Tracy Dana

Screening for prostate cancer: a review of the evidence for the U.S. Preventive Services Task Force.

BACKGROUND Screening can detect prostate cancer at earlier, asymptomatic stages, when treatments might be more effective. PURPOSE To update the 2002 and 2008 U.S. Preventive Services Task Force evidence reviews on screening and treatments for prostate cancer. DATA SOURCES MEDLINE (2002 to July 2011) and the Cochrane Library Database (through second quarter of 2011). STUDY SELECTION Randomized trials of prostate-specific antigen-based screening, randomized trials and cohort studies of prostatectomy or radiation therapy versus watchful waiting, and large observational studies of perioperative harms. DATA EXTRACTION Investigators abstracted and checked study details and quality using predefined criteria. DATA SYNTHESIS Of 5 screening trials, the 2 largest and highest-quality studies reported conflicting results. One found that screening was associated with reduced prostate cancer-specific mortality compared with no screening in a subgroup of men aged 55 to 69 years after 9 years (relative risk, 0.80 [95% CI, 0.65 to 0.98]; absolute risk reduction, 0.07 percentage point). The other found no statistically significant effect after 10 years (relative risk, 1.1 [CI, 0.80 to 1.5]). After 3 or 4 screening rounds, 12% to 13% of screened men had false-positive results. Serious infections or urine retention occurred after 0.5% to 1.0% of prostate biopsies. There were 3 randomized trials and 23 cohort studies of treatments. One good-quality trial found that prostatectomy for localized prostate cancer decreased risk for prostate cancer-specific mortality compared with watchful waiting through 13 years of follow-up (relative risk, 0.62 [CI, 0.44 to 0.87]; absolute risk reduction, 6.1%). Benefits seemed to be limited to men younger than 65 years. Treating approximately 3 men with prostatectomy or 7 men with radiation therapy instead of watchful waiting would each result in 1 additional case of erectile dysfunction. Treating approximately 5 men with prostatectomy would result in 1 additional case of urinary incontinence. Prostatectomy was associated with perioperative death (about 0.5%) and cardiovascular events (0.6% to 3%), and radiation therapy was associated with bowel dysfunction. LIMITATIONS Only English-language articles were included. Few studies evaluated newer therapies. CONCLUSION Prostate-specific antigen-based screening results in small or no reduction in prostate cancer-specific mortality and is associated with harms related to subsequent evaluation and treatments, some of which may be unnecessary. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

Screening for Osteoporosis: An Update for the U.S. Preventive Services Task Force

BACKGROUND This review updates evidence since the 2002 U.S. Preventive Services Task Force recommendation on osteoporosis screening. PURPOSE To determine the effectiveness and harms of osteoporosis screening in reducing fractures for men and postmenopausal women without known previous fractures; the performance of risk-assessment instruments and bone measurement tests in identifying persons with osteoporosis; optimal screening intervals; and the efficacy and harms of medications to reduce primary fractures. DATA SOURCES Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (through the fourth quarter of 2009), MEDLINE (January 2001 to December 2009), reference lists, and Web of Science. STUDY SELECTION Randomized, controlled trials of screening or medications with fracture outcomes published in English; performance studies of validated risk-assessment instruments; and systematic reviews and population-based studies of bone measurement tests or medication harms. DATA EXTRACTION Data on patient populations, study design, analysis, follow-up, and results were abstracted, and study quality was rated by using established criteria. DATA SYNTHESIS Risk-assessment instruments are modest predictors of low bone density (area under the curve, 0.13 to 0.87; 14 instruments) and fractures (area under the curve, 0.48 to 0.89; 11 instruments); simple and complex instruments perform similarly. Dual-energy x-ray absorptiometry predicts fractures similarly for men and women; calcaneal quantitative ultrasonography also predicts fractures, but correlation with dual-energy x-ray absorptiometry is low. For postmenopausal women, bisphosphonates, parathyroid hormone, raloxifene, and estrogen reduce primary vertebral fractures. Trials are lacking for men. Bisphosphonates are not consistently associated with serious adverse events; raloxifene and estrogen increase thromboembolic events; and estrogen causes additional adverse events. LIMITATION Trials of screening with fracture outcomes, screening intervals, and medications to reduce primary fractures, particularly those enrolling men, are lacking. CONCLUSION Although methods to identify risk for osteoporotic fractures are available and medications to reduce fractures are effective, no trials directly evaluate screening effectiveness, harms, and intervals. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

