Long-term multidisciplinary follow-up programs in pediatric cardiac arrest survivors.

Long-term outcome studies after pediatric cardiac arrest (CA) are few. They require a CA registry and dedicated outcome teams. Learning about the long-term outcomes is very important for developing prognostication guidelines, improving post-cardiac care, counseling caregivers about the future of their child, and creating opportunities for therapeutic intervention studies to improve outcomes. Few PICUs worldwide provide a multidisciplinary follow-up program as routine practice at an outpatient clinic with standardized measurements, using validated instruments including neuropsychological assessments by psychologists. The primary goal of such a follow-up program should be to provide excellent care to children and their caregivers, thereby resulting in a high attendance. Pediatric psychologists, neurologists and pediatricians/pediatric intensivists should ideally be involved to screen for delayed development and psychosocial problems and offer appropriate care at the same time. Preferably, outcomes should consist of evaluation of morbidity (physical and neuropsychological), functional health and Health Related Quality Of Life (QoL) of the patient and their caregivers.

Trends in community response and long-term outcomes from pediatric cardiac arrest: A retrospective observational study.

AIM: This study aimed to investigate trends over time in pre-hospital factors for pediatric out-of-hospital cardiac arrest (pOHCA) and long-term neurological and neuropsychological outcomes. These have not been described before in large populations. METHODS: Non-traumatic arrest patients, 1 day-17 years old, presented to the Sophia Children's Hospital from January 2002 to December 2020, were eligible for inclusion. Favorable neurological outcome was defined as Pediatric Cerebral Performance Categories (PCPC) 1-2 or no difference with pre-arrest baseline. The trend over time was tested with multivariable logistic and linear regression models with year of event as independent variable. FINDINGS: Over a nineteen-year study period, the annual rate of long-term favorable neurological outcome, assessed at a median 2.5 years follow-up, increased significantly (OR 1.10, 95%-CI 1.03-1.19), adjusted for confounders. Concurrently, annual automated external defibrillator (AED) use and, among adolescents, initial shockable rhythm increased significantly (OR 1.21, 95% CI 1.10-1.33 and OR 1.15, 95% CI 1.02-1.29, respectively), adjusted for confounders. For generalizability purposes, only the total intelligence quotient (IQ) was considered for trend analysis of all tested domains. Total IQ scores and bystander basic life support (BLS) rate did not change significantly over time. INTERPRETATION: Long-term favorable neurological outcome, assessed at a median 2.5 years follow-up, improved significantly over the study period. Total IQ scores did not significantly change over time. Furthermore, AED use (OR 1.21, 95%CI 1.10-1.33) and shockable rhythms among adolescents (OR1.15, 95%CI 1.02-1.29) increased over time.

Early weight measures and long-term neuropsychological outcome of critically ill neonates and infants: a secondary analysis of the PEPaNIC trial.

Neonates and infants surviving critical illness show impaired growth during critical illness and are at risk for later neuropsychological impairments. Early identification of individuals most at risk is needed to provide tailored long-term follow-up and care. The research question is whether early growth during hospitalization is associated with growth and neuropsychological outcomes in neonates and infants after pediatric intensive care unit admission (PICU). This is a secondary analysis of the PEPaNIC trial. Weight measurements upon PICU admission, at PICU discharge, at hospital discharge, at 2- and 4-year follow-up, and of different subgroups were compared using (paired) t-tests. Multiple linear regression analyses were performed to investigate the association between early growth in weight measures and neuropsychological outcomes at 4-year follow-up. One hundred twenty-one infants were included, and median age upon admission was 21 days. Growth in weight per week was less than the age-appropriate norm, resulting in a decrease in weight-for-age Z-score during hospitalization. Weight is normalized at 2- and 4-year follow-up. Weight gain in kilograms per week and change in weight Z-score were not associated with neurodevelopmental outcome measures at 4-year follow-up. Lower weight-for-age Z-score at PICU admission and at hospital discharge was associated only with lower weight and height Z-scores at 4-year follow-up. CONCLUSION: Growth in weight during hospital stay of young survivors of critical illness is impaired. Worse early growth in weight is associated with lower weight and height but not with neuropsychological outcomes at 4-year follow-up. WHAT IS KNOWN: • Critically ill neonates and infants show impaired early growth during admission and are at risk for later neuropsychological impairments. • Unraveling the association between early growth and later neuropsychological impairments is crucial since the first year of life is critical for brain development. WHAT IS NEW: • Critically ill neonates and infants had age appropriate weight measures at 4-year follow-up. • Poor growth in weight during hospital stay was not associated with poorer cognitive, emotional, or behavioral functioning four years after critical illness.

