Polypharmacy and mortality association by chronic kidney disease status: The REasons for Geographic And Racial Differences in Stroke Study.
ABSTRACT: Many Americans take multiple medications simultaneously (polypharmacy). Polypharmacy's effects on mortality are uncertain. We endeavored to assess the association between polypharmacy and mortality in a large U.S. cohort and examine potential effect modification by chronic kidney disease (CKD) status. The REasons for Geographic And Racial Differences in Stroke cohort data (n = 29 627, comprised of U.S. black and white adults) were used. During a baseline home visit, pill bottle inspections ascertained medications used in the previous 2 weeks. Polypharmacy status (major [≥8 ingredients], minor [6-7 ingredients], and none [0-5 ingredients]) was determined by counting the total number of generic ingredients. Cox models (time-on-study and age-time-scale methods) assessed the association between polypharmacy and mortality. Alternative models examined confounding by indication and possible effect modification by CKD. Over 4.9 years median follow-up, 2538 deaths were observed. Major polypharmacy was associated with increased mortality in all models, with hazard ratios and 95% confidence intervals ranging from 1.22 (1.07-1.40) to 2.35 (2.15-2.56), with weaker associations in more adjusted models. Minor polypharmacy was associated with mortality in some, but not all, models. The polypharmacy-mortality association did not differ by CKD status. While residual confounding by indication cannot be excluded, in this large American cohort, major polypharmacy was consistently associated with mortality.
Project description:Medications can have unintended effects. High medication use populations may benefit from increased regimen oversight. Limited knowledge exists concerning racial and regional polypharmacy variation. We estimated total medication distributions (excluding supplements) of American black and white adults and assessed racial and regional polypharmacy variation.REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort data (n = 30,239 U.S. blacks and whites aged ?45 years) were analyzed. Home pill bottle inspections assessed the last two weeks' medications. Polypharmacy (?8 medications) was determined by summing prescription and/or over-the-counter ingredients. Population-weighted logistic regression assessed polypharmacy's association with census region, race, and sex.The mean ingredient number was 4.12 (standard error = 0.039), with 15.7% of REGARDS using 8 ingredients or more. In crude comparisons, women used more medications than men, and blacks and whites reported similar mean ingredients. A cross-sectional, logistic model adjusting for demographics, socioeconomics, and comorbidities showed increased polypharmacy prevalence in whites versus blacks (OR [95% CI]: 0.63, [0.55-0.72]), women (1.94 [1.68-2.23]), and Southerners (broadly Southeasterners and Texans; 1.48 [1.17-1.87]) versus Northeasterners (broadly New England and upper Mid-Atlantic). Possible limitations include polypharmacy misclassification and model misspecification.Polypharmacy is common. Race and geography are associated with polypharmacy variation. Further study of underlying factors explaining these differences is warranted.
Project description:BACKGROUND:Chronic kidney disease (CKD) afflicts many older adults and increases the risk for medication-related adverse events. OBJECTIVE:The aim of this study was to assess the prevalence and associated morbidity and mortality of polypharmacy (use of several medications concurrently), and potentially inappropriate medication (PIM) use in older adults, looking for differences by CKD status. METHODS:We quantified medication and PIM use (from Beers criteria, the Screening Tool of Older People's Prescriptions, and Micromedex®) by level of estimated glomerular filtration rate (eGFR) for participants aged 65 years or older attending a baseline study visit in the Atherosclerosis Risk in Communities study (n =6392). We used zero-inflated negative binomial and Cox proportional hazards regressions to assess the relationship between baseline polypharmacy, PIM use, and subsequent hospitalization and death. RESULTS:Mean age at baseline was 76 (± 5) years, 59% were female, and 29% had CKD (eGFR < 60 ml/min/1.73 m2). Overall, participants reported 6.1 (± 3.5) medications and 2.3 (± 2.2) vitamins/supplements; 16% reported ≥ 10 medications; 31% reported a PIM based on their age. On average, participants with CKD reported more medications. A PIM based on kidney function was used by 36% of those with eGFR < 30 ml/min/1.73 m2. Over a median of 2.6 years, more concurrent medications were associated with higher risk of hospitalization and death, but PIM use was not. While those with CKD had higher absolute risks, there was no difference in the relative risks associated with greater numbers of medications by CKD status. CONCLUSION:Polypharmacy and PIM use were common, with greater numbers of medications associated with higher risk of hospitalization and death; relative risks were similar for those with and without CKD.
