Positive Airway Pressure and Metabolic Markers in Children With Obstructive Sleep Apnea.

BACKGROUND: Increasing evidence suggests an association between childhood obstructive sleep apnea (OSA) and metabolic syndrome, with more research available on the potential impacts of positive airway pressure (PAP) on metabolic markers in children. The purpose of this systematic review is to provide a systematic synthesis of the evidence on the effect of PAP use on metabolic markers in children with OSA. METHODS: A search strategy with terms for "OSA" and metabolic markers in pediatrics was run to systematically assess 5 databases until August 26, 2022. Two reviewers independently screened eligible articles, extracted data, and conducted quality appraisal. Meta-analysis was done using random-effects models. Body mass index (BMI), glycemic, lipid, cardiovascular, and other metabolic and inflammatory markers were reported. RESULTS: Sixteen studies (N = 1,213) were included, 15 observational studies and 1 randomized controlled trial (RCT); most reported outcomes in children with obesity. Meta-analysis of 4 studies found no changes in BMI at median average follow-up of 12 months after PAP initiation. A reduction in heart rate and blood pressure parameters was demonstrated in several studies in children with OSA with and without obesity at a median average follow-up of 4.9 months after PAP initiation. Research in echocardiographic outcomes is limited, including one RCT in children with Down syndrome and OSA showing no changes in heart rate variability parameters. Evidence of improvements in glycemic and/or lipid control, liver enzymes, and inflammatory markers with PAP therapy is even more limited and of limited clinical importance. Risk of bias was moderate to critical and outcome evidence very low. CONCLUSIONS: Although evidence on effects of PAP on metabolic markers in children with OSA is encouraging, available literature is limited. Longitudinal studies are still required to further assess the long-term influence of PAP on metabolic and inflammatory markers, particularly in children with obesity.

Renal outcomes of children born with posterior urethral valves at a tertiary center: A 15-year retrospective review.

INTRODUCTION: Posterior urethral valves (PUVs) is a congenital condition in which an obstruction in the urethra prevents drainage of urine from the bladder in males, with up to 60% of children diagnosed developing chronic kidney disease (CKD). The primary aim of this study was to identify novel factors that may predict development of CKD and end-stage real disease (ESRD ) in children with PUVs to potentially address modifiable factors and delay progression. The secondary aim was to compare rates of catheterization and incontinence between our patients and other case series to provide information to parents about long-term bladder outcomes. METHODS: A single-center, retrospective cohort study was performed of all children referred to our multidisciplinary clinic for PUV diagnosis between 2005 and 2019. Univariable associations of different variables with the composite outcome CKD or ESRD were evaluated. RESULTS: Thirty of 46 patients (65%) developed CKD, with the majority (40%) being stage 2 CKD (n=12). Seven of 30 patients (23%) developed ESRD requiring renal replacement therapy. Fourteen of 26 (30%) required clean intermittent catheterization (CIC) initiation, with a median CIC initiation age of 4.3 years. Creatinine nadir post-valve ablation, oligohydramnios, and initiation of CIC are significant predictors of CKD development. CONCLUSIONS: This review reiterates that children born with PUVs have a high morbidity rate, with a high proportion developing CKD. Using a multidisciplinary approach to PUV patient care allows for better family education, early intervention of bladder dysfunction, and possibly better long-term preservation of renal function.

Rituximab Use for the Treatment of Childhood Nephrotic Syndrome by Canadian Pediatric Nephrologists: A National Survey.

