The impact of antipsychotic adherence on acute care utilization.

BACKGROUND: Non-adherence to psychotropic medications is common in schizophrenia and bipolar disorders (BDs) leading to adverse outcomes. We examined patterns of antipsychotic use in schizophrenia and BD and their impact on subsequent acute care utilization. METHODS: We used electronic health record (EHR) data of 577 individuals with schizophrenia, 795 with BD, and 618 using antipsychotics without a diagnosis of either illness at two large health systems. We structured three antipsychotics exposure variables: the proportion of days covered (PDC) to measure adherence; medication switch as a new antipsychotic prescription that was different than the initial antipsychotic; and medication stoppage as the lack of an antipsychotic order or fill data in the EHR after the date when the previous supply would have been depleted. Outcome measures included the frequency of inpatient and emergency department (ED) visits up to 12 months after treatment initiation. RESULTS: Approximately half of the study population were adherent to their antipsychotic medication (a PDC ≥ 0.80): 53.6% of those with schizophrenia, 52.4% of those with BD, and 50.3% of those without either diagnosis. Among schizophrenia patients, 22.5% switched medications and 15.1% stopped therapy. Switching and stopping occurred in 15.8% and 15.1% of BD patients and 7.4% and 20.1% of those without either diagnosis, respectively. Across the three cohorts, non-adherence, switching, and stopping therapy were all associated with increased acute care utilization, even after adjusting for baseline demographics, health insurance, past acute care utilization, and comorbidity. CONCLUSION: Non-continuous antipsychotic use is common and associated with high acute care utilization.

Economic outcomes associated with diagnosed behavioral symptoms among patients with dementia in the United States: a health care claims database analysis.

BACKGROUND: Behavioral symptoms are common in patients with dementia. However, there is limited evidence of their economic burden. Among commercially insured patients with dementia in the United States, this study assessed the prevalence of diagnosed behavioral symptoms and whether healthcare resources utilization and costs were associated with these symptoms. METHODS: This retrospective observational study was conducted using the IBM® MarketScan® Commercial Claims and Encounters and Medicare Supplemental database from October 1, 2015, to September 30, 2019. Diagnoses of dementia and behavioral symptoms were identified using the International Classification of Diseases, 10th Modification codes. To test differences in patient characteristics among those with and without diagnosed behavioral symptoms, t-tests were used for continuous variables, and chi-square tests were used for categories. Generalized linear models were used to compare healthcare resource utilization and costs between patients with and without diagnosed behavioral symptoms, adjusted for baseline characteristics. RESULTS: Of the 62,901 patients with dementia included in the analysis, 16.5% had diagnosed behavioral symptoms 12 months post dementia diagnosis. Patients with diagnosed behavioral symptoms used more health care resources (mean annual pharmacy visits per patient: 39.83 vs. 33.08, mean annual outpatient visits per patient: 24.20 vs. 16.94, mean annual inpatient visits per patient: 0.98 vs. 0.47, mean annual ER visits per patient: 2.45 vs. 1.21) and incurred higher cost of care than those without diagnosed behavioral symptoms (mean annual total health care costs per patients: $63,268 versus $33,383). Inpatient care was the most significant contributor to total costs (adjusted annual mean cost per patient: $28,195 versus $12,275). CONCLUSION: Behavioral symptoms were significantly associated with higher healthcare resource utilization and costs among patients with dementia. Further research is warranted to address the unmet medical needs of this patient population.

Diagnosis of behavioral symptoms as a predictor of institutionalization among Medicaid patients with dementia.

