Opioid treatment programs, telemedicine and COVID-19: A scoping review.

Background: Methadone and buprenorphine are effective medications for opioid use disorder (MOUD) that are highly regulated in the United States. The on-going opioid crisis, and more recently COVID-19, has prompted reconsideration of these restrictions in order to sustain and improve treatment access, with renewed interest in telemedicine. We reviewed the evidence on use of telemedicine interventions and applicability to MOUD policy changes in the post-COVID-19 treatment landscape. Methods: Ovid MEDLINE and the Cochrane Database of Systematic Reviews databases were searched from inception to April 2021 and reference lists were reviewed to identify additional studies. Studies were eligible if they examined telemedicine interventions and reported outcomes (e.g. treatment initiation, retention in care). Randomized trials and controlled observational studies were prioritized; other studies were included when stronger evidence was unavailable. One investigator abstracted key information and a second investigator verified data. We described the results qualitatively. Results: We identified nine studies: three controlled trials (two randomized), and six observational studies. Three studies evaluated patients treated with methadone and six studies with buprenorphine, including one study of pregnant women with OUD. All studies showed telemedicine approaches associated with similar outcomes (treatment retention, positive urine toxicology) compared to treatment as usual. Trials were limited by small samples sizes, lack of reporting harms, and most were conducted prior to the COVID-19 pandemic; observational studies were limited by failure to control for confounding. Conclusions: Limited evidence suggests that telemedicine may enhance access to MOUD with similar effectiveness compared with face-to-face treatment. Few studies have been published since COVID-19, and it is unclear the potential impact of these interventions on the existing racial/ethnic disparities in treatment. The COVID-19 pandemic and need for social distancing led to temporary policy changes for prescribing of MOUD that could inform additional research in this area to support comprehensive policy reforms.

Screening for Impaired Visual Acuity in Older Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: A 2016 review for the US Preventive Services Task Force (USPSTF) found that effective treatments are available for refractive errors, cataracts, and wet (advanced neovascular) or dry (atrophic) age-related macular degeneration (AMD), but there were no differences between visual screening vs no screening on visual acuity or other outcomes. Objective: To update the 2016 review on screening for impaired visual acuity in older adults, to inform the USPSTF. Data Sources: Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews (to February 2021); surveillance through January 21, 2022. Study Selection: Randomized clinical trials and controlled observational studies on screening, vascular endothelial growth factor (VEGF) inhibitors (wet AMD), and antioxidant vitamins and minerals (dry AMD); studies on screening diagnostic accuracy. Data Extraction and Synthesis: One investigator abstracted data and a second checked accuracy. Two investigators independently assessed study quality. Results: Twenty-five studies (N = 33 586) were included (13 trials, 11 diagnostic accuracy studies, and 1 systematic review [19 trials]). Four trials (n = 4819) found no significant differences between screening vs no screening in visual acuity or other outcomes. Visual acuity tests (3 studies; n = 6493) and screening question (3 studies; n = 5203) were associated with suboptimal diagnostic accuracy. For wet AMD, 4 trials (n = 2086) found VEGF inhibitors significantly associated with greater likelihood of 15 or more letters visual acuity gain (risk ratio [RR], 2.92 [95% CI, 1.20-7.12]; I2 = 76%; absolute risk difference [ARD], 10%) and less than 15 letters visual acuity loss (RR, 1.46 [95% CI, 1.22-1.75]; I2 = 80%; ARD, 27%) vs sham treatment, with no increased risk of serious harms. For dry AMD, a systematic review (19 trials) found antioxidant multivitamins significantly associated with decreased risk of progression to late AMD (3 trials, n = 2445; odds ratio [OR], 0.72 [95% CI, 0.58-0.90]) and 3 lines or more visual acuity loss (1 trial, n = 1791; OR, 0.77 [95% CI, 0.62-0.96]) vs placebo. Zinc was significantly associated with increased risk of genitourinary events and beta carotene with increased risk of lung cancer in former smokers; other serious harms were infrequent. Conclusions and Relevance: This review found that effective treatments are available for common causes of impaired visual acuity in older adults. However, direct evidence found no significant association between vision screening vs no screening in primary care and improved visual outcomes.

Screening for Glaucoma in Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Two 2013 systematic reviews to inform the US Preventive Services Task Force (USPSTF) found insufficient evidence to assess benefits and harms of screening for primary open-angle glaucoma (OAG) in adults. Objective: To update the 2013 reviews on screening for glaucoma, to inform the USPSTF. Data Sources: Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews (to February 2021); surveillance through January 21, 2022. Study Selection: Randomized clinical trials (RCTs) of screening, referral, and treatment; and studies of screening test diagnostic accuracy. Data Extraction and Synthesis: One investigator abstracted data and a second checked accuracy. Two investigators independently assessed study quality. Results: Eighty-three studies (N = 75 887) were included (30 trials and 53 diagnostic accuracy studies). One RCT (n = 616) found screening of frail elderly persons associated with no difference in vision outcomes vs no screening but with significantly greater falls risk (relative risk [RR], 1.31 [95% CI, 1.13-1.50]). No study evaluated referral to an eye health professional. For glaucoma diagnosis, spectral domain optical coherence tomography (providing high-resolution cross-sectional imaging; 15 studies, n = 4242) was associated with sensitivity of 0.79 (95% CI, 0.75-0.83) and specificity of 0.92 (95% CI, 0.87-0.96) and the Humphrey Visual Field Analyzer (for perimetry, or measurement of visual fields; 6 studies, n = 11 244) with sensitivity of 0.87 (95% CI, 0.69-0.95) and specificity 0.82 (95% CI, 0.66-0.92); tonometry (for measurement of intraocular pressure; 13 studies, n = 32 892) had low sensitivity (0.48 [95% CI, 0.31-0.66]). Medical therapy for ocular hypertension and untreated glaucoma was significantly associated with decreased intraocular pressure and decreased likelihood of glaucoma progression (7 trials, n = 3771; RR, 0.68 [95% CI, 0.49-0.96]; absolute risk difference -4.2%) vs placebo, but 1 trial (n = 461) found no differences in visual acuity, quality of life, or function. Selective laser trabeculoplasty and medical therapy had similar outcomes (4 trials, n = 957). Conclusions and Relevance: This review found limited direct evidence on glaucoma screening, showing no association with benefits. Screening tests can identify persons with glaucoma and treatment was associated with a lower risk of glaucoma progression, but evidence of improvement in visual outcomes, quality of life, and function remains lacking.

