Indulis Rutks

Systematic Review: Comparative Effectiveness and Harms of Treatments for Clinically Localized Prostate Cancer

Context Sorting through the proven benefits and harms of the multiple strategies available to treat clinically localized prostate cancer is difficult. Contribution This systematic review of 18 randomized trials and 473 observational studies found little high-quality evidence that established the superiority of one therapy over another. All treatments, including androgen deprivation, radical prostatectomy, and radiotherapy, caused urinary, bowel, or sexual dysfunction; the frequency, duration, and severity of these adverse events varied among treatments. Implication Available data insufficiently characterize the relative benefits of various treatments for clinically localized prostate cancer, and all therapies cause some harms. The Editors In 2007, prostate cancer was diagnosed in an estimated 218900 men in the United States, and approximately 27050 men died of the disease. Approximately 90% of men have disease confined to the prostate gland (clinically localized disease). Prostate cancer incidence increased and disease-specific mortality rates decreased after introduction of the prostate-specific antigen (PSA) blood test and with greater use of early interventions (1). Treatment goals are to prevent death and disability from prostate cancer while minimizing intervention-related complications. Common treatments include watchful waiting (expectant management or active surveillance), surgery to remove the prostate gland (radical prostatectomy), external-beam radiation therapy (EBRT) and interstitial radiation therapy (brachytherapy), and androgen deprivation. Patient treatment decisions incorporate physician recommendations; estimated likelihood of cancer progression without early intervention; and treatment-related convenience, costs, and potential for eradication and adverse effects (2). Little is known about how patient and tumor characteristics modify treatment outcomes. This report summarizes evidence from a review prepared for the Agency for Healthcare Research and Quality (3). We determined the comparative short- and long-term benefits and harms of therapies for clinically localized prostate cancer and how patient and tumor characteristics affect the outcomes of these therapies, overall and differentially. Methods Data Sources and Selection of Randomized, Controlled Trials We identified randomized, controlled trials (RCTs) published through mid-September 2007 by using the Cochrane Library (through Issue 3, 2007) and the Cochrane Review Group in Prostate Diseases and Urologic Malignancies specialized registry (through November 2007) (Appendix Figure 1). We included studies if they enrolled men with clinically localized disease (tumor stage T1 or T2) and randomly allocated them to any prostate cancer treatment, including usual care or watchful waiting. We included RCTs that enrolled men with advanced disease (tumor stage T3 or T4) if outcomes were reported separately for localized disease. Appendix Figure 1. Study flow diagram. AUA = American Urological Association; RCT = randomized, controlled trial; RP = radical prostatectomy. Data Sources and Selection of Observational Studies Very few RCTs compared major treatment options, especially for PSA-detected prostate cancer (Appendix Figure 1). Therefore, we reanalyzed a database that primarily comprised nonrandomized reports that we had previously extracted under a separate contract with the American Urological Association (AUA) Prostate Cancer Clinical Guideline Panel (4). The AUA panel used PubMed to identify English-language articles published from 1991 through April 2004. We rejected articles if authors did not report or stratify outcomes for localized disease or reported on fewer than 50 patients. Our review indicated that this database varied greatly in effectiveness estimates, outcome reporting, lack of controls or risk adjustment, and likelihood that it contained results from studies using identical or nearly identical samples. Our technical expert panel recommended against updating this search because the panel did not believe that additional data from nonrandomized studies would provide reliable evidence for assessing comparative effectiveness. We used results from the AUA database to evaluate and demonstrate the range of specific outcomes reported with each intervention in nonrandomized studies and to further assess harms. We obtained additional data on harms and patient satisfaction from the Prostate Cancer Outcomes Study because it is a large, nationally representative prospective survey of men with localized prostate cancer (5). Investigators designed the Prostate Cancer Outcomes Study to assess the long-term health-related quality-of-life outcomes in a large, diverse population-based sample of men in whom prostate cancer was diagnosed in 1994 or 1995. Eligible men were treated in community-based settings and resided in 1 of 6 U.S. Surveillance, Epidemiology, and End Result geographic