Effect of weight loss with or without orlistat treatment on adipocytokines, inflammation, and oxidative markers in obese women. Circulating Adipokines and Inflammatory Markers and Postmenopausal Breast Cancer Risk. Nicotine enhances modulation of food‐cue reactivity by leptin and ghrelin in the ventromedial prefrontal cortex Efficacy of vitamin D supplementation in depression in adults: a systematic review protocol Effect of exercise training combined with phytoestrogens on adipokines and C-reactive protein in postmenopausal women: a randomized trial. How to write an evidence-based clinical review article. Validation of the prognostic relevance of plasma C-reactive protein levels in soft-tissue sarcoma patients Comparison of orlistat treatment and placebo in obese type 2 diabetic patients Effects of 1-year orlistat treatment compared to placebo on insulin resistance parameters in patients with type 2 diabetes. Blood glucose lowering by means of lifestyle intervention has different effects on adipokines as compared with insulin treatment in subjects with type 2 diabetes Randomized controlled trials of aprotinin in cardiac surgery: could clinical equipoise have stopped the bleeding? Orlistat and L-carnitine compared to orlistat alone on insulin resistance in obese diabetic patients. Summarizing systematic reviews: methodological development, conduct and reporting of an umbrella review approach Comparison between orlistat plus l-carnitine and orlistat alone on inflammation parameters in obese diabetic patients. A prospective study of circulating C-reactive protein, interleukin-6, and tumor necrosis factor α receptor 2 levels and risk of ovarian cancer. Methodological developments in searching for studies for systematic reviews: past, present and future? Randomized Phase II Study of the Anti-inflammatory Effect of Ghrelin During the Postoperative Period of Esophagectomy. A Systematic Examination of the Citation of Prior Research in Reports of Randomized, Controlled Trials The clinical effectiveness of different parenting programmes for children with conduct problems: a systematic review of randomised controlled trials Estimating the Horizon of Articles to Decide When to Stop Searching in Systematic Reviews: An Example Using a Systematic Review of RCTs Evaluating Osteoporosis Clinical Decision Support Tools Is C-Reactive Protein Specific for Vascular Disease in Women? The effectiveness of yoga to prevent diabetes mellitus type 2 Systematic reviews in endodontics--examples of GIGO?
OBJECTIVE The aim of this study was to evaluate the levels of adipose tissue related hormones , cytokines , and antioxidative substances in obese women before and after intervention with diet alone or with diet plus an inhibitor of gastrointestinental lipase-orlistat .  DESIGN Seventy-one obese women of childbearing age were included in the study and were r and omly assigned into two groups according to the type of intervention : group A1 ( n=35 ) included women who received  orlistat as well as a hypocaloric diet , and group A2 ( n=36 ) included women who were only on hypocaloric diet . The intervention period lasted 6 months . Anthropometric parameters , such as Body Weight ( BW ) , Body Mass Index ( BMI ) , Waist Circumference ( WC ) , and % Body fat ( BF ) were recorded . Insulin , leptin , resistin , interleukin-6 ( IL-6 ) , insulin like growth factor 1 ( IGF-1 ) , tumor necrosis factor alpha ( TNFalpha ) , adiponectin , hsC-reactive protein ( CRP ) , glutathione peroxidase , and isoprostane were determined by appropriate methodology prior to and following the 6-month intervention period . Insulin resistance was measured using the homeostasis model assessment index ( HOMA-IR ) . All participants had normal glucose tolerance . RESULTS In both groups B MI values were lower after intervention and all measured parameters were ameliorated . A statistically significant difference was found between group A1 ( orlistat plus diet ) and group A2 ( diet only ) with regard to the levels of triglycerides , CRP , TNF-alpha , IGF-1 , and isoprostane , even after correcting for weight loss . CONCLUSION Hypocaloric diet plus orlistat in obese women is superior to diet alone with regard to the changes observed in adipokines , CRP , TNFalpha , triglycerides , IGF-1 , and oxidative stress following intervention BACKGROUND Adipokines and inflammation may provide a mechanistic link between obesity and postmenopausal breast cancer , yet epidemiologic data on their associations with breast cancer risk are limited . METHODS In a case-cohort analysis nested within the Women 's Health Initiative Observational Study , a prospect i ve cohort of postmenopausal women , baseline plasma sample s from 875 incident breast cancer case patients and 839 subcohort participants were tested for levels of seven adipokines , namely leptin , adiponectin , resistin , interleukin-6 , tumor necrosis factor-α , hepatocyte growth factor , and plasminogen activator inhibitor-1 , and for C-reactive protein ( CRP ) , an inflammatory marker . Data were analyzed by multivariable Cox modeling that included established breast cancer risk factors and previously measured estradiol and insulin levels . All statistical tests were two-sided . RESULTS The association between plasma CRP levels and breast cancer risk was dependent on hormone therapy ( HT ) use at baseline ( P interaction = .003 ) . In a model that controlled for multiple breast cancer risk factors including body mass index ( BMI ) , estradiol , and insulin , CRP level was positively associated with breast cancer risk among HT nonusers ( hazard ratio for high vs low CRP levels = 1.67 , 95 % confidence interval = 1.04 to 2.68 , P trend = .029 ) . None of the other adipokines were statistically significantly associated with breast cancer risk . Following inclusion of CRP , insulin , and estradiol in a multivariable model , the association of BMI with breast cancer was attenuated by 115 % . CONCLUSION These data indicate that CRP is a risk factor for postmenopausal breast cancer among HT nonusers . Inflammatory mediators , together with insulin and estrogen , may play a role in the obesity-breast cancer relation Endocrine signals such as ghrelin and leptin are known to modulate the mesocorticolimbic dopaminergic system and , consequently , show associations with food and drug reward . In animal models , nicotine was demonstrated to reduce body weight by attenuating food intake and effects of leptin and ghrelin are partly modulated by nicotinic acetylcholine receptors which hint at potential interactions . However , the neuropharmacological modulation of endocrine signals by nicotine in healthy humans remains to be tested experimentally . We used functional magnetic resonance imaging to investigate food‐cue reactivity after an overnight fast and