Relapse Rates With Paliperidone Palmitate in Adult Patients With Schizophrenia: Results for the 6-Month Formulation From an Open-label Extension Study Compared to Real-World Data for the 1-Month and 3-Month Formulations.

BACKGROUND: The 3 paliperidone palmitate (PP) long-acting injectable antipsychotic formulations, PP 1-month (PP1M), PP 3-month (PP3M), and PP 6-month (PP6M), have shown to reduce the risk of relapse in schizophrenia. The current phase-4 study constructed external comparator arms (ECAs) using real-world data for PP3M and PP1M and compared relapse prevention rates with PP6M from an open-label extension (OLE) study in adult patients with schizophrenia. METHODS: PP6M data were derived from a single-arm, 24-month, OLE study (NCT04072575), which included patients with schizophrenia who completed a 12-month randomized, double-blind, noninferiority, phase-3 study (NCT03345342) without relapse. Patients in the PP3M and PP1M ECAs were identified from the IBM® MarketScan® Multistate Medicaid Database based on similar eligibility criteria as the PP6M cohort. RESULTS: A total of 178 patients were included in each cohort following propensity score matching. Most patients were men (>70%; mean age: 39-41 years). Time to relapse (primary analysis based on Kaplan-Meier estimates) was significantly delayed in the PP6M cohort (P < .001, log-rank test). The relapse rate was lower in the PP6M cohort (3.9%) vs PP3M (20.2%) and PP1M (29.8%) cohorts. Risk of relapse decreased significantly (P < .001) by 82% for PP6M vs PP3M (HR = 0.18 [95% CI = 0.08 to 0.40]), 89% for PP6M vs PP1M (HR = 0.11 [0.05 to 0.25]), and 35% for PP3M vs PP1M (HR = 0.65 [0.42 to 0.99]; P = .043). Sensitivity analysis confirmed findings from the primary analysis. Although the ECAs were matched to mimic the characteristics of the PP6M cohort, heterogeneity between the groups could exist due to factors including prior study participation, unmeasured confounders, variations in data capture and quality, and completeness of clinical information. CONCLUSIONS: In a clinical trial setting, PP6M significantly delayed time to relapse and demonstrated lower relapse rates compared with PP3M and PP1M treatments in real-world settings among adult patients with schizophrenia. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04072575; EudraCT number: 2018-004532-30.

Comparing Relapse Rates in Real-World Patients with Schizophrenia Who Were Adequately versus Not Adequately Treated with Paliperidone Palmitate Once-Monthly Injections Before Transitioning to Once-Every-3-Months Injections.

Purpose: This retrospective cohort study evaluated real-world data on relapses in adult patients with schizophrenia who transitioned to long-acting injectable paliperidone palmitate once-every-3-months (PP3M) following treatment with once-monthly paliperidone palmitate (PP1M). Patients and Methods: Data derived from the IBM® MarketScan® Multi-State Medicaid Database were analyzed. Adults aged ≥18 years with ≥1 schizophrenia diagnosis claim and ≥12 months of continuous medical and prescription enrollment before and/or at index date of PP3M were eligible for inclusion. Patients were matched on propensity score to 2 PP3M cohorts: (1) adequately treated (AT), defined as patients treated with PP1M for ≥4 months, with the last 2 doses the same and a PP3M initiation dose meeting the corresponding PP1M-to-PP3M dose conversion, or (2) not adequately treated (NAT), defined as patients who received ≤2 or no PP1M doses. Relapse rates and time to relapse distributions based on the first occurrence of a qualifying event during the 2-year follow-up period were compared between PP3M cohorts using Kaplan-Meier survival curves and log rank test statistics. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. Two sensitivity analyses using different matched populations were performed to assess the robustness of the primary findings. Results: Propensity score matching yielded a sample of 1314 patients (657 per group). Most patients were male (68.9%) and aged 25-64 years (90.1%). The relapse rate was significantly lower in the AT (18.4%) versus NAT cohort (26.8%), P = 0.0002. Risk of relapse decreased by 35% for AT versus NAT (HR: 0.65 [95% CI: 0.51-0.81]). Relapse reductions favored the AT cohort in both sensitivity analyses (HR: 0.67 [95% CI: 0.54-0.83] and HR: 0.74 [95% CI: 0.56-0.97]). Conclusion: In this analysis of Medicaid claims data, patients adequately treated with PP1M before transitioning to PP3M demonstrated significantly lower relapse rates and delayed time to relapse.

Relapse and Treatment Adherence in Patients with Schizophrenia Switching from Paliperidone Palmitate Once-Monthly to Three-Monthly Formulation: A Retrospective Health Claims Database Analysis.

PURPOSE: Relapse and treatment adherence to paliperidone palmitate once-monthly (PP1M) and three-monthly (PP3M) formulations in patients with schizophrenia were evaluated and compared using health claims data. PATIENTS AND METHODS: Data (June 2015─June 2018) obtained from the MarketScan® Multi-State Medicaid Database were retrospectively analyzed. Patients aged ≥18 years with ≥1 claim for schizophrenia diagnosis prior to and/or at index date (i.e., date of first PP3M prescription record for PP3M patients and same month/year as the matched PP3M patients for PP1M patients) and continuous enrollment in the insurance plan for ≥12 months prior to index date (baseline) were included. PP1M cohort included patients who received ≥4 PP1M doses. PP3M patients were matched with PP1M patients (1:3) using propensity score matching and prevalent new user design. Outcome measures were relapse rate, time to relapse, proportion of days covered (PDC), and level of treatment adherence defined by PDC in five levels. Time to relapse was compared by Kaplan-Meier survival curves and log-rank test with the hazard ratio calculated using Cox proportion hazards model; PDC by t-test, and relapse rate and PDC categories by chi-square test. RESULTS: A total of 1564 patients (428 PP3M and 1136 PP1M) were included. Relapse rate was lower in PP3M cohort (10.5%) compared with PP1M cohort (15.7%). Incidence rate of relapse was 8.98/100 person-years (PY) in PP3M cohort and 13.81/100 PY in PP1M cohort. After a mean (SD) follow-up of 456.1 (240.28) days in PP3M cohort and 465.4 (237.95) days in PP1M cohort, PP3M patients had a significantly lower relapse risk (hazard ratio: 0.65, 95% CI: 0.47, 0.90) than PP1M patients. Treatment adherence was significantly (p<0.0001) higher in PP3M versus PP1M cohort. CONCLUSION: Risk of relapse was significantly lower, and treatment adherence was significantly higher in PP3M cohort compared with PP1M cohort. Higher treatment adherence was associated with lower relapse rate.

Body mass index and insulin use as identifiers of high-cost patients with type 2 diabetes: A retrospective analysis of electronic health records linked to insurance claims data.

AIMS: To study the association of body mass index (BMI) and insulin use with type 2 diabetes-related healthcare expenditures (T2D-HE). MATERIALS AND METHODS: Retrospective study using de-identified electronic health records linked to insurance claims data. Study included a prevalence-based sample of overweight or obese patients with antihyperglycaemic-treated T2D. Patients had ≥1 A1c measurement in 2014 (last observed = index A1c), ≥1 BMI measurement within ±90 days of index (average BMI = baseline BMI), and continuous enrolment for 180 days before (baseline) through 395 days after index (day 30-395 = follow-up). BMI was categorized as: 25 to 29.9 kg/m2 = overweight; 30 to 34.9 kg/m2 = obese class I (OCI); 35 to 39.9 kg/m2 = OCII; ≥40 kg/m2 = OCIII. Multivariable regressions were used to examine one-year follow-up T2D-HE as a function of BMI, insulin use, an interaction term between BMI and insulin use, and patient demographics. RESULTS: Study included 13 026 patients (mean age = 63.6 years; 48.1% female; 29.5% overweight, 31.6% OCI, 20.3% OCII, 18.6% OCIII; 25.3% insulin users). Baseline insulin use rates monotonically ranged from 19.7% in overweight patients to 33.0% in OCIII patients (P < 0.001). Together, BMI and insulin use were jointly associated with one-year follow-up T2D-HE, which monotonically ranged from $5842 in overweight patients with no insulin to $17 700 OCIII insulin users, P < 0.001. Within each BMI category, insulin users' one-year T2D-HE was at least double that of non-users. Additional analyses of all-cause healthcare expenditures yielded consistent results. CONCLUSIONS: BMI and insulin use represent simple stratifiers for identifying high-cost patients. OCIII insulin users incurred the greatest annual healthcare expenditures; these patients may be an ideal group for targeted interventions.

Economic impact of atrial fibrillation ablation with radiofrequency contact force catheter versus cryoballoon catheter.

AIM: To compare health utilization among atrial fibrillation (AF) patients undergoing ablation with a contact force-sensing (CF) catheter versus a cryoballoon (CB) catheter. METHODS: AF patients who underwent ablation using the CF catheter (THERMOCOOL SMARTTOUCH® catheter) or CB catheter (Arctic Front™/Arctic Front Advance™ catheter) were identified from the Premier Healthcare database. Propensity score analyses were used to evaluate cost, length of stay and readmissions. RESULTS: The CF catheter (n = 1409) was associated with significantly lower total (∼7%) and supply (∼13%) costs and a significantly lower likelihood of 4-12 month all-cause and CV-related readmission compared with the CB catheter (n = 2306). CONCLUSION: Differential health utilization outcomes are associated with the CF catheter versus the CB catheter in AF ablation.

Comparison of real-world clinical and economic outcomes between the ThermoCool® SF and ThermoCool® catheters in patients undergoing radiofrequency catheter ablation for atrial fibrillation.

INTRODUCTION: This study evaluated the real-world clinical and economic outcomes associated with the use of the ThermoCool® Surround Flow (SF) and ThermoCool® catheters in atrial fibrillation (AF) ablation. METHODS: Adults with AF who underwent catheter ablation between January 1, 2013, and December 31, 2016, in a hospital outpatient setting were identified from the Premier Healthcare Database. Using a search strategy of hospital-charge descriptors, patients were classified into two mutually exclusive groups: ThermoCool® SF catheter and ThermoCool® catheter. A generalized estimating equation was used to compare index admission cost. Survey logistic regression was used to compare the incidence of inpatient readmission, direct-current cardioversion (DCCV), and repeat ablation. Multivariable analyses were adjusted for hospital clustering and demographic, procedural, hospital, and comorbidity characteristics. RESULTS: There were 1,014 and 463 patients in the ThermoCool® SF and ThermoCool® groups, respectively. The ThermoCool® SF group had significantly lower odds of all-cause (odds ratio [OR] 0.45; 95% CI 0.27-0.76) and cardiovascular-related readmissions (OR 0.45; 95% CI 0.21-0.96), and DCCV (OR 0.61; 95% CI 0.42-0.88) than the ThermoCool® group. In patients susceptible to fluid overload, the ThermoCool® SF group had significantly lower odds of 12-month all-cause (OR 0.42; 95% CI 0.23-0.75), cardiovascular-related (OR 0.31; 95% CI 0.10-0.92), and AF-related readmissions (OR 0.18; 95% CI 0.04-0.80), and DCCV (OR 0.52; 95% CI 0.31-0.87) than the ThermoCool® group. CONCLUSIONS: Using the ThermoCool® SF catheter for AF ablation was significantly associated with improved clinical outcomes compared with the ThermoCool® catheter.

The clinical and economic burden of significant bleeding during lung resection surgery: A retrospective matched cohort analysis of real-world data.

OBJECTIVES: The objective of this retrospective study was to quantify the clinical and economic burden of significant bleeding in lung resection surgery in the US. METHODS: This study utilized 2009-2012 data from the Premier Perspective DatabaseTM. Adult patients with primary pulmonary lobectomy or segmentectomy procedures were categorized by the surgical approach (VATS vs open) and primary diagnosis (primary or metastatic lung cancer vs non-lung cancer). Patients requiring ≥3 units of blood products with at least 1 unit of PRBCs: "significant bleeding" cohort; those requiring <3 units: "non-significant bleeding" cohort; and those not requiring blood products: "no bleeding" cohort. A matched cohort analysis was performed between the "significant bleeding" and the "no bleeding cohort" using matching variables: hospital, lung cancer diagnosis, year of surgery, APR-DRG severity score, procedure type and approach, age, and gender. RESULTS: The "All-patient" cohort comprised 21,429 patients: 213 "significant bleeding"; 2,780 "non-significant bleeding"; and 18,436 "no bleeding". Overall incidence of significant chest bleeding was 0.99%. Patients from "significant bleeding" cohort and "non-significant bleeding" cohort had 2.5 days and 2 days (p < 0.0001) longer length of stay in the hospital compared to those in the "no bleeding" cohort, respectively. Overall, hospital costs for "significant bleeding" cohort were higher than "no bleeding" cohort for those who were covered under Medicare ($59,871 vs $23,641), were ≥76 years of age ($64,010 vs $24,243), had greater severity of illness ($97,813 vs $51,871) and underwent open segmentectomy ($74,220 vs $21,903). Hospital costs for "significant bleeding" cohort and "non-significant bleeding" were significantly higher ($11,589 and $5,280, respectively, p < 0.0001) than no bleeding cohort. CONCLUSIONS: Although significant bleeding during lung resection surgery is rare, patients with such complication could stay longer at the hospital and cost an average of $13,103 more than those without.

Clinical and economic burden of surgical site infection in hysterectomy.

