Drugs & Aging

Risk of Cataract Surgery and Age-Related Macular Degeneration After Initiation of Denosumab vs Zoledronic Acid for Osteoporosis: A Multi-Database Cohort Study Abstract Background and Objective There is a relative lack of head-to-head comparisons of denosumab against other osteoporosis drugs on safety. We aimed to explore ocular outcomes in patients with osteoporosis initiating denosumab vs zoledronic acid. Methods We conducted a cohort study using claims data (2010–15) from two large US commercial insurance databases including patients with osteoporosis who were aged 50 years or older and initiators of denosumab or zoledronic acid. The primary outcomes were (1) receipt of cataract surgery and development of (2) wet age-related macular degeneration and (3) dry age-related macular degeneration within 365 days after initiation of denosumab vs zoledronic acid. Propensity score fine stratification and weighting were used to control for potential confounding, and we calculated the incidence rate and hazard ratio for each outcome in the cohorts. The estimates from the two databases were combined with a fixed-effects model meta-analysis. Results The study cohort included 50,821 denosumab and 67,471 zoledronic acid initiators. In the propensity score-weighted analysis, compared to zoledronic acid use, denosumab was associated with a modestly decreased risk of undergoing cataract surgery (hazard ratio 0.91; 95% confidence interval 0.85–0.98) but not with the risk of wet age-related macular degeneration (hazard ratio 1.29; 95% confidence interval 0.99–1.70) or dry age-related macular degeneration (hazard ratio 1.03; 95% confidence interval 0.98–1.09). Conclusions In this large population-based cohort study of 118,292 patients with osteoporosis, initiation of denosumab was associated with a modestly decreased risk of cataract surgery vs zoledronic acid. The risk of age-related macular degeneration was similar between the two drugs.

Persistence on Anti-Tumour Necrosis Factor Therapy in Older Patients with Inflammatory Bowel Disease Compared with Younger Patients: Data from the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD) Abstract Background and Objective Older people with inflammatory bowel disease (IBD) appear to have a lower response to anti-tumour necrosis factor (TNF) therapy, with more frequent complications than younger patients. The objective of this study was to assess persistence on therapy and the safety of anti-TNF therapy in older patients (aged ≥ 60 years). Methods We retrospectively reviewed the database of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD), extracting data regarding IBD patients aged ≥ 60 years and controls < 60 years of age at their first course of anti-TNF treatment. Data concerning persistence on therapy over the first year of treatment (primary objective) together with data on reasons for treatment withdrawal, concomitant diseases and treatments were collected. Results We identified 114 anti-TNF-naϊve patients aged ≥ 60 years (median age 64 years, range 60–80 years; 47 males) compared with 330 younger controls aged < 60 years (median age 39 years, range 18–59 years; 57 males). Older patients with Crohn’s disease (n = 73) showed a significantly lower persistence with every kind of anti-TNF therapy (whether analysed together [p < 0.001] or separately for intravenous and subcutaneous [SC] therapy) than younger controls, whereas older patients with ulcerative colitis (n = 41) showed a lower persistence when combining all kinds of anti-TNF treatment (p = 0.004) and for SC therapy. Secondary failures, infections, and neoplasias, but not primary failure, occurred more frequently in older IBD patients than in younger controls. Conclusion Despite a comparable number of primary failures, older IBD patients treated for the first time with anti-TNF agents showed lower treatment persistence due to higher rates of secondary failure, adverse events, infections, and tumours than younger patients in the first year of follow-up. The reasons for this difference still remain unclear.

