Novel Genes Associated with Atrial Fibrillation and the Predictive Models for AF Incorporating Polygenic Risk Scores and PheWAS-Derived Risk Factors.

BACKGROUND: Atrial fibrillation (AF), the most common atrial arrhythmia, presents varied clinical manifestations. Despite the identification of genetic loci associated with AF, particularly in specific populations, research within Asian ethnicities remains limited. This study aimed to develop predictive models for AF using AF-associated single-nucleotide polymorphisms (SNPs) from a Genome-Wide Association Study (GWAS) on a substantial cohort of Taiwanese individuals, evaluating the models' predictive efficacy. METHODS: Involving 75,121 subjects, including 5,694 AF patients and 69,427 normal controls with GWAS data, the study merged polygenic risk scores (PRS) from AF-associated SNPs with Phenome-wide association study (PheWAS)-derived risk factors. Advanced statistical and machine learning techniques were employed to develop and evaluate AF predictive models for discrimination and calibration. RESULTS: The study identified the top 30 significant SNPs associated with AF, predominantly on chromosomes 10 and 16, implicating genes like NEURL1, SH3PXD2A, INA, NT5C2, STN1, and ZFHX3. Notably, INA, NT5C2, and STN1 were newly linked to AF. The GWAS predictive power using PRS-CS analysis for AF exhibited an area under the curve (AUC) of 0.600 (P < 0.001), improving to 0.855 (P < 0.001) after adjusting for age and gender. PheWAS analysis showed the top 10 diseases associated with these genes were circulatory system diseases. CONCLUSIONS: Integrating genetic and phenotypic data enhanced the accuracy and clinical relevance of AF predictive models. The findings suggest promise for refining AF risk assessment, enabling personalized interventions, and reducing AF-related morbidity and mortality burdens.

Ago2/CAV1 interaction potentiates metastasis via controlling Ago2 localization and miRNA action.

Ago2 differentially regulates oncogenic and tumor-suppressive miRNAs in cancer cells. This discrepancy suggests a secondary event regulating Ago2/miRNA action in a context-dependent manner. We show here that a positive charge of Ago2 K212, that is preserved by SIR2-mediated Ago2 deacetylation in cancer cells, is responsible for the direct interaction between Ago2 and Caveolin-1 (CAV1). Through this interaction, CAV1 sequesters Ago2 on the plasma membranes and regulates miRNA-mediated translational repression in a compartment-dependent manner. Ago2/CAV1 interaction plays a role in miRNA-mediated mRNA suppression and in miRNA release via extracellular vesicles (EVs) from tumors into the circulation, which can be used as a biomarker of tumor progression. Increased Ago2/CAV1 interaction with tumor progression promotes aggressive cancer behaviors, including metastasis. Ago2/CAV1 interaction acts as a secondary event in miRNA-mediated suppression and increases the complexity of miRNA actions in cancer.

Indirect comparisons of relative efficacy estimates of zuranolone and selective serotonin reuptake inhibitors for postpartum depression.

AIMS: Estimate relative efficacy of zuranolone, a novel oral, Food and Drug Administration-approved treatment for postpartum depression (PPD) in adults vs. selective serotonin reuptake inhibitors (SSRIs) and combination therapies used for PPD in the United States. MATERIALS AND METHODS: Randomized controlled trials (RCTs) for zuranolone and SSRIs, identified from systematic review, were used to construct evidence networks, linking via common comparator arms. Due to heterogeneity in placebo responses, matching-adjusted indirect comparison (MAIC) was applied, statistically weighting the zuranolone treatment arm of Phase 3 SKYLARK Study (NCT04442503) to the placebo arm of RCTs investigating SSRIs for PPD. MAIC outputs were applied in Bucher indirect treatment comparisons (ITCs) and network meta-analysis (NMA), using Edinburgh Postnatal Depression Scale (EPDS) and 17-item Hamilton Rating Scale for Depression (HAMD-17) change from baseline (CFB) on Days 3, 15, 28 (Month 1), 45, and last observation (Day 45, Week 12/18). RESULTS: Larger EPDS CFB was observed among zuranolone-treated vs. SSRI-treated patients from Day 15 onward. Zuranolone-treated (vs. SSRI-treated) patients exhibited 4.22-point larger reduction in EPDS by Day 15 (95% confidence interval: -6.16, -2.28) and 7.43-point larger reduction at Day 45 (-9.84, -5.02) with Bucher ITC. NMA showed EPDS reduction for zuranolone was 4.52 (-6.40, -2.65) points larger than SSRIs by Day 15 and 7.16 (-9.47, -4.85) larger at Day 45. Lack of overlap between study populations substantially reduced effective sample size post-matching, making HAMD-17 CFB analysis infeasible. LIMITATIONS: Limited population overlap between SKYLARK Study and RCTs reduced feasibility of undertaking HAMD-17 CFB ITCs and may introduce uncertainty to EPDS CFB ITC results. CONCLUSIONS: Analysis showed zuranolone-treated patients with PPD experienced greater symptom improvement than SSRI-treated patients from Day 15 onward, with largest mean difference at Day 45. Adjusting for differences between placebo arms, zuranolone may be associated with greater PPD symptom improvement (measured by EPDS) vs. SSRIs.

