Effectiveness and Safety of Treatments to Prevent Fractures in People With Low Bone Mass or Primary Osteoporosis: A Living Systematic Review and Network Meta-analysis for the American College of Physicians.

BACKGROUND: The prevalence of osteoporosis is increasing in the United States. PURPOSE: To evaluate low bone mass and osteoporosis treatments to prevent fractures. DATA SOURCES: Ovid MEDLINE ALL, Ovid Evidence Based Medicine Reviews: Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov from 2014 through February 2022. STUDY SELECTION: Adults receiving eligible interventions for low bone mass or osteoporosis. Randomized controlled trials (RCTs) for fracture outcomes, and RCTs and large observational studies (n ≥1000) for harms. DATA EXTRACTION: Abstracted by 1 reviewer and verified by a second. Independent, dual assessments of risk of bias and certainty of evidence (CoE). DATA SYNTHESIS: We included 34 RCTs (in 100 publications) and 36 observational studies. Bisphosphonates and denosumab reduced hip, clinical and radiographic vertebral, and other clinical fractures in postmenopausal females with osteoporosis (moderate to high CoE). Bisphosphonates for 36 months or more may increase the risk for atypical femoral fractures (AFFs) and osteonecrosis of the jaw (ONJ), but the absolute risks were low. Abaloparatide and teriparatide reduced clinical and radiographic vertebral fractures but increased the risk for withdrawals due to adverse events (WAEs; moderate to high CoE). Raloxifene and bazedoxifene for 36 months or more reduced radiographic vertebral but not clinical fractures (low to moderate CoE). Abaloparatide, teriparatide, and sequential romosozumab, then alendronate, may be more effective than bisphosphonates in reducing clinical fractures for 17 to 24 months in older postmenopausal females at very high fracture risk (low to moderate CoE). Bisphosphonates may reduce clinical fractures in older females with low bone mass (low CoE) and radiographic vertebral fractures in males with osteoporosis (low to moderate CoE). LIMITATION: Few studies examined participants with low bone mass, males, or Black-identifying persons, sequential therapy, or treatment beyond 3 years. CONCLUSION: Bisphosphonates, denosumab, abaloparatide, teriparatide, and romosozumab, followed by alendronate, reduce clinical fractures in postmenopausal females with osteoporosis. Abaloparatide and teriparatide increased WAEs; longer duration bisphosphonate use may increase AFF and ONJ risk though these events were rare. PRIMARY FUNDING SOURCE: American College of Physicians. (PROSPERO: CRD42021236220).

Day 4 collection of granulocyte colony-stimulating factor-mobilized HLA-matched sibling donor peripheral blood allografts demonstrates no long-term increase in chronic graft-versus-host disease or relapse rates.

BACKGROUND AIMS: In a previous pilot study of HLA-matched sibling donor hematopoietic cell transplantation (HCT), the authors determined the feasibility of day 4 versus day 5 granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cell (PBSC) collection compared with a historical cohort. Given identified differences in the PBSC product (day 4 cohort with significantly lower infused total nucleated, mononuclear and CD3 cells compared with other collection cohorts), the authors performed a follow-up study to determine long-term post-HCT outcomes, including detailed characterization of chronic graft-versus-host disease (GVHD). METHODS: This was a prospective observational study, and the authors collected data on chronic GVHD, staging, sites of involvement and treatments. Performance status, incidence of relapse, overall survival and duration of immunosuppressive therapy (IST) were also evaluated. Data were examined retrospectively. To account for differences in length of follow-up among cohorts, the authors also determined performance status and chronic GVHD staging, sites and treatment at 2 years post-HCT. RESULTS: At 2 years post-HCT, the overall survival rate was 71.7% in the day 4 cohort compared with 61.5%, 52% and 56% in the day 5, 2-day and historical cohorts, respectively (P = 0.283). The cumulative incidence of chronic GVHD was 65.2% in the day 4 cohort versus 46.4% in the day 5 cohort, 51.1% in the 2-day cohort and 65% in the historical cohort (P = 0.26). There was no significant difference in the maximum overall stage of chronic GVHD (P = 0.513), median number of sites involved (P = 0.401) or cumulative incidence of discontinuation of IST (P = 0.32). Death from chronic GVHD was less common in the day 4 and day 5 cohorts compared with the 2-day and historical cohorts, though this did not reach statistical significance. CONCLUSIONS: The authors' preliminary results demonstrated that collection of allogeneic matched sibling donor PBSCs on day 4 of G-CSF was feasible, reduced donor exposure to growth factor and was associated with an initial cost savings. Importantly, the authors now demonstrate that transplantation of day 4 mobilized PBSCs is not associated with any adverse outcomes post-HCT, including late effects such as chronic GVHD. Further investigation of donor G-CSF collection algorithms is merited in other HCT settings, including unrelated and mismatched related donors.

Cannabis-Based Products for Chronic Pain : A Systematic Review.

