Folic Acid Supplementation to Prevent Neural Tube Defects: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Neural tube defects are among the most common birth defects in the US. Objective: To review new evidence on the benefits and harms of folic acid supplementation for the prevention of neural tube defects to inform the US Preventive Services Task Force. Evidence Review: Sources included PubMed, Cochrane Library, Embase, and trial registries from July 1, 2015, through July 2, 2021; references; and experts, with surveillance through February 10, 2023. Two investigators independently reviewed English-language randomized studies and nonrandomized cohort studies in very highly developed countries that focused on the use of folic acid supplementation for the prevention of neural tube defect-affected pregnancies; methodological quality was dually and independently assessed. Findings: Twelve observational studies (reported in 13 publications) were eligible for this limited update (N = 1 244 072). Of these, 3 studies (n = 990 372) reported on the effect of folic acid supplementation on neural tube defects. For harms, 9 studies were eligible: 1 randomized clinical trial (n = 431) reported on variations in twin delivery, 7 observational studies (n = 761 125) reported on the incidence of autism spectrum disorder, and 1 observational study (n = 429 004) reported on maternal cancer. Two cohort studies and 1 case-control study newly identified in this update reported on the association between folic acid supplementation and neural tube defects (n = 990 372). One cohort study reported a statistically significant reduced risk of neural tube defects associated with folic acid supplementation taken before pregnancy (adjusted relative risk [aRR], 0.54 [95% CI, 0.31-0.91]), during pregnancy (aRR, 0.62 [95% CI, 0.39-0.97]), and before and during pregnancy (aRR, 0.49 [95% CI, 0.29-0.83]), but this association occurred for only the later of 2 periods studied (2006-2013 and not 1999-2005). No other statistically significant benefits were reported overall. No study reported statistically significant harms (multiple gestation, autism, and maternal cancer) associated with pregnancy-related folic acid exposure. Conclusions and Relevance: New evidence from observational studies provided additional evidence of the benefit of folic acid supplementation for preventing neural tube defects and no evidence of harms related to multiple gestation, autism, or maternal cancer. The new evidence was consistent with previously reviewed evidence on benefits and harms.

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

Importance: Latent tuberculosis infection (LTBI) can progress to active tuberculosis disease, causing morbidity and mortality. Objective: To review the evidence on benefits and harms of screening for and treatment of LTBI in adults to inform the US Preventive Services Task Force (USPSTF). Data Sources: PubMed/MEDLINE, Cochrane Library, and trial registries through December 3, 2021; references; experts; literature surveillance through January 20, 2023. Study Selection: English-language studies of LTBI screening, LTBI treatment, or accuracy of the tuberculin skin test (TST) or interferon-gamma release assays (IGRAs). Studies of LTBI screening and treatment for public health surveillance or disease management were excluded. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality; qualitative synthesis of findings; meta-analyses conducted when a sufficient number of similar studies were available. Main Outcomes and Measures: Screening test accuracy; development of active tuberculosis disease, transmission, quality of life, mortality, and harms. Results: A total of 113 publications were included (112 studies; N = 69 009). No studies directly evaluated the benefits and harms of screening. Pooled estimates for sensitivity of the TST were 0.80 (95% CI, 0.74-0.87) at the 5-mm induration threshold, 0.81 (95% CI, 0.76-0.87) at the 10-mm threshold, and 0.60 (95% CI, 0.46-0.74) at the 15-mm threshold. Pooled estimates for sensitivity of IGRA tests ranged from 0.81 (95% CI, 0.79-0.84) to 0.90 (95% CI, 0.87-0.92). Pooled estimates for specificity of screening tests ranged from 0.95 to 0.99. For treatment of LTBI, a large (n = 27 830), good-quality randomized clinical trial found a relative risk (RR) for progression to active tuberculosis at 5 years of 0.35 (95% CI, 0.24-0.52) for 24 weeks of isoniazid compared with placebo (number needed to treat, 112) and an increase in hepatotoxicity (RR, 4.59 [95% CI, 2.03-10.39]; number needed to harm, 279). A previously published meta-analysis reported that multiple regimens were efficacious compared with placebo or no treatment. Meta-analysis found greater risk for hepatotoxicity with isoniazid than with rifampin (pooled RR, 4.22 [95% CI, 2.21-8.06]; n = 7339). Conclusions and Relevance: No studies directly evaluated the benefits and harms of screening for LTBI compared with no screening. TST and IGRAs were moderately sensitive and highly specific. Treatment of LTBI with recommended regimens reduced the risk of progression to active tuberculosis. Isoniazid was associated with higher rates of hepatotoxicity than placebo or rifampin.

End-user understanding of qualitative comparative analysis used within evidence synthesis: A mixed-methods study.

BACKGROUND: Enhanced uptake of systematic reviews that use qualitative comparative analyses (QCA) requires knowing how end-users interpret such findings. The study purpose was to identify effective approaches to communicating results from a QCA within a systematic review. METHODS: Sequential exploratory mixed methods design; thematic analysis of interviews with 11 end-users followed by a randomized experiment with 254 participants that provided QCA results for a hypothetical review presented through three formats (text, table, and figure). A survey administered after the experiment assessed subjective and objective comprehension of QCA results. RESULTS: Interview themes included use of jargon; appropriate use of appendices, tables, figures; and integration of QCA results within the systematic review. In the experiment, we observed a significant difference (p = 0.035) in subjective comprehension across the three presentation formats. Participants randomized to the figure and text formats scored higher compared to the table. No significant differences were observed for objective comprehension overall (p = 0.11). However, for parameter interpretation (a unique component of QCA results), scores among participants that received the figure format were significantly higher than scores for participants who received the text (p = 0.001) or table (p = 0.004). No significant differences (p = 0.09) were observed in objective comprehension for configuration interpretation. CONCLUSIONS: End-users of systematic reviews saw value in the use of QCA, but unfamiliar methods and terminology were barriers to full understanding of the findings. When presenting results, a figure format appears to be superior to text or table formats based on measures of subjective comprehension and some measures of objective comprehension.

