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Importance: Adolescent obesity requires effective and accessible treatment. Intensive dietary interventions have the potential to be used as adjunctive therapy for behavioral weight management. Objective: To examine the effectiveness of 2 diet therapies, delivered as part of an intensive behavioral weight management intervention, in adolescents with metabolic complications associated with obesity. Design, Setting, and Participants: This multisite, 52-week randomized clinical trial was conducted from January 31, 2018, to March 31, 2023, at 2 tertiary pediatric centers in Australia. Adolescents (aged 13-17 years) with obesity and 1 or more associated complications were included. Interventions: Intensive behavioral interventions, delivered by a multidisciplinary team, comparing intermittent energy restriction (IER) or continuous energy restriction (CER), with 3 phases: very low-energy diet (weeks 0-4), intensive intervention (weeks 5-16), and continued intervention and/or maintenance (weeks 17-52). Main Outcomes and Measures: The primary outcome was body mass index (BMI) z score at 52 weeks in the IER vs CER group. Anthropometry, body composition, and cardiometabolic health were assessed at baseline and 52 weeks. The BMI z score and percentiles were determined using Centers for Disease Control and Prevention growth charts. Insulin resistance, dyslipidemia, and elevated hepatic function were assessed. Results: A total of 141 adolescents (median [IQR] age, 14.8 [12.9-17.9] years; 71 male [50.4%]) were enrolled, 71 in the IER group and 70 in the CER group, and 97 (68.8%) completed the intervention, 43 in the IER group and 54 in the CER group. At week 52, both groups had reduced BMI z scores (estimated marginal mean change, -0.28 [95% CI, -0.37 to -0.20] for IER and -0.28 [95% CI, -0.36 to -0.20] for CER) and reduced BMI expressed as a percentage of the 95th percentile (estimated marginal mean change, -9.56 [95% CI, -12.36 to -6.83] for IER and -9.23 [95% CI, -11.82 to -6.64] for CER). No differences were found in body composition or cardiometabolic outcomes between the groups. Both groups had a reduction in the occurrence of insulin resistance (from 52 of 68 [76.5%] to 32 of 56 [57.1%] in the IER group and from 59 of 68 [86.8%] to 31 of 60 [57.1%] in the CER group) at week 16; however, at week 52, this effect was observed in the CER group only (from 59 of 68 [86.7%] to 30 of 49 [61.2%]). The occurrence of dyslipidemia was unchanged between baseline and week 52 (60 of 137 [42.6%] and 37 of 87 [42.5%], respectively), with a small improvement in occurrence of impaired hepatic function tests (37 of 139 [27.0%] and 15 of 87 [17.2%], respectively). No differences were found in dyslipidemia or hepatic function between groups. Conclusions and Relevance: These findings suggest that for adolescents with obesity-associated complications, IER can be incorporated into a behavioral weight management program, providing an option in addition to CER and offering participants more choice. Trial Registration: http://anzctr.org.au Identifier: ACTRN12617001630303.
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Importance: Depression and eating disorders are heightened for adolescents with obesity. Clinical reviews alongside self-report questionnaires are important to ensure appropriate intervention. Objective: To evaluate changes in self-report symptoms of depression, eating disorders, and binge eating in adolescents with obesity during the Fast Track to Health trial. Design, Setting, and Participants: This was a randomized clinical trial conducted from 2018 to 2023. It was a multisite trial conducted at children's hospitals in Sydney, New South Wales, and Melbourne, Victoria, Australia, and included adolescents (13-17 years) with obesity (defined as adult equivalent body mass index ≥30; calculated as weight in kilograms divided by height in meters squared) and 1 or more related complications. Interventions: Duration was 52 weeks including a very low energy diet for 4 weeks followed by intermittent energy restriction (IER) or continuous energy restriction (CER). Main Outcomes and Measures: Self-report symptoms of depression (Center for Epidemiologic Studies Depression Scale-Revised 10-Item Version for Adolescents [CESDR-10]; scores 0-30), eating disorders (Eating Disorder Examination Questionnaire [EDE-Q]; scores 0-6), and binge eating (Binge Eating Scale [BES]; scores 0-46) were assessed. Adolescents were screened for depression and eating disorders (weeks 0, 4, 16, and 52) and monitored for the onset of new symptoms of disordered eating during dietetic consults. Results: Of 141 adolescents (median [IQR] age, 14.8 [12.9-17.9] years; 71 male [50.4%]) enrolled, median baseline EDE-Q score was 2.28 (IQR, 1.43-3.14), median baseline CESDR-10 score was 9.00 (IQR, 4.00-14.50), and median baseline BES score was 11.00 (IQR, 5.00-17.00). There were no differences between groups for change in CESDR-10 (mean difference at week 52, 0.75; 95% CI, -1.86 to 3.37), EDE-Q (mean difference at week 52, 0.02; 95% CI, -0.41 to 0.45), or BES (mean difference at week 52, -2.91; 95% CI, -5.87 to 0.05). The within-group reductions at week 4 were maintained at week 52, for CESDR-10 and EDE-Q, indicating reduced symptoms of depression and eating disorders. Within-group reductions on the BES were maintained in the IER group only. Seventeen adolescents (12.1%) required support or referral for depression and/or disordered eating, including 7 (5%; 5 IER, 2 CER) adolescents who experienced the onset or reemergence of symptoms during the intervention. Conclusions and Relevance: Results suggest that many treatment-seeking adolescents with obesity self-reported symptoms of depression and eating disorders. Although symptoms reduced for most, some required additional support. Obesity treatment is an opportune time to screen and monitor for depression and disordered eating. Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12617001630303.
