Real-world Comorbidity Burden, Health Care Utilization, and Costs of Nonalcoholic Steatohepatitis Patients With Advanced Liver Diseases.

GOALS: This study evaluates the real-world comorbidity burden, health care resource utilization (HRU), and costs among nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) patients with advanced liver diseases [compensated cirrhosis (CC), decompensated cirrhosis (DCC), liver transplantation (LT), hepatocellular carcinoma (HCC)]. BACKGROUND: NAFLD/NASH is a leading cause of liver diseases. MATERIALS AND METHODS: Adult NAFLD/NASH patients were identified retrospectively from MarketScan Commercial claims (2006-2016). Following initial NAFLD/NASH diagnosis, advanced liver diseases were identified using the first diagnosis as their index date. Mean annual all-cause HRU and costs (2016 USD) were reported. Adjusted costs were estimated through generalized linear models. Cumulative costs were illustrated for patient subsets with variable follow-up for each stage. RESULTS: Within the database, 485,774 NAFLD/NASH patients met eligibility criteria. Of these, 93.4% (453,564) were NAFLD/NASH patients without advanced liver diseases, 1.6% (7665) with CC, 3.3% (15,833) with DCC, 0.1% (696) with LT, and 0.1% (428) with HCC. Comorbidity burden was high and increased as patients progressed through liver disease severity stages. Compared with NAFLD/NASH without advanced liver diseases (adjusted costs: $23,860), the annual cost of CC, DCC, LT, and HCC were 1.22, 5.64, 8.27, and 4.09 times higher [adjusted costs: $29,078, $134,448, $197,392, and $97,563 (P<0.0001)]. Inpatient admissions significantly drove increasing HRU. CONCLUSION: Study findings suggest the need for early identification and effective management of NAFLD/NASH patients to minimize comorbidity burden, HRU, and costs in the privately insured US population.

Comparative risk of adverse outcomes associated with nonselective and selective antimuscarinic medications in older adults with dementia and overactive bladder.

OBJECTIVE: The differential muscarinic receptor selectivity could cause selective antimuscarinics to offer advantages over nonselective agents with respect to adverse effects. The objective was to examine the comparative risk of falls/fractures and all-cause hospitalizations among older adults with dementia and overactive bladder (OAB) using nonselective and selective antimuscarinics METHODS/DESIGN: A retrospective cohort study design was conducted among older patients with dementia and OAB using incident antimuscarinics. The primary exposure was classified as nonselective (oxybutynin, tolterodine, trospium, and fesoterodine) and selective (solifenacin and darifenacin). Cox proportional-hazards regression using inverse probability of treatment weighting (IPTW) evaluated the risk of falls/fractures and all-cause hospitalizations within 6 months of nonselective and selective antimuscarinic use. RESULTS: The study cohort consisted of 13,896 (76.9%) nonselective and 4,179 (23.1%) selective antimuscarinic incident users. The unadjusted falls/fractures rate was 27.14% (3,772) for nonselective and 24.55% (1,026) for selective users (p-value< 0.01). The unadjusted all-cause hospitalizations rate was 24.14% (3,354) for nonselective and 21.58% (902) for selective users (p-value <0.01). The IPTW models did not find a significant difference in the risk of falls/fractures (Hazard Ratio [HR] 1.03; 95% Confidence Interval [CI] 0.99-1.07) and risk of all-cause hospitalizations (HR 1.04; 95% CI 0.99-1.08) between nonselective and selective antimuscarinics. Several sensitivity analyses corroborated the main findings. CONCLUSIONS: The study did not find a differential risk of falls/fractures and all-cause hospitalizations in older adults with dementia and OAB using nonselective and selective antimuscarinics. More research is needed to understand the role of pharmacodynamics and pharmacokinetics in the safety profile of antimuscarinics in dementia.

Risk of Mortality Associated with Non-selective Antimuscarinic medications in Older Adults with Dementia: a Retrospective Study.

