UK service level audit of insulin pump therapy in paediatrics.

AIM: To conduct an audit of insulin pump therapy in the UK after the issue of guidelines for the use of continuous subcutaneous insulin infusion by NICE in 2008 (Technology Appraisal 151). METHODS: All centres in the UK, providing pump services to children and young people were invited to participate in an online audit. Audit metrics were aligned to NICE Technology Appraisal 151 and an electronic data collection tool was used. RESULTS: Of the 176 UK centres identified as providing pump services, 166 (94.3%) participated in the study. A total of 5094 children and young people were identified as using continuous subcutaneous insulin infusion (19% of all paediatric patients with Type 1 diabetes), with a median (range) of 16.9 (0.67-69.4)% per centre. Units had a median of 0.58 consultant sessions, 0.43 full-time equivalent diabetic specialist nurses, and 0.1 full-time equivalent dieticians delivering the pump service. The majority of this time was not formally funded. Families could access 24-h clinical and technical support (83% units), although the delivery varied between consultant, diabetic specialist nurse and company representatives. Only 53% of units ran, or accessed, structured education programmes for continuous subcutaneous insulin infusion use. Most units (86%) allowed continuous subcutaneous insulin infusion use for paediatric inpatients, but only 56% had written guidelines for this scenario. Nine percent of units had encountered funding refusal for a patient fulfilling NICE (Technology Appraisal 151) criteria. CONCLUSION: The number of children and young people on continuous subcutaneous insulin infusion therapy is consistent with numbers estimated by NICE. There is a worrying lack of funded healthcare professional time. The audit also identified gaps in the provision of structured education and absence of written inpatient guidelines.

The U.K. service level audit of insulin pump therapy in adults.

AIMS: The National Institute for Health and Clinical Excellence (NICE) published guidelines for the use of continuous subcutaneous insulin infusion in 2008 (technology appraisal 151). The first U.K.-wide insulin pump audit took place in 2012 with the aim of determining adherence to the guidance issued in NICE technology appraisal 151. The results of the adult service level audit are reported here. METHODS: All centres providing continuous subcutaneous insulin infusion services to adults with diabetes in the U.K. were invited to participate. Audit metrics were aligned to technology appraisal 151. Data entry took place online using a DiabetesE formatted data collection tool. RESULTS: One hundred and eighty-three centres were identified as delivering adult continuous subcutaneous insulin infusion services in the U.K., of which 178 (97.3%) participated in the audit. At the time of the audit, 13 428 adults were using insulin pump therapy, giving an estimated prevalence of use of 6%. Ninety-three per cent of centres did not report any barriers in obtaining funding for patients who fulfilled NICE criteria. The mean number of consultant programmed activities dedicated to continuous subcutaneous insulin infusion services was 0.96 (range 0-8), mean whole-time equivalent diabetes specialist nurses was 0.62 (range 0-3) and mean whole-time equivalent dietitian services was 0.3 (range 0-2), of which 39, 61 and 60%, respectively, were not formally funded. CONCLUSIONS: The prevalence of continuous subcutaneous insulin infusion use in the U.K. falls well below the expectation of NICE (15-20%) and that of other European countries (> 15%) and the U.S.A. (40%). This may be attributable, in part, to lack of healthcare professional time needed for identification and training of new pump therapy users.

The role of continuous subcutaneous insulin infusion therapy in patients with diabetic gastroparesis.

