Relapse Prevention: a Cost-Effectiveness Analysis of Brexpiprazole Treatment in Adult Patients with Schizophrenia in the USA

Objective: This study used a decision-analytic framework to assess the cost-effectiveness of brexpiprazole vs comparator branded therapies for reducing relapses and hospitalizations among adults with schizophrenia from a US payer perspective. Methods: An economic model was developed to assess patients with stable schizophrenia initiating treatment with brexpiprazole (1-4 mg), cariprazine (1-6 mg), or lurasidone (40-80 mg) over a 1-year period. After 6 months, patients remained on treatment or discontinued due to relapse, adverse events, or other reasons. Patients who discontinued due to relapse or adverse events were assumed to have switched to other therapy, and those who discontinued due to other reasons were assumed to have received no therapy. Primary outcomes were incremental cost per relapse avoided and hospitalization avoided, and the secondary outcome was cost per quality-adjusted life-year (QALY) gained. Sensitivity and scenario analyses were also conducted. Results: Brexpiprazole was associated with the highest per-patient clinical effectiveness (avoided relapses 0.637, avoided hospitalizations 0.719, QALYs 0.707) among comparators, followed by cariprazine (avoided relapses 0.590, avoided hospitalizations 0.683, QALYs 0.683) and lurasidone (avoided relapses 0.400, avoided hospitalizations 0.536, QALYs 0.623). Annual per-patient health-care costs were lowest for brexpiprazole ($20,510), followed by cariprazine ($22,282) and lurasidone ($25,510). Brexpiprazole was the least costly and most effective treatment strategy for all outcomes. Results were sensitive to relapse rates and daily cost of brexpiprazole. Limitations include data principally obtained from drug-specific randomized withdrawal studies and lack of direct-comparison trials. Conclusion: This analysis evaluated brexpiprazole treatment for the reduction of schizophrenia relapses and hospitalizations over a 1-year period compared to other recently available branded antipsychotics, and excluded generic antipsychotic treatments. Brexpiprazole treatment may lead to clinical benefits and medical cost savings, and provides a cost-effective treatment option for patients relatively to other branded second-generation antipsychotics

Coexistence of anti-SOX1 and anti-GABAB receptor antibodies with paraneoplastic limbic encephalitis presenting with seizures and memory impairment in small cell lung cancer: A case report

PurposeParaneoplastic neurological syndromes associated with autoantibodies are rare diseases that cause abnormal manifestations of the nervous system. Early diagnosis of paraneoplastic neurological syndromes paves the way for prompt and efficient therapy.Case reportwe reported a 56-year-old man presenting with seizures and rapidly progressive cognitive impairment diagnosed as paraneoplastic limbic encephalitis (PLE) with anti-SRY-like high-mobility group box-1 (SOX-1) and anti-γ-aminobutyric acid B (GABAB) receptor antibodies and finally confirmed by biopsy as small cell lung cancer (SCLC). At the first admission, brain magnetic resonance imaging (MRI) showed no abnormal signal in bilateral hippocampal regions and no abnormal enhancement of enhanced scan. The serum anti-GABAB receptor antibody was 1:100 and was diagnosed as autoimmune encephalitis (AE). The computed tomography (CT) scans of the chest showed no obvious tumor signs for the first time. Although positron emission tomography-computed tomography (PET-CT) revealed hypermetabolism in the para mid-esophageal, the patient and his family declined to undertake a biopsy. The patient improved after receiving immunoglobulin, antiepileptic therapy, and intravenous methylprednisolone (IVMP) pulse treatment. However, after 4 months, the symptoms reappeared. Brain MRI revealed abnormal signals in the hippocampal regions. Reexamination of the cerebral fluid revealed anti-GABAB receptor and anti-SOX-1 antibodies, which contributed to the diagnosis of PLE. SCLC was found in a para mid-esophageal pathological biopsy. Antiepileptic medications and immunoglobulin were used to treat the patient, and the symptoms were under control.ConclusionOur findings increase the awareness that patients with limbic encephalitis with cognitive dysfunction and epileptic seizures should be enhanced to detect latent malignancy. Our case also highlights the importance of anti-SOX1 antibodies in the detection of underlying neoplasm, particularly SCLC. Our findings raise awareness of the cognitive impairment seen by patients with limbic encephalitis

Early changes of bone metabolites and lymphocyte subsets may participate in osteoporosis onset: a preliminary study of a postmenopausal osteoporosis mouse model

PurposeMetabolic and immune changes in the early stages of osteoporosis are not well understood. This study aimed to explore the changes in bone metabolites and bone marrow lymphocyte subsets and their relationship during the osteoporosis onset.MethodsWe established OVX and Sham mouse models. After 5, 15, and 40 days, five mice in each group were sacrificed. Humeri were analyzed by microCT. The bone marrow cells of the left femur and tibia were collected for flow cytometry analysis. The right femur and tibia were analyzed by LC-MS/MS for metabolomics analysis.ResultsBone microarchitecture was significantly deteriorated 15 days after OVX surgery. Analysis of bone metabolomics showed that obvious metabolite changes had happened since 5 days after surgery. Lipid metabolism was significant at the early stage of the osteoporosis. The proportion of immature B cells was increased, whereas the proportion of mature B cells was decreased in the OVX group. Metabolites were significantly correlated with the proportion of lymphocyte subsets at the early stage of the osteoporosis.ConclusionLipid metabolism was significant at the early stage of the osteoporosis. Bone metabolites may influence bone formation by interfering with bone marrow lymphocyte subsets

