Impact of anticholinergic burden on emergency department visits among older adults in Korea: A national population cohort study

ObjectivesThis study aimed to evaluate the impact of high anticholinergic burden on overall emergency department (ED) visits and ED visits related to adverse effects of anticholinergic drugs among older adults.MethodsFor this retrospective cohort study, we used claims data from older adults with high representativeness. The average daily Anticholinergic Risk Scale (ARS) score was calculated based on the dosage, treatment duration, and potency of anticholinergic drugs during three months. A high-exposure group (ARS ≥ 2) and a non-exposure group were included in this analysis. The primary outcome was the first ED visit during the follow-up period. Anticholinergic ED visits were defined as ED visits with a main diagnosis of a fall, fracture, dizziness, delirium, constipation, or urinary retention.ResultsIn total, 118,750 subjects (43.6% male) were included in this study. The mean age was 75.4 ± 6.6 years. The adjusted hazard ratios (aHRs) for all-cause and anticholinergic ED visits among those with high ARS scores were 1.28 (95% CI: 1.20–1.36) and 1.55 (95% CI: 1.38–1.74), respectively. The high-exposure group was at higher risk than the non-exposure group for ED visits for falls or fractures (aHR: 1.31, 95% CI: 1.07–1.60), dizziness (aHR: 1.71, 95% CI: 1.36–2.14), delirium (aHR: 2.05, 95% CI: 1.13–3.73), constipation (aHR: 1.65, 95% CI: 1.35–2.02) and urinary retention (aHR: 1.66, 95% CI: 1.30–2.12).ConclusionsThis study demonstrated that a high anticholinergic burden in older adults increased the risk of all-cause ED visits, anticholinergic ED visits and specific-cause ED visits.     

Cognitive and other adverse effects of diphenhydramine use in hospitalized older patients

BACKGROUND: Diphenhydramine hydrochloride is a commonly prescribed medicine in hospitalized patients, but its adverse effects on older patients remain unclear. METHODS: We enrolled 426 hospitalized medical patients aged 70 years or older in a prospective cohort study in a university hospital. Measurements included baseline and daily assessments including Mini-Mental State Examination scores, Confusion Assessment Method ratings, direct observations for medical devices (urinary catheter or physical restraints), and blinded medical record extractions for diphenhydramine use. RESULTS: Of the 426 patients, 114 (27%) received diphenhydramine during hospitalization and shared similar baseline characteristics including age, sex, delirium risk, and Mini-Mental State Examination scores compared with nonexposed patients. The diphenhydramine-exposed group was at an increased risk for any delirium symptoms (relative risk [RR], 1.7; 95% confidence interval [CI], 1.3-2.3) and for individual delirium symptoms, including inattention (RR, 3.0; 95% CI, 1.5-5.9), disorganized speech (RR, 5.5; 95% CI, 1.0-29.8), and altered consciousness (RR, 3.1; 95% CI, 1.6-6.1). Exposed patients also had increased risk for urinary catheter placement (RR, 2.5; 95% CI, 1.0-6.0) and longer median length of stay (7 vs 6 days; P =.009). A dose-response relationship was demonstrated for most adverse outcomes. Overall, 24% of diphenhydramine doses were administered inappropriately. CONCLUSIONS: Diphenhydramine administration in older hospitalized patients is associated with an increased risk of cognitive decline and other adverse effects with a dose-response relationship. Careful review of its use is necessary in this vulnerable population.     

Mortality one-year postdischarge from a Veterans Affairs geriatric evaluation and management unit: assessing mortality risks.

