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Expanding the Exposome: Understanding How Temperature Metrics are Associated with Hospital Admissions
No full textBackground
Extreme weather and temperature can impact human health and influence acute care need, particularly among older patients.
Objective
To examine how weather derived metrics compare with traditional temperature measures in capturing the impact of extreme weather on hospital admissions, particularly among older men and women.
Design
Observational Study
Setting
Hospital Admissions in Central Massachusetts from April 2021 to April 2024.
Patients
Inpatient admissions due to cardiovascular, stroke, renal, and pulmonary disease among adults.
Measurements
Daily Maximum of temperature metrics, Ambient Temperature, Wet Bulb Globe (WBGT) Temperature, Universal Thermal Climate Index (UTCI), and Heat Index
Results
We observed 83,469 hospital admissions that met the study inclusion criteria during the period under study; these were based on data from 44,156 individual patients (mean age 67.9 years; 50.8% male). In comparison with normal temperature indices, we observed a decreased risk for hospital admissions on extreme cold days as measured by ambient temperature (IRR: 0.66 [95% CI, 0.50-0.87]) and UTCI (IRR: 0.89 [0.83-0.95]) but an increased risk for hospital admissions on extreme warm days as measured by WBGT (IRR: 1.06 [1.01-1.13]) and UTCI (IRR: 1.06 [1.01-1.12]). Through stratified trend analysis, we observed stronger associations between weather variables and admissions among patients 65 years and older.
Limitations
Relatively focused area where temperature did not reach extreme heat thresholds often.
Conclusion
Strategies that consider weather patterns and their effects on acute care needs can be helpful in healthcare planning and hold potential to inform individual-level risk for exacerbation of neuro-cardio-pulmonary-renal conditions.Master of Science in Clinical Investigation2 years2027-04-3
Pre-COVID-19 epidemiology of community respiratory viruses at a single US center reveals sex differences in influenza A and a higher ICU incidence of human metapneumovirus in the elderly population
No full textBackground: Few studies have simultaneously examined the epidemiology and sex differences of diverse community respiratory viruses, including human metapneumovirus (HMPV), over more than one season.
Methods: Given that molecular testing for community respiratory viruses was widely performed on patients at UMass Memorial Medical Center between January 2010 and December 2013, a retrospective study was conducted to examine epidemiologic features of positive subjects. Initial testing was done with rapid influenza and respiratory syncytial (RSV) virus antigen testing, with negative testing reflexed to a multiplex nucleic acid amplification platform detecting nine respiratory viruses.
Results: Four thousand ninety-eight (50.6%) of 8092 patients tested positive for at least one virus. The majority (75.3%) of individuals testing positive were inpatients. Rhinovirus/enterovirus was most frequently detected; influenza A was more common in older adults and RSV incidence was highest among patients < 5 years of age. Pronounced seasonality was seen with influenza viruses, RSV, HMPV, and parainfluenza 3 virus. Influenza A was significantly more common in females (11.2% vs. 8.1%; p < 0.001), while parainfluenza 1 virus (2.0% vs. 1.2%; p < 0.01), rhinovirus/enterovirus (23.4% vs. 19.9%; p < 0.001) and adenovirus (2.1% vs. 1.5%; p < 0.05) were significantly higher in males. Of the ICU patients with HMPV, many (40.3%) were ≥ 65 years of age.
