Citations

OBJECTIVES: There is a paucity of literature regarding administrative approvals required for clinical studies during a pandemic. We aimed to evaluate variation in duration of administrative approvals within the Viral Infection and Respiratory illness Universal Study (VIRUS): A Global COVID-19 Registry. DESIGN, SETTING, AND SUBJECTS: Survey analysis of 188 investigators who participated in the VIRUS: COVID-19 registry, a prospective, observational global registry database of 287 sites. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For each study site approved through December 8, 2020, we assessed the duration in days: 1) from institutional review board (IRB) submission to IRB approval, 2) from IRB approval to Research Electronic Data Capture (REDCap) access, 3) from REDCap access to first patient data entry in REDCap, and 4) total duration from IRB submission to first patient data entry in REDCap. Analysis of variance and Wilcoxon rank-sum test were used to compare time durations. Of 287 sites, 188 sites (United States = 155, non-United States = 33) provided complete administrative data. There was considerable variability in duration from IRB submission to first patient data entry with median (interquartile range) of 28 days (16–50 d), with differences not significantly different by country (United States: 30 [17–50] vs non-United States: 23 d [8–46 d]; p = 0.08) or previous “multisite trial experience” (experienced: 27 [15–51] vs not experienced: 29 d [13–47 d]; p = 0.67). The U.S. sites had a higher proportion of female principal investigators (n = 77; 50%), compared with non-U.S. sites (n = 7; 21%; p = 0.002). Non-U.S. sites had a significantly shorter time to first patient data entry after REDCap access: 7 (1–28) versus 3 days (1–6 d) (p = 0.02). CONCLUSIONS: In this Society of Critical Care Medicine global VIRUS: COVID-19 Registry, we identified considerable variability in time from IRB submission to first patient data entry with no significant differences by country or prior multicenter trial experience. However, there was a significant difference between US and non-U.S. sites in the time from REDCap access to first data entry.

Background:: Breast cancer is one of the leading causes of cancer deaths in women. Early diagnosis offers the best hope for a cure. Ductal carcinoma in situ is considered a precursor of invasive ductal carcinoma of the breast. In this study, we carried out microRNA sequencing from 7 ductal carcinoma in situ (DCIS), 6 infiltrating ductal carcinomas (IDC Stage IIA) with paired normal, and 5 unpaired normal breast tissue samples. We identified 76 miRNAs that were differentially expressed in DCIS and IDC. Methods:: Additionally, we provide preliminary evidence of miR-365b-3p and miR-7-1-3p being overexpressed, and miR-6507-5p, miR-487b-3p, and miR-654-3p being downregulated in DCIS relative to normal breast tissue. We also identified a miRNA miR-766-3p that was overexpressed in early-stage IDCs. The overexpression of miR-301a-3p in DCIS and IDC was confirmed in 32 independent breast cancer tissue samples. Results:: Higher expression of miR-301a-3p is associated with poor overall survival in The Can-cer Genome Atlas Breast Cancer (TCGA-BRCA) dataset, indicating that it may be associated with DCIS at high risk of progressing to IDC and warrants deeper investigation. Conclusion:: We also analyzed competing endogenous networks associated with differentially expressed miRNAs and identified LRRC75A-AS1 and MAGI2-AS3 as lncRNAs that potentially play an important role in early-stage breast cancers.

