Altered Inflammatory State and Mitochondrial Function Identified by Transcriptomics in Paediatric Congenital Heart Patients Prior to Surgical Repair.

Congenital heart disease (CHD) remains the most common birth defect, with surgical intervention required in complex cases. Right ventricle (RV) function is known to be a major predictor of sustained cardiac health in these patients; thus, by elucidating the divergent profiles between CHD and the control through tissue analysis, this study aims to identify new avenues of investigation into the mechanisms surrounding reduced RV function. Transcriptomic profiling, in-silico deconvolution and functional network analysis were conducted on RV biopsies, identifying an increase in the mitochondrial dysfunction genes RPPH1 and RMPR (padj = 4.67 × 10-132, 2.23 × 10-107), the cytotoxic T-cell markers CD8a, LAGE3 and CD49a (p = 0.0006, p < 0.0001, and p = 0.0118) and proinflammatory caspase-1 (p = 0.0055) in CHD. Gene-set enrichment identified mitochondrial dysfunctional pathways, predominately changes within oxidative phosphorylation processes. The negative regulation of mitochondrial functions and metabolism was identified in the network analysis, with dysregulation of the mitochondrial complex formation. A histological analysis confirmed an increase in cellular bodies in the CHD RV tissue and positive staining for both CD45 and CD8, which was absent in the control. The deconvolution of bulk RNAseq data suggests a reduction in CD4+ T cells (p = 0.0067) and an increase in CD8+ T cells (p = 0.0223). The network analysis identified positive regulation of the immune system and cytokine signalling clusters in the inflammation functional network, as there were lymphocyte activation and leukocyte differentiation. Utilising RV tissue from paediatric patients undergoing CHD cardiac surgery, this study identifies dysfunctional mitochondrial pathways and an increase in inflammatory T-cell presence prior to reparative surgery.

Off-pump injectable versus on-pump conventional tissue valves for pulmonary valve replacement: the injectable valve implantation randomised trial (INVITE).

OBJECTIVES: To assess the effectiveness of injectable tissue pulmonary valve compared with standard pulmonary valve in patients requiring pulmonary valve replacement surgery. DESIGN: A multicentre, single-blind, parallel two-group randomised controlled trial. Participants were blind to their allocation. Follow-up continued for 6 months. Randomised allocations were generated by a computer using block randomisation, stratified by centre. SETTING: Two National Health Service secondary care centres in the UK. PARTICIPANTS: People aged 12-80 years requiring pulmonary valve replacement. INTERVENTIONS: Participants were randomly allocated (1:1 ratio) to injectable pulmonary valve replacement (IPVR) without cardiopulmonary bypass (CPB) or standard pulmonary valve replacement (SPVR) with CPB. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was chest drainage volume over the first 24 hours after surgery. Secondary outcomes included in-hospital clinical outcomes; valve and heart function 6 months postsurgery and health-related quality of life 6 weeks and 6 months postsurgery. RESULTS: Nineteen participants agreed to take part. Eleven were allocated to IPVR and eight to SPVR. The trial was stopped before the target sample size of 60 participants was reached due to challenges in recruitment. The primary analysis includes all randomised participants; there were no withdrawals. Chest drain volume 24 hours after surgery was on average 277.6 mL lower with IPVR (IPVR mean 340.0 mL; SPVR mean 633.8 mL; mean difference, -277.6; 95% CI, -484.0 to -71.2; p=0.005). There were no statistically significant differences in time to readiness for extubation (p=0.476), time to fitness for discharge (p=0.577) and time to first discharge from the intensive care unit (p=0.209). Six participants with IPVR required CPB. Safety profiles and quality of life scores were similar. CONCLUSIONS: IPVR reduced chest drain volume despite >50% of participants requiring CPB. There was no evidence of any other benefit of IPVR. TRIAL REGISTRATION NUMBER: ISRCTN23538073.

The Relationship Between Postoperative Complications and Children's Quality of Life: A Mediation Analysis to Explore the Role of Family Factors.