Project description:<h4>Background</h4>Polypharmacy, often defined as the concomitant use of ≥ 5 medications, has been identified as a significant global public health threat. Aging and multimorbidity are key drivers of polypharmacy and have been linked to a broad range of adverse health outcomes and mortality. Patients with chronic kidney disease (CKD) are particularly at high risk of polypharmacy and use of potentially inappropriate medications given the numerous risk factors and complications associated with CKD. The aim of this systematic review will be to assess the prevalence of polypharmacy among adult patients with CKD, and the potential association between polypharmacy and adverse health outcomes within this population.<h4>Methods/design</h4>We will search empirical databases such as MEDLINE, Embase, Cochrane Library, CINAHL, Web of Science, and PsycINFO and grey literature from inception onwards (with no language restrictions) for observational studies (e.g., cross-sectional or cohort studies) reporting the prevalence of polypharmacy in adult patients with CKD (all stages including dialysis). Two reviewers will independently screen all citations, full-text articles, and extract data. Potential conflicts will be resolved through discussion. The study methodological quality will be appraised using an appropriate tool. The primary outcome will be the prevalence of polypharmacy. Secondary outcomes will include any adverse health outcomes (e.g., worsening kidney function) in association with polypharmacy. If appropriate, we will conduct random effects meta-analysis of observational data to summarize the pooled prevalence of polypharmacy and the associations between polypharmacy and adverse outcomes. Statistical heterogeneity will be estimated using Cochran's Q and I<sup>2</sup> index. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g., sex, kidney replacement therapy, multimorbidity).<h4>Discussion</h4>Given that polypharmacy is a major and a growing public health issue, our findings will highlight the prevalence of polypharmacy, hazards associated with it, and medication thresholds associated with adverse outcomes in patients with CKD. Our study will also draw attention to the prognostic importance of improving medication practices as a key priority area to help minimize the use of inappropriate medications in patients with CKD.<h4>Systematic review registration</h4>PROSPERO registration number: [ CRD42020206514 ].
Project description:<h4>Background</h4>In geriatric oncology, polypharmacy is often assessed during a comprehensive geriatric assessment. Previous studies about its association with survival among patients with colorectal cancer (CRC) were inconclusive and had high risk for indication bias.<h4>Patients and methods</h4>A cohort study was conducted with 3,239 patients with CRC, aged ≥65 years, who were recruited in Germany between 2003 and 2016, while being hospitalized for CRC surgery. We defined polypharmacy as the concurrent use of five or more drugs, and excessive polypharmacy (EPP) as concurrent use of eight or more drugs. Cox proportional hazards regression models were performed to assess the associations of polypharmacy with 5-year overall (OS), CRC-specific (CSS), and non-cancer-specific survival (NCS) with rigorous adjustment for morbidity to minimize indication bias (e.g., for cancer stage, functional status, and 13 common diseases/conditions).<h4>Results</h4>The prevalence of polypharmacy was 54.7% and that of EPP was 24.2%. During up to 5 years of follow-up, 1,070 participants died, among whom 615 died of CRC and 296 died of other causes than cancer. EPP was statistically significantly associated with poorer up-to-5-year OS (hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.02-1.47) and CSS (HR, 1.31; 95% CI, 1.03-1.68). HR point estimate for NCS was higher than 1 (1.22) but not statistically significant.<h4>Conclusion</h4>Polypharmacy was very common and EPP was a weak risk factor for mortality in this large cohort of older patients with CRC. Clinical trials are needed to address the causality of this relationship because older patients with CRC might benefit from deprescribing drugs without an indication.<h4>Implications for practice</h4>The results of this study support the hypothesis that excessive polypharmacy, defined as use of eight or more concurrently used active substances, has a negative impact on the prognosis of older patients with colorectal cancer (CRC). This study suggests to oncologists that performing a medication review for older patients with CRC with eight drugs or more is indicated (especially when a broader comprehensive geriatric assessment is being performed). Such a medication review should not only focus on reducing the number of medications (by deprescribing drugs without an indication) but also check the appropriateness of indicated drugs for older patients with cancer.
Project description:<h4>Background/objectives</h4>With an aging population suffering from increased prevalence of chronic conditions in the United States (U.S.), a large portion of these patients are on multiple medications. High-risk medications can increase the risk for drug-drug interactions and medication nonadherence. This study aims to describe the prevalence of polypharmacy and high-risk medication prescribing in U.S. physician offices.<h4>Methods</h4>This was a cross-sectional study of the Centers for Disease Control and Prevention's National Ambulatory Medical Care Survey from 2009 to 2016. All patients over 65 years old were included. Polypharmacy was categorized as no polypharmacy (< 2 medications), minor polypharmacy (2-3 medications), moderate polypharmacy (4-5 medications), and major polypharmacy (>5 medications). Medications were further categorized into high-risk medication categories (anticholinergics, cardiovascular agents, central nervous system (CNS) medications, pain medications, and other). Comparisons between the degrees of polypharmacy were performed utilizing chi-square or Wilcoxon rank-sum tests with JMP Pro 14® (SAS Institute, Cary, NC).<h4>Results</h4>Over 2 billion patient visits were included. Overall, Polypharmacy was common (65.1%): minor polypharmacy (16.2%), moderate polypharmacy (12.1%), and major polypharmacy (36.8%). Patients with major polypharmacy were older compared to those with moderate or minor polypharmacy (75 vs. 73 years, respectively) and were most frequently prescribed pain medications (477.3 per 1,000 total visits). NSAIDs were the most frequently prescribed, with 232.4 per 1,000 total visits resulting in one high-risk NSAID prescription, while 21.9 per 1,000 total visits resulted in two or more high-risk NSAIDs.<h4>Conclusion</h4>Most patients over 65 years experienced some degree of polypharmacy, with many experiencing major polypharmacy. This indicates an increased need for expanded pharmacist roles through medication therapy management and safety monitoring in this patient population.
