Synthetic DNA barcodes identify singlets in scRNA-seq datasets and evaluate doublet algorithms.

Single-cell RNA sequencing (scRNA-seq) datasets contain true single cells, or singlets, in addition to cells that coalesce during the protocol, or doublets. Identifying singlets with high fidelity in scRNA-seq is necessary to avoid false negative and false positive discoveries. Although several methodologies have been proposed, they are typically tested on highly heterogeneous datasets and lack a priori knowledge of true singlets. Here, we leveraged datasets with synthetically introduced DNA barcodes for a hitherto unexplored application: to extract ground-truth singlets. We demonstrated the feasibility of our framework, "singletCode," to evaluate existing doublet detection methods across a range of contexts. We also leveraged our ground-truth singlets to train a proof-of-concept machine learning classifier, which outperformed other doublet detection algorithms. Our integrative framework can identify ground-truth singlets and enable robust doublet detection in non-barcoded datasets.

Impact of inflammatory bowel disease on the risk of acute coronary syndrome: A Swedish Nationwide Cohort Study.

BACKGROUND: There are conflicting data on the risk of acute coronary syndrome (ACS) in patients with inflammatory bowel disease (IBD). Only a few previous reports include patients diagnosed during the last decade. AIM: To assess and compare the risk of ACS between patients with IBD and the general population. METHODS: In this cohort study, we used nationwide registers to identify patients diagnosed with IBD in Sweden 2003-2021. Every patient was matched by birth year, sex, calendar year and area of residence with up to 10 general population comparators. The primary outcome was incident ACS. We used semi-parametric Cox proportional hazard models to estimate hazard ratios (HRs). RESULTS: We identified 76,517 patients with IBD (Crohn's disease [CD], N = 22,732; ulcerative colitis [UC], N = 42,194 and IBD-unclassified, N = 11,591) and 757,141 comparators. During a median follow-up of 8 years, 2546 patients with IBD (37.5/10,000 person-years) were diagnosed with ACS compared with 19,598 (28.0/10,000 person-years) among comparators (HR 1.30; 95% confidence interval 1.24-1.35) after adjustments for confounding factors, and approximately one extra case of ACS in 100 IBD patients followed for 10 years. The highest HRs for ACS were in patients with elderly onset IBD (≥60 years) and among patients with CD or UC with extra-intestinal manifestations. No increased HRs were observed in patients diagnosed with IBD before the age of 40. CONCLUSION: In this contemporary cohort of patients with IBD, exposed to modern IBD care, there was an increased risk for ACS compared with individuals from the general population.

Spondyloarthritis in first-degree relatives and spouses of patients with inflammatory bowel disease: A nationwide population-based cohort study from Sweden.

BACKGROUND AND AIMS: Register-based research suggests a shared pathophysiology between inflammatory bowel disease [IBD] and spondyloarthritis [SpA], but the role of familial [genetic and environmental] factors in this shared susceptibility is largely unknown. We compared the risk of SpA in first-degree relatives [FDRs] and spouses of IBD patients with FDRs and spouses of matched population-based reference individuals. METHODS: We identified 147,080 FDRs and 25,945 spouses of patients with incident IBD [N=39,203] during 2006-2016 and 1,453,429 FDRs and 258,098 spouses of matched reference individuals [N=390,490], by linking nationwide Swedish registers and gastrointestinal biopsy data. Study participants were followed 1987-2017. Cox regression was used to estimate hazard ratios [HRs] of SpA. RESULTS: During follow-up, 2,430 FDRs of IBD patients [6.5/10,000 person-years] and 17,761 FDRs of reference individuals [4.8/10,000 person-years] were diagnosed with SpA, corresponding to an HR of 1.35 [95%CI:1.29,1.41]. In subgroup analyses, the increased risk of SpA was most pronounced in FDRs of Crohn's disease patients [HR=1.44; 95%CI:1.34,1.56] and of IBD patients aged <18 years at diagnosis [HR=1.46; 95%CI: 1.27,1.68]. IBD patient's spouses also had a higher SpA rate than reference individuals' spouses, but the difference was less pronounced [4.3 vs. 3.5/10,000 person-years; HR=1.22; 95%CI:1.09,1.37]. No subgroup-specific risk pattern was identified among spouses. CONCLUSIONS: The observed shared familial risks between IBD and SpA support shared genetic factors in their pathogenesis. However, spouses of IBD patients were also at increased risk for SpA, reflecting the influence of environmental exposures or similarities in health-seeking patterns.

