Adherence to a healthy lifestyle behavior composite score and cardiometabolic risk factors in Spanish children from the CORALS cohort.

To assess the associations between the adherence to a composite score comprised of 6 healthy lifestyle behaviors and its individual components with several cardiometabolic risk factors in Spanish preschool children. Cross-sectional analyses were conducted in 938 participants included in the CORALS cohort aged 3-6 years. Six recognized healthy lifestyle behaviors (breastfeeding, sleep duration, physical activity, screentime, adherence to the Mediterranean diet, and eating speed) were assessed in a composite score. Multiple linear and logistic regression models were fitted to assess the associations with cardiometabolic risk factors (weight status, waist circumference, fat mass index, blood pressure, fasting plasma glucose, and lipid profile). In the adjusted multiple linear and logistic regression models, compared with the reference category of adherence to the healthy lifestyle behavior composite score, those participants in the category of the highest adherence showed significant decreased prevalence risk of overweight or obesity [OR (95% CI), 0.4 (0.2, 0.6)] as well as significant lower waist circumference, fat mass index (FMI), systolic blood pressure and fasting plasma glucose concentration [ß (95% CI), - 1.4 cm (- 2.5, - 0.4); - 0.3 kg/m2 (- 0.5, - 0.1); and - 3.0 mmHg (- 5.2, - 0.9); - 1.9 mg/dL (- 3.5, - 0.4), respectively]. Slow eating speed was individually associated with most of the cardiometabolic risk factors.   Conclusions: Higher adherence to the healthy lifestyle behavior composite score was associated with lower waist circumference, FMI, other cardiometabolic risk factors, and risk of overweight or obesity in Spanish preschool children. Further studies are required to confirm these associations. What is Known: • Lifestyle is a well-recognized etiologic factor of obesity and its comorbidities. • Certain healthy behaviors such as adhering to a healthy diet, increasing physical activity, and decreasing screentime are strategies for prevention and treatment of childhood obesity. What is New: • Higher adherence to the healthy lifestyle behavior composite score to 6 healthy behaviors (breastfeeding, sleep duration, physical activity, screentime, eating speed, and adherence to the Mediterranean diet) was associated with decreased adiposity, including prevalence risk of overweight or obesity, and cardiometabolic risk in preschool children. • Slow eating and greater adherence to the Mediterranean diet were mainly associated to lower fasting plasma and serum triglycerides concentration, respectively.

miR-130a expression is related to aortic dilation in bicuspid aortic valve children.

BACKGROUND: Bicuspid aortic valve disease (BAV) is present in 0.5-2% of the population and can promote aortic dilation, eventually leading to fatal consequences. Although some biomarkers have been proposed in adults, no studies have tested these candidates in children. We aimed to evaluate four miRNAs previously described to be related to BAV disease and aortic dilation in adults in a paediatric cohort. METHODS: Eighty participants ≤17 years old (4-17; mean 12) were included. From the BAV group, 40% had a dilated aorta (z score >2). RT‒qPCR were performed in plasma samples to quantify miR-122, miR-130a, miR-486, and miR-718 using the delta-delta Ct method. Functional and enrichment analyses of miR-130a were also performed. RESULTS: miR-130a expression in plasma was found to be significantly lower in BAV patients with a dilated aorta versus nondilated patients (p = 0.008) and healthy TAV controls (p = 0.004). Furthermore, miR-130a expression in plasma was inversely correlated with ascending aorta (r = 0.318, p = 0.004) and aortic root z scores (r = 0.322; p = 0.004). Enrichment analysis showed that miR-130a target genes are related to the TGFß signalling pathway. CONCLUSIONS: miR-130a expression in plasma is decreased in aortic-dilated BAV children compared to nondilated BAV children, helping differentiate low- to high-risk patients. IMPACT: miR-130a expression in plasma is related to aortic dilation in bicuspid aortic valve (BAV) children. To our knowledge, this is the first study that analyses miRNA patterns in bicuspid aortic valve children with aortic dilation. miR-130a expression in plasma could be a biomarker in order to help differentiate low-to high-risk BAV children, which is vitally important for advanced care planning.

