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BACKGROUND AND AIMS: To systematically review the literature for reports on Wolcott-Rallison syndrome, focusing on the spectrum and natural history, genotype-phenotype correlations, patient and native liver survival, and long-term outcomes. METHODS: PubMed, Livio, Google Scholar, Scopus and Web of Science databases were searched. Data on genotype, phenotype, therapy, cause of death and follow-up were extracted. Survival and correlation analyses were performed. RESULTS: Sixty-two studies with 159 patients met the inclusion criteria and additional 30 WRS individuals were collected by personal contact. The median age of presentation was 2.5 months (IQR 2) and of death was 36 months (IQR 50.75). The most frequent clinical feature was neonatal diabetes in all patients, followed by liver impairment in 73%, impaired growth in 72%, skeletal abnormalities in 59.8%, the nervous system in 37.6%, the kidney in 35.4%, insufficient haematopoiesis in 34.4%, hypothyroidism in 14.8% and exocrine pancreas insufficiency in 10.6%. Episodes of acute liver failure were frequently reported. Liver transplantation was performed in six, combined liver-pancreas in one and combined liver-pancreas-kidney transplantation in two individuals. Patient survival was significantly better in the transplant cohort (p = .0057). One-, five- and ten-year patient survival rates were 89.4%, 65.5% and 53.1%, respectively. Liver failure was reported as the leading cause of death in 17.9% of cases. Overall survival was better in individuals with missense mutations (p = .013). CONCLUSION: Wolcott-Rallison syndrome has variable clinical courses. Overall survival is better in individuals with missense mutations. Liver- or multi-organ transplantation is a feasible treatment option to improve survival.
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Epífises , Transplante de Fígado , Osteocondrodisplasias , Humanos , Osteocondrodisplasias/genética , Epífises/anormalidades , Epífises/cirurgia , Seguimentos , Lactente , Insuficiência Pancreática Exócrina/genética , Diabetes Mellitus/genética , Pré-Escolar , Falência Hepática Aguda/genética , Falência Hepática Aguda/mortalidade , Falência Hepática Aguda/cirurgia , Hipotireoidismo/genética , Fenótipo , Estudos de Associação Genética , Diabetes Mellitus Tipo 1 , eIF-2 QuinaseRESUMO
BACKGROUND: Bone health is affected by chronic childhood disorders including type-1 diabetes mellitus (T1DM). We conducted this randomized controlled trial with the objective of investigating the effect of 1-year supplementation of vitamin-D with milk or with pharmacological calcium on bone mass accrual in underprivileged Indian children and youth with T1DM. METHODS: 5 to 23year old (nâ¯=â¯203) underprivileged children and youth with T1DM were allocated to one of three groups: Milk (group A-received 200 ml milk + 1000 international unit (IU) vitamin-D3/day), Calcium supplement (group B-received 500 mg of calcium carbonate + 1000 IU of vitamin-D3/day) or standard of care/control (group C). Anthropometry, clinical details, biochemistry, diet (3-day 24-h recall), physical activity (questionnaires adapted for Indian children) and bone health parameters (using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography- DXA and pQCT respectively) were evaluated at enrolment and end of 12 month intervention. RESULTS: Total body less head(TBLH) bone mineral content (BMC(g)) and bone mineral density (BMD(gm/cm2)) were significantly higher at end of study in girls in both supplemented groups (TBLHBMC-A-1011.8⯱â¯307.8, B-983.2⯱â¯352.9, C-792.8⯱â¯346.8. TBLHBMD-A-± 0.2, B-0.8⯱â¯0.2, C-0.6⯱â¯0.2, pâ¯<â¯0.05). Z score of lumbar spine bone mineral apparent density of supplemented participants of both sexes was significantly higher than controls (Boys- A-0.7⯱â¯1.1, B-0.6⯱â¯1.4, C- -0.7⯱â¯1.1; Girls- A-1.1⯱â¯1.1, B-0.9⯱â¯3.4, C- -1.7⯱â¯1.3, pâ¯<â¯0.05). A significantly higher percentage increase was found in cortical thickness in girls in both supplemented groups (A-17.9⯱â¯28.6, B-15.3⯱â¯16.5, C-7.6⯱â¯26.2); the differences remained after adjusting for confounders. CONCLUSION: Supplementation with milk or pharmacological calcium (+vitaminD3) improved bone outcomes-particularly geometry in children with T1DM with more pronounced effect in girls. Pharmacological calcium may be more cost effective in optimising bone health in T1DM in resource limited settings.