Screening for Hepatitis B Virus Infection in Nonpregnant Adolescents and Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: 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. Objective: To update the 2014 HBV screening review in nonpregnant adolescents and adults to inform the USPSTF. Data Sources: 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: Randomized clinical trials (RCTs) on screening and antiviral therapy; cohort studies on screening, antiviral therapy clinical outcomes, and the association between achieving intermediate outcomes after antiviral therapy and clinical outcomes. Data Extraction and Synthesis: One investigator abstracted data; a second investigator checked accuracy. Two investigators independently assessed study quality. Random-effects profile likelihood meta-analysis was performed. Results: Thirty trials and 20 cohort studies, with a total of 94 168 participants, were included. No study directly evaluated the effects of screening for HBV infection vs 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 and demographic and behavioral risk factors would identify nearly all HBV infection cases. In 1 study (n = 21 008), only screening immigrants from high-prevalence countries would miss approximately two-thirds of infected persons. Based on 18 trials (n = 2972), antiviral therapy compared with placebo or no treatment was associated with greater likelihood of achieving intermediate outcomes, such as virologic suppression and hepatitis B e-antigen (HBeAg) or hepatitis B surface antigen loss or seroconversion; the numbers needed to treat ranged from 2.6 for virologic suppression to 17 for HBeAg seroconversion. Based on 12 trials (n = 4127), first-line antiviral therapies were at least as likely as nonpreferred therapies to achieve intermediate outcomes. Based on 16 trials (n = 4809), antiviral therapy might be associated with improved clinical outcomes, but data were sparse and imprecise. Nine cohort studies (n = 3893) indicated an association between achieving an intermediate outcome following antiviral therapy and improved clinical outcomes but were heterogeneous (hazard ratios ranged from 0.07 to 0.87). Antiviral therapy was associated with higher risk of withdrawal due to adverse events vs placebo or no antiviral therapy. Conclusions and Relevance: There was no direct evidence for the clinical benefits and harms of HBV screening vs no screening. Antiviral therapy for HBV infection was associated with improved intermediate outcomes and may improve clinical outcomes.

Screening for Hepatitis C Virus Infection in Adolescents and Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

IMPORTANCE: A 2013 review for the US Preventive Services Task Force (USPSTF) of hepatitis C virus (HCV) screening found interferon-based antiviral therapy associated with increased likelihood of sustained virologic response (SVR) and an association between achieving an SVR and improved clinical outcomes. New direct-acting antiviral (DAA) regimens are available. OBJECTIVE: To update the 2013 review on HCV screening to inform the USPSTF. DATA SOURCES: Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews through February 2019, with surveillance through September 2019. STUDY SELECTION: Randomized clinical trials (RCTs) and nonrandomized treatment studies of HCV screening and DAA therapy; cohort studies on screening, antiviral therapy, and the association between an SVR after antiviral therapy and clinical outcomes. DATA EXTRACTION AND SYNTHESIS: One investigator abstracted data; a second checked accuracy. Two investigators independently rated study quality. MAIN OUTCOMES AND MEASURES: Mortality, morbidity, quality of life, screening and treatment harms, and screening diagnostic yield. RESULTS: Eight RCTs of DAA therapy vs placebo or an outdated antiviral regimen, 48 other treatment studies, and 33 cohort studies, with a total of 179 230 participants, were included. No study evaluated effects of HCV screening vs no screening. One new study since the 2013 review (n = 5917) found similar diagnostic yield of risk-based screening (sensitivity, 82%; number needed to screen to identify 1 HCV case, 15) and birth cohort screening (sensitivity, 76%; number needed to screen, 29), assuming perfect implementation. Ten open-label studies (n = 3292) reported small improvements in some quality-of-life and functional outcomes (eg, less than 3 points on the 0 to 100 36-Item Short Form Health Survey physical and mental component summary scales) after DAA treatment compared with before treatment. Two cohort studies (n = 24 686) found inconsistent associations of antiviral therapy vs no therapy with risk of hepatocellular carcinoma. Forty-nine treatment studies (n = 10 181) found DAA regimens associated with pooled SVR rates greater than 95% across genotypes, and low short-term rates of serious adverse events (1.9%) and withdrawal due to adverse events (0.4%). An SVR after antiviral therapy was associated with decreased adjusted risk of all-cause mortality (13 studies, n = 36 986; pooled hazard ratio [HR], 0.40 [95% CI, 0.28-0.56) and hepatocellular carcinoma (20 studies, n = 84 491; pooled HR, 0.29 [95% CI, 0.23 to 0.38]) vs no SVR. CONCLUSIONS AND RELEVANCE: Direct evidence on the effects of HCV screening on clinical outcomes remains unavailable, but DAA regimens were associated with SVR rates greater than 5% and few short-term harms relative to older antiviral therapies. An SVR after antiviral therapy was associated with improved clinical outcomes compared with no SVR.

