Telehealth for Women's Preventive Services for Reproductive Health and Intimate Partner Violence: a Comparative Effectiveness Review.

BACKGROUND: Telehealth delivery of preventive health services may improve access to care; however, its effectiveness and adverse effects are unknown. We conducted a comparative effectiveness review on the effectiveness and harms of telehealth interventions for women's reproductive health and intimate partner violence (IPV) services. METHODS: We searched MEDLINE, Cochrane Library, CINAHL, and Scopus for English-language studies (July 2016 to May 2022) for randomized controlled trials (RCTs) and observational studies of telehealth strategies for women's reproductive health and IPV versus usual care. Two investigators identified studies and abstracted data using a predefined protocol. Study quality was assessed using study design-specific standardized methods; disagreements were resolved through consensus. RESULTS: Eight RCTs, 1 nonrandomized trial, and 7 observational studies (n=10 731) were included (7 studies of contraceptive care and 9 of IPV services). Telehealth interventions to supplement contraceptive care demonstrated similar rates as usual care for contraceptive use, sexually transmitted infections, and pregnancy (low strength of evidence [SOE]); evidence on abortion was insufficient. Outcomes were also similar between telehealth interventions to replace or supplement IPV services and comparators for repeat IPV, depression, posttraumatic stress disorder, fear of partner, coercive control, self-efficacy, and safety behaviors (low SOE). In these studies, telehealth barriers included limited internet access, digital literacy, technical challenges, and confidentiality concerns. Strategies to ensure safety increased telehealth use for IPV services. Evidence on access, health equity, or harms was lacking. DISCUSSION: Telehealth interventions for contraceptive care and IPV services demonstrate equivalent clinical and patient-reported outcomes versus in-person care, although few studies are available. Effective approaches for delivering these services and how to best mobilize telehealth, particularly for women facing barriers to care remain uncertain. TRIAL REGISTRATION: PROSPERO CRD42021282298.

Preventing Obesity in Midlife Women: A Systematic Review for the Women's Preventive Services Initiative.

BACKGROUND: Despite high prevalence rates of obesity in the United States, no clinical guidelines exist for obesity prevention in midlife women who commonly experience weight gain. PURPOSE: To evaluate evidence on the effectiveness and harms of behavioral interventions to reduce weight gain and improve health outcomes for women aged 40 to 60 years without obesity. DATA SOURCES: English-language searches of Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews (inception to 26 October 2021); ClinicalTrials.gov (October 2021); and reference lists of studies and reviews. STUDY SELECTION: Randomized controlled trials (RCTs) enrolling predominantly midlife women comparing behavioral interventions to prevent weight gain with control groups and reporting health outcomes and potential harms. DATA EXTRACTION: Dual extraction and quality assessment of individual studies. DATA SYNTHESIS: Seven RCTs in 12 publications (n = 51 638) were included. Four RCTs showed statistically significant favorable differences in weight change for counseling interventions versus control groups (mean difference of weight change, -0.87 to -2.5 kg), whereas 1 trial of counseling and 2 trials of exercise showed no differences; 1 of 2 RCTs reported improved quality-of-life measures. Interventions did not increase measures of depression or stress in 1 trial; self-reported falls (37% vs. 29%; P < 0.001) and injuries (19% vs. 14%; P = 0.03) were higher with exercise counseling in 1 trial. LIMITATION: Trials were generally small, heterogeneous, and lacked data on harms, long-term health outcomes, and specific patient populations. CONCLUSION: Counseling interventions to prevent weight gain in women during midlife may result in modest differences in weight change without causing important harms. More research is needed to determine optimal content, frequency, length, and number of sessions required and should include additional patient populations. PRIMARY FUNDING SOURCE: Health Resources and Services Administration.

Screening for Anxiety in Adolescent and Adult Women: A Systematic Review for the Women's Preventive Services Initiative.

