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Background and Aims: Association of American Medical Colleges (AAMC) and Accreditation Council for Graduate Medical Education (ACGME) mandate training in handoff delivery for students and residents. Communication errors, including errors during handoffs of patient care, account for over 2/3 of sentinel events. This study aims to assess the effectiveness of peer-assisted learning (PAL) in handoff education within a longitudinal framework. Methods: This study involved the analysis of fourth-year medical students (n = 67) enrolled in a transition to residency program designed to reinforce skills essential for success in internal medicine residencies. We modified the I-PASS handoff rubric for a single-encounter evaluation. Before attending the transitions of care workshop, students submitted one written handoff report. During high-fidelity simulation sessions, peers evaluated the written document as well as verbal handoffs, while faculty evaluated a recorded verbal version. The primary outcome measured was improvement in handoff quality and accuracy over time and secondary outcomes compared peer- and self-evaluations to faculty assessments. Results: Overall, students demonstrated a statistically significant improvement in handoff quality and accuracy across all scoring criteria after completing the peer evaluation process. Peer evaluations did not demonstrate statistically significant differences in scores for quality or accuracy questions as compared to faculty. Conclusion: Peer evaluators effectively assessed handoff reports using the modified I-PASS checklist yielding outcomes similar to faculty while providing feedback. These findings provide exciting evidence that should prompt training programs to consider incorporating standardized peer review into handoff education for medical students and, potentially, residents. The detailed evaluation of individual handoff events fosters feedback skills essential for ongoing professional growth and clinical excellence.
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BACKGROUND: Patients from ethnic and racial minority groups with primary hyperparathyroidism may have greater time delays to curative parathyroidectomy. Contributing factors are unclear. METHODS: This was a sequential mixed-methods study. The quantitative phase was a retrospective chart review of adults with primary hyperparathyroidism who underwent parathyroidectomy between 2015 and 2020, collecting demographic and clinical data. Social vulnerability of the patients' residential area, measured with the Social Vulnerability Index, and relevant clinical time intervals were calculated. A multivariable analysis of factors associated with greater time intervals was performed. The qualitative phase involved semistructured interviews with endocrinologists, analyzed inductively for themes. RESULTS: On chart review of 1,083 patients, the median age was determined to be 61 years and 856 (79%) were female. Six hundred twenty-eight (57.9%) were non-Hispanic White and 456 (42.1%) were Hispanic ethnicity or Asian, Pacific Islander, Black, Native American, Other or Unknown race. Patients of Hispanic ethnicity, or Asian or Pacific Islander, Black, Native American, Other or Unknown race were more likely than non-Hispanic White patients to live in the most socially vulnerable areas (19.3% vs 5.9%, P < .01) and had greater time intervals than non-Hispanic White patients between index hypercalcemia and first parathyroid hormone level, surgical referral, or parathyroidectomy (all P < .05). On multivariable analysis, age (coefficient 7.9, 95% CI 2.8-13.0) and living in the most socially vulnerable areas (coefficient 297.9, 95% CI 87-508.7) were associated with greater days between index hypercalcemia and parathyroidectomy. In the study's qualitative phase, identified themes for reasons for care delays included socioeconomic, nonsocioeconomic patient, and nonsocioeconomic nonpatient factors. CONCLUSION: Care delays are driven by a combination of socioeconomic and nonsocioeconomic factors.
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ADCK3 is a member of the UbiB family of atypical protein kinases in humans, with homologues in archaea, bacteria, and eukaryotes. In lieu of protein kinase activity, ADCK3 plays a role in the biosynthesis of coenzyme Q10 (CoQ10), and inactivating mutations can cause a CoQ10 deficiency and ataxia. However, the exact functions of ADCK3 are still unclear, and small-molecule inhibitors could be useful as chemical probes to elucidate its molecular mechanisms. In this study, we applied structure-based virtual screening (VS) to discover a novel chemical series of ADCK3 inhibitors. Through extensive structural analysis of the active-site residues, we developed a pharmacophore model and applied it to a large-scale VS. Out of â¼170,000 compounds virtually screened, 800 top-ranking candidate compounds were selected and tested in both ADCK3 and p38 biochemical assays for hit validation. In total, 129 compounds were confirmed as ADCK3 inhibitors, and among them, 114 compounds are selective against p38, which was used as a counter-target. Molecular dynamics (MD) simulations were then conducted to predict the binding modes of the most potent compounds within the ADCK3 active site. Through metadynamics analysis, we successfully detected the key amino acid residues that govern intermolecular interactions. The findings provided in this study can serve as a promising starting point for drug development.