Background: There is known practice variation in the treatment of frequently relapsing, steroid-dependent, and steroid-resistant nephrotic syndrome in children. Rituximab is an emerging therapy for difficult-to-treat nephrotic syndrome; however, there are no clear treatment guidelines. We therefore hypothesized that a wide variety of approaches to this therapy exist. Objective: To evaluate when and how rituximab is used for the treatment of childhood nephrotic syndrome in Canada. Design and setting: An online survey was used. Participants: Canadian pediatric nephrologists. Methods: A cross-sectional survey was distributed across Canada through the Canadian Association of Pediatric Nephrologists (CAPN) to evaluate rituximab treatment practices. Results: Of a total of 20 responses, 19 (95%) use rituximab in the treatment of nephrotic syndrome, usually as a third or fourth agent. For the number of rituximab doses, the majority (68%) uses 2 doses each time they use it. Eighteen respondents (90%) measure B cells when using this medication, mostly monthly (50%) or every 3 months (39%). Respondents were administered additional doses of rituximab prophylactically (74%) or at first relapse (47%). Long-term drug safety and drug funding were identified as the main barriers to rituximab use. Limitations: This survey represents the practice styles of physicians in a single country, and there is a nonresponse bias of 63%. Also, associations were not calculated. Conclusions: Among Canadian pediatric nephrologists, rituximab use for nephrotic syndrome appears to be increasing, but significant practice variations remain, including approaches to B-cell monitoring. It is reserved mostly for second-line and third-line use due to cost, funding issues, and residual uncertainty regarding long-term safety. Understanding these critical areas of practice uncertainty is a first step to optimize treatment of nephrotic syndrome in children.

Contexte: Des variations sont connues dans les pratiques liées au traitement du syndrome néphrotique infantile, dépendant ou résistant aux stéroïdes, à récidives fréquentes. Le rituximab constitue une nouvelle approche thérapeutique pour soigner le syndrome néphrotique difficile à traiter. Il n'existe cependant aucune directive de traitement claire dans ce contexte. Nous avons donc émis l'hypothèse qu'il existait une grande variété d'approches dans l'utilisation de ce médicament. Objectifs: Examiner les pratiques d'utilisation (quand et comment) du rituximab dans le traitement du syndrome néphrotique infantile au Canada. Cadre et type d'étude: Étude menée par sondage en ligne. Participants: Des néphrologues pédiatriques canadiens. Méthodologie: Un sondage transversal a été distribué partout au Canada par l'entremise de l'Association canadienne des néphrologues pédiatriques (ACPN) afin d'examiner les pratiques de traitement au rituximab. Résultats: Parmi les 20 néphrologues ayant répondu au sondage, 19 (95 %) utilisent le rituximab dans le traitement du syndrome néphrotique, généralement comme 3e ou 4e agent, et la majorité d'entre eux (68 %) administre deux doses à chaque utilisation. Dix-huit répondants (90 %) mesurent les lymphocytes B lorsqu'ils emploient ce médicament, principalement tous les mois (50 %) ou tous les trois mois (39 %). Certains répondants avaient administré des doses additionnelles de rituximab à des fins prophylactiques (74 %) ou lors de la première rechute (47 %). Le recours au rituximab serait principalement freiné par des enjeux liés à son innocuité à long terme et au financement des médicaments. Limitations: Ce sondage représente les pratiques des médecins d'un seul pays et comporte un biais de non-réponse de 63 %. De plus, les associations n'ont pas été calculées. Conclusion: Chez les néphrologues pédiatriques canadiens, l'utilisation du rituximab dans le traitement du syndrome néphrotique semble augmenter; bien que des variations significatives demeurent dans la pratique, notamment en ce qui concerne les approches de surveillance des lymphocytes B. Actuellement, le rituximab est surtout utilisé comme thérapie de deuxième et de troisième ligne en raison de son coût, d'enjeux liés au financement et d'une incertitude résiduelle en ce qui concerne son innocuité à long terme. La compréhension de ces zones critiques d'incertitude dans les pratiques est une première étape pour optimiser le traitement du syndrome néphrotique chez les enfants.

Characteristics Associated with Variation in Corticosteroid Exposure in Children with Steroid-Sensitive Nephrotic Syndrome: Results from a Canadian Longitudinal Study.

