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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.
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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.
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Antipsicóticos , Medicare , Casas de Salud , Enfermedad de Parkinson , Aceptación de la Atención de Salud , Piperidinas , Trastornos Psicóticos , Urea , Humanos , Femenino , Masculino , Estados Unidos , Estudios Retrospectivos , Medicare/estadística & datos numéricos , Antipsicóticos/uso terapéutico , Casas de Salud/estadística & datos numéricos , Anciano , Piperidinas/uso terapéutico , Anciano de 80 o más Años , Enfermedad de Parkinson/tratamiento farmacológico , Trastornos Psicóticos/tratamiento farmacológico , Aceptación de la Atención de Salud/estadística & datos numéricos , Urea/uso terapéutico , Urea/análogos & derivados , Hospitalización/estadística & datos numéricos , Puntaje de PropensiónRESUMEN
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.
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BACKGROUND: Cytomegalovirus (CMV) infections among hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients impose a significant health care resource utilization (HCRU)-related economic burden. Maribavir (MBV), a novel anti-viral therapy (AVT), approved by the United States Food and Drug Administration for post-transplant CMV infections refractory (with/without resistance) to conventional AVTs has demonstrated lower hospital length of stay (LOS) versus investigator-assigned therapy (IAT; valgancilovir, ganciclovir, foscarnet, or cidofovir) in a phase 3 trial (SOLSTICE). This study estimated the HCRU costs of MBV versus IAT. METHODS: An economic model was developed to estimate HCRU costs for patients treated with MBV or IAT. Mean per-patient-per-year (PPPY) HCRU costs were calculated using (i) annualized mean hospital LOS in SOLSTICE, and (ii) CMV-related direct costs from published literature. Probabilistic sensitivity analysis with Monte-Carlo simulations assessed model robustness. RESULTS: Of 352 randomized patients receiving MBV (n = 235) or IAT (n = 117) for 8 weeks in SOLSTICE, 40% had HSCT and 60% had SOT. Mean overall PPPY HCRU costs of overall hospital-LOS were $67,205 (95% confidence interval [CI]: $33,767, $231,275) versus $145,501 (95% CI: $62,064, $589,505) for MBV and IAT groups, respectively. Mean PPPY ICU and non-ICU stay costs were: $32,231 (95% CI: $5,248, $184,524) versus $45,307 (95% CI: $3,957, $481,740) for MBV and IAT groups, and $82,237 (95% CI: $40,397, $156,945) MBV versus $228,329 (95% CI: $94,442, $517,476) for MBV and IAT groups, respectively. MBV demonstrated cost savings in over 99.99% of simulations. CONCLUSIONS: This analysis suggests that Mean PPPY HCRU costs were 29%-64% lower with MBV versus other-AVTs.
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Infecciones por Citomegalovirus , Diclororribofuranosil Benzoimidazol/análogos & derivados , Trasplante de Órganos , Ribonucleósidos , Humanos , Citomegalovirus , Antivirales , Ganciclovir/uso terapéutico , Hospitalización , Receptores de Trasplantes , Bencimidazoles/uso terapéutico , Ribonucleósidos/uso terapéutico , Ribonucleósidos/efectos adversos , Trasplante de Órganos/efectos adversos , Células Madre HematopoyéticasRESUMEN
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.
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Antipsicóticos , Enfermedad de Parkinson , Trastornos Psicóticos , Humanos , Anciano , Estados Unidos/epidemiología , Fumarato de Quetiapina/uso terapéutico , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/epidemiología , Estudios Retrospectivos , Cuidados a Largo Plazo , Medicare , Trastornos Psicóticos/tratamiento farmacológico , Trastornos Psicóticos/epidemiología , Trastornos Psicóticos/complicacionesRESUMEN
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.