Subject(s)
Drug Evaluation, Preclinical , Molecular Dynamics Simulation , Protein Kinase Inhibitors , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/metabolism , Humans , Molecular Docking Simulation , Catalytic Domain , User-Computer Interface , p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors , p38 Mitogen-Activated Protein Kinases/metabolism , p38 Mitogen-Activated Protein Kinases/chemistryABSTRACT
There is a critical need to understand the effectiveness of serum elicited by different SARS-CoV-2 vaccines against SARS-CoV-2 variants. We describe the generation of reference reagents comprised of post-vaccination sera from recipients of different primary vaccines with or without different vaccine booster regimens in order to allow standardized characterization of SARS-CoV-2 neutralization in vitro. We prepared and pooled serum obtained from donors who received a either primary vaccine series alone, or a vaccination strategy that included primary and boosted immunization using available SARS-CoV-2 mRNA vaccines (BNT162b2, Pfizer and mRNA-1273, Moderna), replication-incompetent adenovirus type 26 vaccine (Ad26.COV2·S, Johnson and Johnson), or recombinant baculovirus-expressed spike protein in a nanoparticle vaccine plus Matrix-M adjuvant (NVX-CoV2373, Novavax). No subjects had a history of clinical SARS-CoV-2 infection, and sera were screened with confirmation that there were no nucleocapsid antibodies detected to suggest natural infection. Twice frozen sera were aliquoted, and serum antibodies were characterized for SARS-CoV-2 spike protein binding (estimated WHO antibody binding units/ml), spike protein competition for ACE-2 binding, and SARS-CoV-2 spike protein pseudotyped lentivirus transduction. These reagents are available for distribution to the research community (BEI Resources), and should allow the direct comparison of antibody neutralization results between different laboratories. Further, these sera are an important tool to evaluate the functional neutralization activity of vaccine-induced antibodies against emerging SARS-CoV-2 variants of concern. IMPORTANCE: The explosion of COVID-19 demonstrated how novel coronaviruses can rapidly spread and evolve following introduction into human hosts. The extent of vaccine- and infection-induced protection against infection and disease severity is reduced over time due to the fall in concentration, and due to emerging variants that have altered antibody binding regions on the viral envelope spike protein. Here, we pooled sera obtained from individuals who were immunized with different SARS-CoV-2 vaccines and who did not have clinical or serologic evidence of prior infection. The sera pools were characterized for direct spike protein binding, blockade of virus-receptor binding, and neutralization of spike protein pseudotyped lentiviruses. These sera pools were aliquoted and are available to allow inter-laboratory comparison of results and to provide a tool to determine the effectiveness of prior vaccines in recognizing and neutralizing emerging variants of concern.
Subject(s)
2019-nCoV Vaccine mRNA-1273 , Antibodies, Neutralizing , Antibodies, Viral , BNT162 Vaccine , COVID-19 Vaccines , COVID-19 , Neutralization Tests , SARS-CoV-2 , Humans , SARS-CoV-2/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/prevention & control , COVID-19/immunology , COVID-19/virology , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , 2019-nCoV Vaccine mRNA-1273/immunology , BNT162 Vaccine/immunology , BNT162 Vaccine/administration & dosage , Spike Glycoprotein, Coronavirus/immunology , Reference Standards , Immunization, Secondary , Vaccination , Ad26COVS1/immunologyABSTRACT
Alagille syndrome (ALGS) is an autosomal dominant, multisystemic disorder due to haploinsufficiency in JAG1 or less frequently, mutations in NOTCH2. The disease has been difficult to diagnose and treat due to variable expression. The generation of this iPSC line (TRNDi036-A) carrying a heterozygous mutation (p.Cys693*) in the JAG1 gene provides a means of studying the disease and developing novel therapeutics towards patient treatment.
