Transcriptomic evaluation of skin tape-strips in children with allergic asthma uncovers epidermal barrier dysfunction and asthma-associated biomarkers abnormalities.

INTRODUCTION: Tape-strips, a minimally invasive method validated for the evaluation of several skin diseases, may help identify asthma-specific biomarkers in the skin of children with allergic asthma. METHODS: Skin tape-strips were obtained and analyzed with RNA-Seq from children with moderate allergic asthma (MAA) (n = 11, mean age 7.00; SD = 1.67), severe allergic asthma (SAA) (n = 9, mean age 9.11; SD = 2.37), and healthy controls (HCs) (n = 12, mean age 7.36; SD = 2.03). Differentially expressed genes (DEGs) were identified by fold change ≥2 with a false discovery rate <0.05. Transcriptomic biomarkers were analyzed for their accuracy in distinguishing asthma from HCs, their relationships with asthma-related outcomes (exacerbation rate, lung function-FEV1, IOS-R5-20, and lung inflammation-FeNO), and their links to skin (barrier and immune response) and lung (remodeling, metabolism, aging) pathogenetic pathways. RESULTS: RNA-Seq captured 1113 in MAA and 2117 DEGs in SAA. Epidermal transcriptomic biomarkers for terminal differentiation (FLG/filaggrin), cell adhesion (CDH19, JAM2), lipid biosynthesis/metabolism (ACOT2, LOXL2) were significantly downregulated. Gene set variation analysis revealed enrichment of Th1/IFNγ pathways (p < .01). MAA and SAA shared downregulation of G-protein-coupled receptor (OR4A16, TAS1R3), upregulation of TGF-ß/ErbB signaling-related (ACVR1B, EGFR, ID1/2), and upregulation of mitochondrial-related (HIGD2A, VDAC3, NDUFB9) genes. Skin transcriptomic biomarkers correlated with the annualized exacerbation rate and with lung function parameters. A two-gene classifier (TSSC4-FAM212B) was able to differentiate asthma from HCs with 100% accuracy. CONCLUSION: Tape-strips detected epithelial barrier and asthma-associated signatures in normal-appearing skin from children with allergic asthma and may serve as an alternative to invasive approaches for evaluating asthma endotypes.

Derivation, External Validation and Clinical Implications of a deep learning approach for intracranial pressure estimation using non-cranial waveform measurements.

Importance: Increased intracranial pressure (ICP) is associated with adverse neurological outcomes, but needs invasive monitoring. Objective: Development and validation of an AI approach for detecting increased ICP (aICP) using only non-invasive extracranial physiological waveform data. Design: Retrospective diagnostic study of AI-assisted detection of increased ICP. We developed an AI model using exclusively extracranial waveforms, externally validated it and assessed associations with clinical outcomes. Setting: MIMIC-III Waveform Database (2000-2013), a database derived from patients admitted to an ICU in an academic Boston hospital, was used for development of the aICP model, and to report association with neurologic outcomes. Data from Mount Sinai Hospital (2020-2022) in New York City was used for external validation. Participants: Patients were included if they were older than 18 years, and were monitored with electrocardiograms, arterial blood pressure, respiratory impedance plethysmography and pulse oximetry. Patients who additionally had intracranial pressure monitoring were used for development (N=157) and external validation (N=56). Patients without intracranial monitors were used for association with outcomes (N=1694). Exposures: Extracranial waveforms including electrocardiogram, arterial blood pressure, plethysmography and SpO2. Main Outcomes and Measures: Intracranial pressure > 15 mmHg. Measures were Area under receiver operating characteristic curves (AUROCs), sensitivity, specificity, and accuracy at threshold of 0.5. We calculated odds ratios and p-values for phenotype association. Results: The AUROC was 0.91 (95% CI, 0.90-0.91) on testing and 0.80 (95% CI, 0.80-0.80) on external validation. aICP had accuracy, sensitivity, and specificity of 73.8% (95% CI, 72.0%-75.6%), 99.5% (95% CI 99.3%-99.6%), and 76.9% (95% CI, 74.0-79.8%) on external validation. A ten-percentile increment was associated with stroke (OR=2.12; 95% CI, 1.27-3.13), brain malignancy (OR=1.68; 95% CI, 1.09-2.60), subdural hemorrhage (OR=1.66; 95% CI, 1.07-2.57), intracerebral hemorrhage (OR=1.18; 95% CI, 1.07-1.32), and procedures like percutaneous brain biopsy (OR=1.58; 95% CI, 1.15-2.18) and craniotomy (OR = 1.43; 95% CI, 1.12-1.84; P < 0.05 for all). Conclusions and Relevance: aICP provides accurate, non-invasive estimation of increased ICP, and is associated with neurological outcomes and neurosurgical procedures in patients without intracranial monitoring.