Conclusions: This pre-coronavirus disease 2019 (COVID-19) era study has one of the largest patient populations evaluated for community respiratory virus infections. It confirms known epidemiology, seasonality, and coinfections, and importantly shows a preponderance of influenza A infections among women, contrasting prior studies, which warrants further investigation. It also shows a high HMPV incidence in the ICU among the elderly, underscoring the importance of testing in this population.No embarg
Factors influencing immediate post-angiographic occlusion outcomes in intracranial aneurysms treated with the woven endobridge device: a multi-center analysis and predictive model from the WorldWideWEB consortium
No full textThe Woven EndoBridge (WEB) device treats wide-necked bifurcation aneurysms, but occlusion rates vary. This study aims to identify factors associated with immediate WEB device occlusion. Data from patients treated with WEB devices across 36 sites were analyzed. Machine learning algorithms and ordinal regression models were developed to predict immediate incomplete occlusion for ruptured and unruptured aneurysms. The study included 1565 patients, with 436 ruptured and 1129 unruptured aneurysms. Immediate complete occlusion was achieved in 38.3% of ruptured and 32.8% of unruptured aneurysms. For ruptured aneurysms, the CatBoost classifier achieved an AUROC of 0.69. Key predictors of incomplete occlusion included pretreatment mRS, aneurysm diameter, and MCA location. Ordinal regression revealed that smoking history (OR: 1.95, p < 0.001), neck diameter (Odds Ratio [OR]: 1.50, p < 0.001), and presence of a branch from the aneurysm (OR: 2.06, p = 0.016) were associated with incomplete, while bifurcation aneurysms (OR: 0.55, p = 0.017) were associated with complete immediate occlusion. For unruptured aneurysms, the CatBoost classifier achieved an AUROC of 0.68. Significant predictors of immediate incomplete occlusion included aneurysm neck width, MCA location, and presence of daughter sac. Ordinal regression revealed that smoking history (OR: 1.29, p = 0.032), neck diameter (OR: 1.24, p < 0.001), and presence of a daughter sac (OR: 1.53, p = 0.005) were associated with incomplete, while bifurcation aneurysms (OR: 0.71, p = 0.02) and posterior circulation location (OR: 0.68, p = 0.01) were associated with complete immediate occlusion. Careful evaluation of patient demographics and specific aneurysm characteristics may help improve the outcomes of intracranial aneurysms treated with WEB device.No embarg
Single-Cell Characterization of Genomic and Transcriptomic Changes in the Aging Human Brain
No full textAging brings dysregulation of various processes across organs and tissues often stemming in part from stochastic damage to individual cells over time. Aging-related changes in the brain lead to cognition deficits and can impact quality of life. The molecular basis of neuronal aging remains poorly understood. This work uses a combination of single-nucleus RNA sequencing, single-cell whole-genome sequencing, and spatial transcriptomics to identify transcriptomic and genomic changes in the prefrontal cortex of the human brain across life span, from infancy to centenarian. Infant-specific cell clusters had enriched expression of neurodevelopmental genes, indicating incomplete development at birth. Oligodendrocyte precursor cell proportions were highest in infants and depleted in adult and elderly brains while oligodendrocytes were almost absent in infants and enriched in older brains. Certain subclasses of inhibitory neurons demonstrated increased transcriptional variability during aging along with decreased expression of the canonical marker genes. Elderly brains demonstrated common downregulation of cell-essential homeostatic genes that function in ribosomes, transport, and metabolism during aging across cell types. Conversely, the expression of neuron-specific genes generally remains stable throughout life. Expression of specific DNA repair genes decreased in aging, including genes implicated in generating brain somatic mutations. Furthermore, we detected gene-length-specific somatic mutation rates that shape the transcriptomic landscape of the aged human brain. These findings elucidate critical aspects of human brain aging, shedding light on transcriptomic and genomic dynamics.Interdisciplinary Graduate Program1 year2026-02-2
Engaging trusted messengers in public health response: Key strategies to building community trust among CDC'S prevention research center's vaccine confidence network
Get PDFAs part of Centers for Disease Control and Prevention's (CDC) Prevention Research Center (PRC) Vaccine Confidence Network (PRC VCN), 26 academic institutions were funded to increase COVID-19 vaccine confidence and uptake in their communities. Six sites (in communities located in Alabama, Illinois, Massachusetts, New York, South Carolina, and Texas) formed a workgroup to identify emergent themes, and share challenges and opportunities across projects. This essay describes their efforts to engage trusted messengers in vaccine activities, and discusses strategies to develop and sustain these types of partnerships in the future. All sites recruited trusted messengers with strong community relationships to engage in multiple activities to promote COVID-19 vaccine confidence and uptake. CDC and the PRCs provided data-driven, evidence-based training and support to enable trusted messengers to fully participate in the projects. We posit that trusted messengers are essential partners for informing public health campaigns, developing effective messages, and building trust with local communities. Flexible federal funding and local coordination are essential for creating and sustaining trusted messenger approaches that combine community needs and data-informed evidence to promote timely public health responses.No embarg
Circulating extracellular RNAs, myocardial remodeling, and elevated BMI in patients with acute coronary syndrome
No full textObjective: Given the elevated mortality in individuals with acute coronary syndrome and increased adiposity, delineating the molecular mechanisms underlying obesity-associated adverse cardiac remodeling is critical for the identification of novel pathophysiological biomarkers and potential therapeutic targets. Circulating extracellular RNAs (ex-RNAs) regulate important biological processes and can serve as biomarkers of disease. This study aims to discover circulating extracellular RNAs (ex-RNAs) that serve as biomarkers of obesity-associated adverse cardiac remodeling in ACS survivors.