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BACKGROUND: Intermittent energy restriction (IER) has shown early success in adolescents with obesity, however efficacy trials are needed. This study aims to determine if IER results in lower body mass index (BMI) z-score after 52 weeks in metabolically unhealthy adolescents with obesity compared with continuous energy restriction (CER). METHODS/DESIGN: This is a prospective, randomised, multi-centre trial conducted in tertiary care settings, with three phases: jumpstart (weeks 0-4); intensive intervention (weeks 5-16); continued intervention and/or maintenance (weeks 17-52). During the jumpstart phase, all participants follow a very low energy diet (â¼800kcal/3350kJ/day), then transition to their allocated intervention: IER or CER. IER involves three energy-restricted days/week, consuming one-third of daily energy requirements (â¼600-700kcal/2500-2950kJ/day), and four days/week of a healthy meal plan. The CER, which is current standard care, has individually tailored energy prescription based on age and sex (13-14years, 1430-1670kcal/6000-7000kJ/day; 15-17years, 1670-1900kcal/7000-8000kJ/day). The study will recruit 186 (93 per arm) treatment-seeking adolescents aged 13-17years with obesity and at least one metabolic co-morbidity. The primary outcome is change in BMI z-score at 52 weeks. Secondary outcomes are changes at 4, 16 and 52 weeks in: body composition; diet quality, food choices and food patterns; cardio-metabolic risk factors; physical activity and sedentary behaviour; sleep and psycho-behavioural measures. DISCUSSION: This study challenges existing clinical paradigms that CER is the only method for weight management in metabolically unhealthy adolescents. If successful, IER may offer an alternate medical nutrition therapy approach for those seeking treatment in tertiary settings. CLINICAL TRIAL REGISTRATION NUMBER: ACTRN12617001630303.
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Restricción Calórica/métodos , Dieta Reductora/métodos , Ingestión de Energía/fisiología , Obesidad Infantil/terapia , Pérdida de Peso , Adolescente , Composición Corporal , Índice de Masa Corporal , Conducta Alimentaria/fisiología , Femenino , Humanos , Masculino , Obesidad Infantil/fisiopatología , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
BACKGROUND: Intermittent energy restriction (IER) is an effective obesity management strategy in adults. OBJECTIVE: The aim of this study was to investigate the feasibility, effectiveness, and acceptability of IER in adolescents (aged 12-17 y) with obesity [adult equivalent body mass index (BMI; kg/m2) ≥30]. METHODS: During weeks 1-12 participants followed an IER dietary plan consisting of a very-low-energy diet (VLED) 3 d/wk (500-600 kcal/d) and an eating plan consistent with national dietary guidelines 4 d/wk. For weeks 13-26 participants chose to continue with 1-3 VLED d/wk or follow a prescriptive eating plan. Primary outcomes were feasibility and change in BMI expressed as a percentage of the 95th percentile (BMI %95th percentile) at 12 wk. Secondary outcomes were diet acceptability, body composition, cardiometabolic risk, vascular structure and function, quality of life (Pediatric Quality of Life Inventory), and eating behaviors [Dutch Eating Behavior Questionnaire (DEBQ-C)]. Linear mixed models were used to assess change in outcome measures. RESULTS: Of 45 adolescents invited to participate, 30 adolescents (mean ± SD age: 14.5 ± 1.4 y, female n = 25) with a median BMI of 34.9 (range: 27.7-52.4) were recruited. At 12 wk, 23 participants chose to continue with the VLED 2-3 d/wk, and 21 completed the study, indicating the feasibility of IER. Consistent with intention-to-treat analysis, BMI %95th percentile was reduced at 12 wk (difference in estimated marginal means ± SEMs: -5.6 ± 1.1, P < 0.001) and 26 wk (-5.1 ± 1.9, P = 0.013) compared with baseline. Plasma triglycerides were reduced at 26 wk from baseline (-0.33 ± 0.12 mmol/L, P = 0.03). Body fat percentage reduced between 12 and 26 wk (-1.57% ± 0.76%, P = 0.05). Carotid intima-media thickness (CIMT) (-0.06 ± 0.01 mm, P < 0.001) and flow-mediated dilation (absolute increase 0.44% ± 0.11%, P = 0.001) improved between baseline and 12 wk, with reduced CIMT maintained at 26 wk (P < 0.001). DEBQ-C and Pediatric Quality of Life Inventory scores improved throughout the intervention. Nineteen adolescents completed an acceptability interview, rating IER as easy and pleasant to follow (mean ± SD: +2.1 ± 1.2; +1.9 ± 1.2, respectively) on a Likert scale from -4 to +4. CONCLUSION: IER is a feasible, effective, and acceptable intervention in adolescents with obesity achieving reductions in BMI and cardiovascular disease risk. This trial was registered at www.anzctr.org.au as ACTRN12618000200280.