regions. No RCT evaluated emerging technologies, and the AUA database contained little information on these therapies. Therefore, we used MEDLINE (between April 2004 and September 2007) and contact with Endocare (a manufacturer of cryotherapy devices) to identify and include English-language nonrandomized trials, reviews, and case series of cryotherapy, laparoscopic or robotic-assisted radical prostatectomy, high-intensity focused ultrasonography, proton-beam radiation, and intensity-modulated radiation therapy that reported patient outcomes regardless of size or duration. Study Selection for Effect of Patient and Tumor Characteristics We addressed the effect of patient and tumor characteristics on outcomes of therapies by reviewing RCTs for comparative effectiveness according to age, race, comorbid condition or PSA level, tumor stage, histologic grade, and tumor risk strata. We extracted any study from the AUA database or U.S. populationbased studies that had outcomes stratified according to age or race, looking for comparative effectiveness between treatments according to these factors. We used U.S. populationbased observational studies to evaluate the effect of tumor characteristics on the natural history and survival of men with prostate cancer treated with watchful waiting. Data Extraction and Quality Assessment Two researchers independently abstracted information on study, patient, tumor, and intervention characteristics and outcomes. Outcomes included all-cause and disease-specific mortality, biochemical and clinical progression, adverse events, and patient satisfaction. We assessed the study quality of RCTs on the basis of allocation concealment (6), intention-to-treat-analysis, length of follow-up, and dropouts or loss to follow-up. We rated the strength of the evidence as high (consistent results from 2 high-quality studies with long-term follow-up), medium (data from <2 high-quality studies or studies that did not have long-term follow-up), or low (inconsistent results, studies of low quality or from populations with little relevance to current patients or practice) (3). We considered evidence from nonrandomized trials, case series, and meta-analyses of these studies as low strength. We evaluated applicability of patient populations, clinical settings, and length of follow-up and adjustment for confounding. Data Synthesis and Statistical Analysis Only 3 trials of radical prostatectomy plus neoadjuvant androgen deprivation had data that permitted pooling. We analyzed overall mortality, disease-specific mortality, and biochemical progression or recurrence by using Cochrane Collaboration Review Manager software, version 4.2 (The Cochrane Collaboration, Oxford, United Kingdom) (7). A chi-square test with a P value less than 0.100 and I 2 value greater than 50% indicated statistical heterogeneity (8). We calculated absolute risk differences, odds ratios, and 95% CIs by using random-effects models (9). We present outcomes individually according to study size and duration of follow-up. Role of the Funding Source This project was prepared by the Minnesota Evidence-based Practice Center, Minneapolis, Minnesota, with funding from the Agency for Healthcare Research and Quality. The funding source suggested the initial questions and provided copyright release for this manuscript but did not participate in the literature search, data analysis, or interpretation of the results. Results Summary of Evidence on Treatment Effectiveness The AUA panel search and our additional searches identified 14045 potentially relevant articles. Eighteen RCTs and 473 observational studies met the inclusion criteria. No treatment option had consistent results from at least 2 high-quality RCTs with adequate follow-up and statistical power (Table 1). Only 3 RCTs (1012) compared effectiveness between major treatment categories (radical prostatectomy vs. radiation therapy or watchful waiting). None enrolled men with primarily PSA-detected disease. Many RCTs were inadequately powered to provide long-term survival outcomes. Most reported biochemical progression or recurrence as the main outcomes. No RCT evaluated cryotherapy, laparoscopic or robotic-assisted radical prostatectomy, primary androgen deprivation, high-intensity focused ultrasonography, proton-beam radiation, or intensity-modulated radiation therapy. Table 1. Summary of Evidence on the Comparative Effectiveness and Harms of Therapies for Localized Prostate Cancer Nonrandomized studies varied widely in treatment effectiveness and harms (Figures 1 and 2). The definitions of outcomes (for example, the criteria used to define biochemical progression) and their reporting varied considerably. Investigators rarely stratified outcomes according to patient and tumor characteristics. Many studies included patients with locally advanced disease but did not analyze outcomes on the basis of tumor stage. Figure 1. Overall survival at time points, by treatment, from nonrandomized studies. The symbol size is proportional to the number of patients:

KDOQI Clinical Practice Guideline for Hemodialysis Adequacy: 2015 Update

The National Kidney Foundations Kidney Disease Outcomes Quality Initiative (KDOQI) has provided evidence-based guidelines for all stages of chronic kidney disease (CKD) and related complications since 1997. The 2015 update of the KDOQI Clinical Practice Guideline for Hemodialysis Adequacy is intended to assist practitioners caring for patients in preparation for and during hemodialysis. The literature reviewed for this update includes clinical trials and observational studies published between 2000 and March 2014. New topics include high-frequency hemodialysis and risks; prescription flexibility in initiation timing, frequency, duration, and ultrafiltration rate; and more emphasis on volume and blood pressure control. Appraisal of the quality of the evidence and the strength of recommendations followed the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Limitations of the evidence are discussed and specific suggestions are provided for future research.

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, most commonly mild traumatic brain injury (mTBI), and experiencing posttraumatic stress disorder (PTSD). Clinical guidelines for mTBI and PTSD do not focus on the co-occurrence of these conditions (mTBI/PTSD). A synthesis of the evidence on prevalence, diagnostic accuracy, and treatment effectiveness for mTBI/PTSD would be of use to clinicians, researchers, and policymakers. Methods:We conducted a 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 brain injury and PTSD, or diagnostic accuracy or treatment effectiveness specific to mTBI/PTSD. Results:Thirty-four studies met inclusion criteria. None evaluated diagnostic accuracy or treatment effectiveness. Studies varied considerably in design. Frequency of mTBI/PTSD ranged from 0% to 89%. However, in 3 large studies evaluating Iraq and Afghanistan war veterans, frequencies of probable 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 study parameters, including aims and assessment methods. Studies using consistent, validated methods to define and measure mTBI history and PTSD are needed.

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.

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 physicians 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.

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.

Antiviral Therapy for Adults With Chronic Hepatitis B: A Systematic Review for a National Institutes of Health Consensus Development Conference

