Falls and Fractures among Nursing Home Residents Treated with Pimavanserin versus Other Atypical Antipsychotics: Analysis of Medicare Beneficiaries with Parkinson's Disease Psychosis.

BACKGROUND: Reducing falls and fractures remains an important clinical goal in managing older residents with Parkinson's disease psychosis (PDP) in long-term care/nursing home (LTC/NH) settings. OBJECTIVES: This analysis examined risk of all-cause falls or fractures among PDP residents on continuous monotherapy with pimavanserin (PIM) versus (i) other atypical antipsychotics (AAPs) [quetiapine (QUE), risperidone (RIS), olanzapine (OLA), aripiprazole (ARI)] and (ii) QUE. METHODS: A retrospective analysis of parts A, B, and D claims from a 100% Medicare sample (2013-2019) in LTC/NH settings was conducted. LTC/NH residents in the USA initiating continuous monotherapy (PIM versus other AAPs; PIM versus QUE) for ≥ 6 months between 01 January 2014 and 31 December 2018 were 1:1 propensity score matched (PSM) on 31 variables (age, sex, race, region, and 27 Elixhauser comorbidities). Outcomes included three measures: risks of falls only, fractures only, and falls/fractures during 6-months follow-up. Demographic characteristics were described using chi-square and t-tests. Generalized linear models were used to assess difference in risks of falls/fractures. RESULTS: Of 7187 residents, 47.59% (n = 3420) were female and mean age was 78.8 (± 7.75) years. In total, 14% (n = 1005) were on PIM and 86% (n = 6182) were on other AAPs. After PSM, falls only among PIM residents (n = 1005) was 4.58% (n = 46) versus 7.66% (n = 77) for other AAPs (n = 1005) [relative risk (RR) = 0.63 (0.46, 0.86), p < 0.05] and 8.26% (n = 83) for QUE (n = 1005) residents (p < 0.05). Fractures only among PIM residents was 1.39% (n = 14) compared with 2.09% (n = 21) for other AAPs (p = 0.31) and 1.89% (n = 19) for QUE (p = 0.49), respectively. Taken together, falls/fractures among PIM residents were 5.67% (n = 57) versus 9.05% (n = 91) for other AAPs [RR = 0.63 (0.46, 0.86), p < 0.05] and 9.55% (n = 96) for QUE (p < 0.05), respectively. CONCLUSIONS: In this analysis of LTC/NH residents with PDP, PIM had a 37% and 41% lower risk of all-cause falls/fractures versus other AAPs and versus QUE, respectively.

Healthcare resource utilization among nursing home residents with Parkinson's disease psychosis: an analysis of Medicare beneficiaries treated with pimavanserin or other-atypical antipsychotics.

Aim: Real-world healthcare resource use (HCRU) burden among patients with Parkinson's disease psychosis (PDP) treated with pimavanserin (PIM) versus other atypical antipsychotics (other-AAPs) including quetiapine (QUE) in long term care (LTC) and nursing home (NH) settings are lacking. This analysis examines HCRU differences among residents in LTC/NH settings who initiate PIM versus QUE or other-AAPs. Methods: A retrospective analysis of LTC/NH residents with PDP from the 100% Medicare claims between 1 April 2015 and 31 December 2021 was conducted. Treatment-naive residents who initiated ≥6 months continuous monotherapy with PIM or QUE or other-AAPs between 04/01/16 and 06/30/2021 were propensity score matched (PSM) 1:1 using 31 variables (age, sex, race, region and 27 Elixhauser comorbidity characteristics). Post-index (i.e., 6 months) HCRU outcomes included: proportion of residents with ≥1 all-cause inpatient (IP) hospitalizations and emergency room (ER) visits. HCRU differences were assessed via log binomial regression and reported as relative risk ratios (RR) and 95% confidence intervals after controlling for dementia, insomnia and index year. Results: From a total of PIM (n = 1827), QUE (n = 7770) or other-AAPs (n = 9557), 1:1 matched sample (n = 1827) in each cohort were selected. All-cause IP hospitalizations (PIM [29.8%]) versus QUE [36.7%]) and ER visits (PIM [47.3%] versus QUE [55.8%]), respectively, were significantly lower for PIM. PIM versus QUE cohort also had significantly lower RR for all-cause IP hospitalizations and ER visits, respectively, (IP hospitalizations RR: 0.82 [0.75. 0.9]; ER visits RR: 0.85 [0.8. 0.9]). PIM versus other-AAPs also had lower likelihood of HCRU outcomes. Conclusion: In this analysis, LTC/NH residents on PIM monotherapy (versus QUE) had a lower likelihood of all-cause hospitalizations (18%) and ER (15%) visits. In this setting, PIM also had lower likelihood of all-cause HCRU versus other-AAPs.

Analysis of Medicare Patients Treated with Pimavanserin versus Other Atypical Antipsychotics: A Cost-Offset Model Evaluating Skilled Nursing Facility Stays and Long-Term Care Admissions in Parkinson's Disease Psychosis.

