Cumulative Anticholinergic Burden and its Predictors among Older Adults with Alzheimer's Disease Initiating Cholinesterase Inhibitors.

BACKGROUND: Cumulative anticholinergic burden refers to the cumulative effect of multiple medications with anticholinergic properties. However, concomitant use of cholinesterase inhibitors (ChEIs) and anticholinergic burden can nullify the benefit of the treatment and worsen Alzheimer's disease (AD). A literature gap exists regarding the extent of the cumulative anticholinergic burden and associated risk factors in AD. Therefore, this study evaluated the prevalence and predictors of cumulative anticholinergic burden among patients with AD initiating ChEIs. METHODS: A retrospective longitudinal cohort study was conducted using the Medicare claims data involving parts A, B, and D from 2013 to 2017. The study sample included older adults (65 years and older) diagnosed with AD and initiating ChEIs (donepezil, rivastigmine, or galantamine). The cumulative anticholinergic burden was calculated based on the Anticholinergic Cognitive Burden scale and patient-specific dosing using the defined daily dose over the 1 year follow-up period after ChEI initiation. Incremental anticholinergic burden levels were dichotomized into moderate-high (sum of standardized daily anticholinergic exposure over a year (TSDD) score ≥ 90) versus low-no (score 0-89). The Andersen Behavioral Model was used as the conceptual framework for selecting the predictors under the predisposing, enabling, and need categories. A multivariable logistic regression model was used to evaluate the predictors of high-moderate versus low-no cumulative anticholinergic burden. A multinomial logistic regression model was also used to determine the factors associated with patients having moderate and high burdens compared to low/no burdens. RESULTS: The study included 222,064 older adults with AD with incident ChEI use (mean age 82.24 ± 7.29, 68.9% females, 83.6% White). Overall, 80.48% had some anticholinergic burden during the follow-up, with 36.26% patients with moderate (TSDD scores 90-499), followed by 24.76% high (TSDD score > 500), and 19.46% with low (TSDD score 1-89) burden categories. Predisposing factors such as age; African American, Asian, or Hispanic race; and need factors included comorbidities such as dyslipidemia, syncope, delirium, fracture, pneumonia, epilepsy, and claims-based frailty index were less likely to be associated with the moderate-high anticholinergic burden. The factors that increased the odds of moderate-high burden were predisposing factors such as female sex; enabling factors such as dual eligibility and diagnosis year; and need factors such as baseline burden, behavioral and psychological symptoms of dementia, depression, insomnia, urinary incontinence, irritable bowel syndrome, anxiety, muscle spasm, gastroesophageal reflux disease, heart failure, and dysrhythmia. Most of these findings remained consistent with multinomial logistic regression.  CONCLUSION: Four out of five older adults with AD had some level of anticholinergic burden, with over 60% having moderate-high anticholinergic burden. Several predisposing, enabling, and need factors were associated with the cumulative anticholinergic burden. The study findings suggest a critical need to minimize the cumulative anticholinergic burden to improve AD care.

Risk of incident cardiovascular events with disease-modifying anti-rheumatic drugs among adults with rheumatoid arthritis: a nested case-control study.

OBJECTIVE: This study examined the risk of cardiovascular disease (CVD) associated with the disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA). METHOD: This nested case-control study used the MarketScan database (2012-2014), involving adult RA patients (aged ≥18 years) initiating either a conventional synthetic (cs) DMARD, biologic DMARD, or targeted synthetic (ts) DMARD between January 1, 2013 and December 31, 2014 (cohort entry) and had no CVD history. Cases were individuals with incident CVD identified using diagnosis codes or procedure codes from medical claims. For each case, 10 age- and sex-matched controls were selected using the incident density sampling with replacement. Prescriptions of DMARDs were measured 90 days before the event date. Conditional logistic regression examined the association of risk of CVD with DMARDs in combination treatment or individual use, with reference to methotrexate (MTX) monotherapy, adjusting for baseline confounders. Subgroup analyses were performed separately in DMARD combination therapy users or individual DMARD users, respectively. RESULTS: In total, 270 cases of incident CVD and 2700 controls were included (mean [standard deviation (SD)] age: 54 [1]; 75.6% women). The commonly prescribed DMARD therapies were csDMARD monotherapy (n = 795, 27.04%), followed by  tumor necrosis factor inhibitors (TNFi) monotherapy (n = 367, 12.48%), and TNFi in combination with MTX (n = 314, 10.68%). Compared with MTX monotherapy, overall use of DMARD agents was not associated with the differential risk of CVD, including various types of DMARD combination regimens. The findings were similar across subgroup analyses. CONCLUSIONS: The study found no differential risk of CVD with DMARDs in combination therapy or monotherapy compared to MTX monotherapy in patients with RA. Key Points • This study evaluated the risk of cardiovascular disease (CVD) associated with the disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA). • Findings suggest no differential CVD risk with DMARDs in combination with MTX or used individually compared with MTX monotherapy in patients with early RA. • Further efforts should focus on a better understanding of the mechanism of DMARD combination treatments with MTX in modifying CV risk.

