Effect of an Intrapartum Pelvic Dilator Device on Levator Ani Muscle Avulsion During Primiparous Vaginal Delivery: A Pilot Randomized Controlled Trial.

INTRODUCTION AND HYPOTHESIS: The objective was to evaluate the safety and effectiveness of an intrapartum electromechanical pelvic floor dilator designed to reduce the risk of levator ani muscle (LAM) avulsion during vaginal delivery. METHODS: A multicenter, randomized controlled trial enrolled nulliparous participants planning vaginal delivery. During the first stage of labor, participants were randomized to receive the intravaginal device or standard-of-care labor management. The primary effectiveness endpoint was the presence of full LAM avulsion on transperineal pelvic-floor ultrasound at 3 months. Three urogynecologists performed blinded interpretation of ultrasound images. The primary safety endpoint was adverse events (AEs) through 3 months. RESULTS: A total of 214 women were randomized to Device (n = 113) or Control (n = 101) arms. Of 113 Device assignees, 82 had a device placed, of whom 68 delivered vaginally. Of 101 Control participants, 85 delivered vaginally. At 3 months, 110 participants, 46 Device subjects who received full device treatment, and 64 Controls underwent ultrasound for the per-protocol analysis. No full LAM avulsions (0.0%) occurred in the Device group versus 7 out of 64 (10.9%) in the Control group (p = 0.040; two-tailed Fisher's test). A single maternal serious AE (laceration) was device related; no neonate serious AEs were device related. CONCLUSIONS: The pelvic floor dilator device significantly reduced the incidence of complete LAM avulsion in nulliparous individuals undergoing first vaginal childbirth. The dilator demonstrated an acceptable safety profile and was well received by recipients. Use of the intrapartum electromechanical pelvic floor dilator in laboring nulliparous individuals may reduce the rate of LAM avulsion, an injury associated with serious sequelae including pelvic organ prolapse.

Supplemental Nutrition Assistance Program participation gaps within a pediatric leukemia clinical trial cohort.

Poverty-exposed children with cancer are more likely to experience adverse outcomes. Supplemental Nutrition Assistance Program (SNAP) benefits improve food insecurity and child health outcomes, and could be used to mitigate disparities. We conducted a secondary analysis of parent-reported data collected in a frontline pediatric leukemia trial (NCT03020030) to assess SNAP eligibility (proxied by other means-tested program participation) and participation. At diagnosis, 105/287 families (37%) were SNAP-eligible, of whom 53 (50%) were SNAP participants. At 6 months, 104/257 families (41%) were SNAP-eligible, and 59 (57%) were SNAP participants. Interventions to increase benefits participation during childhood cancer treatment represent an immediate opportunity to reduce disparities.

Integrative multi-omic profiling of triple-negative breast cancer for identifying suitable therapies.

PURPOSE: Triple-negative breast cancer (TNBC) is a heterogenous disease that carries the poorest prognosis of all breast cancers. Although novel TNBC therapies in development are frequently targeted towards tumors carrying a specific genomic, transcriptomic, or protein biomarker, how these biomarkers are correlated is poorly understood. EXPERIMENTAL DESIGN: To better understand the molecular features of TNBC and their correlation with one another, we performed multi-modal profiling on a cohort of 95 TNBCs. Our approach involved quantifying tumor-infiltrating lymphocytes through H&E staining, assessing the abundance of retinoblastoma (Rb), androgen receptor (AR), and PD-L1 proteins through immunohistochemistry, and carrying out transcriptomic profiling using the Nanostring BC360 platform, targeted DNA sequencing on a subset of cases, as well as evaluating associations with overall survival. RESULTS: Levels of RB1 mRNA and RB protein are better correlated with markers of Rb functionality than is RB1 mutational status. Luminal AR tumors clustered into two groups with transcriptomes that cluster with either basal or mesenchymal tumors. Tumors classified as PD-L1-positive by presence of immune or tumor cells showed similar biological characteristics. HER2-low TNBC showed no distinct biological phenotype when compared to HER2-zero. The majority of TNBCs classified as basal or HER2-enriched by PAM50, the latter showing significantly improved overall survival. CONCLUSIONS: Our study contributes new insights into biomarker utility for identifying suitable TNBC therapies and the intercorrelations between genomic, transcriptomic, protein, and cellular biomarkers. Additionally, our rich data resource can be used by other researchers to explore the interplay between DNA, RNA, and protein biomarkers in TNBC.

