Michelle Brasure

Medical Management to Prevent Recurrent Nephrolithiasis in Adults: A Systematic Review for an American College of Physicians Clinical Guideline

BACKGROUNDnOptimum management to prevent recurrent kidney stones is uncertain.nnnPURPOSEnTo evaluate the benefits and harms of interventions to prevent recurrent kidney stones.nnnDATA SOURCESnMEDLINE, Cochrane, and other databases through September 2012 and reference lists of systematic reviews and randomized, controlled trials (RCTs).nnnSTUDY SELECTIONn28 English-language RCTs that studied treatments to prevent recurrent kidney stones and reported stone outcomes.nnnDATA EXTRACTIONnOne reviewer extracted data, a second checked accuracy, and 2 independently rated quality and graded strength of evidence.nnnDATA SYNTHESISnIn patients with 1 past calcium stone, low-strength evidence showed that increased fluid intake halved recurrent composite stone risk compared with no treatment (relative risk [RR], 0.45 [95% CI, 0.24 to 0.84]). Low-strength evidence showed that reducing soft-drink consumption decreased recurrent symptomatic stone risk (RR, 0.83 [CI, 0.71 to 0.98]). In patients with multiple past calcium stones, most of whom were receiving increased fluid intake, moderate-strength evidence showed that thiazides (RR, 0.52 [CI, 0.39 to 0.69]), citrates (RR, 0.25 [CI, 0.14 to 0.44]), and allopurinol (RR, 0.59 [CI, 0.42 to 0.84]) each further reduced composite stone recurrence risk compared with placebo or control, although the benefit from allopurinol seemed limited to patients with baseline hyperuricemia or hyperuricosuria. Other baseline biochemistry measures did not allow prediction of treatment efficacy. Low-strength evidence showed that neither citrate nor allopurinol combined with thiazide was superior to thiazide alone. There were few withdrawals among patients with increased fluid intake, many among those with other dietary interventions and more among those who received thiazide and citrate than among control patients. Reporting of adverse events was poor.nnnLIMITATIONSnMost trial participants had idiopathic calcium stones. Nearly all studies reported a composite (including asymptomatic) stone recurrence outcome.nnnCONCLUSIONnIn patients with 1 past calcium stone, increased fluid intake reduced recurrence risk. In patients with multiple past calcium stones, addition of thiazide, citrate, or allopurinol further reduced risk.nnnPRIMARY FUNDING SOURCEnAgency for Healthcare Research and Quality.

Pharmacologic Treatment of Insomnia Disorder: An Evidence Report for a Clinical Practice Guideline by the American College of Physicians