The magnitude and sustainability of treatment benefit of zuranolone on function and well-being as assessed by the SF-36 in adult patients with MDD and PPD: An integrated analysis of 4 randomized clinical trials.

BACKGROUND: Major depressive disorder (MDD) and postpartum depression (PPD) are disabling conditions. This integrated analysis of MDD and PPD clinical trials investigated the impact of zuranolone-a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors and neuroactive steroid under investigation for adults with MDD and approved as an oral, once-daily, 14-day treatment course for adults with PPD in the US-on health-related quality of life, including functioning and well-being, as assessed using the 36-item Short Form Health Survey V2 (SF-36). METHODS: Integrated data from 3 MDD (201B, MOUNTAIN, WATERFALL) and 1 PPD trial (ROBIN) for individual SF-36 domains were compared for zuranolone (30- and 50-mg) vs placebo at Day (D)15 and D42. Comparisons between zuranolone responders (≥50 % reduction from baseline in 17-item Hamilton Depression Rating Scale total score) and nonresponders were assessed. RESULTS: Overall, 1003 patients were included (zuranolone, n = 504; placebo, n = 499). Significant differences in change from baseline (CFB) to D15 for patients in zuranolone vs placebo groups were observed in 6/8 domains; changes were sustained or improved at D42, with significant CFB differences for all 8 domains. Zuranolone responders had significantly higher CFB scores vs nonresponders for all domains at D15 and D42 (p < 0.001). LIMITATIONS: Two zuranolone doses were integrated across populations of 2 disease states with potential differences in functioning, comorbidities, and patient demographics. All p-values presented are nominal. CONCLUSIONS: Integrated data across 4 zuranolone clinical trials showed improvements in functioning and well-being across all SF-36 domains. Benefits persisted after completion of treatment course at D42.

Effects of Human Leukocyte Antigen DRB1 Genetic Polymorphism on Anti-Cyclic Citrullinated Peptide (ANTI-CCP) and Rheumatoid Factor (RF) Expression in Rheumatoid Arthritis (RA) Patients.

Rheumatoid arthritis (RA) is a systemic disease characterized by non-infectious inflammation of the joints and surrounding tissues, which can cause severe health problems, affect the patient's daily life, and even cause death. RA can be clinically diagnosed by the occurrence of blood serological markers, rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (anti-CCP). However, about 20% of RA patients exhibit negative results for both markers, which makes RA diagnosis difficult and, therefore, may delay the effective treatment. Previous studies found some evidence that human leukocyte antigen (HLA)-related genes might be the susceptibility genes for RA and their polymorphisms might contribute to varieties of susceptibility and disease severity. This study aimed for the genetic polymorphisms of the RA patient genome and their effects on the RA patient's serological makers, RF and anti-CCP. A total of 4580 patients' electronic medical records from 1992 to 2020 were retrieved from the China Medical University Hospital database. The most representative single-nucleotide polymorphisms (SNPs) were identified through a genome-wide association study (GWAS) followed by enzyme-linked immunosorbent assay (ELISA) validation using the blood from 30 additional RA patients. The results showed significant changes at the position of chromosome 6 with rs9270481 being the most significant locus, which indicated the location of the HLA-DRB1 gene. Further, patients with the CC genotype at this locus were more likely to exhibit negative results for RF and anti-CCP than those with the TT genotype. The C allele was also more likely to be associated with negative results for RF and anti-CCP. The results demonstrated that a genetic polymorphism at rs9270481 affected the expression of RF and anti-CCP in RA patients, which might indicate the necessity to develop a personalized treatment plan for each individual patient based on the genetic profile.