BACKGROUND: Selective antimuscarinics may offer a favorable safety profile over non-selective antimuscarinics for the management of overactive bladder (OAB) in patients with dementia. OBJECTIVE: To test the hypothesis that non-selective antimuscarinics are associated with increased risk of mortality compared to selective antimuscarinics in older adults with dementia and OAB. DESIGN: Propensity score-matched retrospective new-user cohort design among Medicare beneficiaries in community settings. PATIENTS: Older adults with dementia and OAB with incident antimuscarinic use. MAIN MEASURES: The primary exposure was antimuscarinic medications classified as non-selective (oxybutynin, tolterodine, trospium, fesoterodine) and selective (solifenacin, darifenacin) agents. All-cause mortality within 180 days of incident antimuscarinic use formed the outcome measure. New users of non-selective and selective antimuscarinics were matched on propensity scores using the Greedy 5 → 1 matching technique. Cox proportional-hazards model stratified on matched pairs was used to evaluate the risk of mortality associated with the use of non-selective versus selective antimuscarinics in the sample. KEY RESULTS: The study identified 16,955 (77.6%) non-selective antimuscarinic users and 4893 (22.4%) selective antimuscarinic users. Propensity score matching yielded 4862 patients in each group. The unadjusted mortality rate at 180 days was 2.6% (126) for non-selective and 1.6% (78) for selective antimuscarinic users in the matched cohort (p value < 0.01). The Cox model stratified on matched pairs found 50% higher risk of 180-day mortality with non-selective antimuscarinics as compared to selective ones (hazard ratio (HR) 1.50; 95% confidence interval (CI) 1.04-2.16). The study findings remained consistent across multiple sensitivity analyses. CONCLUSIONS: Use of non-selective antimuscarinics was associated with a 50% increase in mortality risk among older adults with dementia and OAB. Given the safety concerns regarding non-selective antimuscarinic agents, there is a significant need to optimize their use in the management of OAB for older patients with dementia.

Evaluation of Neuromuscular Blockade Reversal on Postoperative Mechanical Ventilation Time in a Cardiovascular Surgery Population.

OBJECTIVE: To report on postoperative outcomes related to the administration of neostigmine for reversal of nondepolarizing neuromuscular blocking agents in cardiovascular surgery patients, with a specific focus on the duration of postoperative mechanical ventilation as the primary endpoint. DESIGN: A retrospective cohort study design was followed to achieve the study objectives. SETTING: This was a single-center, chart review study conducted at a large academic medical center of adult patients post-cardiovascular surgery. PARTICIPANTS: Patients were included if they had received a bolus dose of perioperative nondepolarizing neuromuscular blocking agent and underwent one of the targeted cardiovascular surgeries. INTERVENTIONS: Final analysis comprised of 175 patients, 95 of whom received neostigmine and 80 who did not receive neostigmine. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was the duration of postoperative mechanical ventilation. When controlling for all covariates, neostigmine use was associated with a 0.34-hour reduction (∼20.4 min) in duration of mechanical ventilation (parameter estimate: 0.66, 95% confidence interval 0.49-0.89; p = 0.0071). More patients who received neostigmine met the early extubation benchmark of less than 6 hours (55 v 34 patients; p = 0.04). Finally, neostigmine use was not found to be associated with increased risk of respiratory complications or postoperative nausea and/or vomiting. CONCLUSIONS: The use of neostigmine was found to have a protective effect on the duration of postoperative mechanical ventilation without increasing the risk of adverse complications.

Utilization of agents to prevent skeletal-related events among patients with multiple myeloma: analysis of real-world data.