Prevalence of Adult Type 2 Diabetes Mellitus and Related Complications in Alberta, Canada: A Retrospective, Observational Study Using Administrative Data.

OBJECTIVES: Type 2 diabetes mellitus (T2DM) is a prevalent chronic disease and a leading cause of morbidity/mortality in Canada. We evaluated the burden of T2DM in Alberta, Canada, by estimating the 5-year period prevalence of T2DM and rates of comorbidities and complications/conditions after T2DM. METHODS: We conducted a population-based, retrospective study linking administrative health databases. Individuals with T2DM (≥18 years of age) were identified between 2008-2009 and 2018-2019 using a published algorithm, with follow-up data to March 2020. The 5-year period prevalence was estimated for 2014-2015 to 2018-2019. Individuals with newly identified T2DM, ascertained between 2010-2011 and 2017-2018 with a lookback period between 2008-2009 and 2009-2010 and a minimum 1 year of follow-up data, were evaluated for subsequent cardiovascular, diabetic, renal, and other complication/condition frequencies (%) and rates (per 100 person-years). Complications/conditions were stratified by atherosclerotic cardiovascular disease (ASCVD) status at index and age. RESULTS: The 5-year period prevalence of T2DM was 11,051 per 100,000 persons, with the highest prevalence in men 65 to <75 years of age. There were 195,102 individuals included in the cohort (mean age 56.7±14.7 years). The most frequently reported complications/conditions (rates per 100 person-years) were acute infection (23.10, 95% confidence interval [CI] 23.00 to 23.30), hypertension (17.30, 95% CI 16.80 to 17.70), and dyslipidemia (12.20, 95% CI 11.90 to 12.40). Individuals who had an ASCVD event/procedure and those ≥75 years of age had higher rates of complications/conditions. CONCLUSIONS: We found that over half of the individuals had hypertension or infection after T2DM. Also, those with ASCVD had higher rates of complications/conditions. Strategies to mitigate complications/conditions after T2DM are required to reduce the burden of this disease on individuals and health-care systems.

Real-world Comparative Effectiveness of Methotrexate-based Combinations for Rheumatoid Arthritis: A Retrospective Cohort Study.

PURPOSE: Guidelines recommend using disease-modifying antirheumatic drugs (DMARDs) in combination with methotrexate (MTX) for patients with rheumatoid arthritis (RA) after monotherapy. Little is known about the real-world comparative effectiveness of these MTX-DMARD combinations. This study compared the effectiveness of various MTX-based DMARD combinations for patients with RA initiating MTX-DMARD combination therapy using administrative claims database. METHODS: This retrospective cohort study included adults (aged ≥18 years) with RA who initiated MTX combination treatment with conventional synthetic DMARDs (csDMARDs), tumor necrosis factor inhibitor (TNFi) biologic DMARDs (bDMARDs), non-TNFi bDMARDs, or targeted synthetic DMARDs (tsDMARDs) between July 1, 2012, and December 31, 2013 (index date), from the MarketScan Commercial Claims Data. Patients had continuous enrollment from the 6 months of preindex period until the 12 months of postindex period. The MTX-based DMARD combination therapy cohort was defined as ≥1 MTX prescription in the first 30 days from the index date and ≥14 days overlapping use of the prescription fills of the MTX and the index DMARD. Effectiveness was measured by using the claims algorithm (dosing, switching, addition, oral glucocorticoid use, or multiple glucocorticoid injection). Propensity score analysis with the inverse probability of treatment weighting (PS-IPTW), estimated by using the generalized boosted machine learning method, was used to balance the distribution of baseline variables between the combination groups. Multivariable logistic regression using PS-IPTW was conducted to compare the effectiveness of the combination groups. Sensitivity analysis evaluated the modified effectiveness algorithms or the time to the first treatment failure. FINDINGS: A total of 3174 adult patients with RA starting an MTX-DMARD combination therapy were identified (mean [SD] age, 50 [9] years), including 1568 (49%) initiating a csDMARD + MTX, 1343 (42%) initiating TNFi + MTX, and 240 (8%) initiating non-TNFi bDMARD + MTX, and 23 (1%) initiating tsDMARD + MTX. Owing to the small sample, the tsDMARD combination group was not included in the comparative analysis. Algorithm-based therapy effectiveness was found in 9.95% of the csDMARD + MTX, 20.48% of the TNFi + MTX, and 20.83% of the non-TNFi + MTX groups. PS-IPTW showed that the csDMARD combination is less effective (adjusted odds ratio, 0.422; 95% CI, 0.341-0.524) than the TNFi combination; however, the non-TNFi biologic combination had similar effectiveness (aOR, 1.063; 95% CI, 0.680-1.662) compared to the TNFi combination. Sensitivity analyses confirmed the main results. IMPLICATIONS: Among RA patients initiating MTX-DMARD combinations, both non-TNFi biologics and TNFi-based combinations with MTX were equally effective, but csDMARD + MTX was less effective than the TNFi plus MTX.

