Event-free survival of maralixibat-treated patients with Alagille syndrome compared to a real-world cohort from GALA.

BACKGROUND AND AIMS: Alagille syndrome (ALGS) is characterized by chronic cholestasis with associated pruritus and extrahepatic anomalies. Maralixibat, an ileal bile acid transporter inhibitor, is an approved pharmacologic therapy for cholestatic pruritus in ALGS. Since long-term placebo-controlled studies are not feasible or ethical in children with rare diseases, a novel approach was taken comparing 6-year outcomes from maralixibat trials with an aligned and harmonized natural history cohort from the G lobal AL agille A lliance (GALA) study. APPROACH AND RESULTS: Maralixibat trials comprise 84 patients with ALGS with up to 6 years of treatment. GALA contains retrospective data from 1438 participants. GALA was filtered to align with key maralixibat eligibility criteria, yielding 469 participants. Serum bile acids could not be included in the GALA filtering criteria as these are not routinely performed in clinical practice. Index time was determined through maximum likelihood estimation in an effort to align the disease severity between the two cohorts with the initiation of maralixibat. Event-free survival, defined as the time to first event of manifestations of portal hypertension (variceal bleeding, ascites requiring therapy), surgical biliary diversion, liver transplant, or death, was analyzed by Cox proportional hazards methods. Sensitivity analyses and adjustments for covariates were applied. Age, total bilirubin, gamma-glutamyl transferase, and alanine aminotransferase were balanced between groups with no statistical differences. Event-free survival in the maralixibat cohort was significantly better than the GALA cohort (HR, 0.305; 95% CI, 0.189-0.491; p <0.0001). Multiple sensitivity and subgroup analyses (including serum bile acid availability) showed similar findings. CONCLUSIONS: This study demonstrates a novel application of a robust statistical method to evaluate outcomes in long-term intervention studies where placebo comparisons are not feasible, providing wide application for rare diseases. This comparison with real-world natural history data suggests that maralixibat improves event-free survival in patients with ALGS.

Evolutionary genomics of the cold-adapted diatom Fragilariopsis cylindrus.

The Southern Ocean houses a diverse and productive community of organisms. Unicellular eukaryotic diatoms are the main primary producers in this environment, where photosynthesis is limited by low concentrations of dissolved iron and large seasonal fluctuations in light, temperature and the extent of sea ice. How diatoms have adapted to this extreme environment is largely unknown. Here we present insights into the genome evolution of a cold-adapted diatom from the Southern Ocean, Fragilariopsis cylindrus, based on a comparison with temperate diatoms. We find that approximately 24.7 per cent of the diploid F. cylindrus genome consists of genetic loci with alleles that are highly divergent (15.1 megabases of the total genome size of 61.1 megabases). These divergent alleles were differentially expressed across environmental conditions, including darkness, low iron, freezing, elevated temperature and increased CO2. Alleles with the largest ratio of non-synonymous to synonymous nucleotide substitutions also show the most pronounced condition-dependent expression, suggesting a correlation between diversifying selection and allelic differentiation. Divergent alleles may be involved in adaptation to environmental fluctuations in the Southern Ocean.

Validation of spot urine in estimating 24-h urinary sodium, potassium and sodium-to-potassium ratio during three different sodium diets in healthy adults.

