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Most cancers and neoplastic progenitor cells have elevated telomerase activity and preservation of telomeres that promote cellular immortality, making telomerase a rational target for the treatment of cancer. Imetelstat is a first-in-class, 13-mer oligonucleotide that binds with high affinity to the template region of the RNA component of human telomerase and acts as a competitive inhibitor of human telomerase enzymatic activity. Pharmacokinetics, pharmacodynamics, exposure-response analyses, efficacy, and safety of imetelstat have been evaluated in vitro, in vivo, and clinically in solid tumor and hematologic malignancies, including lower-risk myelodysplastic syndromes (LR-MDS) and myeloproliferative neoplasms. Imetelstat was approved in the United States in June 2024 for the treatment of adult patients with LR-MDS with transfusion-dependent anemia requiring four or more red blood cell units over 8 weeks who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents, with a recommended dosing regimen of 7.1 mg/kg administered via 2-h intravenous infusion every 4 weeks. In the pivotal trial, significantly more patients treated with imetelstat versus placebo achieved ≥8-week and ≥24-week red blood cell-transfusion independence, and imetelstat was associated with a manageable safety profile characterized primarily by short-lived and manageable neutropenia and thrombocytopenia. This mini-review summarizes the mechanism of action, pharmacokinetic and pharmacodynamic characteristics, clinical development, and clinical efficacy and safety data of imetelstat., (© 2024 Geron Corporation. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Purpose: An observational study of children with severe traumatic brain injury (TBI) (Approaches and Decisions in Acute Pediatric TBI [ADAPT] Trial) demonstrated the benefits of inpatient rehabilitation on functional outcomes for those with more severely impaired consciousness when medically stable. We conducted a secondary analysis to assess whether using an inpatient rehabilitation or skilled nursing facility after acute hospitalization was associated with better motor, neuropsychological, and behavioral outcomes compared to receiving only non-inpatient rehabilitation among children with severe TBI., Materials and Methods: We included 180 children who used an inpatient rehabilitation or skilled nursing facility and 74 children who only received non-inpatient rehabilitation from the ADAPT trial. At 12 months post-injury, children underwent tests of motor skills, intellectual functioning, verbal learning, memory, processing speed, and cognitive flexibility. Parents/guardians rated children's executive function and behaviors. We performed inverse probability weighting to adjust for potential confounders., Results: No significant differences were found in any motor, neuropsychological, or behavioral measures between children receiving inpatient rehabilitation and children receiving only non-inpatient rehabilitation., Conclusions: Analyses of comprehensive outcomes did not show differences between children receiving inpatient rehabilitation and children receiving only non-inpatient rehabilitation, suggesting a need for more research on specific components of the rehabilitation process.

Background and Objectives: Having a limited number of trained faculty is a barrier to successful incorporation of ultrasound into undergraduate medical education. We evaluated the effectiveness of a resident-led extended focused assessment with sonography in trauma (eFAST) session administered to fourth-year medical students during their emergency medicine clerkship by measuring students' end-of-year eFAST performance and confidence., Methods: This was a single-site cross-sectional study of all graduating medical students enrolled in fourth-year clerkships between May 1, 2022 and April 30, 2023. A 60-minute, team-based eFAST session (intervention), taught by emergency medicine residents, was added to students' fourth-year emergency medicine clerkship in September 2022. All students were assigned to review an eFAST video (control). End-of-year performance and self-reported confidence assessments used a 20-point objective structured clinical examination (OSCE) and a 5-point Likert scale, respectively. The mean OSCE and confidence scores for control and intervention groups were compared using two-sample t tests and repeated after removing students exposed to additional US experiences., Results: Of 113 eligible students, 103 students participated: 48 in the control group, 55 in the intervention group. The intervention group scored higher on the OSCE than the control group (11.9 ±4.6 vs 9.9 ±5.1, P=.04) and reported similar confidence (3.2 ±1.0 vs 2.8 ±1.2; P=.09). After removing the 28 students with additional US experiences, the intervention group scored higher (10.8 ± 4.4 vs 8.2 ± 4.0; P=.01) and reported higher confidence (3.0 ±1.0 vs. 2.3 ±1.0, P=.01)., Conclusions: Resident-taught eFAST instruction during emergency medicine clerkships led to improved end-of-year fourth-year medical student eFAST performance and confidence.

In the United States in 2021, an outbreak of 4 cases of Burkholderia pseudomallei, the etiologic agent of melioidosis and a Tier One Select Agent (potential for deliberate misuse and subsequent harm), resulted in 2 deaths. The causative strain, B. pseudomallei ATS2021, was unintentionally imported into the United States in an aromatherapy spray manufactured in India. We established that ATS2021 represents a virulent strain of B. pseudomallei capable of robust formation of biofilm at physiologic temperatures that may contribute to virulence. By using mouse melioidosis models, we determined median lethal dose estimates and analyzed the bacteriologic and histopathologic characteristics of the organism, particularly the potential neurologic pathogenesis that is probably associated with the bimA Bm allele identified in B. pseudomallei strain ATS2021. Our data, combined with previous case reports and the identification of endemic B. pseudomallei strains in Mississippi, support the concept that melioidosis is emerging in the United States.

This review examined the effect of acute heat mitigation strategies on physiological strain and exercise performance in females exercising in the heat. Three databases were searched for original research with an acute heat mitigation (intervention) and control strategy in active females and reporting core temperature, heart rate and/or aerobic exercise performance/capacity with ≥ 24°C wet bulb globe temperature. Hedges' g effect sizes were calculated to evaluate outcomes. Thirteen studies ( n  = 118) were included. Most studies that applied an acute heat mitigation strategy to females did not reduce thermal (9/10) or cardiovascular (6/6) strain or improve exercise performance/capacity (8/10). The most effective strategies for attenuating thermal strain were pre-cooling with ice-slurry (effect size = -2.2 [95% CI, -3.2, -1.1]) and ice-vests (-1.9 [-2.7, -1.1]), and pre- and per-cooling with an ice-vest (-1.8 [-2.9, -0.7]). Only pre-cooling with an ice-vest improved running performance (-1.8 [-2.9, -0.7]; ~0.43 min) whilst sodium hyperhydration improved cycling capacity at 70% V O 2peak (0.8 [0.0, 1.6]; ~20.1 min). There is currently limited research on acute heat mitigation strategies in females, so the evidence for the efficacy is scarce. Some studies show beneficial effects with ice-slurry, ice-vests and sodium hyperhydration, which can guide future research to support female exercise performance in the heat.

