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. Patient-reported outcomes better discriminate active treatment from placebo in randomized controlled trials in rheumatoid arthritis. [Impact of weight loss on adipocytokines, C-reactive protein and insulin sensitivity in hypertensive women with central obesity]. Comparison between orlistat plus l-carnitine and orlistat alone on inflammation parameters in obese diabetic patients. Adding exercise to rosuvastatin treatment: influence on C-reactive protein, monocyte toll-like receptor 4 expression, and inflammatory monocyte (CD14+CD16+) population. Larger effect sizes were associated with higher quality ratings in complementary and alternative medicine randomized controlled trials. Orlistat and L-carnitine compared to orlistat alone on insulin resistance in obese diabetic patients. Orlistat (Ro 18-0647), a lipase inhibitor, in the treatment of human obesity: a multiple dose study. Effect of intensive lifestyle intervention on C-reactive protein in subjects with impaired glucose tolerance and obesity. Results from a randomized controlled trial with 5-year follow-up. Atorvastatin lowers C-reactive protein and improves endothelium-dependent vasodilation in type 2 diabetes mellitus. Evolution of the randomized controlled trial in oncology over three decades. Reductions in C-reactive protein in older adults with type 2 diabetes are related to improvements in body composition following a randomized controlled trial of resistance training Usefulness of C-reactive protein and interleukin-6 as predictors of outcomes in patients with chronic obstructive pulmonary disease receiving pravastatin. Orlistat, a lipase inhibitor, for weight maintenance after conventional dieting: a 1-y study. The efficacy of activated protein C for the treatment of sepsis: incorporating observational evidence with a Bayesian approach Effect of Rosiglitazone Treatment on Nontraditional Markers of Cardiovascular Disease in Patients With Type 2 Diabetes Mellitus
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 BACKGROUND Recent r and omized controlled trials ( RCTs ) in rheumatoid arthritis ( RA ) have used patient- and physician-reported outcomes , ESR and /or CRP as components of ACR response criteria to assess efficacy . OBJECTIVES Mean changes from baseline in patient- and physician-reported outcome measures , ESR and CRP were compared in two RCTs in patients with active RA . Comparisons between active and placebo treatment used mean percentage improvements and st and ard effect sizes ( SESs ) . RESULTS In both protocol s , patient-reported assessment s of disease activity , pain and physical function reflected little or no improvement with placebo , best discriminating between active and placebo therapy , as did ESR and CRP . CONCLUSION Improvements in signs and symptoms of active RA in placebo RCTs appear to be best reflected by patient-reported measures of physical function , as long as reported changes in global assessment s of disease activity and /or pain reflect similar benefit . Patient-reported outcome measures should be considered objective ; treatment-associated changes are congruent with measures of inflammation , and appear less susceptible to the placebo response OBJECTIVE To assess the impact of weight reduction on serum adipocytokines , C-reactive protein ( CRP ) , and insulin sensitivity in hypertensive female patients with central obesity . METHODS This study was performed using the data base and stored serum sample s of female patients who had participated in an intervention study focused on weight loss . Thirty hypertensive women aged 18 to 65 , body mass index ( BMI ) > 27 kg/m2 , and central obesity were selected . They were r and omly assigned to receive either a low-calorie diet plus orlistat 120 mg three times daily or a low-calorie diet alone for 16 weeks . Patients who experienced weight loss greater than 5 % ( n = 24 ) were assessed for blood pressure , anthropometric parameters , visceral fat , insulin resistance ( HOMA-R - homeostasis model assessment of insulin resistance ) and sensitivity ( ISI - Insulin Sensitivity Index ) indices , plus serum lipids , adipocytokines ( adiponectin , leptin , IL-6 , and TNF-alpha ) and CRP levels . RESULTS After BMI had been reduced by approximately 5 % in both groups , visceral fat , fasting glucose , triglycerides , and TNF-alpha decreased . Only the orlistat group , which was more insulin resistant at baseline , showed a significant reduction in blood glucose after oral glucose load , in addition to increased insulin sensitivity . CONCLUSION This study 's findings indicate that a weight loss greater than 5 % is associated with improved inflammatory status and decreased insulin resistance , regardless of changes in adiponectin and TNF-a levels . The greatest improvements in insulin sensitivity experienced by the orlistat-treated patients could not be attributed to the use of this drug because of the higher number of insulin-resistant subjects in this group 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 Statin treatment and exercise training can reduce markers of inflammation when administered separately . The purpose of this study was to determine the effect of rosuvastatin treatment and the addition of exercise training on circulating markers of inflammation including C-reactive protein ( CRP ) , monocyte toll-like receptor 4 ( TLR4 ) expression , and CD14+CD16 + monocyte population size .  