Characteristics and Healthcare Burden of Patients with Schizophrenia Treated in a US Integrated Healthcare System.

BACKGROUND: Schizophrenia is one of 15 major causes of disability worldwide and is responsible for more than USD 150 billion in annual healthcare costs in the United States. Although the burden of schizophrenia as measured by healthcare resource utilization (HRU) is known to be considerable, data generally come from claims databases or healthcare systems/payors representing only a subset of patients, such as Medicare/Medicaid recipients. A broader understanding of HRU across the schizophrenia patient population would help identify underserved groups and inform strategies for improving healthcare delivery. AIMS OF THE STUDY: This observational study examined overall HRU and the influence of sociodemographic factors in adult patients with schizophrenia receiving care in a US integrated healthcare system. METHODS: A retrospective cohort study was conducted using data from electronic medical records (EMRs). Patients were required to have at least two diagnostic codes for schizophrenia recorded in the EMR within a 12-month period from January 2009 to June 2018, and to have received active care (≥ 1 in-system healthcare visit every six months) for at least 12 months before and after the index date (the earlier of the schizophrenia diagnosis dates). Patients were followed until no longer receiving active care or the end of the study. Patient characteristics were assessed during the 12-month pre-index period, and inpatient, readmission, emergency room (ER), and outpatient visits and antipsychotic prescriptions were described during follow-up. Findings were reported overall and in subgroups by race/ethnicity, age, and sex. RESULTS: The study cohort included 2,941 patients (mean age, 48.3 years; 54.5% male, 51.8% black, 45.8% with Medicare). During the follow-up period (mean, 4.6 years), inpatient hospital stays were common, with at least one all-cause, mental health-related, or schizophrenia-related inpatient visit occurring for 48.7%, 47.3%, and 38.8% of patients, respectively. Hospital readmissions within 30 days of an all-cause inpatient visit occurred in 20.4% of patients, with 14.5% of patients readmitted within 30 days of a schizophrenia-related inpatient visit. More than two-thirds of patients had ER visits, and 40.7% had schizophrenia-related ER visits. Only 46.7% of patients with a schizophrenia-related inpatient visit and 58.5% of patients with a mental health-related inpatient visit had a 30-day outpatient follow-up visit. Subgroup analyses revealed that a larger proportion of non-Hispanic black vs non-Hispanic white patients had 30-day outpatient follow-up visits, ER visits, mental health specialist visits, and antipsychotic prescriptions. Moreover, older age was associated with fewer ER and mental health specialist visits and less use of injectable and second-generation antipsychotics, and women were less likely than men to receive antipsychotic therapy, particularly injectable medications. DISCUSSION: Patients with schizophrenia receiving care in a US integrated healthcare system had considerable acute HRU and suboptimal rates of routine and follow-up care. Inequities in schizophrenia burden and care were observed in demographic subgroups. IMPLICATIONS FOR HEALTH POLICIES: Population health management strategies focusing on efficient resource allocation and improving healthcare quality are needed to reduce the burden of schizophrenia. Differential findings by race/ethnicity, age, and sex indicate the need for optimizing approaches to care in these subgroups.

New York State cases of anaphylaxis in elderly patients from 2000 to 2010.

BACKGROUND: Limited information is available on the effect of anaphylaxis, a severe, potentially life-threatening allergic reaction, in the elderly population. OBJECTIVE: To elucidate the frequency of anaphylaxis and the demographic characteristics of elderly patients admitted to New York hospitals from 2000 to 2010. METHODS: A retrospective analysis of hospitalized patients aged 65 years and older in New York from 2000 to 2010 was conducted using the Statewide Planning and Research Cooperative System, a statewide administrative database. Cases were identified using anaphylaxis International Classification of Diseases, Ninth Revision (ICD-9) codes or an ICD-9-based diagnostic algorithm incorporating the National Institutes of Allergy and Infectious Disease diagnostic criteria. The χ2 test was used to measure the association between demographic characteristics and group membership. Regression was used to model group and age as a function of hospital rates. RESULTS: A total of 3673 hospitalizations were analyzed. Anaphylaxis ICD-9 codes identified 1790 cases (48.7%), the algorithms identified 1701 cases (46.3.%), and 182 cases (5.0%) were identified by both. Hospitalization rates increased significantly during this period (P < .001). Women comprised 61.5% and people of white race comprised 69.8% of the sample. Distribution by age differed by ascertainment method (ICD-9 vs algorithm) among the early-old group (65-74 years of age; 53.8% vs 41.8%) and among the late-old group (≥85 years of age; 11.2% vs 19.3%). CONCLUSION: Hospitalization rates and anaphylaxis cases increased during the study period among the hospitalized elderly population of New York. Relying on anaphylaxis ICD-9 codes alone missed approximately half of possible cases. The identification and possibly the effect of anaphylaxis among the elderly population may differ, depending on age, race, payer, New York County, and disposition.

Healthcare Resource Utilization and Costs Among Patients With Schizophrenia Switching From Oral Risperidone/Paliperidone to Once-Monthly Paliperidone Palmitate: A Veterans Health Administration Claims Analysis.

