L-arginine supplementation and risk factors of cardiovascular diseases in healthy men: a double-blind randomized clinical trial. Summarizing systematic reviews: methodological development, conduct and reporting of an umbrella review approach L-Arginine enhances the triglyceride-lowering effect of simvastatin in patients with elevated plasma triglycerides. How to write an evidence-based clinical review article. How Quickly Do Systematic Reviews Go Out of Date? A Survival Analysis Probiotic Therapy of the Irritable Bowel Syndrome: Why Is the Evidence Still Poor and What Can Be Done About It? Arginine supplementation modulates pig plasma lipids, but not hepatic fatty acids, depending on dietary protein level with or without leucine Reporting of prognostic markers: current problems and development of guidelines for evidence-based practice in the future Effects of Arginine-Based Supplements on the Physical Working Capacity at the Fatigue Threshold Identifying, documenting, and examining heterogeneity in systematic reviews of complex interventions. Psychological interventions for pediatric chronic pain – The good news and the challenges ahead Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients. Endocrine and lipid effects of oral L-arginine treatment in healthy postmenopausal women. Protocol for an overview of systematic reviews of interventions to reduce unscheduled hospital admissions among adults Key Steps in Conducting Systematic Reviews for Underpinning Clinical Practice Guidelines: Methodology of the European Association of Urology. [Effect of L-arginine on platelet aggregation, endothelial function adn exercise tolerance in patients with stable angina pectoris]. Publication bias in research synthesis: sensitivity analysis using a priori weight functions. Postprandial hyperglycemia impairs vascular endothelial function in healthy men by inducing lipid peroxidation and increasing asymmetric dimethylarginine:arginine. Dietary l-arginine supplementation enhances placental growth and reproductive performance in sows Seeing the forests and the trees—innovative approaches to exploring heterogeneity in systematic reviews of complex interventions to enhance health system decision-making: a protocol Effectiveness of exercise interventions on physical function in community-dwelling frail older people: an umbrella review of systematic reviews Prevention of cervical cancer in HIV-seropositive women from developing countries: a systematic review protocol Protocol for systematic reviews of determinants/correlates of obesity-related dietary and physical activity behaviors in young children (preschool 0 to 6 years): evidence mapping and syntheses
Context : The effect of L-arginine on risk factors of cardiovascular diseases ( CVD ) has mostly focused on western countries . Since cardiovascular diseases is the second cause of death in Iran and , as far as we are aware , there have been no studies about the effect of L-arginine on CVD risk factors , the aim of this trial was to assess the effects of L-arginine supplementation on CVD risk factors in healthy men . Objective : The purpose of this study was to evaluate the effect of low-dose L-arginine supplementation on CVD risk factors ( lipid profile , blood sugar and blood pressure ) in Iranian healthy men . Design , setting , participants : We conducted a double-blind r and omized controlled trial in 56 patients selected from sport clubs at the Isfahan University of Medical Science between November 2013 and December 2013 . Interventions : Healthy men received L-arginine supplementation ( 2000 mg daily ) in the intervention group or placebo ( 2000 mg maltodextrin daily ) in the control group for 45 days . Main outcome measure : The primary outcome measures were we measured the levels of fasting blood sugar , blood pressure and lipid profile including triglyceride ( TG ) , cholesterol , LDL and HDL in healthy subjects . It was hypothesized that these measures would be significantly improved in those receiving L-arginine supplementation . at the beginning and end of the study . Results : In this trial , we had complete data for 52 healthy participants with mean age of 20.85±4.29 years . At the end of study , fasting blood sugar ( P=0.001 ) and lipid profile ( triglycerideTG ( P<0.001 ) , cholesterol ( P<0.001 ) , LDL ( P=0.04 ) , HDL ( P=0.015 ) ) decreased in the L-arginine group but we found no significant change in the placebo group . In addition , the reduction of fasting blood sugar and lipid profile in L-arginine was significant compared with placebo group . No significant changes were found about systolic ( P=0.81 ) and diastolic blood pressure either in L-arginine or placebo group . ( P=0.532 ) . Conclusion : The use of L-arginine significantly improved outcomes compared to placebo Aims : With the increase in the number of systematic review s available , a logical next step to provide decision makers in healthcare with the evidence they require has been the conduct of review s of existing systematic review s. Syntheses of existing systematic review s are referred to by many different names , one of which is an umbrella review . An umbrella review allows the findings of review s relevant to a review question to be compared and contrasted . An umbrella review 's most characteristic feature is that this type of evidence synthesis only considers for inclusion the highest level of evidence , namely other systematic review s and meta-analyses . A methodology working group was formed by the Joanna Briggs Institute to develop method ological guidance for the conduct of an umbrella review , including diverse types of evidence , both quantitative and qualitative . The aim of this study is to describe the development and guidance for the conduct of an umbrella review . Methods : Discussion and testing of the elements of methods for the conduct of an umbrella review were held over a 6-month period by members of a methodology working group . The working group comprised six participants who corresponded via teleconference , e-mail and face-to-face meeting during this development period . In October 2013 , the methodology was presented in a workshop at the Joanna Briggs Institute Convention . Workshop participants , review authors and method ologists provided further testing , critique and feedback on the proposed methodology . Results : This study describes the methodology and methods developed for the conduct of an umbrella review that includes published systematic review s and meta-analyses as the analytical unit of the review . Details are provided regarding the essential elements of an umbrella review , including presentation of the review question in a Population , Intervention , Comparator , Outcome format , nuances of the inclusion criteria and search strategy . A critical appraisal tool with 10 questions to help assess risk of bias in systematic review s and meta-analyses was also developed and tested . Relevant details to extract from included review s and how to best present the findings of both quantitative and qualitative systematic review s in a reader friendly format are provided . Conclusions : Umbrella review s provide a ready means for decision makers in healthcare to gain a clear underst and ing of a broad topic area . The umbrella review methodology described here is the first to consider review s that report other than quantitative evidence derived from r and omized controlled trials . The methodology includes an easy to use and informative summary of evidence table to readily provide decision makers with the available , highest level of evidence relevant to the question posed We recently noticed a possible triglyceride-lowering effect during dietary supplementation with L-arginine . The major limitation of prior studies on L-arginine , however , was that triglyceride levels were not the primary end point , and patients were not necessarily hypertriglyceridemic . Therefore , we conducted a 2-arm , r and omized , double-blind study in 33 hypertriglyceridemic patients to investigate the hypothesis that oral L-arginine may lower serum triglyceride levels in hypertriglyceridemic patients on and off statins .  