The impact of interactive advertising on consumer engagement, recall, and understanding: A scoping systematic review for informing regulatory science.

We conducted a scoping systematic review with respect to how consumer engagement with interactive advertising is evaluated and if interactive features influence consumer recall, awareness, or comprehension of product claims and risk disclosures for informing regulatory science. MEDLINE, PsycINFO, Business Source Corporate, and SCOPUS were searched for original research published from 1997 through February 2021. Two reviewers independently screened titles/abstracts and full-text articles for inclusion. Outcomes were abstracted into a structured abstraction form. We included 32 studies overall. The types of interactive ads evaluated included website banner and pop up ads, search engine ads, interactive TV ads, advergames, product websites, digital magazine ads, and ads on social network sites. Twenty-three studies reported objective measures of engagement using observational analyses or laboratory-based experiments. In nine studies evaluating the association between different interactivity features and outcomes, the evidence was mixed on whether more interactivity improves or worsens recall and comprehension. Studies vary with respect to populations, designs, ads evaluated, and outcomes assessed.

Minimally invasive sacroiliac joint fusion for chronic sacroiliac joint pain: a systematic review.

BACKGROUND CONTEXT: Sacroiliac (SI) joint pain causes significant disability and impairment to quality of life (QOL). Minimally invasive SI joint fusion is increasingly used to relieve chronic SI joint pain among patients who do not respond to nonsurgical treatment. PURPOSE: To systematically review the existing literature to assess the effectiveness and safety of minimally invasive SI joint fusion. STUDY DESIGN/SETTING: Systematic review. DATA SOURCES: PubMed, Embase, Cochrane, and a clinical trial registry from database inception to June 30, 2021. STUDY SELECTION: Eligible studies were primary research studies published in the English language, enrolled adults with SI joint pain, and compared SI joint fusion to nonsurgical interventions or alternative minimally invasive procedures. We included randomized controlled trials (RCTs) or controlled cohort studies (CCSs) that reported effectiveness (pain, physical function, QOL, opioid use) or safety outcomes (adverse events [AEs], revision surgeries) and uncontrolled studies that reported safety outcomes. DATA ABSTRACTION AND SYNTHESIS: Data were abstracted into structured forms; two independent reviewers assessed risk of bias using standard instruments; certainty of evidence was rated using GRADE. RESULTS: Forty studies (2 RCTs, 3 CCSs, and 35 uncontrolled studies) were included. Minimally invasive SI joint fusion with the iFuse Implant System appeared to result in larger improvements in pain (two RCTs: mean difference in visual analog scale -40.5 mm, 95% CI, -50.1 to -30.9; -38.1 mm, p<.0001) and larger improvements in physical function (mean difference in Oswestry Disability Index -25.4 points, 95% CI, -32.5 to -18.3; -19.8 points, p<.0001) compared to conservative management at 6 months. Improvements in pain and physical function for the RCTs appeared durable at 1- and 2-year follow-up. Findings were similar in one CCS. The two RCTs also found significant improvements in QOL at 6 months and 1 year. Opioid use may be improved at 6 months and 1 to 2 years. AEs appeared higher in the fusion group at 6 months. The incidence of revision surgery varied by study; the highest was 3.8% at 2 years. Two CCSs compared the effectiveness of alternative minimally invasive fusion procedures. One CCS compared iFuse to the Rialto SI Fusion System and reported no differences in pain, function, QOL, and revision surgeries from 6 months to 1 year. One CCS compared iFuse to percutaneous screw fixation and reported significantly fewer revisions among iFuse participants (mean difference -61.0%, 95% CI, -78.4% to -43.5%). The 35 uncontrolled studies had serious limitations and reported heterogeneous safety outcomes. Two of the larger studies reported a 13.2% incidence of complications from minimally invasive SI joint fusion at 90 days using an insurance claims database and a 3.1% incidence of revision surgery over 2.5 years using a postmarket surveillance database. CONCLUSIONS: Among patients meeting diagnostic criteria for SI joint pain and who have not responded to conservative care, minimally invasive SI joint fusion is probably more effective than conservative management for reducing pain and opioid use and improving physical function and QOL. Fusion with iFuse and Rialto appear to have similar effectiveness. AEs appear to be higher for minimally invasive SI joint fusion than conservative management through 6 months. Based on evidence from uncontrolled studies, serious AEs from minimally invasive SI joint fusion may be higher in usual practice compared to what is reported in trials. The incidence of revision surgery is likely no higher than 3.8% at 2 years. Limited evidence is available that compares different minimally invasive devices.