A 12-week lifestyle intervention: effects on fatigue, fear, and nutritional status in children with a Fontan circulation.

Introduction: Children and adolescents with a Fontan circulation are less physically active compared to healthy peers. In the current study, effects of a 12-week lifestyle intervention on fatigue, fears regarding exercise, caloric intake, rest energy expenditure (REE), and body composition were measured in children with a Fontan circulation. Methods: This study was a semi-cross-over randomized controlled trial. The lifestyle intervention consisted of a 12-week high-weight resistance training (three supervised training sessions a week) supported by high-protein diet (>2 g/kg) and tailored recommended caloric intake. Fatigue (measured by the validated PedsQol Multidimensional Fatigue Scale), fears regarding exercise (measured on a fear thermometer), REE (measured using indirect calorimetry), caloric intake and body composition using air displacement plethysmography, and four-skinfold method were measured before and after the intervention and control period. Results: Twenty-seven pediatric Fontan patients, median age 12.9 years (IQR: 10.5-16.2), of the included 28 patients successfully completed the program. Before training, both child- and parent-reported levels of fatigue were significantly worse on all domains (general, sleep/rest, and cognitive fatigue) compared to healthy peers. After training, parent-reported fatigue significantly improved on the general and cognitive fatigue domains [effect size +16 points (7-25), p < 0.001, and +10 points (2-17), p = 0.015, compared to the control period]. Before training, fear regarding exercise scored on the fear thermometer was low for both children and parents (median score 1 and 2, respectively, on a scale of 0-8). After training, child-reported fear decreased further compared to the control period [effect size -1.4 points (-2.3 to -0.6), p = 0.001]. At baseline, children had increased REE +12% compared to reference values, which did not change after exercise. Children ate an average of 637 calories below recommended intake based on REE, caloric deficit became smaller after the intervention, and protein intake increased compared to the control period [-388 calories (-674 to -102), p = 0.008, and +15 g (0.4-30), p = 0.044]. Body fat percentage did not change significantly. Conclusion: A 12-week lifestyle intervention improved parent-reported fatigue symptoms in the children, further decreased child-reported fears, and increased caloric and protein intake.

Physical training and high-protein diet improved muscle strength, parent-reported fatigue, and physical quality of life in children with Pompe disease.

Exercise has proven to be an effective adjuvant treatment to enzyme replacement therapy (ERT) in mildly affected adult Pompe patients. The aim of this study was to investigate the effects of a 12-week tailored lifestyle intervention, consisting of physical training and a high protein diet (2 grams/kg), in children with Pompe disease. This randomized controlled semi-crossover trial investigated the effects of a lifestyle intervention on the primary outcome: exercise capacity. Secondary outcomes were: muscle strength, core stability, motor function, physical activity levels, quality of life, fatigue, fear of exercise, caloric intake, energy balance, body composition, and safety. Fourteen Pompe patients with a median age of 10.6 [IQR: 7.2-14.5], of whom six classic infantile patients, participated in the lifestyle intervention. At baseline, patients had a lower exercise capacity compared to healthy peers (median 70.3% [IQR: 54.8%-98.6%] of predicted). After the intervention, absolute Peak VO2 improved significantly (1279 mL/min [1012.5-2006] vs. 1352 mL/min [1101.5-2069], p = 0.039), but not compared to the control period. Muscle strength of the hip flexors, hip abductors, elbow extensors, neck extensors, knee extensors, and core stability improved significantly compared to the control period. Children reported a significant increase on the change in health domain of quality of life, parents reported significantly better scores on the quality of life domains: physical functioning, change in health, family cohesion, and fatigue. A 12-week tailored lifestyle intervention for children with Pompe disease seemed safe and led to improvements in muscle strength, core stability, quality of life, and parent-reported fatigue. Pompe patients with a stable disease trajectory seemed to benefit the most from the intervention.

Effect of late versus early initiation of parenteral nutrition on weight deterioration during PICU stay: Secondary analysis of the PEPaNIC randomised controlled trial.