Background: Patients with Parkinson's disease psychosis (PDP) treated with pimavanserin (PIM) versus other atypical antipsychotics (AAPs) including quetiapine (QUE) may have health-care cost savings due to fewer skilled nursing facility-stays (SNF-stays) and long-term care admissions (LTCA). Methods: A decision analytic model was developed using the 2019 Medicare Patient Driven Payment Model (PDPM) to estimate SNF-stays and LTCA associated per-patient- per-year (PPPY) facility and rehabilitation costs among patients that initiated PIM vs QUE or vs other-AAPs (i.e, quetiapine, risperidone, olanzapine, aripiprazole). Model inputs were derived for: (i) annual SNF-stay and LTCA rates from an analysis of Medicare beneficiaries with PDP, and (ii) annual mean rehabilitation and resident care-stay costs from PDPM case-mix adjusted value-based payment rates for 5 rehabilitation components (ie, physical-therapy, occupational-therapy, nursing, speech-language pathology, non-therapy ancillary), and an additional variable-per-diem for room/board services. PPPY costs were estimated from (i) SNF-stay and (ii) LTCA rates multiplied by annual mean costs of stay in 2022 USD. Probabilistic sensitivity analysis (PSA) was performed using 1000 Monte Carlo simulations. Results: Overall SNF-stay rates of 20.2%, 31.4%, and 31.7%, and LTCA rates of 23.2%, 33.8%, 34.6% were observed for PIM, QUE, and other-AAPs, respectively. Based on annual mean costs, PPPY SNF-stay rehabilitation and resident related costs for PIM ($41,808) vs QUE ($65,172) or vs other-AAPs ($65,664), resulted in $23,364 and $23,856 PPPY cost savings, respectively. Similarly, PPPY LTCA rehabilitation and resident related costs for PIM ($47,957) vs QUE ($70,091) or vs other-AAPs ($71,566) resulted in $22,134 and $23,609 PPPY cost-savings for PIM, respectively. PSA suggested PIM would provide cost-savings vs QUE or other-AAPs in >99% of iterations. Conclusion: In this analysis, PIM demonstrated nearly 36% and 32% lower PPPY SNF-stays and LTCA costs, respectively, vs QUE or other-AAPs. Research examining additional cost-offsets (i.e., fewer falls/fractures) associated with SNF-stay or LTCA may be needed.

Risk of long-term care admissions among Medicare beneficiaries treated with pimavanserin or quetiapine for Parkinson's disease psychosis in USA: a retrospective administrative claims database analysis.

Aim: Risk of long-term care (LTC) admission (LTCA) associated with atypical antipsychotic (AAP) use among patients with Parkinson's disease psychosis (PDP) is a major concern. However, no comparative studies have examined the differences in risk of LTC admissions between pimavanserin (PIM), the only FDA-approved AAP for PDP, and other off-label AAPs including quetiapine (QUE). Objective: To examine all-cause LTCA rates and risk among PDP patients treated with AAPs such as QUE or PIM. Methods: Analysis of Parts A, B and D claims (100% Medicare sample; 2013-2019) of Medicare beneficiaries with PDP that initiate ≥12-month continuous PIM or QUE monotherapy from 1 January 2014 to 31 December 2018 (i.e., index date) without any AAP use in the 12-month pre-index period was conducted. Outcome assessments among 1:1 propensity score-matched (31 variables - age, sex, race, region and 27 Elixhauser comorbidities) beneficiaries on PIM versus QUE included risk of all-cause skilled nursing facility stays (SNF-stays), LTC-stays, and overall LTCA (i.e., SNF-stays or LTC-stays). All-cause LTCA rates and LTCA risk were compared using logistic regression and cox proportional hazards models, respectively, controlling for demographics, comorbidities and co-existing-dementia or insomnia. Results: Of the matched sample (n = 842 for each group) from total sample (n = 9652), overall all-cause LTCA and SNF-stay rates were 23.2 and 20.2% for PIM versus 33.8 and 31.4% for QUE, respectively (p < 0.05, for each). Hazard ratio (95% CI) for risk of SNF-stay and overall LTCA was 0.78 (0.61, 0.98) and 0.80 (0.66, 0.97), respectively, for PIM versus QUE beneficiaries (p < 0.05, for each). Conclusion: The 20% lower risk of LTCA (i.e., greater delay) with PIM versus QUE in this analysis may suggest that PIM should be started early for the treatment of PDP.

Incremental health care resource utilization and costs associated among patients with Parkinson's disease psychosis and incident dementia: An analysis of medicare beneficiaries.