Factors influencing prescribing the first add-on disease-modifying antirheumatic drugs in patients initiating methotrexate for rheumatoid arthritis.

Background: Advances in Disease-Modifying Antirheumatic Drugs (DMARDs) have expanded the treatment landscape for Rheumatoid Arthritis (RA). Guidelines recommend adding either conventional synthetic (cs), biologic (b), or targeted synthetic (ts) DMARDs to methotrexate (MTX) for managing RA. Limited evidence exists regarding the factors that contribute to adding a DMARD agent to the MTX regimen. This study examined the factors associated with adding the first DMARD in RA patients initiating MTX. Methods: This retrospective cohort study utilized the MarketScan data (2012-2014) involving adults (aged ≥18) with RA initiating an MTX (index date) between Jul 1, 2012 and Dec 30, 2013, and with continuous enrollment for the 6-month pre-index period. The combination therapy users received the first treatment addition of DMARD starting from day 30 after the index MTX over one year period. The study focused on the addition of csDMARDs, Tumor Necrosis Factor Inhibitors (TNFi) bDMARDs, non-TNFi bDMARDs, or tsDMARDs. Baseline covariates were measured in the 6-month pre-index and grouped into predisposing, enabling, and need factors, as per the Andersen Behavior Model. Multivariable logistic regression examined the factors associated with the addition of TNFi compared to adding a csDMARD. An additional regression model evaluated the factors associated with adding any biologic (combining TNFi and non-TNFi biologics). Results: Among 8350 RA patients starting MTX, 31.92% (n = 2665) initiated any DMARD within the 1-year post-index period. Among RA patients initiating a DMARD prescription after starting MTX, 945 (11.32%) received combination therapy with treatment addition of a DMARD to MTX regimen; majority added TNFi (550, 58%), followed by csDMARD (352, 37%); non-TNF biologic (40, 4%), or tsDMARD (3, 0.3%). The tsDMARD group was limited and was not included for further analysis. The multivariable model found Preferred Provider Organization insurance coverage (odds ratio [OR], 1.43; 95% confidence interval (CI), 1.06-1.93), chronic pulmonary disease (OR, 1.98; 95% CI, 1.14-3.44), liver disease (OR, 5.24; 95% CI, 1.77-15.49), and Elixhauser score (OR, 0.91; 95% CI, 0.86-0.97) were significantly associated with the addition of TNF-α inhibitors. The separate multivariable model additionally found that patients from metropolitan areas (OR, 1.50; 95% CI, 1.04-2.16) were positively associated with adding any biological agent. Conclusions: TNFi are often added to MTX for managing RA. Enabling and need factors contribute to the prescribing of a TNFi add-on therapy in RA. Future research should examine the impact of these combination therapies on RA management.

The Bidirectional Association of Chronic Kidney Disease, Type 2 Diabetes, Atherosclerotic Cardiovascular Disease, and Heart Failure: The Cardio-Renal-Metabolic Syndrome.

Background: The cardiometabolic syndrome focuses on the association between type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD), whereas the cardiorenal syndrome focuses on the association between chronic kidney disease (CKD) and heart failure (HF). Consideration of these two syndromes as a single entity has not been well described. Methods: We used the electronic medical records of Kaiser Permanente Northwest to identify 387,985 members aged 18+ years with a serum creatinine measured from 2005 to 2017. If the estimated glomerular filtration rate was <60 mL/min per 1.73 m2, we required a second confirmatory measurement 3-12 months later. Patients were followed through 2019. We calculated the age- and gender-adjusted incidence and progression of CKD per 1000 person-years using generalized estimating equations. We used Cox proportional hazard models to assess the time-dependent effect of each condition on incidence of the other conditions. Results: CKD incidence rates were highest in patients with T2DM, ASCVD, and HF (27.0 per 1000 person-years [95% confidence interval (CI) 24.8-29.4] vs. 5.9 [5.8-6.0] in patients with none of these conditions). Similar results were obtained for CKD progression (309.0, 283.9-336.4 for all three conditions vs. 147.9, 143.3-152.4 for no condition). In time-dependent models, all three conditions were independently associated with CKD incidence, being highest for HF (hazard ratio 2.14, 95% CI 2.07-2.21). All relationships between CKD, T2DM, ASCVD, and HF were significant and bidirectional. Conclusions: The presence of CKD, T2DM, HF, and ASCVD each conveys risk on the others. A cardiometabolic renal syndrome comprising these conditions may be an important disease entity that requires a comprehensive treatment approach.