Subject(s)
Alagille Syndrome , Heterozygote , Induced Pluripotent Stem Cells , Jagged-1 Protein , Mutation , Alagille Syndrome/genetics , Humans , Jagged-1 Protein/genetics , Jagged-1 Protein/metabolism , Induced Pluripotent Stem Cells/metabolism , Cell Line , Male , FemaleABSTRACT
INTRODUCTION: Hypertension (HT) is a major public health problem globally, and it is the commonest chronic disease with a prevalence of 27% among people aged 15 years or above in Hong Kong. There is emerging literature confirmed that patients with resistant hypertension (RHT) give its increased risk for adverse clinical outcomes and higher rate of documented target organ damage. This study aims to identify the prevalence of RHT among Chinese hypertensive patients managed in public primary care setting of Hong Kong and exploring its associated risk factors. METHODOLOGY: This is a cross-sectional descriptive study. Chinese hypertensive patients aged 30 or above with regular follow-up between 1st July 2019 and 30th June 2020 in 10 public primary care clinics under the Hospital Authority of Hong Kong were included. Demographic data, clinical parameters and drug profile of patients were retrieved from its computerized record system. The prevalence of RHT was identified and the associated risk factors of RHT were explored by multivariate logistic regression analysis. RESULTS: Among the 538 sampled Chinese hypertensive patients, the mean age was 67.4 ± 11.5 years old, and 51.9% were female. The mean duration of hypertension was 10.1 ± 6.4 years, with a mean systolic and diastolic blood pressure of 128.8 ± 12.3 and 72.9 ± 10.8 mmHg respectively. 40 out of 538 patients were found to have RHT, giving an overall prevalence of 7.43%. Four factors were found to be associated with increased risk of RHT, in ascending order of odds ratio: duration of hypertension (OR 1.08), male gender (OR 2.72), comorbid with type 2 diabetes mellitus (T2DM, OR 2.99), and congestive heart failure (CHF, OR 5.39). CONCLUSION: The prevalence of RHT among Chinese hypertensive patients in primary care setting of Hong Kong is 7.43%. RHT is more common in male patients, patients with longer duration of hypertension, concomitant T2DM and CHF. Clinicians should be vigilant when managing these groups of patients and provide aggressive treatment and close monitoring.
Subject(s)
Diabetes Mellitus, Type 2 , Hypertension , Humans , Male , Female , Middle Aged , Aged , Prevalence , Antihypertensive Agents/therapeutic use , Cross-Sectional Studies , Hypertension/drug therapy , Hypertension/epidemiology , Risk Factors , Hong Kong/epidemiology , Primary Health CareABSTRACT
Language comprehension involves integrating low-level sensory inputs into a hierarchy of increasingly high-level features. Prior work studied brain representations of different levels of the language hierarchy, but has not determined whether these brain representations are shared between written and spoken language. To address this issue, we analyze fMRI BOLD data that were recorded while participants read and listened to the same narratives in each modality. Levels of the language hierarchy are operationalized as timescales, where each timescale refers to a set of spectral components of a language stimulus. Voxelwise encoding models are used to determine where different timescales are represented across the cerebral cortex, for each modality separately. These models reveal that between the two modalities timescale representations are organized similarly across the cortical surface. Our results suggest that, after low-level sensory processing, language integration proceeds similarly regardless of stimulus modality.