OBJECTIVES: Behavioral symptoms are commonly observed in the course of dementia. This study aimed to assess the association of the diagnosis of a cluster of behavioral symptoms (e.g., agitation, aggression, psychotic symptoms, and delirium/wandering) with the likelihood of subsequent institutionalization. METHODS: A retrospective cohort study of adults aged 65 and above diagnosed with dementia identified in the IBM® MarketScan® Multistate Medicaid database between October 01, 2015, and September 30, 2019, was conducted. The index date was defined as the first diagnosis date of dementia. The presence or absence of behavioral symptoms was identified in the 6 months prior to the index date (baseline). Institutionalization was evaluated 12 months (follow-up) post the index date. The association between diagnosed behavioral symptoms during the baseline period and institutionalization in the follow-up period was assessed using a multivariable logistic regression, adjusting for baseline sociodemographic and clinical characteristics. RESULTS: The study cohort included 40,714 patients with dementia. A diagnosis of behavioral symptoms was found among 2,067 (5.1%) patients during the baseline period. An increased likelihood of institutionalization was found during the follow-up among patients with agitation and aggression in baseline (OR = 1.51 (95% CI: 1.18-1.92)) compared to patients without these symptoms at baseline. Patients with psychotic symptoms in baseline had significantly higher odds of getting institutionalized during the follow-up compared to patients without psychotic symptoms in baseline (OR = 1.36 (95% CI: 1.20-1.54)). Similarly, patients with symptoms of delirium and wandering in baseline had a higher likelihood of institutionalization than patients without these symptoms at baseline (OR = 1.61 (95% CI: 1.30-1.99)). CONCLUSION: Several diagnosed behavioral symptoms were associated with a higher risk of institutionalization among older adults with dementia and should be considered when planning treatment strategies for the effective management of the condition.

Cardiometabolic outcomes among schizophrenia patients using antipsychotics: the impact of high weight gain risk vs low weight gain risk treatment.

OBJECTIVE: Evaluate the prevalence of cardiometabolic conditions among schizophrenia patients before and incidence after initiation of high (HWGR) and low weight gain risk (LWGR) antipsychotic (AP) regimens. METHODS: A retrospective observational cohort study was conducted using administrative claims data from the IBM® MarketScan Commercial and Multi-State Medicaid Databases. Patients with > 1 medical claim with a diagnosis for schizophrenia and newly initiating AP therapy between 1/1/11-6/30/16 were included. Baseline characteristics were assessed in the 12-months before AP initiation; outcomes over 24-months following AP initiation. Patients were characterized by the AP regimen initiated at the index date. Adherence was defined by a medication possession ratio > 0.8 (medication on hand for 80% of follow-up). Multivariate modeling identified predictors of index AP weight gain risk profile and post-index dyslipidemia. RESULTS: Two thousand seven hundred forty-eight commercially-insured and 8,748 Medicaid patients met the inclusion criteria. A majority of patients initiated on atypical AP and approximately 30% were adherent to their index AP regimen. Within both payers, patients indexing on LWGR AP regimens were more likely to have pre-index diagnoses of cardiometabolic conditions including hypertension, dyslipidemia, and diabetes. Significant predictors of post-index dyslipidemia included AP adherence and pre-index diabetes. Within both payers, odds of initiating HWGR AP regimens were higher among patients with evidence of drug abuse. CONCLUSIONS: There is unmet need for reducing cardiometabolic consequences for patients on AP therapy and this analysis provides evidence that cardiometabolic conditions often develop during early stages of AP therapy. However, this does not appear to be related to the weight gain risk profile of the AP regimen.

Quantifying the diagnostic pathway for patients with cognitive impairment: real-world data from Australia.

OBJECTIVES: Rapid diagnosis of dementia is essential to ensure optimum patient care. This study used real-world data to quantify the dementia diagnostic pathway in Australia. DESIGN: A real-world, cross-sectional survey of physicians and patients. SETTING: Clinical practice. PARTICIPANTS: Primary care or specialist physicians managing patients with cognitive impairment (CI). MEASUREMENTS: Descriptive analyses focused on key events in the diagnostic pathway. Regression modeling compared the duration between first consultation and formal diagnosis with various factors. RESULTS: Data for 600 patients were provided by 60 physicians. Mean time from initial symptoms to first consultation was 6.1 ± 4.4 months; 20% of patients had moderate or severe CI at first consultation. Mean time from first consultation to formal diagnosis was 4.0 ± 7.4 months (1.2 ± 3.6 months if not referred to a secondary physician, and 5.3 ± 8.3 months if referred). Time from first consultation to diagnosis was significantly associated with CI severity at first consultation; time was shorter with more severe CI. There was no association of disease severity and referral to a secondary physician; 69.5% of patients were referred, the majority (57.1%) to a geriatrician. The highest proportion of patients were diagnosed by geriatricians (47.4%). Some form of test or scale was used to aid diagnosis in 98.8% of patients. CONCLUSIONS: A substantial number of Australians experience cognitive decline and behavioral changes some time before consulting a physician or being diagnosed with dementia. Increasing public awareness of the importance of early diagnosis is essential to improve the proportion of patients receiving comprehensive support prior to disease progression.

