Orismilast, a PDE4B/D inhibitor, in moderate-to-severe atopic dermatitis: Efficacy and safety from a multicenter, randomized, placebo-controlled, phase 2b dose-ranging study (ADESOS).

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease, characterized by eczematous skin lesions and pruritus. There is an unmet need for effective first-line systemic therapies with good safety profiles, particularly oral medications. Orismilast is a novel first-in-class oral phosphodiesterase-4 (PDE4) B/D inhibitor under investigation for the treatment of moderate-to-severe AD.

Comparative- and Cost-Effectiveness Research Determining the Optimal Intervention for Advancing Transgender Women With HIV to Full Viral Suppression (Text Me, Alexis!): Protocol for a Randomized Controlled Trial.

Background: Many transgender women with HIV achieve suboptimal advancement through the HIV Care Continuum, including poor HIV health care usage, retention in HIV medical care, and rates of viral suppression. These issues are exacerbated by comorbid conditions, such as substance use disorder, which is also associated with reduced quality of life, increased overdose deaths, usage of high-cost health care services, engagement in a street economy, and cycles of incarceration. Thus, it is critical that efforts to End the HIV Epidemic include effective interventions to link and retain transgender women in HIV care through full viral suppression.

Corneal Stromal Stem Cell-Derived Extracellular Vesicles Attenuate ANGPTL7 Expression in the Human Trabecular Meshwork.

Purpose: Regulating intraocular pressure (IOP), mainly via the trabecular meshwork (TM), is critical in developing glaucoma. Whereas current treatments aim to lower IOP, directly targeting the dysfunctional TM tissue for therapeutic intervention has proven challenging. In our study, we utilized Dexamethasone (Dex)-treated TM cells as a model to investigate how extracellular vesicles (EVs) from immortalized corneal stromal stem cells (imCSSCs) could influence ANGPTL7 and MYOC genes expression within TM cells.

Weathering the Pain: Ambient Temperature's Role in Chronic Pain Syndromes.

Purpose Of Review: Chronic pain is highly prevalent and involves a complex interaction of sensory, emotional, and cognitive processes, significantly influenced by ambient temperature. Despite advances in pain management, many patients continue to experience inadequate pain relief. This review aims to consolidate and critically evaluate the current evidence on the impact of ambient temperature on chronic pain conditions such as fibromyalgia (FM), multiple sclerosis (MS), complex regional pain syndrome (CRPS), and osteoarthritis (OA).

A Review of Leveraging Artificial Intelligence to Predict Persistent Postoperative Opioid Use and Opioid Use Disorder and its Ethical Considerations.

Purpose Of Review: Artificial intelligence (AI) offers a new frontier for aiding in the management of both acute and chronic pain, which may potentially transform opioid prescribing practices and addiction prevention strategies. In this review paper, not only do we discuss some of the current literature around predicting various opioid-related outcomes, but we also briefly point out the next steps to improve trustworthiness of these AI models prior to real-time use in clinical workflow.

Recent Findings: Machine learning-based predictive models for identifying risk for persistent postoperative opioid use have been reported for spine surgery, knee arthroplasty, hip arthroplasty, arthroscopic joint surgery, outpatient surgery, and mixed surgical populations.

Prescriptions (Rx) for Prevention: Clinical Tools for Integrating Environmental Health into Pediatric Clinical Care.

The integration of environmental health (EH) into routine clinical care for children is in its early stages. The vision of pediatric EH is that all clinicians caring for children are aware of and able to help connect families to needed resources to reduce harmful environmental exposures and increase health-enhancing ones. Environmental exposures include air pollution, substandard housing, lead, mercury, pesticides, consumer products chemicals, drinking water contaminants, industrial facility emissions and, increasingly, climate change-related extreme weather and heat events.

Outcomes of chronic limb-threatening ischemia revascularization in patients with chronic kidney disease in the BEST-CLI trial.

Background: Chronic limb-threatening ischemia (CLTI) in patients with chronic kidney disease (CKD) has a high risk of poor outcomes. We aimed to compare the outcomes of lower extremity revascularization in patients with CLTI stratified by CKD severity in patients enrolled in the prospective, randomized Best Endovascular vs Best Surgical Therapy in Patients with CLTI (BEST-CLI) trial.

Methods: The BEST-CLI trial dataset was queried to categorize patients into three groups according to CKD stage.

Intrapericardial Corticosteroids and Colchicine Prevent Pericarditis and Atrial Fibrillation After Epicardial Ablation of Ventricular Arrhythmias.

