School Vaccine Coverage and Medical Exemption Uptake After the New York State Repeal of Nonmedical Vaccination Exemptions.

Importance: Although New York State (NYS) recently adopted legislation eliminating nonmedical vaccination exemption options from school-entry requirements, the implications of the law for school vaccine coverage and medical vaccine exemption uptake have not been examined. Objective: To evaluate the implications of the repeal of school-entry nonmedical vaccination exemptions for vaccine coverage and medical exemption uptake at NYS schools outside of New York City (NYC). Design, Setting, and Participants: This cohort study had an interrupted time-series design and used generalized estimating equation models to examine longitudinal school immunization compliance data from the 2012 to 2013 through 2021 to 2022 school years. The cohort comprised NYS public and nonpublic schools, excluding NYC schools, with any students enrolled in kindergarten to 12th grade. Eligible schools had enrollment and immunization data before and after the implementation of the Senate Bill 2994A legislation. Data analyses were conducted in July 2023. Exposure: Senate Bill 2994A was passed in June 2019, eliminating school-entry nonmedical vaccination exemptions. Since compliance with the law was evaluated for most students during the next school year, the 2019 to 2020 school year was considered to be the law's effective date. Main Outcomes and Measures: The primary outcomes were school vaccine coverage (defined as the percentage of students at each school who completed grade-appropriate requirements for all required vaccines) and medical exemption uptake (defined as the percentage of students at each school who received a medical exemption). Results: Among the 3821 eligible schools, 3632 (95.1%) were included in the analysis, representing 2794 (96.9% of eligible) public schools and 838 (89.2% of eligible) nonpublic schools. The implementation of Senate Bill 2994A was associated with absolute increases in mean vaccine coverage of 5.5% (95% CI, 4.5%-6.6%) among nonpublic schools and 0.9% (95% CI, 0.7%-1.1%) among public schools, with additional annual increases in vaccine coverage observed through the 2021 to 2022 school year. The law's implementation was also associated with a 0.1% (95% CI, 0.0%-0.1%) mean absolute decrease in medical vaccination exemption uptake at both public and nonpublic schools, and small but significant mean annual decreases in medical vaccination exemptions (0.02%; 95% CI, 0.01%-0.03%) through the end of the study period. Conclusions and Relevance: Results of this cohort study suggested that repeal of school-entry nonmedical vaccination exemptions was associated with increased vaccine coverage at NYS schools outside of NYC. Coverage gains were not replaced by increases in medical vaccination exemptions.

Exploring the impact of the New York State repeal of nonmedical vaccination exemptions on student enrollment, absenteeism, and school workload: Perspectives from a survey of school administrators.

In June 2019, New York State (NYS) adopted Senate Bill 2994A eliminating nonmedical vaccine exemptions from school entry laws. Since student noncompliance with the law required school exclusion, we sought to evaluate the law's effects on student enrollment and absenteeism, and school workloads related to its implementation. In November 2019, we sent an electronic survey to NYS (excluding New York City) schools. Due to the COVID-19 pandemic, outreach was curtailed in March 2020 with 525 (14%) of 3,759 eligible schools responding. To account for non-response, results were analyzed using inverse probability weighting. After weighting, 39% (95% CI: 34%, 44%) of schools reported enrollment changes and 31% (95% CI: 26%, 36%) of schools reported absenteeism related to the law. In addition, 95% (95% CI: 93%, 98%) of schools reported holding meetings and/or preparing correspondence about the law, spending a mean of 14 (95% CI: 11, 18) hours on these communication efforts. Schools in the highest pre-mandate nonmedical exemption tertile (vs. lowest) were more likely to report enrollment and absenteeism changes, and higher workloads. While our results should be interpreted with caution, changes in student enrollment, absenteeism, and school workloads may represent important considerations for policymakers planning similar legislation.

Real-world impact of glycated hemoglobin reduction on treatment intensification and glycated hemoglobin goal attainment in type 2 diabetes mellitus patients initiated on a sodium glucose co-transporter 2 (SGLT2) inhibitor (SGLT2i).