Abstract Introduction . Dispersion in an accelerator quantifies the deviation of the proton trajectory when there is a momentum deviation. We present for the first time a safe method of measuring dispersion in the clinic, using a scintillator detector and the momentum deviations within a spill. This is an important accelerator quantity as we found that this is the reason behind the large dose fluctuation in our absolute dosimetry measurement. Methods . Dispersions are measured for nine energies in a Hitachi ProBeat system at three locations (isocenter and at two profile monitors) and at two gantry angles (0 and 90 degrees) by first measuring the spot position and momentum drift within a spill. The spot position drift is measured by the XRV-4000 at the isocenter, and by the two profile monitors located at 0.57 and 2.27 m from the isocenter. The momentum drift is calculated from the intra-spill range drift which is measured using the Ranger accessory. The dispersion at isocenter and its gradient are calculated using the weighted least square regression on the measured dispersions at the three locations. A constraint is formulated on the dispersion and its gradient to ensure minimal intra-spill spot position deviation around the isocenter. Results . The measured intra-spill range and spot positional drift at isocenter are less than 0.25 mm and 0.7 mm respectively. The momentum spread calculated from the range drift are less than 0.08%. The dispersion at the isocenter ranged from 0.50 to 4.30 m and the zero-crossing happens upstream of isocenter for all energies. 2 of the 9 energies (168.0 and 187.5 MeV) violated the constraint and has an intra-spill spot positional deviation greater than 1.0 within 5 cm from the isocenter. Conclusion . This measurement is recommended as part of commissioning and annual quality assurance for accelerator monitoring and to ensure intra-spill spot deviations remain low.

Abstract Purpose Clinical practice guidelines recommend altering neurotoxic chemotherapy treatment in patients experiencing intolerable chemotherapy-induced peripheral neuropathy (CIPN). The primary objective of this survey was to understand patient’s perspectives on altering neurotoxic chemotherapy treatment, including their perceptions of the benefits of preventing irreversible CIPN and the risks of reducing treatment efficacy.Methods A cross-sectional online survey was distributed via social networks to patients who were currently receiving or had previously received neurotoxic chemotherapy for cancer. Survey results were analyzed using descriptive statistics and qualitative analysis.Results Following data cleaning, 447 participants were included in the analysis. The median age was 57 years, 93% were white, and most were from the United Kingdom (53%) or United States of America (38%). Most participants who were currently or recently treated expected some CIPN symptom resolution (86%), but 45% of those who had completed treatment more than a year ago reported experiencing no symptom resolution. Participants reported that they would discontinue chemotherapy treatment for less severe CIPN if they knew their symptoms would be permanent than if symptoms would disappear after treatment. Most patients stated that the decision to alter chemotherapy or not was usually made collaboratively between the patient and their treating clinician (61%). The most common reason participants were reluctant to talk with their clinician about CIPN was fear that treatment would be altered. Participants noted a need for improved understanding of CIPN symptoms and their permanence, better patient education relating to CIPN prior to and after treatment, and greater clinician understanding and empathy around CIPN.Conclusions This survey highlights the importance of shared decision-making, including a consideration of both the long-term benefits and risks of altering neurotoxic chemotherapy treatment due to CIPN. Additional work is needed to develop decision aids and other communication tools that can be used to improve shared decision making and help patients with cancer achieve their treatment goals.

This study explores US medical students’ intent to practice in underserved areas, analyzed by demographic characteristics.

Abstract Idecabtagene vicleucel (ide-cel) was the first chimeric antigen receptor T-cell therapy to gain US Food and Drug Administration approval for patients with relapsed/refractory multiple myeloma (RRMM). The clinical outcomes of standard of care (SOC) ide-cel in racially and ethnically diverse populations have been understudied. This study pooled data from 207 patients with RRMM (28% patients of racial and ethnic minority groups) treated with SOC ide-cel across 11 institutions to examine racial and ethnic differences in the incidence of toxicities and adverse events, response to ide-cel, and survival. This study included 22 (11%) Hispanic, 36 (17%) non-Hispanic Black, and 149 (72%) non-Hispanic White patients with RRMM. Compared with Hispanic and non-Hispanic White patients, non-Hispanic Black patients had higher median levels of C-reactive protein (1.0, 0.8, and 3.5 mg/dL, respectively; P = .02) and baseline ferritin (362.0 vs 307.0 vs 680.5, respectively; P = .08) and were more likely to develop cytokine release syndrome (77%, 85%, and 97%, respectively; P = .04). Although best overall response rate was lower among Hispanic patients (59%) than among non-Hispanic Black (86%) and White patients (86%; P = .01), there were no racial and ethnic differences in progression-free or overall survival. We provide, to our knowledge, the first and largest investigation of clinical outcomes of SOC ide-cel by race and ethnicity. Despite differences in safety and response to ide-cel, our findings encourage the use of ide-cel in all patients with RRMM. These findings should be confirmed in larger samples of diverse patients with RRMM, with longer follow-up time.