Thirty-three hypercholesterolemic and physically inactive subjects were r and omly assigned to rosuvastatin ( R ) or rosuvastatin/exercise ( RE ) groups . A third group of physically active hypercholesterolemic subjects served as a control ( AC ) . The R and RE groups received rosuvastatin treatment ( 10 mg/d ) for 20 weeks . From week 10 to week 20 , the RE group also participated in an exercise training program ( 3d/wk ) . Measurements were made at baseline ( Pre ) , week 10 ( Mid ) , and week 20 ( Post ) , and included TLR4 expression on CD14 + monocytes and CD14+CD16 + monocyte population size as determined by 3-color flow cytometry . Serum CRP was quantified by enzyme-linked immunosorbent assay . TLR4 expression on CD14 + monocytes was higher in the R group at week 20 . When treatment groups ( R and RE ) were combined , serum CRP was lower across time . Furthermore , serum CRP and inflammatory monocyte population size were lower in the RE group compared with the R group at the Post time point . When all groups ( R , RE , and AC ) were combined , TLR4 expression was greater on inflammatory monocytes ( CD14+CD16 + ) compared with classic monocytes ( CD14+CD16⁻ ) at all time points . In conclusion , rosuvastatin may influence monocyte inflammatory response by increasing TLR4 expression on circulating monocytes . The addition of exercise training to rosuvastatin treatment further lowered CRP and reduced the size of the inflammatory monocyte population , suggesting an additive anti-inflammatory effect of exercise OBJECTIVE To determine if the quality of  complementary and alternative medicine ( CAM ) placebo controlled r and omized controlled trials ( RCTs ) is related to the effect sizes they produce when the type of interventions and outcome variables are controlled . STUDY DESIGN AND SETTING A sample of 25 CAM meta-analyses was identified from MEDLINE and h and search es containing published effect sizes for at least three efficacy trials employing placebo control groups .  From these 25 review s , 26 pairs of trials were selected : the one reporting the largest effect size and the matching trial reporting the smallest effect size . Quality and publication characteristics were then abstract ed from each trial . RESULTS Unlike the preponderance of past evidence examining the relationship between quality and effect size , the present study found that trials possessing the largest effect sizes within a meta- analysis were also associated with higher quality ratings than their counterparts possessing the lowest effect sizes ( P=.019 ) . CONCLUSIONS Possible theoretical reasons for this unexpected positive relationship include ( a ) sampling error , ( b ) reduced within group variation , ( c ) fraudulent reporting , and ( d ) the restriction of the analyses to placebo controlled trial 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 OBJECTIVE To evaluate efficacy and tolerability of the lipase inhibitor Orlistat ( Ro 18 - 0647 ) in doses of 10 , 60 and 120 mg three times a day in addition to a mild hypocaloric diet containing 30 % of calories as fat . DESIGN 4 week single-blind placebo run-in period of diet alone followed by a 12 week double-blind , placebo-controlled , r and omized treatment period . SETTING S Five European outpatient clinics specializing in endocrinology and /or the treatment of obesity , one central laboratory . SUBJECTS Of 237 healthy obese subjects meeting the inclusion criteria , 188 showed compliance to the diet during the run-in period and were r and omized for the treatment period . MAIN OUTCOME MEASURES Primary efficacy criterion was the difference in weight loss after 12 weeks of treatment between the Orlistat treated groups and the diet alone group . Secondary efficacy criteria were changes in serum total , HDL- and LDL-cholesterol . RESULTS Compared to placebo a mean ( + /- s.e . ) additional weight loss of 0.63 + /- 0.54 kg with 30 mg a day ( P = 0.246 ) , 0.71 + /- 0.55 kg with 180 mg a day ( P = 0.190 ) and 1.75 + /- 0.54 kg with 360 mg a day was seen ( P = 0.001 ) or Orlistat was observed . Overall