Role of dexamethasone in controlling the proinflammatory cytokine cascade in the first episode of paediatric acute pyelonephritis.

AIM: Febrile urinary tract infection is a common bacterial infection in childhood. The kidney damage after acute pyelonephritis (APN) could be related to the stimulation of the proinflammatory response. We aimed to investigate the role of inflammatory cytokines and the effect of dexamethasone after a first episode of APN. METHODS: Subanalysis of the DEXCAR RCT in which children with confirmed APN (1 month-14 years) were randomly assigned to receive a 3 days course of either intravenous dexamethasone or placebo. Urinary cytokine levels at diagnosis and after 72 h of treatment were measured. RESULTS: Ninety-two patients were recruited. Younger patients, males and those with abnormalities in the ultrasound study or vesicoureteral reflux showed higher values of urinary cytokines. Patients with severe APN had higher Tumour Necrosis Factor (TNF)α levels (81.0 ± 75.8 vs. 33.6 ± 48.5 pg/mg creatinine, p = 0.015). Both intervention groups showed similar basal clinical characteristics, including urinary cytokine levels. Treatment reduced urinary cytokine levels irrespective of dexamethasone administration. Neither the intervention group nor the urinary cytokine levels modulated the development of kidney scars. CONCLUSION: Basal urinary cytokines were associated with age, abnormal ultrasound and vesicoureteral reflux. Patients with severe APN had higher TNFa urinary levels. Administration of dexamethasone in children with APN does not improve the control of the proinflammatory cytokine cascade.

Effects of infant feeding with goat milk formula or cow milk formula on atopic dermatitis: protocol of the randomised controlled Goat Infant Formula Feeding and Eczema (GIraFFE) trial.

INTRODUCTION: Atopic dermatitis (AD) is a chronic, inflammatory skin condition significantly affecting quality of life. A small randomised trial showed an approximately one-third lower incidence of AD in goat milk formula-fed compared with cow milk formula-fed infants. However, due to limited statistical power, AD incidence difference was not found to be significant. This study aims to explore a potential risk reduction of AD by feeding a formula based on whole goat milk (as a source of protein and fat) compared with a formula based on cow milk proteins and vegetable oils. METHODS AND ANALYSIS: This two-arm (1:1 allocation), parallel, randomised, double-blind, controlled nutritional trial shall enrol up to 2296 healthy term-born infants until 3 months of age, if parents choose to start formula feeding. Ten study centres in Spain and Poland are participating. Randomised infants receive investigational infant and follow-on formulas either based on whole goat milk or on cow milk until the age of 12 months. The goat milk formula has a whey:casein ratio of 20:80 and about 50% of the lipids are milk fat from whole goat milk, whereas the cow milk formula, used as control, has a whey:casein ratio of 60:40 and 100% of the lipids are from vegetable oils. The energy and nutrient levels in both goat and cow milk formulas are the same. The primary endpoint is the cumulative incidence of AD until the age of 12 months diagnosed by study personnel based on the UK Working Party Diagnostic Criteria. The secondary endpoints include reported AD diagnosis, measures of AD, blood and stool markers, child growth, sleep, nutrition and quality of life. Participating children are followed until the age of 5 years. ETHICS AND DISSEMINATION: Ethical approval was obtained from the ethical committees of all participating institutions. TRIAL REGISTRATION NUMBER: NCT04599946.

Propuesta para mejorar la formación en profesionalismo y en competencias transversales en los estudios de medicina de las universidades de Cataluña / Proposal to improve training in professionalism and transversal competences in medical studies at the universities of Catalonia

Introducción: En un grupo de trabajo de la Administración de la Generalitat de Cataluña y de los decanos de las facultades con estudios de Medicina de las universidades catalanas se creó una comisión para elaborar una propuesta para fomentar la formación en profesionalismo, en humanidades y en competencias transversales de los graduados en Medicina. Desarrollo: Dicha comisión, compuesta por docentes de todas las facultades, elaboró un documento con tres objetivos específicos: a) mostrar el estado real de dicha formación en los currículos; b) proponer actividades docentes concretas para mejorar dicha formación, considerando las buenas prácticas que se están realizando en las universidades; y c) sugerir criterios y métodos de evaluación de la formación en profesionalismo o de competencias transversales y, también, evaluar competencias específicas que pueden favorecer el desarrollo de las competencias genéricas. Conclusiones: Se espera que las sugerencias presentadas puedan servir para aumentar la formación en valores profesionales, en humanidades y en competencias transversales de los futuros profesionales de la medicina, con el objetivo final de mejorar la salud de la población.(AU)