following a caloric load ( oral glucose tolerance test , OGTT ) in 26 healthy normal‐weight never‐smokers . Moreover , we administered either nicotine ( 2 mg ) or placebo gums using a r and omized cross‐over design and assessed blood plasma levels of ghrelin and leptin . During fasting , nicotine administration decreased correlations with ghrelin levels in the mesocorticolimbic system whereas correlations with leptin were increased . After the OGTT , nicotine increased the modulatory effects of ghrelin and leptin on food‐cue reactivity , particularly in the ventromedial prefrontal cortex ( vmPFC ) and the amygdala . Critically , this led to an indirect modulation of the behavioral ‘ appetizer effect ’ ( i.e. cue‐induced increases in subjective appetite ) by homeostatic feedback signals via food‐cue reactivity in vmPFC . We conclude that nicotine enhances the effect of ghrelin and leptin in the valuation and relevance network which might , in turn , reduce appetite . This highlights that amplifying the impact of homeostatic signals such as ghrelin and leptin in normal‐weight individuals might hint at a mechanism contributing to nicotine 's anorexic potential Background The role of vitamin D in management of depression is unclear . Results from observational and emerging r and omized controlled trials ( RCTs ) investigating the efficacy of vitamin D in depression lack consistency - with some suggesting a positive association while others show a negative or inconclusive association . Methods / Design The primary aim of this study is to conduct a systematic review of RCTs to assess the effect of oral vitamin D supplementation versus placebo on depression symptoms measured by scales and the proportion of patients with symptomatic improvement according to the authors ’ original definition . Secondary aims include assessing the change in quality of life , adverse events and treatment discontinuation . We will conduct the systematic review and meta- analysis according to the recommendations of the Cochrane H and book for Systematic Review s of Interventions . We will search the Cochrane Central Register of Controlled Trials ( CENTRAL ) , MEDLINE ( 1966 to present ) , EMBASE ( 1980 to present ) , CINAHL ( 1982 to present ) , PsychINFO ( 1967 to present ) and Clinical Trials.gov . Unpublished work will be identified by search ing two major conferences : the International Vitamin Conference , the Anxiety Disorders and Depression Conference , while grey literature will be acquired by contacting authors of included studies . We will use the r and om-effects meta- analysis to synthesize the data by pooling the results of included studies . Discussion The results of this systematic review will be helpful in clarifying the efficacy of vitamin D supplementation and providing evidence to establish guidelines for implementation of vitamin D for depression in general practice and other relevant setting s. Study registration Unique identifier : CRD42013003849 Phytoestrogens and training could be effective to reduce cardiovascular and type 2 diabetes mellitus risk factors in postmenopausal women . Nevertheless , the impact of their combination on adipokines and systemic inflammation was never investigated . The objective was to verify if 6 months of mixed training combined with phytoestrogens could have an additional effect on adipokine levels and systemic inflammation in obese postmenopausal women . Fifty-two obese women aged between 50 and 70 years were r and omly assigned to ( 1 ) exercise with placebo ( EX + PL ; n = 25 ) or ( 2 ) exercise with phytoestrogens ( EX + PHY ; n = 27 ) . Body weight , waist circumference , fat mass , and lean body mass ( dual-energy x-ray absorptiometry ) were assessed . Fasting plasma glucose and insulin , adiponectin , leptin , and C-reactive protein ( CRP ) levels were obtained after a 12-hour overnight fast . Total energy intake was measured with a 3-day dietary record . All measurements were performed before and after the 6-month intervention . Although energy intake remained unchanged , body composition was improved in all women ( all Ps < .02 ) . Plasma CRP and leptin levels decreased in both groups similarly ( all Ps < .03 ) , whereas plasma adiponectin and insulin did not change with exercise combined with placebo or phytoestrogens . Correlation analyses showed that homeostasis model assessment of insulin resistance ( r = -0.58 , P = .02 ) and fasting insulin levels ( r = -0.42 , P = .02 ) at baseline were both correlated with changes in leptin levels . Baseline fasting glucose ( r = -0.36 , P = .03 ) and adiponectin ( r = 0.45 , P = .005 ) levels were associated with changes in CRP concentrations . Although mixed exercise program combined with phytoestrogens does not seem to provide any additional effect , mixed training improves systemic inflammation and leptin concentrations in obese postmenopausal women 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 Background : The concept of the involvement of systemic inflammation in cancer progression and metastases has gained attraction within the past decade . C-reactive protein ( CRP ) , a non-specific blood-based marker of the systemic inflammatory response , has been associated with decreased survival in several cancer types . The aim of the present study was to vali date the prognostic value of pre-operative plasma CRP levels on clinical outcome in a large cohort of soft-tissue sarcoma ( STS ) patients . Methods : Three hundred and four STS patients , operated between 1998 and 2010 , were retrospectively evaluated .  CRP levels and the impact on cancer-specific survival ( CSS ) , disease-free survival ( DFS ) and overall survival ( OS ) were assessed using Kaplan – Meier curves and univariate as well as multivariate Cox proportional models . Additionally , we developed a nomogram by supplementing the plasma CRP level to the well-established Kattan nomogram and evaluated the improvement of predictive accuracy of this novel nomogram by applying calibration and Harrell ’s concordance index ( c-index ) . Results : An elevated plasma CRP level was significantly associated with established prognostic factors , including age , tumour grade , size and depth ( P<0.05 ) . In multivariate analysis , increased CRP levels were significantly associated with a poor outcome for CSS ( HR=2.05 ; 95 % CI=1.13–3.74 ; P=0.019 ) and DFS ( HR=1.88 ; 95 % CI=1.07–3.34 ; P=0.029 ) . The estimated c-index was 0.74 using the original Kattan nomogram and 0.77 when the plasma CRP level was added . Conclusion : An elevated pre-operative CRP level represents an independent prognostic factor that predicts poor prognosis and improves the predictive ability of the Kattan nomogram in STS patients . Our data suggest to further prospect ively vali date its potential utility for