Screening for Atrial Fibrillation: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Atrial fibrillation (AF), the most common arrhythmia, increases the risk of stroke. Objective: To review the evidence on screening for AF in adults without prior stroke to inform the US Preventive Services Task Force. Data Sources: PubMed, Cochrane Library, and trial registries through October 5, 2020; references, experts, and literature surveillance through October 31, 2021. Study Selection: Randomized clinical trials (RCTs) of screening among asymptomatic persons without known AF or prior stroke; test accuracy studies; RCTs of anticoagulation among persons with AF; systematic reviews; and observational studies reporting harms. Data Extraction and Synthesis: Two reviewers assessed titles/abstracts, full-text articles, and study quality and extracted data; when at least 3 similar studies were available, meta-analyses were conducted. Main Outcomes and Measures: Detection of undiagnosed AF, test accuracy, mortality, stroke, stroke-related morbidity, and harms. Results: Twenty-six studies (N = 113 784) were included. In 1 RCT (n = 28 768) of twice-daily electrocardiography (ECG) screening for 2 weeks, the likelihood of a composite end point (ischemic stroke, hemorrhagic stroke, systemic embolism, all-cause mortality, and hospitalization for bleeding) was lower in the screened group over 6.9 years (hazard ratio, 0.96 [95% CI, 0.92-1.00]; P = .045), but that study had numerous limitations. In 4 RCTs (n = 32 491), significantly more AF was detected with intermittent and continuous ECG screening compared with no screening (risk difference range, 1.0%-4.8%). Treatment with warfarin over a mean of 1.5 years in populations with clinical, mostly persistent AF was associated with fewer ischemic strokes (pooled risk ratio [RR], 0.32 [95% CI, 0.20-0.51]; 5 RCTs; n = 2415) and lower all-cause mortality (pooled RR, 0.68 [95% CI, 0.50-0.93]) compared with placebo. Treatment with direct oral anticoagulants was also associated with lower incidence of stroke (adjusted odds ratios range, 0.32-0.44) in indirect comparisons with placebo. The pooled RR for major bleeding for warfarin compared with placebo was 1.8 (95% CI, 0.85-3.7; 5 RCTs; n = 2415), and the adjusted odds ratio for major bleeding for direct oral anticoagulants compared with placebo or no treatment ranged from 1.38 to 2.21, but CIs did not exclude a null effect. Conclusions and Relevance: Although screening can detect more cases of unknown AF, evidence regarding effects on health outcomes is limited. Anticoagulation was associated with lower risk of first stroke and mortality but with increased risk of major bleeding, although estimates for this harm are imprecise; no trials assessed benefits and harms of anticoagulation among screen-detected populations.

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

Importance: Low serum vitamin D levels have been associated with adverse clinical outcomes; identifying and treating deficiency may improve outcomes. Objective: To review the evidence about screening for vitamin D deficiency in adults. Data Sources: PubMed, EMBASE, the Cochrane Library, and trial registries through March 12, 2020; bibliographies from retrieved articles, outside experts, and surveillance of the literature through November 30, 2020. Study Selection: Fair- or good-quality, English-language randomized clinical trials (RCTs) of screening with serum 25-hydroxyvitamin D (25[OH]D) compared with no screening, or treatment with vitamin D (with or without calcium) compared with placebo or no treatment conducted in nonpregnant adults; nonrandomized controlled intervention studies for harms only. Treatment was limited to studies enrolling or analyzing participants with low serum vitamin D levels. Data Extraction and Synthesis: Two reviewers assessed titles/abstracts and full-text articles, extracted data, and assessed study quality; when at least 3 similar studies were available, meta-analyses were conducted. Main Outcomes and Measures: Mortality, incident fractures, falls, diabetes, cardiovascular events, cancer, depression, physical functioning, and infection. Results: Forty-six studies (N = 16 205) (77 publications) were included. No studies directly evaluated the health benefits or harms of screening. Among community-dwelling populations, treatment was not significantly associated with mortality (pooled absolute risk difference [ARD], 0.3% [95% CI, -0.6% to 1.1%]; 8 RCTs, n = 2006), any fractures (pooled ARD, -0.3% [95% CI, -2.1% to 1.6%]; 6 RCTs, n = 2186), incidence of diabetes (pooled ARD, 0.1% [95% CI, -1.3% to 1.6%]; 5 RCTs, n = 3356), incidence of cardiovascular disease (2 RCTs; hazard ratio, 1.00 [95% CI, 0.74 to 1.35] and 1.09 [95% CI, 0.68 to 1.76]), incidence of cancer (2 RCTs; hazard ratio, 0.97 [95% CI, 0.68 to 1.39] and 1.01 [95% CI, 0.65 to 1.58], or depression (3 RCTs, various measures reported). The pooled ARD for incidence of participants with 1 or more falls was -4.3% (95% CI, -11.6% to 2.9%; 6 RCTs). The evidence was mixed for the effect of treatment on physical functioning (2 RCTs) and limited for the effect on infection (1 RCT). The incidence of adverse events and kidney stones was similar between treatment and control groups. Conclusions and Relevance: No studies evaluated the direct benefits or harms of screening for vitamin D deficiency. Among asymptomatic, community-dwelling populations with low vitamin D levels, the evidence suggests that treatment with vitamin D has no effect on mortality or the incidence of fractures, falls, depression, diabetes, cardiovascular disease, cancer, or adverse events. The evidence is inconclusive about the effect of treatment on physical functioning and infection.