Introduction: In a working group of the Administration of the regional government of Catalonia and the deans of the faculties with medical studies of the Catalan universities, a commission was created to prepare a document to promote training in professionalism and transversal competences of graduates in Medicine. Development: This commission, made up of teachers from all the faculties, prepared a document with three specific objectives: a) show the real state of said training in the curricula; b) propose specific teaching activities to improve said training, considering those good practices that are being carried out in universities; and c) suggest criteria and methods of evaluation of training in professionalism or of transversal competences and, also, evaluate specific competences that can improve the development of generic competences. Conclusions: It is hoped that the suggestions presented can serve to increase training in professional values, in the humanities and in transversal competences of future medical professionals with the ultimate goal of improving the health of the population.(AU)

The Treatment of Pediatric Pain in Spain: A Survey Study.

Pain is a common experience among children and adolescents, and pain management in this population is a challenge to clinicians. The aims of this study were to increase our understanding of current practices in the management of both acute and chronic pediatric pain in Spain, explore potential barriers to ideal practices, and identify professional needs as perceived by healthcare professionals. A total of 277 healthcare professionals took part, all of whom had wide experience in managing children and adolescents with pain (M [SD] age = 44.85, [10.73]; 75% women). Participants had to respond to a web-based survey with 50 questions related to pain education, organizational characteristics of their pain programs (including the characteristics of the patients treated), and current practices in the assessment and treatment of children and adolescents with pain. Almost all the participants (93%) acknowledged important gaps in their training, and only 47% reported that they had received specific education on the management of pediatric pain during their undergraduate and postgraduate studies. A third (31%) were members of multidisciplinary teams, and almost all (99%) understood that protocols to guide the management of pain in young people were necessary. However, only a few of them used a protocol to assess and treat (56% and 48%, respectively) acute and chronic pain (24% and 23%, respectively). The data also showed that a lack of pain education, coordination of professionals, and guidelines was perceived as an important barrier in the care provided to children and adolescents with pain in Spain. The findings of this study can now be used by healthcare professionals in Spain interested in managing pediatric pain, as well as policymakers concerned to improve the education of professionals and the care given to young people with pain.

Diagnosis accuracy of waist-to-height ratio to predict cardiometabolic risk in children with obesity.

BACKGROUND: Waist-to-height ratio (WHtR) predicts abdominal fat and cardiometabolic risk. In children with obesity, the most adequate cut-off to predict cardiometabolic risk as well as its ability to predict risk changes over time has not been tested. Our aim was to define an appropriate WHtR cut-off to predict cardiometabolic risk in children with obesity, and to analyze its ability to predict changes in cardiometabolic risk over time. METHODS: This is an observational prospective study secondary to the OBEMAT2.0 trial. We included data from 218 participants (8-15 years) who attended baseline and final visits (12 months later). The main outcome measure was a cardiometabolic risk score derived from blood pressure, lipoproteins, and HOMA index of insulin resistance. RESULTS: The optimal cut-off to predict the cardiometabolic risk score was WHtR ≥0.55 with an area under the curve of 0.675 (95% CI: 0.589-0.760) at baseline and 0.682 (95% CI: 0.585-0.779) at the final visit. Multivariate models for repeated measures showed that changes in cardiometabolic risk were significantly associated with changes in WHtR. CONCLUSION: This study confirms the clinical utility of WHtR to predict changes in cardiometabolic risk over time in children with obesity. The most accurate cut-off to predict cardiometabolic risk in children with obesity was WHtR ≥0.55. IMPACT: In children, there is no consensus on a unique WHtR cut-off to predict cardiometabolic risk. The present work provides sufficient evidence to support the use of the 0.55 boundary. We have a large sample of children with obesity, with whom we compared the previously proposed boundaries according to cardiometabolic risk, and we found the optimal WHtR cut-off to predict it. We also analyzed if a reduction in the WHtR was associated with an improvement in their cardiometabolic profile.

