Faculty Bibliography

BACKGROUND:Transcranial photobiomodulation (t-PBM) with near-infrared light stimulates mitochondria and may have antidepressant effects. We evaluated dose-dependent effects of t-PBM on the hemodynamic blood-oxygenation-level-dependent (BOLD) power in major depressive disorder (MDD). METHODS:. t-PBM (808 nm) was delivered to the prefrontal cortex, bilaterally. fMRI was recorded at 3T before, during, and after t-PBM. We used mixed-effects linear regression to evaluate changes in BOLD power during stimulation, compared to sham. The analysis was repeated for the middle frontal gyrus (MFG), the prefrontal areas irradiated by t-PBM, and the entire brain cortex. RESULTS:We found similar results in the MFG, the prefrontal cortex directly irradiated, and the entire brain cortex: medium dose t-PBM was associated with a statistically significant increase in BOLD power, whereas low dose t-PBM was associated with a significant decrease in BOLD. There were no significant changes in BOLD power with the high (pulsed) t-PBM dose or with sham. Single administrations of any t-PBM dose did not result in significant changes in depression severity (versus sham). All 3 t-PBM doses were well tolerated. CONCLUSION/CONCLUSIONS:The acute effect of t-PBM on the hemodynamic BOLD power is robust, dose-dependent, bidirectional, and extends beyond the areas directly illuminated. These findings may provide a reference for future dose selection and clinical efficacy studies. CLINICALTRIALS/RESULTS:GOV: NCT04366258.

BACKGROUND:Ischemic/anoxic brain injury is often assumed to occur within minutes of severe cerebral ischemia. However, emerging evidence suggests brain tissue may be more resilient, with important implications for resuscitation. We hypothesized that during prolonged cardiac arrest, cortical electrical activity may be restorable if cerebral oxygenation thresholds are met and may be associated with return of spontaneous circulation (ROSC). METHODS:) during cardiopulmonary resuscitation (CPR). RESULTS:≥16%, and alpha at >40%. Alpha activity was seen up to 35 min, and delta/theta up to 60 min into CPR. Suppression reverted to near-normal in 12% of transitions. Alpha activity was associated with ROSC (OR 5.4; 95% CI 1.08-29.20; p = 0.045), while suppression predicted lower ROSC odds (OR 0.12; 95% CI 0.02-0.53; p = 0.002). Survival analysis was limited by small sample size. CONCLUSION/CONCLUSIONS:Near-physiologic brain activity may be restored during prolonged CPR if oxygenation thresholds are met and is associated with ROSC. Further research is needed to evaluate survival outcomes.

Osteoarthritis, especially knee osteoarthritis, is a leading cause of disability and reduced quality of life. The etiology of pain in osteoarthritis is multifactorial, and one promising potential treatment approach involves targeting chemokine systems. The present study was a phase 2, multisite, multiperiod randomized crossover trial of CNTX-6970, a small molecule and selective oral cytokine chemokine receptor type 2 (CCR2) and CCR5 antagonist, in patients with painful knee osteoarthritis (OA). It represents the first trial performed within the National Institutes of Health's Early Phase Pain Investigation Clinical Network. The primary objectives were to evaluate the safety and efficacy of CNTX-6970, relative to placebo, for the treatment of moderate to severe pain related to knee OA. A total of 55 participants were randomized in this multiperiod crossover trial. Linear mixed effects models revealed no significant pain-related benefits of active medication; indeed, trial participants reported slightly higher knee pain intensity when taking the novel chemokine antagonist CNTX-6970 than when taking placebo. In addition, biomarker analysis revealed notably higher level of serum monocyte chemoattractant protein 1 levels when patients were on CNTX-6970 compared to placebo. Overall, although CNTX-6970 was safe and relatively well-tolerated, pharmacologic blockade of specific chemokine receptors with this compound was not effective in reducing moderate-to-severe knee osteoarthritis pain.

