A measles IgM rapid diagnostic test to address challenges with national measles surveillance and response in Malaysia.

INTRODUCTION: A lateral flow rapid diagnostic test (RDT) enables detection of measles specific immunoglobulin M (IgM) antibody in serum, capillary blood, and oral fluid with accuracy consistent with enzyme immunoassay (EIA). The objectives of the study were: 1) to assess measles RDT inter-reader agreement between two clinic staff; 2) to assess the sensitivity and specificity of the measles RDT relative to standard surveillance testing in a low transmission setting; 3) to evaluate the knowledge, attitudes, and practices of staff in clinics using the RDT; and 4) to assess the impact of RDT testing on the measles public health response in Malaysia. MATERIALS AND METHODS: The clinic-based prospective evaluation included all suspected measles cases captured by routine measles surveillance at 34 purposely selected clinics in 15 health districts in Malaysia between September 2019 and June 2020, following day-long regional trainings on RDT use. Following informed consent, four specimens were collected from each suspected case, including those routinely collected for standard surveillance [serum for EIA and throat swabs for quantitative reverse transcriptase polymerase chain reaction (RT-qPCR)] together with capillary blood and oral fluid tested with RDTs during the study. RDT impact was evaluated by comparing the rapidity of measles public health response between the pre-RDT implementation (December 2018 to August 2019) and RDT implementation periods (September 2019 to June 2020). To assess knowledge, attitudes, and practices of RDT use, staff involved in the public health management of measles at the selected sites were surveyed. RESULTS: Among the 436 suspect cases, agreement of direct visual readings of measles RDT devices between two health clinic staff was 99% for capillary blood (k = 0.94) and 97% for oral fluid (k = 0.90) specimens. Of the total, 45 (10%) were positive by measles IgM EIA (n = 44, including five also positive by RT-qPCR) or RT-qPCR only (n = 1), and 38 were positive by RDT (using either capillary blood or oral fluid). Using measles IgM EIA or RT-qPCR as reference, RDT sensitivity using capillary blood was 43% (95% CI: 30%-58%) and specificity was 98% (95% CI: 96%-99%); using oral fluid, sensitivity (26%, 95% CI: 15%-40%) and specificity (97%, 95% CI: 94%-98%) were lower. Nine months after training, RDT knowledge was high among staff involved with the public health management of measles (average quiz score of 80%) and was highest among those who received formal training (88%), followed by those trained during supervisory visits (83%). During the RDT implementation period, the number of days from case confirmation until initiation of public response decreased by about 5 days. CONCLUSION: The measles IgM RDT shows >95% inter-reader agreement, high retention of RDT knowledge, and a more rapid public health response. However, despite ≥95% RDT specificity using capillary blood or oral fluid, RDT sensitivity was <45%. Higher-powered studies using highly specific IgM assays and systematic RT-qPCR for case confirmation are needed to establish the role of RDT in measles elimination settings.

Child Health Needs and the Pediatric Cardiology Workforce: 2020-2040.

This article evaluates the pediatric cardiology (PC) workforce and forecasts its future supply. Produced as part of a supplement in Pediatrics, this effort represents a collaboration among the American Board of Pediatrics Foundation, the University of North Carolina at Chapel Hill's Carolina Health Workforce Research Center, the Strategic Modeling and Analysis Ltd., and members of the pediatric subspecialty community. PC is a complex subspecialty including care from fetal life through adulthood and in practice settings that range from the outpatient clinic to procedural settings to the cardiac ICU. Complex subdisciplines include imaging, electrophysiology, heart failure, and interventional and critical care. Using American Board of Pediatrics data, US Census Bureau data, and data from the modeling project, projections were created to model the subspecialty workforce through 2040. Across all modeling scenarios considered, there is considerable projected growth in the supply of pediatric cardiologists by 2040. However, there is significant regional variation in the projected supply of trainees relative to demand in terms of local population growth, with evidence of a likely mismatch between areas surrounding training centers versus areas of greatest workforce need. In addition, this article highlights areas for future focus, including efforts to attract more residents to the subspecialty in general, particularly underrepresented minority members; increased support, more part-time career options, and improved academic career advancement for women in PC; and the development of better "real-time" workforce data to guide trainees and training programs in decisions regarding sub-subspecialty job availability.

The experience of fathers of children hospitalised with advanced heart disease.