Outcomes and Follow-Up Data From Two Skin Cancer Screening Events.

This study investigated the outcomes and follow-up behaviors of participants from two free skin cancer screening events in the United States. This survey, with 296 participants and a 31% response rate, gathered information on participant demographics, personal history of skin cancer, knowledge of skin screening practices, and follow-up behaviors. There was a high follow-up rate of 92.3% among individuals recommended for further dermatological consultation, but a low (22%) concordance rate between the preliminary diagnoses from the screening and patient-recalled diagnoses. Additionally, about one-sixth of participants identified limited access to care as a motivation for participating in the screening. The study emphasizes the need to improve awareness about the limitations of free screenings, enhance participant education, and ensure equitable access to skin cancer screening. Future research should focus on factors influencing follow-up behaviors and the development of targeted interventions to increase awareness and access to skin cancer screening.

Unequal racial distribution of immunotherapy for late-stage non-small cell lung cancer.

Immunotherapy has increased survival for non-small cell lung cancer (NSCLC), especially for those diagnosed with late-stage disease. However, it is not known if its use is equally distributed across races. We assessed immunotherapy use in 21 098 pathologically confirmed stage IV NSCLC patients according to race in the Surveillance Epidemiology, and End Results-Medicare linked dataset. Multivariable models were conducted to evaluate the independent association of receipt of immunotherapy with race and overall survival according to race. Black patients had statistically significantly lower odds of receiving immunotherapy (adjusted odds ratio = 0.60, 95% confidence interval = 0.44 to 0.80); receipt of immunotherapy was lower in Asian and Hispanic patients but not statistically significant. When immunotherapy was received, survival was similar across races. Immunotherapy for NSCLC is not used equally among races, underscoring the racial disparities that exist in access to the newest cancer treatment. Efforts should be directed toward expanding access to novel, efficacious treatments for advanced stage lung cancer.

A quantitative model to ensure capacity sufficient for timely access to care in a remote patient monitoring program.

INTRODUCTION: Algorithm-enabled remote patient monitoring (RPM) programs pose novel operational challenges. For clinics developing and deploying such programs, no standardized model is available to ensure capacity sufficient for timely access to care. We developed a flexible model and interactive dashboard of capacity planning for whole-population RPM-based care for T1D. METHODS: Data were gathered from a weekly RPM program for 277 paediatric patients with T1D at a paediatric academic medical centre. Through the analysis of 2 years of observational operational data and iterative interviews with the care team, we identified the primary operational, population, and workforce metrics that drive demand for care providers. Based on these metrics, an interactive model was designed to facilitate capacity planning and deployed as a dashboard. RESULTS: The primary population-level drivers of demand are the number of patients in the program, the rate at which patients enrol and graduate from the program, and the average frequency at which patients require a review of their data. The primary modifiable clinic-level drivers of capacity are the number of care providers, the time required to review patient data and contact a patient, and the number of hours each provider allocates to the program each week. At the institution studied, the model identified a variety of practical operational approaches to better match the demand for patient care. CONCLUSION: We designed a generalizable, systematic model for capacity planning for a paediatric endocrinology clinic providing RPM for T1D. We deployed this model as an interactive dashboard and used it to facilitate expansion of a novel care program (4 T Study) for newly diagnosed patients with T1D. This model may facilitate the systematic design of RPM-based care programs.