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Demencia , Enfermedad de Parkinson , Trastornos Psicóticos , Humanos , Anciano , Estados Unidos/epidemiología , Medicare , Enfermedad de Parkinson/epidemiología , Estudios Retrospectivos , Aceptación de la Atención de Salud , Trastornos Psicóticos/epidemiología , Demencia/epidemiología , Costos de la Atención en SaludRESUMEN
Aim: To investigate real-world chimeric antigen receptor (CAR) T-cell therapy treatment patterns. Patient & methods: Relapsed/refractory large B-cell lymphoma patients who received CAR T-cell therapy were identified. Patient characteristics, setting of CAR T-cell infusion, incidence of CAR T-cell therapy-associated adverse events and healthcare resource utilization were assessed. Results: Of 1175 patients, 83% were infused inpatient. Within three days postinfusion, inpatient-infused patients had a significantly higher risk of CAR T-associated adverse events (hazard ratio: 2.67; 95% CI: 2.09-3.42) compared with outpatient-infused patients. By day 30, 67% of outpatient-infused patients were hospitalized at least once. Conclusion: These findings suggest that physicians were able to select lower-risk patients for outpatient infusion, but postinfusion hospitalizations still occur.
This study tracks outcomes in patients with relapsed/refractory large B-cell lymphoma who received chimeric antigen receptor (CAR) T-cell therapy between 2017 and 2020. The authors used the Anlitiks All-Payor Claims (AAPC) database, which includes insurance claims of patients covered through Medicare, Medicaid or commercial insurance plans. AAPC includes over 80% of insured patients in the USA healthcare system. The study describes where patients received CAR T-cell therapy (inpatient/outpatient), rates of adverse events potentially related to CAR T-cell treatment and how much healthcare the patients received. In the 3 days after receiving CAR T-cell therapy, rates of CAR T-associated adverse events were significantly higher in patients who received CAR T-cell therapy in the inpatient setting, compared with outpatients. The findings suggest that lower-risk patients may receive CAR T-cell therapy as outpatients, but that most outpatient-infused patients will still require inpatient care.
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Linfoma de Células B Grandes Difuso , Receptores Quiméricos de Antígenos , Humanos , Linfocitos T , Linfoma de Células B Grandes Difuso/patología , Inmunoterapia Adoptiva/efectos adversos , Aceptación de la Atención de Salud , Antígenos CD19RESUMEN
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.
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Antipsicóticos , Enfermedad de Parkinson , Trastornos Psicóticos , Humanos , Anciano , Estados Unidos , Fumarato de Quetiapina/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Estudios Retrospectivos , Medicare , Trastornos Psicóticos/tratamiento farmacológico , Antipsicóticos/uso terapéutico , Recursos en SaludRESUMEN
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.
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Antipsicóticos , Clozapina , Enfermedad de Parkinson , Trastornos Psicóticos , Humanos , Antipsicóticos/efectos adversos , Enfermedad de Parkinson/complicaciones , Clozapina/uso terapéutico , Fumarato de Quetiapina/efectos adversos , Metaanálisis en Red , Trastornos Psicóticos/tratamiento farmacológico , Trastornos Psicóticos/complicaciones , Trastornos Psicóticos/psicologíaRESUMEN
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.
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Antipsicóticos , Enfermedad de Parkinson , Trastornos Psicóticos , Humanos , Femenino , Anciano , Estados Unidos , Adulto , Masculino , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/tratamiento farmacológico , Estudios Retrospectivos , Medicare , Trastornos Psicóticos/complicaciones , Trastornos Psicóticos/tratamiento farmacológico , Aceptación de la Atención de SaludRESUMEN
Objective: To investigate the role of (1) antipsychotic medication review (AP-MR) documentation quality of Minimum Data Set 3.0 (MDS) surveys, and (2) treatment-continuity on discharge-to-community and clinical outcomes among long-term care (LTC) residents treated with pimavanserin. Design, Setting, and Participants: A retrospective cohort analysis of Parts A, B, and D claims from Medicare 100% sample merged with MDS data from June 2016 through December 2018 was conducted. Residents with more than 100-day LTC stay and 1 pimavanserin prescription or more with completed antipsychotic-use MDS question were selected. AP-MR documentation quality (ie, gradual dose reduction [GDR] attempts, clinical contraindication to GDR), discharge-to-community, and clinical outcomes (eg, falls, fractures) were obtained from MDS. Treatment-continuity was assessed from Part D claims. Data Analysis: Descriptive statistics (frequencies, proportions, Chi-square tests, and means) and adjusted logistic regressions (ORs with 95% CIs reported association between pimavanserin treatment-continuity and discharge-to-community. Results: Of 4,021 eligible residents, 29% (n = 1,182) attempted a GDR per AP-MR MDS documentation. Approximately 41% (n = 1,665) had documentation showing GDR was clinically contraindicated, yet 39% (n = 645) still attempted GDR. While overall discharge-to-community rates were low, it was significantly higher (P < 0.05) among LTC residents continuing (14.94%; n = 380/2,546) versus discontinuing (11.84%; n = 171/1,444) pimavanserin. OR for treatment-continuity was 1.96, 95% CI 1.50-2.55. Residents continuing pimavanserin had lower incidents of falls (2.8% vs 9.4%), hip fractures (0.29% vs 0.69%), and pelvic/femur fractures (0% vs 0.92%) versus those residents who discontinued it. Conclusions: Among LTC-stay residents, high discordance between GDR rates and AP-MR MDS documentation quality was observed. Pimvanserin treatment-continuity showed greater likelihood of discharge-to-community; continued documentation training can ensure appropriate antipsychotic use with a balanced benefit:risk profile.