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Restricción Calórica , Obesidad/dietoterapia , Adolescente , Antropometría , Niño , Registros de Dieta , Estudios de Factibilidad , Conducta Alimentaria , Femenino , Humanos , Masculino , Cooperación del Paciente , Calidad de Vida , Pérdida de PesoRESUMEN
BACKGROUND: In order to determine the extent to which care delivered to children is appropriate (in line with evidence-based care and/or clinical practice guidelines (CPGs)) in Australia, we developed a set of clinical indicators for 21 common paediatric medical conditions for use across a range of primary, secondary and tertiary healthcare practice facilities. METHODS: Clinical indicators were extracted from recommendations found through systematic searches of national and international guidelines, and formatted with explicit criteria for inclusion, exclusion, time frame and setting. Experts reviewed the indicators using a multi-round modified Delphi process and collaborative online wiki to develop consensus on what constituted appropriate care. RESULTS: From 121 clinical practice guidelines, 1098 recommendations were used to draft 451 proposed appropriateness indicators. In total, 61 experts (n = 24 internal reviewers, n = 37 external reviewers) reviewed these indicators over 40 weeks. A final set of 234 indicators resulted, from which 597 indicator items were derived suitable for medical record audit. Most indicator items were geared towards capturing information about under-use in healthcare (n = 551, 92%) across emergency department (n = 457, 77%), hospital (n = 450, 75%) and general practice (n = 434, 73%) healthcare facilities, and based on consensus level recommendations (n = 451, 76%). The main reason for rejecting indicators was 'feasibility' (likely to be able to be used for determining compliance with 'appropriate care' from medical record audit). CONCLUSION: A set of indicators was developed for the appropriateness of care for 21 paediatric conditions. We describe the processes (methods), provenance (origins and evolution of indicators) and products (indicator characteristics) of creating clinical indicators within the context of Australian healthcare settings. Developing consensus on clinical appropriateness indicators using a Delphi approach and collaborative online wiki has methodological utility. The final indicator set can be used by clinicians and organisations to measure and reflect on their own practice.
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Medicina Basada en la Evidencia , Pediatría/normas , Indicadores de Calidad de la Atención de Salud , Australia , Niño , Humanos , Garantía de la Calidad de Atención de SaludRESUMEN
OBJECTIVE: To evaluate the tolerability and safety of cannabidiol for treating drug-resistant epilepsy in children, and to describe adverse events associated with such treatment. STUDY DESIGN: Prospective, open label cohort study. SETTING: Three tertiary NSW referral centres with paediatric neurology services. PARTICIPANTS: First 40 children enrolled in the NSW Compassionate Access Scheme for children with drug-resistant epilepsy and uncountable daily seizures. INTERVENTION: Children received cannabidiol as an adjunct anti-epileptic drug, titrated to a maximum of 25 mg/kg/day, for up to 12 weeks. OUTCOME MEASURES: Adverse events, withdrawals, and caregiver and physician Global Impression of Change assessments were recorded at 4, 8 and 12 weeks. Seizure frequency could not be reliably recorded because of disease severity. RESULTS: Thirty-nine patients reported at least one adverse event; many were deemed unrelated to cannabidiol treatment. The most frequent treatment-related adverse event was somnolence (15 participants), which resolved spontaneously in ten patients; it was particularly frequent in patients taking higher clobazam doses. Gastrointestinal effects (nausea, vomiting, diarrhoea) were each reported by seven to nine participants. Four children were withdrawn from treatment, including one with elevated transaminase levels. The caregivers of 12 children felt the overall health of their children had much or very much improved; clinicians assessed seven children as being much or very much improved. CONCLUSION: Cannabidiol as an adjunct treatment had some subjective benefit for overall health, with a manageable adverse event profile. Monitoring changes in liver function and awareness of potential drug interactions is essential. Whether the reported benefit is attributable to cannabidiol cannot be established in an open label study of participants with severe intractable epilepsy.
