Aortic Dilatation in Children and Young People With ADPKD.

Introduction: Aortic root dilatation is a reported cardiovascular sequela seen in children and young people (CYP) with chronic kidney disease (CKD) but has yet to be described in those with autosomal dominant polycystic kidney disease (ADPKD). Methods: Single center, cross-sectional study in a dedicated ADPKD clinic. Echocardiograms were evaluated for the presence of dilatation (defined by a z-score ≥2 [≥99th percentile] SDs from the mean) at 4 standardized locations, namely the aortic valve annulus, sinuses of Valsalva (SoV), sinotubular junction (STJ), and the ascending aorta. Measurements were compared with a control group to assess prevalence, severity, and determinants of aortic dilatation. Results: Ninety-seven children, median age (interquartile range) of 9.3 (6.1, 13.6) years were compared with 19 controls without ADPKD or other CKD. The prevalence of dilatation ranged from 5.2% to 17% in ADPKD, depending on anatomical location with no aortic dilatation identified in the control group. In multivariable regression, aortic root dilatation was significantly associated with cyst burden at the aortic valve annulus and SoV (ß = 0.42 and ß = 0.39, both P < 0.001), with age at SoV (ß = -0.26, P = 0.02), systolic blood pressure (SBP) z-score at SoV (ß = -0.20, P = 0.04) and left ventricular mass index (LVMI) at SoV and STJ (ß = 0.24, P = 0.02 and ß = 0.25, P = 0.03, respectively) following adjustment for age, sex (male or female), body mass index (BMI) z-score, estimated glomerular filtration rate (eGFR), SBP z-score, and LVMI. Conclusion: Our data suggests increased prevalence of aortic root and ascending aortic dilatation in CYP with ADPKD compared with controls. Further studies are needed to understand the pathogenesis and its contribution to the high cardiovascular morbidity in ADPKD.

Decline in Left Ventricular Early Systolic Function with Worsening Kidney Function in Children with Chronic Kidney Disease: Insights from the 4C and HOT-KID Studies.

INTRODUCTION: Adults with childhood-onset chronic kidney disease (CKD) have an increased risk of cardiovascular disease. First-phase ejection fraction (EF1), a novel measure of early systolic function, may be a more sensitive marker of left ventricular dysfunction than other markers in children with CKD. OBJECTIVE: To examine whether EF1 is reduced in children with CKD. METHODS: Children from the 4C and HOT-KID studies were stratified according to estimated glomerular filtration rate (eGFR). The EF1 was calculated from the fraction of left ventricular (LV) volume ejected up to the time of peak aortic flow velocity. RESULTS: The EF1 was measured in children ages 10.9 ± 3.7 (mean ± SD) years, 312 with CKD and 63 healthy controls. The EF1 was lower, while overall ejection fraction was similar, in those with CKD compared with controls and decreased across stages of CKD (29.3% ± 3.7%, 23.5% ± 4.5%, 19.8% ± 4.0%, 18.5% ± 5.1%, and 16.7% ± 6.6% in controls, CKD 1, 2, 3, and ≥ 4, respectively, P < .001). The relationship of EF1 to eGFR persisted after adjustment for relevant confounders (P < .001). The effect size for association of measures of LV structure or function with eGFR (SD change per unit change in eGFR) was greater for EF1 (ß = 0.365, P < .001) than for other measures: LV mass index (ß = -0.311), relative wall thickness (ß = -0.223), E/e' (ß = -0.147), and e' (ß = 0.141) after adjustment for confounders in children with CKD. CONCLUSIONS: Children with CKD exhibit a marked and progressive decline in EF1 with falling eGFR. This suggests that EF1 is a more sensitive marker of LV dysfunction when compared to other structural or functional measures and that early LV systolic function is a key feature in the pathophysiology of cardiac dysfunction in CKD.

Reliability of systolic blood pressure measured by parents in young children at home using a hand held doppler device and aneroid sphygmomanometer.