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Absorciometria de Fóton , Densidade Óssea , Diabetes Mellitus Tipo 1 , Suplementos Nutricionais , Humanos , Criança , Feminino , Diabetes Mellitus Tipo 1/tratamento farmacológico , Masculino , Densidade Óssea/efeitos dos fármacos , Adolescente , Índia , Adulto Jovem , Pré-Escolar , Leite , Vitamina D/uso terapêutico , Vitamina D/administração & dosagem , Carbonato de Cálcio/administração & dosagem , Carbonato de Cálcio/uso terapêutico , Tomografia Computadorizada por Raios X , Animais , Colecalciferol/administração & dosagem , Colecalciferol/uso terapêutico , Cálcio da Dieta/administração & dosagem , Conservadores da Densidade Óssea/uso terapêutico , Conservadores da Densidade Óssea/administração & dosagemRESUMO
BACKGROUND: Artificial intelligence (AI)-based applications for the assessment of the paediatric musculoskeletal system like BoneXpert are not only useful to assess bone age (BA) but also to provide a bone health index (BHI) and a standard deviation score (SDS) for both. This allows comparison of the BHI with age- and sex-matched healthy Caucasian children. OBJECTIVE: We conducted this study with the objective of generating BHI curves using BoneXpert in healthy Indian children with BA between 2 and 17 years. METHOD: We retrospectively reviewed anthropometric parameters, BHI, and BHI SDS data of digitalized left-hand radiographs (joint photographic experts group [jpg] format) of a cohort of 788 paediatric patients from a previous study to which they were recruited to compare various methods of BA assessment. The recruited children represented all age groups for both sexes. The corrected BHI for jpg images was calculated using the formula corrected BHI=BHI*(stature/(avL*50))^0.33333 where stature is height of subject and avL is average length of metacarpal bones. The reference Indian BHI curves and centiles were generated using the Lambda-Mu-Sigma method. RESULT: The mean BHI and BHI SDS of the study group were 4.02±0.57 and -1.73±1.09, respectively. The average increase in median BHI from each age group was between 2.5% and 3% in both sexes up to age of 14 years after which it increased to 4.5% to 5%. The mean BHI of Indian children was lower than that of Caucasian children with maximum differences noted in boys at 16 years (21.7%) and girls at 14 years (16%). We report 8.4% SD of BHI for our study sample. Reference percentile curves for BHI according to BA were derived separately for boys and girls. CONCLUSION: Reference data has been provided for the screening of bone health status of Indian children and adolescents.
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Inteligência Artificial , Densidade Óssea , Masculino , Feminino , Criança , Humanos , Adolescente , Estudos Retrospectivos , Radiografia , Mãos , Valores de ReferênciaRESUMO
BACKGROUND: Type 1 Diabetes poses a significant public health threat, especially in low-and-middle countries, where resources are limited. The use of geographical information systems in diabetes research has shown the potential to reveal several epidemiological risk factors. AIMS: This scoping review aimed to identify the scope and extent of the current literature and explore its limitations on the geographical mapping of children with type 1 diabetes. METHODS: A scoping review was conducted using five electronic databases and included studies published between the years 2000 and 2023. The search terms included: "Type 1 Diabetes Mellitus", "GIS mapping", "Juvenile Onset Diabetes Mellitus", "Spatial Epidemiology", "Spatial Clustering", "Spatial analysis", and "Geographic information system". Relevant full-text articles that met the inclusion criteria were selected for review. RESULTS: The search identified 17 studies that met the criteria for inclusion in the review. More than half the studies were conducted before 2015 (n=11; 61%). All studies were conducted in High-Income Countries. More than 10 articles studied environmental factors, 3 of them focused on the environment, 6 of them included sociodemographic factors, and 1 study incorporated nutrition (as a variable) in environmental factors. 2 studies focused on the accessibility of health services by pediatric patients. CONCLUSION: Studies on type 1 diabetes highlight the complex relationship between incidence and risk, suggesting comprehensive prevention and treatment. Geographical mapping has potential in low- and middle-income nations, but further research is needed to develop innovative strategies. The importance of geomappping in understanding the risk factors for Type 1 Diabetes is highlighted in this scoping review, which also suggests a possible direction for focused interventions, particularly in settings with low resources.