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Anticonvulsivantes/administración & dosificación , Cannabidiol/administración & dosificación , Epilepsia Refractaria/tratamiento farmacológico , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Nueva Gales del Sur , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Gestational diabetes mellitus (GDM) causes adverse pregnancy outcomes that can be averted by treatment from 24-28 weeks' gestation. Assessing and treating women for overt diabetes in pregnancy (ODIP) at the first antenatal clinic booking is now recommended in international guidelines. As a consequence, women with milder hyperglycaemia are being diagnosed and treated for early GDM, but randomised controlled trial (RCTs) assessing the benefits and harms of such treatment have not been undertaken. The Treatment Of Booking Gestational diabetes Mellitus (TOBOGM) study is a multi-centre RCT examining whether diagnosing and treating GDM diagnosed at booking improves pregnancy outcomes. Methods and analysis: 4000 adult pregnant women (< 20 weeks' gestation) at risk of ODIP will be recruited from 12 hospital antenatal booking clinics and referred for an oral glucose tolerance test (OGTT). 800 women with hyperglycaemia (ie, booking GDM) according to the 2014 Australasian Diabetes-in-Pregnancy Society criteria for pregnant women at 24-28 weeks' gestation will be randomised to immediate treatment for GDM (intervention) or to no treatment (control), pending the results of a second OGTT at 24-28 weeks' gestation. Antenatal and GDM care will otherwise follow local guidelines. Randomisation will be stratified by site and OGTT glycaemic risk strata. The primary pregnancy outcome is a composite of respiratory distress, phototherapy, birth trauma, birth before 37 weeks' gestation, stillbirth or death, shoulder dystocia, and birthweight ≥ 4.5 kg. The primary neonatal outcome is neonatal lean body mass. The primary maternal outcome is pre-eclampsia. Ethics approval: South Western Sydney Local Health District Research and Ethics Office (reference, 15/LPOOL/551). Dissemination of results: Peer-reviewed publications, scientific meetings, collaboration with research groups undertaking comparable studies, discussions with guideline groups and policy makers. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12616000924459.
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Diabetes Gestacional/terapia , Edad Gestacional , Hiperglucemia/terapia , Complicaciones del Embarazo/terapia , Adulto , Australia , Diabetes Gestacional/diagnóstico , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Hiperglucemia/diagnóstico , Guías de Práctica Clínica como Asunto , Embarazo , Complicaciones del Embarazo/diagnóstico , Resultado del Embarazo , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Importance: The quality of routine care for children is rarely assessed, and then usually in single settings or for single clinical conditions. Objective: To estimate the quality of health care for children in Australia in inpatient and ambulatory health care settings. Design, Setting, and Participants: Multistage stratified sample with medical record review to assess adherence with quality indicators extracted from clinical practice guidelines for 17 common, high-burden clinical conditions (noncommunicable [n = 5], mental health [n = 4], acute infection [n = 7], and injury [n = 1]), such as asthma, attention-deficit/hyperactivity disorder, tonsillitis, and head injury. For these 17 conditions, 479 quality indicators were identified, with the number varying by condition, ranging from 9 for eczema to 54 for head injury. Four hundred medical records were targeted for sampling for each of 15 conditions while 267 records were targeted for anxiety and 133 for depression. Within each selected medical record, all visits for the 17 targeted conditions were identified, and separate quality assessments made for each. Care was evaluated for 6689 children 15 years of age and younger who had 15â¯240 visits to emergency departments, for inpatient admissions, or to pediatricians and general practitioners in selected urban and rural locations in 3 Australian states. These visits generated 160â¯202 quality indicator assessments. Exposures: Quality indicators were identified through a systematic search of local and international guidelines. Individual indicators were extracted from guidelines and assessed using a 2-stage Delphi process. Main Outcomes and Measures: Quality of care for each clinical condition and overall. Results: Of 6689 children with surveyed medical records, 53.6% were aged 0 to 4 years and 55.5% were male. Adherence to quality of care indicators was estimated at 59.8% (95% CI, 57.5%-62.0%; n = 160â¯202) across the 17 conditions, ranging from a high of 88.8% (95% CI, 83.0%-93.1%; n = 2638) for autism to a low of 43.5% (95% CI, 36.8%-50.4%; n = 2354) for tonsillitis. The mean adherence by condition category was estimated as 60.5% (95% CI, 57.2%-63.8%; n = 41â¯265) for noncommunicable conditions (range, 52.8%-75.8%); 82.4% (95% CI, 79.0%-85.5%; n = 14â¯622) for mental health conditions (range, 71.5%-88.8%); 56.3% (95% CI, 53.2%-59.4%; n = 94â¯037) for acute infections (range, 43.5%-69.8%); and 78.3% (95% CI, 75.1%-81.2%; n = 10â¯278) for injury. Conclusions and Relevance: Among a sample of children receiving care in Australia in 2012-2013, the overall prevalence of adherence to quality of care indicators for important conditions was not high. For many of these conditions, the quality of care may be inadequate.