The Economic Burden of Adults with Major Depressive Disorder in the United States (2019).

INTRODUCTION: Previous societal burden estimations for major depressive disorder (MDD) often fail to account for several hidden cost components. This study provides a comprehensive evaluation of societal costs for adults with MDD in the United States (USA) in 2019. The potential impact of a more effective, rapid-acting MDD therapy vs standard of care on the economic burden of MDD was estimated to illustrate the utility of such a framework in evaluating new interventions. METHODS: This study used a prevalence-based human capital approach. Incremental costs (2019 US dollars) per individual with MDD were derived from national survey inputs and published literature and included incremental healthcare costs and indirect costs. For each cost component, the societal costs were extrapolated by multiplying the per-patient costs by the number of individuals with MDD. The impact of a more effective, rapid-acting novel therapy on the economic burden of MDD was then simulated on the basis of these inputs. RESULTS: In 2019, the number of adults with MDD in the USA was estimated at 19.8 million (62.7% female; 32.9% severe MDD), and the incremental societal economic burden of MDD was estimated at $333.7 billion ($382.4 billion in 2023 US dollars), or $16,854 per adult with MDD. The primary cost drivers were healthcare costs ($127.3 billion; 38.1%), household-related costs ($80.1 billion; 24.0%), presenteeism ($43.3 billion; 13.0%), and absenteeism ($38.4 billion; 11.5%). In the simulated scenario, a hypothetical novel therapy with a 50.0% early response rate was associated with a 7.7% reduction in the economic burden of MDD relative to standard of care over 12 months. CONCLUSIONS: The economic burden of MDD is substantial and extends beyond healthcare costs, underscoring the impact of MDD across multiple aspects of life. Such a broad societal perspective should be considered in assessing the impact of the advent of effective, rapid-acting MDD therapies.

Reperfusion by endovascular thrombectomy and early cerebral edema in anterior circulation stroke: Results from the SITS-International Stroke Thrombectomy Registry.

BACKGROUND: A large infarct and expanding cerebral edema (CED) due to a middle cerebral artery occlusion confers a 70% mortality unless treated surgically. There is still conflicting evidence whether reperfusion is associated with a lower risk for CED in acute ischemic stroke. AIM: To investigate the association of reperfusion with development of early CED after stroke thrombectomy. METHODS: From the SITS-International Stroke Thrombectomy Registry, we selected patients with occlusion of the intracranial internal carotid or middle cerebral artery (M1 or M2). Successful reperfusion was defined as mTICI ⩾ 2b. Primary outcome was moderate or severe CED, defined as focal brain swelling ⩾1/3 of the hemisphere on imaging scans at 24 h. We used regression methods while adjusting for baseline variables. Effect modification by severe early neurological deficits, as indicators of large infarct at baseline and at 24 h, were explored. RESULTS: In total, 4640 patients, median age 70 years and median National Institutes of Health Stroke Score (NIHSS) 16, were included. Of these, 86% had successful reperfusion. Moderate or severe CED was less frequent among patients who had reperfusion compared to patients without reperfusion: 12.5% versus 29.6%, p < 0.05, crude risk ratio (RR) 0.42 (95% confidence interval (CI): 0.37-0.49), and adjusted RR 0.50 (95% CI: 0.44-0.57). Analysis of effect modification indicated that severe neurological deficits weakened the association between reperfusion and lower risk of CED. The RR reduction was less favorable in patients with severe neurological deficits, defined as NIHSS score 15 or more at baseline and at 24 h, used as an indicator for larger infarction. CONCLUSION: In patients with large artery anterior circulation occlusion stroke who underwent thrombectomy, successful reperfusion was associated with approximately 50% lower risk for early CED. Severe neurological deficit at baseline seems to be a predictor for moderate or severe CED also in patients with successful reperfusion by thrombectomy.

Cerebral Edema in Patients with severe Hemispheric Syndrome: Incidence, Risk Factors, and Outcomes-Data from SITS-ISTR.

