Combined Effects of Frailty and Polypharmacy on Health Outcomes in Older Adults: Frailty Outweighs Polypharmacy.

OBJECTIVES: Existing studies cannot evaluate the time-varying properties of frailty and polypharmacy despite raising concerns about their combined effects in older individuals. This study investigated the longitudinal association between different combined statuses of frailty and polypharmacy on risks of adverse outcomes. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Subjects aged between 65 and 100 years (n = 100,000) were identified from Taiwan's National Health Insurance Research Database. MEASURES: Frailty was categorized into fit, mild, moderate, and severe frailty based on the multimorbidity frailty index. Concomitant use of 5 to 9 and ≥10 chronic medications was considered polypharmacy and excessive polypharmacy. We used generalized estimating equation models to examine the association among 12 groups of combined effects of frailty and polypharmacy and risks of all-cause mortality, all-cause hospitalization, and unplanned hospitalization. Age-stratified analyses were conducted for those aged 65 to 74, 75 to 84, and 85+ years. RESULTS: Compared with fit without polypharmacy, severe frailty with excess polypharmacy was associated with increased risks of adverse outcomes, particularly unplanned hospitalization (adjusted relative risk (aRR): 20.01 [95% confidence interval (CI)] 19.30-20.75). However, the combined effects varied in distinct groups. Within each polypharmacy category, there were dose-response associations between frailty category and adverse outcomes. For instance, within the polypharmacy group, the aRRs of mortality were 1.58 (1.52-1.64), 2.70 (2.60-2.80), 4.62 (4.44-4.82), and 6.81 (6.50-7.13) for the fit and mild, moderate, and severe frailty groups, respectively. By contrast, within each frailty category, the dose-response association between polypharmacy and adverse outcomes was limited to fit and mildly frail people. Age-stratified analyses yielded similar results. CONCLUSIONS AND RELEVANCE: Both frailty and polypharmacy modified the risks of mortality and hospital admissions in older people, but the combined effects varied in distinct groups. This study thus highlights the potential to optimize care of older people by capturing the dynamic and combined changes related to frailty and polypharmacy.

The preparation, characterization, and pharmacokinetic studies of chitosan nanoparticles loaded with paclitaxel/dimethyl-ß-cyclodextrin inclusion complexes.

A novel biocompatible and biodegradable drug-delivery nanoparticle (NP) has been developed to minimize the severe side effects of the poorly water-soluble anticancer drug paclitaxel (PTX) for clinical use. PTX was loaded into the hydrophobic cavity of a hydrophilic cyclodextrin derivative, heptakis (2,6-di-O-methyl)-ß-cyclodextrin (DM-ß-CD), using an aqueous solution-stirring method followed by lyophilization. The resulting PTX/DM-ß-CD inclusion complex dramatically enhanced the solubility of PTX in water and was directly incorporated into chitosan (CS) to form NPs (with a size of 323.9-407.8 nm in diameter) using an ionic gelation method. The formed NPs had a zeta potential of +15.9-23.3 mV and showed high colloidal stability. With the same weight ratio of PTX to CS of 0.7, the loading efficiency of the PTX/DM-ß-CD inclusion complex-loaded CS NPs was 30.3-fold higher than that of the PTX-loaded CS NPs. Moreover, it is notable that PTX was released from the DM-ß-CD/CS NPs in a sustained-release manner. The pharmacokinetic studies revealed that, compared with reference formulation (Taxol(®)), the PTX/DM-ß-CD inclusion complex-loaded CS NPs exhibited a significant increase in AUC(0→24h) (the area under the plasma drug concentration-time curve over the period of 24 hours) and mean residence time by 2.7-fold and 1.4-fold, respectively. Therefore, the novel drug/DM-ß-CD inclusion complex-loaded CS NPs have promising applications for the significantly improved delivery and controlled release of the poorly water-soluble drug PTX or its derivatives, thus possibly leading to enhanced therapeutic efficacy and less severe side effects.