PURPOSE: To evaluate the validity of spot urine assay methods in estimating the 24-h urinary sodium, potassium and sodium-to-potassium ratio during three different sodium diets. MATERIALS AND METHODS: Twelve healthy volunteers were asked to adhere to 3 dietary sodium targets (3.3-5.0g/day,<3.3 g/day and >5.0 g/day) for three consecutive weeks and to measure salt excretion daily in spot urine samples using a self-monitoring device. On day 7 of each week, 24-h urine was collected to compare measured with estimated 24-h salt excretion (by the Kawasaki, Tanaka and INTERSALT equations). RESULTS: Correlation coefficients relating measured and estimated 24-h sodium excretion were low and not significant for Kawasaki and INTERSALT and moderate for the Tanaka equation (τ 0.56-0.64,p<.05). Bland-Altman plots showed considerable differences between estimated and measured sodium excretion across all salt diets. Over 40% of the participants showed an absolute difference between measured and estimated 24-h sodium of more than 1000 mg/day. The correlation coefficients between 24-h and spot Na/K ratio were 0.67, 0.94 and 0.85(p<.05), and mean differences were 0.59, 0.06 and 0.48 for the intermediate, low and high sodium diets, respectively. CONCLUSION: These findings do not support estimation of individual 24-h salt excretion from spot urine by the Kawasaki, Tanaka, or INTERSALT formula. Plain language summaryAccurate monitoring of salt intake is essential to improve BP control. At present, measurement of sodium and potassium excretion in multiple non-consecutive 24-h urinary collections is considered the gold standard for measuring dietary sodium intake. However, this method is burdensome, time-consuming and error prone.Therefore, we assessed and compared the validity of three formula-based approaches to estimate 24-h urinary sodium and potassium excretion and the Na/K ratio from spot urine samples measured by a self-monitoring device under three different sodium diets using 24-h urine collections as the reference.We conclude that use of three commonly used equations that estimate 24-h urinary sodium and potassium excretion result in substantial bias, poor precision and poor accuracy and are therefore not recommended. The Na/K ratio based on multiple casual urine samples may be a useful, low-burden, low-cost alternative method to 24-h urine collection for monitoring daily salt intake.

The illusion of insight: detailed warnings reduce but do not prevent false "Aha!" moments.

False "Aha!" moments can be elicited experimentally using the False Insight Anagram Task (FIAT), which combines semantic priming and visual similarity manipulations to lead participants into having "Aha!" moments for incorrect anagram solutions. In a preregistered experiment (N = 255), we tested whether warning participants and explaining to them exactly how they were being deceived, would reduce their susceptibility to false insights. We found that simple warnings did not reduce the incidence of false insights. On the other hand, participants who were given a detailed explanation of the methods used to deceive them experienced a small reduction in false insights compared to participants given no warning at all. Our findings suggest that the FIAT elicits a robust false insight effect that is hard to overcome, demonstrating the persuasive nature of false insights when the conditions are ripe for them.

Real-time monitoring of drug laboratory test interactions: a proof of concept.

OBJECTIVES: For the correct interpretation of test results, it is important to be aware of drug-laboratory test interactions (DLTIs). If DLTIs are not taken into account by clinicians, erroneous interpretation of test results may lead to a delayed or incorrect diagnosis, unnecessary diagnostic testing or therapy with possible harm for patients. A DLTI alert accompanying a laboratory test result could be a solution. The aim of this study was to test a multicentre proof of concept of an electronic clinical decision support system (CDSS) for real-time monitoring of DLTIs. METHODS: CDSS was implemented in three Dutch hospitals. So-called 'clinical rules' were programmed to alert medical specialists for possible DLTIs based on laboratory test results outside the reference range in combination with prescribed drugs. A selection of interactions from the DLTI database of the Dutch society of clinical chemistry and laboratory medicine were integrated in 43 clinical rules, including 24 tests and 25 drugs. During the period of one month all generated DTLI alerts were registered in the laboratory information system. RESULTS: Approximately 65 DLTI alerts per day were detected in each hospital. Most DLTI alerts were generated in patients from the internal medicine and intensive care departments. The most frequently reported DLTI alerts were potassium-proton pump inhibitors (16%), potassium-beta blockers (11%) and creatine kinase-statins (11%). CONCLUSIONS: This study shows that it is possible to alert for potential DLTIs in real-time with a CDSS. The CDSS was successfully implemented in three hospitals. Further research must reveal its usefulness in clinical practice.

Racial/Ethnic Disparities in the Management of Pediatric Acute Pancreatitis Across Children's Hospitals.