Sleep problems are common and associated with a decline in overall and sleep-related health (13). Insomnia is more common in women and older adults (4). Aging is often accompanied by disrupted sleep and frequent and early waking (5, 6). Other conditions coexist with, are due to, or lead to poor sleep (7). Insomnia symptoms are typically transient and may not cause distress or impaired activity. However, insomnia disorder as defined by the American Psychiatric Associations Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, requires sleep problems that are chronic, persistent, and associated with daytime dysfunction. Insomnia disorder includes a predominant symptom of difficulty with sleep initiation, difficulty maintaining sleep, or early-morning waking with inability to return to sleep causing clinically significant distress or impairment in activities, occurring at least 3 nights per week. Current definitions require insomnia symptoms to have persisted for 3 months or more (8). Individuals must have adequate opportunity for sleep, and symptoms must not be better explained by another sleep disorder, effects of a substance, or other medical or mental conditions. Treatment goals include meaningful improvements in sleep-associated distress or dysfunction (global outcomes). The Insomnia Severity Index (ISI) and the Pittsburgh Sleep Quality Index measure both problems and worry about sleep and accompanying distress or dysfunction. Sleep measures are based on specific sleep variables that can be assessed in a sleep laboratory with polysomnography or actigraphy or subjectively with patient-reported sleep diaries. These include sleep-onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST), and sleep efficiency (percentage of time in bed sleeping). In general, insomnia disorder is treated by clinicians on the basis of patient-reported sleep-associated distress, not laboratory assessment. Additionally, polysomnography is not indicated for the diagnosis or treatment of insomnia disorder (9). Prescription medications are often used. Several are approved for insomnia, typically for short-term use, by the U.S. Food and Drug Administration (FDA). Although medication indications often focus on specific sleep variables, it is not known how frequently primary care physicians target medications to specific or global measures of insomnia or prescribe them long term. We evaluated the efficacy, comparative effectiveness, and harms of pharmacologic interventions for insomnia disorder. An accompanying article assesses psychological and behavioral interventions (10). These articles summarize findings from a report conducted by the Agency for Healthcare Research and Quality/Minnesota Evidence-based Practice Center (11). The work served, in part, as the evidence base for an American College of Physicians clinical practice guideline. Methods We developed and followed a standard protocol. The protocol was registered at www.crd.york.ac.uk/PROSPERO/ (registration number: CRD42014009908) in May 2014 and published at http://effectivehealthcare.ahrq.gov/index.cfm/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productid=1888. Full details of the findings and evidence tables are available in the report (11). Data Sources and Searches We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and PSYCinfo from 2004 through September 2015 for relevant English-language literature (Table 1 of the Supplement), reference lists of pertinent studies, FDA Web sites and product labels, and ClinicalTrials.gov. Supplement. Data Supplement Study Selection Two investigators independently reviewed titles and abstracts of search results and screened the full text of potentially eligible English-language references. We included randomized, controlled trials (RCTs) of pharmacologic therapies available in the United States, regardless of the comparator (placebo, another medication, nonpharmacologic therapy), if they enrolled adults with insomnia disorder, provided at least 4 weeks of follow-up, and reported global or sleep outcomes. We excluded from analysis studies deemed to have high risk of bias. We included observational studies that reported harms if 1) the population included 100 or more adults with chronic insomnia without other major diagnoses, such as cancer and Parkinson disease; 2) the pharmacologic agents evaluated were FDA-indicated for insomnia and probably administered for sleep disorders; 3) study duration was at least 6 months; and 4) harms were reported by drug class. We also examined harms reported in the following: eligible trials; FDA Web sites for nonbenzodiazepine hypnotics, eszopiclone, zaleplon, zolpidem, and the orexin receptor antagonist suvorexant; FDA product labels for all pharmacologic therapies; and systematic reviews. Data Extraction and Quality Assessment One investigator extracted study data, which was independently checked by a second investigator. Our main outcome of