BACKGROUND: Real-world evidence examining the incremental health care resource use (HCRU) and cost burden of incident dementia among patients with Parkinson's disease psychosis (PDP) are needed within the United States (US). OBJECTIVES: To compare HCRU and cost burden between PDP patients with incident dementia (PDP + D) versus without incident dementia (PDP). METHODS: A retrospective analysis of inpatient (Part A), outpatient (Part B), and prescription drug (Part D) claims from the 100% Medicare sample was conducted to compare PDP + D patients versus PDP patients between 01/01/14-12/31/18. Patients with a diagnosis of dementia, psychosis, secondary parkinsonism, or other psychotic disorders, during 12-month pre-index were excluded. Patients in both groups were matched using 1:1 propensity score matching (PSM) methodology using 31 variables (age, sex, race, region and 27 Elixhauser comorbidity characteristics). Differences in 12-month post-index HCRU rates and mean per patient per year (PPPY) costs for all-cause inpatient (IP) hospitalizations, and by type of IP stay (i.e., short-term [ST-stay], skilled nursing facility [SNF-stay] and long-term [LT-stay]) were analyzed via logistic and gamma log-link regression models. RESULTS: Of the 12,484 patients who met our study criteria, 1855 PSM-matched cohorts were identified. Mean age, gender, and comorbidities were similar in PSM groups. Approximately, 50.3% with PDP + D reported ≥1 all-cause IP hospitalizations versus 36.0% with PDP (p < 0.05) during 12-month follow-up. Specifically, all-cause ST-stay, SNF-stay, and LT-stay among PDP + D versus PDP patients were: 45.2% versus 35.7%, 28.3% versus 15.7%, and 8.5% versus 6.0% (p < 0.05), respectively. Psychiatric-related ST-stay, SNF-stay, and LT-stay among PDP + D versus PDP patients were: 12.3% versus 9.0%, 7.5% versus 3.4%, and 2.4% versus 1.2% (p < 0.05), respectively. Mean PPPY all-cause IP hospitalization costs for PDP + D patients versus PDP patients was $17,891 (±29,882) versus $11,599 (±$25,247) (p < 0.05). CONCLUSIONS: Patients with PDP + D experience significantly higher all-cause and psychiatric-related IP hospitalizations, including ST-stays, LT stays, and SNF stays. They also had 54% greater mean PPPY IP hospitalization costs versus PDP patients.

Patients treated with pimavanserin or quetiapine for Parkinson's disease psychosis: analysis of health resource utilization patterns among Medicare beneficiaries.

BACKGROUND: Pimavanserin (PIM) is the only FDA approved atypical antipsychotic (AAP) for the treatment of Parkinson's Disease Psychosis (PDP) while other off-label AAPs like quetiapine (QUE) are also used. Real-world comparative effects of PIM and QUE on health resource utilization (HCRU) may provide insights about their relative benefits. OBJECTIVES: To examine annual HCRU among newly initiated PIM or QUE monotherapy among patients with PDP. METHODS: Retrospective analysis of 100% Medicare (Parts A, B, and D) claims of patients with PDP during 1 January 2013 to 31 December 2019 was conducted. Treatment-naive patients with first prescription for PIM or QUE from 1 January 2014 to 31 December 2018 were selected if they had ≥12-months continuous monotherapy and had no prior AAP use for ≥12-month pre-index. Post-index 12-month HCRU was compared between 1:1 propensity score matched (PSM) PIM or QUE cohorts. HCRU outcomes included: rates of all-cause and psychiatric-related inpatient hospitalizations by stay-type [i.e., long-term stays (LT-stays), short-term stays (ST-stays), skilled nursing facility stays (SNF-stays)], outpatient hospitalizations, emergency room (ER) visits, and office visits. Relative risk and 95% confidence intervals are reported [RR (95% CI)]. RESULTS: A total of 842 and 7,116 were treated with PIM and QUE, respectively. Mean age and gender distribution were similar among both groups. After PSM, those on PIM (n=842) had significantly lower RR for all-cause: inpatient hospitalizations [RR=0.78 (0.70-0.87)], ST-stays [RR=0.75 (0.66-0.84)], SNF-stays [RR=0.64 (0.54-0.76)], and ER visits [RR=0.91 (0.84-0.97)] vs. QUE (n=842). PIM patients had slightly higher RR for all-cause office visits [RR=1.03 (1.01-1.05)] vs. QUE. Psychiatric-related inpatient hospitalizations were also lower for PIM vs. QUE: [RR=0.63 (0.48-0.82)] ST-stays [RR=0.61 (0.43-0.86)], SNF-stay [RR=0.69 (0.47-1.02)], and ER visits [RR=0.53 (0.37-0.76)]. CONCLUSIONS: In this analysis of PDP patients, PIM monotherapy resulted in nearly 22% and 37% lower all-cause hospitalizations and psychiatric-related inpatient hospitalizations compared to QUE.

Burden of Illness Among Patients with Psychosis due to Dementia with Lewy Bodies and Other Dementias.

Limited research is available on the real-world experiences of patients with dementia with Lewy bodies (DLB). This study evaluated clinical events, healthcare utilization, and healthcare costs of patients with DLB vs other dementia types with psychosis (ODP). Study patients included commercial and Medicare Advantage with Part D enrollees aged ≥40 years with evidence of DLB and ODP from 6/01/2015‒5/31/2019. Compared with patients with ODP, more patients with DLB had clinical events including anticholinergic effects, neurologic effects, and cognitive decline. Patients with DLB used more healthcare resources with greater dementia-related office and outpatient visits and psychosis-related inpatient stays and office, outpatient, and emergency visits compared with their ODP patient counterparts. Patients with DLB also incurred higher healthcare costs for all-cause and dementia-related office visits and pharmacy fills, and psychosis-related total costs. Understanding the clinical and economic impact of DLB and ODP is important to improve care for patients with dementia.

