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

Importance: A 2019 review for the US Preventive Services Task Force (USPSTF) found oral preexposure prophylaxis (PrEP) associated with decreased HIV infection risk vs placebo or no PrEP in adults at increased HIV acquisition risk. Newer PrEP regimens are available. Objective: To update the 2019 review on PrEP, to inform the USPSTF. Data Sources: Ovid MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Embase (January 2018 to May 16, 2022); surveillance through March 24, 2023. Study Selection: Randomized clinical trials of PrEP vs placebo or no PrEP or newer vs older PrEP regimens and diagnostic accuracy studies of instruments for predicting incident HIV infection. 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. Main Outcomes and Measures: HIV acquisition, mortality, and harms; and diagnostic test accuracy. Results: Thirty-two studies were included in the review (20 randomized clinical trials [N = 36 543] and 12 studies of diagnostic accuracy [N = 5 544 500]). Eleven trials in the 2019 review found oral PrEP associated with decreased HIV infection risk vs placebo or no PrEP (n = 18 172; relative risk [RR], 0.46 [95% CI, 0.33-0.66]). Higher adherence was associated with greater efficacy. One new trial (n = 5335) found oral tenofovir alafenamide/emtricitabine (TAF/FTC) to be noninferior to tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in men who have sex with men (RR, 0.47 [95% CI, 0.19-1.14]). Two new trials found long-acting injectable cabotegravir associated with decreased risk of HIV infection vs oral TDF/FTC (RR, 0.33 [95% CI, 0.18-0.62] in cisgender men who have sex with men and transgender women [n = 4490] and RR, 0.11 [95% CI, 0.04-0.31] in cisgender women [n = 3178]). Discrimination of instruments for predicting incident HIV infection was moderate in men who have sex with men (5 studies; n = 25 488) and moderate to high in general populations of persons without HIV (2 studies; n = 5 477 291). Conclusions and Relevance: In adults at increased HIV acquisition risk, oral PrEP was associated with decreased risk of acquiring HIV infection compared with placebo or no PrEP. Oral TAF/FTC was noninferior to oral TDF/FTC, and injectable cabotegravir reduced the risk of HIV infection compared with oral TDF/FTC in the populations studied.

Screening, Referral, Behavioral Counseling, and Preventive Interventions for Oral Health in Children and Adolescents Aged 5 to 17 Years: A Systematic Review for the US Preventive Services Task Force.

Importance: Dental caries is common in children and adolescents aged 5 to 17 years and potentially amenable to primary care screening and prevention. Objective: To systematically review the evidence on primary care screening and prevention of dental caries in children and adolescents aged 5 to 17 years to inform the US Preventive Services Task Force. Data Sources: MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews (to October 3, 2022); surveillance through July 21, 2023. Study Selection: Diagnostic accuracy of primary care screening instruments and oral examination; randomized and nonrandomized trials of screening and preventive interventions and systematic reviews of such studies; cohort studies on primary care oral health screening and preventive intervention harms. Data Extraction and Synthesis: One investigator abstracted data; a second checked accuracy. Two investigators independently rated study quality. Random-effects meta-analysis was performed for fluoride supplements and xylitol; for other preventive interventions, pooled estimates were used from good-quality systematic reviews. Main Outcomes and Measures: Dental caries, morbidity, functional status, quality of life, harms; diagnostic test accuracy. Results: Three systematic reviews (total 20 684 participants) and 19 randomized clinical trials, 3 nonrandomized trials, and 1 observational study (total 15 026 participants) were included. No study compared screening vs no screening. When administered by dental professionals or in school settings, fluoride supplements compared with placebo or no intervention were associated with decreased change from baseline in the number of decayed, missing, or filled permanent teeth (DMFT index) or decayed or filled permanent teeth (DFT index) (mean difference, -0.73 [95% CI, -1.30 to -0.19]) at 1.5 to 3 years (6 trials; n = 1395). Fluoride gels were associated with a DMFT- or DFT-prevented fraction of 0.18 (95% CI, 0.09-0.27) at outcomes closest to 3 years (4 trials; n = 1525), fluoride varnish was associated with a DMFT- or DFT-prevented fraction of 0.44 (95% CI, 0.11-0.76) at 1 to 4.5 years (5 trials; n = 3902), and resin-based sealants were associated with decreased risk of carious first molars (odds ratio, 0.21 [95% CI, 0.16-0.28]) at 48 to 54 months (4 trials; n = 440). No trial evaluated primary care counseling or dental referral. Evidence on screening accuracy, silver diamine fluoride, xylitol, and harms was very limited, although serious harms were not reported. Conclusions and Relevance: Administration of fluoride supplements, fluoride gels, varnish, and sealants in dental or school settings improved caries outcomes. Research is needed on the effectiveness of oral health preventive interventions in primary care settings and to determine the benefits and harms of screening.