OBJECTIVES: To explore whether postoperative morbidities after pediatric cardiac surgery affected children's health-related quality of life (HRQOL) at 6 months, through potentially modifiable parental psychological factors. DESIGN: We undertook a mediation analysis, to explore the causal pathway, based on data from a prospective, case-matched cohort study. PATIENTS: Six hundred sixty-six children undergoing cardiac surgery. SETTING: Five centers in the United Kingdom. INTERVENTIONS: No intervention. MEASUREMENTS AND MAIN RESULTS: Cases of morbidity were identified early after pediatric cardiac surgery, and matched controls with no morbidities were identified at discharge. Four mediators were assessed at 6 weeks after surgery, using the PedsQL Family Impact Module (Parent HRQOL and Family Function) and the PHQ-4 (Anxiety and Depression). The study outcome of child HRQOL was assessed at 6 months with the PedsQL. Of 666 children, 408 (65% of those surviving) contributed to the primary outcome. Children who had extracorporeal life support (ECLS) ( n = 11) ( p < 0.05) and multiple morbidities ( n = 62) ( p < 0.01) had worse 6-month HRQOL than those with a single morbidity ( n = 125) or no morbidity ( n = 209). After adjustment for case mix complexity and sociodemographic variables, there were significant indirect effects of parent HRQOL at 6 weeks, on the PedsQL Total Score (ECLS, -5.1 [-8.4 to -1.8]; p = 0.003; multiple morbidities, -2.1 [-3.7 to -0.5]; p = 0.01), PedsQL Physical Score (ECLS, -5.1 [-8.7 to -1.4]; p = 0.007; multiple morbidities, -2.1 [-3.8 to -0.4]; p = 0.016), and PedsQL Psychosocial Score (ECLS: -5.3 [-8.7 to -1.8); p = 0.003; multiple morbidities, -2.2 [-3.9 to -0.5]; p = 0.01). The proportion of the total effect of ECLS and multiple morbidity on the study outcomes mediated through parent HRQOL ranges between 18% and 61%. There was no evidence that the other three mediators had indirect effects on the study outcome. CONCLUSIONS: Parental HRQOL at 6 weeks after surgery contributes to child HRQOL at 6 months, among those with the severest types of morbidity, and as such should be a target for future interventions.

Warm versus cold blood cardioplegia in paediatric congenital heart surgery: a randomized trial.

OBJECTIVES: Intermittent cold blood cardioplegia is commonly used in children, whereas intermittent warm blood cardioplegia is widely used in adults. We aimed to compare clinical and biochemical outcomes with these 2 methods. METHODS: A single-centre, randomized controlled trial was conducted to compare the effectiveness of warm (≥34°C) versus cold (4-6°C) antegrade cardioplegia in children. The primary outcome was cardiac troponin T over the 1st 48 postoperative hours. Intensive care teams were blinded to group allocation. Outcomes were compared by intention-to-treat using linear mixed-effects, logistic or Cox regression. RESULTS: 97 participants with median age of 1.2 years were randomized (49 to warm, 48 to cold cardioplegia); 59 participants (61%) had a risk-adjusted congenital heart surgery score of 3 or above. There were no deaths and 92 participants were followed to 3-months. Troponin release was similar in both groups [geometric mean ratio 1.07; 95% confidence interval (CI) 0.79-1.44; P = 0.66], as were other cardiac function measures (echocardiography, arterial and venous blood gases, vasoactive-inotrope score, arrhythmias). Intensive care stay was on average 14.6 h longer in the warm group (hazard ratio 0.52; 95% CI 0.34-0.79; P = 0.003), with a trend towards longer overall hospital stays (hazard ratio 0.66; 95% CI 0.43-1.02; P = 0.060) compared with the cold group. This could be related to more unplanned reoperations on bypass in the warm group compared to cold group (3 vs 1). CONCLUSIONS: Warm blood cardioplegia is a safe and reproducible technique but does not provide superior myocardial protection in paediatric heart surgery.

Childhood Protective Factors and Future Adult Health Outcomes in an Urban Environment.

Purpose: To evaluate protective factors that help individuals overcome adverse health outcomes associated with childhood trauma in an urban environment. Methods: This retrospective cohort study included adults born between 1970 and 1995 who grew up in the former Cabrini-Green Homes, a low-income, Chicago public housing development. Participants completed surveys asking about general health, smoking, and mental health status. Surveys included questions related to neighborhood and family support, community safety, and childhood youth program participation. Simple regression models were performed to compare childhood exposure of adverse and protective factors to adult health outcomes. Multivariable logistic regression models were constructed to adjust for age, sex, and educational attainment. Results: 334 former residents completed the survey, and only those that reported an adversity score ≥ 2 were included in the analysis (n = 248). For those individuals who reported that their families cared for them as children, they described feeling hopeful about the future (OR 2.77, 95% CI, 1.28-6.00, aOR 2.63, 95% CI, 1.21-5.75) and reported decreased smoking rates as adults (OR 0.30, 95% CI, 0.14-0.66, aOR 0.35, 95% CI, 0.16-0.78). Better self-reported adult health status was associated with residents who believed the neighborhood looked out for one another (OR 2.31, 95% CI, 1.21-4.42, aOR 2.01, 95% CI, 1.02-3.95). Conclusion: These findings suggest that a caring family and neighborhood connectedness are protective in mitigating childhood adversity. Devoting resources to strengthen families and communities is a promising strategy to promote healthier adult behaviors.

