Clinical outcome and cost-effectiveness of a 1-year nutritional intervention programme in COPD patients with low muscle mass: The randomized controlled NUTRAIN trial.

BACKGROUND AND AIMS: The efficacy of nutritional intervention to enhance short- and long-term outcomes of pulmonary rehabilitation in COPD is still unclear, hence this paper aims to investigate the clinical outcome and cost-effectiveness of a 12-month nutritional intervention strategy in muscle-wasted COPD patients. METHODS: Prior to a 4-month pulmonary rehabilitation programme, 81 muscle-wasted COPD patients (51% males, aged 62.5 ± 0.9 years) with moderate airflow obstruction (FEV1 55.1 ± 2.2% predicted) and impaired exercise capacity (Wmax 63.5 ± 2.4% predicted) were randomized to 3 portions of nutritional supplementation per day (enriched with leucine, vitamin D and polyunsaturated fatty acids) [NUTRITION] or PLACEBO (phase 1). In the unblinded 8-month maintenance phase (phase 2), both groups received structured feedback on their physical activity level assessed by accelerometry. NUTRITION additionally received 1 portion of supplemental nutrition per day and motivational interviewing-based nutritional counselling. A 3-month follow-up (phase 3) was included. RESULTS: After 12 months, physical capacity measured by quadriceps muscle strength and cycle endurance time were not different, but physical activity was higher in NUTRITION than in PLACEBO (Δ1030 steps/day, p = 0.025). Plasma levels of the enriched nutrients (p < 0.001) were higher in NUTRITION than PLACEBO. Trends towards weight gain in NUTRITION and weight loss in PLACEBO led to a significant between-group difference after 12 months (Δ1.54 kg, p = 0.041). The HADS anxiety and depression scores improved in NUTRITION only (Δ-1.92 points, p = 0.037). Generic quality of life (EQ-5D) was decreased in PLACEBO but not in NUTRITION (between-group difference after 15 months 0.072 points, p = 0.009). Overall motivation towards exercising and healthy eating was high and did not change significantly after 12 months; only amotivation towards healthy eating yielded a significant between-group difference (Δ1.022 points, p = 0.015). The cost per quality-adjusted life-year after 15 months was EUR 16,750. CONCLUSIONS: Nutritional intervention in muscle-wasted patients with moderate COPD does not enhance long-term outcome of exercise training on physical capacity but ameliorates plasma levels of the supplemented nutrients, total body weight, physical activity and generic health status, at an acceptable increase of costs for patients with high disease burden.

Efficacy of acetylleucine in vertigo and dizziness: a systematic review of randomised controlled trials.

PURPOSE: To assess the efficacy of acetylleucine to improve or stop an attack of vertigo and dizziness (vertigo/dizziness). METHODS: Systematic review by 2 independent reviewers. Consultation of the Medline, Cochrane and ClinicalTrials.gov databases until September 2018. Keywords used: Acetylleucine, Tanganil®, Acetyl-DL-leucine, Acetyl-leucine. Trial selection: randomised controlled trials (RCTs) comparing acetylleucine against placebo. RESULTS: Up until 2018, no RCTs have been published on the efficacy of acetylleucine in vertigo/dizziness. CONCLUSION: There is no solid evidence of the efficacy of acetylleucine in vertigo/dizziness. Given its frequent prescription and the cost generated for the French social security system, high-quality randomised trials should be carried out to assess its efficacy.

Lexipafant and acute pancreatitis: a critical appraisal of the clinical trials.

The recent clinical trials of lexipafant in the treatment of acute pancreatitis were undertaken with considerable optimism. It was expected that this single agent anticytokine would reduce the morbidity and mortality of this disease. Published clinical trials of lexipafant (BB-882) in acute pancreatitis were retrieved by MEDLINE, EM Base, and Science Citation Index. The critical appraisal included the question asked, design of the study, group and selection of patients, results, and statistical analysis. The historical sequence of the trials and the impact of commerce on their performance were highlighted. Lexipafant did not reduce mortality in severe acute pancreatitis. Comparison between the trials is difficult because of changes in study groups and dose. The clinical trials were designed without the benefit of open discussion of the preliminary pharmacological studies. The results of the trials have not been communicated in an open, timely, and systematic manner, probably because of commercial constraints.

Biochemical assessment of myocardial injury after cardiac surgery: effects of a platelet activating factor antagonist, bilateral internal thoracic artery grafts, and coronary endarterectomy.

OBJECTIVE: Platelet activating factor antagonists reduce ischemia-reperfusion injury in experiments, but there is no supportive clinical evidence. METHODS: A single-center, double-blind, minimized, placebo-controlled, randomized trial of low-dose (10 mg) or high-dose (100 mg) platelet activating factor antagonist was conducted in 150 patients undergoing coronary artery bypass grafting. Myocardial injury was determined by serial measurements of the MB isoenzyme of creatine kinase and cardiac troponin T. The effects of single or bilateral internal thoracic artery grafting and coronary endarterectomy on myocardial injury were also assessed. RESULTS: The placebo and platelet activating factor antagonist groups were similar with respect to preoperative, intraoperative, and postoperative factors. Four patients (2.7%) died before discharge, 3 from cardiac events. Thirteen patients (9%) had biochemical evidence of myocardial infarction, of whom 3 died. Stepwise multiple regression analysis demonstrated that duration of cardiopulmonary bypass was the most important determinant of elevations in creatine kinase MB isoenzyme and cardiac troponin T up to 6 hours after the operation and that the use of a platelet activating factor antagonist and the number of internal thoracic artery grafts did not influence myocardial injury at any time. Endarterectomy was performed in 11 patients (7%), of whom 6 (55%) had biochemically defined myocardial infarction and of whom 1 died (9%). Endarterectomy was the most important determinant of elevated levels of creatine kinase MB isoenzyme and cardiac troponin T 24 and 48 hours after the operation. CONCLUSION: Platelet activating factor antagonists do not reduce perioperative myocardial injury. Bilateral and single internal thoracic artery grafting results in similar levels of myocardial injury, whereas endarterectomy is frequently associated with biochemical evidence of myocardial injury.

Morphometric assessment of drug effects in experimental spinal cord injury.

The effect of large doses of methylprednisolone sodium succinate (MPSS) and two protease inhibitors, leupeptin and bestatin, on experimental acute spinal cord injury was evaluated by morphometric analysis of degenerating axons with the aid of an automated image analyzer. Spinal cord injury was produced by epidural compression with a surgical clip on the T-11 segment in rats. The extent of axonal damage was assessed in Rexed's lamina VIII in the L-6 segment by measuring the amount of silver grains, representing degenerating axons and their terminals, using the Fink-Heimer method. The severity of axonal damage was expressed as the degeneration index: that is, the amount of silver grains in experimental animals/the amount of silver grains in cord-transected animals. When examined on the 7th postoperative day, axonal degeneration in MPSS-treated rats was significantly decreased, with an average degeneration index difference of 6 (p less than 0.05). Increased preservation of axons was seen in the leupeptin-treated rats sacrificed 7, 10, and 14 days after trauma. The difference in the degeneration index between the leupeptin-treated and untreated groups was 16 on Day 7 (p less than 0.001), 12 on Day 10 (p less than 0.001), and 13 on Day 14 (p less than 0.01). Bestatin had no beneficial effect. The implications for the use of calcium-activated neutral protease inhibitors in acute spinal cord injury are discussed.