OBJECTIVE: We report data regarding systolic BP monitoring in children aged <5 years performed over a 2-week period by parents at home using a hand-held doppler device and aneroid sphygmomanometer for SBP measurements (HDBPM). Our objectives were to compare health professional measured office systolic BP by doppler device (Office-SBP Doppler ) with parent measured home systolic BP using the same doppler device (Home-SBP Doppler ). We also report data evaluating reliability and optimal number of days of measurement required. DESIGN AND METHODS: We taught parents to measure systolic BP and assessed their technique using a hand-held doppler device and aneroid sphygmomanometer. We requested parents to perform three consecutive BP measurements twice daily (ideally morning and evening around similar times) when the child was awake, settled and cooperative. RESULTS: Over a 3-year period, data from 48 of 62 children who underwent HDBPM measurements were evaluated with median (IQR) age of 1.9 (0.9, 3.6) years, 27 (56%) boys and 14 (29%) on antihypertensive medication. Office-SBP Doppler was 2.9 ±â€Š8.9 mmHg [95% confidence interval (CI), -14.4 to 20.4, P  = 0.026] higher than Home-SBP Doppler . Mean Home-SBP Doppler between Week-1 and Week-2 monitoring was similar -0.45 ±â€Š3.5 mmHg (95% CI, -7.35 to 6.45, P  = 0.41). Morning HDBPM measurements were lower than evening with a mean difference of -2.77 ±â€Š3.92 mmHg, P  < 0.001). Over Week-1, mean Home-SBP Doppler was closer to mean Office-SBP Doppler with increasing cumulative days of monitoring and with smaller standard deviations suggesting that readings become more reliable from day 4 onwards. CONCLUSIONS: HDBPM is a reliable method for measuring systolic BP in young children with BP levels measured by parents comparable to those performed by health professional in clinic. HDBPM technique described here and performed by parents over a 7-day period with a minimum of 4-days, offers a reliable and reproducible technique to measure blood pressure at home.

Prevalence of Pediatric Masked Hypertension and Risk of Subclinical Cardiovascular Outcomes: A Systematic Review and Meta-Analysis.

Masked hypertension (MH) occurs when office blood pressure is normal, but hypertension is confirmed using out-of-office blood pressure measures. Hypertension is a risk factor for subclinical cardiovascular outcomes, including left ventricular hypertrophy, increased left ventricular mass index, carotid intima media thickness, and pulse wave velocity. However, the risk factors for ambulatory blood pressure monitoring defined MH and its association with subclinical cardiovascular outcomes are unclear. A systematic literature search on 9 databases included English publications from 1974 to 2023. Pediatric MH prevalence was stratified by disease comorbidities and compared with the general pediatric population. We also compared the prevalence of left ventricular hypertrophy, and mean differences in left ventricular mass index, carotid intima media thickness, and pulse wave velocity between MH versus normotensive pediatric patients. Of 2199 screened studies, 136 studies (n=28 612; ages 4-25 years) were included. The prevalence of MH in the general pediatric population was 10.4% (95% CI, 8.00-12.80). Compared with the general pediatric population, the risk ratio (RR) of MH was significantly greater in children with coarctation of the aorta (RR, 1.91), solid-organ or stem-cell transplant (RR, 2.34), chronic kidney disease (RR, 2.44), and sickle cell disease (RR, 1.33). MH patients had increased risk of subclinical cardiovascular outcomes compared with normotensive patients, including higher left ventricular mass index (mean difference, 3.86 g/m2.7 [95% CI, 2.51-5.22]), left ventricular hypertrophy (odds ratio, 2.44 [95% CI, 1.50-3.96]), and higher pulse wave velocity (mean difference, 0.30 m/s [95% CI, 0.14-0.45]). The prevalence of MH is significantly elevated among children with various comorbidities. Children with MH have evidence of subclinical cardiovascular outcomes, which increases their risk of long-term cardiovascular disease.

Efficacy and safety of ciclosporin versus methotrexate in the treatment of severe atopic dermatitis in children and young people (TREAT): a multicentre parallel group assessor-blinded clinical trial.