Diagnosis, access and outcomes: Update of a systematic review of telemedicine services

Telemedicine services are being increasingly used. Although insurers and other payers are covering some services in the USA, the rationale for these coverage decisions is not always evidence-based. We reviewed the literature for telemedicine services that substitute for face-to-face medical diagnosis and treatment. We focused on three types of telemedicine services: store-and-forward, home-based and office/hospital-based services. Studies were included if they were relevant to at least one of the three study areas, addressed at least one key question and contained reported results. We excluded articles that did not study a service requiring face-to-face encounters (i.e. teleradiology was excluded). Our search initially identified 4083 citations. After review, 597 were judged to be potentially relevant at the title/abstract level. Following a full-text review, 106 studies were included. Store-and-forward services have been studied in many specialties, the most common being dermatology, wound care and ophthalmology. The evidence for their efficacy is mixed. Several limited studies showed the benefits of home-based telemedicine interventions in chronic diseases. Studies of office/hospital-based telemedicine suggest that telemedicine is most effective for verbal interactions, e.g. videoconferencing for diagnosis and treatment in specialties like neurology and psychiatry. There are still significant gaps in the evidence base between where telemedicine is used and where its use is supported by high-quality evidence. Further well-designed research is necessary to understand how best to deploy telemedicine services in health care.

Screening Asymptomatic Adults With Resting or Exercise Electrocardiography: A Review of the Evidence for the U.S. Preventive Services Task Force

BACKGROUND Coronary heart disease is the leading cause of death in adults. Screening for abnormalities by using resting or exercise electrocardiography (ECG) might help identify persons who would benefit from interventions to reduce cardiovascular risk. PURPOSE To update the 2004 U.S. Preventive Services Task Force evidence review on screening for resting or exercise ECG abnormalities in asymptomatic adults. DATA SOURCES MEDLINE (2002 through January 2011), the Cochrane Library database (through the fourth quarter of 2010), and reference lists. STUDY SELECTION Randomized, controlled trials and prospective cohort studies. DATA EXTRACTION Investigators abstracted details about the study population, study design, data analysis, follow-up, and results and assessed quality by using predefined criteria. DATA SYNTHESIS No study evaluated clinical outcomes or use of risk-reducing therapies after screening versus no screening. No study estimated how accurately resting or exercise electrocardiography classified participants into high-, intermediate-, or low-risk groups, compared with traditional risk factor assessment alone. Sixty-three prospective cohort studies evaluated abnormalities on resting or exercise ECG as predictors of cardiovascular events after adjustment for traditional risk factors. Abnormalities on resting ECG (ST-segment or T-wave abnormalities, left ventricular hypertrophy, bundle branch block, or left-axis deviation) or exercise ECG (ST-segment depression with exercise, chronotropic incompetence, abnormal heart rate recovery, or decreased exercise capacity) were associated with increased risk (pooled hazard ratio estimates, 1.4 to 2.1). Evidence on harms was limited, but direct harms seemed minimal (for resting ECG) or small (for exercise ECG). No study estimated harms from subsequent testing or interventions, although rates of angiography after exercise ECG ranged from 0.6% to 2.9%. LIMITATIONS Only English-language studies were included. Statistical heterogeneity was present in several of the pooled analyses. CONCLUSION Abnormalities on resting or exercise ECG are associated with an increased risk for subsequent cardiovascular events after adjustment for traditional risk factors, but the clinical implications of these findings are unclear.