Associations Between Eating Speed, Diet Quality, Adiposity, and Cardiometabolic Risk Factors.

OBJECTIVE: To assess the associations between eating speed, adiposity, cardiometabolic risk factors, and diet quality in a cohort of Spanish preschool-children. STUDY DESIGN: A cross-sectional study in 1371 preschool age children (49% girls; mean age, 4.8 ± 1.0 years) from the Childhood Obesity Risk Assessment Longitudinal Study (CORALS) cohort was conducted. After exclusions, 956 participants were included in the analyses. The eating speed was estimated by summing the total minutes used in each of the 3 main meals and then categorized into slow, moderate, or fast. Multiple linear and logistic regression models were fitted to assess the ß-coefficient, or OR and 95% CI, between eating speed and body mass index, waist circumference, fat mass index (FMI), blood pressure, fasting plasma glucose, and lipid profile. RESULTS: Compared with participants in the slow-eating category, those in the fast-eating category had a higher prevalence risk of overweight/obesity (OR, 2.9; 95% CI, 1.8-4.4; P < .01); larger waist circumference (ß, 2.6 cm; 95% CI, 1.5-3.8 cm); and greater FMI (ß, 0.3 kg/m2; 95% CI, 0.1-0.5 kg/m2), systolic blood pressure (ß, 2.8 mmHg; 95% CI, 0.6-4.9 mmHg), and fasting plasma glucose levels (ß, 2.7 mg/dL, 95% CI, 1.2-4.2 mg/dL) but lower adherence to the Mediterranean diet (ß, -0.5 points; 95% CI, -0.9 to -0.1 points). CONCLUSIONS: Eating fast is associated with higher adiposity, certain cardiometabolic risk factors, and lower adherence to a Mediterranean diet. Further long-term and interventional studies are warranted to confirm these associations.

Different protein intake in the first year and its effects on adiposity rebound and obesity throughout childhood: 11 years follow-up of a randomized controlled trial.

BACKGROUND AND OBJECTIVES: Infant feeding affects child growth and later obesity risk. We examined whether protein supply in infancy affects the adiposity rebound, body mass index (BMI) and overweight and obesity up to 11 years of age. METHODS: We enrolled healthy term infants from five European countries in a double blind randomized trial, with anticipated 16 examinations within 11 years follow-up. Formula-fed infants (n = 1090) were randomized to isoenergetic formula with higher or lower protein content within the range stipulated by EU legislation in 2001. A breastfed reference group (n = 588) was included. Adiposity rebound and BMI trajectories were estimated by generalized additive mixed models in 917 children, with 712 participating in the 11 year follow-up. RESULTS: BMI trajectories were elevated in the higher compared to the lower protein group, with significantly different BMI at adiposity rebound (0.24 kg/m2, 0.01-0.47, p = 0.040), and an increased risk for overweight at 11 years (adjusted Odds Ratio 1.70; 1.06-2.73; p = 0.027) but no significant difference for obesity (adjusted Odds Ratio 1.47; 0.66-3.27). The two formula groups did not differ in the timing of adiposity rebound, but all children with obesity at 11 years had an early adiposity rebound before four years. CONCLUSIONS: Compared to conventional high protein formula, feeding lower protein formula in infancy lowers BMI trajectories up to 11 years and achieves similar BMI values at adiposity rebound as observed in breastfed infants.

Effect of maternal smoking during pregnancy on child blood pressure in a European cohort.

