Screening for Speech and Language Delay and Disorders in Children 5 Years or Younger: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Children with speech and language difficulties are at risk for learning and behavioral problems. Objective: To review the evidence on screening for speech and language delay or disorders in children 5 years or younger to inform the US Preventive Services Task Force. Data Sources: PubMed/MEDLINE, Cochrane Library, PsycInfo, ERIC, Linguistic and Language Behavior Abstracts (ProQuest), and trial registries through January 17, 2023; surveillance through November 24, 2023. Study Selection: English-language studies of screening test accuracy, trials or cohort studies comparing screening vs no screening; randomized clinical trials (RCTs) of interventions. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, study quality, and data extraction; results were narratively summarized. Main Outcomes and Measures: Screening test accuracy, speech and language outcomes, school performance, function, quality of life, and harms. Results: Thirty-eight studies in 41 articles were included (N = 9006). No study evaluated the direct benefits of screening vs no screening. Twenty-one studies (n = 7489) assessed the accuracy of 23 different screening tools that varied with regard to whether they were designed to be completed by parents vs trained examiners, and to screen for global (any) language problems vs specific skills (eg, expressive language). Three studies assessing parent-reported tools for expressive language skills found consistently high sensitivity (range, 88%-93%) and specificity (range, 88%-85%). The accuracy of other screening tools varied widely. Seventeen RCTs (n = 1517) evaluated interventions for speech and language delay or disorders, although none enrolled children identified by routine screening in primary care. Two RCTs evaluating relatively intensive parental group training interventions (11 sessions) found benefit for different measures of expressive language skills, and 1 evaluating a less intensive intervention (6 sessions) found no difference between groups for any outcome. Two RCTs (n = 76) evaluating the Lidcombe Program of Early Stuttering Intervention delivered by speech-language pathologists featuring parent training found a 2.3% to 3.0% lower proportion of syllables stuttered at 9 months compared with the control group when delivered in clinic and via telehealth, respectively. Evidence on other interventions was limited. No RCTs reported on the harms of interventions. Conclusions and Relevance: No studies directly assessed the benefits and harms of screening. Some parent-reported screening tools for expressive language skills had reasonable accuracy for detecting expressive language delay. Group parent training programs for speech delay that provided at least 11 parental training sessions improved expressive language skills, and a stuttering intervention delivered by speech-language pathologists reduced stuttering frequency.

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.

Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Persons: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: It is uncertain whether hormone therapy should be used for the primary prevention of chronic conditions such as heart disease, osteoporosis, or some types of cancers. Objective: To update evidence for the US Preventive Services Task Force on the benefits and harms of hormone therapy in reducing risks for chronic conditions. Data Sources: PubMed/MEDLINE, Cochrane Library, EMBASE, and trial registries from January 1, 2016, through October 12, 2021; surveillance through July 2022. Study Selection: English-language randomized clinical trials and prospective cohort studies of fair or good quality. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality; meta-analyses when at least 3 similar studies were available. Main Outcomes and Measures: Morbidity and mortality related to chronic conditions; health-related quality of life. Results: Twenty trials (N = 39 145) and 3 cohort studies (N = 1 155 410) were included. Participants using estrogen only compared with placebo had significantly lower risks for diabetes over 7.1 years (1050 vs 903 cases; 134 fewer [95% CI, 18-237]) and fractures over 7.2 years (1024 vs 1413 cases; 388 fewer [95% CI, 277-489]) per 10 000 persons. Risks per 10 000 persons were statistically significantly increased for gallbladder disease over 7.1 years (1113 vs 737 cases; 377 more [95% CI, 234-540]), stroke over 7.2 years (318 vs 239 cases; 79 more [95% CI, 15-159]), venous thromboembolism over 7.2 years (258 vs 181 cases; 77 more [95% CI, 19-153]), and urinary incontinence over 1 year (2331 vs 1446 cases; 885 more [95% CI, 659-1135]). Participants using estrogen plus progestin compared with placebo experienced significantly lower risks, per 10 000 persons, for colorectal cancer over 5.6 years (59 vs 93 cases; 34 fewer [95% CI, 9-51]), diabetes over 5.6 years (403 vs 482 cases; 78 fewer [95% CI, 15-133]), and fractures over 5 years (864 vs 1094 cases; 230 fewer [95% CI, 66-372]). Risks, per 10 000 persons, were significantly increased for invasive breast cancer (242 vs 191 cases; 51 more [95% CI, 6-106]), gallbladder disease (723 vs 463 cases; 260 more [95% CI, 169-364]), stroke (187 vs 135 cases; 52 more [95% CI, 12-104]), and venous thromboembolism (246 vs 126 cases; 120 more [95% CI, 68-185]) over 5.6 years; probable dementia (179 vs 91 cases; 88 more [95% CI, 15-212]) over 4.0 years; and urinary incontinence (1707 vs 1145 cases; 562 more [95% CI, 412-726]) over 1 year. Conclusions and Relevance: Use of hormone therapy in postmenopausal persons for the primary prevention of chronic conditions was associated with some benefits but also with an increased risk of harms.