Background: Verdinexor (Laverdia-CA1; Dechra Veterinary Products), a selective inhibitor of nuclear export, has been utilised for treatment of non-Hodgkin T-cell lymphoma in dogs. However, the efficacy of verdinexor has not been evaluated for cutaneous epitheliotropic T-cell lymphoma (CETL)., Hypothesis/objectives: To evaluate the efficacy of verdinexor for the treatment of CETL., Animals: Eight client-owned animals with CETL., Materials and Methods: Patients received between 1.28 and 1.45 mg/kg verdinexor per os twice weekly with a minimum of 72 h between doses until disease progression or voluntary withdrawal. Adjunctive therapy with lokivetmab or prednisone was permitted after Day (D)14. Assessment of clinical lesions (canine Response Evaluation Criteria in Solid Tumors [cRECIST v1.0] and novel Canine Epitheliotropic Lymphoma Extent and Severity Index [CELESI]), pruritus (Visual Analog Scale) and treatment efficacy (owner global assessment of treatment efficacy [OGATE]) were evaluated every 14 days for 3 months, then monthly thereafter (mean 70 ± 43.4 days)., Results: Seventy-five percent of patients achieved complete response, partial response or stable disease. The mean time to disease progression was 56 ± 41 days. There was a significant reduction (p = 0.026) in total CELESI score when the lowest score for each dog was compared to their score at D0. Verdinexor did not significantly reduce pruritus at any time point (p = 0.45), including when given as a monotherapy or concurrently with lokivetmab ± glucocorticoids. On D28, 75% of owners rated response to treatment as 'fair' to 'excellent'. The most common adverse effects included weight loss, inappetence, vomiting and lethargy., Conclusions and Clinical Relevance: Verdinexor could be considered a safe, palliative treatment for canine CETL., (© 2024 ESVD and ACVD.)

Several countries are reporting natural populations of P. falciparum with deletions in the pfhrp 2/3 genes that can lead to false-negative results in rapid diagnostic tests. To investigate the prevalence of deletion in the pfhrp 2/3 genes in the Rio Negro basin in the Brazilian Amazon and identify whether there is clinical differentiation between individuals infected by these parasites, clinical samples collected from 2003 to 2016 were analyzed from symptomatic and asymptomatic P. falciparum -infected individuals. The molecular deletion of pfhrp2 and pfhrp3 genes was evaluated using the protocols recommended by the WHO. From 82 samples used, 28 (34.2%) had a single deletion in pfhrp 2, 19 (23.2%) had a single deletion in pfhrp 3, 15 (18.3%) had a double deletion ( pfhrp2/3 ), and 20 (24.4%) did not have a deletion in either gene. In total, 29.3% of individuals had an asymptomatic plasmodial infection and were 3.64 times more likely to have parasites with a double deletion ( pfhrp 2/3) than patients with clinical malaria ( p = 0.02). The high prevalence of parasites with pfhrp 2/3 deletions shows the need to implement a surveillance program in this area. Deletions in parasites may be associated with the clinical pattern of the disease in this area. More studies must be carried out to elucidate these findings.

Background: Gallbladder distention has been described in radiology literature but its value on point-of-care ultrasound (PoCUS) performed by emergency physicians is unclear. We sought to determine the test characteristics of gallbladder distention on PoCUS for cholecystitis (acute or chronic), and secondarily whether distention was associated with an obstructing stone-in-neck (SIN), acute cholecystitis on subsequent pathology report, and longer cholecystectomy operative times., Methods: This was a dual-site retrospective cohort study of all Emergency Department (ED) patients that underwent diagnostic biliary PoCUS and were subsequently admitted from 11/1/2020 to 10/31/2022. Patients with pregnancy, liver failure, ascites, hepatobiliary cancer, prior cholecystectomy, or known cholecystitis were excluded. Gallbladder distention was defined as a width ≥4 cm or a length ≥10 cm. Saved ultrasound images were reviewed by three independent reviewers who obtained measurements during the review. Test characteristics, Cohen's kappa (κ), and strength of association between distention and our variables (acute cholecystitis on pathology report and SIN on PoCUS) were calculated using a Chi Square analysis, where intervention (cholecystectomy, percutaneous cholecystostomy, or intravenous antibiotics) was used as the reference standard for AC. A one-tail two sample t-test was calculated for mean operative times., Results: Of 280 admitted patients who underwent ED biliary PoCUS, 53 were excluded, and 227 were analyzed. Of the 227 patients, 113 (49.8%) had cholecystitis according to our reference standard, and 68 (30.0%) had distention on PoCUS: 32 distended by both width and length, 16 distended by width alone, and 20 distended by length alone. Agreement between investigators was substantial for width (κ 0.630) and length (κ 0.676). Distention was 85.09% (95% CI 77.20-91.07%) specific and 45.1% (95% CI 35.8-54.8%) sensitive for cholecystitis. There was an association between distention and SIN; odds ratio (OR) 2.76 (95% CI 1.54-4.97). Distention of both length and width was associated with acute over chronic cholecystitis; OR 4.32 (95% CI 1.42-13.14). Among patients with acute cholecystitis, mean operative times were 114 min in patients with distention and 89 min in patients without distention (p = 0.03)., Conclusion: Gallbladder distention on PoCUS was specific for cholecystitis (acute or chronic), and associated with SIN, acute cholecystitis on subsequent pathology report, and longer cholecystectomy operative times. Measurement of gallbladder dimensions as part of the assessment of cholecystitis may be advantageous., Competing Interests: Declaration of competing interest This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The COVID-19 pandemic has been associated with increases in pediatric obesity and widening pre-existing disparities. To better understand the pandemic's long-term impacts, we evaluated trends in obesity across different demographic groups during the pandemic through December 2022. Using a retrospective cohort design, we analyzed electronic health record data from a large pediatric primary care network. Logistic regression models fit using generalized estimating equations estimated odds ratios (ORs) for changes in the level and trajectory of obesity across 2-year month-matched periods: prepandemic (June 2017 to December 2019) and pandemic (June 2020 to December 2022). Among a cohort of 153,667 patients with visits in each period, there was a significant increase in the level of obesity at the pandemic onset [OR: 1.229, 95% confidence interval (CI): 1.211-1.247] followed by a significant decrease in the trend for obesity (OR: 0.993, 95% CI: 0.992-0.993). By December 2022, obesity had returned to prepandemic levels. However, persistent sociodemographic disparities remain.

Introduction: Antiretroviral therapy (ART) initiation in infants living with HIV before 12 weeks of age can reduce the risk of mortality by 75%. Point-of-care (POC) diagnostic testing is critical for prompt ART initiation; however, despite its availability, rates of ART initiation are still relatively low before 12 weeks of age. This systematic review describes the barriers to ART initiation in infants before 12 weeks of age, despite the availability of POC., Methods: This systematic review used a narrative synthesis methodology. We searched PubMed and Scopus using search strategies that combined terms of multiple variants of the keywords "early infant initiation on antiretroviral therapy," "barriers" and "sub-Saharan Africa" (initial search 18th January 2023; final search 1st August 2023). We included qualitative, observational and mixed methods studies that reported the influences of early infant initiation on ART. We excluded studies that reported influences on other components of the Prevention of Mother to Child Transmission cascade. Using a deductive approach guided by the updated Consolidated Framework of Implementation Research, we developed descriptive codes and themes around barriers to early infant initiation on ART. We then developed recommendations for interventions for the identified barriers using the action, actor, target and time framework from the codes., Results: Of the 266 abstracts reviewed, 52 full-text papers were examined, of which 12 papers were included. South Africa had most papers from a single country (n = 3) and the most reported study design was retrospective (n = 6). Delays in ART initiation beyond 12 weeks in infants 0-12 months were primarily associated with health facility and maternal factors. The most prominent barriers identified were inadequate resources for POC testing (including human resources, laboratory facilities and patient follow-up). Maternal-related factors, such as limited male involvement and maternal perceptions of treatment and care, were also influential., Discussion: We identified structural barriers to ART initiation at the health system, social and cultural levels. Improvements in the timely allocation of resources for POC testing operations, coupled with interventions addressing social and behavioural barriers among both mothers and healthcare providers, hold a promise for enhancing timely ART initiation in infants., Conclusions: This paper identifies barriers and proposes strategies for timely ART initiation in infants., (© 2024 The Author(s). Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

