Disorders of consciousness: Are we ready for a paradigm shift? - Authors' reply
; ; Laureys, Steven et al
in Lancet (2013), Vol 12Detailed reference viewed: 6 (1 ULg)
Reanalysis of “Bedside detection of awareness in the vegetative state: a cohort study”
; ; Noirhomme, Quentin et al
in Lancet (2013), 381Detailed reference viewed: 160 (8 ULg)
Gliptin versus a sulphonylurea as add-on to metformin.
SCHEEN, André ; Paquot, Nicolas
in Lancet (2012), 380Detailed reference viewed: 37 (5 ULg)
Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial
; ; et al
in Lancet (2011), 378(9806)
Background The outcome of diff use large B-cell lymphoma has been substantially improved by the addition of the anti-CD20 monoclonal antibody rituximab to chemotherapy regimens. We aimed to assess, in ... [more ▼]
Background The outcome of diff use large B-cell lymphoma has been substantially improved by the addition of the anti-CD20 monoclonal antibody rituximab to chemotherapy regimens. We aimed to assess, in patients aged 18–59 years, the potential survival benefi t provided by a dose-intensive immunochemotherapy regimen plus rituximab compared with standard treatment plus rituximab. Methods We did an open-label randomised trial comparing dose-intensive rituximab, doxorubicin, cyclo phosphamide, vindesine, bleomycin, and prednisone (R-ACVBP) with subsequent consolidation versus standard rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone (R-CHOP). Random assignment was done with a computer-assisted randomisation-allocation sequence with a block size of four. Patients were aged 18–59 years with untreated diff use large B-cell lymphoma and an age-adjusted international prognostic index equal to 1. Our primary endpoint was event-free survival. Our analyses of effi cacy and safety were of the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00140595. Findings One patient withdrew consent before treatment and 54 did not complete treatment. After a median follow-up of 44 months, our 3-year estimate of event-free survival was 81% (95% CI 75–86) in the R-ACVBP group and 67% (59–73) in the R-CHOP group (hazard ratio [HR] 0·56, 95% CI 0·38–0·83; p=0·0035). 3-year estimates of progression-free survival (87% [95% CI, 81–91] vs 73% [66–79]; HR 0·48 [0·30–0·76]; p=0·0015) and overall survival (92% [87–95] vs 84% [77–89]; HR 0·44 [0·28–0·81]; p=0·0071) were also increased in the R-ACVBP group. 82 (42%) of 196 patients in the R-ACVBP group experienced a serious adverse event compared with 28 (15%) of 183 in the R-CHOP group. Grade 3–4 haematological toxic eff ects were more common in the R-ACVBP group, with a higher proportion of patients experiencing a febrile neutropenic episode (38% [75 of 196] vs 9% [16 of 183]). Interpretation Compared with standard R-CHOP, inten sifi ed immunochemotherapy with R-ACVBP signifi cantly improves survival of patients aged 18–59 years with diff use large B-cell lymphoma with low-intermediate risk according to the International Prognostic Index. Haematological toxic eff ects of the intensive regimen were raised but manageable. Funding Groupe d’Etudes des Lymphomes de l’Adulte and Amgen. [less ▲]Detailed reference viewed: 45 (3 ULg)
Rimonabant for prevention of cardiovascular events (CRESCENDO): a randomised, multicentre, placebo-controlled trial
; Scheen, André
in Lancet (2010), 376
BACKGROUND: Blockade of the endocannabinoid receptor reduces obesity and improves metabolic abnormalities such as triglycerides, HDL cholesterol, and fasting blood glucose. We assessed whether rimonabant ... [more ▼]
BACKGROUND: Blockade of the endocannabinoid receptor reduces obesity and improves metabolic abnormalities such as triglycerides, HDL cholesterol, and fasting blood glucose. We assessed whether rimonabant would improve major vascular event-free survival. METHODS: This double-blind, placebo-controlled trial was undertaken in 974 hospitals in 42 countries. 18,695 patients with previously manifest or increased risk of vascular disease were randomly assigned to receive either rimonabant 20 mg (n=9381) or matching placebo (n=9314). Randomisation was stratified by centre, implemented with an independent interactive voice response system, and all study personnel and participants were masked to group assignment. The primary endpoint was the composite of cardiovascular death, myocardial infarction, or stroke, as determined via central adjudication. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00263042. FINDINGS: At a mean follow-up of 13.8 months (95% CI 13.6-14.0), the trial was prematurely discontinued because of concerns by health regulatory authorities in three countries about suicide in individuals receiving rimonabant. All randomised participants were analysed. At the close of the trial (Nov 6, 2008), the composite primary endpoint of cardiovascular death, myocardial infarction, or stroke occurred in 364 (3.9%) patients assigned to rimonabant and 375 (4.0%) assigned to placebo (hazard ratio 0.97, 95% CI 0.84-1.12, p=0.68). With rimonabant, gastrointestinal (3038 [33%] vs 2084 [22%]), neuropsychiatric (3028 [32%] vs 1989 [21%]), and serious psychiatric side-effects (232 [2.5%] vs 120 [1.3%]) were significantly increased compared with placebo. Four patients in the rimonabant group and one in the placebo group committed suicide. INTERPRETATION: The premature termination of this trial has important lessons for drug development. A drug that was being marketed for weight loss, but being tested for improving cardiovascular outcomes, induced a level of serious neuropsychiatric effects that was deemed unacceptable by regulatory authorities, and both the drug and the trial were abruptly terminated. [less ▲]Detailed reference viewed: 17 (1 ULg)
Addition of incretin therapy to metformin in type 2 diabetes.
Scheen, André ; Radermecker, Régis
in Lancet (2010), 375(9724), 1410-2Detailed reference viewed: 31 (5 ULg)
Clinical staging: a new scenario for the treatment of psychosis
; Laroi, Frank
in Lancet (2009), 374(9687), 365-367Detailed reference viewed: 11 (2 ULg)
Zoledronic acid and risedronate in the prevention and treatment of glucocorticoid-induced osteoporosis (HORIZON): a multicentre, double-blind, double-dummy, randomised controlled trial.
; ; et al
in Lancet (2009), 373(9671), 1253-63
BACKGROUND: Persistent use of glucocorticoid drugs is associated with bone loss and increased fracture risk. Concurrent oral bisphosphonates increase bone mineral density and reduce frequency of vertebral ... [more ▼]
BACKGROUND: Persistent use of glucocorticoid drugs is associated with bone loss and increased fracture risk. Concurrent oral bisphosphonates increase bone mineral density and reduce frequency of vertebral fractures, but are associated with poor compliance and adherence. We aimed to assess whether one intravenous infusion of zoledronic acid was non-inferior to daily oral risedronate for prevention and treatment of glucocorticoid-induced osteoporosis. METHODS: This 1-year randomised, double-blind, double-dummy, non-inferiority study of 54 centres in 12 European countries, Australia, Hong Kong, Israel, and the USA, tested the effectiveness of 5 mg intravenous infusion of zoledronic acid versus 5 mg oral risedronate for prevention and treatment of glucocorticoid-induced osteoporosis. 833 patients were randomised 1:1 to receive zoledronic acid (n=416) or risedronate (n=417). Patients were stratified by sex, and allocated to prevention or treatment subgroups dependent on duration of glucocorticoid use immediately preceding the study. The treatment subgroup consisted of those treated for more than 3 months (272 patients on zoledronic acid and 273 on risedronate), and the prevention subgroup of those treated for less than 3 months (144 patients on each drug). 62 patients did not complete the study because of adverse events, withdrawal of consent, loss to follow-up, death, misrandomisation, or protocol deviation. The primary endpoint was percentage change from baseline in lumbar spine bone mineral density. Drug efficacy was assessed on a modified intention-to-treat basis and safety was assessed on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT00100620. FINDINGS: Zoledronic acid was non-inferior and superior to risedronate for increase of lumbar spine bone mineral density in both the treatment (least-squares mean 4.06% [SE 0.28] vs 2.71% [SE 0.28], mean difference 1.36% [95% CI 0.67-2.05], p=0.0001) and prevention (2.60% [0.45] vs 0.64% [0.46], 1.96% [1.04-2.88], p<0.0001) subgroups at 12 months. Adverse events were more frequent in patients given zoledronic acid than in those on risedronate, largely as a result of transient symptoms during the first 3 days after infusion. Serious adverse events were worsening rheumatoid arthritis for the treatment subgroup and pyrexia for the prevention subgroup. INTERPRETATION: A single 5 mg intravenous infusion of zoledronic acid is non-inferior, possibly more effective, and more acceptable to patients than is 5 mg of oral risedronate daily for prevention and treatment of bone loss that is associated with glucocorticoid use. [less ▲]Detailed reference viewed: 314 (2 ULg)
Voglibose for prevention of type 2 diabetes mellitus.