OBJECTIVES: Racial or ethnic disparities in health care delivery and resource utilization have been reported in a variety of pediatric diseases. In acute pancreatitis (AP), there is an association between Black race and increased inpatient mortality. Data on the association of race and ethnicity and resource use for managing pediatric AP are lacking. The aim of this study is to investigate this potential association in pediatric AP. METHODS: Retrospective study of children 0-18 years diagnosed with AP in the Pediatric Health Information System (PHIS) database from 2012 to 2018. Descriptive statistics were used to summarize cohort characteristics. Race/ethnicity classifications included non-Hispanic Black (NHB), non-Hispanic White (NHW, used as reference), Hispanic, and "Other." Associations between patient characteristics and race/ethnicity were determined using χ2 tests. Generalized linear mixed regression model was used to determine the association of race/ethnicity with odds of resource utilization, costs, and length of hospital stay after adjusting for covariates with a random intercept for site. RESULTS: Five thousand nine hundred sixty-three patients from 50 hospitals were included. Adjusted analysis showed that NHB children hospitalized with AP were at lower odds of receiving opioids in the first 24 hours [adjusted odds ratio (aOR) = 0.82, 95% confidence interval (CI) = 0.70-0.98] and receiving intravenous fluids during the hospitalization (aOR = 0.64, 95% CI = 0.43-0.96) when compared with NHW children. Additionally, NHB and Hispanic children had a prolonged adjusted mean length of hospital stay and higher hospital costs when compared with NHW children. Although there was no significant association between race/ethnicity and diagnosis of pancreatic necrosis or sepsis, Hispanic and "Other" children were at higher odds of receiving antibiotics during hospitalization for AP (aOR = 1.33, 95% CI = 1.13-1.57 and aOR = 1.37, 95% CI = 1.09-1.73, respectively) than NHW children. CONCLUSIONS: Disparities exist in utilization of health care interventions for pediatric AP patients by race/ethnicity. Future studies should investigate why these disparities exist and if these disparities affect outcomes.

Thinking style and psychosis proneness do not predict false insights.

The FIAT paradigm (Grimmer et al., 2021) is a novel method of eliciting 'Aha' moments for incorrect solutions to anagrams in the laboratory, i.e. false insights. There exist many documented reports of psychotic symptoms accompanying strong feelings of 'Aha!' (Feyaerts, Henriksen, Vanheule, Myin-Germeys, & Sass, 2021; Mishara, 2010; Tulver, Kaup, Laukkonen, & Aru, 2021), suggesting that the newly developed FIAT could reveal whether people who have more false insights are more prone to psychosis and delusional belief. To test this possibility, we recruited 200 participants to take an adapted version of the FIAT and complete measures of thinking style and psychosis proneness. We found no association between experimentally induced false insights and measures of Schizotypy, Need for Cognition, Jumping to Conclusions, Aberrant Salience, Faith in Intuition, or the Cognitive Reflection Task. We conclude that experiencing false insights might not be constrained to any particular type of person, but rather, may arise for anyone under the right circumstances.

A systematic review on the use of quantitative imaging to detect cancer therapy adverse effects in normal-appearing brain tissue.

Cancer therapy for both central nervous system (CNS) and non-CNS tumors has been previously associated with transient and long-term cognitive deterioration, commonly referred to as 'chemo fog'. This therapy-related damage to otherwise normal-appearing brain tissue is reported using post-mortem neuropathological analysis. Although the literature on monitoring therapy effects on structural magnetic resonance imaging (MRI) is well established, such macroscopic structural changes appear relatively late and irreversible. Early quantitative MRI biomarkers of therapy-induced damage would potentially permit taking these treatment side effects into account, paving the way towards a more personalized treatment planning.This systematic review (PROSPERO number 224196) provides an overview of quantitative tomographic imaging methods, potentially identifying the adverse side effects of cancer therapy in normal-appearing brain tissue. Seventy studies were obtained from the MEDLINE and Web of Science databases. Studies reporting changes in normal-appearing brain tissue using MRI, PET, or SPECT quantitative biomarkers, related to radio-, chemo-, immuno-, or hormone therapy for any kind of solid, cystic, or liquid tumor were included. The main findings of the reviewed studies were summarized, providing also the risk of bias of each study assessed using a modified QUADAS-2 tool. For each imaging method, this review provides the methodological background, and the benefits and shortcomings of each method from the imaging perspective. Finally, a set of recommendations is proposed to support future research.