BACKGROUND AND PURPOSE: Cerebral edema (CED) in ischemic stroke can worsen prognosis and about 70% of patients who develop severe CED die if treated conservatively. We aimed to describe incidence, risk factors and outcomes of CED in patients with extensive ischemia. METHODS: Oservational study based on Safe Implementation of Treatments in Stroke-International Stroke Treatment Registry (2003-2019). Severe hemispheric syndrome (SHS) at baseline and persistent SHS (pSHS) at 24 hours were defined as National Institutes of Health Stroke Score (NIHSS) >15. Outcomes were moderate/severe CED detected by neuroimaging, functional independence (modified Rankin Scale 0-2) and death at 90 days. RESULTS: Patients (n=8,560) presented with SHS and developed pSHS at 24 hours; 82.2% received intravenous thrombolysis (IVT), 10.5% IVT+thrombectomy, and 7.3% thrombectomy alone. Median age was 77 and NIHSS 21. Of 7,949 patients with CED data, 3,780 (47.6%) had any CED and 2,297 (28.9%) moderate/severe CED. In the multivariable analysis, age <50 years (relative risk [RR], 1.56), signs of acute infarct (RR, 1.29), hyperdense artery sign (RR, 1.39), blood glucose >128.5 mg/dL (RR, 1.21), and decreased level of consciousness (RR, 1.14) were associated with moderate/severe CED (for all P<0.05). Patients with moderate/severe CED had lower odds to achieve functional Independence (adjusted odds ratio [aOR], 0.35; 95% confidence interval [CI], 0.23 to 0.55) and higher odds of death at 90 days (aOR, 2.54; 95% CI, 2.14 to 3.02). CONCLUSIONS: In patients with extensive ischemia, the most important predictors for moderate/ severe CED were age <50, high blood glucose, signs of acute infarct, hyperdense artery on baseline scans, and decreased level of consciousness. CED was associated with worse functional outcome and a higher risk of death at 3 months.

Genetic and Functional Effects of Adiponectin in Type 2 Diabetes Mellitus Development.

Diabetes mellitus (DM) is a common chronic metabolic disease, and the C57BLKsJ-db/db mice are good animal models for type 2 diabetes mellitus (T2DM). In this study, Western blotting and immunohistochemistry (IHC) were employed to examine the protein expression of adiponectin in the liver tissues of T2DM mice with different disease courses (4, 16, and 32 weeks). Adiponectin expression reduced in the liver tissues of T2DM mice in different disease courses. The genotypic and allelic frequencies of the adiponectin gene rs1063538 and rs2241766 single nucleotide polymorphisms (SNPs) in a Taiwanese population (570 T2DM patients and 1700 controls) were investigated. Based on the genetic distribution of the rs2241766 locus, the distribution frequency of the T allele in the T2DM group (72.8%) was higher than in the control group (68.8%). Individuals carrying the G allele had a 0.82-fold greater risk of developing T2DM than individuals carrying the T allele. Differences were evident in the genotypic and allelic distributions (p < 0.05). Enzyme-linked immunosorbent assay (ELISA) was used to measure changes in serum adiponectin protein concentrations in the healthy population and in patients with T2DM. Serum adiponectin concentration in patients with T2DM was lower than in the control group. In summary, adiponectin was determined to be a T2DM susceptibility gene and may be involved in T2DM progression.

Predicting non-initiation of care and dropout in a blended care CBT intervention: Impact of early digital engagement, sociodemographic, and clinical factors.

Objective: This study examines predictors of non-initiation of care and dropout in a blended care CBT intervention, with a focus on early digital engagement and sociodemographic and clinical factors. Methods: This retrospective cohort analysis included 3566 US-based individuals who presented with clinical levels of anxiety and depression and enrolled in a blended-care CBT (BC-CBT) program. The treatment program consisted of face-to-face therapy sessions via videoconference and provider-assigned digital activities that were personalized to the client's presentation. Multinomial logistic regression and Cox proportional hazard survival analysis were used to identify predictors of an increased likelihood of non-initiation of therapy and dropout. Results: Individuals were more likely to cancel and/or no-show to their first therapy session if they were female, did not disclose their ethnicity, reported poor financial status, did not have a college degree, endorsed more presenting issues during the onboarding triage assessment, reported taking antidepressants, and had a longer wait time to their first appointment. Of those who started care, clients were significantly more likely to drop out if they did not complete the digital activities assigned by their provider early in treatment, were female, reported more severe depressive symptoms at baseline, reported taking antidepressants, and did not disclose their ethnicity. Conclusions: Various sociodemographic and clinical predictors emerged for both non-initiation of care and for dropout, suggesting that clients with these characteristics may benefit from additional attention and support (especially those with poor early digital engagement). Future research areas include targeted mitigation efforts to improve initiation rates and curb dropout.

