Comparative Risk of Gout Flares When Initiating or Escalating Various Urate-Lowering Therapy: A Systematic Review With Network Meta-Analysis.

OBJECTIVE: We systematically examined comparative gout flare risk after initiation or escalation of different urate-lowering therapies (ULTs), comparative flare risk with and without concomitant flare prophylaxis, adverse event rates associated with flare prophylaxis, and optimal duration of flare prophylaxis. METHODS: We searched the Medline, Embase, Web of Science, and Cochrane databases and clinical trial registries from inception to November 2021 for trials investigating adults with gout initiating or escalating ULT. We performed random effects network meta-analyses and calculated risk ratios (RRs) between treatments. Bias was assessed using the revised Cochrane risk-of-bias tool. RESULTS: We identified 3,775 records, of which 29 publications (27 trials) were included. When compared to placebo plus prophylaxis, the RR of flares ranged from 1.08 (95% confidence interval [CI] 0.87-1.33) for febuxostat 40 mg plus prophylaxis to RR 2.65 [95% CI 1.58-4.45] for febuxostat 80 mg plus lesinurad 400 mg plus prophylaxis. Compared to ULT alone, the RR of flares was lower for ULT plus rilonacept 160 mg (RR 0.35 [95% CI 0.25-0.50]), ULT plus rilonacept 80 mg (RR 0.43 [95% CI 0.31-0.60]) and ULT plus colchicine (RR 0.50 [95% CI 0.35-0.72]). There was limited evidence for other flare prophylaxis and on prophylaxis harms and optimal duration. Primarily because of missing outcome data and bias in the selection of reported results, 71.4% and 63.4% of studies were assessed as high risk of bias for flares and adverse events, respectively. CONCLUSION: The RR of flares when introducing ULT varies depending on ULT drug and dosing strategies. There were limited data on ULT escalation. Flare prophylaxis with colchicine and rilonacept reduces flare incidence. More research is required on the harms and optimal duration of prophylaxis.

Alterations in drug disposition in older adults: a focus on geriatric syndromes.

INTRODUCTION: Age-associated physiological changes can alter the disposition of drugs, however, pathophysiological changes associated with geriatric syndromes in older adults may lead to even greater heterogeneity in pharmacokinetics. Geriatric syndromes are common health problems in older adults which have multifactorial causes and do not fit into distinct organ-based disease categories. With older adults being the greatest users of medications, understanding both age- and geriatric syndrome-related changes is important clinically to ensure safe and effective medication use. AREAS COVERED: This review provides an overview of current evidence regarding pharmacokinetic alterations that occur with aging and in common geriatric syndromes, including frailty, sarcopenia, dementia, polypharmacy and enteral feeding. The evidence is presented according to the four primary pharmacokinetic processes (Absorption, Distribution, Metabolism and Excretion). EXPERT OPINION: There is some evidence to inform our understanding of the impact of chronological aging and various geriatric syndromes on drug disposition. However, many areas require more research, including drug induced inhibition and induction of cytochrome P450 enzymes and the clinical utility of emerging methods for estimating renal function. There is a need to develop tools to predict alterations in drug disposition in subgroups of older adults, particularly where the currently available clinical information is sparse.

Potentially inappropriate medication use and related hospital admissions in aged care residents: The impact of dementia.

AIMS: To determine the prevalence of potentially inappropriate medication (PIM) use at hospital admission and discharge, and the contribution to hospital admission among residential aged care facility residents with and without dementia. METHODS: We conducted a secondary analysis using data from a multihospital prospective cohort study involving consecutively admitted older adults, aged 75 years or older, who were taking 5 or more medications prior to hospital admission and discharged to a residential aged care facility in South Australia. PIM use was identified using the 2015 Screening Tool for Older Persons' Prescription and 2019 Beers criteria. An expert panel of clinicians with geriatric medicine expertise evaluated the contribution of PIM to hospital admission. RESULTS: In total, 181 participants were included, the median age was 87.5 years and 54.7% were female. Ninety-one (50.3%) had a diagnosis of dementia. Participants with dementia had fewer PIMs, according to at least 1 of the 2 screening criteria, than those without dementia, at admission (dementia: 76 [83.5%] vs no dementia: 84 [93.3%], P = .04) and discharge (78 [85.7%] vs 83 [92.2%], P = .16). PIM use was causal or contributory to the admission in 28.1% of study participants (n = 45) who were taking at least 1 PIM at admission. CONCLUSIONS: Over 80% of acutely admitted older adults took PIMs at hospital admission and discharge and for over a quarter of these people the admissions were attributable to PIM use. Hospitalisation presents an opportunity for comprehensive medication reviews, and targeted interventions that enhance such a process could reduce PIM use and related harm.