BACKGROUND: Contemporary data are needed about the utility of cannabinoids in chronic pain. PURPOSE: To evaluate the benefits and harms of cannabinoids for chronic pain. DATA SOURCES: Ovid MEDLINE, PsycINFO, EMBASE, the Cochrane Library, and Scopus to January 2022. STUDY SELECTION: English-language, randomized, placebo-controlled trials and cohort studies (≥1 month duration) of cannabinoids for chronic pain. DATA EXTRACTION: Data abstraction, risk of bias, and strength of evidence assessments were dually reviewed. Cannabinoids were categorized by THC-to-CBD ratio (high, comparable, or low) and source (synthetic, extract or purified, or whole plant). DATA SYNTHESIS: Eighteen randomized, placebo-controlled trials (n = 1740) and 7 cohort studies (n = 13 095) assessed cannabinoids. Studies were primarily short term (1 to 6 months); 56% enrolled patients with neuropathic pain, with 3% to 89% female patients. Synthetic products with high THC-to-CBD ratios (>98% THC) may be associated with moderate improvement in pain severity and response (≥30% improvement) and an increased risk for sedation and are probably associated with a large increased risk for dizziness. Extracted products with high THC-to-CBD ratios (range, 3:1 to 47:1) may be associated with large increased risk for study withdrawal due to adverse events and dizziness. Sublingual spray with comparable THC-to-CBD ratio (1.1:1) probably is associated with small improvement in pain severity and overall function and may be associated with large increased risk for dizziness and sedation and moderate increased risk for nausea. Evidence for other products and outcomes, including longer-term harms, were not reported or were insufficient. LIMITATION: Variation in interventions; lack of study details, including unclear availability in the United States; and inadequate evidence for some products. CONCLUSION: Oral, synthetic cannabis products with high THC-to-CBD ratios and sublingual, extracted cannabis products with comparable THC-to-CBD ratios may be associated with short-term improvements in chronic pain and increased risk for dizziness and sedation. Studies are needed on long-term outcomes and further evaluation of product formulation effects. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services. (PROSPERO: CRD42021229579).

Effectiveness and Harms of Contraceptive Counseling and Provision Interventions for Women : A Systematic Review and Meta-analysis.

BACKGROUND: The effectiveness and harms of contraceptive counseling and provision interventions are unclear. PURPOSE: To evaluate evidence of the effectiveness of contraceptive counseling and provision interventions for women to increase use of contraceptives and reduce unintended pregnancy, as well as evidence of their potential harms. DATA SOURCES: English-language searches of Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, PsycINFO, SocINDEX, and MEDLINE (1 January 2000 to 3 February 2022) and reference lists of key studies and systematic reviews. STUDY SELECTION: Randomized controlled trials of interventions providing enhanced contraceptive counseling, contraceptives, or both versus usual care or an active control. DATA EXTRACTION: Dual extraction and quality assessment of studies; results combined using a profile likelihood random-effects model. DATA SYNTHESIS: A total of 38 trials (43 articles [25 472 participants]) met inclusion criteria. Contraceptive use was higher with various counseling interventions (risk ratio [RR], 1.39 [95% CI, 1.16 to 1.72]; I 2 = 85.3%; 10 trials), provision of emergency contraception in advance of use (RR, 2.12 [CI, 1.79 to 2.36]; I 2 = 0.0%; 8 trials), and counseling or provision postpartum (RR, 1.15 [CI, 1.01 to 1.52]; I 2 = 6.6%; 5 trials) or at the time of abortion (RR, 1.19 [CI, 1.09 to 1.32]; I 2 = 0.0%; 5 trials) than with usual care or active controls in multiple clinical settings. Pregnancy rates were generally lower with interventions, although most trials were underpowered and did not distinguish pregnancy intention. Interventions did not increase risk for sexually transmitted infections (STIs) (RR, 1.05 [CI, 0.87 to 1.25]; I 2 = 0.0%; 5 trials) or reduce condom use (RR, 1.03 [CI, 0.94 to 1.13]; I 2 = 0.0%; 6 trials). LIMITATION: Interventions varied; few trials were adequately designed to determine unintended pregnancy outcomes. CONCLUSION: Contraceptive counseling and provision interventions that provide services beyond usual care increase contraceptive use without increasing STIs or reducing condom use. Contraceptive care in clinical practice could be improved by implementing enhanced contraceptive counseling, provision, and follow-up; providing emergency contraception in advance; and delivering contraceptive services immediately postpartum or at the time of abortion. PRIMARY FUNDING SOURCE: Resources Legacy Fund. (PROSPERO: CRD42020192981).

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

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

Systemic corticosteroids for radicular and non-radicular low back pain.