BACKGROUND: There are little reported data on the perspectives of fathers caring for children with chronic conditions. Although survival of children with advanced heart disease has improved, long-term morbidity remains high. This study describes the experience and prognostic awareness of fathers of hospitalised children with advanced heart disease. METHODS: Cross-sectional survey study of parents caring for children hospitalised with advanced heart disease admitted for ≥ 7 days over a one-year period. One parent per patient completed surveys, resulting in 27 father surveys. Data were analysed using descriptive methods. RESULTS: Nearly all (96%) of the fathers reported understanding their child's prognosis "extremely well" or "well," and 59% felt they were "very prepared" for their child's medical problems. However, 58% of fathers wanted to know more about prognosis, and 22% thought their child's team knew something about prognosis that they did not. Forty-one per cent of fathers did not think that their child would have lifelong limitations, and 32% anticipated normal life expectancies. All 13 fathers who had a clinical discussion of what would happen if their child got sicker found this conversation helpful. Nearly half (43%) of the fathers receiving new prognostic information or changes to treatment course found it "somewhat" or "a little" confusing. CONCLUSIONS: Fathers report excellent understanding of their child's illness and a positive experience around expressing their hopes and fears. Despite this, there remain many opportunities to improve communication, prognostic awareness, and participation in informed decision-making of fathers of children hospitalised with advanced heart disease.

Assessing enrollment of eligible infants in the national pediatric cardiology quality improvement collaborative (NPC-QIC) through linkage to the pediatric cardiac critical care consortium (PC4) registry.

BACKGROUND: The National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) lacks a rigorous enrollment audit process, unlike other collaborative networks. Most centers require individual families to consent to participate. It is unknown whether there is variation across centers or biases in enrollment. METHODS: We used the Pediatric Cardiac Critical Care Consortium (PC4) registry to assess enrollment rates in NPC-QIC for those centers participating in both registries using indirect identifiers (date of birth, date of admission, gender, and center) to match patient records. All infants born 1/1/2018-12/31/2020 and admitted 30 days of life were eligible. In PC4, all infants with a fundamental diagnosis of hypoplastic left heart or variant or who underwent a surgical or hybrid Norwood or variant were eligible. Standard descriptive statistics were used to describe the cohort and center match rates were plotted on a funnel chart. RESULTS: Of 898 eligible NPC-QIC patients, 841 were linked to 1,114 eligible PC4 patients (match rate 75.5%) in 32 centers. Match rates were lower in patients of Hispanic/Latino ethnicity (66.1%, p = 0.005), and those with any specified chromosomal abnormality (57.4%, p = 0.002), noncardiac abnormality (67.8%, p = 0.005), or any specified syndrome (66.5%, p = 0.001). Match rates were lower for patients who transferred to another hospital or died prior to discharge. Match rates varied from 0 to 100% across centers. CONCLUSIONS: It is feasible to match patients between the NPC-QIC and PC4 registries. Variation in match rates suggests opportunities for improvement in NPC-QIC patient enrollment.

Tissue formation and host remodeling of an elastomeric biodegradable scaffold in an ovine pulmonary leaflet replacement model.

In pursuit of a suitable scaffold material for cardiac valve tissue engineering applications, an acellular, electrospun, biodegradable polyester carbonate urethane urea (PECUU) scaffold was evaluated as a pulmonary valve leaflet replacement in vivo. In sheep (n = 8), a single pulmonary valve leaflet was replaced with a PECUU leaflet and followed for 1, 6, and 12 weeks. Implanted leaflet function was assessed in vivo by echocardiography. Explanted samples were studied for gross pathology, microscopic changes in the extracellular matrix, host cellular re-population, and immune responses, and for biomechanical properties. PECUU leaflets showed normal leaflet motion at implant, but decreased leaflet motion and dimensions at 6 weeks. The leaflets accumulated α-SMA and CD45 positive cells, with surfaces covered with endothelial cells (CD31+). New collagen formation occurred (Picrosirius Red). Accumulated tissue thickness correlated with the decrease in leaflet motion. The PECUU scaffolds had histologic evidence of scaffold degradation and an accumulation of pro-inflammatory/M1 and anti-inflammatory/M2 macrophages over time in vivo. The extent of inflammatory cell accumulation correlated with tissue formation and polymer degradation but was also associated with leaflet thickening and decreased leaflet motion. Future studies should explore pre-implant seeding of polymer scaffolds, more advanced polymer fabrication methods able to more closely approximate native tissue structure and function, and other techniques to control and balance the degradation of biomaterials and new tissue formation by modulation of the host immune response.