Hepatitis B is highly prevalent, with 350 million chronic cases worldwide (1). Despite immunization efforts, 4713 incident cases of hepatitis B were diagnosed in the United States in 2006 (2). An estimated 2000 to 4000 deaths per year in the United States are related to chronic hepatitis B liver diseases (3), including liver cirrhosis and hepatocellular carcinoma (4). Because most patients are asymptomatic, treatment goals of antiviral therapy include long-term prevention of progression, development of cirrhosis and liver failure, and hepatocellular carcinoma. Short-term intermediate laboratory responses have been proposed as potential surrogate measures of treatment effects on clinical outcomes (1). Normalization of liver enzyme levels, viral suppression and clearance, reduction in histologic scores of liver inflammation or fibrosis, and combinations of these outcomes have been used to measure response to antiviral drugs or development of antiviral resistance (1, 5). Seven antiviral agents are approved to treat hepatitis B in the United States, including oral medications (lamivudine, telbuvidine, adefovir, tenofovir, and entecavir) and injected interferons (standard interferon-2b and pegylated interferon-2a). Other agents are under investigation. The U.S. Food and Drug Administration approved tenofovir for adults in August 2008 on the basis of ongoing, unpublished trials that compared tenofovir with adefovir on intermediate outcomes, the results of which were not available for our review (6). This review was commissioned as background material for the National Institutes of Health Consensus Development Conference on Management of Chronic Hepatitis B in Adults to synthesize the published evidence about the effectiveness of interferon therapy, oral therapy, and various combinations with defined or continuous courses of treatment. The full report, including a detailed description of our methods, is available at www.ahrq.gov/downloads/pub/evidence/pdf/hepb/hepb.pdf (7). Methods Data Sources and Study Selection We searched MEDLINE, PubMed, the Cochrane Library (8), and other databases (911). We included randomized, controlled clinical trials (RCTs) 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 (HBV) DNA; aspartate aminotransferase and alanine aminotransferase (ALT) levels; and histologic necroinflammatory or fibrosis scores after therapy with interferon-2b, pegylated interferon-2a, lamivudine, adefovir, entecavir, and telbivudine (12). Studies that enrolled at least 50 adults and provided treatment for 24 weeks or more were eligible for this review. Interferon studies of any size were eligible if participants were given treatment for at least 12 weeks. We excluded studies evaluating pregnant women, patients with hepatocellular carcinoma or HIV infection at baseline, patients undergoing chemotherapy or liver transplantation, or patients with several causes of hepatitis, unless outcomes for participants meeting our eligibility criteria were reported separately. The full report describes the search strategies (7). We included publications from the multinational HBV 99-01 Study Group assessing pegylated interferon-2b, a treatment that has been intensively examined in patients with chronic hepatitis B but is not yet approved in the United States (13). Three investigators independently measured study eligibility (14). Data Extraction and Quality Assessment Three researchers independently evaluated the studies and extracted data to detect errors and discrepancies (14). We abstracted the number of events among treatment groups to calculate rates, relative risks (RRs), and absolute risk differences (15). We abstracted the number of patients randomly assigned to each treatment group as the denominator to calculate estimates, applying the intention-to-treat principle. We recorded intervals for outcome assessments in weeks from randomization for the active-treatment period and from the end of treatment for follow-up assessments. We prioritized clinical outcomes in the assessment of treatment benefits and harms. Sustained HBsAg loss or seroconversion was considered the criterion for resolution of hepatitis B viral infection and a major goal of antiviral therapy (1). Liver histologic outcomes included improved necroinflammatory and fibrosis scores. Sustained ALT normalization as diagnostic criteria of hepatocyte injury and sustained clearance of HBV DNA were assigned as secondary outcomes. Although positive associations with better clinical outcomes exist in observational studies, both outcomes may reverse after treatment. Because low levels of evidence from observational studies suggested that HBeAg-negative status was associated with worse clinical outcomes, we defined sustained HBeAg seroconversion as a desirable intermediate outcome. We analyzed RCTs for participant selection, duration of and loss to follow-up, intention-to-treat principle, masking of treatment status, randomization scheme and its adequacy, allocation concealment, and justification of sample sizes (16). We assessed the level of evidence on the basis of the Grading of Recommendations Assessment, Development and Evaluation Working Group criteria (17, 18). We assigned a low level of evidence when data were from small RCTs or RCTs with flaws in design or analysis or were from post hoc subgroup analysis. We assigned a moderate level of evidence when a single, large multinational study or several small RCTs reported consistent associations between antiviral agents and outcomes and a high level of evidence when several high-quality studies in applicable patients reported consistent sustained effects at least 6 months after therapy. Data Synthesis and Analysis The full report includes evidence tables that summarize results of individual studies (7). We compared baseline data across the studies to test for differences in the target sample and to detect unusual patterns in the data (1921). Analyses were conducted separately for clinical, biochemical, virologic, and histologic outcomes and for RRs and absolute risk differences. The protocol for meta-analyses was created according to recommendations (22, 23) to assess the consistency of the association between treatments and outcomes with random-effects models (24). Pooling criteria included the same operational definitions of outcomes and drug interventions (23). We used chi-square tests to assess heterogeneity (25, 26). Calculations used Stata statistical software, version 9.2 (StataCorp, College Station, Texas) (27). We assumed the presence of publication bias and did not use statistical tests for bias caused by sparse and heterogeneous data (14, 2830). Role of the Funding Source The Agency for Healthcare Research and Quality suggested the initial questions and provided copyright release for this manuscript. The funding source had no role in the literature search, data analysis, conduct of the study, preparation of the review, or interpretation of the results. The funding source reviewed and approved the submitted manuscript without revisions. Results Ninety-three articles represented 60 unique RCTs (31102). The full report contains the study flow diagram and the appendix with excluded studies (7). Studies enrolled 20 to 1367 patients who were predominately HBeAg-positive. Men constituted 78% of enrollees. Most enrollees were Asian (64%) or white (30%). The estimated duration of infection, reported in 8 studies, ranged from approximately 2 to 6 years. However, individual patient duration of infection ranged from 6 months to 20 years (3140). Clinical Outcomes Studies that reported death, liver-related death, hepatocellular carcinoma, hepatic decompensation, or cirrhosis (Table) were not designed and did not have sufficient power to reliably assess drug effects on these clinical outcomes. Table. Effects of Drug Therapies for Chronic Hepatitis B on Clinical Outcomes Death was assessed in 13 studies, with very few deaths reported (36, 3950). Low-level evidence suggested that lamivudine (41), entecavir (4347), interferon-2b (36, 39, 48), pegylated interferon-2a (49), pegylated interferon-2b (50), and adefovir (42) did not decrease mortality. Two studies assessed cirrhosis with small sample size and relatively short-term treatment with interferon-2b. Reduction in cirrhosis incidence (40) or prevalence (51) was not observed. Few events occurred, and the studies were not sufficiently powered to detect differences in cirrhosis (52). Three studies reported hepatic decompensation with very few events (44, 47, 53). There was no significant difference in hepatic decompensation after administration of lamivudine versus placebo (55) or entecavir versus lamivudine (44, 47). A multicenter study involving 651 Asian patients (58% were HBeAg-positive) with confirmed cirrhosis (61%) or advanced fibrosis (41) reported a decrease in disease progression (7.8% vs. 17.7% [hazard ratio, 0.45; P= 0.001]) for lamivudine versus placebo. Disease progression was the first occurrence of an increase of at least 2 points in the ChildPugh score, hepatic decompensation, bleeding varices, renal insufficiency, bleeding gastric or esophageal varices, spontaneous bacterial peritonitis with proven sepsis, hepatocellular carcinoma, or death related to liver disease. Four studies reported hepatocellular carcinoma. None demonstrated a statistically significant difference compared with no treatment after lamivudine (41), interferon-2b (54), prolonged adefovir therapy (42), or interferon monotherapy with and without corticosteroids (51). Incidence of hepatocellular carcinoma did not differ between lamivudine and placebo in the multicenter study of patients with confirmed cirrhosis or advanced fibrosis mention

