Introduction Telehealth may address healthcare disparities for rural populations. This systematic review assesses the use, effectiveness, and implementation of telehealth-supported provider-to-provider collaboration to improve rural healthcare. Methods We searched Ovid MEDLINE®, CINAHL®, EMBASE, and Cochrane CENTRAL from 1 January 2010 to 12 October 2021 for trials and observational studies of rural provider-to-provider telehealth. Abstracts and full text were dual-reviewed. We assessed the risk of bias for individual studies and strength of evidence for studies with similar outcomes. Results Seven studies of rural uptake of provider-to-provider telehealth documented increases over time but variability across geographic regions. In 97 effectiveness studies, outcomes were similar with rural provider-to-provider telehealth versus without for inpatient consultations, neonatal care, outpatient depression and diabetes, and emergency care. Better or similar results were reported for changes in rural clinician behavior, knowledge, confidence, and self-efficacy. Evidence was insufficient for other clinical uses and outcomes. Sixty-seven (67) evaluation and qualitative studies identified barriers and facilitators to implementing rural provider-to-provider telehealth. Success was linked to well-functioning technology, sufficient resources, and adequate payment. Barriers included lack of understanding of rural context and resources. Methodologic weaknesses of studies included less rigorous study designs and small samples. Discussion Rural provider-to-provider telehealth produces similar or better results versus care without telehealth. Barriers to rural provider-to-provider telehealth implementation are common to practice change but include some specific to rural adaptation and adoption. Evidence gaps are partially due to studies that do not address differences in the groups compared or do not include sufficient sample sizes.

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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.

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.

Objectives. To assess the use, effectiveness, and implementation of telehealth-supported provider-to-provider communication and collaboration for the provision of healthcare services to rural populations and to inform a scientific workshop convened by the National Institutes of Health Office of Disease Prevention on October 12–14, 2021. Data sources. We conducted a comprehensive literature search of Ovid MEDLINE®, CINAHL®, Embase®, and Cochrane CENTRAL. We searched for articles published from January 1, 2015, to October 12, 2021, to identify data on use of rural provider-to-provider telehealth (Key Question 1) and the same databases for articles published January 1, 2010, to October 12, 2021, for studies of effectiveness and implementation (Key Questions 2 and 3) and to identify methodological weaknesses in the research (Key Question 4). Additional sources were identified through reference lists, stakeholder suggestions, and responses to a Federal Register notice. Review methods. Our methods followed the Agency for Healthcare Research and Quality Methods Guide (available at https://effectivehealthcare.ahrq.gov/topics/cer-methods-guide/overview) and the PRISMA reporting guidelines. We used predefined criteria and dual review of abstracts and full-text articles to identify research results on (1) regional or national use, (2) effectiveness, (3) barriers and facilitators to implementation, and (4) methodological weakness in studies of provider-to-provider telehealth for rural populations. We assessed the risk of bias of the effectiveness studies using criteria specific to the different study designs and evaluated strength of evidence (SOE) for studies of similar telehealth interventions with similar outcomes. We categorized barriers and facilitators to implementation using the Consolidated Framework for Implementation Research (CFIR) and summarized methodological weaknesses of studies. Results. We included 166 studies reported in 179 publications. Studies on the degree of uptake of provider-to-provider telehealth were limited to specific clinical uses (pharmacy, psychiatry, emergency care, and stroke management) in seven studies using national or regional surveys and claims data. They reported variability across States and regions, but increasing uptake over time. Ninety-seven studies (20 trials and 77 observational studies) evaluated the effectiveness of provider-to-provider telehealth in rural settings, finding that there may be similar rates of transfers and lengths of stay with telehealth for inpatient consultations; similar mortality rates for remote intensive care unit care; similar clinical outcomes and transfer rates for neonates; improvements in medication adherence and treatment response in outpatient care for depression; improvements in some clinical monitoring measures for diabetes with endocrinology or pharmacy outpatient consultations; similar mortality or time to treatment when used to support emergency assessment and management of stroke, heart attack, or chest pain at rural hospitals; and similar rates of appropriate versus inappropriate transfers of critical care and trauma patients with specialist telehealth consultations for rural emergency departments (SOE: low). Studies of telehealth for education and mentoring of rural healthcare providers may result in intended changes in provider behavior and increases in provider knowledge, confidence, and self-efficacy (SOE: low). Patient outcomes were not frequently reported for telehealth provider education, but two studies reported improvement (SOE: low). Evidence for telehealth interventions for other clinical uses and outcomes was insufficient. We identified 67 program evaluations and qualitative studies that identified barriers and facilitators to rural provider-to-provider telehealth. Success was linked to well-functioning technology; sufficient resources, including time, staff, leadership, and equipment; and adequate payment or reimbursement. Some considerations may be unique to implementation of provider-to-provider telehealth in rural areas. These include the need for consultants to better understand the rural context; regional initiatives that pool resources among rural organizations that may not be able to support telehealth individually; and programs that can support care for infrequent as well as frequent clinical situations in rural practices. An assessment of methodological weaknesses found that studies were limited by less rigorous study designs, small sample sizes, and lack of analyses that address risks for bias. A key weakness was that studies did not assess or attempt to adjust for the risk that temporal changes may impact the results in studies that compared outcomes before and after telehealth implementation. Conclusions. While the evidence base is limited, what is available suggests that telehealth supporting provider-to-provider communications and collaboration may be beneficial. Telehealth studies report better patient outcomes in some clinical scenarios (e.g., outpatient care for depression or diabetes, education/mentoring) where telehealth interventions increase access to expertise and high-quality care. In other applications (e.g., inpatient care, emergency care), telehealth results in patient outcomes that are similar to usual care, which may be interpreted as a benefit when the purpose of telehealth is to make equivalent services available locally to rural residents. Most barriers to implementation are common to practice change efforts. Methodological weaknesses stem from weaker study designs, such as before-after studies, and small numbers of participants. The rapid increase in the use of telehealth in response to the Coronavirus disease 2019 (COVID-19) pandemic is likely to produce more data and offer opportunities for more rigorous studies.

