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

BACKGROUND: Risks for intermediate- and long-term cognitive impairment after cardiovascular procedures in older adults are poorly understood. PURPOSE: To summarize evidence about cognitive outcomes in adults aged 65 years or older at least 3 months after coronary or carotid revascularization, cardiac valve procedures, or ablation for atrial fibrillation. DATA SOURCES: MEDLINE, Cochrane, and Scopus databases from 1990 to January 2015; ClinicalTrials.gov; and bibliographies of reviews and eligible studies. STUDY SELECTION: English-language trials and prospective cohort studies. DATA EXTRACTION: One reviewer extracted data, a second checked accuracy, and 2 independently rated quality and strength of evidence (SOE). DATA SYNTHESIS: 17 trials and 4 cohort studies were included; 80% of patients were men, and mean age was 68 years. Cognitive function did not differ after the procedure between on- and off-pump coronary artery bypass grafting (CABG) (n = 6; low SOE), hypothermic and normothermic CABG (n = 3; moderate to low SOE), or CABG and medical management (n = 1; insufficient SOE). One trial reported lower risk for incident cognitive impairment with minimal versus conventional extracorporeal CABG (risk ratio, 0.34 [95% CI, 0.16 to 0.73]; low SOE). Two trials found no difference between surgical carotid revascularization and carotid stenting or angioplasty (low and insufficient SOE, respectively). One cohort study reported increased cognitive decline after transcatheter versus surgical aortic valve replacement but had large selection and outcome measurement biases (insufficient SOE). LIMITATIONS: Mostly low to insufficient SOE; no pertinent data for ablation; limited generalizability to the most elderly patients, women, and persons with substantial baseline cognitive impairment; and possible selective reporting and publication bias. CONCLUSION: Intermediate- and long-term cognitive impairment in older adults attributable to the studied cardiovascular procedures may be uncommon. Nevertheless, clinicians counseling patients before these procedures should discuss the uncertainty in their risk for adverse cognitive outcomes. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Timing of dialysis initiation, duration and frequency of hemodialysis sessions, and membrane flux: a systematic review for a KDOQI clinical practice guideline.

BACKGROUND: In 2006, NKF-KDOQI (National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) published clinical practice guidelines for hemodialysis adequacy. Recent studies evaluating hemodialysis adequacy as determined by initiation timing, frequency, duration, and membrane type and prompted an update to the guideline. STUDY DESIGN: Systematic review and evidence synthesis. SETTING & POPULATION: Patients with advanced chronic kidney disease receiving hemodialysis. SELECTION CRITERIA FOR STUDIES: We screened publications from 2000 to March 2014, systematic reviews, and references and consulted the NKF-KDOQI Hemodialysis Adequacy Work Group members. We included randomized or controlled clinical trials in patients undergoing long-term hemodialysis if they reported outcomes of interest. INTERVENTIONS: Early versus late dialysis therapy initiation; more frequent (>3 times a week) or longer duration (>4.5 hours) compared to conventional hemodialysis; low- versus high-flux dialyzer membranes. OUTCOMES: All-cause and cardiovascular mortality, myocardial infarction, stroke, hospitalizations, quality of life, depression or cognitive function scores, blood pressure, number of antihypertensive medications, left ventricular mass, interdialytic weight gain, and harms or complications related to vascular access or the process of dialysis. RESULTS: We included 32 articles reporting on 19 trials. Moderate-quality evidence indicated that earlier dialysis therapy initiation (at estimated creatinine clearance [eClcr] of 10-14mL/min) did not reduce mortality compared to later initiation (eClcr of 5-7mL/min). More than thrice-weekly hemodialysis and extended-length hemodialysis during a short follow-up did not improve clinical outcomes compared to conventional hemodialysis and resulted in a greater number of vascular access procedures (very low-quality evidence). Hemodialysis using high-flux membranes did not reduce all-cause mortality, but reduced cardiovascular mortality compared to hemodialysis using low-flux membranes (moderate-quality evidence). LIMITATIONS: Few studies were adequately powered to evaluate mortality. Heterogeneity of study designs and interventions precluded pooling data for most outcomes. CONCLUSIONS: Limited data indicate that earlier dialysis therapy initiation and more frequent and longer hemodialysis did not improve clinical outcomes compared to conventional hemodialysis.

Screening pelvic examinations in asymptomatic, average-risk adult women: an evidence report for a clinical practice guideline from the American College of Physicians.