Screening for Bacterial Vaginosis in Pregnant Adolescents and Women to Prevent Preterm Delivery: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Preterm delivery results in adverse outcomes; identifying and treating bacterial vaginosis may reduce its occurrence. Objective: To update the evidence on screening and treatment of asymptomatic bacterial vaginosis in pregnancy for the US Preventive Services Task Force. Data Sources: MEDLINE, Cochrane Library, and trial registries through May 29, 2019; bibliographies from retrieved articles, experts, and surveillance of the literature through December 31, 2019. Study Selection: Fair- or good-quality English-language studies evaluating diagnostic accuracy of tests feasible within primary care; randomized clinical trials (RCTs); nonrandomized controlled intervention studies (for harms only); or meta-analyses of metronidazole or clindamycin. Data Extraction and Synthesis: Two reviewers independently assessed titles/abstracts and full-text articles, extracted data, and assessed study quality; when at least 3 similar studies were available, meta-analyses were conducted. Main Outcomes and Measures: Sensitivity, specificity, preterm delivery, maternal adverse effects, congenital birth defects, childhood cancer. Results: Forty-four studies (48 publications) were included. No studies evaluated the benefits or harms of screening. Twenty-five studies (n = 15 785) evaluated the accuracy of screening tests; across individual studies and tests, sensitivity ranged from 0.36 to 1.0 and specificity ranged from 0.49 to 1.0. Among trials reporting findings from general obstetric populations (n = 7953), no significant association was observed between treatment and spontaneous delivery before 37 weeks (pooled absolute risk difference [ARD], -1.44% [95% CI, -3.31% to 0.43%]; 8 RCTs, n = 7571) or any delivery before 37 weeks (pooled ARD, 0.20% [95% CI, -1.13% to 1.53%]; 6 RCTs, n = 6307). Among 5 trials reporting findings among women with a prior preterm delivery, findings were inconsistent; 3 showed a significant beneficial effect, while 2 did not. Maternal adverse events from treatment were infrequent and minor (eg, candidiasis) but were slightly more common with active treatment compared with placebo across 8 RCTs. Two meta-analyses of observational studies reported no significant association between metronidazole exposure and congenital malformations (odds ratio, 0.96 [95% CI, 0.75 to 1.22]; odds ratio, 1.08 [95% CI, 0.90 to 1.29]). One cohort study reported no significantly increased incidence of childhood cancer among metronidazole-exposed children (adjusted relative risk, 0.81 [95% CI, 0.41 to 1.59]). However, studies of in utero exposure had important limitations. Conclusions and Relevance: Accuracy of screening tests for bacterial vaginosis varies. The evidence suggests no difference in the incidence of preterm delivery and related outcomes from treatment for asymptomatic bacterial vaginosis in a general obstetric population but was inconclusive for women with a prior preterm delivery. Maternal adverse events from treatment appear to be infrequent and minor, but the evidence about harms from in utero exposure was inconclusive.

Impact of the Agency for Healthcare Research and Quality's Safety Program for Perinatal Care.

BACKGROUND: The Safety Program for Perinatal Care (SPPC) seeks to improve safety on labor and delivery (L&D) units through three mutually reinforcing components: (1) fostering a culture of teamwork and communication, (2) applying safety science principles to care processes; and (3) in situ simulation. The objective of this study was to describe the SPPC implementation experience and evaluate the short-term impact on unit patient safety culture, processes, and adverse events. METHODS: We supported SPPC implementation by L&D units with a program toolkit, trainings, and technical assistance. We evaluated the program using a pre-post, mixed-methods design. Implementing units reported uptake of program components, submitted hospital discharge data on maternal and neonatal adverse events, and participated in semi-structured interviews. We measured changes in safety and quality using the Modified Adverse Outcome Index (MAOI) and other perinatal care indicators. RESULTS: Forty-three L&D units submitted data representing 97,740 deliveries over 10 months of follow-up. Twenty-six units implemented all three program components. L&D staff reported improvements in teamwork, communication, and unit safety culture that facilitated applying safety science principles to clinical care. The MAOI decreased from 5.03% to 4.65% (absolute change -0.38% [95% CI, -0.88% to 0.12%]). Statistically significant decreases in indicators for obstetric trauma without instruments and primary cesarean delivery were observed. A statistically significant increase in neonatal birth trauma was observed, but the overall rate of unexpected newborn complications was unchanged. CONCLUSIONS: The SPPC had a favorable impact on unit patient safety culture and processes, but short-term impact on maternal and neonatal adverse events was mixed.