Prospective Analysis of urINe LAM to Eliminate NTM Sputum Screening (PAINLESS) study: Rationale and trial design for testing urine lipoarabinomannan as a marker of NTM lung infection in cystic fibrosis.

Background: Routine screening for nontuberculous mycobacterial (NTM) lung disease is dependent on sputum cultures. This is particularly challenging in the cystic fibrosis (CF) population due to reduced sputum production and low culture sensitivity. Biomarkers of infection that do not rely on sputum may lead to earlier diagnosis, but validation trials require a unique prospective design. Purpose: The rationale of this trial is to investigate the utility of urine lipoarabinomannan (LAM) as a test to identify people with CF with a new positive NTM culture. We hypothesize that urine LAM is a sensitive, non-invasive screening test with a high negative predictive value to identify individuals with a relatively low risk of having positive NTM sputum culture. Study design: This is a prospective, single-center, non-randomized observational study in adults with CF, 3 years of negative NTM cultures, and no known history of NTM positive cultures. Patients are followed for two year-long observational periods with the primary endpoint being a positive NTM sputum culture within a year of a positive urine LAM result and a secondary endpoint of a positive NTM sputum culture within 3 years of a positive urine LAM result. Study implementation includes remote consent and sample collection to accommodate changes from the COVID-19 pandemic. Conclusions: This report describes the study design of an observational study aimed at using a urine biomarker to assist in the diagnosis of NTM lung infection in pwCF. If successful, urine LAM could be used as an adjunct to traditional sputum cultures for routine NTM screening.

Identification and multimodal characterization of a specialized epithelial cell type associated with Crohn's disease.

Crohn's disease (CD) is a complex chronic inflammatory disorder with both gastrointestinal and extra-intestinal manifestations associated immune dysregulation. Analyzing 202,359 cells from 170 specimens across 83 patients, we identify a distinct epithelial cell type in both terminal ileum and ascending colon (hereon as 'LND') with high expression of LCN2, NOS2, and DUOX2 and genes related to antimicrobial response and immunoregulation. LND cells, confirmed by in-situ RNA and protein imaging, are rare in non-IBD controls but expand in active CD, and actively interact with immune cells and specifically express IBD/CD susceptibility genes, suggesting a possible function in CD immunopathogenesis. Furthermore, we discover early and late LND subpopulations with different origins and developmental potential. A higher ratio of late-to-early LND cells correlates with better response to anti-TNF treatment. Our findings thus suggest a potential pathogenic role for LND cells in both Crohn's ileitis and colitis.

The Impact of COVID-19 on Substance Use and Related Consequences among Patients in Office-Based Opioid Use Disorder Treatment.

OBJECTIVES: The COVID-19 pandemic led to increased substance-related morbidity and mortality and transformed care for opioid use disorder (OUD). We assessed the perceived impacts of the pandemic on substance use and related consequences among patients in office-based addiction treatment (OBAT). METHODS: We recruited patients with OUD on buprenorphine from July 2021 to July 2022, with data collection at baseline and 6 months. Exposures of interest were the following 6 domains potentially impacted by COVID-19: personal or family infection, difficulty accessing healthcare/medication, economic stressors, worsening physical or mental health, social isolation, and conflicts/disruptions in the home. Outcomes were past 30-day alcohol and other substance use, increased use, and substance-related consequences at baseline and 6 months. Generalized estimating equations Poisson regression models quantified associations between increasing impact domain scores and relative risks of each outcome. RESULTS: All participants (N = 150) reported at least one domain negatively impacted by COVID-19 at both time points. Higher "worsening physical or mental health" domain scores were associated with increased relative risk of recent alcohol or drug use (adjusted risk ratio [aRR] 1.04, 95% confidence interval [CI]: 1.01-1.07). Relative risks of experiencing substance-related consequences increased with higher scores in the domains of economic stressors (aRR 1.07, 95% CI: 1.02-1.13), difficulty accessing healthcare/medication (aRR 1.11, 95% CI: 1.04-1.19), and worsening physical or mental health (aRR 1.08, 95% CI: 1.04-1.12). CONCLUSIONS: Among patients with OUD, stressors from COVID-19 were common. Three life domains impacted by COVID-19 appeared to be associated with consequential substance use, highlighting opportunities to address barriers to healthcare access and economic stressors.