PURPOSE: This study examined real-world utilization patterns of bone-targeted agents (BTA) in patients with multiple myeloma (MM). METHODS: In this retrospective cohort study, adults with an MM diagnosis recorded in 2012-2014 were identified from electronic health records in the Oncology Services Comprehensive Electronic Records (OSCER) database. Patients received zoledronic acid (ZA) or pamidronate (PA) on/after first MM diagnosis recorded in the study period, had no BTA use in prior 6 months, and were followed through earliest of May 31, 2015 or last clinic visit. Patients with any solid tumor diagnosis were excluded. Time to BTA initiation, compliance (≥ 12 administrations in a year), switching, and non-persistence (switch or ≥ 90-day gap in therapy) were described by agent and follow-up period. RESULTS: Among 9,617 patients with MM, 3,735 (38.8%) received a BTA. Most patients (90.9%) received ZA, with first BTA use generally seen within 3 months of first observed MM diagnosis (ZA 76.1%, PA 75.1%). A minority of ZA (27.4%) and PA (23.0%) patients were compliant in Year 1, with lower compliance in Year 2 (19.8% and 15.6%, respectively). The median time to non-persistence was 16.2 (95% confidence interval [CI] 15.4-17.4) months for ZA and 13.8 (95% CI 11.5-15.4) months for PA. Persistence was 86% at 6 months and 34% at 24 months for ZA, and 77% and 30% for PA, respectively. CONCLUSIONS: These results highlight the possibility of suboptimal prevention of skeletal-related events due to non-compliant dosing and non-persistence after patients initiate BTA therapy.

Longitudinal patterns of bone-targeted agent use among patients with solid tumors and bone metastases in the United States.

PURPOSE: This study examined real-world long-term use of guideline-recommended bone targeted agents (BTA) among patients with metastatic solid tumors. METHODS: Adults with a solid tumor diagnosis followed by a bone metastasis diagnosis in 2012-2014 were identified from electronic medical records in the Oncology Services Comprehensive Electronic Records (OSCER) database. Patients initiated zoledronic acid (ZA) or denosumab on or after the bone metastasis diagnosis and were followed through last clinic visit by 30 June 2015. We describe time to BTA initiation, compliance (≥12 administrations in a year), switching, and non-persistence (switch or ≥90 day gap in therapy), by agent and follow-up period. RESULTS: The majority of the 14,881 study patients (50% female, 65% age ≥65 years) had breast (33%), prostate (26%), or lung (26%) tumors. Half of all patients initiated on each agent, with denosumab initiations exceeding ZA initiations in 2014. Most (91% denosumab, 93% ZA) initiations occurred within 3 months of bone metastasis diagnosis. At 1, 2, and 3 years post-initiation, denosumab patients were less likely to switch agents (4, 3, and 1% versus 14, 12, and 11%) and more likely to be compliant (50, 37, and 31% versus 41, 26, and 6%). Median time to non-persistence was 25.9 months for denosumab and 17.2 months for ZA, p < 0.0001. CONCLUSIONS: This is the first study reporting long-term treatment patterns for the two primary BTAs used in the USA. The greater compliance and longer persistence observed among denosumab patients may improve treatment effectiveness achieved in the real-world setting.

Potentially inappropriate anticholinergic medication use in older adults with dementia.

OBJECTIVE: To examine the prevalence and predictors of potentially inappropriate anticholinergic medication use in older adults with dementia. DESIGN: A cross-sectional study. SETTING: United States, 2009-2010. PARTICIPANTS: Medical Expenditure Panel Survey household component participants aged 65 years or older identified as having dementia and using potentially inappropriate anticholinergic medication. MAIN OUTCOME MEASURES: Prevalence and predictors of potentially inappropriate anticholinergic medication use as per the updated 2012 American Geriatrics Society Beers criteria. RESULTS: A total of 3.78 million older adult patients (95% confidence interval [CI] 3.17 million to 4.38 million) were identified as having dementia, for an overall prevalence of 4.81%. Of those patients, an estimated 1.02 million (95% CI 0.70 million to 1.30 million) were reported to use potentially inappropriate anticholinergic medications, for an overall prevalence of 26.95% (95% CI 20.10% to 33.79%). The most frequently prescribed drugs were oxybutynin, solifenacin, paroxetine, tolterodine, promethazine, and cyclobenzaprine. Multivariable logistic analysis revealed that those patients with the need characteristics of self-reported anxiety, mood disorders, and "fair/poor" general health status had increased odds of potentially inappropriate anticholinergic use, while patients with the predisposing characteristic of being aged 75-84 years had decreased odds of potentially inappropriate anticholinergic use. CONCLUSION: More than one in four older adults with dementia were found to use potentially inappropriate anticholinergics. Given the adverse cognitive effects of these medications, there is a strong need to monitor and optimize their use in older adult patients with dementia.