Screening for Atrial Fibrillation With Electrocardiography: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Atrial fibrillation is the most common arrhythmia and increases the risk of stroke. Objective: To review the evidence on screening for nonvalvular atrial fibrillation with electrocardiography (ECG) and stroke prevention treatment in asymptomatic adults 65 years or older to inform the US Preventive Services Task Force. Data Sources: MEDLINE, Cochrane Library, and trial registries through May 2017; references; experts; literature surveillance through June 6, 2018. Study Selection: English-language randomized clinical trials (RCTs), prospective cohort studies evaluating detection rates of atrial fibrillation or harms of screening, and systematic reviews evaluating stroke prevention treatment. Eligible treatment studies compared warfarin, aspirin, or novel oral anticoagulants (NOACs) with placebo or no treatment. Studies were excluded that focused on persons with a history of cardiovascular disease. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality. When at least 3 similar studies were available, random-effects meta-analyses were conducted. Main Outcomes and Measures: Detection of previously undiagnosed atrial fibrillation, mortality, stroke, stroke-related morbidity, and harms. Results: Seventeen studies were included (n = 135 300). No studies evaluated screening compared with no screening and focused on health outcomes. Systematic screening with ECG identified more new cases of atrial fibrillation than no screening (absolute increase, from 0.6% [95% CI, 0.1%-0.9%] to 2.8% [95% CI, 0.9%-4.7%] over 12 months; 2 RCTs, n = 15 803), but a systematic approach using ECG did not detect more cases than an approach using pulse palpation (2 RCTs, n = 17 803). For potential harms, no eligible studies compared screening with no screening. Warfarin (mean, 1.5 years) was associated with a reduced risk of ischemic stroke (relative risk [RR], 0.32 [95% CI, 0.20-0.51]) and all-cause mortality (RR, 0.68 [95% CI, 0.50-0.93]) and with increased risk of bleeding (5 trials, n = 2415). Participants in treatment trials were not screen detected, and most had long-standing persistent atrial fibrillation. A network meta-analysis reported that NOACs were associated with a significantly lower risk of a composite outcome of stroke and systemic embolism (adjusted odds ratios compared with placebo or control ranged from 0.32-0.44); the risk of bleeding was increased (adjusted odds ratios, 1.4-2.2), but confidence intervals were wide and differences between groups were not statistically significant. Conclusions and Relevance: Although screening with ECG can detect previously unknown cases of atrial fibrillation, it has not been shown to detect more cases than screening focused on pulse palpation. Treatments for atrial fibrillation reduce the risk of stroke and all-cause mortality and increase the risk of bleeding, but trials have not assessed whether treatment of screen-detected asymptomatic older adults results in better health outcomes than treatment after detection by usual care or after symptoms develop.

Screening to Prevent Osteoporotic Fractures: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Osteoporotic fractures cause significant morbidity and mortality. Objective: To update the evidence on screening and treatment to prevent osteoporotic fractures for the US Preventive Services Task Force. Data Sources: PubMed, the Cochrane Library, EMBASE, and trial registries (November 1, 2009, through October 1, 2016) and surveillance of the literature (through March 23, 2018); bibliographies from articles. Study Selection: Adults 40 years and older; screening cohorts without prevalent low-trauma fractures or treatment cohorts with increased fracture risk; studies assessing screening, bone measurement tests or clinical risk assessments, pharmacologic treatment. Data Extraction and Synthesis: Dual, independent review of titles/abstracts and full-text articles; study quality rating; random-effects meta-analysis. Main Outcomes and Measures: Incident fractures and related morbidity and mortality, diagnostic and predictive accuracy, harms of screening or treatment. Results: One hundred sixty-eight fair- or good-quality articles were included. One randomized clinical trial (RCT) (n = 12 483) comparing screening with no screening reported fewer hip fractures (2.6% vs 3.5%; hazard ratio [HR], 0.72 [95% CI, 0.59-0.89]) but no other statistically significant benefits or harms. The accuracy of bone measurement tests to identify osteoporosis varied (area under the curve [AUC], 0.32-0.89). The pooled accuracy of clinical risk assessments for identifying osteoporosis ranged from AUC of 0.65 to 0.76 in women and from 0.76 to 0.80 in men; the accuracy for predicting fractures was similar. For women, bisphosphonates, parathyroid hormone, raloxifene, and denosumab were associated with a lower risk of vertebral fractures (9 trials [n = 23 690]; relative risks [RRs] from 0.32-0.64). Bisphosphonates (8 RCTs [n = 16 438]; pooled RR, 0.84 [95% CI, 0.76-0.92]) and denosumab (1 RCT [n = 7868]; RR, 0.80 [95% CI, 0.67-0.95]) were associated with a lower risk of nonvertebral fractures. Denosumab reduced the risk of hip fracture (1 RCT [n = 7868]; RR, 0.60 [95% CI, 0.37-0.97]), but bisphosphonates did not have a statistically significant association (3 RCTs [n = 8988]; pooled RR, 0.70 [95% CI, 0.44-1.11]). Evidence was limited for men: zoledronic acid reduced the risk of radiographic vertebral fractures (1 RCT [n = 1199]; RR, 0.33 [95% CI, 0.16-0.70]); no studies demonstrated reductions in clinical or hip fractures. Bisphosphonates were not consistently associated with reported harms other than deep vein thrombosis (raloxifene vs placebo; 3 RCTs [n = 5839]; RR, 2.14 [95% CI, 0.99-4.66]). Conclusions and Relevance: In women, screening to prevent osteoporotic fractures may reduce hip fractures, and treatment reduced the risk of vertebral and nonvertebral fractures; there was not consistent evidence of treatment harms. The accuracy of bone measurement tests or clinical risk assessments for identifying osteoporosis or predicting fractures varied from very poor to good.