AIMS/OBJECTIVE: To describe the effectiveness of continuous subcutaneous insulin infusion (CSII) in patients with symptomatic diabetic gastroparesis and unstable glycaemic control. METHODS: Data from 26 patients with symptomatic diabetic gastroparesis and unstable glycaemic control using multiple-dose insulin (MDI) regimens, and subsequently managed with CSII, were analysed. RESULTS: Following initiation of CSII, the median length of inpatient bed days associated with hospital admissions related to gastroparesis and glycaemic instability was reduced from 8.5 (range 0-144) days patient( -1) year( -1) prior to CSII to 0 (range 0-15) days patient( -1) year( -1). The median HbA(1c) reduction with CSII was 1.8% (22 mmol/mol; p < 0.05). The median capillary blood glucose (CBG) with CSII was significantly lower than with MDI: 7.7 mmol/l (range 3.8-15.4 mmol/l) vs 9.8 mmol/l (range 2.3-27 mmol/l), respectively, p < 0.001. Glycaemic variability with CSII was significantly reduced compared with MDI: CBG CV 0.37 vs CV 0.53, respectively, p < 0.001. CONCLUSIONS/INTERPRETATION: CSII therapy in patients with diabetic gastroparesis results in significant improvement in glycaemic control and reductions in glycaemic variability and number of hospital inpatient bed days.

Cardiac arrhythmia and nocturnal hypoglycaemia in type 1 diabetes--the 'dead in bed' syndrome revisited.

AIMS/HYPOTHESIS: Sudden nocturnal death in type 1 diabetes ('dead in bed' syndrome) is thought to be due to ECG QT prolongation with subsequent ventricular tachyarrhythmia in response to nocturnal hypoglycaemia. We investigated this theoretical mechanism using continuous ECG and continuous glucose monitoring in a group of patients with type 1 diabetes. METHODS: Twenty-five patients with type 1 diabetes (age 20-50 years) underwent two separate 24 h ECG and continuous glucose monitoring periods. Patients were fully ambulant and carried out normal daily activities. RESULTS: There were 13 episodes (26% of recordings) of nocturnal hypoglycaemia, eight of <2.2 mmol/l and five of 2.2-3.4 mmol/l. Corrected QT interval (QTc) was longer during nocturnal hypoglycaemia compared with normoglycaemic control periods (445 +/- 40 vs 415 +/- 23 ms; p = 0.037). Cardiac rate and rhythm disturbances (excluding sinus tachycardia) were seen in eight of the 13 nocturnal hypoglycaemia episodes (62%). These were sinus bradycardia (<40 beats/min; three episodes), ventricular ectopics (three episodes), atrial ectopics (one) and P wave abnormalities (one). CONCLUSIONS/INTERPRETATION: This study demonstrates QTc prolongation and cardiac rate/rhythm disturbances in response to episodes of nocturnal hypoglycaemia in ambulant patients with type 1 diabetes. This may support an arrhythmic basis for the 'dead in bed' syndrome.

Monochorionic diamniotic minimally conjoined twins: a case report.

We present the second case of monochorionic diamniotic (MC/DA) conjoined twins. There was minimal conjunction, which was predominantly extrafetal and confined to the periumbilical ventral region. The omphalopagus twins, attached to a single forked umbilical cord, were connected by a shared umbilical hernia containing the ileum of twin B. The only visceral conjunction, located just within the belly of twin A, was midileal with the 2 separate ileums converging toward a short segment of shared muscularis propria and of side-to-side fistulization. Gastrointestinal and musculoskeletal anomalies were present in both twins with severe amyoplasia and arthrogryposis multiplex in twin A. Possible mechanisms underlying this unusual form of MZ twinning are discussed.

Can abnormalities of ventricular repolarisation identify insulin dependent diabetic patients at risk of sudden cardiac death?