ImportanceTwo 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.ObjectiveTo update the 2013 reviews on screening for glaucoma, to inform the USPSTF.Data SourcesOvid MEDLINE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews (to February 2021); surveillance through January 21, 2022.Study SelectionRandomized clinical trials (RCTs) of screening, referral, and treatment; and studies of screening test diagnostic accuracy.Data Extraction and SynthesisOne investigator abstracted data and a second checked accuracy. Two investigators independently assessed study quality.ResultsEighty-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 RelevanceThis 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.

CONTEXT:Childhood and adolescent misuse and abuse exposures remain a serious public health challenge in the United States. This study aimed to describe recent trends and patterns of intentional substance misuse and abuse exposures among school-aged children and adolescents in the United States. METHODS:This study was a retrospective cohort study of intentional misuse and abuse exposures in children 6 through 18 years reported to the National Poison Data System (NPDS) from January 1, 2000, through December 31, 2020. Demographic trends, reported clinical effects, treatments, management sites, and health outcomes were assessed overall and within four age categories: 6-9, 10-12, 13-15, and 16-18. RESULTS:Between 2000 and 2020, there were 338,727 cases regarding intentional misuse and abuse exposures for children ages 6 through 18 years old. Overall, misuse/abuse ingestions fluctuated over time, with a peak in 2011. The majority of intentional misuse/abuse ingestions occurred in males (58.3%), and more than 80% of all reported exposure cases occurred in youth aged 13 to 18. 32.6% of ingestions resulted in worse than minor clinical outcomes. Older age groups had a greater number of severe medical outcomes compared to younger age groups. Major or life-threatening exposures (including those resulting in death) were more common in males. Overall, deaths were rare (n = 450), 0.1%). Male sex, older age, abuse ingestions, exposure site of a public area or other residence, and multiple ingested substances were other factors associated with increased mortality. Marijuana exposure rates had the highest average monthly increase overall, with the most dramatic rise occurring from 2017 to 2020. Edible marijuana preparations accounted for the highest increase in call rates compared with all other forms of marijuana. DISCUSSION AND CONCLUSION:With over 330,000 poison center cases reported during the 20-year study period, intentional substance misuse and abuse exposures substantially impact the pediatric population. The substances most commonly misused/abused are more widely available substances such as over-the-counter medications, household products and pharmaceuticals commonly prescribed to youth. Differences in age and sex were evident, with males and adolescents more likely to abuse and misuse substances. Our study describes an upward trend in marijuana misuse/abuse exposures among youth, especially those involving edible products. These findings highlight an ongoing concern about the impact of rapidly evolving cannabis legalization on this vulnerable population.

