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BackgroundPrevious studies have assessed the incremental economic burden of treatment-resistant depression (TRD) versus non-treatment-resistant major depressive disorder (i.e., non-TRD MDD) in commercially-insured and Medicaid-insured patients, but none have focused on Medicare-insured patients.ObjectiveTo assess healthcare resource utilization (HRU) and costs of patients with TRD versus non-TRD MDD or without major depressive disorder (MDD; i.e., non-MDD) in a Medicare-insured population.MethodsAdult patients were retrospectively identified from the Chronic Condition Warehouse de-identified 100% Medicare database (01/2010-12/2016). MDD was defined as ≥1 MDD diagnosis and ≥1 claim for an antidepressant. Patients initiated on a third antidepressant following two antidepressant treatment regimens of adequate dose and duration were considered to have TRD. The index date was defined as the date of the first antidepressant claim for the TRD and non-TRD MDD cohorts, and as a randomly imputed date for the non-MDD cohort. Patients with TRD were matched 1:1 to non-TRD MDD patients and randomly selected non-MDD patients based on propensity scores. Analyses were also performed for a subset of patients aged ≥65.ResultsOf 29,543 patients with MDD, 3,225 (10.9%) met the study definition of TRD; 157,611 were included in the non-MDD cohort. Matched patients with TRD and non-TRD MDD were, on average, 58.9 and 59.0 years old, respectively. The TRD cohort had higher per-patient-per-year (PPPY) HRU than the non-TRD MDD (e.g., inpatient visits: incidence rate ratio [IRR] = 1.36) and non-MDD cohorts (e.g., inpatient visits: IRR = 1.84, all PConclusionAmong Medicare-insured patients, those with TRD had higher HRU and costs compared to those with non-TRD MDD and non-MDD.

Objective Our objective was to assess healthcare resource utilization (HRU) and costs among patients with major depressive disorder (MDD) with and without treatment-resistant depression (TRD) and those without MDD in US Integrated Delivery Networks (IDNs). Methods This was a retrospective matched-cohort study. The Optum© Integrated Claims Electronic Health Record de-identified database was used to identify adult patients with TRD (January 2011–June 2017) across US IDNs. TRD patients were propensity score matched 1:1 with non-TRD MDD and non-MDD patients on demographics. Rates of HRU and costs were compared up to 2 years following the first antidepressant pharmacy claim (or randomly imputed date for non-MDD patients) using negative binomial and ordinary least squares regressions, respectively, with 95% confidence intervals (CIs) from nonparametric bootstraps (costs only) adjusted for baseline comorbidity index and costs. Results All 1582 TRD patients were matched to non-TRD MDD and non-MDD patients and evaluated. TRD patients were on average 46 years old, and 67% were female. Mean duration of observation was 20.1, 19.6, and 17.9 months in the TRD, non-TRD MDD, and non-MDD cohorts, respectively. Patients with TRD had significantly higher rates of HRU than did non-TRD MDD patients (inpatient visits 0.35 vs. 0.16 per patient per year [PPPY]; adjusted incidence rate ratio [IRR] 2.04 [95% CI 1.74–2.39]) and non-MDD patients (0.35 vs. 0.09 PPPY, adjusted IRR 3.05 [95% CI 2.54–3.66]). TRD patients incurred significantly higher costs PPPY than did non-TRD MDD patients ($US25,807 vs. 13,701, adjusted cost difference $US9479 [95% CI 7071–11,621]) and non-MDD patients ($US25,807 vs. 8500, adjusted cost difference $US11,433 [95% CI 8668–13,876]). Conclusions HRU and costs associated with TRD are significant in US IDNs. Electronic supplementary material The online version of this article (10.1007/s41669-019-0154-z) contains supplementary material, which is available to authorized users.

[This corrects the article DOI: 10.1371/journal.pone.0223255.].

This retrospective longitudinal cohort study aimed to compare treatment patterns, healthcare resource utilization (HRU), and costs in patients with schizophrenia treated with second-generation antipsychotic long-acting injectables (SGA-LAIs): biweekly risperidone LAI versus once-monthly paliperidone palmitate.Patients who initiated risperidone LAI or paliperidone palmitate between 1 July 2007 and 31 December 2012 (index date) were identified from the Truven MarketScan Commercial, Medicare Supplemental, and Medicaid Multi-State insurance databases. Outcomes were assessed 12 months after the index date. Propensity score matching (1:1) based on patients' demographics and comorbidities was conducted. Outcome differences between the two cohorts were evaluated using t-tests for continuous variables, chi-square tests for categorical variables, and Wilcoxon rank-sum tests for count and cost variables. Regression models estimated the difference in medication use and adherence, likelihood of HRU, number of HRU events, and healthcare costs when comparing risperidone LAI versus paliperidone palmitate, while further adjusting for patient characteristics and pre-index HRU.Patient characteristics were well balanced between the two cohorts (n = 499 each). Significantly lower discontinuation rates (36.5% vs. 53.3%; p 0.001) and longer days of LAI coverage (233.6 vs. 131.7 days; p 0.001) were observed in the paliperidone palmitate cohort versus the risperidone LAI cohort, respectively. Patients treated with paliperidone palmitate were 12.5 (95% confidence interval [CI]: 9.0-17.8) and 11.7 (95% CI: 8.0-17.4) times more likely to be adherent based on medication possession ratio and proportion of days covered, respectively (p 0.001). Patients treated with paliperidone palmitate had reduced likelihood of hospitalization (adjusted odds ratio [95% CI]: 0.72 [0.55-0.95]), fewer emergency department (ED) visits (adjusted incidence rate ratio [aIRR]: 0.67 [0.61-0.73]) and reduced length of inpatient stay (aIRR: 0.86 [0.82-0.90]), which resulted in lower monthly inpatient hospitalization costs (-$77.58; p = 0.038) and ED visits (-$9.77; p = 0.021) relative to risperidone LAI.Pharmacy costs were derived from health plan payment in the claims data and do not account for any discounts or rebates. This may have overestimated the branded drug costs in this analysis.These findings highlight the value of once-monthly paliperidone palmitate in the treatment of patients with schizophrenia.