BACKGROUND: Anxiety disorders are infrequently recognized during routine health care even though they are common in adolescent girls and adult women. PURPOSE: To evaluate evidence on the effectiveness of screening for anxiety disorders in primary care in improving symptoms, function, and quality of life; harms of screening; accuracy of screening instruments; and effectiveness and harms of treatments. DATA SOURCES: English-language searches of Ovid MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Health and Psychosocial Instruments (1 January 1996 to 4 November 2019); ClinicalTrials.gov (November 2019); and reference lists of studies and reviews. STUDY SELECTION: Studies that enrolled adolescent girls and adult women not currently diagnosed with anxiety disorders, including pregnant or postpartum women, and compared clinical outcomes and harms between women who were and were not screened; diagnostic accuracy studies of screening instruments; and systematic reviews of randomized trials of behavioral and pharmacologic treatments. DATA EXTRACTION: Dual extraction and quality assessment of individual studies. DATA SYNTHESIS: No studies evaluated the overall effectiveness or harms of screening. Thirty-three studies and 2 systematic reviews (171 studies; 112 574 participants) evaluated the diagnostic accuracy of 27 screening instruments and their variations against a clinical diagnosis or other instruments. Most demonstrated moderate to high accuracy for adults (Generalized Anxiety Disorder scale: sensitivity, 70% to 97%; specificity, 50% to 89%), pregnant and postpartum women (Edinburgh Postnatal Depression Scale: sensitivity, 74%; specificity, 64%), and adolescents (Screen for Child Anxiety Related Emotional Disorders: sensitivity, 64% to 74%; specificity, 64% to 73%). Anxiety symptoms improved with cognitive behavioral therapy (246 randomized controlled trials; 17 209 participants) and antianxiety medications (126 randomized controlled trials; 8225 participants). LIMITATION: Limited data on long-term harms of treatment and no treatment trials in pregnant or postpartum women. CONCLUSION: Evidence on the overall effectiveness and harms of screening for anxiety is insufficient. Most screening instruments are moderately to highly accurate. Behavioral therapies and antianxiety medications effectively improve anxiety symptoms. PRIMARY FUNDING SOURCE: Health Resources and Services Administration.

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.

Primary Care-Relevant Interventions for Tobacco and Nicotine Use Prevention and Cessation in Children and Adolescents: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Interventions to discourage the use of tobacco products (including electronic nicotine delivery systems or e-cigarettes) among children and adolescents may help decrease tobacco-related illness and injury. Objective: To update the 2013 review on primary care-relevant interventions for tobacco use prevention and cessation in children and adolescents to inform the US Preventive Services Task Force. Data Sources: The Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews, MEDLINE, PsyINFO, and EMBASE (September 1, 2012, to June 25, 2019), with surveillance through February 7, 2020. Study Selection: Primary care-relevant studies; randomized clinical trials and nonrandomized controlled intervention studies of children and adolescents up to age 18 years for cessation and age 25 years for prevention. Trials comparing behavioral or pharmacological interventions with no or a minimal tobacco use intervention control group (eg, usual care, attention control, wait list) were included. Data Extraction and Synthesis: One investigator abstracted data and a second investigator checked data abstraction for accuracy. Two investigators independently assessed study quality. Studies were pooled using random-effects meta-analysis. Main Outcomes and Measures: Tobacco use initiation; tobacco use cessation; health outcomes; harms. Results: Twenty-four randomized clinical trials (N = 44 521) met inclusion criteria. Behavioral interventions were associated with decreased likelihood of cigarette smoking initiation compared with control interventions at 7 to 36 months' follow-up (13 trials, n = 21 700; 7.4% vs 9.2%; relative risk [RR], 0.82 [95% CI, 0.73-0.92]). There was no statistically significant difference between behavioral interventions and controls in smoking cessation when trials were restricted to smokers (9 trials, n = 2516; 80.7% vs 84.1% continued smoking; RR, 0.97 [95% CI, 0.93-1.01]). There were no significant benefits of medication on likelihood of smoking cessation in 2 trials of bupropion at 26 weeks (n = 523; 17% [300 mg] and 6% [150 mg] vs 10% [placebo]; 24% [150 mg] vs 28% [placebo]) and 1 trial of nicotine replacement therapy at 12 months (n = 257; 8.1% vs 8.2%). One trial each (n = 2586 and n = 1645) found no beneficial intervention effect on health outcomes or on adult smoking. No trials of prevention in young adults were identified. Few trials addressed prevention or cessation of tobacco products other than cigarettes; no trials evaluated effects of interventions on e-cigarette use. There were few trials of pharmacotherapy, and they had small sample sizes. Conclusions and Relevance: Behavioral interventions may reduce the likelihood of smoking initiation in nonsmoking children and adolescents. Research is needed to identify effective behavioral interventions for adolescents who smoke cigarettes or who use other tobacco products and to understand the effectiveness of pharmacotherapy.

Screening for Urinary Incontinence in Women: A Systematic Review for the Women's Preventive Services Initiative.