Vitamin D, Calcium, or Combined Supplementation for the Primary Prevention of Fractures in Community-Dwelling Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Osteoporotic fractures result in significant morbidity and mortality. Objective: To update the evidence for benefits and harms of vitamin D, calcium, or combined supplementation for the primary prevention of fractures in community-dwelling adults to inform the US Preventive Services Task Force. Data Sources: PubMed, EMBASE, Cochrane Library, and trial registries through March 21, 2017; references; and experts. Surveillance continued through February 28, 2018. Study Selection: English-language randomized clinical trials (RCTs) or observational studies of supplementation with vitamin D, calcium, or both among adult populations; studies of populations that were institutionalized or had known vitamin D deficiency, osteoporosis, or prior fracture were excluded. Data Extraction and Synthesis: Dual, independent review of titles/abstracts and full-text articles and study quality rating using predefined criteria. Random-effects meta-analysis used when at least 3 similar studies were available. Main Outcomes and Measures: Incident fracture, mortality, kidney stones, cardiovascular events, and cancer. Results: Eleven RCTs (N = 51 419) in adults 50 years and older conducted over 2 to 7 years were included. Compared with placebo, supplementation with vitamin D decreased total fracture incidence (1 RCT [n = 2686]; absolute risk difference [ARD], -2.26% [95% CI, -4.53% to 0.00%]) but had no significant association with hip fracture (3 RCTs [n = 5496]; pooled ARD, -0.01% [95% CI, -0.80% to 0.78%]). Supplementation using vitamin D with calcium had no effect on total fracture incidence (1 RCT [n = 36 282]; ARD, -0.35% [95% CI, -1.02% to 0.31%]) or hip fracture incidence (2 RCTs [n = 36 727]; ARD from the larger trial, -0.14% [95% CI, -0.34% to 0.07%]). The evidence for calcium alone was limited, with only 2 studies (n = 339 total) and very imprecise results. Supplementation with vitamin D alone or with calcium had no significant effect on all-cause mortality or incident cardiovascular disease; ARDs ranged from -1.93% to 1.79%, with CIs consistent with no significant differences. Supplementation using vitamin D with calcium was associated with an increased incidence of kidney stones (3 RCTs [n = 39 213]; pooled ARD, 0.33% [95% CI, 0.06% to 0.60%]), but supplementation with calcium alone was not associated with an increased risk (3 RCTs [n = 1259]; pooled ARD, 0.00% [95% CI, -0.87% to 0.87%]). Supplementation with vitamin D and calcium was not associated with an increase in cancer incidence (3 RCTs [n = 39 213]; pooled ARD, -1.48% [95% CI, -3.32% to 0.35%]). Conclusions and Relevance: Vitamin D supplementation alone or with calcium was not associated with reduced fracture incidence among community-dwelling adults without known vitamin D deficiency, osteoporosis, or prior fracture. Vitamin D with calcium was associated with an increase in the incidence of kidney stones.

Quality improvement, implementation, and dissemination strategies to improve mental health care for children and adolescents: a systematic review.

BACKGROUND: Some outcomes for children with mental health problems remain suboptimal because of poor access to care and the failure of systems and providers to adopt established quality improvement strategies and interventions with proven effectiveness. This review had three goals: (1) assess the effectiveness of quality improvement, implementation, and dissemination strategies intended to improve the mental health care of children and adolescents; (2) examine harms associated with these strategies; and (3) determine whether effectiveness or harms differ for subgroups based on system, organizational, practitioner, or patient characteristics. METHODS: Sources included MEDLINE®, the Cochrane Library, PsycINFO, and CINAHL, from database inception through February 17, 2017. Additional sources included gray literature, additional studies from reference lists, and technical experts. Two reviewers selected relevant randomized controlled trials (RCTs) and observational studies, extracted data, and assessed risk of bias. Dual analysis, synthesis, and grading of the strength of evidence for each outcome followed for studies meeting inclusion criteria. We also used qualitative comparative analysis to examine relationships between combinations of strategy components and improvements in outcomes. RESULTS: We identified 18 strategies described in 19 studies. Eleven strategies significantly improved at least one measure of intermediate outcomes, final health outcomes, or resource use. Moderate strength of evidence (from one RCT) supported using provider financial incentives such as pay for performance to improve the competence with which practitioners can implement evidence-based practices (EBPs). We found inconsistent evidence involving strategies with educational meetings, materials, and outreach; programs appeared to be successful in combination with reminders or providing practitioners with newly collected clinical information. We also found low strength of evidence for no benefit for initiatives that included only educational materials or meetings (or both), or only educational materials and outreach components. Evidence was insufficient to draw conclusions on harms and moderators of interventions. CONCLUSIONS: Several strategies can improve both intermediate and final health outcomes and resource use. This complex and heterogeneous body of evidence does not permit us to have a high degree of confidence about the efficacy of any one strategy because we generally found only a single study testing each strategy. TRIAL REGISTRATION: PROSPERO, CRD42015024759 .

AHRQ series on complex intervention systematic reviews-paper 4: selecting analytic approaches.

BACKGROUND: Systematic reviews of complex interventions can vary widely in purpose, data availability and heterogeneity, and stakeholder expectations. RATIONALE: This article addresses the uncertainty that systematic reviewers face in selecting methods for reviews of complex interventions. Specifically, it lays out parameters for systematic reviewers to consider when selecting analytic approaches that best answer the questions at hand and suggests analytic techniques that may be appropriate in different circumstances. DISCUSSION: Systematic reviews of complex interventions comprising multiple questions may use multiple analytic approaches. Parameters to consider when choosing analytic methods for complex interventions include nature and timing of the decision (clinical practice guideline, policy, or other); purpose of the review; extent of existing evidence; logistic factors such as the timeline, process, and resources for deciding the scope of the review; and value of information to be obtained from choosing specific systematic review methods. Reviewers may elect to revise their analytic approach based on new or changing considerations during the course of the review but should guard against bias through transparency of reporting.

Primary Care Screening and Treatment for Latent Tuberculosis Infection in Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force.