The Diagnostic Pathway From Cognitive Impairment to Dementia in Japan: Quantification Using Real-World Data.

OBJECTIVE: This study aimed to quantify the diagnostic pathway from cognitive impairment (CI) to dementia in Japan. METHODS: This was a real-world, cross-sectional survey of patients with CI and their physicians. RESULTS: Data for 1107 patients were provided by 106 physicians. Mean time from initial symptoms to the first consultation was 7.4±6.9 months; 42% of patients had moderate/severe CI at first consultation. Mean time from the first consultation to formal diagnosis was 2.9±11.0 months (1.9±8.8 mo if not referred to a secondary physician, and 5.1±14.6 mo if referred). Time from the first consultation to diagnosis was shorter with more severe CI at first consultation (P=0.0072). The highest proportion of patients were diagnosed by neurologists (45.8%). Tests or scales were used to aid diagnosis in 81.2% of patients. There was no association of disease severity and referral to a secondary physician; 30.9% of patients were referred, the majority (57.7%) to a neurologist. CONCLUSIONS: A substantial proportion of patients with dementia in Japan experience CI for some time before consulting a physician. Government policy to increase public understanding and awareness of dementia, and a proposed dementia screening system, should increase the proportion of individuals consulting physicians before disease progression.

Association between low muscle mass, functional limitations and hospitalisation in heart failure: NHANES 1999-2004.

BACKGROUND/OBJECTIVES: Muscle mass decreases with age, and heart failure (HF) patients may experience greater reductions due to pathophysiological processes associated with this disease. Reduced muscle mass may predispose HF patients to functional limitations and increased morbidity and mortality. This study estimated the associations between HF, low muscle mass (LMM), functional limitations and hospitalisation, as well as the combined effect of HF and LMM on these outcomes in a nationally representative sample. DESIGN: A cross-sectional survey. SETTING: the National Health and Nutrition Examination Survey 1999-2004. SUBJECTS: A total of 402 HF (weighted 3,994,205) and 7,061 non-HF participants (weighted 91,058,850), ≥45 years with dual-energy X-ray absorptiometry measurements. METHODS: the 20th percentile of the sex-specific distribution of lean appendicular mass residuals from linear regression with height and fat mass as predictors, served as the LMM cut-point. Logistic regression provided adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association of HF and LMM with functional limitations and hospitalisation. RESULTS: There were statistically significant adjusted associations between HF and limitations in household chores, walking one-fourth of a mile and hospitalisation (OR (95% CI): 2.5 (1.7 -3.8), 1.9 (1.2 -3.0) and 1.6 (1.1 -2.4), respectively). LMM was significantly associated with limitations in household chores and walking one-fourth of a mile (OR (95% CI): 1.5 (1.2, 1.9) and 1.4 (1.2, 1.7), respectively). Interaction between HF and LMM was noted for the associations with functional limitations. CONCLUSIONS: This hypothesis-generating study found a synergistic interaction between HF and LMM; the presence of LMM increased the negative effects of HF. HF patients may experience increased disease burden due to LMM.

Impact of rheumatoid arthritis on quality of life, work productivity and resource utilisation: an observational, cross-sectional study in Brazil.