OBJECTIVE: To assess at Geriatric Evaluation and Management Unit (GEM) admission factors that affect mortality 12-months postdischarge and to develop a preliminary risk scoring protocol to guide targeting of GEM care. SETTING: A 24 bed-GEM at a Veterans Affairs (VA) Medical Center. DESIGN: Relative risks (RR) were assessed using prospective data; a risk protocol from 1988-1989 data was tested on 1990-1991 patients. SUBJECTS: A total of 283 male patients, aged 60 to 102, discharged over 4 years. RESULTS: Age at GEM admission did not correlate with death (r = .14; P = .145), but did correlate with risk scores (r = .33, P < .001). The risk protocol had a sensitivity of .67 and specificity of 1.00. High and low risk patients had mortalities of 51% versus 20%, a Wilcoxon (Gehan) statistic of 15.22, df = 1, and P < .001. Differences in mortality ceased about 100 days postdischarge. Three univariate RR exceeded 1.00 at a 99% Confidence Interval (CI): IADL score (RR: 1.12; CI, 1.03-1.21); nursing acuity score (RR: 1.78; CI: 1.02-3.11); and a primary diagnosis of pneumonia/sepsis (RR: 3.95; CI, 1.60-9.78). Four RRs exceeded 1.00 at a 90% CI: dementia (RR: 1.78; CI, 1.02-3.09); transfer into the GEM from a medical service (RR: 1.47; CI, 1.02-2.12); deconditioning/functional decline (RR: 1.67; CI, 1.12-2.48); and use of a Foley catheter (RR: 2.22; CI, 1.11-4.45). Thirteen other potential risk factors were found in a multivariate analysis. CONCLUSIONS: The point estimates of risk factors may help clinicians target GEM care, but the development of a useable risk protocol requires additional work. Causal models may be needed to assess patient conditions related to successful treatment in GEMs.     

Skilled care requirements for elderly patients after coronary artery bypass grafting

OBJECTIVES: To examine the extent to which elderly individuals use various skilled care facilities after coronary artery bypass grafting (CABG). DESIGN: Retrospective cohort study. SETTING: State of Michigan from 1997 to 1998. PARTICIPANTS: Residents aged 65 and older enrolled in Medicare who underwent CABG. MEASUREMENTS: Cumulative incidence of admission within 100 days of hospital discharge, relative risk (RR) of admission, readmission or extended stay at a skilled care facility, and length of stay in a skilled care facility. RESULTS: Fifty percent of patients aged 80 and older used a skilled care facility after CABG, with most requiring admission to a skilled nursing facility (SNF) or readmission to an acute-care hospital within 100 days after discharge. Patients aged 80 and older had a significantly higher risk of admission to a SNF (adjusted RR=3.3, 95% confidence interval (CI)=2.8-4.0) than did those aged 65 to 69, as did patients aged 75 to 79 (adjusted RR=2.2, 95% CI=1.8-2.6) and those aged 70 to 74 (adjusted RR=1.5, 95% CI=1.3-1.8). The length of time spent in skilled care facilities significantly increased with age (mean days=13.3 for aged 65-69, 16.9 for 70-74, 19.6 for 75-79, and 22.9 for 80 and older; P<.001). CONCLUSION: Older patients are more likely to be admitted to a SNF, be readmitted to an acute-care hospital, and have longer institutional stays after CABG. When balancing the risks and benefits of CABG, physicians, patients, families, and policy-makers need to carefully consider the likelihood of follow-up institutional care in elderly patients.     

Primary care-based intervention to reduce at-risk drinking in older adults: a randomized controlled trial

Aims To examine whether a multi‐faceted intervention among older at‐risk drinking primary care patients reduced at‐risk drinking and alcohol consumption at 3 and 12 months. Design Randomized controlled trial. Setting Three primary care sites in southern California. Participants Six hundred and thirty‐one adults aged ≥ 55 years who were at‐risk drinkers identified by the Comorbidity Alcohol Risk Evaluation Tool (CARET) were assigned randomly between October 2004 and April 2007 during an office visit to receive a booklet on healthy behaviors or an intervention including a personalized report, booklet on alcohol and aging, drinking diary, advice from the primary care provider and telephone counseling from a health educator at 2, 4 and 8 weeks. Measurements The primary outcome was the proportion of participants meeting at‐risk criteria, and secondary outcomes were number of drinks in past 7 days, heavy drinking (four or more drinks in a day) in the past 7 days and risk score. Findings At 3 months, relative to controls, fewer intervention group participants were at‐risk drinkers [odds ratio (OR) 0.41; 95% confidence interval (CI) 0.22–0.75]; they reported drinking fewer drinks in the past 7 days [rate ratio (RR) 0.79; 95% CI 0.70–0.90], less heavy drinking (OR 0.46; 95% CI 0.22–0.99) and had lower risk scores (RR 0.77 95% CI 0.63–0.94). At 12 months, only the difference in number of drinks remained statistically significant (RR 0.87; 95% CI 0.76–0.99). Conclusions A multi‐faceted intervention among older at‐risk drinkers in primary care does not reduce the proportions of at‐risk or heavy drinkers, but does reduce amount of drinking at 12 months.     

