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The Importance of Keeping Emergency Ultrasound as a Key Indexed Procedure in Emergency Medicine Residency Training
No full textAn evaluation of paid social media advertising and traditional advertising for addiction research recruitment
No full textBackground: Social media advertising may improve efficiency and reduce costs for research recruitment. However, few studies comparing social media-based and traditional recruitment methods aimed to recruit people with a history of substance use.
Methods: Between May 2022 and September 2024, we enrolled people in treatment and/or recovery from an opioid use disorder into a randomized trial of a mobile app-based peer recovery support program with six months of follow-up. We used multiple recruitment strategies including paid social media advertising (Facebook, Craigslist) and traditional methods (trial website, bus advertisements, flyers). We summarized cost per enrollment, enrollments per month, and the percentage of inquiries that were valid, valid inquiries that were from eligible people, and eligible people who enrolled by advertising modality.
Results: All measures of performance differed by modality (each P < 0.01). Cost per enrollment was lowest for the trial website, flyers, and Craigslist (13.88) and highest for bus advertisements and Facebook (644.26). Recruitment rates were highest for Facebook and Craigslist (10.0-14.7 enrollments/month) and lowest for flyers, bus advertisements, and the trial website (2.9-6.2 enrollments/month). Craigslist was least likely to yield valid inquiries (59.0 % vs. 68.8 %-77.8 %). Valid inquiries from Facebook were least likely to be from eligible people (33.0 % vs. 53.8%-65.2 %), and eligible people identified through Facebook were least likely to enroll (55.2 % vs. 76.3%-91.1 %).
Discussion: Researchers recruiting a national sample of people with a history of substance use may maximize cost-effectiveness and efficiency by using a study website and paid Craigslist advertisements. Flyers may also be highly cost-effective for local recruitment
S3R: Spatially Smooth and Sparse Regression Reveals High-Dimensional Regulatory Networks in Spatial Transcriptomics
No full textSpatial transcriptomics (ST) data demands models that recover how associations among molecular and cellular features change across tissue while contending with noise, collinearity, cell mixing, and thousands of predictors. We present Spatially Smooth Sparse Regression (S3R), a general framework that estimates location-specific coefficients linking a response feature to high-dimensional spatial predictors. S3R unites structured sparsity with a minimum-spanning-tree-guided smoothness penalty, yielding coefficient fields that are coherent within neighborhoods yet permit sharp boundaries. S3R enables large scale data analysis with an efficient implementation using a reduced MST graph, multi-GPU training, and parallel hyperparameter search. In synthetic data, S3R accurately recovers spatially varying effects, selects relevant predictors, and preserves known boundaries. Applied to human dorsolateral prefrontal cortex, S3R recapitulates layer-specific target-TF associations with concordant layer-wise correlations in matched single-cell data. In acute Haemophilus ducreyi skin infection, S3R converts spot-level mixtures into cell type-attributed expression fields and reveals spatial gradients; applying SVG tests to these fields increases concordance and recovers gradients missed by spot-level methods. In pancreatic ductal adenocarcinoma, S3R constructs cross-cell type, cross-gene co-variation tensors that prioritize interactions among cell types with interacting genes enriching pathways consistent with known biology. Because responses and predictors in S3R are user-defined, it could flexibly address diverse ST questions within a single, scalable, and interpretable regression framework
Differences in referral source across racial and ethnic groups at Alzheimer’s Disease Research Centers
No full textBackground:
Despite recognition of the need to increase underrepresented groups (URG) engagement in Alzheimer’s disease and related dementias (ADRD) studies, enrollment remains low. As a first step in examining these disparities, these analyses aimed to compare referral sources for Alzheimer’s Disease Research Centers (ADRC) enrollment of URG participants.