Screening, Referral, Behavioral Counseling, and Preventive Interventions for Oral Health in Adults: A Systematic Review for the US Preventive Services Task Force.

Importance: Dental caries and periodontal disease are common adult oral health conditions and potentially amenable to primary care screening and prevention. Objective: To systematically review the evidence on primary care screening and prevention of dental caries and periodontal disease in adults to inform the US Preventive Services Task Force. Data Sources: MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews (to October 3, 2022); surveillance through July 21, 2023. Study Selection: Diagnostic accuracy studies of primary care screening instruments and oral examination; randomized and nonrandomized trials of screening and preventive interventions; cohort studies on primary care oral health screening and preventive intervention harms. Data Extraction and Synthesis: One investigator abstracted data; a second checked accuracy. Two investigators independently rated study quality. Diagnostic accuracy data were pooled using a bivariate mixed-effects binary regression model. Main Outcomes and Measures: Dental caries, periodontal disease, morbidity, quality of life, harms; and diagnostic test accuracy. Results: Five randomized clinical trials, 5 nonrandomized trials, and 6 observational studies (total 3300 participants) were included. One poor-quality trial (n = 477) found no difference between oral health screening during pregnancy vs no screening in caries, periodontal disease, or birth outcomes. One study (n = 86) found oral health examination by 2 primary care clinicians associated with low sensitivity (0.42 and 0.56) and high specificity (0.84 and 0.87) for periodontal disease and with variable sensitivity (0.33 and 0.83) and high specificity (0.80 and 0.93) for dental caries. Four studies (n = 965) found screening questionnaires associated with a pooled sensitivity of 0.72 (95% CI, 0.57-0.83) and specificity of 0.74 (95% CI, 0.66-0.82) for periodontal disease. For preventive interventions no study evaluated primary care counseling or dental referral, and evidence from 2 poor-quality trials (n = 178) of sealants, and 1 fair-quality and 4 poor-quality trials (n = 971) of topical fluorides, was insufficient. Three fair-quality trials (n = 590) of persons with mean age 72 to 80 years found silver diamine fluoride solution associated with fewer new root caries lesions or fillings vs placebo (mean reduction, -0.33 to -1.3) and decreased likelihood of new root caries lesion (2 trials; adjusted odds ratio, 0.4 [95% CI, 0.3-0.7]). No trial evaluated primary care-administered preventive interventions. Conclusions and Relevance: Screening questionnaires were associated with moderate diagnostic accuracy for periodontal disease. Research is needed to determine benefits and harms of oral health primary care screening and preventive interventions.