Background: Urinary incontinence is infrequently addressed during routine health care despite its high prevalence and adverse effects on health. Purpose: To evaluate whether screening for urinary incontinence in women not previously diagnosed improves outcomes (symptoms, quality of life, and function) and to evaluate the accuracy of screening methods and potential harms of screening. Data Sources: English-language searches of Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews (1 January 1996 to 30 March 2018); ClinicalTrials.gov (April 2018); and reference lists of studies and reviews. Study Selection: Randomized trials, cohort studies, systematic reviews of studies that enrolled nonpregnant women without previously diagnosed urinary incontinence and compared clinical outcomes and adverse effects between women who were and were not screened, and diagnostic accuracy studies that reported performance measures of screening tests. Data Extraction: Dual extraction and quality assessment of individual studies. Data Synthesis: No studies evaluated the overall effectiveness or harms of screening. Seventeen studies evaluated the diagnostic accuracy of 18 screening questionnaires against a clinical diagnosis or results of diagnostic tests. Of these, 14 poor-quality studies were based in referral clinics, enrolled only symptomatic women, or had other limitations. One good-quality and 2 fair-quality studies (evaluating 4 methods) enrolled women not recruited on the basis of symptoms. Areas under the receiver-operating characteristic curve for stress, urge, and any type of incontinence in these studies were 0.79, 0.88, and 0.88 for the Michigan Incontinence Symptom Index; 0.85, 0.83, and 0.87 for the Bladder Control Self-Assessment Questionnaire; and 0.68, 0.82, and 0.75 for the Overactive Bladder Awareness Tool. The Incontinence Screening Questionnaire had a sensitivity of 66% and specificity of 80% for any type of incontinence. Limitation: Studies enrolled few participants, often from symptomatic referral populations; used various reference standards; and infrequently reported CIs. Conclusion: Evidence is insufficient on the overall effectiveness and harms of screening for urinary incontinence in women. Limited evidence in general populations suggests fairly high accuracy for some screening methods. Primary Funding Source: Health Resources and Services Administration.

Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer in Women: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Pathogenic mutations in breast cancer susceptibility genes BRCA1 and BRCA2 increase risks for breast, ovarian, fallopian tube, and peritoneal cancer in women; interventions reduce risk in mutation carriers. Objective: To update the 2013 US Preventive Services Task Force review on benefits and harms of risk assessment, genetic counseling, and genetic testing for BRCA1/2-related cancer in women. Data Sources: Cochrane libraries; MEDLINE, PsycINFO, EMBASE (January 1, 2013, to March 6, 2019, for updates; January 1, 1994, to March 6, 2019, for new key questions and populations); reference lists. Study Selection: Discriminatory accuracy studies, randomized clinical trials (RCTs), and observational studies of women without recently diagnosed BRCA1/2-related cancer. Data Extraction and Synthesis: Data on study methods, setting, population characteristics, eligibility criteria, interventions, numbers enrolled and lost to follow-up, outcome ascertainment, and results were abstracted. Two reviewers independently assessed study quality. Main Outcomes and Measures: Cancer incidence and mortality; discriminatory accuracy of risk assessment tools for BRCA1/2 mutations; benefits and harms of risk assessment, genetic counseling, genetic testing, and risk-reducing interventions. Results: For this review, 103 studies (110 articles; N = 92 712) were included. No studies evaluated the effectiveness of risk assessment, genetic counseling, and genetic testing in reducing incidence and mortality of BRCA1/2-related cancer. Fourteen studies (n = 43 813) of 8 risk assessment tools to guide referrals to genetic counseling demonstrated moderate to high accuracy (area under the receiver operating characteristic curve, 0.68-0.96). Twenty-eight studies (n = 8060) indicated that genetic counseling was associated with reduced breast cancer worry, anxiety, and depression; increased understanding of risk; and decreased intention for testing. Twenty studies (n = 4322) showed that breast cancer worry and anxiety were higher after testing for women with positive results and lower for others; understanding of risk was higher after testing. In 8 RCTs (n = 54 651), tamoxifen (relative risk [RR], 0.69 [95% CI, 0.59-0.84]; 4 trials), raloxifene (RR, 0.44 [95% CI, 0.24-0.80]; 2 trials), and aromatase inhibitors (RR, 0.45 [95% CI, 0.26-0.70]; 2 trials) were associated with lower risks of invasive breast cancer compared with placebo; results were not specific to mutation carriers. Mastectomy was associated with 90% to 100% reduction in breast cancer incidence (6 studies; n = 2546) and 81% to 100% reduction in breast cancer mortality (1 study; n = 639); oophorectomy was associated with 69% to 100% reduction in ovarian cancer (2 studies; n = 2108); complications were common with mastectomy. Conclusions and Relevance: Among women without recently diagnosed BRCA1/2-related cancer, the benefits and harms of risk assessment, genetic counseling, and genetic testing to reduce cancer incidence and mortality have not been directly evaluated by current research.

