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OCD and Autism: Clinician Perspectives
Full text linkObsessive Compulsive Disorder (OCD) and Autism Spectrum Disorder (ASD) present with similar behaviors and symptoms, complicating diagnosis and treatment. Research has found that up to 37% of autistic individuals display OCD behaviors and symptoms. However, when examining clinicians, research found low confidence rates in treating co-occurring psychiatric conditions in autistic clients. The present study aims to (1) better understand the relationship between OCD and autism in realms such as treatment barriers, symptom presentation, and treatment modifications and (2) determine the training needs for clinicians when working with autistic individuals exhibiting OCD behaviors. Eleven community clinicians were interviewed using a semi-structured, open-ended interview style. Questions related to OCD and autism discussed exposure therapy training, experience treating autistic youth with OCD symptoms, and challenges related to this treatment. Interview transcripts were analyzed using thematic analysis. Clinicians discussed topics that fell under three major concepts: treatment barriers, strategies for symptom differentiation, and treatment modifications. Results highlight varied clinician understanding of current research findings related to OCD-autism co-occurrence and many clinicians voiced their desire for more training. Findings indicate training should include information on identifying and treating OCD in autistic clients.Bachelor of Scienc
[SUD-ECHO-NJ] The Evolving Drug Supply - Identifying and Managing Emerging Adulterants
No full textInvited presentation to the SUD-ECHO learning community (virtual)
A novel two-sample Mendelian randomization framework integrating common and rare variants: application to assess the effect of HDL-C on preeclampsia risk
Full text linkMendelian randomization (MR) has become an important technique for establishing causal relationships between risk factors and health outcomes. By using genetic variants as instrumental variables, it can mitigate bias due to confounding and reverse causation in observational studies. Current MR analyses have predominantly used common genetic variants as instruments, which represent only part of the genetic architecture of complex traits. Rare variants, which can have larger effect sizes and provide unique biological insights, have been understudied due to statistical and methodological challenges. We introduce MR-common and annotation-informed rare variants (MR-CARV), a novel framework integrating common and rare genetic variants in two-sample MR. This method leverages comprehensive genetic data made available by high-throughput sequencing technologies and large-scale consortia. Rare variants are aggregated into functional categories, such as gene-coding, gene-noncoding, and nongene regions, by leveraging variant annotations and biological impact as weights. The effects of rare variant sets are then estimated with STAARpipeline and combined with the estimated effects of common variants by the existing MR methods. Simulation studies demonstrate that MR-CARV maintains robust type I error and achieves higher statistical power, with up to a 66.3% relative increase compared with existing methods only based on common variants. Consistent with these findings, application to real data on high-density lipoprotein cholesterol (HDL-C) and preeclampsia showed that MR-CARV [inverse variance weighted (IVW)] yielded a more precise and statistically significant effect estimate (-0.020, SE = 0.0102, =.0470) than IVW using only common variants (-0.023, SE = 0.0123, =.0659)
Global learning opportunities within social innovation in health (GLOWS): A modified Delphi process to identify and pilot core competencies for learning
Full text linkBackground Social innovation in health refers to the community-engaged process that connects health improvement and social change. The aim of this study was to develop a consensus statement on core learning competencies in social innovation in health and pilot them as part of a participatory training workshop. Methods and findings A modified Delphi Process aggregating data from a scoping review, global open call, and participatory process was organized. Participants were recruited from low, middle, and high-income countries with a range of social innovation experiences. Statements focused on social innovation in health core competencies for learning. Consensus was determined using the RAND/UCLA Appropriateness method. After expressing interest in the project, 68 individuals received the survey. 46 participants completed the first survey, and 35 completed the second. All 28 statements reached consensus, and based on the results of this first survey, some statements were added, amended, and merged to reach 30 consensus statements in the second survey. Competencies were categorized into skills, mindsets, and knowledge. Twenty-five statements had a median Likert rating score of >8 indicating strong agreement. Some competencies reached higher levels of agreement. This included community engagement, which can leverage the collective knowledge and problem-solving abilities of a diverse group of individuals to tackle complex challenges; social entrepreneurship skills including business model knowledge, securing funding, team building, and knowledge of intersectional issues and health inequities. Twelve competencies were then piloted as eight one-hour online workshops, which assessed the feasibility of developing them through online open-access social innovation training sessions. Afterwards,137 participants completed a survey rating their competency on a scale from 1 (not competent) to 5 (very competent),most reported a significant 1-point improvement including in entrepreneurship and understanding intersectionality. Conclusion The results from this study will inform the development of a WHO/TDR conceptual framework which will have implications for training program design and policy