Insects frequently form heritable associations with beneficial bacteria that are vertically transmitted from parent to offspring. Long-term vertical transmission has repeatedly resulted in genome reduction and gene loss, rendering many such bacteria incapable of establishment in axenic culture. Among aphids, heritable endosymbionts often provide context-specific benefits to their hosts. Although these associations have large impacts on host phenotypes, experimental approaches are often limited by an inability to cultivate these microbes. Here, we report the axenic culture of Candidatus Fukatsuia symbiotica strain WIR, a heritable bacterial endosymbiont of the pea aphid, Acyrthosiphon pisum . Whole-genome sequencing revealed similar genomic features and high sequence similarity to previously described strains, suggesting that the cultivation techniques used here may be applicable to Ca . F. symbiotica strains from distantly related aphids. Microinjection of cultured Ca . F. symbiotica into uninfected aphids revealed that it can reinfect developing embryos and that infections are maintained in subsequent generations via transovarial maternal transmission. Artificially infected aphids exhibit phenotypic and life history traits similar to those observed for native infections. Our results show that Ca . F. symbiotica may be a useful tool for experimentally probing the molecular mechanisms underlying host-symbiont interactions in a heritable symbiosis., Importance: Diverse eukaryotic organisms form stable, symbiotic relationships with bacteria that provide benefits to their hosts. While these associations are often biologically important, they can be difficult to probe experimentally because intimately host-associated bacteria are difficult to access within host tissues, and most cannot be cultured. This is especially true for the intracellular, maternally inherited bacteria associated with many insects, including aphids. Here, we demonstrate that a pea aphid-associated strain of the heritable endosymbiont, Candidatus Fukatsuia symbiotica, can be grown outside of its host using standard microbiology techniques and can readily re-establish infection that is maintained across host generations. These artificial infections recapitulate the effects of native infections, making this host-symbiont pair a useful experimental system., Competing Interests: The authors declare no conflict of interest.