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Antipsicóticos , Cuidados a Largo Plazo , Anciano , Antipsicóticos/uso terapéutico , Humanos , Medicare , Revisión de Medicamentos , Alta del Paciente , Piperidinas , Estudios Retrospectivos , Estados Unidos , Urea/análogos & derivadosRESUMEN
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.
Asunto(s)
Antipsicóticos , Demencia , Trastornos Psicóticos , Antipsicóticos/uso terapéutico , Aripiprazol/uso terapéutico , Benzodiazepinas/uso terapéutico , Demencia/complicaciones , Demencia/tratamiento farmacológico , Humanos , Metaanálisis en Red , Uso Fuera de lo Indicado , Olanzapina/uso terapéutico , Trastornos Psicóticos/tratamiento farmacológico , Trastornos Psicóticos/etiología , Fumarato de Quetiapina/uso terapéutico , Risperidona/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Selection of schizophrenia or bipolar disorder treatments is complicated by treatment-effect heterogeneity. OBJECTIVES: This study assessed how clinicians' beliefs and health system/ insurace policies impact choice of atypical antipsychotic agent in schizophrenia and bipolar disorder. METHODS: A cross-sectional survey was conducted of members of the American College of Clinical Pharmacy and College of Psychiatric & Neurologic Pharmacists. Beliefs regarding atypical antipsychotic effectiveness and safety, impact of comorbidity on drug selection, and factors influencing atypical antipsychotic therapy selection were assessed. RESULTS: Twenty-four psychiatric pharmacists and 18 psychiatrists participated. Mean age was 39.6 years, 57.1% were female. Most clinicians (64.3%) believed medication effectiveness and safety equally important, while 26.2% believed safety and 9.4% believed effectiveness more important. The most important medication properties for schizophrenia were reducing positive symptoms (92.7%) and hospitalizations (87.8%) and for bipolar disorder were reducing manic episodes (87.8%), episode relapse (53.7%), and hospitalizations (53.7%). Agranulocytosis (78.1%), arrhythmias (70.7%), and extrapyramidal side effects (68.3%) were most concerning. Restrictions affected antipsychotic choice at 80.5% of sites and were believed to affect medication adherence (55.0%) and outcomes (53.4%). CONCLUSION: Efficacy and safety were considered equally important when choosing atypical antipsychotics. Formulary restrictions were perceived as impacting treatment choice and outcomes.
Asunto(s)
Antipsicóticos , Trastorno Bipolar , Psiquiatría , Esquizofrenia , Adulto , Trastorno Bipolar/tratamiento farmacológico , Estudios Transversales , Femenino , Humanos , Masculino , Farmacéuticos , Esquizofrenia/tratamiento farmacológicoRESUMEN
In bacteria, signaling phosphorylation is thought to occur primarily on His and Asp residues. However, phosphoproteomic surveys in phylogenetically diverse bacteria over the past decade have identified numerous proteins that are phosphorylated on Ser and/or Thr residues. Consistently, genes encoding Ser/Thr kinases are present in many bacterial genomes such as in the Escherichia coli genome, which encodes at least three Ser/Thr kinases. Here, we identify a previously uncharacterized ORF, yegI, and demonstrate that it encodes a novel Ser/Thr kinase. YegI lacks several conserved motifs including residues important for Mg2+ binding seen in other bacterial Ser/Thr kinases, suggesting that the consensus may be too stringent. We further find that YegI is a two-pass membrane protein with both N- and C termini located intracellularly.
