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1.
BMJ Open Qual ; 13(1)2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38448042

ABSTRACT

BACKGROUND: Multicentre comparative clinical audits have the potential to improve patient care, allow benchmarking and inform resource allocation. However, implementing effective and sustainable large-scale audit can be difficult within busy and resource-constrained contemporary healthcare settings. There are little data on what facilitates the successful implementation of multicentre audits. As healthcare environments are complex sociocultural organisational environments, implementing multicentre audits within them is likely to be highly context dependent. OBJECTIVE: We aimed to examine factors that were influential in the implementation process of multicentre comparative audits within healthcare contexts-what worked, why, how and for whom? METHODS: A realist review was conducted in accordance with the Realist and Meta-narrative Evidence Syntheses: Evolving Standards reporting standards. A preliminary programme theory informed two systematic literature searches of peer-reviewed and grey literature. The main context-mechanism-outcome (CMO) configurations underlying the implementation processes of multicentre audits were identified and formed a final programme theory. RESULTS: 69 original articles were included in the realist synthesis. Four discrete CMO configurations were deduced from this synthesis, which together made up the final programme theory. These were: (1) generating trustworthy data; (2) encouraging audit participation; (3) ensuring audit sustainability; and (4) facilitating audit cycle completion. CONCLUSIONS: This study elucidated contexts, mechanisms and outcomes influential to the implementation processes of multicentre or national comparative audits in healthcare. The relevance of these contextual factors and generative mechanisms were supported by established theories of behaviour and findings from previous empirical research. These findings highlight the importance of balancing reliability with pragmatism within complex adaptive systems, generating and protecting human capital, ensuring fair and credible leadership and prioritising change facilitation.


Subject(s)
Benchmarking , Health Facilities , Humans , Delivery of Health Care , Leadership , Multicenter Studies as Topic
2.
Eur J Endocrinol ; 186(4): 417-427, 2022 Feb 22.
Article in English | MEDLINE | ID: mdl-35089870

ABSTRACT

OBJECTIVE: The phenotype mediated by HNF4A/HNF1A mutations is variable and includes diazoxide-responsive hyperinsulinaemic hypoglycaemia (HH) and maturity-onset diabetes of the young (MODY). DESIGN: We characterised an international multicentre paediatric cohort of patients with HNF4Aor HNF1Amutations presenting with HH over a 25-year period (1995-2020). METHODS: Clinical and genetic analysis data from five centres were obtained. Diazoxide responsiveness was defined as the ability to maintain normoglycaemia without intravenous glucose. Macrosomia was defined as a birth weight ≥90th centile. SPSS v.27.1 was used for data analysis. RESULTS: A total of 34 patients (70.6% female, n = 24) with a mean age of 7.1 years (s.d. 6.4) were included. A total of 21 different heterozygous HNF4Amutations were identified in 29 patients (four novels). Four different previously described heterozygous HNF1A mutations were detected in five patients. Most (97.1%, n = 33) developed hypoglycaemia by day 2 of life. The mean birth weight was 3.8 kg (s.d. 0.8), with most infants macrosomic (n = 21, 61.8%). Diazoxide was commenced in 28 patients (82.3%); all responded. HH resolved in 20 patients (58.8%) following a median of 0.9 years (interquartile range (IQR): 0.2-6.8). Nine patients (n = 9, 26.5%) had developmental delay. Two patients developed Fanconi syndrome (p.Arg63Trp, HNF4A) and four had other renal or hepatic findings. Five (14.7%) developed MODY at a median of 11.0 years (IQR: 9.0-13.9). Of patients with inherited mutations (n = 25, 73.5%), a family history of diabetes was present in 22 (88.0%). CONCLUSIONS: We build on the knowledge of the natural history and pancreatic and extra-pancreatic phenotypes of HNF4A/HNF1Amutations and illustrate the heterogeneity of this condition.