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 Depression and Suicide Risk in Children and Adolescents: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Depression, suicidal ideation, and self-harm behaviors in youth are associated with functional impairment and suicide. Objective: To review the evidence on screening for depression or suicide risk in children and adolescents to inform the US Preventive Services Task Force (USPSTF). Data Sources: PubMed, Cochrane Library, PsycINFO, CINAHL, and trial registries through July 19, 2021; references, experts, and surveillance through June 1, 2022. Study Selection: English-language, randomized clinical trials (RCTs) of screening for depression or suicide risk; diagnostic test accuracy studies; RCTs of psychotherapy and first-line pharmacotherapy; RCTs, observational studies, and systematic reviews 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: Test accuracy, symptoms, response, remission, loss of diagnosis, mortality, functioning, suicide-related events, and adverse events. Results: Twenty-one studies (N = 5433) were included for depression and 19 studies (N = 6290) for suicide risk. For depression, no studies reported on the direct effects of screening on health outcomes, and 7 studies (n = 3281) reported sensitivity of screening instruments ranging from 0.59 to 0.94 and specificity from 0.38 to 0.96. Depression treatment with psychotherapy was associated with improved symptoms (Beck Depression Inventory pooled standardized mean difference, -0.58 [95% CI, -0.83 to -0.34]; n = 471; 4 studies; and Hamilton Depression Scale pooled mean difference, -2.25 [95% CI, -4.09 to -0.41]; n = 262; 3 studies) clinical response (3 studies with statistically significant results using varying thresholds), and loss of diagnosis (relative risk, 1.73 [95% CI, 1.00 to 3.00; n = 395; 4 studies). Pharmacotherapy was associated with improvement on symptoms (Children's Depression Rating Scale-Revised mean difference, -3.76 [95% CI, -5.95 to -1.57; n = 793; 3 studies), remission (relative risk, 1.20 [95% CI, 1.00 to 1.45]; n = 793; 3 studies) and functioning (Children's Global Assessment Scale pooled mean difference, 2.60 (95% CI, 0.78 to 4.42; n = 793; 3 studies). Other outcomes were not statistically significantly different. Differences in suicide-related outcomes and adverse events for pharmacotherapy when compared with placebo were not statistically significant. For suicide risk, no studies reported on the direct benefits of screening on health outcomes, and 2 RCTs (n = 2675) reported no harms of screening. One study (n = 581) reported on sensitivity of screening, ranging from 0.87 to 0.91; specificity was 0.60. Sixteen RCTs (n = 3034) reported on suicide risk interventions. Interventions were associated with lower scores for the Beck Hopelessness Scale (pooled mean difference, -2.35 [95% CI, -4.06 to -0.65]; n = 644; 4 RCTs). Findings for other suicide-related outcomes were mixed or not statistically significantly different. Conclusion and Relevance: Indirect evidence suggested that some screening instruments were reasonably accurate for detecting depression. Psychotherapy and pharmacotherapy were associated with some benefits and no statistically significant harms for depression, but the evidence was limited for suicide risk screening instruments and interventions.