interest was patient-reported global measure of effectiveness: improvement in sleep variables and daytime functioning and distress. The 7-item ISI (score range, 0 to 28) or the 7-component, 19-item Pittsburgh Sleep Quality Index (score range, 0 to 21) were commonly used instruments measuring both problems and worry about sleep and accompanying distress or dysfunction (Table 2 of the Supplement). We also assessed sleep-specific parameters on the basis of patient-recorded sleep diaries, including SOL, TST, WASO, sleep efficiency, sleep quality, function, mood, and quality of life. Risk of bias for RCTs was independently assessed by 2 investigators using an instrument developed for this project (12). We classified overall risk of bias for each study as low, moderate, or high according to a summary of bias risk across domains and confidence that the results were believable given the studys limitations. We excluded studies with high risk of bias from analysis. Data Synthesis and Analysis We grouped studies and rated strength of evidence by drug. Evidence ratings within each comparison were determined as high, moderate, low, or insufficient (13) by at least 2 trained research associates and the principal investigator; final determinations were ascertained through consensus. For assessments of efficacy, we used established minimum important differences for main outcomes if they were available and statistical significance alone if minimum important differences were not established. We pooled results for doses approved by the FDA if more than 1 study assessed that dose, used a similar comparator (such as placebo), involved a similar study population (for example, elderly patients), and assessed similar outcomes (such as the same sleep variable). Data were analyzed in RevMan 5.3 (Nordic Cochrane Center). DerSimonian and Laird random-effects models were used to calculate pooled risk ratios and absolute risk differences with 95% CIs for categorical outcomes. Weighted mean differences or standardized mean differences with 95% CIs were calculated for continuous outcomes. We assessed statistical heterogeneity with the Cochran Q test and measured magnitude with the I 2 statistic (I 2> 75% indicates substantial heterogeneity) (14). We searched several databases to identify and reduce potential publication bias. Role of Funding Source This review was nominated to the Agency for Healthcare Research and Quality Effective Healthcare Program by an anonymous individual and funded by the Agency for Healthcare Research and Quality. Agency staff and key informants representing various perspectives offered suggestions as we developed and refined the scope of the review. A technical expert panel provided input to the protocol and reviewed the draft report. The American College of Physicians provided support for manuscript preparation. The authors are solely responsible for its content. Results Search results are shown in the Appendix Figure. Thirty-five RCTs with acceptable risk of bias evaluated pharmacologic treatments (1546) (Figure). Six were in older adults (4247). We did not find evidence of publication bias in a search of ClinicalTrials.gov through September 2015. Eleven observational studies provided data for long-term harms (4858). Drug doses used in older adults were lower than those used in general populations. Few antidepressant or benzodiazepine trials met inclusion criteria, primarily because of short treatment durations. Patients were typically diagnosed with insomnia disorder according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria, which require symptoms to be present for at least 1 month (current criteria require symptoms for at least 3 months). Appendix Figure. Evidence search and selection. Intervention type totals do not equal total references because several trials were used in the analysis for 2 different types of interventions. RCT= randomized, controlled trial. Figure. Network of pharmacologic treatments for chronic insomnia disorder. The k values refer to number of studies. CBT= cognitive behavioral therapy. The mean symptom duration was rarely reported. Additional enrollment criteria were based on thresholds for SOL, TST, WASO, or number of awakenings per night during a typical night in the month before enrollment. Only 2 trials based enrollment on, or provided baseline scores of, global measures. Most required TST of 6.5 hours or less or SOL of greater than 30 minutes. When WASO was included, thresholds ranged from 30 to 120 minutes. Common exclusion criteria included psychiatric disorders or substance abuse (Tables 3 and 4 of the Supplement). Trials rarely assessed treatments for longer than 4 weeks. Most participants were women, white, and younger than 50 years. Most studies were industry-sponsored. Doses used in some trials exceeded FDA recommended doses, especially for women and older or debilitated adults (Tables 1 and 2). Table 1. Nonbenzodiazepin