Method:
These analyses included data from 48,330 participants across 46 ADRCs, obtained through the National Alzheimer’s Coordinating Center Uniform Data Set. Generalized logistic regression models with generalized estimating equations were used to examine the association of racial/ethnic group and professional vs non‐professional referral source. The ‘professional’ category included referrals made by healthcare professionals or ADRC staff, while the ‘non‐professional’ category included referrals made by self, family or friends. This association was examined across the entire sample, and then individuals who had completed magnetic resonance imaging (MRI). The analyses were adjusted for age, gender, education, visit year, and categorical CDR with random site effect to adjust for study site.
Result:
Descriptive statistics are shown in Table 1. Non‐Hispanic Black and Asian participants were less likely to have completed an MRI. Across the entire sample, Non‐Hispanic Black and Non‐Hispanic Asian participants were less likely to be referred by a professional contact than Non‐Hispanic White participants (Table 2). In those who had completed an MRI, there were no significant differences across the racial groups, although we note that the sample sizes for those with MRI were much smaller (Table 3). Results for both analyses were similar when only participants who had a diagnosis of MCI or dementia and a global CDR of 0.5 or 1 at baseline were included.
Conclusion:
One major factor leading to lower rates of URG participation in ADRD research is disproportionately fewer healthcare professional referrals. To develop and optimize ADRC recruitment strategies, future studies are needed to explore reasons for differences in URG referrals by healthcare professionals and non‐professionals
Recommended Elements of a Musculoskeletal Course for Fourth-Year Medical Students: A Modified Delphi Consensus
No full textBackground and objectives: A recognized gap exists between primary care physicians' training in musculoskeletal (MSK) medicine and the burden of MSK complaints in primary care. Family medicine interns often lack adequate baseline MSK physical exam skills, which prompted a proposal to introduce a fourth-year preceptorship to reinforce MSK education. The aim of this study was to prioritize the most important elements to include in this new clinical rotation.
Methods: We employed a three-round, modified Delphi method to derive consensus. Eleven panelists with experience and expertise in MSK training, medical education, or both generated a list of 118 elements. Each panelist then ranked each element by level of importance, and we reviewed the results. The ranking process was repeated two more times with a goal of achieving consensus.
Results: Seventy-seven curricular elements (topics, skills, experiences) achieved consensus recommendation by being ranked either "fairly important" or "very important" for inclusion in the curriculum. Twenty-eight items were unanimously ranked "very important," 42 received a mix of "very important" and "fairly important" rankings, and seven received unanimous ranking of "fairly important." Three items were unanimously ranked "neither important nor unimportant."
Conclusions: Longitudinal repetition of physical exam skills, reinforcement of relevant anatomy, and incorporation of specific frameworks for approaching MSK care are important components. Physical examination of the shoulder, knee, back, and hip are especially meaningful clinically
Impact of liver cirrhosis on morbidity and mortality of patients admitted to the hospital with necrotizing fasciitis
No full textBackground: Necrotizing fasciitis (NF) is a potentially fatal bacterial infection of the soft tissues. Liver cirrhosis appears to be a contributing factor to higher morbidity and mortality in patients with NF. This research article explores the relationship between these two conditions.
Aim: To evaluate whether liver cirrhosis increases morbidity and mortality in patients with NF, focusing on inpatient mortality, septic shock, length of stay, and hospital costs.
Methods: This retrospective cohort study utilized data from the Healthcare Cost and Utilization Project 2019 National Inpatient Sample. Cases were identified as patients with both NF and cirrhosis, while controls were non-cirrhotic. The study focused on inpatient mortality as the primary outcome, with secondary outcomes including surgical limb amputation, mechanical ventilation rates, septic shock, length of stay, and hospital costs.
Results: A total of 14920 patients were admitted to the hospital for management of NF, of which 2.11% had liver cirrhosis. Inpatient mortality was higher in cirrhotic patients (9.5% vs 3%; adjusted odds ratio = 3.78; P value = 0.02). Cirrhotic patients also had higher rates of septic shock (10.5% vs 4.9%, P value < 0.01). Length of hospital stay, total charges, and rates of mechanical ventilation were not statistically different between groups.