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Servicios de Salud del Niño/normas , Adhesión a Directriz/estadística & datos numéricos , Indicadores de Calidad de la Atención de Salud , Calidad de la Atención de Salud/estadística & datos numéricos , Adolescente , Australia , Niño , Preescolar , Manejo de la Enfermedad , Femenino , Humanos , Lactante , Recién Nacido , MasculinoRESUMEN
BACKGROUND: Augmentation index (AIx) is a noninvasive measure of pulse wave reflection. AIx is associated with cardiovascular disease. Adult women have a higher AIx than men, but the factors determining this sex-related difference remain to be determined. METHODS: To examine factors associated with AIx in adolescents, participants in the Childhood Asthma Prevention Study, followed from birth, were assessed at age 14 years, with AIx standardized to a heart rate of 75/min (AIx_75) and pulse wave velocity. Associations of AIx_75 and pulse wave velocity with height, change in height, and measures of puberty were assessed. RESULTS: AIx_75 was higher in women compared to men [-24.5 (12.1) versus -32.3 (12.4)%; Pâ<â0.001]. Lower AIx_75 was significantly related to greater change in height between 8 and 14 years, but not to achieved height. The sex difference in AIx was not independently related to puberty variables. Differences between sexes included early life weight gain, lipids, height, BMI-Z-score, change in height from 8 to 14 years, and age at peak height velocity. Change in AIx_75 from 8 to 14 years was highly associated with change in height (m) from 8 to 14 years (Bâ=â-88.8, 95% confidence interval -137.3 to -40.3, Pâ=ââ<â0.001). The difference between sexes established at 8 years was not amplified from 8 to 14 years. CONCLUSION: AIx is higher in girls than boys at 14 years and is closely associated with change in height between 8 and 14 years. Measures of puberty do not appear to independently influence the sex difference in AIx in adolescents.
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Aorta/fisiología , Frecuencia Cardíaca/fisiología , Análisis de la Onda del Pulso/estadística & datos numéricos , Adolescente , Niño , Femenino , Humanos , Masculino , Caracteres SexualesRESUMEN
INTRODUCTION: Australian and international clinical practice guidelines are available for common paediatric conditions. Yet there is evidence that there are substantial variations between the guidelines, recommendations (appropriate care) and the care delivered. This paper describes a study protocol to determine the appropriateness of the healthcare delivered to Australian children for 16 common paediatric conditions in acute and primary healthcare settings. METHODS AND ANALYSIS: A random sample of 6000-8000 medical records representing a cross-section of the Australian paediatric population will be reviewed for appropriateness of care against a set of indicators within three Australian states (New South Wales, Queensland and South Australia) using multistage, stratified sampling. Medical records of children aged <16â years who presented with at least one of the study conditions during 2012 and 2013 will be reviewed. ETHICS AND DISSEMINATION: Human Research Ethics Committee approvals have been received from the Sydney Children's Hospital Network, Children's Health Queensland Hospital and Health Service and Women's and Children's Hospital Network (South Australia). An application is under review for the Royal Australian College of General Practitioners. The authors will submit the results of the study to relevant journals and offer oral presentations to researchers, clinicians and policymakers at national and international conferences.
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Servicios de Salud del Niño/normas , Adhesión a Directriz , Pediatría/normas , Pautas de la Práctica en Medicina/normas , Garantía de la Calidad de Atención de Salud , Adolescente , Australia , Niño , Preescolar , Protocolos Clínicos , Humanos , Lactante , Recién Nacido , Registros Médicos , Indicadores de Calidad de la Atención de Salud , Estudios RetrospectivosRESUMEN
INTRODUCTION: Despite the widespread availability of clinical guidelines, considerable gaps remain between the care that is recommended (appropriate care) and the care provided. This protocol describes a research methodology to develop clinical indicators for appropriate care for common paediatric conditions. METHODS AND ANALYSIS: We will identify conditions amenable to population-level appropriateness of care research and develop clinical indicators for each condition. Candidate conditions have been identified from published research; burden of disease, prevalence and frequency of presentation data; and quality of care priority lists. Clinical indicators will be developed through searches of national and international guidelines, and formatted with explicit criteria for inclusion, exclusion, time frame and setting. Experts will review the indicators using a wiki-based approach and modified Delphi process. A formative evaluation of the wiki process will be undertaken. ETHICS AND DISSEMINATION: Human Research Ethics Committee approvals have been received from Sydney Children's Hospital Network, Children's Health Queensland Hospital and Health Service, and the Women's and Children's Health Network (South Australia). Applications are under review with Macquarie University and the Royal Australian College of General Practitioners. We will submit the results of the study to relevant journals and offer national and international presentations.