BACKGROUND: Pelvic examination is often included in well-woman visits even when cervical cancer screening is not required. PURPOSE: To evaluate the diagnostic accuracy, benefits, and harms of pelvic examination in asymptomatic, nonpregnant, average-risk adult women. Cervical cancer screening was not included. DATA SOURCES: MEDLINE and Cochrane databases through January 2014 and reference lists from identified studies. STUDY SELECTION: 52 English-language studies, 32 of which included primary data. DATA EXTRACTION: Data were extracted on study and sample characteristics, interventions, and outcomes. Quality of the diagnostic accuracy studies was evaluated using a published instrument, and quality of the survey studies was evaluated with metrics assessing population representativeness, instrument development, and response rates. DATA SYNTHESIS: The positive predictive value of pelvic examination for detecting ovarian cancer was less than 4% in the 2 studies that reported this metric. No studies that investigated the morbidity or mortality benefits of screening pelvic examination for any condition were identified. The percentage of women reporting pelvic examination-related pain or discomfort ranged from 11% to 60% (median, 35%; 8 studies [n = 4576]). Corresponding figures for fear, embarrassment, or anxiety ranged from 10% to 80% (median, 34%; 7 studies [n = 10 702]). LIMITATION: Only English-language publications were included; the evidence on diagnostic accuracy, morbidity, and mortality was scant; and the studies reporting harms were generally low quality. CONCLUSION: No data supporting the use of pelvic examination in asymptomatic, average-risk women were found. Low-quality data suggest that pelvic examinations may cause pain, discomfort, fear, anxiety, or embarrassment in about 30% of women. PRIMARY FUNDING SOURCE: Department of Veterans Affairs.

Effectiveness of family and caregiver interventions on patient outcomes in adults with cancer: a systematic review.

BACKGROUND: Family and caregiver interventions typically aim to develop family members' coping and caregiving skills and to reduce caregiver burden. We conducted a systematic review of published randomized controlled trials (RCTs) evaluating whether family-involved interventions improve patient outcomes among adults with cancer. METHODS: RCTs enrolling patients with cancer were identified by searching MEDLINE, PsycInfo and other sources through December 2012. Studies were limited to subjects over 18 years of age, published in English language, and conducted in the United States. Patient outcomes included global quality of life; physical, general psychological and social functioning; depression/anxiety; symptom control and management; health care utilization; and relationship adjustment. RESULTS: We identified 27 unique trials, of which 18 compared a family intervention to usual care or wait list (i.e., usual care with promise of intervention at completion of study period) and 13 compared one family intervention to another individual or family intervention (active control). Compared to usual care, overall strength of evidence for family interventions was low. The available data indicated that overall, family-involved interventions did not consistently improve outcomes of interest. Similarly, with low or insufficient evidence, family-involved interventions were not superior to active controls at improving cancer patient outcomes. DISCUSSION: Overall, there was low or insufficient evidence that family and caregiver interventions were superior to usual or active care. Variability in study populations and interventions made pooling of data problematic and generalizing findings from any single study difficult. Most of the included trials were of poor or fair quality.

Advanced wound care therapies for nonhealing diabetic, venous, and arterial ulcers: a systematic review.

BACKGROUND: Nonhealing ulcers affect patient quality of life and impose a substantial financial burden on the health care system. PURPOSE: To systematically evaluate benefits and harms of advanced wound care therapies for nonhealing diabetic, venous, and arterial ulcers. DATA SOURCES: MEDLINE (1995 to June 2013), the Cochrane Library, and reference lists. STUDY SELECTION: English-language randomized trials reporting ulcer healing or time to complete healing in adults with nonhealing ulcers treated with advanced therapies. DATA EXTRACTION: Study characteristics, outcomes, adverse events, study quality, and strength of evidence were extracted by trained researchers and confirmed by the principal investigator. DATA SYNTHESIS: For diabetic ulcers, 35 trials (9 therapies) met eligibility criteria. There was moderate-strength evidence for improved healing with a biological skin equivalent (relative risk [RR], 1.58 [95% CI, 1.20 to 2.08]) and negative pressure wound therapy (RR, 1.49 [CI, 1.11 to 2.01]) compared with standard care and low-strength evidence for platelet-derived growth factors and silver cream compared with standard care. For venous ulcers, 20 trials (9 therapies) met eligibility criteria. There was moderate-strength evidence for improved healing with keratinocyte therapy (RR, 1.57 [CI, 1.16 to 2.11]) compared with standard care and low-strength evidence for biological dressing and a biological skin equivalent compared with standard care. One small trial of arterial ulcers reported improved healing with a biological skin equivalent compared with standard care. Overall, strength of evidence was low for ulcer healing and low or insufficient for time to complete healing. LIMITATIONS: Only studies of products approved by the U.S. Food and Drug Administration were reviewed. Studies were predominantly of fair or poor quality. Few trials compared 2 advanced therapies. CONCLUSION: Compared with standard care, some advanced wound care therapies may improve the proportion of ulcers healed and reduce time to healing, although evidence is limited. PRIMARY FUNDING SOURCE: Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Quality Enhancement Research Initiative.

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.

Management of hyperglycemia, dyslipidemia, and albuminuria in patients with diabetes and CKD: a systematic review for a KDOQI clinical practice guideline.