Statins for Prevention of Cardiovascular Disease in Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force

Importance Cardiovascular disease (CVD), the leading cause of mortality and morbidity in the United States, may be potentially preventable with statin therapy. Objective To systematically review benefits and harms of statins for prevention of CVD to inform the US Preventive Services Task Force. Data Sources Ovid MEDLINE (from 1946), Cochrane Central Register of Controlled Trials (from 1991), and Cochrane Database of Systematic Reviews (from 2005) to June 2016. Study Selection Randomized clinical trials of statins vs placebo, fixed-dose vs titrated statins, and higher- vs lower-intensity statins in adults without prior cardiovascular events. Data Extraction and Synthesis One investigator abstracted data, a second checked data for accuracy, and 2 investigators independently assessed study quality using predefined criteria. Data were pooled using random-effects meta-analysis. Main Outcomes and Measures All-cause mortality, CVD-related morbidity or mortality, and harms. Results Nineteen trials (n = 71 344 participants [range, 95-17 802]; mean age, 51-66 years) compared statins vs placebo or no statin. Statin therapy was associated with decreased risk of all-cause mortality (risk ratio [RR], 0.86 [95% CI, 0.80 to 0.93]; I2 = 0%; absolute risk difference [ARD], -0.40% [95% CI, -0.64% to -0.17%]), cardiovascular mortality (RR, 0.69 [95% CI, 0.54 to 0.88]; I2 = 54%; ARD, -0.43% [95% CI, -0.75% to -0.11%]), stroke (RR, 0.71 [95% CI, 0.62 to 0.82]; I2 = 0; ARD, -0.38% [95% CI, -0.53% to -0.23%]), myocardial infarction (RR, 0.64 [95% CI, 0.57 to 0.71]; I2 = 0%; ARD, -0.81% [95% CI, -1.19 to -0.43%]), and composite cardiovascular outcomes (RR, 0.70 [95% CI, 0.63 to 0.78]; I2 = 36%; ARD, -1.39% [95% CI, -1.79 to -0.99%]). Relative benefits appeared consistent in demographic and clinical subgroups, including populations without marked hyperlipidemia (total cholesterol level <200 mg/dL); absolute benefits were higher in subgroups at higher baseline risk. Statins were not associated with increased risk of serious adverse events (RR, 0.99 [95% CI, 0.94 to 1.04]), myalgias (RR, 0.96 [95% CI, 0.79 to 1.16]), or liver-related harms (RR, 1.10 [95% CI, 0.90 to 1.35]). In pooled analysis, statins were not associated with increased risk of diabetes (RR, 1.05 [95% CI, 0.91 to 1.20]), although statistical heterogeneity was present (I2 = 52%), and 1 trial found high-intensity statins associated with increased risk (RR, 1.25 [95% CI, 1.05 to 1.49]). No trial directly compared titrated vs fixed-dose statins, and there were no clear differences based on statin intensity. Conclusions and Relevance In adults at increased CVD risk but without prior CVD events, statin therapy was associated with reduced risk of all-cause and cardiovascular mortality and CVD events, with greater absolute benefits in patients at greater baseline risk.

Systemic Pharmacologic Therapies for Low Back Pain: A Systematic Review for an American College of Physicians Clinical Practice Guideline.