A targeted literature review of health economic analyses of human papillomavirus vaccination from various countries.

BACKGROUND: Understanding the cost-effectiveness of the HPV vaccine from a global perspective is important to assess from a policy perspective and to support current and future HPV vaccination programs. OBJECTIVES: The aim of this analysis was to conduct a targeted literature review of published pharmacoeconomic literature on the cost-effectiveness of the HPV vaccine to treat patients in various countries, with a focus on cost-savings and their impact on vaccine recommendations. METHODS: We searched cost-effectiveness studies in HPV published in peer-reviewed literature from 2012 to 2020 using MEDLINE via the PubMed database and Google Scholar. RESULTS: HPV vaccine cost-effectiveness was found to be greatest in low-income countries where screen programs were not yet in place, additionally, in adolescent males and females. The majority of the economic evaluations viewed the implementation of the HPV vaccine as cost-effective and recommended national HPV vaccination. CONCLUSION: The majority of economic studies favored national HPV vaccination for adolescent males and females in various countries. Feasibility of this strategy and implementation remains an open question, in addition to screening coverage rate in countries with no vaccine programs or countries yet to introduce national HPV vaccination.

Comparative Efficacy, Safety, and Acceptability of Pimavanserin and Other Atypical Antipsychotics for Parkinson's Disease Psychosis: Systematic Review and Network Meta-Analysis.

BACKGROUND: The current comparative efficacy, safety, and acceptability of atypical antipsychotics (AAPs) in treating Parkinson's Disease Psychosis (PDP) are not entirely understood. OBJECTIVE: To evaluate comparative efficacy, safety, and acceptability of AAPs in patients with PDP. METHODS: We conducted a systematic review and a network meta-analysis to compare the efficacy, safety, and acceptability of pimavanserin, quetiapine, olanzapine, clozapine, ziprasidone, and risperidone. We estimated relative standardized mean differences (SMDs) for continuous outcomes and odds ratios (OR) for binary outcomes, with their respective 95% confidence intervals (CIs). RESULTS: We included 19 unique studies evaluating AAPs in a total of 1,242 persons with PDP. Based on Clinical Global Impression Scale for Severity, pimavanserin (SMD, -4.81; 95% CI, -5.39, -4.24) and clozapine (SMD, -4.25; 95% CI, -5.24, -3.26) significantly improved symptoms compared with placebo. Also, compared to placebo, pimavanserin (OR, 1.16; 95% CI, 1.07, 1.24) significantly improved psychotic symptoms based on Scale for Assessment of Positive Symptoms for Parkinson's Disease Psychosis/Hallucinations and Delusions scores. In comparison to placebo, clozapine (SMD, -0.69; 95% CI, -1.35, -0.02), pimavanserin (SMD, -0.01; 95% CI, -0.56, 0.53), and quetiapine (SMD, 0.00; 95% CI, -0.68, 0.69) did not impair motor function per Unified Parkinson's Disease Rating scale. Based on Mini-Mental State Examination scale, quetiapine (SMD, 0.60; 95% CI, 0.07, 1.14) significantly impaired cognition compared to placebo. CONCLUSIONS: In patients with PDP, pimavanserin and clozapine demonstrated significant improvement in psychosis without affecting motor function. With quetiapine being associated with a significant decline in cognition and despite not impairing motor function, our findings suggest that it should be avoided in patients with PDP and reduced cognitive abilities.

Health care resource utilization patterns among patients with Parkinson's disease psychosis: analysis of Medicare beneficiaries treated with pimavanserin or other-atypical antipsychotics.