Screening for Anxiety in Children and Adolescents: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Anxiety in children and adolescents is associated with impaired functioning, educational underachievement, and future mental health conditions. Objective: To review the evidence on screening for anxiety in children and adolescents to inform the US Preventive Services Task Force. Data Sources: PubMed, Cochrane Library, PsycINFO, CINAHL, and trial registries through July 19, 2021; references, experts, and surveillance through June 1, 2022. Study Selection: English-language, randomized clinical trials (RCTs) of screening; diagnostic test accuracy studies; RCTs of cognitive behavioral therapy (CBT) or US Food and Drug Administration-approved pharmacotherapy; RCTs, observational studies, and systematic reviews 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: Test accuracy, symptoms, response, remission, loss of diagnosis, all-cause mortality, functioning, suicide-related symptoms or events, adverse events. Results: Thirty-nine studies (N = 6065) were included. No study reported on the direct benefits or harms of screening on health outcomes. Ten studies (n = 3260) reported the sensitivity of screening instruments, ranging from 0.34 to 1.00, with specificity ranging from 0.47 to 0.99. Twenty-nine RCTs (n = 2805) reported on treatment: 22 on CBT, 6 on pharmacotherapy, and 1 on CBT, sertraline, and CBT plus sertraline. CBT was associated with gains on several pooled measures of symptom improvement (magnitude of change varied by outcome measure), response (pooled relative risk [RR], 1.89 [95% CI, 1.17 to 3.05]; n = 606; 6 studies), remission (RR, 2.68 [95% CI, 1.48 to 4.88]; n = 321; 4 studies), and loss of diagnosis (RR range, 3.02-3.09) when compared with usual care or wait-list controls. The evidence on functioning for CBT was mixed. Pharmacotherapy, when compared with placebo, was associated with gains on 2 pooled measures of symptom improvement-mean difference (Pediatric Anxiety Rating Scale mean difference, -4.0 [95% CI, -5.5 to -2.5]; n = 726; 5 studies; and Clinical Global Impression-Severity scale mean difference, -0.84 [95% CI, -1.13 to -0.55]; n = 550; 4 studies) and response (RR, 2.11 [95% CI, 1.58 to 2.98]; n = 370; 5 studies)-but was mixed on measures of functioning. Eleven RCTs (n = 1293) reported harms of anxiety treatments. Suicide-related harms were rare, and the differences were not statistically significantly different. Conclusions and Relevance: Indirect evidence suggested that some screening instruments were reasonably accurate. CBT and pharmacotherapy were associated with benefits; no statistically significant association with harms was reported.

Making Narrative Statements to Describe Treatment Effects.

Accurately describing treatment effects using plain language and narrative statements is a critical step in communicating research findings to end users. However, the process of developing these narratives has not been historically guided by a specific framework. The Agency for Healthcare Research and Quality Evidence-based Practice Center Program developed guidance for narrative summaries of treatment effects that identifies five constructs. We explicitly identify these constructs to facilitate developing narrative statements: (1) direction of effect, (2) size of effect, (3) clinical importance, (4) statistical significance, and (5) strength or certainty of evidence. These constructs clearly overlap. It may not always be feasible to address all five constructs. Based on context and intended audience, investigators can determine which constructs will be most important to address in narrative statements.

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.

Surgical Management of Lumbar Radiculopathy: a Systematic Review.