Genome-wide study identifies novel genes associated with bone toxicities in children with acute lymphoblastic leukaemia.

Bone toxicities are common among paediatric patients treated for acute lymphoblastic leukaemia (ALL) with potentially major negative impact on patients' quality of life. To identify the underlying genetic contributors, we conducted a genome-wide association study (GWAS) and a transcriptome-wide association study (TWAS) in 260 patients of European-descent from the DFCI 05-001 ALL trial, with validation in 101 patients of European-descent from the DFCI 11-001 ALL trial. We identified a significant association between rs844882 on chromosome 20 and bone toxicities in the DFCI 05-001 trial (p = 1.7 × 10-8). In DFCI 11-001 trial, we observed a consistent trend of this variant with fracture. The variant was an eQTL for two nearby genes, CD93 and THBD. In TWAS, genetically predicted ACAD9 expression was associated with an increased risk of bone toxicities, which was confirmed by meta-analysis of the two cohorts (meta-p = 2.4 × 10-6). In addition, a polygenic risk score of heel quantitative ultrasound speed of sound was associated with fracture risk in both cohorts (meta-p = 2.3 × 10-3). Our findings highlight the genetic influence on treatment-related bone toxicities in this patient population. The genes we identified in our study provide new biological insights into the development of bone adverse events related to ALL treatment.

Gauging Public Interest in Pediatric Ophthalmology Conditions Using Google Trends.

Google Trends data were analyzed to assess search trends for pediatric ophthalmology and strabismus terms from 2010 to 2022. The highest average search volumes were "lazy eye," "strabismus," and "vision therapy." "Amblyopia" had the lowest search volume. These data highlight the importance of understanding the utilization of online resources in health care and patient education. [J Pediatr Ophthalmol Strabismus. 2024;61(4):e39-e42.].

Hodgkin Lymphoma Involving the Extra-Axial CNS: An AHOD1331, PHL-C1 and PHL-C2 Report From the COG and EuroNet-PHL.

Hodgkin lymphoma (HL) involving the central nervous system (CNS) is exceedingly rare. Information regarding the presentation, management, treatment and outcome of patients with CNS HL is limited to case reports or small series. We describe 45 pediatric patients with 55 extra-axial CNS lesions at diagnosis with HL from a cohort of 4995 patients enrolled on Children's Oncology Group AHOD1331 and the European Network for Pediatric Hodgkin lymphoma (EuroNet-PHL) C1 and C2 trials (NCT02166463, NCT00433459 and NCT02684708, clinicaltrials.gov), with an overall incidence of 0.9%. 82.2% of patients had a single CNS lesion in the thoracic, lumbar or sacral spine. In the evaluated cohort, HL did not occur within the CNS parenchyma. Lesions extended into the extra-axial CNS space from adjacent soft tissue or bone and never directly infiltrated through the dura into the brain or spinal cord. Patients with CNS involvement had a 2-fold greater incidence of extranodal lesions (E-lesions) than previously reported cohorts without CNS involvement. 89.1% of CNS lesions demonstrated a complete metabolic response and >75% decrease in volume after two cycles of chemotherapy. Thirteen CNS lesions (23.6%) received irradiation, none were sites of disease relapse. Relapse occurred at the site of two lesions involving the CNS, both of which had an adequate interim response to chemotherapy. In summary, we present the largest reported cohort of systemic HL involving the CNS at diagnosis, demonstrating that these lesions originate from surrounding tissues, extend into the extra-axial CNS space, and respond similarly to other nodal and extranodal disease.

Longitudinal Health-Related Quality of Life Among Patients With High-Risk Pediatric Hodgkin Lymphoma Treated on the Children's Oncology Group AHOD 1331 Study.

