Maria E. Craig

Effects of angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists on mortality and renal outcomes in diabetic nephropathy: systematic review

Abstract Objective To evaluate the effects of angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists (AIIRAs) on renal outcomes and all cause mortality in patients with diabetic nephropathy. Data sources Medline, Embase, the Cochrane controlled trials register, conference proceedings, and contact with investigators. Study selection Trials comparing ACE inhibitors or AIIRAs with placebo or with each other in patients with diabetic nephropathy. Data extraction Mortality, renal outcomes (end stage renal disease, doubling of serum creatinine concentration, prevention of progression of microalbuminuria to macroalbuminuria, remission of microalbuminuria), and quality of trials. Data synthesis 36 of 43 identified trials compared ACE inhibitors with placebo (4008 patients), four compared AIIRAs with placebo (3331 patients), and three compared ACE inhibitors with AIIRAs (206 patients). We obtained unpublished data for 11 trials. ACE inhibitors significantly reduced all cause mortality (relative risk 0.79, 95% confidence interval 0.63 to 0.99) compared with placebo but AIIRAs did not (0.99, 0.85 to 1.17), although baseline mortality was similar in the trials. Both agents had similar effects on renal outcomes. Reliable estimates of the unconfounded relative effects of ACE inhibitors compared with AIIRAs could not be obtained owing to small sample sizes. Conclusion Although the survival benefits of ACE inhibitors for patients with diabetic nephropathy are known, the relative effects of ACE inhibitors and AIIRAs on survival are unknown owing to the lack of adequate head to head trials.

Enterovirus infection and type 1 diabetes mellitus: systematic review and meta-analysis of observational molecular studies.

Objective To review the association between current enterovirus infection diagnosed with molecular testing and development of autoimmunity or type 1 diabetes. Design Systematic review and meta-analysis of observational studies, analysed with random effects models. Data sources PubMed (until May 2010) and Embase (until May 2010), no language restrictions, studies in humans only; reference lists of identified articles; and contact with authors. Study eligibility criteria Cohort or case-control studies measuring enterovirus RNA or viral protein in blood, stool, or tissue of patients with pre-diabetes and diabetes, with adequate data to calculate an odds ratio and 95% confidence intervals. Results The 24 papers and two abstracts (all case-control studies) that met the eligibility criteria included 4448 participants. Study design varied greatly, with a high level of statistical heterogeneity. The two separate outcomes were diabetes related autoimmunity or type 1 diabetes. Meta-analysis showed a significant association between enterovirus infection and type 1 diabetes related autoimmunity (odds ratio 3.7, 95% confidence interval 2.1 to 6.8; heterogeneity χ2/df=1.3) and clinical type 1 diabetes (9.8, 5.5 to 17.4; χ2/df=3.2). Conclusions There is a clinically significant association between enterovirus infection, detected with molecular methods, and autoimmunity/type 1 diabetes. Larger prospective studies would be needed to establish a clear temporal relation between enterovirus infection and the development of autoimmunity and type 1 diabetes.

Definition, epidemiology and classification of diabetes in children and adolescents

Diabetes mellitus is a group of metabolic diseases characterised by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The abnormalities in carbohydrate, fat, and protein metabolism that are found in diabetes are due to deficient action of insulin on target tissues. If ketones are present in blood or urine, treatment is urgent, because ketoacidosis can evolve rapidly.

Diabetic ketoacidosis in children and adolescents with diabetes

aDivision of Endocrinology, Children’s Hospital Boston, MA, USA; bSchool of Women’s and Children’s Health, University of New South Wales, Sydney, Australia; cUniversity of Toronto, The Hospital for Sick Children, Toronto, Canada; dDepartment of Paediatrics, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK; eDepartment of Paediatrics, John Radcliffe Hospital, Oxford, UK; fEndocrinology Service Department of Paediatric Medicine, KK Children’s Hospital, Singapore; gDivision of Endocrinology, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA; hDepartment of Pediatric Endocrinology, Children’s Hospital, University of Pittsburgh, PA, USA; iDepartment of Pediatrics, Uddevalla Hospital, Uddevalla, Sweden

ISPAD Clinical Practice Consensus Guidelines 2014. Assessment and monitoring of glycemic control in children and adolescents with diabetes.

Marian J Rewersa, Kuben Pillayb, Carine de Beaufortc, Maria E Craigd, Ragnar Hanase, Carlo L Acerinif and David M Maahsa aBarbara Davis Center, University of Colorado Denver, Aurora, CO, USA; bWestville Hospital, Durban, South Africa; cDECCP, Clinique Pediatrique/CHL, Luxembourg, Luxembourg; dInstitute of Endocrinology and Diabetes, Westmead, Australia; eDepartment of Pediatrics, Uddevalla Hospital, Uddevalla, Sweden and fDepartment of Pediatrics, University of Cambridge, Cambridge, UK

Vitamin D, PTH and calcium levels in pregnant women and their neonates.

