Jacobs Institute of Women's Health
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Real-World Use of Tapinarof Cream 1% Once Daily in Patients with Seborrheic Dermatitis: A Case Series
No full textSeborrheic dermatitis (SD) is an inflammatory skin disease with multifactorial etiology, involving genetic and environmental factors. Many conventional therapies for SD (ie, topical antifungals, topical corticosteroids) are associated with incomplete efficacy, frequent and sometimes rapid disease recurrence, and restrictions on duration of therapy and anatomic sites of application. This may be because they cannot target multiple disease processes and/or are limited by safety considerations. Topical roflumilast foam was approved for the treatment of SD in 2023, but additional options are needed. The pathophysiology of atopic dermatitis (AD) and psoriasis have similarities with SD, supporting the hypothesis that tapinarof cream 1% once daily (QD) may be beneficial and well tolerated for patients with SD. Tapinarof is a non-steroidal, topical aryl hydrocarbon receptor agonist approved for the treatment of plaque psoriasis in adults. Tapinarof downregulates pro-inflammatory cytokines implicated in AD and plaque psoriasis, restores the skin barrier through upregulation of skin barrier components, and reduces oxidative stress. Here, we report that tapinarof cream 1% QD used for the treatment of four adults with mild-to-severe SD affecting the face, neck, back, and chest, demonstrated a rapid onset of efficacy and noticeable improvements in disease activity. Efficacy was maintained after treatment discontinuation, indicating a possible remittive effect as previously described in plaque psoriasis. The efficacy and potential remittive effect may be attributed to the unique mechanism of action and clinical profile of tapinarof cream. Tapinarof is a novel topical therapy that may be beneficial for patients with SD
Population Pharmacokinetics and Dose Optimization of Piperacillin in Infants and Children with Pneumonia
No full textOBJECTIVE: We aimed to determine the piperacillin disposition and optimize the dosing regimens for infants and children with pneumonia. METHODS: An opportunistic sampling strategy was used in this pharmacokinetic study. High-performance liquid chromatography was used to measure the concentrations of piperacillin in plasma samples. A population pharmacokinetic model was conducted using NONMEM. RESULTS: The pharmacokinetic data of 90 samples from 64 infants and children with pneumonia (age range: 0.09-1.72 years for infants and 2.12-11.10 years for children) were available. A two-compartment model with first-order elimination was the most suitable model to describe the population pharmacokinetics of piperacillin. A covariate analysis indicated that body weight and age were significant factors affecting clearance. Monte Carlo simulations showed that a 50-mg/kg every 8 h or every 12 h dosing regimen results in underdosing. Results both in infants and children showed that an extended infusion (3 h) of various dosing regimens (80, 100, or 130 mg/kg) three times daily or a 300-mg/kg continuous infusion can reach a therapeutic level based on the chosen target for the probability of target attainment threshold of 70%, 80%, and 90% at minimum inhibitory concentration breakpoints of 8 mg/L and 16 mg/L. CONCLUSIONS: A population pharmacokinetic model was obtained to evaluate the disposition of piperacillin, and the optimal dosing regimens were provided for use in infants and children with pneumonia
Investigating mechanisms underlying the development of paralysis symptom in a model of MS
No full textMultiple sclerosis (MS) is an autoimmune neurodegenerative disorder with approximately 80 % of patients suffering from pain and 50 % from paralysis. Using a rodent model for MS, experimental autoimmune encephalomyelitis (EAE), researchers have predominately investigated paralysis/motor disease as the clinical symptom of EAE with fewer studying MS/EAE pain. However, in EAE, all mice exhibit a pain like phenotype and only a subset progresses to paralysis. Despite extensive research characterizing the disease pathology, the etiology that contributes to the range of pain and motor symptom occurrence in MS remains understudied. This is the first study to dissect MS symptom pathophysiology, using the non-PTX EAE model, in mice that experience mechanical hypersensitivity (pain-like phenotype) with and without paralysis. We found that mechanical hypersensitivity experienced by mice with or without paralysis is comparable between the two groups, irrespective of sex. In addition, there is a significant increase in the activation and infiltration of immune cells, demyelination, and heightened protein expression of B cell chemoattractant CXCL13 within the spinal cord of mice exhibiting mechanical hypersensitivity and paralysis, compared to mice only experiencing mechanical hypersensitivity