BACKGROUND: Schizophrenia is associated with high health care resource utilization and treatment costs. OBJECTIVE: This study compared treatment patterns, health care resource utilization, and medical costs before and after a switch from oral antipsychotic drug (risperidone or paliperidone [RIS/PALI]) therapy to the long-acting injectable once-monthly paliperidone palmitate (PP1M) in patients with schizophrenia. METHODS: Data for adult patients (aged ≥18 years) with at least 1 diagnosis of schizophrenia who initiated treatment with oral RIS/PALI ≥6 months before switching and had continuous health plan enrollment during the study period before and after the switch were extracted from the Veterans Health Administration database. Treatment patterns, health care resource utilization, and costs were compared between the period 6 or 12 months before and after switching directly from oral RIS/PALI to PP1M. RESULTS: The analysis included 676 and 493 patients in the 6-month and 12-month cohorts, respectively. Adherence to oral RIS/PALI during the 12 months preswitch was 11.0% and 22.1% as measured by proportion of days covered and medication possession ratio ≥80%, respectively. During the 12 months postswitch, adherence to PP1M was 27.0% and 35.9%, respectively. Among patients treated with oral RIS/PALI, from 12 months pre- to 12 months post-PP1M switch, fewer all-cause inpatient stays (2.2 vs 1.1, respectively; P < 0.05) and a shorter mean length of inpatient stay (28.1 and 14.0 days, respectively; P < 0.05) were observed. This pattern was similar for both the number of mental health- and schizophrenia-related inpatient stays and length of stay. Compared with 12 months pre-PP1M switch, significantly higher mean numbers of all-cause outpatient visits and pharmacy visits were observed at 12 months postswitch. In line with health care resource utilization findings, at 12 months pre- versus 12 months post-PP1M switch we observed decreases in all-cause inpatient stay costs ($41,886 vs $20,489; P < 0.05) and increases in outpatient visit costs ($22,005 vs $29,069; P < 0.05). Findings for the 6-month cohort followed a similar pattern. CONCLUSIONS: Post-PP1M switch, a decrease in total medical costs fully offset an increase in pharmacy costs, resulting in similar total costs. The findings suggest potential economic benefits of switching patients with schizophrenia from oral RIS/PALI to PP1M in the Veterans Health Administration.

Mycelial form of dimorphic fungus Malassezia species dictates the microbial interaction.

Dandruff is one of the most common clinically manifested and studied scalp disorders. It has been associated with both bacteria and fungi. Bacteria and fungi inhabiting the scalp are known to influence each other and manifestation of dandruff. Fungal and bacterial isolates from scalp epithelial flakes (dandruff) were identified by rDNA sequencing. Local oils were tested for fungal and bacterial inhibition, interaction and biofilm formation, cell-cell interactions were studied by auto aggregation and surface thermodynamics studies. The isolates Bacillus sp.C2b1 (MK036745) and Malassezia sp. C2y1 (MK036746) were inhibited by Mahabhrungraj oil. The fungal morphological switch was evident and dependent on nutrition. Cell aggregation studies suggested the interaction of bacteria with yeast (non-pathogenic) phase of the fungus. Bacterial and yeast cells were found to be compatible for biofilm formation. The fungal mycelial surfaces were found to be conducive for interaction with both bacterial cells and yeast forms. The results here indicate the significance of mycelial phase of scalp-isolated fungus in interaction with the bacterial surfaces and also with self-yeast phase surface. This is the first report of the interaction between scalp-isolated microorganisms with respect to their surface interaction capabilities.

A post-hoc analysis of the comparative efficacy of canagliflozin and glimepiride in the attainment of type 2 diabetes-related quality measures.

BACKGROUND: The randomized, double-blind CANTATA-SU (CANagliflozin Treatment And Trial Analysis Sulfonyl Urea) clinical trial compared the use of canagliflozin (100 mg or 300 mg) and maximally tolerated glimepiride (6-8 mg) over 104 weeks as add-on therapy for patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin. Compared with glimepiride, canagliflozin use was associated with durable reductions in glycated hemoglobin (A1C), blood pressure (BP), and body weight. The aim of this post-hoc analysis of the CANTATA-SU trial was to assess the comparative efficacy of canagliflozin and glimepiride in the attainment of recently updated diabetes-related quality measures (QMs) for up to 104 weeks of treatment. METHODS: This post-hoc analysis evaluated the proportions of patients achieving individual diabetes-related QMs using data from the randomized, double-blind, Phase 3 CANTATA-SU trial. Change in A1C from baseline, and proportions of the study population achieving QMs: A1C <7.0 %, <8.0 %, and >9.0 % were assessed. Secondary endpoints included change in BP from baseline, and the proportions of the study population achieving QMs related to BP and body weight. RESULTS: The proportions of patients in the canagliflozin 100 mg, canagliflozin 300 mg, and glimepiride groups meeting criteria for all QMs were similar at baseline. At 52 and 104 weeks of treatment, canagliflozin 100 mg and canagliflozin 300 mg provided better or similar reductions in A1C from baseline and achievement of glycemic control QMs compared with glimepiride. At 52 and 104 weeks of treatment, the attainment of QMs related to reductions in body weight and BP all favored canagliflozin compared with glimepiride. Canagliflozin was associated with lower incidence of documented hypoglycemia and severe hypoglycemia compared with glimepiride. CONCLUSIONS: Using the recently adjusted and currently accepted diabetes-related QMs, this analysis observed superior glycemic control with canagliflozin compared with maximally tolerated glimepiride in patients with T2DM who were previously poorly controlled on metformin monotherapy. Compared with maximally tolerated glimepiride, canagliflozin resulted in better achievement of diabetes-related QMs related to weight loss and BP, and was associated with lower incidences of hypoglycemic events. TRIAL REGISTRATION: Clinical trial registry name: CANagliflozin Treatment And Trial Analysis-Sulfonylurea (CANTATA-SU) SGLT2 Add-on to Metformin Versus Glimepiride. CLINICAL TRIAL REGISTRATION NUMBER: NCT00968812 , registered August 28, 2009.