IMPORTANCE: Five to ten percent of individuals with latent tuberculosis infection (LTBI) progress to active tuberculosis (TB) disease. Identifying and treating LTBI is a key component of the strategy for reducing the burden of TB disease. OBJECTIVE: To review the evidence about targeted screening and treatment for LTBI among adults in primary care settings to support the US Preventive Services Task Force in updating its 1996 recommendation. DATA SOURCES: MEDLINE, Cochrane Library, and trial registries, searched through August 3, 2015; references from pertinent articles; and experts. Literature surveillance was conducted through May 31, 2016. STUDY SELECTION: English-language studies of LTBI screening, LTBI treatment with recommended pharmacotherapy, or accuracy of the tuberculin skin test (TST) or interferon-gamma release assays (IGRAs). Studies of individuals for whom LTBI screening and treatment is part of public health surveillance or disease management were excluded. DATA EXTRACTION AND SYNTHESIS: Two investigators independently reviewed abstracts and full-text articles. When at least 3 similar studies were available, random-effects meta-analysis was used to generate pooled estimates of outcomes. MAIN OUTCOMES AND MEASURES: Sensitivity, specificity, reliability, active TB disease, mortality, hepatotoxicity, and other harms. RESULTS: The review included 72 studies (n = 51 711). No studies evaluated benefits and harms of screening compared with no screening. Pooled estimates for sensitivity of the TST at both 5-mm and 10-mm induration thresholds were 0.79 (5-mm: 95% CI, 0.69-0.89 [8 studies, n = 803]; 10 mm: 95% CI, 0.71-0.87 [11 studies; n = 988]), and those for IGRAs ranged from 0.77 to 0.90 (57 studies; n = 4378). Pooled estimates for specificity of the TST at the 10-mm and 15-mm thresholds and for IGRAs ranged from 0.95 to 0.99 (34 studies; n = 23 853). A randomized clinical trial (RCT) of 24 weeks of isoniazid in individuals with pulmonary fibrotic lesions and LTBI (n = 27 830) found a reduction in absolute risk of active TB at 5 years from 1.4% to 0.5% (relative risk [RR], 0.35 [95% CI, 0.24-0.52]) and an increase in absolute risk for hepatoxicity from 0.1% to 0.5% (RR, 4.59 [95% CI, 2.03-10.39]) for 24 weeks of daily isoniazid compared with placebo. An RCT (n = 6886) found that 3 months of once-weekly rifapentine plus isoniazid was noninferior to 9 months of isoniazid alone for preventing active TB. The risk difference for hepatoxicity comparing isoniazid with rifampin ranged from 3% to 7%, with a pooled RR of 3.29 (95% CI, 1.72-6.28 [3 RCTs; n = 1327]). CONCLUSIONS AND RELEVANCE: No studies evaluated the benefits and harms of screening compared with no screening. Both the TST and IGRAs are moderately sensitive and highly specific within countries with low TB burden. Treatment reduced the risk of active TB among the populations included in this review. Isoniazid is associated with higher rates of hepatotoxicity than placebo or rifampin.

Reducing Recreational Sedentary Screen Time: A Community Guide Systematic Review.

CONTEXT: Sedentary time spent with screen media is associated with obesity among children and adults. Obesity has potentially serious health consequences, such as heart disease and diabetes. This Community Guide systematic review examined the effectiveness and economic efficiency of behavioral interventions aimed at reducing recreational (i.e., neither school- nor work-related) sedentary screen time, as measured by screen time, physical activity, diet, and weight-related outcomes. EVIDENCE ACQUISITION: For this review, an earlier ("original") review (search period, 1966 through July 2007) was combined with updated evidence (search period, April 2007 through June 2013) to assess effectiveness of behavioral interventions aimed at reducing recreational sedentary screen time. Existing Community Guide systematic review methods were used. Analyses were conducted in 2013-2014. EVIDENCE SYNTHESIS: The review included 49 studies. Two types of behavioral interventions were evaluated that either (1) focus on reducing recreational sedentary screen time only (12 studies); or (2) focus equally on reducing recreational sedentary screen time and improving physical activity or diet (37 studies). Most studies targeted children aged ≤13 years. Children's composite screen time (TV viewing plus other forms of recreational sedentary screen time) decreased 26.4 (interquartile interval= -74.4, -12.0) minutes/day and obesity prevalence decreased 2.3 (interquartile interval= -4.5, -1.2) percentage points versus a comparison group. Improvements in physical activity and diet were reported. Three study arms among adults found composite screen time decreased by 130.2 minutes/day. CONCLUSIONS: Among children, these interventions demonstrated reduced screen time, increased physical activity, and improved diet- and weight-related outcomes. More research is needed among adolescents and adults.

Medication therapy management interventions in outpatient settings: a systematic review and meta-analysis.