Genome-wide association study of hyperthyroidism based on electronic medical record from Taiwan.

Excess thyroid hormones have complex metabolic effects, particularly hyperthyroidism, and are associated with various cardiovascular risk factors. Previous candidate gene studies have indicated that genetic variants may contribute to this variable response. Electronic medical record (EMR) biobanks containing clinical and genomic data on large numbers of individuals have great potential to inform the disease comorbidity development. In this study, we combined electronic medical record (EMR) -derived phenotypes and genotype information to conduct a genome-wide analysis of hyperthyroidism in a 35,009-patient cohort in Taiwan. Diagnostic codes were used to identify 2,767 patients with hyperthyroidism. Our genome-wide association study (GWAS) identified 44 novel genomic risk markers in 10 loci on chromosomes 2, 6, and 14 (P < 5 × 10-14), including CTLA4, HCP5, HLA-B, POU5F1, CCHCR1, HLA-DRA, HLA-DRB9, TSHR, RPL17P3, and CEP128. We further conducted a comorbidity analysis of our results, and the data revealed a strong correlation between hyperthyroidism patients with thyroid storm and stroke. In this study, we demonstrated application of the PheWAS using large EMR biobanks to inform the comorbidity development in hyperthyroidism patients. Our data suggest significant common genetic risk factors in patients with hyperthyroidism. Additionally, our results show that sex, body mass index (BMI), and thyroid storm are associated with an increased risk of stroke in subjects with hyperthyroidism.

Component analysis of a synchronous and asynchronous blended care CBT intervention for symptoms of depression and anxiety: Pragmatic retrospective study.

Background: Depression and anxiety are leading causes of disability worldwide. Though effective treatments exist, depression and anxiety remain undertreated. Blended care psychotherapy, combining the scalability of online interventions with the personalization and engagement of a live therapist, is a promising approach for increasing access to evidence-based care. Objectives: To evaluate the effectiveness and individual contribution of two components - i) digital tools and ii) video-based therapist-led sessions - in a blended care CBT-based intervention under real world conditions. Methods: A retrospective cohort design was used to analyze N = 1372 US-based individuals who enrolled in blended care psychotherapy. Of these, at baseline, 761 participants had depression symptoms in the clinical range (based on PHQ-9), and 1254 had anxiety symptoms in the clinical range (based on GAD-7). Participants had access to the program as a mental health benefit offered by their employer. The CBT-based blended care psychotherapy program consisted of regular video sessions with therapists, complemented by digital lessons and digital exercises assigned by the clinician and completed in between sessions. Depression and anxiety levels and clients' treatment engagement were tracked throughout treatment. A 3-level individual growth curve model incorporating time-varying covariates was utilized to examine symptom trajectories of PHQ-9 scores (for those with clinical range of depression at baseline) and GAD-7 scores (for those with clinical range of anxiety at baseline). Results: On average, individuals exhibited a significant decline in depression and anxiety symptoms during the initial weeks of treatment (P < .001), and a continued decline over subsequent weeks at a slower rate (P < .001). Engaging in a therapy session in a week was associated with lower GAD-7 (b = -0.81) and PHQ-9 (b = -1.01) scores in the same week, as well as lower GAD-7 (b = -0.58) and PHQ-9 (b = -0.58) scores the following week (all P < .01). Similarly, engaging with digital lessons was independently associated with lower GAD-7 (b = -0.19) and PHQ-9 (b = -0.18) scores during the same week, and lower GAD-7 (b = -0.25) and PHQ-9 (b = -0.27) the following week (all P < .01). Conclusions: Therapist-led video sessions and digital lessons had separate contributions to improvements in symptoms of depression and anxiety over the course of treatment. Future research should investigate whether clients' characteristics are related to differential effects of therapist-led and digital components of care.

Analysis of HLA Variants and Graves' Disease and Its Comorbidities Using a High Resolution Imputation System to Examine Electronic Medical Health Records.

