Farah, MBBS, Bashar Hasan, MD, Samer Mohir, MD, Sahrish Shah, MBBS, Rami Abd-Rabu, MBBS, Lubna Daraz, PhD, Larry J. Prokop, MLS, Mohammad Hassan Murad, MD, MPH, Zhen Wang, PhD
DOI: DOI pending.
Funding Source: AHRQ
Methodology Description: We developed an analytic framework to guide the process of the systematic review. We followed the established methodologies of systematic reviews as outlined in Agency for Healthcare Research and Quality (AHRQ) Methods Guide for Comparative Effectiveness Reviews. The reporting complies with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements. The study protocol is published on AHRQ website and registered in the international prospective register of systematic reviews (PROSPERO #: CRD42020163262). The full report details our literature search strategy, inclusion and exclusion criteria, data synthesis, assessments of risk of bias, and strength of evidence (SOE). We assigned SOE rating as high, moderate, low, or ‘insufficient evidence to estimate an effect’. High was rated when we were very confident that the estimate of effect lies close to the true effect (the body of evidence has few or no deficiencies and is judged to be stable). Moderate was rated if we were moderately confident that the estimate of effect lies close to the true effect (the body of evidence has some deficiencies and is judged to be likely stable). Low, we had limited confidence that the estimate of effect lies close to the true effect (the body of evidence has major or numerous deficiencies and is likely unstable), and insufficient if we had no evidence, are unable to estimate an effect, or have no confidence in the estimate of effect.

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Management of Acute Diverticulitis


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Statistics: 81 Studies, 4 Key Questions, 2 Extraction Forms,
Date Published: Jan 08, 2021 08:15PM
Description: Purpose of the Review The American College of Physicians (ACP) nominated the topic of management of acute diverticulitis to the Agency for Healthcare Research and Quality for systematic review. 45, 46 The ACP develops guidelines based on the needs of its members and the internal medicine community.47 The scope of the current systematic review was developed to support the ACP in its effort to create a new clinical practice guideline that will address diagnosis and staging of acute diverticulitis, nonsurgical treatment of acute diverticulitis, colorectal cancer screening in people with a history of diverticulitis, and interventions to prevent recurrence of acute diverticulitis. Specifically, (1) the systematic review will summarize existing systematic reviews on the test accuracy of CT imaging for diagnosis and staging of acute diverticulitis and conduct a de novo review of harms related to false positive, false negative, and incidental findings on CT imaging for suspected acute diverticulitis; (2) it will address effectiveness, comparative effectiveness, and harms of hospitalization for acute uncomplicated diverticulitis, antibiotics use for acute complicated or uncomplicated diverticulitis, and interventional radiology techniques for acute complicated diverticulitis; (3) it will review the benefits and harms of colonoscopy in people with a history of diverticulitis; and (4) it will evaluate pharmacologic, nonpharmacologic, and elective surgical interventions to prevent recurrent diverticulitis. Of note, this review will not evaluate the need for, or the choice of, surgery for the patient with acute diverticulitis. The intended audience includes guideline developers, clinicians and other providers of care for patients with diverticulitis, healthcare policy makers, and patients.
Contributor(s): Brown Evidence-based Practice Center
DOI: DOI pending.
Funding Source: AHRQ
Methodology Description: Systematic Review

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Treatments for Acute Pain: A Systematic Review


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Statistics: 190 Studies, 9 Key Questions, 1 Extraction Form,
Date Published: Jan 06, 2021 03:46PM
Description: To evaluate the effectiveness and comparative effectiveness of opioid, nonopioid pharmacologic, and nonpharmacologic therapy in patients with specific types of acute pain, including effects on pain, function, quality of life, adverse events, and long-term use of opioids.
Contributor(s): Roger Chou, M.D. Jesse Wagner, M.A. Azrah Y. Ahmed, B.A. Ian Blazina, M.P.H. Erika Brodt, B.S. David I. Buckley, M.D., M.P.H. Tamara P. Cheney, M.D. Esther Choo, M.D., M.P.H. Tracy Dana, M.L.S. Debra Gordon, R.N., D.N.P., FANN Saurabh Khandelwal , M.D. Shelby Kantner, B.A. Marian S. McDonagh, Pharm.D. Christine Sedgley, M.D.S., M.D.Sc., FRACDS, MRACDS (ENDO), FACD, Ph.D. Andrea C. Skelly, Ph.D., M.P.H.
DOI: DOI pending.
Funding Source: AHRQ Contract No. 290-2015-00009-I
Methodology Description: Electronic databases (Ovid® MEDLINE®, PsycINFO®, Embase®, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews) were searched through August 5, 2020 for relevant publications. Searches were supplemented by reviewing reference lists and a Federal Register Notice. Randomized controlled trials (RCTs) of opioid therapy versus nonopioid pharmacologic or nonpharmacologic therapy, nonopioid therapy versus nonpharmacologic therapy, nonpharmacologic therapy versus inactive controls (placebo, sham therapy, attention control, or a minimal intervention), and head-to-head trials of nonopioid pharmacologic and nonpharmacologic therapy were selected using predefined criteria and dual review. Observational studies on the association between being prescribed opioids for acute pain versus no opioids and on factors influencing opioid prescribing for acute pain conditions were also included. This review focused on eight acute pain conditions: low back pain, neck pain, other musculoskeletal pain, neuropathic pain, postoperative pain (excluding inpatient management of pain after major surgical procedures), dental pain, pain due to kidney stones, and pain due to sickle cell disease. The review focused on outpatient management or therapy initiated shortly before discharge (e.g., after surgery or in emergency department). Outcomes were analyzed at <1 day, 1 day to <1 week, 1 week to <2 weeks, 2 to <4 weeks, and ≥4 weeks. Meta-analyses were conducted on pharmacologic therapy for dental pain and kidney stone pain and likelihood of repeat or rescue medication use and adverse events. Otherwise, meta-analyses were not conducted due to small number of studies, methodological limitations and study heterogeneity. The magnitude of effects was classified as small, moderate or large using previously defined criteria, and strength of evidence was assessed.

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