This study assessed real-world treatment patterns and antipsychotic (AP) medication adherence among commercially insured US patients with schizoaffective disorder (SCA). Continuously insured adults aged 18 years or older with a diagnosis of SCA from January 1, 2009, to December 31, 2012, were identified from the Clinformatics Data Mart database. Patients were categorized into 2 cohorts: incident or prevalent SCA. Demographics and clinical characteristics were evaluated during the baseline period. Use of psychiatric medications and adherence to AP medications were evaluated during a 12-month follow-up period after index diagnosis of SCA. Of the overall study population (N = 2713; mean age, 40.2 y; 52.7% female), 1961 patients (72.3%) (mean age, 38.7 y; 51.3% female) had incident SCA, and 752 patients (27.7%) (mean age, 43.9 y; 56.5% female) had prevalent SCA. Antipsychotics were used by 74.8% of patients in the overall study population during the follow-up period. The most commonly prescribed oral AP was risperidone (23.9%), followed by quetiapine (21.4%) and aripiprazole (20.4%). Use of any long-acting injectable APs in the overall study population during the follow-up period was less than 3%. A total of 49.0% and 38.0% of the overall study population had medication possession ratios and proportion of days covered for APs of 80% or greater, respectively. Overall use of long-acting injectable APs for the treatment of SCA is low, and adherence to AP medications, measured by both medication possession ratio and proportion of days covered, is suboptimal among patients with SCA in the real-world setting.

Among patients with major depressive disorder (MDD), those with treatment-resistant depression (TRD) have a higher economic burden. However, the healthcare resource utilization (HRU) and costs may vary by severity status in TRD patients. This study quantified the incremental economic burden of severity status in TRD patients.In a US database of privately insured employees and dependents (07/01/2009-03/31/2015), a claims-based algorithm identified adult TRD patients who were stratified into mild, moderate, and severe cohorts based on the information in the last observed MDD ICD-9-CM code. HRU and costs of moderate and severe cohorts were compared to those of the mild cohort during the 2-year follow-up after the first antidepressant claim.Among 6411 TRD patients, 455 (7.1%) were identified as mild, 2153 (33.6%) as moderate, and 1455 (22.7%) as severe. Moderate and severe patients compared to mild had 45% and 150% more inpatient admissions, 65% and 164% more inpatient days, 18% and 54% more emergency department visits and 8% and 10% more outpatient visits per-patient-per-year (PPPY), respectively (all-cause; all p 0.05). Mean all-cause direct total healthcare costs were $12,123, $16,885, and $18,911 PPPY in mild, moderate, and severe patients, respectively. The all-cause total healthcare cost differences adjusted for baseline characteristics amounted to $3455 in moderate and $5150 in severe versus mild patients, respectively (PPPY; all p 0.05).Not all TRD patients had a severity specifier; the severity specifier was not cross-validated against a depression scale.Increased severity status is associated with incremental economic burden in TRD patients.

Objectives: To compare comorbidity-related outcomes, adherence to antipsychotics (APs), healthcare resource utilization (HRU), and costs pre- and post-transition to once-every-3-months paliperidone palmitate (PP3M) in commercially-insured patients with schizophrenia. Methods: Adults with ≥1 claim for PP3M, ≥2 schizophrenia diagnoses, and adequate treatment with once-monthly paliperidone palmitate (PP1M; i.e. no gap of >45 days in PP1M coverage for ≥4 months, same PP1M dosage for the last two PP1M claims, and appropriate PP1M to PP3M dosing conversion) were selected from the IQVIA PharMetrics Plus database (May 2014–February 2018). Generalized estimating equation models adjusted for repeated measurements were used to compare patient characteristics, adherence to APs, HRU, and costs during the 6-month period pre- vs post-transition to PP3M. Results: Of 152 included patients, the mean age was 41.0 years and 36.2% were females. Post-PP3M transition, patients were less likely to have a claim with a diagnosis for substance-related and addictive disorders (odds ratio [OR] = 0.57), psychoses (OR = 0.57), diabetes without chronic complication (OR = 0.72), and drug abuse (OR = 0.64; all p p = .007), compared to the period pre-PP3M transition. There was no significant difference in HRU pre- vs post-transition. All-cause total (mean monthly cost difference [MMCD] = $242), pre-rebate pharmacy (MMCD = $65), and medical costs (MMCD = $176) remained similar pre- vs post-transition (all p > .05). Conclusions: Transitioning to PP3M was associated with an improvement in adherence and in comorbidity-related outcomes related to substance-related and addictive disorders, psychoses, diabetes without chronic complication, and drug abuse. These findings suggest PP3M may enhance comorbidity-related outcomes and adherence while remaining cost neutral.