Hyperthyroidism is a prevalent endocrine disorder, and genetics play a major role in the development of thyroid-associated diseases. In particular, the inheritance of HLA has been demonstrated to induce the highest susceptibility to Graves' disease (GD). However, thus far, no studies have reported the contribution of HLA to the development of GD and the complications that follow. Thus, in the present study, to the best of our knowledge, for the first time, a powerful imputation method, HIBAG, was used to predict the HLA subtypes among populations with available genome-wide SNP array data from the China Medical University Hospital (CMUH). The disease status was extracted from the CMUH electronic medical records; a total of 2,998 subjects with GD were identified as the cases to be tested and 29,083 subjects without any diagnosis of thyroid disorders were randomly selected as the controls. A total of 12 HLA class I genotypes (HLA-A*02:07-*11:01, HLA-B*40:01-*46:01 and *46:01-*46:01, and HLA-C*01:02-*01:02, *01:02-*03:04, and *01:02-*07:02) and 17 HLA class II genotypes (HLA-DPA1*02:02-*02:02, HLA-DPB1*02:01-*05:01, *02:02-*05:01, and *04:01-*05:01, HLA-DQA1*03:02, HLA-DRB1*09:01-*15:01, and *09:01-*09:01) were found to be associated with GD in the Taiwanese population. Moreover, the HLA subtypes HLA-A*11:01, HLA-B*46:01, HLA-DPA1*01:03, and HLA-DPB1*05:01 were found to be associated with heart disease, stroke, diabetes, and hypertension among subjects with GD. Our data suggest that several HLA alleles are markedly associated with GD and its comorbidities, including heart disease, hypertension, and diabetes.

Telemental Health Collaborative Care Medication Management: Implementation and Outcomes.

Introduction: Access to quality mental health medication management (MM) in the United States is limited, even among those with employment-based health insurance. This implementation, feasibility, and outcome study sought to design and evaluate an evidence-based telemental health MM service using a collaborative care model (CoCM). Materials and Methods: CoCM MM was available to adult employees/dependents through their employer benefits, in addition to therapy. Outcomes included Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7) collected at baseline and throughout participation. This analysis was not deemed to be human subjects research by the Western Institutional Review Board. Results: Over 17 months, 212 people enrolled and completed >2 assessments; the enrollees were 58.96% female with average age of 32.00 years (standard deviation [SD] = 7.38). In people with moderate to severe depression or anxiety, PHQ-9 and GAD-7 scores reduced by an average of 7.27 (SD = 4.80) and 6.71 (SD = 5.18) points after at least 12 ± 4 weeks in the program. At 24 ± 4 weeks, the PHQ-9 and GAD-7 reductions were on average 7.17 (SD = 5.00) and 6.03 (SD = 5.37), respectively. Approximately 65.88% of participants with either baseline depression or anxiety had a response on either the PHQ-9 or GAD-7 at 12 ± 4 weeks and 44.71% of participants experienced remission; at 24 ± 4 weeks, 56.41% had response and 41.03% experienced remission. Conclusions: An evidence-based CoCM telemedicine service within an employee behavioral health benefit is feasible and effective in reducing anxiety and depression symptoms when using measurement-based care. Widespread implementation of a benefit like this could expand access to evidence-based mental health MM.

A Real-World Assessment of Outcomes, Health Resource Utilization, and Costs Associated with Cerebral Edema in US Patients with Large Hemispheric Infarction.

BACKGROUND: Patients with large hemispheric infarction (LHI) are at risk of cerebral edema (CED). This study analyzed health resource use, costs, and outcomes during and after acute hospitalization for LHI in US patients with and without CED. METHODS: Using IBM® MarketScan® Commercial, Medicaid, and Medicare databases, patients with incident hospitalization for LHI (International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes of I63.03x, I63.13x, I63.23x, I63.31x, I63.41x, I63.51x) from 31 March 2016 through 31 December 2018 were identified and further categorized by the presence or absence of CED based on related diagnosis codes or a procedure code of craniectomy. Health resource use, costs, and outcomes were compared in patients with and without CED during hospitalization and after discharge. RESULTS: Of 7336 Commercial, 1946 Medicaid, and 5015 Medicare patients with LHI, 7.8%, 6.9%, and 4.3% had CED, respectively. After adjusting for age, sex, and baseline comorbidities, differences (95% confidence intervals) in mean total costs of the index hospitalization in patients with CED versus without CED were $65,572 ($56,506-$76,335), $44,395 ($26,442-$63,495), and $31,417 ($18,982-$48,543) in the Commercial, Medicaid, and Medicare groups, respectively. Similarly, the adjusted differences (95% confidence intervals) in mean lengths of stay between patients with CED and without CED were 11.75 (10.17-13.48), 10.84 (7.59-14.17), and 3.69 (2.40-5.19) days, respectively. Mortality during index hospitalization was 10-20 times greater in patients with CED versus without CED (p < 0.0001). In those patients who survived and had at least 30-days of follow-up after discharge, CED was also associated with higher post-discharge resource utilization and costs in the commercially insured population who were younger than Medicare patients, and had fewer comorbidities than Medicare and Medicaid patients. This indicates the effect of CED after discharge was particularly burdensome for younger individuals. CONCLUSIONS: In this large cohort study, inpatient mortality, health resource utilization and costs were consistently higher in patients with LHI who developed CED than in those without CED. These findings underscore the need for greater awareness of CED among policymakers and healthcare practitioners.