Cost-effectiveness of switching from tenofovir disoproxil fumarate to tenofovir alafenamide versus entecavir for chronic hepatitis B patients in Greece.

Aim: This study assessed the clinical impact and cost-effectiveness of switching from tenofovir disoproxil fumarate (TDF) to either tenofovir alafenamide (TAF) or entecavir (ETV) in a Greek chronic hepatitis B (CHB) population. Patients & methods: A Markov model from the perspective of a third-party payer in Greece quantified the health and economic benefits of switching from TDF to either TAF or ETV over a lifetime horizon. Results: Over a lifetime, patients who switch from TDF to TAF versus patients who switch from TDF to ETV had an overall lower incidence of compensated cirrhosis (0.4% lower), decompensated cirrhosis (0.04% lower) and hepatocellular carcinoma (0.25% lower). Chronic kidney disease and end-stage renal disease were also lower in patients who switch to TAF; major osteoporotic fractures were similar for both groups. While total costs were higher for switching from TDF to TAF versus TDF to ETV due to the higher cost of TAF, switching from TDF to TAF versus ETV was cost effective with an incremental cost-effectiveness ratio of €17,113 per quality-adjusted life year. Conclusion: Switching from TDF to TAF in patients living with CHB is a cost effective strategy to reduce adverse liver disease outcomes, while improving bone- and renal-related safety outcomes.

Long-term health and economic benefits of switching to tenofovir alafenamide versus continuing on entecavir in chronic hepatitis B patients with low-level viremia in Saudi Arabia.

BACKGROUND: Despite the success of current treatments, many chronic hepatitis B (CHB) patients still live with low-level viremia [LLV] resulting in liver disease progression. This study evaluated the long-term health and economic impact of switching to tenofovir alafenamide (TAF) from entecavir (ETV) in Saudi Arabia (SA) in chronic hepatitis B (CHB) LLV patients. METHODS: A hybrid decision tree Markov state-transition model was developed to simulate a cohort of patients with CHB LLV treated with ETV and switched to TAF over a lifetime horizon in SA. While on treatment, patients either achieved complete virologic response (CVR) or maintained LLV. CVR patients experienced slower progression to advanced liver disease stages as compared to LLV patients. Demographic data, transition probabilities, treatment efficacy, health state costs, and utilities were sourced from published literature. Treatment costs were sourced from publicly available databases. RESULTS: Base case analysis found that over a lifetime horizon, switching to TAF versus remaining on ETV increased the proportion of patients achieving CVR (76% versus 14%, respectively). Switching to TAF versus remaining on ETV resulted in a reduction in cases of compensated cirrhosis (-52%), decompensated cirrhosis (-5%), hepatocellular carcinoma (-22%), liver transplants (-12%), and a 37% reduction in liver-related deaths. Switching to TAF was cost-effective with an incremental cost-effectiveness ratio of $57,222, assuming a willingness-to-pay threshold of three times gross national income per capita [$65,790/QALY]. CONCLUSIONS: This model found that switching to TAF versus remaining on ETV in SA CHB LLV patients substantially reduced long-term CHB-related morbidity and mortality and was a cost-effective treatment strategy.

Antimuscarinic use among older adults with dementia and overactive bladder: a Medicare beneficiaries study.