A Novel Inpatient Buprenorphine Induction Program for Adolescents With Opioid Use Disorder.

BACKGROUND: Morbidity and mortality from nonprescribed opioid use and opioid use disorder (OUD) in adolescents have risen dramatically. Medication for opioid use disorder (MOUD) with buprenorphine reduces nonprescribed opioid use and prevents overdoses, though <5% of adolescents with OUD have timely access, partly because of barriers associated with buprenorphine induction. Induction in an inpatient pediatric setting has the potential to address such barriers and improve adolescent MOUD access. METHODS: We developed and implemented a protocol for inpatient buprenorphine induction and linkage to MOUD care within a safety-net health system. After 1 year, we conducted descriptive analysis of participant characteristics, rates of induction completion and treatment linkage, and adverse events. We analyzed field notes from multidisciplinary huddles to identify implementation facilitators and barriers. RESULTS: During May 2021 to July 2022, we completed 46 admissions for 36 patients aged 12 to 21 years. All used fentanyl and no other opioids. Forty of 46 (87%) admissions resulted in completed induction, and 3 additional patients never developed withdrawal symptoms and were discharged with maintenance buprenorphine. Linkage to ongoing treatment occurred within 2 weeks for 31 of 43 (72%) admissions for which buprenorphine was started. We identified facilitators and barriers to program implementation and maintenance. CONCLUSION: These results provide promising preliminary evidence of the feasibility of inpatient buprenorphine induction for adolescents with OUD. Given the public health urgency and severe shortage of adolescent access to MOUD, these results prompt consideration of broader clinical implementation and research to facilitate rapid expansion of access to evidence-based OUD care.

A model to design financially sustainable algorithm-enabled remote patient monitoring for pediatric type 1 diabetes care.

Introduction: Population-level algorithm-enabled remote patient monitoring (RPM) based on continuous glucose monitor (CGM) data review has been shown to improve clinical outcomes in diabetes patients, especially children. However, existing reimbursement models are geared towards the direct provision of clinic care, not population health management. We developed a financial model to assist pediatric type 1 diabetes (T1D) clinics design financially sustainable RPM programs based on algorithm-enabled review of CGM data. Methods: Data were gathered from a weekly RPM program for 302 pediatric patients with T1D at Lucile Packard Children's Hospital. We created a customizable financial model to calculate the yearly marginal costs and revenues of providing diabetes education. We consider a baseline or status quo scenario and compare it to two different care delivery scenarios, in which routine appointments are supplemented with algorithm-enabled, flexible, message-based contacts delivered according to patient need. We use the model to estimate the minimum reimbursement rate needed for telemedicine contacts to maintain revenue-neutrality and not suffer an adverse impact to the bottom line. Results: The financial model estimates that in both scenarios, an average reimbursement rate of roughly $10.00 USD per telehealth interaction would be sufficient to maintain revenue-neutrality. Algorithm-enabled RPM could potentially be billed for using existing RPM CPT codes and lead to margin expansion. Conclusion: We designed a model which evaluates the financial impact of adopting algorithm-enabled RPM in a pediatric endocrinology clinic serving T1D patients. This model establishes a clear threshold reimbursement value for maintaining revenue-neutrality, as well as an estimate of potential RPM reimbursement revenue which could be billed for. It may serve as a useful financial-planning tool for a pediatric T1D clinic seeking to leverage algorithm-enabled RPM to provide flexible, more timely interventions to its patients.

Effect of a ketogenic diet versus Mediterranean diet on glycated hemoglobin in individuals with prediabetes and type 2 diabetes mellitus: The interventional Keto-Med randomized crossover trial.