data indicated dose-dependency . Small decreases were seen in total and LDL-cholesterol ( significant in the 180 and 360 mg a day groups ) and LDL- to HDL-cholesterol ratio ( significant in the 360 mg a day group only ) . Mild , mostly gastrointestinal side effects were observed more frequently in the Orlistat groups and caused premature withdrawal from the study in only four patients . No marked laboratory abnormalities were shown , including the lipid-soluble vitamins A , D and E. CONCLUSION Orlistat , in an apparently dose-dependent manner , leads to additional weight loss compared to diet alone and overall , is well tolerated C-reactive protein ( CRP ) is a marker of metabolic and cardiovascular disease . To study the effects of lifestyle on CRP in a high-risk population we conducted a r and omized controlled trial on 200 obese subjects ( BMI > 27 kg m(-2 ) ) with impaired glucose tolerance recruited from primary care setting s. They were r and omized to either a 1-month stay at a wellness centre focusing on diet , exercise and stress management ( intervention group ) or 30 - 60 min of oral and written information on lifestyle intervention ( control group ) . A significant reduction of CRP was observed after 1 month and 1 year in the intervention group . They reduced their CRP levels more than the control group 1 year after intervention ( p=0.004 ) . In conclusion lifestyle intervention can decrease CRP  in obese individuals with impaired glucose tolerance for up to 1 year . Further research is needed to evaluate whether the CRP level reduction translates into a decreased risk for cardiovascular morbidity Endothelial dysfunction is frequently found in diabetic subjects . This study was performed to investigate whether atorvastatin therapy was able to reverse endothelial dysfunction in type 2 diabetes and , if so , whether the effect was due to its antiinflammatory action . Eighty patients ( baseline low density lipoprotein , 4.37 + /- 0.71 mmol/liter ) were r and omized to atorvastatin ( 10 mg daily for 3 months , followed by 20 mg daily for 3 months ) or placebo in a double blind study . Endothelial function was assessed by high resolution vascular ultrasound , and high sensitivity C-reactive protein ( CRP ) was assessed by immunoturbidimetric assay . Diabetic patients had higher CRP ( P < 0.01 ) than matched nondiabetic controls , and both endothelium-dependent and independent vasodilation were impaired ( P < 0.01 ) . Atorvastatin ( 10 and 20 mg ) lowered plasma cholesterol by 32.9 % and 38.0 % , triglyceride by 15.4 % and 23.1 % , and low density lipoprotein by 43.4 % and 50.1 % , respectively . At 6 months , plasma CRP decreased in the atorvastatin group compared with baseline ( P < 0.05 ) . Endothelium-dependent vasodilation improved in the atorvastatin group compared with the placebo group ( P < 0.05 ) . The percent change in endothelium-dependent vasodilation at 6 months correlated with the percent change in CRP ( r = -0.44 ; P < 0.05 ) , but not with changes in plasma lipids . In conclusion , treatment with atorvastatin in type 2 diabetes led to a significant improvement in endothelium-dependent vasodilation , which might be partly related to its anti-inflammatory effect PURPOSE The r and omized controlled trial ( RCT ) is the gold st and ard for establishing new therapies in clinical oncology . Here we document changes with time in design , sponsorship , and outcomes of oncology RCTs . METHODS Reports of RCTs evaluating  systemic therapy for breast , colorectal ( CRC ) , and non-small-cell lung cancer ( NSCLC ) published 1975 to 2004 in six major journals were review ed . Two authors abstract ed data regarding trial design , results , and conclusions . Conclusions of authors were grade d using a 7-point Likert scale . For each study the effect size for the primary end point was converted to a summary measure . RESULTS A total of 321 eligible RCTs were included ( 48 % breast , 24 % CRC , 28 % NSCLC ) . Over time , the number and size of RCTs increased considerably . For-profit/mixed sponsorship increased substantially during the study period ( 4 % to 57 % ; P < .001 ) . There was increasing use of time-to-event measures ( 39 % to 78 % ) and decreasing use of response rate ( 54 % to 14 % ) as primary end point ( P < .001 ) . Effect size remained stable over the study period . Authors have become more likely to strongly endorse the experimental arm ( P = .017 ) . A significant P value for the primary end point and industry sponsorship were each independently associated with endorsement of the experimental agent ( odds ratio [ OR ] = 19.6 , 95 % CI , 8.9 to 43.1 , and OR = 3.5 , 95 % CI , 1.6 to 7.5 , respectively ) . CONCLUSION RCTs in oncology have become larger and are more likely to be sponsored