Right Heart Remodeling After Pulmonary Valve Replacement in Patients With Pulmonary Atresia or Critical Stenosis With Intact Ventricular Septum.

Background Patients with pulmonary atresia or critical pulmonary stenosis with intact ventricular septum (PA/IVS) and biventricular circulation may require pulmonary valve replacement (PVR). Right ventricular (RV) remodeling after PVR is well described in tetralogy of Fallot (TOF); we sought to investigate RV changes in PA/IVS using cardiac magnetic resonance imaging. Methods and Results A retrospective cohort of patients with PA/IVS who underwent PVR at Boston Children's Hospital from 1995 to 2021 with cardiac magnetic resonance imaging before and after PVR was matched 1:3 with patients with TOF by age at PVR. Median regression modeling was performed with post-PVR indexed RV end-diastolic volume as the primary outcome. A total of 20 patients with PA/IVS (cases) were matched with 60 patients with TOF (controls), with median age at PVR of 14 years. Pre-PVR indexed RV end-diastolic volume was similar between groups; cases had higher RV ejection fraction (51.4% versus 48.6%; P=0.03). Pre-PVR RV free wall and left ventricular (LV) longitudinal strain were similar, although LV midcavity circumferential strain was decreased in cases (-15.6 versus -17.1; P=0.001). At a median of 2 years after PVR, indexed RV end-diastolic volume was similarly reduced; cases continued to have higher RV ejection fraction (52.3% versus 46.9%; P=0.007) with less reduction in RV mass (Δ4.5 versus 9.6 g/m2; P=0.004). Post-PVR, RV and LV longitudinal strain remained unchanged, and LV circumferential strain was similar, although lower in cases. Conclusions Compared with patients with TOF, patients with PA/IVS demonstrate similar RV remodeling after PVR, with lower reduction in RV mass and comparatively higher RV ejection fraction. Although no differences were detected in peak systolic RV or LV strain values, further investigation of diastolic parameters is needed.

The NEONATE score predicts freedom from interstage mortality or transplant in a modern cohort.

BACKGROUND: Derived from the National Pediatric Cardiology Quality Improvement Collaborative registry, the NEONATE risk score predicted freedom from interstage mortality or heart transplant for patients with single ventricle CHD and aortic arch hypoplasia discharged home following Stage 1 palliation. OBJECTIVES: We sought to validate the score in an external, modern cohort. METHODS: This was a retrospective cohort analysis of single ventricle CHD and aortic arch hypoplasia patients enrolled in the National Pediatric Cardiology Quality Improvement Collaborative Phase II registry from 2016 to 2020, who were discharged home after Stage 1 palliation. Points were allocated per the NEONATE score (Norwood type-Norwood/Blalock-Taussig shunt: 3, Hybrid: 12; extracorporeal membrane oxygenation post-op: 9, Opiates at discharge: 6, No Digoxin at discharge: 9, Arch Obstruction on discharge echo: 9, Tricuspid regurgitation ≥ moderate on discharge echo: 12; Extra oxygen plus ≥ moderate tricuspid regurgitation: 28). The composite primary endpoint was interstage mortality or heart transplant. RESULTS: In total, 1026 patients met inclusion criteria; 61 (6%) met the primary outcome. Interstage mortality occurred in 44 (4.3%) patients at a median of 129 (IQR 62,195) days, and 17 (1.7%) were referred for heart transplant at a 167 (114,199) days of life. The median NEONATE score was 0(0,9) in those who survived to Stage 2 palliation compared to 9(0,15) in those who experienced interstage mortality or heart transplant (p < 0.001). Applying a NEONATE score cut-off of 17 points that separated patients into low- and high-risk groups in the learning cohort provided 91% specificity, negative predictive value of 95%, and overall accuracy of 87% (85.4-89.5%). CONCLUSION: In a modern cohort of patients with single ventricle CHD and aortic arch hypoplasia, the NEONATE score remains useful at discharge post-Stage 1 palliation to predict freedom from interstage mortality or heart transplant.

Association of Digoxin Use With Transplant-Free Interstage Survival in Infants Palliated With a Stage 1 Hybrid Procedure.