BACKGROUND: Corticosteroids are medications with anti-inflammatory and immunosuppressant properties. Systemic corticosteroids administered through the oral, intravenous, or intramuscular routes have been used to treat various types of low back pain, including radicular back pain (not due to spinal stenosis), non-radicular back pain, and spinal stenosis. However, there is uncertainty about the benefits and harms of systemic corticosteroids for low back pain. OBJECTIVES: To evaluate the benefits and harms of systemic corticosteroids versus placebo or no corticosteroid for radicular low back pain, non-radicular low back pain, and symptomatic spinal stenosis in adults. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was September 2021. SELECTION CRITERIA: We included randomized and quasi-randomized trials in adults of systematic corticosteroids versus placebo or no corticosteroid. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. The major outcomes were pain, function, need for surgery, serious adverse effect, and presence of hyperglycemia. The minor outcomes were quality of life, successful outcomes, non-serious adverse events, and withdrawal due to adverse events. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: Thirteen trials (1047 participants) met the inclusion criteria. Nine trials included participants with radicular low back pain, two trial with low back pain, and two trials with spinal stenosis. All trials blinded participants to receipt of systemic corticosteroids. Seven trials were at low risk of bias, five at unclear risk, and one at high risk of selection bias. Two trials were at high risk of attrition bias. Doses and duration of systemic corticosteroid therapy varied. Radicular low back pain For radicular low back pain, moderate-certainty evidence indicated that systemic corticosteroids probably slightly decrease pain versus placebo at short-term follow-up (mean difference (MD) 0.56 points better, 95% confidence interval (CI) 1.08 to 0.04 on a 0 to 10 scale) and may slightly increase the likelihood of experiencing improvement in pain at short-term follow-up (risk ratio (RR) 1.21, 95% CI 0.88 to 1.66; absolute effect 5% better (95% CI 5% worse to 15% better). Systemic corticosteroids may not improve function at short-term follow-up (standardized mean difference (SMD) 0.14 better; range 0.49 better to 0.21 worse) and probably increase the likelihood of improvement in function at short-term follow-up (RR 1.52, 95% CI 1.22 to 1.91; absolute effect 19% better, 95% CI 8% better to 30% better). Systemic corticosteroids were associated with greater improvement in function versus placebo at long-term follow-up (MD -7.40, 95% CI -12.55 to -2.25 on the 0 to 100 Oswestry Disability Index) and greater likelihood of functional improvement (RR 1.29, 95% CI 1.06 to 1.56), based on a single trial. There was no difference in likelihood of surgery (RR 1.00, 95% CI 0.68 to 1.47). Evidence indicated that systemic corticosteroids (administered as a single dose or as a short course of therapy) are not associated with increased risk of any adverse event, serious adverse events, withdrawal due to adverse events, or hyperglycemia, but estimates were imprecise as some trials did not report harms, and harms reporting was suboptimal in trials that did provide data. Limitations included variability across trials in interventions (e.g. corticosteroid used, dose and duration of treatment), clinical settings, and participants (e.g. duration of symptoms, methods for diagnosis); limited utility of subgroup analyses due to small numbers of trials; methodologic limitations or suboptimal reporting of methods by some trials; and too few trials to formally assess for publication bias using graphical or statistical tests for small sample effects. Non-radicular low back pain Evidence on systemic corticosteroids versus placebo for non-radicular pain was limited and suggested that systemic corticosteroids may be associated with slightly worse short-term pain but slightly better function. Spinal stenosis For spinal stenosis, limited evidence indicated that systemic corticosteroids are probably no more effective than placebo for short-term pain or function. AUTHORS' CONCLUSIONS: Systemic corticosteroids appear to be slightly effective at improving short-term pain and function in people with radicular low back pain not due to spinal stenosis, and might slightly improve long-term function. The effects of systemic corticosteroids in people with non-radicular low back pain are unclear and systemic corticosteroids are probably ineffective for spinal stenosis. A single dose or short course of systemic corticosteroids for low back pain does not appear to cause serious harms, but evidence is limited.

Prehospital Airway Management: A Systematic Review.

Objective: To assess comparative benefits and harms across three airway management approaches (bag valve mask [BVM], supraglottic airway [SGA], and endotracheal intubation [ETI]) used by prehospital emergency medical services (EMS) to treat patients with trauma, cardiac arrest, or medical emergencies, and how they differ based on techniques and devices, EMS personnel and patient characteristics. Data sources: We searched electronic citation databases (Ovid® MEDLINE®, CINAHL®, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Scopus®) from 1990 to September 2020. Review methods: We followed Agency for Healthcare Research and Quality Effective Health Care Program Methods guidance. Outcomes included mortality, neurological function, return of spontaneous circulation (ROSC), and successful advanced airway insertion. Meta-analyses using profile-likelihood random effects models were conducted, with analyses stratified by study design, emergency type, and age. Results: We included 99 studies involving 630,397 patients. We found few differences in primary outcomes across airway management approaches. For survival, there was no difference for BVM versus ETI or SGA in adult and pediatric patients with cardiac arrest or trauma. For neurological function, there was no difference for BVM versus ETI and SGA versus ETI in pediatric patients with cardiac arrest. There was no difference in BVM versus ETI in adults with cardiac arrest, but improved neurological function with BVM or ETI versus SGA. There was no difference in ROSC for patients with cardiac arrest for BVM versus ETI or SGA in adults and pediatrics, or SGA versus ETI in pediatrics. There was higher frequency of ROSC in adults with SGA versus ETI. For successful advanced airway insertion, there was higher first-pass success with SGA versus ETI for all patients except adult medical patients (no difference), and no difference in overall success using SGA versus ETI in adults. Conclusions: The currently available evidence does not indicate benefits of more invasive airway approaches based on survival, neurological function, ROSC, or successful airway insertion. Strength of evidence was low or moderate; most included studies were observational. This supports the need for high-quality randomized controlled trials to advance clinical practice and EMS education and policy, and improve patient-centered outcomes.