The study consisted of a 6-week run-in phase , 6 weeks of treatment with L-arginine ( n = 22 , 1.5 g bid ) or placebo ( n = 11 ) , and a 6-week extension period where simvastatin ( 20 mg qd ) was added . All patients received dietary advice during each study visit . Routine and lipid laboratory parameters were determined in the local routine clinical laboratory . Treatment with L-arginine alone had no effects on serum lipids compared to placebo . The combination of L-arginine with simvastatin led to a significantly stronger reduction in triglycerides compared to placebo plus simvastatin ( -140.5 + /- 149.2 mg/dL vs -56.1 + /- 85.0 mg/dL ; P = .048 ) . In addition , we found simvastatin-induced  increases in aspartate transaminase and fibrinogen to be attenuated by L-arginine as compared to placebo . We conclude from our data that L-arginine enhances the effects of simvastatin on lipid metabolism , but it has no triglyceride-lowering effects when given alone Traditional clinical review articles , also known as up date s , differ from systematic review s and meta-analyses . Up date s selectively review the medical literature while discussing a topic broadly . Non-quantitative systematic review s comprehensively examine the medical literature , seeking to identify and synthesize all relevant information to formulate the best approach to diagnosis or treatment . Meta-analyses ( quantitative systematic review s ) seek to answer a focused clinical question , using rigorous statistical analysis of pooled research studies . This article presents guidelines for writing an evidence -based clinical review article for American Family Physician . First , the topic should be of common interest and relevance to family practice . Include a table of the continuing medical education objectives of the review . State how the literature search was done and include several sources of evidence -based review s , such as the Cochrane Collaboration , BMJ 's Clinical Evidence , or the InfoRetriever Web site . Where possible , use evidence based on clinical outcomes relating to morbidity , mortality , or quality of life , and studies of primary care population s. In articles su bmi tted to American Family Physician , rate the level of evidence for key recommendations according to the following scale : level A ( r and omized controlled trial [ RCT ] , meta- analysis ) ; level B ( other evidence ) ; level C ( consensus/expert opinion ) . Finally , provide a table of key summary points Context Clinicians rely on systematic review s for current , evidence -based information . Contribution This survival analysis of 100 meta-analyses indexed in ACP Journal Club from 1995 to 2005 found that new evidence that substantively changed conclusions about the effectiveness or harms of therapies arose frequently and within relatively short time periods . The median survival time without substantive new evidence for the meta-analyses was 5.5 years . Significant new evidence was already available for 7 % of the review s at the time of publication and became available for 23 % within 2 years . Implication Clinical ly important evidence that alters conclusions about the effectiveness and harms of treatments can accumulate rapidly . The Editors Systematic review s have become increasingly common in recent years ( 1 ) and are recommended by many as the best sources of evidence to guide both clinical decisions ( 2 ) and health care policy ( 3 ) . For systematic review s to fulfill these roles , their findings must remain relatively stable for at least several years or effective mechanisms must exist for alerting end users to important changes in evidence . Yet , surprisingly little research has assessed the extent to which systematic review s become out of date or the rate at which this occurs ( 47 ) . Some organizations , such as the Cochrane Collaboration , recommend updating systematic review s every 2 years , but few empirical data guide this or other recommendations about updating . We sought to determine how quickly systematic review s meet explicitly defined criteria for changes in evidence of sufficient importance to warrant updating . We also sought to identify predictors of survival time , the time to such important changes in evidence . Survival time might vary depending on many factors , including the type of question posed by the original review ( for example , therapeutic or diagnostic ) , the types of studies included ( for example , r and omized trials or observational studies ) , and whether the systematic review provided quantitative synthesis . To limit such variation , we focused on systematic review s of r and omized , controlled trials that evaluated therapeutic benefit or harm by providing quantitative synthesis ( meta- analysis ) for at least 1 outcome . Methods Study Design and Sample We used a quasi-r and om process ( alphabetical sort order by author ) to select 100 systematic review s that were indexed in ACP Journal Club with an accompanying commentary between January 1995 and December 2005 ( with a search date no later than 31 December 2004 to ensure at least 1 full year for new evidence to appear ) . We chose this sampling frame because ACP Journal Club selects systematic review s that meet explicit quality st and ards and are deemed directly relevant to clinical practice ( 8) . We regarded the sample size of 100 as sufficiently large to achieve suitably narrow confidence intervals and to permit evaluation of up to 5 potential predictors of survival . Eligibility Criteria Eligible review s evaluated the benefit or harm of a specific drug , class of drug , device , or procedure ( invasive procedure or surgery ) and included r and omized or quasi-r and omized , controlled trials . We excluded evaluations of alternative and complementary medicines because the stability of review s of such therapies might differ substantially from review s of conventional therapies . We required that review s provide a point estimate and 95 % confidence interval for at least 1 outcome in the form of a relative risk , odds ratio , or absolute risk difference for binary outcomes and weighted mean differences for continuous outcomes . We excluded meta-analyses of individual-patient data , meta-regressions , and indirect meta-analyses because of the difficulty of determining whether new data would alter previous quantitative results . Two team members independently assessed eligibility , with disagreements resolved by consensus involving a third review er . When more than 1 review on the same topic was identified , only the earliest was included . Search ing For each review , search es for new trials included identifying new systematic review s on the same topic , su bmi tting relevant content terms to the Clinical Queries function in Ovid , applying the Related Articles function in PubMed to the 3 largest and the 3 most recent trials in the original review ( up to 6 trials in total ) , and using Scopus ( www . scopus .com/ scopus /home.url ) to identify new r and omized trials that cited the original review . When these search strategies yielded no eligible new trials , we conducted more comprehensive electronic search es and review ed relevant chapters in such sources as Clinical Evidence and UpTo Date to ensure that we had not missed new trials . Team members who had background s in both medicine and clinical research screened citations retrieved by the preceding methods to identify trials that would have met the inclusion criteria in the original review . Retrieved articles were screened in chronological order to ascertain quantitative or qualitative signals for the need for updating . The review protocol stopped when any criteria for updating were met . Each systematic review was discussed in detail , with the final statussignal for updating was or was not detectedadjudicated by consensus ( Figure 1 ) . Figure 1 . Overall process for determining updating status . ACP Journal Club Signals for the Need to Up date Systematic Review s In design ing criteria for comparing new findings with those in a previous review , we adapted methods used by other investigators to address similar problems with comparing 2 sets of results relating to the same question ( 913 ) , such as r and omized and nonr and omized studies of the same intervention . These investigators identified conflicting findings among different publications using a combination of quantitative thresholds for differences in effect magnitude and qualitative judgments about the language used to describe the results . We have similarly conceptualized quantitative and qualitative signals of potential changes in evidence that are sufficiently important to warrant updating previous systematic review s. Quantitative Signals Quantitative signals consisted of a change in statistical significance or relative change in effect magnitude of at least 50 % . We restricted these changes to those involving 1 of the primary outcomes of the original review or any mortality outcome . We also ignored trivial changes in statistical significance when the original and up date d meta-analytic results both had P values between 0.04 and 0.06so that quantitative signals of changes in evidence would represent robust indicators of the need to up date previous review s. Quantitative signals were detected by combining data from eligible new trials with the previous results using a fixed-effects approach . Use of fixed-effect models allowed pooling of the new trials with the previous meta-analytic result , as opposed to having to obtain original data from all of the included trials in each of 100 systematic review s. Although r and om-effects models are usually preferred to avoid spurious precision in the face of heterogeneity , our goal was to detect potential changes in evidence that would warrant a formal up date , not produce exact estimates of the up date d results . Qualitative Signals Qualitative signals included new information about harm sufficient to affect clinical decision making , important caveats to the original results , emergence of a superior alternate therapy , and important changes in certainty or direction of effect . Qualitative signals were detected by using explicit criteria for comparing the language in the original review with descriptions of findings in new systematic review s that addressed the same topic , pivotal trials , clinical practice guidelines , or recent editions of major textbooks ( for example , UpTo Date ) . Pivotal trials were defined as trials that had a sample size at least 3 times larger than that of the previous largest trial or were published in 1 of the 5 highest-impact general medical journals ( The New Engl and Journal of Medicine , Lancet , Journal of the American Medical Association , Annals of Internal Medicine , and the British Medical Journal ) . We defined 2 levels of importance for qualitative signals : potentially invalidating changes in evidence , which would make one no longer want clinicians or policymakers to base decisions on the original findings ( such as a pivotal trial that characterized treatment effectiveness in terms opposite of those in the original systematic review ) , and major changes in evidence , which would affect clinical decision making in important ways without invalidating the previous results ( such as the identification of patient population s for whom treatment is more or less beneficial ) . Major changes also included differing characterizations of effectiveness that were less extreme than those for potentially invalidating signals but that would still affect clinical decision making ( for example , a change from possibly beneficial to definitely beneficial ) . Of importance , such characterizations as possibly effective , probably effective , and promising , were all categorized as possibly effective . Thus , qualitative signals for changes in evidence captured substantive differences in the characterization of treatment effects , not merely semantic differences . Full definitions for each of the specific signals can be found at www.ohri.ca/UpdatingSystRevs . Data Collection For each review , we characterized the clinical content area , eligibility criteria for included trials , definitions of reported outcomes , number of included trials and participants , meta-analytic result for each outcome , identification of statistical heterogeneity , and excerpted quotations of the authors ' characterizations of the main results . We also abstract ed whether a given outcome was explicitly identified as 1 of the primary or main outcomes . We discounted identification of more than 3 such outcomes as inconsistent with the Background / Aims Despite numerous r and omized clinical trials and meta-analyses , there is no increased evidence for the efficacy of  probiotics  in the treatment of irritable bowel syndrome ( IBS ) . We review this evidence , identify and analyse the reasons for this lack of evidence and propose method ological improvements for future studies . Methods Based on a literature search , we identified 56 papers that matched the purpose of our analyses . Twenty-seven studies used multi-species bacterial preparations and 29 used single-strain probiotics . They were analysed regarding  patients included , treatment duration , probiotic dosage , and outcome measures . Results Trials in both groups suffered from heterogeneity with respect to probiotic concentration , duration of treatment , and other method ological issues ( crossover design and underpowered studies ) . This heterogeneity did not allow the application of a meta-analytic approach and a systematic review was therefore performed instead . Multi-strain preparations combined 2 to 8 different bacterial