Screening for Unhealthy Drug Use: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Illicit drug use is among the most common causes of preventable morbidity and mortality in the US. Objective: To systematically review the literature on screening and interventions for drug use to inform the US Preventive Services Task Force. Data Sources: MEDLINE, PubMed, PsycINFO, Embase, and Cochrane Central Register of Controlled Trials through September 18, 2018; literature surveillance through September 21, 2019. Study Selection: Test accuracy studies to detect drug misuse and randomized clinical trials of screening and interventions to reduce drug use. Data Extraction and Synthesis: Critical appraisal and data abstraction by 2 reviewers and random-effects meta-analyses. Main Outcomes and Measures: Sensitivity, specificity, drug use and other health, social, and legal outcomes. Results: Ninety-nine studies (N = 84 206) were included. Twenty-eight studies (n = 65 720) addressed drug screening accuracy. Among adults, sensitivity and specificity of screening tools for detecting unhealthy drug use ranged from 0.71 to 0.94 and 0.87 to 0.97, respectively. Interventions to reduce drug use were evaluated in 52 trials (n = 15 659) of psychosocial interventions, 7 trials (n = 1109) of opioid agonist therapy, and 13 trials (n = 1718) of naltrexone. Psychosocial interventions were associated with increased likelihood of drug use abstinence (15 trials, n = 3636; relative risk [RR], 1.60 [95% CI, 1.24 to 2.13]; absolute risk difference [ARD], 9% [95% CI, 5% to 15%]) and reduced number of drug use days (19 trials, n = 5085; mean difference, -0.49 day in the last 7 days [95% CI, -0.85 to -0.13]) vs no psychosocial intervention at 3- to 4-month follow-up. In treatment-seeking populations, opioid agonist therapy and naltrexone were associated with decreased risk of drug use relapse (4 trials, n = 567; RR, 0.75 [95% CI, 0.59 to 0.82]; ARD, -35% [95% CI, -67% to -3%] and 12 trials, n = 1599; RR, 0.73 [95% CI, 0.62 to 0.85]; ARD, -18% [95% CI, -26% to -10%], respectively) vs placebo or no medication. While evidence on harms was limited, it indicated no increased risk of serious adverse events. Conclusions and Relevance: Several screening instruments with acceptable sensitivity and specificity are available to screen for drug use, although there is no direct evidence on the benefits or harms of screening. 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.

Screening for HIV Infection in Pregnant Women: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Prenatal screening for HIV can inform use of interventions to reduce the risk of mother-to-child transmission. The US Preventive Services Task Force (USPSTF) previously found strong evidence that prenatal HIV screening reduced risk of mother-to-child transmission. The previous evidence review was conducted in 2012. Objective: To update the 2012 review on prenatal HIV screening to inform the USPSTF. Data Sources: Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews from 2012 to June 2018, with surveillance through January 2019. Study Selection: Pregnant persons 13 years and older; randomized clinical trials and cohort studies of screening vs no screening; risk of mother-to-child transmission or maternal or infant harms associated with antiretroviral therapy (ART) during pregnancy; screening yield at different intervals or in different risk groups. Data Extraction and Synthesis: One investigator abstracted data; a second checked accuracy. Two investigators independently rated study quality. Main Outcomes and Measures: Mother-to-child transmission; harms of screening and treatment; screening yield. Results: Sixty-two studies were included in this review, including 29 new studies. There remains no direct evidence on effects of prenatal screening vs no screening on risk of mother-to-child HIV transmission, maternal or infant clinical outcomes, or the yield of repeat or alternative screening strategies. New evidence confirms that combination ART is highly effective at reducing the risk of mother-to-child transmission, with some new cohort studies reporting rates of mother-to-child transmission less than 1% when combination ART was started early in pregnancy (when begun in first trimester, 0%-0.4%; when begun after first trimester, or at any time if timing of ART initiation not reported, 0.4%-2.8%). New evidence on harms of ART was also largely consistent with the previous review. Evidence from primarily observational studies found prenatal combination ART with a boosted protease inhibitor associated with increased risk of preterm delivery (range, 14.4%-26.1%). For other birth outcomes (low birth weight, small for gestational age, stillbirth, birth defects, neonatal death), results were mixed and depended on the specific antiretroviral drug or drug regimen given and timing of prenatal therapy. Conclusions and Relevance: Combination ART was highly effective at reducing risk of mother-to-child HIV transmission. Use of certain ART regimens during pregnancy was associated with increased risk of harms that may be mitigated by selection of ART regimen. The 2012 review found that avoidance of breastfeeding and cesarean delivery in women with viremia also reduced risk of transmission and that prenatal screening accurately diagnosed HIV infection.