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Servicios de Salud del Niño/normas , Pediatría/normas , Garantía de la Calidad de Atención de Salud/métodos , Indicadores de Calidad de la Atención de Salud , Adolescente , Australia , Niño , Preescolar , Protocolos Clínicos , Humanos , Lactante , Recién NacidoRESUMEN
BACKGROUND: It is unclear whether the rate of vitamin D deficiency in paediatric cancer survivors is higher than in the background population, and whether this is of pathological significance. PATIENTS AND METHODS: 25OHD was measured in a previously studied group of 208 survivors (n = 108 paediatric 5-17 years, n = 99 adults 18-39 years) and compared with paediatric (5-17 years; n = 132) and adult controls (25-35 years; n = 1393 from the AusDiab cohort) adjusted for age and gender. Relationships with treatment factors (irradiation, bone marrow transplantation and intensity of treatment) along with overweight/obesity (defined by BMI), abdominal adiposity (waist:height ratio >0·5) and hyperinsulinism or abnormal glucose tolerance (HI/aGT) were sought. RESULTS: 25OHD concentrations were similar in paediatric survivors compared with controls (64·3 ± 21·6 nmol/l vs 66·3 ± 22·8 nmol/l), with no effect of age or gender. Adjusted for gender, rates of 25OHD deficiency (<50 nmol/l) were higher in adult survivors compared with AusDiab controls (42·4% vs 20·8%; P < 0·001). Apart from time since diagnosis (P = 0·03), no relationship with treatment factors was detected. In multivariate regression analysis, abdominal adiposity (P = 0·001), but not overweight/obesity by BMI status nor HI/aGT, was associated with significantly lower 25OHD concentrations. CONCLUSIONS: Adult survivors are at increased risk of abnormalities in vitamin D compared to the background population, probably reflecting longer time since diagnosis. Like others, we have not identified any contributory treatment-related factors. Vitamin D deficiency does not appear to be associated with the development of abnormal glucose tolerance in this population.
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Neoplasias/complicaciones , Deficiencia de Vitamina D/complicaciones , Adiposidad , Adolescente , Adulto , Índice de Masa Corporal , Niño , Preescolar , Estudios de Cohortes , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Hiperinsulinismo/sangre , Masculino , Neoplasias/epidemiología , Obesidad/complicaciones , Sobrepeso/patología , Prevalencia , Sobrevivientes , Deficiencia de Vitamina D/epidemiología , Adulto JovenRESUMEN
OBJECTIVE: To compare weight (per kg)- vs body surface area (BSA, per m(2) )-based growth hormone (GH) dosing formats in children and to derive a useful conversion formula between the two formats. PATIENTS AND DESIGN: Growth hormone doses (>33,000) from 1874 children were obtained from the national Australian database (OZGROW) and used to derive conversion formulae and to confirm the accuracy of a conversion formula based on a weight-only BSA estimate. A further 27,000 doses were used to test the accuracy of all formulae. The best conversion formula was used to compare weight- and surface area-based GH dosing, which included an analysis of first year response (∆SDS height or growth velocity, GV). MEASUREMENTS: Growth hormone doses in mg/m(2) /wk and mg/kg/wk, dose estimates, residuals, first year ∆SDS, first year GV. RESULTS: The formula, [Formula: see text] based on a weight-only BSA estimate, provides accurate dose conversion (mean residual, 0·005 mg/kg/week). A constant mg/m(2) /week dose expressed in terms of mg/kg/week declines quickly with increasing body weight to approximately 15 kg after which the decline continues although less dramatically. For Australian patients, despite an increase in mean per m(2) dose with increased starting weight/age, the per kg dose decreased. This was associated with a greater decline in first year GV than estimated if a per kg dose had been maintained. CONCLUSIONS: Growth hormone doses can be accurately converted between formats. Surface area-based GH dosing is likely to result in a reduced height response as children become heavier when compared with weight-based GH dosing.
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Superficie Corporal , Peso Corporal , Cálculo de Dosificación de Drogas , Trastornos del Crecimiento/tratamiento farmacológico , Hormona de Crecimiento Humana/administración & dosificación , Australia/epidemiología , Estatura , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Trastornos del Crecimiento/diagnóstico , Trastornos del Crecimiento/epidemiología , Humanos , Masculino , Resultado del TratamientoRESUMEN
OBJECTIVE: To determine the incidence of and factors associated with vitamin D deficiency rickets in Australian children. DESIGN: 18-month questionnaire-based prospective observational study, using Australian Paediatric Surveillance Unit (APSU) data. SETTING: Australian paediatricians and child health workers, January 2006 - July 2007. PARTICIPANTS: Children aged ≤ 15 years with vitamin D deficiency rickets (25-hydroxyvitamin D [25OHD] ≤ 50 nmol/L, and elevated alkaline phosphatase levels [> 229 IU/L] and/or radiological rickets). MAIN OUTCOME MEASURES: Incidence of vitamin D deficiency rickets. Description of demographics, clinical presentation, identification and further analysis of overrepresented groups, and treatment regimens compared with best-practice guidelines. RESULTS: We identified 398 children with vitamin D deficiency (55% male; median age, 6.3 years [range, 0.2-15 years]). The overall incidence in children ≤ 15 years of age in Australia was 4.9/100 000/year. All had a low 25OHD level (median, 28 nmol/L [range, 5-50 nmol]) and an elevated alkaline phosphatase level (median, 407 IU/L [range, 229-5443 IU/L]), and 48 (12%) were hypocalcaemic. Ninety-five children had wrist x-rays, of whom 67 (71%) had rachitic changes. Most (98%) had dark or intermediate skin colour and 18% of girls were partially or completely veiled. Most children were born in Africa (252; 63%) and 75% of children were refugees. Duration of exclusive breastfeeding was inversely related to serum vitamin D levels in children < 3 years of age. Empirical vitamin D treatment was given to 4% of children before diagnosis. CONCLUSIONS: Vitamin D deficiency rickets is a significant problem in Australia among known high-risk groups. Public health campaigns to prevent, identify and tre@vitamin D deficiency, especially in high-risk groups, are essential.