Background Digoxin prescription in patients with single-ventricle physiology after stage 1 palliation is associated with reduced interstage death. Prior literature has primarily included patients having undergone the Norwood procedure. We sought to determine if digoxin prescription at discharge in infants following hybrid stage 1 palliation was associated with improved transplant-free interstage survival. Methods and Results A retrospective multicenter cohort analysis was conducted using data from the National Pediatric Cardiology Quality Improvement Collaborative registry data from 2008 to 2021. Infants with functional single ventricles and aortic arch obstruction discharged home after the hybrid stage 1 palliation hospitalization were included. Patients were excluded if they had supraventricular tachycardia or conversion to Norwood operation. The primary outcome was transplant-free survival. Multivariable logistic regression analysis including a propensity score for digoxin use identified associations between digoxin use and interstage death or transplant. Of 259 included infants from 45 sites, 158 (61%) had hypoplastic left heart syndrome. Forty-nine percent had a gestational age ≤38 weeks, 18% had a birth weight <2.5 kg, and 58% had a preoperative risk factor. Of the 259 subjects, 129 (50%) were discharged on digoxin. Interstage death or transplant occurred in 30 (23%) patients in the no-digoxin group compared with 18 (14%) in the digoxin group (P=0.06). With multivariate analysis, discharge digoxin prescription was associated with a lower risk of interstage death or transplant (adjusted odds ratio, 0.48 [95% CI, 0.24-0.93]; P=0.03). Conclusions In infants with single-ventricle physiology who underwent hybrid stage 1 palliation, digoxin prescription at hospital discharge was associated with improved interstage transplant-free survival.

Evaluation of a rapid diagnostic test for measles IgM detection; accuracy and the reliability of visual reading using sera from the measles surveillance programme in Brazil, 2015.

Laboratory-based case confirmation is an integral part of measles surveillance programmes; however, logistical constraints can delay response. Use of RDTs during initial patient contact could enhance surveillance by real-time case confirmation and accelerating public health response. Here, we evaluate performance of a novel measles IgM RDT and assess accuracy of visual interpretation using a representative collection of 125 sera from the Brazilian measles surveillance programme. RDT results were interpreted visually by a panel of six independent observers, the consensus of three observers and by relative reflectance measurements using an ESEQuant Reader. Compared to the Siemens anti-measles IgM EIA, sensitivity and specificity of the RDT were 94.9% (74/78, 87.4-98.6%) and 95.7% (45/47, 85.5-99.5%) for consensus visual results, and 93.6% (73/78, 85.7-97.9%) and 95.7% (45/47, 85.5-99.5%), for ESEQuant measurement, respectively. Observer agreement, determined by comparison between individuals and visual consensus results, and between individuals and ESEQuant measurements, achieved average kappa scores of 0.97 and 0.93 respectively. The RDT has the sensitivity and specificity required of a field-based test for measles diagnosis, and high kappa scores indicate this can be accomplished accurately by visual interpretation alone. Detailed studies are needed to establish its role within the global measles control programme.

Living with Congenital Aortic Stenosis: Exercise Restriction, Patterns of Adherence, and Quality of Life.

Modern consensus panel guidelines recommend restriction from most organized sports for patients with moderate or severe aortic stenosis (AS). However, there is little published data on how frequently physicians deviate from guidelines, how well patients adhere to exercise restrictions, or the effect of restriction on patient-reported quality of life. In this study, we surveyed 93 subjects with AS and their cardiologists regarding participation in organized sports, physical activity, weightlifting, and exercise restriction. Subjects completed the pediatric quality of life inventory (PedsQL) and the pediatric cardiac quality of life inventory (PCQLI). We found that subjects with severe AS (n = 3) were commonly, but not universally, restricted from organized sports (n = 2, 66%). Subjects with moderate AS (n = 40) were rarely restricted from organized sports (n = 6, 17%). No physician-specific characteristics were associated with increased likelihood of recommending exercise restriction. Subjects were more likely to be restricted if they were older (16 years vs. 13 years, p 0.02) and had moderate versus mild AS (p 0.013). PCQLI scores for teens and young adults with AS (age 13-25) were lower than a comparison group of patients with mild congenital heart disease. For all age groups, the PedsQL social functioning score was lower for subjects with exercise restriction (p 0.052). In summary, cardiologists apply consensus guidelines leniently when restricting patients with moderate/severe AS from organized sports and weightlifting. Patients with AS routinely adhere to exercise restriction recommendations. Children and young adults with AS and exercise restriction have lower QOL scores in the social functioning domain.