Subject(s)
Language , Reading , Humans , Cerebral Cortex/diagnostic imaging , Brain , Brain Mapping/methodsABSTRACT
BACKGROUND: Decisions regarding resuscitation after cardiac arrest are critical from ethical, patient satisfaction, outcome, and healthcare cost standpoints. Physician-reported discussion barriers include topic discomfort, fear of time commitment, and difficulty articulating end-of-life concepts. The influence of language used in these discussions has not been tested. This study explored whether utilizing the alternate term "allow (a) natural death" changed code status decisions in hospitalized patients versus "do not resuscitate" (DNR). METHODS: All patients age 65 and over admitted to a general medicine hospital teaching service were screened (English-speaking, not ICU-level care, no active psychiatric illness, no substance misuse, no active DNR). Participants were randomized to resuscitation discussions with either DNR or "allow natural death" as the "no code" phrasing. Outcomes included patient resuscitation decision, satisfaction with and duration of the conversation, and decision correlation with illness severity and predicted resuscitation success. RESULTS: 102 participants were randomized to the "allow natural death" (N = 49) or DNR (N = 53) arms. The overall "no code" rate for our sample of hospitalized general medicine inpatients age >65 was 16.7%, with 13% in the DNR and 20.4% in the "allow natural death" arms (p = 0.35). Discussion length was similar in the DNR and "allow natural death" arms (3.9 + 3.2 vs. 4.9 + 3.9 minutes), and not significantly different (p = 0.53). Over 90% of participants were highly satisfied with their code status decision, without difference between arms (p = 0.49). CONCLUSIONS: Participants' code status discussions did not differ in "no code" rate between "allow natural death" and DNR arms but were short in length and had high patient satisfaction. Previously reported code status discussion barriers were not encountered. It is appropriate to screen code status in all hospitalized patients regardless of phrasing used.
Subject(s)
Heart Arrest , Resuscitation Orders , Humans , Male , Female , Resuscitation Orders/ethics , Resuscitation Orders/psychology , Aged , Heart Arrest/therapy , Patient Satisfaction , Aged, 80 and over , Decision Making/ethicsABSTRACT
BACKGROUND: The maternal mortality rate in the United States is unacceptably high. However, the relative contribution of pregnancy to these outcomes is unknown. Studies comparing outcomes among pregnant vs nonpregnant critically ill patients show mixed results and are limited by small sample sizes. RESEARCH QUESTION: What is the association of pregnancy with critical illness outcomes? STUDY DESIGN AND METHODS: We performed a retrospective cohort study of women 18 to 55 years of age who received invasive mechanical ventilation (MV) on hospital day 0 or 1 or who demonstrated sepsis on admission (infection with organ failure) discharged from Premier Healthcare Database hospitals from 2008 through 2021. The exposure was pregnancy. The primary outcome was in-hospital mortality. We created propensity scores for pregnancy (using patient and hospital characteristics) and performed 1:1 propensity score matching without replacement within age strata (to ensure exact age matching). We performed multilevel multivariable mixed-effects logistic regression for propensity-matched pairs with pair as a random effect. RESULTS: Three thousand ninety-three pairs were included in the matched MV cohort, and 13,002 pairs were included in the sepsis cohort. The characteristics of both cohorts were well balanced (all standard mean differences, < 0.1). Among matched pairs, unadjusted mortality was 8.0% vs 13.8% for MV and 1.4% vs 2.3% for sepsis among pregnant and nonpregnant patients, respectively. In adjusted regression, pregnancy was associated with lower odds of in-hospital mortality (MV: OR, 0.50; 95% CI, 0.41-0.60; P < .001; sepsis: OR, 0.52; 95% CI, 0.40-0.67; P < .001). INTERPRETATION: In this large US cohort, critically ill pregnant women receiving MV or with sepsis showed better survival than propensity score-matched nonpregnant women. These findings must be interpreted in the context of likely residual confounding.
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OBJECTIVES: In Korea, the National Health Insurance Service (NHIS) covers essential healthcare expenses, including cataract surgery. To address concerns that private health insurance (PHI) might have inflated the need for such procedures, we investigated the extent of the PHI-attributable increase in cataract surgery and its impact on NHIS-reimbursed expenses. METHODS: This retrospective, observational study uses nationwide claims data for cataract surgery from 2016 to 2020. We examined trends in utilization and cost, and we estimated the excess numbers of (1) cataract operations attributable to PHI and (2) types of intraocular lenses used for cataract surgery in 2020. RESULTS: Between 2016 and 2020, a 36.8% increase occurred in the number of cataract operations, with increases of 63.5% and 731.8% in the total healthcare costs reimbursed by NHIS and PHI, respectively. Over a 5-year period, the surgical rate per 100,000 people doubled for patients aged <65 years (from 328 in 2016 to 664 in 2020). Among the 619,771 cases in 2020 of cataract surgery reimbursed by the Korean diagnosis-related group system, more non-NHIS-covered intraocular lenses were used for patients aged <65 years than ≥65 years (68.1 vs. 14.2%). In 2020 alone, an estimated 129,311 excess operations occurred, accounting for an excess cost of US$115 million. CONCLUSIONS: A dramatic increase in the number and cost of cataract operations has occurred over the last 5 years. The PHI-related increase in operations resulted in increased costs to NHIS. Measures to curtail the non-indicated use of cataract surgery should be implemented regarding PHI.