OBJECTIVE: To study the possible association or QT dispersion and mean QTc intervals, as measured from standard 12 lead electrocardiograms, with baroreceptor-cardiac reflex sensitivity (BRS) in insulin dependent diabetic patients. DESIGN: Comparative study of non-invasive assessment of BRS, QT interval, and QT dispersion. SETTING: Large teaching hospital. SUBJECTS: 31 young asymptomatic, normotensive, insulin dependent diabetic patients, aged 20-55 years with normal clinical autonomic function. METHODS: QT intervals and QT dispersion were measured by a single observer blinded to other data about the patients. BRS was measured after activating the baroreflex with a Valsalva manoeuvre, and the rate in change of R-R interval to increasing systolic pressure during phase 4 was measured; in addition sequence analysis of resting systolic blood pressure and heart rate was performed during standing. The alpha coefficient--an index of the overall gain of the baroreflex mechanisms--was estimated from spectral analysis data of systolic blood pressure and pulse interval variability. RESULTS: Mean (SD) QTc interval was 406 (23) ms, QT dispersion was 44 (13) ms. There was no association between QT dispersion and any measurement of BRS. There was a negative correlation between mean QTc intervals and sequence analysis BRS (r = -0.355, P = 0.049), but no association with Valsalva BRS. The alpha coefficient, showed a significant negative correlation with mean QTc (r = -0.42, P = 0.008). CONCLUSIONS: Abnormal BRS may be reflected in the heart by global prolongation of ventricular repolarisation, but not by dispersion of ventricular repolarisation. This may, in part, explain the increase in sudden cardiac death seen in IDDM patients.

Reproducibility of the circadian blood pressure fall at night in healthy young volunteers.

The aim of this study was to evaluate the reproducibility of the circadian blood pressure (BP) change in normal healthy volunteers. The subjects were 32 healthy, young, normotensive volunteers who underwent 24 h ambulatory BP monitoring on two occasions, at least 4 weeks apart. Data were analysed using standard definitions of day and night (i.e. 07.00-22.00 for daytime and 22.00-07.00 for night time), event diaries to identify individual's day and night time and a time independent method (cusum analysis). Intraindividual variations of BP were assessed using the coefficient of variation (CV). The mean 24 h BP was very reproducible with a CV of 4.7%. Using the fixed definition of day and night, mean night time systolic blood pressure (SBP) was significantly reduced on the second visit compared to the first (P < 0.001). Using fixed times for day and night, day-night difference was poorly reproducible, with a CV of 52% for SBP and 59% for diastolic blood pressure (DBP), however this improved using diary based day-night to 40/41% and cusum analysis to 24.6/28.1%. We recommend that circadian BP changes are studied using individual definitions of day and night or time independent methods such as cusum analysis.

Evidence of defective cardiovascular regulation in insulin-dependent diabetic patients without clinical autonomic dysfunction.

(1) Autonomic dysfunction is a well recognised complication of diabetes mellitus and early detection may allow therapeutic manoeuvres to reduce the associated mortality and morbidity. We sought to identify early cardiovascular autonomic neuropathy using spectral analysis of heart rate and systolic blood pressure variability. (2) Thirty patients with Type 1 (insulin-dependent) diabetes mellitus (DM) and 30 matched control subjects were studied. In addition to standard tests of autonomic function, heart rate and systolic blood pressure variability were assessed using power spectral analysis. From the frequency domain analysis of systolic blood pressure and R-R interval, the overall gain of baroreflex mechanisms was assessed. (3) Standard tests of autonomic function were normal in both groups. Total spectral power of R-R interval was reduced in the Type 1 DM group for low-frequency (473 +/- 63 vs. 747 +/- 78 ms2, mean +/- S.E.M., P = 0.002) and high-frequency bands (125 +/- 13 vs. 459+/-90 ms2, P < 0.0001). Systolic blood pressure low-frequency power was increased in the diabetic group (9.3 +/- 1.2 vs. 6.6+/-0.7 mmHg2, P < 0.05). The low frequency/high frequency ratio for heart rate variability was significantly higher in the Type 1 DM patients (4.6+/-0.5 vs. 2.9+/-0.5, P = 0.002), implying a relative sympathetic predominance. When absolute powers were expressed in normalised units, these differences persisted. There were significant reductions in baroreceptor-cardiac reflex sensitivity in Type 1 DM patients compared to controls while supine (9.7+/-0.7 vs. 18.5 +/- 1.7 ms/mmHg, P < 0.0001) and standing (2.9+/-0.9 vs. 7.18+/-1.9 ms/mmHg, P < 0.001). (4) Spectral analysis of cardiovascular variability detects autonomic dysfunction more frequently in Type 1 DM patients than conventional tests, and is suggestive of an abnormality of parasympathetic function. The abnormality of baroreceptor-cardiac reflex sensitivity could be explained by this impairment of parasympathetic function and this may predispose to the development of hypertension and increase the risk of sudden cardiac death. Using spectral analysis methods may allow detection of early diabetic cardiac autonomic neuropathy and allow therapeutic intervention to slow the progression.