BACKGROUND: Pimavanserin (PIM) is the only FDA-approved atypical antipsychotic (AAP) for hallucinations and delusions associated with Parkinson's disease psychosis (PDP). Comparative real-world analyses demonstrating its benefits are needed. OBJECTIVES: To evaluate health care resource utilization (HCRU) outcomes among PDP patients treated with PIM vs. other-AAPs. METHODS: Retrospective cohort analysis of Parts A, B, and D claims from 100% Medicare sample from 01 January 2013-31 December 2019 was conducted. PDP Patients initiating (i.e. index date) continuous monotherapy (PIM vs. other-AAPs) for ≥12-months during 01 January 2014-31 December 2018 without 12-months pre-index AAP use were selected after 1:1 propensity score matching (PSM) on 31 variables (sex, race, region, age, and 27 Elixhauser comorbidities). HCRU outcomes included: annual all-cause and psychiatric hospitalization (short-term stay, long-term stay, and SNF-stay [skilled nursing facility]) rates, annual all-cause and psychiatric-ER visit rates, mean per-patient-per-year (PPPY) hospitalizations, and average length of stay (ALOS). PIM and other-AAPs were compared using generalized linear models (GLM) controlled for demographic characteristics, comorbidities, coexisting-dementia, and coexisting insomnia. RESULTS: Of 12,164 PDP patients, 48.41% (n = 5,889) were female, and mean age was 77 (±8.14) years. Among 1:1 matched patients (n = 842 in each), 37.8% (n = 319) on PIM vs. 49.8% (n = 420) on other-AAPs (p < .05) reported ≥1 all-cause hospitalizations, respectively. Specifically, short-term and SNF-stay among PIM patients vs. other-AAPs were: 34% (n = 286) vs. 46.2% (n = 389) and 20.2% (n = 170) vs. 31.8% (n = 267) (p < .05), respectively. Similarly, 9.6% (n = 81) of PIM vs. 14.6% (n = 123) of other-AAPs patients had ≥1 psychiatric hospitalization (p < .05). Furthermore, ≥1 all-cause and psychiatric ER visit among PIM vs. other-AAPs were 61.6% (n = 519) vs. 69.4% (n = 584) and 5.2% (n = 43) vs. 10.2% (n = 86) (p < .05), respectively. PIM also had significantly lower ALOS, and mean PPPY short-term hospitalization and SNF-stays. CONCLUSIONS: In this analysis of PDP patients, PIM monotherapy resulted in nearly 12% and 7% lower all-cause hospitalizations and ER visits vs. other-AAPs.

Adverse Outcomes Associated With Off-Label Agents Used to Treat Dementia Patients With Psychosis: A Case-Control Medicare Database Study.

INTRODUCTION: Currently, there are no Food and Drug Administration-approved therapies to treat dementia-related psychosis (DRP). This study investigated the association between using antipsychotics and the anticonvulsant divalproex (sodium valproate) to manage DRP and adverse outcomes. METHODS: A retrospective case/control matching study evaluated the risk of mortality, extrapyramidal symptoms (EPS), ischemic stroke, and cardiac arrest/ventricular arrhythmia (CA/VA) with ever-use of antipsychotics/divalproex in patients with DRP vs never-use. RESULTS: 49 509 patients were included; 76.8% used an antipsychotic/divalproex. Treatment ever-use was associated with an increased risk of all-cause mortality (odds ratio, 1.14; 95% CI, 1.10-1.18) and a smaller increase in the risk of EPS (1.10; 1.00-1.19) relative to never-use (adjusted for matching demographic variables, comorbid conditions, and disability). CONCLUSIONS: Current agents used for DRP were associated with increased risk of death and adverse outcomes. An increased risk of death was evident within 3 months of antipsychotic/divalproex initiation and persisted with long-term use.

Medicare claims analysis of agents used to manage dementia-related psychosis: a treatment pattern study.

Currently, no agents are approved in the USA to treat dementia-related psychosis. After failure of a nonpharmacologic approach to treatment, antipsychotics or divalproex is often prescribed. We characterized existing treatment patterns in patients with dementia-related psychosis. Medicare claims data from 2008 to 2016 were used to identify patients with dementia-related psychosis. The agents and associated dosages prescribed, time to first use, and patterns of use were evaluated for agents prescribed to treat dementia-related psychosis. In total, 49 509 patients were identified as having dementia-related psychosis. Over three-quarters (76.8%) received an antipsychotic or divalproex. The most prescribed first-line agents were quetiapine (30.5%), risperidone (19.5%), and divalproex (11.2%). More than 80% of patients received a low dose of an agent, and 65.5% switched or discontinued their first-line treatment during a mean follow-up period of 1.8 years. In the absence of US FDA-approved therapies to treat dementia-related psychosis, treatment after behavioral intervention involves frequent use of low-dose antipsychotics or divalproex. The high rate of treatment switching or discontinuation is consistent with current treatment guidelines and suggests a need for an improved, standardized pharmacological approach to treat dementia-related psychosis.

Economic Evaluation of Healthcare Resource Utilization and Costs for Newly Diagnosed Dementia-Related Psychosis.

This retrospective cohort study described changes in all-cause healthcare resource utilization (HCRU) and associated costs in dementia patients newly diagnosed with psychosis. Dementia and incident psychosis were identified using diagnostic and pharmacy claims using a Medicare 20% random sample dataset. All-cause HCRU and unweighted and weighted (by person-years of follow-up) HCRU-associated costs were evaluated in the year prior to and the 4 years following diagnosis of psychosis. In 49,509 dementia patients with psychosis, physician visits per patient per year increased from a mean of 26.7 (standard deviation (SD) 20.0) prior to psychosis to 38.4 (SD 41.9) post-psychosis diagnosis. The number of inpatient stay claims increased from 1.0 (SD 1.4) to 1.7 (SD 5.8). Mean unweighted costs for inpatient stays and home healthcare/hospice during 2008-2016 were USD 9989 and USD 3279 prior to a diagnosis of psychosis but increased to USD 25,982 and USD 9901 (weighted: USD 11,779 and USD 6709), respectively, in the year after a psychosis diagnosis. This pattern of a sharp increase in mean costs was also observed in costs adjusted to 2015 USD, and in both unweighted and weighted total and psychosis-related costs. These results indicate the importance of identifying newly diagnosed psychosis in dementia patients as well as the pressing need for management strategies and treatments that can reduce HCRU and costs.