PURPOSE: There have been no previous longitudinal assessments of health-related quality of life (HRQoL) during treatment for pediatric Hodgkin lymphoma (HL). The addition of brentuximab vedotin (BV) to a multidrug chemotherapy backbone demonstrated superior efficacy to standard chemotherapy for patients with pediatric high-risk HL in the AHOD 1331 trial. However, the impact on HRQoL is unknown. PATIENTS AND METHODS: After treatment random assignment, 268 participants older than 11 years were enrolled in a prespecified, longitudinal, patient-reported outcomes substudy. HRQoL was assessed using the seven-item Child Health Ratings Inventories (CHRIs)-Global scale before treatment (T1) and at cycle 2 (T2), cycle 5 (T3), and end of treatment (T4). A clinically meaningful increase in HRQoL was considered 7 points on the CHRIs-Global. Multivariable linear regression estimated associations between demographic/clinical variables and HRQoL at T1. Linear mixed models estimated changes in HRQoL across the treatment arm. RESULTS: Participant characteristics were balanced by treatment arm. Ninety-three percent of participants completed the CHRIs at T1, 92% at T2, 89% at T3, and 77% at T4. At T1, female sex and fever (P < .05) were each associated with worse HRQoL. By T2, participants in the BV arm experienced a statistically and clinically significant improvement in HRQoL (ß = 7.3 [95% CI, 3.2 to 11.4]; P ≤ .001), which was greater than the change in the standard arm (difference in change ß = 5.1 [95% CI, -0.2 to 10.3]; P = .057). The standard arm did not experience a statistically or clinically significant increase in HRQoL until T4 (ß = 9.3 [95% CI, 4.7 to 11.5]; P < .001). CONCLUSION: These data demonstrate successful collection of serial HRQoL from youth with high-risk pediatric HL and improvement in HRQoL over the course of initial therapy, sooner and to a greater extent in the group receiving the novel agent BV.

Sociodemographic Factors Associated with Emergent Eye-Related Emergency Department Visits: A Multicenter Analysis.

OBJECTIVE: To compare sociodemographic factors in patients presenting to the emergency department (ED) with emergent and non-emergent eye-related concerns. DESIGN: Cross-sectional multicenter study. SUBJECTS: 60,677 patients with eye-related concerns who visited EDs at Bascom Palmer Eye Institute, Wills Eye Hospital, Massachusetts Eye and Ear, and Johns Hopkins Hospital/Wilmer Eye Institute from January 1st, 2019 until December 31st, 2019. METHODS: Descriptive statistics were performed using STATA 17. MAIN OUTCOME MEASURES: 1) Sociodemographic factors associated with emergent diagnoses, 2) Visit patterns across ED settings (i.e. standard ED vs eye ED), and 3) the most common emergent and non-emergent diagnoses. RESULTS: A total of 60,677 eye-related ED encounters were included in the study, including 22,434 at Bascom Palmer Eye Institute, 16,124 at Wills Eye Hospital, 15,487 at Massachusetts Eye and Ear, and 6,632 at Johns Hopkins Hospital/Wilmer Eye Institute. Most patients had non-emergent diagnoses (56.7%). Males (OR 1.85, 95% CI 1.79-1.92) were more likely to have an emergent diagnosis than females. Patients with private/employer-based insurance (OR 0.88, 95% CI 0.81-0.96), Medicare (OR 0.80, 95% CI 0.72-0.87), and Medicaid (OR 0.81, 95% CI 0.74-0.89) were all less likely to have an emergent diagnosis than uninsured patients. Those with veteran/military insurance (OR 1.08, 95% CI 0.87-1.34) were equally likely to have an emergent diagnosis compared to uninsured patients. Non-White Hispanic patients (OR 1.26, 95% CI 1.12-1.42) were more likely to present with an emergent condition than White patients. Patient seen in the standard ED setting were more likely to have emergent diagnoses than those who visited standalone eye EDs (P < 0.001). The most common emergent diagnoses were corneal abrasion (12.97%), extraocular foreign body (7.61%), and corneal ulcer (7.06%). The most common non-emergent diagnoses were dry eye (7.90%), posterior vitreous detachment (7.76%), and chalazion (6.57%). CONCLUSIONS: ED setting was associated with the acuity of patient diagnoses. Lack of insurance coverage and non-White Hispanic race/ethnicity were associated with emergent eye-related ED visits. Improving access to ophthalmic care in these populations may reduce the incidence of preventable eye emergencies related to untreated chronic conditions. This combined with measures to redirect non-emergent issues to outpatient clinics may alleviate ED overload.

Inequities in Alcohol Screening of Primary Care Patients with Chronic Conditions.

INTRODUCTION: Routine alcohol screening of people with chronic health conditions that are exacerbated by alcohol can help to prevent morbidity and mortality. The U.S. Affordable Care Act and other recent health reforms expanded insurance coverage and supported alcohol screening in primary care. This study assessed increases in alcohol screening following health reform and insurance-related and racial and ethnic disparities in screening. METHODS: Data are from the 2013 to 2019 National Surveys on Drug Use and Health for adults with alcohol-related chronic conditions who received primary care in the past year (N=46,014). The outcome was receipt of alcohol screening (yes/no) in which a healthcare provider inquired whether, how often, or how much the respondent drank, or about having alcohol-related problems. Multivariable logistic regression models assessed temporal changes in screening overall and by insurance type and race/ethnicity, adjusting for demographics, health conditions, and primary care utilization. Statistical analysis was performed in 2023. RESULTS: Alcohol screening prevalence rose from 69% to 77% from 2013 through 2019, with a notable increase in 2014-2015 for both Medicaid-insured and privately-insured patients. Black and Asian American patients were generally less likely to be screened than White patients. Importantly, racial disparities in screening were found among privately-insured patients, patients with hypertension, patients with heart disease, and patients with diabetes who drink alcohol. CONCLUSIONS: Alcohol screening of primary care patients with chronic conditions increased following health reform, but persistent disparities among patients with private insurance and specific chronic conditions underscore the need to address drivers of unequal preventive care.

Design and rationale for a randomized clinical trial testing the efficacy of a lifestyle physical activity intervention for people with HIV and engaged in unhealthy drinking.

BACKGROUND: Among people living with HIV (PLWH), unhealthy drinking presents an increased risk for negative outcomes. Physical inactivity and sedentariness raise additional health risks. Despite evidence that physical activity (PA) is associated with improved physical and mental functioning and reduced alcohol cravings, there have been no PA studies conducted with PLWH engaged in unhealthy drinking. We describe a study protocol of a remote lifestyle physical activity (LPA) intervention to increase PA and reduce alcohol consumption among PLWH. METHODS: Using online advertisements, 220 low-active PLWH engaged in unhealthy drinking will be recruited and randomized nationwide. After providing informed consent and completing a baseline interview, participants will receive a Fitbit. Participants will complete 15 days of ecologic momentary assessment through a phone application and up to 15 days of Fitbit wear time. Following this period, participants will be randomly assigned to a Fitbit-only control condition or a LPA and Fitbit intervention condition. Health counselors meet with control participants once (and have 6 subsequent brief check ins on Fibit use) and with intervention participants 7 times for PA counseling over a 12-week period. Follow-up assessments will be conducted at 3- and 6-months post-randomization. We hypothesize that individuals in the LPA and Fitbit condition will have lower rates of alcohol consumption and higher rates of PA at 6-month follow-up. CONCLUSION: The randomized controlled trial described in this paper investigates remote methods to influence multimorbidity among PLWH using a LPA approach for increasing PA and reducing alcohol consumption.

Characteristics and Surgical Outcomes of Comitant Esotropia in an Adult Population Between 18 and 60 Years Old.

PURPOSE: To describe the clinical characteristics and surgical outcomes of adults with comitant nonaccommodative esotropia. DESIGN: Retrospective case series. METHODS: Retrospective review of medical records of patients 18 to 60 years old with comitant esotropia who underwent strabismus surgery at a tertiary eye care center between 2014 and 2023. The etiology of esotropia was categorized into three groups based on the disparity between near-distance angles of deviation: (1) basic esotropia (ETBA); (2) esotropia divergence insufficiency pattern; or (3) esotropia convergence excess pattern. The main outcome measures were strabismus characteristics and motor and sensory surgical outcomes. Surgical motor success was defined as a deviation that measured ≤10 prism diopters (PD). RESULTS: Of the 219 that met the inclusion criteria, most patients were female (140, 64%) and had a mean age of 36.7 ± 12.3 years (range 18-60 years). The majority were myopic (157, 72%) and reported diplopia (176/219, 80.3%). The esotropia convergence excess pattern group had the largest mean deviations at both distance (45.5 ± 11.5 PD) and near (64 ± 12.3 PD) while the ETBA group had the largest ranges at distance (31 ± 13.5 PD, range 3-90) and near (30 ± 15 PD, range 2-85). Bilateral medial rectus recession and unilateral recess-resect procedures were performed with equal frequency (both 48%). Motor and sensory success were achieved more often with recess-resect than bilateral medial rectus recession, although only motor success was statistically significant (87.8% vs. 73.2%, P = .0375 and 93.3% vs. 85.5%, P = 15, respectively). At the last encounter, 88.1% (119/135) of patients with preoperative diplopia achieved single binocular vision. CONCLUSIONS: Regardless of the pattern of esotropia, strabismus surgery in adults with comitant nonaccommodative esotropia resulted in good motor and sensory outcomes.