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OBJECTIVE: To assess weight velocity and the age at peak weight velocity and to construct weight velocity percentiles in 4-17-year-old apparently healthy Indian children. METHOD: This longitudinal study enrolled 1045 children (588 boys) from Pune belonging to middle and upper socioeconomic class aged 4-17 years. The study parameters included annual height and weight measurements recorded longitudinally from 2007 to 2013. A total of 5225 weight velocity measurements (2940 on boys) were computed. Age- and gender-specific smoothened weight velocity percentiles (3rd, 10th, 25th, 50th, 75th, 90th and 97th) were constructed using LMS chart maker. RESULTS: The median weight velocity was low in boys and girls at 4 years, thereafter it increased to a peak of 4.6 kg/year at 13 years in boys, then declined to 1.1 kg/year at 17.5 years. In girls, median weight velocity peaked to 4.0 kg/year at 11 years, then declined to 0.8 kg/year at 17.5 years. Peak velocity-centred analysis revealed higher peak velocities of 7.5 kg/year at 13.1 years and 6.6 kg/year at 12 years in boys and girls respectively. CONCLUSION: Weight velocity percentiles are presented for 4-17-year-old apparently healthy Indian children.
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Peso Corporal , Humanos , Criança , Masculino , Feminino , Adolescente , Pré-Escolar , Índia/epidemiologia , Estudos Longitudinais , Peso Corporal/fisiologia , Valores de ReferênciaRESUMO
The role of physical inactivity as a contributor to non-communicable disease risk in children and youth is widely recognized. Air pollution and the built environment can limit participation in physical activity and exacerbate non-communicable disease risk; however, the relationships between perceptions of air pollution, built environment, and health behaviours are not fully understood, particularly among children and youth in low and middle-income countries. Currently, there are no studies capturing how child and youth perceptions of air pollution and built environment are associated with physical activity in India, thus, this study investigated the association between perceived air pollution and built environment on moderate-to-vigorous physical activity (MVPA) levels of Indian children and youth. Online surveys captured MVPA, perception of air pollution as a problem, built environment factors, as well as relevant sociodemographic characteristics from parents and children aged 5-17 years in partnership with 41 schools across 28 urban and rural locations during the Coronavirus disease lockdowns in 2021. After adjusting for age, gender, and location, a significant association was found between the perception of air pollution as a problem and MVPA levels (ß = -18.365, p < 0.001). Similarly, the perception of a high crime rate was associated with lower MVPA levels (ß = -23.383, p = 0.002). Reporting the presence of zebra crossings, pedestrian signals, or attractive natural sightings were associated with higher MVPA levels; however, this association varied across sociodemographic groups. These findings emphasize the importance of addressing air pollution and improving the built environment to facilitate outdoor active living, including active transportation, among children and youth - solutions that are particularly relevant not only for preventing non-communicable disease risk but also for climate change mitigation.
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Poluição do Ar , Doenças não Transmissíveis , Criança , Humanos , Adolescente , Exercício Físico , Atividade Motora , Ambiente Construído , Características de Residência , Planejamento AmbientalRESUMO
Physical inactivity is one of the four key preventable risk factors, along with unhealthy diet, tobacco use, and alcohol consumption, underlying most noncommunicable diseases. Promoting physical activity is particularly important among children and youth, whose active living behaviours often track into adulthood. Incorporating yoga, an ancient practice that originated in India, can be a culturally-appropriate strategy to promote physical activity in India. However, there is little evidence on whether yoga practice is associated with moderate-to-vigorous physical activity (MVPA) accumulation. Thus, this study aims to understand how yoga practice is associated with MVPA among children and youth in India. Data for this study were obtained during the coronavirus disease lockdown in 2021. Online surveys capturing MVPA, yoga practice, contextual factors, and sociodemographic characteristics, were completed by 5 to 17-year-old children and youth in partnership with 41 schools across 28 urban and rural locations in five states. Linear regression analyses were conducted to assess the association between yoga practice and MVPA. After controlling for age, gender, and location, yoga practice was significantly associated with MVPA among children and youth (ß = 0.634, p < 0.000). These findings highlight the value of culturally-appropriate activities such as yoga, to promote physical activity among children and youth. Yoga practice might have a particularly positive impact on physical activity among children and youth across the world, owing to its growing global prevalence.