Subject(s)
Genetic Heterogeneity , Hepatocyte Nuclear Factor 1-alpha/genetics , Hepatocyte Nuclear Factor 4/genetics , Hyperinsulinism/genetics , Hypoglycemia/genetics , Mutation , Adolescent , Birth Weight , Child , Child, Preschool , Cohort Studies , Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 2/genetics , Diazoxide/therapeutic use , Fanconi Syndrome/genetics , Female , Humans , Hyperinsulinism/drug therapy , Hypoglycemia/drug therapy , Infant , Infant, Newborn , Male , Medical History Taking
3.
J Pediatr Endocrinol Metab ; 34(9): 1123-1129, 2021 Sep 27.
Article in English | MEDLINE | ID: mdl-34167176

ABSTRACT

BACKGROUND: The aim of this study was to describe the incidence and spectrum of early clinical presentations of congenital adrenal hyperplasia (CAH) in an unscreened population. METHODS: A national retrospective observational study was undertaken to identify all children diagnosed with CAH in the Republic of Ireland, between January 2005 and December 2019. Reporting clinicians completed anonymized clinical questionnaires. RESULTS: There were 103 cases of CAH reported and 69 cases met the study inclusion criteria. The estimated annualized incidence of CAH in the Republic of Ireland was 1:14,754 or 0.07 cases per 1,000 live births. Forty-seven children presented clinically in the first six months of life, but only 17 of these had a confirmed diagnosis by day 10. Of these early presentations, there were 28 infants with salt-wasting, 15 females presented with virilized genitalia and four infants were detected due to a family history of CAH. Female infants presented at a median age of 0 days [IQR 0-1] and males at 14 days [IQR 9-21]. Seventy-eight percent of salt-wasting presentations occurred after day 10. Delays in clinical presentation, biochemical diagnosis and treatment initiation were identified. CONCLUSIONS: The incidence of CAH is higher in Ireland than in other unscreened populations. In the absence of screening, clinicians should be aware of the possibility of CAH and appropriate investigations should be urgently requested. Life-threatening salt-wasting is the most frequent clinical presentation and many cases could be detected prior to decompensation if newborn screening were introduced.


Subject(s)
Adrenal Hyperplasia, Congenital/diagnosis , Infant, Newborn, Diseases/diagnosis , Neonatal Screening/methods , Virilism/pathology , Wasting Syndrome/pathology , Adrenal Hyperplasia, Congenital/epidemiology , Female , Follow-Up Studies , Humans , Incidence , Infant , Infant, Newborn , Infant, Newborn, Diseases/epidemiology , Ireland/epidemiology , Male , Prognosis , Retrospective Studies , Sodium/metabolism
5.
Ir J Med Sci ; 188(1): 135-139, 2019 Feb.
Article in English | MEDLINE | ID: mdl-29855860

ABSTRACT

BACKGROUND AND AIMS: Coeliac disease (CD) is more common in those with type 1 diabetes mellitus (T1DM) and may be asymptomatic despite the presence of intestinal histological changes. Optimal screening practice guidelines differ internationally. We undertook a retrospective audit to determine the efficacy of current screening practice for CD in T1DM in our centre. METHODS: All children and adolescents < 16 years, diagnosed with T1DM in our service and continuing to attend the service in January 2017 were included. Data on CD screening was collected and compared to current NICE, NASPGHAN and ESPGHAN guidelines. RESULTS: Of the 355 patients attending our service, 253 attended from T1DM diagnosis and all had CD screening performed in our centre. In 37 of 253 patients, IgA-TTG was positive, providing a cumulative prevalence of 14.6%. Of these, 31(83.78%) with an elevated TTG on screening had no recorded gastrointestinal symptoms or CD-related clinical signs. Of the 35 TTG plus EMA-positive patients, 22/35 (59.46%) had diagnostic endoscopic biopsy. Nineteen (83.4%) had CD confirmed, 1 (4.54%) had negative biopsy and 2 (9%) had equivocal, non-diagnostic changes. CONCLUSIONS: Timely diagnosis of CD can prevent chronic ill health in affected individuals, and in patients with T1DM, CD is an independent risk factor for increased morbidity and mortality. Given the high prevalence of atypical symptoms and silent CD in those with T1DM, in this and other studies, and the benefits of detection and treatment of CD, screening is essential. Large-scale data collection allowing for the development of evidence-based guidelines is required.