Can Google Help Your Nearsightedness? A Google Trend Analysis of Public Interest in Myopic Progression.

Purpose: To explore public interest in myopia progression and management and to correlate these trends to available treatments. Methods: Keywords were chosen for interest in myopia overall and those signifying interest in myopia treatments. Treatment options were separated into four main categories: atropine, glasses, contact lenses, and orthokeratology. Search terms were queried across ten years of Google Trends data and the relative search volume was analyzed to quantify the change in search volume over time. Results: A positive linear trend over time was present for all myopia interest keywords except "nearsighted" (p = 0.074) and "near work myopia" (p = 0.086). Interest in the four myopia treatment categories included in this study also displayed a significant positive trend over time. There is also a statistically significant positive correlation between all four treatment options and four of the seven categories of population interest, "myopia control", "myopia", "myopia progression", and "screen time myopia". Conclusion: This study demonstrates the utility of GT to correlate public interest in myopia treatments over time. All treatment terms had statistically significant linear search volume growth over a ten-year period. The positive correlation between interest in myopia as a health problem and available treatments supports existing evidence that GT can track rising public health concerns and corresponding treatment-seeking behaviors.

[Latent Macrophage and Immature B Cell Lines Generated with Hygromycin-Resistant Murine Gammaherpesvirus 68 Genome Expresses Modest Levels of Viral miRNAs].

Murine gammaherpesvirus 68 (MHV68) establishes latency mainly in B cells and causes lymphomas reminiscent of human gammaherpesvirus diseases in laboratory mice. To study the molecular mechanism of virus infection and how the viral determinants control cell and eventually cause tumorigenesis, readily available latently infected cell lines are essential. For in vitro MHV68 latency studies, only two cell culture systems have been available. Gammaherpesviruses are known to infect developing B cells and macrophages, therefore we aimed to expand the MHV68 latently infected cell line repertoire. Here, several latently infected immature B cell and macrophage-like cell line clones were generated. Hygromycin-resistant recombinant MHV68 was isolated from a laboratory-made latent cell line, HE2.1, and propagated to develop stable cell lines that carry the viral genome under hygromycin selection. Subclones of these cells lines were analyzed for viral miRNA expression by TaqMan qPCR and assessed for expression of a lytic viral transcript M3. The cell lines maintain the viral genome as an episome shown by the digestion-circularization PCR assay. Latently infected cell lines generated here do not express viral miRNAs higher than the parental cell line. However, these cell lines may provide an alternative tool to study latency mechanisms and miRNA target identification studies.

The study of ableism in population health: a critical review.

Over the past three decades, health equity has become a guiding framework for documenting, explaining, and informing the promotion of population health. With these developments, scholars have widened public health's aperture, bringing systems of oppression sharply into focus. Additionally, some researchers in disability and health have advocated for utilizing socially grounded frameworks to investigate the health of disabled people. Yet, naming ableism, much less operationalizing it for the empirical study of health, remains scant. This paper critically reviews the study of ableism as a social determinant of disabled people's health within population health research. First, we provide an orientation to the present state of this literature by looking to the past. We briefly trace a history of traditional approaches to studying disability and health and alternatives that have emerged from critiques of the individualized lens that has dominated this work. Next, we delineate the operation of ableism across social levels. We characterize how ableism has been studied in population health in terms of levels of analysis (intrapersonal, interpersonal, institutional, and structural) and measures of interest. To conclude, we discuss hinderances to and promising avenues toward population health research that advances health equity for disabled people.

Exposure-Response and Subgroup Analyses to Support Body Weight-Based Dosing of Brentuximab Vedotin in Children and Young Adults with Newly Diagnosed High-risk Classical Hodgkin Lymphoma.