BACKGROUND: Owing to a lack of current understanding of outcomes and costs by type of hysterectomy procedure, we attempt to quantify the incidence and impact of surgical site infection (SSI) in laparoscopic and non-laparoscopic approaches to abdominal and vaginal hysterectomy. METHODS: Patients whose data were contained in the Premier Perspectives Database of 600 hospitals in the United States were selected on the basis of a post-operative diagnosis of SSI and treatment with antibiotics. The incidence of SSI and associated hospital length of stay (LOS) and costs were estimated. The effect of SSI on readmission was also analyzed. RESULTS: Of 210,916 hysterectomies included in the study, 55% were open abdominal procedures. Although the overall incidence of SSI in hysterectomy was low, its incidence was greater in open abdominal hysterectomy than in other approaches to hysterectomy. Patients with an SSI experienced a three- to five-fold greater LOS, two-fold greater cost, and three-fold greater risk of hospital readmission than those without an SSI. CONCLUSIONS: This study provides clinical evidence in support of less invasive approaches to hysterectomy. In addition to other documented benefits of such less invasive procedures, the lower incidence of SSIs and lower rates of associated complications and costs with these procedures than with open abdominal hysterectomy should be taken into account when weighing the risks and benefits of a surgical approach for patients whose condition warrants hysterectomy.

The association of self-monitoring of blood glucose use with medication adherence and glycemic control in patients with type 2 diabetes initiating non-insulin treatment.

BACKGROUND: The value of self-monitoring of blood glucose (SMBG) for persons with type 2 diabetes who do not use insulin remains controversial. This observational study compares the likelihood of medication adherence and change in glycated hemoglobin (A1C) for non-insulin-using patients using SMBG versus those not using SMBG. The study also assessed the association between diabetes medication adherence and SMBG use. PATIENTS AND METHODS: Data were extracted on 5,172 patients who began non-insulin diabetes medication between October 1, 2006, and March 31, 2009. The study assessed change in A1C associated with SMBG use and testing frequency at different categorical levels of baseline A1C. The likelihood of medication adherence for SMBG users was compared with that for non-SMBG users at different categorical levels of baseline A1C. The study further explored the interactions between SMBG use and medication adherence on change in A1C. RESULTS: SMBG users had greater reductions in A1C compared with nonusers when the baseline A1C was ≥ 7%. Increasing SMBG frequency was associated with greater reductions in A1C. The study also examined the associations among SMBG use, medication adherence, and change in A1C. SMBG users had greater decreases in A1C for both medication-adherent and -nonadherent patients. As expected, medication adherence was associated with greater reductions in A1C for both SMBG nonusers and users. It is interesting that medication-nonadherent SMBG users had similar reductions in A1C compared with medication-adherent non-SMBG users. CONCLUSIONS: Both SMBG use and medication adherence were associated with similar degrees of A1C reduction after controlling for baseline A1C, suggesting that both factors may be important for attaining glycemic control.

Association between sitagliptin adherence and self-monitoring of blood glucose.

BACKGROUND: We evaluated the association between self-monitoring of blood glucose (SMBG) use and sitagliptin or sitagliptin/metformin (SSMT) adherence. SSMT was chosen as these medications have little risk of hypoglycemia and are believed to not require SMBG data for titration. METHODS: This was an observational study using data extracted from a large United States insurance claims database (i3 InVision™ Data Mart, Ingenix, Inc.). Data were extracted on noninsulin-using patients initiating SSMT for each 12-month period pre- and post-SSMT initiation. Logistic regression was used to assess the relationship between SMBG use and the likelihood of being medication adherent (defined as a medication possession ratio of ≥75%) while controlling for covariates. RESULTS: This analysis included 7,306 patients (57.6% male; mean age 54.2 years). Mean pre-SSMT hemoglobin A1c (HbA1c) was 8.0%. In the post-SSMT initiation period, 58% of patients were adherent with SSMT. Older age, male gender, prior use of oral diabetes medication, and lower HbA1c were associated with improved SSMT adherence. SMBG use was associated with improved adherence [odds ratio (OR) ranged from 1.198 to 1.338; p < .05] compared with patients with no SMBG use pre- or post-SSMT initiation. For patients who began SMBG after starting SSMT, greater SMBG use was associated with better adherence (OR 1.449 for higher vs 1.246 for lower strip use; p < .05). CONCLUSIONS: This study demonstrated that SMBG is associated with improved SSMT adherence. This relationship is strengthened with greater SMBG use.

Rates of venous thromboembolism among patients with major surgery for cancer.