Postoperative morbidities with infant cardiac surgery and toddlers' neurodevelopment.

OBJECTIVE: To evaluate the relationship between morbidities after infant cardiac surgery and neurodevelopment and behaviour at age 2-3 years. DESIGN/SETTING: A prospective cohort follow-up study, in four paediatric cardiac centres. We excluded children with known syndromes. Home-based neurodevelopmental assessments using the Bayley Scales of Infant and Toddler Development 3rd Edition (Bayley-III) were undertaken in 81 children and secondary outcome measures of development and behaviour were completed by parents. A further 41 families completed the secondary outcome measures remotely. RESULTS: Children were grouped as multiple morbidities/extracorporeal life support (ECLS) (n=19), single morbidities (n=36) and no morbidities (n=59). Group comparisons found that children with multiple morbidities/ECLS, compared with no morbidities, had: (a) lower adjusted mean scores for core Bayley-III composites (none reached the level of statistical significance), with mean differences of cognitive -6.1 (95% CI -12.4 to 0.1) p=0.06, language -9.1 (95% CI -18.6 to 0.3) p=0.06 and motor -4.4 (95% CI -12.0 to 3.1) p=25; (b) greater adjusted odds of at least one low or borderline Bayley-III composite result 4.0 (95% CI 1.0 to 16.0) (p=0.05); (c) greater adjusted risk of an abnormal Ages and Stages Questionnaire (ASQ) result 5.3 (95% CI 1.3 to 21.1) (p=0.03) and a borderline ASQ result 4.9 (95% CI 1.0 to 25.0) (p=0.05); and no difference in the risk of an abnormal Strengths and Difficulties Questionnaire result 1.7 (95% CI 0.3 to 10.4) p=0.58. These outcomes were not statistically different between the single morbidity and no morbidity groups. CONCLUSIONS: Children who experience multiple morbidities/ECLS after infant heart surgery are at a greater risk of neurodevelopmental difficulties than their peers who had no complications and should be prioritised for neurodevelopmental follow-up.

Challenges and solutions to recruitment of neonates and children having cardiac surgery into a study using a novel sampling device.

OBJECTIVE: To narratively describe the challenges and solutions required in delivering a non-commercial study of children undergoing cardiac surgery using a novel subcutaneous hormone collection device. RESULTS: The challenges faced by the research team are divided into those of conducting healthcare research in children and those specific to this study. Many of the issues of conducting healthcare research in children can and have been overcome by structural and institutional culture change-normalising and embedding research as part of good clinical care. The issues specific to insertion and maintenance of the novel collection device can be overcome by education and support of the clinical teams. The increased incentives and resources of commercial research may have overcome many of these.

Characterizing physical trauma in children and youth with special health care needs.

BACKGROUND: Children and youth with special health care needs (CYSHCN) have or are at an increased risk for a chronic condition necessitating medical and related services beyond what children usually require. While evidence suggests that CYSHCN are at an increased risk of injury, little is known about this population within the trauma system. This study describes CYSHCN within the pediatric trauma system and examines patterns of injury risk (i.e., intent, place of injury, trauma type, and mechanism of injury) based on special health care need (SHCN) status. METHODS: For this cross-sectional study, we used data from the 2018 National Trauma Data Bank to identify pediatric encounters (1-18 years, N = 115,578) and compare demographics (sex, race/ethnicity, insurance status, and age) by CYSHCN status using χ 2 and t tests. Children and youth with special health care needs encounters were compared with non-SHCN encounters using multinomial logistic regression models, controlling for demographics. RESULTS: Overall, 16.7% pediatric encounters reported an SHCN. Children and youth with special health care needs encounters are older, and a higher proportion is publicly insured than non-SHCN encounters ( p < 0.001). Furthermore, CYSHCN encounters have a higher risk of assault (relative risk, 1.331) and self-inflicted (relative risk, 4.208) injuries relative to unintentional injury ( p < 0.001), as well as a higher relative risk of traumatic injury occurring in a private residence ( p < 0.01) than other locations such as school (relative risk, 0.894). Younger CYSHCN encounters have a higher risk of assault relative to unintentional injury when compared with non-SHCN encounters ( p < 0.01). Pediatric trauma encounters reporting mental health and alcohol/substance use disorder SHCN have a higher probability of self-inflicted and assault injuries than non-SHCN encounters ( p < 0.001). CONCLUSIONS: These findings suggest that CYSHCN have different traumatic injury patterns than their non-SHCN peers, particularly in terms of intentional and private residence injury, and deserve a special focus for traumatic injury prevention. LEVEL OF EVIDENCE: Prognostic/epidemiologic, level III.