Hypertension is a public health issue that can have its origin in the early phases of development. Maternal smoking during pregnancy (MSDP) could play a role in offspring's cardio-metabolic programming. To assess the relationship between MSDP and later blood pressure (BP) in children we conducted a secondary analysis of a randomized dietary intervention trial (EU-Childhood Obesity Project). Healthy term infants with normal birth weight were recruited during the first 8 weeks of life in 5 European countries and followed until 11 years of age. Data on MSDP was collected at recruitment. BP and anthropometry were assessed at 11 years of age. Children were classified according to AAP guidelines as normal BP: BP < 90th percentile; high BP: ≥ 90th percentile with the subset of children having BP > 95th percentile categorized as hypertensive. Out of 572 children, 20% were exposed to MSDP. At 11 years, 26.8% had BP over the 90th centile. MSDP beyond 12 weeks of gestation was associated with higher systolic BP percentile (adjusted B 6.935; 95% CI 0.454, 13.429; p = 0.036) and over twofold increase likelihood of hypertension (OR 2.195; 95% CI 1.089, 4.423; p = 0.028) in children at 11 years. MSDP was significantly associated with later BP in children.

Pharmacological interventions for preventing complications in patients with idiopathic hypercalciuria: A systematic review / Intervenciones farmacológicas para prevenir complicaciones en pacientes con hipercalciuria idiopática: una revisión sistemática

Objective: To assess the effects of pharmacological interventions in patients with idiopathic hypercalciuria. Methods: We performed a search of multiple databases, trial registries, grey literature and conference proceedings up to October 2019. We included randomized and quasi-randomized controlled trials that examined any pharmacological intervention for preventing complications of idiopathic hypercalciuria (given for at least four months and six of follow-up). The primary outcomes were stone-free patients, urinary symptoms and severe adverse events. Results: We included five RCTs (n=446 patients, all adults, 4 in individuals with kidney stones and 1 in postmenopausal women with osteoporosis). Diuretics were likely to increase the number of stone-free patients (RR 1.61, 95% CI 1.33–1.96, moderate quality of evidence (QoE)); 274 more stone-free patients/1000 patients treated (95% CI: 148–432) and produced a slight decrease in the stone formation rate (mean difference −0.18, 95% CI −0.30 to −0.06, low QoE); 180 fewer stones/year/1000 patients treated (95% CI: 300 r to 60). No data on urinary symptoms were reported. The association between diuretic use and severe adverse events was uncertain (RR 5.00, 95% CI 0.60–41.88, very low QoE); 4 more severe adverse events/1000 patients treated (95% CI: 0 fewer to 39 more). Conclusions: The addition of diuretics to a normal or modified diet probably reduces the number of stone recurrences and may decrease the stone formation rate. It is uncertain whether diuretics increase the occurrence of severe adverse events. There were no studies investigating other outcomes or in children. (AU)

Objetivo: Evaluar los efectos de intervenciones farmacológicas en pacientes con hipercalciuria idiopática. Métodos: Realizamos una búsqueda en múltiples bases de datos, registros de ensayos, literatura gris y actas de congresos hasta octubre de 2019. Incluimos ensayos clínicos aleatorizados y cuasialeatorizados que examinaban cualquier intervención farmacológica para prevenir las complicaciones de la hipercalciuria idiopática (mínimo 4 meses de intervención y 6 meses de seguimiento). Los outcomes primarios fueron pacientes libres de cálculos, síntomas urinarios y efectos adversos graves. Resultados: Incluimos 5 RCT (n=446 pacientes, todos adultos, 4 en individuos con cálculos renales y uno en mujeres posmenopáusicas con osteoporosis). Los diuréticos aumentaban probablemente el número de pacientes libres de cálculos (RR 1,61; IC 95%: 1,33 a 1,96, moderada calidad de evidencia [QoE]); 274 más pacientes libres de cálculos/1.000 pacientes tratados (IC 95%: 148 a 432) y producían una ligera disminución en la tasa de formación de cálculos (diferencia media −0,18; IC 95%: −0,30 a −0,06, baja QoE); 180 menos cálculos/año/1.000 pacientes tratados (IC 95%: 300 a 60). No se informaron datos sobre síntomas urinarios. La asociación entre el uso de diuréticos y los efectos adversos graves fue incierta (RR 5,00; IC 95%: 0,60 a 41,88, muy baja QoE); 4 efectos adversos severos más/1.000 pacientes tratados (IC 95%: 0 a 39). Conclusiones: Los diuréticos añadidos a una dieta normal o modificada probablemente reducen la aparición de cálculos y pueden disminuir su tasa de formación. Es incierto si los diuréticos incrementan la ocurrencia de efectos adversos graves. No se encontraron estudios que investigaran otros outcomes o realizados en niños. (AU)

Usefulness of the waist-to-height ratio for predicting cardiometabolic risk in children and its suggested boundary values.