Comparative Outcomes of Commonly Used Off-Label Atypical Antipsychotics in the Treatment of Dementia-Related Psychosis: A Network Meta-analysis.

INTRODUCTION: Dementia-related psychosis (DRP) is characterized by hallucinations and delusions, which may increase the debilitating effects of underlying dementia. This network meta-analysis (NMA) evaluated the comparative efficacy, safety, and acceptability of atypical antipsychotics (AAPs) commonly used off label to treat DRP. METHODS: We included 22 eligible studies from a systematic literature review of AAPs (quetiapine, risperidone, olanzapine, aripiprazole, and brexpiprazole) used off label to treat DRP. Study outcomes were: (1) efficacy-neuropsychiatric inventory-nursing home (NPI-NH psychosis subscale), (2) safety-mortality, cerebrovascular events (CVAEs), and others (somnolence, falls, fractures, injuries, etc.), and (3) acceptability-discontinuations due to all causes, lack of efficacy, and adverse events (AEs). We used random-effects modeling to estimate pooled standardized mean differences (SMDs) for NPI-NH psychosis subscale scores and odds ratios (OR) for other dichotomous outcomes, with their respective 95% confidence intervals (CIs). RESULTS: Compared with placebo, aripiprazole (SMD - 0.12; 95% CI - 0.31, 0.06), and olanzapine (SMD - 0.17; 95% CI - 0.04; 0.02) demonstrated small, non-significant numerical improvements in NPI-NH psychosis scores (5 studies; n = 1891), while quetiapine (SMD 0.04; 95% CI - 0.23, 0.32) did not improve symptoms. The odds of mortality (15 studies, n = 4989) were higher for aripiprazole (OR 1.58; 95% CI 0.62, 4.04), brexpiprazole (OR 2.22; 95% CI 0.30, 16.56), olanzapine (OR 2.21; 95% CI 0.84, 5.85), quetiapine (OR 1.68; 95% CI 0.70, 4.03), and risperidone (OR 1.63; 95% CI 0.93, 2.85) than for placebo. Risperidone (OR 3.68; 95% CI 1.68, 8.95) and olanzapine (OR 4.47; 95% CI 1.36, 14.69) demonstrated significantly greater odds of CVAEs compared to placebo. Compared with placebo, odds of all-cause discontinuation were significantly lower for aripiprazole (OR 0.71; 95% CI 0.51, 0.98; 20 studies; 5744 patients) and higher for other AAPs. Aripiprazole (OR 0.5; 95% CI 0.31, 0.82) and olanzapine (OR 0.48; 95% CI 0.31, 0.74) had significantly lower odds of discontinuation due to lack of efficacy (OR 12 studies; n = 4382) compared to placebo, while results for quetiapine and risperidone were not significant. Compared with placebo, the odds of discontinuation due to AEs (19 studies, n = 5445) were higher for olanzapine (OR 2.62; 95% CI 1.75, 3.92), brexpiprazole (OR 1.80; 95% CI 0.80, 4.07), quetiapine (OR 1.25; 95% CI 0.82, 1.91), aripiprazole (OR 1.38; 95% CI 0.90, 2.13), and risperidone (OR 1.41; 95% CI 1.02, 1.94). CONCLUSIONS: Overall results demonstrate that, compared with placebo, quetiapine is not associated with improvement in psychosis in patients with dementia, while olanzapine and aripiprazole have non-significant small numerical improvements. These off-label AAPs (quetiapine, risperidone, olanzapine, aripiprazole, and brexpiprazole) are associated with greater odds of mortality, CVAEs, and discontinuations due to AEs than placebo. These results underscore the ongoing unmet need for newer pharmacological options with a more favorable benefit-risk profile for the treatment of DRP.

Treatment Patterns With Antipsychotics in Long-Term Care Patients With Parkinson's Disease Psychosis.

This study assessed treatment change patterns in Parkinson's disease psychosis (PDP) residents receiving antipsychotic (AP) therapies in U.S. long-term care (LTC) facilities. Residents with PDP in LTC between 01/01/13 and 06/30/16 were identified with ≥1 claim of psychosis, hallucinations, or delusions after PD diagnosis. Treatment patterns were evaluated during the 12 months post index. We identified 864 PDP residents: 408 (47.2%) on AP therapy and 456 (52.8%) on no AP therapy. A total of 335 residents (82.1%) continued, 13 (3.2%) discontinued, 11 (2.7%) switched, and 49 (12.0%) augmented (used ≥2 APs) their index AP therapy. Based on the multivariate regression analysis, younger age, male gender, anemia, anxiolytic use or anxiety, sedatives/hypnotic use, bladder disorders including urinary tract infections, coronary conditions, diabetes, hypertension, and dementia were associated with a higher likelihood of treatment change. Understanding the factors associated with treatment change may inform ways to improve management of PDP in the U.S. LTC setting.

Real-World Medication Treatment Patterns for Long-Term Care Residents with Dementia-Related Psychosis.