BACKGROUND: Conventional systemic drugs are used to treat children and young people (CYP) with severe atopic dermatitis (AD) worldwide, but no robust randomized controlled trial (RCT) evidence exists regarding their efficacy and safety in this population. While novel therapies have expanded therapeutic options, their high cost means traditional agents remain important, especially in lower-resource settings. OBJECTIVES: To compare the safety and efficacy of ciclosporin (CyA) with methotrexate (MTX) in CYP with severe AD in the TREatment of severe Atopic Eczema Trial (TREAT) trial. METHODS: We conducted a parallel group assessor-blinded RCT in 13 UK and Irish centres. Eligible participants aged 2-16 years and unresponsive to potent topical treatment were randomized to either oral CyA (4 mg kg-1 daily) or MTX (0.4 mg kg-1 weekly) for 36 weeks and followed-up for 24 weeks. Co-primary outcomes were change from baseline to 12 weeks in Objective Severity Scoring of Atopic Dermatitis (o-SCORAD) and time to first significant flare (relapse) after treatment cessation. Secondary outcomes included change in quality of life (QoL) from baseline to 60 weeks; number of participant-reported flares following treatment cessation; proportion of participants achieving ≥ 50% improvement in Eczema Area and Severity Index (EASI 50) and ≥ 75% improvement in EASI (EASI 75); and stratification of outcomes by filaggrin status. RESULTS: In total, 103 participants were randomized (May 2016-February 2019): 52 to CyA and 51 to MTX. CyA showed greater improvement in disease severity by 12 weeks [mean difference in o-SCORAD -5.69, 97.5% confidence interval (CI) -10.81 to -0.57 (P = 0.01)]. More participants achieved ≥ 50% improvement in o-SCORAD (o-SCORAD 50) at 12 weeks in the CyA arm vs. the MTX arm [odds ratio (OR) 2.60, 95% CI 1.23-5.49; P = 0.01]. By 60 weeks MTX was superior (OR 0.33, 95% CI 0.13-0.85; P = 0.02), a trend also seen for ≥ 75% improvement in o-SCORAD (o-SCORAD 75), EASI 50 and EASI 75. Participant-reported flares post-treatment were higher in the CyA arm (OR 3.22, 95% CI 0.42-6.01; P = 0.02). QoL improved with both treatments and was sustained after treatment cessation. Filaggrin status did not affect outcomes. The frequency of adverse events (AEs) was comparable between both treatments. Five (10%) participants on CyA and seven (14%) on MTX experienced a serious AE. CONCLUSIONS: Both CyA and MTX proved effective in CYP with severe AD over 36 weeks. Participants who received CyA showed a more rapid response to treatment, while MTX induced more sustained disease control after discontinuation.

Epidemiology of childhood acute kidney injury in England using e-alerts.

Background: Few studies describe the epidemiology of childhood acute kidney injury (AKI) nationally. Laboratories in England are required to issue electronic (e-)alerts for AKI based on serum creatinine changes. This study describes a national cohort of children who received an AKI alert and their clinical course. Methods: A cross-section of AKI episodes from 2017 are described. Hospital record linkage enabled description of AKI-associated hospitalizations including length of stay (LOS) and critical care requirement. Risk associations with critical care (hospitalized cohort) and 30-day mortality (total cohort) were examined using multivariable logistic regression. Results: In 2017, 7788 children (52% male, median age 4.4 years, interquartile range 0.9-11.5 years) experienced 8927 AKI episodes; 8% occurred during birth admissions. Of 5582 children with hospitalized AKI, 25% required critical care. In children experiencing an AKI episode unrelated to their birth admission, Asian ethnicity, young (<1 year) or old (16-<18 years) age (reference 1-<5 years), and high peak AKI stage had higher odds of critical care. LOS was higher with peak AKI stage, irrespective of critical care admission. Overall, 30-day mortality rate was 3% (n = 251); youngest and oldest age groups, hospital-acquired AKI, higher peak stage and critical care requirement had higher odds of death. For children experiencing AKI alerts during their birth admission, no association was seen between higher peak AKI stage and critical care admission. Conclusions: Risk associations for adverse AKI outcomes differed among children according to AKI type and whether hospitalization was related to birth. Understanding the factors driving AKI development and progression may help inform interventions to minimize morbidity.