Objectives The aim was to compare adherence to antipsychotics (APs), healthcare resource utilization (HRU), and costs before and after once-every-3-months paliperidone palmitate (PP3M) initiation in patients with schizophrenia. Methods Medicaid data (Iowa, Kansas, and Missouri; 1/2014–3/2017) were used to identify adults with at least one PP3M claim, ≥ 12 months of pre-index enrollment, and at least two schizophrenia diagnoses. Adequate treatment with once-monthly paliperidone palmitate (PP1M) was required pre-PP3M transition. Generalized estimating equations were used to assess linear trends in adherence to APs, HRU, and costs over the four quarters pre-PP3M transition, and to compare monthly HRU and costs 6 months pre- and 12 months post-PP3M transition as well as adherence to APs 12 months pre- and post-PP3M transition. Results Among 324 patients initiated on PP3M, the mean age was 41.4 years and 36.1% were females. Over the four quarters pre-PP3M transition, the monthly number of emergency room visits, medical costs, and inpatient costs decreased, while pharmacy costs and adherence to APs increased. For patients with ≥ 12 months of follow-up (n = 151), adherence to APs (66.2 vs. 70.2%, p = 0.3758), total (US$3371 vs. US$3456; p = 0.7000), pharmacy (US$1805 vs. US$1870; p = 0.2960), and medical costs (US$1565 vs. US$1586; p = 0.9040) remained similar pre- and post-PP3M transition, while mean monthly number of 1-day mental institute visits (1.71 vs. 1.51; p

Purpose The aim of this study was to conduct a systematic literature review on the burden of schizophrenia in privately insured US patients. Materials and methods A systematic literature review of English language peer-reviewed journal articles of observational studies published from 2006 to 2016 was conducted using EMBASE/MEDLINE databases. Abstracts covering substantial numbers of patients with schizophrenia or schizoaffective disorder (i.e., N ≥ 100) were included for full-text review. Articles that did not clearly specify private insurance types were excluded. Results A total of 25 studies were reviewed; 10 included only privately insured patients; and 15 included a mix of different types of insurance. The review of the clinical burden of schizophrenia revealed the following: compared to patients with no mental disorders, those with schizophrenia had significantly increased odds of systemic disorders and both alcohol and substance abuse. Antipsychotic (AP) adherence was low, ranging from 31.5% to 68.7%. The medication possession ratio for AP adherence ranged from 0.22 to 0.73. The review of the health economic burden of schizophrenia revealed the following: patients with a recent (vs. chronic) diagnosis of schizophrenia had significantly higher frequencies of emergency department visits and hospitalizations and greater length of stay (LOS) and total annual per-capita costs. Mean all-cause hospitalizations and LOS decreased significantly after (vs. before) initiating long-acting injectable APs (LAIs). Patients also had significantly decreased mean all-cause, and schizophrenia-related, hospitalization costs after initiating LAIs. Total direct per-capita costs of care (but not pharmacy costs) for patients who were nonadherent to their oral APs within the first 90 days of their index event were significantly higher (vs. early adherent patients). Despite these potential benefits, only 0.25%-13.1% of patients were treated with LAIs across all studies. Conclusion Privately insured US patients with schizophrenia experience a substantial clinical and health economic burden related to comorbidities, acute care needs, nonadherence, and polypharmacy and have relatively low use of LAIs. Further study is warranted to understand prescribing patterns and clinical policies related to this patient population.

This study evaluated the biopsychosocial characteristics of adults undergoing substance abuse evaluation with potential schizophrenia/psychotic disorder, or possible schizophrenia/psychosis-like symptoms, compared with those with no schizophrenia/psychosis-like symptoms. A cross-sectional, observational study examined 170,201 adults, aged 18 to 30, who completed the Addiction Severity Index-Multimedia Version (ASI-MV). Approximately 10% were classified as having possible schizophrenia/psychosis-like symptoms or potential schizophrenia/psychotic disorder. These patients were more likely to exhibit moderate to extreme severity on employment, medical, legal, substance use, social, and psychiatric status than nonsymptomatic patients. The potential schizophrenia or psychotic disorder cohort was also more likely to have ever experienced physical abuse (odds ratio [OR] = 4.30, 95% confidence interval [CI] = 4.12-4.48) and/or sexual abuse (OR = 4.32, 95% CI = 4.15-4.51) versus the no schizophrenia/psychosis-like symptoms cohort. Findings support a recommendation for routine screening for mental health issues, particularly schizophrenia/psychosis-like symptoms, for adults entering substance use disorder treatment settings. This may increase the likelihood of appropriate and earlier intervention.