Objective: To evaluate the impact of a 0.2% reduction in glycated hemoglobin (HbA1c) on treatment intensification, poor HbA1c control and HbA1c goal attainment in patients with type 2 diabetes mellitus (T2DM) initiated on a sodium glucose co-transporter 2 (SGLT2) inhibitor (SGLT2i).Methods: IQVIATM Health Plan Claims Data - US and IQVIATM Ambulatory EMR Data - US databases (29 October 2012-31 March 2016) were used to identify adults with T2DM initiated on an SGLT2i (index date) who had HbA1c measurements pre- and post-index, and ≥6 months of eligibility pre-index (baseline). HbA1c change was defined as the difference between the first post-index and the last pre-index measurements. Cox regression models were used to assess treatment intensification, poor HbA1c control (i.e. HbA1c > 9%, among patients <9% at baseline) and goal attainment (HbA1c < 7%, <8%; among patients with HbA1c above goal at baseline) adjusting for HbA1c change and baseline characteristics. Patients were observed up to one year after the first HbA1c measurement or end of eligibility. Hazard ratios (HRs) and 95% confidence intervals (CIs) were reported.Results: A total of 938 patients (mean age 54.9, 42.5% female, mean HbA1c 8.5%) were selected. Following SGLT2i initiation, each 0.2% reduction in HbA1c levels was associated with a decreased risk of treatment intensification (HR [95% CI] = 0.90 [0.86-0.92]), a decreased likelihood of reaching HbA1c > 9% (HR [95% CI] = 0.85 [0.79-0.88]) and higher likelihoods of achieving a treatment goal of HbA1c < 7% (HR [95% CI] = 1.17 [1.12-1.21]) and HbA1c < 8% (HR [95% CI] = 1.08 [1.04-1.10]).Conclusions: In T2DM patients, each HbA1c reduction of 0.2% following the initiation of an SGLT2i was associated with a significant positive impact on treatment intensification and HbA1c goal attainment.

Short-term rehospitalizations in young adults with schizophrenia treated with once-monthly paliperidone palmitate or oral atypical antipsychotics: a retrospective analysis.

Objective: To compare rehospitalizations in patients with schizophrenia treated with paliperidone palmitate (PP1M) vs oral atypical antipsychotics (OAAs), with a focus on young adults (18-35 years).Methods: The Premier Healthcare database (January 2009-December 2016) was used to identify hospitalizations of adults (≥18 years) with schizophrenia treated with PP1M or OAA between September 2009 and October 2016 (index hospitalizations). Rehospitalizations were assessed at 30, 60, and 90 days after each index hospitalization in young adults and in all patients. Proportions of index hospitalizations resulting in rehospitalization were reported and compared between groups using odds ratios (ORs) and 95% confidence intervals (CIs).Results: A total of 8578 PP1M and 306,252 OAA index hospitalizations were included. Hospitalized young adults treated with PP1M (n = 3791) were more likely to be seen by a psychiatrist (94.0% vs 90.0%), and had a longer length of stay (12.5 vs 8.6 days) compared to hospitalized young adults treated with OAA (n = 96,502). Following their discharge, young adults receiving PP1M during an index hospitalization had a 25-27% lower odds of rehospitalization within 30, 60, and 90 days compared to young adults receiving OAAs (all p < .001). Similarly, when observing all patients, those receiving PP1M during an index hospitalization had 19-22% lower odds of rehospitalization within 30, 60, and 90 days compared to those receiving OAAs (all p < .001).Conclusions: Following a hospitalization for schizophrenia, PP1M treatment was associated with fewer 90-day rehospitalizations among young adults (18-35 years) relative to OAA treatment. This finding was also observed in other hospitalized adults with schizophrenia.

An investigation into the durability of glycemic control in patients with type II diabetes initiated on canagliflozin or sitagliptin: A real-world analysis of electronic medical records.

AIMS: The aims of this study were to assess glycemic control, weight loss, and durability of glycemic control in patients initiated on canagliflozin (CANA) versus sitagliptin (SITA). METHODS: Adults with type II diabetes mellitus initiated on CANA or SITA (index date) were identified from IQVIA™ Real-World Data Electronic Medical Records - US database (03/29/2012-04/30/2016). Inverse probability of treatment weighting accounted for baseline differences between cohorts. Outcomes were compared using weighted Cox regression and Kaplan-Meier curves and included time to reaching HbA1c thresholds (<7%[53 mmol/mol], <8%[64 mmol/mol], <9%[75 mmol/mol]), weight loss ≥5%, failure to maintain HbA1c below threshold, new antihyperglycemic (AHA) prescription, and failure to maintain HbA1c/new AHA prescription. RESULTS: Weighted cohorts were well balanced (NCANA = 14,542; NSITA = 15,151). CANA patients were 12-15% more likely to reach the HbA1c thresholds, 47% more likely to lose ≥5% of body weight, 31% less likely to have a new AHA prescription, 10-15% less likely to fail to maintain HbA1c, and 13-26% less likely to fail to maintain HbA1c or have a new AHA, versus SITA patients. CONCLUSIONS: CANA patients were more likely to reach HbA1c and weight loss thresholds and maintain HbA1c below threshold versus SITA patients, while being less likely to have a prescription for a new AHA, suggesting more durable glycemic control with CANA.

Economic modelling of costs associated with outcomes reported for type 2 diabetes mellitus (T2DM) patients in the CANVAS and EMPA-REG cardiovascular outcomes trials.