Randomised trial of dopamine compared with hydrocortisone for the treatment of hypotensive very low birthweight infants.

AIM: To compare the efficacy of hydrocortisone with dopamine for the treatment of hypotensive, very low birthweight (VLBW) infants. METHODS: Forty infants were randomly allocated to receive either hydrocortisone (n = 21) or dopamine (n = 19). RESULTS: All 19 infants randomised to dopamine responded; 17 of 21 (81%) did so in the hydrocortisone group. Three of the four non-responders in the hydrocortisone group had clinically significant left to right ductal shunting. The incidence of bronchopulmonary dysplasia, retinopathy of prematurity, intraventricular haemorrhage, necrotising enterocolitis, symptomatic patent ductus arteriosus, hyperglycaemia, sepsis (bacterial or fungal) or survival did not differ between groups. The adrenocorticotrophic hormone (ACTH) stimulated plasma cortisol activity, either before or after treatment, did not differ between the two groups of infants. Although a significant difference in efficacy between dopamine and hydrocortisone was not noted (P = 0.108), there were four treatment failures in the hydrocortisone group, compared with none in the dopamine group. CONCLUSION: Both hydrocortisone and dopamine are effective treatments for hypotension in very low birthweight infants.

Postneonatal mortality in a cohort of very low birthweight infants.

A cohort of very low birthweight (VLBW) infants (ie, less than 1500 g) who were admitted to the newborn unit, Waikato Hospital between 1984 and 1988 were followed to the age of 12 months. Four hundred and twenty-five infants were admitted with 385 surviving the neonatal period. A further 29 infants died in the postneonatal period (68.2 per 1000 livebirths). Sixteen of the infants died during their initial hospitalisation - primarily from complications of prematurity, while the remaining 13 died following discharge from hospital (9 from sudden infant death syndrome). The postneonatal mortality rate was 3-5 fold greater than that described in similar studies, reflecting the generally increased rate in New Zealand and a lower neonatal mortality rate. The duration of mechanical ventilation was associated with an increased risk of postneonatal death, but no risk factors for posthospital discharge death could be identified.

Mothers of babies enrolled in a randomized trial immediately after birth report a positive experience.

OBJECTIVE: Randomized trials are essential for improving outcomes, but researchers can be hesitant about undertaking clinical trials in newborn babies because of perceived vulnerability of the baby and risk of increasing parental anxiety. There is a paucity of evidence about the parental experience. We investigated mothers' experiences of having their newborn baby participate in a randomized double-blind placebo-controlled trial soon after birth. STUDY DESIGN: Eligible mothers had consented to their baby's participation in the Sugar Babies Study. Mothers of potentially eligible babies were invited to join the study antenatally, but others were approached postnatally. Babies were enrolled in the study soon after birth and remained in the study for 48 h. After 2 weeks the birth mothers were interviewed by phone about their experience. RESULT: Four hundred and eighty-one mothers were enrolled, of whom 310 (64%) gave consent antenatally. All mothers were contacted and 477 (99%) were interviewed. The majority of mothers (458, 96%) reported they would consent to participating again, if they had another eligible baby, and 460 mothers (96%) reported they would recommend participation to family and friends. Nineteen mothers (4%) reported they did not like the heel lance blood tests, which were part of routine clinical care and not part of the trial protocol. CONCLUSION: Most mothers reported the experience of having their newborn baby participate in a clinical trial as positive. Most negative responses were related to aspects of routine care rather than the trial protocol.

