Thrombosis risk prediction in lymphoma patients: A multi-institutional, retrospective model development and validation study.

Venous thromboembolism (VTE) poses a significant risk to cancer patients receiving systemic therapy. The generalizability of pan-cancer models to lymphomas is limited. Currently, there are no reliable risk prediction models for thrombosis in patients with lymphoma. Our objective was to create a risk assessment model (RAM) specifically for lymphomas. We performed a retrospective cohort study to develop Fine and Gray sub-distribution hazard model for VTE and pulmonary embolism (PE)/ lower extremity deep vein thrombosis (LE-DVT) respectively in adult lymphoma patients from the Veterans Affairs national healthcare system (VA). External validations were performed at the Harris Health System (HHS) and the MD Anderson Cancer Center (MDACC). Time-dependent c-statistic and calibration curves were used to assess discrimination and fit. There were 10,313 (VA), 854 (HHS), and 1858 (MDACC) patients in the derivation and validation cohorts with diverse baseline. At 6 months, the VTE incidence was 5.8% (VA), 8.2% (HHS), and 8.8% (MDACC), respectively. The corresponding estimates for PE/LE-DVT were 3.9% (VA), 4.5% (HHS), and 3.7% (MDACC), respectively. The variables in the final RAM included lymphoma histology, body mass index, therapy type, recent hospitalization, history of VTE, history of paralysis/immobilization, and time to treatment initiation. The RAM had c-statistics of 0.68 in the derivation and 0.69 and 0.72 in the two external validation cohorts. The two models achieved a clear differentiation in risk stratification in each cohort. Our findings suggest that easy-to-implement, clinical-based model could be used to predict personalized VTE risk for lymphoma patients.

Development of an integrated milestone assessment tool across multiple early-adopter programs for breaking bad news: a pilot project.

BACKGROUND: The transition of the Accreditation Council for Graduate Medical Education (ACGME) to milestone assessment creates opportunities for collaboration and shared assessments across graduate medical programs. Breaking bad news is an essential communication skill that is a common milestone across almost every medical specialty. The purpose of this study was to develop and pilot an integrated milestone assessment (IMA) tool for breaking bad news using ACGME milestone criteria and to compare the IMA tool with the existing SPIKES protocol. METHODS: The IMA tool was created using sub-anchors in professionalism and interpersonal communication skills that are applicable to every specialty and to the ability to break bad news. Two cases of breaking bad news, designed to be "easy" and "intermediate" in difficulty, were used to assess basic skills in breaking bad news in first-year medical residents from six residency specialties. Eight standardized patients were trained to portray the cases in sessions held in November 2013 and May 2014. Standardized patients completed an assessment checklist to evaluate each resident's performance in breaking bad news based on their use of the SPIKES protocol and IMA tool. Residents answered post-encounter questions about their training and comfort in breaking bad news. The association between SPIKES and IMA scores was investigated by simple linear regression models and Spearman rank correlations. RESULTS: There were 136 eligible medical residents: 108 (79.4%) participated in the first session and 97 (71.3%) participated in the second session, with 96 (70.6%) residents participating in both sessions. Overall, we were able to identify residents that performed at both extremes of the assessment criteria using the integrated milestone assessment (IMA) and the SPIKES protocol. Interestingly, residents rated themselves below "comfortable" on average. CONCLUSION: We developed an integrated milestone assessment (IMA) that was better than the SPIKES protocol at assessing the skill of breaking bad news. This collaborative assessment tool can be used as supplement tool in the era of milestone transformation. We aim assess our tool in other specialties and institutions, as well as assess other shared milestones across specialties.

Natural history of cancer-associated splanchnic vein thrombosis.

BACKGROUND: There is uncertainty in the management of cancer-associated isolated splanchnic vein thrombosis (SpVT). OBJECTIVES: To describe the natural history of SpVT by cancer type and thrombus composition and to review anticoagulation (AC) practices and associated rates of usual-site venous thromboembolism (VTE), major and clinically relevant nonmajor bleeding (MB/CRNMB), recanalization/progression, and mortality. METHODS: We performed a retrospective cohort study in patients with SpVT at 2 cancer care centers in Houston, Texas. We estimated the incidence of usual-site VTE and MB/CRNMB at 6 months using competing risk methods and examined venous patency in a subset of patients with repeat imaging. We assessed associations with mortality using Cox regression. RESULTS: Among 15 342 patients with an incident cancer diagnosis from 2011 to 2020, we identified 298 with isolated SpVT. Patients with hepatocellular carcinoma (HCC) and SpVT (n = 146) had the highest disease prevalence (20%), lowest rate of AC treatment (2%), and similar rate of usual-site VTE (4.2%) vs those without SpVT (5.2%) at 6 months, though tumor thrombus vs bland was associated with worse overall survival. In patients with non-HCC bland SpVT (n = 114), AC (n = 37) was more common in those with non-upper gastrointestinal cancers and fewer comorbidities. AC was associated with more recanalization (44% vs 15%, P = .041) but no differences in usual-site VTE, MB/CRNMB, or mortality at 6 months. CONCLUSION: Cancer-associated isolated SpVT is a common but heterogeneous thrombotic disease that is treated differently from usual-site VTE. Tumor thrombus is a negative prognostic factor. Initiation of AC in bland thrombi requires judicious consideration of thrombotic and bleeding risk.