Screening for HIV Infection in Asymptomatic, Nonpregnant Adolescents and Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Untreated HIV infection can result in significant morbidity, mortality, and HIV transmission. A 2012 review for the US Preventive Services Task Force (USPSTF) found antiretroviral therapy (ART) associated with improved clinical outcomes and decreased transmission risk in persons with CD4 cell counts less than 500/mm3. Objective: To update the 2012 review on HIV screening to inform the USPSTF. Data Sources: Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews from 2012 to June 2018, with surveillance through January 2019. Study Selection: Nonpregnant individuals 12 years and older; randomized clinical trials (RCTs) and controlled observational studies of screening vs no screening, alternative screening strategies, earlier vs later initiation of ART, and long-term harms of ART. Data Extraction and Synthesis: One investigator abstracted data; a second checked accuracy. Two investigators independently rated study quality. Main Outcomes and Measures: Mortality, AIDS events, quality of life, function, and HIV transmission; harms of screening and long-term (≥2 years) harms of ART; screening yield. Results: Eighteen new studies (5 RCTs, 11 cohort studies, and 2 systematic reviews; N = 266 563) were included, and 11 studies (2 RCTs and 9 cohort studies; N = 218 542) were carried forward from the prior USPSTF report. No study directly evaluated effects of HIV screening vs no screening on clinical outcomes or harms, or the yield of alternative screening strategies. Two newly identified RCTs conducted completely or partially in low-resource settings found ART initiation at CD4 cell counts greater than 500/mm3 associated with lower risk of a composite outcome of mortality, AIDS-defining events, or serious non-AIDS events (relative risk [RR], 0.44 [95% CI, 0.31-0.63] and RR, 0.57 [95% CI, 0.35-0.95]); results were consistent with those from a large observational study. Early ART was not associated with increased risk of cardiovascular events. Early ART initiation was associated with sustained reduction in risk of HIV transmission at 5.5 years (RR, 0.07 [95% CI, 0.02-0.22] for linked transmission). New evidence regarding the association between abacavir use and risk of cardiovascular events was inconsistent. Certain antiretroviral regimens were associated with increased risk of long-term neuropsychiatric, renal, hepatic, and bone adverse events. Conclusions and Relevance: In nonpregnant adolescents and adults there was no direct evidence on the clinical benefits and harms of screening for HIV infections vs no screening, or the yield of repeat or alternative screening strategies. New evidence extends effectiveness of ART to asymptomatic individuals with CD4 cell counts greater than 500/mm3 and shows sustained reduction in risk of HIV transmission at longer-term follow-up, although certain ART regimens may be associated with increased risk of long-term harms.

Screening for Elevated Blood Lead Levels in Childhood and Pregnancy: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Elevated blood lead level is associated with serious, often irreversible, health consequences. Objective: To synthesize evidence on the effects of screening, testing, and treatment for elevated blood lead level in pregnant women and children aged 5 years and younger in the primary care setting to inform the US Preventive Services Task Force. Data Sources: Cochrane CENTRAL and Cochrane Database of Systematic Reviews (through June 2018) and Ovid MEDLINE (1946 to June 2018); surveillance through December 5, 2018. Study Selection: English-language trials and observational studies of screening for and treating elevated lead levels in asymptomatic children and pregnant women. Data Extraction and Synthesis: Independent critical appraisal and data abstraction by 2 reviewers using predefined criteria. Main Outcomes and Measures: Elevated blood lead level, morbidity, mortality, clinical prediction tools, test accuracy, adverse events. Results: A total of 24 studies (N = 11 433) were included in this review. No studies evaluated the benefits or harms of screening vs no screening in children. More than 1 positive answer on the 5-item 1991 Centers for Disease Control and Prevention (CDC) screening questionnaire was associated with a pooled sensitivity of 48% (95% CI, 31.4% to 65.6%) and specificity of 58% (95% CI, 39.9% to 74.0%) for identifying children with a venous blood lead level greater than 10 µg/dL (5 studies [n = 2265]). Adapted versions of the CDC questionnaire did not demonstrate improved accuracy. Capillary blood lead testing demonstrated sensitivity of 87% to 91% and specificity greater than 90%, compared with venous measurement (4 studies [n = 1431]). Counseling and nutritional interventions or residential lead hazard control techniques did not reduce blood lead concentrations in asymptomatic children, but studies were few and had methodological limitations (7 studies [n = 1419]). One trial (n = 780) of dimercaptosuccinic acid (DMSA) chelation therapy found reduced blood lead levels in children at 1 week to 1 year but not at 4.5 to 6 years, while another trial (n = 39) found no effect at 1 and 6 months. Seven-year follow-up assessments showed no effect on neuropsychological development, a small deficit in linear growth (height difference, 1.17 cm [95% CI, 0.41 to 1.93]), and poorer cognitive outcomes reported as the Attention and Executive Functions subscore of the Developmental Neuropsychological Assessment (unadjusted difference, -1.8 [95% CI, -4.5 to 1.0]; adjusted P = .045) in children treated with DMSA chelation. Evidence was too limited to determine the accuracy of screening questionnaires or benefits and harms of treatment in pregnant women. Conclusions and Relevance: Screening questionnaires were not accurate for identifying children with elevated blood lead levels. Chelating agents in children were not significantly associated with sustained effects on blood level levels but were associated with harms.