Low back pain is one of the most frequently encountered conditions in clinical practice (1, 2). The most commonly prescribed medications for low back pain are nonsteroidal anti-inflammatory drugs (NSAIDs), skeletal muscle relaxants, antidepressants, and opioids (35); benzodiazepines, systemic corticosteroids, and antiseizure medications are also prescribed (3). Patients often use over-the-counter acetaminophen and NSAIDs. A 2007 guideline (6) and associated systematic review (7) from the American College of Physicians (ACP) and American Pain Society (APS) found evidence to support the use of acetaminophen and NSAIDs as first-line pharmacologic options for low back pain; secondary options were skeletal muscle relaxants, benzodiazepines, and antidepressants. New evidence and medications are now available. Here, we review the current evidence on benefits and harms of medications for low back pain. This article has been used by ACP to update a clinical practice guideline, also in this issue. Methods Detailed methods and data for our review, including the analytic framework, additional medications (topical capsaicin and lidocaine), nonpharmacologic therapies (addressed in a separate article) (8), search strategies, inclusion criteria, data extraction and quality-rating methods, and additional outcomes (for example, quality of life, global improvement, and patient satisfaction), are available in the full report (9). The protocol was developed by using a standardized process (10) with input from experts and the public and is registered in the PROSPERO database (11). This article addresses the key question, what are the comparative benefits and harms of different systemic pharmacologic therapies for acute or chronic nonradicular low back pain, radicular low back pain, or spinal stenosis? Data Sources and Searches A research librarian searched Ovid MEDLINE (January 2007 through April 2015), the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews (through April 2015). We used the prior ACP/APS review (12) to identify earlier studies. Updated searches were performed through November 2016. We also reviewed reference lists and searched ClinicalTrials.gov. Study Selection Two investigators independently reviewed abstracts and full-text articles against prespecified eligibility criteria. The population was adults with nonradicular or radicular low back pain of any duration (categorized as acute [<4 weeks], subacute [4 to 12 weeks], and chronic [12 weeks]). Excluded conditions were low back pain due to cancer, infection, inflammatory arthropathy, high-velocity trauma, or fracture; low back pain during pregnancy; and presence of severe or progressive neurologic deficits. We evaluated acetaminophen, NSAIDs, opioids, tramadol and tapentadol, antidepressants, skeletal muscle relaxants, benzodiazepines, corticosteroids, and antiseizure medications versus placebo, no treatment, or other therapies. We also evaluated the combination of 2 medications versus 1 medication alone. Outcomes were long-term (1 year) or short-term (6 months) pain or function, mood (for antidepressants), risk for surgery (for corticosteroids), and harms. Given the large number of medications addressed, we included systematic reviews of randomized trials (13, 14). For each medication, we selected the most recent, most relevant, and highest-quality comprehensive systematic review based on a validated assessment tool (14, 15). If more than 1 good-quality systematic review was available, we preferentially selected updates of those used in the ACP/APS review. We supplemented systematic reviews with additional trials. Although we did not include systematic reviews identified in update searches, we checked reference lists for additional studies. We excluded nonEnglish-language articles and abstract-only publications. Data Extraction and Quality Assessment One investigator extracted study data, and a second verified accuracy. For systematic reviews, we abstracted details about inclusion criteria, search strategy, databases searched, search dates, number and characteristics of included studies, quality assessment methods and ratings, synthesis methods, and results. For randomized trials, we abstracted details about the setting, sample size, eligibility criteria, population characteristics, treatment characteristics, results, and funding source. Two investigators independently assessed the quality of each study as good, fair, or poor using criteria developed by the U.S. Preventive Services Task Force (for randomized trials) (16) and AMSTAR (A Measurement Tool to Assess Systematic Reviews) (14). For primary studies included in systematic reviews, we used both the quality ratings and the overall grade (for example, good, fair, or poor, or high or low) as determined in the reviews. We classified the magnitude of effects as small/slight, moderate, or large/substantial based on the definitions in the ACP/APS review (Table 1) (6, 17). We also reported risk estimates based on the proportion of patients achieving successful pain or function outcomes (for example, >30% or >50% improvement). Table 1. Definitions for Magnitude of Effects, Based on Mean Between-Group Differences Data Synthesis and Analysis We synthesized data qualitatively for each medication, stratified according to the duration of symptoms (acute, subacute, or chronic) and presence or absence of radicular symptoms. We reported meta-analysis results from systematic reviews. When statistical heterogeneity was present, we examined the degree of inconsistency and evaluated subgroup and sensitivity analyses. We did not conduct an updated meta-analysis; rather, we qualitatively examined whether results of new studies were consistent with pooled or qualitative findings from prior systematic reviews. Qualitative assessments were based on whether the findings from the new studies were in the same direction as the prior systematic reviews and whether the magnitude of effects was similar; when prior meta-analyses were available, we analyzed whether the estimates and CIs from new studies were encompassed in the CIs from pooled estimates. We assessed the strength of evidence (SOE) for each body of evidence as high, moderate, low, or insufficient based on aggregate study quality, precision, consistency, and directness (18). Role of the Funding Source The Agency for Healthcare Research and Quality (AHRQ) of the U.S. Department of Health and Human Services funded this review. AHRQ staff assisted in developing the scope and key questions. The AHRQ had no role in study selection, quality assessment, or synthesis. Results Literature Search The search and selection of articles are summarized in the Figure. Database searches found 2847 potentially relevant articles. After dual review of abstracts and titles, we selected 746 articles for full-text dual review; 46 publications met inclusion criteria. Quality ratings are summarized in Supplement Tables 1 and 2. Supplement. Data Supplement. Figure. Summary of evidence search and selection. ACP = American College of Physicians; AHRQ = Agency for Healthcare Research and Quality; APS = American Pain Society; NSAID = nonsteroidal anti-inflammatory drug; RCT = randomized, controlled trial; SR = systematic review. * Cochrane databases include the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews. Other sources include prior reports, reference lists of relevant articles, and systematic reviews. Publications may be included or excluded for multiple reasons. Acetaminophen Ten trials evaluated acetaminophen; 9 of these (sample sizes, 39 to 456) were included in the ACP/APS review (19). We identified 1 additional large (n= 1643), good-quality, placebo-controlled trial (20). Six trials compared acetaminophen with NSAIDs and were included in a systematic review of NSAIDs (Supplement Table 3) (21, 22). Along with the new trial, 3 others (2325) were rated good- or high-quality. For acute low back pain, 1 new trial found no differences between 4 weeks or less of scheduled or as-needed acetaminophen (about 4 g/d) and placebo in pain (differences, 0.20 point on a 0- to 10-point scale), function (differences, 0.60 point on the 0- to 24-point RolandMorris Disability Questionnaire [RDQ]), or risk for serious adverse events (about 1% in each group) after 12 weeks (Supplement Table 4) (20). One trial of acetaminophen versus no treatment included in the ACP/APS review (26) also found no differences. We found no difference between acetaminophen and NSAIDs in pain intensity (standardized mean difference [SMD], 0.21 [95% CI, 0.02 to 0.43]) at 3 weeks or less based on 3 low-quality trials, although estimates favored NSAIDs (22). Acetaminophen had a lower risk for adverse events than NSAIDs (relative risk [RR], 0.57 [CI, 0.36 to 0.89]). Evidence was insufficient to determine the effects of acetaminophen versus various nonpharmacologic therapies (24, 27, 28) or amitriptyline (25); each comparison was evaluated in 1 trial with methodological shortcomings. No study evaluated acetaminophen for chronic or radicular low back pain. NSAIDs Seventy trials evaluated NSAIDs; 57 were in the ACP/APS review. Sixty-five trials (total n= 11237; sample sizes, 20 to 690), 28 of which were high-quality, were included in a systematic review (Supplement Table 3) (22). We identified 5 additional trials (n= 54 to 525) (Supplement Table 5) (2933). One trial was rated good-quality (31), and 4 were rated fair-quality (29, 30). For acute back pain, 1 systematic review (22) found that NSAIDs were associated with greater mean improvements in pain intensity than placebo (4 trials: weighted mean difference, 8.39 points on a 0- to 100-point scale [CI, 12.68 to 4.10 points]; chi-square test, 3.47 points; P> 0.10) (3437). One additional trial (n= 171) reported consistent findings (29). Three trials in this review found no differences between an NSAID and placeb

