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Tapinarof cream 1% once daily was well tolerated in adults and children with atopic dermatitis in two phase 3 randomized trials
No full textBackground: Tapinarof cream 1% once daily (QD) demonstrated significant efficacy in patients down to age 2 years with atopic dermatitis (AD) in the ADORING 1 and 2 phase 3 trials. We report local tolerability outcomes.
Methods: Patients received Tapinarof or vehicle cream QD for 8 weeks. Tolerability was evaluated using patient/parent/caregiver and investigator 5-point Local Tolerability Scales (LTS). Investigators assessed tolerability for sensitive skin areas, including face/neck.
Results: 813 patients were randomized (∼80% pediatric). Mean pretreatment baseline overall LTS scores were similar across groups and trials: 1.0-1.9 (patient-assessed) indicating slight burning/stinging and itching; and 0.3-0.6 (investigator-assessed) indicating no-to-minimal irritation. Tapinarof was well tolerated with improvement from pretreatment baseline and no-to-minimal burning/stinging and itching from first application through Week 8 (patient-reported): mean Week 8 LTS scores were 0.2-0.4 (burning/stinging) and 0.6-0.8 (itching). Investigators reported improvement from pretreatment baseline with no-to-minimal irritation (dryness/erythema/peeling) from first Tapinarof application through Week 8 (mean LTS scores: 0.2 and 0.1 in ADORING 1 and 2, respectively). Across sensitive skin, investigators reported no-to-minimal irritation from first application through Week 8 (mean scores [Tapinarof versus vehicle]: 0-0.3 versus 0-1.0).
Conclusion: Tapinarof was well tolerated locally from first application through Week 8, including on sensitive skin areas. Clinicaltrials.gov numbers NCT05014568, NCT05032859
Early Autonomic Dysfunction in Traumatic Brain Injury: An Article Review on the Impact on Multiple Organ Dysfunction
No full textBackground/Objectives: Traumatic brain injury (TBI) is a complex condition and a leading cause of injury-related disability and death, with significant impacts on patient outcomes. Extracranial organ involvement plays a critical role in the outcome of patients following TBI. Method: This review aims to provide a comprehensive overview of the pathophysiology, clinical presentation, and challenges in diagnosing patients with autonomic dysfunction after TBI. The databases used in this review include PubMed/MEDLINE, Cochrane Central Register, and Scopus.
Results: Of 172 articles identified for screening, 98 were ultimately included in the review.
Conclusion: This review summarized the current evidence on the pathophysiology, clinical presentation, and diagnosis of early autonomic dysfunction. It also emphasizes the effects of autonomic dysfunction on end-organ damage. These insights aim to guide clinicians and researchers toward improving the care for and understanding of autonomic dysfunction in TBI patients, while underscoring the need for further research in this area
A mixed-methods observational study of strategies for success in implementation science: overcoming emergency departments hurdles
No full textBACKGROUND: Heart failure is a major public health concern, affecting 6.7 million Americans. An estimated 16% of emergency department (ED) patients with acute heart failure (AHF) are discharged home. Our Get with the Guidelines in Emergency Department Patients with Heart Failure (GUIDED-HF) toolkit aims to improve AHF self-care and facilitate safer transitions in care for these patients. We describe implementation barriers and facilitators, and the selection and refinement of implementation strategies, to facilitate future GUIDED-HF implementation.
METHODS: A mixed-methods cross-sectional observational study was conducted in four United States EDs in two diverse healthcare systems in the Pacific West and Midwest. Data were collected using a survey and interviews with ED providers, nurses, and leaders. The survey assessed the ED context using the context scale of the Organizational Readiness to Change Assessment (ORCA). The Consolidated Framework for Implementation Research informed interviews. Quantitative data were summarized using medians (interquartile ranges) or percentages (frequencies). Wilcoxon rank-sum tests and Kruskal-Wallis tests were used to assess differences in the healthcare system and profession. Qualitative data were analyzed and summarized using rapid qualitative analysis. Convergence of quantitative and qualitative data was used to inform specific refining of implementation strategies to the local context (e.g., who should serve as champions, how best practice alerts should be implemented).
RESULTS: Participants were predominately white (76%) with median (IQR) age 37.0 (32.0, 41.0). ED leaders/administrators, providers, and nurses comprised 15%, 55%, and 29% of participants, respectively. Sites reported an ORCA context scale score of 3.7 [3.4, 4.0] (scale of 1 = strongly disagree to 5 = strongly agree). Comparison of scores by profession showed a significant difference in the context score among providers (3.9 [3.5, 4.0]), leaders (3.7 [3.5, 4.0]), and nurses (3.6 [3.0, 3.9]) (p = 0.048). Qualitative data indicated implementation barriers (e.g., resource limitations, patient health literacy), facilitators (e.g., GUIDED-HF is patient-centric; site and intervention congruent values, norms, and goals), and site-specific needs due to contextual factors (e.g., education needs, feedback mechanisms, champions).
CONCLUSIONS: Specific determinants of implementation exist in ED settings and require the refining of implementation strategies to overcome site-specific barriers and enhance facilitators.
