A self-rating scale for patient-perceived side effects of inhaled corticosteroids

BACKGROUND: Patient-reported side effect questionnaires offer a simple method for the systematic measurement of drug-related side effects. In order to measure patients' inhaled corticosteroids (ICS) related side effect perceptions the 14-day retrospective Inhaled Corticosteroid Questionnaire (ICQ) was developed. In this research we aim to assess the construct validity and reliability of the ICQ and test its responsiveness to dose changes in adult asthma patients. METHODS: In a cross-sectional study, current inhaler users with asthma completed the ICQ (27 with non ICS inhaler; 61 BDP equivalent daily ICS low dose ≤400 μg; 62 mid dose 401–800 μg; and 105 with high dose >800 μg). We generated 3 construct validity hypotheses: 1) a hierarchical dose-response pattern for scoring of the individual items on the ICQ, and statistically significant differences in the scores of each of the 15 ICQ domains by ICS dose group 2) an association between ICS dose and ICQ scoring after adjusting for appropriate confounders in multiple regression; 3) greater convergence between local side effect domains than between systemic and local domains of the scale. Test-retest reliability was assessed on a randomly selected subgroup of patients (n = 73) who also completed the ICQ a second time after 7 days. In a separate longitudinal study, 61 patients with asthma completed the ICQ at baseline and after changing their daily ICS dose, at 2- and 6- months, in order to test the ICQ's responsiveness. RESULTS: All three construct validity hypotheses were well supported: 1) a statistically significant difference existed in scores for 14 domains, the high ICS dose group scoring highest; 2) ICS dose independently predicted ICQ scoring after adjusting for confounders; 3) greater convergence existed between local ICQ domains than between local and systemic domains. The ICQ had good reproducibility: test-retest intraclass correlation coefficients were ≥0.69 for all but the 'Facial Oedema' domain. In the longitudinal study, ICQ scores for 'Voice Problems' changed significantly at 2- and 6-months from baseline and other ICQ domains displayed trends in scoring change accordant with dose modulation at 6-months. CONCLUSION: The ICQ has good dose-related discriminative properties, is valid, reliable, and shows potential responsiveness to ICS dose change

An unusual evolutionary strategy: the origins, genetic repertoire, and implications of doubly uniparental inheritance of mitochondrial DNA in bivalves

International audienceMitochondrial DNA (mtDNA) is typically passed on to progeny only by the female parent. The phenomenon of "doubly uniparental inheritance" (DUI) of mtDNA in many bivalve species is a fascinating exception to the paradigm of strict maternal inheritance of mtDNA. In this review, we survey the current state of knowledge of DUI, and discuss several active areas of research in this field. Topics/questions covered include: the number of times DUI evolved (once or multiple origins), the link between DUI and sex determination, the role(s) of mtDNA-encoded non-oxidative phosphorylation genes (i.e., ORFan/orf genes) in freshwater mussels, the function of conserved sequence motifs and sperm transmission elements in mtDNA of marine mussels, the challenges of annotating mtDNA genomes of DUI species, the presence of unorthodox features in venerid mtDNA, whether or not orf DNA sequences are useful in species-level identification of freshwater mussel, and finally, whether or not there are obvious benefits of DUI. For each topic we also highlight important avenues for future research within this fascinating field of mitochondrial evolutionary biology