Screening for hypertension in children and adolescents to prevent cardiovascular disease

BACKGROUND AND OBJECTIVE: The prevalence of hypertension is increasing in children, and may persist into adulthood. This systematic review was conducted for the US Preventive Services Task Force recommendation on the effectiveness of screening asymptomatic children and adolescents for hypertension in order to prevent cardiovascular disease. METHODS: Eligible studies were identified from Medline and the Cochrane Library (through July 2012). We included trials and controlled observational studies in asymptomatic children and adolescents on the effectiveness and harms of screening and treatment, as well as accuracy of blood pressure measurement. One author extracted study characteristics and results, which were checked for accuracy by a second author. RESULTS: No studies evaluated the effects of screening for hypertension on health outcomes. Two studies of screening tests for elevated blood pressure reported moderate sensitivities (0.65, 0.72) and specificities (0.75, 0.92). Sensitivities and specificities of child hypertension for the later presence of adult hypertension (7 studies) were wide ranging (0–0.63 and 0.77–1.0, respectively), and associations between child hypertension and carotid intima media thickening and proteinuria in young adults (3 studies) were inconsistent. Seven studies reported that drug interventions effectively lowered blood pressure in adolescents over short follow-up periods. No serious treatment-related adverse effects were reported. CONCLUSIONS: There is no direct evidence that screening for hypertension in children and adolescents reduces adverse cardiovascular outcomes in adults. Additional studies are needed to improve diagnosis and risk stratification of children with elevated blood pressure and to quantify risks and benefits of interventions.