Risk of Serious Adverse Events Associated With Individual Cholinesterase Inhibitors Use in Older Adults With Dementia: A Population-Based Cohort Study.

BACKGROUND AND OBJECTIVE: Cholinesterase inhibitors (ChEIs) are used as first-line pharmacotherapy to manage dementia. However, there are limited data regarding their relative safety. This study evaluated the risk of serious adverse events (SAEs) associated with individual ChEIs in older adults with dementia and also examined sex-based and dose-based effects on this risk. METHODS: This was a retrospective cohort study using 2013-2015 US Medicare claims data involving Parts A, B, and D. Patients aged ≥ 65 years with a dementia diagnosis and incident use of the ChEIs, namely donepezil, galantamine, or rivastigmine, were included. The primary outcome of interest was SAEs defined as emergency department visits, inpatient hospitalizations, or death within 6 months of ChEI initiation. Multivariable Cox proportional hazards regression with propensity score (PS) as a covariate and inverse probability of treatment weighting generated using generalized boosted models was used to assess the risk of SAEs across individual ChEIs. RESULTS: The study included 767,684 older adults with dementia who were incident new users of ChEIs (donepezil 79.42%, rivastigmine 17.67%, galantamine 2.91%). SAEs were observed in 15.5% of the cohort within 6 months of ChEI prescription. Cox regression model with PS as covariate found that patients prescribed rivastigmine (adjusted hazard ratio [aHR] 1.12; 95% CI 1.03-1.33) and galantamine (aHR 1.51; 95% CI 1.24-1.84) were at increased risk of SAEs compared with patients on donepezil. Stratified analyses revealed that rivastigmine was associated with an 18% increased risk for SAEs in females (aHR 1.18; 95% CI 1.06-1.31), and galantamine was associated with a 71% increased risk in males (aHR 1.71; 95% CI 1.17-2.51) compared with donepezil. High and recommended index doses of rivastigmine and galantamine were associated with an increased risk of SAEs compared with donepezil. The findings were consistent in sensitivity analyses. CONCLUSION: The study found that the risk of SAEs varied across individual ChEIs, with sex and dose moderating these effects. Therefore, these moderating effects should be carefully considered in personalizing dementia care.

Risk of overactive bladder associated with cholinesterase inhibitors in dementia.

BACKGROUND: Although cholinesterase inhibitors (ChEIs) are the primary treatment for dementia, they are associated with overactive bladder (OAB), necessitating antimuscarinic use. Limited data exist regarding the risk of OAB across individual ChEIs in dementia. This study evaluated the risk of OAB associated with individual ChEIs in older adults with dementia. METHODS: This was a new user retrospective cohort study using Medicare claims data involving Parts A, B, and D claims dataset from 2013 to 2015. The study included older adults (aged 65 and older) with a diagnosis of dementia using donepezil, galantamine, or rivastigmine. New ChEI claims were identified with a 6-month baseline washout period. Patients with OAB diagnosis or any antimuscarinic or mirabegron use in the baseline period were excluded. The primary outcome of interest was OAB diagnosis or prescription of antimuscarinics or mirabegron within 6 months of ChEI initiation. Multivariable cox proportional hazards regression with propensity scores (PS) as covariates and inverse probability of treatment weighting generated using generalized boosted models was used to assess the risk of OAB among donepezil, galantamine, and rivastigmine users. RESULTS: The study included 524,975 older adults with dementia who were incident users of ChEIs (donepezil 80.72%, rivastigmine 16.41%, galantamine 2.87%). Overall, OAB diagnosis/antimuscarinic/mirabegron prescription was observed in 5.07% of the cohort within 6 months of ChEIs prescription. The Cox regression model with PS as covariate approach found that donepezil use increased the risk of OAB compared to rivastigmine (aHR, 1.13; 95% CI, 1.08-1.28; p < 0.0001). However, there was no differential risk of OAB between galantamine and rivastigmine. The findings were consistent with the generalized boosted models. CONCLUSIONS: The study found that the risk of OAB varies across individual ChEIs with an increased risk of OAB with donepezil compared to rivastigmine. The study findings suggest the need to understand and manage medication-related morbidity in older adults with dementia.

The Costs and Healthcare Resource Utilization Associated with Anticholinergic Burden in Long-Stay Nursing Home Residents with Overactive Bladder in the US.