A Wolf in Sheep's Clothing: Reuse of Routinely Obtained Laboratory Data in Research.

Electronic health records (EHRs) contain valuable data for reuse in science, quality evaluations, and clinical decision support. Because routinely obtained laboratory data are abundantly present, often numeric, generated by certified laboratories, and stored in a structured way, one may assume that they are immediately fit for (re)use in research. However, behind each test result lies an extensive context of choices and considerations, made by both humans and machines, that introduces hidden patterns in the data. If they are unaware, researchers reusing routine laboratory data may eventually draw incorrect conclusions. In this paper, after discussing health care system characteristics on both the macro and micro level, we introduce the reader to hidden aspects of generating structured routine laboratory data in 4 steps (ordering, preanalysis, analysis, and postanalysis) and explain how each of these steps may interfere with the reuse of routine laboratory data. As researchers reusing these data, we underline the importance of domain knowledge of the health care professional, laboratory specialist, data manager, and patient to turn routine laboratory data into meaningful data sets to help obtain relevant insights that create value for clinical care.

How does image quality affect radiologists' perceived ability for image interpretation and lesion detection in digital mammography?

OBJECTIVES: To study how radiologists' perceived ability to interpret digital mammography (DM) images is affected by decreases in image quality. METHODS: One view from 45 DM cases (including 30 cancers) was degraded to six levels each of two acquisition-related issues (lower spatial resolution and increased quantum noise) and three post-processing-related issues (lower and higher contrast and increased correlated noise) seen during clinical evaluation of DM systems. The images were shown to fifteen breast screening radiologists from five countries. Aware of lesion location, the radiologists selected the most-degraded mammogram (indexed from 1 (reference) to 7 (most degraded)) they still felt was acceptable for interpretation. The median selected index, per degradation type, was calculated separately for calcification and soft tissue (including normal) cases. Using the two-sided, non-parametric Mann-Whitney test, the median indices for each case and degradation type were compared. RESULTS: Radiologists were not tolerant to increases (medians: 1.5 (calcifications) and 2 (soft tissue)) or decreases (median: 2, for both types) in contrast, but were more tolerant to correlated noise (median: 3, for both types). Increases in quantum noise were tolerated more for calcifications than for soft tissue cases (medians: 3 vs. 4, p = 0.02). Spatial resolution losses were considered less acceptable for calcification detection than for soft tissue cases (medians: 3.5 vs. 5, p = 0.001). CONCLUSIONS: Perceived ability of radiologists for image interpretation in DM was affected not only by image acquisition-related issues but also by image post-processing issues, and some of those issues affected calcification cases more than soft tissue cases. KEY POINTS: • Lower spatial resolution and increased quantum noise affected the radiologists' perceived ability to interpret calcification cases more than soft tissue lesion or normal cases. • Post-acquisition image processing-related effects, not only image acquisition-related effects, also impact the perceived ability of radiologists to interpret images and detect lesions. • In addition to current practices, post-acquisition image processing-related effects need to also be considered during the testing and evaluation of digital mammography systems.

Accounting for Heterogeneity in Resource Allocation Decisions: Methods and Practice in UK Cancer Technology Appraisals.