Subject(s)
Celiac Disease/diagnosis , Celiac Disease/epidemiology , Diabetes Mellitus, Type 1/epidemiology , Practice Guidelines as Topic , Adolescent , Asymptomatic Diseases/epidemiology , Biopsy , Celiac Disease/pathology , Child , GTP-Binding Proteins/immunology , Humans , Immunoglobulin A/blood , Mass Screening , Prevalence , Protein Glutamine gamma Glutamyltransferase 2 , Retrospective Studies , Risk Factors , Transglutaminases/immunology
6.
Pediatrics ; 142(4)2018 10.
Article in English | MEDLINE | ID: mdl-30242075

ABSTRACT

BACKGROUND AND OBJECTIVES: Congenital hypothyroidism (CHT) is one of the most common preventable causes of learning disability. Newborn screening with whole-blood thyroid-stimulating hormone measurements was introduced in the Republic of Ireland in 1979 and is coordinated from a single center with an unchanged protocol since its inception. Our objective in this study was to describe the incidence of CHT in the Republic of Ireland over the past 37 years in the context of a complete national population and an unchanged screening protocol. METHODS: The newborn screening records of all individuals who were diagnosed with CHT between 1979 and 2016 were reviewed. Infants with positive screening results had a whole-blood thyroid-stimulating hormone value of ≥15 mU/L at 72 to 120 hours of life; values of 8 to 15 mU/L required a repeat whole-blood screening test. RESULTS: Of 2 361 174 infants who were screened between July 1979 and December 2016, 1063 (662 girls) were diagnosed with CHT (incidence: 0.45 cases per 1000 live births). The number of detected cases increased from 0.27 cases per 1000 live births treated between 1979 and 1991 to 0.41 cases per 1000 live births treated between 1992 and 2004 to 0.65 cases per 1000 live births treated between 2005 and 2016. The increase in detected cases of CHT was predominantly in the normal or hyperplastic gland category. CONCLUSIONS: The incidence of CHT has increased significantly in the Republic of Ireland over the past 37 years despite a consistent screening cutoff. The increased rate was not explained by an increased survival rate of preterm infants or a changing population heterogeneity.


Subject(s)
Congenital Hypothyroidism/blood , Congenital Hypothyroidism/epidemiology , Neonatal Screening/trends , Thyrotropin/blood , Congenital Hypothyroidism/diagnosis , Female , Humans , Incidence , Infant, Newborn , Ireland/epidemiology , Male , Neonatal Screening/methods , Prospective Studies
7.
Pediatr Diabetes ; 19(7): 1294-1301, 2018 11.
Article in English | MEDLINE | ID: mdl-30054967

ABSTRACT

BACKGROUND AND OBJECTIVE: Outcomes of using flash glucose monitoring have been reported in adults. This trial evaluated use in children and teenagers with type 1 diabetes. METHODS: Prospective, single arm, non-inferiority multicenter study to demonstrate equivalence of time in range (TIR [70-180 mg/dL]) by comparing 14-day masked sensor wear (baseline) with self-monitored blood glucose (SMBG) testing to the final 14-days of 8-week open-label system use for diabetes self-management including insulin dosing. RESULTS: A total of 76 children and teenagers (46.1% male; age 10.3 ± 4.0 years, type 1 diabetes duration 5.4 ± 3.7 years; mean ± SD) from 10 sites participated. TIR improved significantly by 0.9 ± 2.8 h/d (P = 0.005) vs SMBG baseline. Time in hyperglycemia (>180 mg/dL) reduced by -1.2 ± 3.3 h/d (P = 0.004). HbA1c reduced by -0.4% (-4.4 mmol/mol), from 7.9 ± 1.0% (62.9 ± 11.2 mmol/mol) baseline to 7.5 ± 0.9% (58.5 ± 9.8 mmol/mol) study end (P < 0.0001) with reductions across all age-subgroups (4-6, 7-12 and 13-17 years). Time in hypoglycemia (<70 mg/dL) was unaffected. Throughout the treatment phase system utilization was 91% ± 9; sensor scanning was 12.9 ± 5.7/d with SMBG dropping to 1.6 ± 1.9 from 7.7 ± 2.5/d. Diabetes Treatment Satisfaction Questionnaire "Total Treatment Satisfaction" score improved for parents (P < 0.0001) and teenagers (P < 0.0001). No adverse events (n = 121) were associated with sensor accuracy, 42 participants experienced sensor insertion signs and symptoms. Three participants experienced three mild device-related (sensor wear) symptoms, resolving quickly (without treatment [n = 2], non-prescription antihistamines [n = 1]). CONCLUSIONS: Children with diabetes improved glycemic control safely and effectively with short-term flash glucose monitoring compared to use of SMBG in a single arm study.