Joint statement for assessing and managing high blood pressure in children and adolescents: Chapter 1. How to correctly measure blood pressure in children and adolescents.

The joint statement is a synergistic action between HyperChildNET and the European Academy of Pediatrics about the diagnosis and management of hypertension in youth, based on the European Society of Hypertension Guidelines published in 2016 with the aim to improve its implementation. The first and most important requirement for the diagnosis and management of hypertension is an accurate measurement of office blood pressure that is currently recommended for screening, diagnosis, and management of high blood pressure in children and adolescents. Blood pressure levels should be screened in all children starting from the age of 3 years. In those children with risk factors for high blood pressure, it should be measured at each medical visit and may start before the age of 3 years. Twenty-four-hour ambulatory blood pressure monitoring is increasingly recognized as an important source of information as it can detect alterations in circadian and short-term blood pressure variations and identify specific phenotypes such as nocturnal hypertension or non-dipping pattern, morning blood pressure surge, white coat and masked hypertension with prognostic significance. At present, home BP measurements are generally regarded as useful and complementary to office and 24-h ambulatory blood pressure for the evaluation of the effectiveness and safety of antihypertensive treatment and furthermore remains more accessible in primary care than 24-h ambulatory blood pressure. A grading system of the clinical evidence is included.

Joint statement for assessing and managing high blood pressure in children and adolescents: Chapter 2. How to manage high blood pressure in children and adolescents.

The joint statement is a synergistic action between HyperChildNET and the European Academy of Pediatrics about the diagnosis and management of hypertension in youth, based on the European Society of Hypertension Guidelines published in 2016 with the aim to improve its implementation. Arterial hypertension is not only the most important risk factor for cardiovascular morbidity and mortality, but also the most important modifiable risk factor. Early hypertension-mediated organ damage may already occur in childhood. The duration of existing hypertension plays an important role in risk assessment, and structural and functional organ changes may still be reversible or postponed with timely treatment. Therefore, appropriate therapy should be initiated in children as soon as the diagnosis of arterial hypertension has been confirmed and the risk factors for hypertension-mediated organ damage have been thoroughly evaluated. Lifestyle measures should be recommended in all hypertensive children and adolescents, including a healthy diet, regular exercise, and weight loss, if appropriate. If lifestyle changes in patients with primary hypertension do not result in normalization of blood pressure within six to twelve months or if secondary or symptomatic hypertension or hypertension-mediated organ damage is already present, pharmacologic therapy is required. Regular follow-up to assess blood pressure control and hypertension-mediated organ damage and to evaluate adherence and side effects of pharmacologic treatment is required. Timely multidisciplinary evaluation is recommended after the first suspicion of hypertension. A grading system of the clinical evidence is included.

Bone Mineral Density and Vascular Calcification in Children and Young Adults With CKD 4 to 5 or on Dialysis.

Introduction: Older adults with chronic kidney disease (CKD) can have low bone mineral density (BMD) with concurrent vascular calcification. Mineral accrual by the growing skeleton may protect young people with CKD from extraosseous calcification. Our hypothesis was that children and young adults with increasing BMD do not develop vascular calcification. Methods: This was a multicenter longitudinal study in children and young people (5-30 years) with CKD stages 4 to 5 or on dialysis. BMD was assessed by tibial peripheral quantitative computed tomography (pQCT) and lumbar spine dual-energy X-ray absorptiometry (DXA). The following cardiovascular imaging tests were undertaken: cardiac computed tomography for coronary artery calcification (CAC), ultrasound for carotid intima media thickness z-score (cIMTz), pulse wave velocity z-score (PWVz), and carotid distensibility for arterial stiffness. All measures are presented as age-adjusted and sex-adjusted z-scores. Results: One hundred participants (median age 13.82 years) were assessed at baseline and 57 followed up after a median of 1.45 years. Trabecular BMD z-score (TrabBMDz) decreased (P = 0.01), and there was a nonsignificant decrease in cortical BMD z-score (CortBMDz) (P = 0.09). Median cIMTz and PWVz showed nonsignificant increase (P = 0.23 and P = 0.19, respectively). The annualized increase in TrabBMDz (ΔTrabBMDz) was an independent predictor of cIMTz increase (R 2 = 0.48, ß = 0.40, P = 0.03). Young people who demonstrated statural growth (n = 33) had lower ΔTrabBMDz and also attenuated vascular changes compared with those with static growth (n = 24). Conclusion: This hypothesis-generating study suggests that children and young adults with CKD or on dialysis may develop vascular calcification even as their BMD increases. A presumed buffering capacity of the growing skeleton may offer some protection against extraosseous calcification.