subspecies , mostly lactobacilli or bifidobacteria , and used variable lengths of treatments . Overall , more than 50 % of trials presented negative outcomes . The majority of the single-strain probiotic trials employing lactobacilli or Saccharomyces were negative , whereas trials employing bifidobacteria showed positive results . Conclusions The heterogeneity of the studies of probiotics in IBS questions the value of meta-analyses . The use of different bacterial strains and different mixtures of these strains , as well as different dosages , are the main contributors to this heterogeneity . Current data provides limited evidence for the efficacy of a small number of  single-strain probiotics  in IBS ( mostly bifidobacteria ) and sound studies following strict trial guidelines ( Food and Drug Administration and European Medicines Agency guidelines for clinical trials ) are needed . We summarised and proposed some method ological issues for future studies in the field Background In the present study , the effect of arginine and leucine supplementation , and dietary protein level , were investigated in commercial crossbred pigs to clarify their individual or combined impact on plasma metabolites , hepatic fatty acid composition and mRNA levels of lipid sensitive factors . The experiment was conducted on fifty-four entire male pigs ( Duroc × Pietrain × Large White × L and race crossbred ) from 59 to 92 kg of live weight . Each pig was r and omly assigned to one of six experimental treatments ( n = 9 ) . The treatments followed a 2 × 3 factorial arrangement , providing two levels of arginine supplementation ( 0 vs. 1 % ) and three levels of basal diet ( normal protein diet , NPD ; reduced protein diet , RPD ; reduced protein diet with 2 % of leucine , RPDL ) . Results Significant interactions between arginine supplementation and protein level were observed across plasma lipids . While dietary arginine  increased total lipids , total cholesterol , HDL-cholesterol , LDL-cholesterol , VLDL-cholesterol and triacylglycerols in NPD , the inverse effect was observed in RPD . Overall , dietary treatments had a minor impact on hepatic fatty acid composition . RPD increased 18:1c9 fatty acid while the combination of leucine and RPD reduced 18:0 fatty acid . Arginine supplementation increased the gene expression of FABP1 , which contributes for triacylglycerols synthesis without affecting hepatic fatty acids content . RPD , with or without leucine addition , upregulated the lipogenic gene CEBPA but downregulated the fat oxidation gene LPIN1 . Conclusions Arginine supplementation was responsible for a modulated effect on plasma lipids , which is dependent on dietary protein level . It consistently increased lipaemia in NPD , while reducing the correspondent metabolites in RPD . In contrast , arginine had no major impact , neither on hepatic fatty acids content nor on fatty acid composition . Likewise , leucine supplementation of RPD , regardless the presence of arginine , promoted no changes on total fatty acids in the liver . Ultimately , arginine , leucine and dietary protein reduction seem to be unrelated with fatty liver development Prognostic markers help to stratify patients for treatment by identifying patients with different risks of outcome ( e.g. recurrence of disease ) , and are important tools in the management of cancer and many other diseases . Systematic review and meta-analytical approaches to identifying the most valuable prognostic markers are needed because ( sometimes conflicting ) evidence relating to markers is often published across a number of studies . To investigate the practicality of this approach , an empirical investigation of a systematic review of  tumour markers for neuroblastoma was performed ; 260 studies of prognostic markers were identified , which considered 130 different markers . The reporting of these studies was often inadequate , in terms of both statistical analysis and presentation , and there was considerable heterogeneity for many important clinical /statistical factors . These problems restricted both the extraction of data and the meta- analysis of results from the primary studies , limiting feasibility of the evidence -based approach . Guidelines for reporting the results of primary prognostic marker studies in cancer , and other diseases , are given in order to facilitate both the interpretation of individual studies and the undertaking of systematic review s , meta- analysis and , ultimately , evidence -based practice . General availability of full individual patient data is a necessary step forward and would overcome the majority of problems encountered , including poorly reported summary statistics and variability in cutoff level , outcome assessed and adjustment factors used . It would also limit the problem of reporting bias , although publication bias will remain a concern until studies are prospect ively registered . Such changes in practice would help important evidence -based review s to be conducted in order to establish the most appropriate prognostic markers for clinical use , which should ultimately improve patient care Camic , CL , Housh , TJ , Zuniga , JM , Hendrix , CR , Mielke , M , Johnson , GO , and Schmidt , RJ . Effects of arginine-based supplements on the physical working capacity at the fatigue threshold . J Strength Cond Res 24(5 ) : 1306 - 1312 , 2010-The purpose of the present study was to examine the effects of daily oral administration of arginine-based supplements for 4 weeks on the physical working capacity at the fatigue threshold ( PWCFT ) . The PWCFT test is an electromyographic ( EMG ) procedure for estimating the highest power output that can be maintained without neuromuscular evidence of fatigue . The study used a double-blind , placebo-controlled design . Fifty college-aged men ( mean age ± SD = 23.9 ± 3.0 ) were r and omized into 1 of 3 groups : ( a ) placebo ( n = 19 ) ; ( b ) 1.5 g arginine ( n = 14 ) ; or ( c ) 3.0 g arginine ( n = 17 ) . The placebo was microcrystalline cellulose . The 1.5-g arginine group ingested 1.5 g of arginine and 300 mg of grape seed extract , whereas the 3.0 g arginine group ingested 3.0 g of arginine and 300 mg of grape seed extract . All subjects performed an incremental test to exhaustion on a cycle ergometer to determine their PWCFT before supplementation ( PRE ) and after 4 weeks of supplementation ( POST ) . Surface EMG signals were recorded from the vastus lateralis using a bipolar electrode arrangement during the incremental tests for the determination of the PRE and POST supplementation PWCFT values . There were significant mean increases ( PRE to POST ) in PWCFT for the 1.5 g ( 22.4 % ) and 3.0 g ( 18.8 % ) supplement groups , but no change for the placebo group ( −1.6 % ) . These findings supported the use of arginine-based supplements , at the dosages examined in the present investigation , as an ergogenic aid for untrained individuals This article describes approaches for planning , dealing , and analyzing heterogeneity in a systematic review of complex interventions . Approaches aim to generate a priori hypotheses of the mechanism of action of a complex intervention to identify the key variables that might contribute to variation among studies and guide statistical analysis . In