Subject(s)
Blood Glucose/analysis , Diabetes Mellitus, Type 1/blood , Wearable Electronic Devices/statistics & numerical data , Adolescent , Blood Glucose Self-Monitoring , Body Mass Index , Child , Child, Preschool , Female , Humans , Hypoglycemic Agents/administration & dosage , Insulin/administration & dosage , Male
8.
Horm Res Paediatr ; 89(4): 265-270, 2018.
Article in English | MEDLINE | ID: mdl-29804122

ABSTRACT

BACKGROUND: Congenital hypothyroidism (CHT) has a reported incidence of approximately 1 in 2,000-4,000 births. There is no consensus on the optimal cut-off whole-blood thyroid-stimulating hormone (TSH) concentration that should be used for newborn screening (NBS). The NBS programme in the Republic of Ireland has used a cut-off of 8 mU/L since 1979. The aim of this study was to determine if raising the cut-off to 10 mU/L would have resulted in undetected cases of permanent or decompensated CHT. METHODS: All cases of CHT with a screening whole-blood TSH concentration between 8.0 and 9.9 mU/L were identified from the Republic of Ireland's NBS programme. Baseline demographics and imaging results were recorded. All cases over 3 years of age were evaluated to determine if CHT was permanent or transient. RESULTS: Of 2,361,174 infants screened in the Republic of Ireland between July 1979 and December 2016, a total of 1,063 babies were diagnosed with CHT and treated with levothyroxine. This included 33 (3.5%) infants with a whole-blood TSH concentration between 8 and 9.9 mU/L. Thirteen of these 33 infants had decompensated hypothyroidism with low plasma free thyroxine level at diagnosis and 9 (41%) of the 21 evaluable cases have confirmed permanent CHT. CONCLUSION: Although lowering screening TSH cut-offs can increase the cost of NBS, as well as anxiety for families, many infants with borderline increases in whole-blood TSH concentrations on NBS have persistent CHT and low thyroxine concentrations in infancy. We recommend that this is considered when developing and reviewing NBS protocols for identifying infants with CHT.


Subject(s)
Congenital Hypothyroidism/blood , Congenital Hypothyroidism/diagnosis , Congenital Hypothyroidism/epidemiology , Thyrotropin/blood , Female , Humans , Infant, Newborn , Ireland , Male , Mass Screening , Retrospective Studies
9.
J Pediatr Endocrinol Metab ; 30(6): 623-628, 2017 May 24.
Article in English | MEDLINE | ID: mdl-28599389

ABSTRACT

BACKGROUND: Neonatal central diabetes insipidus (NCDI) remains a therapeutic challenge, as extremely low doses of enteral desmopressin cannot be titrated with current preparations. The aim of this study was to describe the use of orally administered dilute desmopressin in NCDI. METHODS: Nasal desmopressin (100 µg/mL) was diluted in 0.9% saline to 10 µg/mL. Infants were treated with 1-5 µg and doses were titrated to a twice-daily regimen. The feed volume was 150 mL/kg/day and titrated according to weight gain. RESULTS: Five infants aged 6-105 days were included. Stabilizing treatment doses ranged from 2 to 5 µg twice daily in neonates, and 12 µg twice daily in the older infant who was diagnosed at 105 days. CONCLUSIONS: Dilution of nasal desmopressin with saline facilitates safe administration and dose titration in NCDI. We recommend considering this therapeutic approach to NCDI, particularly in small infants or where alternative treatment regimens have been unsuccessful.