OBJECTIVES: The availability of novel, more efficacious and expensive cancer therapies is increasing, resulting in significant treatment effect heterogeneity and complicated treatment and disease pathways. The aim of this study is to review the extent to which UK cancer technology appraisals (TAs) consider the impact of patient and treatment effect heterogeneity. METHODS: A systematic search of National Institute for Health and Care Excellence TAs of colorectal, lung and ovarian cancer was undertaken for the period up to April 2020. For each TA, the pivotal clinical studies and economic evaluations were reviewed for considerations of patient and treatment effect heterogeneity. The study critically reviews the use of subgroup analysis and real-world translation in economic evaluations, alongside specific attributes of the economic modeling framework. RESULTS: The search identified 49 TAs including 49 economic models. In total, 804 subgroup analyses were reported across 69 clinical studies. The most common stratification factors were age, gender, and Eastern Cooperative Oncology Group performance score, with 15% (119 of 804) of analyses demonstrating significantly different clinical outcomes to the main population; economic subgroup analyses were undertaken in only 17 TAs. All economic models were cohort-level with the majority described as partitioned survival models (39) or Markov/semi-Markov models. The impact of real-world heterogeneity on disease progression estimates was only explored in 2 models. CONCLUSION: The ability of current modeling approaches to capture patient and treatment effect heterogeneity is constrained by their limited flexibility and simplistic nature. This study highlights a need for the use of more sophisticated modeling methods that enable greater consideration of real-world heterogeneity.

Clinical usefulness of drug-laboratory test interaction alerts: a multicentre survey.

OBJECTIVES: Knowledge of possible drug-laboratory test interactions (DLTIs) is important for the interpretation of laboratory test results. Failure to recognize these interactions may lead to misinterpretation, a delayed or erroneous diagnosis, or unnecessary extra diagnostic tests or therapy, which may harm patients. The aim of this multicentre survey was to evaluate the clinical value of DLTI alerts. METHODS: A survey was designed with six predefined clinical cases selected from the clinical laboratory practice with a potential DLTI. Physicians from several departments, including internal medicine, cardiology, intensive care, surgery and geriatrics in six participating hospitals were recruited to fill in the survey. The survey addressed their knowledge of DLTIs, motivation to receive an alert and opinion on the potential influence on medical decision making. RESULTS: A total of 210 physicians completed the survey. Of these respondents 93% had a positive attitude towards receiving DLTI alerts; however, the reported value differed per case and per respondent's background. In each clinical case, medical decision making was influenced as a consequence of the reported DLTI message (ranging from 3 to 45% of respondents per case). CONCLUSIONS: In this multicentre survey, most physicians stated DLTI messages to be useful in laboratory test interpretation. Medical decision making was influenced by reporting DLTI alerts in each case. Alerts should be adjusted according to the needs and preferences of the receiving physicians.

Glucocorticoids Improve Enteral Feeding Tolerance in Pediatric Short Bowel Syndrome With Chronic Intestinal Inflammation.

OBJECTIVES: A group of short bowel syndrome (SBS) patients developed chronic intestinal inflammation while struggling weaning off parenteral nutrition (PN). They did not respond to standard management of SBS and food allergy. We treated them with glucocorticoids and described the outcome. METHODS: Our study is a retrospective descriptive study. We reviewed records from the intestinal rehabilitation program from 2006 to 2017. We identified 15 patients whose lab values, pathology results, and clinic notes were reviewed. RESULTS: We had more patients (n = 10) with diagnosis of gastroschisis, and more female patients (n = 9). Seven patients weaned off PN with median treatment duration of 5 months, 5 of which remained on budesonide for significant period of time (median: 7.5 months). One of these 7 patients relapsed, as the patient resumed glucocorticoids because of recurrence of chronic intestinal inflammation. Six of 15 children had significant eosinophils in their initial biopsy, 5 of these children weaned off PN whereas 1 child's gastrointestinal (GI) bleeding stopped. Four patients were not able to decrease PN calorie. Two of these patients' GI bleeding stopped, the other 2 had normalized histology. CONCLUSIONS: For SBS children with histologically confirmed chronic intestinal inflammation, glucocorticoids may help promote enteral feeding tolerance. Glucocorticoids regimen should be chosen individually. Patients are more likely to respond if initial histology has significant eosinophilic infiltration. Patients may need to remain on glucocorticoids for over 6 months.

Getting a grip on insight: real-time and embodied Aha experiences predict correct solutions.