The aim of this article was to describe and compare treatment patterns, health care resource utilization (HRU), and health care costs before and after transition in veterans with schizophrenia who were transitioned from paliperidone palmitate given once monthly (PP1M) to paliperidone palmitate given every 3 months (PP3M) according to prescribing-information guidelines.This retrospective, longitudinal study was conducted using electronic health records data from the Veterans Health Administration (VHA). Veterans were eligible for inclusion if they were aged 18years or older, had ≥1 dispensation of PP3M, were enrolled with VHA benefits for ≥24 months prior to transition to PP3M, had ≥1 schizophrenia diagnosis, were transitioned to PP3M according to prescribing-information guidelines (operationalized as no gap in PP1M treatment of45days during the 4 months prior to PP3M transition, with the same dosage in the last 2 PP1M dispensations), and had appropriate dose conversion. Treatment patterns, HRU, and costs 6 months pre and post PP3M transition were described and compared using the McNemar test and the Wilcoxon signed rank test.Of the 277 veterans identified, the majority were men (92.8%); the median age was 56.5years. Among 197 veterans who had at least 6 months of follow-up pre and post PP3M transition, oral antipsychotic use was significantly decreased (from 49.7% to 43.1%; P = 0.0326). Additionally, the mean number of days spent in an inpatient setting (41.4vs 21.6; P = 0.0164), the mean number of outpatient visits per patient (31.0vs 25.6; P0.0001), and the mean total health care costs ($27,745vs $23,772; P = 0.0050) were significantly decreased.After transitioning to PP3M treatment, veterans had significantly reduced use of oral antipsychotics, HRU, and costs. Although generalizability may be limited due to the veteran population and to those who transitioned according to PP3M prescribing guidelines, future studies in other patient populations may be used to extend these conclusions.

The objective of this economic model was to estimate the difference in medical costs among patients treated with paliperidone palmitate once-monthly injectable antipsychotic (PP1M) vs placebo, based on clinical event rates reported in the 15-month randomized, double-blind, placebo-controlled, parallel-group study of paliperidone palmitate evaluating time to relapse in subjects with schizoaffective disorder.Rates of psychotic, depressive, and/or manic relapses and serious and non-serious treatment-emergent adverse events (TEAEs) were obtained from the long-term paliperidone palmitate vs placebo relapse prevention study. The total annual medical cost for a relapse from a US payer perspective was obtained from published literature and the costs for serious and non-serious TEAEs were based on Common Procedure Terminology codes. Total annual medical cost differences for patients treated with PP1M vs placebo were then estimated. Additionally, one-way and Monte Carlo sensitivity analyses were conducted.Lower rates of relapse (-18.3%) and serious TEAEs (-3.9%) were associated with use of PP1M vs placebo as reported in the long-term paliperidone palmitate vs placebo relapse prevention study. As a result of the reduction in these clinical event rates, the total annual medical cost was reduced by $7140 per patient treated with PP1M vs placebo. One-way sensitivity analysis showed that variations in relapse rates had the greatest impact on the estimated medical cost differences (range: -$9786, -$4670). Of the 10,000 random cycles of Monte Carlo simulations, 100% showed a medical cost difference$0 (reduction) for patients using PPIM vs placebo. The average total annual medical differences per patient were -$8321 for PP1M monotherapy and -$6031 for PPIM adjunctive therapy.Use of PP1M for treatment of patients with schizoaffective disorder was associated with a significantly lower rate of relapse and a reduction in medical costs compared to placebo. Further evaluation in the real-world setting is warranted.

OBJECTIVE To compare treatment patterns and Medicaid spending between schizophrenia patients initiating once-monthly paliperidone palmitate (PP1M) and oral atypical antipsychotics (OAAs) within four comorbid populations: cardiovascular disease (CVD), diabetes, hypertension and obesity. METHODS Five-state Medicaid data identified comorbid adults with schizophrenia initiating PP1M or OAAs (index) from September 2009 balanced with inverse probability of treatment weighting. Chi-squared and t-tests compared index antipsychotic (AP) exposure (no gap >90 days) duration, AP polypharmacy, and index AP adherence (proportion of days covered ≥80%) and persistence (no gap ≥60 days) at 12 months post-index. Linear models with a non-parametric bootstrap procedure compared costs. RESULTS PP1M patients consistently had longer index AP exposure (e.g. CVD: 244 vs. 189 days; p