Subject(s)
Antidiuretic Agents/administration & dosage , Deamino Arginine Vasopressin/administration & dosage , Diabetes Insipidus/drug therapy , Administration, Intranasal , Administration, Oral , Female , Humans , Infant , Infant, Newborn , Male , Retrospective Studies , Treatment Outcome
10.
Eur J Pediatr ; 176(1): 137-142, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27826649

ABSTRACT

Haploinsufficiency of the insulin-like growth factor-1 receptor (IGF1R) gene on chromosome 15q26.3 is associated with impaired prenatal and postnatal growth, developmental delay, dysmorphic features and skeletal abnormalities. Terminal deletions of chromosome 15q26 arising more proximally may also be associated with congenital heart disease, epilepsy, diaphragmatic hernia and renal anomalies. We report three additional cases of 15q26 terminal deletions with novel features which may further expand the spectrum of this rarely reported contiguous gene syndrome. Phenotypic features including neonatal lymphedema, aplasia cutis congenita and aortic root dilatation have not been reported previously. Similarly, laboratory features of insulin-like growth factor 1 (IGF-1) resistance are described, including markedly elevated IGF-1 of up to +4.7 SDS. In one patient, the elevated IGF-1 declined over time and this coincided with a period of spontaneous growth acceleration. CONCLUSION: Deletions of 15q26 are a potential risk factor for aortic root dilatation, neonatal lymphedema and aplasia cutis in addition to causing growth restriction. What is Known: • Terminal deletions of chromosome 15q26 are associated with impaired prenatal and postnatal growth, developmental delay, dysmorphic features and skeletal abnormalities. What is New: • Neonatal lymphedema, aplasia cutis congenita and aortic root dilatation have not been previously described in 15q26 terminal deletions and may represent novel features. • IGF-1 levels may be increased up to 4.7 SDS.


Subject(s)
Chromosome Deletion , Chromosomes, Human, Pair 15/genetics , Developmental Disabilities/genetics , Growth Disorders/genetics , Haploinsufficiency , Insulin-Like Growth Factor I/analysis , Aortic Valve , Autism Spectrum Disorder/diagnosis , Bicuspid Aortic Valve Disease , Failure to Thrive/etiology , Female , Heart Defects, Congenital/genetics , Heart Valve Diseases/genetics , Humans , Infant, Newborn , Infant, Premature , Male
11.
BMJ Case Rep ; 20152015 Feb 26.
Article in English | MEDLINE | ID: mdl-25721834

ABSTRACT

A fatigued 8-year-old boy was found to have sideroblastic anaemia (haemoglobin 7.8 g/dL) which over time became transfusion dependent. Subtle neurological dysfunction, initially manifesting as mild spastic diplegia, was slowly progressive and ultimately led to wheelchair dependence. Elevated plasma lactate and urinary 3-methylglutaconate led to a muscle biopsy which confirmed partial complex IV deficiency. PCR in leucocytes and muscle was negative for mitochondrial DNA (mtDNA) deletions. Faltering growth prompted an insulin tolerance test which confirmed growth hormone sufficiency and adrenal insufficiency. Plasma renin was elevated and adrenal androgens were low, suggesting primary adrenal insufficiency. Glucocorticoid and mineralocorticoid replacement therapy was initiated. A renal tubular Fanconi syndrome and diabetes mellitus developed subsequently. Sideroblastic anaemia and primary adrenal insufficiency, both individually and collectively, are associated with mtDNA deletion; however, absence of the same does not exclude the possibility that sideroblastic anaemia and primary adrenal insufficiency are of mitochondrial origin.


Subject(s)
Adrenal Insufficiency/diagnosis , Anemia, Sideroblastic/diagnosis , DNA, Mitochondrial/genetics , Developmental Disabilities/diagnosis , Diabetes Mellitus/diagnosis , Fanconi Syndrome/diagnosis , Fatigue/etiology , Hormone Replacement Therapy , Adrenal Insufficiency/genetics , Adrenal Insufficiency/physiopathology , Anemia, Sideroblastic/genetics , Anemia, Sideroblastic/physiopathology , Child , Developmental Disabilities/etiology , Developmental Disabilities/physiopathology , Disabled Children , Fanconi Syndrome/physiopathology , Fructosamine/administration & dosage , Glucocorticoids/administration & dosage , Humans , Hypoglycemic Agents , Insulin Detemir/administration & dosage , Male , Mineralocorticoids/administration & dosage , Treatment Outcome
12.
Nat Genet ; 46(8): 812-814, 2014 Aug.
Article in English | MEDLINE | ID: mdl-25038750

ABSTRACT

Monogenic causes of autoimmunity provide key insights into the complex regulation of the immune system. We report a new monogenic cause of autoimmunity resulting from de novo germline activating STAT3 mutations in five individuals with a spectrum of early-onset autoimmune disease, including type 1 diabetes. These findings emphasize the critical role of STAT3 in autoimmune disease and contrast with the germline inactivating STAT3 mutations that result in hyper IgE syndrome.