OBJECTIVES: Increasing severity in rheumatoid arthritis (RA) may result in poorer health-related quality of life (HRQoL), reduced work productivity and increased resource utilisation. This study investigated the impact of RA severity on HRQoL and healthcare resource utilisation among RA patients in Brazil. METHODS: Data were drawn from an observational cross-sectional study of consulting RA patients undertaken in November-December 2007. Rheumatologists (n=55) provided information for 526 RA patients, 521 of whom also completed patient self-completion (PSC) questionnaires. Physicians subjectively rated each patient's RA as mild, moderate or severe. The PSC included the Work Productivity and Activity Impairment questionnaire (WPAI), Health Assessment Questionnaire Disability Index (HAQ-DI) and HAQ-Pain score, EuroQoL-5D (EQ-5D) and Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue. Data on the number of hospitalisations and consultations to healthcare professionals in the past 12 months and RA drug therapy class received were also collected. RESULTS: Patients with severe RA had significantly impaired health and work status compared to those with mild/moderate disease. Overall work and activity impairment rose with increasing disease severity. Health status deteriorated as disease severity increased with worsening disability, pain, fatigue, quality of life and perceived general health status. Hospitalisation rate and frequency of physician consultations were also significantly greater among those with severe RA. CONCLUSIONS: In Brazil, moderate to severe RA is associated with significant functional disability and morbidity. Disease severity should be considered when treating patients with RA. More aggressive treatment strategies may be needed to effectively manage patients with moderate to severe RA.

Improved health outcomes with etanercept versus usual DMARD therapy in an Asian population with established rheumatoid arthritis.

BACKGROUND: Patient reported outcomes (PROs) are especially useful in assessing treatments for rheumatoid arthritis (RA) since they measure dimensions of health-related quality of life that cannot be captured using strictly objective physiological measures. The aim of this study was to compare the effects of combination etanercept and methotrexate (ETN + MTX) versus combination synthetic disease modifying antirheumatic drugs (DMARDs) and methotrexate (DMARD + MTX) on PRO measures among RA patients from the Asia-Pacific region, a population not widely studied to date. Patients with established moderate to severe rheumatoid arthritis who had an inadequate response to methotrexate were studied. METHODS: Patients were randomized to either ETN + MTX (N = 197) or DMARD + MTX (N = 103) in an open-label, active-comparator, multicenter study, with PRO measures designed as prospective secondary endpoints. The Health Assessment Questionnaire (HAQ), Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-Fatigue), Medical Outcomes Short Form-36 Health Survey (SF-36), Hospital Anxiety and Depression Scale (HADS) and the Work Productivity and Activity Impairment Questionnaire: General Health (WPAI:GH) were used. RESULTS: Significantly greater improvements were noted for the ETN + MTX group at week16 for HAQ mean scores and for proportion of patients achieving HAQ score ≤ 0.5, compared to patients in the DMARD + MTX group. SF-36 Summary Scores for physical and mental components and for 6 of 8 health domains showed significantly greater improvements at week16 for the ETN + MTX group; only scores for physical functioning and role-emotional domains did not differ significantly between the two treatment arms. Greater improvements at week16 were noted for the ETN + MTX group for FACIT-Fatigue, HADS, and WPAI:GH mean scores. CONCLUSION: Combination therapy using ETN + MTX demonstrated superior improvements using a comprehensive set of PRO measures, compared to combination therapy with usual standard of care DMARDs plus MTX in patients with established rheumatoid arthritis from the Asia-Pacific region. TRIAL REGISTRATION: clintrials.gov # NCT00422227.

Prevalence and impact of antipsychotic discontinuation among commercially-insured patients with bipolar disorder.