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Exercício Físico , Yoga , Humanos , Índia/epidemiologia , Adolescente , Masculino , Feminino , Criança , Pré-EscolarRESUMO
BACKGROUND: Increasing dietary diversity is a sustainable solution to combat micronutrient deficiencies. Given the large slum population in urban India, double burden of malnutrition, nutritional transition among slum-dwellers, and limited studies focusing on dietary intake and diversity among pregnant slum-dwellers, this study aimed to 1) describe macro- and micronutrient intakes and compare them with guidelines, 2) describe dietary diversity and intake of unhealthy foods and, 3) investigate the sociodemographic and lifestyle determinants of adequate dietary diversity among pregnant slum-dwellers in Pune, Maharashtra, India. METHODS: This study presents cross-sectional data of 454 pregnant slum-dwelling women completing mid-pregnancy visit collected from a larger cohort study. Sociodemographic and lifestyle data were collected at baseline (< 12 weeks gestation). Dietary data (24-h dietary recall) were collected in mid-pregnancy (23 ± 2 weeks). Nutrient intakes were compared with the Estimated Average Requirements (EAR) for pregnant Indian women. Dietary diversity score (DDS, range 0-10) and unhealthy food (sweet snacks, sweet beverages, fried and salty food) group score (range 0-3) were calculated as per FAO guidelines. Multivariate logistic regression was conducted to examine determinants of adequate dietary diversity (DDS ≥ 5). RESULTS: The average age of women was 25 (4.5) years. The median (Q1, Q3) total energy and protein intakes were 1771 (1456, 2185) kcal/d and 44.7 (34.7, 55.0) g/d, respectively. Total energy and protein were consumed as per EAR by 37% and 54% of women, respectively. Forty percent of women exceeded the recommended energy intake from carbohydrates. Diets of slum-dwelling women were lacking in multiple micronutrients (especially iron, zinc, riboflavin, thiamine, folate). The mean DDS was 4.2 ± 1.2 and 36.5% of the women had DDS ≥ 5. All women consumed mainly cereal-based starchy staples; 80% consumed pulses and legumes, and 60% consumed other vegetables. Fifty-nine percent of women consumed ≥ 2 unhealthy food groups. Higher educational and occupational status of the primary earning members of the family and lower parity were determinants of adequate dietary diversity. CONCLUSION: The diets of pregnant slum-dwelling women were lacking in numerous micronutrients. Dietary counselling programs need to be tailored to the socioeconomic backgrounds of pregnant slum-dwelling women and involve their family members to improve reach and effectiveness.
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Introduction: Insulin resistance (IR) and obesity are common presentations of double diabetes (DD) in subjects with type-1 diabetes (T1D). There is evidence that dietary composition has an impact on developing IR. Objectives were to assess the impact of macronutrient and fibre intake on glycaemic control and the role of macronutrient composition of diet in the development of DD in subjects with T1D. Methods: This cross-sectional study included 77 young adults (10-25 years) with T1D. Data related to demography, anthropometry, biochemistry and body composition were collected. Dietary data was collected by fourteen-day food diary. IR was calculated using eGDR, SEARCH and CACTI equations, and metabolic syndrome (MS) was diagnosed using the International Diabetes Federation Consensus Definition. Results: Subjects at risk of DD had higher age, leptin levels, percentage carbohydrate consumption in diet and IR. A positive association of insulin sensitivity with fibre intake and %protein intake was noted. Poor glycaemic control, adiponectin/leptin ratio, fibre intake and insulin/carbohydrate ratio were significant negative predictors of IR. Addition of dietary factors to the regression model improved the R square and percentage of subjects identified correctly. Inclusion of dietary parameters significantly improves the prediction of the risk of development of DD in subjects with T1D. Conclusion: Good glycaemic control and increased intake of dietary fibre may prevent the development of IR in subjects with T1D and reduce the burden of DD.
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Introduction: Recent evidence reveals that type 1 diabetes mellitus (T1DM) impairs muscle function (MF) in adolescents. However, despite its importance in physical well-being, data on dynamic MF in Indian children and adolescents (C and Y) with T1DM are scarce. We assessed MF using Jumping Mechanography (JM, a measurement method for motion analysis and assessment of muscle power and force). (1) To assess dynamic MF by JM in C and Y with T1DM as compared to healthy controls (2) To determine predictors of MF in children with T1DM. Methods: A cross-sectional observational study on 266 children (133 - T1DM duration >1 year with no known comorbidities + 133 age and gender-matched healthy controls) aged 6-19 years. Anthropometry, body composition, and MF (maximum relative power Pmax/mass, maximum relative force Fmax/BW by JM) were recorded. The lean mass index (LMI) was calculated as lean mass (kg)/height (m2). HbA1c was assessed in T1DM. Independent sample t-test and linear regression were performed. Results: MF parameters (Pmax/mass 33.5 ± 7.2 vs 38.0 ± 8.6 W/kg and Fmax/BW 10.5 ± 2.9 vs 11.4 ± 4.1 N/kg, P < 0.05) were significantly lower in T1DM group vs controls. Positive association of body mass index and LMI with both MF parameters and negative association of insulin requirement and HbA1c with Fmax was observed in T1DM. Predictors of MF identified were MMI (Pmax/mass:b = 1.6,95%CI = 0.6-2.6; Fmax/BW:b =2.0,95%CI = 1.6-2.4) and HbA1c (Pmax/mass:b = -2.1,95%CI = -4.5--0.5; Fmax/BW:b = -1.1,95%CI = -2.0--0.2) (P < 0.05). Conclusion: C and Y with T1DM exhibits compromised muscle function. Poor glycaemic control increases the risk of having decreased MF, irrespective of diabetes duration and may contribute to sarcopenia in adulthood.