Background: Postprocedural pericarditis (PP) can occur in up to 29.4% of patients undergoing epicardial catheter ablation of ventricular tachycardia (VT). Despite several proposed strategies to mitigate this adverse outcome, rates of PP and pericarditic pain remain high.

First-in-Human Phase 1 study of a CD16A bispecific innate cell engager, AFM24, targeting EGFR-expressing solid tumors.

Purpose: Innate immune cell-based therapies have shown promising antitumor activity against solid and hematologic malignancies. AFM24, a bispecific innate cell engager, binds CD16A on natural killer (NK) cells/macrophages and EGFR on tumor cells, redirecting antitumor activity towards tumors. The safety and tolerability of AFM24 was evaluated in this Phase 1/2a dose escalation/dose expansion study in patients with recurrent or persistent, advanced solid tumors known to express EGFR.

Multiple Model Optimal Sampling Promotes Accurate Vancomycin Area-Under-the-Curve Estimation Using a Single Sample in Critically Ill Children.

Background: Area-under-the-curve (AUC)-directed vancomycin therapy is recommended; however, AUC estimation in critically ill children is difficult owing to the need for multiple samples and lack of informative models.

Methods: The authors prospectively enrolled critically ill children receiving intravenous (IV) vancomycin for suspected infection and evaluated the accuracy of Bayesian estimation of AUC from a single, optimally timed sample. During the dosing interval, when clinical therapeutic drug monitoring was performed, an optimally timed sample was collected, which was determined for each subject using an established population pharmacokinetic model and the multiple model optimal function of Pmetrics, a nonparametric population pharmacokinetic modeling software.

Multidimensional, integrative profiling identifies BCL2L1 methylation as a predictor of MCL1 dependency in pediatric malignancies.

Pediatric high-grade gliomas (pHGGs) are the most aggressive brain tumors in children, necessitating innovative therapies to improve outcomes. Unlike adult gliomas, recent research reveals that childhood gliomas have distinct biological features, requiring specific treatment strategies. Here, we focused on deciphering unique genetic dependencies specific to childhood gliomas.

Pegloticase and Methotrexate Cotherapy in Patients With Uncontrolled Gout With Prior Pegloticase Monotherapy Failure: Findings of an Open-Label Trial.

Objective: Patients with uncontrolled gout have few treatment options. Pegloticase lowers serum urate (SU) levels, but antidrug antibodies limit SU-lowering response and increase infusion reaction (IR) risk. Methotrexate (MTX) cotherapy increases pegloticase response rates and lowers IR risk in pegloticase-naïve patients.

Can an Acceptance and Commitment Therapy-Based Smartphone App Help Individuals with Mental Health Disorders Quit Smoking?

Background: Individuals with mental health disorders face major barriers in accessing smoking cessation care, often due to the stigmas associated with mental disorders and addiction. Consequently, accessible population-based smoking cessation interventions are needed for this vulnerable group.

Objective: This secondary analysis utilized data from a 12-month randomized trial to examine whether an acceptance and commitment therapy-based app (iCanQuit) demonstrated greater efficacy, engagement, and satisfaction compared to a United States (US) Clinical Practice Guidelines-based app (QuitGuide) in helping adults with mental health disorders quit smoking.

Nutraceutical and low energy shockwave treatments improved sexual function recovery in a rat pelvic neurovascular injury model.

Background: Pelvic trauma can have long-lasting debilitating effects, including severe erectile dysfunction (ED) in men. While there are effective treatments for ED, these treat the symptoms not the cause. Those who suffer from an acute traumatic injury to the neurovascular supply of penis, may benefit from regenerative therapy.

The prevalence and burden of musculoskeletal disorders amongst Indigenous people in Pimicikamak, northern Manitoba, Canada: A community health survey.

Objectives: To investigate the prevalence of spine symptoms and spine disability, self-care and care seeking behaviors in a random sample of Indigenous adults residing in Cross Lake, northern Manitoba, Canada.

Study Design And Setting: Orally administered survey in Cree or English to a representative sample of Pimicikamak citizens from the treaty ( = 150/1931 houses) and non-treaty ( = 20/92 houses) land, between May and July 2023. Questions ( = 154) were derived from the 2018 First Nations Regional Health Survey, 2020 Canadian Community Health Survey, and 2021 The Global Burden of Disease study, covering demographics, spine symptoms, chronic conditions, activity limitations, general health, self-care, medication, and satisfaction with care.

Non-contact electroacoustic tomography with optical interferometer for electroporation therapy monitoring.