BACKGROUND:The Enhanced Quality in Primary Care for Elders with Diabetes-ADRD (EQUIPED-ADRD) is a quality improvement and pragmatic cluster-randomized controlled trial that uses clinical decision guidelines to streamline the care of older adults with diabetes mellitus and Alzheimer's disease/Alzheimer's disease-related Dementia (DM-AD/ADRD). This study tests whether the EQUIPED-ADRD intervention will increase the proportion of older adults with DM and AD/ADRD with desirable glycemic ranges, and reduce treatment burden, dementia severity, and healthcare utilization among participants and their care partners in the intervention arm compared to those in the control arm. METHODS:We will recruit older adults (≥65 years) with both DM and AD/ADRD diagnoses, who have care partners, and receive care at the enrolled New York University clinics. The intervention involves the use of panel managers to streamline the integration of clinical decision guidelines among primary care providers and improve the experiences of care partners and patients. Those in the control arm will have no panel management. We will conduct surveys and interviews, and extract data from EMR and Medicare claims to assess the association between the intervention and primary and secondary outcomes. The primary outcome is achieving within-range HbA1c, while the secondary outcomes include measures of healthcare utilization. Patient and care partner treatment burden, dementia symptoms, and care partner diabetes care distress. CONCLUSIONS:The EQUIPED-ADRD intervention (implemented between 2018 and 2021) will assess the effect of an institutional guideline on the quality of life and health outcomes of older adults with DM-AD/ADRD and their care partners. Clinical Trial NumberNCT03723707.

IMPORTANCE/UNASSIGNED:With acute care utilization and mortality rates increasing among people with opioid use disorder, hospital addiction consult services can provide an important touchpoint for care, potentially leading to improved outcomes. OBJECTIVE/UNASSIGNED:To study the effectiveness of interprofessional hospital addiction consultation services on postdischarge acute care utilization and mortality. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:In this pragmatic stepped-wedge cluster randomized implementation and effectiveness (hybrid type 1) clinical trial, 6 New York City public hospitals were randomized to an intervention start date, and outcomes were compared during treatment as usual (TAU) and intervention conditions. Participants included adults with hospitalizations identified in Medicaid claims data between October 2017 and January 2021. Eligible patients had an admission or discharge diagnosis of opioid use disorder or opioid poisoning or adverse effects, were hospitalized at least 1 night in a medical or surgical inpatient unit, and were not receiving medication for opioid use disorder before hospitalization. INTERVENTION/UNASSIGNED:Hospitals implemented the Consult for Addiction Treatment and Care in Hospitals (CATCH) program, an interprofessional inpatient addiction consult service providing specialty care for substance use disorders, with teams consisting of a medical clinician, social worker or addiction counselor, and peer counselor. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Acute care utilization (hospitalizations and emergency department [ED] visits) and mortality rates (all-cause deaths, overdose deaths, and opioid-involved overdose deaths) 1 year after hospital discharge. Data for the eligible patients were analyzed July 2023 to September 2024. RESULTS/UNASSIGNED:In total, 1355 eligible admissions were identified (968 [71.4%] men; mean [SD] age, 46.6 [12.4] years). A majority of patients (835 [61.5%]) had at least 1 subsequent hospitalization or ED visit. There were 113 deaths, including 34 overdose deaths (30.1%), of which 28 (82.4%) involved opioids. ED admissions were lower in the intervention period compared with TAU (incidence rate ratio, 0.79 [95% CI, 0.72-0.88]; P < .001). There were no statistically significant differences between CATCH and TAU periods in numbers of hospitalizations (incidence rate ratio, 0.99 [95% CI, 0.87-1.13]) or mortality (eg, hazard ratio for all-cause death, 1.14 [95% CI, 0.98-1.92]). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this prespecified secondary analysis of a cluster randomized clinical trial, postdischarge ED visits decreased with the CATCH program, highlighting the potential of hospital-based addiction consult services to address needs of patients with opioid use. Nonetheless, high rates of acute care utilization and mortality persisted, underscoring the need for comprehensive care strategies that extend beyond the hospital walls, and addressing the complex health and social needs of individuals with opioid use. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT03611335.

