63 research outputs found

    Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials

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    Background Patients with chronic obstructive pulmonary disease (COPD) have few options for treatment. The efficacy and safety of the phosphodiesterase-4 inhibitor roflumilast have been investigated in studies of patients with moderate-to-severe COPD, but not in those concomitantly treated with longacting inhaled bronchodilators. The effect of roflumilast on lung function in patients with COPD that is moderate to severe who are already being treated with salmeterol or tiotropium was investigated. Methods In two double-blind, multicentre studies done in an outpatient setting, after a 4-week run-in, patients older than 40 years with moderate-to-severe COPD were randomly assigned to oral roflumilast 500 mu g or placebo once a day for 24 weeks, in addition to salmeterol (M2-127 study) or tiotropium (M2-128 study). The primary endpoint was change in prebronchodilator forced expiratory volume in 1s (FEV(1)). Analysis was by intention to treat. The studies are registered with ClinicalTrials.gov, number NCT00313209 for M2-127, and NCT00424268 for M2-128. Findings In the salmeterol plus roflumilast trial, 466 patients were assigned to and treated with roflumilast and 467 with placebo; in the tiotropium plus roflumilast trial, 371 patients were assigned to and treated with roflumilast and 372 with placebo. Compared with placebo, roflumilast consistently improved mean prebronchodilator FEV(1) by 49 mL (p<0.0001) in patients treated with salmeterol, and 80 mL (p<0.0001) in those treated with tiotropium. Similar improvement in postbronchodilator FEV(1) was noted in both groups. Furthermore, roflumilast had beneficial effects on other lung function measurements and on selected patient-reported outcomes in both groups. Nausea, diarrhoea, weight loss, and, to a lesser extent, headache were more frequent in patients in the roflumilast groups. These adverse events were associated with increased patient withdrawal. Interpretation Roflumilast improves lung function in patients with COPD treated with salmeterol or tiotropium, and could become an important treatment for these patients

    Is increased time to diagnosis and treatment in symptomatic cancer associated with poorer outcomes?:Systematic review

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    background: It is unclear whether more timely cancer diagnosis brings favourable outcomes, with much of the previous evidence, in some cancers, being equivocal. We set out to determine whether there is an association between time to diagnosis, treatment and clinical outcomes, across all cancers for symptomatic presentations. methods: Systematic review of the literature and narrative synthesis. results: We included 177 articles reporting 209 studies. These studies varied in study design, the time intervals assessed and the outcomes reported. Study quality was variable, with a small number of higher-quality studies. Heterogeneity precluded definitive findings. The cancers with more reports of an association between shorter times to diagnosis and more favourable outcomes were breast, colorectal, head and neck, testicular and melanoma. conclusions: This is the first review encompassing many cancer types, and we have demonstrated those cancers in which more evidence of an association between shorter times to diagnosis and more favourable outcomes exists, and where it is lacking. We believe that it is reasonable to assume that efforts to expedite the diagnosis of symptomatic cancer are likely to have benefits for patients in terms of improved survival, earlier-stage diagnosis and improved quality of life, although these benefits vary between cancers

    Central pathways causing fatigue in neuro-inflammatory and autoimmune illnesses

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    Early rebleeding and death at 6 weeks in alcoholic cirrhotic patients with acute variceal bleeding treated with emergency endoscopic injection sclerotherapy

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    Background. This study evaluated the incidence of rebleeding and death at 6 weeks after a first episode of acute variceal haemorrhage (AVH) treated by emergency endoscopic sclerotherapy in a large cohort of alcoholic cirrhotic patients. Methods. From January 1984 to December 2006, 310 alcoholic cirrhotic patients (242 men, 68 women; mean age 51.7 years) with AVH underwent 786 endoscopic variceal injection treatments (342 emergency, 444 elective) during 919 endoscopy sessions in the first 6 weeks after the first variceal bleed. Endoscopic control of initial bleeding, variceal rebleeding and survival at 6 weeks were recorded. Results. Endoscopic intervention controlled AVH in 304 of 310 patients (98.1%). Seventy-five patients (24.2%) rebled, 38 (12.3%) within 5 days and 37 (11.9%) within 6 weeks. No patient scored as Child-Pugh A died. Seventy-seven (24.8%) Child-Pugh B and C patients died, 29 (9.3%) within 5 days and 48 (15.4%) between 6 and 42 days. Mortality increased exponentially as the Child-Pugh score increased, reaching 80% when the score exceeded 13. Conclusion. Despite initial control of variceal haemorrhage, 1 in 4 patients (24.2%) rebled within 6 weeks. Survival at 6 weeks was 75.2% and was influenced by the severity of liver failure, with most deaths occurring in Child-Pugh grade C patients
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