AIMS: To model direct medical costs associated with reductions in cardiovascular disease (CVD) events in T2DM patients reported in the CANVAS and EMPA-REG trials, which assessed the cardiovascular safety of canagliflozin and empagliflozin, respectively. MATERIALS AND METHODS: Costs were modeled from a US managed care organization (MCO) perspective for the CVD outcomes included in both trials: three-point major adverse cardiovascular event (MACE) and its components (cardiovascular-related death, nonfatal myocardial infarction, nonfatal stroke), as well as heart failure requiring hospitalization. The rate of CVD events averted (difference between study drug and placebo) was projected to the portion of an MCO T2DM population matching the respective trial's inclusion criteria. A targeted literature search for paid amounts directly associated with each CVD event provided the unit costs, which were applied to the projected number of events averted, to calculate costs avoided per member per year (PMPY). One-way sensitivity analyses were performed on events averted, unit costs, and percentages of trial-applicable patients. RESULTS: Based on three-point MACE events averted, costs avoided PMPY of $6.17 (range: $1.27-$10.94) for CANVAS and $2.75 ($0.19-$4.83) for EMPA-REG were estimated. Costs avoided for individual components of MACE ranged from $0.77 to $3.84 PMPY for CANVAS and from -$0.97 (additional costs) to $1.54 for EMPA-REG. PMPY costs avoided for heart failure were $2.72 for CANVAS and $1.32 for EMPA-REG. LIMITATIONS AND CONCLUSIONS: Models assumed independent, non-recurrent outcomes and were restricted to medical costs directly associated with the trial-reported events. The reductions in CVD events in T2DM patients reported for both CANVAS and EMPA-REG project to a positive cost avoidance for these events in an MCO population. The analysis did not include an assessment of the impact on total cost, as the costs associated with adverse events, drug utilization or other clinical outcomes were not examined.

HBA1C CONTROL AND COST-EFFECTIVENESS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS INITIATED ON CANAGLIFLOZIN OR A GLUCAGON-LIKE PEPTIDE 1 RECEPTOR AGONIST IN A REAL-WORLD SETTING.

OBJECTIVE: To compare glycated hemoglobin (HbA1c) control and medication costs between patients with type 2 diabetes mellitus (T2DM) treated with canagliflozin 300 mg (CANA) or a glucagon-like peptide 1 receptor agonist (GLP-1 RA) in a real-world setting. METHODS: Adults with T2DM newly initiated on CANA or a GLP-1 RA (index date) were identified from IQVIA™ Real-World Data Electronic Medical Records U.S. database (March 29, 2012-April 30, 2016). Inverse probability of treatment weighting accounted for differences in baseline characteristics. HbA1c levels at 3-month intervals were compared using generalized estimating equations. Medication costs used wholesale acquisition costs. RESULTS: For both cohorts (CANA: n = 11,435; GLP-1 RA: n = 11,582), HbA1c levels decreased at 3 months postindex and remained lower through 30 months. Absolute changes in mean HbA1c from index to 3 months postindex for CANA and GLP-1 RA were -1.16% and -1.21% (patients with baseline HbA1c ≥7% [53 mmol/mol]); -1.54% and -1.51% (patients with baseline HbA1c ≥8% [64 mmol/mol]); and -2.13% and -1.99% (patients with baseline HbA1c ≥9% [75 mmol/mol]), respectively. Postindex, CANA patients with baseline HbA1c ≥7% had similar HbA1c levels at each interval versus GLP-1 RA patients, except 9 months (mean HbA1c, 7.75% [61 mmol/mol] vs. 7.86% [62 mmol/mol]; P = .0305). CANA patients with baseline HbA1c ≥8% and ≥9% had consistently lower HbA1c numerically versus GLP-1 RA patients and statistically lower HbA1c at 9 (baseline HbA1c ≥8% or ≥9%), 27, and 30 months (baseline HbA1c ≥9%). Continuous 12-month medication cost $3,326 less for CANA versus GLP-1 RA. CONCLUSION: This retrospective study demonstrated a similar evolution of HbA1c levels among CANA and GLP-1 RA patients in a real-world setting. Lower medication costs suggest CANA is economically dominant over GLP-1 RA (similar effectiveness, lower cost). ABBREVIATIONS: AHA = antihyperglycemic agent BMI = body mass index CANA = canagliflozin 300 mg DCSI = diabetes complications severity index eGFR = estimated glomerular filtration rate EMR = electronic medical record GLP-1 RA = glucagon-like peptide 1 receptor agonist HbA1c = glycated hemoglobin ICD-9-CM = International Classification of Diseases-Ninth Revision-Clinical Modification ICD-10-CM = International Classification of Diseases-Tenth Revision-Clinical Modification IPTW = inverse probability of treatment weighting ITT = intent-to-treat MPR = medication possession ratio PDC = proportion of days covered PS = propensity score PSM = propensity score matching Quan-CCI = Quan-Charlson comorbidity index SGLT2 = sodium-glucose cotransporter 2 T2DM = type 2 diabetes mellitus WAC = wholesale acquisition cost.