BACKGROUND: Previous studies have reported VTE rates during surgical stays in hospitals or by diagnoses over extended periods without being linked to specific surgical events. The purpose of this project was to assess the potential rate of venous thromboembolism in patients with cancer after a surgical procedure within the immediate posthospital admission period of 30 days, with special emphasis in increased sensitivity of detection. METHODS: Patients with cancer who had a major surgery were identified in a large commercial (non-Medicare) database containing data from more than 22 million patients in the United States. Those with a new diagnosis of VTE within 30 days postadmission for surgery were identified. Additional drug-based criteria were used to vary the VTE definition in a sensitivity analysis. VTE rates are reported for each of the surgical procedure group and overall. RESULTS: The overall 30-day VTE rate was 3.5% with a diagnosis based definition, with rates ranging by procedure from 1.8 to 13.2%. Esophageal resection patients have a VTE rate of 13.2% (95% confidence interval (CI), 8.8-18.9%), whereas prostatectomy patients have a VTE rate of 1.8% (95% CI, 1.5-2.1%). Of the 3.5% of patients with a VTE diagnosis on or before postoperative day 30, 73% of those have the VTE diagnosis by day 14. Another 1.15% is added to the overall VTE rate as the definition sensitivity is increased with outpatient pharmacy claims data. CONCLUSIONS: Using administrative data from large populations provides valuable insight into the potential VTE rates that occur within the 30-day post period after various cancer-related surgeries. The information can be used by surgeons as one component of the benefit-risk decision regarding postoperative VTE prophylaxis in surgical patients.

Prevalence of obesity, type II diabetes mellitus, hyperlipidemia, and hypertension in the United States: findings from the GE Centricity Electronic Medical Record database.

This study analyzed GE Centricity Electronic Medical Record (EMR) data to examine the effects of body mass index (BMI) and obesity, key risk factor components of metabolic syndrome, on the prevalence of 3 chronic diseases: type II diabetes mellitus, hyperlipidemia, and hypertension. These chronic diseases occur with high prevalence and impose high disease burdens. The rationale for using Centricity EMR data is 2-fold. First, EMRs may be a good source of BMI/obesity data, which are often underreported in surveys and administrative databases. Second, EMRs provide an ideal means to track variables over time and, thus, allow longitudinal analyses of relationships between risk factors and disease prevalence and progression. Analysis of Centricity EMR data showed associations of age, sex, race/ethnicity, and BMI with diagnosed prevalence of the 3 conditions. Results include uniform direct correlations between age and BMI and prevalence of each disease; uniformly greater disease prevalence for males than females; varying differences by race/ethnicity (ie, African Americans have the highest prevalence of diagnosed type II diabetes and hypertension, while whites have the highest prevalence of diagnosed hypertension); and adverse effects of comorbidities. The direct associations between BMI and disease prevalence are consistent for males and females and across all racial/ethnic groups. The results reported herein contribute to the growing literature about the adverse effects of obesity on chronic disease prevalence and about the potential value of EMR data to elucidate trends in disease prevalence and facilitate longitudinal analyses.

Comparison of GE Centricity Electronic Medical Record database and National Ambulatory Medical Care Survey findings on the prevalence of major conditions in the United States.

The study objective was to facilitate investigations by assessing the external validity and generalizability of the Centricity Electronic Medical Record (EMR) database and analytical results to the US population using the National Ambulatory Medical Care Survey (NAMCS) data and results as an appropriate validation resource. Demographic and diagnostic data from the NAMCS were compared to similar data from the Centricity EMR database, and the impact of the different methods of data collection was analyzed. Compared to NAMCS survey data on visits, Centricity EMR data shows higher proportions of visits by younger patients and by females. Other comparisons suggest more acute visits in Centricity and more chronic visits in NAMCS. The key finding from the Centricity EMR is more visits for the 13 chronic conditions highlighted in the NAMCS survey, with virtually all comparisons showing higher proportions in Centricity. Although data and results from Centricity and NAMCS are not perfectly comparable, once techniques are employed to deal with limitations, Centricity data appear more sensitive in capturing diagnoses, especially chronic diagnoses. Likely explanations include differences in data collection using the EMR versus the survey, particularly more comprehensive medical documentation requirements for the Centricity EMR and its inclusion of laboratory results and medication data collected over time, compared to the survey, which focused on the primary reason for that visit. It is likely that Centricity data reflect medical problems more accurately and provide a more accurate estimate of the distribution of diagnoses in ambulatory visits in the United States. Further research should address potential methodological approaches to maximize the validity and utility of EMR databases.