Background:The current lack of an effective cure for dementia would exacerbate its prevalence and incidence globally. Growing evidence has linked mindfulness to cognitive and psychological improvements that could be relevant for mild cognitive impairment (MCI).Objective:To investigate whether mindfulness practice can improve health outcomes of MCI.Methods:The study is the first longitudinal mixed-methods observational study with a one-year follow-up period, that customized an eight-week group-based mindfulness training program for older adults with MCI (n = 14). Measures included cognitive function, psychological health, trait mindfulness, adherence to mindfulness practice, and everyday activities functioning as assessed at pre-intervention, post-intervention, and one-year follow-up. Repeated measures ANOVAs, Pearson’s correlation analyses, and Mann-Whitney U tests were performed.Results:The MCI participants showed significant improvements in cognitive function (p < 0.05) and trait mindfulness (p < 0.05) after completing the intervention. Between program intervention and one-year follow-up (59 weeks), positive correlations were found between their cognitive function (p < 0.05) and everyday activities functioning (p < 0.05) with the duration of mindfulness meditation; and between trait mindfulness and the level of informal mindfulness practice (p < 0.05). Those who meditated more during these 59 weeks, showed greater improvements in cognitive function (p < 0.05) and everyday activities functioning (p < 0.05), with large effect sizes at the one-year follow-up. Qualitative findings will be reported separately.Conclusion:Long-term mindfulness practice may be associated with cognitive and functional improvements for older adults with MCI. Mindfulness training could be a potential efficacious non-pharmacological therapeutic intervention for MCI.

Keywords: herd effect, incremental cost-effectiveness ratio (ICER), Markov transition-state model, pneumococcal disease, 13-valent pneumococcal conjugate vaccine (PCV13), 10-valent pneumococcal conjugate vaccine (PCV10)Pneumococcal disease causes large morbidity, mortality and health care utilization and medical and non-medical costs, which can all be reduced by effective infant universal routine immunization programs with pneumococcal conjugate vaccines (PCV). We evaluated the clinical and economic benefits of such programs with either 10-or 13-valent PCVs in Malaysia and Hong Kong by using an age-stratified Markov cohort model with many country-specific inputs. The incremental cost per quality-adjusted life year (QALY) was calculated to compare PCV10 or PCV13 against no vaccination and PCV13 against PCV10 over a 10-year birth cohort's vaccination. Both payer and societal perspectives were used. PCV13 had better public health and economic outcomes than a PCV10 program across all scenarios considered. For example, in the base case scenario in Malaysia, PCV13 would reduce more cases of IPD (C2,296), pneumonia (C705,281), and acute otitis media (C376,967) and save more lives (C6,122) than PCV10. Similarly, in Hong Kong, PCV13 would reduce more cases of IPD cases (C529), pneumonia (C172,185), and acute otitis media (C37,727) and save more lives (C2,688) than PCV10. During the same time horizon, PCV13 would gain over 74,000 and 21,600 additional QALYs than PCV10 in Malaysia and Hong Kong, respectively. PCV13 would be cost saving when compared against similar program with PCV10, under both payer and societal perspective in both countries. PCV13 remained a better choice over PCV10 in multiple sensitivity, scenario, and probabilistic analyses. PCV13s broader serotype coverage in its formulation and herd effect compared against PCV10 were important drivers of differences in outcomes.

A modular interdisciplinary platform was developed to investigate the economic impact of oseltamivir treatment by dosage regimen under simulated influenza pandemic scenarios. METHODSThe pharmacology module consisted of a pharmacokinetic distribution of oseltamivir carboxylate daily area under the concentration-time curve at steady state (simulated for 75 mg and 150 mg twice daily regimens for 5 days) and a pharmacodynamic distribution of viral shedding duration obtained from phase II influenza inoculation data. The epidemiological module comprised a susceptible, exposed, infected, recovered (SEIR) model to which drug effect on the basic reproductive number (R 0 ), a measure of transmissibility, was linked by reduction of viral shedding duration. The number of infected patients per population of 100 000 susceptible individuals was simulated for a series of pandemic scenarios, varying oseltamivir dose, R 0 (1.9 vs. 2.7), and drug uptake (25%, 50%, and 80%). The number of infected patients for each scenario was entered into the health economics module, a decision analytic model populated with branch probabilities, disease utility, costs of hospitalized patients developing complications, and case-fatality rates. Change in quality-adjusted life years was determined relative to base case. British Journal of Clinical Pharmacology RESULTSOseltamivir 75 mg relative to no treatment reduced the median number of infected patients, increased change in quality-adjusted life years by deaths averted, and was cost-saving under all scenarios; 150 mg relative to 75 mg was not cost effective in low transmissibility scenarios but was cost saving in high transmissibility scenarios. CONCLUSIONThis methodological study demonstrates proof of concept that the disciplines of pharmacology, disease epidemiology and health economics can be linked in a single quantitative framework. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• To date, modelling of influenza has been conducted in discrete discipline areas.• The discrete pharmacology, epidemiology and health economic models are not linked and make assumptions about the adjacent disciplines that are inappropriate.• There are no epidemiological or health economic models which have taken into account between subject variability in the pharmacology of influenza treatments. WHAT THIS STUDY ADDS• This study provides the first integrated interdisciplinary framework to understand the cost-utility of antiviral therapy under various influenza pandemic scenarios linking drug pharmacokinetics/pharmacodynamics, epidemiological and health economics endpoints. • This quantitative framework was able to show that oseltamivir reduced the median number of infected individuals, increased quality-adjusted life years by deaths averted, and was cost-saving under most pandemic scenarios.• Given the growing need to justify pricing of medicines to society and payer, the methodology of interdisciplinary pharmacometrics can be applied across all disease areas where the pharmacokinetics/pharmacodynamics, clinical or epidemi...

Although both study drugs provide safe and effective empiric treatment for moderate-to-severe infected diabetic foot ulcers, piperacillin/tazobactam has the advantage of covering Pseudomonas aeruginosa (bacteriologic success rate of 85.7%), the most commonly isolated gram-negative pathogen in this study.