The relationship between number of medications and weight loss or impaired balance in older adults

OBJECTIVES: To examine the relationship between cumulative medication exposure and risk of two common manifestations of adverse drug effects: weight loss and impaired balance. DESIGN: Cross-sectional and longitudinal cohort. SETTING: Urban Connecticut community. PARTICIPANTS: Eight hundred eighty-five community-dwelling residents aged 72 and older. MEASUREMENTS: Weight loss (> or =10 pounds) and balance, a composite of four balance measures. RESULTS: Participants took a mean+/-standard deviation of 2.2+/-1.9 medications (range 0-15). After adjustment for age, depressive symptoms, cognitive impairment, vision and hearing impairments, number of chronic diseases, and number of hospitalizations in the previous year, the adjusted odds ratio (OR) for weight loss was 1.48 (95% confidence interval (CI)=0.85-2.59) for those taking one to two medications, 1.96 (95% CI=1.08-3.54) for three to four medications, and 2.78 (95% CI=1.38-5.60) for five or more medications. For impaired balance, adjusted ORs were 1.44 (95% CI=0.94-2.19), 1.72 (95% CI=1.09-2.71), and 1.80 (95% CI=1.02-3.19), respectively. CONCLUSION: A greater number of medications were associated with increased risk of adverse drug outcomes, after extensive adjustment for chronic illness. Clinicians should consider the adverse effects of total drug use and not merely the benefits or risks of individual medications for specific diseases.     

Inhaled and nasal corticosteroid use and the risk of fracture

Studies of the risk of fracture associated with inhaled corticosteroids are inconclusive and are limited to short-term effects. We assessed whether long-term use increases this risk. We conducted a case control study nested within a population-based cohort of all Quebec elderly dispensed respiratory medications and followed for at least 4 years during 1988-2001. There were 9,624 new cases of fracture of the hip or upper extremities and 191,622 age-matched control subjects (mean age of 81 years). The rate of any such fracture for current inhaled corticosteroid use was not elevated (rate ratio [RR], 0.97; 95% confidence interval [CI], 0.92-1.03). For upper-extremity fracture, the rate increased by 12% (RR, 1.12; 95% CI, 1.04-1.19) with every 1,000-microg increase in the daily dose of inhaled corticosteroids, but not for hip fracture (RR, 0.97; 95% CI, 0.88-1.07). Among subjects followed for over 8 years, the rate of hip fracture was only elevated with daily doses of more than 2,000 microg of inhaled corticosteroids (RR, 1.61; 95% CI, 1.04-2.50). The rate was not elevated at any dose of nasal corticosteroids. In conclusion, the long-term use of inhaled and nasal corticosteroids at the usual recommended doses is not associated with a risk of fracture in older patients with respiratory disease.     

A Cohort Study of Anticholinergic Medication Burden and Incident Dementia and Stroke in Older Adults

