Contribution of Potentially Inappropriate Medications to Polypharmacy-Associated Risk of Mortality in Middle-Aged Patients: A National Cohort Study.

BACKGROUND: The role of potentially inappropriate medications (PIMs) in mortality has been studied among those 65 years or older. While middle-aged individuals are believed to be less susceptible to the harms of polypharmacy, PIMs have not been as carefully studied in this group. OBJECTIVE: To estimate PIM-associated risk of mortality and evaluate the extent PIMs explain associations between polypharmacy and mortality in middle-aged patients, overall and by sex and race/ethnicity. DESIGN: Observational cohort study. SETTING: Department of Veterans Affairs (VA), the largest integrated healthcare system in the US. PARTICIPANTS: Patients aged 41 to 64 who received a chronic medication (continuous use of ≥ 90 days) between October 1, 2008, and September 30, 2017. MEASUREMENT: Patients were followed for 5 years until death or end of study period (September 30, 2019). Time-updated polypharmacy and hyperpolypharmacy were defined as 5-9 and ≥ 10 chronic medications, respectively. PIMs were identified using the Beers criteria (2015) and were time-updated. Cox models were adjusted for demographic, behavioral, and clinical characteristics. RESULTS: Of 733,728 patients, 676,935 (92.3%) were men, 479,377 (65.3%) were White, and 156,092 (21.3%) were Black. By the end of follow-up, 104,361 (14.2%) patients had polypharmacy, 15,485 (2.1%) had hyperpolypharmacy, and 129,992 (17.7%) were dispensed ≥ 1 PIM. PIMs were independently associated with mortality (HR 1.11, 95% CI 1.04-1.18). PIMs also modestly attenuated risk of mortality associated with polypharmacy (HR 1.07, 95% CI 1.03-1.11 before versus HR 1.05, 95% CI 1.01-1.09 after) and hyperpolypharmacy (HR 1.18, 95% CI 1.09-1.28 before versus HR 1.12, 95% CI 1.03-1.22 after). Patterns varied when stratified by sex and race/ethnicity. LIMITATIONS: The predominantly male VA patient population may not represent the general population. CONCLUSION: PIMs were independently associated with increased mortality, and partially explained polypharmacy-associated mortality in middle-aged people. Other mechanisms of injury from polypharmacy should also be studied.

Potentially inappropriate medication use by level of polypharmacy among US Veterans 49-64 and 65-70 years old.

BACKGROUND: Potentially inappropriate medications (PIMs) are medications contra-indicated in particular circumstances. We sought to characterize PIMs by level of polypharmacy by age, sex, and race/ethnicity. METHODS: We performed a cross-sectional drug dispensing study using electronic health records available through the US Department of Veterans Affairs. We extracted pharmacy fill and refill records during fiscal year 2016 (i.e., October 1, 2015-September 30, 2016) for all patients aged 49-70 who accessed care in the preceding fiscal year. PIMs were defined by the combined Beers and Laroche (henceforth Beers Laroche) criteria used for older patients and the PROMPT criteria used for middle-aged. RESULTS: In the 1 499 586 patients aged 49-64, PIMs prevalence by PROMPT in patients with 0-4, 5-9, and ≥10 medications was 14.0%, 62.2%, and 86.1%, respectively, and by Beers Laroche was 14.3%, 63.4%, and 85.7%, respectively. In the 1 249 119 patients aged 65-70, PIMs prevalence by Beers Laroche was 14.8%, 59.9%, and 83.3%, and by PROMPT was 13.9%, 57.4%, and 82.0%, respectively. Meaningful differences in prevalence were shown by sex and race/ethnicity according to both set of criteria (e.g. PROMPT in patients with 5-9 medications: 66.1% women vs. 59.3% men; standardized-mean-differences [SMD] = 0.14; 61.7% of White vs. 54.5% of non-White; SMD = 0.15). The most common PIMs were digestive, analgesic, antidiabetic, and psychotropic medications. CONCLUSION: Prevalence of PIMs was high and increased with polypharmacy. Beers Laroche and PROMPT provided similar estimations inside and outside their target age, suggesting that PIMs are common among those with polypharmacy regardless of age.

Chronic polypharmacy at all age: A population-based drug utilization study.

Polypharmacy is a growing concern often described only in older people by cumulating all drugs taken. We aimed to describe chronic polypharmacy in France, regardless of age. A cross-sectional descriptive study was performed using the 1/97th representative sample of the French health insurance nationwide database (EGB). All subjects alive on January 1, 2015, and covered by the French healthcare insurance were included, and their information collected until December 31, 2015, or date of death. Drug exposures were estimated from drug dispensing dates and treatment durations. Chronic uses of drug were defined as drugs used daily for more than 6 months. Chronic polypharmacy corresponded to the exposure to five chronic uses of drug or more. In 2015, information of 584 862 subjects was collected (mean age: 42.2 years). Prevalence of chronic polypharmacy was 5.6% and incidence 1.1%. Prevalence of chronic polypharmacy increased noticeably from 0.2% for subjects aged 18 to 40 years to a maximum of 29.2% for subjects aged 80 to 90 years and then decreased to 23.6% for subjects aged 90 years and more. Lipid-modifying agents were the most frequent drugs involved in chronic polypharmacy (10% of exposure). According to age, the most important differences between the younger and older people were found for cardiovascular drugs (43.5% vs. 45.7% of exposure, respectively) and nervous system drugs (13.7% vs. 11.5% of exposure, respectively). This population-based study showed increasing of chronic polypharmacy and evolution of chronic drug patterns with age.

Polypharmacy: A general review of definitions, descriptions and determinants.

