Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Long-term nutritional management of an obese German Spitz with paroxysmal dyskinesia, calcium oxalate urolithiasis, and suspected pancreatitis—A case report

BackgroundTo our knowledge, this is the first description of long-term nutritional management in a dog with paroxysmal dyskinesia.Case summaryAn obese 9-year-old, male entire, German Spitz was presented for dietary management after being diagnosed with calcium oxalate urolithiasis and suspected pancreatitis. Since he was seven years old, the dog has had a history of neurological signs, which were thought to be epileptic seizures. He was treated with phenobarbital and potassium bromide and was clinically controlled. For his nutritional advice, aiming to minimize one of the most important risk factors for the diseases, a weight loss program was started and successfully executed. However, 10 months later, the dog restarted presenting neurological episodes at a high frequency (3x/week). Based on videos and the characteristics of the neurological signs, the dog was diagnosed with paroxysmal dyskinesia. To investigate the role of gluten intake on this patient's neurological signs, a dietary trial with a commercial hypoallergenic diet (gluten-free; hydrolyzed protein) was followed. During the 3 months of the dietary trial, four neurologic episodes related to food indiscretion occurred. Upon the decrease in neurological episodes, the anti-seizure drugs were slowly discontinued. During this period, the dog presented only two neurologic episodes that were related to the days that the anti-seizure drugs were decreased. For 4 months the dog remained episode-free. However, a change in the dog's diet to another gluten-free diet (higher fat) led the dog to vomit and experience another neurologic episode. Once the dog was back to the previous gluten-free diet, it clinically improved, and no other clinical signs were reported by the client during the next 5 months.ConclusionAlthough a relationship between gluten and paroxysmal dyskinesia cannot be confirmed, the dog's improvement after the nutritional management and the removal of the anti-seizure therapy is supportive of dietary association

Development and feasibility of an exercise training program in primary care for patients with COPD experiencing an acute exacerbation

Background Starting rehabilitation soon after an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is crucial to diminish the detrimental effects of this acute event on muscle function. However, uptake in outpatient pulmonary rehabilitation is low. Objectives To design and test a feasible, acceptable and accessible exercise training program (ETP) in primary care for patients experiencing an AECOPD. Design (1) A literature review and qualitative study to develop an ETP and (2) A feasibility study of the ETP implemented in primary care. Methods (1) The development of the ETP proceeded in several phases with input from different stakeholders through focus group discussions. (2) Patients experiencing a moderate or severe AECOPD were included and followed the ETP for two weeks with a physiotherapist in primary care. Interviews with the participants took place and patients were given the choice to complete the eight-week program. Results (1) Six discussion sessions took place. The ETP contained a flexible set of progressively more difficult exercises applicable in a primary care practice. (2) Eight patients experiencing a moderate (n = 1) or severe (n = 7) AECOPD were included. Patients started the first physiotherapy session 5 (2-6) days after the start of their symptoms or hospital discharge. Seven patients wanted to complete the ETP. Conclusions An ETP in primary care is feasible, acceptable and accessible for patients experiencing a moderate or severe AECOPD, and for physiotherapists. The effectiveness of this ETP on muscle function and physical activity is currently under investigation in a RCT

The association of weather conditions with day-to-day variability in physical activity in patients with COPD

Background While patients with COPD often cite weather conditions as a reason for inactivity, little is known about the relationship between physical activity (PA) and weather conditions. The present study investigated the association of day-to-day weather changes on PA in patients with COPD and investigated patient characteristics related to being more or less influenced by weather conditions. Methods In this longitudinal analysis, device-based day-by-day step counts were objectively measured in COPD patients for up to 12 months. Daily meteorological data (temperature, precipitation, wind speed, hours of sunlight and daylight) were linked to the daily step count and individual and multivariable relationships were investigated using mixed-model effects. Individual R-2 was calculated for every subject to investigate the estimated influence of weather conditions on a patient level and its relationship with patient characteristics. Results We included 50 patients with a mean +/- SD follow-up time of 282 +/- 93 days, totalling 14 117 patient-days. Daily temperature showed a positive linear pattern up until an inflexion point, after which a negative association with increasing temperature was observed (p<0.0001). Sunshine and daylight time had a positive association with PA ( p<0.0001). Precipitation and wind speed were negatively associated with PA ( p<0.0001). The median per-patient R-2 for overall weather conditions was 0.08, ranging from 0.00 to 0.42. No strong associations between patient characteristics and per-patient R-2 were observed. Conclusion Weather conditions are partly associated with PA in patients with COPD, yet the overall explained variance of PA due to weather conditions is rather low and varied strongly between individuals