BACKGROUND: Antipsychotic discontinuation is common among patients with bipolar disorder, especially when psychotic symptoms are remitted. This analysis describes the prevalence, predictors, and economic impact of antipsychotic discontinuation among patients with bipolar disorder. METHODS: A retrospective, observational study was conducted using administrative claims data in the IBM MarketScan Commercial Database. Patients with ≥1 claim with a diagnosis for bipolar disorder (manic or mixed) and newly-initiating antipsychotic therapy between 1 January 2011 and 30 June 2016 were included. Baseline characteristics were assessed in the 12 months prior to the initiation. Outcomes were assessed during a 24-month follow-up. Discontinuation of antipsychotic therapy was utilized as a predictor of healthcare costs in models adjusted for baseline characteristics. Using limited set of variables in the claims database, predictors of discontinuation were also assessed. RESULTS: A total of 18,259 commercially-insured patients were identified as initiators of antipsychotics. Common comorbidities among the cohorts included major depressive disorder and dyslipidemia. Discontinuation was very common among these patients (85%). Major depressive disorder, drug abuse, and other substance abuse/dependency were predictive of discontinuation. Controlling for differences in baseline characteristics, discontinuation was associated with 33% higher inpatient and emergency visit costs (p <.001) among those using these services, and 24% higher total healthcare costs (p <.001) for the overall cohort. CONCLUSIONS: Most patients with bipolar mania or mixed states discontinue antipsychotic treatment in less than 2 years. Antipsychotic discontinuation contributes to excess healthcare costs. Future research focusing on the reasons for discontinuation and tailoring disease management based on comorbidities may inform adherence improvement initiatives.

Modeling acute care utilization: practical implications for insomnia patients.

Machine learning models can help improve health care services. However, they need to be practical to gain wide-adoption. In this study, we investigate the practical utility of different data modalities and cohort segmentation strategies when designing models for emergency department (ED) and inpatient hospital (IH) visits. The data modalities include socio-demographics, diagnosis and medications. Segmentation compares a cohort of insomnia patients to a cohort of general non-insomnia patients under varying age and disease severity criteria. Transfer testing between the two cohorts is introduced to demonstrate that an insomnia-specific model is not necessary when predicting future ED visits, but may have merit when predicting IH visits especially for patients with an insomnia diagnosis. The results also indicate that using both diagnosis and medications as a source of data does not generally improve model performance and may increase its overhead. Based on these findings, the proposed evaluation methodologies are recommended to ascertain the utility of disease-specific models in addition to the traditional intra-cohort testing.

Development and Temporal Validation of an Electronic Medical Record-Based Insomnia Prediction Model Using Data from a Statewide Health Information Exchange.

This study aimed to develop and temporally validate an electronic medical record (EMR)-based insomnia prediction model. In this nested case-control study, we analyzed EMR data from 2011-2018 obtained from a statewide health information exchange. The study sample included 19,843 insomnia cases and 19,843 controls matched by age, sex, and race. Models using different ML techniques were trained to predict insomnia using demographics, diagnosis, and medication order data from two surveillance periods: -1 to -365 days and -180 to -365 days before the first documentation of insomnia. Separate models were also trained with patient data from three time periods (2011-2013, 2011-2015, and 2011-2017). After selecting the best model, predictive performance was evaluated on holdout patients as well as patients from subsequent years to assess the temporal validity of the models. An extreme gradient boosting (XGBoost) model outperformed all other classifiers. XGboost models trained on 2011-2017 data from -1 to -365 and -180 to -365 days before index had AUCs of 0.80 (SD 0.005) and 0.70 (SD 0.006), respectively, on the holdout set. On patients with data from subsequent years, a drop of at most 4% in AUC is observed for all models, even when there is a five-year difference between the collection period of the training and the temporal validation data. The proposed EMR-based prediction models can be used to identify insomnia up to six months before clinical detection. These models may provide an inexpensive, scalable, and longitudinally viable method to screen for individuals at high risk of insomnia.

Association of Antipsychotic-Related Weight Gain With Treatment Adherence and Switching Using Electronic Medical Records Data.

Objective: To leverage electronic health record (EHR) data to explore the relationship between weight gain and antipsychotic adherence among patients with schizophrenia and bipolar disorder (BD).Methods: EHR data were used to identify individuals with at least 60 days of continuous antipsychotic use between 2005 and 2019. Patients were diagnosed with schizophrenia, schizoaffective disorder, BD, or neither diagnosis (psychiatric controls). We examined the association of weight gain in the first 90 days with the proportion of days covered (PDC) with an antipsychotic and with the frequency of medication switching or stopping.Results: We identified 590 adults with schizophrenia or schizoaffective disorder, 819 adults with BD, and 642 psychiatric controls. In the first 90 days, the percentages of patients with a PDC ≥ 0.80 were 76.8% (schizophrenia), 77.1% (BD), and 70.7% (controls). Logistic regression models revealed that weight gain of ≥ 7% trended toward being significantly associated with greater adherence in the first 90 days (odds ratio = 1.29, P = .077) and was significantly associated with an increased likelihood of a medication switch in the first 180 days (odds ratio = 1.60, P = .003).Discussion: Patients whose weight increased by 7% or more in the first 90 days were more adherent but were also more likely to switch medications during the first 180 days.