OBJECTIVES: This study examined the incidence and predictors of antimuscarinic medication use including non-selective antimuscarinics among older adults with dementia and overactive bladder (OAB). METHODS: The study used a new-user cohort design involving older adults (≥65 years) with dementia and OAB based on 2013-2015 Medicare data. Antimuscarinics included non-selective (oxybutynin, tolterodine, trospium, fesoterodine) and selective (solifenacin, darifenacin) medications. Descriptive statistics and multivariable logistic regression models were used to determine the incidence and predictors of new antimuscarinic use including non-selective antimuscarinics, respectively. RESULTS: Of the 3.38 million Medicare beneficiaries with dementia, over one million (1.05) had OAB (31.03%). Of those, 287,612 (27.39%) were reported as prevalent antimuscarinics users. After applying continuous eligibility criteria, 21,848 (10.34%) incident antimuscarinic users were identified (77.6% non-selective; 22.4% selective). Most frequently reported antimuscarinics were oxybutynin (56.3%) and solifenacin (21.4%). Multivariable analysis revealed that patients ≥75 years, of black race, and those with schizophrenia, epilepsy, delirium, and Elixhauser's score were less likely to initiate antimuscarinics. Women, those with abnormal involuntary movements, bipolar disorder, gastroesophageal reflux disease, insomnia, irritable bowel syndrome, muscle spasm/low back pain, neuropathic pain, benign prostatic hyperplasia, falls/fractures, myasthenia gravis, narrow-angle glaucoma, Parkinson's disease, syncope, urinary tract infection and vulvovaginitis were more likely to initiate antimuscarinics. Further, patients with muscle spasms/low back pain, benign prostatic hyperplasia and those taking higher level anticholinergics had lower odds of receiving non-selective antimuscarinics, whereas white patients, black patients and those with schizophrenia and delirium were more likely to receive them. CONCLUSIONS: Nearly one-third of dementia patients had OAB and over one-fourth of them used antimuscarinics. Majority of the incident users were prescribed non-selective antimuscarinics with several demographic and clinical factors contributing to their use. Given the high prevalence of OAB among dementia patients, there is a need to optimize their antimuscarinic use, considering their vulnerability for anticholinergic adverse effects.

Healthcare resource utilization and costs among nonalcoholic fatty liver disease patients in Germany.

BACKGROUND: Patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are associated with progression to advanced liver diseases that include compensated cirrhosis, decompensated cirrhosis, liver transplantation, and hepatocellular carcinoma (HCC). This study characterized comorbidities, healthcare resource utilization (HRU), and associated costs among NAFLD patients in Germany. METHODS: German healthcare claims data between 2011 and 2016 were analyzed retrospectively. Adult patients diagnosed with NAFLD and/or NASH were categorized as NAFLD, NAFLD non-progressors, compensated cirrhosis, decompensated cirrhosis, liver transplant, or HCC. Within each stage, annual all-cause HRU and costs were measured during the pre- and post-index periods. RESULTS: Among 4,580,434 patients in the database, proportion of NAFLD was 4.7% (n=215,655). Of them, 36.8% were non-progressors, 0.2% compensated cirrhosis, 9.6% decompensated cirrhosis, 0.0005% liver transplant, and 0.2% HCC. Comorbidity rates were significantly higher in compensated cirrhosis, decompensated cirrhosis, and HCC compared with non-progressors (52.07%, 56.46%, 57.58% vs. 27.49% for cardiovascular disease; 77.13%, 76.61%, 83.47% vs. 54.89% for hypertension; 47.20%, 53.81%, 52.89% vs. 35.21% for hyperlipidemia; 49.88%, 36.67%, 48.21% vs. 20.38% for type 2 diabetes mellitus). The mean annual numbers of post-index outpatient visits and inpatient hospitalizations were significantly higher in patients with advanced liver diseases versus non-progressors. Mean annual costs were significantly higher among patients with advanced liver diseases (compensated cirrhosis, €10,291; decompensated cirrhosis, €22,561; liver transplant, €34,089; HCC, €35,910) than non-progressors (€3,818, P<0.001, except liver transplant cohort). This trend remained consistent after adjusting for baseline demographics and comorbidities. CONCLUSIONS: NAFLD patients in Germany are grossly underdiagnosed and exert substantial healthcare resource use and economic burden, particularly those with advanced liver diseases. Optimal strategies for early identification and management are needed to prevent disease progression and limit the rising costs.

Disease severity predicts higher healthcare costs among hospitalized nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) patients in Spain.

