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BackgroundThis study aimed to assess the efficacy of MP-AzeFlu (a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate in a single spray) in children with seasonal allergic rhinitis (SAR) and explore the importance of child symptom severity assessment in paediatric allergic rhinitis (AR) trials. MethodsA total of 348 children (4-11years) with moderate/severe SAR were randomized into a double-blind, placebo-controlled, 14-day, parallel-group trial. Efficacy was assessed by changes from baseline in reflective total nasal symptom score (rTNSS), reflective total ocular symptom score (rTOSS) and individual symptom scores over 14days (children 6-11years; n=304), recorded by either children or caregivers. To determine whether a by-proxy effect existed, efficacy outcomes were assessed according to degree of child/caregiver rating. Moreover, total Paediatric Rhinitis Quality of Life Questionnaire (PRQLQ) score was compared between the groups. ResultsA statistically superior, clinically relevant efficacy signal of MP-AzeFlu versus placebo was apparent for PRQLQ overall score (diff: -0.29, 95% CI -0.55, -0.03; p=0.027), but not for rTNSS (diff: -0.80; 95% CI: -1.75; 0.15; p=0.099). However, as the extent of children's self-rating increased, so too did the treatment difference between MP-AzeFlu and placebo; MP-AzeFlu provided significantly better relief than placebo for rTNSS (p=0.002), rTOSS (p=0.009) and each individual nasal and ocular symptom assessed (except rhinorrhoea; p=0.064) when children mostly rated their own symptoms. ConclusionsMP-AzeFlu is an effective treatment for AR in childhood. Caregivers are less able than children to accurately assess response to treatment with available tools. A simple paediatric-specific tool to assess efficacy in AR trials in children is needed.

Contains fulltext : 52374.pdf (Publisher’s version ) (Closed access) Most X-linked diseases show a recessive pattern of inheritance in which female carriers are unaffected. In X-linked retinitis pigmentosa (XLRP), however, both recessive and semi-dominant inheritance patterns have been reported. We identified an Israeli family with semi-dominant XLRP due to a missense mutation (p.G275S) in the RPGR gene. The mutation was previously reported in two Danish families with recessive XLRP. Obligate carriers from the two Danish families had no visual complaints and normal to slightly reduced retinal function, while those from the Israeli family suffered from high myopia, low visual acuity, constricted visual fields, and severely reduced electroretinogram (ERG) amplitudes. The disease-related RPGR haplotype of the Israeli family was found to be different from the one found in the two Danish families, indicating that the mutation arose twice independently on different X-chromosome backgrounds. A series of genetic analyses excluded skewed X-inactivation pattern, chromosomal abnormalities, distorted RPGR expression level, and mutations in candidate genes as the cause for the differences in disease severity of female carriers. To the best of our knowledge, this is the first detailed analysis of an identical mutation causing either a recessive or a semi-dominant X-linked pattern of disease in different families. Our results indicate that an additional gene (or genes), linked to RPGR, modulate disease expression in severely affected carriers. These may be related to the high myopia concomitantly found in affected carriers from the Israeli family.

L'insulinothérapie intensive conventionnelle exige une adaptation stricte du mode de vie. L'insulinothérapie fonctionnelle (FIT) permet une adaptation flexible selon les besoins d'insuline de base, les repas et les valeurs de glucose. Durant les années 1990 à 1996, 183 des 221 patients de la consultation ambulatoire de diabétologie de l'hôpital cantonal de Bâle qui avaient suivi les cours d'enseignement d'insulinothérapie fonctionnelle ont été évalués. L'instruction structurée a été effectuée de façon ambulatoire en 16 heures de cours durant trois mois (1 séminaire d'une journée complète et 7 séminaires de 90 minutes le soir). En plus de l'insulinothérapie intensive, les patients ont été sensibilisés aux principes nutritionnels conventionnels. La valeur moyenne de HbA1c était de 7.0% (référence: 3.7–5.6%). Après le passage à une insulinothérapie fonctionnelle, on a constaté une diminution significative du nombre d'hypoglycémies sévères avec un contrôle métabolique similaire: le pourcentage des patients avec des hypoglycémies sévères (degré 3 et 4) a diminué de 26 à 14 % pour les hypoglycémies de degré 3 et de 13 à 7% pour les hypoglycémies de degré 4. En plus de l'augmentation documentée précédemment de la qualité de vie, cette étude démontre que l'insulinothérapie fonctionnelle diminue de façon durable le risque d'hypoglycémie sévère. Ces résultats mettent en évidence un grand besoin d'enseignement de l'insulinothérapie fonctionnelle pour les diabétiques de type 1 en Suisse.

Background and objective: MP29-02 (Dymista), a novel intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP), is significantly better than first-line therapy for the treatment of moderate-to-severe seasonal allergic rhinitis (SAR), and is well tolerated following 52 weeks of continuous use in chronic rhinitis. The aim of this study was to evaluate the long-term efficacy of MP29-02 versus FP in patients with chronic rhinitis. Patients and methods: In total, 612 chronic rhinitis patients (perennial allergic rhinitis [PAR], n=424; nonallergic rhinitis, n=188) aged 12 years or older were enrolled into this open-label, parallel-group study and randomized to MP29-02 (1 spray/nostril bid) or FP nasal spray (2 sprays/nostril qd) for 52 weeks. Efficacy was assessed by change from baseline in PM reflective total nasal symptom score (rTNSS), time to first achieve 100% PM rTNSS reduction from baseline, and percentage of symptom-free days in the total and PAR populations posthoc. Results: MP29-02 reduced patients' PM rTNSS from baseline significantly more than FP, from Day 1 up to and including week 28 (-2.88 vs -2.53; P=.0048), with treatment difference maintained for 52 weeks. Fluctuation in significance after week 28 might be explained, at least in part, by decreasing sample size, permitted according to ICH guidelines. By Day 1 almost twice as many MP29-02-patients were symptom free. After 1 month, 71.1% of MP29-02 patients experienced 100% rTNSS reduction (60.3% for FP), and did on a median of 9 days faster (P=.0024). Over 52 weeks MP29-02 patients experienced 8.4% more symptom-free days (P=.0005). These results were mirrored in the PAR subpopulation. Conclusion: These results confirm MP29-02's wide therapeutic spectrum and assert its consistent superiority over an intranasal corticosteroid