Objectives: Accurate risk stratification of patients with stage II and III colorectal cancer (CRC) prior to treatment selection enables limited health resources to be efficiently allocated to patients who are likely to benefit from adjuvant chemotherapy. We aimed to investigate the cost-effectiveness of a recently developed deep learning-based prognostic method, Histotyping, from the perspective of the Norwegian healthcare system., Methods: Two partitioned survival models were developed to assess the cost-effectiveness of Histotyping for two treatment cohorts: patients with CRC stage II and III. For each of the two cohorts, Histotyping was used for risk stratification to assign adjuvant chemotherapy and was compared with the standard of care (SOC) (adjuvant chemotherapy to all patients). Health outcomes measured in the model were quality-adjusted life years (QALYs) and life years (LYs) gained. Deterministic and probabilistic sensitivity analyses were performed to determine the impact of uncertainty. Scenario analyses were performed to assess the impact of the parameters with the greatest uncertainty., Results: Risk-stratifying patients with CRC stage II and III using Histotyping was dominant (less costly and more effective) compared to SOC. In patients with CRC stage II, the net monetary benefit of Histotyping was 270,934 Norwegian kroners (NOK) (year of valuation is 2021), and the net health benefit of Histotyping was 0.99. In stage III, the net monetary benefit of Histotyping was 195,419 NOK, and the net health benefit of Histotyping was 0.71., Conclusions:  Risk-stratifying patients with CRC using Histotyping prior to the administration of adjuvant chemotherapy is likely to be a cost-effective strategy in Norway., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: Machine learning (ML) is increasingly employed to diagnose medical conditions, with algorithms trained to assign a single label using a black-box approach. We created an ML approach using deep learning that generates outcomes that are transparent and in line with clinical, diagnostic rules. We demonstrate our approach for autism spectrum disorders (ASD), a neurodevelopmental condition with increasing prevalence., Methods: We use unstructured data from the Centers for Disease Control and Prevention (CDC) surveillance records labeled by a CDC-trained clinician with ASD A1-3 and B1-4 criterion labels per sentence and with ASD cases labels per record using Diagnostic and Statistical Manual of Mental Disorders (DSM5) rules. One rule-based and three deep ML algorithms and six ensembles were compared and evaluated using a test set with 6773 sentences (N = 35 cases) set aside in advance. Criterion and case labeling were evaluated for each ML algorithm and ensemble. Case labeling outcomes were compared also with seven traditional tests., Results: Performance for criterion labeling was highest for the hybrid BiLSTM ML model. The best case labeling was achieved by an ensemble of two BiLSTM ML models using a majority vote. It achieved 100% precision (or PPV), 83% recall (or sensitivity), 100% specificity, 91% accuracy, and 0.91 F-measure. A comparison with existing diagnostic tests shows that our best ensemble was more accurate overall., Conclusions: Transparent ML is achievable even with small datasets. By focusing on intermediate steps, deep ML can provide transparent decisions. By leveraging data redundancies, ML errors at the intermediate level have a low impact on final outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Background: Despite similar diagnostic effectiveness for renal colic, computed tomography (CT) is more resource intensive than point-of-care ultrasound (PoCUS). We sought to compare Emergency Department (ED) length of stay (LOS) among patients with renal colic according to imaging modality utilized. We secondarily compared rates of infection, return ED visits, missed significant pathology, and urologic intervention., Methods: This was a 12-month (1/1/22-12/31/22) multi-site retrospective cohort study of all patients diagnosed with renal colic who presented to the ED on days when at least one patient had a billable renal PoCUS examination performed. Patients with a history of genitourinary malignancy, pregnancy, renal transplant, hemodialysis, single kidney, prior visit for renal colic in the previous 30 days, or an incomplete workup were excluded. Median ED LOS was compared using a Wilcoxon rank sum test, and the 95% confidence limits for the difference between medians was calculated. Secondary outcomes were compared using a Fisher's Exact test., Results: Of 415 patients screened, 325 were included for analysis: 150 had CT alone, 80 had PoCUS alone, 54 had PoCUS plus CT, and 41 had neither. Median LOS for PoCUS alone was 75.0 (95% CI 39.3-110.7) minutes shorter than CT alone (231.5 vs. 307.0 min, p < 0.0001). Similar rates of infection, return visits, and missed pathology occurred across all groups (p > 0.10). Urologic interventions were higher in the PoCUS plus CT (25.9%) group compared to CT alone (7.3%), PoCUS alone (2.5%), and neither (7.3%), p < 0.0001., Conclusion: Among patients with renal colic, PoCUS was associated with shorter ED LOS compared to CT, without differences in infection rates, return visits, or missed pathology. Patients with PoCUS plus CT had a higher rate of urologic interventions, suggesting PoCUS may have a role in identifying patients who would most benefit from CT., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: We assessed the impact of an online intervention using clinician prompts for human papillomavirus (HPV) vaccination with a cluster randomized controlled trial., Methods: The randomized trial occurred July 2021-January 2022 in 48 primary care pediatric practices (24 intervention, 24 control) across the US. We trained clinicians via two online learning modules, plus weekly ''quick tips'' delivered via text or email. The training taught practices to implement a staff prompt to the clinician (e.g., printed reminders placed on the keyboard) plus electronic health record (EHR) prompts (if not already done) at well and acute/chronic visits for initial and subsequent HPV vaccination. We assessed missed opportunities for HPV vaccination using logistic regression models accounting for clustering by practice on an intent to treat basis. Surveys assessed facilitators and barriers to using prompts., Results: During the 6-month intervention, missed opportunities for HPV vaccination increased (worsened) in both intervention and control groups. However, at well child care visits, missed opportunities for the initial HPV vaccine increased by 4.5 (95% CI: -9.0%, -0.1%) percentage points less in intervention versus control practices. Change in missed opportunities for subsequent doses at well child care and non-well child care visits did not differ between trial groups. An end-of trial survey found understaffing as a common challenge., Conclusions: Clinician prompts reduced missed opportunities for HPV vaccination at well child care visits. Understaffing related to the COVID-19 pandemic may have led to worsening missed opportunities for both groups and likely impeded practices in fully implementing changes., Competing Interests: Declaration of Competing Interest Dr. Humiston has the following conflicts of interest: until 9/2022, Dr. Humiston’s employer received grant money for her work sponsored by the Pediatric Infectious Diseases Society (PIDS) Foundation, a not-for-profit organization. PIDS is funded for the project through unrestricted joint educational grants from Sanofi US, Merck & Co., Inc., Pfizer, Inc., GlaxoSmithKline, and Seqirus USA, Inc., (Copyright © 2024 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Despite the growing use of point of care ultrasound (POCUS) in contemporary medical practice and the existence of clinical guidelines addressing its specific applications, there remains a lack of standardization and agreement on optimal practices for several areas of POCUS use. The Society of Point of Care Ultrasound (SPOCUS) formed a working group in 2022 to establish a set of recommended best practices for POCUS, applicable to clinicians regardless of their training, specialty, resource setting, or scope of practice. Using a three-round modified Delphi process, a multi-disciplinary panel of 22 POCUS experts based in the United States reached consensus on 57 statements in domains including: (1) The definition and clinical role of POCUS; (2) Training pathways; (3) Credentialing; (4) Cleaning and maintenance of POCUS devices; (5) Consent and education; (6) Security, storage, and sharing of POCUS studies; (7) Uploading, archiving, and reviewing POCUS studies; and (8) Documenting POCUS studies. The consensus statements are provided here. While not intended to establish a standard of care or supersede more targeted guidelines, this document may serve as a useful baseline to guide clinicians, leaders, and systems considering initiation or enhancement of POCUS programs., Competing Interests: AG has received grants from NIH and consulting fees from Butterfly Network and Ultrasight. AK has received research funding from KidneyCure and the American Society of Nephrology. JK is the chair of the American Society of Echocardiography’s Scientific Statement Writing Group on Nomenclature of cardiac POCUS, and a member of the Critical Care Echocardiography Council Leadership Group., (Copyright (c) 2024 Brandon Oto, PA-C, FCCM, Robert Baeten, PA-C, FCCP, Leon Chen, DNP, AGACNP-BC, FCCP, FAANP, FCCM, Puja Dalal, MD, FAAFP, Ria Dancel, MD, FACP, SFHM, FAAP, Steven Fox, MD, Carl William Lange, IV, MSBS, EM-CAQ, PA-C, Cameron Baston, MD, MSCE, FACP, Paul Bornemann, MD, RMSK, RPVI, Siddharth Dugar, MD, FCCM, FASE, FCCP, Andrew Goldsmith, MD, MBA, Meghan Kelly Herbst, MD, FACEP, James N. Kirkpatrick, MD, FASE, FACC, Abhilash Koratala, MD, FASN, Michael J. Lanspa, MD, Viveta Lobo, MD, FACEP, Jason T Nomura, MD, FACEP, FAAEM, FACP, FAHA, Aliaksei Pustavoitau, MD, MHS, FCCM, Mourad H Senussi, MD, MS, Vincent L. Sorrell, MD, FACP (honorary), FACC, FASE, FSCCT, FSCMR, Frances Mae West, MD, MS, FACP, Aarti Sarwal, MD, FNCS, FAAN, FCCM, FASN, RPNI.)

Background: Point of care ultrasound (POCUS) is specific for acute cholecystitis (AC), but surgeons request radiology imaging (RI) prior to admitting patients with POCUS-diagnosed AC., Objectives: We sought to determine the test characteristics of POCUS for AC when performed and billed by credentialed emergency physicians (EPs), the accuracy rate of RI when performed after POCUS, and the time added when RI is requested after POCUS demonstrates AC., Methods: We performed a dual-site retrospective cohort study of admitted adult ED patients who had received biliary POCUS from November 1, 2020 to April 30, 2022. Patients with previously diagnosed AC, liver failure, ascites, hepatobiliary cancer, or cholecystectomy were excluded. Descriptive statistics and 95% confidence intervals for point estimates were calculated. Medians were compared using a Wilcoxon signed-rank test. Test characteristics of POCUS for AC were calculated using inpatient intervention for AC as the reference standard., Results: Of 473 screened patients, 143 were included for analysis: 80 (56%) had AC according to our reference standard. POCUS was positive for AC in 46 patients: 44 true positives and two false positives, yielding a positive likelihood ratio of 17.3 (95%CI 4.4-69.0) for AC. The accuracy rate of RI after positive POCUS for AC was 39.0%. Median time from ED arrival to POCUS and ED arrival to RI were 115 (IQR 64, 207) and 313.5 (IQR 224, 541) minutes, respectively; p < 0.01., Conclusion: RI after positive POCUS performed by credentialed EPs takes additional time and may increase diagnostic uncertainty., Competing Interests: Acknowledgements: The authors would like to thank Jonah Haber MS for his contributions to an earlier version of this work; João Delgado MD for his assistance in reviewing and editing the manuscript; and James Grady PhD for his statistical assistance. None, (Copyright (c) 2024 David Cannata, Callista Love, Pascale Carrel, Trent She, Seth Lotterman, Felix Pacheco, Meghan Herbst.)