BackgroundAnticholinergic medications may increase risk of dementia and stroke, but prospective studies in healthy older people are lacking.ObjectiveCompare risk of incident dementia and stroke by anticholinergic burden among initially healthy older people.DesignProspective cohort study.SettingPrimary care (Australia and USA).Participants19,114 community-dwelling participants recruited for the ASPREE trial, aged 70+ years (65+ if US minorities) without major cardiovascular disease, dementia diagnosis, or Modified Mini-Mental State Examination score below 78/100.MeasurementsBaseline anticholinergic exposure was calculated using the Anticholinergic Cognitive Burden (ACB) score. Dementia was adjudicated using Diagnostic and Statistical Manual of Mental Disorders volume IV criteria, and stroke using the World Health Organization definition.ResultsAt baseline, 15,000 participants (79%) had an ACB score of zero, 2930 (15%) a score of 1–2, and 1184 (6%) a score of ≥ 3 (indicating higher burden). After a median follow-up of 4.7 years and adjusting for baseline covariates, a baseline ACB score of ≥ 3 was associated with increased risk of ischemic stroke (adjusted HR 1.58, 95% CI 1.06, 2.35), or dementia (adjusted HR 1.36, 95% CI 1.01, 1.82), especially of mixed etiology (adjusted HR 1.53, 95% CI 1.06, 2.21). Results were similar for those exposed to moderate/highly anticholinergic medications.LimitationsResidual confounding and reverse causality are possible. Assessment of dose or duration was not possible.ConclusionsHigh anticholinergic burden in initially healthy older people was associated with increased risk of incident dementia and ischemic stroke. A vascular effect may underlie this association. These findings highlight the importance of minimizing anticholinergic exposure in healthy older people.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-020-06550-2.KEY WORDS: anticholinergic burden, dementia, stroke, potentially inappropriate medication     

Prospective cohort study of comprehensive prevention to gastric cancer

AIM: To evaluate the preliminary effects of comprehensive prevention of gastric cancer in Zhuanghe County epidemiologically. METHODS: Stratified sampling and cluster sampling were applied to define the intervention group and the control group. The prospective cohort study was used for evaluating the effect of preventing gastric cancer. The relative risk (RR) and attributable risk percent (AR %) of intervention on gastric cancer death were calculated. Potential years of life lost (PLYY) of the disease was analyzed, and the RR and AR % of PYLL were calculated. Survival analysis was applied among the screened patients. RESULTS: In the first 4 years after intervening, the relative risk (RR) of intervention on death was 0.5059 (95 % CI: 0.3462-0.7392, P<0.05) with significance statistically. AR % of the intervention on death was 49.41 %. The RR of intervention on cumulative PYLL was 0.6778 (95 % CI: 0.5604-0.8198, P<0.05) with statistic significance. AR % of the intervention on cumulative PYLL was 30.32 %. The four-year survival rate of the screened patients was 0.6751 (95 % CI: 0.5298-0.9047). CONCLUSION: The initiative intervention results showed that the intervention approach used in the trial was effective, it reduced mortality and increased survival rate, and alleviated the adverse effect of gastric cancer on the health and life of screened population.     

The role of physical proximity in nosocomial diarrhea.

To examine physical proximity as a risk factor for the nosocomial acquisition of Clostridium difficile-associated diarrhea (CDAD) and of antibiotic-associated diarrhea (AAD), we assessed a retrospective cohort of 2859 patients admitted to a community hospital from 1 March 1987 through 31 August 1987. Of these patients, 68 had nosocomial CDAD and 54 had nosocomial AAD. In multivariate analysis, physical proximity to a patient with CDAD (relative risk [RR], 1.86; 95% confidence interval [CI], 1.06-3.28), exposure to clindamycin (RR, 4.22; 95% CI, 2.11-8.45), and the number of antibiotics taken (RR, 1.49; 95% CI, 1.23-1.81) were significant. For patients with nosocomial AAD, exposure to a roommate with AAD (RR, 3.94; 95% CI, 1. 27-12.24), a stay in an intensive care unit or cardiac care unit (RR, 1.93; 95% CI, 1.05-3.53), and the number of antibiotics taken (RR, 2.01; 95% CI, 1.67-2.40) were significant risk factors. Physical proximity may be an independent risk factor for acquisition of nosocomial CDAD and AAD.     

