The impact of influenza vaccination on infection, hospitalisation and mortality in the Netherlands between 2003 and 2015.

Influenza epidemics annually cause substantial morbidity and mortality. For this reason, vaccination is offered yearly to persons with an elevated risk for complications. Assessments of the impact of vaccination are, however, hampered by year-to-year variation in epidemic size and vaccine effectiveness. We estimate the impact of the current vaccination programme comparing simulations with vaccination to counterfactual simulations without vaccination. The simulations rely on an age- and risk-structured transmission model that tracks the build-up and loss of immunity over successive seasons, and that allows the vaccine match to vary between seasons. The model parameters are estimated with a particle Monte Carlo method and approximate Bayesian computation, using epidemiological data on vaccine effectiveness and epidemic size in the Netherlands over a period of 11 years. The number of infections, hospitalisations and deaths vary greatly between years because waning of immunity and vaccine match may differ every season, which is in line with observed variation in influenza epidemic sizes. At an overall coverage of 21%, vaccination has averted on average 13% (7.2-19%, 95% range) of infections, 24% (16-36%) of hospitalisations, and 35% (16-50%) of deaths. This suggests that vaccination is mainly effective in protecting vaccinees from infection rather than reducing transmission. As the Dutch population continues to grow and age, the vaccination programme is projected (up to 2025) to gain in impact, despite a decreasing infection attack rate

Influence of single and multiple doses of amifostine on the efficacy and the pharmacokinetics of carboplatin in mice.

We have previously reported that amifostine potentiates the anti-tumour activity of carboplatin in mice. The present study was carried out in well-established human ovarian cancer xenografts OVCAR-3, A2780 and FMa grown subcutaneously in the nude mouse. It was found that a single dose of amifostine resulted in a higher increase in the anti-tumour activity of carboplatin than three doses of amifostine. A single dose of amifostine increased the AUC (area under the curve) values of total platinum in plasma ultrafiltrate (30.1 vs 18.2 microM x h), liver (307.7 vs 236.4 nmol g(-1) x h), kidney (500.8 vs 368.3 nmol g(-1) x h) and OVCAR-3 tumour tissue (184.0 vs 146.8 nmol g(-1) x h). Despite this increase in total platinum, a decrease in platinum (Pt)-DNA adduct levels was observed in liver, kidney and bone marrow, which was significant in liver. In tumour tissue an insignificant increase in Pt-DNA adduct levels, specifically the Pt-GG adduct, was observed after treatment with a single dose of amifostine, which may explain the increase in anti-tumour activity. The increase in the AUC of total platinum was probably caused by a reduction in body temperature, which was most severe after three doses of amifostine. The extreme hypothermia may be the reason that three doses of amifostine resulted in less potentiation of the efficacy of carboplatin

Personalized medication adherence management in asthma and COPD:a review of effective interventions and development of a practical adherence toolkit

BACKGROUND: Medication non-adherence management of patients with asthma/COPD remains challenging. Given the multitude of underlying causes, a personalized approach is required. The Test of Adherence to Inhalers (TAI) can identify reasons for non-adherence, but does not provide guidance on how to effectively act on results. OBJECTIVE: To develop a practical, evidence-based decision support toolkit for healthcare professionals managing adult patients with asthma and/or COPD, by matching TAI-identified adherence barriers to proven effective adherence enhancing interventions. METHODS: A literature review in PubMed and Embase was performed identifying interventions that enhanced medication adherence in adult patients with asthma and/or COPD. Randomised controlled trials (RCTs) published in English with full-texts available were included. Effective interventions were assessed by the Cochrane risk of bias tool, categorized, matched with specific TAI responses and developed into a practical TAI Toolkit. The Toolkit was assessed on content and usability (System Usability Scale, SUS) by a multidisciplinary group of healthcare professionals. RESULTS: Forty RCTs were included in the review. In total, seven effective interventions catergories were identified, informing the TAI Toolkit: reminders, educational interventions, motivational strategies, feedback on medication use, shared decision making, simplifying medication regimen and multiple component interventions. Healthcare professionals rated the TAI Toolkit with a mean SUS score of 71.4 (range: 57.5-80.0). CONCLUSION: Adherence can be improved using different interventions that the TAI Toolkit helps selecting. The TAI Toolkit was well received by healthcare professionals. Further research is required to test its validity, practicality and effectiveness in practice

A personalised screening strategy for diabetic retinopathy:a cost-effectiveness perspective

Aims/hypothesis: In this study we examined the cost-effectiveness of three different screening strategies for diabetic retinopathy: using a personalised adaptive model, annual screening (fixed intervals), and the current Dutch guideline (stratified based on previous retinopathy grade). Methods: For each individual, optimal diabetic retinopathy screening intervals were determined, using a validated risk prediction model. Observational data (1998–2017) from the Hoorn Diabetes Care System cohort of people with type 2 diabetes were used (n = 5514). The missing values of retinopathy grades were imputed using two scenarios of slow and fast sight-threatening retinopathy (STR) progression. By comparing the model-based screening intervals to observed time to develop STR, the number of delayed STR diagnoses was determined. Costs were calculated using the healthcare perspective and the societal perspective. Finally, outcomes and costs were compared for the different screening strategies. Results: For the fast STR progression scenario, personalised screening resulted in 11.6% more delayed STR diagnoses and €11.4 less costs per patient compared to annual screening from a healthcare perspective. The personalised screening model performed better in terms of timely diagnosis of STR (8.8% less delayed STR diagnosis) but it was slightly more expensive (€1.8 per patient from a healthcare perspective) than the Dutch guideline strategy. Conclusions/interpretation: The personalised diabetic retinopathy screening model is more cost-effective than the Dutch guideline screening strategy. Although the personalised screening strategy was less effective, in terms of timely diagnosis of STR patients, than annual screening, the number of delayed STR diagnoses is low and the cost saving is considerable. With around one million people with type 2 diabetes in the Netherlands, implementing this personalised model could save €11.4 million per year compared with annual screening, at the cost of 658 delayed STR diagnoses with a maximum delayed time to diagnosis of 48 months. Graphical abstract: [Figure not available: see fulltext.]

Systematic Review and Quality Appraisal of Cost-Effectiveness Analyses of Pharmacologic Maintenance Treatment for Chronic Obstructive Pulmonary Disease:Methodological Considerations and Recommendations

Worldwide, chronic obstructive pulmonary disease (COPD) is a highly prevalent chronic lung disease with considerable clinical and socioeconomic impact. Pharmacologic maintenance drugs (such as bronchodilators and inhaled corticosteroids) play an important role in the treatment of COPD. The cost effectiveness of these treatments has been frequently assessed, but studies to date have largely neglected the impact of treatment sequence and the exact stage of disease in which the drugs are used in real life. We aimed to systematically review recently published articles that reported the cost effectiveness of COPD maintenance treatments, with a focus on key findings, quality and methodological issues. We performed a systematic literature search in Embase, PubMed, the UK NHS Economic Evaluation Database (NHS-EED) and EURONHEED (European Network of Health Economics Evaluation Databases) and included all relevant articles published between 2011 and 2015 in either Dutch, English or German. Main study characteristics, methods and outcomes were extracted and critically assessed. The Quality of Health Economic Studies (QHES) instrument was used as basis for quality assessment, but additional items were also addressed. The search identified 18 recent pharmacoeconomic analyses of COPD maintenance treatments. Papers reported the cost effectiveness of long-acting muscarinic antagonist (LAMA) monotherapy (n = 6), phosphodiesterase (PDE)-4 inhibitors (n = 4), long-acting beta agonist/inhaled corticosteroid (LABA/ICS) combinations (n = 4), LABA monotherapy (n = 2) and LABA/LAMA combinations (n = 2). All but two studies were funded by the manufacturer, and all studies indicated favourable cost effectiveness; however, the number of quality-adjusted life-years (QALYs) gained was small. Less than half of the studies reported a COPD-specific outcome in addition to a generic outcome (mostly QALYs). Exacerbation and mortality rates were found to be the main drivers of cost effectiveness. According to the QHES, the quality of the studies was generally sufficient, but additional assessment revealed that most studies poorly represented the cost effectiveness of real-life medication use. The majority of studies showed that pharmacologic COPD maintenance treatment is cost effective, but most studies poorly reflected real-life drug use. Consistent and COPD-specific methodology is recommended

Burden and socioeconomics of asthma, allergic rhinitis, atopic dermatitis and food allergy

INTRODUCTION: Asthma, allergic rhinitis, atopic dermatitis, and food allergy affect approximately 20% of the global population. Few studies describe the burden of the totality of these diseases and only a handful studies provide a comprehensive overview of the socioeconomic impact of these diseases. AREAS COVERED: For this narrative review, we searched Pubmed using selected keywords and inspected relevant references using a snowballing process. We provide an overview of the socioeconomic burden of allergic diseases (in particular, asthma, allergic rhinitis, atopic dermatitis, and food allergy). The focus of this review is on their epidemiology (incidence, prevalence), burden (disability-adjusted life years, quality of life), and direct and indirect costs (absenteeism and presenteeism). We have put special emphasis on differences between countries. EXPERT COMMENTARY: Both the prevalence and the burden of allergic diseases are considerable with prevalence varying between 1% and 20%. We identified a plethora of studies on asthma, but studies were generally difficult to compare due to the heterogeneity in measures used. There were only few studies on the burden of food allergy; therefore, more studies on this allergy are required. For future studies, we recommend standardizing epidemiologic, socioeconomic impact, and quality of life measures of allergic diseases

Can electronic monitoring with a digital smart spacer support personalised medication adherence and inhaler technique education in patients with asthma?:Protocol of the randomised controlled OUTERSPACE trial

INTRODUCTION: Medication adherence and inhaler technique in patients with asthma remain suboptimal. A digital, smart spacer may support personalised adherence and inhaler technique education. The aim of this study is to assess the feasibility of undertaking a definitive randomised controlled trial of personalised, smart spacer data-driven education and explore clinical benefits. METHODS AND ANALYSIS: We present the design of the multicentre, randomised controlled OUtcomes following Tailored Education and Retraining: Studying Performance and AdherenCE feasibility trial of 2 months. Patients will be recruited from four Dutch general practices. At t=-1, patients with asthma ≥18 years using inhaled corticosteroids±long-acting beta-agonists±short-acting beta-agonists administered with a pressurised-metered-dose-inhaler and spacer (n=40) will use a smart spacer for 1 month. The rechargeable CE-marked smart spacer (Aerochamber Plus with Flow Vu) includes a sensor that monitors adherence and inhalation technique to prescribed dosing regimen of both maintenance and reliever inhalers. After 1 month (t=0), patients are 1:1 randomised into two groups: control group (usual care) versus intervention group (personalised education). At t=-1, t=0 and t=1 month, the Asthma Control Questionnaire (ACQ), Work Productivity and Activity Impairment (WPAI) questionnaire and Test of Adherence to Inhalers (TAI) are administered and fractional exhaled nitric oxide (FeNO) is assessed. At t=0 and t=1, spirometry is performed. At t=1, usability and satisfaction will be analysed using the System Usability Scale and interviews with patients and healthcare providers. Primary outcome is the overall feasibility of a definitive trial assessed by patient recruitment speed, participation and drop-out rate. Secondary outcomes are patient and healthcare provider satisfaction and exploratory clinical outcomes are adherence, inhaler technique, TAI score, FeNO, lung function, ACQ and WPAI. ETHICS AND DISSEMINATION: Ethical approval was obtained from the RTPO in Leeuwarden, Netherlands (number: NL78361.099.21). Patients will provide written informed consent. Study findings will be disseminated through conferences and peer-reviewed scientific and professional journals. TRIAL REGISTRATION NUMBER: NL9637