BACKGROUND & AIMS: Only limited information is available on the usefulness of the waist-to-height ratio (WHtR) as an abdominal obesity marker in children. Our aim was to compare the ability of a WHtR >90th percentile, a WHtR ≥0.50, a WHtR ≥0.55 and a BMI z-score ≥2 SD to predict cardiometabolic risk in children followed-up at different ages. METHODS: We evaluated data from 660 children at 5, 8 and 11 years of age who participated in the Childhood Obesity Project trial in 5 European countries. We classified children with or without cardiometabolic (CMet) risk (yes vs. no) according to the presence of ≥2 parameters (blood pressure, HOMA-IR, triglyceride levels and high-density lipoprotein (HDL) cholesterol levels) ≥90th percentile. RESULTS: The odds ratio for CMet risk in children at all followed-up ages was statistically significant for all measures. The OR for the WHtR≥0.55 cut-off was 29.1 (5.6, 151.7) at 5 years of age, 11.8 (4.1, 33.8) at 8 year of age and 3.6 (1.7, 7.7) at 11 years of age, compared to the WHtR<0.55 cut-off. The WHtR≥0.55 cut-off showed a higher OR at younger ages than the BMI z-score ≥2SD, WHtR ≥90th percentile and WHtR≥0.50 cut-offs and a higher positive predictive value (82% at 5 years of age compared to 55%, 36% and 41%, respectively). CONCLUSION: A WHtR≥0.55 is a suitable cut-off for screening children at high cardiometabolic risk in the general young European population.

Dexamethasone to prevent kidney scarring in acute pyelonephritis: a randomized clinical trial.

BACKGROUND: Urinary tract infection (UTI) is one of the most common bacterial infections in childhood and is associated with long-term complications. We aimed to assess the effect of adjuvant dexamethasone treatment on reducing kidney scarring after acute pyelonephritis (APN) in children. METHODS: Multicenter, prospective, double-blind, placebo-controlled, randomized clinical trial (RCT) where children from 1 month to 14 years of age with proven APN were randomly assigned to receive a 3-day course of either an intravenous corticosteroid (dexamethasone 0.30 mg per kg/day) twice daily or placebo. The late technetium 99 m-dimercaptosuric acid scintigraphy (> 6 months after acute episode) was performed to assess kidney scar persistence. Kidney scarring risk factors (vesicoureteral reflux, kidney congenital anomalies, or urinary tract dilatation) were also assessed. RESULTS: Ninety-one participants completed the follow-up and were finally included (dexamethasone n = 49 and placebo n = 42). Both groups had similar baseline characteristics. Twenty participants showed persistent kidney scarring after > 6 months of follow-up without differences in incidence between groups (22% and 21% in the dexamethasone and placebo groups, p = 0.907). Renal damage severity in the early DMSA (ß = 0.648, p = 0.023) and procalcitonin values (ß = 0.065 p = 0.027) significantly modulated scar development. Vesicoureteral reflux grade showed a trend towards significance (ß = 0.545, p = 0.054), but dexamethasone treatment showed no effect. CONCLUSION: Dexamethasone showed no effect on reducing the risk of scar formation in children with APN. Hence, there is no evidence for an adjuvant corticosteroid treatment recommendation in children with APN. However, the study was limited by not achieving the predicted sample size and the expected scar formation. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02034851. Registered in January 14, 2014. "A higher resolution version of the Graphical abstract is available as Supplementary information."

Pharmacological interventions for preventing complications in patients with idiopathic hypercalciuria: A systematic review.