Objective: Multi-center implementation of rapid whole genome sequencing with assessment of the clinical utility of rapid whole genome sequencing (rWGS), including positive, negative and uncertain results, in admitted infants with a suspected genetic disease., Study Design: rWGS tests were ordered at eight hospitals between November 2017 and April 2020. Investigators completed a survey of demographic data, Human Phenotype Ontology (HPO) terms, test results and impacts of results on clinical care., Results: A total of 188 patients, on general hospital floors and intensive care unit (ICU) settings, underwent rWGS testing. Racial and ethnic characteristics of the tested infants were broadly representative of births in the country at large. 35% of infants received a diagnostic result in a median of 6 days. The most common HPO terms for tested infants indicated an abnormality of the nervous system, followed by the cardiovascular system, the digestive system, the respiratory system and the head and neck. Providers indicated a major change in clinical management because of rWGS for 32% of infants tested overall and 70% of those with a diagnostic result. Also, 7% of infants with a negative rWGS result and 23% with a variant of unknown significance (VUS) had a major change in management due to testing., Conclusions: Our study demonstrates that the implementation of rWGS is feasible across diverse institutions, and provides additional evidence to support the clinical utility of rWGS in a demographically representative sample of admitted infants and includes assessment of the clinical impact of uncertain rWGS results in addition to both positive and negative results., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Thompson, Larson, Salz, Veith, Tsai, Jayakar, Chapman, Gupta, Kingsmore, Dimmock, Bedrick, Galindo, Casas, Mohamed, Straight, Khan and Salyakina.)

The aim of this audit was to quantify female representation in research on heat adaptation. Using a standardized audit tool, the PubMed database was searched for heat adaptation literature from inception to February 2023. Studies were included if they investigated heat adaptation among female and male adults (≥18-50 years) who were free from noncommunicable diseases, with heat adaptation the primary or secondary outcome of interest. The number and sex of participants, athletic caliber, menstrual status, research theme, journal impact factor, Altmetric score, Field-Weighted Citation Impact, and type of heat exposure were extracted. A total of 477 studies were identified in this audit, including 7,707 participants with ∼13% of these being female. Most studies investigated male-only cohorts (∼74%, n = 5,672 males), with ∼5% (n = 360 females) including female-only cohorts. Of the 126 studies that included females, only 10% provided some evidence of appropriate methodological control to account for ovarian hormone status, with no study meeting best-practice recommendations. Of the included female participants, 40% were able to be classified to an athletic caliber, with 67% of these being allocated to Tier 2 (i.e., trained/developmental) or below. Exercise heat acclimation was the dominant method of heat exposure (437 interventions), with 21 studies investigating sex differences in exercise heat acclimation interventions. We recommend that future research on heat adaptation in female participants use methodological approaches that consider the potential impact of sexual dimorphism on study outcomes to provide evidence-based guidelines for female athletes preparing for exercise or competition in hot conditions.

This narrative review evaluated the evidence for buffering agents (sodium bicarbonate, sodium citrate and beta-alanine), with specific consideration of three discrete scenarios: female athletes, extreme environments and combined buffering agents. Studies were screened according to exclusion and inclusion criteria and were analysed on three levels: (1) moderating variables (supplement dose and timing, and exercise test duration and intensity), (2) design factors (e.g., use of crossover or matched group study design, familiarisation trials) and (3) athlete-specific factors (recruitment of highly trained participants, buffering capacity and reported performance improvements). Only 19% of the included studies for the three buffering agents reported a performance benefit, and only 10% recruited highly trained athletes. This low transferability of research findings to athletes' real-world practices may be due to factors including the small number of sodium citrate studies in females (n = 2), no studies controlling for the menstrual cycle (MC) or menstrual status using methods described in recently established frameworks, and the limited number of beta-alanine studies using performance tests replicating real-world performance efforts (n = 3). We recommend further research into buffering agents in highly trained female athletes that control or account for the MC, studies that replicate the demands of athletes' heat and altitude camps, and investigations of highly trained athletes' use of combined buffering agents. In a practical context, we recommend developing evidence-based buffering protocols for individual athletes which feature co-supplementation with other evidence-based products, reduce the likelihood of side-effects, and optimise key moderating factors: supplement dose and timing, and exercise duration and intensity., (© 2023. The Author(s).)

Background: Point-of-care ultrasound (PoCUS) is commonly utilized in the setting of renal colic. The presence of perinephric fluid may be an overlooked finding associated with ureteral obstruction. Our aims were to determine the prevalence of perinephric fluid on emergency physician-performed PoCUS and to determine whether perinephric fluid was associated with stone size or urologic intervention., Methods: This was a 12-month cross-sectional study at an academic emergency department (ED) that took place from January 1, 2022, to December 31, 2022. All adult ED patients ≥18 years of age who had a renal PoCUS examination performed were included. Patients with missing or inadequate PoCUS images were excluded. Investigators blinded to PoCUS images and interpretations performed chart review for demographic data and outcome variables, while separate investigators blinded to clinical data reviewed PoCUS images to assess for perinephric fluid and hydronephrosis. A chi-square analysis was used to determine significance of association between perinephric fluid and outcome variables (stone size, urologic intervention)., Results: There were 442 patients screened; 18 were excluded due to inadequate images and 4 were repeat visits of which only the initial visit was analyzed. Of the remaining 420 patients included, the prevalence of perinephric fluid was 6.2% (n = 26). Most patients (23/26) with perinephric fluid had final diagnoses consistent with ureterolithiasis. Hydronephrosis was present in 115 of the 420 patients (27.4%) and of these, 22 (19.1%) had perinephric fluid which was significantly associated with a need for urologic intervention; odds ratio (OR) 10.38 (95% CI 2.70-39.85), p < 0.01. Among the 67 patients with confirmed ureterolithiasis on computed tomography, perinephric fluid was associated with stone size ≥5 mm; OR 4.00 (95% CI 1.01-15.85), p = 0.04., Conclusion: The prevalence of perinephric fluid on emergency physician-performed renal PoCUS was 6.2% of all studies and 19.1% of patients with hydronephrosis. In the setting of ureterolithiasis, perinephric fluid was associated with larger stone size and need for urologic intervention., Competing Interests: Declaration of Competing Interest DC, ZB, CX, LM, and MKH report no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The prevalence of phantom scanning, or point of care ultrasound (POCUS) performed without saving images, has not been well studied. Phantom scanning can negatively affect patient care, reduce billed revenue, and can increase medicolegal liability. We sought to quantify and compare the prevalence of phantom scanning among emergency department (ED) cardiac arrests and trauma resuscitations. Methods: This was a single center, retrospective cohort study from July 1, 2019, to July 1, 2021, of all occurrences of POCUS examination documented on the resuscitation run sheet during cardiac arrest and trauma resuscitations. Two investigators reviewed the run sheets to screen for POCUS documentation. Instances where documentation was present were matched with saved images in the picture archiving and communication system. Instances where documentation was present but no images could be located were considered phantom scans. A two-tailed student's t test was utilized to compare the phantom scanning rate between cardiac arrest and trauma resuscitations. Results: A total of 1,862 patients were included in the study period, with 329 cardiac arrests and 401 trauma resuscitations having run sheet documentation of POCUS performance. The phantom scanning rate in cardiac arrests and trauma resuscitations was 70.5% (232/329) and 86.5% (347/401), respectively (p < 0.001). Conclusion: Phantom scanning is common in both cardiac arrests and trauma resuscitations in the ED at our institution, but is significantly higher in trauma resuscitations. Further research is needed to assess causes and develop potential solutions to reduce the high prevalence of phantom scanning., Competing Interests: The authors report no disclosures related to this work., (Copyright (c) 2023 Zachary Boivin, Curtis Xu, Donias Doko, Meghan Kelly Herbst, Trent She.)

