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.

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.

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.

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.

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.

Antimicrobial stewardship programs in inpatient hospital settings: a systematic review.

OBJECTIVE: Evaluate the evidence for effects of inpatient antimicrobial stewardship programs (ASPs) on patient, prescribing, and microbial outcomes. 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 (ie, infectious conditions and prescriptions required for antimicrobials) that evaluated ASP interventions and reported outcomes of interest. Study characteristics and outcomes data were extracted and reviewed by investigators and trained research personnel. RESULTS: Few intervention types (eg, audit and feedback, guideline implementation, and decision support) substantially impacted patient outcomes, including mortality, length of stay, readmission, or incidence of Clostridium difficile infection. However, most interventions were not powered adequately to demonstrate impacts on patient outcomes. Most interventions were associated with improved prescribing patterns as measured by decreased antimicrobial use or increased appropriate use. Where reported, ASPs were generally associated with improvements in microbial outcomes, including institutional resistance patterns or resistance in the study population. Few data were provided on harms, sustainability, or key intervention components. Studies were typically of short duration, low in methodological quality, and varied in study design, populations enrolled, hospital setting, ASP intent, intervention composition and implementation, comparison group, and outcomes assessed. CONCLUSIONS: Numerous studies suggest that ASPs can improve prescribing and microbial outcomes. Strength of evidence was low, and most studies were not designed adequately to detect improvements in mortality or other patient outcomes, but obvious adverse effects on patient outcomes were not reported.

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.

Pharmacologic therapy for primary restless legs syndrome: a systematic review and meta-analysis.

IMPORTANCE: Restless legs syndrome (RLS) is a neurological disorder characterized by unpleasant sensations in the legs and a distressing, irresistible urge to move them. We conducted a systematic review to evaluate efficacy, safety, and comparative effectiveness of pharmacologic treatments for primary RLS. EVIDENCE ACQUISITION: We included randomized controlled trials (RCTs), published in English, reporting efficacy outcomes and harms of pharmacologic treatments for primary RLS of at least 4 weeks' duration. MEDLINE and other databases were searched through June 2012. Reviewers extracted outcomes and adverse events and rated the strength of evidence. RESULTS: We identified 29 eligible RCTs. We found high-strength evidence that the proportion of patients who had a clinically important response (International Restless Legs Syndrome [IRLS] responders), defined as a 50% or greater reduction from baseline in mean IRLS symptom scale scores, was greater with dopamine agonist therapy compared with placebo (61% vs 41%) (risk ratio, 1.60 [95% CI, 1.38-1.86]; 7 trials). Dopamine agonists also improved patient-reported sleep scale scores and quality-of-life measures. High-strength evidence demonstrated that calcium channel alpha-2-delta ligands increased the proportion of IRLS responders compared with placebo (61% vs 37%) (risk ratio, 1.66 [95% CI, 1.33-2.09]; 3 trials). Adverse events associated with dopamine agonists included nausea, vomiting, and somnolence. Alpha-2-delta ligands adverse events included somnolence and unsteadiness or dizziness. CONCLUSIONS AND RELEVANCE: On the basis of short-term RCTs that enrolled highly selected populations with long-term high-moderate to very severe symptoms, dopamine agonists and calcium channel alpha-2-delta ligands reduced RLS symptoms and improved sleep outcomes and disease-specific quality of life. Adverse effects and treatment withdrawals due to adverse effects were common.

Couple and family involvement in adult mental health treatment: a systematic review.

We reviewed randomized controlled trials conducted in the United States from January, 1996 through December, 2011 that examined family interventions for adult mental health conditions. We identified 51 articles (39 trials) evaluating 21 different family interventions. Findings for behavioral couple or family therapy (BCT/BFT) and community reinforcement and training (CRAFT) for substance use disorders were each pooled separately for examination in meta-analyses. Findings suggest BCT/BFT reduced substance use (small-to-moderate effects) and improved relationship adjustment (large effects) compared to individually-oriented treatments. CRAFT increased treatment initiation three-fold but did not improve substance use or family functioning over alternative family interventions. Family focused therapy for bipolar disorder improved symptoms over less intensive treatments with mixed findings when compared to equally intensive treatments. For both bipolar disorder and schizophrenia spectrum disorders, the few trials meeting our search criteria and heterogeneity among trials precluded generating broader conclusions regarding which family interventions are most effective for US populations. Overall, trials were limited in their methodological quality, and many interventions were evaluated in one trial. Future research is needed to replicate findings for these single trials, examine relationship distress as a moderator of outcome, and examine BCT/BFT among dual substance using couples and outside the research group frequently represented.

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.

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.

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.

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.

Lactose intolerance and health.

OBJECTIVES: We systematically reviewed evidence to determine lactose intolerance (LI) prevalence, bone health after dairy-exclusion diets, tolerable dose of lactose in subjects with diagnosed LI, and management. DATA SOURCES: We searched multiple electronic databases for original studies published in English from 1967-November 2009. REVIEW METHODS: We extracted patient and study characteristics using author's definitions of LI and lactose malabsorption. We compared outcomes in relation to diagnostic tests, including lactose challenge, intestinal biopsies of lactase enzyme levels, genetic tests, and symptoms. Fractures, bone mineral content (BMC) and bone mineral density (BMD) were compared in categories of lactose intake. Reported symptoms, lactose dose and formulation, timing of lactose ingestion, and co-ingested food were analyzed in association with tolerability of lactose. Symptoms were compared after administration of probiotics, enzyme replacements, lactose-reduced milk and increasing lactose load. RESULTS: Prevalence was reported in 54 primarily nonpopulation based studies (15 from the United States). Studies did not directly assess LI and subjects were highly selected. LI magnitude was very low in children and remained low into adulthood among individuals of Northern European descent. For African American, Hispanic, Asian, and American Indian populations LI rates may be 50 percent higher in late childhood and adulthood. Small doses of lactose were well tolerated in most populations. Low level evidence from 55 observational studies of 223,336 subjects indicated that low milk consumers may have increased fracture risk. Strength and significance varied depended on exposure definitions. Low level evidence from randomized controlled trials (RCTs) of children (seven RCTs) and adult women (two RCTs) with low lactose intake indicated that dairy interventions may improve BMC in select populations. Most individuals with LI can tolerate up to 12 grams of lactose, though symptoms became more prominent at doses above 12 grams and appreciable after 24 grams of lactose; 50 grams induced symptoms in the vast majority. A daily divided dose of 24 grams was generally tolerated. We found insufficient evidence that use of lactose reduced solution/milk, with lactose content of 0-2 grams, compared to a lactose dose of greater than 12 grams, reduced symptoms of lactose intolerance. Evidence was insufficient for probiotics (eight RCTs), colonic adaptation (two RCTs) or varying lactose doses (three RCTs) or other agents (one RCT). Inclusion criteria, interventions, and outcomes were variable. Yogurt and probiotic types studied were variable and results either showed no difference in symptom scores or small differences in symptoms that may be of low clinical relevance. CONCLUSIONS: There are race and age differences in LI prevalence. Evidence is insufficient to accurately assess U.S. population prevalence of LI. Children with low lactose intake may have beneficial bone outcomes from dairy interventions. There was evidence that most individuals with presumed LI or LM can tolerate 12-15 grams of lactose (approximately 1 cup of milk). There was insufficient evidence regarding effectiveness for all evaluated agents. Additional research is needed to determine LI treatment effectiveness.