Background: Variation in dose and duration of corticosteroids for childhood-onset steroid-sensitive nephrotic syndrome occurs worldwide, likely reflecting the evolving evidence on optimal dosing and variable severity of the disease observed between patients. We conducted a study to determine the associations between site, physician, and patient factors, and average daily corticosteroid dose and duration of therapy. Methods: Data were derived from the Canadian Childhood Nephrotic Syndrome (CHILDNEPH) Project, an observational longitudinal study from 2013 to 2019 of children with nephrotic syndrome involving pediatric nephrologists in 11 sites across Canada. The primary outcome was average daily corticosteroid dose prescribed per episode of proteinuria, reported as mg/m2 prednisone equivalents. Secondary outcome was duration of treatment for each episode of proteinuria in days. Exposure variables were categorized into site-, physician-, and patient-level variables. Results: In total, 328 children, median age at enrollment of 4.3 years old (interquartile range [IQR], 3.6), participated and were followed for a median time of 2.62 years (IQR, 2.6). The observed variability in average daily corticosteroid dose and in duration of therapy was mostly attributed to the site where the patient was treated. Accounting for between patient, physician, and site differences, average daily corticosteroid dose decreased with increasing age (beta coefficient, -0.07; 95% confidence interval [95% CI], -0.09 to -0.05], P<0.001). African and Indigenous ethnicity was associated with longer treatment duration compared with White patients (beta coefficient: African, 42.29, 95% CI, 7.85 to 76.73, P=0.02; Indigenous, 29.65, 95% CI, 2.79 to 56.52, P=0.03). Conclusions: We found practice variation with respect to corticosteroid prescriptions across 11 Canadian sites, and that variation is mostly explained at the site level. Age and ethnicity are important factors to be considered, because they are significantly associated with the average corticosteroid dose and duration of therapy.

Does obstructive sleep apnoea contribute to obesity, hypertension and kidney dysfunction in children? A systematic review protocol.

INTRODUCTION: Childhood obstructive sleep apnoea (OSA) is a highly prevalent disorder that may directly contribute to the development of obesity, hypertension and renal injury. Although those associations seem to be clearer in adults, studies in children have revealed conflicting results and updated synthesis of the evidence is lacking. The aim of this systematic review is to summarise the available evidence on the effect of OSA on obesity, systemic blood pressure and kidney function, to help to elucidate whether respiratory interventions to correct OSA would have the potential to improve those outcomes. METHODS AND ANALYSIS: A systematic literature review search was created by a medical librarian and peer-reviewed by a second librarian prior to running. Ovid Medline, Ovid Embase, CINAHL via EbscoHOST, Wiley Cochrane Library and ProQuest Dissertations and Theses Global were searched on 25 February 2020. Titles and abstracts will be screened by two independent reviewers for inclusion, followed by full-text screening of relevant articles. Studies in children will be included if they report data on OSA and weight, systemic blood pressure or kidney parameters. The extracted data will be combined for analysis and the information subcategorised in groups based on outcome. Risk of bias will be determined using tools specific to study methodology and certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluations approach. ETHICS AND DISSEMINATION: This study will provide essential information for healthcare professionals to better understand the relationship between childhood OSA and changes in body mass index, systemic blood pressure and kidney function indicators. Our findings will be disseminated through conferences and publications. The results of this review may guide the initiation of new strategies and the development of future research studies. This research did not involve human subjects and therefore did not undergo research ethical review. PROSPERO REGISTRATION NUMBER: CRD42020171186.

Does non-invasive ventilation change metabolic markers in children with obstructive sleep apnoea? A systematic review and meta-analysis study protocol.

INTRODUCTION: Obstructive sleep apnoea (OSA) is not only common within paediatrics but is associated with critical childhood metabolic morbidity such as obesity, cardiovascular disease and glucose tolerance impairment. Increasing evidence suggests an association between childhood OSA and metabolic syndrome such as markers of cardiovascular disease, systemic hypertension, glucose intoleranceand increased lipid profile. Recent studies have targeted changes in metabolic markers in children using non-invasive ventilation (NIV) but no systematic reviews are available to summarise this emerging evidence. The purpose of this systematic review is to provide systematic synthesis of the evidence on the effect of NIV use on metabolic markers in children with OSA. METHODS AND ANALYSIS: A systematic search of electronic databases and grey literature will include paediatric interventional studies (random controlled trials, cohort studies) with and without a comparison group. Two reviewers will independently undertake the two step process of title/abstract and full-text screening. Data will be extracted and assessed, with aggregate data being reported. When the data allow, meta-analysis will be performed. ETHICS AND DISSEMINATION: There are no ethical concerns with this systematic review, as data have previously been published. This review will inform clinicians taking care of children with OSA and obesity/metabolic syndrome about the potential effects of NIV therapies on metabolic markers and has the potential to change the approach to childhood OSA and obesity. Results of this systematic review will be submitted for dissemination in abstract and manuscript form.