Prediction of Bleeding in Pediatric Cardiac Surgery Using Clinical Characteristics and Prospective Coagulation Test Results.

Bleeding caused by coagulopathy is common in children undergoing cardiac surgery and causes adverse outcomes. Coagulation testing assists selection of treatments to stop bleeding but has an uncertain role for predicting bleeding. We aimed to evaluate how well prospective coagulation testing predicted excessive bleeding during and after cardiac surgery compared to prediction using clinical characteristics alone. The study was a single-center, prospective cohort study in children having a range of cardiac surgery procedures with coagulation testing at anesthetic induction and immediately after cardiopulmonary bypass. The primary outcome was clinical concern about bleeding (CCB), a composite of either administration of prohemostatic treatments in response to bleeding or a high chest drain volume after surgery. In 225 children, CCB occurred in 26 (12%) during surgery and in 68 (30%) after surgery. Multivariable fractional polynomial models using the clinical characteristics of the children alone predicted CCB during surgery (c-statistic 0.64; 95% confidence interval 0.53, 0.76) and after surgery (0.74; 0.67, 0.82). Incorporating coagulation test results into these models improved prediction (c-statistics 0.79; 0.70, 0.87, and 0.80; 0.74, 0.87, respectively). However, this increased the overall proportion of children classified correctly as CCB or not CCB during surgery by only 0.9% and after surgery by only 0.4%. Incorporating coagulation test results into predictive models had no effect on prediction of blood transfusion or postoperative complications. Prospective coagulation testing marginally improves prediction of CCB during and after cardiac surgery but the clinical impact of this is small when compared to prediction using clinical characteristics.

Screening Students and Staff for Asymptomatic Coronavirus Disease 2019 in Chicago Schools.

OBJECTIVES: To assess rates of asymptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) positivity in K-8 schools with risk mitigation procedures in place, and to evaluate SARS-CoV-2 transmission in school and household contacts of these positive individuals. STUDY DESIGN: In this prospective observational study, screening testing for SARS-CoV-2 was performed by oropharyngeal swabbing and polymerase chain reaction (PCR) analysis in students and staff at K-8 private schools in high-risk Chicago ZIP codes. New coronavirus disease 2019 (COVID-19) diagnoses or symptoms among participants, household contacts, and nonparticipants in each school were queried. RESULTS: Among 11 K-8 private schools across 8 Chicago ZIP codes, 468 participants (346 students, 122 staff members) underwent screening testing. At the first school, 17 participants (36%) tested positive, but epidemiologic investigation suggested against in-school transmission. Only 5 participants in the subsequent 10 schools tested positive for an overall 4.7% positivity rate (1.2% excluding school 1). All but 1 positive test among in-person students had high PCR cycle threshold values, suggesting very low SARS-CoV-2 viral loads. In all schools, no additional students, staff, or household contacts reported new diagnoses or symptoms of COVID-19 during the 2 weeks following screening testing. CONCLUSIONS: We identified infrequent asymptomatic COVID-19 in schools in high-risk Chicago communities and did not identify transmission among school staff, students, or their household contacts. These data suggest that COVID-19 mitigation procedures, including masking and physical distancing, are effective in preventing transmission of COVID-19 in schools. These results may inform future strategies for screening testing in K-8 schools.

Treatment of Barth Syndrome by Cardiolipin Manipulation (CARDIOMAN) With Bezafibrate: Protocol for a Randomized Placebo-Controlled Pilot Trial Conducted in the Nationally Commissioned Barth Syndrome Service.