Subject(s)
Autoimmune Diseases/genetics , Germ-Line Mutation , STAT3 Transcription Factor/genetics , Amino Acid Sequence , Cell Line , Genetic Predisposition to Disease , HEK293 Cells , Humans , Job Syndrome/genetics , Molecular Sequence Data , Sequence Homology, Amino Acid
13.
Clin Pediatr (Phila) ; 53(14): 1345-51, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25006113

ABSTRACT

BACKGROUND: Vitamin D has important skeletal and extraskeletal roles but those living at northerly latitudes are at risk of suboptimal levels because of reduced sunlight exposure. AIM: To describe the vitamin D status of Irish children and identify factors predictive of vitamin D status. METHODS: A prospective cross sectional study was undertaken over a 12 month period. Two hundred and fifty two healthy children attending for minor medical or surgical procedures were recruited. All had 25-hydroxyvitamin D (25OHD), parathyroid hormone and bone profiles measured. RESULTS: The mean (standard deviation) for 25OHD was 51(25) nmol/L (20.4 (10) ng/mL). Forty-five percent had levels >50 nmol/L (20 ng/mL). The following variables were significantly associated with 25OHD levels >50 nmol/L (20 ng/mL): sample drawn in April-September, use of vitamin D supplements, consumption of formula milk, and non-African ethnicity. CONCLUSION: More than half of the children in this study had 25OHD levels less than 50 nmol/L (20 ng/mL). Vitamin D status was significantly improved by augmented oral vitamin D intake.


Subject(s)
Diet , Dietary Supplements , Food, Fortified , Racial Groups/statistics & numerical data , Vitamin D Deficiency/epidemiology , Vitamin D/analogs & derivatives , Adolescent , Bone Density , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Infant , Ireland , Male , Parathyroid Hormone/blood , Prospective Studies , Seasons , Vitamin D/blood
14.
Br J Nutr ; 110(1): 156-63, 2013 Jul 14.
Article in English | MEDLINE | ID: mdl-23182428

ABSTRACT

Little is known about vitamin D status in preterm infants and their response to supplementation. To investigate this, we assessed serum 25-hydroxyvitamin D (25OHD) levels using RIA in a consecutive sample of stable preterm very low birth weight (VLBW) infants (born ≤ 32 weeks gestation or birth weight ≤ 1·5 kg), and we explored associated factors. Serum 25OHD level was first assessed once infants were tolerating feeds (n 274). If this first 25OHD level was below 50 nmol/l (20 ng/ml), which is the level associated with covering requirements in terms of skeletal health in the majority, then we recommended prolonged augmented vitamin D intake ( ≥ 10 µg (400 IU) daily) from a combination of fortified feeds and vitamin supplements and follow-up re-assessment at approximately 6 weeks corrected age (n 148). The first assessment, conducted at a median for chronological age of 18 (interquartile range (IQR) 11-28) d, found that 78 % had serum 25OHD levels below 50 nmol/l. Multivariable analysis demonstrated that the determinants of serum 25OHD levels were duration of vitamin D supplementation and gestational age at birth (r 2 0·215; P< 0·001). At follow-up, after a median of 104 (IQR 78-127) d, 87 % achieved levels ≥ 50 nmol/l and 8 % had levels >125 nmol/l, a level associated with potential risk of harm. We conclude that low 25OHD levels are an issue for preterm VLBW infants, warranting early nutritional intervention. In infants with serum 25OHD levels < 50 nmol/l, a vitamin D intake of ≥ 10 µg (400 IU) daily achieves target levels in the majority; however, further work is needed to determine the exact dose to safely meet target levels without overcorrection.