individual risk stratification and clinical management of STS patients Aim : To evaluate the effects of 1-year treatment with orlistat compared with placebo on different inflammatory parameters in type 2 obese diabetic patients . Material s and methods : Two hundred and fifty-four type 2 diabetic patients were r and omized to take orlistat 120 mg three times a day or placebo for 12 months . We evaluated at baseline and after 3 , 6 , 9 and 12 months : leptin , tumor necrosis factor (TNF)-α , adiponectin ( ADN ) , vaspin and high-sensitivity C-reactive protein ( HS-CRP ) , body weight , waist circumference , body mass index ( BMI ) , lipid profile , glycemic profile , fasting plasma insulin ( FPI ) and homeostasis model assessment insulin resistance index ( HOMA-IR ) . Results : Regarding inflammatory parameters , there was a significant improvement of ADN and TNF-α , and a faster decrease of leptin and HS-CRP in the orlistat group compared with the control group . We also recorded a significant reduction of body weight and BMI with orlistat , but not with placebo . A faster improvement of glycemic profile and FPI was obtained with orlistat compared with the controls . Also , there was a significant reduction of lipid profile  with orlistat , not reached with placebo . Conclusions : Orlistat was more effective than placebo in ameliorating inflammatory parameters such as ADN and TNF-α , and anthropometric parameters WHAT IS KNOWN AND OBJECTIVE The behavioural approach is usually slow and not always sufficient to achieve optimal targets in weight and metabolic control in obese diabetic patients , and a pharmacological treatment is often necessary . The aim of this study was to compare the effects of orlistat and placebo on body weight , glycaemic and lipid profile and insulin resistance in patients with type 2 diabetes . METHODS Two hundred and fifty-four obese , diabetic patients were enrolled in this study and r and omized to take orlistat 360 mg or placebo for 1year . We evaluated at baseline and after 3 , 6 , 9 and 12months body weight , waist circumference ( WC ) , body mass index ( BMI ) , glycated haemoglobin ( HbA(1c ) ) , fasting plasma glucose ( FPG ) , post-pr and ial plasma glucose ( PPG ) , fasting plasma insulin ( FPI ) , homeostasis model assessment insulin resistance index ( HOMA-IR ) , lipid profile , retinol-binding protein-4 ( RBP-4 ) , resistin , visfatin and high-sensitivity C-reactive protein ( Hs-CRP ) . RESULTS AND DISCUSSION We observed a significant reduction in body weight , WC , BMI , lipid profile , RBP-4 and visfatin in the orlistat group but not in control group . Faster improvements in HbA(1c ) , PPG , FPI , HOMA-IR , resistin and Hs-CRP were recorded with orlistat than with placebo . A similar decrease in FPG was seen in the two groups . Significant predictors of change in insulin resistance ( HOMA-IR ) were RBP-4 and resistin concentration in the orlistat group ( r=-0·53 , P<0·05 , and r=-0·59 , P<0·01 , respectively ) . WHAT IS NEW AND CONCLUSION To the best of our knowledge , this is the first study investigating the effect of orlistat on insulin resistance and markers of inflammation . Orlistat improved lipid profile and led to faster glycaemic control and insulin resistance parameters than the control , without any serious adverse event . Orlistat also improved RBP-4 and visfatin , effects not observed with placebo Aims /hypothesisAdipokines may be important in mediating signals from adipocytes to insulin-sensitive tissue and vasculature . We studied the effect of different glucose-lowering therapies on serum levels of plasminogen activator inhibitor-1 ( PAI-1 ) , high-sensitivity C-reactive protein ( hs-CRP ) , TNF-α , leptin , adiponectin and ghrelin in patients with type 2 diabetes . Subjects and methods Twenty-eight patients with poorly controlled type 2 diabetes who were receiving oral hypoglycaemic agents  were allocated to one of the following groups , and treated for 1 year : ( 1 ) lifestyle intervention ( L ) ; ( 2 ) insulin treatment ( I ) ; and ( 3 ) combined treatment ( L+I ) . Results Similar improvements in glycaemic control occurred in all three groups . There was a reduction in body weight of 3.0 kg ( median ) ( 95 % CI −5.9 to −2.0 ) in group L , whereas in groups L+I and I body weight increased by 3.5 kg ( 95 % CI 1.5–4.9 ) and 4.9 kg ( 95 % CI −3.1 to 8.2 ) , respectively . By trend analyses , group L had reduced levels of PAI-1 ( p=0.002 ) , hs-CRP ( p<0.0001 ) and TNF-α ( p=0.006 ) , while no significant changes were observed in the levels of leptin or adiponectin . In group I , the median levels of PAI-1 ( p=0.008 ) , TNF-α ( p=0.058 ) and leptin ( p=0.004 ) increased . In the L+I group there was a reduction in PAI-1 levels ( p=0.014 ) and an increase in levels of leptin ( p<0.001 ) . The differences in changes in the levels of PAI-1 , hs-CRP , TNF-α and leptin between groups were also significant ( all p<0.01 ) . Conclusions /interpretationImprovement of glycaemic control through lifestyle intervention in type 2 diabetes had more beneficial effects on adipokine levels than when the same lowering of HbA1c was achieved with insulin treatment Background Aprotinin is a serine protease inhibitor used to limit perioperative bleeding and reduce the need for donated blood transfusions during cardiac surgery . R and omized controlled trials of aprotinin evaluating its effect on the outcome of perioperative transfusion have been published since 1987 , and systematic review s were conducted in 1992 and 1997 . Methods A systematic search was conducted for all RCTs of aprotinin  that used placebo controls or were open-label with no active control treatment . Data collected included the primary outcome , objective of each study , whether a systematic review was cited or conducted as part of the background and /or rationale for the study and the number of previously published RCTs cited . Cumulative meta-analyses were performed . Results Sixty-four r and omized , controlled trials of aprotinin were found , conducted between 1987 and 2002 , reporting an endpoint of perioperative transfusion .  