Wheeled Mobility (Wheelchair) Service Delivery: Scope of the Evidence

Identifying the appropriate wheelchair for a person who needs one has implications for both disabled persons and society. For someone with severe locomotive problems, the right wheelchair can affect mobility and quality of life. However, policymakers are concerned about the increasing demand for unnecessarily elaborate chairs. The Office of Inspector General, U.S. Department of Health and Human Services, issued 4 reports between 2009 and 2011 detailing fraud and misapplication of Medicare funds for powered wheelchairs, more than a decade after similar concerns were first raised by 4 contractors who process claims for durable medical equipment. Subsequent concerns have arisen about whether some impaired persons who need wheeled mobility devices may now be inappropriately denied coverage. A transparent, evidence-based approach to wheeled mobility service delivery (the matching of mobility-impaired persons to appropriate devices and supporting services) might lessen these concerns. This review describes the process of wheeled mobility service delivery for long-term wheelchair users with complex rehabilitation needs and presents findings from a survey of the literature (published and gray) and interviews with key informants. Recommended steps in the delivery process were identified in textbooks, guidelines, and published literature. Delivery processes shared many commonalities; however, no research supports the recommended approaches. A search of bibliographic databases through March 2011 identified 24 studies that evaluated aspects of wheeled mobility service delivery. Most were observational, exploratory studies designed to determine consumer use of and satisfaction with the process. The evidence base for the effectiveness of approaches to wheeled mobility service delivery is insufficient, and additional research is needed to develop standards and guidelines.

Psychological and Behavioral Interventions for Managing Insomnia Disorder: An Evidence Report for a Clinical Practice Guideline by the American College of Physicians