Medication Use for the Risk Reduction of Primary Breast Cancer in Women: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Medications to reduce risk of breast cancer are effective for women at increased risk but also cause adverse effects. Objective: To update the 2013 US Preventive Services Task Force systematic review on medications to reduce risk of primary (first diagnosis) invasive breast cancer in women. Data Sources: Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, EMBASE, and MEDLINE (January 1, 2013, to February 1, 2019); manual review of reference lists. Study Selection: Discriminatory accuracy studies of breast cancer risk assessment methods; randomized clinical trials of tamoxifen, raloxifene, and aromatase inhibitors for primary breast cancer prevention; studies of medication adverse effects. Data Extraction and Synthesis: Investigators abstracted data on methods, participant characteristics, eligibility criteria, outcome ascertainment, and follow-up. Results of individual trials were combined by using a profile likelihood random-effects model. Main Outcomes and Measures: Probability of breast cancer in individuals (area under the receiver operating characteristic curve [AUC]); incidence of breast cancer, fractures, thromboembolic events, coronary heart disease events, stroke, endometrial cancer, and cataracts; and mortality. Results: A total of 46 studies (82 articles [>5 million participants]) were included. Eighteen risk assessment methods in 25 studies reported low accuracy in predicting the probability of breast cancer in individuals (AUC, 0.55-0.65). In placebo-controlled trials, tamoxifen (risk ratio [RR], 0.69 [95% CI, 0.59-0.84]; 4 trials [n = 28 421]), raloxifene (RR, 0.44 [95% CI, 0.24-0.80]; 2 trials [n = 17 806]), and the aromatase inhibitors exemestane and anastrozole (RR, 0.45 [95% CI, 0.26-0.70]; 2 trials [n = 8424]) were associated with a lower incidence of invasive breast cancer. Risk for invasive breast cancer was higher for raloxifene than tamoxifen in 1 trial after long-term follow-up (RR, 1.24 [95% CI, 1.05-1.47]; n = 19 747). Raloxifene was associated with lower risk for vertebral fractures (RR, 0.61 [95% CI, 0.53-0.73]; 2 trials [n = 16 929]) and tamoxifen was associated with lower risk for nonvertebral fractures (RR, 0.66 [95% CI, 0.45-0.98]; 1 trial [n = 13 388]) compared with placebo. Tamoxifen and raloxifene were associated with increased thromboembolic events compared with placebo; tamoxifen was associated with more events than raloxifene. Tamoxifen was associated with higher risk of endometrial cancer and cataracts compared with placebo. Symptomatic effects (eg, vasomotor, musculoskeletal) varied by medication. Conclusions and Relevance: Tamoxifen, raloxifene, and aromatase inhibitors were associated with lower risk of primary invasive breast cancer in women but also were associated with adverse effects that differed between medications. Risk stratification methods to identify patients with increased breast cancer risk demonstrated low accuracy.

Predictive Utility of the Total Glasgow Coma Scale Versus the Motor Component of the Glasgow Coma Scale for Identification of Patients With Serious Traumatic Injuries.

STUDY OBJECTIVE: The motor component of the Glasgow Coma Scale (mGCS) has been proposed as an easier-to-use alternative to the total GCS (tGCS) for field assessment of trauma patients by emergency medical services. We perform a systematic review and meta-analysis to compare the predictive utility of the tGCS versus the mGCS or Simplified Motor Scale in field triage of trauma for identifying patients with adverse outcomes (inhospital mortality or severe brain injury) or who underwent procedures (neurosurgical intervention or emergency intubation) indicating need for high-level trauma care. METHODS: Ovid MEDLINE, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, Health and Psychosocial Instruments, and the Cochrane databases were searched through June 2016 for English-language cohort studies. We included studies that compared the area under the receiver operating characteristic curve (AUROC) of the tGCS versus the mGCS or Simplified Motor Scale assessed in the field or shortly after arrival in the emergency department for predicting the outcomes described above. Meta-analyses were performed with a random-effects model, and subgroup and sensitivity analyses were conducted. RESULTS: We included 18 head-to-head studies of predictive utility (n=1,703,388). For inhospital mortality, the tGCS was associated with slightly greater discrimination than the mGCS (pooled mean difference in [AUROC] 0.015; 95% confidence interval [CI] 0.009 to 0.022; I2=85%; 12 studies) or the Simplified Motor Scale (pooled mean difference in AUROC 0.030; 95% CI 0.024 to 0.036; I2=0%; 5 studies). The tGCS was also associated with greater discrimination than the mGCS or Simplified Motor Scale for nonmortality outcomes (differences in AUROC from 0.03 to 0.05). Findings were robust in subgroup and sensitivity analyses. CONCLUSION: The tGCS is associated with slightly greater discrimination than the mGCS or Simplified Motor Scale for identifying severe trauma. The small differences in discrimination are likely to be clinically unimportant and could be offset by factors such as convenience and ease of use.

Effectiveness of Breast Cancer Screening: Systematic Review and Meta-analysis to Update the 2009 U.S. Preventive Services Task Force Recommendation.