BACKGROUND: Lumbar radiculopathy is characterized by radiating pain with or without motor weakness or sensory disturbances; the point prevalence ranges from 1.6 to 13.4%. The objective of this review was to determine the efficacy, safety, and cost of surgical versus nonsurgical management of symptomatic lumbar radiculopathy in adults. METHODS: We searched PubMed from January 1, 2007, to April 10, 2019 with hand searches of systematic reviews for studies prior to 2007. One reviewer extracted data and a second checked for accuracy. Two reviewers completed independent risk of bias and strength of evidence ratings. RESULTS: We included seven RCTs (N = 1158) and three cost-effectiveness analysis. Surgery reduced leg pain by 6 to 26 points more than nonsurgical interventions as measured on a 0- to 100-point visual analog scale of pain at up to 26 weeks follow-up; differences between groups did not persist at 1 year or later. The evidence was somewhat mixed for function and disability in follow-up through 26 weeks (standardized mean difference [SMD] - 0.16 (95% CI, - 0.30 to - 0.03); minimal differences were observed at 2 years (SMD - 0.06 (95% CI, - 0.20 to 0.07). There were similar improvements in quality of life, neurologic symptoms, and return to work. No surgical deaths occurred and surgical morbidity was infrequent. The incidence of reoperations ranged from 0 to 10%. The average cost per quality-adjusted life year gained from a healthcare payor perspective ranged from $51,156 to $83,322 for surgery compared to nonsurgical interventions. DISCUSSION: Most findings are based on a body of RCT evidence graded as low to very low certainty. Compared with nonsurgical interventions, surgery probably reduces pain and improves function in the short- and medium-term, but this difference does not persist in the long-term. Although surgery appears to be safe, it may or may not be cost-effective depending on a decision maker's willingness to pay threshold.