BACKGROUND: Barth syndrome is a rare, life-threatening, X-linked recessive genetic disease that predominantly affects young males and is caused by abnormal mitochondrial lipid metabolism. Currently, there is no definitive treatment for Barth syndrome other than interventions to ameliorate acute symptoms, such as heart failure, cardiac arrhythmias, neutropenia, and severe muscle fatigue. Previous mechanistic studies have identified the lipid-lowering drug bezafibrate as a promising potential treatment; however, to date, no human trials have been performed in this population. OBJECTIVE: The aim of this study is to determine whether bezafibrate (and resveratrol in vitro) will increase mitochondrial biogenesis and potentially modify the cellular ratio of monolysocardiolipin (MLCL) to tetralinoleoyl-cardiolipin (L4-CL), ameliorating the disease phenotype in those living with the disease. METHODS: The CARDIOMAN (Cardiolipin Manipulation) study is a UK single-center, double-blinded, randomized, placebo-controlled crossover study investigating the efficacy of bezafibrate in participants with Barth syndrome. Treatment was administered in two 15-week phases with a minimum washout period of 1 month between the phases where no treatment was administered. The primary outcome is peak oxygen consumption (VO2 peak). Secondary outcomes include MLCL/L4-CL ratio and CL profile in blood cells, amino acid expression, phosphocreatine to adenosine triphosphate ratio in cardiac muscle and skeletal muscle oxidative function on phosphorus-31 magnetic resonance spectroscopy, quality of life using the Pediatric Quality of Life Inventory questionnaire, absolute neutrophil count, cardiac function and rhythm profiles at rest and during exercise, and mitochondrial organization and function assessments. Outcomes were assessed at baseline and during the final week of each treatment phase. RESULTS: A total of 12 patients were scheduled to participate across three consecutive research clinics between March and April 2019. In total, 11 participants were recruited, and the follow-up was completed in January 2020. Data analysis is ongoing, with publication expected in 2021. CONCLUSIONS: This trial was approved by the United Kingdom National Research Ethics Service Committee and the Medicines and Healthcare products Regulatory Agency. The feasibility of the CARDIOMAN study will help to inform the future conduct of randomized controlled trials in rare disease populations as well as testing the efficacy of bezafibrate as a potential treatment for the disease and advancing the mechanistic understanding of Barth syndrome. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 58006579; https://www.isrctn.com/ISRCTN58006579. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/22533.

A randomized controlled trial comparing controlled reoxygenation and standard cardiopulmonary bypass in paediatric cardiac surgery.

OBJECTIVES: Controlled reoxygenation on starting cardiopulmonary bypass (CPB) rather than hyperoxic CPB may confer clinical advantages during surgery for congenital cyanotic heart disease. METHODS: A single-centre, randomized controlled trial was carried out to compare the effectiveness of controlled reoxygenation (normoxia) versus hyperoxic CPB in children with congenital cyanotic heart disease undergoing open-heart surgery (Oxic-2). The co-primary clinical outcomes were duration of inotropic support, intubation time and postoperative intensive care unit (ICU) and hospital stay. Analysis of the primary outcomes included data from a previous trial (Oxic-1) conducted to the same protocol. RESULTS: Ninety participants were recruited to Oxic-2 and 79 were recruited to the previous Oxic-1 trial. There were no significant differences between the groups for any of the co-primary outcomes: inotrope duration geometric mean ratio (normoxia/hyperoxic) 0.97, 95% confidence interval (CI) (0.69-1.37), P-value = 0.87; intubation time hazard ratio (HR) 1.03, 95% CI (0.74-1.42), P-value = 0.87; postoperative ICU stay HR 1.14 95% CI (0.77-1.67), P-value = 0.52, hospital stay HR 0.90, 95% CI (0.65-1.25), P-value = 0.53. Lower oxygen levels were successfully achieved during the operative period in the normoxic group. Serum creatinine levels were lower in the normoxic group at day 2, but not on days 1, 3-5. Childhood developmental outcomes were similar. In the year following surgery, 85 serious adverse events were reported (51 normoxic group and 34 hyperoxic group). CONCLUSIONS: Controlled reoxygenation (normoxic) CPB is safe but with no evidence of a clinical advantage over hyperoxic CPB. CLINICAL TRIAL REGISTRATION NUMBER: Current Controlled Trials-ISRCTN81773762.

Intermittent antegrade warm-blood versus cold-blood cardioplegia in children undergoing open heart surgery: a protocol for a randomised controlled study (Thermic-3).