addition to characteristics related to the population , intervention , and outcomes , we describe study -related variables , such as the way the interventions have been implemented and the context and conduct of studies . These approaches will guide review ers planning a meta- analysis and provide a rationale for not meta-analyzing data if there is too much variability . Potential difficulties in applying meta-analytical techniques to examine statistical association among study results and sources of potential heterogeneity are described ; these include the selection of a fixed or r and om-effects model , the risk of multiple testing and confounding when studies include different aspects of a complex intervention or different sub sample s of the intended participant pool In a 2002 systematic review of pediatric clinical trials Eccleston et al. [ 1 ] found that psychological therapies had a significant effect on pain reduction . Although that review sought to include all pain conditions , the available studies at the time focused almost exclusively on treatment of pediatric headache . In recent years , r and omized clinical trials ( RCTs ) have been published on other pediatric pain conditions , including abdominal pain and fibromyalgia . In addition , effects of psychological therapies on clinical outcomes beyond pain reduction , such as functional disability and emotional distress were examined . In this issue of Pain , Palermo et al. [ 4 ] present a timely meta-analytic review paper that reflects on these new developments OBJECTIVE This study was conducted to develop evidence -based clinical practice guidelines for nutrition support ( ie , enteral and parenteral nutrition ) in mechanically ventilated critically ill adults . OPTIONS The following interventions were systematic ally review ed for inclusion in the guidelines : enteral nutrition ( EN ) versus parenteral nutrition ( PN ) , early versus late EN , dose of EN , composition of EN ( protein , carbohydrates , lipids , immune-enhancing additives ) , strategies to optimize delivery of EN and minimize risks ( ie , rate of advancement , checking residuals , use of bedside algorithms , motility agents , small bowel versus gastric feedings , elevation of the head of the bed , closed delivery systems , probiotics , bolus administration ) , enteral nutrition in combination with supplemental PN , use of PN versus st and ard care in patients with an intact gastrointestinal tract , dose of PN and composition of PN ( protein , carbohydrates , IV lipids , additives , vitamins , trace elements , immune enhancing substances ) , and the use of intensive insulin therapy . OUTCOMES The outcomes considered were mortality ( intensive care unit [ ICU ] , hospital , and long-term ) , length of stay ( ICU and hospital ) , quality of life , and specific complications . EVIDENCE We systematic ally search ed MEDLINE and CINAHL ( cumulative index to nursing and allied health ) , EMBASE , and the Cochrane Library for r and omized controlled trials and meta-analyses of r and omized controlled trials that evaluated any form of nutrition support in critically ill adults . We also search ed reference lists and personal files , considering all articles published or unpublished available by August 2002 . Each included study was critically appraised in duplicate using a st and ard scoring system . VALUES For each intervention , we considered the validity of the r and omized trials or meta-analyses , the effect size and its associated confidence intervals , the homogeneity of trial results , safety , feasibility , and the economic consequences . The context for discussion was mechanically ventilated patients in Canadian ICUs .  BENEFITS , HARMS , AND COSTS The major potential benefit from implementing these guidelines is improved clinical outcomes of critically ill patients ( reduced mortality and ICU stay ) . Potential harms of implementing these guidelines include increased complications and costs related to the suggested interventions . SUMMARIES OF EVIDENCE AND RECOMMENDATIONS : When considering nutrition support in critically ill patients , we strongly recommend that EN be used in preference to PN . We recommend the use of a st and ard , polymeric enteral formula that is initiated within 24 to 48 hours after admission to ICU , that patients be cared for in the semirecumbent position , and that arginine-containing enteral products not be used . Strategies to optimize delivery of EN ( starting at the target rate , use of a feeding protocol using a higher threshold of gastric residuals volumes , use of motility agents , and use of small bowel feeding ) and minimize the risks of EN ( elevation of the head of the bed ) should be considered . Use of products with fish oils , borage oils , and antioxidants should be considered for patients with acute respiratory distress syndrome . A glutamine-enriched formula should be considered for patients with severe burns and trauma . When initiating EN , we strongly recommend that PN not be used in combination with EN . When PN is used , we recommend that it be supplemented with glutamine , where available . Strategies that maximize the benefit and minimize the risks of PN ( hypocaloric dose , withholding lipids , and the use of intensive insulin therapy to achieve tight glycemic control ) should be considered . There are insufficient data to generate recommendations in the following areas : use of indirect calorimetry ; optimal pH of EN  ; supplementation with trace elements , antioxidants , or fiber ; optimal mix of fats and carbohydrates ; use of closed feeding systems ; continuous versus bolus feedings ; use of probiotics ; type of lipids ; and mode of lipid delivery . VALIDATION This guideline was peer- review ed and endorsed by official representatives of the Canadian Critical Care Society , Canadian Critical Care Trials Group , Dietitians of Canada , Canadian Association of Critical Care Nurses , and the Canadian Society for Clinical Nutrition . SPONSORS This guideline is a joint venture of the Canadian Critical Care Society , the Canadian Critical Trials Group , the Canadian Society for Clinical Nutrition , and Dietitians of Canada . The Canadian Critical Care Society and the Institute of Nutrition , Metabolism , and Diabetes of the Canadian Institutes of Health Research provided funding for development of this guideline As a substrate for nitric oxide synthesis , L-arginine may give the same protection as estrogen , but its other biologic effects may adversely affect atherogenesis . Therefore , possible endocrine and lipid effects of L-arginine were investigated in a double-blind , placebo-controlled , single crossover study . After r and omization , oral L-arginine ( 9 g ) or placebo was given daily for 1 month , with crossover to the alternate therapy after a 1-month washout period , to 10 postmenopausal women receiving no estrogen .  