Early identification of autism spectrum disorder in children with CHD attending a Cardiac Developmental Outcomes Program.

OBJECTIVE: To determine the prevalence and timing of autism spectrum disorder diagnosis in a cohort of congenital heart disease (CHD) patients receiving neurodevelopmental follow-up and identify associated risk factors. METHOD: Retrospective single-centre observational study of 361 children undergoing surgery for CHD during the first 6 months of life. Data abstracted included age at autism spectrum disorder diagnosis, child and maternal demographics, and medical history. RESULTS: Autism spectrum disorder was present in 9.1% of children with CHD, with a median age at diagnosis of 34 months and 87.9% male. Prematurity, history of post-operative extracorporeal membrane oxygenation, and seizures were higher among those with autism (p = 0.013, p = 0.023, p = 0.001, respectively). Infants with autism spectrum disorder were older at the time of surgery (54 days vs 13.5 days, p = 0.002), and infants with surgery at ≥ 30 days of age had an increased risk of autism spectrum disorder (OR 2.31; 95% CI =1.12, 4.77, p = 0.023). On multivariate logistic regression analysis, being male (OR 4.85, p = 0.005), surgery ≥ 30 days (OR 2.46, p = 0.025), extracorporeal membrane oxygenation (OR 4.91, p = 0.024), and seizures (OR 4.32, p = 0.003) remained associated with increased odds for autism spectrum disorder. Maternal age, race, ethnicity, and surgical complexity were not associated. CONCLUSIONS: Children with CHD in our cohort had more than three times the risk of autism spectrum disorder and were diagnosed at a much earlier age compared to the general population. Several factors (male, surgery at ≥ 30 days, post-operative extracorporeal membrane oxygenation, and seizures) were associated with increased odds of autism. These findings support the importance of offering neurodevelopmental follow-up after cardiac surgery in infancy.

Plasma amino acid signatures define types of pediatric diabetes.

BACKGROUND & AIMS: Metabolic biomarkers with pathophysiological relevance is lacking in pediatric diabetes. We aimed to identify novel metabolic biomarkers in pediatric type 1 (T1D) and type 2 diabetes (T2D). We hypothesized that (1) targeted plasma metabolomics, focused on plasma amino acid concentrations, could identify distinctively altered patterns in children with T1D or T2D, and (2) there are specific changes in concentrations of metabolites related to branch chain amino acids (BCAA) and arginine metabolism in children with T2D. METHODS: In a pilot study, we enrolled children with T1D (n = 15) and T2D (n = 13), and healthy controls (n = 15). Fasting plasma amino acid concentrations were measured by ultra-performance liquid chromatography, and compared between the groups after adjustment for confounding factors. RESULTS: The mean age (SD) of participants was 16.4 (0.9) years. There were no group differences in age, gender, race/ethnicity, or 24-h protein intake. Mean BMI percentile was higher in the T2D than the T1D group or controls (p < 0.001). The T2D group had lower arginine, citrulline, glutamine, glycine, phenylalanine, methionine, threonine, asparagine and symmetric dimethylarginine (SDMA) but higher aspartate than controls, after adjusting for BMI percentiles (all p < 0.05). Children with T2D also had lower glycine but higher ornithine, proline, leucine, isoleucine, valine, total BCAA, lysine and tyrosine than those with T1D after adjusting for confounding factors (all p < 0.05). Children with T1D had lower phenylalanine, methionine, threonine, glutamine, tyrosine, asymmetric dimethylarginine (ADMA) and SDMA than controls (all p < 0.05). CONCLUSIONS: Children with T2D and T1D have distinct fasting plasma amino acid signatures that suggest varying pathogenic mechanisms and could serve as biomarkers for these conditions.

Prospective Clinical and Biomarker Validation of the American Society for Transplantation and Cellular Therapy Consensus Definition for Transplantation-Associated Thrombotic Microangiopathy.