Preexposure Prophylaxis for the Prevention of HIV Infection: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Effective prevention strategies for HIV infection are an important public health priority. Preexposure prophylaxis (PrEP) involves use of antiretroviral therapy (ART) daily or before and after sex to decrease risk of acquiring HIV infection. Objective: To synthesize the evidence on the benefits and harms of PrEP, instruments for predicting incident HIV infection, and PrEP adherence to inform the US Preventive Services Task Force. Data Sources: Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and EMBASE through June 2018, with surveillance through January 2019. Study Selection: English-language placebo-controlled randomized clinical trials of oral PrEP with tenofovir disoproxil fumarate/emtricitabine or tenofovir disoproxil fumarate monotherapy; studies on the diagnostic accuracy of instruments for predicting incident HIV infection; and studies on PrEP adherence. Data Extraction and Synthesis: Dual review of titles and abstracts, full-text articles, study quality, and data abstraction. Data were pooled using the Dersimonian and Laird random-effects model for effects of PrEP on HIV infection, mortality, and harms. Main Outcomes and Measures: HIV acquisition, mortality, and harms; adherence to PrEP; and diagnostic test accuracy and discrimination. Results: Fourteen RCTs (N = 18 837), 8 observational studies (N = 3884), and 7 studies of diagnostic accuracy (N = 32 279) were included. PrEP was associated with decreased risk of HIV infection vs placebo or no PrEP after 4 months to 4 years (11 trials; relative risk [RR], 0.46 [95% CI, 0.33-0.66]; I2 = 67%; absolute risk reduction [ARD], -2.0% [95% CI, -2.8% to -1.2%]). Greater adherence was associated with greater efficacy (RR with adherence ≥70%, 0.27 [95% CI, 0.19-0.39]; I2 = 0%) in 6 trials. PrEP was associated with an increased risk of renal adverse events (12 trials; RR, 1.43 [95% CI, 1.18-1.75]; I2 = 0%; ARD, 0.56% [95% CI, 0.09%-1.04%]) and gastrointestinal adverse events (12 trials; RR, 1.63 [95% CI, 1.26-2.11]; I2 = 43%; ARD, 1.95% [95% CI, 0.48%-3.43%]); most adverse events were mild and reversible. Instruments for predicting incident HIV infection had moderate discrimination (area under the receiver operating characteristic curve, 0.49-0.72) and require further validation. Adherence to PrEP in the United States in men who have sex with men varied widely (22%-90%). Conclusions and Relevance: In adults at increased risk of HIV infection, PrEP with oral tenofovir disoproxil fumarate monotherapy or tenofovir disoproxil fumarate/emtricitabine was associated with decreased risk of acquiring HIV infection compared with placebo or no PrEP, although effectiveness decreased with suboptimal adherence.

Systemic Pharmacologic Therapies for Low Back Pain: A Systematic Review for an American College of Physicians Clinical Practice Guideline.

BACKGROUND: A 2007 American College of Physicians guideline addressed pharmacologic options for low back pain. New evidence and medications have now become available. PURPOSE: To review the current evidence on systemic pharmacologic therapies for acute or chronic nonradicular or radicular low back pain. DATA SOURCES: Ovid MEDLINE (January 2008 through November 2016), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and reference lists. STUDY SELECTION: Randomized trials that reported pain, function, or harms of systemic medications versus placebo or another intervention. DATA EXTRACTION: One investigator abstracted data, and a second verified accuracy; 2 investigators independently assessed study quality. DATA SYNTHESIS: The number of trials ranged from 9 (benzodiazepines) to 70 (nonsteroidal anti-inflammatory drugs). New evidence found that acetaminophen was ineffective for acute low back pain, nonsteroidal anti-inflammatory drugs had smaller benefits for chronic low back pain than previously observed, duloxetine was effective for chronic low back pain, and benzodiazepines were ineffective for radiculopathy. For opioids, evidence remains limited to short-term trials showing modest effects for chronic low back pain; trials were not designed to assess serious harms. Skeletal muscle relaxants are effective for short-term pain relief in acute low back pain but caused sedation. Systemic corticosteroids do not seem to be effective. For effective interventions, pain relief was small to moderate and generally short-term; improvements in function were generally smaller. Evidence is insufficient to determine the effects of antiseizure medications. LIMITATIONS: Qualitatively synthesized new trials with prior meta-analyses. Only English-language studies were included, many of which had methodological shortcomings. Medications injected for local effects were not addressed. CONCLUSION: Several systemic medications for low back pain are associated with small to moderate, primarily short-term effects on pain. New evidence suggests that acetaminophen is ineffective for acute low back pain, and duloxetine is associated with modest effects for chronic low back pain. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (PROSPERO: CRD42014014735).

Primary Care-Based Models for the Treatment of Opioid Use Disorder: A Scoping Review.

Greater integration of medication-assisted treatment (MAT) for opioid use disorder (OUD) in U.S. primary care settings would expand access to treatment for this condition. Models for integrating MAT into primary care vary in structure. This article summarizes findings of a technical report for the Agency for Healthcare Research and Quality describing MAT models of care for OUD, based on a literature review and interviews with key informants in the field. The report describes 12 representative models of care for integrating MAT into primary care settings that could be considered for adaptation across diverse health care settings. Common components of existing care models include pharmacotherapy with buprenorphine or naltrexone, provider and community education, coordination and integration of OUD treatment with other medical and psychological needs, and psychosocial services and interventions. Models vary in how each component is implemented. Decisions about adopting MAT models of care should be individualized to address the unique milieu of each implementation setting.

Nonpharmacologic Therapies for Low Back Pain: A Systematic Review for an American College of Physicians Clinical Practice Guideline.