BACKGROUND & AIMS: Critically ill children are at increased risk of weight deterioration in the paediatric intensive care unit (PICU). Whether early initiation of parenteral nutrition (PN) prevents weight deterioration is unknown. The aims of this study were to assess the effect of withholding supplemental PN during the first week on weight Z-score change in PICU and to evaluate the association between weight Z-score change in the PICU and clinical outcomes. METHODS: This is a secondary analysis of the Paediatric Early versus Late Parenteral Nutrition in Intensive Care Unit (PEPaNIC) randomised controlled trial (N = 1440), which focused on the subgroup of patients with longitudinal weight Z-scores available on admission and on the last day in PICU. Patients were randomly allocated to initiation of supplemental PN after one week (Late-PN) or within 24 h (Early-PN) when enteral nutrition was insufficient. The effect of Late-PN versus Early-PN on the change in weight Z-score was investigated, adjusted for risk factors. Moreover, the association between weight Z-score change and clinical outcomes was explored, adjusted for risk factors. RESULTS: Longitudinal weight Z-scores were available for 470 patients. Enteral nutrition intake was equal in the Early-PN and Late-PN group. Less weight Z-score deterioration during PICU stay was associated with a lower risk of new infections (adjusted OR per Z-score increase 0.72 [0.55-0.96], p = 0.02), and with a higher likelihood of an earlier discharge from PICU alive (adjusted HR per Z-score increase 1.22 [1.10-1.37], p < 0.001). During PICU-stay, the change in weight Z-score did not differ among both groups (Late-PN median 0.00 [-0.34-0.12] vs Early-PN median -0.03 [-0.48-0.01], adjusted ß = 0.10 [-0.05-0.25], p = 0.18). CONCLUSIONS: Weight deterioration during the PICU stay was associated with worse clinical outcomes. Withholding supplemental PN during the first week did not aggravate weight Z-score deterioration during PICU stay. TRIAL REGISTRATION: clinicaltrials.gov NCT01536275.

The association between type D personality, and depression and anxiety ten years after PCI.

OBJECTIVE: There are indications that type D personality and depression are associated in patients treated with percutaneous coronary intervention (PCI). However, at present it is unclear whether this relationship holds in the long term. This study's aim was to investigate the association between type D personality at 6 months post-PCI (baseline), and depression at 10-year follow-up. A secondary aim was to test the association between type D personality at baseline and anxiety at 10-year follow-up. METHODS: A cohort of surviving consecutive patients (N = 534) who underwent PCI between October 2001 and October 2002. Patients completed the type D personality scale (DS14) measuring type D personality at baseline, and the Hospital Anxiety and Depression Scale (HADS) measuring anxiety and depression at baseline and at 10 years post-PCI. RESULTS: At baseline, the prevalence of type D personality was 25 % (135/534). Type D personality patients were more often depressed (42 %) than non-type D personality patients (9 %). Response rate of anxiety and depression questionnaires at 10 years was 75 %. At 10-year follow-up, 31 % of type D personality patients were depressed versus 13 % of non-type D personality patients. After adjustments, baseline type D personality remained independently associated with depression at 10 years (OR = 3.69; 95 % CI [1.89-7.19]). Type D showed a similar association with anxiety at 10 years, albeit somewhat lower (OR = 2.72; 95 % CI [1.31-5.63]). CONCLUSIONS: PCI patients with type D personality had a 3.69-fold increased risk for depression and a 2.72-fold increased risk for anxiety at 10 years of follow-up.

Long-term quality of life in children after open airway surgery for laryngotracheal stenosis.

OBJECTIVES: The purpose of this study is to evaluate the long-term health related quality of life (HRQoL) in a cohort of children surgically treated for laryngotracheal stenosis (LTS). STUDY DESIGN: Prospective cohort study. METHODS: Parents of children between 4 and 18 years at follow-up completed the Child Health Questionnaire Parent Form (CHQ-PF50). Children between 11 and 18 years at follow-up completed the Child Health Questionnaire Child Form (CHQ-CF87). Biographical and pre-operative data were extracted from the hospital records. Post-operative measurements consisted of the Bruce treadmill test and pulmonary function testing (PFT). RESULTS: Fifty-four parents completed the CHQ-PF50; twenty-one children completed the CHQ-CF87. The CHQ-PF50 was significantly worse than the norm population on the subscales physical functioning, role functioning: emotional/behavior, general health perceptions, family activities, parental impact: emotional, and time. CHQ-CF87 was significantly worse than the norm population on physical functioning and better on mental health. After multivariate analysis, presence of co-morbidities and glottic stenosis are the most important pre-operative factors for worse scores on general health. As post-operative measurements, the Bruce treadmill test and peak expiratory flow (PEF) correlate well with HRQoL physical subscales. CONCLUSIONS: At long-term follow-up after treatment for LTS, deficits in HRQoL may still exist. Presence of co-morbidities and glottic stenosis are important negative factors for long-term HRQoL. The Bruce treadmill test and peak expiratory flow on pulmonary function testing correlate well with physical subscales on HRQoL. A long-term multidisciplinary follow-up with assessment of HRQoL is advised in patients treated for LTS. LEVEL OF EVIDENCE: 2B, individual prospective cohort study.