Follow-up after neonatal heart disease repair: watch out for chronic kidney disease and hypertension!

BACKGROUND: With advances in care, neonates undergoing cardiac repairs are surviving more frequently. Our objectives were to 1) estimate the prevalence of chronic kidney disease (CKD) and hypertension 6 years after neonatal congenital heart surgery and 2) determine if cardiac surgery-associated acute kidney injury (CS-AKI) is associated with these outcomes. METHODS: Two-center prospective, longitudinal single-visit cohort study including children with congenital heart disease surgery as neonates between January 2005 and December 2012. CKD (estimated glomerular filtration rate < 90 mL/min/1.73m2 or albumin/creatinine ≥3 mg/mmol) and hypertension (systolic or diastolic blood pressure ≥ 95th percentile for age, sex, and height) prevalence 6 years after surgery was estimated. The association of CS-AKI (Kidney Disease: Improving Global Outcomes definition) with CKD and hypertension was determined using multiple regression. RESULTS: Fifty-eight children with median follow-up of 6 years were evaluated. CS-AKI occurred in 58%. CKD and hypertension prevalence were 17% and 30%, respectively; an additional 15% were classified as having elevated blood pressure. CS-AKI was not associated with CKD or hypertension. Classification as cyanotic postoperatively was the only independent predictor of CKD. Postoperative days in hospital predicted hypertension at follow-up. CONCLUSIONS: The prevalence of CKD and hypertension is high in children having neonatal congenital heart surgery. This is important; early identification of CKD and hypertension can improve outcomes. These children should be systematically followed for the evolution of these negative outcomes. CS-AKI defined by current standards may not be a useful clinical tool to decide who needs follow-up and who does not.

Paucity of renal follow-up by school age after neonatal cardiac surgery.

INTRODUCTION: There are little data about renal follow-up of neonates after cardiovascular surgery and no guidelines for long-term renal follow-up. Our objectives were to assess renal function follow-up practice after neonatal cardiac surgery, evaluate factors that predict follow-up serum creatinine measurements including acute kidney injury following surgery, and evaluate the estimated glomerular filtration rate during follow-up using routinely collected laboratory values. METHODS: Two-centre retrospective cohort study of children 5-7 years of age with a history of neonatal cardiac surgery. Univariable and multivariable analyses were performed to determine factors associated with post-discharge creatinine measurements. Glomerular filtration rate was estimated for each creatinine using a height-independent equation. RESULTS: Seventeen of 55 children (30%) did not have any creatinine measured following discharge after surgery until the end of study follow-up, which occurred at a median time of 6 years after discharge. Of the 38 children who had the kidney function checked, 15 (40%) had all of their creatinine drawn only in the context of a hospitalisation or emergency department visit. Acute kidney injury following surgery did not predict the presence of follow-up creatinine measurements. CONCLUSIONS: A large proportion of neonates undergoing congenital heart repair did not have a follow-up creatinine measured in the first years following surgery. In those that did have a creatinine measured, there did not appear to be any identified pattern of follow-up. A follow-up system for children who are discharged from cardiac surgery is needed to identify children with or at risk of chronic kidney disease.

Implementation and Performance of Automated Software for Computing Right-to-Left Ventricular Diameter Ratio From Computed Tomography Pulmonary Angiography Images.