Anti-rheumatic drug use and risk of hospitalization for congestive heart failure in rheumatoid arthritis

OBJECTIVE: To assess the risk of hospitalization for congestive heart failure (CHF) associated with the use of disease-modifying anti-rheumatic drugs (DMARDs) and other medications used in RA. METHODS: We used a case-control design nested within an administrative database cohort of patients with rheumatoid arthritis (RA) who were dispensed a DMARD between September 1998 and December 2001. Subjects identified with a prior history of CHF were excluded. For each hospitalized case of CHF identified during follow-up, 10 controls matched on age and time were randomly selected from the cohort. Conditional logistic regression was used to estimate the rate ratio (RR) of hospitalizations for CHF associated with the current use of specific drugs, adjusted for sex and co-morbidity. RESULTS: The cohort included 41 885 patients; 75% were women, with an average age at cohort entry of 51 yr. During follow-up, 520 hospitalizations for CHF occurred, for a rate of 10.1 per 1000 per year. The adjusted RR of CHF for current use of any DMARD was 0.7 (95% CI 0.6-0.9) relative to no current use. By DMARD category, there was evidence of a beneficial effect for both tumour necrosis factor-alpha antagonists (RR 0.5, 95% CI 0.2-0.9) and methotrexate monotherapy (RR 0.8, 95% CI 0.6-1.0). For non-DMARD medications, the rate of CHF was not clearly increased or decreased, except for COX-2 inhibitors. The data suggested an increased risk of CHF with rofecoxib (RR 1.3, 95% CI 1.0-3.1) and a decreased risk of CHF with celecoxib (RR 0.6, 95% CI 0.4, 1.0). CONCLUSIONS: The use of DMARDs was associated with a reduction in the risk of hospitalizations for CHF in this RA cohort. The increased risk with rofecoxib alongside a decreased risk with celecoxib suggests the absence of a class effect with respect to COX-II inhibitors for some types of cardiovascular morbidity.     

Adverse drug events resulting from patient errors in older adults

OBJECTIVES: To characterize the types of patient-related errors that lead to adverse drug events (ADEs) and identify patients at high risk of such errors. DESIGN: A subanalysis within a cohort study of Medicare enrollees. SETTING: A large multispecialty group practice. PARTICIPANTS: Thirty thousand Medicare enrollees followed over a 12-month period. MEASUREMENTS: Primary outcomes were ADEs, defined as injuries due to a medication, and potential ADEs, defined as medication errors with the potential to cause an injury. The subset of these events that were related to patient errors was identified. RESULTS: The majority of patient errors leading to adverse events (n=129) occurred in administering the medication (31.8%), modifying the medication regimen (41.9%), or not following clinical advice about medication use (21.7%). Patient-related errors most often involved hypoglycemic medications (28.7%), cardiovascular medications (21.7%), anticoagulants (18.6%), or diuretics (10.1%). Patients with medication errors did not differ from a comparison group in age or sex but were taking more regularly scheduled medications (compared with 0-2 medications, odds ratio (OR) for 3-4 medications=2.0, 95% confidence interval (CI)=0.9-4.2; OR for 5-6 medications=3.1, 95% CI=1.5-7.0; OR for >or=7 medications=3.3, 95% CI=1.5-7.0). The strongest association was with the Charlson Comorbidity Index (compared with a score of 0, OR for a score of 1-2=3.8, 95% CI=2.1-7.0; OR for a score of 3-4=8.6, 95% CI=4.3-17.0; OR for a score of >or=5=15.0, 95% CI=6.5-34.5). CONCLUSION: The medication regimens of older adults present a range of difficulties with the potential for harm. Strategies are needed that specifically address the management of complex drug regimens.     

Investigating the adverse respiratory effects of beta-blocker treatment: six years of prospective longitudinal data in a cohort with cardiac disease