BACKGROUND: Overactive bladder (OAB) is a prevalent condition commonly treated with anticholinergic medications. The extent to which anticholinergic burden is associated with costs and healthcare resource use (HCRU) in the long-stay nursing home (LSNH) setting is currently unknown. OBJECTIVES: This research evaluated the impact of anticholinergic burden on HCRU and related costs among LSNH residents with OAB. METHODS: This was a cohort study based on 2013-2015 Minimum Data Set-linked Medicare claims data involving LSNH residents aged ≥ 65 years with OAB and having Parts A, B and D coverage 6 months pre- and ≥ 12 months post-nursing home admission date (index date). Cumulative anticholinergic burden was determined using the Anticholinergic Cognitive Burden scale and defined daily dose. Direct medical costs related to HCRU were examined. HCRU included inpatient, outpatient, emergency room (ER), and physician office visits. Costs and HCRU associated with levels of anticholinergic burden were evaluated using generalized linear models. RESULTS: A total of 123,308 LSNH residents with OAB were included in this study. Most residents (87.2%) had some level (12.8%, none; 18.0%, low; 41.9%, moderate; and 27.3%, high) of cumulative anticholinergic burden. Results indicate that all types of resource utilization were higher among those with any level of anticholinergic burden than those with no burden. The outpatient, ER, and physician costs tended to be higher with increasing anticholinergic burden. CONCLUSIONS: Costs and HCRU patterns reflected increasing trends with anticholinergic burden. Targeted efforts towards reducing anticholinergic burden among LSNH residents with OAB may result in decreases in costs and HCRU.

Antimuscarinic Cascade Across Individual Cholinesterase Inhibitors in Older Adults with Dementia.

BACKGROUND: Acetylcholinesterase inhibitors (AChEIs) have been associated with an increased risk of starting antimuscarinic treatment to treat overactive bladder (OAB)-an example of a prescribing cascade. Limited comparative data exist regarding the prescribing cascade of antimuscarinics across individual AChEIs in older adults with dementia. OBJECTIVE: This study examined the association between individual AChEI use and antimuscarinic cascade in older adults with dementia. METHODS: We conducted a new user retrospective cohort study from January 2005 to December 2018 using data from the TriNetX electronic medical record database, a federated electronic medical records network in the US. The cohort included patients 65 years or older with a diagnosis of dementia using AChEIs (donepezil, galantamine, or rivastigmine). Individual AChEIs were identified with index dates from 1 January 2006 to 31 June 2018, with a 1-year washout period. The study excluded patients with any antimuscarinic use and OAB diagnosis 1 year before the AChEI index date. The primary outcome of interest was the prescription of antimuscarinics within 6 months of the AChEI index date. A Cox proportional hazard model was used to assess the association between individual incident AChEI use and antimuscarinic prescribing cascade after controlling for several covariates. RESULTS: The study included 47,059 older adults with dementia who were incident users of AChEIs. Most of these patients were initiated with donepezil (83.1%), followed by rivastigmine (12.3%) and galantamine (4.6%). Overall, 8.16% of the study cohort had incident OAB diagnosis or antimuscarinic prescription. Antimuscarinics were initiated by 1725 (3.7%) older adults with dementia within 6 months of AChEI prescription, and cascade varied widely across individual agents-donepezil (3.9%), rivastigmine (2.6%), and galantamine (2.9%). Cox proportional hazard analyses revealed that donepezil users had an increased risk of receiving antimuscarinics (adjusted hazard ratio 1.55, 95% confidence interval 1.31-1.83) compared with rivastigmine. The findings were consistent in sensitivity analyses. CONCLUSION: This study found that donepezil use is more likely to lead to antimuscarinic cascade than rivastigmine. Future studies are needed to determine the potential consequences of this cascade in dementia.

Application of machine learning in predicting hospital readmissions: a scoping review of the literature.

BACKGROUND: Advances in machine learning (ML) provide great opportunities in the prediction of hospital readmission. This review synthesizes the literature on ML methods and their performance for predicting hospital readmission in the US. METHODS: This review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews (PRISMA-ScR) Statement. The extraction of items was also guided by the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS). Electronic databases PUBMED, MEDLINE, and EMBASE were systematically searched from January 1, 2015, through December 10, 2019. The articles were imported into COVIDENCE online software for title/abstract screening and full-text eligibility. Observational studies using ML techniques for hospital readmissions among US patients were eligible for inclusion. Articles without a full text available in the English language were excluded. A qualitative synthesis included study characteristics, ML algorithms utilized, and model validation, and quantitative analysis assessed model performance. Model performances in terms of Area Under the Curve (AUC) were analyzed using R software. Quality in Prognosis Studies (QUIPS) tool was used to assess the quality of the reviewed studies. RESULTS: Of 522 citations reviewed, 43 studies met the inclusion criteria. A majority of the studies used electronic health records (24, 56%), followed by population-based data sources (15, 35%) and administrative claims data (4, 9%). The most common algorithms were tree-based methods (23, 53%), neural network (NN) (14, 33%), regularized logistic regression (12, 28%), and support vector machine (SVM) (10, 23%). Most of these studies (37, 85%) were of high quality. A majority of these studies (28, 65%) reported ML algorithms with an AUC above 0.70. There was a range of variability within AUC reported by these studies with a median of 0.68 (IQR: 0.64-0.76; range: 0.50-0.90). CONCLUSIONS: The ML algorithms involving tree-based methods, NN, regularized logistic regression, and SVM are commonly used to predict hospital readmission in the US. Further research is needed to compare the performance of ML algorithms for hospital readmission prediction.