Median trial size was 64 subjects , with a range of 20 to 1784 . A cumulative meta- analysis indicated that aprotinin greatly decreased the need for perioperative transfusion , stabilizing at an odds ratio of 0.25 ( p , 10 2 6 ) by the 12th study , published in June of 1992 . The upper limit of the confidence interval never exceeded 0.65 and results were similar in all subgroups . Citation of previous RCTs was extremely low , with a median of 20 % of prior trials cited . Only 7 of 44 ( 15 % ) of subsequent reports referenced the largest trial ( N 1/4 1784 ) , which was 28 times larger than the median trial size . Conclusions This study demonstrates that investigators evaluating aprotinin were not adequately citing previous research , result ing in a large number of RCTs being conducted to address efficacy questions that prior trials had already definitively answered . Institutional review boards and journals could reduce the number of redundant trials by requiring investigators to conduct adequate search es for prior evidence and conducting systematic review Our study wants to evaluate the effects of one year treatment with orlistat plus L-carnitine compared to orlistat alone on body weight , glycemic and lipid control , and insulin resistance state in type 2 diabetic patients . Two hundred and fifty-eight patients with uncontrolled type 2 diabetes mellitus ( T2DM ) [ glycated hemoglobin ( HbA(1c ) ) > 8.0 % ] in therapy with different oral hypoglycemic agents or insulin  were enrolled in this study and r and omised to take orlistat 120 mg three times a day plus L-carnitine 2 g one time a day or orlistat 120 mg three times a day . We evaluated at baseline , and after 3 , 6 , 9 , and 12 months these parameters : body weight , body mass index ( BMI ) , HbA(1c ) , fasting plasma glucose ( FPG ) , post-pr and ial plasma glucose ( PPG ) , fasting plasma insulin ( FPI ) , homeostasis model assessment insulin resistance index ( HOMA-IR ) , total cholesterol ( TC ) , low density lipoprotein-cholesterol ( LDL-C ) , high density lipoprotein-cholesterol ( HDL-C ) , triglycerides ( Tg ) , retinol binding protein-4 ( RBP-4 ) , resistin , visfatin , high sensitivity-C reactive protein ( Hs-CRP ) . We observed a faster , and better decrease of body weight , HbA(1c ) , FPG , PPG , LDL-C , HOMA-IR with orlistat plus L-carnitine compared to orlistat . A faster improvement of TC , Tg , FPI , resistin , RBP-4 , visfatin , and Hs-CRP was reached with orlistat plus L-carnitine compared to orlistat . We can safely conclude that the association of orlistat plus L-carnitine was better than orlistat in improving body weight , glycemic and lipid profile , insulin resistance , and inflammatory parameters and no significant adverse events were recorded 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 To evaluate the effects of 1-year treatment with orlistat plus L-carnitine compared to orlistat alone on body weight , glycemic and lipid control , and inflammatory parameters in obese type 2 diabetic patients . Two hundred and fifty-eight patients with uncontrolled type 2 diabetes mellitus ( T2DM ) [ glycated hemoglobin ( HbA(1c ) ) > 8.0 % ] in therapy with different oral hypoglycemic agents or insulin  were enrolled in this study and r and omized to take orlistat 120 mg three times a day plus L-carnitine 2 g one time a day or orlistat 120 mg three times a day . We evaluated the following parameters at baseline and after 3 , 6 , 9 , and 12 months : body weight , body mass index ( BMI ) , glycated hemoglobin ( HbA(1c ) ) , fasting plasma glucose ( FPG ) , postpr and ial plasma glucose ( PPG ) , fasting plasma insulin ( FPI ) , homeostasis model assessment insulin resistance index ( HOMA-IR ) , total cholesterol ( TC ) , low-density lipoprotein cholesterol ( LDL-C ) , high-density lipoprotein cholesterol ( HDL-C ) , triglycerides ( Tg ) , adiponectin ( ADN ) , leptin , tumor necrosis factor-α ( TNF-α ) , vaspin , and high-sensitivity C-reactive protein ( Hs-CRP ) . We observed a better decrease in body weight , glycemic profile , HOMA-IR , LDL-C , and ADN and a faster improvement in FPI , TC , Tg , leptin , TNF-α , Hs-CRP  with orlistat plus L-carnitine compared to orlistat alone . We also recorded an improvement in vaspin  with orlistat plus l-carnitine not reached with orlistat alone . Orlistat plus L-carnitine gave a better improvement in body weight , glycemic and lipid profile compared to orlistat alone ; furthermore , a faster and better improvement in inflammatory parameters was observed with orlistat plus L-carnitine compared to orlistat alone Chronic inflammation may play a role in ovarian carcinogenesis . We examined associations between 3 plasma biomarkers of inflammation-C-reactive protein ( CRP ) , interleukin 6 , and tumor necrosis factor α receptor 2- and  risk of invasive epithelial ovarian cancer in prospect ively collected sample s from the Nurses ' Health Study ( NHS ; 1989 - 2010 ) , Nurses ' Health Study II ( NHS II ; 1996 - 2009 ) , and the Women 's Health Study ( WHS ; 1992 - 2011 ) and performed a meta- analysis including data from previous publications . Associations with ovarian cancer risk were calculated using logistic regression ( NHS/NHS II ; n = 217 cases ) or Cox proportional hazards regression ( WHS ; n = 159 cases ) . Study -specific results were combined using r and om-effects meta- analysis . In the NHS/NHS II and WHS , we observed a 53 % increased risk of invasive ovarian cancer when comparing women in the fourth quartile of CRP with women in the first quartile ( 95 % confidence interval ( CI ) : 1.05 , 2.23 ) . A CRP level of > 10 mg/L versus a level of ≤1 mg/L was associated with a 2.16-fold increased risk ( 95 % CI : 1.23 , 3.78 ) . In a meta- analysis of published studies , women in the third tertile of CRP had a 35 % increased risk ( 95 % CI : 1.10 , 1.67 ) compared with women in the first tertile . There were no significant associations between interleukin 6 or tumor necrosis factor α receptor 2 and risk in the NHS/NHS II . Our results support the hypothesis that higher levels of circulating CRP are associated with increased risk of ovarian cancer  , indicating that the role of inflammation in ovarian cancer requires further elucidation The Cochrane Collaboration was established in 1993 , following the opening of the UK Cochrane Centre in 1992 , at a time when search ing for studies for inclusion in systematic review s was not well-developed . Review authors largely conducted their own search es or depended on medical librarians , who often possessed limited awareness and experience of systematic review s. Guidance on the conduct and reporting of search es was limited . When work began to identify reports of r and omized controlled trials ( RCTs ) for inclusion in Cochrane Review s in 1992 , there were only approximately 20,000 reports indexed as RCTs in MEDLINE and none indexed as RCTs in Embase . No search filters had been developed with the aim of identifying all RCTs in MEDLINE or other major data bases . This presented The Cochrane Collaboration with a considerable challenge in identifying relevant studies .Over time , the number of studies indexed as RCTs in the major data bases has grown considerably and the Cochrane Central Register of Controlled Trials ( CENTRAL ) has become the best single source of published controlled trials , with approximately 700,000 records , including records identified by the Collaboration from Embase and MEDLINE . Search filters for various study types , including