Sleep difficulties, including the inability to initiate or maintain sleep, are common in adults. Sleep difficulties are typically transient; however, when they become chronic and cause distress or daytime dysfunction, insomnia disorder may be present. The American Psychiatric Associations Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, defines insomnia disorder as a predominant symptom of difficulty with sleep initiation, difficulty maintaining sleep, or early-morning waking with inability to return to sleep causing clinically significant distress or impairment in activities, occurring at least 3 nights per week for 3 months or more (1). Furthermore, individuals must have adequate opportunity for sleep and the symptoms cannot be better explained by medical or mental conditions, including another sleep disorder (such as breathing-related sleep disorder), or medication or substance use. The term previously used for insomnia disorder is chronic insomnia (14), for which diagnostic criteria required sleep problems lasting from weeks to months. These criteria are empirically similar to current criteria for insomnia disorder. We use the term insomnia disorder even though much of the primary research has used other terminology (such as chronic insomnia and persistent insomnia). Between 6% and 10% of adults meet the diagnostic criteria for insomnia disorder (4). Duration ranges from 1 to 20 years across longitudinal studies (5). Insomnia disorder is more common in female patients and older adults (6, 7). Older adults typically report difficulty maintaining sleep as opposed to initiating sleep, which is common in younger adults (8). Many treatment types are available once insomnia disorder is accurately diagnosed by using established diagnostic criteria (4, 9). These include psychological and behavioral treatments, pharmacologic therapies, and complementary and alternative medicine. The American Academy of Sleep Medicine recommends psychological and behavioral interventions and supports short-term supplementary medication (9, 10). Psychological and behavioral interventions include cognitive behavioral therapy for insomnia (CBT-I), multicomponent behavioral therapy (brief behavioral therapy for insomnia), and single-component interventions (such as sleep hygiene and education, stimulus control, sleep restriction, and relaxation) (Table). Cognitive behavioral therapy for insomnia most commonly includes behavioral therapies (sleep restriction, stimulus control, relaxation training), cognitive therapy (cognitive restructuring) to change dysfunctional beliefs about sleep, as well as sleep hygiene education (3). Multicomponent behavioral therapies combine several behavioral therapies and do not include a cognitive component. Table. Psychological and Behavioral Interventions for Insomnia Disorder* Treatment goals include improving quality and quantity of sleep and associated impairments (10). Ideally, meaningful improvements in global outcomes measuring sleep and associated distress and dysfunction are realized. The Insomnia Severity Index (ISI) and the Pittsburgh Sleep Quality Index (PSQI) are commonly used for measuring global outcomes. Sleep outcomes include specific sleep variables (sleep-onset latency [SOL], wake time after sleep onset [WASO], total sleep time [TST], sleep efficiency (sleep time/time in bed), and sleep quality. Sleep variables can be measured objectively (with polysomnography or actigraphy) or subjectively (sleep diaries). Guidelines suggest monitoring symptoms with sleep diaries and polysomography is not indicated (10). We conducted a systematic review on the management of insomnia disorder for the Agency for Healthcare Research and Quality (11). This article reports evidence on psychological and behavioral interventions. Another article reports on the evidence on pharmacologic interventions and the comparison of pharmacologic interventions with psychological and behavioral interventions (12), and the full report provides evidence on complementary and alternative interventions. This evidence was used by the American College of Physicians to develop the guideline on the treatment of insomnia disorder in primary care. Evidence summarized here enhances previous reports (1315) by providing a comprehensive evaluation of psychological and behavioral interventions across all delivery modes with a primary emphasis on global outcomes. Methods Data Sources and Searches We searched bibliographic databases, including MEDLINE, Embase, and PsycINFO via Ovid, as well as the Cochrane Library, to identify randomized, controlled trials published from 2004 through September 2015 (Supplement). We identified studies published before 2004 by searching the citations in relevant systematic reviews. Supplement. Supplementary Material Study Selection Two investigators independently reviewed titles and abstracts of search results to identify potentially eligible references. Two investigators independently screened full texts of those references to determine whether inclusion criteria were met. We included randomized, controlled trials of psychological and behavioral interventions if they enrolled adults, provided at least 4 weeks of treatment, reported global or sleep outcomes, and were published in English. We excluded trials enrolling pure subgroups of patients with major medical conditions or conditions that may explain the sleep problems (such as menopause, pregnancy, and neurologic conditions). Data Extraction and Quality Assessment Risk of bias was independently assessed by two investigators using an instrument developed using Agency for Healthcare Research and Quality guidance (16) and was summarized as low, medium, or high on the basis of summary risk of bias and confidence that results were believable given limitations. Study, participant, and treatment characteristics; outcomes; and adverse events were extracted from eligible trials with low or moderate risk of bias. Data Synthesis and Analysis We used RevMan 5.2 (Nordic Cochrane Center) for pooling when adequate data were provided and populations, interventions, and outcomes were similar (17). DerSimonian and Laird random-effects estimates of risk ratios and absolute risk differences with 95% CIs were calculated for categorical outcomes, and weighted mean differences (WMDs) and/or standardized mean differences with 95% CIs were calculated for continuous outcomes. We assessed heterogeneity with the Cochran Q test and I 2 statistic (75% indicates substantial heterogeneity) (18). We analyzed the general adult population and older adults separately because sleep measures vary. We used established minimum important differences (MIDs) to capture clinical significance in global outcomes. The MID for the ISI is a 6-point change from baseline (19). Trials that conducted remitter or responder analysis on the basis of established MID offer simplistic interpretation. When trials provided mean scores, we interpreted WMDs in relation to MID by using the method of Johnson and colleagues (20). Weighted mean differences equal to or greater than the MID suggest that many patients gain important benefits, WMDs greater than half the MID but less than the MID suggest that an appreciable number of patients benefit, and WMDs less than half of the MID suggest that patients do not achieve important benefits (20). One investigator assessed strength of evidence for unique comparisons as high, moderate, low, or insufficient (21); assessments were confirmed through consensus. Role of Funding Source This topic was nominated to and funded by the Agency for Healthcare Research and Quality Effective Health Care Program. Key informants representing various perspectives offered suggestions as refined the review scope. Our draft protocol was shared with a technical expert panel that had the opportunity to review the draft report. The American College of Physicians provided support for this manuscript preparation. The authors are solely responsible for its contents. Results We identified 3572 citations; 559 required full-text review after title and abstract screening (Appendix Figure 1). Seventy-six articles (2297) reporting on 70 trials that compared psychological and behavioral interventions with inactive controls or other psychological and behavioral interventions were eligible. We extracted data and analyzed results for 60 trials with low to moderate risk of bias. We grouped trials by intervention type and comparison. Interventions for CBT-I had cognitive and behavioral components; multicomponent behavioral therapy interventions had several behavioral components and no cognitive component; and single-component interventions included sleep restriction, stimulus control, and relaxation. Appendix Figure 1. Summary of evidence search and selection. Intervention type totals do not equal total references because several trials were used in the analysis for 2 different types of interventions. RCT = randomized, controlled trial. Eligible trials (Tables 1 and 2 of the Supplement) enrolled individuals most commonly diagnosed with chronic insomnia according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, with mean durations of several years. Participants were predominantly female and white. Trials were conducted in the United States, Canada, the United Kingdom, Sweden, Australia, Norway, Scotland, the Netherlands, and China. Mean age was mid-40s in general adult populations and lower 70s in older adults. Baseline ISI scores were approximately 17, indicating moderate severity, and baseline SOL was more than 45 minutes. Comparisons varied across trials. Inactive controls included information (such as sleep hygiene education) or waitlist; trials infrequently used sham treatments. Adverse effects were rarely reported. Withdrawals were not always reported by group. Evidence on adverse effects and withdrawals was insufficient for all comparisons. We assessed strength of