Quality goal attainment and maintenance in patients with type II diabetes mellitus initiated on canagliflozin or a glucagon-like peptide-1 receptor agonist in an actual practice setting.

OBJECTIVE: To compare achievement of quality goals (HbA1c, weight loss/body mass index [BMI], systolic blood pressure [SBP]), including maintaining HbA1c, between patients with type 2 diabetes mellitus (T2DM) treated with canagliflozin 300 mg (CANA) or a GLP-1 in an actual practice setting. METHODS: Adults with T2DM newly initiated on CANA or a GLP-1 were identified from the IQVIATM Real-World Data Electronic Medical Records-US database (2012Q2-2016Q1). To account for differences in baseline characteristics, inverse probability of treatment weighting was used. Outcomes were compared using Cox models (hazard ratios [HRs] and 95% confidence intervals [CIs]) and Kaplan-Meier analyses. RESULTS: CANA (n = 11,435) and GLP-1 (n = 11,582) cohorts had similar attainment of HbA1c < 8.0% (64 mmol/mol) and HbA1c < 9.0% (75 mmol/mol; HbA1c < 8.0%: HR [CI] = 0.98 [0.91-1.06]; HbA1c < 9.0%: HR [CI] = 1.02 [0.93-1.12]), while GLP-1 patients were 10% more likely to achieve HbA1c < 7.0% (53 mmol/mol). CANA and GLP-1 patients were similar in maintaining HbA1c < 7.0%, < 8.0%, or <9.0%, achieving weight loss ≥5% (HR [CI] = 1.05 [0.99-1.12]), achieving BMI <30 kg/m2 (HR [CI] = 1.11 [0.98-1.27]), and achieving SBP <140 mmHg (HR [CI] = 1.07 [0.98-1.17]). CANA patients were 30% less likely to discontinue treatment, 28% less likely to have a prescription for a new anti-hyperglycemic, and 17-21% less likely to fail to maintain HbA1c < 8.0% or 9.0% or have a prescription for a new anti-hyperglycemic (composite outcome) vs GLP-1. No significant difference was observed for the composite outcome using the HbA1c < 7.0% threshold. CONCLUSIONS: This retrospective study in an actual practice setting showed that CANA patients were generally as likely as GLP-1 patients to achieve HbA1c, weight, and blood pressure thresholds, and to maintain glycemic control while being less likely to discontinue treatment and/or have a new anti-hyperglycemic prescribed.

Direct and Indirect Cost Burden and Change of Employment Status in Treatment-Resistant Depression: A Matched-Cohort Study Using a US Commercial Claims Database.

BACKGROUND: Treatment-resistant depression (TRD) poses a substantial burden to health care payers including employers, costing an estimated $29 billion-$48 billion yearly in the United States. Furthermore, variation of burden across increasing levels of resistance and the potential impact of TRD on employment status remain largely unexplored. OBJECTIVE: To evaluate health care resource utilization (HRU) and costs, work loss, indirect costs, and employment status change in TRD. METHODS: A claims-based algorithm identified adults with TRD from a US claims database of privately insured employees and dependents (January 2010-March 2015). TRD patients were matched 1:1 on demographics to patients with major depressive disorder (MDD) (non-TRD MDD) and without MDD (non-MDD), who were identified using ICD-9-CM codes. Costs, HRU, and employment status change were compared over 2 years following the first antidepressant (randomly imputed date for non-MDD), adjusting for baseline comorbidity index and costs. RESULTS: TRD patients (N = 6,411) had more HRU than either matched control cohort, translating into higher per patient per year (PPPY) health care costs: $6,709 and $9,917 more than non-TRD MDD and non-MDD patients, respectively (P < .001 for both). TRD patients with work loss data (N = 1,908) had 35.8 work loss days PPPY (1.7 and 6.2 times the work loss rate in non-TRD MDD and non-MDD patients, respectively). Work loss-related costs in TRD patients were $1,811 higher than non-TRD MDD and $3,460 higher than in non-MDD patients (P < .001). TRD patients had 1.3-1.4 times the rate of employment status change versus control cohorts (all P < .05). CONCLUSIONS: TRD, even compared to MDD, poses a significant direct and indirect cost burden to US employers and may be associated with higher rates of employment status change.

Treatment patterns and Medicaid spending in comorbid schizophrenia populations: once-monthly paliperidone palmitate versus oral atypical antipsychotics.