The rising prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) presents many public health challenges, including a substantial impact on healthcare resource utilization and costs. There are important regional differences in the burden of NAFLD/NASH, and Spain-specific data are lacking. This retrospective, observational study examined the impact of liver disease severity, comorbidities, and demographics on healthcare resource utilization and costs in Spain.NAFLD/NASH patients in the Spanish National Health System's Hospital Discharge Records Database (1/1/2006 to 4/30/2017) were categorized into disease severity cohorts as NAFLD/NASH overall, NAFLD/NASH non-progressors, compensated cirrhosis (CC), decompensated cirrhosis (DCC), liver transplant (LT), or hepatocellular carcinoma (HCC). Patients were followed from index date until the earliest of 6 months, disease progression, end of coverage, death, or end of study. Within each cohort, pre- and post-index healthcare resource utilization and costs per patient per month (PPPM) were calculated.A total of 8,205 patients (mean age 58.4; 54% male) were identified; 5,984 (72.9%) were non-progressors, 139 (1.7%) progressed to CC, 2,028 (24.7%) to DCC, 115 (1.4%) to LT, and 61 (0.7%) to HCC. Pre-index comorbidity burden was high across disease cohorts, and the frequency of comorbidities increased with disease severity. From pre- to post-index, average length of stay (LOS) increased significantly (23%-41%) as did all-cause PPPM costs (44%-46%), with significantly longer LOS and costs in patients with increasing disease severity.Progression of NAFLD/NASH was associated with significantly higher costs and longer LOS. A coordinated approach is needed to manage resources and costs in Spain.

Use of disease modifying agents in patients with multiple sclerosis: Analysis of ten years of national data.

BACKGROUND: Disease modifying agents (DMAs) are used to reduce relapses and decrease disability progression in Multiple Sclerosis (MS) patients. However, limited national level data exists regarding the prescribing patterns for MS, especially after the introduction of oral DMAs. OBJECTIVE: This study examined the prescribing patterns and trends of DMAs using national level data and determined the factors associated with prescribing DMAs among MS patients in the United States. METHODS: This cross-sectional study utilized 2006-2015 National Ambulatory Medical Care Survey (NAMCS) data to examine office-based visits involving MS (ICD-9-CM code 340). Descriptive weighted analyses were performed to assess the prescribing patterns of DMAs. Multivariable logistic regression model within the conceptual framework of Andersen Behavioral Model was used to determine the factors associated with prescribing of DMAs among MS patients. RESULTS: An estimated 8.5 million (95% Confidence Interval [CI] 7.01-10.09 million) MS patient visits were identified from 2006 to 2015. During the ten-year study period, 3.84 million (45%) MS visits involved prescribing of DMAs. The majority of DMA prescriptions were injectables (78%), followed by infusions (11%) and orals (11%). Oral DMAs use increased (from 11% in 2010-2011 to 40% in 2014-2015), whereas the use of injectable DMAs decreased (from 96% in 2006-2007 to 52% in 2014-2015) during the study period. Multivariable analyses revealed that predisposing (age and region) and enabling (physician specialty) factors were significantly associated with prescribing of DMAs among MS patients. Visits to neurologists (Odds Ratio [OR] 6.61, 95% CI 3.66-11.93) were associated with higher odds of being prescribed with DMAs. CONCLUSION: During the ten-year study period, increasing use of oral DMAs and declining use of injectable DMAs was observed. Both predisposing and enabling factors influenced the prescribing of DMAs. With increasing availability of oral DMAs, the DMAs use is likely to increase among MS patients.

Patterns and predictors of mortality and disease progression among patients with non-alcoholic fatty liver disease.

BACKGROUND: Factors associated with mortality and disease progression in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are poorly understood. AIMS: To assess the impact of liver disease severity, demographics and comorbidities on all-cause mortality and liver disease progression in a large, real-world cohort of NAFLD patients. METHODS: Claims data from the German Institut für angewandte Gesundheitsforschung database between 2011 and 2016 were analyzed retrospectively. Adult patients diagnosed with NAFLD and/or NASH were categorised as NAFLD, NAFLD non-progressors, compensated cirrhosis, decompensated cirrhosis, liver transplant or hepatocellular carcinoma (HCC). The longitudinal probability of mortality and incidence of progression were calculated for disease severity cohorts and multivariable analyses performed for adjusted mortality. RESULTS: Among 4 580 434 patients in the database, prevalence of NAFLD was 4.7% (n = 215 655). Of those, 36.8% were non-progressors, 0.2% compensated cirrhosis, 9.6% decompensated cirrhosis, 0.0005% liver transplant and 0.2% HCC. Comorbidity rates were significantly higher in compensated cirrhosis, decompensated cirrhosis and HCC compared with non-progressors. The longitudinal probability of mortality for non-progressors, compensated cirrhosis, decompensated cirrhosis and HCC was 3.6%, 18.7%, 28.8% and 68%, respectively. Independent predictors of mortality included cardiovascular disease, type 2 diabetes mellitus, hypertension, obesity and renal impairment. The cumulative incidence of progression in NAFLD and compensated cirrhosis patients was 10.7% and 16.7%, respectively, over 5 years of follow-up. CONCLUSION: NAFLD patients were severely under-diagnosed and had a high probability of mortality that increased with disease progression. Early identification and effective management to halt or reverse fibrosis are essential to prevent progression.