Subject(s)
Cataract Extraction , National Health Programs , Humans , Republic of Korea/epidemiology , Cataract Extraction/statistics & numerical data , Retrospective Studies , Aged , Middle Aged , Male , Female , Insurance, Health/statistics & numerical data , Private Sector/statistics & numerical data , AdultABSTRACT
OBJECTIVES: Few data on alveolar hypoventilation in Prader-Willi syndrome (PWS) are available and the respiratory follow-up of these patients is not standardized. The objectives of this study were to evaluate the prevalence of alveolar hypoventilation in children with PWS and identify potential risk factors. STUDY DESIGN: This retrospective study included children with PWS recorded by polysomnography (PSG) with transcutaneous carbon dioxide pressure (PtcCO2) or end-tidal CO2 (ETCO2) measurements, between 2007 and 2021, in a tertiary hospital center. The primary outcome was the presence of alveolar hypoventilation defined as partial pressure of carbon dioxide (pCO2) ≥ 50 mmHg during ≥2% of total sleep time (TST) or more than five consecutive minutes. RESULTS: Among the 57 included children (38 boys, median age 4.8 years, range 0.1-15.6, 60% treated with growth hormone [GH], 37% obese), 19 (33%) had moderate-to-severe obstructive sleep apnea syndrome (defined as obstructive apnea-hypopnea index ≥5/h) and 20 (35%) had hypoventilation. The median (range) pCO2 max was 49 mmHg (38-69). Among the children with hypoventilation, 25% were asymptomatic. Median age and GH treatment were significantly higher in children with hypoventilation compared to those without. There was no significant difference in terms of sex, BMI, obstructive or central apnea-hypopnea index between both groups. CONCLUSION: The frequency of alveolar hypoventilation in children and adolescents with PWS is of concern and may increase with age and GH treatment. A regular screening by oximetry-capnography appears to be indicated whatever the sex, BMI, and rate of obstructive or central apneas.
Subject(s)
Prader-Willi Syndrome , Sleep Apnea, Obstructive , Male , Adolescent , Child , Humans , Infant , Child, Preschool , Hypoventilation/etiology , Hypoventilation/complications , Prader-Willi Syndrome/complications , Prader-Willi Syndrome/epidemiology , Retrospective Studies , Carbon Dioxide , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/epidemiology , Sleep Apnea, Obstructive/diagnosisABSTRACT
Climate change undeniably impacts the social and environmental determinants of one's health. The healthcare sector, encompassing medications and the pharmaceutical industry supply chain, accounts for a significant portion of global health care contributions to greenhouse gas (GHG) and waste production. Despite these realities, healthcare professionals - physicians, pharmacists, nurses, and others - may be unaware of GHG emissions and the long-term environmental effects of the medications they prescribe, dispense, and administer daily. In this commentary, we identify existing challenges and explore potential strategies to recognize and reduce the climate change impacts associated with medication use.