BACKGROUND: Consensus has not been reached on what constitutes an optimal diet in individuals with prediabetes and type 2 diabetes mellitus (T2DM), especially between low-carbohydrate options. OBJECTIVES: We compared 2 low-carbohydrate diets with 3 key similarities (incorporating nonstarchy vegetables and avoiding added sugars and refined grains) and 3 key differences (incorporating compared with avoiding legumes, fruits, and whole, intact grains) for their effects on glucose control and cardiometabolic risk factors in individuals with prediabetes and T2DM. METHODS: Keto-Med was a randomized, crossover, interventional trial. Forty participants aged ≥18 years with prediabetes or T2DM followed the well-formulated ketogenic diet (WFKD) and the Mediterranean-plus diet (Med-Plus) for 12 weeks each, in random order. The diets shared the 3 key similarities noted above. The Med-Plus incorporated legumes, fruits, and whole, intact grains, while the WFKD avoided them. The primary outcome was the percentage change in glycated hemoglobin (HbA1c) after 12 weeks on each diet. Secondary and exploratory outcomes included percentage changes in body weight, fasting insulin, glucose, and blood lipids; average glucose from continuous glucose monitor (CGM), and nutrient intake. RESULTS: The primary analysis was of 33 participants with complete data. The HbA1c values did not differ between diets at 12 weeks. Triglycerides decreased more for the WFKD [percentage changes, -16% (SEM, 4%) compared with -5% (SEM, 6%) for the Med-Plus; P = 0.02] and LDL cholesterol was higher for the WFKD [percentage changes, +10% (SEM, 4%) compared with -5% (SEM, 5%) for the Med-Plus; P = 0.01]. Weight decreased 8% (SEM, 1%) compared with 7% (SEM, 1%) and HDL cholesterol increased 11% (SEM, 2%) compared with 7% (SEM, 3%) for the WFKD compared with the Med-Plus, respectively; however, there was a significant interaction of diet × order for both. Participants had lower intakes of fiber and 3 nutrients on the WFKD compared with the Med-Plus. Twelve-week follow-up data suggest the Med-Plus is more sustainable. CONCLUSIONS: HbA1c values were not different between diet phases after 12 weeks, but improved from baseline on both diets, likely due to several shared dietary aspects. The WFKD led to a greater decrease in triglycerides, but also had potential untoward risks from elevated LDL cholesterol and lower nutrient intakes from avoiding legumes, fruits, and whole, intact grains, as well as being less sustainable. This trial was registered at clinicaltrials.gov as NCT03810378.

Large-scale labeling and assessment of sex bias in publicly available expression data.

BACKGROUND: Women are at more than 1.5-fold higher risk for clinically relevant adverse drug events. While this higher prevalence is partially due to gender-related effects, biological sex differences likely also impact drug response. Publicly available gene expression databases provide a unique opportunity for examining drug response at a cellular level. However, missingness and heterogeneity of metadata prevent large-scale identification of drug exposure studies and limit assessments of sex bias. To address this, we trained organism-specific models to infer sample sex from gene expression data, and used entity normalization to map metadata cell line and drug mentions to existing ontologies. Using this method, we inferred sex labels for 450,371 human and 245,107 mouse microarray and RNA-seq samples from refine.bio. RESULTS: Overall, we find slight female bias (52.1%) in human samples and (62.5%) male bias in mouse samples; this corresponds to a majority of mixed sex studies in humans and single sex studies in mice, split between female-only and male-only (25.8% vs. 18.9% in human and 21.6% vs. 31.1% in mouse, respectively). In drug studies, we find limited evidence for sex-sampling bias overall; however, specific categories of drugs, including human cancer and mouse nervous system drugs, are enriched in female-only and male-only studies, respectively. We leverage our expression-based sex labels to further examine the complexity of cell line sex and assess the frequency of metadata sex label misannotations (2-5%). CONCLUSIONS: Our results demonstrate limited overall sex bias, while highlighting high bias in specific subfields and underscoring the importance of including sex labels to better understand the underlying biology. We make our inferred and normalized labels, along with flags for misannotated samples, publicly available to catalyze the routine use of sex as a study variable in future analyses.

What happens when we forget our own narrative: Transgender dementia case study.