BACKGROUND: A 2007 American College of Physicians guideline addressed nonpharmacologic treatment options for low back pain. New evidence is now available. PURPOSE: To systematically review the current evidence on nonpharmacologic therapies for acute or chronic nonradicular or radicular low back pain. DATA SOURCES: Ovid MEDLINE (January 2008 through February 2016), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and reference lists. STUDY SELECTION: Randomized trials of 9 nonpharmacologic options versus sham treatment, wait list, or usual care, or of 1 nonpharmacologic option versus another. DATA EXTRACTION: One investigator abstracted data, and a second checked abstractions for accuracy; 2 investigators independently assessed study quality. DATA SYNTHESIS: The number of trials evaluating nonpharmacologic therapies ranged from 2 (tai chi) to 121 (exercise). New evidence indicates that tai chi (strength of evidence [SOE], low) and mindfulness-based stress reduction (SOE, moderate) are effective for chronic low back pain and strengthens previous findings regarding the effectiveness of yoga (SOE, moderate). Evidence continues to support the effectiveness of exercise, psychological therapies, multidisciplinary rehabilitation, spinal manipulation, massage, and acupuncture for chronic low back pain (SOE, low to moderate). Limited evidence shows that acupuncture is modestly effective for acute low back pain (SOE, low). The magnitude of pain benefits was small to moderate and generally short term; effects on function generally were smaller than effects on pain. LIMITATION: Qualitatively synthesized new trials with prior meta-analyses, restricted to English-language studies; heterogeneity in treatment techniques; and inability to exclude placebo effects. CONCLUSION: Several nonpharmacologic therapies for primarily chronic low back pain are associated with small to moderate, usually short-term effects on pain; findings include new evidence on mind-body interventions. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (PROSPERO: CRD42014014735).

Management of Suspected Opioid Overdose With Naloxone in Out-of-Hospital Settings: A Systematic Review.

BACKGROUND: Naloxone is effective for reversing opioid overdose, but optimal strategies for out-of-hospital use are uncertain. PURPOSE: To synthesize evidence on 1) the effects of naloxone route of administration and dosing for suspected opioid overdose in out-of-hospital settings on mortality, reversal of overdose, and harms, and 2) the need for transport to a health care facility after reversal of overdose with naloxone. DATA SOURCES: Ovid MEDLINE (1946 through September 2017), PsycINFO, Cochrane Central Register of Controlled Trials, CINAHL, U.S. Food and Drug Administration (FDA) materials, and reference lists. STUDY SELECTION: English-language cohort studies and randomized trials that compared different doses of naloxone, administration routes, or transport versus nontransport after reversal of overdose with naloxone. Main outcomes were mortality, reversal of overdose, recurrence of overdose, and harms. DATA EXTRACTION: Dual extraction and quality assessment of individual studies; consensus assessment of overall strength of evidence (SOE). DATA SYNTHESIS: Of 13 eligible studies, 3 randomized controlled trials and 4 cohort studies compared different administration routes. At the same dose (2 mg), 1 trial found similar efficacy between higher-concentration intranasal naloxone (2 mg/mL) and intramuscular naloxone, and 1 trial found that lower-concentration intranasal naloxone (2 mg/5 mL) was less effective than intramuscular naloxone but was associated with decreased risk for agitation (low SOE). Evidence was insufficient to evaluate other comparisons of route of administration. Six uncontrolled studies reported low rates of death and serious adverse events (0% to 1.25%) in nontransported patients after successful naloxone treatment. LIMITATION: There were few studies, all had methodological limitations, and none evaluated FDA-approved autoinjectors or highly concentrated intranasal formulations. CONCLUSION: Higher-concentration intranasal naloxone (2 mg/mL) seems to have efficacy similar to that of intramuscular naloxone for reversal of opioid overdose, with no difference in adverse events. Nontransport after reversal of overdose with naloxone seems to be associated with a low rate of serious harms, but no study evaluated risks of transport versus nontransport. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (PROSPERO: CRD42016053891).

Comparative Effectiveness of Fluorescent Versus White Light Cystoscopy for Initial Diagnosis or Surveillance of Bladder Cancer on Clinical Outcomes: Systematic Review and Meta-Analysis.

PURPOSE: We systematically reviewed the comparative effectiveness of fluorescent vs white light cystoscopy on bladder cancer clinical outcomes. MATERIALS AND METHODS: Systematic literature searches of Ovid MEDLINE® (January 1990 through September 2015), Cochrane databases and reference lists were performed. A total of 14 randomized trials of fluorescent cystoscopy using 5-aminolevulinic acid or hexaminolevulinic acid vs white light cystoscopy for the diagnosis of initial or recurrent bladder cancer that reported bladder cancer recurrence, progression, mortality and harms were selected for review. RESULTS: Fluorescent cystoscopy was associated with a decreased risk of bladder cancer recurrence vs white light cystoscopy at short-term (less than 3 months, 10 trials, RR 0.59, 95% CI 0.40 to 0.88, I2=69%), intermediate-term (3 months to less than 1 year, 6 trials, RR 0.70, 95% CI 0.56 to 0.88, I2=19%) and long-term followup (1 year or more, 12 trials, RR 0.81, 95% CI 0.70 to 0.93, I2=49%). However, the findings were inconsistent, and potentially susceptible to performance and publication bias (strength of evidence low). There were no differences between cystoscopic methods in risk of mortality (3 trials, RR 1.28, 95% CI 0.55 to 2.95, I2=41%) (strength of evidence low) or progression (9 trials, RR 0.74, 95% CI 0.52 to 1.03, I2=0%) (strength of evidence moderate). Estimates for short-term recurrence (6 trials, RR 0.62, 95% CI 0.38 to 1.00), long-term recurrence (7 trials, RR 0.75, 95% CI 0.62 to 0.92) and progression (4 trials, RR 0.51, 95% CI 0.28 to 0.96) were statistically significant in the subgroup of trials that used hexaminolevulinic acid, but there were no statistically significant interactions based on the photosensitizer used. Fluorescent cystoscopy was not associated with a decreased risk of long-term recurrence in 3 trials that used methods to reduce performance bias with initial cystoscopy (RR 0.96, 95% CI 0.79 to 1.18, I2=36%). Data on harms were sparse. CONCLUSIONS: Fluorescent cystoscopy was associated with a reduced risk of bladder cancer recurrence vs white light cystoscopy. However, additional trials that adequately guard against performance bias are needed to confirm these findings. Fluorescent cystoscopy with hexaminolevulinic acid may be associated with a decreased risk of progression, but more studies with long-term followup are needed to better understand the effects of the photosensitizer used on progression.