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Introduction: A good screening tool, such as a growth chart, should distinguish between children with normal growth and those with perturbed growth. Suitability of synthetic Indian growth references for diagnosing growth-related disorders for under-five children has not been evaluated. To assess the validity of World Health Organization (WHO) 2006 standards vs synthetic Indian references (2019) (by comparing weight, height, body mass index (BMI), standard deviation scores (SDS) and the composite index of anthropometric failure (CIAF)) in differentiating normal children and children with growth-related disorders. Methods: Records of 2188 children (0-60 months) attending a tertiary centre paediatric outpatient department (OPD) were retrospectively studied; 1854 children were healthy and 334 were diagnosed with growth-related disorders as per the European Society for Paediatric Endocrinology (ESPE) classification. The anthropometric parameters converted to Z-scores for weight-for-age (WAZ), height-for-age (HAZ), BMI-for-age (BAZ) and a CIAF were computed using WHO and synthetic charts; Student's t-test was used for assessing differences and Youden's index for validity. Results: Disease status of children and anthropometric failure on WAZ, HAZ, BAZ and CIAF on both WHO and synthetic charts had a significant association (P-value <0.05). WAZ, HAZ on both charts and CIAF on synthetic chart had a fair to moderate agreement (Kappa statistics) with disease status as per diagnosis (P-value <0.05). The sensitivity and negative predictive value for all anthropometric parameters were higher for synthetic charts. Conclusion: Indian charts were more sensitive for diagnosing growth-related disorders from birth to 60 months of age when compared to WHO growth standards.
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OBJECTIVE: To design a specific advanced life support (ALS) tape based on recent Indian multicenter height/length and weight data to accurately estimate the weight from the recumbent length. METHODS: We designed the new ALS tape by matching the median weights to median heights/lengths from the recently published Indian multicenter growth data, maintaining the same color codes as the Broselow tape. The accuracy of weight estimation for the newly designed ALS tape was validated and compared with the Broselow estimated weights at a tertiary care hospital. RESULTS: The color (weight) band matched median heights (cm) from the new ALS tape were higher (53.0 vs 53.9 for grey, 63.1 vs 67.4 for pink, 70.6 vs 76.4 for red, 79 vs 85.5 for purple, 89.6 vs 95.5 for yellow, 101.9 vs 107.5 for white, 126.1 vs 130.5 for orange and 137 vs 140.5 for green) than the Broselow tape. For every color band on the newly designed ALS tape, a sizable proportion of children (27% for grey, 78% for pink, 83% for red, 38% for purple, 63% for yellow, 41% for white, 35% for blue, 54% for orange) recorded a higher Broselow color band, suggesting overestimated weights at each color band. The percentage difference in the estimated weight from the actual weight was very small (-0.5% for under-5 years and 0.2% for older children) using the new ALS tape as compared to Broselow tape. CONCLUSION: This Indianized ALS tape estimated Indian children's weights more accurately. Use of the newly designed ALS tape may reduce the errors in calculating emergency medications, fluids and equipment sizes. Further studies are required to validate this tape in pediatric emergency departments in India.
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BACKGROUND AND OBJECTIVES: BoneXpert (BX) is an artificial intelligence software used primarily for bone age assessment. Besides, it can also be used to screen for bone health using the digital radiogrammetry tool called bone health index (BHI) for which normative reference values available are calculated from healthy European children. Due to ethnic difference in bone geometry, in a previous study, we generated reference curves based on healthy Indian children. The objectives of this study were: 1) To assess and compare bone health of Indian children with Type 1 diabetes (T1D) using both European and Indian BHI SDS reference data and 2) To identify determinants of poor bone health in Indian children and youth with T1D by using BHI tool (based on BHI-SDS Indian reference data) of BX. METHOD: The BHI was assessed retrospectively in 1159 subjects with T1D using digitalised left-hand x-rays and SDS were computed using European and Indian data. The demographic, anthropometric, clinical, biochemistry, dual x-ray absorptiometry (DXA) data and peripheral quantitative computed tomography (pQCT) data collection were performed using standard protocols and were extracted from hospital records. RESULTS: The BHI correlated well with DXA and pQCT parameters in subjects with T1D. BHI-SDS calculated using Indian reference data had better correlation with height and DXA parameters. 8.6% study participants had low (less than -2) BHI-SDS (Indian), with height SDS having significant effect. Subjects with low BHI-SDS were older, shorter and had higher duration of diabetes. They also had lower IGF1 and vitamin D concentrations, bone mineral density, and trabecular density. Female gender, increased duration of illness, poor glycaemic control, and vitamin D deficiency/insufficiency were significant predictors of poor BHI-SDS. CONCLUSION: Our study highlights the utility of digital radiogrammetry AI tool to screen for bone health of children with T1D and demonstrates and highlights the necessity of interpretation using ethnicity specific normative data.