BACKGROUND: In 2009, the U.S. Preventive Services Task Force recommended biennial mammography screening for women aged 50 to 74 years and selective screening for those aged 40 to 49 years. PURPOSE: To review studies of the effectiveness of breast cancer screening in average-risk women. DATA SOURCES: MEDLINE and Cochrane databases to 4 June 2015. STUDY SELECTION: English-language randomized, controlled trials and observational studies of screening with mammography, magnetic resonance imaging, and ultrasonography that reported breast cancer mortality, all-cause mortality, or advanced breast cancer outcomes. DATA EXTRACTION: Investigators extracted and confirmed data and dual rated study quality; discrepancies were resolved through consensus. DATA SYNTHESIS: Fair-quality evidence from a meta-analysis of mammography trials indicated relative risks (RRs) for breast cancer mortality of 0.92 for women aged 39 to 49 years (95% CI, 0.75 to 1.02) (9 trials; 3 deaths prevented per 10,000 women over 10 years); 0.86 for those aged 50 to 59 years (CI, 0.68 to 0.97) (7 trials; 8 deaths prevented per 10,000 women over 10 years); 0.67 for those aged 60 to 69 years (CI, 0.54 to 0.83) (5 trials; 21 deaths prevented per 10,000 women over 10 years); and 0.80 for those aged 70 to 74 years (CI, 0.51 to 1.28) (3 trials; 13 deaths prevented per 10,000 women over 10 years). Risk reduction was 25% to 31% for women aged 50 to 69 years in observational studies of mammography screening. All-cause mortality was not reduced with screening. Advanced breast cancer was reduced for women aged 50 years or older (RR, 0.62 [CI, 0.46 to 0.83]) (3 trials) but not those aged 39 to 49 years (RR, 0.98 [CI, 0.74 to 1.37]) (4 trials); less evidence supported this outcome. LIMITATIONS: Most trials used imaging technologies and treatments that are now outdated, and definitions of advanced breast cancer were heterogeneous. Studies of effectiveness based on risk factors, intervals, or other modalities were unavailable or methodologically limited. CONCLUSION: Breast cancer mortality is generally reduced with mammography screening, although estimates are not statistically significant at all ages and the magnitudes of effect are small. Advanced cancer is reduced with screening for women aged 50 years or older. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Harms of Breast Cancer Screening: Systematic Review to Update the 2009 U.S. Preventive Services Task Force Recommendation.

BACKGROUND: In 2009, the U.S. Preventive Services Task Force recommended biennial mammography screening for women aged 50 to 74 years and selective screening for those aged 40 to 49 years. PURPOSE: To review studies of screening in average-risk women with mammography, magnetic resonance imaging, or ultrasonography that reported on false-positive results, overdiagnosis, anxiety, pain, and radiation exposure. DATA SOURCES: MEDLINE and Cochrane databases through December 2014. STUDY SELECTION: English-language systematic reviews, randomized trials, and observational studies of screening. DATA EXTRACTION: Investigators extracted and confirmed data from studies and dual-rated study quality. Discrepancies were resolved through consensus. DATA SYNTHESIS: Based on 2 studies of U.S. data, 10-year cumulative rates of false-positive mammography results and biopsies were higher with annual than biennial screening (61% vs. 42% and 7% vs. 5%, respectively) and for women aged 40 to 49 years, those with dense breasts, and those using combination hormone therapy. Twenty-nine studies using different methods reported overdiagnosis rates of 0% to 54%; rates from randomized trials were 11% to 22%. Women with false-positive results reported more anxiety, distress, and breast cancer-specific worry, although results varied across 80 observational studies. Thirty-nine observational studies indicated that some women reported pain during mammography (1% to 77%); of these, 11% to 46% declined future screening. Models estimated 2 to 11 screening-related deaths from radiation-induced cancer per 100,000 women using digital mammography, depending on age and screening interval. Five observational studies of tomosynthesis and mammography indicated increased biopsies but reduced recalls compared with mammography alone. LIMITATIONS: Studies of overdiagnosis were highly heterogeneous, and estimates varied depending on the analytic approach. Studies of anxiety and pain used different outcome measures. Radiation exposure was based on models. CONCLUSION: False-positive results are common and are higher for annual screening, younger women, and women with dense breasts. Although overdiagnosis, anxiety, pain, and radiation exposure may cause harm, their effects on individual women are difficult to estimate and vary widely. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Screening for vitamin D deficiency: a systematic review for the U.S. Preventive Services Task Force.

BACKGROUND: Vitamin D deficiency has been associated with adverse health outcomes. PURPOSE: To systematically review benefits and harms of vitamin D screening in asymptomatic adults. DATA SOURCES: Ovid MEDLINE (through the third week of August 2014), Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. STUDY SELECTION: Randomized trials of screening for and treatment of vitamin D deficiency and case-control studies nested within the Women's Health Initiative. DATA EXTRACTION: One investigator abstracted data, a second reviewed data for accuracy, and 2 investigators independently assessed study quality using predefined criteria. DATA SYNTHESIS: No study examined the effects of vitamin D screening versus no screening on clinical outcomes. Vitamin D treatment was associated with decreased mortality versus placebo or no treatment (11 studies; risk ratio [RR], 0.83 [95% CI, 0.70 to 0.99]), although benefits were no longer seen after trials of institutionalized persons were excluded (8 studies; RR, 0.93 [CI, 0.73 to 1.18]). Vitamin D treatment was associated with possible decreased risk for having at least 1 fall (5 studies; RR, 0.84 [CI, 0.69 to 1.02]) and falls per person (5 studies; incidence rate ratio, 0.66 [CI, 0.50 to 0.88]) but not fractures (5 studies; RR, 0.98 [CI, 0.82 to 1.16]). Vitamin D treatment was not associated with a statistically significant increased risk for serious adverse events (RR, 1.17 [CI, 0.74 to 1.84]). LIMITATION: Variability across studies in 25-hydroxyvitamin D assays and baseline levels, treatment doses, use of calcium, and duration of follow-up. CONCLUSION: Treatment of vitamin D deficiency in asymptomatic persons might reduce mortality risk in institutionalized elderly persons and risk for falls but not fractures. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Diagnostic Methods for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop.