A breath of toxic air: The relationship between appraised air pollution, abusive supervision, and laissez-faire leadership through the dual-mediating pathways of negative affect and somatic complaints.

Air pollution has become a global public health hazard leading to debilitating effects on physical, mental, and emotional health. Management research has just begun to explore the effects of air pollution on employees' work life. Drawing from the transactional theory of stress (Lazarus & Folkman, 1984) and crossover theory (Westman, 2001), we argue that appraisal of air pollution is an important factor that influences leaders and their behavior with subordinates. Specifically, we propose that when leaders appraise severe air pollution, they are more likely to behave abusively toward their subordinates and engage in laissez-faire leadership. We also propose that this relationship is mediated by leaders' experience of somatic complaints and negative affect. We test our model using an experience sampling study in India of leaders and followers who were located in different cities from each other. Overall, our results highlight how air pollution appraisals can harm not only the leader experiencing the pollution but also subordinates of those leaders. In other words, our counterintuitive finding is that subordinates may be harmed by air pollution to which they are not even directly exposed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Optimizing Computer-Aided Diagnosis with Cost-Aware Deep Learning Models.

Classical machine learning and deep learning models for Computer-Aided Diagnosis (CAD) commonly focus on overall classification performance, treating misclassification errors (false negatives and false positives) equally during training. This uniform treatment overlooks the distinct costs associated with each type of error, leading to suboptimal decision-making, particularly in the medical domain where it is important to improve the prediction sensitivity without significantly compromising overall accuracy. This study introduces a novel deep learning-based CAD system that incorporates a cost-sensitive parameter into the activation function. By applying our methodologies to two medical imaging datasets, our proposed study shows statistically significant increases of 3.84% and 5.4% in sensitivity while maintaining overall accuracy for Lung Image Database Consortium (LIDC) and Breast Cancer Histological Database (BreakHis), respectively. Our findings underscore the significance of integrating cost-sensitive parameters into future CAD systems to optimize performance and ultimately reduce costs and improve patient outcomes.

Post Hospitalization Clinical Quality Outcomes Among US Patients with Schizophrenia Treated with a Long-Acting Injectable or Switched to a New Oral Antipsychotic: A Retrospective Cohort Study.

BACKGROUND:  Adherence to antipsychotic medication and care discontinuity remain a challenge to healthcare practitioners providing care to patients with schizophrenia. OBJECTIVE: This study used real-world data from a US hospital-based, all-payer database to examine clinical quality measures among patients with schizophrenia initiated on a long-acting injectable (LAI) or switched to a new oral antipsychotic medication (OAP) following a hospitalization. METHODS: A retrospective cohort study using the PINC AI™ Healthcare Database compared two cohorts of patients with schizophrenia on post-index hospitalization clinical quality and care continuity endpoints. Patients initiated on an LAI (n = 7292) or switched to a new OAP (n = 31,956) during an index hospitalization between April 2017 and April 2020 were included. Propensity score weighting addressed differences in patient, hospital, and clinical characteristics between the two cohorts. RESULTS: Patients who initiated an LAI experienced significantly greater adjusted 30-day antipsychotic medication continuation to index therapy, higher rate of 30-day outpatient follow-up care, longer mean time to discontinuation of index therapy, and lower risk of discontinuing their index treatment compared to patients who switched to a new OAP (all p values < 0.001). Probability of 30-day antipsychotic medication continuation was significantly higher for LAI initiators than for patients who switched to a new OAP, even after controlling for patient, clinical, and hospital characteristics (adjusted odds ratio = 1.2, 95% CI 1.1-1.3, p < 0.001). CONCLUSION: Patients who initiated an LAI in a hospital setting experienced better clinical quality and care continuity outcomes compared to patients who were switched to a new OAP. These findings may be useful in identifying solutions to help improve the quality of medication management post-hospital discharge among patients with schizophrenia.

Out-of-Pocket Costs for Long-Acting Injectable and Oral Antipsychotics Among Medicare Patients With Schizophrenia.