Compared with placebo , L-arginine increased growth hormone ( 1.5+/-1.8 mg/L vs. 0.6+/-0.6 mg/L , P = .04 ) but had no effect on insulin and catecholamines . Total cholesterol , triglyceride , apolipoprotein E , and low- , very-low- , and high-density lipoprotein cholesterol levels were also unaffected . Lipoprotein(a ) measured by an immunoturbidimetric method was increased by L-arginine in 9 of 10 women relative to placebo ( 0.46+/-0.35 g/L vs. 0.38+/-0.30 g/L , P = .053 ) , and the changes in lipoprotein(a ) levels significantly correlated with the relative increase in growth hormone ( r = 0.85 , P = .03 ) . However , lipoprotein(a ) measured by an enzyme-linked immunosorbent assay failed to demonstrate significant changes . Lack of an increase by  L-arginine in lipoprotein(a ) with a verifiable apolipoprotein(a ) isoform-independent method , despite an increase in growth hormone , questions the validity of previous observations for growth hormone-induced increases in lipoprotein(a ) . The observed lack of effect on major endocrine hormones and lipid profile support the safety of oral L-arginine administration Introduction Unscheduled hospital admissions are an increasing burden on health systems worldwide . To date , initiatives to reduce admissions have had limited success as it is unclear which strategies effectively reduce admissions and are supported by a strong evidence -base . Therefore , we will conduct an overview to find , assess and summarise all published peer- review ed systematic review s of r and omised controlled trials that examine the effect of an intervention on  unplanned admissions among adults . Methods and analysis This is a protocol for a systematic overview of review s. We will search four data bases : Ovid MEDLINE , PubMed , Cochrane Data base of Systematic Review s and the Cochrane Data base of Abstract s of Review s of Effects . We will consider systematic review s and meta-analyses of r and omised controlled trials in adults ( ≥16 years old ) evaluating the effect of any intervention on unscheduled hospital admissions including those to treat , monitor , diagnose or prevent a health problem . We will only include review s that identified unscheduled hospitalisations as a prespecified outcome . Two authors will independently screen articles for inclusion using a priori criteria . We will assess the quality of included review s and extract ratings of the quality of evidence from within each review . We will create a hierarchical list of interventions based on estimates of absolute admission reductions and the quality of the evidence . Presentation of results will align with guidelines in the Cochrane H and book of Systematic Review s of Interventions and the Preferred Reporting Items for Systematic Review s and Meta- Analysis statement . Ethics and dissemination Ethics approval is not required . We will su bmi t the results of this study for peer- review publication . The results will inform future research and could be used by healthcare managers , administrators and policymakers to guide re source allocation decisions and inform local implementation and optimisation of interventions to reduce unscheduled hospital admissions CONTEXT The findings of systematic review s ( SRs ) and meta-analyses ( MAs ) are used for clinical decision making . The European Association of Urology has committed increasing re sources into the development of high quality clinical guidelines based on such SRs and MAs . OBJECTIVE In this paper , we have summarised the process of conducting SRs for underpinning clinical practice guidelines under the auspices of the European Association of Urology Guidelines Office . EVIDENCE ACQUISITION The process involves explicit methods and the findings should be reproducible . When conducting a SR , the essential first step is to formulate a clear and answerable research question . An extensive literature search lays the foundation for evidence synthesis . Data are extracted independently by two review ers and any disagreements are resolved by discussion or arbitration by a third review er . EVIDENCE SYNTHESIS In SRs , data for particular outcomes in individual r and omised controlled trials may be combined statistically in a meta- analysis to increase power when the studies are similar enough . Biases in studies included in a SR/MA can lead to either an over estimation or an under estimation of true intervention effect size , result ing in heterogeneity in outcome between studies . A number of different tools are available such as Cochrane Risk of Bias assessment tool for r and omised controlled trials . In circumstances where there is too much heterogeneity , or when a review has included nonr and omised comparative studies , it is more appropriate to conduct a narrative synthesis . The GRADE tool for assessing quality of evidence strives to be a structured and transparent system , which can be applied to all evidence , regardless of quality . A SR not only identifies , evaluates , and summarises the best available evidence , but also the gaps to be targeted by future studies . CONCLUSIONS SRs and MAs are integral in developing sound clinical practice guidelines and recommendations . PATIENT SUMMARY Clinical practice guidelines should be evidence based , and systematic review s and meta-analyses are essential in their production . We have discussed the key steps of conducting systematic review s and meta-analyses in this paper AIM Examination of the action of donor NO ( L-arginine ) on platelet aggregation , endothelial function and exercise tolerance in patients with stable angina of effort ( SAE ) . MATERIAL AND METHODS 42 patients with SAE ( functional class I-II ) and 10 healthy volunteers ( control group ) were assigned to two groups . 22 patients of group 1 were r and omized to cross-over . They received cardiket ( 60 mg/day for 10 days or cardiket ( 60 mg/day ) in combination with L-arginine ( 15 g/day for 10 days ) . 20 SAE patients of group 2 and control group received L-arginine ( 15 g/day for 10 days ) . In each group blood lipids were examined , and  bicycle exercise test ( BET ) was performed . In addition , platelet aggregation and endothelial function were studied in group 2 and control group before and after the course of L-arginine . RESULTS Compared to control group , endothelial function significantly improved in group 2 ( from 5.0 + /- 2.9 to 7.8 + /- 4.1 % vs 7.1 + /- 1.9 to 6.6 + /- 4.8 % ) ( M + /- SD ) . BET duration increased in all the patients . After ADP addition in concentrations 1.5 , 2.0 , and 5.0 micromol/l platelet aggregation declined in 17 patients except 3 in whom the aggregation remained unchanged . CONCLUSION Positive effect of L-arginine on endothelial function , exercise tolerance and platelet aggregation was observed in patients with stable angina of effort ( functional class I-II ) . Therefore , arginine can be recommended as an adjuvant in the treatment of patients with ischemic heart disease Publication bias , sometimes known as the " file-drawer problem " or " funnel-plot asymmetry , " is common in empirical research . The authors review the implication s of publication bias for quantitative research synthesis ( meta- analysis ) and describe existing techniques for detecting and correcting it . A new approach is proposed that is suitable for application to meta-analytic data sets that are too small for the application of existing methods . The model estimates parameters relevant to fixed-effects , mixed-effects or r and om-effects meta- analysis contingent on a hypothetical pattern of bias that is fixed independently of the data . The authors illustrate this approach for sensitivity analysis using 3 