Examining the Impact of Digital Components Across Different Phases of Treatment in a Blended Care Cognitive Behavioral Therapy Intervention for Depression and Anxiety: Pragmatic Retrospective Study.

BACKGROUND: Depression and anxiety incur significant personal and societal costs. Effective psychotherapies exist, such as cognitive behavioral therapy (CBT); however, timely access to quality care is limited by myriad barriers. Blended care therapy models incorporate traditional face-to-face therapy with scalable, digital components of care, expanding the reach of evidence-based care. OBJECTIVE: The aim of this study is to determine the effectiveness of a blended care CBT program (BC-CBT) in real-world settings and examine the unique impacts of the (1) digital components of care (video lessons and digital exercises) and (2) phase of treatment (early versus late) in decreasing symptoms of anxiety and depression. METHODS: This retrospective cohort analysis included 3401 US-based individuals enrolled in a BC-CBT program, who presented with clinical levels of depression and/or anxiety. The treatment program consisted of regular therapy sessions augmented by clinician-assigned digital video lessons and exercises. A growth curve model incorporating time-varying covariates examined the relationship between engagement with BCT components (ie, therapy sessions, digital video lessons, and digital exercises) during the early (weeks 0-7) and late (weeks 8-15) phases of treatment, and weekly symptom reports on depression and anxiety measures. RESULTS: On average, a significant decline in depression and anxiety symptoms was observed during the initial weeks of treatment (P<.001), with a continued, though slower, decline over subsequent weeks (P<.001). Each session completed was associated with significant decreases in anxiety (b=-0.72) and depression (b=-0.83) in the early phase, as well as in the late phase (anxiety, b=-0.47; depression, b=-0.27). Significant decreases in anxiety (b=-0.15) and depression (b=-0.12) were observed for time spent on video lessons (measured in 10-minute intervals) in the early phase of treatment. Engaging with exercises was associated with statistically significant increases in anxiety symptoms (b=0.03) during the early phase of treatment. However, sensitivity analyses examining the effects of exercises in isolation revealed significant decreases in anxiety (b=-0.05) in the early phase, suggesting a potential suppression effect in the larger model. CONCLUSIONS: Using a retrospective cohort design, therapy sessions and digital video lessons were uniquely predictive of improvements in depression and anxiety symptoms, and their effects were modulated based on the phase of treatment (early vs late). Future research should investigate whether other treatment variables, such as therapeutic alliance or familiarity with technology, are related to differential effects on various components of care.

Outcomes of a Blended Care Coaching Program for Clients Presenting With Moderate Levels of Anxiety and Depression: Pragmatic Retrospective Study.

BACKGROUND: Depression and anxiety are leading causes of disability worldwide, but access to quality mental health care is limited by myriad factors. Cognitive-behavioral coaching is rooted in evidence-based principles and has the potential to address some of these unmet care needs. Harnessing technology to facilitate broader dissemination within a blended care model shows additional promise for overcoming barriers to care. OBJECTIVE: The aim of this study is to evaluate the outcomes of a blended care coaching (BCC) program for clients presenting with moderate levels of anxiety and depression in real-world settings. METHODS: This study examined retrospective data from US-based individuals (N=1496) who presented with moderate levels of depression and anxiety symptoms and who received blended care coaching services. Using a short-term framework, clients met with coaches via a secure video conference platform and also received digital video lessons and exercises. To evaluate the effectiveness of the BCC program, mixed effects modeling was used to examine growth trajectories of anxiety and depression scores over the course of care. RESULTS: Out of the total sample of 1496 clients, 75.9% (n=1136) demonstrated reliable improvement, and 88.6% (n=1326) recovered based on either the Generalized Anxiety Disorder-7 scale (anxiety) or Patient Health Questionnaire-9 (depression). On average, clients exhibited a significant decline in anxiety and depression symptoms during the initial weeks of coaching, with a continued decline over subsequent weeks at a lower rate. Engaging in a coaching session was associated with lower anxiety (b=-1.04) and depression (b=-0.79) symptoms in the same week, as well as lower anxiety (b=-0.74) and depression (b=-0.91) symptoms the following week (P<.001). CONCLUSIONS: The BCC program demonstrated strong outcomes in decreasing symptomology for clients presenting with moderate levels of anxiety and depression. When clients received coaching sessions, significant decreases in symptoms were observed, reflecting the importance of session attendance. Additionally, the steepest declines in symptoms tended to occur during the initial weeks of coaching, emphasizing the importance of client buy-in and early engagement. Collectively, these findings have implications for addressing unmet mental health care needs in a more accessible, cost-effective manner.