BACKGROUND: In 2007, the National Kidney Foundation (NKF) published clinical practice guidelines and recommendations for treating patients with diabetes and kidney diseases. Given recent studies that may enhance our understanding of the benefits and harms of glycemic, lipid, and albuminuria management in patients with diabetes and chronic kidney disease (CKD), the NKF commissioned a systematic review to evaluate data on the management of these patients. STUDY DESIGN: Systematic review and evidence synthesis. SETTING & POPULATION: Patients with type 1 or 2 diabetes with or without CKD. SELECTION CRITERIA FOR STUDIES: English-language publications indexed in the MEDLINE database from January 2003 to October 2010, as well as cited references in these publications and publications identified after consultation with the NKF Diabetes Work Group were screened. Randomized controlled trials providing evidence for the management of hyperglycemia, dyslipidemia, and albuminuria in individuals with diabetes were included. INTERVENTIONS: (1) Intensive glycemic control; (2) lipid management; (3) interventions aimed at prevention of incident albuminuria and/or progression of albuminuria in normotensive patients. OUTCOMES: For all interventions, all-cause mortality was the primary outcome and secondary clinical outcomes included death from cardiovascular causes, incident kidney failure, and nonfatal cardiovascular events. Intermediate outcomes included changes in albuminuria and measures of kidney function. For intensive glycemic control only, severe and mild hypoglycemia were secondary and intermediate outcomes, respectively. RESULTS: 5 studies (n=27,159) assessed the impact of intensive versus conventional glycemic control strategies on clinical outcomes in type 2 diabetes. Intensive glycemic control reduced the development of micro- and macroalbuminuria, but did not reduce the incidence of primary or secondary clinical outcomes and was associated with a 2.5-fold increase in severe hypoglycemia. 11 studies (n=7,539) assessed lipid management. Statins did not reduce all-cause mortality or stroke compared to placebo in adults with diabetes and CKD. Fenofibrate increased regression of microalbuminuria to normoalbuminuria compared to placebo. 3 studies reported inconsistent effects of different angiotensin II receptor blockers on the incidence of microalbuminuria, and one study reported that telmisartan reduced macroalbuminuria in normotensive participants. No study demonstrated a benefit on primary or secondary clinical outcomes. LIMITATIONS: Patients with CKD constituted a subgroup in most studies. Substantial heterogeneity with respect to population, interventions, outcome measures, and duration of follow-up. CONCLUSIONS: Intensive glycemic control and lipid interventions did not improve clinical outcomes in patients with type 2 diabetes. Although interventions typically improved albuminuria, evidence was insufficient to determine whether treatment of albuminuria in normotensive patients provides beneficial effects on clinical outcomes. More intensive clinical management of patients with diabetes and CKD has inherent risks, including severe hypoglycemia, which should be considered when formulating treatment strategies.

Serenoa repens monotherapy for benign prostatic hyperplasia (BPH): an updated Cochrane systematic review.

UNLABELLED: What's known on the subject? and What does the study add? For the past 30 years Serenoa repens has become a widely used phytotherapy in the USA and in Europe, mostly because of positive comparisons to α-blockers and 5α-reductase inhibitors. During the last 4 years we have seen two very high quality trials comparing Serenoa repens to placebo and up to 72 weeks' duration. These trials found Serenoa repens no better than placebo, even (in one trial) at escalating doses. OBJECTIVE: • To estimate the effectiveness and harms of Serenoa repens monotherapy in the treatment of lower urinary tract symptoms (LUTS) consistent with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: • We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and other sources through to January 2012 to identify randomised trials. • Trials were eligible if they randomised men with symptomatic BPH to receive Serenoa repens extract monotherapy for at least 4 weeks in comparison with placebo, and assessed clinical outcomes and urodynamic measurements. • Our primary outcome was improvement in LUTS, based on change in urological symptom-scale scores. RESULTS: • In all, 17 randomised controlled trials (N= 2008) assessing Serenoa repens monotherapy (typically 320 mg/day) vs placebo met inclusion criteria, although only five reported American Urological Association Symptom Index (AUASI) or International Prostate Symptom Scores (IPSS). Trial lengths ranged from 4 to 72 weeks. The mean age of all enrolees was 64.3 years and most participants were of White race. The mean baseline total score was 14 points, indicating moderately severe symptoms. In all, 16 trials were double blinded and adequate treatment allocation concealment was reported in six trials. • In a meta-analysis of three high quality long-to-moderate term trials (n= 661), Serenoa repens therapy was no better than placebo in reducing LUTS based on the AUASI/IPSS (weighted mean difference [WMD]-0.16 points, 95% confidence interval [CI]-1.45 to 1.14) or maximum urinary flow rate (Q(max) ; WMD 0.40 mL/s, 95% CI -0.30 to 1.09). Based on mostly short-term studies, Q(max) measured at study endpoint were also not significantly different between treatment groups (WMD 1.15 mL/s, 95% CI -0.23 to 2.53) with evidence of substantial heterogeneity (I(2) 58%). • One long-term dose escalation trial (72 weeks) found double and triple doses of Serenoa repens extract did not improve AUASI compared with placebo and the proportions of clinical responders (≥ 3 point decrease in the AUASI) were nearly identical (43% vs 44% for Serenoa repens and placebo, respectively) with a corresponding risk ratio of 0.96 (95% CI 0.76-1.22). • Long-term, Serenoa repens therapy was no better than placebo in improving nocturia in one high-quality study (P= 0.19). Pooled analysis of nine short-term Permixon® trials showed a reduction in the frequency of nocturia (WMD -0.79 times/night, 95% CI-1.28 to -0.29), although there was evidence of heterogeneity (I(2) 76%) • Adverse events of Serenoa repens extracts were few and mild, and incidences were not statistically significantly different vs placebo. Study withdrawals occurred in ≈ 10% and did not differ between Serenoa repens and placebo. CONCLUSIONS: • Serenoa repens therapy does not improve LUTS or Q(max ) compared with placebo in men with BPH, even at double and triple the usual dose. • Adverse events were generally mild and comparable to placebo.