Screening adults aged 50 years or older for hearing loss: a review of the evidence for the U.S. preventive services task force.

BACKGROUND Hearing loss is common in older adults. Screening could identify untreated hearing loss and lead to interventions to improve hearing-related function and quality of life. PURPOSE To update the 1996 U.S. Preventive Services Task Force evidence review on screening for hearing loss in primary care settings in adults aged 50 years or older. DATA SOURCES MEDLINE (1950 and July 2010) and the Cochrane Library (through the second quarter of 2010). STUDY SELECTION Randomized trials, controlled observational studies, and studies on diagnostic accuracy were selected. DATA EXTRACTION Investigators abstracted details about the patient population, study design, data analysis, follow-up, and results and assessed quality by using predefined criteria. DATA SYNTHESIS Evidence on benefits and harms of screening for and treatments of hearing loss was synthesized qualitatively. One large (2305 participants) randomized trial found that screening for hearing loss was associated with increased hearing aid use at 1 year, but screening was not associated with improvements in hearing-related function. Good-quality evidence suggests that common screening tests can help identify patients at higher risk for hearing loss. One good-quality randomized trial found that immediate hearing aids were effective compared with wait-list control in improving hearing-related quality of life in patients with mild or moderate hearing loss and severe hearing-related handicap. We did not find direct evidence on harms of screening or treatments with hearing aids. LIMITATION Non-English-language studies were excluded, and studies of diagnostic accuracy in high-prevalence specialty settings were included. CONCLUSION Additional research is needed to understand the effects of screening for hearing loss compared with no screening on health outcomes and to confirm benefits of treatment under conditions likely to be encountered in most primary care settings. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

Screening for Type 2 Diabetes Mellitus: A Systematic Review for the U.S. Preventive Services Task Force