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 < .001) and less AP polypharmacy (e.g. CVD: 21.1% vs. 28.1%; p < .001) versus OAA patients. Relative to OAA patients, adherence was more likely in PP1M patients with CVD or obesity (e.g. CVD: 28.6% vs. 22.1%; p < .001) and less likely for patients with diabetes (22.0% vs. 24.4%; p = .031). Persistence was consistently more likely for PP1M versus OAA patients (e.g. CVD: 49.9% vs. 27.4%; p < .001). Total costs were not significantly different between PP1M and OAA patients for any comorbidity. PP1M patients with diabetes, hypertension or obesity had higher pharmacy and lower medical costs (all p < .05). CONCLUSIONS: Treatment with PP1M versus OAAs may reduce AP polypharmacy and increase AP persistence in comorbid patients with schizophrenia, without increasing total healthcare costs. Comorbidities are a highly prevalent driver of excess mortality in this vulnerable population; thus, future studies should specifically address the real-world effectiveness of therapies, including long acting injectable therapies (LAIs), for these patients.

Economic Impact in Medicaid Beneficiaries with Schizophrenia and Cardiometabolic Comorbidities Treated with Once-Monthly Paliperidone Palmitate vs. Oral Atypical Antipsychotics.

OBJECTIVE: The objective of this study was to compare persistence, costs, and healthcare resource utilization in patients with schizophrenia and cardiometabolic comorbidities treated with once-monthly paliperidone palmitate or an oral atypical antipsychotic. METHODS: Medicaid data from six states (07/2009-03/2015) were used to identify adults with schizophrenia and cardiometabolic comorbidities initiated on once-monthly paliperidone palmitate or an oral atypical antipsychotic (index date) on 01/2010 or after. Persistence to index medication at 12 months (no gap ≥ 90 days) was compared between patients taking once-monthly paliperidone palmitate and an oral atypical antipsychotic using Chi-squared tests. The 12-month post-index healthcare costs and healthcare resource utilization were compared using multivariate ordinary least squares and Poisson regression, respectively. RESULTS: Selected patients taking once-monthly paliperidone palmitate (n = 371) were younger (mean age: 45.0 vs. 47.5 years, standardized difference = 24%) than patients taking oral atypical antipsychotics (n = 8296). Persistence at 12 months was higher in patients taking once-monthly paliperidone palmitate (40 vs. 33%, p = 0.006). Adjusted all-cause medical costs were lower in patients taking once-monthly paliperidone palmitate vs. patients taking oral atypical antipsychotics (mean monthly cost differences = US $ - 369, p = 0.004) while all-cause pharmacy costs were higher (mean monthly cost differences = US $279, p < 0.001), resulting in no significant difference in total costs (mean monthly cost differences = US $ - 90, p = 0.357). No significant difference was observed in cardiometabolic comorbidity-related pharmacy or medical costs. Compared with patients taking oral atypical antipsychotics, patients taking once-monthly paliperidone palmitate had more schizophrenia-related outpatient visits (incidence rate ratio = 1.44, p < 0.001) but fewer cardiometabolic comorbidity-related inpatient admissions (incidence rate ratio = 0.73, p < 0.001) with shorter lengths of stay (incidence rate ratio = 0.72, p = 0.020), and fewer cardiometabolic comorbidity-related long-term care admissions (incidence rate ratio = 0.56, p = 0.016). CONCLUSIONS: Medicaid beneficiaries with schizophrenia and cardiometabolic comorbidities who were initiated on once-monthly paliperidone palmitate had similar 12-month total healthcare costs compared with oral atypical antipsychotics. Cardiometabolic comorbidity-related utilization of inpatient and long-term care services was lower in patients taking once-monthly paliperidone palmitate.

Real-world adherence and economic outcomes associated with paliperidone palmitate versus oral atypical antipsychotics in schizophrenia patients with substance-related disorders using Medicaid benefits.

AIM: Compare medication utilization, costs and healthcare resource use in schizophrenia patients with substance-related disorders initiated on once-monthly paliperidone palmitate (PP1M) or an oral atypical antipsychotic (OAA). MATERIALS & METHODS: Data from six Medicaid states (07/2009-03/2015) were used to compare outcomes between PP1M and OAA patients. RESULTS: PP1M patients had higher 12-month antipsychotic adherence and persistence than OAA patients. PP1M patients had lower medical (mean monthly cost difference [MMCD] = US$-191, p = 0.020), higher pharmacy (MMCD = US$250, p < 0.001) and similar total costs (MMCD = US$59, p = 0.517) during the overall follow-up. PP1M patients had lower rates of outpatient visits and inpatient days but higher rates of mental health-related utilization. CONCLUSION: PP1M was associated with higher antipsychotic adherence and persistence, and similar total costs versus OAA.

Treatment Patterns, Health Care Resource Utilization, and Spending in Medicaid Beneficiaries Initiating Second-generation Long-acting Injectable Agents Versus Oral Atypical Antipsychotics.