Clonally heritable gene expression imparts a layer of diversity within cell types.

Cell types can be classified according to shared patterns of transcription. Non-genetic variability among individual cells of the same type has been ascribed to stochastic transcriptional bursting and transient cell states. Using high-coverage single-cell RNA profiling, we asked whether long-term, heritable differences in gene expression can impart diversity within cells of the same type. Studying clonal human lymphocytes and mouse brain cells, we uncovered a vast diversity of heritable gene expression patterns among different clones of cells of the same type in vivo. We combined chromatin accessibility and RNA profiling on different lymphocyte clones to reveal thousands of regulatory regions exhibiting interclonal variation, which could be directly linked to interclonal variation in gene expression. Our findings identify a source of cellular diversity, which may have important implications for how cellular populations are shaped by selective processes in development, aging, and disease. A record of this paper's transparent peer review process is included in the supplemental information.

Adverse Safety Events in Emergency Medical Services Care of Children With Out-of-Hospital Cardiac Arrest.

Importance: Survival for children with out-of-hospital cardiac arrest (OHCA) remains poor despite improvements in adult OHCA survival. Objective: To characterize the frequency of and factors associated with adverse safety events (ASEs) in pediatric OHCA. Design, Setting, and Participants: This population-based retrospective cohort study examined patient care reports from 51 emergency medical services (EMS) agencies in California, Georgia, Oregon, Pennsylvania, Texas, and Wisconsin for children younger than 18 years with an OHCA in which resuscitation was attempted by EMS personnel between 2013 and 2019. Medical record review was conducted from January 2019 to April 2022 and data analysis from October 2022 to February 2023. Main Outcomes and Measure: Severe ASEs during the patient encounter (eg, failure to give an indicated medication, 10-fold medication overdose). Results: A total of 1019 encounters of EMS-treated pediatric OHCA were evaluated; 465 patients (46%) were younger than 12 months. At least 1 severe ASE occurred in 610 patients (60%), and 310 patients (30%) had 2 or more. Neonates had the highest frequency of ASEs. The most common severe ASEs involved epinephrine administration (332 [30%]), vascular access (212 [19%]), and ventilation (160 [14%]). In multivariable logistic regression, the only factor associated with severe ASEs was young age. Neonates with birth-related and non-birth-related OHCA had greater odds of a severe ASE compared with adolescents (birth-related: odds ratio [OR], 7.0; 95% CI, 3.1-16.1; non-birth-related: OR, 3.4; 95% CI, 1.2-9.6). Conclusions and Relevance: In this large geographically diverse cohort of children with EMS-treated OHCA, 60% of all patients experienced at least 1 severe ASE. The odds of a severe ASE were higher for neonates than adolescents and even higher when the cardiac arrest was birth related. Given the national increase in out-of-hospital births and ongoing poor outcomes of OHCA in young children, these findings represent an urgent call to action to improve care delivery and training for this population.

Comparative study of a point-of-care test and an enzyme-linked immunosorbent assay (ELISA) for infliximab levels.