in Lancet (2009), 373(9675), 1579-80Detailed reference viewed: 48 (1 ULg)
Efficacy and safety of the weight-loss drug rimonabant.
; ; et al
in Lancet (2008), 371(9612), 555556-7Detailed reference viewed: 29 (4 ULg)
Calcium and vitamin D for osteoporotic fracture risk
in Lancet (2007), 370(9588), 632-634Detailed reference viewed: 14 (2 ULg)
Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study.
Scheen, André ; ; et al
in Lancet (2006), 368(9548), 1660-72
BACKGROUND: Rimonabant, a selective cannabinoid type 1 receptor blocker, reduces bodyweight and improves cardiovascular and metabolic risk factors in non-diabetic overweight or obese patients. The aim of ... [more ▼]
BACKGROUND: Rimonabant, a selective cannabinoid type 1 receptor blocker, reduces bodyweight and improves cardiovascular and metabolic risk factors in non-diabetic overweight or obese patients. The aim of the RIO-Diabetes trial was to assess the efficacy and safety of rimonabant in overweight or obese patients with type 2 diabetes that was inadequately controlled by metformin or sulphonylureas. METHODS: 1047 overweight or obese type 2 diabetes patients (body-mass index 27-40 kg/m2) with a haemoglobin A1c (HbA1c) concentration of 6.5-10.0% (mean 7.3% [SD 0.9] at baseline) already on metformin or sulphonylurea monotherapy were given a mild hypocaloric diet and advice for increased physical activity, and randomly assigned placebo (n=348), 5 mg/day rimonabant (360) or 20 mg/day rimonabant (339) for 1 year. Two individuals in the 5 mg/day group did not receive double-blind treatment and were thus not included in the final analysis. The primary endpoint was weight change from baseline after 1 year of treatment. Analyses were done on an intention-to-treat basis. This trial is registered at ClinicalTrials.gov, number NCT00029848. FINDINGS: 692 patients completed the 1 year follow-up; numbers in each group after 1 year were much the same. Weight loss was significantly greater after 1 year in both rimonabant groups than in the placebo group (placebo: -1.4 kg [SD 3.6]; 5 mg/day: -2.3 kg [4.2], p=0.01 vs placebo; 20 mg/day: -5.3 kg [5.2], p<0.0001 vs placebo). Rimonabant was generally well tolerated. The incidence of adverse events that led to discontinuation was slightly greater in the 20 mg/day rimonabant group, mainly due to depressed mood disorders, nausea, and dizziness. INTERPRETATION: These data indicate that 20 mg/day rimonabant, in combination with diet and exercise, can produce a clinically meaningful reduction in bodyweight and improve HbA1c and a number of cardiovascular and metabolic risk factors in overweight or obese patients with type 2 diabetes inadequately controlled by metformin or sulphonylureas. [less ▲]Detailed reference viewed: 167 (3 ULg)
Does the metabolic syndrome help to select patients requiring high statin dose?