Intravesical Therapy for the Treatment of Nonmuscle Invasive Bladder Cancer: A Systematic Review and Meta-Analysis.

PURPOSE: We systematically review the benefits and harms of intravesical therapies for nonmuscle invasive bladder cancer. MATERIALS AND METHODS: Systematic literature searches were performed of Ovid MEDLINE (January 1990 through February 2016), the Cochrane databases and reference lists. Randomized and quasi-randomized trials of intravesical bacillus Calmette-Guérin, mitomycin C, gemcitabine, thiotepa, valrubicin, doxorubicin, epirubicin and interferon vs transurethral bladder tumor resection alone, and head-to-head trials of intravesical therapies were selected. Data were pooled using a random effects model. RESULTS: Overall 39 trials evaluated adjuvant intravesical therapy vs transurethral bladder tumor resection alone. Bacillus Calmette-Guérin was associated with a decreased risk of bladder cancer recurrence (3 trials, RR 0.56, 95% CI 0.43-0.71) and progression (4 trials, RR 0.39, 95% CI 0.24-0.64) (strength of evidence low). Mitomycin C, doxorubicin, epirubicin and thiotepa were also associated with a decreased risk of recurrence, with no difference in risk of progression (strength of evidence low). There were 55 trials that compared one intravesical therapy agent against another. There were no differences between bacillus Calmette-Guérin vs mitomycin C in recurrence risk (RR 0.95, 95% CI 0.81-1.11), but bacillus Calmette-Guérin was associated with a decreased risk of recurrence in the subgroup of trials of maintenance regimens (RR 0.79, 95% CI 0.71-0.87, strength of evidence low). Bacillus Calmette-Guérin was associated with a lower recurrence risk vs doxorubicin, epirubicin, interferon alpha-2a, bacillus Calmette-Guérin plus interferon alpha-2b, and thiotepa (strength of evidence low to moderate). Bacillus Calmette-Guérin was associated with higher rates of local and systemic adverse events than other intravesical agents (strength of evidence low). Head-to-head trials showed no clear differences between standard and lower doses of bacillus Calmette-Guérin in recurrence, progression or mortality risk (strength of evidence low). Limited evidence suggested that bacillus Calmette-Guérin maintenance regimens are associated with reduced recurrence risk vs no further intravesical therapy in responders to induction therapy (strength of evidence low). CONCLUSIONS: For nonmuscle invasive bladder cancer several intravesical therapies are associated with a decreased risk of recurrence vs transurethral bladder tumor resection alone. Bacillus Calmette-Guérin is the only agent associated with a decreased progression risk vs transurethral bladder tumor resection alone, but may be associated with a higher risk of adverse events than other intravesical therapies, indicating trade-offs between potential benefits and harms.

Predictive Utility of the Total Glasgow Coma Scale Versus the Motor Component of the Glasgow Coma Scale for Identification of Patients With Serious Traumatic Injuries.

STUDY OBJECTIVE: The motor component of the Glasgow Coma Scale (mGCS) has been proposed as an easier-to-use alternative to the total GCS (tGCS) for field assessment of trauma patients by emergency medical services. We perform a systematic review and meta-analysis to compare the predictive utility of the tGCS versus the mGCS or Simplified Motor Scale in field triage of trauma for identifying patients with adverse outcomes (inhospital mortality or severe brain injury) or who underwent procedures (neurosurgical intervention or emergency intubation) indicating need for high-level trauma care. METHODS: Ovid MEDLINE, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, Health and Psychosocial Instruments, and the Cochrane databases were searched through June 2016 for English-language cohort studies. We included studies that compared the area under the receiver operating characteristic curve (AUROC) of the tGCS versus the mGCS or Simplified Motor Scale assessed in the field or shortly after arrival in the emergency department for predicting the outcomes described above. Meta-analyses were performed with a random-effects model, and subgroup and sensitivity analyses were conducted. RESULTS: We included 18 head-to-head studies of predictive utility (n=1,703,388). For inhospital mortality, the tGCS was associated with slightly greater discrimination than the mGCS (pooled mean difference in [AUROC] 0.015; 95% confidence interval [CI] 0.009 to 0.022; I2=85%; 12 studies) or the Simplified Motor Scale (pooled mean difference in AUROC 0.030; 95% CI 0.024 to 0.036; I2=0%; 5 studies). The tGCS was also associated with greater discrimination than the mGCS or Simplified Motor Scale for nonmortality outcomes (differences in AUROC from 0.03 to 0.05). Findings were robust in subgroup and sensitivity analyses. CONCLUSION: The tGCS is associated with slightly greater discrimination than the mGCS or Simplified Motor Scale for identifying severe trauma. The small differences in discrimination are likely to be clinically unimportant and could be offset by factors such as convenience and ease of use.

