Jeannine Ouellette

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

BACKGROUND Optimum management to prevent recurrent kidney stones is uncertain. PURPOSE To evaluate the benefits and harms of interventions to prevent recurrent kidney stones. DATA SOURCES MEDLINE, Cochrane, and other databases through September 2012 and reference lists of systematic reviews and randomized, controlled trials (RCTs). STUDY SELECTION 28 English-language RCTs that studied treatments to prevent recurrent kidney stones and reported stone outcomes. DATA EXTRACTION One reviewer extracted data, a second checked accuracy, and 2 independently rated quality and graded strength of evidence. DATA SYNTHESIS In 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. LIMITATIONS Most trial participants had idiopathic calcium stones. Nearly all studies reported a composite (including asymptomatic) stone recurrence outcome. CONCLUSION In 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. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

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

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

OBJECTIVE To 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. DATA SOURCES MEDLINE, Cochrane Central Register of Controlled Trials, and PsycINFO; hand searches of previous relevant reviews. STUDY SELECTION We 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. DATA EXTRACTION We 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. DATA SYNTHESIS Twelve 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. CONCLUSIONS Our 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.

Intermediate- and Long-Term Cognitive Outcomes After Cardiovascular Procedures in Older Adults: A Systematic Review

Approximately 200000 coronary artery bypass graft (CABG) surgeries, 50000 carotid revascularizations, 50000 cardiac valve replacements or repairs, and 10000 catheter ablations for atrial fibrillation are performed annually in U.S. adults aged 65 years or older (16). The older U.S. population also has a high rate of cognitive impairment and dementia, with a combined incidence of 77.5 cases per 1000 person-years in adults aged 72 years or older with normal cognition at baseline (7). However, great uncertainty surrounds the relationship between these cardiovascular interventions and subsequent cognitive outcomes in older patients. Most attention has addressed the possible relationship between CABG and cognitive impairment. Early studies reported a high prevalence of cognitive impairment after CABG, possibly attributable to surgical factors, such as anesthesia and cardiopulmonary bypass (8, 9). Later studies suggested that much cognitive impairment after CABG predated the procedure (10) and was related to patient factors, such as age, education, and vascular disease (8, 1114). Studies of carotid revascularization have reported mixed cognitive outcomes, with some suggesting early improvement (15). Studies of cardiac valve procedures and catheter ablation for atrial fibrillation commonly report imaging-detected cerebral emboli, but cognitive outcomes have been less clear (16, 17). However, understanding the longer-term cognitive outcomes attributable to these cardiovascular procedures in older adults has been limited because many studies had no control group, had short follow-up, had a predominance of middle-aged patients, or used surrogate outcomes for cognitive function. Meanwhile, older adults, who have the highest risk for intermediate- and long-term cognitive impairment, increasingly are having these procedures. Therefore, improved understanding of any relationship between these cardiovascular procedures and cognitive outcomes in older patients could enhance physicianpatient clinical decision making. This systematic review evaluates the evidence from randomized, controlled trials (RCTs) and prospective cohort studies on the association of coronary and carotid revascularization, cardiac valve replacement and repair, and ablation for atrial fibrillation on intermediate- and long-term cognitive outcomes in adults aged 65 years or older. We further sought to evaluate whether these associations were modified by procedural and patient characteristics and by procedure-related stroke or transient ischemic attack (TIA). Methods We followed a protocol developed with input from the Agency for Healthcare Research Quality (AHRQ) and the Coverage and Analysis Group at the Centers for Medicare & Medicaid Services (CMS) (Supplement). The full technical report, which incorporated AHRQ, CMS, peer, and public review, is available on the CMS Web site (www.cms.gov/Medicare/Coverage/DeterminationProcess/Downloads/id97ta.pdf). Supplement. Evidence-based Practice Center Systematic Review Protocol Data Sources We searched the MEDLINE, Cochrane Library, Scopus, and ClinicalTrials.gov databases using a combination of search terms for cognitive function, cardiovascular procedures of interest, and study design (Supplement). We also reviewed reference lists of eligible studies, relevant review articles, and articles suggested by experts. We included only studies published from 1990 to January 2015 to reasonably reflect current clinical practice. Study Selection We included English-language RCTs, controlled clinical trials, and prospective cohort studies. Eligible studies predominately consisted of adults aged 65 years or older. They also reported clinically diagnosed cognitive impairment (such as dementia or mild cognitive impairment) or results of neuropsychological tests (such as Trail Making Test B) or global cognitive screening tests (such as the Mini-Mental State Examination) at least 3 months after coronary or carotid artery revascularization, cardiac valve replacement or repair, or ablation for atrial fibrillation. Clinically diagnosed cognitive impairment must have been