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 Gestational Diabetes: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Gestational diabetes is associated with several poor health outcomes. Objective: To update the 2012 review on screening for gestational diabetes to inform the US Preventive Services Task Force. Data Sources: MEDLINE, EMBASE, and CINAHL (2010 to May 2020), ClinicalTrials.gov, reference lists; surveillance through June 2021. Study Selection: English-language intervention studies for screening and treatment; observational studies on screening; prospective studies on screening test accuracy. Data Extraction and Synthesis: Dual review of titles/abstracts, full-text articles, and study quality. Single-reviewer data abstraction with verification. Random-effects meta-analysis or bivariate analysis (accuracy). Main Outcomes and Measures: Pregnancy, fetal/neonatal, and long-term health outcomes; harms of screening; accuracy. Results: A total of 76 studies were included (18 randomized clinical trials [RCTs] [n = 31 241], 2 nonrandomized intervention studies [n = 190], 56 observational studies [n = 261 678]). Direct evidence on benefits of screening vs no screening was limited to 4 observational studies with inconsistent findings and methodological limitations. Screening was not significantly associated with serious or long-term harm. In 5 RCTs (n = 25 772), 1-step (International Association of Diabetes and Pregnancy Study Group) vs 2-step (Carpenter and Coustan) screening was significantly associated with increased likelihood of gestational diabetes (11.5% vs 4.9%) but no improved health outcomes. At or after 24 weeks of gestation, oral glucose challenge tests with 140- and 135-mg/dL cutoffs had sensitivities of 82% and 93%, respectively, and specificities of 82% and 79%, respectively, against Carpenter and Coustan criteria, and a test with a 140-mg/dL cutoff had sensitivity of 85% and specificity of 81% against the National Diabetes Group Data criteria. Fasting plasma glucose tests with cutoffs of 85 and 90 mg/dL had sensitivities of 88% and 81% and specificities of 73% and 82%, respectively, against Carpenter and Coustan criteria. Based on 8 RCTs and 1 nonrandomized study (n = 3982), treatment was significantly associated with decreased risk of primary cesarean deliveries (relative risk [RR], 0.70 [95% CI, 0.54-0.91]; absolute risk difference [ARD], 5.3%), shoulder dystocia (RR, 0.42 [95% CI, 0.23-0.77]; ARD, 1.3%), macrosomia (RR, 0.53 [95% CI, 0.41-0.68]; ARD, 8.9%), large for gestational age (RR, 0.56 [95% CI, 0.47-0.66]; ARD, 8.4%), birth injuries (odds ratio, 0.33 [95% CI, 0.11-0.99]; ARD, 0.2%), and neonatal intensive care unit admissions (RR, 0.73 [95% CI, 0.53-0.99]; ARD, 2.0%). The association with reduction in preterm deliveries was not significant (RR, 0.75 [95% CI, 0.56-1.01]). Conclusions and Relevance: Direct evidence on screening vs no screening remains limited. One- vs 2-step screening was not significantly associated with improved health outcomes. At or after 24 weeks of gestation, treatment of gestational diabetes was significantly associated with improved health outcomes.

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 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.

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.

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.

Screening for Dyslipidemia in Younger Adults: A Systematic Review for the U.S. Preventive Services Task Force.

BACKGROUND: Dyslipidemia may occur in younger adults (defined as persons aged 21 to 39 years) and is an important risk factor for cardiovascular disease. Screening might identify younger adults with asymptomatic dyslipidemia who may benefit from lipid-lowering therapies. PURPOSE: To update the 2008 U.S. Preventive Services Task Force review on dyslipidemia screening in younger adults. DATA SOURCES: The Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and MEDLINE through May 2016, and reference lists. STUDY SELECTION: Randomized, controlled trials; cohort studies; and case-control studies on screening for or treatment of asymptomatic dyslipidemia in adults aged 21 to 39 years. DATA EXTRACTION: The plan was for 1 investigator to abstract data and a second to check their accuracy, and for 2 investigators to independently assess study quality; however, no studies met the inclusion criteria. DATA SYNTHESIS: No study evaluated the effects of lipid screening versus no screening, treatment versus no treatment, or delayed versus earlier treatment on clinical outcomes in younger adults. In addition, no study evaluated the diagnostic yield of alternative screening strategies (such as targeted screening of persons with a family history of hyperlipidemia vs. general screening) in younger adults. LIMITATION: No direct relevant evidence. CONCLUSION: Direct evidence on the benefits and harms of screening for or treatment of dyslipidemia in younger adults remains unavailable. Estimating the potential effects of screening for dyslipidemia in this population requires extrapolation from studies performed in older adults. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

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.

Screening and treatment of thyroid dysfunction: an evidence review for the U.S. Preventive Services Task Force.

BACKGROUND: In 2004, the U.S. Preventive Services Task Force found insufficient evidence to recommend thyroid screening. PURPOSE: To update the 2004 U.S. Preventive Services Task Force review on the benefits and harms of screening and treatment of subclinical and undiagnosed overt hypothyroidism and hyperthyroidism in adults without goiter or thyroid nodules. DATA SOURCES: MEDLINE and Cochrane databases through July 2014. STUDY SELECTION: Randomized, controlled trials and observational studies of screening and treatment. DATA EXTRACTION: One investigator abstracted data, and a second investigator confirmed; 2 investigators independently assessed study quality. DATA SYNTHESIS: No study directly assessed benefits and harms of screening versus no screening. For subclinical hypothyroidism (based on thyroid-stimulating hormone levels of 4.1 to 11.0 mIU/L), 1 fair-quality cohort study found that treatment of subclinical hypothyroidism was associated with decreased risk for coronary heart disease events versus no treatment. No study found that treatment was associated with improved quality of life, cognitive function, blood pressure, or body mass index versus no treatment. Effects of treatment versus no treatment showed potential beneficial effects on lipid levels, but effects were inconsistent, not statistically significant in most studies, and of uncertain clinical significance (difference, -0.7 to 0 mmol/L [-28 to 0 mg/dL] for total cholesterol levels and -0.6 to 0.1 mmol/L [-22 to 2 mg/dL] for low-density lipoprotein cholesterol levels). Treatment harms were poorly studied and sparsely reported. Two poor-quality studies evaluated treatment of subclinical hyperthyroidism but examined intermediate outcomes. No study evaluated treatment versus no treatment of screen-detected, undiagnosed overt thyroid dysfunction. LIMITATION: English-language articles only, no treatment study performed in the United States, and small trials with short duration that used different dosage protocols. CONCLUSION: More research is needed to determine the clinical benefits associated with thyroid screening. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Screening for type 2 diabetes mellitus: a systematic review for the U.S. Preventive Services Task Force.