Insight experiences are sudden, persuasive, and can accompany valuable new ideas in science and art. In this preregistered experiment, we aim to validate a novel visceral and continuous measure of insight problem solving and to test whether real-time and embodied feelings of insight can predict correct solutions. We report several findings. Consistent with recent work, we find a strong positive relationship between Aha moments and accuracy for problems that demand implicit processing. We also found that the intensity of the insight experience further predicted the accuracy of solutions and participants naturally embodied the intensity of their insight experiences by squeezing the dynamometer more tightly. Intriguingly, this unintentional embodiment further predicted the accuracy of solutions. We suggest that the dynamometer complements previous measures by (1) simultaneously capturing both process and feeling in real-time, (2) highlights the value of measuring Aha moments on a continuum of intensity, and (3) firmly establishes that the impulsive feeling of Aha can carry information about the veracity of an idea. We discuss the findings in light of a recent theoretical account of how feelings of insight may act as a heuristic to select ideas from the stream of consciousness.

Parasitoids indicate major climate-induced shifts in arctic communities.

Climatic impacts are especially pronounced in the Arctic, which as a region is warming twice as fast as the rest of the globe. Here, we investigate how mean climatic conditions and rates of climatic change impact parasitoid insect communities in 16 localities across the Arctic. We focus on parasitoids in a widespread habitat, Dryas heathlands, and describe parasitoid community composition in terms of larval host use (i.e., parasitoid use of herbivorous Lepidoptera vs. pollinating Diptera) and functional groups differing in their closeness of host associations (koinobionts vs. idiobionts). Of the latter, we expect idiobionts-as being less fine-tuned to host development-to be generally less tolerant to cold temperatures, since they are confined to attacking hosts pupating and overwintering in relatively exposed locations. To further test our findings, we assess whether similar climatic variables are associated with host abundances in a 22 year time series from Northeast Greenland. We find sites which have experienced a temperature rise in summer while retaining cold winters to be dominated by parasitoids of Lepidoptera, with the reverse being true for the parasitoids of Diptera. The rate of summer temperature rise is further associated with higher levels of herbivory, suggesting higher availability of lepidopteran hosts and changes in ecosystem functioning. We also detect a matching signal over time, as higher summer temperatures, coupled with cold early winter soils, are related to high herbivory by lepidopteran larvae, and to declines in the abundance of dipteran pollinators. Collectively, our results suggest that in parts of the warming Arctic, Dryas is being simultaneously exposed to increased herbivory and reduced pollination. Our findings point to potential drastic and rapid consequences of climate change on multitrophic-level community structure and on ecosystem functioning and highlight the value of collaborative, systematic sampling effort.

Colloid osmotic pressure of contemporary and novel transfusion products.

BACKGROUND AND OBJECTIVES: Colloid osmotic pressure (COP) is a principal determinant of intravascular fluid homeostasis and a pillar of fluid therapy and transfusion. Transfusion-associated circulatory overload (TACO) is a leading complication of transfusion, and COP could be responsible for recruiting additional fluid. Study objective was to measure COP of blood products as well as investigate the effects of product concentration and storage lesion on COP. MATERIALS AND METHODS: Three units of each product were sampled longitudinally. COP was measured directly as well as the determinants thereof albumin and total protein. Conventional blood products, that is red blood cell (RBC), fresh-frozen plasma (FFP) and platelet concentrates (PLTs), were compared with their concentrated counterparts: volume-reduced RBCs, hyperconcentrated PLTs, and fully and partially reconstituted lyophilized plasma (prLP). Fresh and maximally stored products were measured to determine changes in protein and COP. We calculated potential volume load (PVL) to estimate volume recruited using albumin's water binding per product. RESULTS: Colloid osmotic pressure varies widely between conventional products (RBCs, 1·9; PLTs, 7·5; and FFP, 20·1 mmHg); however, all are hypooncotic compared with human plasma COP (25·4 mmHg). Storage lesion did not increase COP. Concentrating RBCs and PLTs did not increase COP; only prLP showed a supraphysiological COP of 47·3 mm Hg. The PVL of concentrated products was lower than conventional products. CONCLUSION: Colloid osmotic pressure of conventional products was low. Therefore, third-space fluid recruitment is an unlikely mechanism in TACO. Concentrated products had a lower calculated fluid load and may prevent TACO. Finally, storage did not significantly increase oncotic pressure of blood products.

