Elucidating the risk of cardiopulmonary consequences of an exacerbation of COPD: results of the EXACOS-CV study in Germany.

BACKGROUND: Exacerbations of chronic obstructive pulmonary disease (COPD) represent a period of vulnerability. This study explored the association between time periods following an exacerbation and the risk of severe cardiovascular (CV) events or death in Germany. METHODS: A longitudinal cohort study was conducted using routinely collected healthcare data. Individuals with COPD were identified between 2014 and 2018. Exposure was moderate or severe exacerbation of COPD. Periods at risk were the 1-7, 8-14, 15-30, 31-180 and 181-365 days following each exacerbation onset occurring after cohort entry. The main outcome of interest was the first hospitalisation for a CV event or all-cause death. Time-dependent Cox proportional hazards models estimated the HR for the association between subperiods versus periods outside exacerbations, and the risk of outcome. RESULTS: Among 126 795 patients, 58 720 (46.3%) exacerbated at least once and 48 982 (38.6%) experienced at least one CV event or died during a median follow-up of 36 months. The rate of outcome was increased during 1-7 days following a severe exacerbation onset (HR 15.84, 95% CI 15.26 to 16.45), and remained elevated for up to a year (181-365 days HR 1.17, 95% CI 1.11 to 1.23). In the 1-7 days following a moderate exacerbation onset, the increased rate was HR 1.17, 95% CI 1.05 to 1.31). CONCLUSION: The risk of a CV event or death increased in time periods following both moderate and severe exacerbations of COPD, emphasising the need to promptly manage the risk of CV events following the onset of an exacerbation, to prevent exacerbations of any severity, and more generally, to address the cardiopulmonary risk in patients with COPD.

Patterns of Lisdexamfetamine Dimesylate Use in Children, Adolescents, and Adults with Attention-Deficit/Hyperactivity Disorder in Europe.

Objectives: Lisdexamfetamine dimesylate (LDX) is approved in some European countries for the second-line treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents when response to previous methylphenidate (MPH) treatment is considered clinically inadequate, and as a first-line treatment in adults. Limited evidence exists on the real-world use of LDX across Europe. This retrospective study evaluated LDX drug utilization patterns from eight European countries for up to 5 years. Methods: Data were collected from national registries (Denmark, Finland, Norway, Sweden), electronic medical records (Germany, Spain, United Kingdom), and prescription databases (Switzerland) in eight European countries. Patients were included if they were prescribed LDX at least once since the LDX launch date in each country. Demographic and clinical characteristics, and LDX prescription data included patient age and gender, a recorded diagnosis of ADHD, the number of prescriptions per participant, previous MPH prescription recorded, average daily dose, treatment persistence, discontinuation, and switching of medications. Results: Overall, information for 59,292 patients (437,272 LDX prescriptions) was analyzed. Most patients were male (58.1%-84.3%) and fewer than 1% were under 6 years of age. Extensive use of LDX in adults was observed in four countries (Denmark, Finland, Norway, and Sweden), including countries where LDX was not approved for this age group. Most patients had a recorded diagnosis of ADHD (61.9%-95.4%). The mean number of prescriptions per patient ranged from 5.4 to 10.0. At least 79.6% of patients with ADHD had a recorded previous MPH prescription. Mean duration of LDX exposure ranged from 233.1 to 410.8 days. The average daily dose of LDX was ≤70 mg/day for most patients (79.4%-99.7%). The 5-year discontinuation rate ranged from 22.8% to 70.6% and was below 40% for most countries. The proportion of patients switching from LDX to other medications was ≤33.8. Conclusions: This study provides the first long-term, real-world information related to LDX use by children, adolescents, and adults in Europe in the 5 years since its first launch in the region. Most LDX prescriptions fulfilled label requirements regarding a recorded diagnosis of ADHD before treatment initiation, previous MPH use, and an average daily dose of ≤70 mg/day. LDX was largely prescribed within the indicated age range, although adult use of LDX was high in some countries where LDX is not approved for this population.

Phosphopeptide enrichment by IEF.

In our efforts to improve the identification of phosphopeptides by MS we have used peptide IEF on IPG strips. Phosphopeptides derived from trypsin digests of single proteins as well as complex cellular protein mixtures can be enriched by IEF and recovered in excellent yields at the acidic end of an IPG strip. IPG peptide fractionation in combination with MS/MS analysis has allowed us to identify phosphopeptides from tryptic digests of a cellular protein extract.