Drug Saf

Introduction Quantitative benefit-risk models (qBRm) applied to vaccines are increasingly used by public health authorities and pharmaceutical companies as an important tool to help decision makers with supporting benefit-risk assessment (BRA). However, many publications on vaccine qBRm provide insufficient details on the methodological approaches used. Incomplete and/or inadequate qBRm reporting may affect result interpretation and confidence in BRA, highlighting a need for the development of standard reporting guidance. Objectives Our objective was to provide an operational checklist for improved reporting of vaccine qBRm. Methods The consolidated standards of reporting quantitative Benefit-RIsk models applied to VACcines (BRIVAC) were designed as a checklist of key information to report in qBRm scientific publications regarding the assessed vaccines, the methodological considerations and the results and their interpretation. Results In total, 22 items and accompanying definitions, recommendations, explanations and examples were provided and divided into six main sections corresponding to the classic subdivisions of a scientific publication: title and abstract (items 1–2), introduction (items 3–4), methods (items 5–15), results (items 16–17), discussion (items 18–20) and other (items 21–22). Conclusions The BRIVAC checklist is the first initiative providing an operational checklist for improved reporting of qBRm applied to vaccines in scientific articles. It is intended to assist authors, peer-reviewers, editors and readers in their critical appraisal. Future initiatives are needed to provide methodological guidance to perform qBRm while taking into account the vaccine specificities

Influence of degree of specific allergic sensitivity on severity of rhinitis and asthma in Chinese allergic patients

<p>Abstract</p> <p>Background</p> <p>The association between sensitizations and severity of allergic diseases is controversial.</p> <p>Objective</p> <p>This study was to investigate the association between severity of asthma and rhinitis and degree of specific allergic sensitization in allergic patients in China.</p> <p>Method</p> <p>A cross-sectional survey was performed in 6304 patients with asthma and/or rhinitis from 4 regions of China. Patients completed a standardized questionnaire documenting their respiratory and allergic symptoms, their impact on sleep, daily activities, school and work. They also underwent skin prick tests with 13 common aeroallergens. Among the recruited subjects, 2268 provided blood samples for serum measurement of specific IgE (sIgE) against 16 common aeroallergens.</p> <p>Results</p> <p>Significantly higher percentage of patients with moderate-severe intermittent rhinitis were sensitized to outdoor allergens while percentage of patients sensitized to indoor allergens was increased with increasing severity of asthma. Moderate-severe intermittent rhinitis was associated with the skin wheal size and the level of sIgE to <it>Artemisia vulgaris </it>and <it>Ambrosia artemisifolia </it>(p < 0.001). Moderate-severe asthma was associated with increasing wheal size and sIgE response to <it>Dermatophagoides </it>(<it>D</it>.) <it>pteronyssinus </it>and <it>D. farinae </it>(p < 0.001). Moderate-severe rhinitis and asthma were also associated with increase in number of positive skin prick test and sIgE.</p> <p>Conclusions</p> <p><it>Artemisia vulgaris </it>and <it>Ambrosia artemisifolia </it>sensitizations are associated with the severity of intermittent rhinitis and <it>D. pteronyssinus </it>and <it>D. farinae </it>sensitizations are associated with increasing severity of asthma in China. Increase in number of allergens the patients are sensitized to may also increase the severity of rhinitis and asthma.</p

The Help for Hay Fever community pharmacy-based pilot randomised controlled trial for intermittent allergic rhinitis

Management of intermittent allergic rhinitis (IAR) is suboptimal in the UK. An Australian community pharmacy-based intervention has been shown to help patients better self-manage their IAR. We conducted a pilot cluster RCT in 12 Scottish community pharmacies to assess transferability of the Australian intervention. Trained staff in intervention pharmacies delivered the intervention to eligible customers (n = 60). Non-intervention pharmacy participants (n = 65) received usual care. Outcome measures included effect size of change in the mini-Rhinoconjunctivitis Quality of Life Questionnaire (miniRQLQ) between baseline, 1-week and 6-week follow-up. Trial procedures were well received by pharmacy staff, and customer satisfaction with the intervention was high. The standardised effect size for miniRQLQ total score was −0.46 (95% CI, −1.05, 0.13) for all participants and −0.14 (95% CI,−0.86, 0.57) in the complete case analysis, suggesting a small overall treatment effect in the intervention group. A full-scale RCT is warranted to fully evaluate the effectiveness of this service

ADVANCE system testing: Can safety studies be conducted using electronic healthcare data? An example using pertussis vaccination