Immunisation rates and predictors of undervaccination in infants with CHD.

Vaccination coverage for infants with CHD is unknown, yet these patients are at high risk for morbidity and mortality associated with vaccine-preventable illnesses. We determined vaccination rates for this population and identified predictors of undervaccination. We prospectively enrolled infants with CHD born between 1 January, 2012 and 31 December, 2015, seen in a single-centre cardiology clinic between 15 February, 2016 and 28 February, 2017. We assessed vaccination during the first year of life. Subjects who by age 1 year received all routine immunisations recommended during the first 6 months of life were considered fully vaccinated. We also evaluated influenza vaccination during subjects' first eligible influenza season. We obtained immunisation histories from primary care providers and collected demographic and clinical data via a parent survey and chart review. We used multivariable logistic regression to identify predictors of undervaccination. Among 260 subjects, only 60% were fully vaccinated. Vaccination rates were lowest for influenza (64.6%), rotavirus (71.1%), and Haemophilus influenzae type b (79.3%). Cardiac surgery with cardiopulmonary bypass during the first year of life was associated with undervaccination (51.5% versus 76.4% fully vaccinated, adjusted odds ratio 2.1 [95% confidence interval 1.1-3.9]). Other predictors of undervaccination were out-of-state primary care (adjusted odds ratio 2.7 [1.5-4.9]), multiple comorbidities (≥2 versus 0-1, adjusted odds ratio 2.0 [1.1-3.6]), and hospitalisation for >25% of the first year of life (>25% versus ≤25%, adjusted odds ratio 2.1 [1.1-3.9]). Targeted quality improvement initiatives focused on improving vaccination coverage for these infants, especially surrounding cardiac surgery, are needed.

Prenatal care coordination, racial and socioeconomic inequities, and pre- and post-operative outcomes in hypoplastic left heart syndrome.

OBJECTIVE: We sought to identify associations between prenatal care coordination (PNC) and outcomes in hypoplastic left heart syndrome (HLHS). STUDY DESIGN: We hypothesized that suboptimal PNC is associated with worse pre-operative status. HLHS patients from 2016 through 2019 were identified using a multicenter registry. Optimal PNC was defined as (1) a completed interdisciplinary conference and (2) closed-loop communication with the obstetric team. Associations between PNC and outcomes were identified. RESULTS: Of 1441 patients, 1242 (86%) had prenatal diagnosis. Among those with a prenatal diagnosis, PNC was achieved in only 845 (68%). Suboptimal PNC was associated with adverse events (50% vs 40%, p < 0.001), inotrope need (19% vs 13%, p = 0.007), mechanical ventilation (22% vs 16%, p = 0.016), and parenteral feeding (60% vs 46%, p < 0.001). African-American race and non-commercial insurance were associated with a lower likelihood of optimal PNC (p = 0.006 and p < 0.001, respectively). CONCLUSION: Improving PNC and overcoming racial and socioeconomic barriers are important targets to improve HLHS perinatal care.

Acute seizure risk in patients with encephalitis: development and validation of clinical prediction models from two independent prospective multicentre cohorts.

Objective: In patients with encephalitis, the development of acute symptomatic seizures is highly variable, but when present is associated with a worse outcome. We aimed to determine the factors associated with seizures in encephalitis and develop a clinical prediction model. Methods: We analysed 203 patients from 24 English hospitals (2005-2008) (Cohort 1). Outcome measures were seizures prior to and during admission, inpatient seizures and status epilepticus. A binary logistic regression risk model was converted to a clinical score and independently validated on an additional 233 patients from 31 UK hospitals (2013-2016) (Cohort 2). Results: In Cohort 1, 121 (60%) patients had a seizure including 103 (51%) with inpatient seizures. Admission Glasgow Coma Scale (GCS) ≤8/15 was predictive of subsequent inpatient seizures (OR (95% CI) 5.55 (2.10 to 14.64), p<0.001), including in those without a history of prior seizures at presentation (OR 6.57 (95% CI 1.37 to 31.5), p=0.025).A clinical model of overall seizure risk identified admission GCS along with aetiology (autoantibody-associated OR 11.99 (95% CI 2.09 to 68.86) and Herpes simplex virus 3.58 (95% CI 1.06 to 12.12)) (area under receiver operating characteristics curve (AUROC) =0.75 (95% CI 0.701 to 0.848), p<0.001). The same model was externally validated in Cohort 2 (AUROC=0.744 (95% CI 0.677 to 0.811), p<0.001). A clinical scoring system for stratifying inpatient seizure risk by decile demonstrated good discrimination using variables available on admission; age, GCS and fever (AUROC=0.716 (95% CI 0.634 to 0.798), p<0.001) and once probable aetiology established (AUROC=0.761 (95% CI 0.6840.839), p<0.001). Conclusion: Age, GCS, fever and aetiology can effectively stratify acute seizure risk in patients with encephalitis. These findings can support the development of targeted interventions and aid clinical trial design for antiseizure medication prophylaxis.