Less dropout from prolonged exposure sessions prescribed at least twice weekly: A meta-analysis and systematic review of randomized controlled trials.

Trauma-focused psychotherapies, such as prolonged exposure (PE), are strongly recommended to treat posttraumatic stress disorder due to their effects in reducing symptoms. However, such therapies may also suffer from high dropout rates. To investigate how clients might benefit from trauma-focused therapy while minimizing dropout, we conducted a meta-analysis of 1,508 adults from 35 randomized controlled trials (RCTs) of outpatient PE programs to evaluate treatment frequency as a predictor of dropout. When an RCT prescribed PE sessions at least twice weekly compared to less frequently, the dropout rate was significantly lower at 21.0%, 95% CI [13.9%, 30.4%], compared to 34.0%, 95% CI [28.9%, 39.4%], OR = 0.52, 95% CI [0.30, 0.89], p = .018. It was not possible to draw causal conclusions, as only one RCT compared two PE treatment frequencies head-to-head. Nonetheless, the findings remained significant after controlling for study characteristics. These data invite reconsideration of the common practice of weekly psychotherapy in favor of twice-weekly sessions in standard outpatient treatment.

Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: A 2016 review for the US Preventive Services Task Force (USPSTF) found use of statins for primary prevention of cardiovascular disease (CVD) was associated with reduced mortality and cardiovascular outcomes. Objective: To update the 2016 review on statins for primary prevention of CVD to inform the USPSTF. Data Sources: Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews (to November 2021); surveillance through May 20, 2022. Study Selection: Randomized clinical trials on statins vs placebo or no statin and statin intensity in adults without prior cardiovascular events; large cohort studies on harms. Data Extraction and Synthesis: One investigator abstracted data; a second checked accuracy. Two investigators independently rated study quality. Main Outcomes and Measures: All-cause and cardiovascular mortality, myocardial infarction, stroke, composite cardiovascular outcomes, and adverse events. Results: Twenty-six studies were included: 22 trials (N = 90 624) with 6 months to 6 years of follow-up compared statins vs placebo or no statin, 1 trial (n = 5144) compared statin intensities, and 3 observational studies (n = 417 523) reported harms. Statins were significantly associated with decreased risk of all-cause mortality (risk ratio [RR], 0.92 [95% CI, 0.87 to 0.98]; absolute risk difference [ARD], -0.35% [95% CI, -0.57% to -0.14%]), stroke (RR, 0.78 [95% CI, 0.68 to 0.90]; ARD, -0.39% [95% CI, -0.54% to -0.25%]), myocardial infarction (RR, 0.67 [95% CI, 0.60 to 0.75]; ARD, -0.85% [95% CI, -1.22% to -0.47%]), and composite cardiovascular outcomes (RR, 0.72 [95% CI, 0.64 to 0.81]; ARD, -1.28% [95% CI, -1.61% to -0.95%]); the association with cardiovascular mortality was not statistically significant (RR, 0.91 [95% CI, 0.81 to 1.02]; ARD, -0.13%). Relative benefits were consistent in groups defined by demographic and clinical characteristics, although data for persons older than 75 years were sparse. Statin therapy was not significantly associated with increased risk of serious adverse events (RR, 0.97 [95% CI, 0.93 to 1.01]), myalgias (RR, 0.98 [95% CI, 0.86 to 1.11]), or elevated alanine aminotransferase level (RR, 0.94 [95% CI, 0.78 to 1.13]). Statin therapy was not significantly associated with increased diabetes risk overall (RR, 1.04 [95% CI, 0.92 to 1.19]), although 1 trial found high-intensity statin therapy was significantly associated with increased risk (RR, 1.25 [95% CI, 1.05 to 1.49]). Otherwise, there were no clear differences in outcomes based on statin intensity. Conclusions and Relevance: In adults at increased CVD risk but without prior CVD events, statin therapy for primary prevention of CVD was associated with reduced risk of all-cause mortality and CVD events. Benefits of statin therapy appear to be present across diverse demographic and clinical populations, with consistent relative benefits in groups defined by demographic and clinical characteristics.