BACKGROUND: Proactive therapeutic drug monitoring (TDM) is often challenged by long turnaround time when using enzyme-linked immunosorbent assays (ELISAs), especially when analyses are centralised. Point-of-care tests (POCTs) allow rapid assessments, but data on their agreement with existing in-house methodologies are scarce. OBJECTIVE: To examine the agreement between a POCT by ProciseDx (San Diego, CA) and the most frequently used in-house ELISA for infliximab (IFX) quantification in Sweden. METHODS: Serum samples were analysed using the in-house ELISA, Karolinska University Hospital, Stockholm, Sweden and a POCT by ProciseDx (San Diego, CA). Agreement was assessed and differences were examined. RESULTS: Samples from 61 inflammatory bowel disease (IBD) patients were analysed with a median IFX concentration of 7.9 µg/mL (interquartile range (IQR) 5.5-13) for the POCT and 7.9 µg/mL (IQR 5.2-12) for the ELISA (Pearson's correlation coefficient = 0.95 (95% CI 0.92-0.97, p < .01)). A Passing-Bablok regression yielded an intercept of -0.44 and a slope of 1.09. The Bland-Altman plot showed a systemic bias of -0.77 µg/mL (95% CI -0.18 to -1.4) between the methods. The upper limit of agreement was 3.7 (95% CI 2.7-4.8) (µg/mL), whereas the lower limit agreement was -5.3 (95% CI -6.3 to -4.3) (µg/mL). An excellent reliability was observed, intraclass correlation showed = 0.94 (95% CI 0.89-0.96, p < .0001). When defining IFX concentration as subtherapeutic (<3.0 µg/mL), therapeutic (3.0-7.0 µg/mL) or supratherapeutic (>7.0 µg/mL) drug levels, Kappa statistics showed a substantial agreement (0.79). CONCLUSIONS: The POCT by ProciseDx (San Diego, CA) demonstrated a good agreement with the in-house ELISA, supporting its use for rapid IFX quantification.

Identifying high cognitive load activities during simulated pediatric cardiac arrest using functional near-infrared spectroscopy.

Aim: To identify specific activities associated with high cognitive load during simulated pediatric out-of-hospital cardiac arrest (POHCA) resuscitation using physiological monitoring with functional near-infrared spectroscopy (fNIRS). Methods: We recruited teams of emergency medical services (EMS) responders from fire departments located throughout the Portland, OR metropolitan area to participate in POHCA simulations. Teams consisted of both paramedics and emergency medical technicians (EMTs), with one paramedic serving as the person in charge (PIC). The PIC was outfitted with the OctaMon to collect fNIRS signals from the prefrontal cortex. Signals reported changes in oxygenated and deoxygenated hemoglobin concentrations, which were used to determine moments of increased cognitive activity. Increased cognitive activity was determined by significant increases in oxygenated hemoglobin and decreases in deoxygenated hemoglobin. Significant changes in fNIRS signals were associated with specific concurrent clinical tasks recorded by two independent researchers using video review. Results: We recorded cognitive activity of EMS providers in 18 POHCA simulations. We found that a proportion of PIC's experienced relatively high cognitive load during medication administration, defibrillation, and rhythm checks compared to other events. Conclusion: EMS providers commonly experienced increased cognitive activity during key resuscitation tasks that were related to safely coordinating team members around calculating and administering medications, defibrillation, and rhythm and pulse checks. Understanding more about activities that require high cognitive demand can inform future interventions that reduce cognitive load.

Using Two Statewide Medical Operations Coordination Centers to Load Balance in Pediatric Hospitals During a Severe Respiratory Surge in the United States.