Feasibility of a multidisciplinary pilot intervention for parent/caregiver diabetes distress
No full textAIMS: Caregiver diabetes distress (DD) consists of negative emotions about a child\u27s T1D diagnosis and has been associated with increased child haemoglobin A1c and family conflict. The primary aim was to identify the feasibility and acceptability of a multidisciplinary pilot intervention for caregiver DD in a diverse academic pediatric diabetes centre. Another primary aim was to determine the percentage of local caregivers with DD. A secondary aim was to determine if the intervention affected caregiver DD. We also explored potential associations between caregiver DD and demographic and diabetes-related characteristics. METHODS: Individual interviews with five caregivers with DD (who did not participate in the intervention) were held pre-intervention, in order to gather qualitative, open-ended feedback on prepared educational materials. As a pilot feasibility study, we held 3 monthly, one-hour educational and support group virtual sessions per cohort (6-8 caregivers) on Nutrition, Fear of Hypoglycemia and Parent/Child Collaboration. Sessions were attended by an endocrinologist with leaders from other disciplines including dietician, diabetes educator and/or social worker. Target enrollment was 30 caregivers with DD (PAID-PR/Problem Areas in Diabetes-Parent Revised score of ≥56/100) of children 5-17 years old with T1D for ≥6 months. Data include demographic information, pre-/post- PAID-PR scores, caregivers\u27 session satisfaction ratings and open-ended written feedback. We also examined data from 26 parents of children who did not have elevated scores on DD (the comparison group) and were not invited to attend the intervention sessions. RESULTS: Caregiver participants were 85% women, ages 42.5 ± 11.3 years; children\u27s characteristics: 38% girls, ages 11.1 ± 2.1 years, 47.6% Black, 33.3% Caucasian, 9.5% Hispanic, 9.6% other, 43% public insurance, mean diabetes duration 4.3 ± 0.18 years and A1c 8.5 ± 0.7% (69.4 mmol/mol). Pre- and post-intervention PAID-PR scores improved from 68 to 51 (p \u3c 0.05). This was sustained 3 months post-intervention with a mean PAID-PR of 42 (p \u3c 0.05). CONCLUSION: The pilot intervention was feasible, with two-thirds of caregivers attending ≥2 sessions. Reported DD improved over time. Limitations include a small initial sample. Future directions include expanding this study to a larger population and ultimately incorporating a similar support program into the clinical setting as part of routine outpatient diabetes care
In-hospital outcomes of patients with antiphospholipid syndrome undergoing transcatheter and surgical aortic valve replacement: A population-based analysis of national inpatient sample from 2015-2021
No full textBACKGROUND: Valvular abnormalities are common in antiphospholipid syndrome (APS). For patients who undergo aortic valve replacement (AVR), previous single institutional studies or case reports reported higher risks of mortality and thromboembolic complications among APS patients. This study aimed to investigate in-hospital outcomes of APS patients undergoing transcatheter (TAVR) and surgical aortic valve replacement (SAVR) using the largest all-payer database in the United States. METHODS: Patients who underwent TAVR and SAVR were selected from National Inpatient Sample from Q4 2015-2021. Exclusion criteria were age under 18 years and concomitant procedures. Preoperative characteristics were matched between APS and non-APA patients using a 1:5 propensity-score matching in TAVR and SAVR, separately. In-hospital outcomes were examined. RESULTS: After propensity-score matching, 504 non-APS patients were matched to 100 APS patients in TAVR, while 581 non-APS patients were matched to 119 APS patients in SAVR. All outcomes between APS and non-APS patients were comparable after TAVR. In