Prevalence and Factors Associated with Analgesic Prescribing in Poly-Medicated Elderly Patients Abstract Background Pain is common in older patients and management guidelines rarely consider the effect of multiple comorbidities and concurrent medications on analgesic selection. Objectives The objectives of this study were to identify the prevalence and pattern of analgesic prescribing and associated factors in older patients with polypharmacy. Methods Older patients (aged ≥ 75 years) admitted to the Royal Adelaide Hospital between September 2015 and August 2016 and with polypharmacy were included and their comorbidities and medications prescribed at discharge were recorded. Drug Burden Index and Charlson Comorbidity Index were calculated. The number of medications that increased the risk of orthostatic hypotension were recorded. Logistic regression was used to compute the association between analgesic use and participant characteristics, and results were presented as odds ratios and 95% confidence intervals, adjusted for age, sex, Charlson Comorbidity Index, Drug Burden Index and orthostatic hypotension. Results Over 15,000 admissions were identified, of which 1192 patients were included, 824 (69%) of whom were prescribed an analgesic medication. Paracetamol (used by 89% of analgesic users), opioids (34%) and adjuvants (17%) were used more frequently than non-steroidal anti-inflammatory drugs (8%). Analgesic users had a higher Drug Burden Index, were prescribed more medications and were less likely to be male compared with non-users. Charlson Comorbidity Index across the cohort was high (7.3 ± 1.9) but there was no difference between analgesic users and non-users, but analgesic users were more likely to have a documented diagnosis of osteoarthritis, osteoporosis and falls. Opioid use was associated with the Drug Burden Index, while adjuvant use was associated with orthostatic hypotension. Opioid use was associated with having a diagnosis of osteoporosis and falls. Conclusions In our cohort of poly-medicated elderly patients, prescription of analgesic medications was common, and these patients are likely to have an increased rate of adverse drug reactions and falls compared with those who were not prescribed analgesic medications.

Correction to: Interventions to Reduce Adverse Drug Event-Related Outcomes in Older Adults: A Systematic Review and Meta-analysis Unfortunately, the co-author name was incorrectly published as ‘ ‘Lamona’’ instead of ‘ ‘Lamorna’’ in the original article

Topical Treatment of Localized Neuropathic Pain in the Elderly Abstract The prevalence of neuropathic pain in the older population has been reported to be very high and is most commonly localized to a circumscribed area. Treatment failure is frequent in neuropathic pain and is accompanied by central side effects with recommended oral drugs acting on the central nervous system. A number of topical pharmaceuticals are available on prescription and also sold over the counter. This review in persons aged older than 60 years shows the efficacy of lidocaine 5% and capsaicin 8% for localized neuropathic pain while results with other pharmaceuticals are rather inconsistent. Local application of drugs has a very limited systemic effect and the pharmacological advantages of local over systemic treatment are particularly interesting in older persons who often have comorbidities and take multiple medications. However, more information is needed on the efficacy and safety of lidocaine 5% and capsaicin 8% in older old persons and on the long-term effects of these pharmaceuticals. These studies should also pave the way for research and development in the field of topical analgesics with a satisfactory level of evidence-based medicine.

The Prevalence and Factors Associated with Antiepileptic Drug Use in US Nursing Home Residents Abstract Background Antiepileptic drugs (AEDs) are commonly used by nursing home residents, both on- and off-label. The landscape of AED use has changed over the past two decades; however, despite this, contemporaneous research on AED use in US nursing home residents is scant. Objective The aim of this study was to estimate the prevalence of AED use, describe prescribing patterns, identify factors associated with AED use, and assess whether these factors differ among AEDs with expanded indications in older adults (i.e. gabapentin, pregabalin, topiramate, and lamotrigine). Methods We conducted a cross-sectional study among 549,240 long-stay older residents who enrolled in fee-for-service Medicare and lived in 15,111 US nursing homes on 1 September 2016. Demographics and conditions associated with AED indications, epilepsy comorbidities, and safety data came from the Minimum Data Set Version 3.0 (MDS 3.0). Medicare Part D claims were used to identify AED use. Robust Poisson models and multinomial logistic models for clustered data estimated adjusted prevalence ratios (aPR), adjusted odds ratios (aOR), and 95% confidence intervals (CIs). Results Overall, 24.0% used AEDs (gabapentin [13.3%], levetiracetam [4.7%], phenytoin [1.9%], pregabalin [1.8%], and lamotrigine [1.2%]). AED use was associated with epilepsy (aPR 3.73, 95% CI 3.69–3.77), bipolar disorder (aPR 1.20, 95% CI 1.18–1.22), pain (aPRmoderate/severe vs. no pain 1.42, 95% CI 1.40–1.44), diabetes (aPR 1.27, 95% CI 1.26–1.28), anxiety (aPR 1.12, 95% CI 1.11–1.13), depression (aPR 1.17, 95% CI 1.15–1.18), or stroke (aPR 1.08, 95% CI 1.06–1.09). Residents with advancing age (aPR85+ vs. 65–74 years 0.73, 95% CI 0.73–0.74), Alzheimer’s disease/dementia (aPR 0.87, 95% CI 0.86–0.88), or cognitive impairment (aPRsevere vs. no impairment 0.62, 95% CI 0.61–0.63) had decreased AED use. Gabapentinoid use was highly associated with pain (aORmoderate/severe vs. no pain 2.07, 95% CI 2.01–2.12) and diabetes (aOR 1.79, 95% CI 1.76–1.82), but not with an epilepsy indication. Conclusions AED use was common in nursing homes, with gabapentin most commonly used (presumably for pain). That multiple comorbidities were associated with AED use underscores the need for future studies to investigate the safety and effectiveness of AED use in nursing home residents.