based on an assessment of symptoms, function, and formal neuropsychological testing. Treatment group cognitive outcomes must have been compared with those in a control group. The Supplement shows the detailed eligibility criteria. Two reviewers independently examined titles, abstracts, and full articles for eligibility and resolved discrepancies by discussion and consensus. Data Extraction and Quality Assessment For each article, 1 reviewer extracted details on study design, patient characteristics, cardiovascular procedure characteristics, and cognitive outcomes, and a second reviewer checked accuracy. Using Cochrane Collaboration (for trials) and AHRQ (for prospective cohort studies) criteria (18, 19), 2 reviewers rated individual-study risk of bias as low, moderate, high, or unknown (Appendix Tables 1 and 2). For trials, ratings were based on adequacy of randomization and allocation concealment, masking, accounting for attrition bias, use of intention-to-treat analyses, and selectiveness of outcome reporting. For prospective cohort studies, ratings were based on similarity of prognostic factors between comparison groups, accounting for attrition bias, masking, and selectiveness of outcome reporting. Following AHRQ Effective Health Care Program methods (20), 2 reviewers graded the strength of evidence (SOE) for the association of each treatment comparison with subsequent cognitive outcomes as high, moderate, low, or insufficient based on risk of bias, consistency, precision, and directness (Appendix Table 3). We resolved discrepancies in risk-of-bias ratings and SOE grades by discussion and consensus. Appendix Table 1. Risk of Bias in RCTs Appendix Table 2. Risk of Bias in Prospective Cohort Studies Appendix Table 3. Strength of Evidence Appendix Table 3.Continued Data Synthesis and Analysis We used Review Manager, version 5.2 (Cochrane Collaboration), to estimate relative risks and 95% CIs for the incidence of dichotomous outcomes and standardized mean differences and 95% CIs for continuous outcomes. We did not pool results between studies because no 2 studies had clinically similar patient populations, cardiovascular procedure and control groups, and definitions of cognitive outcomes. Role of the Funding Source This review was nominated to AHRQ by the CMS and was funded by AHRQ. Staff at AHRQ and CMS helped to develop and refine the scope of the study and reviewed the draft AHRQ report. Results Twenty-five reports of 21 unique studies (17 RCTs and 4 prospective cohort studies) met eligibility criteria (Figure) (2145). Sixteen of these reports studied CABG; 2 studied cardiac valve replacement, including 1 study of CABG combined with cardiac valve replacement; and 3 studied carotid revascularization. Figure. Summary of evidence search and selection. * Some references were identified in several databases. Sixty-five additional references were identified by hand searching; 61 of them were excluded at the title and abstract review stage, and 4 were excluded after full-text review. Ninety studies were identified from ClinicalTrials.gov. Among studies not already included in the review, 2 seemed possibly eligible: 1 (NCT02108093) that was still enrolling patients and the other (NCT01743456) that is listed as completed but for which no results appear reported. Included 21 unique studies. We rated risk of bias as high in 3 studies, moderate in 11, and unclear in 7. Eighty percent of study patients were men, and mean age was 68 years (mean age was between 65 and 69 years in all but 4 studies). In the 6 studies that reported education, patients completed a mean of 11 years (range, 7 to 14). Few patients had a history of stroke (study range, 0% to 8%; 10 studies) except in the 3 carotid revascularization studies (range, 50% to 100%). All studies reported baseline results for individual neuropsychological tests (such as attention, memory, and executive functioning). Five studies excluded patients with baseline dementia (39, 40), abnormal baseline cognitive screening (25, 26, 30, 39, 40), or a learning disorder (36, 40). Among included patients, mean baseline scores in individual studies were similar to estimated age-based norms for IQ and global cognitive screening tests, but more than half of studies reported mean baseline scores in the impaired range for at least 1 neuropsychological test, most frequently with impairment in timed tests. All studies reported follow-up results for individual neuropsychological tests. Twelve studies reported incident cognitive impairment as defined by a composite of neuropsychological test results (definitions differed in every study [Appendix Table 4]), but none reported incidence of mild cognitive impairment or dementia. Only 2 studies reported cognitive outcomes more than 1 year after the procedure. Appendix Table 4. Individual Study Definitions of Incident Cognitive Impairment Based on Combining Results of Individual Neuropsychological Tests Coronary Artery Revascularization CABG Versus Medical Management One prospective cohort study (n=326) compared on- or off-pump CABG versus medical management in older adults with catheter-proven coronary artery disease (Table 1) (2729). It found that both the CABG and medical groups had small to moderate improvements in memory versus baseline at 1 year and no changes versus baseline at 6 years for all neuropsychological tests measured. Further, there were no between-group differences at any follow-up or in change from baseline to any follow-up. Risk of bias for this study was high due to important baseline differences between treatment groups and substantial loss to follow-up. The higher dropout rates in the CABG group could have biased the results if they were related to cognitive decline. We rated SOE as insufficient because of these limitations and the absence of corroborating studies. Table 1. Cor