BACKGROUND: The diagnosis of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is based on clinical criteria, yet there has been no consensus regarding which set of criteria best identifies patients with the condition. The Institute of Medicine has recently proposed a new case definition and diagnostic algorithm. PURPOSE: To review methods to diagnose ME/CFS in adults and identify research gaps and needs for future research. DATA SOURCES: MEDLINE, PsycINFO, and Cochrane databases (January 1988 to September 2014); clinical trial registries; and reference lists. STUDY SELECTION: English-language studies describing methods of diagnosis of ME/CFS and their accuracy. DATA EXTRACTION: Data on participants, study design, analysis, follow-up, and results were extracted and confirmed. Study quality was dual-rated by using prespecified criteria, and discrepancies were resolved through consensus. DATA SYNTHESIS: Forty-four studies met inclusion criteria. Eight case definitions have been used to define ME/CFS; a ninth, recently proposed by the Institute of Medicine, includes principal elements of previous definitions. Patients meeting criteria for ME represent a more symptomatic subset of the broader ME/CFS population. Scales rating self-reported symptoms differentiate patients with ME/CFS from healthy controls under study conditions but have not been evaluated in clinically undiagnosed patients to determine validity and generalizability. LIMITATIONS: Studies were heterogeneous and were limited by size, number, applicability, and methodological quality. Most methods were tested in highly selected patient populations. CONCLUSION: Nine sets of clinical criteria are available to define ME/CFS, yet none of the current diagnostic methods have been adequately tested to identify patients with ME/CFS when diagnostic uncertainty exists. More definitive studies in broader populations are needed to address these research gaps.

Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop.

BACKGROUND: Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is a debilitating multisystem condition affecting more than 1 million adults in the United States. PURPOSE: To determine benefits and harms of treatments for adults with ME/CFS and identify future research needs. DATA SOURCES: MEDLINE, PsycINFO, and Cochrane databases (January 1988 to September 2014); clinical trial registries; reference lists; and manufacturer information. STUDY SELECTION: English-language randomized trials of the effectiveness and adverse effects of ME/CFS treatments. DATA EXTRACTION: Data on participants, study design, analysis, follow-up, and results were extracted and confirmed. Study quality was dual-rated by using prespecified criteria; discrepancies were resolved through consensus. DATA SYNTHESIS: Among 35 treatment trials enrolling participants primarily meeting the 1994 Centers for Disease Control and Prevention and Oxford case definitions of CFS, the immune modulator rintatolimod improved some measures of exercise performance compared with placebo in 2 trials (low strength of evidence). Trials of galantamine, hydrocortisone, IgG, valganciclovir, isoprinosine, fluoxetine, and various complementary medicines were inconclusive (insufficient evidence). Counseling therapies and graded exercise therapy compared with no treatment, relaxation, or support improved fatigue, function, global improvement, and work impairment in some trials; counseling therapies also improved quality of life (low to moderate strength of evidence). Harms were rarely reported across studies (insufficient evidence). LIMITATION: Trials were heterogeneous and were limited by size, number, duration, applicability, and methodological quality. CONCLUSION: Trials of rintatolimod, counseling therapies, and graded exercise therapy suggest benefit for some patients meeting case definitions for CFS, whereas evidence for other treatments and harms is insufficient. More definitive studies comparing participants meeting different case definitions, including ME, and providing subgroup analysis are needed to fill research gaps.

Imaging Techniques for the Diagnosis of Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

BACKGROUND: Several imaging modalities are available for diagnosis of hepatocellular carcinoma (HCC). PURPOSE: To evaluate the test performance of imaging modalities for HCC. DATA SOURCES: MEDLINE (1998 to December 2014), the Cochrane Library Database, Scopus, and reference lists. STUDY SELECTION: Studies on test performance of ultrasonography, computed tomography (CT), or magnetic resonance imaging (MRI). DATA EXTRACTION: One investigator abstracted data, and a second investigator confirmed them; 2 investigators independently assessed study quality and strength of evidence. DATA SYNTHESIS: Few studies have evaluated imaging for HCC in surveillance settings. In nonsurveillance settings, sensitivity for detection of HCC lesions was lower for ultrasonography without contrast than for CT or MRI (pooled difference based on direct comparisons, 0.11 to 0.22), and MRI was associated with higher sensitivity than CT (pooled difference, 0.09 [95% CI, 0.07 to 12]). For evaluation of focal liver lesions, there were no clear differences in sensitivity among ultrasonography with contrast, CT, and MRI. Specificity was generally 0.85 or higher across imaging modalities, but this item was not reported in many studies. Factors associated with lower sensitivity included use of an explanted liver reference standard, and smaller or more well-differentiated HCC lesions. For MRI, sensitivity was slightly higher for hepatic-specific than nonspecific contrast agents. LIMITATIONS: Only English-language articles were included, there was statistical heterogeneity in pooled analyses, and costs were not assessed. Most studies were conducted in Asia and had methodological limitations. CONCLUSION: CT and MRI are associated with higher sensitivity than ultrasonography without contrast for detection of HCC; sensitivity was higher for MRI than CT. For evaluation of focal liver lesions, the sensitivities of ultrasonography with contrast, CT, and MRI for HCC are similar. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. ( PROSPERO: CRD42014007016).