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Raquitismo/epidemiología , Deficiencia de Vitamina D/epidemiología , Adolescente , África/etnología , Fosfatasa Alcalina/sangre , Australia/epidemiología , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Masculino , Refugiados , Raquitismo/diagnóstico , Raquitismo/etiología , Vitamina D/análogos & derivados , Vitamina D/sangre , Deficiencia de Vitamina D/diagnósticoRESUMEN
CONTEXT: IGF-I, essential for normal human growth in utero and postnatally, mediates its effects through the IGF-I receptor (IGF1R). More than nine heterozygous mutations, including one compound heterozygous mutation, of the IGF1R gene have been reported in patients with varying degrees of intrauterine and postnatal growth retardation. OBJECTIVE: The objective of the study was the analysis of the IGF1R gene in a short-statured patient. PATIENT: The male patient, with a height of -5.91 sd score (aged 20.3 yr), had consistently elevated circulating serum concentrations of IGF-I. A diagnosis of antibody-negative insulin-requiring diabetes was made at age 14 yr. His deceased sister was also severely short statured (-3.75 sd score). RESULTS: The patient and his sister carried novel, compound heterozygous IGF1R missense mutations, E121K (exon 2) and E234K (exon 3), inherited from the mother and father, respectively. In vitro reconstitution studies demonstrated that neither the E121K nor E234K mutation affected IGF1R prepeptide expression, but levels of the proteolytically cleaved α- and ß-subunit were consistently low. As a consequence, each IGF1R variant exhibited significantly reduced IGF-I-induced signal transduction. Correlating to these studies, expression of functional IGF1R and the IGF-I-induced activation of the IGF1R pathway were markedly reduced in the primary dermal fibroblasts established from the patient. CONCLUSIONS: Only the second compound heterozygous IGF1R mutations to be identified, the p.E121K/E234K variant is the cause of intrauterine growth retardation and the most severe postnatal growth failure described to date in a patient with IGF1R defects. Whether the mutant IGF1R also contributes to the diabetic phenotype, however, remains to be determined.
Asunto(s)
Enanismo/genética , Mutación Missense , Receptor IGF Tipo 1/genética , Preescolar , Resultado Fatal , Femenino , Predisposición Genética a la Enfermedad , Células HEK293 , Heterocigoto , Humanos , Masculino , Mutación Missense/fisiología , Índice de Severidad de la Enfermedad , Hermanos , Adulto JovenRESUMEN
There are limited data on the use of bisphosphonate therapy for secondary osteoporoses in childhood, and no previous reports of the use of zoledronic acid in this group. We report 20 children with a variety of underlying primary diagnoses with associated secondary osteoporosis, who were treated with 3 monthly zoledronic acid for 2 years (annualised dose 0.1mg/kg/year). There was a significant improvement in lumbar spine (by 1.88 SD±1.24 over first 12 months, p<0.001) and total bone mineral density as assessed by dual energy absorptiometry (DXA) scans, with a similar increase in bone mineral content for lean tissue mass (mean increase 1.34 SD in first 12 months, p<0.001). Bone turnover was reduced with a suppression of both osteocalcin and alkaline phosphatase in the first 12 months of treatment. Skeletal architecture was improved, with increased second metacarpal cortical thickness from 2.44mm to 2.72mm (p<0.001) and improved vertebral morphometry, with 7 patients who had vertebral wedging at baseline showing improved anterior (p=0.017) and middle (p=0.001) vertebral height ratios. Aside from well reported transient side effects with the first dose, there were no adverse effects reported. No adverse effects on anthropometric parameters were seen over the course of the study. Despite all patients having sustained fragility fractures prior to treatment, no fractures were reported during the study period. Further evidence is required to confirm efficacy, with long term follow up required to assess the impact of treatment on fracture risk.