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

Importance: Two 2013 systematic reviews to inform the US Preventive Services Task Force (USPSTF) found insufficient evidence to assess benefits and harms of screening for primary open-angle glaucoma (OAG) in adults. Objective: To update the 2013 reviews on screening for glaucoma, to inform the USPSTF. Data Sources: Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews (to February 2021); surveillance through January 21, 2022. Study Selection: Randomized clinical trials (RCTs) of screening, referral, and treatment; and studies of screening test diagnostic accuracy. Data Extraction and Synthesis: One investigator abstracted data and a second checked accuracy. Two investigators independently assessed study quality. Results: Eighty-three studies (N = 75 887) were included (30 trials and 53 diagnostic accuracy studies). One RCT (n = 616) found screening of frail elderly persons associated with no difference in vision outcomes vs no screening but with significantly greater falls risk (relative risk [RR], 1.31 [95% CI, 1.13-1.50]). No study evaluated referral to an eye health professional. For glaucoma diagnosis, spectral domain optical coherence tomography (providing high-resolution cross-sectional imaging; 15 studies, n = 4242) was associated with sensitivity of 0.79 (95% CI, 0.75-0.83) and specificity of 0.92 (95% CI, 0.87-0.96) and the Humphrey Visual Field Analyzer (for perimetry, or measurement of visual fields; 6 studies, n = 11 244) with sensitivity of 0.87 (95% CI, 0.69-0.95) and specificity 0.82 (95% CI, 0.66-0.92); tonometry (for measurement of intraocular pressure; 13 studies, n = 32 892) had low sensitivity (0.48 [95% CI, 0.31-0.66]). Medical therapy for ocular hypertension and untreated glaucoma was significantly associated with decreased intraocular pressure and decreased likelihood of glaucoma progression (7 trials, n = 3771; RR, 0.68 [95% CI, 0.49-0.96]; absolute risk difference -4.2%) vs placebo, but 1 trial (n = 461) found no differences in visual acuity, quality of life, or function. Selective laser trabeculoplasty and medical therapy had similar outcomes (4 trials, n = 957). Conclusions and Relevance: This review found limited direct evidence on glaucoma screening, showing no association with benefits. Screening tests can identify persons with glaucoma and treatment was associated with a lower risk of glaucoma progression, but evidence of improvement in visual outcomes, quality of life, and function remains lacking.

Associations of Unintended Pregnancy With Maternal and Infant Health Outcomes: A Systematic Review and Meta-analysis.

Importance: Unintended pregnancy is common in the US and is associated with adverse maternal and infant health outcomes; however, estimates of these associations specific to current US populations are lacking. Objective: To evaluate associations of unintended pregnancy with maternal and infant health outcomes during pregnancy and post partum with studies relevant to current clinical practice and public health in the US. Data Sources: Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, PsycINFO, SocINDEX, and MEDLINE databases (January 1, 2000, to June 15, 2022) and manual review of reference lists. Study Selection: Epidemiologic studies relevant to US populations that compared key maternal and infant health outcomes for unintended vs intended pregnancies and met prespecified eligibility criteria were included after investigators' independent dual review of abstracts and full-text articles. Data Extraction and Synthesis: Investigators abstracted data from publications on study methods, participant characteristics, settings, pregnancy intention, comparators, confounders, and outcomes; data were validated by a second investigator. Risk of bias was independently dual rated by investigators using criteria developed by the US Preventive Services Task Force. Results of studies controlling for confounders were combined by using a profile likelihood random-effects model. Main Outcomes and Measures: Prenatal depression, postpartum depression, maternal experience of interpersonal violence, preterm birth, and infant low birth weight. Results: Thirty-six studies (N = 524 522 participants) were included (14 cohort studies rated good or fair quality; 22 cross-sectional studies); 12 studies used large population-based data sources. Compared with intended pregnancy, unintended pregnancy was significantly associated with higher odds of depression during pregnancy (23.3% vs 13.9%; adjusted odds ratio [aOR], 1.59 [95% CI, 1.35-1.92]; I2 = 85.0%; 15 studies [n = 41 054]) and post partum (15.7% vs 9.6%; aOR, 1.51 [95% CI, 1.40-1.70]; I2 = 7.1%; 10 studies [n = 82 673]), interpersonal violence (14.6% vs 5.5%; aOR, 2.22 [95% CI, 1.41-2.91]; I2 = 64.1%; 5 studies [n = 42 306]), preterm birth (9.4% vs 7.7%; aOR, 1.21 [95% CI, 1.12-1.31]; I2 = 1.7%; 10 studies [n = 94 351]), and infant low birth weight (7.3% vs 5.2%; aOR, 1.09 [95% CI, 1.02-1.21]; I2 = 0.0%; 8 studies [n = 87 547]). Results were similar in sensitivity analyses based on controlling for history of depression for prenatal and postpartum depression and on study design and definition of unintended pregnancy for relevant outcomes. Studies provided limited sociodemographic data and measurement of confounders and outcomes varied. Conclusions and Relevance: In this systematic review and meta-analysis of epidemiologic observational studies relevant to US populations, unintended pregnancy, compared with intended pregnancy, was significantly associated with adverse maternal and infant outcomes. Trial Registration: PROSPERO Identifier: CRD42020192981.

Epidemiology of and Risk Factors for Coronavirus Infection in Health Care Workers: A Living Rapid Review.