Transplantation-associated thrombotic microangiography (TA-TMA) is a disorder that causes severe complications after allogeneic hematopoietic cell transplantation (allo-HCT). Diagnosing TA-TMA is challenging because of the lack of standardized criteria. In this study, we aimed to evaluate the new TA-TMA consensus definition from the American Society for Transplantation and Cellular Therapy (ASTCT) panel as part of an ongoing prospective pediatric cohort study, and also to compare the impact and outcomes of using the current definition of clinical TMA (cTMA) versus the new consensus definition. We included patients age 0 to 18 years who underwent their first allo-HCT between May 2021 and January 2023 at Texas Children's Hospital. We compared the incidence, biomarkers, and outcomes of TA-TMA applying the previous and recently proposed screening algorithms and definitions. Whereas use of the classic microangiopathic hemolytic anemia (MAHA)-based cTMA definition led to an incidence of 12.7% by day 100 post-transplantation, the ASTCT-HR definition doubled the incidence to 28.5% by day 100. In contrast to patients with a concordant diagnosis (+/+), who had significantly worse post-transplantation survival, those reclassified as TA-TMA only by the new definition (-/+) had a significantly different prognosis (100% survival at day 100) despite the lack of TMA-directed therapy. Furthermore, biomarkers of the terminal and alternative complement pathways (sC5b9 and Ba, respectively) were significantly elevated compared with non-TMA patients around day 15 in the concordant group (+/+) but not in the discordant group (-/+). The recently proposed ASTCT consensus TA-TMA diagnosis is more sensitive and allows earlier recognition of manifestation that requires closer clinical monitoring but risks overdiagnosis and overtreatment. We recommend additional prospective validation.

Critical Care Unit Characteristics and Extracorporeal Cardiopulmonary Resuscitation Survival in the Pediatric Cardiac Population: Retrospective Analysis of the Virtual Pediatric System Database.

OBJECTIVES: Existing literature provides limited data about ICU characteristics and pediatric extracorporeal cardiopulmonary resuscitation (E-CPR) outcomes. We aimed to evaluate the associations between patient and ICU characteristics, and outcomes after E-CPR in the pediatric cardiac population. DESIGN: Retrospective analysis of the Virtual Pediatric System database (VPS, LLC, Los Angeles, CA). SETTING: PICUs categorized as either cardiac-only versus mixed ICU cohort type. PATIENTS: Consecutive cardiac patients less than 18 years old experiencing cardiac arrest in the ICU and resuscitated using E-CPR. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Event and time-stamp filtering identified E-CPR events. Patient, hospital, and event-related variables were aggregated for independent and multivariable mixed effects logistic regression to assess the association between ICU cohort type and survival. Among ICU admissions in the VPS database, 2010-2018, the prevalence of E-CPR was 0.07%. A total of 671 E-CPR events (650 patients) comprised the final cohort; congenital heart disease (84%) was the most common diagnosis versus acquired heart diseases. The majority of E-CPR events occurred in mixed ICUs (67%, n = 449) and in ICUs with greater than 20 licensed bed capacity (65%, n = 436). Survival to hospital discharge was 51% for the overall cohort. Independent logistic regression failed to reveal any association between survival to hospital discharge and ICU type (ICU type: cardiac ICU, odds ratio [OR], 1.01; 95% CI, 0.71-1.44; p = 0.95). However, multivariable logistic regression revealed an association between cardiac surgical patients and greater odds for survival (OR, 2.03; 95% CI, 1.40-2.95; p < 0.001). Also, there was an association between ICUs with capacity greater than 20 (vs not) and lower survival odds (OR, 0.65; 95% CI, 0.43-0.96). CONCLUSIONS: The overall prevalence of E-CPR among critically ill children with cardiac disease observed in the VPS database is low. We failed to identify an association between ICU cohort type and survival. Further investigation into organizational factors is warranted.

Rapid response events with multiple triggers are associated with poor outcomes in children.

Objective: We describe the characteristics and outcomes of pediatric rapid response team (RRT) events within a single institution, categorized by reason for RRT activation (RRT triggers). We hypothesized that events with multiple triggers are associated with worse outcomes. Patients and Methods: Retrospective 3-year study at a high-volume tertiary academic pediatric hospital. We included all patients with index RRT events during the study period. Results: Association of patient and RRT event characteristics with outcomes including transfers to ICU, need for advanced cardiopulmonary support, ICU and hospital length of stay (LOS), and mortality were studied. We reviewed 2,267 RRT events from 2,088 patients. Most (59%) were males with a median age of 2 years and 57% had complex chronic conditions. RRT triggers were: respiratory (36%) and multiple (35%). Transfer to the ICU occurred after 1,468 events (70%). Median hospital and ICU LOS were 11 and 1 days. Need for advanced cardiopulmonary support was noted in 291 events (14%). Overall mortality was 85 (4.1%), with 61 (2.9%) of patients having cardiopulmonary arrest (CPA). Multiple RRT trigger events were associated with transfer to the ICU (559 events; OR 1.48; p < 0.001), need for advanced cardiopulmonary support (134 events; OR 1.68; p < 0.001), CPA (34 events; OR 2.36; p = 0.001), and longer ICU LOS (2 vs. 1 days; p < 0.001). All categories of triggers have lower odds of need for advanced cardiopulmonary support than multiple triggers (OR 1.73; p < 0.001). Conclusions: RRT events with multiple triggers were associated with cardiopulmonary arrest, transfer to ICU, need for cardiopulmonary support, and longer ICU LOS. Knowledge of these associations can guide clinical decisions, care planning, and resource allocation.