OBJECTIVE: To assess the effects of pharmacological interventions in patients with idiopathic hypercalciuria. METHODS: We performed a search of multiple databases, trial registries, grey literature and conference proceedings up to October 2019. We included randomized and quasi-randomized controlled trials that examined any pharmacological intervention for preventing complications of idiopathic hypercalciuria (given for at least four months and six of follow-up). The primary outcomes were stone-free patients, urinary symptoms and severe adverse events. RESULTS: We included five RCTs (n=446 patients, all adults, 4 in individuals with kidney stones and 1 in postmenopausal women with osteoporosis). Diuretics were likely to increase the number of stone-free patients (RR 1.61, 95% CI 1.33-1.96, moderate quality of evidence (QoE)); 274 more stone-free patients/1000 patients treated (95% CI: 148-432) and produced a slight decrease in the stone formation rate (mean difference -0.18, 95% CI -0.30 to -0.06, low QoE); 180 fewer stones/year/1000 patients treated (95% CI: 300 r to 60). No data on urinary symptoms were reported. The association between diuretic use and severe adverse events was uncertain (RR 5.00, 95% CI 0.60-41.88, very low QoE); 4 more severe adverse events/1000 patients treated (95% CI: 0 fewer to 39 more). CONCLUSIONS: The addition of diuretics to a normal or modified diet probably reduces the number of stone recurrences and may decrease the stone formation rate. It is uncertain whether diuretics increase the occurrence of severe adverse events. There were no studies investigating other outcomes or in children.

Effect of milk protein content in Toddler formula on later BMI and obesity risk: protocol of the multicentre randomised controlled Toddler Milk Intervention (ToMI) trial.

INTRODUCTION: Reduction of milk protein content in infant formula provided during the first year of life has been shown to reduce early weight gain and obesity later in life. While rapid weight gain during the first 2 years of life is one of the strongest early predictors of obesity, the role of animal protein intake beyond the first year of life is unclear. The aim of this study is to examine the role of milk protein during the second year of life in healthy children on weight gain and obesity risk in preschool age. METHODS AND ANALYSIS: This randomised, double-blinded study enrolled 1618 children aged 11.5-13.5 months in Spain and Germany into two groups receiving isocaloric toddler milk with differing protein content during the second year of life. The experimental formula contains 1.5 g/100 kcal and the control formula 6.15 g/100 kcal protein and otherwise equal formula composition, except for modified fat content to achieve equal energy density. The primary endpoint is body mass index (BMI)-for-age z-score at the age of 24 months adjusted for BMI at 12 months of age. The children are followed until 6 years of age. ETHICS AND DISSEMINATION: Ethics approval was obtained from the ethical committees of the LMU University Hospital Munich, Germany (Nr. 555-15) and at Institut d'Investigació Sanitaria Pere Virgili, Reus, Spain (Ref. CEIm IISPV 013/2016). We aim at publishing results in peer-reviewed journals and sharing of results with study participants. TRIAL REGISTRATION NUMBER: NCT02907502.

Pharmacological interventions for preventing complications in patients with idiopathic hypercalciuria: A systematic review.

OBJECTIVE: To assess the effects of pharmacological interventions in patients with idiopathic hypercalciuria. METHODS: We performed a search of multiple databases, trial registries, grey literature and conference proceedings up to October 2019. We included randomized and quasi-randomized controlled trials that examined any pharmacological intervention for preventing complications of idiopathic hypercalciuria (given for at least four months and six of follow-up). The primary outcomes were stone-free patients, urinary symptoms and severe adverse events. RESULTS: We included five RCTs (n=446 patients, all adults, 4 in individuals with kidney stones and 1 in postmenopausal women with osteoporosis). Diuretics were likely to increase the number of stone-free patients (RR 1.61, 95% CI 1.33-1.96, moderate quality of evidence (QoE)); 274 more stone-free patients/1000 patients treated (95% CI: 148-432) and produced a slight decrease in the stone formation rate (mean difference -0.18, 95% CI -0.30 to -0.06, low QoE); 180 fewer stones/year/1000 patients treated (95% CI: 300 r to 60). No data on urinary symptoms were reported. The association between diuretic use and severe adverse events was uncertain (RR 5.00, 95% CI 0.60-41.88, very low QoE); 4 more severe adverse events/1000 patients treated (95% CI: 0 fewer to 39 more). CONCLUSIONS: The addition of diuretics to a normal or modified diet probably reduces the number of stone recurrences and may decrease the stone formation rate. It is uncertain whether diuretics increase the occurrence of severe adverse events. There were no studies investigating other outcomes or in children.