OBJECTIVES: To systematically review literature describing the clinical presentation, risk factors, and treatment for dexmedetomidine withdrawal in the PICU (PROSPERO: CRD42022307178). DATA SOURCES: MEDLINE/PubMed, Cochrane, Web of Science, and Scopus databases were searched. STUDY SELECTION: Eligible studies were published from January 2000 to January 2022 and reported clinical data for patients younger than 21 years old following discontinuation of dexmedetomidine after greater than or equal to 24 hours of infusion. DATA EXTRACTION: Abstracts identified during an initial search were screened and data were manually abstracted after full-text review of eligible articles. The Newcastle-Ottawa Scale was used to assess study quality. Summary statistics were provided and Spearman rank correlation coefficient was used to identify relationships between covariates and withdrawal signs. A weighted prevalence for each withdrawal sign was generated using a random-effects model. DATA SYNTHESIS: Twenty-three studies (22 of which were retrospective cohort studies) containing 28 distinct cohorts were included. Median cumulative dexmedetomidine exposure by dose was 105.95 μg/kg (range, 30–232.7 μg/kg), median dexmedetomidine infusion duration was 131.75 hours (range, 20.5–525.6 hr). Weighted estimates for proportion (95% CI) of subjects experiencing withdrawal signs across all cohorts were: hypertension 0.34 (range, 0.0–0.92), tachycardia 0.26 (range, 0.0–0.87), and agitation 0.26 (range, 0.09–0.77). Meta-analysis revealed no correlation between dexmedetomidine exposure variables and withdrawal signs. A moderate negative monotonic relationship existed between the proportion of patients who had undergone cardiac surgery and the proportion experiencing hypertension (correlation coefficient, –0.47; p = 0.048) and tachycardia (correlation coefficient, –0.57; p = 0.008), indicating that in cohorts with a higher proportion of patients who were postcardiac surgery, there were fewer occurrences of hypertension and or tachycardia. CONCLUSIONS: On review of the 2000–2022 literature, dexmedetomidine withdrawal may be characterized by tachycardia, hypertension, or agitation, particularly with higher cumulative doses or prolonged durations. Since most studies included in the review were retrospective, prospective studies are needed to further clarify risk factors, establish diagnostic criteria, and identify optimal management strategies.

Purpose To describe injury epidemiology in U.S. adolescent tennis players between 2014 and 2018 via the High School Reporting Information Online (HS RIO) database. Methods The HS RIO database was queried for injury data on high school tennis players as reported by athletic trainers between 2014 and 2018. Injuries were analyzed according to athlete demographics, injury type, location, and context. Variables of interest between male and female athletes were compared using Pearson χ 2 test or Fisher exact test. Results In total, 176 injuries in high school tennis players between 2014 and 2018 were identified in the HS RIO database. Overall, 25.6% (45/176) occurred in the ankle, 12.5% (22/176) in the knee, and 9.7% (17/176) in the wrist. The most common types of injuries were ligament sprains and muscle strains at 35.2% (62/176) and 17.6% (31/176) of injuries, respectively. Although most injuries were unrelated to contact, such as overuse and heat exertion or stroke, 28.7% (47/176) of injuries were the result of rotation around a planted foot/inversion of the foot. We found no difference in injury patterns between male and female high school tennis athletes. Conclusions We found no difference in injury patterns between male and female U.S. high school tennis athletes. The ankles, knees, and wrists were the most commonly injured areas in this population. The most common types of injuries were ligament sprains and muscle strains. Although many injuries were new, athletes rarely required surgery and returned to play. Finally, we found no difference in injury patterns between male and female high school tennis athletes. Clinical Relevance The epidemiology of injuries among high school tennis players is poorly understood. The information from this study will help us to understand these injuries and how we may be able to better prevent them.

Abstract The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs.