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Background: Despite the existence of efficacious vaccines, the burden of vaccine-preventable diseases remains high and the potential health benefits of paediatric, adolescent and adult vaccination are not being achieved due to suboptimal vaccine coverage rates. Based on emerging evidence that pharmacy-based vaccine interventions are feasible and effective, the European Interdisciplinary Council for Ageing (EICA) brought together stakeholders from the medical and pharmacy professions, the pharmaceutical industry, patient/ageing organisations and health authorities to consider the potential for pharmacy-based interventions to increase vaccine uptake. We report here the proceedings of this 3-day meeting held in March 2018 in San Servolo island, Venice, Italy, focussing firstly on examples from countries that have introduced pharmacy-based vaccination programmes, and secondly, listing the barriers and solutions proposed by the discussion groups., Conclusions: A range of barriers to vaccine uptake have been identified, affecting all target groups, and in various countries and healthcare settings. Ease of accessibility is a potentially modifiable determinant in vaccine uptake, and thus, improving the diversity of settings where vaccines can be provided to adults, for example by enabling community pharmacists to vaccinate, may increase the number of available opportunities for vaccination.

Background: This study reports the findings of the first large-scale Phase III investigator-driven clinical trial to slow the rate of cognitive decline in Alzheimer disease with a dihydropyridine (DHP) calcium channel blocker, nilvadipine. Nilvadipine, licensed to treat hypertension, reduces amyloid production, increases regional cerebral blood flow, and has demonstrated anti-inflammatory and anti-tau activity in preclinical studies, properties that could have disease-modifying effects for Alzheimer disease. We aimed to determine if nilvadipine was effective in slowing cognitive decline in subjects with mild to moderate Alzheimer disease., Methods and Findings: NILVAD was an 18-month, randomised, placebo-controlled, double-blind trial that randomised participants between 15 May 2013 and 13 April 2015. The study was conducted at 23 academic centres in nine European countries. Of 577 participants screened, 511 were eligible and were randomised (258 to placebo, 253 to nilvadipine). Participants took a trial treatment capsule once a day after breakfast for 78 weeks. Participants were aged >50 years, meeting National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's disease Criteria (NINCDS-ADRDA) for diagnosis of probable Alzheimer disease, with a Standardised Mini-Mental State Examination (SMMSE) score of ≥12 and <27. Participants were randomly assigned to 8 mg sustained-release nilvadipine or matched placebo. The a priori defined primary outcome was progression on the Alzheimer's Disease Assessment Scale Cognitive Subscale-12 (ADAS-Cog 12) in the modified intention-to-treat (mITT) population (n = 498), with the Clinical Dementia Rating Scale sum of boxes (CDR-sb) as a gated co-primary outcome, eligible to be promoted to primary end point conditional on a significant effect on the ADAS-Cog 12. The analysis set had a mean age of 73 years and was 62% female. Baseline demographic and Alzheimer disease-specific characteristics were similar between treatment groups, with reported mean of 1.7 years since diagnosis and mean SMMSE of 20.4. The prespecified primary analyses failed to show any treatment benefit for nilvadipine on the co-primary outcome (p = 0.465). Decline from baseline in ADAS-Cog 12 on placebo was 0.79 (95% CI, -0.07-1.64) at 13 weeks, 6.41 (5.33-7.49) at 52 weeks, and 9.63 (8.33-10.93) at 78 weeks and on nilvadipine was 0.88 (0.02-1.74) at 13 weeks, 5.75 (4.66-6.85) at 52 weeks, and 9.41 (8.09-10.73) at 78 weeks. Exploratory analyses of the planned secondary outcomes showed no substantial effects, including on the CDR-sb or the Disability Assessment for Dementia. Nilvadipine appeared to be safe and well tolerated. Mortality was similar between groups (3 on nilvadipine, 4 on placebo); higher counts of adverse events (AEs) on nilvadipine (1,129 versus 1,030), and serious adverse events (SAEs; 146 versus 101), were observed. There were 14 withdrawals because of AEs. Major limitations of this study were that subjects had established dementia and the likelihood that non-Alzheimer subjects were included because of the lack of biomarker confirmation of the presence of brain amyloid., Conclusions: The results do not suggest benefit of nilvadipine as a treatment in a population spanning mild to moderate Alzheimer disease., Trial Registration: Clinicaltrials.gov NCT02017340, EudraCT number 2012-002764-27., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: SH is a paid employee of Pentara Corporation, which received payment to verify the primary outcome analysis of this study, and is also a paid consultant for Acumen Pharmaceuticals, Affiris AG, Affirmativ Diagnostics PLLC, Alkahest, Allergan, Alzheon, Amylyx Pharmaceuticals, Apodemus, Avanir Pharmaceuticals, Banner Alzheimer's Institute, Biogen, Dr. Richard Isaacson, Gerson Lehrman Group, Grifols Shared Services North America, Ionis Pharmaceuticals, M3 Biotechnology, Neurotrope BioScience, Nutricia Research B.V., PhotoPharmics, Regenera Pharma, Roche (F. Hoffmann-La Roche--Switzerland), Toyama Chemical Co., and vTv Therapeutics; MM and FC are paid employees of Archer Pharmaceuticals, which owns patents for the use of nilvadipine in Alzheimer disease; MM, FC, SK, RS, and BL are named as inventors in a pending patent for the use of nilvadipine based on the results of this clinical trial. No other authors have declared competing interests.

Introduction: This study is a European multicentre, randomised, double-blind, placebo-controlled trial investigating the efficacy and safety of nilvadipine as a disease course modifying treatment for mild-to-moderate Alzheimer's disease (AD) in a phase III study that will run for a period of 82 weeks with a treatment period of 78 weeks., Methods and Analysis: Adult patients, males and females over 50 years with mild-to-moderate AD as defined by the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's disease and Related Disorders Association (NINCDS-ADRDA) criteria, will be included in the study. It aims to recruit a total of 500 patients with AD; 250 in the nilvadipine group and 250 in the placebo group. Participants will be randomised to receive nilvadipine, an 8 mg overencapsulated, sustained release capsule, or a matching overencapsulated placebo (sugar pill) for a period of 78 weeks of treatment. The primary efficacy outcome measure in this study is the change in cognitive function as assessed by the Alzheimer's disease Assessment Scale (ADAS-Cog 12) from baseline to the end of treatment duration (78 weeks). There are two key secondary outcome measures, the Clinical Dementia Rating Scale Sum of Boxes (CDR-sb) and the Disability Assessment for Dementia (DAD). If a statistically significant effect is seen in the primary outcome, CDR-sb will be considered to be a coprimary end point and only the DAD will contribute to the secondary outcome analysis., Ethics and Dissemination: The study and all subsequent amendments have received ethical approval within each participating country according to national regulations. Each participant will provide written consent to participate in the study. All participants will remain anonymised throughout and the results of the study will be published in an international peer-reviewed journal., Trial Registration Number: EUDRACT Reference Number: 2012-002764-27., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)