OBJECTIVE: The aim of this study was to prospectively test the performance and potential for clinical integration of software that automatically calculates the right-to-left ventricular (RV/LV) diameter ratio from computed tomography pulmonary angiography images. METHODS: Using 115 computed tomography pulmonary angiography images that were positive for acute pulmonary embolism, we prospectively evaluated RV/LV ratio measurements that were obtained as follows: (1) completely manual measurement (reference standard), (2) completely automated measurement using the software, and (3 and 4) using a customized software interface that allowed 2 independent radiologists to manually adjust the automatically positioned calipers. RESULTS: Automated measurements underestimated (P < 0.001) the reference standard (1.09 [0.25] vs1.03 [0.35]). With manual correction of the automatically positioned calipers, the mean ratio became closer to the reference standard (1.06 [0.29] by read 1 and 1.07 [0.30] by read 2), and the correlation improved (r = 0.675 to 0.872 and 0.887). The mean time required for manual adjustment (37 [20] seconds) was significantly less than the time required to perform measurements entirely manually (100 [23] seconds). CONCLUSIONS: Automated CT RV/LV diameter ratio software shows promise for integration into the clinical workflow for patients with acute pulmonary embolism.

A clinical method for mapping and quantifying blood stasis in the left ventricle.

In patients at risk of intraventrcular thrombosis, the benefits of chronic anticoagulation therapy need to be balanced with the pro-hemorrhagic effects of therapy. Blood stasis in the cardiac chambers is a recognized risk factor for intracardiac thrombosis and potential cardiogenic embolic events. In this work, we present a novel flow image-based method to assess the location and extent of intraventricular stasis regions inside the left ventricle (LV) by digital processing flow-velocity images obtained either by phase-contrast magnetic resonance (PCMR) or 2D color-Doppler velocimetry (echo-CDV). This approach is based on quantifying the distribution of the blood Residence Time (TR) from time-resolved blood velocity fields in the LV. We tested the new method in illustrative examples of normal hearts, patients with dilated cardiomyopathy and one patient before and after the implantation of a left ventricular assist device (LVAD). The method allowed us to assess in-vivo the location and extent of the stasis regions in the LV. Original metrics were developed to integrate flow properties into simple scalars suitable for a robust and personalized assessment of the risk of thrombosis. From a clinical perspective, this work introduces the new paradigm that quantitative flow dynamics can provide the basis to obtain subclinical markers of intraventricular thrombosis risk. The early prediction of LV blood stasis may result in decrease strokes by appropriate use of anticoagulant therapy for the purpose of primary and secondary prevention. It may also have a significant impact on LVAD device design and operation set-up.

Automated axial right ventricle to left ventricle diameter ratio computation in computed tomography pulmonary angiography.

BACKGROUND AND PURPOSE: Right Ventricular to Left Ventricular (RV/LV) diameter ratio has been shown to be a prognostic biomarker for patients suffering from acute Pulmonary Embolism (PE). While Computed Tomography Pulmonary Angiography (CTPA) images used to confirm a clinical suspicion of PE do include information of the heart, a numerical RV/LV diameter ratio is not universally reported, likely because of lack in training, inter-reader variability in the measurements, and additional effort by the radiologist. This study designs and validates a completely automated Computer Aided Detection (CAD) system to compute the axial RV/LV diameter ratio from CTPA images so that the RV/LV diameter ratio can be a more objective metric that is consistently reported in patients for whom CTPA diagnoses PE. MATERIALS AND METHODS: The CAD system was designed specifically for RV/LV measurements. The system was tested in 198 consecutive CTPA patients with acute PE. Its accuracy was evaluated using reference standard RV/LV radiologist measurements and its prognostic value was established for 30-day PE-specific mortality and a composite outcome of 30-day PE-specific mortality or the need for intensive therapies. The study was Institutional Review Board (IRB) approved and HIPAA compliant. RESULTS: The CAD system analyzed correctly 92.4% (183/198) of CTPA studies. The mean difference between automated and manually computed axial RV/LV ratios was 0.03±0.22. The correlation between the RV/LV diameter ratio obtained by the CAD system and that obtained by the radiologist was high (r=0.81). Compared to the radiologist, the CAD system equally achieved high accuracy for the composite outcome, with areas under the receiver operating characteristic curves of 0.75 vs. 0.78. Similar results were found for 30-days PE-specific mortality, with areas under the curve of 0.72 vs. 0.75. CONCLUSIONS: An automated CAD system for determining the CT derived RV/LV diameter ratio in patients with acute PE has high accuracy when compared to manual measurements and similar prognostic significance for two clinical outcomes.