Objectives: To compare comorbidity-related outcomes, adherence to APs, healthcare resource utilization (HRU), and costs pre- and post-transition to once-every-three-month paliperidone palmitate (PP3M) in commercially-insured patients with schizophrenia. Methods: Adults with ≥1 claim for PP3M, ≥2 schizophrenia diagnoses, and adequate treatment with once-monthly paliperidone palmitate (PP1M; i.e., no gap of >45 days in PP1M coverage for ≥4 months, same PP1M dosage for the last two PP1M claims, and appropriate PP1M to PP3M dosing conversion) were selected from the IQVIATM PharMetrics Plus database (05/2014-02/2018). Generalized estimating equation models adjusted for repeated measurements were used to compare patient characteristics, adherence to antipsychotics, HRU, and costs during the 6-month period pre- versus post-transition to PP3M. Results: Of 152 included patients, mean age was 41.0 years and 36.2% were females. Post-PP3M transition, patients were less likely to have a claim with a diagnosis for substance-related and addictive disorders (odds ratio [OR] = 0.57), psychoses (OR =0.57), diabetes without chronic complication (OR =0.72), and drug abuse (OR =0.64; all P P = 0.007), compared to the period pre-PP3M transition. There was no significant difference in HRU pre- versus post-transition. All-cause total (mean monthly cost difference [MMCD]=$242), pre-rebate pharmacy (MMCD=$65), and medical costs (MMCD=$176) remained similar pre- versus post-transition (all P > 0.05). Conclusions: Transitioning to PP3M was associated with an improvement in adherence and in comorbidity-related outcomes related to substance-related and addictive disorders, psychoses, diabetes without chronic complication, and drug abuse. These findings suggest PP3M may enhance comorbidity-related outcomes and adherence while remaining cost neutral.

Ethics committees by study site. (DOCX 13Â kb)

Schizophrenia is a serious public health problem that affects ∼1% of the US population.To examine treatment patterns and evaluate healthcare resource utilization (HRU) and costs among young adults (18-35 years) with schizophrenia who were early in the disease.Patients aged 18-64 years with ≥2 schizophrenia diagnoses in the identification period (January 1, 2012-September 30, 2015) and continuous enrollment for ≥12 months pre- and post-index date were identified from the OptumInsight Clinformatics DataMart. Demographics, clinical characteristics, HRU, costs, and treatment patterns were compared between schizophrenia and non-schizophrenia "controls" cohorts and between young (18-35 years) and older adults (36-64 years) with schizophrenia.Among 9,889 schizophrenia patients, 23.70% were young adults (aged 18-35), had higher all-cause per-patient-per-year (PPPY) costs ($22,338 vs $7,332; p .0001), higher inpatient costs ($8,857 vs $1,289; p .0001), and longer inpatient length-of-stay (LOS) (5.0 vs 0.4 days, p .0001; adjusted incidence rate ratio [aIRR] = 12.8; 95% confidence interval [CI] = 11.5-14.3) than controls. Among young adults with schizophrenia, there were more mental-health-related and fewer non-mental-health-related diagnoses compared to older adults with schizophrenia; 63.40% were male. Young adults with schizophrenia incurred higher inpatient costs ($15,692 vs $10,274; p .0001) and longer inpatient LOS (9.6 vs 5.9 days, p .0001; aIRR = 1.6; 95% CI = 1.4-1.8) compared to older adults with schizophrenia. A substantial proportion of patients were treated with oral antipsychotics vs long-acting injectables in both cohorts (young adults: 98.72% vs 9.71%; older adults: 98.10% vs 13.31%).Claims data are collected for payment and not research. The presence of a prescription claim does not indicate medication was consumed or taken as prescribed.The economic burden for schizophrenia patients is substantial, especially among young adults. Based on this analysis, further research is warranted to better understand the association between adherent treatment patterns earlier in the disease and long-term health outcomes among patients with schizophrenia.

Outpatient utilization at enrollment and at the 12-month follow-up visit. (DOCX 14Â kb)

Since May 2015, adult patients with schizophrenia adequately treated with once monthly paliperidone palmitate (PP1M) may be transitioned to once-every-three-months paliperidone palmitate (PP3M). This study aims to describe baseline characteristics and treatment patterns of patients with schizophrenia initiated on PP3M in a real-world setting.Pharmacy and medical claims from May 2014 to September 2016 for adult patients with schizophrenia initiated on PP3M (index date) in the Symphony Health Solutions database were analyzed. The cohort consisting of all patients and the one restricted to those transitioning from PP1M as per prescribing guideline recommendations were considered. Baseline characteristics were assessed during the 12 month baseline period. PP1M treatment patterns, proportion of days covered (PDC) by mental-health-related medications, and healthcare resource utilization (HRU) patterns were evaluated for each baseline quarter. PP3M treatment patterns were assessed post-index.Among the 1545 adult patients initiated on PP3M who formed the first cohort, 68.8% transitioned from PP1M based on prescribing guidelines and on an adaptation of the strict clinical trial protocol for PP1M to PP3M transition, forming the second cohort. In both cohorts, the proportion of patients with a PDC ≥80% for antipsychotics, antidepressants, anxiolytics, and mood stabilizers increased while the proportion of patients with ≥1 emergency room, inpatient, or outpatient visit decreased in baseline quarters closer to PP3M initiation. Among patients with ≥4 months of follow-up after the first dose, 85-88% had a second dose. Similarly, among those with ≥4 months of follow-up after the second dose, 87-90% received a third dose.Patients initiated on PP3M demonstrated decreased HRU and increased adherence in quarters closer to PP3M initiation, and were persistent on their PP3M treatment.

