BACKGROUND An improvement in overall survival among patients with metastatic melanoma has been an elusive goal. In this phase 3 study, ipilimumab — which blocks cytotoxic T-lymphocyte–associated antigen 4 to potentiate an antitumor T-cell response — administered with or without a glycoprotein 100 (gp100) peptide vaccine was compared with gp100 alone in patients with previously treated metastatic melanoma. METHODS A total of 676 HLA-A⋆0201–positive patients with unresectable stage III or IV melanoma, whose disease had progressed while they were receiving therapy for metastatic disease, were randomly assigned, in a 3:1:1 ratio, to receive ipilimumab plus gp100 (403 patients), ipilimumab alone (137), or gp100 alone (136). Ipilimumab, at a dose of 3 mg per kilogram of body weight, was administered with or without gp100 every 3 weeks for up to four treatments (induction). Eligible patients could receive reinduction therapy. The primary end point was overall survival. RESULTS The median overall survival was 10.0 months among patients receiving ipilimumab plus gp100, as compared with 6.4 months among patients receiving gp100 alone (hazard ratio for death, 0.68; P<0.001). The median overall survival with ipilimumab alone was 10.1 months (hazard ratio for death in the comparison with gp100 alone, 0.66; P = 0.003). No difference in overall survival was detected between the ipilimumab groups (hazard ratio with ipilimumab plus gp100, 1.04; P = 0.76). Grade 3 or 4 immune-related adverse events occurred in 10 to 15% of patients treated with ipilimumab and in 3% treated with gp100 alone. There were 14 deaths related to the study drugs (2.1%), and 7 were associated with immune-related adverse events. CONCLUSIONS Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma. Adverse events can be severe, long-lasting, or both, but most are reversible with appropriate treatment. (Funded by Medarex and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00094653.)
This systematic review and meta-analysis aimed to quantify weight gain after smoking cessation and the difference in weight gain between quitters and continuing smokers. Five electronic databases were searched before January 2015. Population-based prospective cohort studies were included if they recorded the weight change of adult smokers from baseline (before smoking cessation) to follow-up (at least 3 months after cessation). Thirty-five cohort studies were identified, including 63,403 quitters and 388,432 continuing smokers. The mean weight gain was 4.10 kg (95% confidence interval [CI]: 2.69, 5.51) and body mass index (BMI) gain was 1.14 kg m(-2) (95% CI: 0.50, 1.79) among quitters. Compared with continuing smoking, quitting smoking was significantly associated with absolute weight (adjusted mean difference [MD]: 2.61 kg; 95% CI: 1.61, 3.60) and BMI gain (adjusted MD: 0.63 kg m(-2) ; 95% CI: 0.46, 0.80). Subgroup analyses using geographic region found that the difference in weight gain was considerably greater in studies from North America than from Asia. Follow-up length was identified as a source of heterogeneity, such that studies with longer follow-up showed greater difference in weight gain. Effective strategies are needed to encourage smokers to quit irrespective of potential weight gain and to help quitters avoid excess weight gain.
Distinct pain trajectories identified suggest that homogeneous subgroups exist, which might be useful for phenotypic assessment for pain management, particularly in knee osteoarthritis. Structural pathology was associated with worse pain trajectories, suggesting that peripheral stimuli are critical for the development and maintenance of pain severity. Environmental and psychological factors may exacerbate pain perception.
Objectives: To examine the association of metabolic syndrome (MetS) and its components with knee pain severity trajectories. Methods: Data from a population-based cohort study were utilised. Baseline blood pressure, glucose, triglycerides and high-density lipoprotein (HDL) cholesterol were measured. MetS was defined according to the National Cholesterol Education Program-Adult Treatment Panel III criteria. Radiographic knee osteoarthritis (ROA) was assessed by X-ray. Pain severity was measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain questionnaire at each time-point. Groupbased trajectory modelling was used to identify pain trajectories and multi-nominal logistic regression was used for analysis. Mediation analysis was performed to assess whether body mass index (BMI)/ central obesity mediated the association between MetS, its components and pain trajectories. Results: Among 985 participants (Mean ± SD age: 62.9 ± 7.4, 50% female), 32% had MetS and 60% had ROA. Three pain trajectories were identified: 'Minimal pain' (52%), 'Mild pain' (33%) and 'Moderate pain' (15%). After adjustment for potential confounders, central obesity increased risk of belonging to both 'Mild pain' and 'Moderate pain' trajectories as compared to the 'Minimal pain' trajectory group, but MetS [relative risk ratio (RRR): 2.26, 95%CI 1.50e3.39], hypertriglyceridemia (RRR: 1.75, 95%CI 1.16e2.62) and low HDL (RRR: 1.67, 95%CI 1.10e2.52) were only associated with 'Moderate pain' trajectory. BMI/central obesity explained 37e70% of these associations. Results were similar in those with ROA. Conclusion: MetS and its components are predominantly associated with worse pain trajectories through central obesity, suggesting that the development and maintenance of worse pain trajectories may be caused by MetS.
Psychological and structural factors interact with each other to exacerbate pain perception, suggesting that tailored treatment approaches for older people with knee pain in clinical practice are needed.
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