Meta-analysis: effect of patient self-testing and self-management of long-term anticoagulation on major clinical outcomes.

BACKGROUND: Anticoagulation with vitamin K antagonists reduces major thromboembolic complications in at-risk patients. With portable monitoring devices, patients can conduct their own international normalized ratio testing and dose adjustment at home. PURPOSE: To determine whether patient self-testing (PST), alone or in combination with self-adjustment of doses (patient self-management [PSM]), is associated with a reduction in thromboembolic complications and all-cause mortality without an increase in major bleeding events compared with usual care. DATA SOURCES: MEDLINE and the Cochrane Central Register of Controlled Trials. STUDY SELECTION: Studies published in English from 1966 to October 2010 that enrolled outpatient adults receiving long-term (>3 months) oral anticoagulant therapy and that compared PST or PSM with care in a physician's office or an anticoagulation clinic were included. DATA EXTRACTION: Two investigators reviewed each article. Three investigators extracted data from articles that met inclusion criteria by using standardized data abstraction forms. Studies were assessed for quality, and the overall strength of evidence was rated for each clinical outcome. DATA SYNTHESIS: Twenty-two trials, with a total of 8413 patients, were included. In one half of the trials, fewer than 50% of potentially eligible persons successfully completed the training and agreed to be randomly assigned. Patients randomly assigned to PST or PSM had lower total mortality (Peto odds ratio [OR], 0.74 [95% CI, 0.63 to 0.87]), lower risk for major thromboembolism (Peto OR, 0.58 [CI, 0.45 to 0.75]), and no increased risk for a major bleeding event (Peto OR, 0.89 [CI, 0.75 to 1.05]). The strength of evidence was moderate for the bleeding and thromboembolism outcomes but low for mortality. Eight of 11 trials reported that patient satisfaction, quality of life, or both was better with PST or PSM than with usual care. LIMITATIONS: In one half of the trials, fewer than 50% of the potentially eligible patients were randomly assigned. Only 5 trials were considered high quality, and only 2 were conducted in the United States. No studies addressed whether PST or PSM is safe during the high-risk initiation phase. CONCLUSION: Compared with usual care, PST with or without PSM is associated with significantly fewer deaths and thromboembolic events, without increased risk for a serious bleeding event, for a highly selected group of motivated adult patients requiring long-term anticoagulation with vitamin K antagonists. Whether this care model is cost-effective and can be implemented successfully in typical U.S. health care settings requires further study. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs Health Services Research and Development Service.

Interventions to improve veterans' access to care: a systematic review of the literature.

OBJECTIVES: To conduct a systematic review to address the following key questions: (1) what interventions have been successful in improving access for veterans with reduced health care access? (2) Have interventions that have improved health care access led to improvements in process and clinical outcomes? DATA SOURCES: OVID MEDLINE, CINAHL, PsychINFO. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: English language articles published in peer-reviewed journals from 1990 to June 2010. All interventions designed to improve access to health care for US veterans that reported the impact of the intervention on perceived (e.g., satisfaction with access) or objective (e.g., travel time, wait time) access were included. APPRAISAL AND SYNTHESIS METHODS: Investigators abstracted data on study design, study quality, intervention, and impact of the intervention on access, process outcomes, and clinical outcomes. RESULTS: Nineteen articles (16 unique studies) met the inclusion criteria. While there were a small number of studies in support of any one intervention, all showed a positive impact on either perceived or objective measures of access. Implementation of Community Based Outpatient Clinics (n = 5 articles), use of Telemedicine (n = 5 articles), and Primary Care Mental Health Integration (n = 6 articles) improved access. All 16 unique studies reported process outcomes, most often satisfaction with care and utilization. Four studies reported clinical outcomes; three found no differences. LIMITATIONS: Included studies were largely of poor to fair methodological quality. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Interventions can improve access to health care for veterans. Increased access was consistently linked to increased primary care utilization. There was a lack of data regarding the link between access and clinical outcomes; however, the limited data suggest that increased access may not improve clinical outcomes. Future research should focus on the quality and appropriateness of care and clinical outcomes.

