Trends in intentional abuse and misuse ingestions in school-aged children and adolescents reported to US poison centers from 2000-2020.

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.

Telehealth-guided provider-to-provider communication to improve rural health: A systematic review.

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.

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 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.

Psychosocial Interventions for Adults With Schizophrenia: An Overview and Update of Systematic Reviews.

OBJECTIVE: The authors of this systematic review (SR) sought to provide evidence for effects of commonly used psychosocial interventions on several outcomes among adults with schizophrenia. METHODS: MEDLINE, 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. RESULTS: Nine 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. CONCLUSIONS: Compared 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.

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.

Effectiveness of and Access to Medications for Opioid Use Disorder for Adolescents and Young Adults: A Scoping Review.

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.

Office-Based Methadone Treatment for Opioid Use Disorder and Pharmacy Dispensing: A Scoping Review.

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.

Mobile methadone medication units: A brief history, scoping review and research opportunity.

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.

Interim methadone - Effective but underutilized: A scoping review.

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.

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

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

Updating the Comparative Evidence on Second-Generation Antipsychotic Use With Schizophrenia.

Objective: 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. Methods: 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. Results: 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. Conclusions: 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.

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.

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

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

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

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