OBJECTIVE: Neuropsychological evaluations in a geriatric population have an assortment of challenges due to increased risk in the population for chronic/acute medical conditions, varied psychiatric disorders, and chronic negative lifestyle behaviors, all which impact one's cognitive functioning. One relatively new challenge is conducting cognitive evaluations within an elderly transgender population. There is a considerable lack of specific normative data in neuropsychological evaluations for transgender individuals due to the prevalence of binary gender categorization in current scoring protocols. However, a reasonable question is whether gender is such a significant normative factor, as the field of neuropsychology once thought? METHOD: The current article reports on these issues in the context of a case of an 85-year-old transgender female who was referred to an outpatient neuropsychology service due to cognitive and functional declines. RESULTS: Her performance on the neuropsychological evaluation indicated significant decline across many of the cognitive domains measured. When using binary male and female normative data, scores did not statistically differ across the majority of the domains. CONCLUSIONS: Overall, it was difficult to determine nuanced gender differences due to the patient's marked cognitive impairment. Potentially, differences may be more obvious in a less impaired individual.

Nutrition and Health Improvements After Participation in an Urban Home Garden Program.

OBJECTIVE: To elucidate the perceived health benefits of an urban home gardening and nutritional education program in a population at high cardiometabolic risk. DESIGN: Qualitative data collected via in-depth, semistructured interviews in Spanish or English. SETTING: Community-based program offering supported urban home gardening together with nutrition education in Santa Clara County, CA. PARTICIPANTS: A total of 32 purposively sampled low-income participants in an urban home gardening program. Participants were primarily female (n = 24) and Latino/a (n = 22). PHENOMENON OF INTEREST: Perceptions of the nutrition and health benefits of education-enhanced urban home gardening. ANALYSIS: Bilingual researchers coded transcripts using a hybrid inductive and deductive approach. Two coders double coded at intervals, independently reviewed coding reports, organized content into key themes, and selected exemplary quotations. RESULTS: The most salient perceived impacts were greater food access, increased consumption of fresh produce, a shift toward home cooking, and decreased fast food consumption. Participants attributed these changes to greater affordability, freshness, flavor, and convenience of their garden produce; increased health motivation owing to pride in their gardens; and improved nutritional knowledge. Participants also reported improved physical activity, mental health, and stress management; some reported improved weight and adherence to diabetes-healthy diets. CONCLUSIONS AND IMPLICATIONS: Education-enhanced urban home gardening may facilitate multidimensional nutrition and health improvements in marginalized populations at high cardiometabolic risk.

Marginalization and Community Perception of HIV Care, Treatment, and Support on Mfangano Island, Kenya.

BACKGROUND: In rural sub-Saharan Africa (SSA), the human immunodeficiency virus (HIV)/AIDS pandemic has exerted effects on nearly every aspect of life. Yet despite the pandemic's near ubiquitous impacts, major barriers to HIV care, treatment, and support persist. Compounding the barriers to care is the incredible complexity and diversity of experience across different sociocultural contexts. OBJECTIVES: This exploratory community-based participatory study aimed to generate an explanatory model about how geographic and socioeconomic marginalization shape community perception of HIV care, treatment, and support among rural communities of Mfangano Island, Kenya. METHODS: Twelve focus groups with a total of 105 participants were conducted as a part of a mixed-methods cross-sectional health study. RESULTS: Study findings are organized within an ecological framework with the following themes: readiness at the individual level, social capital at the household level, and collective efficacy at the community level. Potential solutions were also described within this framework; enabling encouragement at the individual level, enhancing productivity at the household level, and addressing underlying socioeconomic inequities at the community level. CONCLUSIONS: HIV-related consequences at the individual, household, and community levels have adversely affected how Mfangano communities respond to the HIV/AIDS epidemic. Community-based strategies are needed to address interrelated inequities at multiple levels. Changing community perception may overcome HIV stigma to enable individual readiness to seek care. Access to care and treatment enhances productivity and hence social capital in HIV-affected households. Addressing socioeconomic inequities at the community level increases access to social and instrumental support and, thus, may decrease risk and vulnerability for HIV/AIDS.

One Hundred False-Positive Amphetamine Specimens Characterized by Liquid Chromatography Time-of-Flight Mass Spectrometry.