Almost half of all patients diagnosed with schizophrenia have a history of substance abuse (SA). However, data on treatment of schizophrenia with paliperidone palmitate (PP) among patients with comorbid SA are limited. The objective of this study was to compare all-cause and SA-related health care resource utilization and costs in veterans with schizophrenia and co-occurring SA who were treated with PP versus oral atypical antipsychotics (OAAs).Veterans Health Administration electronic health record data were used to conduct a retrospective longitudinal study in veterans with schizophrenia who initiated PP or OAA between January 1, 2010 and June 30, 2016, had ≥12 months of enrollment before treatment initiation (baseline), were diagnosed with SA, and had ≥1 Global Assessment of Functioning score during baseline. Differences in baseline characteristics were adjusted for using inverse probability of treatment weighting. Adjusted cost differences and incidence rate ratios (IRR) for the association between PP versus OAA and all-cause and SA-related health care costs and health care resource utilization in the 12 months after treatment initiation were estimated with corresponding 95% CIs using weighted linear and Poisson regression models, respectively.Of 6872 veterans in the study, 1684 (25%) and 5188 (75%) were treated with PP and OAA, respectively. After adjustment, PP was associated with fewer all-cause inpatient (IRR = 0.88; 95% CI, 0.85 to 0.90), mental health-related inpatient (IRR = 0.88; 95% CI, 0.85 to 0.91), and long-term care stays (IRR = 0.53; 95% CI, 0.44 to 0.64), but more frequent mental health intensive case management visits (IRR = 1.51; 95% CI, 1.49 to 1.53) compared with OAA (all P0.001). Similarly, PP was associated with significantly lower rates of SA-related inpatient stays (IRR = 0.80; 95% CI, 0.77 to 0.83), mental health stays (IRR = 0.85; 95% CI, 0.82 to 0.88), long-term care stays (IRR = 0.22; 95% CI, 0.15 to 0.32), and outpatient visits (IRR = 0.78; 95% CI, 0.77 to 0.79) than OAA (all P0.001). Relative to OAA, patients treated with PP also had lower mean annual all-cause (cost difference = -$10,473; 95% CI, -$17,827 to -$3491) and SA-related (cost difference = -$8457; 95% CI, -$12,710 to -$3638) medical costs (all P0.001).PP was associated with significant total medical cost savings resulting from fewer hospitalizations and lower rates of SA-related health care resource utilization compared with OAA in patients with schizophrenia and comorbid SA. Thus, PP appears to be a valuable treatment option for patients in this subpopulation.

Background Nonadherence to antipsychotic treatment increases the likelihood of relapse and progressive symptomatology in patients with schizophrenia. Atypical long-acting injectables, including paliperidone palmitate (PP), may increase adherence and improve symptoms. This study compared and assessed predictors of treatment patterns and symptom remission among schizophrenia patients treated with PP versus atypical oral antipsychotic therapy (OAT) in community behavioral health organizations (CBHOs). Methods This retrospective cohort analysis evaluated 763 patients with schizophrenia and new (PP-N; N = 174) or continuing (PP-C; N = 308) users of PP, or new users of OAT (N = 281) at enrollment in the REACH-OUT study (2010–2013). Treatment outcomes assessed at 1 year were discontinuation, and adherence, measured by proportion of days covered (PDC) or medication possession ratio (MPR). Remission status was assessed using the Structured Clinical Interview for Symptoms of Remission (SCI-SR). A machine learning platform, Reverse Engineering and Forward Simulation (REFS™), was used to identify predictors of study outcomes. Multivariate Cox and generalized linear regressions estimated the adjusted hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals. Results Among PP-N users, 27% discontinued their initial treatment regimen versus 51% (p

The importance of improvement in the ejection fraction to the prognosis of revascularized patients with ischaemic left ventricular (LV) dysfunction is uncertain.Eighty-seven patients with ischaemic LV dysfunction (mean ejection fraction 29 ± 8% by biplane Simpson's) had dobutamine echocardiography before revascularization (coronary bypass graft surgery-81, percutaneous intervention-6). Follow-up echocardiograms were performed a mean of 4.8 ± 6.2 months after revascularization. An 8% increase in the ejection fraction was considered significant (two times the inter-observer difference of 3.7%). Patients were followed for cardiac death. During a mean follow-up of 5.2 ± 3.9 years, there were 20 (23%) cardiac deaths. Class 3/4 heart failure, increasing low-dose wall motion score, increasing % non-viable myocardium, and digoxin use in follow-up were univariate predictors of death. Beta-blocker use, ejection fraction improvement, angina, aspirin use, and increasing fractional shortening were univariate predictors of survival. Ejection fraction improvement [P= 0.02, hazard ratio (HR) = 0.26], digoxin use in follow-up (P= 0.006, HR = 5.85), and low-dose wall motion score (P= 0.017, HR = 4.78) were independent predictors of outcome. In step-wise analysis, low-dose wall motion score added incremental prognostic value to ejection fraction improvement (P= 0.003), and digoxin use in follow-up (P= 0.003) added incremental value to a low-dose score and ejection fraction improvement.Ejection fraction improvement is an independent predictor of long-term outcome in revascularized patients but viability (low-dose wall motion score) and digoxin use in follow-up are also independent predictors and add incremental prognostic value to ejection fraction improvement.