Purpose: Coffin-Siris and Nicolaides-Baraitser syndromes are recognizable neurodevelopmental disorders caused by germline variants in BAF complex subunits. The SMARCC2 BAFopathy was recently reported. Herein, we present clinical and molecular data on a large cohort., Methods: Clinical symptoms for 41 novel and 24 previously published affected individuals were analyzed using the Human Phenotype Ontology. For genotype-phenotype correlations, molecular data were standardized and grouped into non-truncating and likely gene-disrupting (LGD) variants. Missense variant protein expression and BAF-subunit interactions were examined using 3D protein modeling, co-immunoprecipitation, and proximity-ligation assays., Results: Neurodevelopmental delay with intellectual disability, muscular hypotonia, and behavioral disorders were the major manifestations. Clinical hallmarks of BAFopathies were rare. Clinical presentation differed significantly, with LGD variants being predominantly inherited and associated with mildly reduced or normal cognitive development, whereas non-truncating variants were mostly de novo and presented with severe developmental delay. These distinct manifestations and non-truncating variant clustering in functional domains suggest different pathomechanisms. In vitro testing showed decreased protein expression for N-terminal missense variants similar to LGD., Conclusion: This study improved SMARCC2 variant classification and identified discernible SMARCC2-associated phenotypes for LGD and non-truncating variants, which were distinct from other BAFopathies. The pathomechanism of most non-truncating variants has yet to be investigated., Competing Interests: Conflict of Interest Renee Bend and Julie Rath are employees of PreventionGenetics, part of Exact Sciences. Michelle M. Morrow and Francisca Millan are employees of GeneDx, LLC. All other authors declare no conflicts of interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The objective of this study was to evaluate the effects of sunflower cake inclusion and its association with crude glycerin in the diet of laying hens. A total of 320 laying hens with 39 weeks of age were distributed in a completely randomized design in a 4 × 2 factorial scheme with 5 replications of 8 birds. The studied factors were 4 inclusion levels of sunflower cake and 2 levels of crude glycerin. The inclusion of 210 g/kg of sunflower cake reduced egg mass and worsened feed conversion, and after the level 70 g/kg there was reduction in yolk coloration and specific density of eggs with or without the addition of glycerin in the diet. The addition of 70 g/kg of crude glycerin reduced the specific density of eggs in all levels of sunflower cake. There was increase in phenolic compounds, antioxidant capacity and antioxidant activity in eggs and reduction in lipid oxidation of yolks from fresh and stored eggs, with the inclusion of sunflower cake. The addition of crude glycerin increased the lipid oxidation of egg yolks. Therefore, it is possible to include up to 140 g/kg sunflower cake in the diet of laying hens, with or without crude glycerin, without impairing performance and egg quality, obtaining higher antioxidant capacity of eggs and lower lipid oxidation in yolks from fresh and stored eggs. The inclusion of 70 g/kg crude glycerin does not affect laying hens performance, however, it worsens shell quality and increases lipid oxidation in the liver and egg yolks., Competing Interests: Declaration of Competing Interest The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Limited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations., Methods: This is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 2020 and June 2021 in the US. Primary outcome was COVID-19 severity measured on a five-level ordinal scale, including none of the following complications, hospitalization, intensive care unit admission, mechanical ventilation, and all-cause mortality. Multivariable ordinal logistic regression model identified characteristics associated with COVID-19 severity., Results: 1383 female patient records with BC and COVID-19 were included in the analysis, the median age was 61 years, and median follow-up was 90 days. Multivariable analysis revealed higher odds of COVID-19 severity for older age (aOR per decade, 1.48 [95% CI, 1.32-1.67]); Black patients (aOR 1.74; 95 CI 1.24-2.45), Asian Americans and Pacific Islander patients (aOR 3.40; 95 CI 1.70-6.79) and Other (aOR 2.97; 95 CI 1.71-5.17) racial/ethnic groups; worse ECOG performance status (ECOG PS ≥2: aOR, 7.78 [95% CI, 4.83-12.5]); pre-existing cardiovascular (aOR, 2.26 [95% CI, 1.63-3.15])/pulmonary comorbidities (aOR, 1.65 [95% CI, 1.20-2.29]); diabetes mellitus (aOR, 2.25 [95% CI, 1.66-3.04]); and active and progressing cancer (aOR, 12.5 [95% CI, 6.89-22.6]). Hispanic ethnicity, timing, and type of anti-cancer therapy modalities were not significantly associated with worse COVID-19 outcomes. The total all-cause mortality and hospitalization rate for the entire cohort was 9% and 37%, respectively however, it varied according to the BC disease status., Conclusions: Using one of the largest registries on cancer and COVID-19, we identified patient and BC-related factors associated with worse COVID-19 outcomes. After adjusting for baseline characteristics, underrepresented racial/ethnic patients experienced worse outcomes compared to non-Hispanic White patients., Funding: This study was partly supported by National Cancer Institute grant number P30 CA068485 to Tianyi Sun, Sanjay Mishra, Benjamin French, Jeremy L Warner; P30-CA046592 to Christopher R Friese; P30 CA023100 for Rana R McKay; P30-CA054174 for Pankil K Shah and Dimpy P Shah; KL2 TR002646 for Pankil Shah and the American Cancer Society and Hope Foundation for Cancer Research (MRSG-16-152-01-CCE) and P30-CA054174 for Dimpy P Shah. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH). The funding sources had no role in the writing of the manuscript or the decision to submit it for publication., Clinical Trial Number: CCC19 registry is registered on ClinicalTrials.gov, NCT04354701., Competing Interests: GN, SV, AK, TS, NK, DA, JA, JA, ZB, NB, TB, BB, SB, MB, PB, SB, BB, HB, CC, HC, JD, AD, NE, LF, DF, CF, MG, CG, PG, SG, MH, HH, DH, CH, CJ, SJ, MJ, VK, EK, NK, VK, AK, DK, CL, PL, KL, ML, XL, GL, GL, DM, AM, MM, SM, RM, IM, VM, RN, SN, RN, TN, TO, OP, KP, JP, KP, JP, HP, MP, YR, PR, SR, JR, DR, MR, SR, AR, LS, PS, MS, LS, MS, DS, MS, LT, MT, ST, LW, GW, MW, EW, SM, BF, JW, ML, MA, DS No competing interests declared