This paper presents a Bayesian regression model relating scalar outcomes to brain functional connectivity represented as symmetric positive definite (SPD) matrices. Unlike many proposals that simply vectorize the matrix-valued connectivity predictors, thereby ignoring their geometric structure, the method presented here respects the Riemannian geometry of SPD matrices by using a tangent space modeling. Dimension reduction is performed in the tangent space, relating the resulting low-dimensional representations to the responses. The dimension reduction matrix is learned in a supervised manner with a sparsity-inducing prior imposed on a Stiefel manifold to prevent overfitting. Our method yields a parsimonious regression model that allows uncertainty quantification of all model parameters and identification of key brain regions that predict the outcomes. We demonstrate the performance of our approach in simulation settings and through a case study to predict Picture Vocabulary scores using data from the Human Connectome Project.

OBJECTIVES/OBJECTIVE:We explored medications for opioid use disorder treatment (MOUD) utilization in six New York City public hospitals that implemented the "Consultation for Addiction Care and Treatment in Hospitals (CATCH)" program. METHODS:CATCH rolled out between October 2018 and February 2020. Data from the electronic health record were analyzed for the first year post-implementation. Eligible cases included adults with an opioid-related diagnosis admitted to inpatient departments served by CATCH, with a stay of ≥1 night. Patients were classified as receiving an MOUD order if there was at least 1 order of buprenorphine, methadone, or naltrexone. Logistic regression modeled the impact of CATCH consults on MOUD orders, controlling for demographic and clinical characteristics with hospital as a random effect. RESULT/RESULTS:Among 2117 eligible patients, 71.4% were male, with a mean age of 51.2 years, and 27.2% identified as Black, 21.2% as White, and 34.5% as Hispanic. MOUD was ordered in 60.9% of admissions, and 41.5% had a completed CATCH consult. Patients identified as Black had lower odds of receiving a MOUD order than those identified as White (OR: 0.52, 95% CI: 0.38-0.71; P < 0.001). Patients with a CATCH consult had higher odds of receiving a MOUD order (OR: 3.22, 95% CI: 2.54-4.07; P < 0.001). CONCLUSION/CONCLUSIONS:Majority of patients in our sample received a MOUD order, with higher odds among those with a CATCH consult. Further research is needed on the drivers of racial disparities in MOUD, and other contextual, organizational, and population-specific barriers and facilitators contributing to receipt of hospital-based addiction consult services and MOUD.

BACKGROUND:The optimal management of patients with intermediate-risk pulmonary embolism (PE), who have right heart dysfunction (determined by a combination of imaging and cardiac biomarkers) but a normal blood pressure, is uncertain. These patients suffer from reduced functional capacity and a lower quality of life over the long-term, despite use of anticoagulant therapy. Catheter-directed therapy (CDT) is a promising treatment for acute PE that rapidly removes thrombus and potentially improves cardiac dysfunction. However, CDT has risk and is costly, and it is not known whether it improves long-term cardiorespiratory fitness and/or quality of life compared with anticoagulation alone. METHODS:) with cardiopulmonary exercise testing at 3 months and reduce New York Heart Association (NYHA) Class at 12 months compared with No-CDT. These 2 primary efficacy outcomes will be analyzed sequentially using a "gatekeeping" procedure; for NYHA class to be compared, peak oxygen consumption must first be shown to be significantly increased by CDT. Safety and cost-effectiveness will also be assessed. CONCLUSION/CONCLUSIONS:When completed, PE-TRACT will provide important evidence regarding the benefits and risks of CDT to treat intermediate-risk PE compared with anticoagulation alone. TRIAL REGISTRATION/BACKGROUND:clinicaltrials.gov: NCT05591118.