BACKGROUND: Screening for type 2 diabetes mellitus could lead to earlier identification and treatment of asymptomatic diabetes, impaired fasting glucose (IFG), or impaired glucose tolerance (IGT), potentially resulting in improved outcomes. PURPOSE: To update the 2008 U.S. Preventive Services Task Force review on diabetes screening in adults. DATA SOURCES: Cochrane databases and MEDLINE (2007 through October 2014) and relevant studies from previous Task Force reviews. STUDY SELECTION: Randomized, controlled trials; controlled, observational studies; and systematic reviews. DATA EXTRACTION: Data were abstracted by 1 investigator and checked by a second; 2 investigators independently assessed study quality. DATA SYNTHESIS: In 2 trials, screening for diabetes was associated with no 10-year mortality benefit versus no screening (hazard ratio, 1.06 [95% CI, 0.90 to 1.25]). Sixteen trials consistently found that treatment of IFG or IGT was associated with delayed progression to diabetes. Most trials of treatment of IFG or IGT found no effects on all-cause or cardiovascular mortality, although lifestyle modification was associated with decreased risk for both outcomes after 23 years in 1 trial. For screen-detected diabetes, 1 trial found no effect of an intensive multifactorial intervention on risk for all-cause or cardiovascular mortality versus standard control. In diabetes that was not specifically screen-detected, 9 systematic reviews found that intensive glucose control did not reduce risk for all-cause or cardiovascular mortality and results for intensive blood pressure control were inconsistent. LIMITATION: The review was restricted to English-language articles, and few studies were conducted in screen-detected populations. CONCLUSION: Screening for diabetes did not improve mortality rates after 10 years of follow-up. More evidence is needed to determine the effectiveness of treatments for screen-detected diabetes. Treatment of IFG or IGT was associated with delayed progression to diabetes. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Routine iron supplementation and screening for iron deficiency anemia in pregnancy: a systematic review for the U.S. Preventive Services Task Force.

BACKGROUND: Routine screening and supplementation for iron deficiency anemia (IDA) in asymptomatic, nonanemic pregnant women could improve maternal and infant health outcomes. PURPOSE: Update of a 2006 systematic review by the U.S. Preventive Services Task Force on screening and supplementation for IDA in pregnancy. DATA SOURCES: MEDLINE and the Cochrane Library (1996 to August 2014) and reference lists of relevant systematic reviews to identify studies published since 1996. STUDY SELECTION: English-language trials and controlled observational studies about effectiveness of screening and routine supplementation for IDA in developed countries. DATA EXTRACTION: Data extraction and quality assessment confirmed and dual-rated by a second investigator using prespecified criteria. DATA SYNTHESIS: No study directly compared clinical outcomes or harms of screening or not screening pregnant women for IDA. Twelve supplementation trials were included, and no controlled observational studies met inclusion criteria. On the basis of 11 trials, routine maternal iron supplementation had inconsistent effects on rates of cesarean delivery, small size for gestational age, and low birthweight and no effect on maternal quality of life, gestational age, Apgar scores, preterm birth, or infant mortality. Twelve trials reported improvements in maternal hematologic indices, although not all were statistically significant. Pooled analysis of 4 trials resulted in a statistically significant difference in IDA incidence at term, favoring supplementation (risk ratio, 0.29 [95% CI, 0.17 to 0.49]; I2 = 0%). Maternal iron supplementation did not affect infant iron status at 6 months. Harms, none of which were serious or had long-term consequences, were inconsistently reported in 10 of the trials, with most finding no difference between groups. LIMITATIONS: Data from trials in countries with limited generalizability to U.S. populations were included. Studies were methodologically heterogeneous, and some were small and underpowered. CONCLUSION: There is inconclusive evidence that routine prenatal supplementation for IDA improves maternal or infant clinical health outcomes, but supplementation may improve maternal hematologic indices. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Epidural Corticosteroid Injections for Radiculopathy and Spinal Stenosis: A Systematic Review and Meta-analysis.