IMPORTANCE: Medication therapy management (MTM) services (also called clinical pharmacy services) aim to reduce medication-related problems and their downstream outcomes. OBJECTIVE: To assess the effect of MTM interventions among outpatients with chronic illnesses. DATA SOURCES: MEDLINE, Cochrane Library, and International Pharmaceutical Abstracts through January 9, 2014. STUDY SELECTION: Two reviewers selected studies with comparators and eligible outcomes of ambulatory adults. DATA EXTRACTION AND SYNTHESIS: Dual review of titles, abstracts, full-text, extractions, risk of bias, and strength of evidence grading. We conducted meta-analyses using random-effects models. MAIN OUTCOMES AND MEASURES: Medication-related problems, morbidity, mortality, quality of life, health care use, costs, and harms. RESULTS: Forty-four studies met the inclusion criteria. The evidence was insufficient to determine the effect of MTM interventions on most evaluated outcomes (eg, drug therapy problems, adverse drug events, disease-specific morbidity, disease-specific or all-cause mortality, and harms). The interventions improved a few measures of medication-related problems and health care use and costs (low strength of evidence) when compared with usual care. Specifically, MTM interventions improved medication appropriateness (4.9 vs 0.9 points on the medication appropriateness index, P < .001), adherence (approximately 4.6%), and percentage of patients achieving a threshold adherence level (odds ratios [ORs] ranged from 0.99 to 5.98) and reduced medication dosing (mean difference, -2.2 doses; 95% CI, -3.738 to -0.662). Medication therapy management interventions reduced health plan expenditures on medication costs, although the studies reported wide CIs. For patients with diabetes mellitus or heart failure, MTM interventions lowered the odds of hospitalization (diabetes: OR, 0.91 to 0.93 based on type of insurance; adjusted hazard rate for heart failure: 0.55; 95% CI, 0.39 to 0.77) and hospitalization costs (mean differences ranged from -$363.45 to -$398.98). The interventions conferred no benefit for patient satisfaction and most measures of health-related quality of life (low strength). CONCLUSIONS AND RELEVANCE: We graded the evidence as insufficient for most outcomes because of inconsistency and imprecision that stem in part from underlying heterogeneity in populations and interventions. Medication therapy management interventions may reduce the frequency of some medication-related problems, including nonadherence, and lower some health care use and costs, but the evidence is insufficient with respect to improvement in health outcomes.

Using qualitative comparative analysis to understand and quantify translation and implementation.

Understanding the factors that facilitate implementation of behavioral medicine programs into practice can advance translational science. Often, translation or implementation studies use case study methods with small sample sizes. Methodological approaches that systematize findings from these types of studies are needed to improve rigor and advance the field. Qualitative comparative analysis (QCA) is a method and analytical approach that can advance implementation science. QCA offers an approach for rigorously conducting translational and implementation research limited by a small number of cases. We describe the methodological and analytic approach for using QCA and provide examples of its use in the health and health services literature. QCA brings together qualitative or quantitative data derived from cases to identify necessary and sufficient conditions for an outcome. QCA offers advantages for researchers interested in analyzing complex programs and for practitioners interested in developing programs that achieve successful health outcomes.

Predictors of initial weight loss after gastric bypass surgery in twelve Veterans Affairs Medical Centers.

The objective of this study was to identify determinants of significant weight loss one year after gastric bypass surgery among United States veterans. Using data from the Veterans Affairs (VA) Surgical Quality Improvement Program, we identified 516 veterans who had gastric bypass surgery (24% laparoscopic) in one of twelve VA bariatric centers in 2000-2006 and one or more postoperative weight measures. The probability of losing 30% or more of baseline weight at one year was estimated via logistic regression, examining the following potential predictor variables: age, gender, race, marital status, body mass index (BMI), American Society of Anesthesiologists class, comorbidity burden, smoking status, diabetes medications taken and surgical procedure (open or laparoscopic). The 516 cases had a mean BMI of 49 kg/m(2), mean age of 51.5 years, 74% were male, 77% were Caucasian, and 55% were married. The predicted mean weight loss was 76 (95% CI: 73-79) pounds (22%) at six months and 109 (95% CI: 104-114) pounds (32%) at one-year. Based upon estimated individual trajectories of 370 patients with adequate follow-up data, 58% of the sample lost 30% or more of their baseline weight at one year; and <1% lost <10% of their baseline weight at 1 year. In the logistic regression, patients were more likely to lose 30% or more of their baseline weight if they were female (odds ratio (OR) = 2.5, p < 0.01) or Caucasian (OR = 2.3, p < 0.01). We conclude that gastric bypass surgery yields significant weight loss for most patients in Veterans Affairs Medical Centers, but is particularly effective for female and Caucasian patients.

Training veterans to provide peer support in a weight-management program: MOVE!

INTRODUCTION: The Veterans Health Administration (VHA) has implemented MOVE!, a weight-management program for veterans designed to address the increasing proportion of overweight and obese veterans. The objective of our study was to determine whether peer support employing motivational interviewing (MI) could positively influence lifestyle changes, thus expanding the reach of the MOVE! program. We describe the initial evaluation of the peer training program. METHODS: We developed an MI peer ounselor training program for volunteer veterans, the "Buddies" program, to provide one-on-one telephone support for veterans enrolled in MOVE!. Buddies were recruited at 5 VHA sites and trained to provide peer support for the 6-month MOVE! intervention. We used a DVD to teach MI skills and followed with 2 to 3 booster sessions. We observed training, conducted pre- and posttraining surveys, and debriefed focus groups to assess training feasibility. RESULTS: Fifty-six Buddies were trained. Results indicate positive receipt of the program (89% reported learning about peer counseling and 87% reported learning communication skills). Buddies showed a small improvement in MI self-efficacy on posttraining surveys. We also identified key challenges to learning MI and training implementation. CONCLUSIONS: MI training is feasible to implement and acceptable to volunteer Buddies. Trainers must assess how effectively volunteers learn MI skills in order to enhance its effective use in health promotion.