OBJECTIVE: The authors sought to describe out-of-pocket (OOP) costs among beneficiaries with schizophrenia differing in Medicare Part D low-income subsidy (LIS) status. METHODS: National 100% Medicare claims were used to identify all adult fee-for-service Medicare Part D beneficiaries with schizophrenia who used antipsychotics in 2019 (N=283,813). Proportions of patients by LIS status, OOP costs per prescription, and annual OOP costs were reported. Results were stratified by type of antipsychotic received (oral antipsychotic [OAP], first-generation long-acting injectable [FGA-LAI], or second-generation long-acting injectable [SGA-LAI]). RESULTS: In the final sample, 90.3% of beneficiaries had full LIS status, paying minimal copayments (29.6% institutionalized full LIS, paying $0; 42.2% noninstitutionalized full LIS, ≤100% federal poverty level [FPL], paying $1.25-$3.80; and 18.5% noninstitutionalized full LIS, >100% FPL, paying $3.40-$8.50). Only 0.9% of the sample received partial LIS status, and 8.8% had a non-LIS status. Non-LIS beneficiaries had the highest OOP costs, followed by partial LIS beneficiaries. Before entering catastrophic coverage, median OOP costs per prescription for generic OAPs, brand-name OAPs, FGA-LAIs, and SGA-LAIs were $10.85, $171.97, $26.09, and $394.28, respectively, for non-LIS beneficiaries and $3.69, $105.82, $9.35, and $229.20, respectively, for partial LIS beneficiaries. The annual total OOP costs varied substantially by LIS status (full LIS, $0-$130.79; partial LIS, $458.96; non-LIS, $998.81). CONCLUSIONS: Most Medicare beneficiaries with schizophrenia qualified for full LIS and faced minimal OOP costs for both OAPs and LAIs. The remainder (i.e., partial LIS and non-LIS beneficiaries) faced substantial OOP costs, both per prescription and annually, especially for SGA-LAIs.

Treatment patterns and hospitalizations following rejection, reversal, or payment of the initial once-monthly paliperidone palmitate long-acting injectable antipsychotic claim among patients with schizophrenia or schizoaffective disorder.

BACKGROUND: Once-monthly paliperidone palmitate (PP1M) is a long-acting injectable antipsychotic approved for the treatment of schizophrenia and schizoaffective disorder (SCA) in adults. OBJECTIVE: To assess treatment patterns and schizophrenia/SCA-related hospitalization following payer rejection, patient reversal, or payment of an initial PP1M claim. METHODS: This was a retrospective cohort study using the IQVIA Formulary Impact Analyzer database linked to the Medical Claims, Hospital Charge Detail Master, and Experian consumer databases. Patients with schizophrenia/SCA and ≥1 PP1M pharmacy claim from January 1, 2018, to February 28, 2022, were identified and stratified into 3 cohorts based on the transaction status of the initial PP1M claim (index date): rejected (payer not approved), reversed (payer approved, patient abandoned), and paid (payer approved, patient filled). Patient characteristics during the 12 months before the index date, subsequent treatment patterns, and schizophrenia/SCA-related hospitalization for patients with >6 months of follow-up were assessed by cohort. RESULTS: The rejected, reversed, and paid cohorts included 1,260, 1,046, and 1,686 patients, respectively. Across these cohorts, the mean ages ranged between 39.2 and 44.5 years; more than half were male (50.8%-51.6%) and White (50.6%-58.3%); 19.8%-24.6% of patients had a Quan-Charlson Comorbidity Index score of ≥2. Rates of prior atypical oral and long-acting injectable antipsychotic use ranged between 76.4%-80.3% and 7.8%-12.7%, respectively. Among patients with ≥6 months of follow-up, 52.2% in the rejected and 53.1% in the reversed cohorts had a subsequent paid PP1M claim during the study period; the median (quartile 1-quartile 3) time to the first paid PP1M claim was 22 (5-74) days for rejection and 11 (1-41) days for reversal. In the rejected and reversed cohorts, 10.2% (n = 111) and 9.8% (n = 90) of patients, respectively, did not receive any paid claim for an antipsychotic after the initial PP1M rejection/reversal. The prevalence of schizophrenia/SCA-related hospitalization during follow-up was similar between patients with a paid (7.4%) and rejected PP1M claim (7.0%; P = 0.689) but higher among patients with a reversed claim (10.8%; P = 0.004). After adjusting for confounders, patients in the reversed cohort were 39% more likely to have a schizophrenia/SCA-related hospitalization than those in the paid cohort (odds ratio = 1.39; 95% CI = 1.03-1.87). CONCLUSIONS: Payer rejection and patient reversal of initial PP1M claims is a form of primary nonadherence and may influence patient trajectory. Data from this study suggest that patient reversal of PP1M may lead to an increased risk of schizophrenia/SCA-related hospitalizations, potentially caused by missed or delayed treatment. Policy initiatives that remove barriers to primary adherence or fulfillment may help improve patients' clinical outcomes.

Low-grade mucoepidermoid carcinoma mimicking benign cystic lesions in the salivary gland: A diagnostic dilemma.

