Diabetic ketoacidosis in an adolescent and young adult population in the UK in 2014: a national survey comparison of management in paediatric and adult settings:Special Issue on Diabetes and Childhood

Aims: To assess the management of diabetic ketoacidosis in young people, which differs in the UK between paediatric and adult services, and to evaluate outcomes and extent to which national guidelines are used. Methods: A standardized questionnaire was sent to all paediatric and adult diabetes services in England, requesting details of all diabetic ketoacidosis admissions in young people aged > 14 years in paediatric services (‘paediatric’ patients), and in young adults up to the age of 22 years in adult services (‘adult’ patients). Results: A total of 64 adult patients aged ≤ 22 years (mean age 19.2 years) were reported, of whom seven were aged between 10 and 16 years. A total of 71 paediatric patients were reported [mean (range) age 14.9 (11–18) years]. We found that 85% of paediatric and 69% of adult patients were treated according to national guidelines, 99% of paediatric and 89% of adult patients were treated with 0.9% saline and fixed-rate insulin infusions and 16% of adult patients received an insulin bolus. Insulin treatment was initiated later in paediatric patients than in adult patients (100 vs 39 min; P < 0.001). In 23% of adult patients and 8.8% of paediatric patients, potassium levels were < 3.5 mmol/l (P < 0.005). The lowest mean potassium levels were 3.8 mmol/l in paediatric and 3.5 mmol/l in adult patients (P < 0.005). Hypoglycaemia occurred in 42.3% of paediatric and 36% of adult patients. Time to resolution was similar in paediatric and adult patients (16.0 vs 18.2 h), as was duration of hospital stay (2.35 vs 2.53 days). Conclusions: Young people were treated according to national guidelines, but the quality of monitoring was variable in both paediatric and adult settings. The incidence of hypoglycaemia and hypokalaemia was unacceptably high

The cost of treating diabetic ketoacidosis in the UK: a national survey of hospital resource use

Aims: Diabetic ketoacidosis (DKA) is a commonly encountered metabolic emergency. In 2014 a national survey was conducted looking at the management of DKA in adult patients across the UK. The survey reported the clinical management of individual patients as well as institutional factors that teams felt were important in helping to deliver that care. However, costs of treating DKA were not reported. Methods: We used a ‘bottom up’ approach to cost analysis to determine the total expense associated with treating DKA in a mixed population sample. The data were derived from the source data from the national UK survey of 283 individual patients collected via questionnaires sent to hospitals across the country. Results: Because the initial survey collection tool was not designed with a health economic model in mind, several assumptions were made when analysing the data. The mean and median time in hospital was 5.6 and 2.7 days, respectively. Based on the individual patient data and using the Joint British Diabetes Societies Inpatient Care Group guidelines, the cost analysis shows that for this cohort, the average cost for an episode of DKA was £2064 per patient (95% CI: £1800, 2563). Conclusion: Despite relatively short stays in hospital, costs for managing episodes of DKA in adults were relatively high. Assumptions made in calculations did not take into account prolonged hospital stay due to co-morbidities nor costs incurred as a loss of productivity. Therefore the actual costs to the healthcare system and society in general are likely to be substantially higher

Cerebral Blood Flow and Cerebral Edema in Rats With Diabetic Ketoacidosis

OBJECTIVE— Cerebral edema (CE) is a potentially life-threatening complication of diabetic ketoacidosis (DKA) in children. Osmotic fluctuations during DKA treatment have been considered responsible, but recent data instead suggest that cerebral hypoperfusion may be involved and that activation of cerebral ion transporters may occur. Diminished cerebral blood flow (CBF) during DKA, however, has not been previously demonstrated. We investigated CBF and edema formation in a rat model of DKA and determined the effects of bumetanide, an inhibitor of Na-K-Cl cotransport

A randomized controlled trial comparing intravenous ferric carboxymaltose with oral iron for treatment of iron deficiency anaemia of non-dialysis-dependent chronic kidney disease patients

Background. Iron deficiency is a common cause of anaemia and hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) in non-dialysis-dependent chronic kidney disease (ND-CKD) patients. Current intravenous iron agents cannot be administered in a single high dose because of adverse effects. Ferric carboxymaltose, a non-dextran parenteral iron preparation, can be rapidly administered in high doses

Specific Thiazolidinediones Inhibit Ovarian Cancer Cell Line Proliferation and Cause Cell Cycle Arrest in a PPARγ Independent Manner

Peroxisome Proliferator Activated Receptor gamma (PPARγ) agonists, such as the thiazolinediones (TZDs), have been studied for their potential use as cancer therapeutic agents. We investigated the effect of four TZDs--Rosiglitazone (Rosi), Ciglitazone (CGZ), Troglitazone (TGZ), and Pioglitazone (Pio)--on ovarian cancer cell proliferation, PPARγ expression and PPAR luciferase reporter activity. We explored whether TZDs act in a PPARγ dependent or independent manner by utilizing molecular approaches to inhibit or overexpress PPARγ activity.Treatment with CGZ or TGZ for 24 hours decreased proliferation in three ovarian cancer cell lines, Ovcar3, CaOv3, and Skov3, whereas Rosi and Pio had no effect. This decrease in Ovcar3 cell proliferation was due to a higher fraction of cells in the G(0)/G(1) stage of the cell cycle. CGZ and TGZ treatment increased apoptosis after 4 hours of treatment but not after 8 or 12 hours. Treatment with TGZ or CGZ increased PPARγ mRNA expression in Ovcar3 cells; however, protein levels were unchanged. Surprisingly, luciferase promoter assays revealed that none of the TZDs increased PPARγ activity. Overexpression of wild type PPARγ increased reporter activity. This was further augmented by TGZ, Rosi, and Pio indicating that these cells have the endogenous capacity to mediate PPARγ transactivation. To determine whether PPARγ mediates the TZD-induced decrease in proliferation, cells were treated with CGZ or TGZ in the absence or presence of a dominant negative (DN) or wild type overexpression PPARγ construct. Neither vector changed the TZD-mediated cell proliferation suggesting this effect of TZDs on ovarian cancer cells may be PPARγ independent.CGZ and TGZ cause a decrease in ovarian cancer cell proliferation that is PPARγ independent. This concept is supported by the finding that a DN or overexpression of the wild type PPARγ did not affect the changes in cell proliferation and cell cycle

Understanding renal posttransplantation anemia in the pediatric population

Advances in renal transplantation management have proven to be beneficial in improving graft and patient survival. One of the properties of a well-functioning renal allograft is the secretion of adequate amounts of the hormone erythropoietin to stimulate erythropoiesis. Posttransplantation anemia (PTA) may occur at any point in time following transplantation, and the cause is multifactoral. Much of our understanding of PTA is based on studies of adult transplant recipients. The limited number of studies that have been reported on pediatric renal transplant patients appear to indicate that PTA is prevalent in this patient population. Erythropoietin deficiency or resistance is commonly associated with iron deficiency. An understanding of the risk factors, pathophysiology and management of PTA in the pediatric renal transplant population may provide guidelines for clinicians and researchers in the pursuit of larger prospective randomized control studies aimed at improving our limited knowledge of PTA. Recognition of PTA through regular screening and evaluation of the multiple factors that may contribute to its development are recommended after transplantation