Methods: We analyzed extracellular RNA (ex-RNA) profiles in 296 survivors of acute coronary syndrome enrolled in the Transitions, Risks, and Actions in Coronary Events - Center for Outcomes Research and Education (TRACE-CORE) cohort. A total of 317 ex-RNAs were quantified, selected a priori based on prior findings from a large population-based study. We employed a two-step, mechanism-driven approach to identify ex-RNAs associated with echocardiographic phenotypes, including left atrial (LA) dimension, LA volume index, left ventricular (LV) ejection fraction, LV mass, and LV end-diastolic volume, then tested the relations of these ex-RNAs with obesity. We performed further bioinformatics analysis of the gene ontology categories and molecular pathways associated with predicted miRNA targets.
Results: We identified 45 ex-RNAs associated with at least one echocardiographic phenotype, of which miR-1185-1-3p, miR-550a-3p, and miR-885-5p were also associated with prevalent obesity. Bioinformatic analysis of their predicted gene targets (n=1,930) revealed enrichment in key pathways related to inflammation, fibrosis, and cellular toxicity, including Wnt/β-catenin signaling, TGF-β signaling, and hypoxia-inducible factor (HIF) signaling. Targets such as DICER1, VEGF, and EPO were implicated. Gene ontology analysis further highlighted associations with angiogenesis, FGF signaling, and interleukin pathways.
Conclusions: Among ACS survivors, we observed that miR-1185-1-3p, miR-550a-3p, and miR-885-5p were associated with both echocardiographic markers of adverse cardiac remodeling and elevated BMI. Relevance for patients: miR-1185-1-3p, miR-550a-3p, and miR-885-5p were associated with echocardiographic phenotypes and obesity and are potential biomarkers for adverse cardiac remodeling in obesity.No embarg
Five-year analysis of efficacy and safety of a bidirectional AAV gene therapy in Tay-Sachs sheep
Get PDFTay-Sachs and Sandhoff disease are fatal neurodegenerative diseases without an effective therapy that are caused by mutations in the HEXA and HEXB genes, respectively. Together they encode the heterodimeric isozyme of hexosaminidase (HexA) that degrades GM2 ganglioside. This report describes a 5 year-long study using a bidirectional AAV9 vector (AAV9-Bic_HexA/HexB) encoding both HEXA and HEXB in the Tay-Sachs sheep model. Bidirectional AAV9 was delivered intravenously or through various cerebral spinal fluid (CSF) delivery routes: intracerebroventricular (ICV), cisterna magna (CM) and lumbar delivery (LIT). The longest survival and best distribution were achieved by multipoint CSF delivery (combined CM, ICV and LIT) with treated animals survived up to 5 years of age (untreated Tay-Sachs animals die ~9 months). Extension in survival was accompanied by lasting improvement in neurological examination and maze testing. Improvement in biomarkers of efficacy including MRI, MR spectroscopy, diffusion tensor imaging as well as CSF levels of GM2 ganglioside and hexosaminidase A (HexA) activity was evident. Post-mortem assessments showed broad HexA distribution, GM2 ganglioside clearance and vector genome distribution, especially in deep brain structures. Therapeutic efficacy documented in this study supports translation of bidirectional vector and multipoint CSF delivery to a clinical trial in Tay-Sachs and Sandhoff disease patients.No embarg
A Comprehensive Review of Non-Rapid Eye Movement (NREM) Parasomnias
No full textNREM (Non-Rapid Eye Movement) sleep is necessary for normal physical and intellectual performance and behavior. NREM parasomnias are defined as conditions where different symptomologies are associated with various behaviors happening during NREM sleep. Moreover, the underlying mechanism and proper treatment of the various conditions are yet to be explored in the realm of NREM parasomnias. In this review article, we summarize the fundamental mechanisms underlying the NREM sleep parasomnias as well as portray an algorithm to treat those conditions. We also briefly discuss important studies associated with NREM parasomnias and their related advancements in the treatment.No embarg
Using routinely available electronic health record data elements to develop and validate a digital divide risk score
Get PDFBackground: Digital health (patient portals, remote monitoring devices, video visits) is a routine part of health care, though the digital divide may affect access.