Some amphetamine (AMP) and ecstacy (MDMA) urine immunoassay (IA) kits are prone to false-positive results due to poor specificity of the antibody. We employed two techniques, high-resolution mass spectrometry (HRMS) and an in silico structure search, to identify compounds likely to cause false-positive results. Hundred false-positive IA specimens for AMP and/or MDMA were analyzed by an Agilent 6230 time-of-flight (TOF) mass spectrometer. Separately, SciFinder (Chemical Abstracts) was used as an in silico structure search to generate a library of compounds that are known to cross-react with AMP/MDMA IAs. Chemical formulas and exact masses of 145 structures were then compared against masses identified by TOF. Compounds known to have cross-reactivity with the IAs were identified in the structure-based search. The chemical formulas and exact masses of 145 structures (of 20 chemical formulas) were compared against masses identified by TOF. Urine analysis by HRMS correlates accurate mass with chemical formulae, but provides little information regarding compound structure. Structural data of targeted antigens can be utilized to correlate HRMS-derived chemical formulas with structural analogs.

Effect of Bifidobacterium breve M-16V supplementation on fecal bifidobacteria in preterm neonates--a randomised double blind placebo controlled trial.

BACKGROUND: Probiotic supplementation significantly reduces the risk of necrotising enterocolitis (NEC) and all cause mortality in preterm neonates. Independent quality assessment is important before introducing routine probiotic supplementation in this cohort. AIM: To assess product quality, and confirm that Bifidobacterium breve (B. breve) M-16V supplementation will increase fecal B. breve counts without adverse effects. METHODS AND PARTICIPANTS: Strain identity (16S rRNA gene sequencing), viability over 2 year shelf-life were confirmed, and microbial contamination of the product was ruled out. In a controlled trial preterm neonates (Gestation <33 weeks) ready to commence or on feeds for <12 hours were randomly allocated to either B. breve M-16V (3×109 cfu/day) or placebo (dextrin) supplementation until the corrected age 37 weeks. Stool samples were collected before (S1) and after 3 weeks of supplementation (S2) for studying fecal B. breve levels using quantitative PCR (Primary outcome). Secondary outcomes included total fecal bifidobacteria and NEC≥Stage II. Categorical and continuous outcomes were analysed using Chi-square and Mann-Whitney tests, and McNemar and Wilcoxon signed-rank tests for paired comparisons. RESULTS: A total of 159 neonates (Probiotic: 79, Placebo: 80) were enrolled. Maternal and neonatal demographic characteristics were comparable between the groups. The proportion of neonates with detectable B. breve increased significantly post intervention: Placebo: [S1:2/66 (3%), S2: 25/66 (38%), p<0.001] Probiotic: [S1: 29/74 (40%), S2: 67/74 (91%), p<0.001]. Median S1 B. breve counts in both groups were below detection (<4.7 log cells x g(-1)), increasing significantly in S2 for the probiotic group (log 8.6) while remaining <4.7 log in the control group (p<0.001). There were no adverse effects including probiotic sepsis and no deaths. NEC≥Stage II occurred in only 1 neonate (placebo group). CONCLUSION: B. breve M-16V is a suitable probiotic strain for routine use in preterm neonates. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN 12609000374268.

Verbal and nonverbal learning and recall in dementia with lewy bodies and Alzheimer's disease.

The present study compares groups of patients with dementia with Lewy bodies (DLB) or dementia of the Alzheimer's type (DAT) on components of memory. The Hopkins Verbal-Learning Test-Revised (HVLT-R) and the Brief Visuospatial Memory Test-Revised (BVMT-R) were utilized. The DAT group performed significantly worse than the DLB group on the learning, delayed free recall, and percent retained scores of the HVLT-R, as well as on the delayed free recall and percent retained scores of the BVMT-R. There were no significant differences on BVMT-R learning. Discriminant function analysis yielded a classification rate of 75.9%. This supports previous research indicating that individuals with DLB have impairments in visuospatial abilities that extend into the domain of memory components, specifically learning. Pattern of performance may be useful in discriminating between individuals with DLB and those with DAT.