Reducing Inappropriate Drug Use in Older Patients by Use of Clinical Decision Support in Community Pharmacy: A Mixed-Methods Evaluation Abstract Introduction Older people are prone to drug-related harm. Clinical decision support systems (CDSSs) in community pharmacies may improve appropriate prescribing in this population. Objective This study investigated (persistent) drug therapy changes and its determinants to reduce potentially inappropriate medication (PIM) in older patients based on CDSS alerts and to investigate barriers and facilitators for implementation of drug therapy changes based on these CDSS alerts. Methods Five clinical decision rules based on national guidelines for inappropriate drugs in older patients were incorporated in a web-based CDSS in 31 community pharmacies between February and April 2017. The CDSS generated alerts for patients aged > 70 years who had prescriptions for one of the following drugs: alprazolam, amitriptyline, barnidipine, duloxetine, fluoxetine, trazodone, quetiapine and olanzapine. The registered alert management data and medication dispensing histories were analysed to find potential determinants of persistent drug therapy changes. Ten pharmacists were interviewed about the barriers and facilitators for implementing drug therapy changes based on CDSS alerts. An inductive thematic analysis of the transcripts was performed. Results The pharmacists recorded the management of 1810 of the 2589 generated alerts, and 158 (8.7%) alerts were associated with a persistent drug therapy change. A logistic regression analysis found that the drug triggering the alert and the type of prescription [first dispensing vs. repeat; odds ratio 2.1 (95% confidence interval 1.4–3.2)] were significantly associated with persistent drug therapy changes. No association was found between persistent changes and age, sex, number of medicines in use, or recent clinical medication review. Analysis of the interviews revealed nine barriers and facilitators associated with drug therapy change. Conclusion When community pharmacists implemented CDSS alerts to reduce inappropriate drug use in older patients, they registered a persistent drug therapy change in 8.7% of the cases. Alerts triggered by a first prescription were two times more likely to be associated with a persistent drug therapy change than alerts triggered by repeat prescriptions. This study found that clinical rules can be used to detect inappropriate drug use in older patients and that drug therapy can change based on the alerts. This suggests that CDSS alerts are a useful tool for implementing guidelines on PIM in older patients in daily practice.