Universal screening for SARS-CoV-2 infection: a rapid review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by the novel betacoronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Most people infected with SARS-CoV-2 have mild disease with unspecific symptoms, but about 5% become critically ill with respiratory failure, septic shock and multiple organ failure. An unknown proportion of infected individuals never experience COVID-19 symptoms although they are infectious, that is, they remain asymptomatic. Those who develop the disease, go through a presymptomatic period during which they are infectious. Universal screening for SARS-CoV-2 infections to detect individuals who are infected before they present clinically, could therefore be an important measure to contain the spread of the disease. OBJECTIVES: We conducted a rapid review to assess (1) the effectiveness of universal screening for SARS-CoV-2 infection compared with no screening and (2) the accuracy of universal screening in people who have not presented to clinical care for symptoms of COVID-19. SEARCH METHODS: An information specialist searched Ovid MEDLINE and the Centers for Disease Control (CDC) COVID-19 Research Articles Downloadable Database up to 26 May 2020. We searched Embase.com, the CENTRAL, and the Cochrane Covid-19 Study Register on 14 April 2020. We searched LitCovid to 4 April 2020. The World Health Organization (WHO) provided records from daily searches in Chinese databases and in PubMed up to 15 April 2020. We also searched three model repositories (Covid-Analytics, Models of Infectious Disease Agent Study [MIDAS], and Society for Medical Decision Making) on 8 April 2020. SELECTION CRITERIA: Trials, observational studies, or mathematical modelling studies assessing screening effectiveness or screening accuracy among general populations in which the prevalence of SARS-CoV2 is unknown. DATA COLLECTION AND ANALYSIS: After pilot testing review forms, one review author screened titles and abstracts. Two review authors independently screened the full text of studies and resolved any disagreements by discussion with a third review author. Abstracts excluded by a first review author were dually reviewed by a second review author prior to exclusion. One review author independently extracted data, which was checked by a second review author for completeness and accuracy. Two review authors independently rated the quality of included studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool for diagnostic accuracy studies and a modified form designed originally for economic evaluations for modelling studies. We resolved differences by consensus. We synthesized the evidence in narrative and tabular formats. We rated the certainty of evidence for days to outbreak, transmission, cases missed and detected, diagnostic accuracy (i.e. true positives, false positives, true negatives, false negatives) using the GRADE approach. MAIN RESULTS: We included 22 publications. Two modelling studies reported on effectiveness of universal screening. Twenty studies (17 cohort studies and 3 modelling studies) reported on screening test accuracy. Effectiveness of screening We included two modelling studies. One study suggests that symptom screening at travel hubs, such as airports, may slightly slow but not stop the importation of infected cases (assuming 10 or 100 infected travellers per week reduced the delay in a local outbreak to 8 days or 1 day, respectively). We assessed risk of bias as minor or no concerns, and certainty of evidence was low, downgraded for very serious indirectness. The second modelling study provides very low-certainty evidence that screening of healthcare workers in emergency departments using laboratory tests may reduce transmission to patients and other healthcare workers (assuming a transmission constant of 1.2 new infections per 10,000 people, weekly screening reduced infections by 5.1% within 30 days). The certainty of evidence was very low, downgraded for high risk of bias (major concerns) and indirectness. No modelling studies reported on harms of screening. Screening test accuracy All 17 cohort studies compared an index screening strategy to a reference reverse transcriptase polymerase chain reaction (RT-PCR) test. All but one study reported on the accuracy of single point-in-time screening and varied widely in prevalence of SARS-CoV-2, settings, and methods of measurement. We assessed the overall risk of bias as unclear in 16 out of 17 studies, mainly due to limited information on the index test and reference standard. We rated one study as being at high risk of bias due to the inclusion of two separate populations with likely different prevalences. For several screening strategies, the estimates of sensitivity came from small samples. For single point-in-time strategies, for symptom assessment, the sensitivity from 12 cohorts (524 people) ranged from 0.00 to 0.60 (very low-certainty evidence) and the specificity from 12 cohorts (16,165 people) ranged from 0.66 to 1.00 (low-certainty evidence). For screening using direct temperature measurement (3 cohorts, 822 people), international travel history (2 cohorts, 13,080 people), or exposure to known infected people (3 cohorts, 13,205 people) or suspected infected people (2 cohorts, 954 people), sensitivity ranged from 0.00 to 0.23 (very low- to low-certainty evidence) and specificity ranged from 0.90 to 1.00 (low- to moderate-certainty evidence). For symptom assessment plus direct temperature measurement (2 cohorts, 779 people), sensitivity ranged from 0.12 to 0.69 (very low-certainty evidence) and specificity from 0.90 to 1.00 (low-certainty evidence). For rapid PCR test (1 cohort, 21 people), sensitivity was 0.80 (95% confidence interval (CI) 0.44 to 0.96; very low-certainty evidence) and specificity was 0.73 (95% CI 0.39 to 0.94; very low-certainty evidence). One cohort (76 people) reported on repeated screening with symptom assessment and demonstrates a sensitivity of 0.44 (95% CI 0.29 to 0.59; very low-certainty evidence) and specificity of 0.62 (95% CI 0.42 to 0.79; low-certainty evidence). Three modelling studies evaluated the accuracy of screening at airports. The main outcomes measured were cases missed or detected by entry or exit screening, or both, at airports. One study suggests very low sensitivity at 0.30 (95% CI 0.1 to 0.53), missing 70% of infected travellers. Another study described an unrealistic scenario to achieve a 90% detection rate, requiring 0% asymptomatic infections. The final study provides very uncertain evidence due to low methodological quality. AUTHORS' CONCLUSIONS: The evidence base for the effectiveness of screening comes from two mathematical modelling studies and is limited by their assumptions. Low-certainty evidence suggests that screening at travel hubs may slightly slow the importation of infected cases. This review highlights the uncertainty and variation in accuracy of screening strategies. A high proportion of infected individuals may be missed and go on to infect others, and some healthy individuals may be falsely identified as positive, requiring confirmatory testing and potentially leading to the unnecessary isolation of these individuals. Further studies need to evaluate the utility of rapid laboratory tests, combined screening, and repeated screening. More research is also needed on reference standards with greater accuracy than RT-PCR. Given the poor sensitivity of existing approaches, our findings point to the need for greater emphasis on other ways that may prevent transmission such as face coverings, physical distancing, quarantine, and adequate personal protective equipment for frontline workers.

Direct-to-Consumer Advertising of Prescription Drugs and the Patient-Prescriber Encounter: A Systematic Review.