Health Care Use and Costs Among Patients With Nonalcoholic Steatohepatitis With Advanced Fibrosis Using the Fibrosis-4 Score.

Limited evidence exists on the clinical and economic burden of advanced fibrosis in patients with nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) due to the invasiveness of liver biopsies for accurately staging liver disease. The fibrosis-4 (FIB-4) score allows for noninvasive assessment of liver fibrosis by using clinical and laboratory data alone. This study aimed to characterize the comorbidity burden, health care resource use (HCRU), and costs among patients with NAFLD/NASH with FIB-4-defined F3 (bridging fibrosis) and F4 (compensated cirrhosis) fibrosis. Using the Optum Research Database, a retrospective cohort study was conducted among 251,725 commercially insured adult patients with ≥1 NAFLD/NASH diagnosis from January 1, 2008, to August 31, 2016, and laboratory data required to calculate FIB-4 scores. Five criteria using varying FIB-4 score cutoffs were identified based on expert clinical opinion and published literature. Date of the first valid FIB-4 score marked the index date. Mean annual HCRU and costs were calculated during the pre-index and post-index periods. The prevalence of FIB-4-based F3 and F4 fibrosis was 0.40%-2.72% and 1.03%-1.61%, respectively. Almost 50% of patients identified with FIB-4-based F3 or F4 had type 2 diabetes, cardiovascular disease, or renal impairment. Total all-cause health care costs increased significantly from pre-index to post-index for patients with FIB-4-based F3 fibrosis across most criteria (17%-29% increase) and patients with FIB-4-based F4 fibrosis across all criteria (47%-48% increase). Inpatient costs were the primary drivers of this increment. Conclusion: Significant increases in HCRU and costs were observed following FIB-4-based identification of F3 and F4 fibrosis among U.S. adults with NAFLD/NASH. These data suggest the importance of early identification and management of NAFLD/NASH that may halt or reduce the risk of disease progression and limit the underlying burden.

Antimuscarinic Medication Use in Elderly Patients with Overactive Bladder.

BACKGROUND: Antimuscarinic medications are the first-line pharmacological treatment for overactive bladder (OAB); however, little is known about the utilization pattern of antimuscarinic agents in elderly patients with OAB. OBJECTIVE: This study examined the prevalence and predictors of antimuscarinic medication prescribing in elderly patients with OAB, using national ambulatory survey data. METHODS: This cross-sectional study utilized the 2009-2010 National Ambulatory Medical Care Survey and the outpatient component of the National Hospital Ambulatory Medical Care Survey. The study included patients aged ≥65 years diagnosed with OAB based on the International Classification of Diseases. Antimuscarinic medications were operationally defined using the American Hospital Formulary Service classification and identified using Multum Lexicon codes. Descriptive statistics using sampling weights were used to estimate the prevalence of antimuscarinic medication prescription, while multivariable logistic regression within the conceptual framework of the Anderson Behavioral Model was used to identify the factors associated with antimuscarinic medication prescription in elderly patients with OAB. RESULTS: According to the national surveys, 2.18 million (95 % confidence interval [CI] 1.62-2.75) elderly outpatient visits were made for OAB, of which 0.90 million (41.43 %) visits involved prescribing of antimuscarinic medications. The most frequently prescribed drugs were solifenacin (14.25 %), oxybutynin (10.50 %), and tolterodine (6.89 %). Multivariable analysis revealed that patients ≥85 years of age (odds ratio [OR] 3.50, 95 % CI 1.23-9.92) were more likely to receive antimuscarinic medications, and the South region (OR 2.78, 95 % CI 1.01-7.66) increased the likelihood of receiving antimuscarinic medications in elderly patients with OAB. CONCLUSIONS: This study found that antimuscarinic medications are commonly prescribed for elderly patients with OAB and there is variation in antimuscarinic use across age and region.