Intensive compared with less intensive blood pressure control to prevent adverse cardiac remodelling in children with chronic kidney disease (HOT-KID): a parallel-group, open-label, multicentre, randomised, controlled trial.

BACKGROUND: Optimal target blood pressure to reduce adverse cardiac remodelling in children with chronic kidney disease is uncertain. We hypothesised that lower blood pressure would reduce adverse cardiac remodelling. METHODS: HOT-KID, a parallel-group, open-label, multicentre, randomised, controlled trial, was done in 14 clinical centres across England and Scotland. We included children aged 2-15 years with stage 1-4 chronic kidney disease-ie, an estimated glomerular filtration rate (eGFR) higher than 15 mL/min per 1·73 m2-and who could be followed up for 2 years. Children on antihypertensive medication were eligible as long as it could be changed to angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) if they were not already receiving these therapies. Participants were randomly assigned (1:1) to standard treatment (auscultatory office systolic blood pressure target between the 50th and 75th percentiles) or intensive treatment (systolic target <40th percentile) by the chief investigator using a rapid, secure, web-based randomisation system. ACE inhibitors or ARBs were used as first-line agents, with the dose titrated every 2-4 weeks to achieve the target blood pressure levels. The primary outcome was mean annual difference in left ventricular mass index (LVMI) by echocardiography measured by a masked observer and was assessed in the intention-to-treat population, defined as all the children who underwent randomisation irrespective of the blood pressure reached. Secondary and safety outcomes were the differences between groups in mean left ventricular relative wall thickness, renal function, and adverse effects and were also assessed in the intention-to-treat population. This trial is registered with ISRCTN, ISRCTN25006406. FINDINGS: Between Oct 30, 2012, and Jan 5, 2017, 64 participants were randomly assigned to the intensive treatment group and 60 to the standard treatment group (median age of participants was 10·0 years [IQR 6·8-12·6], 69 [56%] were male and 107 [86%] were of white ethnicity). Median follow-up was 38·7 months (IQR 28·1-52·2). Blood pressure was lower in the intensive treatment group compared with standard treatment group (mean systolic pressure lower by 4 mm Hg, p=0·0012) but in both groups was close to the 50th percentile. The mean annual reduction in LVMI was similar for intensive and standard treatments (-1·9 g/m2·7 [95% CI -2·4 to -1·3] vs -1·2 g/m2·7 [-1·5 to 0·8], with a treatment effect of -0·7 g/m2·7 [95% CI -1·9 to 2·6] per year; p=0·76) and mean value in both groups at the end of follow-up within the normal range. At baseline, elevated relative wall thickness was more marked than increased LVMI and a reduction in relative wall thickness was greater for the intensive treatment group than for the standard treatment group (-0·010 [95% CI 0·015 to -0·006] vs -0·004 [-0·008 to 0·001], treatment effect -0·020 [95% CI -0·039 to -0·009] per year, p=0·0019). Six (5%) participants reached end-stage kidney disease (ie, an eGFR of <15 mL/min per 1·73 m2; three in each group) during the course of the study. The risk difference between treatment groups was 0·02 (95% CI -0·15 to 0·19, p=0·82) for overall adverse events and 0·07 (-0·05 to 0·19, p=0·25) for serious adverse events. Intensive treatment was not associated with worse renal outcomes or greater adverse effects than standard treatment. INTERPRETATION: These results suggest that cardiac remodelling in children with chronic kidney disease is related to blood pressure control and that a target office systolic blood pressure at the 50th percentile is close to the optimal target for preventing increased left ventricular mass. FUNDING: British Heart Foundation.