Risks factors and outcomes for isolated catheter-related deep venous thrombosis in patients undergoing allogeneic hematopoietic stem cell transplantation.

INTRODUCTION: Patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) require indwelling central venous catheters. The comparative incidence, risk, and outcome of isolated catheter-related deep venous thrombosis (CR-DVT) versus pulmonary embolism/lower-extremity DVT (PE/LE-DVT) remains unclear. MATERIALS AND METHODS: We conducted a retrospective cohort study for patients undergoing allo-HSCT from 2006 to 2019. CR-DVT and PE/LE-DVT outcomes were screened using ICD codes and radiology reports and confirmed by medical record reviews. Cox regression models were used to assess the association between thrombotic outcomes and pertinent baseline and time-varying covariates. The impact of thrombotic events within 1-year post-transplant (time-varying) on overall mortality was also assessed. RESULTS: Among 2879 patients, the cumulative incidence of isolated CR-DVT and PE/LE-DVT at 12 months was 4.2 % and 4.8 %, respectively. The strongest time-varying predictor for onset of CR-DVT and PE/LE-DVT was hospitalization inpatient status (HR 3.71 [95 % CI 2.16-6.37] and 3.99 [95 % CI 2.00-7.99], respectively). Other overlapping variables included lymphoma diagnosis and BMI > 35 kg/m2, whereas acute GVHD grades 2-4 were found to be significantly associated with risk of PE/LE-DVT but not CR-DVT. After adjusting for baseline variables and acute GVHD, the occurrences of CR-DVT and PE/LE-DVT were both independently associated with increased overall mortality (HR 1.58 [95 % CI 1.23-2.02] and HR 1.53 [95 % CI 1.19-1.97], respectively). CONCLUSIONS: We observed a high incidence of both CR-DVT and PE/LE-DVT with overlapping and unique risk factors. CR-DVT was also associated with increased mortality similar to PE/LE-DVT. Standardized strategies targeting high-risk hospitalization periods may help mitigate the development of thrombotic outcomes post-transplant.

Multi-center retrospective study of children with sickle cell disease admitted to pediatric intensive care units in the United States.

Data on outcomes and interventions for children with sickle cell disease (SCD) admitted to a pediatric intensive care units (PICU) are unknown. We provide the first comprehensive multi-center report on PICU interventions associated with death, the need for invasive respiratory support or stroke among critically ill children with SCD. We collected retrospective multi-center cohort data from January 1, 2012 to December 31, 2019 utilizing the Virtual Pediatric Systems, LLC database. We identified 3388 unique children with SCD, accounting for a total of 5264 PICU admissions from 138 PICUs. The overall mortality rate for the PICU admissions cohort was 1.8% (95/5264 PICU admissions, 95/3388 [2.8%] of all unique patients), the rate of needing of needing Invasive Respiratory Support (IRS, a composite category of exposure) was 21.3% (872/4093 PICU admissions with complete data) and the overall rate of stroke (ischemic or hemorrhagic) was 12.5% (657/5264 PICU admissions). In multivariable analysis adjusting for admission age category, sex, race/ethnicity, PRISM-3 score at admission, exposure to IRS, quartile of unit volume of patients with SCD, and patient origin, admitted children who needed invasive respiratory support (IRS) had higher adjusted odds ratios for mortality (adjusted odds ratio [aOR], 19.72; 95% confidence interval [CI] 8.98-43.29; p < 0.001), although admitted children > 2 years old had decreased aOR for needing IRS (aOR 0.25-0.62; 95% CI 0.16-0.94; p < 0.001-0.025). By contrast, admitted children > 2 years old had a strikingly increased aOR for stroke (aOR 7.57-16.32; 95% CI 2.25-52.15; p < 0.001). These groups may represent PICU-specific subsets of patients with SCD who are at higher risk for more serious illness and should deserve early consideration for referral to a pediatric institution providing comprehensive care for patients with SCD.

Retrospective observational study of chloral hydrate use in mechanically-ventilated pediatric intensive care unit (PICU) patients 2012-2017.

