Acceptance and timeliness of standard vaccination in children with chronic neurological deficits in north-western Switzerland

There are no special recommendations for basic vaccinations in patients with chronic neurological deficits distinct from the nationwide advocated schedule in Switzerland. Reports describing adverse neurological events possibly related to vaccinations have attracted public attention. It is unclear if patients with chronic neurological deficits are more reluctantly vaccinated compared to healthy children. We therefore investigated the acceptance of vaccinations in such patients and healthy controls in a retrospective case-control study. At the University Children's Hospital, Basel, Switzerland we investigated 100 patients with chronic neurological deficits and 200 age-matched healthy controls regarding the issue of vaccination rates and ages. The total number of administered vaccinations against diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type b (Hib), mumps, measles, rubella and hepatitis B were significantly lower in patients compared to healthy controls ( P <0.01 for each of the respective vaccines). Patients had an increased risk to receive the third pertussis, diphtheria, and tetanus vaccinations (relative risks (RR) for late vaccination 1.53, 1.53, and 1.54 respectively, P <0.01 for all comparisons), the second (RR=1.60, P <0.05) and third Hib vaccinations (RR=1.52, P <0.05), and the third polio vaccination (RR=1.43, P <0.05) later than controls. Conclusion:Children with chronic neurological deficits received fewer vaccinations than healthy controls. In addition, patients received vaccinations later than healthy children. Hence, it may be assumed that children with chronic neurological deficits are at an increased risk to acquire preventable infections. Therefore, vaccination should be promoted as part of the consultation during a routine appointment with the specialis

Dose bridging data for mometasone furoate in once-daily fixed-dose inhaled combinations of mometasone furoate/indacaterol and mometasone furoate/ indacaterol/glycopyrronium in patients with asthma

Once-daily (o.d.) fixed-dose combinations of mometasone furoate/indacaterol acetate and mometasone furoate/indacaterol acetate/glycopyrronium bromide, both delivered via the Breezhaler® device, are approved for the maintenance treatment of asthma. Across these fixed-dose combinations, while the doses of bronchodilators remain the same, the nominal doses of mometasone furoate in micrograms differ. This article presents the steps followed in bridging the mometasone furoate doses at the corresponding dose strengths in the mometasone furoate formulation delivered via the Twisthaler® and mometasone furoate/indacaterol acetate and mometasone furoate/indacaterol acetate/glycopyrronium bromide formulations delivered via the Breezhaler®. These were: (i) bridging the mometasone furoate doses in the Twisthaler® (previously approved) to mometasone furoate doses in the Breezhaler®; (ii) bridging the mometasone furoate doses in the Breezhaler® to mometasone furoate/indacaterol acetate and mometasone furoate/indacaterol acetate/glycopyrronium bromide formulation. Following this stepwise approach, it was determined that mometasone furoate 80 μg o.d. (medium dose strength) and 160 μg o.d. (high dose strength) in mometasone furoate/indacaterol acetate/glycopyrronium bromide formulation provided comparable inhaled corticosteroid efficacy to mometasone furoate 160 μg o.d. (medium dose strength) and 320 μg o.d. (high dose strength) in the mometasone furoate/indacaterol acetate formulation, respectively. These doses were used in the PLATINUM Phase III clinical program that investigated the efficacy and safety of mometasone furoate/indacaterol acetate and mometasone furoate/indacaterol acetate/glycopyrronium bromide combinations in patients with asthma

Mometasone/Indacaterol/Glycopyrronium (MF/IND/GLY) and MF/IND at Different MF Strengths versus Fluticasone Propionate/ Salmeterol Xinafoate (FLU/SAL) and FLU/SAL+ Tiotropium in Patients with Asthma

Background: Once-daily, single-inhaler mometasone furoate/indacaterol acetate/glycopyrronium bromide (MF/IND/GLY, an ICS/ LABA/LAMA) and MF/IND (an ICS/LABA) via Breezhaler® have been approved for the maintenance treatment of patients with asthma inadequately controlled with medium-or high-dose ICS or medium-or high-dose ICS/LABA treatment. Objective: Once-daily (o.d.) formulations of MF/IND/GLY and MF/IND at different MF dose strengths have been compared with twice-daily (b.i.d.) fluticasone propionate/salmeterol xinafoate (FLU/SAL), and b.i.d. FLU/SAL+ o.d. tiotropium (TIO) in the PALLADIUM, IRIDIUM and ARGON studies. Methods: The similarity in study design and consistent outcomes in these studies prompted the pooling of data in this review to better characterise these novel once-daily controller formulations. Results: Pooled data from PALLADIUM and IRIDIUM studies showed comparable or greater efficacy with o.d. MF/IND formulations versus b.i.d. FLU/SAL. The o.d. MF/IND/GLY was superior to b.i.d. FLU/SAL in the IRIDIUM study, and similar to, if not more efficacious than b.i.d. FLU/SAL + o.d. TIO in the ARGON study. Conclusion: These formulations therefore provide novel once-daily treatment options for patients across asthma severity and flexibility for clinicians to step-up or step-down the treatment using the same device and formulations.</p