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Densidade Óssea , Diabetes Mellitus Tipo 1 , Criança , Humanos , Feminino , Adolescente , Diabetes Mellitus Tipo 1/diagnóstico por imagem , Inteligência Artificial , Estudos Retrospectivos , Absorciometria de Fóton/métodos , AntropometriaRESUMO
The well-known Greulich and Pyle (GP) method of bone age assessment (BAA) relies on comparing a hand X-ray against templates of discrete maturity classes collected in an atlas. Automated methods have recently shown great success with BAA, especially using deep learning. In this perspective, we first review the success and limitations of various automated BAA methods. We then offer a novel hypothesis: When networks predict bone age that is not aligned with a GP reference class, it is not simply statistical error (although there is that as well); they are picking up nuances in the hand X-ray that lie "outside that class." In other words, trained networks predict distributions around classes. This raises a natural question: How can we further understand the reasons for a prediction to deviate from the nominal class age? We claim that segmental aging, that is, ratings based on characteristic bone groups can be used to qualify predictions. This so-called segmental GP method has excellent properties: It can not only help identify differential maturity in the hand but also provide a systematic way to extend the use of the current GP atlas to various other populations.
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Introduction: Insulin resistance is being increasingly reported in type-1 Diabetes (T1D) and is known to accelerate microvascular complications. The Asian Indian population has a higher risk of double diabetes development compared to Caucasians. Hence, we studied the effect of adding Metformin to standard insulin therapy on glycemic control, insulin sensitivity (IS), cardiometabolic parameters and body composition in Indian adolescents with T1D. Methods: A Randomized controlled trial was conducted spanning 9 months (Registration number:CTRI/2019/11/022126). Inclusion: Age 10-19 years, T1D duration>1year, HbA1c>8% Exclusion: Uncontrolled vascular complications/comorbidities, Metformin intolerance, concomitant drugs affecting insulin sensitivity. Participants were randomized to Metformin/Placebo (n=41 each) groups and age, sex, duration-matched. Assessments were performed at baseline, 3 and 9 months. Results: 82 participants aged 14.7 ± 3years (40 females) were enrolled, with a mean diabetes duration of 5.2 ± 2.3 years. Over 9 months, HbA1c decreased significantly by 0.8 (95% confidence interval: -1.2 to -0.3) from 9.8 ± 1.8% to 9.1 ± 1.7% on Metformin but remained largely unchanged (difference of 0.2, 95% confidence interval: -0.7 to 0.2) i.e. 9.9 ± 1.6% and 9.7 ± 2.2% on placebo. HbA1c improvement correlated negatively with baseline IS (EGDR:r= -0.3;SEARCH:r = -0.24, p<0.05) implying better HbA1c-lowering in those with decreased initial IS. CGM-based glycemic variability (standard deviation) reduced by 6.3 mg/dL (95% confidence interval: -12.9 to 0.2) from 100.2 ± 19.1 mg/dL to 93.7 ± 19.9 mg/dL in those on Metformin (p=0.05) but not placebo (94.0 ± 20.5; 90.0 ± 22.6 mg/dL). Insulin sensitivity: CACTIexa & SEARCH scores demonstrated no change with Metformin but significant worsening on placebo. Significant increase in LDL-C(42%), total cholesterol(133.6 to 151.1 mg/dL), triglyceride (60.0 to 88.0 mg/dL) and carotid intima-media thickness was noted on placebo but not Metformin. Weight, BMI, fat Z-scores increased significantly on placebo but not Metformin. Adverse events (AE) were minor; AE, compliance and safety parameters were similar between the two groups. Conclusion: Metformin as an adjunct to insulin in Asian Indian adolescents with T1D demonstrated beneficial effect on glycemic control, glycemic variability, IS, lipid profile, vascular function, weight and body fat, with a good safety profile when administered for 9 months.