PURPOSE: The purpose of the study was to evaluate the relationships between brentuximab vedotin (BV) pharmacokinetics, age, and body weight (BW) with efficacy and safety in pediatric and young adult patients with previously untreated, high-risk classical Hodgkin lymphoma in the phase III AHOD1331 study. EXPERIMENTAL DESIGN: Overall, 296 patients (age 2-21 years) in the overall population were randomized to and received BV + chemotherapy; the pharmacokinetic subpopulation comprised 24 patients (age <13 years). Age- and/or BW-based (pharmacokinetic surrogates) subgroup analyses of efficacy and safety were conducted for the overall population. Exposure-response analyses were limited to the pharmacokinetic subpopulation. RESULTS: There were no visible trends in disease characteristics across pediatric age subgroups, whereas BW increased with age. Observed antibody-drug conjugate exposures in patients ages <12 years were lower than those in adults administered BV 1.8 mg/kg every 3 weeks, as exposure increased with BW. Nevertheless, no detrimental impact on event-free survival was seen in younger subgroups: 3-year event-free survival rates were 96.2% (2-<12 years) and 92.0% (12-<18 years), with no events observed in those ages <6 years. Neither early response nor lack of need for radiation therapy was associated with high pharmacokinetic exposure. No evidence of exposure-driven grade ≥2 or ≥3 peripheral neuropathy or grade ≥3 neutropenia was seen in exposure-safety and BW-based subgroup analyses; the incidence of these safety events was comparable across pediatric age subgroups, despite lower exposure in younger children. CONCLUSIONS: No further adjustments based on age or BW are required for the BV dosage (1.8 mg/kg every 3 weeks) approved in children.

[Waiting time to transcatheter aortic valve implantation (TAVI) and mortality during wait period in Algeria]. / Délais d'attente d'implantation de valve aortique transcutanée (TAVI) et mortalité durant la période d'attente en Algérie.

BACKGROUND: Trans Aortic Valve Implantation (TAVI) has become the primary treatment for aortic stenosis in patients over 75 years old. Despite its clinical efficacy, it's adoption in emerging countries remains low due to the high cost of prostheses and limited healthcare funding resources. This leads to prolonged waiting times for the TAVI procedure, which may lead to complications; these data are missing particularly in emerging countries. AIMS: To describe waiting time for TAVI and mortality rate in this waiting period. MATERIALS AND METHODS: This was prospective registry, patients referred for TAVI were prospectively followed; waiting time was calculated from the first visit after referral to TAVI implantation, clinical and, call fellow up was performed every 3 months. We divided patients into two groups: Group 1 (G1) patients still awaiting TAVI (105 patients), and those who underwent TAVI (36 patients). Group 2 (G2) patients who died while awaiting TAVI (16 patients, 10,2 %). RESULTS: Demographic characteristics were similar, with a tendency for older age in G2 (79.5 ± 5.7 years vs. 82.5 ± 7.4 years, p=0,06). G2 exhibited more left ventricular ejection fraction (LVEF) impairment (8.5% vs. 25%, p=0,03) and a higher rate of severe heart failure with dyspnea stages III or IV (2.8% vs. 12.5%, p<0,001). The mean follow-up in G1 was 242.9 ± 137.4 days; the waiting time for TAVI was 231.7 ± 134.1 days, and the average time between the first consultation and death while awaiting TAVI (G2) was 335.1 ± 167.4 days. CONCLUSION: in our series, waiting time is high due to limited Trans aortic heart valve availability, mortality during this wait exceeds 10%. Adverse prognostic factors include impaired LVEF and severe dyspnea stages III or IV.

A Qualitative Study Describing Experiences of Pregnancy Discrimination in the Workplace.

OBJECTIVES: Qualitatively assess experiences of occupational pregnancy discrimination. METHODS: A fully remote phenomenological qualitative study was completed leveraging semistructured interviews with a sample of pregnant employees in the United States. Inclusion criteria included being pregnant, working at least 35 hours per week, employed at least 1 year at current employer, and without diagnosed depression/anxiety. RESULTS: Participants (N = 20) were, on average, 30 years of age, worked 42.6 hours per week, self-identified as non-Hispanic black (50%), and earned least a bachelor's degree (85%). Individuals successfully identified various forms of pregnancy discrimination, believing it occurred due to systemic issues or perceptions that women are weak. Most did not report experiences of discrimination fearing retaliation or being unaware of workplace protections. CONCLUSION: Pregnancy discrimination in the workplaces comes in various forms and is an issue for some working pregnant individuals.