Dietary patterns acquired in early life are associated with cardiometabolic markers at school age.

BACKGROUND & AIMS: it has previously been described that dietary patterns established early in life tracked to late childhood. The aim of the present work was to analyse the association of dietary patterns that tracked from 2 to 8y with cardiometabolic markers at 8y of age. METHODS: The 3 identified patterns at 2y (that previous analyses showed to track to age 8y) were: "CoreDP", loaded for vegetables, fruits, fish, olive oil, etc.; "F&SDP", loaded by poor-quality fats and sugars; and "ProteinDP", mainly loaded by animal protein sources. Cardiometabolic markers at 8y were systolic blood pressure (SBP), insulin resistance (HOMA-IR), and triglycerides, and BMI z-score. To examine whether the association of diet with the outcomes was the result of a direct effect of diet at either two or 8y, or synergy between them, we used structural equation models. RESULTS: the associations between the patterns and the health outcomes were: CoreDP was inversely associated with SBP and HOMA-IR; ProteinDP was directly associated with HOMA-IR and SBP; and adherence to F&SDP was directly associated with triglycerides and SBP. The associations between the patterns and the health outcomes were independent of BMI and were the result of a direct effect of diet at 2y, an indirect effect of diet at 2y through diet at 8y or a combination between both pathways. CONCLUSION: dietary patterns acquired in early life, persisting to later childhood, were associated with cardiometabolic markers at school age independently of BMI.

Association of Protein Intake during the Second Year of Life with Weight Gain-Related Outcomes in Childhood: A Systematic Review.

There is accumulating evidence that early protein intake is related with weight gain in childhood. However, the evidence is mostly limited to the first year of life, whereas the high-weight-gain-velocity period extends up to about 2 years of age. We aimed to investigate whether protein intake during the second year of life is associated with higher weight gain and obesity risk later in childhood. We conducted a systematic review with searches in both PubMed®/MEDLINE® and the Cochrane Central Register of Controlled Trials. Ten studies that assessed a total of 46,170 children were identified. We found moderate-quality evidence of an association of protein intake during the second year of life with fat mass at 2 years and at 7 years. Effects on other outcomes such as body mass index (BMI), obesity risk, or adiposity rebound onset were inconclusive due to both heterogeneity and low evidence. We conclude that higher protein intakes during the second year of life are likely to increase fatness in childhood, but there is limited evidence regarding the association with other outcomes such as body mass index or change in adiposity rebound onset. Further well-designed and adequately powered clinical trials are needed since this issue has considerable public health relevance.

Validation of bioelectrical impedance analysis for body composition assessment in children with obesity aged 8-14y.

BACKGROUND & AIMS: The aim was to generate a predictive equation to assess body composition (BC) in children with obesity using bioimpedance (BIA), and avoid bias produced by different density levels of fat free mass (FFM) in this population. METHODS: This was a cross-sectional validation study using baseline data from a randomized intervention trial to treat childhood obesity. Participants were 8 to 14y (n = 315), underwent assessments on anthropometry and BC through Air Displacement Plethysmography (ADP), Dual X-Ray Absorptiometry and BIA. They were divided into a training (n = 249) and a testing subset (n = 66). In addition, the testing subset underwent a total body water assessment using deuterium dilution, and thus obtained results for the 4-compartment model (4C). A new equation to estimate FFM was created from the BIA outputs by comparison to a validated model of ADP adjusted by FFM density in the training subset. The equation was validated against 4C in the testing subset. As reference, the outputs from the BIA device were also compared to 4C. RESULTS: The predictive equation reduced the bias from the BIA outputs from 14.1% (95%CI: 12.7, 15.4) to 4.6% (95%CI: 3.8, 5.4) for FFM and from 18.4% (95%CI: 16.9, 19.9) to 6.4% (95% CI: 5.3, 7.4) for FM. Bland-Altman plots revealed that the new equation significantly improved the agreement with 4C; furthermore, the observed trend to increase the degree of bias with increasing FM and FFM also disappeared. CONCLUSION: The new predictive equation increases the precision of BC assessment using BIA in children with obesity.