data sets adapted from a commonly cited reference work on research synthesis ( H. M. Cooper & L. V. Hedges , 1994 ) Postpr and ial hyperglycemia induces  vascular endothelial dysfunction ( VED )  and increases future cardiovascular disease risk . We hypothesized that postpr and ial hyperglycemia would decrease vascular function in healthy men by inducing oxidative stress and proinflammatory responses and increasing asymmetric dimethylarginine : arginine ( ADMA : arginine ) , a biomarker that is predictive of reduced NO bio synthesis . In a r and omized , cross-over design , healthy men ( n = 16 ; 21.6 ± 0.8 y ) ingested glucose or fructose  ( 75 g  )  after an  overnight fast  . Brachial artery flow-mediated dilation ( FMD ) , plasma glucose and insulin , antioxidants , malondialdehyde ( MDA ) , inflammatory proteins , arginine , and ADMA were measured at regular intervals during the 3-h postpr and ial period . Baseline FMD did not differ between trials ( P > 0.05 ) . Postpr and ial FMD was reduced following the ingestion of glucose only . Postpr and ial MDA concentrations increased to a greater extent following the ingestion of glucose compared to fructose . Plasma arginine decreased and the ratio of ADMA : arginine increased to a greater extent following the ingestion of glucose . Inflammatory cytokines and cellular adhesion molecules were unaffected by the ingestion of either sugar . Postpr and ial AUC(0 - 3 h ) for FMD and MDA were inversely related ( r = -0.80 ; P < 0.05 ) , suggesting that hyperglycemia-induced lipid peroxidation suppresses postpr and ial vascular function . Collectively , these findings suggest that postpr and ial hyperglycemia in healthy men  reduces endothelium-dependent vasodilation by increasing lipid peroxidation independent of inflammation . Postpr and ial alterations in arginine and ADMA : arginine also suggest that acute hyperglycemia may induce VED by decreasing NO bioavailability through an oxidative stress-dependent mechanism . Additional work is warranted to define whether inhibiting lipid peroxidation and restoring arginine metabolism would mitigate hyperglycemia-mediated decreases in vascular function Suboptimal embryonic/fetal survival and growth remains a significant problem in mammals . Using a swine model , we tested the hypothesis that dietary l-arginine supplementation during gestation may improve pregnancy outcomes through enhancing placental growth and modulating hormonal secretions . Gestating pigs ( Yorkshire × L and race , n = 108 ) were assigned r and omly into two groups based on parity and body weight , representing dietary supplementation with 1.0 % l-arginine – HCl or 1.7 % l-alanine ( isonitrogenous control ) between days 22 and 114 of gestation . Blood sample s were obtained from the ear vein on days 22 , 40 , 70 and 90 of gestation . On days 40 , 70 and 90 of gestation , concentrations of estradiol in plasma were higher ( P < 0.05 ) in arginine-supplemented than in control sows . Moreover , arginine supplementation increased ( P < 0.05 ) the concentrations of arginine , proline and ornithine in plasma , but concentrations of urea or progesterone in plasma did not differ between the two groups of sows . Compared with the control , arginine supplementation increased ( P < 0.05 ) the total number of piglets by 1.31 per litter , the number of live-born piglets by 1.10 per litter , the litter birth weight for all piglets by 1.36 kg , and the litter birth weight for live-born piglets by 1.70 kg . Furthermore , arginine supplementation enhanced ( P < 0.05 ) placental weight by 16.2 % . The weaning-to-estrus interval of sows was not affected by arginine supplementation during gestation . These results indicate that dietary arginine supplementation beneficially enhances placental growth and the reproductive performance of sows Background To improve quality of care and patient outcomes , health system decision-makers need to identify and implement effective interventions . An increasing number of systematic review s document the effects of quality improvement programs to assist decision-makers in developing new initiatives . However , limitations in the reporting of primary studies and current meta- analysis methods ( including approaches for exploring heterogeneity ) reduce the utility of existing syntheses for health system decision-makers . This study will explore the role of innovative meta- analysis approaches and the added value of enriched and up date d data for increasing the utility of systematic review s of complex interventions . Methods / Design We will use the data set from our recent systematic review of 142 r and omized trials of diabetes quality improvement programs  to evaluate novel approaches for exploring heterogeneity . These will include exploratory methods , such as multivariate meta-regression analyses and all-subsets combinatorial meta- analysis . We will then up date our systematic review to include new trials and enrich the data set by surveying authors of all included trials . In doing so , we will explore the impact of variables not , reported in previous publications , such as details of study context , on the effectiveness of the intervention . We will use innovative analytical methods on the enriched and up date d data set to identify key success factors in the implementation of  quality improvement interventions  for diabetes . Decision-makers will be involved throughout to help identify and prioritize variables to be explored and to aid in the interpretation and dissemination of results . Discussion This study will inform future systematic review s of complex interventions and describe the value of enriching and updating data for exploring heterogeneity in meta- analysis . It will also result in an up date d comprehensive systematic review of diabetes quality improvement interventions that will be useful to health system decision-makers in developing interventions to improve outcomes for people with diabetes . Systematic review registration PROSPERO registration no. Objectives : This umbrella review aim ed to determine the effectiveness of exercise interventions , alone or in combination with other interventions , in improving physical function in community-dwelling older people identified as pre-frail or frail . Introduction : Exercise is said to have a positive impact on muscle mass and strength which improves physical function and hence is beneficial for the treatment of frailty . Several systematic review s discuss the effects of exercise interventions on physical function parameters , such as strength , mobility , gait , balance and physical performance , and indicate that multi-component exercise , including resistance , aerobic , balance and flexibility training , appears to be the best way in which to improve physical function parameters in frail older people . However , there is still uncertainty as to which exercise characteristics ( type , frequency , intensity , duration and combinations ) are the most effective and sustainable over the long-term . Inclusion criteria : Participants were adults , 60 years or over , living in the community and identified as pre-frail or frail . Quantitative systematic review s , with or without meta- analysis that examined the effectiveness of exercise interventions of any