Prognostic value of type D personality for 10-year mortality and subjective health status in patients treated with percutaneous coronary intervention.

OBJECTIVE: Given the debate around limitations and controversies in type D personality studies, we aimed to evaluate the prognostic value of 'synergistically' analyzed type D personality (interaction z-scores negative affectivity NA, and social inhibition SI) on 10-year mortality and on 10-year subjective health status in percutaneous coronary intervention (PCI) patients. METHODS: This prospective study comprised a cohort of 1190 consecutive patients who underwent PCI between October 2001 and September 2002 (73% male, mean age: 62years, range [27-90]years). At baseline, type D personality (DS14), and depression/anxiety (HADS) were assessed. Primary endpoint was 10year all-cause mortality; secondary endpoint was 10-year subjective health status (SF-36). RESULTS: After a median follow-up of 10.3years (IQR 9.8-10.8), 293 deaths of any cause (24.6%) were recorded. After adjustment for significant baseline characteristics, personality categories approached and dichotomously approached type D personality were associated with 10-year mortality, p<.05. Synergistically approached type D personality was not associated with all-cause mortality or subjective health status at 10years. In survivors, higher NA was associated with lower subjective health status. Type D was not associated with mortality after adjusting for continuous depression and anxiety in all approaches. CONCLUSIONS: Synergistically analyzed type D was not associated with 10-year all-cause mortality in PCI patients whereas dichotomous type D was. However, after adjustment for depression most of the findings had disappeared. Depression played an important role in this. Type D was not associated with 10-year subjective health status.

The effect of exercise training on cardiac remodelling in children and young adults with corrected tetralogy of Fallot or Fontan circulation: a randomized controlled trial.

BACKGROUND: Exercise can improve physical fitness in children and adults with congenital heart disease. We hypothesized that exercise training would not lead to adverse cardiac remodelling in this population. METHODS AND RESULTS: This multi-centre randomized controlled trial included children and young adults (10 to 25 years) with either corrected tetralogy of Fallot or Fontan circulation. The exercise-group was enrolled in a 12 week standardized aerobic dynamic exercise training program. The control-group continued their life-style and received care as usual. Both groups underwent cardiopulmonary exercise testing, cardiac magnetic resonance imaging (MRI), echocardiography and neurohormonal assessment, within 2 weeks before and 2 weeks after the intervention period. Fifty-six patients were randomized to the exercise-group and 37 to the control-group. We assessed changes between the pre- and the post-intervention period for the exercise group compared to the changes in the control-group. Peak load increased significantly in the exercise-group compared to the control-group (exercise-group 6.9 ± 11.8 W; control-group 0.8 ± 13.9 W; p=0.047). There were no adverse events linked to the study. Ventricular systolic parameters, cardiac dimensions and neurohormonal markers during follow-up did not change in patients allocated to the exercise-group and control-group. Although there were some isolated minor changes in inflow parameters, there was no consistent pattern of changes, indicating a lack of true change in the diastolic function. CONCLUSION: We demonstrated that no clinically relevant adverse cardiac remodelling occurred after 12 weeks of exercise training in patients with either corrected tetralogy of Fallot or Fontan circulation. CLINICAL TRIAL REGISTRATION: www.trialregister.nl, identification NTR2731.

Systematic review of the effects of physical exercise training programmes in children and young adults with congenital heart disease.

BACKGROUND: Most patients with congenital heart disease (ConHD) do not perform regular physical exercise. Consensus reports have stated that exercise should be encouraged and regularly performed in these patients, but this is not common practise. We reviewed the literature on actual evidence for either negative or positive effects of physical exercise training programmes in children and young adults with ConHD. METHODS: Using the Medline database, we systematically searched for articles on physical exercise training programmes in ConHD. RESULTS: A total of 31 articles met all inclusion criteria; in total, 621 subjects (age range 4 to 45 years) were included. Most studies used training programmes with a duration of 12 weeks. On average, the number of training sessions was 3 times per week. In 12 studies, training intensity was set at a percentage of peak heart rate. Outcome measures reported were PeakVO2, activity levels and muscle strength. Twenty-three studies (72%) found a significant positive change in the main outcome measure after the physical exercise training period. None of the studies reported negative findings related to physical exercise training in ConHD. Cardiac effects have hardly been studied. CONCLUSION: In most studies, participation in a physical exercise training programme was safe and improved fitness in children and young adults with ConHD. We recommend that patients with ConHD participate in physical exercise training. Cardiac effects need to be studied more extensively.