Prevalence and Factors Associated with Cumulative Anticholinergic Burden Among Older Long-Stay Nursing Home Residents with Overactive Bladder.

BACKGROUND: Overactive bladder (OAB), the primary cause of urinary incontinence in nursing homes, is commonly treated with anticholinergic medications; however, the elderly population is vulnerable to the adverse effects associated with anticholinergic burden. Given the relatively high prevalence of OAB among nursing home residents, it is important to understand the magnitude of anticholinergic burden in this population. OBJECTIVES: The objectives of this study were to (1) examine the prevalence of cumulative anticholinergic burden among long-stay nursing home (LSNH) residents with OAB; and (2) identify the factors associated with varying levels of cumulative anticholinergic burden. METHODS: This was a retrospective, cohort study using Minimum Data Set-linked Medicare claims data. Anticholinergic burden was determined based on the Anticholinergic Cognitive Burden scale and patient-specific dosing using defined daily dose. The Andersen Behavioral Model framework was used to identify the predisposing, enabling, and need factors associated with levels of anticholinergic burden. Multivariable logistic regression models were developed to determine the factors associated with levels of anticholinergic burden. RESULTS: A total of 123,308 LSNH residents with OAB were identified; 87.2% had some degree of anticholinergic burden and 27.3% had high cumulative burden. Multiple factors were associated with higher levels of burden, including younger age, female sex, and non-Hispanic White ethnicity (predisposing factors); dual eligibility, Southern geographic region, and rural residence (enabling factors); and a number of comorbidities and concomitant medications (need factors). CONCLUSIONS: This study revealed a high level of anticholinergic burden among LSNH residents. Multiple factors were associated with a high level of burden. There is a need to optimize the use of anticholinergics due to their significant safety concerns in the LSNH setting.

Opioid Prescribing Among Outpatients with Rheumatoid Arthritis.

STUDY OBJECTIVES: To examine the outpatient opioid prescribing practices and the factors associated with opioid prescriptions in patient visits with rheumatoid arthritis (RA). DESIGN: This cross-sectional study used the 2011-2016 National Ambulatory Medical Care Survey. Descriptive weighted analyses were used to examine the trends in opioid prescribing practices for RA. Multivariable logistic regression was used to examine the factors associated with opioid prescriptions among RA visits. SUBJECTS: Adult patients (>18 years of age) with a primary diagnosis of RA based on the International Classification of Diseases. RESULTS: According to the national surveys, an average of 4.45 (95% confidence interval [CI], 2.30-6.60) million office visits were made annually for RA. Approximately 24.28% of these visits involved opioid prescriptions. The RA visits involving opioid prescriptions increased from 1.43 million in 2011-2012 to 3.69 million in 2015-2016 (P < .0001). Being in the age group of 50-64 years (odds ratio [OR] = 3.40; 95% CI, 1.29-9.00), being Hispanic or Latino (OR = 2.92, 95% CI, 1.10-7.74), visiting primary physician (OR = 4.67; 95% CI, 1.86-11.75), prescribing of muscle relaxants (OR = 64.32; 95% CI, 9.71-426.09), acetaminophen (OR = 93.40; 95% CI, 26.19-333.04), antidepressants (OR = 6.10; 95% CI, 2.63-14.14), and glucocorticoids (OR = 3.20; 95% CI, 1.61-6.38), were associated with an increased likelihood of receiving opioid prescriptions in RA. CONCLUSIONS: One in four adult RA visits resulted in opioid prescriptions, and the opioid visits more than doubled during the study period. Several patient and provider factors were associated with the opioid prescribing among RA visits. Understanding these prescribing practices can help to devise strategies for safe opioid prescribing practices in RA.

Anticholinergic medications and risk of dementia in older adults: Where are we now?