Conclusion: Liver cirrhosis is an independent risk factor of in-hospital mortality and morbidity in patients with NF. Clinicians should be aware of this association to ensure better clinical outcomes and spare healthcare expenditure
Sex, racial/ethnic, and APOE‐ε4 allele differences in longitudinal white matter microstructure in multiple cohorts of aging
No full textBackground:
There is growing recognition that white matter microstructural integrity is affected in Alzheimer’s disease. The goal of this study was to characterize sex, racial/ethnic, and apolipoprotein (APOE)‐ε4 allele differences in white matter integrity.
Methods:
This study included participants from ADNI, BLSA, ROS/MAP/MARS, and VMAP, all longitudinal cohorts of aging. This combined dataset included 6,837 imaging sessions from 2,619 participants age 50+ with diffusion MRI (dMRI) and demographic and clinical data (60% female, 31.4% APOE‐ε4 carriers, 78.9% White). dMRI was preprocessed using the PreQual pipeline. Free‐water (FW) correction was used to generate FW and FW‐corrected intracellular metrics including fractional anisotropy (FAFWcorr), mean diffusivity (MDFWcorr), axial diffusivity (AxDFWcorr), and radial diffusivity (RDFWcorr). Conventional and FW‐corrected metrics were harmonized using the Longitudinal ComBat package. Linear mixed‐effects models related sex, race/ethnicity, and APOE‐ε4 allele status to longitudinal diffusion metrics in 48 white matter tracts, adjusting for age at baseline, sex, education, race/ethnicity, APOE‐ε4 carrier status, cognitive status at baseline, and converter status. All models were corrected for multiple comparisons using the FDR approach.
Result:
Sex differences in white matter were most notable in projection tracts (Figure 1A) and were primarily in FW‐corrected metrics. Females had lower FAFWcorr and higher RDFWcorr, indicative of worse microstructure, but lower AxDFWcorr. This sex difference was most pronounced for FAFWcorr in the ventral premotor projection tract (p=1.53x10‐62). There were global differences in white matter integrity by race/ethnicity (Figure 1B). Non‐Hispanic White participants tended to have higher conventional FA, FAFWcorr and AxDFWcorr and lower RDFWcorr. There was no association between APOE‐ε4 status and white matter integrity and no significant sex x race/ethnicity, sex x APOE‐ε4, or race/ethnicity x APOE‐ε4 interactions for conventional or FW‐corrected metrics when corrected for multiple comparisons.
Conclusion:
There were striking sex and racial/ethnic (but not APOE‐ε4) differences in white matter tract integrity in a large cohort of aging adults. Female participants tended to have measures reflective of worse white matter integrity, and non‐Hispanic White participants tended to have measures reflective of greater integrity. Additional research exploring the etiology of these differences will be important to better understand disparities in Alzheimer’s disease
Sabirnetug (ACU193) Lowers CSF Levels of Synaptic Biomarkers in INTERCEPT‐AD Phase 1 Study in Early AD
No full textBackground:
Sabirnetug (ACU193) is a humanized IgG2 antibody targeting soluble, synaptotoxic amyloid β oligomers (AβOs). AβOs accumulate in Alzheimer’s disease (AD) and induce pre‐ and post‐synaptic changes, resulting in dendritic spine loss, neuronal degeneration, and release of synaptic proteins into the CSF. Recently, we reported that three administrations of sabirnetug in an early AD population (INTERCEPT‐AD Phase 1 study, NCT04931459) significantly lowered CSF levels of the post‐synaptic protein neurogranin as well as pTau181. Here, we present data on additional CSF synaptic biomarkers and AD plasma biomarkers measured in INTERCEPT‐AD.