contrast, APS patients undergoing SAVR had higher risks of pulmonary embolism (PE; 5.13% vs 0.86%, p \u3c .01) and acute kidney injury (AKI; 35.04% vs 22.55%, p = .01). CONCLUSION: This study represents one of the first large-scale, population-based analyses of AVR outcomes for APS patients using a national registry. APS patients had all comparable outcomes after TAVR, while they had higher risks of PE and AKI after SAVR. This highlights the necessity for close perioperative antithrombotic management and careful monitoring of renal function in APS patients. TAVR may offer a safer alternative to SAVR for appropriately selected patients, including those with APS
Unmet Needs of Effective Advanced Systemic Therapies in Moderate-to-Severe Atopic Dermatitis Patients in the TARGET-DERM AD Registry
No full textIn the United States, 40-50% of patients with atopic dermatitis (AD) have moderate-to-severe disease, often necessitating advanced systemic therapies (ASTs; biologics or Janus kinase inhibitors). TARGET-DERM AD is an observational, longitudinal registry that tracks the natural history and treatment of AD, including patients with moderate-to-severe disease. Among enrollees, we defined 4 patient subgroups: AST-Naïve, AST-Retrospective (AST initiated prior to enrollment), AST-Prospective (AST initiated at or after enrollment), and AST-Failed (failed at any point). This analysis describes AST-patient demographics, treatment patterns, and longitudinal outcomes. Of 598 qualifying participants (22% adolescent, 78% adult), 34% were AST-Naive, 27% AST-Retrospective, 31% AST-Prospective, and 8% AST-Failed. Comparing the adult subgroups showed significant differences in enrollment age, and race/ethnicity, but not among adolescents. There was no significant difference in AST prescription rates. Literature-based validated thresholds were used to define unchanged or worsening for each outcome, which was combined into a single category, lacked improvement. At 52 weeks of AST, AST-Prospective adolescents lacked improvement on Validated Investigator\u27s Global Assessment of Atopic Dermatitis (vIGA-AD) (26%), body surface area (BSA) (34%), Numeric Rating Scale (NRS)-Pain (63%), and NRS-Sleep (52%); AST-Prospective adults lacked improvement on vIGA-AD (21%), BSA (51%), NRS-Pain (66%), and NRS-Sleep (60%). As one-third of participants did not progress to AST, and noteworthy proportions of patients lacked improvement, this study highlights unmet needs and treatment inadequacies in patients with moderate-to-severe AD
TROPOMI Satellite Data Reshape NO Air Pollution Land-Use Regression Modeling Capabilities in the United States
No full textNitrogen dioxide (NO) pollution is associated with adverse health effects, but its spatial variability between ground monitors is poorly characterized. NO column observations from the Tropospheric Monitoring Instrument (TROPOMI) have unprecedented spatial resolution and high accuracy over the globe. Land-use regression (LUR) models predict surface-level NO with relevance for epidemiological and environmental justice studies. We use TROPOMI NO columns in a land use regression (LUR) model to improve surface NO concentration estimates over the United States. The TROPOMI LUR predictions have improved correlation with ground monitors (Adj. R = 0.72) and bias (Mean Bias, MB = 14.2%) compared with an existing LUR using less granular NO data from a legacy satellite instrument (Adj. R = 0.54 and MB = 49%; for North America). Removing TROPOMI NO from the LUR decreased R by 29.1%, 8.1 times the impact of removing road system information. These findings reveal that novel Earth observing satellites can enhance surface NO surveillance by capturing pollution variation between monitors without relying heavily on other data sources
Exposed and Vulnerable: Sources and Health Implications of Chemical Exposures in Neonatal, Pediatric, and Cardiac Intensive Care Units