Teledermatology for diagnosis and management of skin conditions: a systematic review.

OBJECTIVE: We performed a systematic review of the literature addressing teledermatology: (1) diagnostic accuracy/concordance; (2) management accuracy/concordance; (3) clinical outcomes; and (4) costs. METHODS: Peer-reviewed controlled trials published in English between 1990 and 2009 were identified through MEDLINE and PubMed searches. RESULTS: Of 78 included studies, approximately two-thirds comparing teledermatology and clinic dermatology found better diagnostic accuracy with clinic dermatology. Diagnostic concordance of store and forward with clinic dermatology was good; concordance rates for live interactive and clinic dermatology were higher, but based on fewer patients. Overall rates of management accuracy were equivalent, but teledermatology and teledermatoscopy were inferior to clinic dermatology for malignant lesions. Management concordance was fair to excellent. There was insufficient evidence to evaluate clinical course outcomes. Patient satisfaction and preferences were comparable. Teledermatology reduced time to treatment and clinic visits and was cost-effective if certain assumptions were met. LIMITATIONS: Heterogeneity in studies (design, skin conditions, outcomes) limited the ability to pool data. CONCLUSION: The benefits of teledermatology need to be evaluated in the context of potential limitations.

Prevalence, assessment, and treatment of mild traumatic brain injury and posttraumatic stress disorder: a systematic review of the evidence.

BACKGROUND: Iraq and Afghanistan war veterans are returning from combat having sustained traumatic brain injury, mostcommonly mild traumatic brain injury (mTBI), and experiencing posttraumatic stress disorder (PTSD). Clinical guidelines for mTBI and PTSDdo not focus on the co-occurrence of these conditions (mTBI/PTSD). A synthesis of the evidence on prevalence, diagnostic accuracy, andtreatment effectiveness for mTBI/PTSD would be of use to clinicians, researchers, and policymakers. METHODS: We conducteda systematic review of studies identified through PubMed, PsycINFO, REHABDATA, Cochrane Library, pearling, and expert recommendations. Peer-reviewed English language studies published between 1980 and June, 2009 were included if they reported frequencies of traumatic braininjury and PTSD, or diagnostic accuracy or treatment effectiveness specific to mTBI/PTSD. RESULTS: Thirty-four studies metinclusion criteria. None evaluated diagnostic accuracy or treatment effectiveness. Studies varied considerably in design. Frequency ofmTBI/PTSD ranged from 0% to 89%. However, in 3 large studies evaluating Iraq and Afghanistan war veterans, frequencies ofprobable mTBI/PTSD were from 5% to 7%; among those with probable mTBI, frequencies of probable PTSD were from 33% to 39%. DISCUSSION: The wide range of mTBI/PTSD frequency levels was likely due to variation across studyparameters, including aims and assessment methods. Studies using consistent, validated methods to define and measure mTBI history andPTSD are needed.

Antiviral therapy for adults with chronic hepatitis B: a systematic review for a National Institutes of Health Consensus Development Conference.

BACKGROUND: Chronic hepatitis B infection can lead to liver failure, hepatocellular carcinoma, and death. PURPOSE: To evaluate the effectiveness of antiviral therapy for adults with chronic hepatitis B infection. DATA SOURCES: Randomized, controlled trials (RCTs) of interferon (alpha2b and pegylated alpha2a), lamivudine, adefovir, entecavir, and telbivudine published from 1990 to 2008. STUDY SELECTION: Randomized, controlled clinical trials of adults with chronic hepatitis B published in English after 1989 that reported death; incidence of hepatocellular carcinoma or liver failure; prevalence and incidence of cirrhosis; presence or seroconversion of hepatitis B e antigen (HBeAg) or surface antigen (HBsAg), viral load of hepatitis B virus DNA; aspartate aminotransferase and alanine aminotransferase (ALT) levels; or fibrosis scores after therapy with interferon-alpha2b, pegylated interferon-alpha2a, lamivudine, adefovir, entecavir, and telbivudine. DATA EXTRACTION: Data extracted with standard protocols to calculate risk difference for clinical outcomes, viral load, HBeAg and HBsAg, ALT, histologic scores, and adverse events. DATA SYNTHESIS: In 16 RCTs (4431 patients), drug treatment did not improve clinical outcomes of chronic hepatitis B infection, but the trials were underpowered. In 60 RCTs that examined intermediate outcomes, no single treatment improved all intermediate outcomes. Low-quality evidence suggested HBsAg clearance after interferon-alpha2b (2 RCTs; 211 patients). Moderate-quality evidence suggested ALT normalization at follow-up after treatment with adefovir (2 RCTs; 600 patients) and HBeAg loss with lamivudine (2 RCTs; 318 patients). With interferon-alpha2b, moderate-quality evidence suggested HBeAg loss (3 RCTs; 351 patients), seroconversion (2 RCTs; 304 patients), and ALT normalization (2 RCTs; 131 patients). Pegylated interferon-alpha2a versus lamivudine improved HBeAg seroconversion (1 RCT; 814 patients) and ALT normalization (2 RCTs; 905 patients) off treatment. Pegylated interferon-alpha2a combined with lamivudine versus lamivudine improved HBeAg loss (1 RCT; 543 patients) and ALT normalization (2 RCTs; 905 patients). Adverse events during antiretroviral therapy occurred in more than 50% of patients but were not associated with increased treatment discontinuation. However, most studies excluded patients with hepatic or renal insufficiency or other serious comorbid conditions. LIMITATION: Marked heterogeneity in study samples, interventions, and measured outcomes preclude definitive conclusions. CONCLUSION: Evidence was insufficient to assess treatment effect on clinical outcomes or determine whether inconsistent improvements in selected intermediate measures are reliable surrogates. Future research is needed to provide evidence-based recommendations about optimal antiviral therapy in adults with chronic hepatitis B infection.