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

IMPORTANCE: Screening for syphilis infection is currently recommended for high-risk individuals, including those with previous syphilis infection, an infected sexual partner, HIV infection, or more than 4 sex partners in the preceding year. OBJECTIVE: To update a 2004 systematic review of studies of syphilis screening effectiveness, test accuracy, and screening harms in nonpregnant adults and adolescents. DATA SOURCES: Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews through October 2015 and Ovid MEDLINE (January 2004 to October 2015), with updated search through March 2016. STUDY SELECTION: English-language trials and observational studies of screening effectiveness, test accuracy, and screening harms in nonpregnant adults and adolescents. DATA EXTRACTION AND SYNTHESIS: One investigator abstracted data, a second checked data for accuracy, and 2 investigators independently assessed study quality using predefined criteria. MAIN OUTCOMES AND MEASURES: Transmission of disease, including HIV; complications of syphilis; diagnostic accuracy; and harms of screening. RESULTS: No evidence was identified regarding the effectiveness of screening on clinical outcomes or the effectiveness of risk assessment instruments; the harms of screening; or the effectiveness of screening in average-risk, nonpregnant adolescents or adults or high-risk individuals other than men who have sex with men (MSM) or men who are HIV positive. Four non-US studies indicated higher rates of syphilis detection with screening every 3 months vs 6 or 12 months for early syphilis in HIV-positive men or MSM. For example, there was an increased proportion of asymptomatic, higher-risk MSM in Australia (n = 6789 consultations) receiving a diagnosis of early syphilis when tested every 3 months vs annually (53% vs 16%, P = .001), but no difference among low-risk MSM. Treponemal and nontreponemal tests were accurate in asymptomatic individuals (sensitivity >85%, specificity >91%) in 3 studies but required confirmatory testing. Reverse sequence testing with an initial automated treponemal test yielded more false reactive test results than with rapid plasma reagin in 2 studies, one with a low-prevalence US population (0.6% vs 0.0%, P = .03) and another in a higher-prevalence Canadian population (0.26% vs 0.13%). CONCLUSIONS AND RELEVANCE: Screening HIV-positive men or MSM for syphilis every 3 months is associated with improved syphilis detection. Treponemal or nontreponemal tests are accurate screening tests but require confirmation. Research is needed on the effect of screening on clinical outcomes; effective screening strategies, including reverse sequence screening, in various patient populations; and harms of screening.

Screening for gonorrhea and Chlamydia: a systematic review for the U.S. Preventive Services Task Force.

BACKGROUND: Previous research has supported screening for gonorrhea and chlamydia in asymptomatic, sexually active women (including pregnant women) who are younger than 25 years or at increased risk but not in other patient populations. PURPOSE: To update the 2005 and 2007 systematic reviews for the U.S. Preventive Services Task Force on screening for gonorrhea and chlamydia in men and women, including pregnant women and adolescents. DATA SOURCES: MEDLINE (1 January 2004 to 13 June 2014), Cochrane databases (May 2014), ClinicalTrials.gov, and reference lists. STUDY SELECTION: English-language trials and observational studies about screening effectiveness, test accuracy, and screening harms. DATA EXTRACTION: Extracted study data were confirmed by a second investigator, and study quality and applicability were dual-rated using prespecified criteria. DATA SYNTHESIS: Screening a subset of asymptomatic young women for chlamydia in a good-quality trial did not significantly reduce the incidence of pelvic inflammatory disease over the following year (relative risk, 0.39 [95% CI, 0.14 to 1.08]); however, 1 previous trial reported a reduction. An observational study evaluating a risk prediction tool to identify persons with chlamydia in high-risk populations had low predictive ability and applicability. In 10 new studies of asymptomatic patients, nucleic acid amplification tests demonstrated sensitivity of 86% or greater and specificity of 97% or greater for diagnosing gonorrhea and chlamydia, regardless of specimen type or test. LIMITATIONS: There were few relevant studies of screening benefits and harms. Only screening tests and methods cleared by the U.S. Food and Drug Administration for current clinical practice were included to determine diagnostic accuracy. CONCLUSION: Chlamydia screening in young women may reduce the incidence of pelvic inflammatory disease. Nucleic acid amplification tests are accurate for diagnosing gonorrhea and chlamydia in asymptomatic persons. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: a systematic review to update the U.S. Preventive Services Task Force recommendation.