In the United States, approximately 21 million persons received diabetes diagnoses in 2010, and an estimated 8 million cases were undiagnosed; roughly 90% to 95% of them have type 2 diabetes mellitus (1, 2). Prevalence of diabetes among U.S. adults has increased, from approximately 5% in 1995 to 8% in 2010 (3). Diabetes is the leading cause of kidney failure, nontraumatic lower-limb amputations, and blindness; a major cause of heart disease and stroke; and the seventh-leading cause of death in the United States (1). Risk factors for diabetes include obesity, physical inactivity, smoking, and older age (1). Diabetes is more common among certain ethnic and racial minorities (1, 3). Type 2 diabetes is caused by insulin resistance and relative insulin deficiency, resulting in the inability to maintain normoglycemia. Diabetes typically develops slowly (4, 5), although microvascular disease, such as retinopathy and neuropathy, may be present at the time of diagnosis due to vascular damage during the subclinical phase (4, 6). Screening asymptomatic persons (those without signs or symptoms of hyperglycemia and no clinical sequelae) may lead to earlier identification and earlier or more-intensive treatments, potentially improving health outcomes (2). Strategies for screening include routine screening or targeted screening based on the presence of risk factors, such as obesity or hypertension. In 2008, the U.S. Preventive Services Task Force (USPSTF) recommended diabetes screening in asymptomatic adults with sustained blood pressure (BP) (treated or untreated) greater than 135/80 mm Hg (B recommendation). Although direct evidence on benefits and harms of screening was not available, the recommendation was based on the ability of screening to identify persons with diabetes and evidence that more-intensive BP treatment was associated with reduced risk for cardiovascular events, including cardiovascular mortality, in patients with diabetes and hypertension. The USPSTF found insufficient evidence to assess the balance of benefits and harms of screening in adults without elevated BP (I statement). It also found that lifestyle and drug interventions for impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), defined as a hemoglobin A1c level of 5.7% to 6.4% or a fasting blood glucose level between 5.55 and 6.94 mmol/L (100 and 125 mg/dL) (2), were associated with reduced risk for progression to diabetes (714). Other groups also recommend screening persons with risk factors (1520). This article updates previous USPSTF reviews (2123) on diabetes screening in nonpregnant adults. Methods Scope of the Review We developed a review protocol and analytic framework (Appendix Figure 1) that included the following key questions: Appendix Figure 1. Analytic framework. DM = diabetes mellitus; IFG = impaired fasting glucose; IGT = impaired glucose tolerance; KQ = key question; MI = myocardial infarction. 1. Is there direct evidence that screening for type 2 diabetes, IFG, or IGT among asymptomatic adults improves health outcomes? 2. What are the harms of screening for type 2 diabetes, IFG, or IGT? 3. Do interventions for screen-detected or early diabetes, IFG, or IGT provide an incremental benefit in health outcomes compared with no interventions or initiating interventions after clinical diagnosis? 4. What are the harms of interventions for screen-detected or early diabetes, IFG, or IGT? 5. Is there evidence that more-intensive glucose, BP, or lipid control interventions improve health outcomes in adults with type 2 diabetes, IFG, or IGT compared with traditional control? Is there evidence that aspirin use improves health outcomes in these populations compared with nonuse? 6. What are the harms of more-intensive interventions compared with traditional control in adults with type 2 diabetes, IFG, or IGT? 7. Do interventions for IFG or IGT delay or prevent the progression to type 2 diabetes? The full report (24), on which this article is based, provides detailed methods and data for the review, including search strategies, evidence tables, and quality ratings of individual studies (available at www.uspreventiveservicestaskforce.org). The full report includes an additional key question on whether the effects of screening or interventions for screen-detected or early diabetes, IFG, or IGT vary by subgroup; effects of treatments on microvascular outcomes; and evidence on effects of more- versus less-intensive lipid control and aspirin use (24). Data Sources and Searches A research librarian searched the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews and MEDLINE (2007 to October 2014). We supplemented electronic searches by reviewing previous USPSTF reports and reference lists of relevant articles. Study Selection At least 2 reviewers independently evaluated each study to determine inclusion eligibility using predefined inclusion and exclusion criteria (Appendix Figure 2). Because of the limited evidence on treatment of screen-detected diabetes (key question 5), we also included studies of treatment of early diabetes (defined as a pharmacologically untreated hemoglobin A1c level <8.5% or diabetes diagnosis in the past year) that was not specifically screen-detected. Appendix Figure 3 summarizes the selection of literature. Appendix Figure 2. Inclusion and exclusion criteria per KQ. BP = blood pressure; DM = diabetes mellitus; IFG = impaired fasting glucose; IGT = impaired glucose tolerance; KQ = key question; MI = myocardial infarction. Appendix Figure 3. Summary of evidence search and selection. KQ = key question. * Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews. Other sources include previous reports, reference lists of relevant articles, and systematic reviews. An additional 27 publications are included in the full report (23). Some studies have several publications and some are included for more than 1 KQ. Data Abstraction and Quality Rating One investigator abstracted details about the study design, patient population, setting, screening method, interventions, analysis, follow-up, and results. A second investigator reviewed data abstraction for accuracy. Two investigators independently applied criteria developed by the USPSTF (25) to rate the quality of each study as good, fair, or poor. Discrepancies were resolved through a consensus process. Data Synthesis and Analysis We conducted meta-analyses to calculate risk ratios (RRs) on effects of interventions with the DerSimonianLaird random-effects model using Stata, version 12 (StataCorp). Statistical heterogeneity was assessed using the I 2 statistic (26). When statistical heterogeneity was present, we performed sensitivity analyses using the profile likelihood method because the DerSimonianLaird model results in overly narrow 95% CIs (27). Two studies (2830) that used a 22 factorial design reported no interaction between treatments and were analyzed as a 2-group parallel group trial for the comparison of interest. When studies evaluated several lifestyle strategies, we combined the lifestyle groups. We included all studies in meta-analyses, regardless of event rates. For rare events (incidence <1%), we calculated the Peto odds ratio (31). We stratified results by drug class or lifestyle intervention and performed additional sensitivity analyses based on study quality and presence of outlier trials. We assessed the aggregate internal validity (quality) of the body of evidence for each key question (good, fair, or poor) using methods developed by the USPSTF, based on the quality of studies, precision of estimates, consistency of results, and directness of evidence (25). Role of the Funding Source This research was funded by the Agency for Healthcare Research and Quality (AHRQ) under a contract to support the work of the USPSTF. Investigators worked with USPSTF members and AHRQ staff to develop and refine the scope, analytic framework, and key questions; resolve issues arising during the project; and finalize the report. The AHRQ had no role in study selection, quality assessment, synthesis, or development of conclusions. The AHRQ provided project oversight; reviewed the draft report; and distributed the draft for peer review, including to representatives of professional societies and federal agencies. It also performed a final review of the manuscript to ensure that the analysis met methodological standards. The investigators are solely responsible for the content and the decision to submit the manuscript for publication. Results Benefits of Screening Two randomized, controlled trials (ADDITION [Anglo-Danish-Dutch Study of Intensive Treatment in People With Screen Detected Diabetes in Primary Care]Cambridge [Cambridge, United Kingdom] trial [n=19226] [32], rated good-quality, and a trial conducted in Ely, United Kingdom [n=4936] [33], rated fair-quality) evaluated effects of diabetes screening versus no screening on mortality (Appendix Table 1). The ongoing ADDITION trial includes sites in Cambridge, the Netherlands, and Denmark on intensive versus standard treatment of screen-detected diabetes; however, only the Cambridge site had a no-screening component (34). Mean age ranged from 51 to 58 years, 36% to 54% of participants were women, and follow-up was 10 years in both studies (32, 33). In ADDITION-Cambridge, persons at high risk for diabetes, based on known risk factors, were randomly assigned in clusters by clinic site to screening or no screening (32). The Ely study randomly enrolled participants (not selected based on high risk for diabetes) to screening or no screening from a single practice site (33). Seventy-eight percent of participants (11737 of 15089) invited to screening had screening in the ADDITION trial (32); 68% of participants in the Ely study were screened (33). Methodological shortcomings in the Ely study included unclear randomization and allocation concealment method