Mometasone/Indacaterol/Glycopyrronium (MF/IND/GLY) and MF/IND at Different MF Strengths versus Fluticasone Propionate/ Salmeterol Xinafoate (FLU/SAL) and FLU/SAL+ Tiotropium in Patients with Asthma

Background: Once-daily, single-inhaler mometasone furoate/indacaterol acetate/glycopyrronium bromide (MF/IND/GLY, an ICS/ LABA/LAMA) and MF/IND (an ICS/LABA) via Breezhaler® have been approved for the maintenance treatment of patients with asthma inadequately controlled with medium-or high-dose ICS or medium-or high-dose ICS/LABA treatment. Objective: Once-daily (o.d.) formulations of MF/IND/GLY and MF/IND at different MF dose strengths have been compared with twice-daily (b.i.d.) fluticasone propionate/salmeterol xinafoate (FLU/SAL), and b.i.d. FLU/SAL+ o.d. tiotropium (TIO) in the PALLADIUM, IRIDIUM and ARGON studies. Methods: The similarity in study design and consistent outcomes in these studies prompted the pooling of data in this review to better characterise these novel once-daily controller formulations. Results: Pooled data from PALLADIUM and IRIDIUM studies showed comparable or greater efficacy with o.d. MF/IND formulations versus b.i.d. FLU/SAL. The o.d. MF/IND/GLY was superior to b.i.d. FLU/SAL in the IRIDIUM study, and similar to, if not more efficacious than b.i.d. FLU/SAL + o.d. TIO in the ARGON study. Conclusion: These formulations therefore provide novel once-daily treatment options for patients across asthma severity and flexibility for clinicians to step-up or step-down the treatment using the same device and formulations.</p

Mometasone/Indacaterol/Glycopyrronium (MF/IND/GLY) and MF/IND at Different MF Strengths versus Fluticasone Propionate/ Salmeterol Xinafoate (FLU/SAL) and FLU/SAL+ Tiotropium in Patients with Asthma

Background: Once-daily, single-inhaler mometasone furoate/indacaterol acetate/glycopyrronium bromide (MF/IND/GLY, an ICS/ LABA/LAMA) and MF/IND (an ICS/LABA) via Breezhaler® have been approved for the maintenance treatment of patients with asthma inadequately controlled with medium-or high-dose ICS or medium-or high-dose ICS/LABA treatment. Objective: Once-daily (o.d.) formulations of MF/IND/GLY and MF/IND at different MF dose strengths have been compared with twice-daily (b.i.d.) fluticasone propionate/salmeterol xinafoate (FLU/SAL), and b.i.d. FLU/SAL+ o.d. tiotropium (TIO) in the PALLADIUM, IRIDIUM and ARGON studies. Methods: The similarity in study design and consistent outcomes in these studies prompted the pooling of data in this review to better characterise these novel once-daily controller formulations. Results: Pooled data from PALLADIUM and IRIDIUM studies showed comparable or greater efficacy with o.d. MF/IND formulations versus b.i.d. FLU/SAL. The o.d. MF/IND/GLY was superior to b.i.d. FLU/SAL in the IRIDIUM study, and similar to, if not more efficacious than b.i.d. FLU/SAL + o.d. TIO in the ARGON study. Conclusion: These formulations therefore provide novel once-daily treatment options for patients across asthma severity and flexibility for clinicians to step-up or step-down the treatment using the same device and formulations.</p

Mometasone/Indacaterol/Glycopyrronium (MF/IND/GLY) and MF/IND at Different MF Strengths versus Fluticasone Propionate/ Salmeterol Xinafoate (FLU/SAL) and FLU/SAL+ Tiotropium in Patients with Asthma

Background: Once-daily, single-inhaler mometasone furoate/indacaterol acetate/glycopyrronium bromide (MF/IND/GLY, an ICS/ LABA/LAMA) and MF/IND (an ICS/LABA) via Breezhaler® have been approved for the maintenance treatment of patients with asthma inadequately controlled with medium-or high-dose ICS or medium-or high-dose ICS/LABA treatment. Objective: Once-daily (o.d.) formulations of MF/IND/GLY and MF/IND at different MF dose strengths have been compared with twice-daily (b.i.d.) fluticasone propionate/salmeterol xinafoate (FLU/SAL), and b.i.d. FLU/SAL+ o.d. tiotropium (TIO) in the PALLADIUM, IRIDIUM and ARGON studies. Methods: The similarity in study design and consistent outcomes in these studies prompted the pooling of data in this review to better characterise these novel once-daily controller formulations. Results: Pooled data from PALLADIUM and IRIDIUM studies showed comparable or greater efficacy with o.d. MF/IND formulations versus b.i.d. FLU/SAL. The o.d. MF/IND/GLY was superior to b.i.d. FLU/SAL in the IRIDIUM study, and similar to, if not more efficacious than b.i.d. FLU/SAL + o.d. TIO in the ARGON study. Conclusion: These formulations therefore provide novel once-daily treatment options for patients across asthma severity and flexibility for clinicians to step-up or step-down the treatment using the same device and formulations.</p