We systematically reviewed the research on patients' and prescribers' perceptions of, and self-reported behaviors prompted by, exposure to direct-to-consumer advertising (DTCA) (For ease of reading we use the term "advertising" to encompass advertising and promotional labeling. Broad use of this term does not imply endorsement by FDA) of prescription drugs that occurs in the context of a clinical encounter. This research offers an important perspective on the broader goal of incorporating patient and prescriber voices in decision-making. Outcomes included patient information seeking, medication adherence, patient requests for DTCA-promoted prescription drugs, prescribing behaviors, and perceptions of the patient-prescriber relationship and interactions. We searched PubMed and other databases from 1982-2017 and identified 38 studies meeting our study criteria. Of these, 24 studies used patient-reported outcomes and 18 used prescriber-reported outcomes (four used both). Studies suggested some potential benefits of exposure to DTCA, including patients' enhanced information-seeking, increased patient requests for appropriate prescriptions (when addressing potential underuse) and patients' perceptions of higher-quality interactions with prescribers. Most prescribers perceived a neutral influence on the quality of their clinical interactions with patients regarding DTCA. Harms included patients receiving prescriptions for drugs that were not appropriate for them or that the patients did not need, and the potential for DTCA to interfere with medication adherence in some populations, such as those with mental illness. The potential benefits of DTCA on the patient-provider encounter must be balanced with the potential for harms.

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.

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.

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.

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.

Advancing perinatal patient safety through application of safety science principles using health IT.

BACKGROUND: The use of health information technology (IT) has been shown to promote patient safety in Labor and Delivery (L&D) units. The use of health IT to apply safety science principles (e.g., standardization) to L&D unit processes may further advance perinatal safety. METHODS: Semi-structured interviews were conducted with L&D units participating in the Agency for Healthcare Research and Quality's (AHRQ's) Safety Program for Perinatal Care (SPPC) to assess units' experience with program implementation. Analysis of interview transcripts was used to characterize the process and experience of using health IT for applying safety science principles to L&D unit processes. RESULTS: Forty-six L&D units from 10 states completed participation in SPPC program implementation; thirty-two (70%) reported the use of health IT as an enabling strategy for their local implementation. Health IT was used to improve standardization of processes, use of independent checks, and to facilitate learning from defects. L&D units standardized care processes through use of electronic health record (EHR)-based order sets and use of smart pumps and other technology to improve medication safety. Units also standardized EHR documentation, particularly related to electronic fetal monitoring (EFM) and shoulder dystocia. Cognitive aids and tools were integrated into EHR and care workflows to create independent checks such as checklists, risk assessments, and communication handoff tools. Units also used data from EHRs to monitor processes of care to learn from defects. Units experienced several challenges incorporating health IT, including obtaining organization approval, working with their busy IT departments, and retrieving standardized data from health IT systems. CONCLUSIONS: Use of health IT played an integral part in the planning and implementation of SPPC for participating L&D units. Use of health IT is an encouraging approach for incorporating safety science principles into care to improve perinatal safety and should be incorporated into materials to facilitate the implementation of perinatal safety initiatives.

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.

Individual, facility, and program factors affecting retention in a national weight management program.

BACKGROUND: High attrition is a common problem for weight loss programs and directly affects program effectiveness. Since 2006, the Veterans Health Administration (VHA) has offered obesity treatment to its beneficiaries through the MOVE! Weight Management Program for Veterans (MOVE!). An early evaluation of this program showed that attrition rate was high. The present study examines how individual, facility, and program factors relate to retention for participants in the on-site MOVE! group program. METHODS: Data for all visits to MOVE! group treatment sessions were extracted from the VHA outpatient database. Participants were classified into three groups by their frequency of visits to the group program during a six month period after enrollment: early dropouts (1 - 3 visits), late dropouts (4 - 5 visits), and completers (6 or more visits). A generalized ordered logit model was used to examine individual, facility, and program factors associated with retention. RESULTS: More than 60% of participants were early dropouts and 11% were late dropouts. Factors associated with retention were older age, presence of one or more comorbidities, higher body mass index at baseline, lack of co-payment requirement, geographic proximity to VA facility, addition of individual consultation to group treatment, greater program staffing, and regular, on-site physical activity programming. A non-completion rate of 74% for on-site group obesity treatment poses a major challenge to reducing the population prevalence of obesity within the VHA. CONCLUSIONS: Greater attention to individualized consultation, accessibility to the program, and facility factors including staffing and physical activity resources may improve retention.