Screening adults for bladder cancer: a review of the evidence for the U.S. preventive services task force.

BACKGROUND Bladder cancer is 1 of the 10 most frequently diagnosed types of cancer. Screening could identify high-grade bladder cancer at earlier stages, when it may be more easily and effectively treated. PURPOSE To update the 2004 U.S. Preventive Services Task Force evidence review on screening for bladder cancer in adults in primary care settings. DATA SOURCES MEDLINE (2002 to December 2009), the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials (through the fourth quarter of 2009), and the CancerLit subsection of PubMed (through March 2010) were searched for studies published in English. STUDY SELECTION Randomized trials and controlled observational studies that directly evaluated screening for bladder cancer in adults, studies on the diagnostic accuracy of screening tests for bladder cancer, and randomized trials and controlled observational studies on clinical outcomes associated with treatment compared with no treatment of screen-detected or superficial bladder cancer. DATA EXTRACTION Details were abstracted about the patient sample, study design, data analysis, follow-up, and results. Quality was assessed by using methods developed by the U.S. Preventive Services Task Force. DATA SYNTHESIS No randomized trials or high-quality controlled observational studies evaluated clinical outcomes associated with screening compared with no screening or treatment of screen-detected bladder cancer compared with no treatment. No study evaluated the sensitivity or specificity of tests for hematuria, urinary cytology, or other urinary biomarkers for bladder cancer in asymptomatic persons without a history of bladder cancer. The positive predictive value of screening is less than 10% in asymptomatic persons, including higher-risk populations. No study evaluated harms associated with treatment of screen-detected bladder cancer compared with no treatment. LIMITATION High-quality evidence was not available for any of the key questions. CONCLUSION Additional research is needed to determine whether screening of adults for bladder cancer leads to better outcomes compared with no screening. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.