PURPOSE: 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. METHODS: 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. FINDINGS: 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; P < 0.001) and be persistent (eg, no gap ≥60 days; OR, 1.45; P < 0.001) to the index treatment. Relative to OAA patients, SGA-LAI patients had fewer long-term care days (incidence rate ratio [IRR], 0.75; P < 0.001) and home care visits (IRR, 0.75; P < 0.001) but more mental health institute (IRR, 1.16; P < 0.001) and 1-day mental health institute (IRR, 1.16; P < 0.001) 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; P < 0.001) than OAA patients, offsetting more than one half of the higher pharmacy costs (MMCD, $271; P < 0.001). Compared with OAAs, only PP-LAI was associated with significant medical cost savings (MMCD, -$225; P < 0.001). IMPLICATIONS: 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.

Quality measure and weight loss assessment in patients with type 2 diabetes mellitus treated with canagliflozin or dipeptidyl peptidase-4 inhibitors.

BACKGROUND: Achieving control of glycated hemoglobin (HbA1c), blood pressure (BP), and body weight (BW) remains a challenge for most patients with type 2 diabetes mellitus (T2DM). In clinical trials, canagliflozin (CANA), an inhibitor of sodium-glucose co-transporter 2, has shown significant improvement compared to some dipeptidyl peptidase-4 (DPP-4) inhibitors in the achievement of such quality measures. This study used recent electronic medical records (EMR) data to assess quality measure achievement of HbA1C, BP, and BW loss in patients treated with CANA versus DPP-4 inhibitors. METHODS: Adult patients with ≥1 T2DM diagnosis and ≥12 months of clinical activity (baseline) before first CANA or DPP-4 prescription (index) were identified in the QuintilesIMS Health Real-World Data EMRs-US database (03/29/2012-10/30/2015). Patients were observed from the index to last encounter. Inverse probability of treatment weighting (IPTW) was used to adjust for observed baseline confounders between groups. Kaplan-Meier (KM) rates and Cox proportional hazard models were used to compare achievement of HbA1c < 7% (among patients <65 years old), HbA1c < 8%, systolic BP < 140 mmHg, diastolic BP < 90 mmHg, and BW loss ≥ 5% among patients not meeting these respective targets at baseline. RESULTS: A total of 10,702 CANA and 17,679 DPP-4 patients were selected. IPTW resulted in balanced baseline demographic, comorbidity, and disease characteristics (CANA: N = 13,793, mean age: 59.0 years; DPP-4: N = 14,588, mean age: 58.9 years). Up until 24 months post-index, CANA patients were more likely to reach an HbA1c < 7% (hazard ratio [HR] = 1.10, P = 0.007, KM rates: 42.8% vs. 40.3%), an HbA1c < 8% (HR = 1.16, P < 0.001, KM rates: 63.7% vs. 60.0%), and a BW loss ≥ 5% (HR = 1.46, P < 0.001, KM rates: 55.2% vs. 46.2%), compared to DPP-4 patients. Up until 12 months post-index, CANA patients were more likely to reach a systolic BP < 140 mmHg (HR = 1.07, P = 0.04, KM rates: 87.8% vs. 83.9%). but not a diastolic BP < 90 mmHg (HR = 0.95, P = 0.361), compared to DPP-4 patients. CONCLUSIONS: This retrospective study of EMR data covering up to 30 months after CANA approval (March 2013) suggests that patients initiated on CANA were more likely to reach HbA1c, systolic BP, and weight loss objectives specified by general diabetes care guidelines than patients initiated on DPP-4 inhibitors.

Adherence, healthcare resource utilization and Medicaid spending associated with once-monthly paliperidone palmitate versus oral atypical antipsychotic treatment among adults recently diagnosed with schizophrenia.

BACKGROUND: Once-monthly paliperidone palmitate (PP1M) is a long-acting injectable antipsychotic that may increase adherence rates, reduce hospitalizations, and lower medical costs compared to oral atypical antipsychotics (OAAs) among schizophrenia patients. However, the impact of PP1M in recently diagnosed patients remains unknown. The present study compared adherence, healthcare resource utilization and Medicaid spending between schizophrenia patients initiating PP1M versus OAA, among patients recently diagnosed (defined using ages 18-25 years as a proxy) and among the overall population. METHODS: Medicaid data from five states (09/2008-03/2015) were used to identify adults with schizophrenia initiated on PP1M or OAAs (index date) on or after 09/2009. Outcomes were compared between PP1M and OAA groups following inverse probability of treatment weighting (IPTW). Univariate linear and Poisson regression models with nonparametric bootstrap procedures were used to compare the 12-month healthcare resource utilization and costs using rate ratios (RRs) and mean monthly cost differences (MMCDs), respectively. RESULTS: Overall, patients initiated on PP1M (N = 2053) were younger (mean age: 41 vs. 44 years) and had more baseline antipsychotic use (88% vs. 62%) compared to OAA patients (N = 22,247). IPTW resulted in balanced baseline characteristics. Among recently diagnosed patients, PP1M was associated with better adherence (PDC ≥ 80%: 29% vs. 21%, P < 0.001) on the index medication as well as less use of other psychiatric medications, compared to OAAs. Adherence findings were similar for the overall cohort. Among recently diagnosed patients, lower medical costs associated with PP1M (MMCD = $-466; P = 0.028) outweighed the higher pharmacy costs (MMCD = $322; P < 0.001) resulting in similar total healthcare costs across groups (MMCD = $-144; P = 0.553). Overall, findings were similar but there was a trend toward a lower magnitude of medical cost savings (MMCD = $-286; P < 0.001). Reductions in medical costs were mainly driven by reductions in inpatient days (recently diagnosed RR = 0.85, P = 0.353; overall RR = 0.84, P = 0.004) and in home care visits (recently diagnosed RR = 0.43, P = 0.008; overall RR = 0.78, P = 0.048). CONCLUSIONS: PP1M patients demonstrated significantly lower medical costs offsetting higher pharmacy costs relative to OAA patients. Recently diagnosed patients using PP1M may have greater medical cost savings relative to OAAs than that observed in the overall population, highlighting the potential economic impact of PP1M in adults recently diagnosed with schizophrenia.