Objectives: This study evaluated treatment patterns and factors associated with medication treatment changes in residents with dementia-related psychosis in a long-term care (LTC) setting. Methods: A retrospective database cohort study was conducted using the national PharMerica® database and included dementia residents with or without incident psychosis. Treatment patterns were assessed and a multivariate logistic regression model was used to identify factors associated with any treatment change (discontinuation, switch, or sporadic use) in dementia-related psychosis therapy. Results: Among 11,921 residents with incident dementia-related psychosis, 11,246 (94.3%) were prescribed ≥1 index medication to treat psychosis, including 77.3% who received ≥1 typical or atypical antipsychotic. Treatment change was evaluated during the post-index period: 38.7% of residents with dementia-related psychosis discontinued treatment, 13.9% switched treatments, and 7.9% had sporadic use. Factors associated with treatment change were age ≥65 years, Medicare insurance, and comorbid conditions (anemia, coronary heart disease, diabetes, falls, depression, hypertension, or hyperlipidemia) during the pre-index period. Discussion: Approximately 60% of dementia-related psychosis LTC residents experienced a medication treatment change. This treatment change was associated with higher age and higher comorbidities. Medications that treat symptoms of dementia-related psychosis without adding to safety concerns are needed to facilitate long-term, consistent treatment.

Burden of illness among patients with dementia-related psychosis.

BACKGROUND: More than 5.6 million Americans suffer from dementia, and that number is expected to double by 2060. This comes at a considerable burden to the health care system with costs estimated at $157-$215 billion in 2010. Depending on dementia type and disease progression, approximately 20%-70% of patients experience dementia-related psychosis (DRP), characterized by hallucinations and/or delusions resulting in worse clinical outcomes and greater caregiver burden compared with patients without DRP. OBJECTIVE: To compare real-world clinical events, health care resource utilization (HCRU), and health care costs among matched cohorts of DRP versus dementia-only patients. METHODS: This retrospective database analysis examined commercial and Medicare Advantage with Part D enrollees aged ≥ 40 years with evidence of DRP and dementia from January 1, 2010, through March 31, 2017. The first observed indicator of psychosis (≥ 2 diagnoses and/or antipsychotic pharmacy fills) co-occurring with or following evidence of dementia (≥ 2 diagnoses and/or dementia medication pharmacy fills) was the index date among patients with DRP. DRP patients were propensity score matched 1:1 to patients with dementia only based on demographics, comorbidities, dementia type, dementia severity, and pre-index all-cause HCRU. Continuous health plan enrollment ≥ 12 months before evidence of dementia through the index date and ≥ 12 months following the index date was required. Outcomes included clinical events, HCRU, and health care costs. RESULTS: A significantly higher percentage of DRP patients had ≥1 diagnosis for behavioral health conditions in the pre-index period compared with dementia-only patients (depression: 32.4% vs. 22.8%; anxiety: 19.1% vs. 11.5%; and insomnia: 9.0% vs. 6.3%; P < 0.001 for all comparisons). Diagnoses of post-index clinical events were significantly more likely among DRP patients compared with dementia-only patients including falls/fractures (28.3% vs. 14.1%), neurologic effects (17.7% vs. 12.9%), sedation (15.0% vs. 2.4%), cardiovascular effects (7.0% vs. 4.1%), and extrapyramidal reactions (3.2% vs. 1.7%; P < 0.001 for all comparisons). Higher percentages of DRP patients had an all-cause outpatient visit (80.2% vs. 68.9%), emergency visit (65.0% vs. 36.6%), or inpatient stay (47.2% vs. 20.0%) during the post-index period (P < 0.001 for all comparisons). The proportions of DRP patients with a post-index dementia-related office visit, outpatient visit, emergency visit, or inpatient stay was 48%, 147%, 339%, and 286% higher, respectively, compared with patients with dementia only. Compared with patients with dementia only, patients with DRP had significantly higher mean total post-index all-cause costs ($21,657 vs. $12,026; P < 0.001) and dementia-related costs ($11,852 vs. $3,013; P < 0.001). CONCLUSIONS: Patients with DRP were more likely to have diagnoses for behavioral health conditions, experience clinical events, and have higher mean all-cause and dementia-related HCRU and costs compared with patients with dementia only. These results reflect the unmet need of patients with DRP and an urgency for new treatment options to reduce substantial clinical and economic burden in this population. DISCLOSURES: This study was funded by Acadia Pharmaceuticals, which participated in the study design, interpretation of study results, and critical review of the manuscript. Abler, Skoog, and Rashid were employees of Acadia Pharmaceuticals at the time this study was conducted. Frazer and Halpern were employees of Optum at the time this study was conducted and were funded by Acadia Pharmaceuticals to conduct the study.

Effect Of Justicia Adhatoda (Malabar Nut) Leaf Extract On Drug-Induced Coagulopathy In Mice And In-Vitro Platelet Aggregation Of Human Blood.