OBJECTIVES: Report on the use of two statewide Medical Operations Coordination Centers (MOCCs) to manage a rapid surge in pediatric acute and critical care patient needs. DESIGN: Brief report. SETTING: The states of Washington and Oregon during the pediatric respiratory surge in November 2022/December 2022 which overwhelmed existing pediatric acute and critical care hospital capacity. PATIENTS: Pediatric patients requiring hospitalization in Washington and Oregon. INTERVENTIONS: Adaptations to the use of two existing statewide MOCCs to provide pediatric patient load balancing through surveillance, modifications of existing referral agreements, coordinated expansion of resources, activation of regional crisis standards of care, and integration of pediatric critical care physicians from Harborview Medical Center as subject matter experts (SMEs). MEASUREMENTS AND MAIN RESULTS: The Washington and Oregon MOCCs managed 183 pediatric requests from hospitals unable to transfer pediatric patients between November 1, 2022, and December 14, 2022. Sixteen percent of requests were for children younger than 3 months and 37% were for children between 3 months and 1 year; most had acute viral respiratory disease. Requests for children older than 13 years old were primarily intentional drug ingestions. Fifty-eight percent were for critically ill children and 17% originated from critical access hospitals. Washington's SMEs were utilized in nearly a quarter of cases with the disposition changing in 38% of these. CONCLUSIONS: Washington and Oregon statewide MOCCs have leveraged centralized coordination to effectively load balance a surge in pediatric patients which has overwhelmed existing pediatric hospital resources. Centralized coordination and surveillance informed pediatric hospitals and policy makers of unmet clinical needs and facilitated rapid expansion of clinical capacity and modifications to referral processes. Integration of pediatric SMEs enabled efficient triage of these resources. MOCCs provide an adaptable centralized resource for addressing surge and have been effective in managing overwhelmed pediatric hospital resources in Washington and Oregon.

Outcomes of bariatric surgery for patients with prevalent inflammatory bowel disease: A nationwide registry-based cohort study.

BACKGROUND: Obesity is becoming more prevalent in patients with inflammatory bowel disease. Although bariatric surgery is an effective treatment for obesity, questions remain regarding its safety and effectiveness for patients with inflammatory bowel disease. The aim of this study was to evaluate the safety and effectiveness of bariatric surgery in patients with inflammatory bowel disease. METHOD: This registry-based, propensity-matched cohort study included all patients who had primary Roux-en-Y gastric bypass or sleeve gastrectomy in Sweden from January 2007 to June 2020 who had an inflammatory bowel disease diagnosis and matched control patients without an inflammatory bowel disease diagnosis. The study included data from the Scandinavian Obesity Surgery Registry, the National Patient Register, the Swedish Prescribed Drugs Register, the Total Population Register, and the Education Register from Statistics Sweden. RESULTS: In total, 71,093 patients who underwent bariatric surgery, including 194 with Crohn's disease and 306 with ulcerative colitis, were 1:5 matched to non-inflammatory bowel disease control patients. The patients with Crohn's disease had a higher readmission rate within 30 days (10.7% vs 6.1%, odds ratio = 1.84, 95% confidence interval 1.02-3.31) than the control patients, with no significant difference between the surgical methods. The patients with ulcerative colitis had a higher risk for serious postoperative complications after Roux-en-Y gastric bypass (8.0% vs 3.7%, odds ratio = 2.64, 95% confidence interval 1.15-6.05) but not after sleeve gastrectomy compared to control patients (0.8% vs 2.3%). No difference was observed in postoperative weight loss or postoperative health-related quality of life. CONCLUSION: Sleeve gastrectomy appears to be a safe and effective treatment for obesity in patients with inflammatory bowel disease, whereas Roux-en-Y gastric bypass was associated with a higher risk for postoperative complications in patients with ulcerative colitis.

Long-term outcomes of vedolizumab in inflammatory bowel disease: the Swedish prospective multicentre SVEAH extension study.