The evaluating prescription opioid changes in veterans (EPOCH) study: Design, survey response, and baseline characteristics.

In the United States (US), long-term opioid therapy has been commonly prescribed for chronic pain. Since recognition of the opioid overdose epidemic, clinical practice guidelines have recommended tapering long-term opioids to reduced doses or discontinuation. The Effects of Prescription Opioid Changes for veterans (EPOCH) study is a national population-based prospective observational study of US Veterans Health Administration primary care patients designed to assess effects of evolving opioid prescribing practice on patients treated with long-term opioids for chronic pain. A stratified random sampling design was used to identify a survey sample from the target population of patients treated with opioid analgesics for ≥ 6 months. Demographic, diagnostic, visit, and pharmacy dispensing data were extracted from existing datasets. A 2016 mixed-mode mail and telephone survey collected patient-reported data, including the main patient-reported outcomes of pain-related function (Brief Pain Inventory interference; BPI-I scores 0-10, higher scores = worse) and health-related quality of life. Data on survey participants and non-participants were analyzed to assess potential nonresponse bias. Weights were used to account for design. Linear regression models were used to assess cross-sectional associations of opioid treatment with patient-reported measures. Of 14,160 patients contacted, 9253 (65.4%) completed the survey. Participants were older than non-participants (63.9 ± 10.6 vs. 59.6 ± 13.0 years). The mean number of bothersome pain locations was 6.8 (SE 0.04). Effectiveness of pain treatment and quality of pain care were rated fair or poor by 56.1% and 45.3%, respectively. The opioid daily dosage range was 1.6 to 1038.2 mg, with mean = 50.6 mg (SE 1.1) and median = 30.9 mg (IQR 40.7). Among the 73.2% of patients who did not receive long-acting opioids, the mean daily dosage was 30.4 mg (SE 0.6) and mean BPI-I was 6.4 (SE 00.4). Among patients who received long-acting opioids, the mean daily dosage was 106.2 mg (SE 2.8) and mean BPI-I was 6.8 (SE 0.07). Higher daily dosage was associated with worse pain-related function and quality of life among patients without long-acting opioids, but not among patients with long-acting opioids. Future analyses will use follow-up data to examine effects of opioid dose reduction and discontinuation on patient outcomes.

Systematic review: comparative effectiveness and harms of treatments for clinically localized prostate cancer.