OBJECTIVE:The authors conducted a scoping review to survey the evidence landscape for studies that assessed outcomes of treating patients with opioid use disorder with methadone in office-based settings.METHODS:Ovid MEDLINE and the Cochrane Database of Systematic Reviews were searched, and reference lists were reviewed to identify additional studies. Studies were eligible if they focused on methadone treatment in office-based settings conducted in the United States or other highly developed countries and reported outcomes (e.g., retention in care). Randomized trials and controlled observational studies were prioritized; uncontrolled and descriptive studies were included when stronger evidence was unavailable. One investigator abstracted key information, and a second verified data. A scoping review approach broadly surveyed the evidence, and therefore study quality was not rated formally.RESULTS:Eighteen studies of patients treated with office-based methadone were identified, including six trials, eight observational studies, and four additional articles discussing use of pharmacies to dispense methadone. Studies on office-based methadone treatment, including primary care-based dispensing, were limited but consistently found that stable methadone patients valued office-based care and remained in care with low rates of drug use; outcomes were similar compared with stable patients in regular care. Office-based methadone treatment was associated with higher treatment satisfaction and quality of life. Limitations included underpowered comparisons and small samples.CONCLUSIONS:Limited research suggests that office-based methadone treatment and pharmacy dispensing could enhance access to methadone treatment for patients with opioid use disorder without adversely affecting patient outcomes and, potentially, inform modifications to federal regulations. Research should assess the feasibility of office-based care for less stable patients.

OBJECTIVEThe authors of this systematic review (SR) sought to provide evidence for effects of commonly used psychosocial interventions on several outcomes among adults with schizophrenia.METHODSMEDLINE, the Cochrane Library, and PsycINFO databases were searched through July 2020. Eligible studies were SRs and trials of at least 12 weeks duration and with ≥50 participants that compared psychosocial interventions with treatment as usual among adults with schizophrenia. Study design, year, setting, country, sample size, eligibility criteria, population, clinical and intervention characteristics, results, and funding source were extracted, along with quality criteria. The evidence was evaluated on quality and strength of evidence stratified by intervention area and outcome, according to the Evidence-Based Practice Centers Methods Guide of the Agency for Healthcare Research and Quality.RESULTSNine SRs and 30 trials (N=23,921 patients) in 11 intervention areas were included. Trials were mostly of fair quality and had low-to-moderate strength of evidence. Compared with treatment as usual, most psychosocial interventions were more effective in improving intervention-targeted outcomes, including core illness symptoms. Compared with treatment as usual, assertive community treatment, cognitive-behavioral therapy (CBT), family interventions, psychoeducation, social skills training, supported employment, and early interventions for first-episode psychosis (FEP) improved various functional outcomes. CBT and early interventions for FEP improved quality of life. Family interventions, psychoeducation, illness self-management, and early interventions for FEP reduced relapse.CONCLUSIONSCompared with treatment as usual, most psychosocial interventions improved functional outcomes, quality of life, and core illness symptoms, and several reduced relapse frequency among adults with schizophrenia.

Background: The Drug Enforcement Administration (DEA) approved the first mobile medication unit (i.e., a van to administer methadone) in 1988 and approved units on an ad hoc basis until issuing a moratorium in 2007 citing concerns about safety and diversion. In February 2020, the DEA released a notice of proposed rulemaking to permit a resumption of mobile medication units. The Biden Administration plans to release the final rule in 2021. Because a preliminary scan suggested limited evidence, a scoping review examined the research related to methadone vans to identify and assess the extent of mobile methadone research and inform the development and implementation of new mobile services. Methods: A scoping review, supplemented with key informant interviews, identified and described the most relevant evidence. Ovid MEDLINE and the Cochrane Database of Systematic Reviews databases were searched from inception to July 2020. Results: Informant interviews provided perspective on the need for and the use of mobile medication units, the history of methadone vans, and benefits and problems associated with the units. The scoping review found limited evidence: three cohort analyses (one prospective) and one before and after analysis (four studies) of individuals using mobile medication services. Mobile services were associated with enhanced retention in care (relative to patients in fixed site programs) and mobile units appeared to facilitate access for underserved populations with opioid use disorders. Discussion: The key informants addressed the history of methadone vans, the potential use to serve rural communities and correctional facilities and the benefits and problems associated with mobile services. The scoping review found evidence that mobile services increase methadone access among underserved populations and may enhance retention in care. The DEA's proposed regulatory modification creates opportunities to further evaluate the implementation and the effects of mobile medication units.