Objectives: The National Institute for Health and Care Excellence (NICE) recently completed a review of its methods for health technology assessment, involving a 2-stage public consultation. We appraise proposed methodological changes and analyze key decisions., Methods: We categorize all changes proposed in the first consultation as "critical," "moderate" or "limited" updates, considering the importance of the topic and the degree of change or the level of reinforcement. Proposals were followed through the review process, for their inclusion, exclusion, or amendment in the second consultation and the new manual., Results: The end-of-life value modifier was replaced with a new "disease severity" modifier and other potential modifiers were rejected. The usefulness of a comprehensive evidence base was emphasized, clarifying when nonrandomized studies can be used, with further guidance on "real-world" evidence developed separately. A greater degree of uncertainty was accepted in circumstances when evidence generation raised challenges, in particular for children, rare diseases, and innovative technologies. For some topics, such as health inequality, discounting, unrelated healthcare costs, and value of information, significant changes were possibly warranted, but NICE decided not to make any revisions at present., Conclusion: Most of the changes to NICE's health technology assessment methods are appropriate and modest in impact. Nevertheless, some decisions were not well justified and further research is needed on several topics, including investigation of societal preferences. Ultimately, NICE's role of protecting National Health Services resources for valuable interventions that can contribute toward improving overall population health must be safeguarded, without accepting weaker evidence., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: The Coronavirus Disease 2019 pandemic disrupted healthcare, but the impact on vaccination missed opportunities (MOs, vaccine-eligible visits without vaccination) is unknown. We evaluated pandemic-related trends in MOs at adolescent well-care visits for three vaccines: human papillomavirus; quadrivalent meningococcal conjugate; and tetanus, diphtheria, and acellular pertussis (Tdap)., Methods: We analyzed electronic health record data from 24 pediatric primary care practices in 13 states from 1/1/2018 to 12/31/2021. Segmented logistic regression estimated risk differences for MOs during the pandemic relative to prepandemic trends., Results: Among 106,605 well-care visits, we observed decreases in MOs prepandemic followed by an increase in MOs during the pandemic for all three vaccines. Relative to prepandemic, MOs increased for human papillomavirus (+15.9%, 95% confidence interval [CI]: 11.7%, 20.1%), meningococcal conjugate (+9.4%, 95% CI: 5.2%, 13.7%), and tetanus, diphtheria, and acellular pertussis (Tdap) (+ 8.2%, 95% CI: 4.3%, 12.1%)., Discussion: Increases in vaccine MOs during the pandemic equaled or exceeded pre-pandemic decreases. Reducing MOs in adolescent well-care could raise vaccine coverage., (Copyright © 2023 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: While point-of-care ultrasound (PoCUS) is a safe, versatile tool that can improve patient care, the perceived time investment needed to incorporate PoCUS into clinical care is cited as a barrier to performance. We sought to determine the time it takes to perform a PoCUS examination and whether this time was influenced by training level and prior ultrasound experience., Methods: This was a retrospective study looking at time stamps of all emergency medicine (EM) provider-performed PoCUS examinations during clinical shifts from August 10, 2019, to June 7, 2022, at a suburban academic emergency department that is the site for a 3-year EM residency. Our workflow is order-based; when PoCUS is ordered, that patient's information populates the ultrasound machine worklist. Selecting the patient's name from the worklist generates a time-stamped patient information page (PIP). We defined the PIP time stamp as the start of the PoCUS examination. The duration of one PoCUS examination was defined as the time of the last image acquired minus the time of the PIP. General estimating equations were used to estimate differences between training level and between prior scan status using an exchangeable correlation and Tukey adjusted pairwise comparisons. A two-tailed chi-square analysis was used for comparing accuracy according to training level., Results: Of 4187 PoCUS examinations abstracted, 2144 met study criteria. The median (IQR) time spent per examination was 6.0 (3-9) min. First-year residents took the longest to perform PoCUS among all providers ( p  < 0.0001). Residents with fewer than 250 prior scans took longer than residents with 501-800 ( p  = 0.0002) and >800 ( p  = 0.0013). Resident accuracy was not significantly different according to training level., Conclusions: Overall median time to perform PoCUS was 6.0 min. EM residents became more efficient in performing PoCUS as they advanced from first- to third-year, without compromising accuracy., Competing Interests: The authors declare no conflicts of interest., (© 2023 Society for Academic Emergency Medicine.)

Competing Interests: Declaration of Competing Interest No potential conflicts of interest.

Objective: Adolescent mental health concerns increased during COVID-19, but it is unknown whether early increases in depression and suicide risk have been sustained. We examined changes in positive screens for depression and suicide risk in a large pediatric primary care network through May 2022., Methods: Using an observational repeated cross-sectional design, we examined changes in depression and suicide risk during the pandemic using electronic health record data from adolescents. Segmented logistic regression was used to estimate risk differences (RD) for positive depression and suicide risk screens during the early pandemic (June 2020-May 2021) and late pandemic (June 2021-May 2022) relative to before the pandemic (March 2018-February 2020). Models adjusted for seasonality and standard errors accounted for clustering by practice., Results: Among 222,668 visits for 115,627 adolescents (mean age 15.7, 50% female), the risk of positive depression and suicide risk screens increased during the early pandemic period relative to the prepandemic period (RD, 3.8%; 95% CI, 2.9, 4.8; RD, 2.8%; 95% CI, 1.7, 3.8). Risk of depression returned to baseline during the late pandemic period, while suicide risk remained slightly elevated (RD, 0.7%; 95% CI, -0.4, 1.7; RD, 1.8%; 95% CI, 0.9%, 2.7%)., Conclusions: During the early months of the pandemic, there was an increase in positive depression and suicide risk screens, which later returned to prepandemic levels for depression but not suicide risk. Results suggest that pediatricians should continue to prioritize screening adolescents for depressive symptoms and suicide risk and connect them to treatment., (Copyright © 2023 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Importance: Neighborhood conditions are known to broadly impact child health. Research to date has not examined the association of the Childhood Opportunity Index (COI), a multidimensional indicator of neighborhood environment conditions, specifically with pediatric primary care outcomes., Objective: To determine the association of neighborhood opportunity measured by the COI with health metrics commonly captured clinically in pediatric primary care, reflecting both access to preventive care and child well-being., Design, Setting, and Participants: This cross-sectional observational study used electronic health record data from a large pediatric primary care network in the northeastern US. Participants included patients aged 0 to 19 years who were active in the primary care network between November 2020 and November 2022. Data were analyzed in December 2022., Exposure: Census tract-level COI overall score (in quintiles)., Main Outcomes and Measures: Outcomes included up-to-date preventive care and immunization status and presence of obesity, adolescent depression and suicidality, and maternal depression and suicidality. Multivariable mixed-effects logistic regressions estimated associations of these outcomes with COI quintiles, adjusted for age, sex, race and ethnicity, and insurance type., Results: Among 338 277 patients (mean [SD] age, 9.8 [5.9] years; 165 223 female [48.8%]; 158 054 [46.7%] non-Hispanic White, 209 482 [61.9%] commercially insured), 81 739 (24.2%) and 130 361 (38.5%) lived in neighborhoods of very low and very high COI, respectively. Living in very high COI neighborhoods (vs very low COI) was associated with higher odds of being up-to-date on preventive visits (odds ratio [OR], 1.40; 95% CI, 1.32-1.48) and immunizations (OR, 1.77; 95% CI, 1.58-2.00), and with lower odds of obesity (OR, 0.55; 95% CI, 0.52-0.58), adolescent depression (OR, 0.78; 95% CI, 0.72-0.84) and suicidality (OR, 0.79; 95% CI, 0.73-0.85), and maternal depression (OR, 0.78; 95% CI, 0.72-0.86) and suicidality (OR, 0.71; 95% CI, 0.61-0.83)., Conclusions and Relevance: This cross-sectional study of electronic health record data found that neighborhood opportunity was associated with multiple pediatric primary care outcomes. Understanding these associations can help health systems identify neighborhoods that need additional support and advocate for and develop partnerships with community groups to promote child well-being. The findings underscore the importance of improving access to preventive care in low COI communities.