Burden of Insomnia and Sleep Disturbances and the Impact of Sleep Treatments in Patients with Probable or Possible Alzheimer's Disease: A Structured Literature Review.

BACKGROUND: Sleep disturbances are frequent in Alzheimer's disease (AD). OBJECTIVE: To summarize the impact of sleep disturbances on AD patients and their caregivers and the effects of currently available sleep therapies. METHODS: Published studies (January 1985-March 2020) assessing the burden associated with insomnia/sleep disturbances in the AD population and insomnia treatment effects were identified by searching PubMed, Embase, and Cochrane Library and screened against inclusion criteria. RESULTS: 58 studies assessing patient and caregiver burden, institutionalization, and insomnia treatments in AD patients with sleep disturbances were identified. Sleep disturbances were associated with worse cognition, functional ability, and behavioral and neuropsychological functioning. Health status and quality of life of both patients and caregivers were reduced in the presence of sleep disturbances. Sleep disturbances were also associated with institutionalization. Although significant associations between sleep problems and clinical outcomes were apparent, there was generally no control for other influencing factors (e.g., cognitive status). Bright light and behavioral therapies as well as drugs showed some promise in AD patients, but studies were primarily small and limited data were available, particularly in regard to the effect on associated clinical burden. CONCLUSION: Sleep disturbances are a significant problem for AD patients and caregivers, associated with behavioral and psychological problems and cognitive decline. However, they remain poorly characterized and under-researched. As the global population is aging and AD is on thes rise, data from larger, prospective trials are required to fully understand the clinical correlates of sleep disturbances and the impact insomnia treatments can have.

Atypical Treatment Switches in Schizophrenia Patients: Drivers and Associated Outcomes.

Objective: To describe and compare demographics and outcomes among patients with schizophrenia who have switched atypical treatments versus non-switchers. Methods: Data were extracted from the Adelphi Schizophrenia Disease Specific Programme™ conducted from January to May 2014 in the United States. Participating physicians provided information on their next 10 consulting schizophrenia patients aged ≥ 18 years; the same patients were invited to voluntarily complete a patient self-completion form (PSC). Patients were considered switchers (S) or non-switchers (NS) based on their physician-provided treatment history. S were patients who had switched, stopped or added an atypical treatment within the last 2 years. NS had no treatment changes within the last 2 years or were receiving their first-line treatment (for ≥ 3 months). Demographics, clinical characteristics and outcomes among S and NS were compared using both descriptive and multivariate statistics. Results: One-hundred fifty physicians provided data on 1003 patients with schizophrenia (395 S, 608 NS); 500 patients completed a PSC (170 S, 330 NS). When compared with NS, S were more likely to be unemployed (p=0.0060), have a caregiver (p<0.0001), have greater activity impairment as assessed by Work and Productivity Activity Impairment (p=0.0031), be hospitalized for schizophrenia (p<0.0001) and have had a greater mean number of hospitalizations in the last 12 months (p=0.0012). NS vs S were more likely to have much or very much improved illness (p<0.0001) and less severe disease (p<0.0001) as assessed by Clinical Global Impression. Conclusion: Despite switching drugs, some schizophrenia patients continue to have high levels of disease burden, suggesting that currently available therapies are insufficiently effective in these patients.

Improvements in patient-reported outcomes, symptoms of depression and anxiety, and their association with clinical remission among patients with moderate-to-severe active early rheumatoid arthritis.