Subject(s)
Dietary Supplements , Infant, Premature/blood , Infant, Very Low Birth Weight/blood , Nutrition Assessment , Nutritional Status , Vitamin D Deficiency/prevention & control , Vitamin D/therapeutic use , Bone Density Conservation Agents/administration & dosage , Bone Density Conservation Agents/blood , Bone Density Conservation Agents/therapeutic use , Diet , Female , Food, Fortified , Gestational Age , Humans , Infant, Newborn , Male , Nutritional Requirements , Vitamin D/administration & dosage , Vitamin D/analogs & derivatives , Vitamin D/blood , Vitamin D Deficiency/blood , Vitamins/administration & dosage , Vitamins/blood , Vitamins/therapeutic use
16.
Pediatr Diabetes ; 7(1): 11-5, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16489969

ABSTRACT

OBJECTIVE: To ascertain whether initial depression of conscious level in children with diabetic ketoacidosis (DKA) is related to hyperosmolality, acidosis or other factors. METHODS: In 225 episodes of DKA without evidence of cerebral edema, we examined the relationship between conscious level and initial biochemical variables. We contrasted these findings with those in 42 children who later developed cerebral oedema. RESULTS: On admission, 42/225 (19%) had mild (pH 7.26-7.35); 96 (44%) moderate (pH 7.11-7.25); and 80 (37%) severe DKA (pH

Subject(s)
Blood Glucose/metabolism , Brain Edema/etiology , Consciousness/physiology , Diabetes Mellitus, Type 1/complications , Diabetic Ketoacidosis/physiopathology , Unconsciousness/physiopathology , Adolescent , Age Factors , Child , Child, Preschool , Diabetes Mellitus, Type 1/blood , Diabetic Ketoacidosis/classification , Diabetic Ketoacidosis/etiology , Female , Humans , Hydrogen-Ion Concentration , Infant , Male , Multivariate Analysis , Osmolar Concentration , Sodium Bicarbonate/blood , Unconsciousness/etiology
17.
Diabetes Care ; 26(3): 799-804, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12610040

ABSTRACT

OBJECTIVE: To compare blood glucose control and incidence of nocturnal hypoglycemia in adolescents with type 1 diabetes on multiple injection regimens managed with either an insulin analog combination or NPH insulin plus regular human insulin. RESEARCH DESIGN AND METHODS: In a randomized cross-over study, 28 adolescents with type 1 diabetes on multiple injection therapy received either insulin glargine prebedtime plus lispro preprandially (LIS/GLAR) or NPH insulin prebedtime plus regular human insulin preprandially (R/NPH). During each 16-week treatment arm, subjects completed home blood glucose profiles, and at the end of each treatment arm, they were admitted for an overnight metabolic profile. A total of 25 subjects completed the study. RESULTS: Compared with R/NPH therapy, LIS/GLAR was associated with lower mean blood glucose levels (LIS/GLAR versus R/NPH): fasting (8.0 vs. 9.2 mmol/l, P < 0.0001), 2 h postbreakfast (8.1 vs. 10.7 mmol/l, P < 0.0005), prelunch (8.9 vs. 10.1 mmol/l, P < 0.01), and 2 h postlunch (8.0 vs. 9.5 mmol/l, P < 0.002). However, there was no difference in mean blood glucose levels before or after the evening meal. Incidence of nocturnal hypoglycemia on overnight profiles was 43% lower on LIS/GLAR compared with R/NPH therapy; however, there was no difference in rates of self-reported symptomatic hypoglycemia. Total insulin dose required to achieve target blood glucose control was lower on LIS/GLAR (1.16 IU/kg) compared with R/NPH therapy (1.26 IU/kg, P < 0.005), but there was no significant difference in HbA(1c) levels (LIS/GLAR versus R/NPH: 8.7 vs. 9.1%, P = 0.13). CONCLUSIONS: Combination therapy with insulin glargine plus lispro reduced the incidence of nocturnal hypoglycemia and was at least as effective as R/NPH insulin therapy in maintaining glycemic control in adolescents on multiple injection regimens.


Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Hypoglycemic Agents/administration & dosage , Insulin, Isophane/administration & dosage , Insulin/analogs & derivatives , Insulin/administration & dosage , Adolescent , Blood Glucose/drug effects , Blood Glucose Self-Monitoring , Child , Cross-Over Studies , Drug Therapy, Combination , Female , Glycated Hemoglobin/analysis , Humans , Hypoglycemia/chemically induced , Hypoglycemic Agents/adverse effects , Insulin/adverse effects , Insulin Glargine , Insulin Lispro , Insulin, Isophane/adverse effects , Insulin, Long-Acting , Male
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