Objectives  To determine the prevalence of vitamin D deficiency in pregnant women and their neonates and to examine factors associated with vitamin D deficiency.

The re-emerging burden of rickets: a decade of experience from Sydney

Aim: To define the demographics and clinical characteristics of cases presenting with nutritional rickets to paediatric centres in Sydney, Australia. Methods: Retrospective descriptive study of 126 cases seen from 1993 to 2003 with a diagnosis of vitamin D deficiency and/or confirmed rickets defined by long bone x ray changes. Results: A steady increase was seen in the number of cases per year, with a doubling of cases from 2002 to 2003. Median age of presentation was 15.1 months, with 25% presenting at less than 6 months of age. The most common presenting features were hypocalcaemic seizures (33%) and bowed legs (22%). Males presented at a younger age, with a lower weight SDS, and more often with seizures. The caseload was almost exclusively from recently immigrated children or first generation offspring of immigrant parents, with the region of origin predominantly the Indian subcontinent (37%), Africa (33%), and the Middle East (11%). Seventy nine per cent of the cases were born in Australia. Eleven cases (all aged <7 months) presented atypically with hyperphosphataemia. Conclusions: This large case series shows that a significant and increasing caseload of vitamin D deficiency remains, even in a developed country with high sunlight hours. Cases mirror recent immigration trends. Since birth or residence in Australia does not appear to be protective, screening of at risk immigrant families should be implemented through public health policies.

Diabetic ketoacidosis and hyperglycemic hyperosmolar state

aDivision of Endocrinology, Boston Children’s Hospital, Boston, MA, USA; bBarts Health NHS Trust, Royal London Hospital, London, UK; cInstitute of Endocrinology and Diabetes, The Children’s Hospital at Westmead; School of Women’s and Children’s Health, University of New South Wales, Sydney, Australia; dOxfordshire Children’s Diabetes Service, Oxford Children’s Hospital, Oxford, UK; eSection of Endocrinology, University of California, Davis School of Medicine, Sacramento, CA, USA; fPediatric Endocrinology Division, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India; gEndocrinology Service, Department of Paediatrics, KK Women’s and Children’s Hospital, Singapore; hDepartment of Paediatrics and Child Health, University of Nairobi, Nairobi, Kenya ; iDepartment of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA; jDivision of Endocrinology, Diabetes and Metabolism, Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA and kDepartment of Pediatrics, NU Hospital Group, Uddevalla and Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden

Growth Hormone Research Society Workshop Summary: Consensus Guidelines for Recombinant Human Growth Hormone Therapy in Prader-Willi Syndrome

Context: Recombinant human GH (rhGH) therapy in Prader-Willi syndrome (PWS) has been used by the medical community and advocated by parental support groups since its approval in the United States in 2000 and in Europe in 2001. Its use in PWS represents a unique therapeutic challenge that includes treating individuals with cognitive disability, varied therapeutic goals that are not focused exclusively on increased height, and concerns about potential life-threatening adverse events. Objective: The aim of the study was to formulate recommendations for the use of rhGH in children and adult patients with PWS. Evidence: We performed a systematic review of the clinical evidence in the pediatric population, including randomized controlled trials, comparative observational studies, and long-term studies (>3.5 y). Adult studies included randomized controlled trials of rhGH treatment for ≥ 6 months and uncontrolled trials. Safety data were obtained from case reports, clinical trials, and pharmaceutical registries. Methodology: Forty-three international experts and stakeholders followed clinical practice guideline development recommendations outlined by the AGREE Collaboration (www.agreetrust.org). Evidence was synthesized and graded using a comprehensive multicriteria methodology (EVIDEM) (http://bit.ly.PWGHIN). Conclusions: Following a multidisciplinary evaluation, preferably by experts, rhGH treatment should be considered for patients with genetically confirmed PWS in conjunction with dietary, environmental, and lifestyle interventions. Cognitive impairment should not be a barrier to treatment, and informed consent/assent should include benefit/risk information. Exclusion criteria should include severe obesity, uncontrolled diabetes mellitus, untreated severe obstructive sleep apnea, active cancer, or psychosis. Clinical outcome priorities should vary depending upon age and the presence of physical, mental, and social disability, and treatment should be continued for as long as demonstrated benefits outweigh the risks.

Definition, epidemiology, and classification of diabetes in children and adolescents: Definition, epidemiology, and classification of diabetes

Maria E Craiga,b, Craig Jefferiesc, Dana Dabelead, Naby Baldee, Anju Sethf and Kim C Donaghuea aInstitute of Endocrinology and Diabetes, The Children’s Hospital at Westmead and University of Sydney, Sydney, Australia; bSchool of Women’s and Children’s Health, University of New South Wales, Sydney, Australia; cPaediatric Endocrinology, Starship Children’s Hospital, Auckland, New Zealand; dDepartment of Epidemiology, Colorado School of Public Health, University of Colorado, Aurora, CO, USA; eDepartment of Endocrinology, University Hospital, Conakry, Guinea and fLady Hardinge Medical College, New Delhi, India