BACKGROUND: Health care workers (HCWs) are at risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. PURPOSE: To examine the burden of SARS-CoV-2, SARS-CoV-1, and Middle East respiratory syndrome (MERS)-CoV on HCWs and risk factors for infection, using rapid and living review methods. DATA SOURCES: Multiple electronic databases, including the WHO database of publications on coronavirus disease and the medRxiv preprint server (2003 through 27 March 2020, with ongoing surveillance through 24 April 2020), and reference lists. STUDY SELECTION: Studies published in any language reporting incidence of or outcomes associated with coronavirus infections in HCWs and studies on the association between risk factors (demographic characteristics, role, exposures, environmental and administrative factors, and personal protective equipment [PPE] use) and HCW infections. New evidence will be incorporated on an ongoing basis by using living review methods. DATA EXTRACTION: One reviewer abstracted data and assessed methodological limitations; verification was done by a second reviewer. DATA SYNTHESIS: 64 studies met inclusion criteria; 43 studies addressed burden of HCW infections (15 on SARS-CoV-2), and 34 studies addressed risk factors (3 on SARS-CoV-2). Health care workers accounted for a significant proportion of coronavirus infections and may experience particularly high infection incidence after unprotected exposures. Illness severity was lower than in non-HCWs. Depression, anxiety, and psychological distress were common in HCWs during the coronavirus disease 2019 outbreak. The strongest evidence on risk factors was on PPE use and decreased infection risk. The association was most consistent for masks but was also observed for gloves, gowns, eye protection, and handwashing; evidence suggested a dose-response relationship. No study evaluated PPE reuse. Certain exposures (such as involvement in intubations, direct patient contact, or contact with bodily secretions) were associated with increased infection risk. Infection control training was associated with decreased risk. LIMITATION: There were few studies on risk factors for SARS-CoV-2, the studies had methodological limitations, and streamlined rapid review methods were used. CONCLUSION: Health care workers experience significant burdens from coronavirus infections, including SARS-CoV-2. Use of PPE and infection control training are associated with decreased infection risk, and certain exposures are associated with increased risk. PRIMARY FUNDING SOURCE: World Health Organization.

Screening and Interventions to Prevent Dental Caries in Children Younger Than 5 Years: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: A 2014 review for the US Preventive Services Task Force (USPSTF) found that oral fluoride supplementation and topical fluoride use were associated with reduced caries incidence in children younger than 5 years. Objective: To update the 2014 review on dental caries screening and preventive interventions to inform the USPSTF. Data Sources: Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews (to September 2020); surveillance through July 23, 2021. Study Selection: Randomized clinical trials (RCTs) on screening, preventive interventions, referral to dental care; cohort studies on screening and referral; studies on diagnostic accuracy of primary care oral examination or risk assessment; and a systematic review on risk of fluorosis included in prior USPSTF reviews. Data Extraction and Synthesis: One investigator abstracted data; a second checked accuracy. Two investigators independently rated study quality. Results: Thirty-two studies (19 trials, 9 observational studies, and 4 nonrandomized clinical intervention studies [total 106 694 participants] and 1 systematic review [19 studies]) were included. No study evaluated effects of primary care screening on clinical outcomes. One study (n = 258) found primary care pediatrician examination associated with a sensitivity of 0.76 (95% CI, 0.55 to 0.91) and specificity of 0.95 (95% CI, 0.92 to 0.98) for identifying a child with cavities, and 1 study found a risk assessment tool associated with sensitivity of 0.53 and specificity of 0.77 (n = 697, CIs not reported) for a child with future caries. No new trials of dietary fluoride supplementation were identified. For prevention, topical fluoride compared with placebo or no topical fluoride was associated with decreased caries burden (13 trials, n = 5733; mean caries increment [difference in decayed, missing, and filled teeth or surfaces], -0.94 [95% CI, -1.74 to -0.34]) and likelihood of incident caries (12 trials, n = 8177; RR, 0.80 [95% CI, 0.66 to 0.95]; absolute risk difference, -7%) in higher-risk populations or settings, with no increased fluorosis risk. Evidence on other preventive interventions was limited (education, xylitol) or unavailable (silver diamine fluoride), and no study directly evaluated primary care dentistry referral vs no referral. Conclusions and Relevance: There was no direct evidence on benefits and harms of primary care oral health screening or referral to dentist. Dietary fluoride supplementation and fluoride varnish were associated with improved caries outcomes in higher-risk children and settings.