No full textPURPOSE OF REVIEW: Exposures to endocrine disrupting chemicals (EDCs) in early life have demonstrable adverse implications on child health and development. Yet, there is a dearth of studies evaluating the potential exposures to EDCs, such as bisphenols, parabens, phthalates, and volatile organic compounds (VOCs), in hospital-based settings among children who are critically ill and/or particularly vulnerable. This narrative review seeks to provide up-to-date evidence on the sources and magnitude of exposure to EDCs in neonatal-, pediatric-, and cardiac intensive care units (NICUs/PICUs/CICUs) as well as resulting health impacts. RECENT FINDINGS: Thirty-three studies were included in this review. The most frequently studied and characterized EDCs in NICUs/PICUs/CICUs were phthalates followed by terephthalates and alternative plasticizers. Evaluations of health outcomes resulting from such exposures were scarce, and few studies assessed health outcomes after hospital discharge. EDCs are pervasive in NICU/PICU/CICU settings and pediatric exposure levels are much higher than in other environments. However, the existing evidence has multiple limitations that should be addressed in future work. Specifically, studies evaluating a more expansive array of chemicals, including contemporary and emerging replacements for legacy compounds, are needed, as are studies that consider chemical mixtures. Additionally, few studies evaluated the health impacts of chemical exposures, and their mixtures, in NICU/PICU/CICU settings, especially long-term health outcomes observed after hospital discharge. Such studies could be invaluable in supporting policy as well as development of medical products without toxic chemicals
Intestinal Gastrin/CCKBR Axis Protects against Type 2 Diabetes by Reducing Intestinal Glucose Absorption through the PI3K/Akt/eIF4B Signaling Pathway
No full textThe Gastrin/CCKBR axis is essential for inhibiting intestinal sodium absorption, but its effects on intestinal glucose metabolism remain elusive. This study aims to determine the role of intestinal Gastrin/CCKBR on glucose absorption in the development of type 2 diabetes (T2D). Intestinal epithelial cell-specific Cckbr knockout mice and control wild-type mice are fed normal diet (ND, 10% fat) or high fat diet (HFD, 60% fat) to study the effect of intestinal Gastrin/CCKBR on blood glucose levels. Gastrin-SiO microspheres (20 mg kg d) are designed so that gastrin specifically stimulates intestinal CCKBR, without its absorption into the circulation. Mice with silenced intestinal Cckbr has pre-diabetes mellitus (Pre-DM) that rapidly progressed into T2D when fed HFD. Moreover, Gastrin-SiO microspheres markedly reduce glucose absorption in duodenum obtained from patients with T2D. In mice with HFD-induced T2D, Gastrin-SiO microspheres reduce intestinal glucose absorption by down-regulating intestinal SGLT1 and GLUT2 expressions and stimulating incretin secretion. This study shows the important role of intestinal Gastrin/CCKBR in intestinal glucose absorption. Gastrin-SiO microspheres may be a promising strategy for the treatment of patients with T2D
Timing of Physical Activity and Associations with BMI and Weekly Physical Activity in Young Adults: A Cross-Sectional Analysis
No full textThe timing of physical activity has been associated with weight and moderate-to-vigorous physical activity (MVPA) in adults. However, few studies have tested associations in young adults, who are biologically and behaviorally different from adults. Young adults (18-35 yr) enrolled in a weight management program provided body mass index (BMI) and 4-7days of ActiGraph accelerometer wear time at baseline. Activity time of day was divided into the following quartiles: morning (06:00-11:59), afternoon (12:00-15:59), evening (16:00-18:59), and night (19:00-00:59). The proportion of weekly MVPA minutes occurring in each time category was used to predict BMI and total weekly MVPA using linear regression models. Marginal trends were estimated for the full sample and by sex. The analytic sample (N = 408, mAge = 23.8±4.5, mBMI = 31.1±4.4) was 79% female, 49% non-Hispanic White, with a mean weekly MVPA of 311±167minutes. MVPA timing was associated with total weekly MVPA but not BMI. Afternoon MVPA was inversely associated with total weekly MVPA in women (-1.72 [95% CI: -3.19, -0.26] min). When considering only bouted MVPA as a predictor, morning (all: 1.43 [95% CI: 0.86, 2.00] min) and night (women: 0.87 [95% CI: 0.15, 1.58] min) MVPA were positively associated with total weekly MVPA. Activity-based interventions designed to improve behavioral health may be improved by providing time-based recommendations tailored to the demographic characteristics of the target population. For example, morning may be an optimal time for both female and male young adults to engage in bouted physical activity to improve total weekly activity levels