Polypharmacy is considered as the administration of many drugs. It is a major public health concern, which is growing worldwide. The identification of polypharmacy relies on drug count on a given time window. Polypharmacy exists if this count exceeds a predefined threshold. Although there is no consensus among scientists, five is the most frequently used number. Depending on the time-windows, polypharmacy can be qualified as simultaneous, cumulative, or continuous. Drugs can be selected according to the duration or the recurrence of their use thereby introducing the concept of chronic polypharmacy. This general review aimed to compile data from the literature regarding descriptions and determinants of polypharmacy, according to used definitions and studied populations. The prevalence of polypharmacy varied according to the definition used (from 4% to 57%). It was high in elderly people but was also non negligible in younger subjects such as middle aged. Cardiovascular, digestive and metabolism drugs were among the most frequent drugs involved in polypharmacy. The determinants of polypharmacy included factors linked to the patient (sociodemographic parameters such as age, sex, income, and place of residence, ethnicity, behaviour), factors linked to the disease (certain diseases such as cardiovascular or metabolic disease, multiple comorbidity status), as well as factors linked to the healthcare system or to the physician. Finally, to date, little data is available regarding polypharmacy appropriateness, although these data are needed to have clinically important information beyond a quantitative estimation. Further research is warranted to fill this gap.

The Burden of Potentially Inappropriate Medications in Chronic Polypharmacy.

We aimed to describe the burden represented by potentially inappropriate medications (PIMs) in chronic polypharmacy in France. We conducted a nationwide cross-sectional study using data from the French National Insurance databases. The study period was from 1 January 2016 to 31 December 2016. Chronic drug use was defined as uninterrupted daily use lasting ≥6 months. Chronic polypharmacy was defined as the chronic use of ≥5 medications, and chronic hyperpolypharmacy as the chronic use of ≥10 medications. For individuals aged ≥65 (older adults), PIMs were defined according to the Beers and Laroche lists, and for individuals aged 45-64 years (middle-aged) PIMs were defined according to the PROMPT (Prescribing Optimally in Middle-aged People's Treatments) list. Among individuals with chronic polypharmacy, 4009 (46.2%) middle-aged and 18,036 (64.8%) older adults had at least one chronic PIM. Among individuals with chronic hyperpolypharmacy, these figures were, respectively, 570 (75.0%) and 2544 (88.7%). The most frequent chronic PIM were proton pump inhibitors (43.4% of older adults with chronic polypharmacy), short-acting benzodiazepines (older adults: 13.7%; middle-aged: 16.1%), hypnotics (6.1%; 7.4%), and long-acting sulfonylureas (3.9%; 12.3%). The burden of chronic PIM appeared to be very high in our study, concerning almost half of middle-aged adults and two-thirds of older adults with chronic polypharmacy. Deprescribing interventions in polypharmacy should primarily target proton pump inhibitors and hypnotics.

Anticholinergic burden in middle-aged women and recurrent falls in later life: findings from the Aberdeen prospective osteoporosis screening study (APOSS).

BACKGROUND: Anticholinergic burden (ACB) is a recognised risk factor for falls in older people; however, whether ACB in middle age predicts falls in later life is unknown. METHODS: We examined this association in the middle-aged women of the Aberdeen Prospective Osteoporosis Screening Study (APOSS). ACB was calculated at the second health visit (1997-1999, study baseline) using the Anticholinergic Cognitive Burden Scale. Outcomes were incidence of 1 fall and recurrent falls (⩾2 falls) during the 12 months prior to follow up 2007-2011. Multinomial logistic regression analyses adjusted for potential confounders including demographics, comorbidities and falls history. RESULTS: A total of 2125 women {mean age (standard deviation [SD]): 54.7 (2.2) years at baseline and 66.0 (2.2) years at follow up} were included. Prevalence of baseline ACB score of 0, 1 and ⩾2 was 87.1%, 7.3% and 5.6%, respectively. Compared with no ACB, ACB ⩾2 was associated with recurrent falls in the previous 12 months [adjusted odds ratio (OR): 2.34, 95% confidence interval (CI): 1.31, 4.19] at an average of 11 years after initial exposure. No such association was found for an ACB score of 1. CONCLUSIONS: These findings highlight the potential negative effects of anticholinergic medications in middle age. While cautious use of anticholinergic medications is advisable, further longitudinal research should be conducted to confirm these findings before any specific clinical recommendations can be made.

A high anticholinergic burden is associated with a history of falls in the previous year in middle-aged women: findings from the Aberdeen Prospective Osteoporosis Screening Study.

PURPOSE: To examine the cross-sectional association between anticholinergic medication burden (ACB) and a history of falls, bone mineral density, and low trauma fractures in middle-aged women aged under 65 years from the Aberdeen Prospective Osteoporosis Screening Study. METHODS: ACB (0 = none, 1 = possible, ≥2 = definite) was calculated from medication use for 3883 Caucasian women [mean age (SD) = 54.3 (2.3) years] attending the second Aberdeen Prospective Osteoporosis Screening Study visit (1997-2000). Outcomes were examined using logistic regression. Model adjustments were selected a priori based on expert opinion. RESULTS: Of 3883 participants, 3293 scored ACB = 0, 328 scored ACB = 1, and 262 scored ACB ≥2. High ACB burden (≥2) was associated with increased odds (ACB = 0 reference) for falls (fully adjusted odds ratio [95% confidence intervals] = 1.81 [1.25-2.62]; P = 0.002) and having low bone mineral density (lowest quintile-20%) at Ward's triangle (3.22 [1.30-7.99]; P = 0.01). A history of falls over the year prior to the study visit in participants with ACB score ≥2 was 32 per 100. For ACB categories 1 and 0, a history of falls per 100 was 21 and 22, respectively. CONCLUSIONS: The risk of falling associated with ACB observed in older age may also extend to middle-aged women.