Drugs & Aging最新文献

Background: Patients, family members, and clinicians express concerns about potential adverse drug withdrawal events (ADWEs) following medication discontinuation or fears of upsetting a stable medical equilibrium as key barriers to deprescribing. Currently, there are limited methods to pragmatically assess the safety of deprescribing and ascertain ADWEs. We report the methods and results of safety monitoring for the OPTIMIZE trial of deprescribing education for patients, family members, and clinicians.

Methods: This was a pragmatic cluster randomized trial with multivariable Poisson regression comparing outcome rates between study arms. We conducted clinical record review and adjudication of sampled records to assess potential causal relationships between medication discontinuation and outcomes. This study included adults aged 65+ with dementia or mild cognitive impairment, one or more additional chronic conditions, and prescribed 5+ chronic medications. The intervention included an educational brochure on deprescribing that was mailed to patients prior to primary care visits, a clinician notification about individual brochure mailings, and an educational tip sheets was provided monthly to primary care clinicians. The outcomes of the safety monitoring were rates of hospitalizations and mortality during the 4 months following brochure mailings and results of record review and adjudication. The adjudication process was conducted throughout the trial and included classifications: likely, possibly, and unlikely.

Results: There was a total of 3012 (1433 intervention and 1579 control) participants. There were 420 total hospitalizations involving 269 (18.8%) people in the intervention versus 517 total hospitalizations involving 317 (20.1%) people in the control groups. Adjusted risk ratios comparing intervention to control groups were 0.92 [95% confidence interval (CI) 0.72, 1.16] for hospitalization and 1.19 (95% CI 0.67, 2.11) for mortality. Both groups had zero deaths "likely" attributed to a medication change prior to the event. A total of 3 out of 30 (10%) intervention group hospitalizations and 7 out of 35 (20%) control group hospitalizations were considered "likely" due to a medication change.

Conclusions: Population-based deprescribing education is safe in the older adult population with cognitive impairment in our study. Pragmatic methods for safety monitoring are needed to further inform deprescribing interventions.

Trial registration: NCT03984396. Registered on 13 June 2019.

Background: Proton pump inhibitors (PPIs) are largely used in older adults and data are needed in off-label indications, such as the prevention of upper gastrointestinal bleeding (UGIB) in patients receiving oral anticoagulants (OACs). This study aimed to assess whether PPIs reduce the risk of UGIB in patients initiating oral anticoagulation.

Methods: We conducted a longitudinal study based on the French national health database. The study population included 109,693 patients aged 75-110 years with a diagnosis of atrial fibrillation who initiated OACs [vitamin K antagonist (VKA) or direct OAC (DOAC)] between 2012 and 2016. We used multivariable Cox models weighted by inverse of probability of treatment to estimate the adjusted hazard ratio (aHR) of UGIB between PPI users and nonusers over a 6- and 12-month follow-up.

Results: PPI users represented 23% of the study population (28% among VKA initiators and 17% among DOAC initiators). The mean age (83 ± 5.3 years) and proportion of women (near 60%) were similar between groups. The risk of UGIB in the first 6 months after initiation of OAC decreased by 20% in PPI users compared with PPI nonusers [aHR_{6 months} = 0.80, 95% confidence interval (CI) 0.65-0.98], but was not significantly modified when the follow-up was extended to 12 months (aHR_{12 months} = 0.90, 95% CI 0.76-1.07), with a stronger effect among patients treated with vitamin K antagonists (aHR_{6 months} = 0.73, 95% CI 0.58-0.93; aHR_{12 months} = 0.81, 95% CI 0.67-0.99).

Conclusions: This study suggests that PPIs were associated with reduced risk of gastrointestinal bleeding after initiation of oral anticoagulation in older patients with atrial fibrillation, particularly within 6 months after initiation of an antivitamin K antagonist.

Though more common earlier in life, increasing attention is being focused on the development of cutaneous lupus erythematosus (CLE) in patients with advancing age. Studies show that CLE is more common in older populations than previously thought, and all CLE subtypes are possible in this group. Just like patients in the third or fourth decade of life, CLE may appear alongside or independent of systemic lupus erythematosus. Older populations manifesting CLE for the first time seem to have a lower risk of progression to systemic disease than younger peers, and are more commonly White. CLE must be carefully distinguished from other skin conditions that have a predilection for presentation in older populations, including rosacea, lichen planus, and other autoimmune conditions such as dermatomyositis or pemphigus/pemphigoid. It is thought that most CLE in older populations is drug-induced, with drug-induced subacute cutaneous lupus erythematosus being the most common subtype. Management of CLE in older patients focuses on eliminating unnecessary medications known to induce CLE, and otherwise treatment proceeds similarly to that in younger patients, with a few special considerations.