Systolic and diastolic left ventricular function in children with primary hypertension: a systematic review and meta-analysis.

OBJECTIVE: Evaluation of left ventricular function provides early evidence of target-organ damage in children with primary hypertension. We performed a systematic review and meta-analysis of left ventricular systolic and diastolic function in children and adolescents with primary hypertension. METHODS: Literature search was performed in PubMed database and out of 718 articles (published between 2000 and 2021) 22 studies providing comparison of left ventricular function parameters between children with primary hypertension and normotensive controls were selected. RESULTS: Overall, 3460 children (5-21 years) with primary hypertension were analyzed. Meta-analysis showed that hypertensive patients when compared with normotensives, had an increased heart rate (mean difference [MD] 5.59; 95% confidence interval [CI] 3.28, 7.89; 10 studies) and increased fractional shortening (MD 1.04; 95% CI 0.48, 1.60; 9 studies) but did not differ in ejection fraction (MD -0.03; 95% CI -1.07, 1.02; 12 studies). Stroke volume was higher in one out of three studies, whereas no differences in cardiac output were found in two studies with available data. Hypertensive children had also lower E/A values (MD -0.21; -0.33, -0.09; 14 studies), greater values of E/e' (MD 0.59; 0.36, 0.82; 8 studies) and greater global longitudinal stress (MD 2.50; 2.03, 2.96; 4 studies) when compared to those with normotension. CONCLUSION: Our results indicate that hypertensive children and adolescents present with signs of hyperkinetic function of the left ventricle, demonstrate evidence of increased left ventricular strain and impaired diastolic function compared to normotensive controls.

Nutritional and Anthropometric Indices in Children Receiving Haemodiafiltration vs Conventional Haemodialysis - The HDF, Heart and Height (3H) Study.

BACKGROUND: The "HDF-Heart-Height" study showed that haemodiafiltration (HDF) is associated with improved growth compared to conventional haemodialysis (HD). We report a post-hoc analysis of this study assessing the effect of extracorporeal dialysis therapies on nutritional indices. METHODS: 107 children were included in the baseline cross-sectional analysis, of whom 79 (43 HD, 36 HDF) completed the 12-month follow-up. Height (Ht), optimal 'dry' weight (Wt), and body mass index (BMI) standard deviations scores (SDS), waist-to-hip ratio, des-acyl ghrelin (DAG), adiponectin, leptin, insulin-like growth factor-1 (IGF-1)-SDS and insulin were measured. RESULTS: The levels of nutritional indices were comparable between HDF and HD patients at baseline and 12-month. On univariable analyses Wt-SDS positively correlated with leptin and IGF-1-SDS, and negatively with DAG, while Ht-SDS of the overall cohort positively correlated with IGF1-SDS and inversely with DAG and adiponectin. On multivariable analyses, higher 12-month Ht-SDS was inversely associated with baseline DAG (beta = -0.13 per 500 higher; 95%CI -0.22, -0.04; P = .004). Higher Wt-SDS at 12-month was positively associated with HDF modality (beta = 0.47 vs HD; 95%CI 0.12-0.83; P = .01) and inversely with baseline DAG (beta = -0.18 per 500 higher; 95%CI -0.32, -0.05; P = .006). Growth Hormone (GH) treated patients receiving HDF had higher annualized increase in Ht SDS compared to those on HD. CONCLUSIONS: In children on HD and HDF both Wt- and Ht-SDS independently correlated with lower baseline levels of the anorexygenic hormone DAG. HDF may attenuate the resistance to GH, but further studies are required to examine the mechanisms linking HDF to improved growth.

Prevalence of cardiac valvar abnormalities in children and young people with autosomal dominant polycystic kidney disease.