BACKGROUND: Use of epidural corticosteroid injections is increasing. PURPOSE: To review evidence on the benefits and harms of epidural corticosteroid injections in adults with radicular low back pain or spinal stenosis of any duration. DATA SOURCES: Ovid MEDLINE (through May 2015), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, prior systematic reviews, and reference lists. STUDY SELECTION: Randomized trials of epidural corticosteroid injections versus placebo interventions, or that compared epidural injection techniques, corticosteroids, or doses. DATA EXTRACTION: Dual extraction and quality assessment of individual studies, which were used to determine the overall strength of evidence (SOE). DATA SYNTHESIS: 30 placebo-controlled trials evaluated epidural corticosteroid injections for radiculopathy, and 8 trials were done for spinal stenosis. For radiculopathy, epidural corticosteroids were associated with greater immediate-term reduction in pain (weighted mean difference on a scale of 0 to 100, -7.55 [95% CI, -11.4 to -3.74]; SOE, moderate), function (standardized mean difference after exclusion of an outlier trial, -0.33 [CI, -0.56 to -0.09]; SOE, low), and short-term surgery risk (relative risk, 0.62 [CI, 0.41 to 0.92]; SOE, low). Effects were below predefined minimum clinically important difference thresholds, and there were no longer-term benefits. Limited evidence showed no clear effects of technical factors, patient characteristics, or comparator interventions on estimates. There were no clear effects of epidural corticosteroid injections for spinal stenosis (SOE, low to moderate). Serious harms were rare, but harms reporting was suboptimal (SOE, low). LIMITATIONS: The review was restricted to English-language studies. Some meta-analyses were based on small numbers of trials (particularly for spinal stenosis), and most trials had methodological shortcomings. CONCLUSION: Epidural corticosteroid injections for radiculopathy were associated with immediate reductions in pain and function. However, benefits were small and not sustained, and there was no effect on long-term surgery risk. Limited evidence suggested no effectiveness for spinal stenosis.

The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a National Institutes of Health Pathways to Prevention Workshop.

BACKGROUND: Increases in prescriptions of opioid medications for chronic pain have been accompanied by increases in opioid overdoses, abuse, and other harms and uncertainty about long-term effectiveness. PURPOSE: To evaluate evidence on the effectiveness and harms of long-term (>3 months) opioid therapy for chronic pain in adults. DATA SOURCES: MEDLINE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, PsycINFO, and CINAHL (January 2008 through August 2014); relevant studies from a prior review; reference lists; and ClinicalTrials.gov. STUDY SELECTION: Randomized trials and observational studies that involved adults with chronic pain who were prescribed long-term opioid therapy and that evaluated opioid therapy versus placebo, no opioid, or nonopioid therapy; different opioid dosing strategies; or risk mitigation strategies. DATA EXTRACTION: Dual extraction and quality assessment. DATA SYNTHESIS: No study of opioid therapy versus no opioid therapy evaluated long-term (>1 year) outcomes related to pain, function, quality of life, opioid abuse, or addiction. Good- and fair-quality observational studies suggest that opioid therapy for chronic pain is associated with increased risk for overdose, opioid abuse, fractures, myocardial infarction, and markers of sexual dysfunction, although there are few studies for each of these outcomes; for some harms, higher doses are associated with increased risk. Evidence on the effectiveness and harms of different opioid dosing and risk mitigation strategies is limited. LIMITATIONS: Non-English-language articles were excluded, meta-analysis could not be done, and publication bias could not be assessed. No placebo-controlled trials met inclusion criteria, evidence was lacking for many comparisons and outcomes, and observational studies were limited in their ability to address potential confounding. CONCLUSION: Evidence is insufficient to determine the effectiveness of long-term opioid therapy for improving chronic pain and function. Evidence supports a dose-dependent risk for serious harms. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.