Treatment patterns in Medicaid patients with schizophrenia initiated on a first- or second-generation long-acting injectable versus oral antipsychotic.

BACKGROUND: Poor antipsychotic (AP) adherence is a key issue in patients with schizophrenia. First-generation antipsychotic (FGA) and second-generation antipsychotic (SGA) long-acting injectable therapies (LAI) may improve adherence compared to oral antipsychotics (OAP). The objective of the study was to compare treatment adherence and persistence in Medicaid patients with schizophrenia initiated on first-generation long-acting injectable therapies (FGA-LAI) or second-generation long-acting injectable therapies (SGA-LAI) versus OAP. METHODS: Adults with schizophrenia initiated on FGA-LAI, SGA-LAI, or OAP on or after January 2010 were identified using a six-state Medicaid database (January 2009-March 2015). Outcomes were assessed during the 12 months following treatment initiation. Index medication adherence was assessed using the proportion of days covered ≥80%, while persistence was assessed as no gap of ≥30, ≥60, or ≥90 days between days of supply. Outcomes were compared between FGA/SGA-LAI and OAP cohorts using chi-squared tests and adjusted odds ratios (OR). RESULTS: During follow-up, AP polypharmacy was more common in FGA-LAI patients (N=1,089; 36%; P=0.029) and less common in SGA-LAI patients (N=2,209; 27%; P<0.001) versus OAP patients (N=20,478; 33%). After adjustment, SGA-LAI patients had 24% higher odds of adherence at 12 months (OR: 1.24; P<0.001), in contrast to FGA-LAI patients who had 48% lower odds of adherence (OR: 0.52; P<0.001) relative to OAP patients. SGA-LAI patients were more likely to be persistent (no gap ≥60 days) at 12 months than OAP patients (37% vs 30%; P<0.001), but not FGA-LAI patients (31% vs 30%; P=0.776). In comparison to OAP patients, SGA-LAI patients had 46% higher adjusted odds of persistence (no gap ≥60 days; OR: 1.46; P<0.001), while FGA-LAI patients were not significantly different (OR: 0.95; P=0.501). CONCLUSION: Medicaid patients initiated on SGA-LAI demonstrated better treatment adherence and persistence compared to OAP patients, while those initiated on FGA-LAI did not show significant improvement in adherence or persistence and had more AP polypharmacy relative to OAP patients. These findings suggest the potential value of SGA-LAI in the treatment of schizophrenia.

Hospitalizations in Immigrants and Nonimmigrants Diagnosed With Chronic Hepatitis C Infection in Québec.

BACKGROUND: Rates of hospitalization due to chronic hepatitis C virus (HCV) are increasing in Canada and the United States. A large proportion of immigrants originate from countries with intermediate to high HCV prevalence but are not screened for HCV post-arrival and may therefore have increased risks of liver-related complications and hospitalization. METHODS: We conducted a retrospective cohort study of reported HCV cases in Québec, Canada, from 1998 to 2007 that were linked to administrative health databases. Outcomes included all-cause and liver-related hospitalizations and in-hospital days in immigrants compared with nonimmigrants adjusted for age, sex, and comorbidities. RESULTS: We identified 20 139 HCV cases; 9% (N = 1821) were immigrants. At diagnosis, immigrants were older (47.6 vs 43.2 years) and more likely to have hepatocellular carcinoma (HCC; 0.93% vs 0.31%), while nonimmigrants were 2- to 10-fold more likely to have substance use-related comorbidities. Mean time to HCV diagnosis after arrival was 9.8 years. Nonimmigrants had higher rates of all-cause hospitalization (adjusted rate ratio [95% confidence interval], 1.42 [1.35-1.47]), driven by mental illness and injury and/or poisoning. Unadjusted liver-related hospitalization rates were similar between cohorts. After adjustment, immigrant status was associated with lower rates of liver-related hospitalization (0.68 [.53-.88]). CONCLUSIONS: Higher burden of all-cause hospitalization in nonimmigrants likely reflects more prevalent behavioral comorbidities. Similar liver-related hospitalization rates appear to be driven by older age in immigrants who were more likely to have HCC at diagnosis possibly reflecting delayed HCV diagnosis. These findings suggest that earlier screening and treatment in immigrants could play an important role in preventing HCV complications in this population.