BACKGROUND: Valvar abnormalities in children and adults with autosomal dominant polycystic kidney disease (ADPKD) have previously been reported as a frequent occurrence. Mitral valve prolapse (MVP), in particular, has been reported in almost one-third of adult patients and nearly 12% of children with ADPKD. Our objective in this study was to establish the prevalence of valvar abnormalities in a large, contemporary series of children and young people (CYP) with ADPKD. METHODS: A retrospective, single centre, cross-sectional analysis of the echocardiograms performed on all consecutive children seen in a dedicated paediatric ADPKD clinic. Full anatomical and functional echocardiograms were performed and analysed for valvar abnormalities. RESULTS: The echocardiograms of 102 CYP with ADPKD (range 0.25-18 years, mean age 10.3 years, SD ± 5.3 years) were analysed. One (0.98%), 3-year-old boy, had MVP. There was no associated mitral regurgitation. Evaluating variations in normal valvar anatomy, 9 (8.8%) patients, aged 7.1 to 18 years, had minor bowing ± visual elongation of either the anterior or posterior leaflet of the mitral valve, none of which fell within the criteria of true MVP. Three (1.9%) patients, 2 boys and 1 girl aged between 7 and 14 years, had trivial or mild aortic regurgitation. No patients had echocardiographic evidence of tricuspid valve prolapse (TVP). CONCLUSION: In this contemporary cohort of CYP with ADPKD, the incidence of MVP and other valvar lesions is significantly lower than previously reported. A higher resolution version of the Graphical abstract is available as Supplementary information.

Sex Differences in Blood Pressure and Potential Implications for Cardiovascular Risk Management.

BACKGROUND: Accurate blood pressure (BP) measurement is critical for optimal cardiovascular risk management. Age-related trajectories for cuff-measured BP accelerate faster in women compared with men, but whether cuff BP represents the intraarterial (invasive) aortic BP is unknown. This study aimed to determine the sex differences between cuff BP, invasive aortic BP, and the difference between the 2 measurements. METHODS: Upper-arm cuff BP and invasive aortic BP were measured during coronary angiography in 1615 subjects from the Invasive Blood Pressure Consortium Database. This analysis comprised 22 different cuff BP devices from 28 studies. RESULTS: Subjects were 64±11 years (range 40-89) and 32% women. For the same cuff systolic BP (SBP), invasive aortic SBP was 4.4 mm Hg higher in women compared with men. Cuff and invasive aortic SBP were higher in women compared with men, but the sex difference was more pronounced from invasive aortic SBP, was the lowest in younger ages, and the highest in older ages. Cuff diastolic blood pressure overestimated invasive diastolic blood pressure in both sexes. For cuff and invasive diastolic blood pressure separately, there were sex*age interactions in which diastolic blood pressure was higher in younger men and lower in older men, compared with women. Cuff pulse pressure underestimated invasive aortic pulse pressure in excess of 10 mm Hg for both sexes in older age. CONCLUSIONS: For the same cuff SBP, invasive aortic SBP was higher in women compared with men. How this translates to cardiovascular risk prediction needs to be determined, but women may be at higher BP-related risk than estimated by cuff measurements.

Developing a trigger tool to monitor adverse events during haemodialysis in children: a pilot project.

BACKGROUND: We developed a paediatric haemodialysis trigger tool (pHTT) for application per haemodialysis (HD) session in children receiving intermittent in-centre HD and systematically monitored adverse events. METHODS: Single-centre quality improvement study performed over two 8-week cycles. Data collected prospectively using a 'per-dialysis session' pHTT tool including 54 triggers across six domains, adapted from a recently described haemodialysis trigger tool (HTT) for adults. Each trigger was evaluated for level of harm following assessment by two authors. Following a period of training, HD nurses completed the HTT at the end of each dialysis session. RESULTS: There were 241 triggers over 182 dialysis sessions, with 139 triggers in 91 HD sessions for 15 children, age range 28-205 months, over an 8-week period (first cycle) and 102 triggers in 91 HD sessions for 13 children, age range 28-205 months, over a further 8-week period (second cycle). After interventions informed by the pHTT, the harm rate per session was significantly reduced from 1.03 (94/91) to 0.32 (29/91), P < 0.001. There was a significant difference between the distribution of triggers by harm category (P < 0.001) and between the proportion of triggers across the various domains of the pHTT (P = 0.004) between the two cycles. No triggers were evaluated as causing permanent harm. CONCLUSIONS: This pilot study demonstrates potential benefits of a bedside tool to monitor adverse events during haemodialysis in children. Thus, following interventions informed by the pHTT, the harm rate per session was significantly reduced. Under standard patient safety systems, the vast majority of triggers identified by the pHTT would remain unreported and perhaps lead to missed opportunities to improve patient safety. We propose the use of a paediatric HTT as part of standard care by centres providing HD to children in the future. A higher resolution version of the Graphical abstract is available as Supplementary information.