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Escherichia coli/enzimología , Membranas Intracelulares/metabolismo , Proteínas de la Membrana/química , Proteínas de la Membrana/metabolismo , Proteínas Serina-Treonina Quinasas/química , Proteínas Serina-Treonina Quinasas/metabolismo , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Secuencia Conservada , Activación Enzimática , Escherichia coli/genética , Células Eucariotas/enzimología , Membranas Intracelulares/química , Manganeso/farmacología , Proteínas de la Membrana/antagonistas & inhibidores , Fosforilación/efectos de los fármacos , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Estaurosporina/farmacologíaRESUMEN
OBJECTIVE: The objective of this study was to examine the relationship between adherence to treatment with sodium channel blockers (SCBs) and health-related quality of life (HRQoL), work productivity and activity impairment (WPAI), healthcare resource utilization (HRU), and associated costs among patients with epilepsy. METHODS: This retrospective cross-sectional study used data from the 2017 US National Health and Wellness Survey (NHWS; Nâ¯=â¯75,004). Health-related quality of life (Study Short-Form 36-Item Health Survey version 2 [SF-36v2]), WPAI (Work Productivity and Activity Impairment-General Health [WPAI-GH] questionnaire), HRU, and annual costs were compared among respondents with epilepsy using SCBs categorized as low/medium adherence (nâ¯=â¯120) and high adherence (nâ¯=â¯80) using generalized linear models, controlling for patient characteristics. RESULTS: Mental component score, Short-Form 6-Dimension (SF-6D) health utility index, bodily pain, mental health, physical functioning, role emotional, social functioning, and vitality scores were significantly lower in low/medium adherence respondents than in high adherence respondents (for all, pâ¯<â¯0.05). Only activity impairment was significantly higher in low/medium adherence respondents compared with the high adherence group (pâ¯<â¯0.001). Healthcare resource utilization did not differ significantly between the two groups; however, the number of emergency room (ER) visits and total costs were lower in the high adherence group (pâ¯=â¯0.038) compared with the low/medium adherence group (pâ¯=â¯0.040). CONCLUSION: High adherence to SCBs was associated with improved HRQoL, lower WPAI, and lower HRU and associated costs among patients with epilepsy. Therefore, adherence to SCBs may be an important factor in improving the abovementioned patient-reported outcomes. Findings from this study can help provide further impetus to healthcare policymakers and clinicians for addressing the low antiepileptic drug (AED) adherence levels in adult patients with epilepsy.