Method:
INTERCEPT‐AD was a randomized, placebo‐controlled study with two parts: single ascending dose (SAD) randomized in a 6:2 ratio to sabirnetug (2, 10, 25, 60 mg/kg) or placebo and multiple ascending dose (MAD) randomized 8:2 to sabirnetug (three administrations at 10 or 60 mg/kg every 4 weeks [Q4W] or 25 mg/kg Q2W) or placebo. Biomarkers were measured blinded in CSF and EDTA‐plasma, before and after drug administration, by Amsterdam UMC.
Result:
CSF levels of vesicle‐associated membrane protein 2 (VAMP2), a protein involved in pre‐ and post‐synaptic vesicle trafficking, were significantly normalized (lowered) in sabirnetug treated participants relative to placebo in all three MAD cohorts. Levels of the pre‐synaptic protein neuronal pentraxin 2 (NPTX2), which acts on post‐synaptic excitatory synapses, regulates complement activity, and lowers with cognitive decline, trended lower with sabirnetug than placebo. Plasma levels of GFAP, pTau181, and pTau217 trended towards normalization (lowering) of AD‐dependent changes in the 60 mg/kg Q4W cohort.
Conclusion:
In INTERCEPT‐AD, three administrations of sabirnetug lowered CSF levels of both pre‐ and post‐synaptic proteins, consistent with sabirnetug’s proposed mechanism of action to inhibit AβO synaptic binding. VAMP2 appeared most sensitive to sabirnetug in this study, lowering significantly in all three MAD cohorts; other markers previously reported to have a statistically significant response to sabirnetug ‐ neurogranin and pTau181 ‐ did so at the highest dose. No statistically significant changes in plasma biomarkers were observed in this short study. Long‐term changes in biomarker levels and their relationship to clinical efficacy will be evaluated in the 18‐month ALTITUDE‐AD phase 2 study of sabirnetug beginning in the first half of 2024
Traumatic brain injury and cognitive resilience in the Framingham Heart Study
No full textBackground:
Some evidence supports an association between traumatic brain injury (TBI) and greater risk of dementia, but the role of cognitive resilience in this association is poorly understood.
Method:
2,050 participants from the Framingham Heart Study Offspring cohort who were aged ≥60 year and had a plasma total tau (t‐tau) measure at Exam 8 (2005‐2008), and a neuropsychological (NP) exam visit within five years were included. Plasma t‐tau was measured using the Simoa assay (Quanterix). NP factor scores were previously derived for memory, language, and executive function using confirmatory factor analysis. Information on TBIs was collected by comprehensive review of medical records, health history updates, exams, and self‐report. TBI occurrence and severity were operationalized using modified ACRM & VA/DoD criteria, respectively. Cognitive resilience was operationalized using a residual approach by regressing each NP factor score on the plasma t‐tau measure, adjusting for age at Exam 8, sex, education, time from blood draw, and APOE ε4 genotype. The adjusted residuals were then regressed on history of TBI (yes versus no), and severity of TBI (moderate‐to‐severe versus mild versus none).
Result:
The sample was, on average, 67 years of age at Exam 8, 54% female, and college educated. No differences were observed in plasma t‐tau levels between those with and without TBI. Having a history of TBI was significantly associated with a reduction in resilience in executive function (β: ‐0.110; 95% CI: ‐0.175, ‐0.044; p: 0.001) as compared to not having a history of TBI. No significant associations were observed between history of TBI and resilience in memory or language. Greater TBI severity was significantly associated with worse resilience in executive function in a dose‐response manner (Ptrend: <0.001), with the association being strongest in the moderate‐to‐severe TBI group (β: ‐0.209; 95% CI: ‐0.340, ‐0.078; p: 0.002) followed by the mild TBI group (β: ‐0.082; 95% CI: ‐0.155, ‐0.010; p: 0.026).
Conclusion:
Having a TBI was associated with worse resilience to neurodegeneration in executive function, and most strongly among individuals with moderate‐to‐severe TBI. These results suggest that having a TBI may increase vulnerability to late‐life executive dysfunction after accounting for a primary neurodegenerative disease process