A multi-center study of fidaxomicin use for Clostridium difficile infection.

PURPOSE: Fidaxomicin use in real-world clinical practice, especially for severe Clostridium difficile infection (CDI), is mainly based on single-center observational studies. The purpose of this pharmacoepidemiology study was to assess outcomes of patients given fidaxomicin based on episode number and use of concomitant antibiotics. METHODS: Fidaxomicin use over time across included hospitals in the United States was assessed using a large inpatient drug utilization database. A multicenter retrospective chart review was also conducted of hospitalized patients with CDI that received fidaxomicin between 2011 and 2013. Fidaxomicin utilization and clinical outcomes were stratified by use of fidaxomicin for first or second episode (early episodes) versus greater than or equal to episodes (later episodes). RESULTS: The overall fidaxomicin use rate was 2.16 % which increased from 0.22 % in the last two quarters of 2011 to 3.16 % in the first two quarters of 2013. A total of 102 hospitalized patients that received fidaxomicin from 11 hospitals were identified in the multicenter study. Sixty-nine patients received fidaxomicin for early (68 % with severe CDI) and 33 received for later episodes. The majority of patients received other CDI therapy including 61 patients (88 %) for early episodes and 27 (82 %) for later episodes. Concomitant non-CDI antibiotics were received by 48 patients (47 %). Rates of clinical outcomes were similar regardless of CDI episode. CONCLUSION: This study demonstrated a slow but steady increase in fidaxomicin utilization over time; most of which was combined with other systemic antibiotics. Antimicrobial stewardship teams should provide guidance on appropriate use of fidaxomicin to optimize therapy and assess the need to continue other antibiotics during CDI treatment.

Potentially inappropriate anticholinergic medication use in community-dwelling older adults: a national cross-sectional study.

BACKGROUND: Inappropriate medications are often used in older adults despite their unfavourable risk-to-benefit profile. Although many of the medications in the American Geriatrics Society (AGS) Beers list are potentially inappropriate because of their anticholinergic properties, little is known regarding the nature and extent of potentially inappropriate anticholinergic medication use in older adults. OBJECTIVES: To determine the prevalence of, and factors associated with, potentially inappropriate anticholinergic medication use in the older population. METHODS: A retrospective, cross-sectional study was conducted, involving older adults (aged 65 years and older), using 2009-2010 Medical Expenditure Panel Survey (MEPS) data. The 2012 AGS Beers Criteria were used to define potentially inappropriate anticholinergic medications on the basis of the list of medications to avoid using in older adults irrespective of the diagnosis. Descriptive analyses were used to examine the nature and extent of potentially inappropriate anticholinergic medication use. Multivariable logistic regression within the conceptual framework of the Andersen Behavioral Model was used to identify the factors associated with potentially inappropriate anticholinergic use in older adults. RESULTS: According to the MEPS, there were 78.60 million older adults in the USA; an estimated 7.51 million (9.56 %) of these older adults used potentially inappropriate anticholinergic medications in 2009-2010. The most frequently used potentially inappropriate anticholinergics were cyclobenzaprine, promethazine, amitriptyline, hydroxyzine and dicyclomine. Multivariable regression analyses revealed that female sex, residing in the South and the presence of anxiety disorder increased the likelihood of receiving potentially inappropriate anticholinergic medications, whereas older adults aged 75-84 or ≥ 85 years, and those with over 15 years of education, had a decreased likelihood of receiving potentially inappropriate anticholinergic medications. CONCLUSION: The study found that approximately one in ten older adults used potentially inappropriate anticholinergic medications. Several predisposing, enabling and need factors were associated with the use of potentially inappropriate anticholinergic medications. Concerted efforts are needed to optimize potentially inappropriate anticholinergic medication use in older adults.