Association Between Depression and Polypharmacy in Older Adults—A Systematic Review and Meta‐Analysis
Full text linkBackground Depression and polypharmacy are both common among older adults and may be closely interrelated. Methods This systematic review and meta‐analysis examined the association between depression and polypharmacy by searching EMBASE, PubMed, Web of Science, and PsycINFO from inception to 18 May 2023. The review was registered in PROSPERO (CRD42022343619). Results Eight studies met the inclusion criteria, with six rated high quality and two medium quality. Pooled analysis using a random‐effects model demonstrated a strong association between depression and polypharmacy (OR = 2.49; 95% CI: 1.88–3.29; I² = 83%). Subgroup analyses revealed consistently elevated associations in both community‐based and institutional/clinic‐based populations. Conclusions Depression is associated with polypharmacy among older adults. These findings underscore the importance of integrating mental health assessment into medication management strategies for older adults
Outcomes of Bispecific Antibodies After CAR T-Cell Failure for Large B-cell Lymphoma- Results from the ABC Consortium
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TO THE EDITOR:
Anti-CD19 chimeric antigen receptor T-cell therapy (CART) is an effective treatment for relapsed/refractory large B-cell lymphoma (R/R LBCL) and can be curative in a subset of patients. However, 40% to 60% of patients experience disease progression or relapse after CART, resulting in poor survival outcomes with a median overall survival (OS) of 5 to 6 months. Epcoritamab and glofitamab, novel CD20 × CD3 bispecific T-cell–engaging monoclonal antibodies approved by the Food and Drug Administration, have shown remarkable efficacy for managing R/R LBCL after ≥2 lines of therapy, with overall response rates (ORRs) of 56% to 62% and complete response (CR) rates of 38% to 43%. T-cell exhaustion has been proposed as a mechanism of resistance to CART, raising the question of whether bispecific antibodies (BsAbs) are an effective therapy in patients with relapsed disease after CART. Pivotal trials examining both epcoritamab and glofitamab included a fraction of patients previously treated with CART and demonstrated a CR rate of 34% with epcoritamab (n = 61 [31%]) and 35% with glofitamab (n = 51 [33%]), with data diluted by smaller numbers of CART-refractory patients. Additionally, little is known about this subset of patients, including disease characteristics and prior lines of therapy. To our knowledge, we performed the largest retrospective analysis reported in literature examining the real-world application of BsAbs after CART failure, providing insights into disease and patient-related factors associated with response and survival outcomes
Conformational Preferences for N‑Glycans at the Surface of CEACAM1-Ig1
Full text linkGlycans on glycoproteins play roles that range from quality control in protein folding, to mediation of interactions with other proteins, to stabilization of the protein to which they are attached. Computation can suggest structures that underlie these roles, but confidence is limited by the accuracy of energetic calculations and their applicability to the aqueous environment in which proteins function. Experimental validation of suggested structures is therefore of primary importance. Here we use NMR data, including long-range pseudocontact shifts (PCSs) and residual dipolar couplings (RDCs), to screen structures produced by a version of accelerated molecular dynamics (Pep-GaMD). This version was designed to improve the search for peptide-protein interactions, but here it is successfully applied to glycans attached to a target protein. The target protein, the N-terminal domain of human CEACAM1, is expressed with homogeneous GlcNAc2Man5 glycans at its three N-glycosylation sites. One site (N104) is found to have preferred conformations that exploit hydrophobic interactions between its glycans and protein hydrophobic residues, potentially adding to protein stability and protection from adverse interactions
Residential proximity to Superfund sites and breast cancer incidence in a nationwide cohort
Full text linkBackground:
The United States Environmental Protection Agency-designated Superfund sites are a source of potential exposure to harmful contaminants, including endocrine-disrupting chemicals and carcinogens, that may be relevant to breast cancer risk. However, there is limited research on the possible association between residential proximity to Superfund sites and the risk of breast cancer.