North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Position Paper on Entrustable Professional Activities: Development of Pediatric Gastroenterology, Hepatology, and Nutrition Entrustable Professional Activities.

Quality training in pediatric gastroenterology, hepatology, and nutrition is essential for the future of our specialty from advancing the science through research to providing clinical care for children with gastrointestinal, hepatic and nutritional disorders. As educational theory has developed, both the American Board of Pediatrics (ABP) and the Accreditation Council for Graduate Medical Education (ACGME) have commissioned projects to better define training including core competencies, and milestones with the goal of competency-based assessment. Seeking to provide a clinical context for these competencies and milestones, the ABP commissioned a project for each pediatric subspecialty to develop entrustable professional activities (EPA) while at the same time developing EPAs that are common to all pediatric subspecialties. North American Society for Pediatric Gastroenterology, Hepatology, Nutrition (NASPGHAN) commissioned an EPA Task Force to develop the pediatric gastroenterology, hepatology and nutrition EPAs. This document serves as an introduction to EPAs, including their historical background, underlying educational theory, and the process used to develop the pediatric gastroenterology, hepatology and nutrition EPAs in the United States of America.

Pediatric Gastroenterology, Hepatology, and Nutrition Entrustable Professional Activities: Development of an Assessment Tool and Curricular Resources.

BACKGROUND: Entrustable professional activities (EPAs) are critical activities performed by medical professionals, which can be observed and assessed. Adding on to common EPAs for all pediatric subspecialty trainees, specialty-specific EPAs for pediatric gastroenterology, hepatology, and nutritional fellowship were developed by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) EPA Task Force. METHODS: Having developed specialty-specific EPAs, building EPA assessments is the next logical step, as EPAs are included under a larger umbrella of competency-based assessment. Thus, the NASPGHAN EPA Task Force and Training Committee collaborated on an assessment tool and associated curricular resources to aid in tracking trainees' progression to entrustment within individual EPAs and readiness for independent practice. RESULTS: This manuscript reports the development of an EPA assessment tool, including guiding principles and the theory behind the assessment tool, with a focus on simple, meaningful assessments that can provide crucial performance feedback to trainees. In addition, curricular resources were developed, based on the assessment tool, to support training. Ultimately, it is the hope of the NASPGHAN EPA Task Force and Training Committee that this tool can aid training programs in providing formative feedback for trainees, and can be used by training programs and clinical competency committees for summative evaluation.

The heterogeneous causal effects of neonatal care: a model of endogenous demand for multiple treatment options based on geographical access to care.

Neonatal units in the UK are organised into three levels, from highest Neonatal Intensive Care Unit (NICU), to Local Neonatal Unit (LNU) to lowest Special Care Unit (SCU). We model the endogenous treatment selection of neonatal care unit of birth to estimate the average and marginal treatment effects of different neonatal designations on infant mortality, length of stay and hospital costs. We use prognostic factors, survival and hospital care use data on all preterm births in England for 2014-2015, supplemented by national reimbursement tariffs and instrumental variables of travel time from a geographic information system. The data were consistent with a model of demand for preterm birth care driven by physical access. In-hospital mortality of infants born before 32 weeks was 8.5% overall, and 1.2 (95% CI: -0.7, 3.2) percentage points lower for live births in hospitals with NICU or SCU compared to those with an LNU according to instrumental variable estimates. We find imprecise differences in average total hospital costs by unit designation, with positive unobserved selection of those with higher unexplained absolute and incremental costs into NICU. Our results suggest a limited scope for improvement in infant mortality by increasing in-utero transfers based on unit designation alone.