Introduction: Chloral hydrate (CH) has long been utilized as a pediatric procedural sedation agent. However, very little is published describing CH use in a pediatric intensive care unit (PICU) setting. The aim of this retrospective observational cohort study was to investigate and describe the use of CH in mechanically-ventilated, critically ill children at a large pediatric tertiary referral hospital. Methods: Data were extracted from the hospital electronic medical record and a locally maintained registry of all children admitted to the PICU between 2012 and 2017. Patients admitted to the cardiovascular ICU were not included in this review. The clinical and pharmacy data for 3806 consecutive PICU admissions of mechanically-ventilated, critically ill children were examined. Results: 283 admissions received CH during their first ICU stay. CH-exposed children were younger (16 months vs. 35 months, p < 0.001), the median total dose of CH (indexed to duration of ventilation) was 11 mg/kg/day, the median time to first CH dose was 3 days and more CH doses were administered at night (1112 vs. 958, p < 0.001). We constructed a propensity score to adjust for the differences in patients with and without CH exposure using logistic regression including variables of age, sex, diagnosis, and PRISM3 score. After adjustment, the median length of mechanical ventilation was 5 days longer in the CH-exposed group (95% Confidence Interval [CI] 4-6) compared to unexposed CH patients. Similarly, the median length of ICU duration was 9.4 days longer (95% CI 7.1-11.6) and median length of hospital admission duration was 13.2 days longer (95% CI 7.8-18.6) in CH-exposed patients compared to CH-non-exposed. After adjustment, CH-exposed patients had a 9% higher median exposure to HFOV (95% CI 3.9-14.6), but did not have higher median exposures to new tracheostomy (95% CI -0.4-2.2) or ECMO (95% CI -0.2-5.0). Discussion: As part of an extended sedation regimen in mechanically-ventilated and critically ill children, CH is associated with somewhat higher complexity of illness and longer ICU durations.

Barriers to care in juvenile localized and systemic scleroderma: an exploratory survey study of caregivers' perspectives.

BACKGROUND: Juvenile localized scleroderma (LS) and systemic sclerosis (SSc) are rare pediatric conditions often associated with severe morbidities. Delays in diagnosis are common, increasing the risk for permanent damage and worse outcomes. This study explored caregiver perspectives on barriers they encountered while navigating diagnosis and care for their child's scleroderma. METHODS: In this cross-sectional study, caregivers of juvenile LS or SSc patients were recruited from a virtual family scleroderma educational conference and a juvenile scleroderma online interest group. The survey queried respondents about their child's condition and factors affecting diagnosis and treatment. RESULTS: The response rate was 61% (73/120), with 38 parents of LS patients and 31 parents of SSc patients. Most patients were female (80%) and over half were non-Hispanic white (55%). Most families had at least one person with a college education or higher (87%), traveled ≤ 2 h to see their rheumatologist (83%), and had private insurance (75%). Almost half had an annual household income ≥ $100,000 (46%). Families identified the following factors as barriers to care: lack of knowledge about scleroderma in the medical community, finding reliable information about pediatric scleroderma, long wait times/distances for a rheumatology/specialist appointment, balance of school/work and child's healthcare needs, medication side effects, and identifying effective medications. The barrier most identified as a major problem was the lack of knowledge about juvenile scleroderma in the medical community. Public insurance, household income less than $100,000, and Hispanic ethnicity were associated with specific barriers to care. Lower socioeconomic status was associated with longer travel times to see the rheumatologist/specialist. Diagnosis and systemic treatment initiation occurred at greater than one year from initial presentation for approximately 28% and 36% of patients, respectively. Families of LS patients were commonly given erroneous information about the disease, including on the need and importance of treating active disease with systemic immunosuppressants in patients with deep tissue or rapidly progressive disease. CONCLUSION: Caregivers of children with LS or SSc reported numerous common barriers to the diagnosis, treatment, and ongoing care of juvenile scleroderma. The major problem highlighted was the lack of knowledge of scleroderma within the general medical community. Given that most of the caregiver respondents to the survey had relatively high socioeconomic status, additional studies are needed to reach a broader audience, including caregivers with limited English proficiency, geographical limitations, and financial constraints, to determine if the identified problems are generalizable. Identifying key care barriers will help direct efforts to address needs, reduce disparities in care, and improve patient outcomes.

Extracorporeal Membrane Oxygenation Cannulation Timing in the Pediatric Myocarditis Population: An Exploratory Analysis From the Extracorporeal Life Support Organization Registry.