Real‐world treatment patterns of metastatic non‐small cell lung cancer patients receiving epidermal growth factor receptor tyrosine kinase inhibitors

Abstract Background Several epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI) have been approved for first‐line (1L) treatment of EGFR‐mutated metastatic non‐small cell lung cancer (mNSCLC) in the United States (US). Real‐world analyses of 1L treatment patterns with EGFR TKIs, including the third‐generation EGFR TKI osimertinib which was most recently approved in 2018, are still sparse. Methods This retrospective observational study used data from IQVIA's prescription claims (LRx) and medical claims (Dx) databases. mNSCLC patients newly treated with any EGFR TKI in the 1L setting were identified from January 1, 2015 to April 30, 2020; the first date of EGFR TKI (third‐generation osimertinib, first‐generation [erlotinib, gefitinib], or second‐generation [afatinib, dacomitinib]) was the index date. Treatment patterns were reported in the cohorts stratified by 1L EGFR TKI. Results A total of 2505 patients were included in the study (982 osimertinib, 1060 first‐generation, and 463 second‐generation EGFR TKI). Beginning in 2018, osimertinib became the most common 1L EGFR TKI (66.7%) and in early 2020, it accounted for 90.6% of 1L EGFR TKIs. Nearly all patients (>97%) were treated with 1L EGFR TKI monotherapy. Patients with 1L osimertinib had longer treatment duration compared to patients with 1L first‐ or second‐generation EGFR TKI (median months: 17.8 vs. 8.7 vs. 10.5, respectively; log‐rank test for comparisons with osimertinib p < 0.0001) over median follow‐up times of 9.8, 20.5, and 19.3 months. 32.5% and 36.3% of the first‐ and second‐generation EGFR TKI cohorts, respectively, had evidence of 2L treatment. Osimertinib monotherapy accounted for the majority of 2L treatments (58.3%/60.7%) and 11.3%/8.9% had 2L chemotherapy or immuno‐oncology therapy following 1L first‐ or second‐generation EGFR TKI. Conclusion In this real‐world study of a US claims database, 1L treatment duration was longer with osimertinib compared with other EGFR TKIs. Future studies with longer follow‐up are recommended to understand treatment patterns after progression on EGFR TKIs

Estimating Full-Coverage PM2.5 Concentrations Based on Himawari-8 and NAQPMS Data over Sichuan-Chongqing

Fine particulate matter (PM2.5) has attracted extensive attention due to its harmful effects on humans and the environment. The sparse ground-based air monitoring stations limit their application for scientific research, while aerosol optical depth (AOD) by remote sensing satellite technology retrieval can reflect air quality on a large scale and thus compensate for the shortcomings of ground-based measurements. In this study, the elaborate vertical-humidity method was used to estimate PM2.5 with the spatial resolution 1 km and the temporal resolution 1 hour. For vertical correction, the scale height of aerosols (Ha) was introduced based on the relationship between the visibility data and extinction coefficient of meteorological observations to correct the AOD of the Advance Himawari Imager (AHI) onboard the Himawari-8 satellite. The hygroscopic growth factor (f(RH)) was fitted site-by-site and month by month (1&ndash;12 months). Meanwhile, the spatial distribution of the fitted coefficients can be obtained by interpolation assuming that the aerosol properties vary smoothly on a regional scale. The inverse distance weighted (IDW) method was performed to construct the hygroscopic correction factor grid for humidity correction so as to estimate the PM2.5 concentrations in Sichuan and Chongqing from 09:00 to 16:00 in 2017&ndash;2018. The results indicate that the correlation between &ldquo;dry&rdquo; extinction coefficient and PM2.5 is slightly improved compared to the correlation between AOD and PM2.5, with r coefficient values increasing from 0.12&ndash;0.45 to 0.32&ndash;0.69. The r of hour-by-hour verification is between 0.69 and 0.85, and the accuracy of the afternoon is higher than that of the morning. Due to the missing rate of AOD in the southwest is very high, this study utilized inverse variance weighting (IVW) gap-filling method combine satellite estimation PM2.5 and the nested air-quality prediction modeling system (NAQPMS) simulation data to obtain the full-coverage hourly PM2.5 concentration and analyze a pollution process in the fall and winter

New findings on choroidal features in healthy people by ultra-widefield swept-source optical coherence tomography angiography

Abstract To evaluate the distribution of choroidal thickness (CT) and its trend with age in healthy people using 120° ultra-wide field swept-source optical coherence tomography angiography (UWF SS-OCTA). In this cross-sectional observational study, healthy volunteers underwent single imaging of the fundus with UWF SS-OCTA at a field of view (FOV) of 120° (24 mm × 20 mm) centered on the macula. The characteristics of CT distribution in different regions and its changes with age were analyzed. A total of 128 volunteers with a mean age of 34.9 ± 20.1 years and 210 eyes were enrolled in the study. The thickest mean choroid thickness (MCT) was located at the macular region and supratemporal region, followed by the nasal side of the optic disc, and thinnest below the optic disc. The maximum MCT was: 213.40 ± 36.65 μm for the group aged 20–29, and the minimum MCT was: 162.11 ± 31.96 μm for the group aged ≥ 60. After the age of 50, MCT was significantly and negatively correlated decreased with age (r = − 0.358, p = 0.002), and the MCT in the macular region decreased more remarkably compared to other regions. The 120° UWF SS-OCTA can observe the distribution of choroidal thickness in the range of 24 mm × 20 mm and its variation with age. It was revealed that MCT decreased more rapidly in the macular region relative to other regions after 50 years old