BACKGROUND: Mutations in breast cancer susceptibility genes (BRCA1 and BRCA2) are associated with increased risks for breast, ovarian, and other types of cancer. PURPOSE: To review new evidence on the benefits and harms of risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women. DATA SOURCES: MEDLINE and PsycINFO between 2004 and 30 July 2013, the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews from 2004 through the second quarter of 2013, Health Technology Assessment during the fourth quarter of 2012, Scopus, and reference lists. STUDY SELECTION: English-language studies about accuracy of risk assessment and benefits and harms of genetic counseling, genetic testing, and interventions to reduce cancer incidence and mortality. DATA EXTRACTION: Individual investigators extracted data on participants, study design, analysis, follow-up, and results, and a second investigator confirmed key data. Investigators independently dual-rated study quality and applicability by using established criteria. DATA SYNTHESIS: Five referral models accurately estimated individual risk for BRCA mutations. Genetic counseling increased the accuracy of risk perception and decreases the intention for genetic testing among unlikely carriers and cancer-related worry, anxiety, and depression. No trials evaluated the effectiveness of intensive screening or risk-reducing medications in mutation carriers, although false-positive rates, unneeded imaging, and unneeded surgeries were higher with screening. Among high-risk women and mutation carriers, risk-reducing mastectomy decreased breast cancer by 85% to 100% and breast cancer mortality by 81% to 100% compared with women without surgery; risk-reducing salpingo-oophorectomy decreased breast cancer incidence by 37% to 100%, ovarian cancer by 69% to 100%, and all-cause mortality by 55% to 100%. LIMITATION: The analysis included only English-language articles;efficacy trials in mutation carriers were lacking. CONCLUSION: Studies of risk assessment, genetic counseling, genetic testing, and interventions to reduce cancer and mortality indicate potential benefits and harms that vary according to risk.

Screening for lung cancer with low-dose computed tomography: a systematic review to update the US Preventive services task force recommendation.

BACKGROUND: Lung cancer is the leading cause of cancer-related death in the United States. Because early-stage lung cancer is associated with lower mortality than late-stage disease, early detection and treatment may be beneficial. PURPOSE: To update the 2004 review of screening for lung cancer for the U.S. Preventive Services Task Force, focusing on screening with low-dose computed tomography (LDCT). DATA SOURCES: MEDLINE (2000 to 31 May 2013), the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (through the fourth quarter of 2012), Scopus, and reference lists. STUDY SELECTION: English-language randomized, controlled trials or cohort studies that evaluated LDCT screening for lung cancer. DATA EXTRACTION: One reviewer extracted study data about participants, design, analysis, follow-up, and results, and a second reviewer checked extractions. Two reviewers rated study quality using established criteria. DATA SYNTHESIS: Four trials reported results of LDCT screening among patients with smoking exposure. One large good-quality trial reported that screening was associated with significant reductions in lung cancer (20%) and all-cause (6.7%) mortality. Three small European trials showed no benefit of screening. Harms included radiation exposure, overdiagnosis, and a high rate of false-positive findings that typically were resolved with further imaging. Smoking cessation was not affected. Incidental findings were common. LIMITATIONS: Three trials were underpowered and of insufficient duration to evaluate screening effectiveness. Overdiagnosis, an important harm of screening, is of uncertain magnitude. No studies reported results in women or minority populations. CONCLUSION: Strong evidence shows that LDCT screening can reduce lung cancer and all-cause mortality. The harms associated with screening must be balanced with the benefits. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Increased Risk for Clinically Significant Sleep Disturbances in Mild Traumatic Brain Injury: An Approach to Leveraging the Federal Interagency Traumatic Brain Injury Research Database.

STUDY OBJECTIVES: The Federal Interagency Traumatic Brain Injury Research (FITBIR) Informatics System contains individual-patient-level traumatic brain injury (TBI) data, which when combined, allows for the examination of rates and outcomes for key subpopulations at risk for developing sleep disturbance. METHODS: This proof-of-concept study creates a model system for harmonizing data (i.e., combining and standardizing data) across FITBIR studies for participants with and without a history of TBI to estimate rates of sleep disturbance and identify risk factors. RESULTS: Three studies were eligible for harmonization (N = 1753). Sleep disturbance was common among those with a history of mild TBI (63%). Individuals with mild TBI were two to four times more likely to have sleep disturbance compared to those with no history of TBI. CONCLUSIONS: This study established methods, harmonization code, and meta-databases that are publicly available on the FITBIR website. We demonstrated how the harmonization of FITBIR studies can answer TBI research questions, showing that associations between TBI and sleep disturbance may be influenced by demographic factors.