INTRODUCTION: Surgical repair of congenital heart defects often requires the use of cardiopulmonary bypass (CPB) and cardioplegic arrest. Cardioplegia is used during cardiac surgery requiring CPB to keep the heart still and to reduce myocardial damage as a result of ischaemia-reperfusion injury. Cold cardioplegia is the prevalent method of myocardial protection in paediatric patients; however, warm cardioplegia is used as part of usual care throughout the UK in adults. We aim to provide evidence to support the use of warm versus cold blood cardioplegia on clinical and biochemical outcomes during and after paediatric congenital heart surgery. METHODS AND ANALYSIS: We are conducting a single-centre randomised controlled trial in paediatric patients undergoing operations requiring CPB and cardioplegic arrest at the Bristol Royal Hospital for Children. We will randomise participants in a 1:1 ratio to receive either 'cold-blood cardioplegia' or 'warm-blood cardioplegia'. The primary outcome will be the difference between groups with respect to Troponin T levels over the first 48 postoperative hours. Secondary outcomes will include measures of cardiac function; renal function; cerebral function; arrythmias during and postoperative hours; postoperative blood loss in the first 12 hours; vasoactive-inotrope score in the first 48 hours; intubation time; chest and wound infections; time from return from theatre until fit for discharge; length of postoperative hospital stay; all-cause mortality to 3 months postoperative; myocardial injury at the molecular and cellular level. ETHICS AND DISSEMINATION: This trial has been approved by the London - Central Research Ethics Committee. Findings will be disseminated to the academic community through peer-reviewed publications and presentation at national and international meetings. Patients will be informed of the results through patient organisations and newsletters to participants. TRIAL REGISTRATION NUMBER: ISRCTN13467772; Pre-results.

What are the important morbidities associated with paediatric cardiac surgery? A mixed methods study.

OBJECTIVES: Given the current excellent early mortality rates for paediatric cardiac surgery, stakeholders believe that this important safety outcome should be supplemented by a wider range of measures. Our objectives were to prospectively measure the incidence of morbidities following paediatric cardiac surgery and to evaluate their clinical and health-economic impact over 6 months. DESIGN: The design was a prospective, multicentre, multidisciplinary mixed methods study. SETTING: The setting was 5 of the 10 paediatric cardiac surgery centres in the UK with 21 months recruitment. PARTICIPANTS: Included were 3090 paediatric cardiac surgeries, of which 666 patients were recruited to an impact substudy. RESULTS: Families and clinicians prioritised:Acute neurological event, unplanned re-intervention, feeding problems, renal replacement therapy, major adverse events, extracorporeal life support, necrotising enterocolitis, postsurgical infection and prolonged pleural effusion or chylothorax.Among 3090 consecutive surgeries, there were 675 (21.8%) with at least one of these morbidities. Independent risk factors for morbidity included neonatal age, complex heart disease and prolonged cardiopulmonary bypass (p<0.001). Among patients with morbidity, 6-month survival was 88.2% (95% CI 85.4 to 90.6) compared with 99.3% (95% CI 98.9 to 99.6) with none of the morbidities (p<0.001). The impact substudy in 340 children with morbidity and 326 control children with no morbidity indicated that morbidity-related impairment in quality of life improved between 6 weeks and 6 months. When compared with children with no morbidities, those with morbidity experienced a median of 13 (95% CI 10.2 to 15.8, p<0.001) fewer days at home by 6 months, and an adjusted incremental cost of £21 292 (95% CI £17 694 to £32 423, p<0.001). CONCLUSIONS: Evaluation of postoperative morbidity is more complicated than measuring early mortality. However, tracking morbidity after paediatric cardiac surgery over 6 months offers stakeholders important data that are of value to parents and will be useful in driving future quality improvement.

Normothermic versus hypothermic cardiopulmonary bypass in low-risk paediatric heart surgery: a randomised controlled trial.