N-(2,4)-dinitrophenyl-L-arginine Interacts with EphB4 and Functions as an EphB4 Kinase Modulator.

The erythropoietin-producing hepatocellular carcinoma receptor B4 is a receptor tyrosine kinase whose expression is preserved in various malignancies, including colon, gastric, and breast carcinoma. Hepatocellular carcinoma receptor B4 presence in tumor cells and involvement in cancer suppression makes it a potential therapeutic target for activating compounds. Moreover, modulators of its activity also have a strong potential to be used in diagnosis and therapy monitoring. We used virtual ligand screening to identify novel hepatocellular carcinoma receptor B4 kinase modulators for experimental testing. Three independent assay platforms confirmed that dinitrophenyl-L-arginine is likely to affect the kinase activity of hepatocellular carcinoma receptor B4. An enzyme-coupled spectrophotometric assay has been used to examine this possibility and may prove to be useful for assessing other novel kinase modulator candidates. Overall, our observations suggest that dinitrophenyl-L-arginine has an activating effect on hepatocellular carcinoma receptor B4 and, therefore, more efficient derivatives may have therapeutic effects in tumors where hepatocellular carcinoma receptor B4 exhibits antimalignant properties. The hepatocellular carcinoma receptor B4-activating effect is discussed with respect to previously described mechanisms, using predicted and experimental structures for docked ligands. As a novel kinase activity modulator, dinitrophenyl-L-arginine may provide new insights into molecular mechanisms by which kinases are activated or regulated, and may serve as a lead compound for the generation of novel hepatocellular carcinoma receptor B4-activating therapeutic compounds.

Identifying potential selective fluorescent probes for cancer-associated protein carbonic anhydrase IX using a computational approach.

Carbonic anhydrase IX (CAIX) is a biomarker for tumor hypoxia. Fluorescent inhibitors of CAIX have been used to study hypoxic tumor cell lines. However, these inhibitor-based fluorescent probes may have a therapeutic effect that is not appropriate for monitoring treatment efficacy. In the search for novel fluorescent probes that are not based on known inhibitors, a database of 20,860 fluorescent compounds was virtually screened against CAIX using hierarchical virtual ligand screening (HierVLS). The screening database contained 14,862 compounds tagged with the ATTO680 fluorophore plus an additional 5998 intrinsically fluorescent compounds. Overall ranking of compounds to identify hit molecular probe candidates utilized a principal component analysis (PCA) approach. Four potential binding sites, including the catalytic site, were identified within the structure of the protein and targeted for virtual screening. Available sequence information for 23 carbonic anhydrase isoforms was used to prioritize the four sites based on the estimated "uniqueness" of each site in CAIX relative to the other isoforms. A database of 32 known inhibitors and 478 decoy compounds was used to validate the methodology. A receiver-operating characteristic (ROC) analysis using the first principal component (PC1) as predictive score for the validation database yielded an area under the curve (AUC) of 0.92. AUC is interpreted as the probability that a binder will have a better score than a non-binder. The use of first component analysis of binding energies for multiple sites is a novel approach for hit selection. The very high prediction power for this approach increases confidence in the outcome from the fluorescent library screening. Ten of the top scoring candidates for isoform-selective putative binding sites are suggested for future testing as fluorescent molecular probe candidates.

Creating and virtually screening databases of fluorescently-labelled compounds for the discovery of target-specific molecular probes.

Our group has recently demonstrated that virtual screening is a useful technique for the identification of target-specific molecular probes. In this paper, we discuss some of our proof-of-concept results involving two biologically relevant target proteins, and report the development of a computational script to generate large databases of fluorescence-labelled compounds for computer-assisted molecular design. The virtual screening of a small library of 1,153 fluorescently-labelled compounds against two targets, and the experimental testing of selected hits reveal that this approach is efficient at identifying molecular probes, and that the screening of a labelled library is preferred over the screening of base compounds followed by conjugation of confirmed hits. The automated script for library generation explores the known reactivity of commercially available dyes, such as NHS-esters, to create large virtual databases of fluorescence-tagged small molecules that can be easily synthesized in a laboratory. A database of 14,862 compounds, each tagged with the ATTO680 fluorophore was generated with the automated script reported here. This library is available for downloading and it is suitable for virtual ligand screening aiming at the identification of target-specific fluorescent molecular probes.