INTRODUCTION: Anticholinergic medications are effective for a wide variety of indications, but are associated with significant central adverse effects, especially cognitive decline and dementia in older adults. AREAS COVERED: We conducted a review of relevant literature in the past decade to address anticholinergic scales and evidence of anticholinergic-related dementia/cognitive decline in older adults. We discussed various anticholinergic scales used to classify anticholinergic medications. The review focused on the evidence from previous reviews and individual studies evaluating the anticholinergic-related risk of developing cognitive decline/dementia. This review also discussed clinical and methodological issues of studies along with recommendations for practice and research. EXPERT OPINION: The review demonstrates moderate to strong risk of dementia with anticholinergic use in multiple studies involving older adults, irrespective of the study design, analytical approach, anticholinergic exposure and outcome definition. This risk is particularly significant with the cumulative burden and high-level anticholinergics. There also exists a dose-response relationship between anticholinergic use and increased risk for dementia. Therefore, anticholinergic agents can be considered as a modifiable risk factor for dementia and cognitive decline in older adults. Based on the current evidence, regular assessment and optimization of anticholinergic burden prior to prescribing these medications can minimize anticholinergic-related morbidity in older adults.

Anticholinergic burden and risk of cognitive impairment in elderly nursing home residents with depression.

BACKGROUND: Although the adverse cognitive effects of anticholinergic medications in the elderly are well-documented, little is known regarding the cognitive impact of anticholinergics among nursing home residents with depression. OBJECTIVE: This study examined the risk of mild-to-moderate cognitive impairment due to anticholinergic burden among elderly nursing home residents with depression. METHODS: A population-based nested case-control study was conducted using Minimum Data Set (MDS)-linked Medicare data where the base cohort included patients ≥ 65 years with depression who had intact cognition (MDS Cognition score of 0 or 1) and no dementia. Cases were identified as those who had mild-to-moderate cognition (MDS Cognition score of 2-4). Each case was matched on age and sex to one control using incidence density sampling. The study evaluated cumulative anticholinergic burden (defined as score of 3 or more) within 30, 60 and 90 days preceding the event date based on the Anticholinergic Drug Scale (ADS). Conditional logistic regression model stratified on matched case-control sets was performed to evalaute cognitive impairment due to cumulative anticholinergic burden after controlling for other risk factors. RESULTS: The study sample included 3707 cases with mild-to-moderate cognition and 3707 matched controls with intact cognition. Bivariate analysis showed significant association between cumulative anticholinergic exposure and cognitive impairment (Odds Ratio [OR], 1.15; 95% Confidence Interval [CI],1.04-1.30); after controlling for potential risk factors, cumulative anticholinergic exposure 30 days preceding the event was no longer associated with cognitive impairment, (aOR, 1.07; 95% CI, 0.95-1.21). However, the odds of cognitive impairment increased with cumulative anticholinergic exposure 60 days (aOR 1.16; 1.04-1.30) and 90 days (aOR 1.28; 1.14-1.44) before the event date. CONCLUSION: Cumulative anticholinergic use for prolonged exposure periods was associated with modestly increased risk of cognitive impairment in elderly residents with depression who had intact cognition. The findings suggest the need to be cautious when prescribing multiple anticholinergic drugs in residents, including those with intact cognition.

Understanding Patient Preferences and Unmet Needs in Non-alcoholic Steatohepatitis (NASH): Insights from a Qualitative Online Bulletin Board Study.

INTRODUCTION: The aim of this work was to understand how patients with non-alcoholic steatohepatitis (NASH) perceive their disease, unmet needs, and expectations regarding future treatment through online bulletin board (OBB) qualitative research. METHODS: OBB is an asynchronous online qualitative market research tool that provides an open forum for interactive discussion among participants. Patients with NASH were recruited via physician referral and completed a screener questionnaire to ensure their eligibility and willingness to participate. A trained moderator managed the discussion that allowed open answers and responses to other participants' posts. Patient responses were analyzed using a combination of different qualitative analytical tools. RESULTS: The OBB ran for 4 days and included 16 patients (n = 8, UK; n = 8, US) with NASH (fibrosis stages F1-F3) and comorbidities including diabetes/prediabetes (n = 9) and obesity (n = 12). The key insights were (1) patients with NASH have a poor understanding of the disease, its progression, and management-they feel a lack of adequate educational support from their physicians; (2) diagnosis of NASH is incidental in most cases, mainly because patients fail to spontaneously associate their signs or symptoms with their liver condition; (3) comorbidities (obesity and diabetes) are more concerning to patients than NASH; and (4) patients perceive that NASH impacts their social life and work performance in more advanced stages. CONCLUSIONS: This OBB provided valuable patient insights into NASH disease perception and management and revealed unmet need areas. In light of no approved therapies, these patient insights can inform early drug development strategies and stakeholder discussions on NASH. FUNDING: Novartis Pharma AG, Basel.

Risk of Mortality Associated with Anticholinergic Use in Elderly Nursing Home Residents with Depression.