Introduction: The Accelerated Development of Vaccine benefit-risk Collaboration in Europe (ADVANCE) public-private collaboration, aimed to develop and test a system for rapid benefit-risk monitoring of vaccines using healthcare databases in Europe. The objective of this proof-of-concept (POC) study was to test the feasibility of the ADVANCE system to generate incidence rates (IRs) per 1000 person-years and incidence rate ratios (IRRs) for risks associated with whole cell- (wP) and acellular- (aP) pertussis vaccines, occurring in event-specific risk windows in children prior to their pre-school-entry booster. Methods: The study population comprised almost 5.1 million children aged 1 month to <6 years vaccinated with wP or aP vaccines during the study period from 1 January 1990 to 31 December 2015. Data from two Danish hospital (H) databases (AUH and SSI) and five primary care (PC) databases from, UK (THIN and RCGP RSC), Spain (SIDIAP and BIFAP) and Italy (Pedianet) were analysed. Database-specific IRRs between risk vs. non-risk periods were estimated in a self-controlled case series study and pooled using random-effects meta-analyses. Results: The overall IRs were: fever, 58.2 (95% CI: 58.1; 58.3), 96.9 (96.7; 97.1) for PC DBs and 8.56 (8.5; 8.6) for H DBs; convulsions, 7.6 (95% CI: 7.6; 7.7), 3.55 (3.5; 3.6) for PC and 12.87 (12.8; 13) for H; persistent crying, 3.9 (95% CI: 3.8; 3.9) for PC, injection-site reactions, 2.2 (95% CI 2.1; 2.2) for PC, hypotonic hypo-responsive episode (HHE), 0.4 (95% CI: 0.4; 0.4), 0.6 (0.6; 0.6) for PC and 0.2 (0.2; 0.3) for H; and somnolence: 0.3 (95% CI: 0.3; 0.3) for PC. The pooled IRRs for persistent crying, fever, and ISR, adjusted for age and healthy vaccinee period were higher after wP vs. aP vaccination, and lower for convulsions, for all doses. The IRR for HHE was slightly lower for wP than aP, while wP was associated with somnolence only for dose 1 and dose 3 compared with aP. Conclusions: The estimated IRs and IRRs were comparable with published data, therefore demonstrating that the ADVANCE system was able to combine several European healthcare databases to assess vaccine safety data for wP and aP vaccination

Morphometrics as an Insight Into Processes Beyond Tooth Shape Variation in a Bank Vole Population

Phenotype variation is a key feature in evolution, being produced by development and the target of the screening by selection. We focus here on a variable morphological feature: the third upper molar (UM3) of the bank vole, aiming at identifying the sources of this variation. Size and shape of the UM3 occlusal surface was quantified in successive samples of a bank vole population. The first source of variation was the season of trapping, due to differences in the age structure of the population in turn affecting the wear of the teeth. The second direction of variation corresponded to the occurrence, or not, of an additional triangle on the tooth. This intra-specific variation was attributed to the space available at the posterior end of the UM3, allowing or not the addition of a further triangle.This size variation triggering the shape polymorphism is not controlled by the developmental cascade along the molar row. This suggests that other sources of size variation, possibly epigenetic, might be involved. They would trigger an important shape variation as side-effect by affecting the termination of the sequential addition of triangles on the tooth

Subtropical grass pollen allergens are important for allergic respiratory diseases in subtropical regions

Background: Grass pollen allergens are a major cause of allergic respiratory disease but traditionally prescribing practice for grass pollen allergen-specific immunotherapy has favoured pollen extracts of temperate grasses. Here we aim to compare allergy to subtropical and temperate grass pollens in patients with allergic rhinitis from a subtropical region of Australia. Methods. Sensitization to pollen extracts of the subtropical Bahia grass (Paspalum notatum), Johnson grass (Sorghum halepense) and Bermuda grass (Cynodon dactylon) as well as the temperate Ryegrass (Lolium perenne) were measured by skin prick in 233 subjects from Brisbane. Grass pollen-specific IgE reactivity was tested by ELISA and cross-inhibition ELISA. Results: Patients with grass pollen allergy from a subtropical region showed higher skin prick diameters with subtropical Bahia grass and Bermuda grass pollens than with Johnson grass and Ryegrass pollens. IgE reactivity was higher with pollen of Bahia grass than Bermuda grass, Johnson grass and Ryegrass. Patients showed asymmetric cross-inhibition of IgE reactivity with subtropical grass pollens that was not blocked by temperate grass pollen allergens indicating the presence of species-specific IgE binding sites of subtropical grass pollen allergens that are not represented in temperate grass pollens. Conclusions: Subtropical grass pollens are more important allergen sources than temperate grass pollens for patients from a subtropical region. Targeting allergen-specific immunotherapy to subtropical grass pollen allergens in patients with allergic rhinitis in subtropical regions could improve treatment efficacy thereby reducing the burden of allergic rhinitis and asthma

Adolescent seasonal allergic rhinitis and the impact of health-care professional training:cluster randomised controlled trial of a complex intervention in primary care

BACKGROUND: Seasonal allergic rhinitis is typically poorly managed, particularly in adolescents, in whom it is responsible for considerable morbidity. Our previous work has demonstrated that if poorly controlled this can impair educational performance. AIM: The primary aim of this trial was to assess the impact of a primary care-based professional training intervention on clinical outcomes in adolescents with seasonal allergic rhinitis. METHODS: Cluster trial in which UK general practice staff were randomised to a short, intensive workshop on the evidence-based management of seasonal allergic rhinitis. The primary outcome measure was the change in the validated Rhinoconjunctivitis Quality of Life Questionnaire with Standardized Activities (RQLQ(S)) score between baseline and 6 weeks post intervention (minimal clinically important difference=0.5). Secondary outcome measures of interest included health-care professionals' knowledge and confidence in managing seasonal allergic rhinitis, number of seasonal allergic rhinitis-related consultations, relevant treatments prescribed and symptom scores. RESULTS: Thirty-eight general practices were randomised (20 in the intervention arm) and 246 patients (50.2% males, mean age 15 years) were included in the primary outcome analysis. Health-care professionals' knowledge and confidence of the clinical management of seasonal allergic rhinitis improved. This did not, however, result in clinically or statistically significant improvements in RQLQ(S): -0.15, (95% confidence interval, -0.5 to +0.2). There were no differences in consultation frequency, treatments issued for seasonal allergic rhinitis or symptom scores. CONCLUSIONS: Although associated with increases in professionals' self-assessed confidence and understanding of seasonal allergic rhinitis management, this intensive training workshop did not translate into improvements in adolescents' disease-specific quality of life or a reduction in rhinitis symptoms