Objectives: To test and validate an electronic health record (EHR) screening tool to identify patients at risk of the digital divide.
Materials and methods: We conducted a retrospective EHR data extraction and cross-sectional survey of participants within 1 health care system. We identified 4 potential digital divide markers from the EHR: (1) mobile phone number, (2) email address, (3) active patient portal, and (4) >2 patient portal logins in the last year. We mailed surveys to patients at higher risk (missing all 4 markers), intermediate risk (missing 1-3 markers), or lower risk (missing no markers). Combining EHR and survey data, we summarized the markers into risk scores and evaluated its association with patients' report of lack of Internet access. Then, we assessed the association of EHR markers and eHealth Literacy Scale survey outcomes.
Results: A total of 249 patients (39.4%) completed the survey (53%>65 years, 51% female, 50% minority race, 55% rural/small town residents, 46% private insurance, 45% Medicare). Individually, the 4 EHR markers had high sensitivity (range 81%-95%) and specificity (range 65%-79%) compared with survey responses. The EHR marker-based score (high risk, intermediate risk, low risk) predicted absence of Internet access (receiver operator characteristics c-statistic=0.77). Mean digital health literacy scores significantly decreased as her marker digital divide risk increased (P <.001).
Discussion: Each of the four EHR markers (Cell phone, email address, patient portal active, and patient portal actively used) compared with self-report yielded high levels of sensitivity, specificity, and overall accuracy.
Conclusion: Using these markers, health care systems could target interventions and implementation strategies to support equitable patient access to digital health.No embarg
Predictive modeling of long-term improvement in occlusion outcomes following Woven EndoBridge treatment of cerebral aneurysms: A machine learning approach
No full textBackgroundThe Woven EndoBridge (WEB) device represents an innovative solution for cerebral aneurysm occlusion, particularly for challenging wide-neck bifurcation aneurysms. However, factors affecting sustained occlusion remain poorly understood. We utilized machine learning to attempt to identify predictors of favorable long-term outcomes following WEB treatment.MethodsIn this multicenter retrospective study, we collected patient demographics, aneurysm characteristics, procedural details, and clinical outcomes. The primary endpoint was improvement in occlusion status, defined as maintained Raymond-Roy Occlusion Classification (RROC) grade 1, or improvement from grade 2 to 1, or from grade 3 to either 2 or 1 on final angiographic follow up. The dataset was split into training (75%) and validation (25%) sets. The CatBoost algorithm was selected based on performance metrics, with Shapley Additive exPlanations (SHAP) values calculated to determine feature importance. Furthermore, a multivariable binomial logistic regression model was performed to validate machine learning findings.ResultsAmong 720 aneurysms from 36 hospitals, 84% showed improvement in occlusion at follow up. Both machine learning and multivariable logistic regression identified aneurysm height as the most consistent correlate of nonimprovement (odds ratio (OR) 0.90 per mm, p = 0.022). In the CatBoost model, the highest-ranking features by SHAP included aneurysm height, patient age, treatment acuity, ACom location, WEB-SLS device, bifurcation anatomy, aneurysm multiplicity, baseline modified Rankin Scale, access route, and partial thrombosis.ConclusionsMachine-learning and regression analyses identified consistent predictors of occlusion improvement after WEB treatment, with aneurysm height most strongly linked to nonimprovement. These insights may guide patient selection and follow up. Findings require cautious interpretation and external validation in larger cohorts.No embarg