Project description:BACKGROUND:Quality of life (QoL) refers to the physical, psychological, social and medical aspects of life that are influenced by health status and function. The purpose of this study was to measure the self-perceived health status among the elderly population across Europe in different stages of Chronic Kidney Disease (CKD). METHODS:Our series consisted of 2255 community-dwelling older adults enrolled in the Screening for Chronic Kidney Disease (CKD) among Older People across Europe (SCOPE) study. All patients underwent a comprehensive geriatric assessment (CGA), including included demographics, clinical and physical assessment, number of medications taken, family arrangement, Geriatric Depression Scale (GDS), Cumulative Illness Rating Scale, History of falls, Lower urinary tract symptoms, and Short Physical Performance Battery (SPPB). Estimated glomerular filtration rate (eGFR) was calculated by Berlin Initiative Study (BIS) equation. Quality of life was assessed by Euro Qol questionnaire (Euro-Qol 5D) and EQ-Visual Analogue Scale (EQ-VAS). The association between CKD (eGFR?<?60, <?45?ml or?<?30?ml/min/1.73m2) and low EQoL-VAS was investigated by multivariable logistic regression models. RESULTS:CKD was found to be significantly associated with low EQoL-VAS in crude analysis (OR?=?1.47, 95%CI?=?1.16-1.85 for eGFR<?60; OR?=?1.38, 95%CI?=?1.08-1.77 for eGFR<?45; OR?=?1.57, 95%CI?=?1.01-2.44). Such association was no longer significant only when adjusting for SPPB (OR?=?1.20, 95%CI?=?0.93-1.56 for eGFR<?60; OR?=?0.87, 95%CI?=?0.64-1.18 for eGFR<?45; OR?=?0.84, 95%CI?=?0.50-1.42), CIRS and polypharmacy (OR?=?1.16, 95%CI?=?0.90-1.50 for eGFR<?60; OR?=?0.86, 95%CI?=?0.64-1.16 for eGFR<?45; OR?=?1.11, 95%CI?=?0.69-1.80) or diabetes, hypertension and chronic obstructive pulmonary disease (OR?=?1.28, 95%CI?=?0.99-1.64 for eGFR<?60; OR?=?1.16, 95%CI?=?0.88-1.52 for eGFR<?45; OR?=?1.47, 95%CI?=?0.92-2.34). The association between CKD and low EQoL-VAS was confirmed in all remaining multivariable models. CONCLUSIONS:CKD may significantly affect QoL in community-dwelling older adults. Physical performance, polypharmacy, diabetes, hypertension and COPD may affect such association, which suggests that the impact of CKD on QoL is likely multifactorial and partly mediated by co-occurrent conditions/risk factors.
Project description:Aging, multimorbidity, and polypharmacy are associated with medication-related problems (MRPs). This study aimed to assess the association that multimorbidity and mortality have with MRPs in older people over time. We followed multimorbid, older (65-99 years) people in Catalonia from 2012 to 2016, using longitudinal data and Cox models to estimate adjusted hazard ratios (HR). We reviewed electronic health records to collect explanatory variables and MRPs (duplicate therapy, drug-drug interactions, potentially inappropriate medications (PIM), and contraindicated drugs in chronic kidney disease (CKD) or liver disease). There were 723,016 people (median age: 74 years; 58.9% women) who completed follow-up. We observed a significant (<i>p</i> < 0.001) increase in the proportion with at least one MRP (2012: 66.9% to 2016: 75.5%); contraindicated drugs in CKD (11.1 to 18.5%) and liver disease (3.9 to 5.3%); and PIMs (62.5 to 71.1%), especially drugs increasing fall risk (67.5%). People with ?10 diseases had more MRPs (in 2016: PIMs, 89.6%; contraindicated drugs in CKD, 34.4%; and in liver disease, 9.3%). All MRPs were independently associated with mortality, from duplicate therapy (HR 1.06; 95% confidence interval (CI) 1.04-1.08) to interactions (HR 1.60; 95% CI 1.54-1.66). Ensuring safe pharmacological treatment in elderly, multimorbid patient remains a challenge for healthcare systems.