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Anticonvulsivantes/administración & dosificación , Epilepsia/tratamiento farmacológico , Cumplimiento de la Medicación , Medición de Resultados Informados por el Paciente , Bloqueadores de los Canales de Sodio/administración & dosificación , Adulto , Anciano , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: Based on data from 2003 to 2007, the prevalence of epilepsy was significantly higher in the institutionalized elderly population than in the noninstitutionalized population, but the recent prevalence and economic impact of epilepsy specifically in the institutionalized Medicare population have not been reported. OBJECTIVES: To estimate the prevalence and economic burden of epilepsy and inpatient utilization rates among institutionalized Medicare beneficiaries and to provide a 10-year projection of their population size and the associated costs. METHODS: We performed a cross-sectional analysis of the institutionalized Medicare population with and without epilepsy using Medicare 5% sample claims data from 2013 and 2014. The identification of epilepsy required ≥1 qualifying claims with an epilepsy diagnosis, or ≥2 qualifying claims ≥30 days apart with a diagnosis of convulsion, in 2014. Institutionalized status was identified by having ≥6 consecutive months of nursing facility claims in 2013 or 2014. Inpatient admissions and 30-day readmissions, average allowed costs, and risk-adjusted incremental costs of epilepsy were calculated and compared between the institutionalized population of Medicare beneficiaries with and without epilepsy. The 2015 Medicare 100% and 5% sample data and inputs from other external sources were used to project the 10-year trends in the size and cost of the institutionalized Medicare population with epilepsy. RESULTS: The prevalence of epilepsy in 2014 was 11.1% in the institutionalized Medicare population. The institutionalized population with epilepsy had significantly higher per-patient per-month (PPPM) costs ($3479 vs $2381, respectively; P <.001), inpatient admissions per 1000 beneficiaries (1105 vs 697, respectively; P <.001), and 30-day readmissions per 1000 beneficiaries (287 vs 145, respectively; P <.001) versus the institutionalized population without epilepsy. The risk-adjusted incremental cost of epilepsy for the institutionalized population was $507.33 PPPM. Based on our model, between 2017 and 2027 an 18% increase in size and a 72% increase in cost are projected for the institutionalized Medicare beneficiaries with epilepsy. CONCLUSION: The high cost and inpatient resource utilization, as well as the projected growth of the institutionalized Medicare population with epilepsy highlight the need for further investigation of care management opportunities to reduce the cost burden associated with this condition.
RESUMEN
Folded proteins show a high degree of structural order and undergo (fairly constrained) collective motions related to their functions. On the other hand, intrinsically disordered proteins (IDPs), while lacking a well-defined three-dimensional structure, do exhibit some structural and dynamical ordering, but are less constrained in their motions than folded proteins. The larger structural plasticity of IDPs emphasizes the importance of entropically driven motions. Many IDPs undergo function-related disorder-to-order transitions driven by their interaction with specific binding partners. As experimental techniques become more sensitive and become better integrated with computational simulations, we are beginning to see how the modest structural ordering and large amplitude collective motions of IDPs endow them with an ability to mediate multiple interactions with different partners in the cell. To illustrate these points, here, we use Prostate-associated gene 4 (PAGE4), an IDP implicated in prostate cancer (PCa) as an example. We first review our previous efforts using molecular dynamics simulations based on atomistic AWSEM to study the conformational dynamics of PAGE4 and how its motions change in its different physiologically relevant phosphorylated forms. Our simulations quantitatively reproduced experimental observations and revealed how structural and dynamical ordering are encoded in the sequence of PAGE4 and can be modulated by different extents of phosphorylation by the kinases HIPK1 and CLK2. This ordering is reflected in changing populations of certain secondary structural elements as well as in the regularity of its collective motions. These ordered features are directly correlated with the functional interactions of WT-PAGE4, HIPK1-PAGE4 and CLK2-PAGE4 with the AP-1 signaling axis. These interactions give rise to repeated transitions between (high HIPK1-PAGE4, low CLK2-PAGE4) and (low HIPK1-PAGE4, high CLK2-PAGE4) cell phenotypes, which possess differing sensitivities to the standard PCa therapies, such as androgen deprivation therapy (ADT). We argue that, although the structural plasticity of an IDP is important in promoting promiscuous interactions, the modulation of the structural ordering is important for sculpting its interactions so as to rewire with agility biomolecular interaction networks with significant functional consequences.