Methods:
Using data from the prospective US-wide Sister Study cohort (N = 49,594), geocoded enrollment addresses were linked to active United States Environmental Protection Agency Superfund sites to determine residential proximity to sites. Proximity metrics included residing within 3-, 5-, and 10-miles of Superfund sites. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the relationship between residential proximity to Superfund sites and breast cancer incidence. We further evaluated whether associations for residential proximity and breast cancer incidence varied according to individual contaminants and latent classes that grouped Superfund sites based on the mixture of contaminants present at the site.
Results:
Over an average of 12 years of follow-up, 4,565 breast cancer cases were identified. Overall, there was little evidence to support that living within three miles of a single Superfund site was strongly related to breast cancer incidence. However, living within three miles of two or more sites was associated with a 20% higher breast cancer incidence (HR = 1.20; 95% CI = 1.00, 1.45). There was little evidence of an association by contaminant latent classes, although when considering individual contaminants, we observed a possible association with proximity to sites containing organophosphates (HR = 1.33, 95% CI = 0.90, 1.96).
Conclusion:
In this large, US-wide cohort, no overall pattern of association between residential proximity to Superfund sites and breast cancer incidence was found. However, elevated HRs were observed for living near two or more sites or sites that are contaminated with organophosphates
Neurosymptomatic CSF escape is a CNS-focused form of ART treatment failure
Full text linkBackground While on antiretroviral therapy (ART), people with HIV-1 (PWH) occasionally present with new symptoms and signs of central nervous system (CNS) injury accompanied by higher HIV-1 RNA levels in cerebrospinal fluid (CSF) than in blood, a condition defined as neurosymptomatic HIV CSF escape (NSE). PWH meeting these general criteria but with plasma HIV-1 RNA levels > 500 copies/ml have typically been assumed to be experiencing systemic treatment failure without special consideration for HIV-1 dynamics in the CNS. Thus, people experiencing CNS-focused treatment failure may receive suboptimal treatment, targeted at controlling replication in the periphery, not the CNS. Methods We genetically and phenotypically characterized HIV-1 RNA in the CSF and blood of PWH (N = 9) on ART who met definitions of both NSE and systemic treatment failure and defined them as having NSE high (NSE-h). Results While plasma viral loads were higher during NSE-h than during NSE, the conditions have many shared features including elevated CSF:plasma viral load ratios, elevated CSF white blood cell counts and drug-resistant, T-tropic HIV-1 replicating in the CNS. During NSE-h, HIV-1 populations in blood and CSF were genetically equilibrated, indicating that they were not independently replicating in both compartments. Conclusions Both NSE and NSE-h are driven by replication of drug-resistant HIV-1 in CD4+ T cells in the CNS with NSE-h having higher CSF viral loads reflecting more HIV-1 replication in the CNS. This suggests that people presenting with neurologic symptoms and treatment failure may be experiencing CNS-focused treatment failure that could require specialized treatment
The Microbiota-Gut-Brain Axis as a Fundamental Regulator of Neuroplasticity: A Systematic Review and Meta-Analytic Synthesis
Full text linkThe classical neurocentric view of the central nervous system (CNS) as an isolated, immune-privileged entity has been superseded by a systemic paradigm acknowledging the profound influence of peripheral systems on neural function. Central to this paradigm shift is the microbiota-gut-brain axis (MGBA), a bidirectional communication network linking the enteric environment with the cognitive and emotional centers of the brain. Neuroplasticity—the brain's intrinsic capacity to reorganize structural and functional connectivity in response to stimuli—is now understood to be heavily modulated by signals originating from the gut microbiome. Dysbiosis, or the maladaptive alteration of microbial communities, is increasingly implicated in the pathophysiology of neurodegenerative and psychiatric disorders characterized by deficits in synaptic plasticity, neurogenesis, and circuit refinement