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OBJECTIVES: Wolfram syndrome is characterised by insulin-dependent diabetes (IDDM), diabetes insipidus (DI), optic atrophy, sensorineural deafness and neurocognitive disorders. The DIDMOAD acronym has been recently modified to DIDMOAUD suggesting the rising awareness of the prevalence of urinary tract dysfunction (UD). End stage renal disease is the commonest cause of mortality in Wolfram syndrome. We present a case series with main objective of long term follow up in four children having Wolfram syndrome with evaluation of their urodynamic profile. METHODS: A prospective follow up of four genetically proven children with Wolfram syndrome presenting to a tertiary care pediatric diabetes clinic in Pune, India was conducted. Their clinical, and urodynamic parameters were reviewed. RESULTS: IDDM, in the first decade, was the initial presentation in all the four children (three male and one female). Three children had persistent polyuria and polydipsia despite having optimum glycemic control; hence were diagnosed to have DI and treated with desmopressin. All four patients entered spontaneous puberty. All patients had homozygous mutation in WFS1 gene; three with exon 8 and one with exon 6 novel mutations. These children with symptoms of lower urinary tract malfunction were further evaluated with urodynamic studies; two of them had hypocontractile detrusor and another had sphincter-detrusor dyssynergia. Patients with hypocontractile bladder were taught clean intermittent catheterization and the use of overnight drain. CONCLUSIONS: We report a novel homozygous deletion in exon 6 of WFS-1 gene. The importance of evaluation of lower urinary tract malfunction is highlighted by our case series. The final bladder outcome in our cases was a poorly contractile bladder in three patients.
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Urodinâmica , Síndrome de Wolfram , Adolescente , Criança , Feminino , Humanos , Masculino , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/fisiopatologia , Seguimentos , Proteínas de Membrana/genética , Mutação , Prognóstico , Estudos Prospectivos , Síndrome de Wolfram/genética , Síndrome de Wolfram/complicações , Síndrome de Wolfram/fisiopatologiaRESUMO
Introduction: Bone age (BA) assessment is important in evaluating disorders of growth and puberty; the Greulich and Pyle atlas method (GP) is most used. We aimed to determine the weightage to be attributed by raters to various segments of the hand x-ray, namely, distal end of radius-ulna (RU), carpals, and short bones for rating bone age using the GP atlas method. Methods: 692 deidentified x-rays from a previous study (PUNE-dataset) and 400 from the Radiological Society of North America (RSNA-dataset) were included in the study. Mean of BA assessed by experienced raters was termed reference rating. Linear regression was used to model reference age as function of age ratings of the three segments. The root-mean-square-error (RMSE) of segmental arithmetic mean and weighted mean with respect to reference rating were computed for both datasets. Results: Short bones were assigned the highest weightage. Carpals were assigned higher weightage in pre-pubertal PUNE participants as compared to RSNA, vice-versa in RU segment of post-pubertal participants. The RMSE of weighted mean ratings was significantly lower than for the arithmetic mean in the PUNE dataset. Conclusion: We thus determined weightage to be attributed by raters to segments of the hand x-ray for assessment of bone age by the GP method.
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Though the Greulich and Pyle (GP) method is easy, inter-observer variability, differential maturation of hand bones influences ratings. The Tanner-Whitehouse (TW) method is more accurate, but cumbersome. A simpler method combining the above, such that it utilizes fewer bones without affecting accuracy, would be widely used and more applicable in clinical practice. OBJECTIVES: 1. Devising a simplified method utilizing three bones of the hand and wrist for bone age (BA) assessment. 2. Testing whether the 3 bone method gives comparable results to standard methods (GP,TW2,TW3) in Indian children. METHODS: Developmental stages and corresponding BA for radius, hamate, terminal phalanx (left middle finger) epiphyses combining stages from GP,TW3 atlases were described; BA were rated by two blinded observers. 3 bone method ratings were compared with the same dataset analyzed earlier using GP,TW2,TW3 (4 raters). RESULTS: Radiographs analysed:493 (Girls=226). Mean chronological age:9.4 ± 4.6 yrs, mean BA 3 bone:9.8 ± 4.8 yrs, GP:9.6 ± 4.8 yrs, TW3:9.3 ± 4.5 yrs, TW2:9.9 ± 5.0 yrs. The 3 bone method demonstrated no significant inter-observer variability (p = 0.3, mean difference = 0.02 ± 0.6 yrs); a strong positive correlation (p < 0.0001) with GP (r = 0.985), TW3 (r = 0.983) and TW2 (r = 0.982) was noted. Bland-Altman plots demonstrated good agreement; the root mean square errors between 3 bone and GP,TW3,TW2 ratings were 0.6,0.7,0.6 years; mean differences were 0.19,0.49,-0.14 years respectively. Greatest proportion of outliers (beyond ±1.96 SD of mean difference) was between 6 and 8 years age for difference in 3 bone and GP, and between 4-6 years for difference in 3 bone and TW3,TW2. CONCLUSION: The 3 bone method has multiple advantages; it is easier, tackles differential maturation of wrist and hand bones, has good reproducibility, without compromising on accuracy rendering it suitable for office practice.