Background: Real-world data on long-term outcomes of vedolizumab (VDZ) are scarce. Objective: To assess long-term outcomes (up to 3 years) of VDZ in treating inflammatory bowel disease (IBD). Design: A nationwide, prospective multicentre extension of a Swedish observational study on VDZ assessing Effectiveness And Healthcare resource utilization in patients with IBD (SVEAH). Methods: After re-consent, data of patients with Crohn's disease (CD) (n = 68) and ulcerative colitis (UC) (n = 46) treated with VDZ were prospectively recorded using an electronic case report form integrated with the Swedish IBD Register (SWIBREG). The primary outcome was clinical remission (defined as Harvey-Bradshaw Index ⩽4 in CD and partial Mayo score ⩽2 in UC) at 104 and 156 weeks in patients with a response and/or remission 12 weeks after starting VDZ. Secondary outcomes included health-related quality of life (HRQoL) and biochemical outcomes. Results: VDZ continuation rates were high at weeks 104 and 156, 88% and 84%, respectively, for CD and 87% and 78%, respectively, for UC. Of the 53 CD patients with a response/remission at 12 weeks, 40 (75%) patients were in remission at 104 weeks and 42 (79%) patients at 156 weeks. For UC, these numbers were 25/31 (81%) and 22/31 (71%), respectively. Improvements were seen in the Short Health Scale (p < 0.01 for each dimension; CD, n = 51; UC, n = 33) and the EuroQol 5-Dimensions, 5-levels index value (p < 0.01; CD, n = 39; UC, n = 30). Median plasma-C-reactive protein concentrations (mg/L) decreased from 5 at baseline to 4 in CD (p = 0.01, n = 53) and from 5 to 4 in UC (p = 0.03, n = 34) at 156 weeks. Correspondingly, median faecal-calprotectin (µg/g) decreased from 641 to 114 in CD patients (p < 0.01, n = 26) and from 387 to 37 in UC patients (p = 0.02, n = 17). Conclusion: VDZ demonstrated high continuation rates and was associated with improvements in clinical outcomes, HRQoL measures and inflammatory markers at 2 and 3 years after treatment initiation in this prospective national SVEAH extension study. Registration: ENCePP registration number: EUPAS22735.

Comparison of Resuscitation Quality in Simulated Pediatric and Adult Out-of-Hospital Cardiac Arrest.

Importance: Mortality from pediatric out-of-hospital cardiac arrest (OHCA) is high and has not improved in decades, unlike adult mortality. The low frequency of pediatric OHCA and weight-based medication and equipment needs may lead to lower quality of pediatric resuscitation compared with adults. Objective: To compare the quality of pediatric and adult resuscitation from OHCA in a controlled simulation environment and to evaluate whether teamwork, knowledge, experience, and cognitive load are associated with resuscitation performance. Design, Setting, and Participants: This cross-sectional in-situ simulation study was conducted between September 2020 and August 2021 in the metropolitan area of Portland, Oregon, and included engine companies from fire-based emergency services (EMS) agencies. Exposures: Participating EMS crews completed 4 simulation scenarios presented in random order: (1) adult female with ventricular fibrillation; (2) adult female with pulseless electrical activity; (3) school-aged child with ventricular fibrillation; and (4) infant with pulseless electrical activity. All patients were pulseless on EMS arrival. Data were captured by the research team in real time during the scenarios. Main outcomes and measures: The primary outcome was defect-free care, which included correct cardiopulmonary resuscitation depth, rate, and compression to ventilation ratio, time to bag-mask ventilation, and time to defibrillation, if applicable. Outcomes were determined by direct observation by an experienced physician. Secondary outcomes included additional time-based interventions and the use of correct medication doses and equipment size. We measured teamwork using the clinical teamwork scale, cognitive load with the National Aeronautics and Space Administration task load index (NASA-TLX), and knowledge using advanced life support resuscitation tests. Results: Among the 215 clinicians (39 crews) who participated in 156 simulations, 200 (93%) were male, and the mean (SD) age was 38.7 (0.6) years. No pediatric shockable scenario was defect free and only 5 pediatric nonshockable scenarios (12.8%) were defect free, while 11 (28.2%) adult shockable scenarios and 27 adult nonshockable scenarios (69.2%) were defect free. The mental demand subscale of the NASA-TLX was higher in the pediatric compared with the adult scenarios (mean [SD] pediatric score, 59.1 [20.7]; mean [SD] adult score, 51.4 [21.1]; P = .01). Teamwork scores were not associated with defect-free care. Conclusions and Relevance: In this simulation study of OHCA, resuscitation quality was significantly lower for pediatric than adult resuscitation. Mental demand may have been a contributor.

Measuring cognitively demanding activities in pediatric out-of-hospital cardiac arrest.