Diet, Fluid, or Supplements for Secondary Prevention of Nephrolithiasis: A Systematic Review and Meta-Analysis of Randomized Trials

CONTEXT Although numerous trials have evaluated efficacy of diet, fluid, or supplement interventions for secondary prevention of nephrolithiasis, few are included in previous systematic reviews or referenced in recent nephrolithiasis management guidelines. OBJECTIVE To determine efficacy and safety of diet, fluid, or supplement interventions for secondary prevention of nephrolithiasis. EVIDENCE ACQUISITION Systematic review and meta-analysis of trials published January 1950 to March 2008. Sources included Medline and bibliographies of retrieved articles. Eligible trials included adults with a history of nephrolithiasis; compared diet, fluids, or supplements with control; compared relevant outcomes between randomized groups (eg, stone recurrence); had > or = 3 mo follow-up; and were published in the English language. Data were extracted on participant and trial characteristics, including study methodologic quality. EVIDENCE SYNTHESIS Eight trials were eligible (n=1855 participants). Study quality was mixed. In two trials, water intake > 2 l/d or fluids to achieve urine output > 2.5 l/d reduced stone recurrence (relative risk: 0.39; 95% confidence interval: 0.19-0.80). In one trial, fewer high soft drink consumers assigned to reduced soft drink intake had renal colic than controls (34% vs 41%, p=0.023). Content and results of multicomponent dietary interventions were heterogeneous; in one trial, fewer participants assigned increased dietary calcium, low animal protein, and low sodium had stone recurrence versus controls (20% vs 38%, p=0.03), while in another trial, more participants assigned diets that included low animal protein, high fruit and fiber, and low purine had recurrent stones than controls (30% vs 4%, p=0.004). No trials examined the independent effect of altering dietary calcium, sodium, animal protein, fruit and fiber, purine, oxalate, or potassium. Two trials showed no benefit of supplements over control treatment. Adverse event reporting was poor. CONCLUSIONS High fluid intake decreased risk of recurrent nephrolithiasis. Reduced soft drink intake lowered risk in patients with high baseline soft drink consumption. Data for other dietary interventions were inconclusive, although limited data suggest possible benefit from dietary calcium.

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.

Pygeum africanum for the treatment of patients with benign prostatic hyperplasia : A systematic review and quantitative meta-analysis

PURPOSE To conduct a systematic review and quantitative meta-analysis of the therapeutic efficacy and tolerability of Pygeum africanum in men with symptomatic benign prostatic hyperplasia. METHODS Studies were identified through the search of Medline (1966 to 2000), Embase, Phytodok, the Cochrane Library, bibliographies of identified trials and review articles, and contact with relevant authors and drug companies. Randomized trials were included if participants had symptomatic benign prostatic hyperplasia, the intervention was a preparation of P. africanum alone or in combination with other phytotherapeutic agents, a control group received placebo or other pharmacologic therapies for benign prostatic hyperplasia, and treatment duration was at least 30 days. Two investigators independently extracted key data on design features, subject characteristics, and therapy allocation. RESULTS A total of 18 randomized controlled trials involving 1,562 men met the inclusion criteria and were analyzed. Many studies did not report results in a method that permitted meta-analysis. Only 1 of the studies reported a method of treatment allocation concealment, although 17 were double-blinded. The mean study duration was 64 days (range 30 to 122). Compared with placebo in 6 studies, P. africanum provided a moderately large improvement in the combined outcome of urologic symptoms and flow measures as assessed by an effect size defined by the difference of the mean change for each outcome divided by the pooled standard deviation for each outcome (-0.8 SD [95% confidence interval (CI): -1.4 to -0.3]). Summary estimates of individual outcomes were also improved by P. africanum. Men were more than twice as likely to report an improvement in overall symptoms (risk ratio = 2.1, 95% CI: 1.40 to 3.1). Nocturia was reduced by 19% and residual urine volume by 24%; peak urine flow was increased by 23%. Adverse effects due to P. africanum were mild and similar to placebo. The overall dropout rate was 12% and was similar for P. africanum (13%), placebo (11%), and other controls (8%; P = 0.4 versus placebo and P = 0.5 versus other controls). CONCLUSIONS The literature on P. africanum for the treatment of benign prostatic hyperplasia is limited by the short duration of studies and the variability in study design, the use of phytotherapeutic preparations, and the types of reported outcomes. However, the evidence suggests that P. africanum modestly, but significantly, improves urologic symptoms and flow measures. Further research is needed using standardized preparations of P. africanum to determine its long-term effectiveness and ability to prevent complications associated with benign prostatic hyperplasia.