Assuntos
Determinação da Idade pelo Esqueleto , Ossos da Mão , Determinação da Idade pelo Esqueleto/métodos , Humanos , Feminino , Criança , Masculino , Ossos da Mão/diagnóstico por imagem , Ossos da Mão/crescimento & desenvolvimento , Ossos da Mão/anatomia & histologia , Adolescente , Pré-Escolar , Rádio (Anatomia)/diagnóstico por imagem , Rádio (Anatomia)/anatomia & histologia , Variações Dependentes do Observador , Falanges dos Dedos da Mão/diagnóstico por imagem , Falanges dos Dedos da Mão/anatomia & histologia , Reprodutibilidade dos Testes , Punho/diagnóstico por imagem , Punho/anatomia & histologia , Desenvolvimento Ósseo/fisiologiaRESUMO
INTRODUCTION: Global surveillance of physical activity (PA) of children and adolescents with questionnaires is limited by the use of instruments developed in high-income countries (HICs) lacking sociocultural adaptation, especially in low- and middle-income countries (LMICs); under-representation of some PA domains; and omission of active play, an important source of PA. Addressing these limitations would help improve international comparisons, and facilitate the cross-fertilisation of ideas to promote PA. We aim to develop and assess the reliability and validity of the app-based Global Adolescent and Child Physical Activity Questionnaire (GAC-PAQ) among 8-17 years old in 14 LMICs and HICs representing all continents; and generate the 'first available data' on active play in most participating countries. METHODS AND ANALYSIS: Our study involves eight stages: (1) systematic review of psychometric properties of existing PA questionnaires for children and adolescents; (2) development of the GAC-PAQ (first version); (3) content validity assessment with global experts; (4) cognitive interviews with children/adolescents and parents in all 14 countries; (5) development of a revised GAC-PAQ; (6) development and adaptation of the questionnaire app (application); (7) pilot-test of the app-based GAC-PAQ; and, (8) main study with a stratified, sex-balanced and urban/rural-balanced sample of 500 children/adolescents and one of their parents/guardians per country. Participants will complete the GAC-PAQ twice to assess 1-week test-retest reliability and wear an ActiGraph wGT3X-BT accelerometer for 9 days to test concurrent validity. To assess convergent validity, subsamples (50 adolescents/country) will simultaneously complete the PA module from existing international surveys. ETHICS AND DISSEMINATION: Approvals from research ethics boards and relevant organisations will be obtained in all participating countries. We anticipate that the GAC-PAQ will facilitate global surveillance of PA in children/adolescents. Our project includes a robust knowledge translation strategy sensitive to social determinants of health to inform inclusive surveillance and PA interventions globally.
Assuntos
Exercício Físico , Psicometria , Humanos , Adolescente , Criança , Inquéritos e Questionários/normas , Reprodutibilidade dos Testes , Masculino , Feminino , Países em Desenvolvimento , Projetos de PesquisaRESUMO
Background: Non-genetic factors like microbial dysbiosis may be contributing to the increasing incidence/progression of type 1 diabetes mellitus (T1DM). Objectives: To analyse the gut microbiota profile in Indian children with T1DM and its effect on glycaemic control. Methodology: Faecal samples of 29 children with T1DM were collected and faecal microbial DNA was extracted and subjected to 16S rRNA (ribosomal RNA) sequencing and further analysis. Results: The dominant phyla in children with T1DM were Firmicutes and Bacteroidetes. Butyrate-producing bacteria Blautia and Ruminococcus showed a significant negative correlation with the glycosylated haemoglobin (HbA1C) levels (p < 0.05). Coprococcus and Propionibacterium were important negative predictors of glycaemic control (p < 0.05). Conclusion: Our study suggests that Indian children with T1DM have a distinct gut microbiome taxonomic composition and that short-chain fatty acid-producing bacteria like Ruminococcus and Blautia (butyrate-producing) may play an important role in the glycaemic control of subjects with T1DM.