Isometric Exercise Increases the Diameter of the Ascending Aorta in Youth with Bicuspid Aortic Valves.

Central arterial pressure rises to much higher levels during heavy isometric exercise compared to other forms of exercise. For this reason, patients with bicuspid aortic valves (BAV) are often restricted from heavy isometric exercise. Although this approach may be theoretically appealing, no data exist regarding the efficacy of this activity restriction.Patients between 12 and 21 years old with isolated BAV were enrolled if they had a previous echocardiogram at least 2 years prior to the current clinic visit. Patients were excluded if they had additional congenital heart disease, a diagnosed syndrome, or had undergone a procedure involving the aortic valve or ascending aorta. Patients completed a questionnaire regarding frequency and intensity of isometric exercise during the 3-month period prior to the visit. We compared aortic dimensions (Z-score), aortic stenosis, and aortic insufficiency between an echocardiogram performed as part of the current visit and one obtained 2-5 years previously using paired t tests and multivariable regression controlling for age, gender, degree of aortic stenosis, and the presence of isometric exercise. In this sample of 50 adolescents with isolated bicuspid aortic valve, 30 (60%) subjects did not participate in any isometric exercise. Over an average of 2.9 years (SD 0.9 years), we did not find a significant difference between changes in the Z-score diameters of the aortic root (0.9 vs 0.9, p = 0.913) and ascending aorta Z-score (2.9 vs 2.9, p = 0.757), between subjects engaging and not engaging in isometric exercise. Further, we did not find that changes in valve function (i.e., aortic stenosis and aortic insufficiency) differed between the two groups.In this sample of adolescents with isolated bicuspid aortic valve, there was no medium-term increase in aortic dilation or worsening valve function in those who engaged in isometric exercise versus those who refrained from isometric exercise.

Parent-Provider Communication in Hospitalized Children with Advanced Heart Disease.

Communication between parents and providers of children with cardiac disease is essential to parental decision-making. This study explored how parents of hospitalized children with advanced heart disease perceived communication with their child's providers. We performed a prospective survey study of parents and physicians of children with advanced heart disease age 30 days to 19 years admitted to the hospital for > 7 days over a 1-year period at a single institution (n = 160 parent-provider pairs). Descriptive statistics were primarily used and Fisher exact tests and kappa statistics were used to assess agreement. All parents rated communication with their child's care team as excellent, very good, or good, but 56% of parents reported having received conflicting information. Parental perception of "too many" people giving them information was associated with overall poorer communication and less preparedness for decision-making. One-third (32%) of parents felt unprepared for decision-making, despite 88% feeling supported. Parents and physicians showed poor agreement with respect to overall adequacy of communication, receipt of conflicting information, and evaluation of the most effective way for parents to receive information. Interventions involving physician communication training and proactive assessment of parent communication preferences may be beneficial.

Digoxin Associated With Greater Transplant-Free Survival in High- vs Low-Risk Interstage Patients.