BACKGROUND: The comparative effectiveness of localized prostate cancer treatments is largely unknown. PURPOSE: To compare the effectiveness and harms of treatments for localized prostate cancer. DATA SOURCES: MEDLINE (through September 2007), the Cochrane Library (through Issue 3, 2007), and the Cochrane Review Group in Prostate Diseases and Urologic Malignancies registry (through November 2007). STUDY SELECTION: Randomized, controlled trials (RCTs) published in any language and observational studies published in English that evaluated treatments and reported clinical or biochemical outcomes in localized prostate cancer. DATA EXTRACTION: 2 researchers extracted information on study design, sample characteristics, interventions, and outcomes. DATA SYNTHESIS: 18 RCTs and 473 observational studies met inclusion criteria. One [one randomized controlled trial] [corrected] RCT enrolled mostly men without prostate-specific antigen (PSA)-detected disease and reported that, compared with watchful waiting, radical prostatectomy reduced crude [corrected] all-cause mortality (24% vs. 30%; P = 0.04) and prostate cancer-specific mortality (10% [corrected] vs. 15% [corrected]; P = 0.01) at 10 years [corrected] Effectiveness was limited to men younger than age 65 years but was not associated with Gleason score or baseline PSA level. An older, smaller trial found no significant overall survival differences between radical prostatectomy and watchful waiting (risk difference, 0% [95% CI, -19% to 18%]). Radical prostatectomy reduced disease recurrence at 5 years compared with external-beam radiation therapy in 1 small, older trial (14% vs. 39%; risk difference, 21%; P = 0.04). No external-beam radiation regimen was superior to another in reducing mortality. No randomized trials evaluated primary androgen deprivation. Androgen deprivation used adjuvant to radical prostatectomy did not improve biochemical progression compared with radical prostatectomy alone (risk difference, 0% [CI, -7% to 7%]). No randomized trial evaluated brachytherapy, cryotherapy, robotic radical prostatectomy, or photon-beam or intensity-modulated radiation therapy. Observational studies showed wide and overlapping effectiveness estimates within and between treatments. Adverse event definitions and severity varied widely. The Prostate Cancer Outcomes Study reported that urinary leakage (> or =1 event/d) was more common with radical prostatectomy (35%) than with radiation therapy (12%) or androgen deprivation (11%). Bowel urgency occurred more often with radiation (3%) or androgen deprivation (3%) than with radical prostatectomy (1%). Erectile dysfunction occurred frequently after all treatments (radical prostatectomy, 58%; radiation therapy, 43%; androgen deprivation, 86%). A higher risk score incorporating histologic grade, PSA level, and tumor stage was associated with increased risk for disease progression or recurrence regardless of treatment. LIMITATIONS: Only 3 randomized trials compared effectiveness between primary treatments. No trial enrolled patients with prostate cancer primarily detected with PSA testing. CONCLUSION: Assessment of the comparative effectiveness and harms of localized prostate cancer treatments is difficult because of limitations in the evidence.

Design, recruitment outcomes, and sample characteristics of the Strategies for Prescribing Analgesics Comparative Effectiveness (SPACE) trial.

This manuscript describes the study protocol, recruitment outcomes, and baseline participant characteristics for the Strategies for Prescribing Analgesics Comparative Effectiveness (SPACE) trial. SPACE is a pragmatic randomized comparative effectiveness trial conducted in multiple VA primary care clinics within one VA health care system. The objective was to compare benefits and harms of opioid therapy versus non-opioid medication therapy over 12months among patients with moderate-to-severe chronic back pain or hip/knee osteoarthritis pain despite analgesic therapy; patients already receiving regular opioid therapy were excluded. Key design features include comparing two clinically-relevant medication interventions, pragmatic eligibility criteria, and flexible treat-to-target interventions. Screening, recruitment and study enrollment were conducted over 31months. A total of 4491 patients were contacted for eligibility screening; 53.1% were ineligible, 41.0% refused, and 5.9% enrolled. The most common reasons for ineligibility were not meeting pain location and severity criteria. The most common study-specific reasons for refusal were preference for no opioid use and preference for no pain medications. Of 265 enrolled patients, 25 withdrew before randomization. Of 240 randomized patients, 87.9% were male, 84.1% were white, and age range was 21-80years. Past-year mental health diagnoses were 28.3% depression, 17% anxiety, 9.4% PTSD, 7.9% alcohol use disorder, and 2.6% drug use disorder. In conclusion, although recruitment for this trial was challenging, characteristics of enrolled participants suggest we were successful in recruiting patients similar to those prescribed opioid therapy in usual care.

Sildenafil for male erectile dysfunction: a systematic review and meta-analysis.

OBJECTIVE: To determine the efficacy and safety of sildenafil citrate in the treatment of male erectile dysfunction. DATA SOURCES: The MEDLINE, HealthSTAR, Current Contents, and Cochrane Library databases (January 1, 1995, through December 31, 2000); bibliographies of retrieved articles and review articles; conference proceedings abstracts; the Food and Drug Administration Web site; and the manufacturer. STUDY SELECTION: Trials were eligible if they included men with erectile dysfunction, compared sildenafil with control, were randomized, were of at least 7 days' duration, and assessed clinically relevant outcomes. DATA EXTRACTION: Two reviewers independently evaluated study quality and extracted data in a standardized fashion. DATA SYNTHESIS: Twenty-seven trials (6659 men) met the inclusion criteria. In results pooled from 14 parallel-group, flexible as-needed dosing trials, sildenafil was more likely than placebo to lead to successful sexual intercourse, with a higher percentage of successful intercourse attempts (57% vs 21%; weighted mean difference, 33.7; 95% confidence interval [CI], 29.2-38.2; 2283 men) and a greater percentage of men experiencing at least 1 intercourse success during treatment (83% vs 45%; relative benefit increase, 1.8; 95% CI, 1.7-1.9; 2205 men). In data pooled from 6 parallel-group, fixed-dose trials, efficacy appeared slightly greater at higher doses. Treatment response appeared to vary between patient subgroups, although relative to placebo, sildenafil significantly improved erectile function in all evaluated subgroups. In trials with parallel-group design and flexible dosing, men randomized to receive sildenafil were less likely than those receiving placebo to drop out for any reason and no more likely to drop out due to an adverse event or laboratory abnormality. Specific adverse events with sildenafil included flushing (12%), headache (11%), dyspepsia (5%), and visual disturbances (3%); all adverse events were significantly less likely to occur with placebo. Sildenafil was not significantly associated with serious cardiovascular events or death. CONCLUSIONS: Sildenafil improves erectile function and is generally well tolerated. Treatment response seems to vary between patient subgroups, although sildenafil has greater efficacy than placebo in all evaluated subgroups.