form , duration , frequency and intensity , alone or in combination with other interventions design ed to alter physical function parameters in frail older people , were considered . The quantitative outcome measures were physical function , including muscular strength , gait , balance , mobility and physical performance . Methods : An iterative search strategy for ten bibliometric data bases and gray literature was developed . Critical appraisal of seven systematic review s was conducted independently by two review ers using a st and ard Joanna Briggs Institute tool . Data was extracted independently by two review ers using a st and ard Joanna Briggs Institute data extraction tool and summarized using a narrative synthesis approach . Results : Seven systematic review s were included in this umbrella review , with a total of 58 relevant r and omized controlled trials and 6927 participants . Five systematic review s examined the effects of exercise only , while two systematic review s reported on exercise in combination with a nutritional approach , including protein supplementations , as well as fruit and dairy products . The average  exercise frequency was 2–3 times per week ( mean 3.0 ± 1.5 times per week ; range 1–7 weekly ) for 10–90 minutes per session ( mean of 52.0 ± 16.5 mins ) and a total duration of 5–72 weeks with the majority lasting a minimum of 2.5 months ( mean 22.7 ± 17.7 weeks ) . Multi-component exercise interventions can currently be recommended for pre-frail and frail older adults to improve muscular strength , gait speed , balance and physical performance , including resistance , aerobic , balance and flexibility tasks . Resistance training alone also appeared to be beneficial , in particular for improving muscular strength , gait speed and physical performance . Other types of exercise were not sufficiently studied and their effectiveness is yet to be established . Conclusions : Interventions for pre-frail and frail older adults should include multi-component exercises , including in particular resistance training , as well as aerobic , balance and flexibility tasks . Future research should adopt a consistent definition of frailty and investigate the effects of other types of exercise alone or in combination with nutritional interventions so that more specific recommendations can be made Background Over 85 % of cervical cancer cases and deaths occur in developing countries . HIV-seropositive women are more likely to develop precancerous lesions that lead to cervical cancer than HIV-negative women . However , the literature on cervical cancer prevention in seropositive women in developing countries has not been review ed . The aim of this study is to systematic ally review cervical cancer prevention modalities available for HIV-seropositive women in developing countries . Methods / design This protocol was developed by following the Preferred Reporting Items for Systematic Review s and Meta-Analyses Protocol s ( PRISMA -P ) statement , and the systematic review will be reported in accordance with the PRISMA guidelines . Embase , MEDLINE , PubMed , CINAHL and Cochrane Library will be search ed from inception up to date of final search , and additional studies will be located through citation and reference list tracking . Eligible studies will be r and omised controlled trials , prospect i ve and retrospective cohort studies , case-control and cross-sectional studies carried out in developing countries . Studies will be included if they are published in English and examine cervical cancer prevention modalities in HIV-seropositive women . Results will be summarised in tables and , where appropriate , combined using meta- analysis . Discussion This review will address the gap in evidence by systematic ally review ing the published literature on the different prevention modalities being used to prevent  cervical cancer in HIV-seropositive women in developing countries . The findings may be used to inform evidence -based guidelines for prevention of cervical cancer in seropositive women as well as future research . Systematic review registration PROSPERO CRD42017054678 Background The aim of these review s is to inform the design and content of interventions to reduce obesity in young children . The behaviors that are associated with obesity/overweight have been studied extensively ; however , the factors associated with these behaviors in young children ( 0 to 6 years ) have not been systematic ally review ed . Over the past few years the focus of obesity prevention has shifted to preschool children because of the high prevalence of obesity at school entry and recognition that habits formed in early life could track into adulthood . In order to develop effective interventions and change behavior , it is important to underst and the factors that are associated with those behaviors . For example , we need to underst and whether it would be more important to target the family , childcare setting s or the wider environment and identify the most effective way of changing these energy balance related behaviors . Methods / Design Quantitative ( intervention and observational ) and qualitative literature on determinants/correlates of fruit and vegetable intake , sugar sweetened beverage and other unhealthy diet intake , and physical activity and sedentary behaviors in young children will be systematic ally identified , mapped and review ed . A common search strategy ( no language or period restrictions ) will be used to identify papers from eight electronic data bases and this will be supplemented by h and - search ing . Next , studies in developed countries that examine the factors associated with these behaviors in children aged 0 to 6 years ( at baseline ) will be screened and mapped descriptively followed by in-depth data extraction , quality assessment and synthesis . Data from quantitative studies will be summarized using either forest plots or harvest plots and narrative synthesis , and qualitative studies using thematic analysis . Qualitative evidence will be integrated with the quantitative evidence , using a parallel synthesis approach , to provide a deeper underst and ing of effective strategies to influence these energy balance related behaviors . Discussion In addition to updating and mapping current research , these review s will be the first to comprehensively synthesize and integrate both the quantitative and qualitative evidence pertaining to determinants/correlates/barriers/facilitators of obesity related behaviors in this young age group ( 0 to 6 years ) with the aim of informing future interventions . Systematic review registration International Prospect i ve Register for Systematic Review s ( PROSPERO ) Registration number :
This meta- analysis concludes that l-arginine supplementation can significantly reduce blood TAG levels ; however , there is insufficient evidence to support its hypocholesterolaemic effects .
A number of clinical trials have examined the effect of l-arginine on lipid profile in recent years ; however , the results remain equivocal .
Therefore , the present study aims to summarise and quantitatively examine the available evidence on the effectiveness l-arginine supplementation on lipid parameters using a systematic review and meta-analytic approach .