BACKGROUND: Digoxin has been associated with reduced interstage mortality for patients with functional single ventricles with aortic hypoplasia or ductal-dependent systemic circulation. The NEONATE (type of stage 1 palliation operation, postoperative extracorporeal membrane oxygenation, discharge with opiates, no digoxin at discharge, postoperative arch obstruction, moderate to severe tricuspid regurgitation without an oxygen requirement, and extra oxygen required at discharge in patients with moderate to severe tricuspid regurgitation) score can stratify patients by risk of death or transplantation (DTx) on the basis of clinical factors. The study investigators suspected a variable transplant-free survival benefit of digoxin in high-risk vs low-risk patients. METHODS: National Pediatric Cardiology Quality Improvement Collaborative patients discharged after stage 1 palliation with complete data were categorized as high- or low-risk on the basis of a modified NEONATE score. The primary outcome of DTx was evaluated. A mixed-effect regression evaluated associations between digoxin prescription and risk factors. RESULTS: A total of 1199 patients were included; 399 (33%) were high risk. Baseline demographics were similar between the cohorts. Blalock-Taussig shunt or a hybrid operation, postoperative extracorporeal membrane oxygenation, opiate prescription, and significant tricuspid regurgitation or arch obstruction were more common in high-risk patients. The odds of DTx were 65% lower in high-risk patients prescribed digoxin compared with patients who were not (P = .001). Digoxin prescription was associated with 60.8% lower DTx in the high-risk cohort (7.8% vs 19.9%; P = .001). There was no significant difference in the DTx rate according to digoxin prescription in the low-risk cohort (4.7% vs 5.7%; P = .46). Blalock-Taussig shunt, aortic arch obstruction, and significant tricuspid regurgitation were most strongly associated with deriving a benefit from digoxin. CONCLUSIONS: Digoxin use is associated with significant improvement in transplant-free survival in high-risk but not in low-risk interstage patients. A tailored approach to the use of digoxin in interstage patients may be warranted.

Native Bicuspid Pulmonary Valve in D-Loop Transposition of the Great Arteries: Outcomes of the Neo-Aortic Valve Function and Root Dilation After Arterial Switch Operation.

Background Neo-aortic root dilation and neo-aortic regurgitation (AR) are common after arterial switch operation for D-loop transposition of the great arteries. We sought to evaluate these outcomes in patients with bicuspid native pulmonary valve (BNPV). Methods and Results A retrospective analysis of patients with transposition of the great arteries undergoing arterial switch operation at Boston Children's Hospital from 1989 to 2018 matched BNPV patients 1:3 with patients with tricuspid native pulmonary valve by year of arterial switch operation. Kaplan-Meier analyses with log-rank test compared groups for time to first neo-aortic valve reoperation, occurrence of ≥moderate AR, and neo-aortic root dilation (root z score ≥4). A total of 83 patients with BNPV were matched with 217 patients with tricuspid native pulmonary valve. Patients with BNPV more often had ventricular septal defects (73% versus 43%; P<0.001). Hospital length of stay (11 versus 10 days) and 30-day surgical mortality (3.6% versus 2.8%) were similar. During median 11 years follow-up, neo-aortic valve reoperation occurred in 4 patients with BNPV (6.0%) versus 6 patients with tricuspid native pulmonary valve (2.8%), with no significant difference in time to reoperation. More BNPV had AR at discharge (4.9% versus 0%; P=0.014) and during follow-up (13.4% versus 4.3%; hazard ratio [HR], 3.9; P=0.004), with shorter time to first occurrence of AR; this remained significant after adjusting for ventricular septal defects. Similarly, neo-aortic root dilation was more common in BNPV (45% versus 38%; HR, 1.64; P=0.026) with shorter time to first occurrence. Conclusions While patients with BNPV have similar short-term arterial switch operation outcomes, AR and neo-aortic root dilation occur more frequently and earlier compared with patients with tricuspid native pulmonary valve. Further long-term studies are needed to determine whether this results in greater need for neo-aortic valve reoperation.

A Systematic Evaluation of IgM and IgG Antibody Assay Accuracy in Diagnosing Acute Zika Virus Infection in Brazil: Lessons Relevant to Emerging Infections.

Accurate diagnostics underpin effective public health responses to emerging viruses. For viruses, such as Zika virus (ZIKV), where the viremia clears quickly, antibody-based (IgM or IgG) diagnostics are recommended for patients who present 7 days after symptom onset. However, cross-reactive antibody responses can complicate test interpretation among populations where closely related viruses circulate. We examined the accuracy (proportion of samples correctly categorized as Zika positive or negative) for antibody-based diagnostics among Brazilian residents (Rio de Janeiro) during the ZIKV outbreak. Four ZIKV enzyme-linked immunosorbent assays (ELISAs; IgM and IgG Euroimmun, IgM Novagnost, and CDC MAC), two dengue ELISAs (IgM and IgG Panbio), and the ZIKV plaque reduction neutralization test (PRNT) were evaluated. Positive samples were ZIKV PCR confirmed clinical cases collected in 2015-2016 (n = 169); negative samples (n = 236) were collected before ZIKV was present in Brazil (≤2013). Among serum samples collected ≥7 days from symptom onset, PRNT exhibited the highest accuracy (93.7%), followed by the Euroimmun IgG ELISA (77.9%). All IgM assays exhibited lower accuracy (<75%). IgG was detected more consistently than IgM among ZIKV cases using Euroimmun ELISAs (68% versus 22%). Anti-dengue virus IgM ELISA was positive in 41.1% of confirmed ZIKV samples tested. The Euroimmun IgG assay, although misdiagnosing 22% of samples, provided the most accurate ELISA. Anti-ZIKV IgG was detected more reliably than IgM among ZIKV patients, suggesting a secondary antibody response to assay antigens following ZIKV infection. Antibody ELISAs need careful evaluation in their target population to optimize use and minimize misdiagnosis, prior to widespread deployment, particularly where related viruses cocirculate.