Project description:<h4>Objectives</h4>Polypharmacy (≥5 concurrent medications) is common among older patients with cancer (48%-80%) and associated with increased frailty, morbidity, and mortality. This study examined the relationship between polypharmacy and inpatient hospitalization among older adults with cancer treated with intravenous (IV) chemotherapy.<h4>Materials and methods</h4>The main data source was the Surveillance, Epidemiology, and End Results-Medicare linked files. Patients (≥65 years) were included if they were diagnosed with prostate (n = 1430), breast (n = 5490), or lung cancer (n = 7309) in 1991-2013 and received IV chemotherapy in 2011-2014. The number of medications during the six-month window pre-IV chemotherapy initiation determined polypharmacy status. Negative binomial models were used to assess the association between polypharmacy and post-chemotherapy inpatient hospitalization. The results were presented as incidence rate ratios.<h4>Results</h4>We identified 13,959 patients with prostate, breast, or lung cancer treated with IV chemotherapy. The median number of prescription medications during the six-month window pre-IV chemotherapy initiation was high: ten among patients with prostate cancer, nine among patients with breast cancer, and eleven among patients with lung cancer. Compared to patients taking <5 prescriptions, post-chemotherapy hospitalization rate for patients with prostate cancer was 42%, 75%, and 114% higher among those taking 5-9, 10-14, and 15+ medications, respectively. Patients with breast and lung cancer demonstrated similar patterns.<h4>Conclusion</h4>This large population-based study found that polypharmacy during the six-month window pre-IV chemotherapy is highly predictive of post-chemotherapy inpatient hospitalization. Further studies are needed to evaluate whether medication management interventions can reduce post-chemotherapy inpatient hospitalization among older patients with cancer.
Project description:Background:Patients with chronic kidney disease (CKD) bear a substantial burden of comorbidities leading to the prescription of multiple drugs and a risk of polypharmacy. However, data on medication use in this population are scarce. Methods:A total of 5217 adults with an estimated glomerular filtration rate (eGFR) between 30 and 60?mL/min/1.73 m2 or an eGFR ?60?mL/min/1.73m2 and overt proteinuria (>500?mg/day) were studied. Self-reported data on current medication use were assessed at baseline (2010-12) and after 4?years of follow-up (FU). Prevalence and risk factors associated with polypharmacy (defined as the regular use of five or more drugs per day) as well as initiation or termination of polypharmacy were evaluated using multivariable logistic regression. Results:The prevalence of polypharmacy at baseline and FU was almost 80%, ranging from 62% in patients with CKD Stage G1 to 86% in those with CKD Stage G3b. The median number of different medications taken per day was eight (range 0-27). ?-blockers, angiotensin-converting enzyme inhibitors and statins were most frequently used. Increasing CKD G stage, age and body mass index, diabetes mellitus, cardiovascular disease and a history of smoking were significantly associated with both the prevalence of polypharmacy and its maintenance during FU. Diabetes mellitus was also significantly associated with the initiation of polypharmacy [odds ratio (OR) 2.46, (95% confidence interval 1.36-4.45); P?=?0.003]. Conclusion:Medication burden in CKD patients is high. Further research appears warranted to address the implications of polypharmacy, risks of drug interactions and strategies for risk reduction in this vulnerable patient population.
Project description:With the aim to expand the randomized controlled trial evidence of cinacalcet treatment to the unselected, general chronic kidney disease (CKD) population we analysed a large inception cohort of CKD patients in the region of Stockholm, Sweden 2006-2012 (both non-dialysis, dialysis and transplanted) with evidence of secondary hyperparathyroidism (SHPT). We used marginal structural models to account for both confounding by indication and time-dependent confounding. Over 37 months, 435/3,526 (12%) initiated cinacalcet de novo. Before cinacalcet initiation, parathyroid hormone (PTH) had increased progressively to a median of 636ng/L. After cinacalcet initiation, PTH declined, as did serum calcium and phosphate. In total, 42% of patients experienced a fatal/non-fatal cardiovascular event, 32% died and 9% had a new fracture. The unadjusted cardiovascular odds ratio (OR) associated with cinacalcet treatment was 1.01 (95% confidence interval: 0.83, 1.22). In the fully weighted model, the cardiovascular odds was lower in cinacalcet treated patients (OR 0.67: 0.48, 0.93). The adjusted ORs for all-cause mortality and for fractures were 0.79 (0.56, 1.11) and 1.08 (0.59, 1.98) respectively. Our study suggests cinacalcet treatment improves biochemical abnormalities in the wider CKD population, and adds real-world support that treating SHPT with cinacalcet may have beneficial effects on cardiovascular outcomes.