by industry . Authors of modern RCTs are more likely to strongly endorse novel therapies . For-profit sponsorship and statistically significant results are independently associated with endorsement of the experimental arm Background Reductions in skeletal muscle mass and increased adiposity are key elements in the aging process and in the pathophysiology of several chronic diseases . Systemic low grade inflammation associated with obesity has been shown to accelerate the age-related decline in skeletal muscle . The aim of this investigation was to determine the effects of 12 months of progressive resistance training ( PRT ) on systemic inflammation , and whether reductions in systemic inflammation were associated with changes in body composition . We hypothesized that reductions in systemic inflammation following 12 months of PRT in older adults with type 2 diabetes would be associated with reductions in adiposity and increases in skeletal muscle mass . Methods Participants ( n = 103 ) were r and omized to receive either PRT or sham-exercise , 3 days a week for 12 months . C-reactive protein ( CRP ) was used to assess systemic inflammation . Skeletal muscle mass and total fat mass were determined using bioelectrical impedance . Results Twelve months of PRT tended to reduce CRP compared to sham exercise ( β = −0.25 , p = 0.087 ) . Using linear mixed-effects models , the hypothesized relationships between body composition adaptations and CRP changes were significantly stronger for skeletal muscle mass ( p = 0.04 ) and tended to be stronger for total fat mass ( p = 0.07 ) following PRT when compared to sham-exercise . Using univariate regression models , stratified by group allocation , reductions in CRP were associated with increases in skeletal muscle mass ( p = 0.01 ) and reductions in total fat mass ( p = 0.02 ) in the PRT group , but not in the sham-exercise group ( p = 0.87 and p = 0.32 , respectively ) . Conclusions We have shown for the first time that reductions in systemic inflammation in older adults with type 2 diabetes following PRT were associated with increases in skeletal muscle mass . Furthermore , reductions in CRP were associated with reductions in adiposity , but only when associated with PRT . Lifestyle interventions aim ed at reducing systemic inflammation in older adults with type 2 diabetes should therefore incorporate anabolic exercise such as PRT to optimize the anti-inflammatory benefits of favorable body composition adaptations Inflammation is increased in chronic obstructive pulmonary disease ( COPD ) and plays a role in exercise intolerance . We investigated whether pravastatin administration is effective in improving exercise capacity in patients with COPD , and whether baseline or serial changes in high-sensitivity C-reactive protein ( hs-CRP ) over time are associated with corresponding changes in exercise capacity . In a r and omized , double-blinded , and parallel design , 125 patients with clinical ly stable COPD were r and omly assigned to receive placebo or pravastatin ( 40 mg/day ) over a period of 6 months . Plasma hs-CRP levels were measured before r and omization and during follow-up . Baseline characteristics were similar in the 2 groups . Exercise time remained stable throughout the study in the placebo group . Exercise time increased by 54 % from 599 + /- 323 seconds at baseline to 922 + /- 328 seconds at the end ( p < 0.0001 ) in pravastatin-treated patients . A decrease in hs-CRP over baseline values was observed in 79 % of patients ( 42 of 53 ) treated with pravastatin . Pravastatin-treated patients with a greater percent decrease in hs-CRP had a significant improvement in exercise time compared with those without hs-CRP decrease . A significant correlation was found in univariate analysis between decrease of log-transformed hs-CRP and increase of exercise time . Baseline hs-CRP and change of hs-CRP were significantly correlated with exercise time , even after adjustment for lipid profiles and hemodynamics . In conclusion , these data reinforce hs-CRP as a significant surrogate marker in COPD and underscore an important guide to the efficacy of treatment in COPD trials BACKGROUND Long-term maintenance of weight loss remains a therapeutic challenge in obesity treatment . OBJECTIVE This multicenter , double-blind , placebo-controlled study was design ed to test the hypothesis that orlistat , a gastrointestinal lipase inhibitor , is significantly more effective than a placebo in preventing weight regain . DESIGN Obese subjects who lost > or = 8 % of their initial body weight during a 6-mo lead-in of a prescribed hypoenergetic diet ( 4180-kJ/d deficit ) with no adjunctive pharmacotherapy  were r and omly assigned to receive placebo , 30 mg orlistat , 60 mg orlistat , or 120 mg orlistat 3 times daily for 1 y in combination with a maintenance diet to help prevent weight regain . Of 1313 recruited subjects [ body mass index ( in kg/m2 ) : 28 - 43 ] , 729 subjects lost > or = 8 % of their initial body weight during the 6-mo weight-loss lead-in period and were enrolled in the double-blind phase . RESULTS After 1 y , subjects treated with 120 mg orlistat 3 times daily regained less weight than did placebo-treated subjects ( 32.8 + /- 4.5 % compared with 58.7 + /- 5.8 % regain of lost weight ; P < 0.001 ) . Moreover , more subjects in the 120-mg orlistat group than in the placebo group regained < or = 25 % of lost weight ( 47.5 % of subjects compared with 29.9 % ) . In addition , orlistat treatment ( 120 mg 3 times daily ) was associated with significantly greater reductions in total and LDL-cholesterol concentrations than was placebo ( P < 0.001 ) . CONCLUSION The use of orlistat during periods of attempted weight maintenance minimizes weight readjustment and facilitates long-term improvement in obesity-related disease risk factors Objective The present study aim ed to combine observational evidence with r and omised controlled trials ( RCTs ) by using the Bayesian approach . Data sources Electronic data bases , including PubMed , Cochrane Central Register of Controlled Trials ( CENTRAL ) , ISI Web of Science , EMBASE and EBSCO were search ed from inception to January 2014 . Study eligibility RCTs and observational studies ( OS ) investigating the effectiveness of activated protein C ( aPC ) on mortality reduction were included for analysis . Participants Patients with sepsis . Intervention aPC . Synthesis methods Observational evidence was incorporated into the analysis by using power transformed priors in a Bayesian . Trial sequential analysis was performed to examine changes over time and whether further studies need to be conducted . Main results a total of 7 RCTs and 12 OS were included for the analysis . There was moderate heterogeneity among included RCTs ( I2=48.6 % , p=0.07 ) . The pooled OR for mortality from RCTs was 1.00 ( 95 % CI 0.84 to 1.19 ) . In OS , there was potential publication bias as indicated by the funnel plot and the pooled OR for mortality with the use of aPC was 0.67 ( 95 % CI 0.62 to 0.72 ) . The pooled effect sizes of RCTs were changed by using different power transform priors derived from observational evidence . When observational evidence was used at its ‘ face value ’ , the treatment effect of aPC was statistically significant in reducing mortality . Conclusions while RCT evidence showed no beneficial effect of aPC on sepsis , observational evidence showed a significant treatment effect of aPC . By using power transform priors in Bayesian model , we explicitly demonstrated how RCT evidence could be changed by observational evidence . Trial registration number The protocol for the current study was registered in PROSPERO ( registration number : CRD42014009562 ) Background —Markers of systemic inflammation ( eg , C-reactive protein [ CRP ] and interleukin-6 [ IL-6 ] ) have been proposed to be “ nontraditional ” risk factors for cardiovascular disease in patients with type 2 diabetes mellitus . Matrix metalloproteinase-9 ( MMP-9 ) has been implicated in the pathogenesis of atherosclerotic plaque rupture , which raises the possibility of the use of MMP-9 levels as a marker for future myocardial infa rct ion or unstable angina . In vitro and animal studies suggest that thiazolidinediones can reduce the expression of these markers . The purpose of this analysis was to determine whether rosiglitazone alters serum concentrations of CRP , IL-6 , MMP-9 , and white blood cell count ( WBC ) and to examine the relationship of these effects with demographic and disease variables . Methods and Results —CRP , IL-6 , MMP-9 , and WBC were analyzed from stored frozen serum sample s obtained from patients with type 2 diabetes who completed a 26-week r and omized , double-blind , placebo-controlled study . After 26 weeks of rosiglitazone treatment , the percentage reductions in mean CRP , MMP-9 , and WBC levels were statistically significant compared with baseline and placebo ( P < 0.01 ) . The percentage reduction in mean IL-6 was small and similar in the rosiglitazone and placebo groups . The change in each inflammatory marker from baseline to week 26 was significantly correlated ( P < 0.05 ) with each of the other markers , as well as with the homeostasis model assessment estimate of insulin resistance . Conclusions —Rosiglitazone reduces serum levels of MMP-9 and the proinflammatory marker CRP in patients with type 2 diabetes , which indicates potentially beneficial effects on overall cardiovascular risk
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 ) .