A Tale of Two Bounties: The Impact of Competing Fees on Physician Behavior

This study examines how the volume of privately insured services provided in hospital inpatient and outpatient departments changes in response to reductions in Medicare physician payments. We hypothesize that physicians consider relative payment rates when choosing which patients to treat in their practices. When Medicare reduces its payments for surgical procedures, as it did in the late 1980s, physicians are predicted to treat more privately insured patients because they become more lucrative. We use data from 182 hospitals for seventeen major procedures groups, covering a forty-five-month period between 1988 and 1991 that encom passes a twenty-four-month period before the reduction in Medicare fees and twenty-one months after the reduction. Our findings are consistent with the predictions for a number of procedure groups, but not for all of them. One implication of the findings is that societal savings from Medicare fee reductions are overstated if one does not also consider spillover effects in the private insurance market.

Care-Delivery Interventions to Manage Agitation and Aggression in Dementia Nursing Home and Assisted Living Residents: A Systematic Review and Meta-analysis

To evaluate the efficacy of nonpharmacological care‐delivery interventions (staff training, care‐delivery models, changes to the environment) to reduce and manage agitation and aggression in nursing home and assisted living residents.

Participation After Multidisciplinary Rehabilitation for Moderate to Severe Traumatic Brain Injury in Adults: A Systematic Review

OBJECTIVEnTo determine the effectiveness and comparative effectiveness of multidisciplinary rehabilitation programs for moderate to severe traumatic brain injury (TBI) in improving participation-related outcomes in adults. This article presents results of select key questions from a recent Agency for Healthcare Quality and Research comparative effectiveness review.nnnDATA SOURCESnMEDLINE, Cochrane Central Register of Controlled Trials, and PsycINFO; hand searches of previous relevant reviews.nnnSTUDY SELECTIONnWe included prospective controlled studies that evaluated the effectiveness or comparative effectiveness of multidisciplinary rehabilitation programs delivered to adults with moderate to severe TBI on their participation in life and community.nnnDATA EXTRACTIONnWe extracted data, assessed risk of bias, and evaluated strength of evidence. Participation was selected as our primary outcome and included measures of productivity (eg, return to employment or military service) and select scales measuring community integration. Only data from studies with a low or moderate risk of bias were synthesized.nnnDATA SYNTHESISnTwelve studies met our inclusion criteria; of these, 8 were of low or moderate risk of bias (4 randomized controlled trials of 680 patients and 4 cohort studies of 190 patients, sample size 36-366). Heterogeneous populations, interventions, and outcomes precluded pooled analysis. Evidence was insufficient to draw conclusions about effectiveness. Evidence on comparative effectiveness often demonstrated that improvements were not different between groups; however, this evidence was low strength and may have limited generalizability.nnnCONCLUSIONSnOur review used a rigorous systematic review methodology and focused on participation after multidisciplinary rehabilitation programs for impairments from moderate to severe TBI. The available evidence did not demonstrate the superiority of one approach over another. This conclusion is consistent with previous reviews that examined other patient-centered outcomes. While these findings will have little clinical impact, they do point out the limited evidence available to assess effectiveness and comparative effectiveness while highlighting important issues to consider in future comparative effectiveness research on this topic.

Comparative Effectiveness of Newer Medications for Lower Urinary Tract Symptoms Attributed to Benign Prostatic Hyperplasia: A Systematic Review and Meta-analysis

CONTEXTnAlpha-blockers (ABs) and 5-alpha reductase inhibitors have an established role in treating male lower urinary tract symptoms (LUTS) attributed to benign prostatic hyperplasia (BPH). Recently, newer drugs have shown promise for this indication.nnnOBJECTIVEnTo assess the comparative effectiveness and adverse effects (AEs) of newer drugs to treat LUTS attributed to BPH through a systematic review and meta-analysis.nnnEVIDENCE ACQUISITIONnOvid MEDLINE, the Cochrane Central Register of Controlled Trials, and Ovid Embase bibliographic databases (through June 2016) were hand searches for references of relevant studies. Eligible studies included randomized controlled trials published in English of newer ABs, antimuscarinics, a beta-3 adrenoceptor agonist, phosphodiesterase type-5 inhibitors, or combination therapy with one of these medications as an active comparator. Observational studies of the same agents with a duration ≥1 yr that reported AEs were also included.nnnEVIDENCE SYNTHESISnWe synthesized evidence from 43 randomized controlled trials as well as five observational studies. Based on improvement of mean International Prostate Symptom Score and quality of life scores, the effectiveness of the newer ABs was not different from the older ABs (moderate strength of evidence [SOE]), but had more AEs (low SOE). Antimuscarinics/AB combination therapy had similar outcomes as AB monotherapy (all moderate SOE), but often had more AEs. Phosphodiesterase type-5 inhibitors alone or in combination with ABs had similar or inferior outcomes than ABs alone. Evidence was insufficient for the beta-3 adrenoceptor agonist. For all newer agents, the evidence was generally insufficient to assess long-term efficacy, prevention of symptom progression, or AEs.nnnCONCLUSIONSnNone of the drugs or drug combinations newly used to treat LUTS attributed to BPH showed outcomes superior to traditional AB treatment. Given the lack of superior outcomes, the studies short time-horizon, and less assurance of their safety, their current value in treating LUTS attributable to BPH appears low.nnnPATIENT SUMMARYnIn this paper, we reviewed the evidence of newer drugs to treat men with urinary problems attributable to an enlarged prostate. We found none of the new drugs to be better but there was more concern about side effects.