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Greenhouse Effect , Greenhouse Gases , Humans , Greenhouse Gases/analysis , Global HealthABSTRACT
PURPOSE: We sought to evaluate the synergistic risk of postoperative thrombosis in patients with a history of COVID-19 who undergo major surgery. Major surgery and SARS-CoV-2 infection are independently associated with an increased risk of thrombosis, but the magnitude of additional risk beyond surgery conferred by a COVID-19 history on the development of perioperative thrombotic events has not been clearly elucidated in the literature. METHODS: We conducted a retrospective cohort study among commercially insured adults in the USA from March 2020 to June 2021 using the Optum Labs Data Warehouse (OLDW), a longitudinal, real-world data asset containing deidentified administrative claims and electronic health records. We compared patients with prior COVID-19 who underwent surgery with control individuals who underwent surgery without a COVID-19 history and with control individuals who did not undergo surgery with and without a COVID-19 history. We assessed the interaction of surgery and previous COVID-19 on perioperative thrombotic events (venous thromboembolism and major adverse cardiovascular events) within 90 days using multivariable logistic regression and interaction analysis. RESULTS: Two million and two-hundred thousand eligible patients were identified from the OLDW. Patients in the surgical cohorts were older and more medically complex than nonsurgical population controls. After adjusting for confounders, only surgical exposure-not COVID-19 history-remained associated with perioperative thrombotic events (adjusted odds ratio [aOR], 4.07; 95% confidence interval [CI], 3.81 to 4.36). The multiplicative interaction term (aOR, 1.25; 95% CI, 0.96 to 1.61) and the synergy index (0.76; 95% CI, 0.56 to 1.04) suggest minimal effect modification of prior COVID-19 on surgery with regards to overall thrombotic risk. CONCLUSIONS: We found no evidence of synergistic thrombotic risk from previous COVID-19 in patients who underwent selected major surgery relative to the baseline thrombotic risk from surgery alone.
RéSUMé: OBJECTIF: Nous avons cherché à évaluer le risque synergique de thrombose postopératoire chez les patient·es ayant des antécédents de COVID-19 qui bénéficient d'une intervention chirurgicale majeure. La chirurgie majeure et l'infection par le SRAS-CoV-2 sont indépendamment associées à un risque accru de thrombose, mais l'ampleur du risque supplémentaire d'apparition de complications thrombotiques périopératoires, au-delà de la chirurgie et conféré par des antécédents de COVID-19, n'a pas été clairement élucidée dans la littérature. MéTHODE: Nous avons mené une étude de cohorte rétrospective auprès d'adultes assuré·es commercialement aux États-Unis de mars 2020 à juin 2021 à l'aide de la base de données Optum Labs Data Warehouse (OLDW), un actif de données longitudinales du monde réel contenant des requêtes administratives anonymisées et des dossiers de santé électroniques. Nous avons comparé les patient·es ayant déjà souffert de COVID-19 et ayant bénéficié d'une intervention chirurgicale avec des personnes témoins ayant bénéficié d'une intervention chirurgicale sans antécédents de COVID-19 et avec des personnes témoins n'ayant pas bénéficié de chirurgie, avec et sans antécédents de COVID-19. Nous avons évalué l'interaction de la chirurgie et des antécédents de COVID-19 avec les complications thrombotiques périopératoires (thromboembolie veineuse et événements cardiovasculaires indésirables majeurs) dans les 90 jours à l'aide d'une régression logistique multivariée et d'une analyse des interactions. RéSULTATS: Deux millions deux cent mille personnes admissibles ont été identifiées à partir du registre OLDW. Les patient·es des cohortes chirurgicales étaient plus âgé·es et présentaient une plus grande complexité médicale que les personnes témoins de la population non chirurgicale. Après ajustement pour tenir compte des facteurs de confusion, seule l'exposition chirurgicale et non les antécédents de COVID-19 est restée associée aux complications thrombotiques périopératoires (rapport de cotes ajusté [RCa], 4,07; intervalle de confiance [IC] à 95 %, 3,81 à 4,36). Le terme d'interaction multiplicative (RCa, 1,25; IC 95 %, 0,96 à 1,61) et l'indice de synergie (0,76; IC 95 %, 0,56 à 1,04) suggèrent une modification minimale de l'effet d'un diagnostic antérieur de COVID-19 sur la chirurgie en matière de risque thrombotique global. CONCLUSION: Nous n'avons trouvé aucune preuve de risque thrombotique synergique lié à une COVID-19 antérieure chez les patient·es ayant bénéficié d'une intervention chirurgicale par rapport au risque thrombotique de base lié à la chirurgie seule.