Mucoepidermoid carcinoma (MEC) is a common malignancy arising in the parotid gland. The diagnosis of MEC is typically based on its morphological features alone, characteristically containing mucocytes, intermediate cells and epidermoid cells. However, when cystic degeneration is diffuse, it is challenging to distinguish MEC from other benign cystic tumors. This is a case report of a 58-year-old Caucasian man who presented with a parotid mass. H&E sections of the mass reveal multiloculated cysts lined by bland-looking epithelium with only rare papillary architectures. The papillary proliferation contains mucocytes, and epidermoid cells highlighted by the p63 immunohistochemistry study. The diagnosis was confirmed by FISH result of positive MAML2 (11q21) rearrangement. Patient underwent parotidectomy and is disease-free 6 months post-surgery. MEC with cystic degeneration is a common diagnostic pitfall which can mimic many benign lesions in the salivary gland. We present a rare case with MEC with extensive cystic change, its molecular and pathologic findings and review the diagnostic features of MEC, its benign mimickers and useful tools for distinguishing these entities.

Adherence, health care utilization, and costs between long-acting injectable and oral antipsychotic medications in South Carolina Medicaid beneficiaries with schizophrenia.

BACKGROUND: Schizophrenia and schizoaffective disorder require long-term antipsychotic treatment with antipsychotic medications, but poor medication adherence can lead to increased health care utilization and costs. Long-acting injectable antipsychotics (LAIs) offer potential therapeutic advantages in that they require less frequent dosing and improved medication adherence. South Carolina has the highest adoption of LAIs among US states, making it an ideal population for comparing the effectiveness of LAIs vs oral antipsychotics (OAPs) in treating schizophrenia or schizoaffective disorder. OBJECTIVE: To evaluate the effect of LAIs compared with OAPs on medication adherence, health care resource utilization, and costs among South Carolina Medicaid beneficiaries with schizophrenia or schizoaffective disorder. METHODS: South Carolina Medicaid beneficiaries with at least 1 claim for an LAI or OAP between January 1, 2015, and December 31, 2018, aged 18 to 65, with at least 2 claims with diagnoses of schizophrenia or schizoaffective disorder were included. Propensity scores (PSs) were calculated using logistic regression adjusting for confounders and predictors of the outcome. We estimated the "average treatment effect on the treated" by employing PS-weighted t-tests and chi-square tests. RESULTS: A total of 3,531 patients met the inclusion criteria, with 1,537 (44.5%) treated with LAIs and 1,994 (56.5%) treated with OAPs. In PS-weighted analyses, the LAI cohort had a greater proportion of days covered than the OAP cohort with a 365-day fixed denominator (69% vs 64%; P < 0.0001), higher medication possession ratio with a variable denominator while on therapy (85% vs 80%; P < 0.0001), and higher persistence (82% vs 64%; P < 0.0001). The average number of inpatient visits and emergency department visits did not significantly differ between cohorts (0.28 hospitalizations, P = 0.90; 3.68 vs 2.96 emergency department visits, P = 0.19). The number of outpatient visits, including visits for medication administration, were greater in the LAI cohort (23.1 [SD 24.2]) vs OAP (16.9 [SD 21.2]; P < 0.0001); however, including the costs for medication administration visits, outpatient costs (per member) were approximately $2,500 lower in the LAI cohort (P < 0.0001). The number of pharmacy visits was greater in the OAP cohort (LAI 21.0 [SD 17.0] vs OAP 23.0 [SD 15.0]; P = 0.006). All-cause total costs were greater in the LAI cohort ($26,025 [SD $29,909]) vs the OAP cohort ($17,291 [SD $25,261]; P < 0.0001) and were driven by the difference in pharmaceutical costs (LAI $15,273 [SD $16,183] vs OAP $4,696 [SD $10,371]; P < 0.0001). CONCLUSIONS: Among South Carolina Medicaid beneficiaries, treatment with LAIs for schizophrenia or schizoaffective disorder was associated with greater medication adherence rates. Patients using LAIs had higher drug costs and total costs, but lower outpatient and total nondrug costs compared with those using OAPs.

MRI prediction of islet yield for autologous transplantation after total pancreatectomy for chronic pancreatitis.

OBJECTIVE: The relationship between magnetic resonance imaging (MRI), histopathology, and islet yield was examined for chronic pancreatitis patients undergoing total pancreatectomy and autologous islet cell transplant (TP-AIT) to determine if the yield can be predicted by pre-operative MRI. METHODS: MRI sequences and histopathology were scored and compared for patients from whom ≤2,500 islet equivalents/kg were obtained with those from whom >2,500 islet equivalents/kg were obtained. RESULTS: Twenty patients, 14 female, mean age 40.20 ± 12.5 years, (range 19-63) underwent MRI before TP-AIT; mean 3,724 ± 891 islet equivalents/kg body weight, median 2,970, (range 76-17,770) were procured. There was no correlation between islet cell numbers and pancreas weight, HgbA1c, or c-peptide. The most common MRI sequence abnormality was the delayed interstitial phase, 14/18 (78 %). The other common MRI sequence abnormalities were, precontrast T1W 3D GRE sequence, 13/19 (68 %), and the arterial perfusion phase, 11/18 (61 %). The pancreatic duct was dilated in 10/20 (50 %). Parenchymal atrophy was noted in 10/20 (50 %). Median scores for individual MRI sequences were greater in patients with an islet cell yield of ≤2,500 islet equivalents/kg; for the delayed interstitial phase the difference was significant (median 2.5, range 1-3 versus median 0.5, range 0-3, P = 0.034). Histologically the most common feature was fibrosis, (17/17, 100 %); the score for fibrosis was greater for patients with an islet cell yield of ≤2,500 islet equivalents/kg (median 6.0, range 5-7 versus median 4.0, range 3-7, P = 0.024). CONCLUSION: A diminished islet yield may be predicted on the basis of the delayed interstitial phase MRI sequence.