Researching, co-creating and testing innovations in paper-based health information systems (PHISICC) to support health workers' decision-making: protocol of a multi-country, transdisciplinary, mixed-methods research programme in three sub-Saharan countries.

BACKGROUND: Health information systems are crucial to provide data for decision-making and demand for data is constantly growing. However, the link between data and decisions is not always rational or linear and the management of data ends up overloading frontline health workers, which may compromise quality of healthcare delivery. Despite limited evidence, there is an increasing push for the digitalization of health information systems, which poses enormous challenges, particularly in remote, rural settings in low- and middle-income countries. Paper-based tools will continue to be used in combination with digital solutions and this calls for efforts to make them more responsive to local needs. Paper-based Health Information Systems in Comprehensive Care (PHISICC) is a transdisciplinary, multi-country research initiative to create and test innovative paper-based health information systems in three sub-Saharan African countries. METHODS/DESIGN: The PHISICC initiative is being carried out in remote, rural settings in Côte d'Ivoire, Mozambique and Nigeria through partnership with ministries of health and research institutions. We began with research syntheses to acquire the most up-to-date knowledge on health information systems. These were coupled with fieldwork in the three countries to understand the current design, patterns and contexts of use, and healthcare worker perspectives. Frontline health workers, with designers and researchers, used co-creation methods to produce the new PHISICC tools. This suite of tools is being tested in the three countries in three cluster-randomized controlled trials. Throughout the project, we have engaged with a wide range of stakeholders and have maintained the highest scientific standards to ensure that results are relevant to the realities in the three countries. DISCUSSION: We have deployed a comprehensive research approach to ensure the robustness and future policy uptake of findings. Besides the innovative PHISICC paper-based tools, our process is in itself innovative. Rather than emphasizing the technical dimensions of data management, we focused instead on frontline health workers' data use and decision-making. By tackling the whole scope of primary healthcare areas rather than a subset of them, we have developed an entirely new design and visual language for a suite of tools across healthcare areas. The initiative is being tested in remote, rural areas where the most vulnerable live.

Parent-Reported Symptoms and Perceived Effectiveness of Treatment in Children Hospitalized with Advanced Heart Disease.

OBJECTIVE: To characterize parent-reported symptom burden and effectiveness of symptom management in children hospitalized with advanced heart disease. STUDY DESIGN: Prospective survey study of 161 parents whose child was admitted to a single institution with advanced heart disease between March 2018 and February 2019 using the Survey about Caring for Children with Heart Disease. RESULTS: Of the 161 patients, 54% were under 2 years old with a diagnosis of single ventricle physiology (39%), pulmonary hypertension (12%), and other congenital heart disease (28%). Over one-half (56%) of parents reported that their child was experiencing a high degree ("a great deal"/"a lot") of symptoms. The most frequently reported symptoms were pain (68%), fatigue (63%), and breathing difficulties (60%). Of the symptoms that were treated, parents perceived successful treatment to be least likely for their child's sleep disturbance (24%), depression (29%), and fatigue (35%). Parents who reported their child's functional status as New York Heart Association class III/IV were more likely to report that their child was experiencing "a great deal" of symptoms, compared with those who reported class I/II (51% vs 19%, P < .001). Parents who reported their child was experiencing a high degree of suffering from fatigue were also more likely to report a high symptom burden (P < .001). CONCLUSIONS: Parents of children with advanced heart disease reported high symptom burden with a broad spectrum of symptoms. Parents reported fatigue and psychiatric symptoms frequently and rarely reported treatment as successful. Parents' view of their child's symptom burden was concordant with their perception of their child's functional status.