Competitive behavior in local physician markets

Competition often is viewed as a mechanism for controlling cost. Competition may work well in urban areas with many providers; competition may not exist in rural areas with few providers. The authors use the empirical framework developed by Bresnahan and Reiss to analyze the entry behavior of physicians into local markets to determine the level of physician supply consistent with competitive behavior. The study estimates entry patterns for total and specialty physicians located in nonmetropolitan health service areas using longitudinal data. The authors find a surprising drop in the population increments necessary for entry by the second provider, possibly due to the unattractiveness of being the solo physician in an area. Subsequent population increments stabilize at three to five physicians. Since more than 93 percent of the U.S. population lives in areas that can support three to five physicians, competition between physicians through mechanisms such as managed care may be feasible.

Physical Activity Interventions in Preventing Cognitive Decline and Alzheimer-Type Dementia: A Systematic Review

Forty-seven million people worldwide live with dementia (1), and this number is expected to triple by 2050 (2). Despite evidence that the overall incidence of dementia has declined in the United States (3, 4), the number of U.S. adults older than 70 years with dementia or mild cognitive impairment (MCI) increases as our population ages (5, 6). Dementia severely erodes functioning and quality of life, creates burden and stress on families, and leads to institutionalization. Dementia-related costs exceed those of heart disease and cancer and often are paid directly by families (7). Therefore, preventing dementia is an urgent public health priority. Many believe that an active lifestyle may prevent cognitive decline and dementia. Findings of several reviews, primarily those looking at cohort studies, suggest that physical activity may reduce or delay the development of potential modifiable risk factors for cognitive decline, such as obesity, diabetes, and hypertension (813). However, the relationships among physical activity, other risk factors, and cognitive decline are complex and interrelated. Findings of associations from cohort studies alone cannot clarify whether physical activity affects cognitive decline directly, indirectly through the reduction of medical risk factors, or both. Previous systematic reviews of randomized controlled trials report some cognitive benefits of physical activity interventions, although the certainty and clinical importance of these findings have not always been clear (14, 15). This systematic review reports a synthesis of the evidence assessing the effectiveness of physical activity interventions in slowing cognitive decline and delaying the onset of cognitive impairment and dementia in adults without diagnosed cognitive impairments. Methods We developed and followed a standard protocol (16). Our full technical report (17) contains details on methods and findings, an analysis of studies addressing secondary prevention in adults with MCI, and an evaluation of comparative effectiveness. Data Sources and Searches We searched bibliographic databases, including MEDLINE, EMBASE, and PsycINFO via Ovid, as well as the Cochrane Library, to identify controlled trials published in any language from January 2009 through July 2017. (See Part A of the Supplement, for search strategies.) We identified studies published before 2009 by citation searching relevant systematic reviews. Supplement. Data Supplement Study Selection Two investigators independently reviewed titles and abstracts of search results and screened the full text of potentially eligible references. Disagreements about eligibility were resolved by consensus. We included randomized controlled trials of physical activity interventions with any sample size and large (n > 500) prospective quasi-experimental cohort studies with comparator groups if they enrolled adults without diagnosed cognitive impairments, had follow-up of at least 6 months, were published in English, and reported 1 of our preselected primary or intermediate outcomes. We excluded trials enrolling pure subgroups of patients with major medical conditions or conditions that may explain changes in cognitive function (namely stroke, Parkinson disease, cancer, and traumatic brain injury). Our main outcomes of interest were MCI or dementia. Intermediate outcomes included measures of cognitive function assessed by instruments that tested cognition across several domains or those that specifically tested executive function, attention, and processing speed, or memory. Intermediate outcomes were categorized as follows: broad measures intended to capture several cognitive domains that were either brief cognitive tests (category 1) or more comprehensive multidomain neuropsychological tests (category 2) and domain-specific neuropsychological tests or subscales of broader instruments that assessed executive function, attention, and processing speed (category 3) or memory (category 4). Part B of the Supplement shows a list of the intermediate outcomes reported from the studies and our categorization of those outcomes. Data Extraction and Quality Assessment One reviewer extracted the study population, treatment characteristics, and funding source from all eligible studies. Risk of bias was assessed independently by 2 investigators using an instrument developed with guidance from the Agency for Healthcare