Ivabradine drug utilization study in five European countries: A multinational, retrospective, observational study to assess effectiveness of risk-minimization measures.

PURPOSE: This drug utilization study of ivabradine evaluated prescriber compliance with the new risk minimization measures (RMMs), communicated starting 2014 following preliminary results from the SIGNIFY study. METHODS: This was a multinational (five European countries) chart review study with two study periods: pre-RMM and post-RMM. Patients initiating ivabradine for chronic stable angina pectoris in routine clinical practice were identified across general practitioners and specialists. The primary outcome analysis evaluated the compliance with the new RMMs, ie, use in patients with a heart rate greater than or equal to 70 bpm at initiation, no doses higher than those recommended in the summary of product characteristics (SmPC) at initiation and during 6 months of follow-up, and no concomitant use of verapamil or diltiazem. RESULTS: Overall, 711 and 506 eligible patients were included in the pre-RMM and post-RMM periods, respectively. The percentage of patients prescribed ivabradine according to the new RMMs increased significantly in the post-RMM period (70.6% and 78.4% in the pre- and post-RMM periods respectively; P value = .0035). The compliance to RMMs increased for all the criteria assessed independently: the proportions of patients with (a) heart rate ≥ 70 bpm at initiation (79.4% and 85.2%, respectively; P value = .0141), (b) no dose higher than the SmPC doses at initiation and during follow-up (92.8% and 94.1%, respectively; P value = .3957), and (c) no concomitance with verapamil or diltiazem (96.1% and 99.2%, respectively; P value = .0007). CONCLUSIONS: The RMMs for ivabradine were well implemented across the five participating European countries confirming a favorable benefit-risk balance of ivabradine in chronic stable angina pectoris.

WITHDRAWN: Relocation of blood gas laboratory to the emergency department helps decrease lactic acid values.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.ajem.2018.03.017. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Relocation of blood gas laboratory to the emergency department helps decrease lactic acid values.

IMPORTANCE: Emergency Physicians often rely on Lactic Acid (LA) values to make important clinical decisions. Accuracy of LA values improve when blood gas analysis is performed in the emergency department (ED) as opposed to a satellite laboratory (SL). OBJECTIVE: To investigate an association between blood gas laboratory location and accuracy of ED lactic acid samples. METHODS: The study team evaluated lactic acid values from venous and arterial blood gas samples drawn between June 1, 2015 and September 30, 2016. The study was exempt from institutional review board approval. Samples were separated into two groups: those which were drawn prior to and after relocation of the blood gas laboratory to the ED. The data, including patient demographic characteristics, acute illness severity indices, and blood gas results were compared within and between each group using t-test for continuous variables and chi-square test for categorical variables. The primary outcome was the mean lactate value measured in the SL group in 2015 compared to the ED group in 2016. Potassium and creatinine values were measured between the two groups as secondary outcomes. RESULTS: Of the 21,595 consecutive samples drawn, 10,363 samples were from the SL group and 11,232 from the ED group. The SL group included 5458 (52.7%) women; mean (SD) age was 61.8 (21.0). The ED group contained 5860 (52.2%) women; mean (SD) age was 61.7 (20.5). Mean Emergency Severity Index (ESI) were the same in each group at 2.31 and rates of Systemic Inflammatory Response Syndrome (SIRS) were also equivalent in each group at 22.2%. Significant differences were found between LA values in the SL group (mean 2.21mmol/L) and in the ED group (mean 1.99mmol/L) with a p value of <0.0001. There was a small statistical significance between the difference in potassium values in the SL group (mean 3.98meq/L) compared to the ED Group (mean 3.96meq/L) with a p value of 0.022. No significant difference was found between the creatinine values. CONCLUSIONS AND RELEVANCE: These results suggest that mean lactate values decreased when measured in an ED blood gas laboratory and may provide more accurate LA results than blood gas samples analyzed at an SL blood gas laboratory within the same institution. Hospitals may consider moving blood gas laboratories to the ED to improve accuracy of one of the most important early blood markers used in the definition of sepsis and in the identification of the critically ill.

Insulin-Like Growth Factor-1 but Not Insulin Predicts Cognitive Decline in Huntington's Disease.

BACKGROUND: Huntington's disease (HD) is one of several neurodegenerative disorders that have been associated with metabolic alterations. Changes in Insulin Growth Factor 1 (IGF-1) and/or insulin input to the brain may underlie or contribute to the progress of neurodegenerative processes. Here, we investigated the association over time between changes in plasma levels of IGF-1 and insulin and the cognitive decline in HD patients. METHODS: We conducted a multicentric cohort study in 156 patients with genetically documented HD aged from 22 to 80 years. Among them, 146 patients were assessed at least twice with a follow-up of 3.5 ± 1.8 years. We assessed their cognitive decline using the Unified Huntington's Disease Rating Scale, and their IGF-1 and insulin plasmatic levels, at baseline and once a year during the follow-up. Associations were evaluated using a mixed-effect linear model. RESULTS: In the cross-sectional analysis at baseline, higher levels of IGF-1 and insulin were associated with lower cognitive scores and thus with a higher degree of cognitive impairment. In the longitudinal analysis, the decrease of all cognitive scores, except the Stroop interference, was associated with the IGF-1 level over time but not of insulin. CONCLUSIONS: IGF-1 levels, unlike insulin, predict the decline of cognitive function in HD.

The most appropriate primary outcomes to design clinical trials on Huntington's disease: meta-analyses of cohort studies and randomized placebo-controlled trials.

Huntington's disease (HD) is a rare multifactorial neurodegenerative disease. Both its natural course and any placebo effect are poorly known. All are obstacles to design randomized controlled trials (RCTs). We conducted meta-analyses of RCTs and cohorts on all parameters of the Unified Huntington's Disease Rating Scale to determine the most appropriate outcomes and to minimize the number of patients required to design RCTs in HD. Twenty-four RCTs were included, involving 838 patients with a mean age of 50.0 ± 2.3 years and a mean total functional capacity (TFC) score of 9.8 ± 0.6. Nineteen cohorts were included involving 1939 patients with a mean age of 48.9 ± 2.3 years and a mean TFC of 10.1 ± 0.7. Significant deterioration was observed in RCTs for all scores except behavioral score. Effect sizes were comparable between RCTs and cohorts for each test except that there was a significant difference for TFC. The weighted mean deterioration per year on the TFC scale was -0.5 (0.2) in RCTs and -0.8 (0.2) in cohorts. The lowest number of patients required per group in a RCT was for TFC (19 per group), whereas 30 patients would be required per group for the total motor score (TMS). For cognition, the verbal fluency test required the smallest number of patients: 104 per group. In conclusion, TMS and TFC are the most appropriate outcomes to design RCTs on HD likewise the verbal fluency test for cognition. Our results suggest an effect of placebo administration on the total functional capacity.