Children presenting with acute myocarditis may experience rapid clinical deterioration requiring extracorporeal membrane oxygenation (ECMO); however, our understanding of best practices and timing of ECMO initiation are lacking. We explored the relationships between pre-cannulation factors and survival in this high-acuity patient population. DESIGN: Retrospective review of a large international registry. Primary outcome was survival to hospital discharge, stratified by incident cardiac arrest (CA) prior to ECMO and time to cannulation after intubation. SETTING AND SUBJECTS: The Extracorporeal Life Support Organization registry was queried for patients less than or equal to 18 years old receiving ECMO support for myocarditis between 2007 and 2018. Exclusion criteria included being nonindex runs, non-venoarterial ECMO or missing data points for main variables studied. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Population characteristics and survival were compared using t test, Wilcoxon rank-sum test, or Fisher exact test. Multivariable logistic regression was used for significant factors in the unadjusted logistic regression. Among 506 index ECMO runs in pediatric patients with myocarditis, survival for the cohort was 72%, with no difference between early and late eras (2007-2012 vs 2013-2018; p = 0.69). Survivors demonstrated higher pre-ECMO pH levels as well as shorter intubation-to-cannulation (ITC) times (3 hr [interquartile range (IQR)], 1-14 hr vs 6 hr [IQR, 2-20 hr]; p = 0.021). CA occurred within 24 hours prior to ECMO cannulation, including extracorporeal cardiopulmonary resuscitation, in 54% of ECMO runs (n = 273). Accounting for the interaction between pre-ECMO CA occurrence and ITC time, longer ITC time remained associated with lower survival for patients who did not experience a CA prior to ECMO, with adjusted odds ratio of 0.09 (IQR, 0.02-0.40; p = 0.002) for ITC time greater than or equal to 18 hours. CONCLUSIONS: The results of this multicenter analysis of ECMO utilization and outcomes for pediatric myocarditis suggest that patients approaching ECMO cannulation who have not experienced CA may have better survival outcomes if cannulated onto ECMO early after intubation.

Derivation and Validation of a Clinical Risk Assessment Model for Cancer-Associated Thrombosis in Two Unique US Health Care Systems.

PURPOSE: Venous thromboembolism (VTE), especially pulmonary embolism (PE) and lower extremity deep vein thrombosis (LE-DVT), is a serious and potentially preventable complication for patients with cancer undergoing systemic therapy. METHODS: Using retrospective data from patients diagnosed with incident cancer from 2011-2020, we derived a parsimonious risk assessment model (RAM) using least absolute shrinkage and selection operator regression from the Harris Health System (HHS, n = 9,769) and externally validated it using the Veterans Affairs (VA) health care system (n = 79,517). Bootstrapped c statistics and calibration curves were used to assess external model discrimination and fit. Dichotomized risk strata using integer scores were created and compared against the Khorana score (KS). RESULTS: Incident VTE and PE/LE-DVT at 6 months occurred in 590 (6.2%) and 437 (4.6%) patients in HHS and 4,027 (5.1%) and 3,331 (4.2%) patients in the VA health care system. Assessed at the time of systemic therapy initiation, the new RAM included components of the KS with the modified cancer subtype, cancer staging, systemic therapy class, history of VTE, history of paralysis/immobility, recent hospitalization, and Asian/Pacific Islander race. The c statistic was 0.71 in HHS and 0.68 in the VA health care system (compared with 0.65 and 0.60, respectively, for KS). Furthermore, the new RAM appropriately reclassified 28% of patients and increased the proportion of VTEs in the high-risk group from 37% to 68% in the validation data set. CONCLUSION: The novel RAM stratified patients with cancer into a high-risk group with 8%-10% cumulative incidence of VTE and 7% PE/LE-DVT at 6 months (v 3% and 2%, respectively, in the low-risk group). The model had improved performance over the original KS and doubled the number of VTE events in the high-risk stratum. We encourage additional external validation from prospective studies.[Media: see text].

Impact of psychosocial factors on medication level variability index and outcomes in pediatric liver transplant recipients.

BACKGROUND: Caregivers play an important role in maintaining a functioning graft after pediatric liver transplantation. Therefore, the psychosocial factors of both patients and caregivers can have a critical impact on transplant outcomes. Appropriate assessment and recognition of these factors pre-transplantation may allow transplant teams to better define the needs of pediatric organ recipients and develop specific countermeasures, which may then contribute toward improving transplant outcomes. METHODS: We studied 136 pediatric LT recipients followed at Texas Children's Hospital. Licensed social workers conducted comprehensive pre-transplant assessments on each patient, consisting of 22 psychosocial variables that were thought to impact adherence, which were reviewed during our study period. Non-adherence was determined using the MLVI for up to 4 years after transplantation. Biopsy-confirmed rejection episodes were assessed in the first 3 years after liver transplantation. RESULTS: Factors significantly associated with non-adherence (defined as MLVI >2) included parental age and parental education level at assessment, type of insurance, and household income. The number of ACR episodes trended higher in patients with non-adherence, and these patients had a higher number of moderate to severe rejection episodes but this trend was not statistically significant. CONCLUSIONS: Psychosocial characteristics such as parental age, education level, insurance, and household income may contribute significantly to suboptimal adherence to medications after transplantation. Identification of these psychosocial factors and early intervention is essential to the success and equitable care of our pediatric LT recipients.