Real-world calibration and transportability of the Disease Recovery Evaluation and Modification (DREaM) randomized clinical trial in adult Medicaid beneficiaries with recent-onset schizophrenia.

BACKGROUND: The Disease Recovery Evaluation and Modification study (DREaM; NCT02431702) assessed the benefit of initiating paliperidone palmitate (PP), a long-acting injectable antipsychotic, in patients with recent-onset schizophrenia or schizophreniform disorder. OBJECTIVE: To determine whether reductions in psychiatric hospitalizations with early initiation of PP vs oral antipsychotic (OAP) therapy observed in a DREaM post hoc analysis are transportable to a real-world population of patients with recent-onset schizophrenia. METHODS: Patients enrolled in DREaM were randomized to receive OAP or PP for 9 months, after which OAP recipients were re-randomized to receive OAP or PP for another 9 months. We used this design to form treatment arms: OAP-OAP, OAP-PP, and PP-PP. Inclusion/exclusion criteria were used to identify a Medicaid Managed Care (MMC) OAP-treated cohort of 1,000 patients diagnosed with schizophrenia using IBM Truven databases from 2015 to 2019. The MMC cohort was combined with the subset of patients diagnosed with schizophrenia enrolled in DREaM from US sites (N = 45, 43, and 44 for OAP-OAP, OAP-PP, and PP-PP, respectively). Propensity scores for the MMC cohort were estimated using baseline variables identified via double-lasso regression. Estimated propensity scores were used to weight psychiatric hospitalizations in the DREaM OAP-OAP group and compared with observed MMC OAP cohort psychiatric hospitalizations. After the successful calibration of the DREaM OAP-OAP group, similar approaches were taken for the OAP-PP and PP-PP groups to transport DREaM effects to MMC data. RESULTS: Standardized mean differences in baseline covariates between DREaM treatment arms and MMC groups were substantially reduced after calibration. The 18-month cumulative numbers of psychiatric hospitalizations per patient (SE) were 0.83 (0.14) for the MMC cohort, 0.43 (0.14) for the unweighted OAP-OAP, and 0.80 (0.37) for the calibrated OAP-OAP. The difference between the calibrated OAP-OAP and MMC was not statistically significant (difference, 0.03 [95% CI = -0.67 to 0.81]), indicating successful calibration. The mean difference in 18-month cumulative psychiatric hospitalizations relative to the MMC cohort was -0.77 (95% CI = -1.08 to -0.47) for OAP-PP and -0.83 (95% CI = -1.15 to -0.60) for PP-PP. CONCLUSIONS: Our study demonstrates that results from the DREaM OAP-OAP group reflect psychiatric hospitalizations in a real-world population when calibrated using specific baseline characteristics. Transporting the DREaM effects, we find that using OAP-PP and PP-PP treatment strategies for patients with recent-onset schizophrenia in the MMC population could reduce psychiatric hospitalizations compared with the use of OAP. These findings, along with the potential reduction in associated costs, should be considered when assessing the value of PP formulations. DISCLOSURES: Dr Basu reports consulting fees through Salutis Consulting LLC related to this work. Dr Mavros is a former employee of the Janssen Pharmaceutical Companies of Johnson & Johnson, Inc, and holds stock in the company. Ms Benson, Dr Fu, Ms Patel, and Dr Brown are employees of Janssen Scientific Affairs, LLC, and hold stock in Johnson & Johnson. This research was funded by Janssen Scientific Affairs, LLC. The sponsor was involved in the study design; collection, analysis, and interpretation of data; and development and review of the manuscript. All authors had full access to the study data and take responsibility for data integrity and the accuracy of the analyses. All authors provided direction and comments on the manuscript, reviewed and approved the final version prior to submission, made the final decision about where to publish these data, and approved submission to this journal.

Continuity of care among patients newly initiated on second-generation oral or long-acting injectable antipsychotics during a schizophrenia-related inpatient stay.