Asunto(s)
Antígenos de Neoplasias/química , Proteínas Intrínsecamente Desordenadas/química , Simulación de Dinámica Molecular , Antígenos de Neoplasias/metabolismo , Humanos , Proteínas Intrínsecamente Desordenadas/metabolismo , Conformación ProteicaRESUMEN
PURPOSE: While antiepileptic drug (AED) treatment effectiveness is traditionally assessed based on seizure frequency reduction (SFR), the overall value of AEDs in managing epilepsy and associated sequelae may be best assessed by how patients feel and function in terms of overall health-related quality of life (HRQoL). We conducted a pooled analysis of the Quality of Life in Epilepsy-31 (QOLIE-31) questionnaire from two phase 3 trials to explore the effect of response to conversion to eslicarbazepine acetate (ESL) monotherapy on HRQoL. METHODS: Data were pooled from two multicenter, randomized, double-blind, historical control phase 3 trials examining conversion to ESL monotherapy in adults with inadequately controlled partial-onset seizures (POS). The relationship between HRQoL and ESL treatment response was examined through the analysis of week 18 QOLIE-31 scores between patients who met the SFR ≥50% threshold (responders) and patients with SFR <50% (nonresponders). The analysis was conducted in the efficacy population (intent-to-treat (ITT) patients who entered the AED taper/conversion period) and completer population (efficacy patients who completed the ESL monotherapy period) and was repeated using an SFR ≥75% threshold. RESULTS: In the efficacy population, week 18 QOLIE-31 total score least squares mean (LSM) was significantly higher for responders with ≥50% SFR (LSM difference: 3.0; 95% confidence interval (CI): 0.2-5.8; pâ¯=â¯0.037) and with ≥75% SFR (LSM difference: 7.0; 95% CI: 3.6-10.3; pâ¯<â¯0.001) than nonresponders. In the completer population, overall quality of life (QoL) (LSM difference: 5.1; 95% CI: 1.5-8.6; pâ¯=â¯0.006) and social functioning (LSM difference: 5.4; 95% CI: 0.1-10.7; pâ¯=â¯0.046) were significantly higher for responders with ≥50% SFR than nonresponders, and all domain LSMs were higher for responders with ≥75% SFR (all pâ¯<â¯0.05) than nonresponders. CONCLUSIONS: This analysis of data from the phase 3 trials demonstrated significantly higher HRQoL among ESL responders with SFR of ≥75% and also at the lower SFR threshold of ≥50% compared with nonresponders.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Ensayos Clínicos Fase III como Asunto/métodos , Dibenzazepinas/uso terapéutico , Epilepsia/tratamiento farmacológico , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Adulto , Método Doble Ciego , Epilepsia/diagnóstico , Epilepsia/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto/métodos , Calidad de Vida/psicología , Resultado del TratamientoRESUMEN
OBJECTIVE: This observational study compared the risk of hospitalization for patients with bipolar disorder when treated with lurasidone versus other oral atypical antipsychotics. METHODS: This US commercial claims analysis (4 April 2010 through 24 September 2014) used the Optum Research Database to identify adult patients with bipolar disorder treated with oral atypical antipsychotics (N = 11,132). The first claim for an atypical antipsychotic defined the index date, with pre-index and post-index periods of 180 and 360 days, respectively. Every month of the post-index period was categorized as monotherapy treatment with lurasidone, aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone, no/minimal treatment or other. Starting with the initial month of treatment, the risk of psychiatric or all-cause hospitalization in the subsequent month was examined based on treatment in the current month and pre-index covariates (age, gender, hospitalizations, emergency room visits, diagnoses for anxiety, alcohol abuse, substance abuse, hypertension, type 2 diabetes and obesity) and time-varying versions of the pre-index covariates using a marginal structural model. RESULTS: After controlling for covariates, relative to lurasidone, the odds of psychiatric and all-cause hospitalization, respectively, were 2-3 times higher for olanzapine (odds ratio [OR] = 2.78, CI 1.09, 7.08, p = .032; OR = 3.20, CI 1.24, 8.26, p = .016), quetiapine (OR = 2.80, CI 1.13, 6.95, p = .026; OR = 3.23, CI 1.29, 8.11, p = .013), risperidone (OR = 2.50, CI 1.01, 6.21, p = .048; OR = 2.79, CI 1.11, 7.02, p = .029), aripiprazole (OR = 2.13, CI 0.87, 5.20, p = .097; OR = 2.57, CI 1.04, 6.37, p = .041) and ziprasidone (OR =2.31, CI 0.91, 5.85, p = .079; OR = 2.49, CI 0.97, 6.40, p = .058). CONCLUSIONS: In this claims database analysis, lurasidone-treated patients with bipolar disorder had a significantly lower risk of psychiatric hospitalization compared to quetiapine, olanzapine and risperidone, but not aripiprazole or ziprasidone. Lurasidone-treated patients had a significantly lower risk of all-cause hospitalization compared to quetiapine, olanzapine, risperidone and aripiprazole, but not ziprasidone.