Screening for Celiac Disease: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Silent or subclinical celiac disease may result in potentially avoidable adverse health consequences. Objective: To review the evidence on benefits and harms of screening for celiac disease in asymptomatic adults, adolescents, and children 3 years and older for the US Preventive Services Task Force. Data Sources: Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews, searched to June 14, 2016. Study Selection: Randomized clinical trials and cohort or case-control studies on clinical benefits and harms of screening vs no screening for celiac disease or treatment vs no treatment for screen-detected celiac disease; studies on diagnostic accuracy of serologic tests for celiac disease. Data Extraction and Synthesis: One investigator abstracted data, a second checked data for accuracy, and 2 investigators independently assessed study quality using predefined criteria. Main Outcomes and Measures: Cancer incidence, gastrointestinal outcomes, psychological outcomes, child growth outcomes, health outcomes resulting from nutritional deficiencies, quality of life, mortality, and harms of screening. No meta-analytic pooling was done. Results: One systematic review and 3 primary studies met inclusion criteria. No trials of screening for celiac disease were identified. One recent, good-quality systematic review of 56 original studies and 12 previous systematic reviews (sample sizes of primary studies ranging from 62 to more than 12 000 participants) found IgA tissue transglutaminase was associated with high accuracy (sensitivity and specificity both >90%) for diagnosing celiac disease. IgA endomysial antibodies tests were associated with high specificity. Only 2 studies of serologic tests for celiac disease involving 62 and 158 patients were conducted in asymptomatic populations and reported lower sensitivity (57% and 71%). One fair-quality, small (n = 40) Finnish treatment trial of asymptomatic adults with screen-detected celiac disease based on positive serologic findings found initiation of a gluten-free diet associated with small improvement in gastrointestinal symptoms compared with no gluten-free diet (difference less than 1 point on a scale of 1 to 7) at 1 year, with no differences on most measures of quality of life. No withdrawals due to adverse events occurred during the trial; no other harms were reported. No studies were identified that addressed the other outcomes. Conclusions and Relevance: Although some evidence was found regarding diagnostic accuracy of tests for celiac disease, little or no evidence was identified to inform most of the key questions related to benefits and harms of screening for celiac disease in asymptomatic individuals. More research is needed to understand the effectiveness of screening and treatment for celiac disease, accuracy of screening tests in asymptomatic persons, and optimal screening strategies.

Treatment of muscle-invasive bladder cancer: A systematic review.

There is uncertainty regarding the use of bladder-sparing alternatives to standard radical cystectomy, optimal lymph node dissection techniques, and optimal chemotherapeutic regimens. This study was conducted to systematically review the benefits and harms of bladder-sparing therapies, lymph node dissection, and systemic chemotherapy for patients with clinically localized muscle-invasive bladder cancer. Systematic literature searches of MEDLINE (from 1990 through October 2014), the Cochrane databases, reference lists, and the ClinicalTrials.gov Web site were performed. A total of 41 articles were selected for review. Bladder-sparing therapies were found to be associated with worse survival compared with radical cystectomy, although the studies had serious methodological shortcomings, findings were inconsistent, and only a few studies evaluated currently recommended techniques. More extensive lymph node dissection might be more effective than less extensive dissection at improving survival and decreasing local disease recurrence, but there were methodological shortcomings and some inconsistency. Six randomized trials found cisplatin-based combination neoadjuvant chemotherapy to be associated with a decreased mortality risk versus cystectomy alone. Four randomized trials found adjuvant chemotherapy to be associated with decreased mortality versus cystectomy alone, but none of these trials reported a statistically significant effect. There was insufficient evidence to determine optimal chemotherapeutic regimens.

Urinary Biomarkers for Diagnosis of Bladder Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: Urinary biomarkers may be a useful alternative or adjunct to cystoscopy for diagnosis of bladder cancer. PURPOSE: To systematically review the evidence on the accuracy of urinary biomarkers for diagnosis of bladder cancer in adults who have signs or symptoms of the disease or are undergoing surveillance for recurrent disease. DATA SOURCES: Ovid MEDLINE (January 1990 through June 2015), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and reference lists. STUDY SELECTION: 57 studies that evaluated the diagnostic accuracy of quantitative or qualitative nuclear matrix protein 22 (NMP22), qualitative or quantitative bladder tumor antigen (BTA), fluorescence in situ hybridization (FISH), fluorescent immunohistochemistry (ImmunoCyt [Scimedx]), and Cxbladder (Pacific Edge Diagnostics USA) using cystoscopy and histopathology as the reference standard met inclusion criteria. Case-control studies were excluded. DATA EXTRACTION: Dual extraction and quality assessment of individual studies. Overall strength of evidence (SOE) was also assessed. DATA SYNTHESIS: Across biomarkers, sensitivities ranged from 0.57 to 0.82 and specificities ranged from 0.74 to 0.88. Positive likelihood ratios ranged from 2.52 to 5.53, and negative likelihood ratios ranged from 0.21 to 0.48 (moderate SOE for quantitative NMP22, qualitative BTA, FISH, and ImmunoCyt; low SOE for others). For some biomarkers, sensitivity was higher for initial diagnosis of bladder cancer than for diagnosis of recurrence. Sensitivity increased with higher tumor stage or grade. Studies that directly compared the accuracy of quantitative NMP22 and qualitative BTA found no differences in diagnostic accuracy (moderate SOE); head-to-head studies of other biomarkers were limited. Urinary biomarkers plus cytologic evaluation were more sensitive than biomarkers alone but missed about 10% of bladder cancer cases. LIMITATION: Restricted to English-language studies; no search for studies published only as abstracts; statistical heterogeneity present in most analyses; few studies for qualitative NMP22, quantitative BTA, and Cxbladder; and methodological shortcomings in almost all studies. CONCLUSION: Urinary biomarkers miss a substantial proportion of patients with bladder cancer and are subject to false-positive results in others. Accuracy is poor for low-stage and low-grade tumors. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (PROSPERO registration number: CRD42014013284).