BACKGROUND: This methodological intersection article demonstrates a method to measure cognitive load in clinical simulations. Researchers have hypothesized that high levels of cognitive load reduce performance and increase errors. This phenomenon has been studied primarily by experimental designs that measure responses to predetermined stimuli and self-reports that reduce the experience to a summative value. Our goal was to develop a method to identify clinical activities with high cognitive burden using physiologic measures. METHODS: Teams of emergency medical responders were recruited from local fire departments to participate in a scenario with a shockable pediatric out-of-hospital cardiac arrest (POHCA) patient. The scenario was standardized with the patient being resuscitated after receiving high-quality CPR and 3 defibrillations. Each team had a person in charge (PIC) who wore a functional near-infrared spectroscopy (fNIRS) device that recorded changes in oxygenated and deoxygenated hemoglobin concentration in their prefrontal cortex (PFC), which was interpreted as cognitive activity. We developed a data processing pipeline to remove nonneural noise (e.g., motion artifacts, heart rate, respiration, and blood pressure) and detect statistically significant changes in cognitive activity. Two researchers independently watched videos and coded clinical tasks corresponding to detected events. Disagreements were resolved through consensus, and results were validated by clinicians. RESULTS: We conducted 18 simulations with 122 participants. Participants arrived in teams of 4 to 7 members, including one PIC. We recorded the PIC's fNIRS signals and identified 173 events associated with increased cognitive activity. [Defibrillation] (N = 34); [medication] dosing (N = 33); and [rhythm checks] (N = 28) coincided most frequently with detected elevations in cognitive activity. [Defibrillations] had affinity with the right PFC, while [medication] dosing and [rhythm checks] had affinity with the left PFC. CONCLUSIONS: FNIRS is a promising tool for physiologically measuring cognitive load. We describe a novel approach to scan the signal for statistically significant events with no a priori assumptions of when they occur. The events corresponded to key resuscitation tasks and appeared to be specific to the type of task based on activated regions in the PFC. Identifying and understanding the clinical tasks that require high cognitive load can suggest targets for interventions to decrease cognitive load and errors in care.

Ustekinumab Versus Anti-tumour Necrosis Factor Alpha Agents as Second-Line Biologics in Crohn's Disease.

BACKGROUND: There are little data on positioning biologics in Crohn's disease (CD). AIMS: We aimed to assess the comparative effectiveness and safety of ustekinumab vs tumour necrosis factor-alpha (anti-TNF) agents after first-line treatment with anti-TNF in CD. METHODS: We used Swedish nationwide registers to identify patients with CD, exposed to anti-TNF who initiated second-line biologic treatment with ustekinumab or second-line anti-TNF therapy. Nearest neighbour 1:1 propensity score matching (PSM) was used to balance the groups. The primary outcome was 3-year drug survival used as a proxy for effectiveness. Secondary outcomes included drug survival without hospital admission, CD-related surgery, antibiotics, hospitalization due to infection and exposure to corticosteroids. RESULTS: Some 312 patients remained after PSM. Drug survival at 3 years was 35% (95% CI 26-44%) in ustekinumab compared to 36% (95% CI 28-44%) in anti-TNF-treated patients (p = 0.72). No statistically significant differences were observed between the groups in 3-year survival without hospital admission (72% vs 70%, p = 0.99), surgery (87% vs 92%, p = 0.17), hospital admission due to infection (92% vs 92%, p = 0.31) or prescription of antibiotics (49% vs 50%, p = 0.56). The proportion of patients continuing second-line biologic therapy did not differ by reason for ending first-line anti-TNF (lack of response vs intolerance) or by type of first-line anti-TNF (adalimumab vs infliximab). CONCLUSION: Based on data from Swedish routine care, no clinically relevant differences in effectiveness or safety of second-line ustekinumab vs anti-TNF treatment were observed in patients with CD with prior exposure to anti-TNF.

Ustekinumab treatment in ulcerative colitis: Real-world data from the Swedish inflammatory bowel disease quality register.