While atypical long-acting injectable antipsychotics (LAIs) offer the potential for increased adherence, access to medication poses challenges that may hinder their use. Janssen Connect * *Janssen Connect is a registered trade name of Janssen Scientific Affairs, LLC, Titusville, NJ, USA. (JC), a comprehensive information and assistance program, was designed to help patients who received a Janssen LAI initiate and maintain treatment after their health care professional (HCP) determined that the medication was the most clinically appropriate option. We conducted a formative and impact evaluation on early medication adherence of patients enrolled in JC and prescribed paliperidone palmitate.Using the program administrative files (December 2010-April 2014), 9354 patients whose HCP ordered paliperidone palmitate were included. Patient demographics, clinical characteristics, and request of JC program offerings were reported overall, and compared between patients requesting the injection center versus those who did not. Medication adherence based on the first 6 months of treatment while in the program and defined as achieving ≥80% proportion of days covered (PDC) was measured for patients receiving ≥2 paliperidone palmitate injections (n = 2659). Logistic models evaluated the association between requests for injection centers on medication adherence.Mean age of program enrollees was 40.6 (standard deviation = 13.9 years), 59.3% were men, and 42.5% were Medicare covered. While in the program, 79.9% did not experience a medication gap of ≥7 weeks and 87.0% achieved adherence. Injection center request was associated with medication adherence (adjusted odds ratio (aOR) ≤5 months: 0.03; 95% confidence interval (CI): 0.02-0.05; ≥6 months: aOR: 4.16; 95% CI: 2.72-6.36).The data sources used were designed for program implementation and not for research purposes.The high percentage of patients requesting injection center support and medication shipment in addition to other insurance-related program offerings signals the need for and value of a comprehensive support program for patients seeking LAI therapy. Providing patients with the option of alternative and more conveniently located injection centers may help them start and maintain their treatment.

Second-generation long-acting injectable therapies (SGA-LAIs) may reduce health care resource utilization (HRU) and health care costs compared with daily oral atypical antipsychotics (OAAs) in patients with schizophrenia due to reduced dosing frequency, delivery/monitoring by a health care provider, and improved adherence. The aim of the present study was to compare treatment patterns, HRU, and Medicaid spending in patients with schizophrenia initiated on SGA-LAIs (overall and according to agent) versus OAAs.Medicaid claims data (2010-2015) from 6 states were used to identify adult schizophrenia patients initiated on SGA-LAIs or OAAs. Treatment patterns (proportion of days covered [PDC] ≥80% and persistence [no gap ≥30, 60, or 90 days] to index treatment), HRU, and costs were evaluated over 12 months and compared by using multivariable logistic, Poisson, and ordinary least squares regression models, respectively. P values for HRU and cost outcomes were obtained from a nonparametric bootstrap procedure. Costs (2015 US dollars) reflect the Medicaid payer's perspective before any rebate.Overall, 3307 and 21,355 patients initiated SGA-LAIs and OAAs, respectively (paliperidone palmitate LAI [PP-LAI; n = 2182], risperidone LAI [n = 968], aripiprazole LAI [n = 108], and olanzapine LAI [n = 49]). During follow-up and compared with OAA patients, SGA-LAI patients were more likely to reach PDC ≥80% (odds ratio [OR], 1.28; P0.001) and be persistent (eg, no gap ≥60 days; OR, 1.45; P0.001) to the index treatment. Relative to OAA patients, SGA-LAI patients had fewer long-term care days (incidence rate ratio [IRR], 0.75; P0.001) and home care visits (IRR, 0.75; P0.001) but more mental health institute (IRR, 1.16; P0.001) and 1-day mental health institute (IRR, 1.16; P0.001) admissions. Moreover, PP-LAI patients had fewer inpatient days (IRR, 0.78; P = 0.004) versus OAA patients. SGA-LAI patients had lower medical costs (mean monthly cost difference [MMCD], -$168; P0.001) than OAA patients, offsetting more than one half of the higher pharmacy costs (MMCD, $271; P0.001). Compared with OAAs, only PP-LAI was associated with significant medical cost savings (MMCD, -$225; P0.001).Medicaid beneficiaries with schizophrenia initiated on SGA-LAIs had better adherence and persistence to therapy over 12 months than patients initiated on OAAs. SGA-LAIs, particularly PP-LAI, were associated with lower medical costs that successfully offset more than one half of the higher pharmacy costs relative to OAA.