BACKGROUND: Maintaining continuity of care after schizophrenia-related hospitalization is challenging for patients and healthcare providers and systems. Prior evidence suggests that second-generation long-acting injectable antipsychotics (SGLAIs) may reduce the risk of treatment nonadherence and readmission versus oral atypical antipsychotics (OAAs). Therefore, quality measures were compared between patients initiated on SGLAIs and OAAs in the United States. METHODS: Adults newly initiated on an SGLAI or OAA during a schizophrenia-related inpatient stay were identified in HealthVerity databases (01/2015-12/2020); the index date was the hospital discharge date. Patients had continuous health insurance coverage for pharmacy and medical services for 6 months pre-admission and post-discharge from the inpatient stay and ≥1 pharmacy or medical claim (i.e. treatment as indicated by the observed insurance claims) for an antipsychotic other than the index SGLAI or OAA in the 6 months pre-admission. Antipsychotic use and adherence, and schizophrenia-related readmissions and outpatient visits were compared during the 6-month period post-discharge. Characteristics between cohorts were balanced using inverse probability weights. RESULTS: Post-discharge, only 36.9% and 40.7% of weighted SGLAI (N = 466) and OAA (N = 517) patients had ≥1 pharmacy or medical claim for the antipsychotic initiated during the inpatient stay, among whom SGLAI patients were 4.4 times more likely to be adherent to that antipsychotic compared to OAA patients (p < .001). Additionally, SGLAI patients were 2.3 and 3.0 times more likely to have a pharmacy or medical claim for and be adherent to any antipsychotic relative to OAA patients (including index antipsychotic; all p < .001). Within 7 and 30 days post-discharge, 1.7% and 13.0% of SGLAI patients and 4.1% and 12.6% of OAA patients had a readmission. Further, SGLAI patients were 51% more likely to have an outpatient visit compared to OAA patients (p = .044). CONCLUSIONS: Less than half of patients initiated on antipsychotics during a schizophrenia-related inpatient stay continued the same treatment post-discharge. However, SGLAI patients were more likely to be adherent to the initiated antipsychotic and to have an outpatient visit, which may suggest improved continuity of care post-discharge relative to OAA patients.

Antipsychotic utilization, healthcare resource use and costs, and quality of care among fee-for-service Medicare beneficiaries with schizophrenia in the United States.

BACKGROUND: No research to date has examined antipsychotic (AP) use, healthcare resource use (HRU), costs, and quality of care among those with schizophrenia in the Medicare program despite it serving as the primary payer for half of individuals with schizophrenia in the US. OBJECTIVES: To provide national estimates and assess regional variation in AP treatment utilization, HRU, costs, and quality measures among Medicare beneficiaries with schizophrenia. METHODS: Cross-sectional descriptive analysis of 100% Medicare claims data from 2019. The sample included all adult Medicare beneficiaries with continuous fee-for-service coverage and ≥1 inpatient and/or ≥2 outpatient claims with a diagnosis for schizophrenia in 2019. Summary statistics on AP use; HRU and cost; and quality measures were reported at the national, state, and county levels. Regional variation was measured using the coefficient of variation (CoV). RESULTS: We identified 314,888 beneficiaries with schizophrenia. About 91% used any AP; 20% used any long-acting injectable antipsychotic (LAI); and 14% used atypical LAIs. About 28% of beneficiaries had ≥1 hospitalization and 47% had ≥1 emergency room (ER) visits, the vast majority of which were related to mental health (MH). Total annual all-cause, MH, and schizophrenia-related costs were $23,662, $15,000 and $12,109, respectively. Among those with hospitalizations, 18.4% and 27.3% had readmission within 7 and 30 days and 56% and 67% had a physician visit and AP fill within 30 days post-discharge, respectively. Overall, 81% of beneficiaries were deemed adherent to their AP medications. Larger interstate variations were observed in LAI use than AP use (CoV: 0.21 vs 0.02). County-level variations were larger than state-level variations for all measures. CONCLUSIONS: In this first study examining a national sample of Medicare beneficiaries with schizophrenia, we found low utilization rates of LAIs and high levels of hospital admissions/readmissions and ER visits. State and county-level variations were also found in these measures.

Analysis of recurrent research pathways for assessing and improving effectiveness in life sciences laboratories.

Background: Life sciences research often turns out to be ineffective. Our aim was to develop a method for mapping repetitive research processes, detecting practice variations, and exploring inefficiencies. Methods: Three samples of R&I projects were used: companion diagnostics of cancer treatments, identification of COVID-19 variants, and COVID-19 vaccine development. Major steps involved: defined starting points, desired end points; measurement of transition times and success rates; exploration of variations, and recommendations for improved efficiency. Results: Over 50% of CDX developments failed to reach market simultaneously with new drugs. There were significant variations among phases of co-development (Bartlett test P<0.001). Length of time in vaccine development also shows variations (P<0.0001). Similarly, subject participation indicates unexplained variations in trials (Phase I: 489.7 (±461.8); Phase II: 857.3 (±450.1); Phase III: 35402 (±18079). Conclusion: Analysis of repetitive research processes can highlight inefficiencies and show ways to improve quality and productivity in life sciences.

Comparison of clinical outcomes in patients with schizophrenia following different long-acting injectable event-driven initiation strategies.