Background: Globally, cardiovascular disease (CVD) is the leading cause of death. Beta‐blocker medications have well‐established survival benefit for myocardial infarction and heart failure. However, CVD frequently coexists with chronic obstructive airways disease (COPD), a disease in which beta‐blockers are traditionally avoided. Aim: We sought to investigate the adverse respiratory effects associated with long‐term beta‐blocker treatment in patients with cardiac disease, and presumed high risk of COPD. Methods: In this prospective cohort study, patients admitted with acute cardiac disease were recruited from the cardiology unit of a tertiary referral hospital. The treating cardiologist determined beta‐blocker treatment, independent of the study. Repeated measures of spirometry and respiratory symptom scores were assessed over 12 months. Respiratory exacerbations, cardiac events and survival were recorded over 6 years. Outcomes were compared according to beta‐blocker exposure. Results: Sixty‐four subjects participated, 30 of whom received beta‐blockers. Beta‐blockers did not adversely affect spirometry, respiratory symptoms or survival. However, considering two categories of respiratory exacerbations (symptom‐based vs treated), subjects taking beta‐blockers accumulated increased annual risk (relative risk (RR) 1.30, 95% confidence interval (CI) 1.11–1.53, P= 0.001 and RR 1.37, 95% CI 1.09–1.72, P= 0.008) and concluded with overall increased risk (RR 3.67, 95% CI 1.65–8.18, P= 0.001 and RR 4.03, 95% CI 1.26–12.9, P= 0.019), when compared with the group not taking beta‐blockers. Conclusion: Long‐term beta‐blocker treatment did not adversely affect lung function, respiratory symptom scores or survival, but was associated with increased risk of respiratory exacerbations.     

Blood transfusion, alcohol use, and anthropometric risk factors for rheumatoid arthritis in older women

OBJECTIVE: To evaluate whether blood transfusion, alcohol use, or anthropometric characteristics are risk factors for rheumatoid arthritis (RA) in older women. METHODS: These factors were evaluated in a prospective cohort study that was initiated in 1986, and included 31,336 women aged 55-69 years without a history of RA. Risk factor data were self-reported using a mailed questionnaire. Through 1997, 158 cases of RA meeting at least 4 of 7 American College of Rheumatology criteria were identified and validated by medical record review. The relative risk (RR) and 95% confidence interval (CI) were used as the measure of association, and were adjusted for the potential confounding effects of age, marital status, smoking history, age at menopause, and use of estrogen replacement therapy. RESULTS: History of blood transfusion was inversely associated with RA (multivariate RR = 0.72; 95% CI 0.48-1.08), and this association was stronger for rheumatoid factor (RF) positive disease (RR = 0.59; 95% CI 0.35-1.00). There were no associations for use of medications for hyper- or hypothyroidism or adult onset diabetes. Anthropometric factors (height, weight, body mass index, body fat distribution), leisure time physical activity, and alcohol use were not associated with risk of RA. CONCLUSION: A history of blood transfusion was inversely associated with RA, particularly RF positive RA. Anthropometric factors, physical activity, and alcohol use did not influence the risk of RA in this cohort of older women.     

Systematic review on the use of anticholinergic scales in poly pathological patients

PurposeAnticholinergic drugs may increase the risk of cognitive and functional disorders in older patients. There are anticholinergic scales on which said risk is estimated. The objectives of this study are: to identify the scales described in literature that are applicable to polypathological patients and analyze their clinical outcomes.Material and methodsA systematic review was performed. Data sources were MEDLINE, EMBASE and Web of Science which were consulted until August 2014. Inclusion criteria: (1) studies that specify the list of drugs, describe the methodology for their elaboration and how they calibrate the anticholinergic potential and (2) studies that use the scales identified as a tool to measure exposure to anticholinergic drugs in polypathological patients or those with similar characteristics. The main differences between the scales and main results on cognitive, functional and mortality status were collected.Results25 articles were included. 10 scales were identified. For their preparation, 8 were based on literature about drugs with anticholinergic activity and/or previously published scales as well as expert opinions. Exposure to anticholinergic drugs has been linked to cognitive disorders (basically measured with Anticholinergic Risk Scale (ARS), Anticholinergic Cognitive Burden Scale (ACB) and Drug Burden Index (DBI)) and functional scale (with ARS and DBI). However, there is no clear relationship with mortality. The Anticholinergic Drug Scale was the only one that obtained no association with any of the variables studied.ConclusionsThere is a great variety of scales published and applied to older patients. The clinical results are different depending on the scale used which is probably due to the different methodology in their elaboration.