STUDY DESIGN: A prospective study using data from the Australian Longitudinal Study on Women's Health. Women aged 77-82 years in 2003, and 91-96 years in 2017 were analysed, linking the Pharmaceutical Benefits Scheme data to participants' survey data.
MAIN OUTCOME MEASURES: The association between frailty and continuous polypharmacy was determined using generalised estimating equations for log binomial regressions, controlling for confounding variables. Descriptive statistics were used to determine the proportion of women with polypharmacy, and medications that contributed to polypharmacy.
RESULTS: The proportion of women with continuous polypharmacy increased over time as they aged. Among participants who were frail (n = 833) in 2017, 35.9 % had continuous polypharmacy and 1.32 % had hyperpolypharmacy. Among those who were non-frail (n = 1966), 28.2 % had continuous polypharmacy, and 1.42 % had hyperpolypharmacy. Analgesics (e.g. paracetamol) and cardiovascular medications (e.g. furosemide and statins) commonly contributed to continuous polypharmacy among frail and non-frail women. Accounting for time and other characteristics, frail women had an 8% increased risk of continuous polypharmacy (RR 1.08; 95 % CI 1.05, 1.11) compared to non-frail women.
CONCLUSIONS: Combined, polypharmacy and frailty are key clinical and public health challenges. Given that one-third of women had continuous polypharmacy, monitoring and review of medication use among older women are important, and particularly among women who are frail.
METHODS: The study is a randomised double-blind placebo-controlled phase-II single-site clinical trial conducted in Perth, Australia. The target sample is to recruit 240 participants diagnosed with chronic frequent episodic migraines between 18 and 80 years of age. Participants will be randomised to one of four treatment groups for 14 weeks (placebo induction for 2 weeks, followed by 12 weeks on one of the respective treatment arms): placebo, L-arginine, AGE, or a combination of L-arginine and AGE. The doses of L-arginine and AGE are 1.5 g and 1 g daily, respectively. The primary outcome is to assess migraine response using change in migraine frequency and intensity between baseline and 12 weeks. Secondary outcomes include the impact of L-arginine and/or AGE on photosensitivity, retinal vessel changes, and blood biomarker concentrations of vascular tone, following a 12-week intervention.
DISCUSSION: The protocol describes the oral administration of 2 nutraceutical-based interventions as possible prophylactic treatments for chronic frequent episodic migraines, with potential for direct clinical translation of outcomes. Potential limitations of the study include the fixed-dose design of each treatment arm and that in vivo neuroimaging methods, such as magnetic resonance imaging (MRI), will not be conducted to determine putative cerebro-vasodilatory changes to coincide with the outcome measures. Dose-response studies may be indicated.
TRIAL REGISTRATION: The trial was retrospectively registered with the Australian New Zealand Clinical Trials Registry ACTRN12621001476820 (Universal Trial Number: U1111-1268-1117) on 04/08/2021. This is protocol version 1, submitted on 25/11/2022.