Background: Older adults are at an increased risk of drug-related problems, especially following discharge from hospital. Drug-related readmissions place a large burden on the patient and the healthcare system. However, previous studies report inconsistent results on the prevalence and associated risk factors for drug-related hospital readmissions in older adults.

Objectives: We aimed to assess the prevalence of drug-related readmissions in older adults aged 65 years and older and investigate the drug classes, preventability and risk factors most associated with these readmissions.

Methods: A systematic review and meta-analysis were undertaken to answer our objectives. A search of four databases (MEDLINE, Embase, CINAHL and Scopus) was conducted. Three authors independently performed title and abstract screening, full-text screening and data extraction of all included studies. A meta-analysis was conducted to calculate the pooled prevalence of drug-related readmissions across all studies, and a subgroup analysis was performed to explore heterogeneity among studies reporting on adverse drug reaction-related readmissions.

Results: A total of 1978 studies were identified in the initial search, of which four studies were included in the final synthesis. Three studies focused on readmissions due to adverse drug reactions and one study focused on readmissions due to drug-related problems. A pooled prevalence of 9% (95% confidence interval 2-18) was found for drug-related readmissions across all studies, and a pooled prevalence of 6% (95% confidence interval 4-10) was found for adverse drug reaction-related readmissions. Three studies explored the preventability of readmissions and 15.4-22.2% of cases were deemed preventable. The drug classes most associated with adverse drug reaction readmissions included anticoagulants, antibiotics, psychotropics and chemotherapy agents. Polypharmacy (the use of five or more medications) and several comorbidities such as cancer, liver disease, ischaemic heart disease and peptic ulcer disease were identified as risk factors for drug-related readmissions.

Conclusions: Almost one in ten older adults discharged from hospital experienced a drug-related hospital readmission, with one fifth of these deemed preventable. Several comorbidities and the use of polypharmacy and high-risk drugs were identified as prominent risk factors for readmission. Further research is needed to explore possible causes of drug-related readmissions in older adults for a more guided approach to the development of effective medication management interventions.

Aim: Polypharmacy in multimorbid older patients with atrial fibrillation (AF) is a risk factor for potentially inappropriate prescribing (PIP). We aimed to systematically assess the evidence on the prevalence of PIP and its impact on adverse health outcomes in this patient group.

Methods: A systematic search of the published peer-reviewed literature describing the prevalence of PIP and/or its association with adverse health outcomes in multimorbid (AF plus one comorbidity) and polymedicated (≥ 2 drugs) adults ≥ 65 years was done up to March 2023. A meta-analysis of the prevalence of PIP of (direct) oral anticoagulants ((D)OACs) was conducted using a random-effects model. Leave-one-out analysis was performed with R (version 4.2.2) and RStudio (version 2022.12.0+353).

Results: Of the 12 studies included, only one reported on the prevalence of overall PIP (65%). The meta-analysis of 10 studies assessing PIP of (D)OACs produced a pooled prevalence [95% confidence interval (CI)] of 35% [30-40%], with significant heterogeneity between the included studies (I² 95%). No statistically significant association was reported in three studies between PIP of (D)OACs, cardiovascular (CV) and all-cause mortality, hospital readmission, CV hospitalisation and stroke. Reported associations between PIP and major bleeding differed, with one study demonstrating a significant association (odds ratio 2.17; 95% CI 1.14-4.12) and the other study not showing such association.

Conclusion: This systematic review highlights the scarce evidence regarding the prevalence of PIP and its association with adverse health outcomes in multimorbid older adults with AF. Large, prospective and better-designed studies are needed.

Background

While the effectiveness of tyrosine kinase inhibitors (TKIs) seems similar in older patients with gastrointestinal stromal tumors (GIST) compared with younger patients, toxicities in older patients treated with TKIs more often lead to discontinuation of treatment.

Objective

To better understand the age-related pharmacology and pharmacodynamic differences in patients with GIST treated with TKIs, the primary aim of this study was to evaluate TKI dosing patterns in older patients with GIST, while the secondary aims were to evaluate differences in imatinib trough plasma concentrations between age groups and to compare the overall survival (OS) in patients with and without dose reductions in all treatment lines in a palliative setting.

Methods

Patients (18 years of age or older) with histologically proven GIST diagnosed between January 2009 and June 2021 and treated with one or more lines of TKIs were selected from the Dutch GIST Registry (DGR) database. Age groups were divided into younger patients (age <70 years) and older patients (age ≥70 years). All imatinib trough plasma concentrations of blood withdrawals taken from initiation of imatinib until a maximum of 1 year of treatment with imatinib were collected. Reasons for first adjustment of treatment were classified as adverse event, dose modification, progressive disease and other reasons. The next treatment steps after first adjustment of treatment were defined as dose escalation, dose reduction, dose interruption, or end of treatment. The association of dose reduction and OS was analyzed using the landmark approach.