BACKGROUND:Opioid treatment programs (OTPs) may provide interim methadone services - up to 120 days of methadone dosing without counseling. Regulatory requirements limit use of interim methadone services. We summarized the evidence on interim methadone and other strategies to minimize wait lists in OTPs. METHODS:A scoping review selected studies of interim methadone and strategies that facilitated access to methadone. Randomized trials and controlled observational studies were prioritized; if evidence was lacking, lesser quality evidence was included. RESULTS:Six studies examined interim methadone and three studies examined alternatives: low threshold services, an open access policy, and a medication first policy. The studies included four randomized clinical trials of interim methadone (with three follow-up reports and five secondary analyses), one prospective cohort of interim methadone, one retrospective cohort of interim methadone, one randomized trial of low threshold services and two pre-post assessments of changes in program or state policies. The clinical trials and observational cohorts reported reductions in heroin use during interim methadone and participants were more likely to enter OTPs than those on wait lists. Retention rates in interim methadone were similar to patients in active treatment. Studies testing strategies to facilitate access to methadone were effective without interim methadone's restrictions. CONCLUSION:Interim methadone appears to be effective and safe compared to wait list controls and provided similar outcomes to standard services. Interim methadone could increase access to OTPs. More research is needed on the alternative approaches to facilitate access to medication with comparisons to wait list controls and assessment of patient outcomes.

Objective A scoping review assessed access to medications for opioid use disorder (MOUD) and treatment outcomes among adolescents (12 – 17 years) and young adults (18 – 25 years). Methods Studies addressing adolescent and young adult opioid use disorder and treatment with MOUD on patient outcomes (eg, retention in care) were included. Randomized trials and controlled observational studies were prioritized. Investigators extracted key information, summarized findings, noted methodological weaknesses, and tabled the details. Results The search identified 4 randomized trials (N = 241), 1 systematic review with 52 studies (total N = 125,994), and 5 retrospective analyses of health insurance claims. The trials reported buprenorphine and extended-release naltrexone reduced opioid use. Return to use was observed when pharmacotherapy ceased. A systematic review concluded that adolescents and young adults had lower retention in care than older adults. The observational studies found that adolescents were unlikely to receive MOUD. There was some evidence that non-Hispanic Black adolescents and young adults were less likely than non-Hispanic Whites to receive MOUD. Conclusions MOUD therapies reduce opioid use among adolescent and young adults but few receive MOUD. MOUD services for adolescents and young adults should be developed and tested. Randomized clinical trials are necessary to develop appropriate clinical guidelines for using MOUD with adolescents and young adults.

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 95% 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.

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

The objective of this study was to conduct a systematic review of literature comparing second-generation antipsychotics (SGAs) with each other and with first-generation antipsychotics (FGAs) in treating schizophrenia. MEDLINE, the Cochrane Library, and PsycINFO databases were searched through January 2020. Following standard methods, recent high-quality systematic reviews of each drug comparison and subsequently published primary studies were included to update the meta-analyses with any new data. Two reviewers independently conducted study selection, abstraction, and quality assessment. Two systematic reviews and 29 newer trials (total of 162 trials of SGAs, N=53,861; 116 trials of SGAs versus FGAs, N=119,558) were included. Most trials were of fair quality, industry-funded, and included older SGAs and a few recently approved SGAs (asenapine, lurasidone, iloperidone, cariprazine, brexpiprazole and long-acting injection [LAI] formulations of aripiprazole and paliperidone). Older SGAs had similar effects on function, quality of life, mortality, and adverse event incidence, although clozapine improved symptoms more than most other drugs and olanzapine and risperidone were superior to some other drugs. Olanzapine, risperidone, ziprasidone, and aripiprazole performed similarly on outcomes of benefit compared with haloperidol. Risperidone LAI and olanzapine resulted in fewer withdrawals due to adverse events, but risk of diabetes increased with olanzapine. Haloperidol had greater incidence of adverse events than did olanzapine and risperidone, but similar effects on other outcomes. Most comparative evidence favored older SGAs, with clozapine, olanzapine, and risperidone superior on more outcomes than other SGAs. Older SGAs had similar benefits as haloperidol but with fewer adverse events.

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.