OBJECTIVE: To compare normothermic (35°C-36°C) versus hypothermic (28°C) cardiopulmonary bypass (CPB) in paediatric patients undergoing open heart surgery to test the hypothesis that normothermic CPB perfusion maintains the functional integrity of major organ systems leading to faster recovery. METHODS: Two single-centre, randomised controlled trials (known as Thermic-1 and Thermic-2, respectively) were carried out to compare the effectiveness and acceptability of normothermic versus hypothermic CPB in children with congenital heart disease undergoing open heart surgery. In both studies, the co-primary clinical outcomes were duration of inotropic support, intubation time and postoperative hospital stay. RESULTS: In total, 200 participants were recruited; 59 to the Thermic-1 study and 141 to the Thermic-2 study. 98 patients received normothermic CPB and 102 patients received hypothermic CPB. There were no significant differences between the treatment groups for any of the co-primary outcomes: inotrope duration HR=1.01, 95% CI (0.72 to 1.41); intubation time HR=1.14, 95% CI (0.86 to 1.51); postoperative hospital stay HR=1.06, 95% CI (0.80 to 1.40). Differences favouring normothermia were found in urea nitrogen at 2 days geometric mean ratio (GMR)=0.86 95% CI (0.77 to 0.97); serum creatinine at 3 days GMR=0.89, 95% CI (0.81 to 0.98); urinary albumin at 48 hours GMR=0.32, 95% CI (0.14 to 0.74) and neutrophil gelatinase-associated lipocalin at 4 hours GMR=0.47, 95% CI (0.22 to 1.02), but not at other postoperative time points. CONCLUSIONS: Normothermic CPB is as safe and effective as hypothermic CPB and can be routinely adopted as a perfusion strategy in low-risk infants and children undergoing open heart surgery. TRIAL REGISTRATION NUMBER: ISRCTN93129502.

Factors associated with intimate partner homicide in Illinois, 2005-2010: Findings from the Illinois Violent Death Reporting System.

BACKGROUND: Critical elements in intimate partner homicides (IPH) often go undocumented. Previous studies have highlighted precipitating causes, but few have examined the place of injury that led to the victim's death. We sought to describe IPH cases in Illinois and in particular to examine factors surrounding the location of injury that led to the victim's death. METHODS: We analyzed data collected in the Illinois Violent Death Reporting System to assess victim demographics, perpetrator characteristics, the victim/perpetrator relationship, and circumstances surrounding the location of injury that led to the victim's death. RESULTS: From 2005 to 2010, 275 cases were identified as IPH. Women comprised 60.4% of victims and men 39.6%. Among perpetrators, 78.5% were identified as male and 21.5% as female. Of the 31 corollary victims, 54.8% were less than 18 years and 58.1% were injured in front of a family member. Females were 1.6 times more likely to have the injury that led to their death occur at their residence, as compared to males (OR 1.6, 95% CI 1.1-2.9). Cases in which the perpetrator had documented history of abuse were 2.4 times more likely to have the fatal injury occur at the victim's residence compared to those that did not have previous history (OR 2.4, 95% CI 1.2-4.8). IPH cases in which the perpetrator was the current partner of the victim were twice as likely to have the injury leading to the victim's death occur at the victim's residence compared to those perpetrators who were not a current partner (OR 2.1, 95% CI 1.2-3.5). CONCLUSIONS: Considering the increased risk of IPH occurring at the place of residence for women at the hands of current intimate partners and by perpetrators with a previous history of abuse, prevention efforts may wish to prioritize in-home and relocation intervention strategies. LEVEL OF EVIDENCE: Epidemiologic, level IV.

Child deaths of undetermined intent: An analysis of circumstances using Illinois Violent Death Reporting System data.

BACKGROUND: There is little information available about the circumstances surrounding the deaths of children aged 0 to 14 years in which the manner of death is of undetermined intent. METHODS: We analyzed data collected in the Illinois Violent Death Reporting System to describe victim demographics, location of injury, seasonality, day of week, and circumstances surrounding the victims' deaths. RESULTS: From 2005 to 2010 in Cook County, Illinois, 192 cases were identified of children aged 0 to 14 years, in which the manner of death was of undetermined intent. The majority of cases were younger than 1 year (81%), male (62%), and non-Hispanic black (66%); occurred in the City of Chicago (65%); and also occurred most frequently during the months of May (15%) and July (13%) and on Sunday (19%). Circumstances of note were having information on the location of death available for the victim (90%); scene investigation was not performed/unknown/not documented (81%); and the victim not presenting with red petechiae (84%). By ethnicity, a lower proportion of Hispanic victims had parental drug information available compared with non-Hispanic victims (17% and 40%, respectively; p = 0.017); Hispanic victims were more likely than non-Hispanic victims to have a documented acute illness at the time of injury leading to death (57% and 33%, respectively; p = 0.015). The availability of scene information and the successful contact of one or both parents of the victim following the victim's death varied by location. CONCLUSIONS: No public health surveillance system exists for the collection of this type of death. There is not enough information provided to develop an effective intervention. The systematic, thorough collection of information surrounding these deaths is necessary to pinpoint possible contributing mechanisms of death for these children. LEVEL OF EVIDENCE: Epidemiologic, level IV.

