Pharmacokinetics, Efficacy, and Safety of a SARS-CoV-2 Antibody Treatment in Pediatric Participants: An Open-Label Addendum of a Placebo-Controlled, Randomized Phase 2/3 Trial.

INTRODUCTION: Bamlanivimab and etesevimab (BAM + ETE) are monoclonal antibodies (mAbs) effective in reducing COVID-19-related hospitalizations and all-cause mortality in adult participants at increased risk for severe disease. We present pharmacokinetic (PK), efficacy, and safety results from pediatric participants (< 18 years of age) with COVID-19 who were treated with BAM + ETE. METHODS: In an addendum to the phase 2/3 BLAZE-1 clinical trial (NCT04427501), pediatric participants received open-label weight-based dosing (WBD, n = 94) based on exposure-matching to the authorized dose of BAM + ETE in adult participants. For efficacy and safety assessments, placebo (n = 14) and BAM + ETE (n = 20)-treated adolescent participants (> 12 to < 18 years of age) from the BLAZE-1 trial were included in the overall pediatric population (N = 128). All participants had mild to moderate COVID-19 upon enrollment and ≥ 1 risk factor for severe COVID-19. The primary objective was to characterize the PK of BAM and ETE in the WBD population. RESULTS: The median age of the participants was 11.2 years, 46.1% were female, 57.9% were Black/African American, and 19.7% were Hispanic/Latino. The area under the curve for BAM and ETE in the WBD population was similar to that previously observed in adults. There were no COVID-19-related hospitalizations or deaths. All adverse events (AE) except one were mild or moderate, with one participant reporting a serious AE. CONCLUSION: WBD in pediatric participants achieved similar drug exposures compared to adult participants that received the authorized BAM + ETE dose. The pediatric efficacy and safety data were consistent with adults receiving mAbs for COVID-19. TRIAL REGISTRATION NUMBER: NCT04427501.

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.

The Impact of Once-Monthly Paliperidone Palmitate on Healthcare Utilization Among Patients With Schizophrenia Treated in an Integrated Healthcare System: A Retrospective Mirror-Image Study.

INTRODUCTION: Previous evidence demonstrated that patients with schizophrenia consumed substantial healthcare resources in an integrated healthcare system. This study evaluated the impact of initiating once-monthly paliperidone palmitate (PP1M) on healthcare resource utilization (HRU) among patients with schizophrenia treated in a US integrated healthcare system. METHODS: This retrospective study used electronic medical records from Atrium Health. Adults with at least two diagnoses of schizophrenia who received an initial PP1M dose between September 2009 and April 2019 (the corresponding date defined the index date) and at least one subsequent dose within 90 days were included. Additionally, patients were required to have received active care (at least one healthcare visit every 6 months) during 12-month pre- and post-index periods and at least one oral antipsychotic prescription during the 12-month pre-index period. Inpatient, emergency room (ER), and outpatient visits were compared over 12-month pre- versus post-index periods within the same cohort using McNemar's and Wilcoxon signed rank tests. Findings were reported for all patients and separately in patients with at least one schizophrenia relapse (schizophrenia-related inpatient or ER visit) during the 12-month pre-index period. RESULTS: The study cohort included 210 patients (mean age 34.2 years, 69.5% male, 39.1% had Medicaid). From the 12-month pre- to post-index period, the proportion of patients with visits and mean number of visits reduced for all-cause inpatient (67.6% to 22.4%, 1.2 to 0.4), 30-day readmission (12.4% to 2.4%, 0.2 to 0.1), and ER (68.6% to 45.7%, 2.3 to 1.2) visits, whereas the mean number of outpatient visits increased (8.7 to 11.6) (all P < 0.05). Similar trends were observed for mental health- and schizophrenia-related HRU. The trends in HRU in patients with prior relapse were similar with a higher extent of reduction in inpatient and ER use compared to the overall cohort. CONCLUSION: Initiation of PP1M was associated with reduced acute HRU in patients with schizophrenia, indicating potential clinical and economic benefits, especially in patients with prior relapse.

Effect of a Virtual Patient Navigation Program on Behavioral Health Admissions in the Emergency Department: A Randomized Clinical Trial.

IMPORTANCE: The number of patients presenting to emergency departments (EDs) for psychiatric care continues to increase. Psychiatrists often make a conservative recommendation to admit patients because robust outpatient services for close follow-up are lacking. OBJECTIVE: To assess whether the availability of a 45-day behavioral health-virtual patient navigation program decreases hospitalization among patients presenting to the ED with a behavioral health crisis or need. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial enrolled 637 patients who presented to 6 EDs spanning urban and suburban locations within a large integrated health care system in North Carolina from June 12, 2017, through February 14, 2018; patients were followed up for up to 45 days. Eligible patients were aged 18 years or older, with a behavioral health crisis and a completed telepsychiatric ED consultation. The availability of the behavioral health-virtual patient navigation intervention was randomly allocated to specific days (Monday through Friday from 7 am to 7 pm) so that, in a 2-week block, there were 5 intervention days and 5 usual care days; 323 patients presented on days when the program was offered, and 314 presented on usual care days. Data analysis was performed from March 7 through June 13, 2018, using an intention-to-treat approach. INTERVENTIONS: The behavioral health-virtual patient navigation program included video contact with a patient while in the ED and telephonic outreach 24 to 72 hours after discharge and then at least weekly for up to 45 days. MAIN OUTCOMES AND MEASURES: The primary outcome was the conversion of an ED encounter to hospital admission. Secondary outcomes included 45-day follow-up encounters with a self-harm diagnosis and postdischarge acute care use. RESULTS: Among 637 participants, 358 (56.2%) were men, and the mean (SD) age was 39.7 (16.6) years. The conversion rates were 55.1% (178 of 323) in the intervention group vs 63.1% (198 of 314) in the usual care group (odds ratio, 0.74; 95% CI, 0.54-1.02; P = .06). The percentage of patient encounters with follow-up encounters having a self-harm diagnosis was significantly lower in the intervention group compared with the usual care group (36.8% [119 of 323] vs 45.5% [143 of 314]; P = .03). CONCLUSIONS AND RELEVANCE: Although the primary result did not reach statistical significance, there is a strong signal of potential positive benefit in an area that lacks evidence, suggesting that there should be additional investment and inquiry into virtual behavioral health programs. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03204643.

Combining Lean and Applied Research methods to improve rigor and efficiency in acute care outcomes research: A case study.

Hospital care is the single, largest contributor to health spending, yet evidence to guide value transformation is lacking. The large, real-world studies required to fill this void are challenging to conduct in the complex and fast-paced acute care environment. To address these challenges, we created a framework that combines Lean manufacturing methodology and Applied Research principles. We deployed this framework to design, pilot, and iteratively improve a study protocol testing the effectiveness of an innovative care pathway for patients hospitalized with acute exacerbations of Chronic Obstructive Pulmonary Disease. Over a three month period, the protocol was successfully piloted and refined at a single site, subsequently becoming the basis for a large system-wide randomized controlled trial. This framework combining Lean and Applied Research methods resulted in synergies that neither method could accomplish alone and may serve as a template for learning healthcare systems to efficiently generate real-world evidence in the acute care setting.