Background Prior reviews on hepatitis C (HCV) infection screening and treatment used by the U.S. Preventive Services Task Force (USPSTF) to inform its 2013 recommendation found interferon-containing antiviral therapies associated with sustained virologic response (SVR) rates of 68 percent to 78 percent and an association between SVR after antiviral therapy and improved clinical outcomes. Interferon-containing regimens were associated with a high rate of harms. Since the prior reviews, interferon-containing antiviral therapies have been replaced by all-oral direct acting antiviral (DAA) regimens. Purpose To systematically review the evidence on screening for HCV infection in asymptomatic adults and adolescents, including effects of DAA regimens and interventions to prevent mother-to-child transmission. Data Sources We searched the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews, Ovid MEDLINE and ClinicalTrials.gov through February 2019, manually reviewed reference lists, and conducted literature surveillance through November 22, 2019. Study Selection Randomized controlled trials (RCTs), non-randomized trials, and cohort studies of HCV screening, antiviral therapy, and interventions to prevent mother-to-child transmission of HCV infection on SVR and clinical outcomes; and cohort studies on the association between an SVR after antiviral therapy versus no SVR and clinical outcomes. Treatment studies focused on populations without cirrhosis who are more likely to be asymptomatic and identified by screening. Data Extraction One investigator abstracted data, and a second investigator checked data abstraction for accuracy. Two investigators independently assessed study quality using methods developed by the USPSTF. Data Synthesis (Results) No study evaluated the benefits of HCV screening versus no screening, or the yield of repeat versus one-time screening. Previously reviewed studies found that HCV screening might be associated with negative psychological and social consequences, but had important methodological limitations; no new studies were identified. One new study found similar diagnostic yield of risk-based and birth cohort screening, but it was retrospective and assumed perfect implementation of risk-based screening. Ten trials reported improvements in some quality of life and functional outcomes following DAA treatment compared with prior to treatment, but differences were small, studies were open-label, and there was no non-DAA comparison group. Forty-nine trials found DAA regimens associated with pooled SVR rates that ranged from 95.5 percent to 98.9 percent across genotypes; rates of serious adverse events (1.9%) and withdrawal due to adverse events (0.4%) were low. Seven trials reported SVR rates in adolescents with DAA therapy similar to those observed in adults. An SVR after antiviral therapy was associated with decreased risk of all-cause mortality (13 studies, pooled hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.28 to 0.56), liver mortality (4 studies, pooled HR 0.11, 95% CI, 0.04 to 0.27), cirrhosis (4 cohorts in 3 studies, pooled HR 0.36, 95% CI, 0.33 to 0.40), and hepatocellular carcinoma (20 studies, pooled HR 0.29, 95% CI, 0.23 to 0.38) versus no SVR, after adjustment for potential confounders. New evidence on interventions to reduce the risk of mother-to-infant transmission was limited and did not change the conclusion from the prior review that no intervention has been clearly demonstrated to reduce risk. Limitations Most DAA trials were not randomized and did not have a non-DAA comparison group, almost all DAA trials relied on SVR as the main efficacy outcome, observational studies varied in how well they adjusted for confounders, and few studies evaluated the effectiveness of DAA regimens in adolescents. Conclusions The USPSTF previously determined that HCV screening is highly accurate. Currently recommended all-oral DAA regimens are associated with very high SVR rates (95.5% to 98.9% across genotypes) and few harms relative to older antiviral therapies. An SVR after antiviral therapy is associated with improved clinical outcomes compared with no SVR, after adjusting for potential confounders. Direct evidence on the benefits of HCV screening remains unavailable, and direct evidence on the effects of antiviral therapy on clinical outcomes remains limited but indicates improved long-term outcomes.

Importance An estimated 862 000 persons in the US are living with chronic infection with hepatitis B virus (HBV). Persons born in regions with a prevalence of HBV infection of 2% or greater, such as countries in Africa and Asia, the Pacific Islands, and parts of South America, often become infected at birth and account for up to 95% of newly reported chronic infections in the US. Other high-prevalence populations include persons who inject drugs; men who have sex with men; persons with HIV infection; and sex partners, needle-sharing contacts, and household contacts of persons with chronic HBV infection. Up to 60% of HBV-infected persons are unaware of their infection, and many remain asymptomatic until onset of cirrhosis or end-stage liver disease. Objective To update its 2014 recommendation, the USPSTF commissioned a review of new randomized clinical trials and cohort studies published from 2014 to August 2019 that evaluated the benefits and harms of screening and antiviral therapy for preventing intermediate outcomes or health outcomes and the association between improvements in intermediate outcomes and health outcomes. New key questions focused on the yield of alternative HBV screening strategies and the accuracy of tools to identify persons at increased risk. Population This recommendation statement applies to asymptomatic, nonpregnant adolescents and adults at increased risk for HBV infection, including those who were vaccinated before being screened for HBV infection. Evidence Assessment The USPSTF concludes with moderate certainty that screening for HBV infection in adolescents and adults at increased risk for infection has moderate net benefit. Recommendation The USPSTF recommends screening for HBV infection in adolescents and adults at increased risk for infection. (B recommendation)

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.