Counseling and Behavioral Interventions for Healthy Weight and Weight Gain in Pregnancy: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Counseling and active behavioral interventions to limit excess gestational weight gain (GWG) during pregnancy may improve health outcomes for women and infants. The 2009 National Academy of Medicine (NAM; formerly the Institute of Medicine) recommendations for healthy GWG vary according to prepregnancy weight category. Objective: To review and synthesize the evidence on benefits and harms of behavioral interventions to promote healthy weight gain during pregnancy to inform the US Preventive Services Task Force recommendation. Data Sources: Ovid MEDLINE and the Cochrane Library to March 2020, with surveillance through February 2021. Study Selection: Randomized clinical trials and nonrandomized controlled intervention studies focused on diet, exercise, and/or behavioral counseling interventions on GWG. Data Extraction and Synthesis: Independent data abstraction and study quality rating with dual review. Main Outcomes and Measures: Gestational weight-related outcomes; maternal and infant morbidity and mortality; harms. Results: Sixty-eight studies (N = 25 789) were included. Sixty-seven studies evaluated interventions during pregnancy, and 1 evaluated an intervention prior to pregnancy. GWG interventions were associated with reductions in risk of gestational diabetes (43 trials, n = 19 752; relative risk [RR], 0.87 [95% CI, 0.79 to 0.95]; absolute risk difference [ARD], -1.6%) and emergency cesarean delivery (14 trials, n = 7520; RR, 0.85 [95% CI, 0.74 to 0.96]; ARD, -2.4%). There was no significant association between GWG interventions and risk of gestational hypertension, cesarean delivery, or preeclampsia. GWG interventions were associated with decreased risk of macrosomia (25 trials, n = 13 990; RR, 0.77 [95% CI, 0.65 to 0.92]; ARD, -1.9%) and large for gestational age (26 trials, n = 13 000; RR, 0.89 [95% CI, 0.80 to 0.99]; ARD, -1.3%) but were not associated with preterm birth. Intervention participants experienced reduced weight gain across all prepregnancy weight categories (55 trials, n = 20 090; pooled mean difference, -1.02 kg [95% CI, -1.30 to -0.75]) and demonstrated lower likelihood of GWG in excess of NAM recommendations (39 trials, n = 14 271; RR, 0.83 [95% CI, 0.77 to 0.89]; ARD, -7.6%). GWG interventions were associated with reduced postpartum weight retention at 12 months (10 trials, n = 3957; mean difference, -0.63 kg [95% CI, -1.44 to -0.01]). Data on harms were limited. Conclusions and Relevance: Counseling and active behavioral interventions to limit GWG were associated with decreased risk of gestational diabetes, emergency cesarean delivery, macrosomia, and large for gestational age. GWG interventions were also associated with modest reductions in mean GWG and decreased likelihood of exceeding NAM recommendations for GWG.

Effectiveness of Patient Navigation to Increase Cancer Screening in Populations Adversely Affected by Health Disparities: a Meta-analysis.

BACKGROUND: This study evaluates the effectiveness of patient navigation to increase screening for colorectal, breast, and cervical cancer in populations adversely affected by health care disparities. METHODS: Eligible studies were identified through English-language searches of Ovid® MEDLINE®, PsycINFO®, SocINDEX, and Veterans Affairs Health Services database (January 1, 1996, to July 5, 2019) and manual review of reference lists. Randomized trials and observational studies of relevant populations that evaluated the effectiveness of patient navigation on screening rates for colorectal, breast, or cervical cancer compared with usual or alternative care comparison groups were included. Two investigators independently abstracted study data and assessed study quality and applicability using criteria adapted from the U.S. Preventive Services Task Force. Discrepancies were resolved by consensus with a third reviewer. Results were combined using profile likelihood random effects models. RESULTS: Thirty-seven studies met inclusion criteria (28 colorectal, 11 breast, 4 cervical cancers including 3 trials with multiple cancer types). Screening rates were higher with patient navigation for colorectal cancer overall (risk ratio [RR] 1.64; 95% confidence interval [CI] 1.42 to 1.92; I2 = 93.7%; 22 trials) and by type of test (fecal occult blood or immunohistochemistry testing [RR 1.69; 95% CI 1.33 to 2.15; I2 = 80.5%; 6 trials]; colonoscopy/endoscopy [RR 2.08; 95% CI 1.08 to 4.56; I2 = 94.6%; 6 trials]). Screening was also higher with navigation for breast cancer (RR 1.50; 95% CI 1.22 to 1.91; I2 = 98.6%; 10 trials) and cervical cancer (RR 1.11; 95% CI 1.05 to 1.19; based on the largest trial). The high heterogeneity of cervical cancer studies prohibited meta-analysis. Results were similar for colorectal and breast cancer regardless of prior adherence to screening guidelines, follow-up time, and study quality. CONCLUSIONS: In populations adversely affected by disparities, colorectal, breast, and cervical cancer screening rates were higher in patients provided navigation services. Registration: PROSPERO: CRD42018109263.

Impact of maintenance rituximab on duration of response in primary central nervous system lymphoma.

PURPOSE: The role of maintenance immunotherapy with anti-CD20 monoclonal antibody rituximab in primary central nervous system lymphoma (PCNSL) is unclear. We retrospectively reviewed the medical records of all immunocompetent adults with newly diagnosed PCNSL treated at our institution between1996 and 2017. METHODS: We identified 66 patients who attained complete response (CR) after completion of first-line regimen; 20 received maintenance therapy (maintenance therapy group) and 46 were observed with serial MRI scans without maintenance therapy (no-maintenance therapy group). RESULTS: Compared to the surveillance group, there was a significant increase in duration of survival (HR 0.27, 95% CI 0.08-0.98, P = 0.046) in the maintenance therapy group while the reduction in the risk of progression was not significant (HR: 0.61, 95% CI 0.26-1.43, P = 0.259). CONCLUSION: We are evaluating the effectiveness of maintenance immunotherapy in PCNSL in a prospective multicenter randomized clinical trial.