BACKGROUND: Justicia adhatoda is widely used in traditional medicine for treatment of menorrhagia, piles and bleeding disorders. Oral antiplatelet and anticoagulant drugs are routinely prescribed to patients with cardiovascular diseases. These drugs have one major adverse effect that they can cause spontaneous haemorrhage, which can be fatal. Development of a haemostatic agent can help in effective management of drug-induced haemorrhages. This study was devised to observe the effect of leaf extract of Justicia adhatoda on coagulation profile in mice and to evaluate its effect on in-vitro platelet aggregation. METHODS: The study was divided into two parts. First part was designed to evaluate the effect of J. adhatoda leaf extract on coagulation parameters. Three drugs were used to induce coagulopathy viz., warfarin, aspirin and dabigatran. Bleeding time, platelet count, PT and APTT were estimated. Second part of this study was devised to observe the effect of J. adhatoda leaf extract on in vitro platelet aggregation of human. Percent aggregation was recorded by light transmission aggregometer for three minutes. RESULTS: Leaf extract of Justicia adhatoda decreased bleeding time from 6.1±2.36 minutes in normal control to 1.9±1.03 minutes in extract treated mice. There was no effect on the coagulation parameters. Platelet count increased significantly only in the aspirin treated group that received the extract to 540±46.8x103 /µl from 436.9±37.9x103 /µl of aspirin treated group. Platelet aggregation in vitro increased in a dose dependent manner. CONCLUSION: Justicia adhatoda leaf extract is effective in controlling excessive bleeding in vivo, in mice with acquired platelet defect produced by aspirin. This haemostatic effect is probably due to increased platelet aggregation as indicated by the in vitro results.

Association of Dementia-Related Psychosis With Long-term Care Use and Death.

OBJECTIVE: To determine the association of dementia-related psychosis (DRP) with death and use of long-term care (LTC); we hypothesized that DRP would be associated with increased risk of death and use of LTC in patients with dementia. METHODS: A retrospective cohort study was performed. Medicare claims from 2008 to 2016 were used to define cohorts of patients with dementia and DRP. Outcomes were LTC, defined as nursing home stays of >100 consecutive days, and death. Patients with DRP were directly matched to patients with dementia without psychosis by age, sex, race, number of comorbid conditions, and dementia index year. Association of DRP with outcomes was evaluated using a Cox proportional hazard regression model. RESULTS: We identified 256,408 patients with dementia. Within 2 years after the dementia index date, 13.9% of patients developed DRP and 31.9% had died. Corresponding estimates at 5 years were 25.5% and 64.0%. Mean age differed little between those who developed DRP (83.8 ± 7.9 years) and those who did not (83.1 ± 8.7 years). Patients with DRP were slightly more likely to be female (71.0% vs 68.3%) and white (85.7% vs 82.0%). Within 2 years of developing DRP, 16.1% entered LTC and 52.0% died; corresponding percentages for patients without DRP were 8.4% and 30.0%, respectively. In the matched cohort, DRP was associated with greater risk of LTC (hazard ratio [HR] 2.36, 2.29-2.44) and death (HR 2.06, 2.02-2.10). CONCLUSIONS: DRP was associated with a more than doubling in the risk of death and a nearly 2.5-fold increase in risk of the need for LTC.

Evaluation of Intravenous Immunoglobulin in Pediatric Acute-Onset Neuropsychiatric Syndrome.

Objectives: Pediatric acute-onset neuropsychiatric syndrome (PANS) is a clinical diagnosis in children who have an acute manifestation of varied neuropsychiatric symptoms, including obsessive compulsive disorder, eating disorders, tics, anxiety, irritability, and problems with attention/concentration. PANS may develop as a result of a postinfectious syndrome and may represent a new form of postinfectious autoimmunity. To test the hypothesis that multiple, consecutive infusions of intravenous immunoglobulin (IVIG) for PANS can be efficacious, a multisite, open-label study was designed. Methods: The primary endpoint was evaluation of the efficacy of IVIG [Octagam 5%] in PANS over a period of 6 months (six infusions) based on mean changes in psychological evaluation scores using 6 different assessments, including the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), Clinical Global Impression of Severity, and the Parent-Rated Pediatric Acute Neuropsychiatric Symptom Scale (PANS Scale). Results: The final cohort consisted of 21 subjects (7 per site) with moderate to severe PANS. The mean age was 10.86 years (range: 4-16 years). Results demonstrated statistically significant reductions in symptoms from baseline to end of treatment in all six assessments measured. CY-BOCS results demonstrated statistically significant reductions in obsessive compulsive symptoms (p < 0.0001), resulting in >50% improvement sustained for at least 8 weeks after the final infusion and up to 46 weeks in a subset of subjects. Conclusions: In PANS, which may be associated with an underlying immune dysregulation, sequential infusions of IVIG [Octagam 5%] successfully ameliorated psychological symptoms and dysfunction, with sustained benefits for at least 8 weeks, and up to 46 weeks in a subset of subjects. In addition, baseline immune and autoimmune profiles demonstrated significant elevations in a majority of subjects, which requires further evaluation, characterization, and study to clarify the potential immune dysfunction by which PANS manifests and progresses.