OBJECTIVES: To assess the association between clinical remission in RA and patient-reported outcomes (PROs), including depression/anxiety symptoms, in adults with moderate-to-severe active early RA. METHODS: Patients from the COmbination of Methotrexate and ETanercept in Active Early Rheumatoid Arthritis (COMET) trial (104 weeks) with measures on the Hospital Anxiety and Depression Scale at baseline and subsequent visits (n = 389) were included. PROs investigated were the HAQ disability index, pain and fatigue visual analogue scales (VASs), EuroQoL health status VAS and the Medical Outcomes Short Form-36 physical and mental component summaries. The impact of clinical remission as measured by 28-joint DAS (DAS-28) on depression/anxiety symptoms at Week 104 was assessed using logistic regression. Least square means for PRO improvements from baseline were estimated by analysis of covariance. Missing data were imputed using the last observation carried forward method. RESULTS: When depression/anxiety symptoms were absent at baseline, significantly more patients achieved clinical remission, low disease activity and normal functioning at Week 104. Reciprocally, patients who achieved clinical remission were less likely to maintain symptoms of depression or anxiety compared with non-remitters [depression odds ratio (OR): 0.35, P = 0.0233; anxiety OR: 0.48, P = 0.0371]. Fatigue and pain had a significant impact on changes in depression status, but did not influence anxiety status. Finally, clinical remission was significantly associated with improvements in all PRO measures (P < 0.001); conversely, depression/anxiety symptoms reduced PRO improvements. CONCLUSIONS: Among moderate-to-severe active early RA patients, clinical remission reduces symptoms of depression/anxiety, and independently improves PROs, thereby suppressing the negative impact of depression/anxiety on these measures.

Impact of Dementia-Related Behavioral Symptoms on Healthcare Resource Use and Caregiver Burden: Real-World Data from Europe and the United States.

BACKGROUND: Dementia is commonly accompanied by neurobehavioral symptoms; however, the relationship between such symptoms and health-related outcomes is unclear. OBJECTIVE: To investigate the impact of specific neurobehavioral symptoms in dementia on healthcare resource use (HCRU), patient quality of life (QoL), and caregiver burden. METHODS: Data were taken from the 2015/16 Adelphi Real World Dementia Disease Specific Programme™, a point-in-time survey of physicians and their consulting dementia patients. Multiple regression analyses were used to examine associations between patient symptom groups and health-related outcomes. RESULTS: Each patient symptom group of interest (patients with agitation/aggression and related symptoms [AARS] with psychosis, patients with AARS without psychosis, and patients with other behavioral symptoms) had a positive association with HCRU variables (i.e., HCRU was greater), a negative association with proxy measures of patient QoL (i.e., QoL was decreased), and a positive association with caregiver burden (i.e., burden was greater) compared with patients with no behavioral symptoms (control group). The magnitude of effect was generally greatest in patients with AARS with psychosis. Regression analysis covariates that were found to be most often significantly related to the outcomes were dementia severity and the patients' living situation (i.e., whether they were in nursing homes or living in the community). CONCLUSION: Combinations of behavioral symptoms, particularly involving AARS plus psychosis, may have a detrimental impact on health-related outcomes such as HCRU, patient QoL, and caregiver burden in dementia. Our results have implications for intervention development in patients who report clusters of symptoms and caregivers, and for identifying at-risk individuals.

Incremental Healthcare Utilization and Cost Burden of Comorbid Insomnia in Alzheimer's Disease Patients.

BACKGROUND: Insomnia is associated with worsened clinical outcomes among Alzheimer's disease dementia (AD) patients, increased caregiver burden, and healthcare utilization. OBJECTIVE: This study aimed to characterize the incremental healthcare burden of insomnia in AD using real-world data. METHODS: A retrospective observational study was conducted on AD patients selected from the IBM® MarketScan Commercial and Medicare Supplemental Databases. AD patients with claims-based evidence of insomnia were direct matched to a non-insomnia cohort based on demographic factors. Healthcare utilization and associated costs were assessed for a 12-month follow-up period. RESULTS: A total of 3,500 insomnia AD patients and 9,884 non-insomnia AD patients were analyzed. The insomnia cohort had a higher comorbidity burden at baseline (mean score on Charlson Comorbidity Index 2.5 versus 2.2, p < 0.001) and higher proportions of patients with baseline diagnoses for other conditions including depression: 40%, insomnia cohort versus 25%, non-insomnia (p < 0.001). AD patients with insomnia were more likely to have a claim for inpatient hospitalizations (39.8%versus 32.3%), emergency room services (56.4%versus 48.0%), and skilled-nursing services (42.6%versus 31.9%) (all p < 0.05). Mean total annual healthcare costs during the 12-month follow-up period were significantly higher among AD patients with insomnia as compared to those without. (Mean costs: $37,356 versus $27,990, p < 0.001). CONCLUSION: AD patients with comorbid insomnia are more likely to use higher-cost healthcare services such as inpatient hospitalization, and skilled nursing, and have higher total healthcare costs. This real-world analysis provides evidence that AD disease management should consider proper treatment of comorbid insomnia due to the incremental burden and cost implications.