Results

Overall, 871 patients were included in this study, including 577 younger patients and 294 older patients. Older patients more often had an adverse event as the reason for first adjustment of treatment with both imatinib (45.6%; p < 0.001) and sunitinib (58.6%; p = 0.224) compared with younger patients (19.5% and 42.7%, respectively). Adjustment of imatinib and sunitinib after starting on a standard dose because of an adverse event most often resulted in dose reduction in both age groups. Median trough plasma concentrations of all samples taken within the first year after initiation of imatinib were higher in older patients (1228 ng/mL, interquartile range [IQR] 959–1687) compared with younger patients (1035 ng/mL [IQR 773–1377]; p < 0.001). No significant differences were seen between OS in patients with or without dose reduction in all treatment lines (imatinib: p = 0.270; sunitinib: p = 0.547; and regorafenib: p = 0.784).

Conclusion

Older patients showed higher imatinib trough plasma concentrations compared with younger patients and also had earlier and more often adverse events as th

Background: A growing body of research supports the negative impact of anticholinergic drug burden on physical frailty. However, prior research has been limited to homogeneous white European populations, and few studies have evaluated how anticholinergic burden tools compare in their measurement function and reliability with minority community-dwelling adult populations. This study investigated the association between anticholinergic drug exposure and frailty by conducting a sensitivity analysis using multiple anticholinergic burden tools in a diverse cohort.

Methods: A comprehensive psychometric approach was used to assess the performance of five clinical Anticholinergic Burden Tools: Anticholinergic Cognitive Burden Scale (ACB), Anticholinergic Drug Scale (ADS), average daily dose, total standardized daily doses (TSDD), and Cumulative Anticholinergic Burden scale (CAB). Spearman correlation matrix and intraclass correlation coefficients (ICC) were used to determine the association among the variables. Ordinal logistic regression is used to evaluate the anticholinergic burden measured by each scale to determine the prediction of frailty. Model performance is determined by the area under the curve (AUC).

Results: The cohort included 80 individuals (mean age 69 years; 55.7% female, 71% African American). All anticholinergic burden tools were highly correlated (p < 0.001), ICC3 0.66 (p < 0.001, 95% confidence interval (CI) 0.53-0.73). Among individuals prescribed anticholinergics, 33% were robust, 44% were prefrail, and 23% were frail. All five tools predicted prefrail and frail status (p < 0.05) with low model misclassification rates for frail individuals (AUC range 0.78-0.85).

Conclusion: Anticholinergic burden tools evaluated in this cohort of low-income African American older adults were highly correlated and predicted prefrail and frail status. Findings indicate that clinicians can select the appropriate instrument for the clinic setting and research question while maintaining confidence that all five tools will produce reliable results. Future anticholinergic research is needed to unravel the association between interventions such as deprescribing on incident frailty in longitudinal data.

Background: To reduce prescribing cascades occurring in clinical practice, healthcare providers require information on the prescribing cascades they can recognize and prevent.

Objective: This systematic review aims to provide an overview of prescribing cascades, including dose-dependency information and recommendations that healthcare providers can use to prevent or reverse them.

Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was followed. Relevant literature was identified through searches in OVID MEDLINE, OVID Embase, OVID CINAHL, and Cochrane. Additionally, Web of Science and Scopus were consulted to analyze reference lists and citations. Publications in English were included if they analyzed the occurrence of prescribing cascades. Prescribing cascades were included if at least one study demonstrated a significant association and were excluded when the adverse drug reaction could not be confirmed in the Summary of Product Characteristics. Two reviewers independently extracted and grouped similar prescribing cascades. Descriptive summaries were provided regarding dose-dependency analyses and recommendations to prevent or reverse these prescribing cascades.

Results: A total of 95 publications were included, resulting in 115 prescribing cascades with confirmed adverse drug reactions for which at least one significant association was found. For 52 of these prescribing cascades, information regarding dose dependency or recommendations to prevent or reverse prescribing cascades was found. Dose dependency was analyzed and confirmed for 12 prescribing cascades. For example, antipsychotics that may cause extrapyramidal syndrome followed by anti-parkinson drugs. Recommendations focused on dosage lowering, discontinuing medication, and medication switching. Explicit recommendations regarding alternative options were given for three prescribing cascades. One example was switching to ondansetron or granisetron when extrapyramidal syndrome is experienced using metoclopramide.

Conclusions: In total, 115 prescribing cascades were identified and an overview of 52 of them was generated for which recommendations to prevent or reverse them were provided. Nonetheless, information regarding alternative options for managing prescribing cascades was scarce.