in Lancet (2006), 368(9539), 893-4Detailed reference viewed: 23 (0 ULg)
Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial
; ; et al
in Lancet (2005), 366(9493), 1279-1289
Background Patients with type 2 diabetes are at high risk of fatal and non-fatal myocardial infarction and stroke. There is indirect evidence that agonists of peroxisome proliferator-activated receptor ... [more ▼]
Background Patients with type 2 diabetes are at high risk of fatal and non-fatal myocardial infarction and stroke. There is indirect evidence that agonists of peroxisome proliferator-activated receptor gamma (PPAR gamma) could reduce macrovascular complications. Our aim, therefore, was to ascertain whether pioglitazone reduces macrovascular morbidity and mortality in high-risk patients with type 2 diabetes. Methods We did a prospective, randomised controlled trial in 5238 patients with type 2 diabetes who had evidence of macrovascular disease. We recruited patients from primary-care practices and hospitals. We assigned patients to oral pioglitazone titrated from 15 mg to 45 mg (n=2605) or matching placebo (n=2633), to be taken in addition to their glucose-lowering drugs and other medications. Our primary endpoint was the composite of all-cause mortality, non-fatal myocardial infarction (including silent myocardial infarction), stroke, acute coronary syndrome, endovascular or surgical intervention in the coronary or leg arteries, and amputation above the ankle. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN NCT00174993. Findings Two patients were lost to follow-up, but were included in analyses. The average time of observation was 34.5 months. 514 of 2605 patients in the pioglitazone group and 572 of 2633 patients in the placebo group had at least one event in the primary composite endpoint (HR 0.90, 95% CI 0.80-1.02, p=0.095). The main secondary endpoint was the composite of all-cause mortality, non-fatal myocardial infarction, and stroke. 301 patients in the pioglitazone group and 358 in the placebo group reached this endpoint (0.84, 0.72-0.98, p=0.027). Overall safety and tolerability was good with no change in the safety profile of pioglitazone identified. 6% (149 of 2065) and 4% (108 of 2633) of those in the pioglitazone and placebo groups, respectively, were admitted to hospital with heart failure; mortality rates from heart failure did not differ between groups. Interpretation Pioglitazone reduces the composite of all-cause mortality, non-fatal myocardial infarction, and stroke in patients with type 2 diabetes who have a high risk of macrovascular events. [less ▲]Detailed reference viewed: 1079 (4 ULg)
Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study.
; ; Scheen, André et al
in Lancet (2005), 365(9468), 1389-97
BACKGROUND: In animal models, cannabinoid-1 receptor (CB1) blockade produces a lean phenotype, with resistance to diet-induced obesity and associated dyslipidaemia. We assessed the effect of rimonabant, a ... [more ▼]
BACKGROUND: In animal models, cannabinoid-1 receptor (CB1) blockade produces a lean phenotype, with resistance to diet-induced obesity and associated dyslipidaemia. We assessed the effect of rimonabant, a selective CB1 blocker, on bodyweight and cardiovascular risk factors in overweight or obese patients. METHODS: patients with body-mass index 30 kg/m2 or greater, or body-mass index greater than 27 kg/m2 with treated or untreated dyslipidaemia, hypertension, or both, were randomised to receive double-blind treatment with placebo, 5 mg rimonabant, or 20 mg rimonabant once daily in addition to a mild hypocaloric diet (600 kcal/day deficit). The primary efficacy endpoint was weight change from baseline after 1 year of treatment in the intention-to-treat population. FINDINGS: Weight loss at 1 year was significantly greater in patients treated with rimonabant 5 mg (mean -3.4 kg [SD 5.7]; p=0.002 vs placebo) and 20 mg (-6.6 kg [7.2]; p<0.001 vs placebo) compared with placebo (-1.8 kg [6.4]). Significantly more patients treated with rimonabant 20 mg than placebo achieved weight loss of 5% or greater (p<0.001) and 10% or greater (p<0.001). Rimonabant 20 mg produced significantly greater improvements than placebo in waist circumference, HDL-cholesterol, triglycerides, and insulin resistance, and prevalence of the metabolic syndrome. The effects of rimonabant 5 mg were of less clinical significance. Rimonabant was generally well tolerated with mild and transient side effects. INTERPRETATION: CB1 blockade with rimonabant 20 mg, combined with a hypocaloric diet over 1 year, promoted significant decrease of bodyweight and waist circumference, and improvement in cardiovascular risk factors. [less ▲]Detailed reference viewed: 14 (0 ULg)