systematic review s and the Cochrane Highly Sensitive Search Strategies for RCTs , have been developed . There have been considerable advances in the evidence base for method ological aspects of information retrieval . The Cochrane H and book for Systematic Review s of Interventions now provides detailed guidance on the conduct and reporting of search es . Initiatives across The Cochrane Collaboration to improve the quality inter alia of information retrieval include : the recently introduced Method ological Expectations for Cochrane Intervention Review s ( MECIR ) programme , which stipulates ' m and atory ’ and ' highly desirable ’ st and ards for various aspects of review conduct and reporting including search ing , the development of St and ard Training Material s for Cochrane Review s and work on peer review of electronic search strategies . Almost all Cochrane Review Groups and some Cochrane Centres and Fields now have a Trials Search Co-ordinator responsible for study identification and medical librarians and other information specialists are increasingly experienced in search ing for studies for systematic review s. Prospect i ve registration of clinical trials is increasing and search ing trials registers is now m and atory for Cochrane Review s , where relevant . Portals such as the WHO International Clinical Trials Registry Platform ( ICTRP ) are likely to become increasingly attractive , given concerns about the number of trials which may not be registered and /or published . The importance of access to information from regulatory and reimbursement agencies is likely to increase . Cross- data base search ing , gateways or portals and improved access to full-text data bases will impact on how search es are conducted and reported , as will services such as Google Scholar , Scopus and Web of Science . Technologies such as textual analysis , semantic analysis , text mining and data linkage will have a major impact on the search process but efficient and effective updating of review s may remain a challenge . In twenty years ’ time , we envisage that the impact of universal social networking , as well as national and international legislation , will mean that all trials involving humans will be registered at inception and detailed trial results will be routinely available to all . Challenges will remain , however , to ensure the discoverability of relevant information in diverse and often complex sources and the availability of meta data to provide the most efficient access to information . We envisage an ongoing role for information professionals as experts in identifying new re sources , research ing efficient ways to link or mine them for relevant data and managing their content for the efficient production of systematic review OBJECTIVE A prospect i ve r and omized phase II trial was conducted to evaluate the efficacy of ghrelin administration in reducing systemic inflammatory response syndrome ( SIRS ) duration after esophagectomy . BACKGROUND Esophagectomy for esophageal cancer is highly invasive and leads to prolonged SIRS duration and postoperative complications . Ghrelin has multiple effects , including anti-inflammatory effects . METHODS Forty patients undergoing esophagectomy were r and omly assigned to either the ghrelin group ( n = 20 ) , which received continuous infusion of ghrelin ( 0.5 μg/kg/h ) for 5 days , or the placebo group ( n = 20 ) , which received pure saline for 5 days . The primary endpoint was SIRS duration . The secondary endpoints were the incidence of postoperative complications , time of a negative nitrogen balance , changes in body weight and composition , and levels of inflammatory markers , including C-reactive protein ( CRP ) and interleukin-6 ( IL-6 ) . RESULTS The ghrelin group had a shorter SIRS duration and lower CRP and IL-6 levels than did the placebo group . The incidence of pulmonary complications was lower in the ghrelin group than in the placebo group , whereas other complications did not differ between the groups . Although time of the negative nitrogen balance was shorter in the ghrelin group than in the placebo group , changes in total body weight and lean body weight did not differ significantly . CONCLUSIONS Postoperative ghrelin administration was effective for inhibiting inflammatory mediators and improving the postoperative clinical course of patients with esophageal cancer BACKGROUND A r and omized , controlled trial ( RCT ) should not be started or interpreted without accounting for evidence from preceding RCTs addressing the same question . Research has suggested that evidence from prior trials is often not accounted for in reports of subsequent RCTs . OBJECTIVE To assess the extent to which reports of RCTs cite prior trials study ing the same interventions . DESIGN Meta-analyses published in 2004 that combined 4 or more trials were identified ; within each meta- analysis , the extent to which each trial report cited the trials that preceded it by more than 1 year was assessed . MEASUREMENTS The proportion of prior trials that were cited  ( prior research citation index ) , the proportion of the total participants from prior trials that were in the cited trials  ( sample size citation index ) , and the absolute number of trials cited were calculated . RESULTS 227 meta-analyses were identified , comprising 1523 trials published from 1963 to 2004 . The median prior research citation index was 0.21 ( 95 % CI , 0.18 to 0.24 ) , meaning that less than one quarter of relevant reports were cited . The median sample size citation index ( 0.24 [ CI , 0.21 to 0.27 ] ) was similar , suggesting that larger trials were not selectively cited . Of the 1101 RCTs that had 5 or more prior trials to cite , 254 ( 23 % ) cited no prior RCTs and 257 ( 23 % ) cited only 1 . The median number of prior cited trials was 2 , which did not change as the number of citable trials increased . The mean number of preceding trials cited by trials published after 2000 was 2.4 , compared with 1.5 for those published before 2000 ( P < 0.001 ) . LIMITATION The investigators could not ascertain why prior trials were not cited , and noncited trials may have been taken into account in the trial design and proposal stages . CONCLUSION In reports of RCTs published over 4 decades , fewer than 25 % of preceding trials were cited , comprising fewer than 25 % of the participants enrolled in all relevant prior trials . A median of 2 trials was cited , regardless of the number of prior trials that had been conducted . Research is needed to explore the explanations for and consequences of this phenomenon . Potential implication s include ethically unjustifiable trials , wasted re sources , incorrect conclusions , and unnecessary risks for trial participants . PRIMARY FUNDING SOURCE None Background Conduct problems are common , disabling and costly . The prognosis for children with conduct problems is poor , with outcomes in adulthood including criminal behaviour , alcoholism , drug abuse , domestic violence , child abuse and a range of psychiatric disorders . There has been a rapid expansion of group based parent-training programmes for the treatment of children with conduct problems  in a number of countries over the past 10 years . Existing review s of parent training have method ological limitations such as inclusion of non-r and omised studies , the absence of investigation for heterogeneity prior to meta- analysis or failure to report confidence intervals . The objective of the current study was to systematic ally review r and omised controlled trials of parenting programmes for the treatment of children with conduct problems .  