BACKGROUND: Real-world data on clinical outcomes of ustekinumab in ulcerative colitis are lacking. OBJECTIVE: To assess short- and long-term clinical outcomes of ustekinumab in ulcerative colitis. METHODS: Adult ulcerative colitis patients without previous colectomy starting ustekinumab treatment up until 11 December 2020 were identified through the Swedish Inflammatory Bowel Disease Register (SWIBREG). Prospectively recorded data were extracted from the SWIBREG. The primary outcome was persistence to ustekinumab 16 weeks after treatment initiation. Secondary outcomes included drug persistence beyond week 16, clinical remission (defined as a patient-reported Mayo rectal bleeding subscore = 0 and stool frequency subscore ≤1), biochemical remission (defined as faecal-calprotectin <250 µg/g) and changes in health-related quality of life (HRQoL), as measured by the Short Health Scale (SHS). Logistic regression was used to identify potential predictors of ustekinumab persistence at 16 weeks. RESULTS: Of the 133 patients with ulcerative colitis, only three were naïve to biologics and tofacitinib. The persistence rates of ustekinumab were 115/133 (86%) at 16 weeks and 89/133 (67%) at last follow-up, that is, after a median follow-up of 32 (interquartile range 19-56) weeks. The clinical remission rates were 17% at 16 weeks and 32% at the last follow-up. The corresponding rates for biochemical remission were 14% and 23%. The median faecal-calprotectin concentration decreased from 740 µg/g at baseline to 98 µg/g at the last follow-up (p < 0.01, n = 37). Improvement was seen in each dimension of the SHS between baseline and last follow-up (p < 0.01 for each dimension, n = 46). Male sex was associated with ustekinumab persistence at 16 weeks (adjusted odds ratio = 4.00, 95% confidence interval: 1.35-11.83). CONCLUSION: In this nationwide real-world cohort of ulcerative colitis patients with prior drug failures, including other biologics and tofacitinib, ustekinumab was associated with high drug persistence rates and improvements in clinical, biochemical and HRQoL measures.

A chart review tool to systematically assess the safety of prehospital care for children with out-of-hospital cardiac arrest.

Objective: Create an easy-to-use pediatric out-of-hospital cardiac arrest (OHCA)-specific chart review tool to reliably detect severe adverse safety events (ASEs) in the prehospital care of children with OHCA. Methods: We revised our previously validated pediatric prehospital adverse event detection system (PEDS) tool, used to evaluate ASEs in the prehospital care of children during emergent calls, to create an OHCA-specific chart review tool. We developed decision support for reviewers, reviewer training, and a dedicated section for chart data abstraction. We randomly selected 28 charts for independent review by 2 expert reviewers who determined the presence or absence of a severe ASE for each care episode and identified the domain of care and preventability for each ASE. We calculated inter-rater agreement in the assessment of the presence or absence of a severe ASE using Gwet's first-order agreement coefficient (AC1). Results: The PEDS-OHCA chart review tool has 6 sections, with a minimum of 70 and maximum of 667 total possible fields. We found inter-rater agreement of 0.83 (95% confidence interval, 0.63-0.99) between our 2 reviewers for the overall detection of a severe ASE and an average time to complete of 8 minutes (range, 2-25 minutes). Inter-rater agreement in the detection of a severe ASE in each individual domain ranged from 0.36 to 0.96. Conclusions: The PEDS-OHCA is the first chart review tool to systematically evaluate the safety and quality of EMS care for children with OHCA. This tool may help improve understanding of the quality of EMS care for children with OHCA, which is essential to improving outcomes.

Universal Level Designations for Hospitalized Pediatric Patients in Evacuation.

Children comprise approximately 22% of the population in the United States.1 In a widespread disaster such as a hurricane, pandemic, wildfire or major earthquake, children are at least proportionately affected to their share of the population, if not more so. They also have unique vulnerabilities including physical, mental, and developmental differences from adults, which make them more prone to adverse health effects of disasters.2-4 There are about 5000 pediatric critical care beds and 23 000 neonatal intensive care beds out of 900 000 total hospital beds in the United States.5 While no mechanism exists to consistently track pediatric acute care beds nationally (especially in real time), a previous study6 showed a 7% decline in pediatric medical-surgical beds between 2002 and 2011. This study also estimated there are about 30 000 acute care pediatric beds nationally. Finding appropriate hospital resources for the provision of care for pediatric disaster victims is an important concern for those charged with triaging patients in a major event.