Subject(s)
COVID-19 , Thrombosis , Venous Thromboembolism , Adult , Humans , United States/epidemiology , Retrospective Studies , COVID-19/epidemiology , SARS-CoV-2 , Thrombosis/epidemiology , Thrombosis/etiology , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiologyABSTRACT
BACKGROUND: Pediatric renal trauma is rare and lacks sufficient population-specific data to generate evidence-based management guidelines. A non-operative approach is preferred and has been shown to be safe. However, bleeding risk assessment and management of collecting system injury is not well understood. We introduce the Multi-institutional Pediatric Acute Renal Trauma Study (Mi-PARTS), a retrospective cohort study designed to address these questions. This manuscript describes the demographics and contemporary management of pediatric renal trauma at Level I trauma centers in the United States. METHODS: Retrospective data were collected at 13 participating Level I trauma centers on pediatric patients presenting with renal trauma between 2010-2019. Data were gathered on demographics, injury characteristics, management, and short-term outcomes. Descriptive statistics were used to report on demographics, acute management and outcomes. RESULTS: In total 1216 cases were included in this study. 67.2% were male, and 93.8% had a blunt injury mechanism. 29.3% had isolated renal injuries. 65.6% were high-grade (AAST Grade III-V) injuries. The mean Injury Severity Score (ISS) was 20.5. Most patients were managed non-operatively (86.4%) 3.9% had an open surgical intervention, including 2.7% having nephrectomy. Angioembolization was performed in 0.9%. Collecting system intervention was performed in 7.9%. Overall mortality was 3.3% and was only observed in polytrauma. The rate of avoidable transfer was 28.2%. CONCLUSION: The management and outcomes of pediatric renal trauma lacks data to inform evidence-based guidelines. Non-operative management of bleeding following renal injury is a well-established practice. Intervention for renal trauma is rare. Our findings reinforce differences from the adult population, and highlights opportunities for further investigation. With data made available through Mi-PARTS we aim to answer pediatric specific questions, including a pediatric-specific bleeding risk nomogram, and better understanding indications for interventions for collecting system injuries. LEVEL OF EVIDENCE: IV, Epidemiological (prognostic/epidemiological, therapeutic/care management, diagnostic test/criteria, economic/value-based evaluations, and Systematic Review and Meta-Analysis).
ABSTRACT
Alagille syndrome (ALGS) is an autosomal dominant, multisystemic disorder due to haploinsufficiency in either the JAG1 gene (ALGS type 1) or the NOTCH2 gene (ALGS type 2). The disease has been difficult to diagnose and treat due to its muti-system clinical presentation, variable expressivity, and prenatal onset for some of the features. The generation of this iPSC line (TRNDi032-A) carrying a heterozygous mutation, p.Cys682Leufs*7 (c.2044dup), in the JAG1 gene provides a means of studying the disease and developing novel therapeutics towards patient treatment.
Subject(s)
Alagille Syndrome , Induced Pluripotent Stem Cells , Humans , Alagille Syndrome/genetics , Alagille Syndrome/diagnosis , Alagille Syndrome/metabolism , Induced Pluripotent Stem Cells/metabolism , Jagged-1 Protein/genetics , Jagged-1 Protein/metabolism , Mutation/geneticsABSTRACT
BACKGROUND: Pediatric trauma triage and transfer decisions should incorporate the likelihood that an injured child will require pediatric trauma center (PTC) resources. Resource utilization may be a better basis than mortality risk when evaluating pediatric injury severity. However, there is currently no consensus definition of PTC resource utilization that encompasses the full scope of PTC services. METHODS: Consensus criteria were developed in collaboration with the Pediatric Trauma Society (PTS) Research Committee using a modified Delphi approach. An expert panel was recruited representing the following pediatric disciplines: prehospital care, emergency medicine, nursing, general surgery, neurosurgery, orthopedics, anesthesia, radiology, critical care, child abuse, and rehabilitation medicine. Resource utilization criteria were drafted from a comprehensive literature review, seeking to complete the following sentence: "Pediatric patients with traumatic injuries have used PTC resources if they..." Criteria were then refined and underwent three rounds of voting to achieve consensus. Consensus was defined as agreement of 75% or more panelists. Between the second and third voting rounds, broad feedback from attendees of the PTS annual meeting was obtained. RESULTS: The Delphi panel consisted of 18 members from 15 institutions. Twenty initial draft criteria were developed based on literature review. These criteria dealt with airway interventions, vascular access, initial stabilization procedures, fluid resuscitation, blood product transfusion, abdominal trauma/solid organ injury management, intensive care monitoring, anesthesia/sedation, advanced imaging, radiologic interpretation, child abuse evaluation, and rehabilitative services. After refinement and panel voting, 14 criteria achieved the >75% consensus threshold. The final consensus criteria were reviewed and endorsed by the PTS Guidelines Committee. CONCLUSIONS: This study defines multidisciplinary consensus-based criteria for PTC resource utilization. These criteria are an important step toward developing a gold standard, resource-based, pediatric injury severity metric. Such metrics can help optimize system-level pediatric trauma triage based on likelihood of requiring PTC resources. LEVEL OF EVIDENCE/STUDY TYPE: Level II, diagnostic test/criteria.
ABSTRACT
Liver Transplantation is complicated by recurrent fibrosis in 40% of recipients. We evaluated the ability of clinical and radiomic features to flag patients at risk of developing future graft fibrosis. CT scans of 254 patients at 3-6 months post-liver transplant were retrospectively analyzed. Volumetric radiomic features were extracted from the portal phase using an Artificial Intelligence-based tool (PyRadiomics). The primary endpoint was clinically significant (≥F2) graft fibrosis. A 10-fold cross-validated LASSO model using clinical and radiomic features was developed. In total, 75 patients (29.5%) developed ≥F2 fibrosis by a median of 19 (4.3-121.8) months. The maximum liver attenuation at the venous phase (a radiomic feature reflecting venous perfusion), primary etiology, donor/recipient age, recurrence of disease, brain-dead donor, tacrolimus use at 3 months, and APRI score at 3 months were predictive of ≥F2 fibrosis. The combination of radiomics and the clinical features increased the AUC to 0.811 from 0.793 for the clinical-only model (p = 0.008) and from 0.664 for the radiomics-only model (p < 0.001) to predict future ≥F2 fibrosis. This pilot study exploring the role of radiomics demonstrates that the addition of radiomic features in a clinical model increased the model's performance. Further studies are required to investigate the generalizability of this experimental tool.
Subject(s)
Artificial Intelligence , Liver Transplantation , Humans , Infant , Pilot Projects , Retrospective Studies , FibrosisABSTRACT
Background and Aims: Interns must be proficient in obtaining informed consent (IC), which is the Association of American Medical College's 11th of 13 Entrustable Professional Activities (EPAs). Medical students have limited opportunity to practice IC during clerkships, resulting in inconsistent proficiency. We aimed to create a tool to assess whether our transition to residency (TTR) workshop enables fourth-year medical students to meet a minimum standard of obtaining IC. Methods: Sixty fourth-year medical students were enrolled in the internal medicine virtual TTR course during AY2021. The curriculum prioritizes deliberate practice activities. Pre- and postworkshop assignments involved students typing verbatim what they would say during IC encounters. We modified an IC abstraction tool created by Spatz et al. to assess a minimum standard for students' IC assignments. Our final 7-item tool consisted of the following domains: "What," "Why," "How," "Benefits," "Quantitative Risks," "Qualitative Risks," and "Alternatives," weighing 1 point each. A minimum standard was obtained with a score of 6 or more points by appropriately discussing at least one domain involving risk and all other domains. Results: Students scored highly on the prework domains pertaining to "What," "Why," and "How" of the procedure with no significant difference on postwork. Significant improvement was achieved on postwork domains covering "Benefits" (p = 0.039) and "Alternatives" (p = 0.031). For domains involving "Qualitative" and "Quantitative Risks," there were no statistically significant improvements from pre- to postwork scores. Fifteen and 22 students met the minimum standard for IC on pre- and postwork, respectively. Conclusion: Our students demonstrated a good a priori understanding of the "What," "Why," and "How" domains. After the workshop, they more reliably discussed "Benefits" and "Alternatives." Our abstraction tool helped assess the strengths and weaknesses in our students' IC skillset and helped recognize areas of our curriculum that will benefit from improvements to bring students to meet the minimum standard.