Methods St and ard systematic review methods were followed including duplicate inclusion decisions , data extraction and quality assessment . Twenty electronic data bases from the fields of medicine , psychology , social science and education were comprehensively search ed for RCTs and systematic review s to February 2006 . Inclusion criteria were : r and omised controlled trial ; of structured , repeatable parenting programmes ; for parents/carers of children up to the age of 18 with a conduct problem ; and at least one measure of child behaviour . Meta- analysis and qualitative synthesis were used to summarise included studies . Results 57 RCTs were included . Studies were small with an average group size of 21 . Meta-analyses using both parent ( SMD -0.67 ; 95 % CI : -0.91 , -0.42 ) and independent ( SMD -0.44 ; 95 % CI : -0.66 , -0.23 ) reports of outcome showed significant differences favouring the intervention group . There was insufficient evidence to determine the relative effectiveness of different approaches to delivering parenting programmes . Conclusion Parenting programmes are an effective treatment for children with conduct problems . The relative effectiveness of different parenting programmes requires further research Research ers conducting systematic review s need to search multiple bibliographic data bases such as MEDLINE and EMBASE . However , research ers have no rational search stopping rule when looking for potentially-relevant articles . We empirically tested a stopping rule based on the concept of  capture-mark-recapture ( CMR ) , which was first pioneered in ecology . The principles of CMR can be adapted to systematic review s and meta-analyses to estimate the Horizon of articles in the literature with its confidence interval . We retrospectively tested this Horizon Estimation using a systematic review of r and omized controlled trials ( RCTs ) that evaluated clinical decision support tools for osteoporosis disease management . The Horizon Estimation was calculated based on 4 bibliographic data bases that were included as the main data sources for the review in the following order : MEDLINE , EMBASE , CINAHL , and EBM Review s. The systematic review captured 68 % of known articles from the 4 data sources , which represented 592 articles that were estimated as missing from the Horizon Context Inflammatory markers , such as C-reactive protein ( CRP ) , independently predict future coronary artery disease in patients without known disease at baseline . However , an elevated CRP level also predicts all-cause mortality ; therefore , it may not be specific for cardiovascular disease . Contribution This prospect i ve casecontrol study showed that CRP level predicted the development of acute cardiovascular events but not cancer among 28 345 women followed for a mean of 58 months . Clinical Implication s parental history of coronary heart disease . In women , CRP level appears specifically predictive of car-diovascular disease but not cancer . This study adds further evidence that CRP levels may be useful in the clinical prediction of cardiovascular risk , at least in population s. The Editors Recent evidence suggests that atherosclerosis is in part a chronic low- grade inflammatory condition ( 1 ) , and prospect i ve epidemiologic studies have demonstrated that plasma markers of inflammation , such as C-reactive protein ( CRP ) , are strong independent predictors of future coronary events in apparently healthy persons ( 2 - 6 ) . However , as an acute-phase reactant , CRP increases dramatically in various pathologic conditions . Moreover , CRP has been shown to predict all-cause mortality ( 7 , 8) , an observation that raises the possibility that CRP may not be specific for vascular disease . To evaluate this hypothesis , we directly compared the predictive value of CRP for incident cancer and cardiovascular disease , the two most important determinants of all-cause mortality in the western world . Methods We performed a prospect i ve , nested casecontrol analysis within the Women 's Health Study , an ongoing r and omized , double-blind , placebo-controlled trial of aspirin and vitamin E for primary prevention of heart disease and cancer , which involves 39 876 U.S. women 45 years of age and older . Of these study participants , 28 345 ( 71 % ) provided baseline blood sample s  , which were stored at 70 C until the time of laboratory analysis . In the Women 's Health Study , all participants are followed prospect ively for incident health events , including cancer and cardiovascular events . The methods used for cohort follow-up , end-point ascertainment , and adjudication for both cancer and cardiovascular events are described in detail elsewhere ( 5 , 9 ) . For this study , we defined case- patients as apparently healthy women who provided an adequate baseline plasma sample and who subsequently developed cancer ( n = 513 ) or an acute cardiovascular event ( myocardial infa rct ion , stroke , or cardiovascular death ) ( n = 130 ) over a mean follow-up period of 58 months . For each woman who had confirmed cancer or cardiovascular event during follow-up , one control of the same age ( 1 year ) and smoking habit ( former smoker , current smoker , or nonsmoker ) was selected from among participants who provided baseline plasma sample s and remained free of reported disease during the same follow-up period . Using these criteria , we evaluated 643 case- patients and an equal number of controls in two separate matched pairs , one for cancer ( n = 513 ) and another for cardiovascular events ( n = 130 ) . The Institutional Review Board of the Brigham and Women 's Hospital approved this study . For each case-patient and control , plasma stored since the baseline examination was thawed and assayed for CRP levels by using a high-sensitivity assay ( Dade Behring , Newark , Delaware ) ( 10 ) . Blood specimens were analyzed in blinded pairs with the position of the patient 's specimen varied at r and om to reduce the possibility of systematic bias and to decrease interassay variability . The day-to-day precision values , at CRP concentrations of 0.15 mg/L and 0.49 mg/L , were 4.9 % and 6.4 % , respectively . Because CRP values are skewed rightward , median plasma concentrations were computed , and the significance of any difference in the distributions between the case- patients and controls was assessed by performing the Wilcoxon rank-sum test . We then used conditional logistic regression models to determine the risk for developing cancer or cardiovascular end points after dividing the study sample into quartiles on the basis of the distribution of the control group . Adjusted estimates of risk were obtained by use of similar models that accounted for the matching variables and that controlled for r and omized treatment assignment ( for vitamin E , aspirin , or both ) , body mass index , diabetes mellitus , history of hyperlipidemia , history of hypertension , and parental history of coronary heart disease . All analyses were performed by using SAS software , release 8.2 ( SAS Institute , Inc. , Cary , North Carolina ) . All P values were two tailed , and CIs were computed at the 95 % level . The funding sources played no role in the design , conduct , or reporting of the study . Results Table 1 shows the baseline characteristics of the study participants . We noted no significant differences at baseline between women who subsequently developed cancer and those who did not . As expected , women who subsequently developed cardiovascular events had an increased baseline prevalence of hyperlipidemia , hypertension , diabetes , and obesity compared with controls who did not develop vascular events during follow-up . Table 1 . Baseline Clinical Characteristics of the Study Participants Overall , median levels of CRP  at baseline among women who subsequently developed cancer ( 2.6 mg/L [ interquartile range , 1.1 to 5.9 mg/L ] ) were not significantly different from those of the control group ( 2.5 mg/L [ interquartile range , 0.9 to 5.5 mg/L ] ) ( P > 0.2 ) . Furthermore , we observed no evidence of an association between baseline CRP level and the development of cancer in site-specific analyses evaluating carcinoma of the breast ( n = 223 ) , ovary or uterus ( n = 75 ) , colon ( n = 44 ) , lung ( n = 32 ) , hematopoietic system ( n = 31 ) , thyroid ( n = 14 ) , bladder ( n = 9 ) , brain ( n = 8) , or pancreas ( n = 8) ; melanoma ( n = 31 ) ; or other types of cancer ( n = 38 ) . In contrast , and consistent with previous work in this cohort for the end point of any vascular event ( 5 ) , median CRP levels at baseline among women who subsequently developed cardiovascular disease ( 5.1 mg/L [ interquartile range , 2.6 to 8.5 mg/L ] ) were significantly higher than those of the control group ( P < 0.001 ) . Table 2 presents relative risks for developing either cancer or cardiovascular disease according to increasing quartiles of CRP levels obtained at study entry . As Table 2 shows , there was little evidence that baseline levels of CRP predicted incident cancer in either crude or adjusted analyses . We found similar results after additional correction for alcohol use and age at menarche ( data not shown ) . In contrast , increasing quartiles of baseline CRP level were a strong marker of risk for incident cardiovascular disease in crude and adjusted analyses . For example , the adjusted relative risks from the lowest to the highest quartiles of baseline CRP levels were 1.0 , 2.9 , 3.4 , and 5.6 , respectively ( P for trend < 0.001 ) . Table 2 . Relative Risk for Future Cancer and Cardiovascular Events , according to Baseline Plasma C-Reactive Protein Level Discussion In this prospect i ve study of apparently healthy middle-aged and older women , baseline plasma CRP concentrations were not significantly related to the incidence of future cancer but were a strong independent predictor of future myocardial infa rct ion , stroke , and cardiovascular death . We believe these data have importance for general medical practice for several reasons . First , our data corroborate the findings in several previous reports ( 2 - 6 ) that baseline levels of CRP predict future vascular events among apparently healthy men and women ( 2 - 6 ) and that CRP level adds to the predictive value of total and high-density lipoprotein cholesterol levels ( 5 , 11 ) . As a result of these earlier findings , outpatient screening for CRP has recently become available . However , if CRP is clinical ly nonspecific , as two recent studies evaluating all-cause mortality suggest ( 7 , 8) , then screening for this inflammatory marker might have reduced diagnostic utility . Thus , our finding that CRP appears to be specific for incident vascular disease but not for incident cancer has substantial clinical importance and suggests that data linking CRP level to overall death rates may have been due to the large contribution that vascular disorders make to all-cause mortality , particularly in the western world . Second , the relative risks for future myocardial infa rct ion or stroke observed among women in the top versus bottom quartile of baseline CRP in this analysis are somewhat greater than those previously reported from this cohort for the end point of any vascular eventan end point that included not only myocardial infa rct ion , stroke , and cardiovascular disease mortality , but also coronary revascularization ( 5 ) . Thus , these data also suggest that CRP level may be a stronger marker for events involving atherosclerotic plaque rupture and acute thrombosis than for events primarily involving progression of lesional stenosis . These epidemiologic data are thus consistent with the hypothesis that inflammation is an important determinant of plaque vulnerability ( 12 ) . Finally , we believe that our observation that CRP levels do not strongly predict future cancers is itself of pathophysiologic interest ; this is of particular interest because levels of CRP and other inflammatory biomarkers are known to increase after development of certain malignancies ( 13 , 14 ) . As such , our data also suggest that the systemic inflammatory component of cancer previously reported in cross-sectional studies may be a late development in the genesis of that disease but is not likely to prove useful in determining risk among healthy persons . Several limitations of our study deserve attention . Plasma CRP levels increase acutely in a wide variety of pathologic conditions , including febrile illness , various inflammatory states , and trauma ( 15 ) . In Background : Type 2 diabetes mellitus ( T2DM ) is becoming a leading problem worldwide . Emerging reports reveal alarming evidence of increasing prevalence of T2DM that has reached p and emic levels . Despite the significant incidence , there are limited reliable data re sources and comprehensive systematic review and meta- analysis on the effects of yoga on people who are a prediabetic or high risk for developing T2DM . Objective : The objective of this protocol is to conduct a full-scale systematic review and meta-analyses on the effects of yoga on people who are prediabetes or high risk of developing T2DM . Methods : The articles enrolled in the study will be retrieved from the online data bases between 2002 and the date the search es are executed . The search es will be repeated just before the final analyses and further relevant studies for inclusion . We will conduct a bibliographic search in data bases : Medline / PubMed , Scopus , Cochrane Library , EBSCO , and IndMED using keywords including prediabetes state , high risk for diabetes , metabolic syndrome , and yoga . A defined search strategy will be implemented along with selection criteria to obtain full-text articles of relevant studies . This study protocol was prepared according to the Preferred Reporting Items for Systematic Review s and Meta- Analysis for Protocol s 2015 guidelines . There will be no language restrictions . Ethics and dissemination : The proposed study will be based on published studies and publicly available anonymized data without directly involving human participants and therefore requires neither formal human ethical review nor approval by a human research ethics committee . We published an outline of the protocol in the International Prospect i ve Register of Systematic Review s ( PROSPERO ) in 2018 . We plan to disseminate the findings of this systematic review and meta- analysis through publication in a peer- review ed journal and presentation at relevant conference proceedings . In addition , we believe the results of the systematic review will have implication s for policy and practice . We will prepare policymaker summary using a vali date d format , disseminate through social media and email discussion groups . Review registration number : PROSPERO registration number CRD In many areas of medicine the amount of published information is increasing at an exponential rate , making it difficult for the clinician to condense the data to a manageable amount of valuable and useful information . Systematic review s have been suggested as a remedy for this information overload . Such review s are regarded as the highest level of evidence . Certain statistical methods , e.g. , meta- analysis , have also been introduced for the calculation of a more comprehensive summation of the compiled results from studies with small sample sizes . These findings would then serve as an authoritarian guide for evidence -based practice . Endodontists have lately jumped on the b and wagon of systematic review s and meta-analyses , and papers on various topics are being published . Well done , such comprehensive information would be very useful and authoritative for the practitioner . Alarmingly , the quality of these recent publications is negatively correlated to the frequency . This can have serious consequences in the clinical arena if spurious information is given a seal of approval when communicated as facts in refereed journals . A systematic literature review is design ed to focus on a single question and to synthesize all high- quality research reports relevant to the question . In these studies , however , sources of bias are often not controlled . Therefore , even the best review and meta- analysis becomes useless if it is based on poorly design ed research . Furthermore , these review s are mostly based on published data which are too often biased toward studies that show significant differences in results and /or outcome . “ Uninteresting ” conclusions tend not to be published . Endodontic literature , thus far , is short on well design ed and executed r and omized clinical trials . Furthermore , clinical protocol s often have many important “ proprietary ” modifications that make comparison difficult . This makes it very hard to undertake a systematic review to answer a narrow question . Such GIGO ( garbage in , garbage out ) can easily lead to biased conclusions and reinforce already existing biased comclusions . An example of such bias can be illustrated by a meta- analysis recently published . The study focused on assessing if there were differences in outcome between 1 and 2 treatment visits when treating teeth with apical periodontitis . Relevant publications on this topic are rare , and with the narrow inclusion criteria only 3 investigations were available for the review . However , the only factors connecting these 3 studies was the words “ single ” and “ two visits ” in the title . Beyond that , the selected studies are too different and inadequate for the study . Only 1 study is somewhat demonstrably r and omized , and outcome assessment s are based on 3 vastly different criteria . Two of the studies use calcium hydroxide as intracanal dressing , whereas the third uses no intervisit medication . Complexity of initial pathology and healing time are also clearly factors of great importance but not controlled . In addition , sample sizes in the component studies as well as the final cohort are all too small for the conclusions that there was no significant difference between 1or 2-visit treatment protocol s. To undertake and publish a meta- analysis on such an incomplete sample is counterproductive . Although the publication noted its numerous limitations , it will still communicate erroneous conclusions with a poor scientific foundation to the less informed reader . There are other examples of recently published systematic review s that are very ambiguous and tend to communicate spurious facts . One of these studies looks at the effect of smear-layer removal on sealing ability of root canal obturation . The study is entirely limited to laboratory experiments , with the majority of evaluations using dye leakage which is generally considered to be unreliable . This is an example of review ers lacking content expertise . The authors draw the conclusion , using defective review material , that removal of smear layer enhances the seal of the root filling . We may generally believe that this is the truth
In meta-regression , changes in plasma concentrations of adiponectin , leptin and CRP were associated with duration of treatment , but not with either change in BMI or baseline BMI values .
CONCLUSION Orlistat is effective in increasing plasma concentrations of adiponectin and decreasing those of leptin and CRP
AIMS To conduct a systematic review and meta- analysis of relevant r and omized clinical trials ( RCTs ) to ascertain the effect size of orlistat in modulating plasma levels of adipokines , ghrelin and C-reactive protein ( CRP ) .