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Conservadores de la Densidad Ósea/farmacología , Densidad Ósea/efectos de los fármacos , Remodelación Ósea/efectos de los fármacos , Difosfonatos/farmacología , Imidazoles/farmacología , Osteoporosis/tratamiento farmacológico , Absorciometría de Fotón , Adolescente , Conservadores de la Densidad Ósea/efectos adversos , Conservadores de la Densidad Ósea/uso terapéutico , Niño , Preescolar , Difosfonatos/efectos adversos , Difosfonatos/uso terapéutico , Femenino , Humanos , Imidazoles/efectos adversos , Imidazoles/uso terapéutico , Masculino , Ácido ZoledrónicoRESUMEN
Dual-energy X-ray absorptiometry (DXA) has been used extensively for bone mineral density and body composition assessments. Surprisingly, the role of DXA in monitoring changes in children's body composition, using direct imaging methods such as magnetic resonance imaging (MRI) as reference, is still yet to be validated. We aimed at validating the use of DXA in monitoring change in the thigh lean soft tissue mass (LSTM) and fat mass (FM) when compared with thigh skeletal muscle mass (SM) and FM, measured using MRI as the reference standard, from childhood to midadolescence. At baseline, 22 healthy children (16 boys and 6 girls) aged 8-11yr were included, and then recalled at pubertal stage Tanner2-Tanner4. LSTM-DXA and FM-DXA of the mid-third femur and SM-MRI and FM-MRI of the same region were measured on the same day. The same protocol was repeated 26-48mo later. At baseline, DXA overestimated LSTM-DXA on average by 222g (95% confidence interval [CI]: 33-410g) with a concordance C-LSTM=0.576. FM-MRI and FM-DXA were not significantly different (95% CI=213 to 199g, the C-FM=0.907). At follow-up, change in LSTM-DXA and FM-DXA were not significantly different to change in SM-MRI and FM-MRI, respectively (95% CI of the difference was -278 to 208g for LSTM, and -148 to 236g for FM). The coefficient of concordance between the 2 techniques was 0.88 for both LSTM and FM. This study validates the use of DXA in monitoring changes in LSTM and FM in children, confirming its significant potential in clinical and research roles in pediatric body composition.
Asunto(s)
Absorciometría de Fotón , Composición Corporal , Imagen por Resonancia Magnética , Adolescente , Niño , Femenino , Fémur/anatomía & histología , Fémur/diagnóstico por imagen , Humanos , Estudios Longitudinales , Masculino , Valores de Referencia , Muslo/anatomía & histología , Muslo/diagnóstico por imagen , Imagen de Cuerpo EnteroRESUMEN
The aim of this study was to characterize expression profiles of visceral and subcutaneous adipose tissue in children. Adipose tissue samples were collected from children having elective surgery (n = 71, [54 boys], 6.0 ± 4.3 years). Affymetrix microarrays (n = 20) were performed to characterize the functional profile and identify genes of interest in adipose tissue. Visceral adipose tissue had an overrepresentation of Gene Ontology themes related to immune and inflammatory responses and subcutaneous adipose tissue had an overrepresentation of themes related to adipocyte growth and development. Likewise, qPCR performed in the whole cohort showed a 30-fold increase in haptoglobin (P = 0.005), 7-fold increase in IL-10 (P < 0.001), 8-fold decrease in VEGF (P = 0.01) and a 28-fold decrease in TBOX15 (P < 0.001) in visceral compared to subcutaneous adipose tissue. The inflammatory pattern in visceral adipose tissue may represent an early stage of the adverse effects of this depot, and combined with chronic obesity, may contribute to increased metabolic and cardiovascular risk.
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Perfilación de la Expresión Génica , Mediadores de Inflamación/análisis , Inflamación/genética , Grasa Intraabdominal/inmunología , Grasa Subcutánea/inmunología , Biopsia , Niño , Femenino , Perfilación de la Expresión Génica/métodos , Regulación de la Expresión Génica , Haptoglobinas/genética , Humanos , Inflamación/inmunología , Interleucina-10/genética , Grasa Intraabdominal/cirugía , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa , Grasa Subcutánea/cirugía , Proteínas de Dominio T Box/genética , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
BACKGROUND AND AIMS: Correct gene dosage of SOX3 is critical for the development of the hypothalamo-pituitary axis. Both overdosage of SOX3, as a result of gene duplication, and loss of function resulting from expansion of the first polyalanine (PA) tract are associated with variable degrees of hypopituitarism, with or without mental retardation. The aim of this study was to further investigate the contribution of SOX3 in the etiology of hypopituitarism and the mechanisms involved in the phenotypic variability. METHODS: We screened 154 patients with congenital hypopituitarism and an undescended posterior pituitary for mutations in SOX3 and variability in the length of the first PA tract. In addition, 300 patients with variable septooptic dysplasia were screened for variability of the PA tract. RESULTS: We report a novel 18-base pair deletion (p.A243_A248del6, del6PA) in a female patient with hypopituitarism resulting in a 2-fold increase in transcriptional activation in vitro, compared with wild-type SOX3. We also identified a previously reported seven-alanine expansion (p.A240_A241ins7, +7PA) in two male siblings with isolated GH deficiency and a distinct phenotype, in addition to the nonsynonymous variant p.R5Q in an unrelated individual; this appears to have no functional effect on the protein. In contrast to +7PA, del6PA maintained its ability to repress ß-catenin mediated transcription in vitro. CONCLUSION: This is the first study to report that PA tract deletions associated with hypopituitarism have functional consequences in vitro, possibly due to increased activation of SOX3 target genes. In addition, we have expanded the phenotypic spectrum associated with PA tract expansion (+7PA) mutations to include panhypopituitarism or isolated GH deficiency, with or without mental retardation.