Quality of Life and Caregiver Burden of Alzheimer's Disease Among Community Dwelling Patients in Europe: Variation by Disease Severity and Progression.

BACKGROUND: Alzheimer's disease (AD) is a significant burden on patients and caregivers. How this burden increases as disease progresses has not been well researched. OBJECTIVE: To assess the association of caregiver burden and quality of life with Alzheimer's disease severity and disease progression in community-dwelling patients in Germany, Spain, and the UK. METHODS: This was a prospective observational longitudinal study of mild-to-moderate AD patients (assessed by Mini-Mental State Examination, MMSE), and their caregivers. The humanistic burden was assessed using these instruments: [Rapid Assessment of Physical Activity (RAPA), EuroQoL-5-Dimension Level (EQ-5D-5L)] and caregiver-reported [Dependence Scale (DS), EQ-5D-5L, Zarit Burden Interview (ZBI)]. Caregiver-reported healthcare resource use was assessed using the Resource Use in Dementia (RUD) and ad-hoc questions. RESULTS: Of 616 patients recruited, 338 and 99 were followed-up at 12 and 18 months, respectively. The caregiver-reported EQ-5D-5L scores of patients' health-related quality of life (HRQoL) showed a negative trend over time (baseline: 0.76; 18 months: 0.67) while patient-reported HRQoL remained at 0.85. DS scores tended to worsen. Disease progression was an independent predictor of HRQoL and increased dependence.Mean ZBI score increased over time reflecting an increase in caregiver burden; MMSE being an independent predictor for caregiver burden. Patient resource utilization and caregiver time for caregiving tended to increase over time. CONCLUSION: We found significant association between disease progression and caregiver and patient burden. Independently, both disease-specific outcomes and disease burden measures increased over time, but as disease progresses, we also found incremental burden associated with it.

Medications in Patients with Dementia and Behavioral Disturbance.

BACKGROUND: Behavioral disturbance (BD) is common in dementia patients, with no FDA approved medications for this condition. Little data exists on the real-world medication use in this population. OBJECTIVE: To describe real-world medications use in this population. METHODS: A cross-sectional study was conducted using the MarketScan database for outpatient medications and the Cerner database for inpatient medications. The study period was Oct 2015-Jun 2018. Patients with dementia and BD were identified through ICD-10-CM. We examined outpatient medications prescribed during 6-month before or after BD event date, and inpatient medications during inpatient visits, especially on central nervous systems (CNS) drugs including antidementia drugs, antidepressants, antipsychotics, anxiolytics, and anticonvulsants. RESULTS: A total of 56,544 outpatients and 34,245 patient hospitalizations were assessed separately. Among outpatients, patients filled more medications after a BD event. The use of the five CNS drug classes generally increased after a BD event, and the largest increase was seen in antipsychotics (23%to 33%). Among inpatients, the median number of medications used in each hospitalization was 14. The use of antipsychotics was particularly high (64%), followed by anxiolytics (51%). A list of 60 unique medications were suggested to be the commonly used drugs in dementia patients with BD. CONCLUSION: In dementia patients with BD, anti-dementia medications, antidepressants, anticonvulsants, hypnotics and antipsychotics were the most used drug classes. Antidepressants and antipsychotics use were more frequent after a BD event, which suggests a need for safe drugs targeting BD in dementia patients.