Outcomes and resource use of patients with large hemispheric infarction and cerebral edema: analysis of real-world data.

OBJECTIVE: Large hemispheric infarction (LHI) is associated with a high likelihood of the evolution of life-threatening edema. Few studies have assessed real-world clinical outcomes and management strategies among patients with LHI. The objective of this study was to describe the management, in-hospital outcomes, and direct healthcare resource burden of patients with LHI, as well as those of patients with subsequent cerebral edema. METHODS: This observational, retrospective cohort study analyzed de-identified data from US adult patients using the IBM MarketScan Hospital Drug Database (Q4-2015 to Q4-2017). Patients were included in the "Possible LHI" or the "Other Ischemic Strokes" cohorts using ICD-10 diagnosis codes. Patients with possible LHI were further categorized into "LHI with Edema" and "LHI without Edema" subgroups using diagnosis and procedure codes. Select clinical and economic outcomes were compared between cohorts and subgroups using multivariable regressions. RESULTS: Of 79,201 eligible encounters with ischemic strokes, 11,772 unique patients were assigned to the Possible LHI cohort while 67,429 were assigned to the Other Ischemic Strokes cohort. Among patients with possible LHI, 869 (7%) were assigned to the LHI with Edema subgroup and 10,903 (93%) were assigned to the LHI without Edema subgroup. Patients in the Possible LHI cohort had longer hospital stays (mean difference [MD] [95%CI] = 2.6 [2.4;2.8] days), higher total facility charges (MD [95%CI] = $28,656 [26,794;30,524]), and higher odds of death (odds ratio [95%CI] = 2.2 [2.0;2.4]) than the Other Ischemic Strokes cohort. Among patients with possible LHI, the incremental clinical and resource burden was further exacerbated in the subgroup of patients with edema (hospital days: MD [95%CI] = 5.0 [3.9;6.2] days; total facility charges: MD [95%CI] = $59,585 [50,816;67,583]; mortality: odds ratio [95%CI] = 10.3 [8.5;12.4]). CONCLUSIONS: Among patients with ischemic strokes, LHI was associated with increased clinical management and direct healthcare resource burden in real-world hospital settings. The burden was substantially increased among patients who developed cerebral edema.

Effectiveness of a Cognitive Behavioral Coaching Program Delivered via Video in Real World Settings.

Background: Many employees experience high levels of stress in the workplace, which negatively impact their productivity and well-being. Effective stress management interventions exist, but are inaccessible due to insufficient numbers of mental health providers, long waiting times to initiate care, high out-of-pocket cost of care, and stigma related to receiving psychotherapy. Introduction: The purpose of this study was to test the efficacy, in real-world circumstances, of a structured, cognitive behavioral coaching (CBC) program delivered through video or telephone. Materials and Methods: Retrospective data on 289 subjects who had sought support for emotional health through a behavioral health benefit offered through employers were examined. Changes in perceived stress and well-being over the course of the program were measured using the Perceived Stress Scale (PSS) and Warwick-Edinburgh Mental Well-being Scale (WEMWBS), respectively. Rates of reliable change and satisfaction with the coaching program were also assessed. Results: Scores on both the PSS and WEMWBS improved between baseline and follow-up. Approximately 61.9% (n = 289) of participants demonstrated reliable improvement on either measure. Discussion: CBC is a promising intervention that has the potential to significantly expand access to effective and more affordable interventions for emotional health care. Conclusions: Coaching, when delivered by accredited professionals trained in cognitive behavioral theory and interventions and working in real-world settings, can be efficacious in decreasing perceived stress and increasing well-being when delivered through video or telephone.