TRIAL REGISTRATION: n/a
The geriatric emergency literature 2023
No full textCaring for older adults in the Emergency Department demands compassion, expertise, and adaptability to address the intricate medical and emotional needs of this vulnerable population. Key geriatric emergency medicine articles from 2023 highlight the evolving landscape of this field: updates to the Beers Criteria for potentially inappropriate medications, medications most implicated in causing delirium, geriatric trauma centers, behavioral problems in persons with dementia, geriatric syndrome detection, and emergency department (ED) process outcomes in geriatric EDs. As healthcare organizations shift to focus on the larger continuum of care that extends beyond the ED visit, we also highlight a novel program from the Veterans Affairs bringing former military medics to the home to improve outcomes after ED discharge. This review highlights practice-changing updates to improve the management of older adults in the ED
Interval Advanced Adenomas and Neoplasia in Patients with Negative Colonoscopy Following Positive Stool-Based Colorectal Cancer Screening Test
No full textBACKGROUND/AIMS: Fecal occult blood test (FOBT) and fecal immunohistochemical test (FIT) are used for colorectal cancer (CRC) screening. However, when no adenomas are found following a positive FOBT/FIT, the future risk of advanced adenomas or colorectal cancer (CRC) is unclear. We determined the incidence and determinants of advanced adenomas or CRC after a negative index colonoscopy following a positive FOBT/FIT.
METHODS: We identified patients in the Harris Health System (Houston, Texas) who underwent a colonoscopy following a positive FOBT/FIT from 01/2010 to 01/2013. We compared the incidence rates of advanced adenomas (≥ 1 cm, villous histopathology, or high-grade dysplasia) or CRC through 12/2023 for patients without polyps on index colonoscopy (negative colonoscopy) to patients with polyps (positive colonoscopy). We examined risk factors for incident adenomas using Cox regression models.
RESULTS: Of 2096 patients, 1293 (61.7%) had negative index colonoscopy and 803 (38.3%) had positive index colonoscopy. Overall, 411 patients (19.6%) underwent subsequent colonoscopy with incident adenomas in 241 patients and no incident CRC over mean 12.5 years. The incidence rate of advanced adenomas was 2.08 per 100 person-years after positive index colonoscopy compared to 0.65 per 100 person-years after negative index colonoscopy (age-adjusted incidence rate ratio 3.08, 95% CI 1.27-7.48). Non-Hispanic white race was the strongest risk factor for incident adenomas among patients with negative index colonoscopy.
CONCLUSIONS: We found a low likelihood of advanced adenomas and no interval CRC following negative index colonoscopy after positive FOBT/FIT. Non-Hispanic white race was a risk factor for incident adenomas, and these patients may warrant closer surveillance
HMGA2 Expression Predicts Subtype, Survival, and Treatment Outcome in Pancreatic Ductal Adenocarcinoma
No full textPURPOSE: The purpose of this study was to establish HMGA2 as a marker of basal-like disease in pancreatic ductal adenocarcinoma (PDAC) and explore its use as a biomarker for prognosis and treatment resistance.
EXPERIMENTAL DESIGN: We identified high-mobility group A2 (HMGA2) protein expression in basal PDAC cells in a single-cell RNA sequencing (RNA-seq) atlas of 172 patient samples. We then analyzed HMGA2 expression, along with expression of the classic marker GATA-binding factor 6 (GATA6), in a cohort of 580 PDAC samples with multiplex IHC. We further supplemented these data with an additional 30 diverse patient samples and multiple independent single-cell RNA-seq databases.
RESULTS: We found that expression of HMGA2, but not previously described basal markers cytokeratins 5 or 17, predicted overall survival in our cohort. Combining HMGA2 and GATA6 statuses allowed for the identification of two key study groups: an HMGA2+/GATA6- cohort with worse survival, low tumor-infiltrating CD8+ T cells, increased FAP+ fibroblasts, and poorer response to gemcitabine-based chemotherapies (n = 94, median survival = 11.2 months after surgery) and an HMGA2-/GATA6+ cohort with improved survival, increased CD8+ T-cell infiltrate, decreased FAP+ fibroblasts, and improved survival with gemcitabine-based chemotherapy (n = 198, median survival = 21.7 months after surgery). HMGA2 was also prognostic for overall survival in RNA-seq from an independent cohort.
CONCLUSIONS: IHC stratification of primary tumors by HMGA2 and GATA6 statuses in pancreatic cancer is associated with differential outcomes, survival following chemotherapy, and tumor microenvironments. As a nuclear marker for basal disease, HMGA2 complements GATA6 to identify disease subtypes in PDAC
Chronic and infectious respiratory mortality and short-term exposures to four types of pollen taxa in older adults in Michigan, 2006-2017
No full textINTRODUCTION: Levels of plant-based aeroallergens are rising as growing seasons lengthen and intensify with anthropogenic climate change. Increased exposure to pollens could increase risk for mortality from respiratory causes, particularly among older adults. We determined short-term, lag associations of four species classes of pollen (ragweed, deciduous trees, grass pollen and evergreen trees) with respiratory mortality (all cause, chronic and infectious related) in Michigan, USA.