Filamenting temperature-sensitive mutant (FtsZ) is a novel target for the treatment of tuberculosis. A series of (R)-2-(4′-chlorophenyl)-3-(4′-nitrophenyl)-1,2,3,5-tetrahydrobenzo[4,5] imidazo[1,2-c]pyrimidin-4-ol derivatives were designed and docked on the FtsZ protein crystal structure (PDB Id: 1RLU, resolution 2.08 A). Compound 7t showed the highest docking score and H-bond interaction with Arg140 and Gly19. Our strategy for synthesis of (R)-2-(4′-chlorophenyl)-3-(4′-nitrophenyl)-1,2,3,5-tetrahydrobenzo[4,5]imidazo[1,2-c]pyrimidin-4-ol derivatives from o-phenylenediamine as illustrated in scheme. All the synthesized compounds were characterized by FTIR, Mass spectra, 1H NMR, 13C NMR, elemental analysis and purity was confirmed by HPLC and LCMS. Compound 7g was also confirmed by single crystal X-ray analysis. The in silico results are also validated with in vitro antitubercular activity of compound 7t. Compound 7b exhibited in vitro antitubercular activity 3.13 μg/mL and 4.7 μg/mL whereas compound 7t exhibited in vitro antitubercular activity 6.25 μg/mL and 9.4 μg/mL using GAST/Fe medium after week 1 and week 2 respectively against Mycobacterium tuberculosis H37Rv. Medium 7H9/ADC/Tween was found to be very less effective for in vitro antitubercular activity of all the benzimidazole derivatives. Assays for in vitro cytotoxicity against VERO cells of all the synthesized compounds was found to be very less cytotoxic.

To compare the incidence of contrast-induced nephropathy (CIN) and vascular complications in patients undergoing cardiac catheterization using traditional manual contrast injection techniques with those in which an automated contrast injector device was used.It has been suggested that use of automated contrast injectors in coronary interventions could reduce complications by reducing contrast volume usage and allowing the use of smaller sheaths.This was a retrospective cohort study with review of patient's electronic medical charts and the Heartbase registry. Complete data were available for 13107 patients between 1999 and 2009. Of those patients, 5137 procedures were performed with traditional manual contrast injection and 7970 procedures used automated contrast injection. The CIN event rate and vascular complication rates were compared between patients who underwent catheterization using these differing techniques.Overall, the incidence of CIN was comparable in traditional and automated contrast injector assisted catheterizations (9.07% vs 8.73%; P=.5). However, for the subgroup of patients that had a diagnostic cardiac catheterization and went on to have an ad hoc angioplasty, incidence of CIN was much lower in the automated contrast injector group (7.04% vs 5.50%; P=.007). The incidence of vascular complications was lower in the automated contrast injector group vs the traditional method (2.85% vs 2.17%; P=.02), irrespective of an ad hoc angioplasty.Use of automated contrast injectors resulted in a significant decrease in vascular complications across all cardiac catheterizations. Additionally, there was a significant decrease in CIN when the automated contrast injector was used for catheterizations that included a percutaneous coronary intervention.

Purpose: To compare medication adherence rates for once-weekly (QW) versus once-daily (QD) dosing regimens in patients with chronic disease. Methods: A systematic literature review was conducted to identify articles published in Englishlanguage journals examining the rate of adherence to medications in patients with chronic disease. Relevant studies were identified from January 2002 through August 2013 using PubMed, EMBASE, and the Cochrane Library databases. Twenty-two published observational studies reporting adherence were identified by 2 independent reviewers, and 7 articles reported relevant measures for analysis. All studies were conducted in patients with osteoporosis. Metaanalyses estimated (1) mean difference (MD) in adherence (defined using the mean medication possession ratio [MPR]) between QW and QD dosing groups and (2) odds ratio (OR) for adherence (defined using an MPR cutoff of Z80%) for QW versus QD dosing. Heterogeneity was assessed using Cochran’ sQ and I 2 values, and meta-analyses used both fixed- and random-effects models. Findings: The random-effects meta-analysis revealed a significantly greater MPR with QW compared with QD dosing (pooled MD ¼ 12.29%; 95% CI, 10.76%–13.82%; n ¼ 9 [data reported in 7 publications]). Because of the high level of heterogeneity (I 2 ¼ 83.4%), the fixed-effects model results were not appropriate to report for the pooled MD. When examining the OR for adherence, both fixed- and random-effects models provided similar results due to the low level of heterogeneity (I 2 ¼ 7.9%; n ¼ 5 [data reported in 3 publications]). Using either model, the pooled odds of being adherent (MPR Z80%) in the QW dosing group was approximately 1.9 times the odds in the QD dosing group (random-effects OR ¼ 1.90; 95% CI, 1.81–2.00; fixed-effects OR ¼ 1.92; 95% CI, 1.84–1.99). Implications: In our meta-analysis, QW dosing was associated with better adherence levels and greater odds of being adherent compared with QD dosing in patients with osteoporosis. (Clin Ther. 2015;37:1813– 1821) & 2015 Elsevier HS Journals, Inc. All rights reserved.

We appreciate the insightful comments of Shah regarding geometry and function for prognostic assessment in ischaemic cardiomyopathy.1 We agree with him about the prognostic importance of end-systolic volume (ESV). As Shah points out, in our investigation, there was a trend towards larger baseline ESV before revascularization in patients with cardiac death ( P = 0.052).2 For the purposes of responding to Shah's query, we assessed the prognostic value of ESV following revascularization. Larger ESV on follow-up echocardiography was a univariate predictor ( P = 0.003) of cardiac death. However, neither baseline nor follow-up ESV was an independent predictor of outcome …

A 49 year old female with repaired tetralogy of Fallot and previously normal exercise capacity presented with abdominal pain, fatigue, and dyspnea three months after a visit to Peru. Initially she was treated for possible pancreatitis without improvement. Physical exam revealed jugular venous