This retrospective study evaluated the benefit of following different long-acting injectable (LAI) initiation strategies based on the timing of behavioral and clinical events among Medicaid beneficiaries with schizophrenia. Adults with schizophrenia initiating oral antipsychotics (OAPs) after 12 months without antipsychotic use or schizophrenia-related inpatient/emergency room (ER) visits (index date) were identified. Patients were categorized into four event-driven LAI initiation strategy cohorts based on observed sequences of behavioral (i.e., OAP adherence) and clinical (i.e., schizophrenia-related inpatient/ER visits) events between index and LAI initiation or censoring-strategy #1: adherent to OAPs without schizophrenia-related inpatient/ER visits; strategy #2: nonadherent to OAPs without schizophrenia-related inpatient/ER visits; strategy #3: one schizophrenia-related inpatient/ER visit; strategy #4: ≥2 schizophrenia-related inpatient/ER visits. Clinical outcomes (i.e., all-cause inpatient/ER visits) were evaluated between OAP initiation and end of follow-up. Comparisons between LAI initiation strategy cohorts were conducted using a dynamic marginal structural model adjusting for baseline characteristics and time-varying confounders. Among 13,444 eligible patients, 13.1%, 53.6%, 15.7%, and 17.6% were following strategies #1-4, respectively; of these, 21.9%, 4.3%, 9.2%, and 6.5% started an LAI (the remaining were censored). Strategy #1 was associated with a greater clinical benefit, with 43%, 69%, and 80% fewer inpatient days (all p < 0.05); and 57%, 59%, and 79% fewer ER visits (all p < 0.01) vs strategies #2-4, respectively; the clinical benefit was also observed for strategy #2 vs #3-4. Therefore, starting an LAI prior to OAP nonadherence or occurrence of a schizophrenia-related inpatient/ER visit was associated with fewer all-cause inpatient days of inpatient stay and ER visits.

Adherence, Persistence, Readmissions, and Costs in Medicaid Members with Schizophrenia or Schizoaffective Disorder Initiating Paliperidone Palmitate Versus Switching Oral Antipsychotics: A Real-World Retrospective Investigation.

INTRODUCTION: Long-acting injectable antipsychotic agents have been suggested to improve adherence and patient outcomes in schizophrenia or schizoaffective disorder. The purpose of this study was to assess medication use patterns (i.e., medication adherence, persistence), hospital and emergency department readmissions, and total direct medical costs of Oklahoma Medicaid members with schizophrenia or schizoaffective disorder switching from an oral antipsychotic (OAP) to once-monthly paliperidone palmitate (PP1M) or to another OAP (OAP-switch). METHODS: A historical cohort analysis was conducted from 1 January 2016 to 31 December 2020 among adults aged ≥ 18 and ≤ 64 years with schizophrenia or schizoaffective disorder who were previously treated with an OAP. The first claim for PP1M or a new OAP defined the study index date. Members who transitioned from PP1M to 3-month formulation (PP3M) were included (i.e., PP1M/PP3M). Proportion of days covered (PDC), 45-day treatment gaps, 30-day readmissions to hospitals or emergency department, and total direct medical costs were assessed using multivariable, machine-learning least absolute shrinkage, and selection operator (Lasso) regressions controlling for numerous demographic, clinical, mental health, and provider characteristics. RESULTS: Among 295 Medicaid members meeting full inclusion criteria, 183 involved PP1M/PP3Ms (44 PP1M cases transitioned to PP3M) and 112 involved an OAP-switch. The multivariable-adjusted odds of readmission were significantly associated with a 45-day treatment gap (p < 0.05) and non-adherence (i.e., PDC < 80%) (p < 0.05). Relative to PP1M/PP3Ms, the multivariable analyses also indicated that OAP-switch was associated with an 18.5% lower PDC, 92.3% higher number of 45-day treatment gaps, and an approximately 90% higher odds of all-cause 30-day readmission (p < 0.05). The adjusted pre- to post-index change in cost was approximately 49% lower for OAP-switches versus PP1M/PP3Ms (p < 0.001), although unadjusted post-index costs did not differ between groups (p = 0.440). CONCLUSION: This real-world investigation of adult Medicaid members with schizophrenia or schizoaffective disorder observed improved adherence and persistence with fewer readmissions with PP1M/PP3Ms versus OAP-switches.

The effects of strEngth aNd BaLance exercise on Executive function in people living with Dementia (ENABLED): Study protocol for a pilot randomized controlled trial.

BACKGROUND: Exercise may improve executive function among people living with all-cause dementia (PWD), but more evidence is needed. The aim of this pilot randomized controlled trial (RCT) is to examine whether exercise plus usual care improves the primary outcome of executive function, and secondary physiological (inflammation, metabolic aging, epigenetics) and behavioral (cognition, psychological health, physical function, and falls) outcomes compared to usual care alone among PWD. METHODS AND STUDY DESIGN: The strEngth aNd BaLance exercise on Executive function in people living with Dementia (ENABLED) protocol is a pilot parallel, 6-month assessor-blinded RCT (1:1) in residential care facilities, including n = 21 receiving exercise plus usual care and n = 21 usual care alone [NCT05488951]. We will collect primary (Color-Word Stroop Test) and secondary physiological (inflammation, metabolic aging, epigenetics) and behavioral (cognition, psychological health, physical function, and falls) outcomes at baseline and 6 months. We will obtain falls monthly from medical charts. We will collect physical activity, sedentary behavior, and sleep via wrist-worn accelerometers over 7 days at baseline and 6 months. The physical therapist-led adapted Otago Exercise Program will involve 1-h of strength, balance and walking 3×/week for 6 months in groups of 5-7. We will use generalized linear mixed models to examine differences over time in primary and secondary outcomes between groups and examine potential interactions with sex and race. DISCUSSION: This pilot RCT will examine the direct effects and potential underlying physiological mechanisms of exercise on executive function and other behavioral outcomes in PWD, which may have implications for clinical care management.