METHODS: We obtained records for all Michigan deaths from 2006-2017 from the Michigan Department of Health and Human Services (MDHHS). Deaths from infectious and chronic respiratory-related causes were selected using International Classification of Diseases (ICD-10) codes. Pollen data were obtained from a prognostic model of daily pollen concentrations at 25 km resolution. Case-crossover models with distributed lag non-linear crossbases for pollen were used to estimate associations between lags of daily pollen concentrations with mortality and to explore effect modification by sex and racial groups.
RESULTS: 127,163 deaths were included in the study. Cumulative daily high concentrations (90th percentile) of deciduous broadleaf, grass and ragweed were associated with all-cause respiratory mortality at early lags with e.g., a 1.81 times higher risk of all respiratory deaths at cumulative 7 day lag exposure to deciduous broadleaf pollen at the 90th percentile (95% confidence interval: 1.04, 3.15). Exposure to high concentrations of grass and ragweed pollens was associated with increased risk for death from chronic respiratory causes. No association was found for any pollen species with death from infectious respiratory causes though there was a positive but non-significant association of exposure to deciduous broadleaf and ragweed pollens. We found no evidence to suggest effect modification by race or sex.
CONCLUSIONS: Modelled exposures to high concentrations of pollen taxa were associated with increased all-cause and chronic respiratory mortality among older adults. Results suggest that pollen exposure may become more important to respiratory mortality as the temperatures increase and pollen seasons lengthen
Ultrafiltration for Management of Decompensated Heart Failure: A Reappraisal of AVOID-HF.
No full textCarcinoid Heart Disease: A Rare Complication of Metastatic Neuroendocrine Tumor
No full textCarcinoid heart disease (CHD), also known as Hedinger syndrome, is a rare but significant cardiac complication associated with metastatic neuroendocrine tumors (NETs). These tumors secret bioactive substances such as serotonin, leading to fibrotic changes primarily affecting the right-sided heart valves. A case study involving a 69-year-old male presented with a four-month history of diarrhea and a new systolic heart murmur. Transthoracic echocardiogram (TTE) results indicated a left ventricular ejection fraction (LVEF) of 60% to 65%, with severe tricuspid regurgitation and pulmonary valve stenosis. Elevated levels of 5-hydroxyindoleacetic acid (5-HIAA) were detected in a 24-hour urine test, and imaging revealed multiple hypoechoic masses in the liver and mesenteric masses adherent to the small intestine. Furthermore, a biopsy confirmed the diagnosis of a NET. Medical therapy like long-acting somatostatin injection and a peptide receptor radionuclide therapy was ineffective in reversing established valvular pathology, and the patient continued to experience clinical decline, suffering from right-sided heart failure. The patient was able to undergo combined tricuspid and pulmonary valve replacement, which resolved his symptoms. This case exemplifies the successful treatment of a rare syndrome leading to right heart failure
The difference-making role of staff support in implementing nurse care management for opioid use disorder treatment: A configurational analysis
No full textINTRODUCTION: Understanding conditions in which interventions succeed or fail is critical. The PRimary care Opioid Use Disorders treatment (PROUD) trial, a cluster-randomized hybrid study, tested whether implementation of office-based addiction treatment supported by a nurse increased medication of OUD. Six health systems each provided two primary care (PC) clinics that were randomly assigned to implement the intervention or usual care. This secondary, exploratory study used an innovative mixed methods approach to understand contextual factors that consistently distinguished intervention clinics that increased OUD treatment from those that did not.
METHODS: The study collected contextual information through field notes, health system debriefs, and nurse interviews. Rapid qualitative analysis using a template based on the Practical, Robust Implementation and Sustainability Model identified themes reflecting the external environment, recipients, and implementation infrastructure. The study used qualitative themes to create binary factors reflecting barriers and facilitators potentially critical to implementation success and assigned clinics a factor value of 1 if present and 0 if absent. Two clinic-level outcomes were defined: 1) significant increase in patient-years of OUD treatment from baseline to two-year follow-up; and 2) high rate of OUD treatment at two-year follow-up (≥20 per 10,000 patient-years). Coincidence analysis, a cross-case configurational method, identified difference-makers for both OUD outcomes across intervention clinics.
RESULTS: Qualitative analysis yielded 11 themes which were dichotomized and consolidated into 9 factors. Two factor values perfectly distinguished between intervention clinics with and without increased OUD treatment (outcome #1): (a) presence of strong support from PC staff and providers and (b) lack of OUD treatment in the community. Intervention clinics increased OUD treatment when either factor value was present; when both were absent, clinics did not increase treatment. Strong support from PC staff and providers was independently sufficient to achieve high rates of OUD treatment (outcome #2) while the absence of support explained low rates of treatment. Importantly, strong support from leadership was not sufficient for either outcome.
CONCLUSION: Strong support from staff and providers consistently differentiated between clinics with increased OUD treatment across both outcomes in the PROUD trial from those without. OUD programs should consider increasing support across clinic roles