Calcium Channel Blockers Co-prescribed with Loop Diuretics: A Potential Marker of Poor Prescribing? Abstract Prescribing cascades are where a drug adverse reaction is wrongly attributed to the emergence of a new condition, which leads to further drug prescribing. This promotes polypharmacy, adverse drug reactions and therapeutic burden. An example of a prescribing cascade is the co-prescribing of loop diuretics to treat the peripheral oedema caused by calcium channel blocker (CCB) drugs. Although well recognised, this is still a combination of medications taken by millions of people worldwide. CCBs have no prognostic benefit in heart failure and have an absolute risk increase for oedema of around 8–18% (number needed to harm 6–13). In the treatment of hypertension, they also increase the risk of oedema and a new diagnosis of heart failure without having any major advantages over alternative drugs. The best way to manage the oedema caused by CCBs is to switch to an alternative medication. Only where this is not possible or fails to achieve therapeutic goals would the CCB–loop diuretic combination appear to be justified. In many cases, therapeutic practice could be improved by targeting people on CCB–loop diuretic combinations for medication review. This could improve quality of life and reduce polypharmacy, adverse drug reactions, therapeutic burden and financial costs for millions of people worldwide.

Interventions to Reduce Adverse Drug Event-Related Outcomes in Older Adults: A Systematic Review and Meta-analysis Abstract Background Many studies focus on interventions that reduce the processes that lead to adverse drug events (ADEs), such as inappropriate or high-risk prescribing, without assessing whether they result in a reduction in ADEs or associated adverse health outcomes. Objectives Our objective was to systematically review interventions to reduce the incidence of ADEs measured by health outcomes in older patients in primary care settings. Methods The review included randomised controlled trials, controlled clinical trials, controlled before and after studies, interrupted time series studies and cohort studies conducted in the community care setting. Older patients (aged ≥ 65 years) receiving medical treatment in primary care were included. Interventions were aimed at reducing adverse health outcomes associated with ADEs in older patients. Risk of bias was assessed using the Cochrane Collaboration’s tool. Outcomes were measured by reductions in hospitalisation, emergency department (ED) visits, mortality and improvements in quality of life (QoL), mental health and physical function. Fixed and random-effects models were used to calculate pooled effect estimates comparing interventions and control groups for the outcomes, where feasible. Results The literature search identified 1566 abstracts, seven of which were included in the systematic review. The interventions for reducing ADEs included prescription or medication reviews by a pharmacist (n = 4), primary care physician (n = 1) or research team (n = 1), and an educational intervention (n = 1) for nursing staff to improve the recognition of potentially harmful medications and corresponding ADEs. Meta-analysis found no statistically significant benefit from any interventions on hospitalisation, ED visits, mortality, QoL or mental health and physical function. Conclusions No significant benefit was gained from any of the interventions in terms of the outcomes considered. New approaches are required to reduce ADEs in older adults.

Analysis by Age Group of Disease Outcomes in Patients with Psoriatic Arthritis: A Cross-Sectional Multicentre Study Abstract Objectives Elderly psoriatic arthritis (PsA) patients may show greater inflammatory activity and worse prognoses than patients of other ages. However, these patients may be at risk of receiving fewer systemic treatments. In this report, we have analysed disease outcomes in PsA by age groups. Methods This cross-sectional, multicentre study included 227 PsA patients under biological and non-biological systemic therapies. The study population was divided into four categories by age: < 40, 40‒49, 50‒65 and > 65 years. Physical functioning, disease activity, remission rates and disease impact were compared. Results Thirty-one patients (13.7%) were under 40 years, 26.9% (n = 61) were 40–49 years, 26.4% (n = 60) were 50–65 years and 33.0% (n = 75) were patients > 65 years. Compared with the other age groups, disease duration was significantly higher in subjects older than 65 years (p < 0.001). Only 8% of patients older than 65 years received corticosteroids compared with 29% of patients aged < 40 years, 13.1% of patients aged 40–49 years and 26.7% of patients aged 50–65 years (p = 0.007). Similarly, only 36% of patients over 65 years of age received a biological therapy compared with between 51.6 and 59% for the other age groups (p = 0.036). However, remission rates were not statistically different between groups. Disease-associated physical disability was similar among groups. Compared with patients aged < 40 years, more patients > 65 years achieved low disease impact (10.7% vs 37.7%, respectively; p < 0.05). Conclusions Fewer older patients received corticosteroids and biological therapy. However, disease outcomes were similar or even better compared with those observed in younger patients. Therefore, treatment strategies for older patients with PsA should be similar to those offered to younger individuals.