Ferumoxytol-Enhanced MRI Is Not Inferior to Gadolinium-Enhanced MRI in Detecting Intracranial Metastatic Disease and Metastasis Size.

OBJECTIVE. The goal of this intraindividual comparison study was to investigate whether ferumoxytol-enhanced MRI is as effective as standard-of-care gadolinium-enhanced MRI in detecting intracranial metastatic disease. MATERIALS AND METHODS. We retrospectively reviewed all patients who underwent imaging as part of two ongoing ferumoxytol-enhanced and gadolinium-enhanced MRI protocol studies to compare the number and size of enhancing metastatic lesions. Two neuroradiologists independently measured enhancing metastases on ferumoxytol-enhanced MR images and on control gadolinium-enhanced MR images. The number and size of metastases were compared on an intraindividual basis. Primary diagnoses were recorded. A linear mixed-effects model was used to compare differences in cubic root of volume between gadolinium-enhanced and ferumoxytol-enhanced MRI. A signed rank test was used to evaluate differences between reviewers. RESULTS. MR images from 19 patients with brain metastases were analyzed (seven with lung cancer, three with breast cancer, three with melanoma, two with ovarian cancer, one with colon cancer, one with renal cell carcinoma, one with carcinoid tumor, and one with uterine cancer). Reviewer 1 identified 77 masses on ferumoxytol-enhanced MRI and 72 masses on gadolinium-enhanced MRI. Reviewer 2 identified 83 masses on ferumoxytol-enhanced MRI and 78 masses on gadolinium-enhanced MRI. For reviewer 1, ferumoxytol-enhanced MRI showed a mean tumor size measuring 1.1 mm larger in each plane compared with gadolinium-enhanced MRI (p = 0.1887). For reviewer 2, ferumoxytol-enhanced MRI showed a mean tumor size measuring 1.0 mm larger in each plane (p = 0.2892). No significant differences in number of metastases or tumor sizes were observed between contrast agents or reviewers. CONCLUSION. Intracranial metastatic disease detection with ferumoxytol-enhanced MRI was not inferior to detection with gadolinium-enhanced MRI. Ferumoxytol-enhanced MRI could improve workup and monitoring of patients with brain metastases if gadolinium-enhanced MRI is contraindicated.

Effectiveness of Emergency Department Treatment of Pediatric Headache and Relation to Rebound Headache.

OBJECTIVE: This study aimed to assess the association between the degree of headache relief obtained in the pediatric emergency department (PED) with abortive treatment and unscheduled return visits to the PED for a recurrent or persistent headache within 72 hours. METHODS: This was a retrospective observational study with 369 patients, all younger than 18 years, who presented to the PED with a primary complaint of either a headache or migraine. Patient and visit details were collected from the medical chart, along with presenting and discharge pain score. Percent pain reduction at discharge was determined through the following calculation: (Presenting Pain Score - Discharge Pain Score)/Presenting Pain Score. Associations were assessed using multivariable logistic regression. RESULTS: No significant association was found between the percent pain reduction and return to the PED (P = 0.49). Mean presenting pain score at the index visit was statistically higher for those who ended up returning to the PED versus those who did not (8.1 vs 7.4; P = 0.02). A trend toward increase in return visits was seen among patients who had a headache duration greater than 3 days (odds ratio, 1.99) and patients who experienced less than 50% pain reduction in the PED (odds ratio, 1.77). CONCLUSIONS: Complete resolution in the PED may not be necessary, given the lack of association between the degree of pain relief and revisit rates. Perhaps, the goal should be to achieve at least 50% pain reduction before discharge.

Clinical Factors Associated With Pediatric Brain Neoplasms Versus Primary Headache: A Case-Control Analysis.

OBJECTIVE: Pediatric headaches are a common presentation to emergency departments accounting for almost half a million annual visits. Providers are left with the difficult task of deciding who has a secondary headache etiology that warrants neuroimaging. METHODS: We conducted a retrospective case-control study. Patients from a pediatric neuro-oncology clinic database with brain cancer and a headache at presentation were identified as cases. Controls were patients from 2 local pediatric tertiary care emergency departments with a final diagnosis of headache after negative neuroimaging. Clinical factors were decided a priori, and logistic regression was used to determine which clinical factors were related to case/control status. RESULTS: A total of 334 patients (203 controls and 131 cases) were included. Patients with a history of headaches had 0.5 (95% confidence interval [CI]: 0.3-0.9; P = 0.03) times the odds of being a case. Patients with vomiting had increased odds of being a case compared with controls regardless of the time of day (early morning 1.8 [95% CI: 1.0-3.2; P = 0.04] and non-early morning 6.6 [95% CI: 2.0-21.7; P < 0.01]). Patients with neurological signs had 10.3 (95% CI: 5.4-19.4; P < 0.01) times the odds of being a case, and patients with an associated seizure had 10.9 (95% CI: 3.8-30.7; P < 0.01) times the odds of being a case. CONCLUSIONS: This study identified clinical factors associated with pediatric brain neoplasms that may guide acute neuroimaging decisions. This study also provides insight into potential clinical factors to be studied prospectively to derive a clinical decision rule.

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

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