Factors associated with suicide among adolescents and young adults not in mental health treatment at time of death.

BACKGROUND: Suicide is the third-leading cause of death among Illinois residents aged 15 to 24 years. The Illinois Violent Death Reporting System (IVDRS) was developed to help prevent these deaths by providing timely, complete data. Understanding the circumstances surrounding suicide for those aged 15 to 24 years who are not receiving mental health treatment can help others: (1) recognize signs of potential crisis and (2) connect them to mental health treatment. METHODS: The IVDRS data were collected from five Illinois counties-Cook, DuPage, Kane, McHenry, and Peoria-from 2005 to 2010. All cases with the manner suicide, aged 15 to 24 years, were extracted for analysis. Data were described using frequencies and percentages, and statistical differences between groups were determined using χ analysis. RESULTS: There were a total of 386 suicides in those aged 15 to 24 years in IVDRS from 2005 to 2010. Most 15- to 19-year-olds (67%) and 20- to 24-year-olds (78%) were not receiving mental health treatment at the time of death. Among those not receiving mental health treatment, 22% and 13% of those aged 15 to 19 and 20 to 24 years, respectively, had disclosed their intent to commit suicide to another. One third were identified as being depressed or in a depressed mood (not necessarily a clinical diagnosis) in both age groups. One quarter in both age groups experienced a crisis (current, acute precipitating, or forthcoming event) within 2 weeks of their suicides. CONCLUSIONS: The majority of adolescents and young adults were not in mental health treatment at the time death. Among those not in mental health treatment at the time of death, the 15- to 19-year-olds were more likely to share their suicidal intentions than the 20- to 24-year-olds. LEVEL OF EVIDENCE: Epidemiological study, level IV.

Rates of firearm homicide by Chicago region, age, sex, and race/ethnicity, 2005-2010.

BACKGROUND: The United States reports the highest levels of firearm homicide incidences compared to other high income countries, and the focus and causes of these incidences within the US differ by demographic characteristics and location such as urban versus rural environment. Despite these findings, few studies have published on rates varied by region within a city. OBJECTIVE: This study aims to provide descriptive analysis of the rates of firearm homicide by age, sex, and race/ethnicity in each of the seven City of Chicago regions, and to determine if the rates of firearm homicide differ by demographics among the seven City of Chicago regions. METHODS: The Illinois Violent Death Reporting System conducts routine surveillance of violent deaths. Decedents were selected according to the following criteria: manner of death was homicide, weapon type was firearm, and location of injury that led to death was the City of Chicago. Location of injury was broken down by regions: North, Northwest, Center, West, South, Southwest, and Far South. Multiyear rates per 100,000 and corresponding 95% confidence intervals were calculated. RESULTS: There were 2,254 victims of homicide by firearm in the City of Chicago. The overall rate across Chicago for all demographics was 12.9 (12.1-13.5 per 100,000) with an average age of 27.4. The highest age group (20-24) for firearm homicide rates was 43.2 (39.7-46.7) per 100,000. For the youngest age group (10-14), only the Southwest (3.3-10.4) region reported any firearm incidence. The 20 to 24 age group reported the highest rates of all age groups within the South (107.9-151.7), West (80.3-108.2), and Far South (69.6-105.3) regions, whereas the North and Northwest reported the lowest rates for all regions by age. Black firearm homicide rates were 33.5 (31.9-35.1) per 100,000 versus Hispanic and non-Hispanic white firearm homicide rates of 8.5 (7.7-9.3) and 1.2 (1-1.5) per 100,000, respectively. Lastly, the West reported the highest firearm rates at 29.1 (657). CONCLUSION: In conclusion, Chicago is a large city that has high variation in firearm homicide rates among its constituent regions; therefore, an overall firearm homicide rate for the city of Chicago as a whole is not an accurate representation of the true nature of firearm homicides. Policy implementation may be made more effective by providing more regional analysis and targeted interventions via multipronged initiatives to help reduce future firearm rates, and funding for issues that address systemic poverty and adequate access to care and medical facilities. LEVEL OF EVIDENCE: Epidemiologic study, level IV.