Electroacoustic imaging is an imaging modality used to detect electric field energy distribution during electroporation, offering valuable guidance for clinical procedures, particularly in deep tissues. Traditionally, single-element piezoelectric transducers or arrays have been employed for this purpose. However, these piezoelectric sensors are sensitive to electromagnetic interference and require physical contact with the sample through a coupling medium, raising concerns for both clinical and preclinical applications.

Effect of long and short half-life PDE5 inhibitors on HbA1c levels: a systematic review and meta-analysis.

Background: Phosphodiesterase 5 (PDE5) inhibitors, owing to their mechanism of action, have been gaining recognition as a potential case of drug repurposing and combination therapy for diabetes treatment. We aimed to examine the effect of long and short half-life PDE5 inhibitors have on Haemoglobin A1c (HbA1c) levels.

Methods: A systematic review and meta-analysis was conducted of randomised controlled trials (RCTs) in people with elevated HbA1c (>6%) to assess mean difference in HbA1c levels from baseline versus controls after any PDE5 inhibitor intervention of ≥4 weeks, excluding multiple interventions.

Travel Burden of Radiation Therapy in the Philippines.

Purpose: Travel burden negatively impacts the stage at diagnosis, treatment, outcome, and quality of life among patients with cancer. Travel burden-quantified as distance, time, and cost of travel-is magnified in low- and middle-income countries like the Philippines, where radiation therapy (RT) resources are lacking and are inequitably distributed.

Methods And Materials: We compared Philippine Radiation Oncology Society data and the population census to determine the distribution and density of RT facilities across the country's 17 regions.

Access to CARe: A Narrative of Real-World Medical Decision-Making to Access Chimeric Antigen Receptor (CAR) T-Cell Therapy in Children, Adolescents, and Young Adults.

Chimeric antigen receptor (CAR) T-cell therapy is a potentially life-saving treatment for children with relapsed/refractory B-cell hematologic malignancies, and remains an important investigational therapy for other childhood cancers. Yet, access to this class of therapies remains suboptimal through both commercial use and clinical trials, especially in children, adolescents, and young adults. Using a series of case-based discussions, we outline guidance on real-world medical decision-making, and offer potential solutions to enhancing access to CAR T-cell therapy as a treatment modality.

A single-site randomized controlled trial of partner navigation to HCV treatment for people who inject drugs: a study protocol for the You're Empowered for Treatment Initiation (YETI) partner trial.

Background: Disparities persist in testing and treatment for hepatitis C virus (HCV), leaving socially marginalized populations, including people who inject drugs (PWID), less likely to benefit from curative treatment. Linkage services are often insufficient to overcome barriers to navigating the medical system and contextual factors.

Methods: The You're Empowered for Treatment Initiation (YETI) Partner trial is a single-site randomized controlled trial evaluating the efficacy of a two-session behavioral intervention that engages injecting partners as peer navigators for HCV treatment.

Within-session propulsion asymmetry changes have a limited effect on gait asymmetry post-stroke.

Background: Biomechanical gait impairments, such as reduced paretic propulsion, are common post-stroke. Studies have used biofeedback to increase paretic propulsion and reduce propulsion asymmetry, but it is unclear if these changes impact overall gait asymmetry. There is an implicit assumption that reducing propulsion asymmetry will improve overall gait symmetry, as paretic propulsion has been related to numerous biomechanical impairments.

Assessing public support for air pollution mitigation and control policies: health, socioeconomic, and ideological predictors in an overburdened and vulnerable region of the U.S.

Background: The San Joaquin Valley (SJV) in California is one of the most polluted regions in the U.S. This study examined favorability for air pollution mitigation policies, interventions, and identified predictors amongst region's residents.

Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

Evaluation of disparities in hospitalisation outcomes for deaf and hard of hearing patients with COVID-19: a multistate analysis of statewide inpatient databases from Florida, Maryland, New York and Washington.

Objective: Investigate whether deaf or hard of hearing (D/HH) patients with COVID-19 exhibited different hospitalisation outcomes compared with hearing patients with COVID-19.

Design: Cohort study SETTING: Statewide Inpatient Databases for Florida, Maryland, New York and Washington, for the year 2020.

Participants: Records of patients aged 18-64 years with COVID-19 PRIMARY OUTCOMES AND MEASURES: Differences in in-hospital death, 90-day readmission, length of stay, hospitalisation cost, hospitalisation cost per day, intensive care unit (ICU) or coronary care unit (CCU) utilisation and ventilation use were evaluated.