BACKGROUND: Few studies have evaluated the association between anticholinergic use and mortality in elderly nursing home residents. OBJECTIVE: The aim of this study was to examine the risk of mortality associated with anticholinergic use among elderly nursing home residents with depression. METHODS: The study employed a population-based nested case-control design using 2007-2010 Minimum Data Set (MDS)-linked Medicare data from all states. The base cohort included Medicare beneficiaries aged ≥65 years, diagnosed with depression as of 2007, and with any MDS assessment in 2007. Cases were identified as patients who died anytime between January 1, 2008 and December 31, 2010. For each case, four age- and sex-matched controls were selected using incidence density sampling. Anticholinergic exposure was defined using the Anticholinergic Drug Scale (ADS). Prescription of clinically significant anticholinergic medications (ADS level 2/3) 60 days preceding the event date formed the primary exposure. Conditional logistic regression model stratified on matched case-control sets was performed to assess mortality risk, after controlling for other risk factors. RESULTS: The study sample included 44,948 cases who died and 179,792 matched controls. After adjusting for other risk factors, clinically significant anticholinergic use was associated with significant risk of death (odds ratio [OR] 1.31; 95% CI 1.28-1.34) compared with non-use. Level-specific analysis indicated high mortality risk with only markedly anticholinergic (ADS level 3) medication use (OR 1.46; 95% CI 1.42-1.51). CONCLUSIONS: Use of clinically significant anticholinergic medications was associated with a 31% increase in risk of mortality among elderly nursing home residents with depression. With increasing safety concerns, there is a significant need to optimize anticholinergic use in the vulnerable population.

Risk of Mortality in Elderly Nursing Home Patients with Depression Using Paroxetine.

OBJECTIVE: Among selective serotonin reuptake inhibitors (SSRIs), paroxetine is strongly anticholinergic and might lead to a higher risk of adverse outcomes such as mortality. This study examined the risk of mortality in depressed elderly nursing home patients using paroxetine and other SSRIs. METHODS: This study used 2007-2010 Minimum Data Set-linked Medicare data and a propensity score (PS)-matched retrospective cohort study design to achieve the study objective. New users of paroxetine and other SSRIs were followed until they reached the end of the follow-up period (1 year), switched to a different antidepressant class, used psychotherapy, or had a gap of more than 15 days in the use of index antidepressant class, whichever occurred earlier. A robust Cox proportional hazard (PH) model was used to evaluate the risk of mortality associated with the use of paroxetine and other SSRIs in depressed elderly nursing home residents. RESULTS: The PS matching yielded 4620 patients each in the two treatment groups. The unadjusted incidence of mortality was 269 (2.9%) for paroxetine and 288 (3.1%) for other SSRIs users in the matched cohort. The robust Cox PH model did not find any significant difference in the risk mortality between the two groups (hazard ratio 1.01; 95% confidence interval 0.86-1.19). CONCLUSIONS: This study did not find any significant difference in the risk of mortality between users of paroxetine and other SSRIs among elderly nursing home patients with depression. There is a need for further evaluation of other adverse effects of paroxetine due to its anticholinergic effects in the geriatric population.

Prevalence and predictors of non-evidence based proton pump inhibitor use among elderly nursing home residents in the US.

BACKGROUND: Proton pump inhibitors (PPIs) can lead to several adverse effects among the elderly, particularly when used inappropriately or in contrast to evidence suggested protocols. OBJECTIVE: The aim of this study was to examine the prevalence and predictors of non-evidence based PPI use in elderly nursing home residents. METHODS: A cross-sectional study was conducted using data from the 2004 National Nursing Home Survey (NNHS). The study sample included nursing home residents 65 years and older. Descriptive statistics were used to examine the prevalence of non-evidence based PPI use. Multivariable logistic regression was used to evaluate the patient and facility-level factors associated with non-evidence based PPI use among the elderly nursing home residents. RESULTS: A total of 355,600 elderly nursing home residents received at least one PPI for an overall prevalence of 26.99%. Among those elderly receiving PPIs, 48.59% of the use was not evidence based. Multivariable logistic regression revealed that residents with osteoporosis (Odds Ratio (OR): 0.55, 95% CI: 0.45-0.68), SSRI users (OR: 0.81, 95% CI: 0.68-0.97) and those residing in micropolitan area (OR: 0.79, 95% CI: 0.63-0.98) were negatively associated with prescription of PPIs without an indication. Patients with chronic cough (OR: 2.10, 95% CI: 1.12-3.96) and Medicare insurance (OR: 1.23, 95% CI: 1.01-1.50) were positively associated with prescription of PPIs without an indication. CONCLUSIONS: The current study found that almost half of the elderly nursing home residents used PPIs for non-evidence based indications. Given the safety concerns and high non-evidence based use of PPIs in nursing homes, there is an urgent need to optimize PPI use in the elderly.