Cumulative comorbid conditions influence mortality risk after staged palliation for hypoplastic left heart syndrome and variants.

OBJECTIVE: Prematurity, low birth weight, genetic syndromes, extracardiac conditions, and secondary cardiac lesions are considered high-risk conditions associated with mortality after stage 1 palliation. We report the impact of these conditions on outcomes from a prospective multicenter improvement collaborative. METHODS: The National Pediatric Cardiology Quality Improvement Collaborative Phase II registry was queried. Comorbid conditions were categorized and quantified to determine the cumulative burden of high-risk diagnoses on survival to the first birthday. Logistic regression was applied to evaluate factors associated with mortality. RESULTS: Of the 1421 participants, 40% (575) had at least 1 high-risk condition. The aggregate high-risk group had lower survival to the first birthday compared with standard risk (76.2% vs 88.1%, P < .001). Presence of a single high-risk diagnosis was not associated with reduced survival to the first birthday (odds ratio, 0.71; confidence interval, 0.49-1.02, P = .066). Incremental increases in high-risk diagnoses were associated with reduced survival to first birthday (odds ratio, 0.23; confidence interval, 0.15-0.36, P < .001) for 2 and 0.17 (confidence interval, 0.10-0.30, P < .001) for 3 to 5 high-risk diagnoses. Additional analysis that included prestage 1 palliation characteristics and stage 1 palliation perioperative variables identified multiple high-risk diagnoses, poststage 1 palliation extracorporeal membrane oxygenation support (odds ratio, 0.14; confidence interval, 0.10-0.22, P < .001), and cardiac reoperation (odds ratio, 0.66; confidence interval, 0.45-0.98, P = .037) to be associated with reduced survival odds to the first birthday. CONCLUSIONS: The presence of 1 high-risk diagnostic category was not associated with decreased survival at 1 year. Cumulative diagnoses across multiple high-risk diagnostic categories were associated with decreased odds of survival. Further patient accrual is needed to evaluate the impact of specific comorbid conditions within the broader high-risk categories.

Serum biomarkers correlated with liver stiffness assessed in a multicenter study of pediatric cholestatic liver disease.

BACKGROUND AND AIMS: Detailed investigation of the biological pathways leading to hepatic fibrosis and identification of liver fibrosis biomarkers may facilitate early interventions for pediatric cholestasis. APPROACH AND RESULTS: A targeted enzyme-linked immunosorbent assay-based panel of nine biomarkers (lysyl oxidase, tissue inhibitor matrix metalloproteinase (MMP) 1, connective tissue growth factor [CTGF], IL-8, endoglin, periostin, Mac-2-binding protein, MMP-3, and MMP-7) was examined in children with biliary atresia (BA; n = 187), alpha-1 antitrypsin deficiency (A1AT; n = 78), and Alagille syndrome (ALGS; n = 65) and correlated with liver stiffness (LSM) and biochemical measures of liver disease. Median age and LSM were 9 years and 9.5 kPa. After adjusting for covariates, there were positive correlations among LSM and endoglin ( p = 0.04) and IL-8 ( p < 0.001) and MMP-7 ( p < 0.001) in participants with BA. The best prediction model for LSM in BA using clinical and lab measurements had an R2 = 0.437; adding IL-8 and MMP-7 improved R2 to 0.523 and 0.526 (both p < 0.0001). In participants with A1AT, CTGF and LSM were negatively correlated ( p = 0.004); adding CTGF to an LSM prediction model improved R2 from 0.524 to 0.577 ( p = 0.0033). Biomarkers did not correlate with LSM in ALGS. A significant number of biomarker/lab correlations were found in participants with BA but not those with A1AT or ALGS. CONCLUSIONS: Endoglin, IL-8, and MMP-7 significantly correlate with increased LSM in children with BA, whereas CTGF inversely correlates with LSM in participants with A1AT; these biomarkers appear to enhance prediction of LSM beyond clinical tests. Future disease-specific investigations of change in these biomarkers over time and as predictors of clinical outcomes will be important.

Developing and optimizing a computable phenotype for incident venous thromboembolism in a longitudinal cohort of patients with cancer.