A meta-analysis of the haemodynamics of primary hypertension in children and adults.

We performed a systematic review and meta-analysis to determine the relative contributions of elevated cardiac output and systemic vascular resistance to hypertension in children and adults. This included 27 studies on 11 765 hypertensive and normotensive children and adults in whom cardiac output was measured. Cardiac output but not systemic vascular resistance was elevated in hypertensive compared to normotensive children and young adults (difference in means 1.15 [0.78-1.52] l/min, P < 0.001). In older hypertensive adults, both were elevated compared to normotensive individuals (0.40 [0.26-0.55] l/min, P < 0.001 and 3.21 [1.91-4.51] mmHg min/l, P < 0.001 for cardiac output and systemic vascular resistance, respectively). The main haemodynamic alteration in primary hypertension (including obesity-hypertension) in both children and young to middle-aged adults is an elevation of cardiac output. With longer duration and greater severity of hypertension there may be progression from a 'cardiac' to a 'vascular' phenotype with increased systemic vascular resistance.

Utilizing 3D printing to facilitate surgical in-situ paediatric renal artery aneurysm repair for refractory hypertension.

Renal artery aneurysmal (RAA) disease is a rare, but potentially life-threatening cause of renovascular disease presenting with hypertension. Conventional management involves aneurysmal excision followed by renal auto-transplantation. We present the management of a 13-year-old girl with complex multiple saccular aneurysmal disease of the left renal artery with hilar extension and symptomatic hypertension. We used 3D printing to print a patient-specific model that was not implanted in the patient but was used for surgical planning and discussion with the patient and their family. Endovascular options were precluded due to anatomical complexities. Following multi-disciplinary review and patient-specific 3D printing, she underwent successful in-situ RAA repair with intraoperative cooling, without the need for auto-transplantation. 3D printing enabled appreciation of aneurysmal spatial configuration and dimensions that also helped plan the interposition graft length needed following aneurysmal excision. The models provided informed multidisciplinary communications and proved valuable during the consent process with the family for this high-risk procedure. To our knowledge, this is the first reported case utilizing 3D printing to facilitate in-situ complex repair of RAA with intra-hilar extension for paediatric renovascular disease.

Variation in paediatric 24-h ambulatory blood pressure monitoring interpretation by Canadian and UK physicians.

Twenty-four-hour ambulatory blood pressure monitoring (ABPM) is widely accepted as a more accurate method for measurement of blood pressure (BP) compared to a single office-based measurement of BP. However, it is unclear how physicians interpret ABPM and make management decisions. This study's goal is to investigate variation in ABPM interpretation among paediatric nephrologists (Canada and UK) and paediatric cardiologists (Canada only) via an online survey. The survey content included baseline demographics, questions on the use and indications for ABPM, interpretation of results, and subsequent management decisions in various clinical scenarios. The survey was sent to 196 Canadian physicians, with 69 (35.2%) total responses. Thirty-five UK clinicians also completed the survey. Most respondents were >44 years old, were in practice for at least 11 years, and were university-based. There were substantial differences among clinicians in ABPM interpretation for isolated systolic, diastolic, and night-time hypertension. For example, only 53.1% of physicians would initiate or modify treatment in those with diastolic HTN in CKD. Further, even for the same abnormal ABPM parameter, the decision to start or alter treatment was influenced by the underlying medical condition. There is significant variation in clinical practice among physicians for interpretation and management of hypertension when using ABPM. Differences in guidelines among various jurisdictions, as well as knowledge gaps in the research on which guidelines are based, create ambiguity regarding ABPM interpretation and management decisions. A more protocolized approach and further insight into the reasoning behind the variation in physicians' interpretation may help to standardise practice.