Effectiveness of statin therapy in adults with coronary heart disease.

BACKGROUND: We conducted a meta-analysis of patients with coronary heart disease (CHD) to determine the effectiveness of statin therapy; whether effectiveness varied according to patient characteristics, outcomes, or pretreatment low-density lipoprotein cholesterol (LDL-C) levels; and the optimal LDL-C goal and the level at which to initiate statin therapy. METHODS: Randomized trials or systematic reviews for secondary prevention of CHD with statin therapy published between January 1966 and December 2002 were identified through MEDLINE and the Cochrane Library. Studies were included if they randomly assigned adults with CHD to statin therapy or control, enrolled at least 100 individuals per arm, reported clinical outcomes and LDL-C levels, and were published as full studies in English. Two reviewers abstracted data using a prospectively designed protocol. RESULTS: Twenty-five studies enrolling 69 511 individuals were included. Participants in 19 placebo-controlled trials had a mean age of 63 years and a mean pretreatment LDL-C level of 149 mg/dL (3.85 mmol/L); 23% were women. Statin therapy reduced CHD mortality or nonfatal myocardial infarction 25% (relative risk [RR], 0.75; 95% confidence interval [CI], 0.71-0.79), all-cause mortality 16% (RR, 0.84; 95% CI, 0.79-0.89), and CHD mortality 23% (RR, 0.77; 95% CI, 0.71-0.83). Beneficial effects were seen in women and the elderly. There were no data to determine whether lowering the LDL-C level to less than 100 mg/dL (<2.59 mmol/L) was superior to lowering it to 100 to 130 mg/dL (2.59-3.36 mmol/L). Meta-regression analyses revealed risk reductions for CHD mortality or nonfatal myocardial infarction and major vascular events across available pretreatment LDL-C levels. CONCLUSION: Statin therapy reduces mortality and morbidity in adults with CHD, even at pretreatment LDL-C levels as low as 100 mg/dL (2.59 mmol/L).

Antimicrobial stewardship in outpatient settings: a systematic review.

OBJECTIVE: Evaluate the effect of outpatient antimicrobial stewardship programs on prescribing, patient, microbial outcomes, and costs. DESIGN: Systematic review METHODS: Search of MEDLINE (2000 through November 2013), Cochrane Library, and reference lists of relevant studies. We included English language studies with patient populations relevant to the United States (eg, infectious conditions, prescription services) evaluating stewardship programs in outpatient settings and reporting outcomes of interest. Data regarding study characteristics and outcomes were extracted and organized by intervention type. RESULTS: We identified 50 studies eligible for inclusion, with most (29 of 50; 58%) reporting on respiratory tract infections, followed by multiple/unspecified infections (17 of 50; 34%). We found medium-strength evidence that stewardship programs incorporating communication skills training and laboratory testing are associated with reductions in antimicrobial use, and low-strength evidence that other stewardship interventions are associated with improved prescribing. Patient-centered outcomes, which were infrequently reported, were not adversely affected. Medication costs were generally lower with stewardship interventions, but overall program costs were rarely reported. No studies reported microbial outcomes, and data regarding outpatient settings other than primary care clinics are limited. CONCLUSIONS: Low- to moderate-strength evidence suggests that antimicrobial stewardship programs in outpatient settings improve antimicrobial prescribing without adversely effecting patient outcomes. Effectiveness depends on program type. Most studies were not designed to measure patient or resistance outcomes. Data regarding sustainability and scalability of interventions are limited.

Effectiveness of Caregiver Interventions on Patient Outcomes in Adults With Dementia or Alzheimer's Disease: A Systematic Review.

Objective: We conducted a systematic review to evaluate whether caregiver-involved interventions improve patient outcomes among adults with dementia or Alzheimer's disease. Method: We identified and summarized data from randomized controlled trials enrolling adults with dementia or Alzheimer's disease by searching MEDLINE, PsycINFO, and other sources. Patient outcomes included global quality of life, physical and cognitive functioning, depression/anxiety, symptom control and management, and health care utilization. Results: We identified 31 trials; 20 compared a caregiver intervention with usual care or usual care with promise of intervention at completion of study period. Fifteen compared one caregiver intervention with another individual or caregiver intervention (active control). Compared with usual care or active controls, caregiver-involved interventions had low to insufficient strength of evidence and did not consistently improve patient outcomes. Discussion: Evidence is insufficient to endorse use of most caregiver interventions to improve outcomes for patients with dementia or Alzheimer's disease.