Background: Research on venous thromboembolism (VTE) that relies only on the International Classification of Diseases (ICD) can misclassify outcomes. Our study aims to discover and validate an improved VTE computable phenotype for people with cancer. Methods: We used a cancer registry electronic health record (EHR)-linked longitudinal database. We derived three algorithms that were ICD/medication based, natural language processing (NLP) based, or all combined. We then randomly sampled 400 patients from patients with VTE codes (n = 1111) and 400 from those without VTE codes (n = 7396). Weighted sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated on the entire sample using inverse probability weighting, followed by bootstrapped receiver operating curve analysis to calculate the concordance statistic (c statistic). Results: Among 800 patients sampled, 280 had a confirmed acute VTE during the first year after cancer diagnosis. The ICD/medication algorithm had a weighted PPV of 95% and a weighted sensitivity of 81%, with a c statistic of 0.90 (95% confidence interval [CI], 0.89-0.91). Adding Current Procedural Terminology codes for inferior vena cava filter removal or early death did not improve the performance. The NLP algorithm had a weighted PPV of 80% and a weighted sensitivity of 90%, with a c statistic of 0.93 (95% CI, 0.92-0.94). The combined algorithm had a weighted PPV of 98% at the higher cutoff and a weighted sensitivity of 96% at the lower cutoff, with a c statistic of 0.98 (95% CI, 0.97-0.98). Conclusions: Our ICD/medication-based algorithm can accurately identify VTE phenotype among patients with cancer with a high PPV of 95%. The combined algorithm should be considered in EHR databases that have access to such capabilities.

Risky self-management behaviors in adolescents with type 1 diabetes: Measurement validation for the Diabetes-Specific Risk-Taking Inventory.

OBJECTIVE: Among persons with type 1 diabetes (T1D), adolescents often experience the greatest challenge achieving optimal treatment engagement and glycemic targets. Risk-taking behaviors often increase during adolescence and may interfere with engagement in T1D care. We developed the Diabetes-Specific Risk-Taking Inventory (DSRI) to assess risky T1D self-management behaviors in adolescents with T1D. In the current study, we aimed to examine the DSRI's psychometric properties. RESEARCH DESIGN AND METHODS: We surveyed a national sample of 224 adolescents from the T1D Exchange registry (M age = 16.9 ± 1.1, 49% female, M A1c = 8.5% ± 1.3, 76.8% on insulin pumps) in a cross-sectional design. Participants completed the DSRI and measures of engagement, general risk-taking, and executive functioning and reported on incidence of severe hypoglycemia and diabetic ketoacidosis over the past year. RESULTS: The DSRI demonstrated reliability (internal consistency: α = 0.89; test-retest reliability: r = 0.86, p < 0.01). Concurrent validity was demonstrated through significant associations between the DSRI and T1D engagement (r = -0.75), general risk-taking (r = 0.57), executive dysfunction (r = 0.34), and report of severe hypoglycemia over the past year (r = 0.22). The DSRI accounted for unique variance in adolescents' most recent glycated hemoglobin, above and beyond other variables, indicating its incremental validity. CONCLUSIONS: Overall, initial psychometrics suggest the DSRI is a reliable and valid measure of risks that adolescents may take with their T1D care. This innovative self-report measure has potential to be an actionable clinical tool to screen for high-risk behaviors not routinely assessed in T1D clinical care.

Palliative Care Impact on COVID-19 Patients Requiring Extracorporeal Membrane Oxygenation.

CONTEXT: Patients with severe respiratory failure from COVID-19 refractory to conventional therapies may be treated with extracorporeal membrane oxygenation (ECMO). ECMO requirement is associated with high mortality and prolonged hospital course. ECMO is a high-resource intervention with significant burdens placed on caregivers and families with limited data on the integration of palliative care consultation (PCC). OBJECTIVES: To explore the role of standard vs. automatic PCC in the management of COVID patients on ECMO. METHODS: Retrospective chart review of all COVID patients on ECMO admitted from March 2020 to May 2021 at a large volume academic medical center with subsequent analysis. RESULTS: Forty-eight patients were included in the analysis. Twenty-six (54.2%) received PCC of which 42% of consults were automatically initiated. PCC at any point in admission was associated with longer duration on ECMO (24.5 vs. 37 days; P < 0.05). Automatic PCC resulted in more family meetings than standard PCC (0 vs. 3; P < 0.05) and appears to trend with reduced time on ECMO, shorter length of stay, and higher DNAR rates at death, though results were not significant. Decedents not receiving PCC had higher rates of no de-escalation of interventions at time of death (31% vs. 11%), indicating full intensive care measures continued through death. CONCLUSIONS: Among patients with COVID-19 receiving ECMO, PCC may be associated with a shift to DNAR status particularly with automatic PCC. There may be a further impact on length of stay, duration of time on ECMO and care plan at end of life.