Clinical effectiveness of golimumab in ulcerative colitis: a prospective multicentre study based on the Swedish IBD Quality Register, SWIBREG.

OBJECTIVES: Clinical trials demonstrated that golimumab is effective in anti-TNF naïve patients with ulcerative colitis. We aimed to assess the clinical effectiveness of golimumab in a real-world setting. MATERIALS AND METHODS: This was a prospective cohort study, conducted at 16 Swedish hospitals. Data were collected using an electronic case report form. Patients with active ulcerative colitis, defined as Mayo endoscopic subscore ≥2 were eligible for inclusion. The primary outcomes were clinical effectiveness at 12 weeks and 52 weeks, i.e. response (defined as a decrease in Mayo score by ≥3 points or 30% from baseline) and remission (defined as a Mayo score of ≤2 with no individual subscores >1). RESULTS: Fifty patients were included. At study entry, 70% were previously exposed to anti-TNF, 16% to vedolizumab, and 96% to immunomodulators. The 12 and 52-week drug continuation rates were 37/50 (74%) and 23/50 (46%), respectively. The 12-week response rate was 14/50 (28%), the remission rate, 8/50 (16%) and the corresponding figures at week 52 were 13/50 (26%) and 10/50 (20%). Among patients who continued golimumab, the median Mayo score decreased from 7 (6-9) at baseline to 1 (0-5) at 52 weeks (p < .01) and the faecal calprotectin decreased from 862 (335-1759) µg/g to 90 (34-169) µg/g (p < .01). Clinical response at week 12 was highly predictive of clinical remission at week 52 (adjusted OR: 73.1; 95% CI: 4.5‒1188.9). CONCLUSIONS: The majority of golimumab treated patients represented a treatment refractory patient-group. Despite this, our results confirm that golimumab is an effective therapy in ulcerative colitis.

Real-world effectiveness of vedolizumab in inflammatory bowel disease: week 52 results from the Swedish prospective multicentre SVEAH study.

BACKGROUND: Prospectively and systematically collected real-world data on vedolizumab are scarce. We aimed to assess the long-term clinical effectiveness of vedolizumab in inflammatory bowel disease (IBD). METHODS: This study was a prospective, observational, multicentre study. Overall, 286 patients with active IBD were included (Crohn's disease, n = 169; ulcerative colitis, n = 117). The primary outcomes were clinical response at week 12 and clinical remission at week 52, based on the Harvey Bradshaw Index and the partial Mayo Clinic score. Secondary outcomes included clinical remission at week 12, clinical response at week 52, corticosteroid-free clinical remission at week 52, changes in biochemical measures, and health-related quality of life (HRQoL). RESULTS: At baseline, 88% of the patients were exposed to anti-TNF and 41% of the patients with Crohn's disease had undergone ⩾1 surgical resection. At week 12, clinical response was 27% and remission 47% in Crohn's disease; corresponding figures in ulcerative colitis were 52% and 34%. Clinical response, remission and corticosteroid-free remission at week 52 were 22%, 41% and 40% in Crohn's disease and 49%, 47% and 46% in ulcerative colitis, respectively. A statistically significant decrease in median faecal-calprotectin and C-reactive protein was observed at 12 and 52 weeks in patients with Crohn's disease and ulcerative colitis. The HRQoL measures Short Health Scale and EuroQol 5-Dimensions improved in both Crohn's disease and ulcerative colitis patients (p < 0.001). Clinical disease activity at baseline was inversely associated with clinical remission at week 52. CONCLUSION: Vedolizumab proved effective for the treatment of refractory IBD in clinical practice.