Research and Quality (AHRQ) (18). Risk of bias for each reported outcome was rated as low, medium, or high on the basis of adequacy of randomization and allocation concealment, masking, attrition, use of intention-to-treat analyses, selectiveness of outcome reporting, and confidence that results were believable given limitations. Outcomes and adverse effects were extracted from eligible trials with low or moderate risk of bias, and a second investigator checked the extraction. Data Synthesis and Analysis We grouped studies by type of physical activity intervention and analyzed results by direction of effect and statistical significance. We found it impossible to assess the clinical significance of findings of the intermediate outcomes across all studies, because many different instruments were used and we did not always find information on the degree of change in specific instrument scores or subscores that would indicate clinical importance. (Part B of the Supplement shows the information we did find about clinically important changes in specific instrument scores.) In addition, results were measured, analyzed, and reported in many different ways. When sufficient data were available (from more than 1 study or 1 study with 500 participants), 1 investigator assessed the strength of evidence for unique comparisons. These assessments were confirmed through consensus. We assessed strength of evidence by using 5 required domains: study limitations (risk of bias of eligible studies for a given comparison), directness (single, direct link between intervention and outcome), consistency (similarity of effect direction and size), precision (degree of certainty around an estimate that includes attention to small sample sizes with power to detect only large differences), and reporting bias (19). On the basis of these factors, the overall strength of evidence for each outcome from a given intervention was rated as high, moderate, low, or insufficient. Role of the Funding Source This review was funded by the National Institute on Aging and AHRQ. These agencies and members of the National Academies Committee on Preventing Dementia and Cognitive Impairment helped refine the scope and reviewed a draft report of findings. The authors are solely responsible for the content preparation, writing of the manuscript, and decision to submit the manuscript for publication. Results Of 32 eligible studies that compared interventions using physical activity components with an inactive control in adults without a cognitive impairment diagnosis (2051), 16all of which were randomized trialswere considered to have low to medium risk of bias (20, 23, 25, 29, 30, 33, 3537, 39, 40, 43, 45, 46, 48, 50). Inactive controls in the trials with low to medium risk of bias included waitlist, usual care, no-intervention, and attention (that is, education and information) groups. Most trials were government funded. Most studies enrolled older adults; some limited enrollment to men or women. Total sample sizes ranged from 42 to 1635 participants. Trials rarely reported adverse effects; those that did showed no differences between groups, with 1 exception. Intervention components, frequency, and duration varied. (Part C of the Supplement contains the literature flow diagram; part D contains evidence tables.) The Table shows overall conclusions and strength-of-evidence ratings. Details of studies considered to have low to medium risk of bias are described later. For any cognitive outcome, evidence was insufficient to draw conclusions about most interventions (aerobic training, resistance training, tai chi, physical activity with diet, and physical activity with a cognitive component). Low-strength evidence showed that multicomponent physical activity interventions of 1 to 2 years did not improve multidomain neurologic performance; executive function, attention, and processing speed; or memory compared with an attention control. Low-strength evidence showed that an intervention combining physical activity, diet, and cognitive training benefited multidomain neuropsychological test performance and executive function, attention, and processing speed compared with an attention control; however, evidence was insufficient to draw conclusions about the efficacy of this intervention on memory. Moderate-strength evidence showed that more participants in the intervention than the control groups had musculoskeletal pain. Table. Conclusions: Physical Activity Versus Inactive Comparisons in Adults Physical Activity Interventions Multicomponent Physical Activity Four trials (n= 1885) with low to medium risk of bias examined multicomponent physical activity interventions. Components included flexibility, strength, balance, endurance, and aerobic training (36, 45, 46, 50). Enrollment criteria varied by trial. Sink and colleagues (45) and Williamson and colleagues (50) enrolled sedentary adults older than 70 years, most of whom were white women. Mean Modified Mini-Mental State Examination (MMSE) scores were higher than 90 points (on a scale of 0 to 100 points). Taylor-Piliae and colleagues (46) enrolled adults, mostly white college-educated women, older than 60 years. Napoli and colleagues (36) enrolled frail, obese older adults, most of whom were white women; mean Modified MMSE score was 96 points. Interventions during the trials lasted from 6 months to 2 years. Sink and colleagues (45) (n= 1635) reported diagnostic outcomes that showed no difference in the incidence of MCI (odds ratio, 1.14 [95% CI, 0.79 to 1.62]) or dementia (odds ratio, 0.9