Background: Procaspase-3 (PC-3) is overexpressed in various tumor types, including gliomas. Targeted PC-3 activation combined with chemotherapy is a novel strategy for treating patients with high-grade gliomas, with promising preclinical activity. This study aimed to define safety and tolerability of procaspase-activating compound-1 (PAC-1) in combination with temozolomide (TMZ) for patients with recurrent high-grade astrocytomas., Methods: A modified-Fibonacci dose-escalation 3 + 3 design was used. PAC-1 was administered at increasing dose levels (DL; DL1 = 375 mg) on days 1-21, in combination with TMZ 150 mg/m 2 /5 days, per 28-day cycle. Dose-limiting toxicity was assessed during the first 2 cycles. Neurocognitive function (NCF) testing was conducted throughout the study., Results: Eighteen patients were enrolled (13 GBM, IDH-wild type; 2 astrocytoma, IDH-mutant, grade 3; 3 astrocytoma, IDH-mutant, grade 4). Dose escalation was discontinued after DL3 (ie, PAC-1, 625 mg) due to lack of additional funding. Grade 3 toxicity was observed in 1 patient at DL1 (elevated liver transaminases) and 1 at DL 2 (headache). Two partial responses were observed at DL1 in patients with GBM, O 6 -methylguanine-DNA methyltransferase (MGMT) promoter methylated. Two patients had stable disease, and 11 experienced progression. NCF testing did not show a clear relationship between PAC-1 dose, treatment duration, and declines in NCF., Conclusions: Combination of PAC-1 and TMZ was well tolerated up to 625 mg orally daily and TMZ orally 150 mg/m 2 /5 days per 28-day cycle. The maximum tolerated dose was not reached. Further dose escalation of PAC-1 in combination with TMZ is advised before conducting a formal prospective efficacy study in this patient population., Competing Interests: The University of Illinois has filed a patent on PAC-1 in which T.M.T., T.F.M. and P.J.H. are inventors. The University of Illinois has licensed the patents on PAC-1 to Vanquish Oncology, Inc, and P.J.H. and T.M.F. serve as consultants for Vanquish Oncology, Inc. P.J.H. also serves as Chief Scientific Officer and has equity in Vanquish Oncology, Inc. T.M.T. serves as Chief Executive Officer and has equity in Vanquish Oncology, Inc. A.Z.D served as Chief Medical Officer in Vanquish Oncology. J.S.W. was a paid consultant to Vanquish Oncology, Inc. during this study. M.H. serves on a data safety monitoring board of Parexel and Advarra and a steering committee for Novartis., (© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Background: Mobile health (mHealth) is quickly expanding as a method of health promotion, but some interventions may not be familiar or comfortable for potential users. SMS text messaging has been investigated as a low-cost, accessible way to provide vaccine reminders. Most (97%) US adults own a cellphone and of those adults most use SMS text messaging. However, understanding patterns of SMS text message plan type and use in diverse primary care populations needs more investigation., Objective: We sought to use a survey to examine baseline SMS text messaging and data plan patterns among families willing to accept SMS text message vaccine reminders., Methods: As part of a National Institutes of Health (NIH)-funded national study (Flu2Text) conducted during the 2017-2018 and 2018-2019 influenza seasons, families of children needing a second seasonal influenza vaccine dose were recruited in pediatric primary care offices at the time of their first dose. Practices were from the American Academy of Pediatrics' (AAP) Pediatric Research in Office Settings (PROS) research network, the Children's Hospital of Philadelphia, and Columbia University. A survey was administered via telephone (Season 1) or electronically (Season 2) at enrollment. Standardized (adjusted) proportions for SMS text message plan type and texting frequency were calculated using logistic regression that was adjusted for child and caregiver demographics., Results: Responses were collected from 1439 participants (69% of enrolled). The mean caregiver age was 32 (SD 6) years, and most children (n=1355, 94.2%) were aged 6-23 months. Most (n=1357, 94.3%) families were English-speaking. Most (n=1331, 92.8%) but not all participants had an unlimited SMS text messaging plan and sent or received texts at least once daily (n=1313, 91.5%). SMS text messaging plan type and use at baseline was uniform across most but not all subgroups. However, there were some differences in the study population's SMS text messaging plan type and usage. Caregivers who wanted Spanish SMS text messages were less likely than those who chose English to have an unlimited SMS text messaging plan (n=61, 86.7% vs n=1270, 94%; risk difference -7.2%, 95% CI -27.1 to -1.8). There were no significant differences in having an unlimited plan associated with child's race, ethnicity, age, health status, insurance type, or caregiver education level. SMS text messaging use at baseline was not uniform across all subgroups. Nearly three-quarters (n=1030, 71.9%) of participants had received some form of SMS text message from their doctor's office; most common were appointment reminders (n=1014, 98.4%), prescription (n=300, 29.1%), and laboratory notifications (n=117, 11.4%). Even the majority (n=64, 61.5%) of those who did not have unlimited plans and who texted less than daily (n=72, 59%) reported receipt of these SMS text messages., Conclusions: In this study, most participants had access to unlimited SMS text messaging plans and texted at least once daily. However, infrequent texting and lack of access to an unlimited SMS text messaging plan did not preclude enrolling to receive SMS text message reminders in pediatric primary care settings., (©Chelsea S Wynn, Alexander G Fiks, Russell Localio, Justine Shults, Ekaterina Nekrasova, Laura P Shone, Alessandra Torres, Miranda Griffith, Rebecca Unger, Leigh Ann Ware, Mary Kate Kelly, Melissa S Stockwell. Originally published in JMIR Formative Research (https://formative.jmir.org), 30.06.2023.)

Abstract: The diagnosis of Duchenne and Becker muscular dystrophy (DBMD) is made by genetic testing in approximately 95% of cases. Although specific mutations can be associated with skeletal muscle phenotype, pulmonary and cardiac comorbidities (leading causes of death in Duchenne) have not been associated with Duchenne muscular dystrophy mutation type or location and vary within families. Therefore, identifying predictors for phenotype severity beyond frameshift prediction is important clinically. We performed a systematic review assessing research related to genotype-phenotype correlations in DBMD. While there are severity differences across the spectrum and within mild and severe forms of DBMD, few protective or exacerbating mutations within the dystrophin gene were reported. Except for intellectual disability, clinical test results reporting genotypic information are insufficient for clinical prediction of severity and comorbidities and the predictive validity is too low to be useful when advising families. Including expanded information coupled with proposed severity predictions in clinical genetic reports for DBMD is critical for improving anticipatory guidance., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)