Opportunities and Challenges in Developing a Cryptosporidium Controlled Human infection Model For Testing antiparasitic agents

Cryptosporidiosis is a leading cause of moderate-to-severe diarrhea in low- and middle-income countries, responsible for high mortality in children younger than two years of age, and it is also strongly associated with childhood malnutrition and growth stunting. There is no vaccine for cryptosporidiosis and existing therapeutic options are suboptimal to prevent morbidity and mortality in young children. Recently, novel therapeutic agents have been discovered through high-throughput phenotypic and target-based screening strategies, repurposing malaria hits, etc., and these agents have a promising preclinical in vitro and in vivo anti

Population Pharmacokinetic Analysis of Indacaterol/Glycopyrronium/Mometasone Furoate After Administration of Combination Therapies Using the Breezhaler® Device in Patients with Asthma

Background and Objective: Clinical evidence suggests no clinically relevant pharmacokinetic interactions between indacaterol (IND), glycopyrronium (GLY) and mometasone furoate (MF). A population pharmacokinetic (popPK) analysis was conducted to identify structural models describing systemic pharmacokinetic profiles of IND, GLY and MF, and estimate the effect of covariates on their pharmacokinetics following inhalation as IND/GLY/MF. Methods: Pharmacokinetic data from 698 patients with asthma were pooled from two Phase III studies that evaluated IND/MF medium- (150/160 µg) and high-dose (150/320 µg), IND/GLY/MF medium- (150/50/80 μg) and high-dose (150/50/160 μg), and a device bridging Phase II study with MF. One popPK model was developed each for IND, GLY and MF using a nonlinear mixed-effect modelling approach. Maximal and trough plasma concentrations were compared across formulations and studies, including data for IND/GLY from chronic obstructive pulmonary disease (COPD) patients. The effect of predefined covariates on the pharmacokinetics of components was evaluated using a full covariate modelling approach. Results: The final pharmacokinetic models were two-compartment disposition models with first-order elimination and sequential zero-order/first-order absorption (IND), with bolus administration and first-order elimination (GLY), and with mixed zero-order/first-order absorption and first-order elimination (MF). All model parameters were estimated with good precision (% relative standard error: IND and MF ≤25%; GLY <10%). No clinically relevant covariate effect was observed on the pharmacokinetics of IND, GLY and MF. IND and GLY pharmacokinetic profiles were similar across different formulations. Conclusion: Two-compartment popPK models adequately described the pharmacokinetics of IND, GLY and MF. The effect of covariates was not clinically relevant. The pharmacokinetic profiles of MF were comparable for combination products at corresponding medium- or high-dose inhaled corticosteroids. On a population level, the pharmacokinetics of IND and GLY were comparable between patients with asthma and COPD

Lung function improvements following inhaled indacaterol/glycopyrronium/ mometasone furoate are independent of dosing time in asthma patients:A randomised trial

Once-daily asthma treatment should prevent night-time deterioration, irrespective of the time of dosing. IND/GLY/MF, a fixed-dose combination of inhaled indacaterol acetate (IND, long-acting β2-agonist (LABA)), glycopyrronium bromide (GLY, long-acting muscarinic antagonist) and mometasone furoate (MF, inhaled corticosteroid (ICS)) delivered by Breezhaler, is indicated in adult asthma patients inadequately controlled on LABA/ICS. A randomised, double-blind, placebo-controlled, three-period, crossover, phase II study was performed to investigate the bronchodilator effect of IND/GLY/MF (150/50/80 μg) dosed morning and evening versus placebo in patients with mild-moderate asthma. The primary end-point was weighted mean forced expiratory volume in 1 s (FEV1) over 24 h following 14 days of IND/GLY/MF dosed a.m. and p.m. versus placebo. Secondary end-points included the effect of dosing time on peak expiratory flow (PEF) and safety/tolerability. Of 37 randomised patients (age 18–72 years; 21 male, 16 female) 34 completed all three treatment periods. At screening, median (range) pre-bronchodilator FEV1 was 75.8% (60–96%). Patients were using stable low-(83.8%) or medium-dose (16.2%) ICS. Morning and evening dosing of IND/GLY/MF improved FEV1 (area under the curve from 0 to 24 h) by 610 mL (90% CI 538–681 mL) and 615 mL (90% CI 544–687 mL), respectively, versus placebo. Mean PEF over 14 days increased by 70.7 L·min−1 (90% CI 60.5–80.9 L·min−1) following a.m. dosing, and by 59.7 L·min−1 (90% CI 49.5–69.9 L·min−1) following p.m. dosing of IND/GLY/ MF versus placebo. IND/GLY/MF demonstrated a safety profile comparable with placebo. Once-daily inhaled IND/GLY/MF was well tolerated and provided sustained lung function improvements over 24 h, irrespective of a.m. or p.m. dosing, in patients with mild–moderate asthma.</p