Feasibility and safety of early transfer of premature infants from incubators to cots: a pilot study.

OBJECTIVES: To document whether medically stable infants can be transferred safely from incubators to unheated, open cots at 1500 g. METHODS: Four cohorts were recruited in a stepwise observational trial of transfer from incubators to unheated, open cots. We aimed to transfer the first 15 infants into cots on reaching a weight of 1800 g, the second at 1700 g, the third at 1600 g and the fourth at 1500 g. Nursery temperatures were set at 25 degrees C. The primary outcome measure was failure of transfer defined as the inability to maintain body temperatures in a cot despite additional coverings, with two consecutive axillary temperatures below 36.6 degrees C 1 h apart. Secondary aims were to determine temperature stability, growth, medical complications and time to discharge for these infants. Weight and corrected gestation at discharge were recorded. RESULTS: A total of 61 infants were recruited and transferred into cots. Cohorts were similar in gestation and sex. Infants recruited to the 1500 g cohort had higher birthweights than the other cohorts. There was no difference in the rate of infants failing transfer into cots between cohorts. Rate of weight gain before and after transfer and the number of high and low temperatures per infant after transfer was not different between cohorts. There were no differences between cohorts for discharge weight or corrected gestation. CONCLUSIONS: The results of this pilot study indicate the potential to transfer very low birthweight infants to an open unheated cot at a bodyweight of 1500 g. This study provides information for the design of future randomized controlled trials that are required to confirm the findings of this study before routine adoption of this intervention into clinical practice.

Non islet cell tumor hypoglycaemia in a metastatic Leydig cell tumor.

Non islet cell tumour hypoglycaemia (NICTH) is a rare cause of hypoglycaemia associated with malignancy and can be considered as a paraneoplastic syndrome. The hormonal factor associated with this condition is big IGF II, which exerts negative feedback effect and decreases the production of growth hormone and insulin. Due to low growth hormone levels, hepatic production of IGFBP 3 (the main binding protein of IGF II) is impaired. Excess free big IGF II is thus available for binding with insulin receptors to cause hypoglycaemia. Treatment options are either surgical removal of the tumour, administration of growth hormone, glucocorticoids or combination of treatments. A case of metastatic Leydig cell tumour causing NICTH has been discussed and the mechanism of NICTH hypoglycaemia and the treatment is outlined.

The effect of dexamethasone upon platelets and neutrophils of preterm infants with chronic lung disease.

The effect of a 21-day (reducing dose) course of dexamethasone upon platelet numbers, neutrophil numbers and neutrophil morphology in ventilator-dependent preterm infants with chronic lung disease is reported. Forty-one infants, who were sepsis-free throughout the treatment period, received 46 courses of dexamethasone. In these infants the circulating platelet count increased significantly from 235 +/- 157 to 476 +/- 208 X 10(9)/L. Both total neutrophil numbers (7.94 +/- 7.16 to 19.56 +/- 12.40 X 10(9)/L) and immature neutrophil numbers (1.19 +/- 1.22 to 2.68 +/- 2.58 X 10(9)/L) also showed a significant increase reaching a peak on day 7 of treatment and decreasing thereafter. The immature:total (I:T) neutrophil ratio remained essentially unchanged. Eight other infants who developed serious sepsis during the treatment period showed a fall in both platelets (293 +/- 236 to 140 +/- 170 X 10(9)/L) and total neutrophil numbers (18.61 +/- 10.83 to 15.76 +/- 10.53 X 10(9)/L), together with an increase in immature neutrophils (2.30 +/- 2.80 to 8.22 +/- 13.91 X 10(9)/L) and consequent increase in I:T ratio.

Is undetected autonomic dysfunction responsible for sudden death in Type 1 diabetes mellitus? The 'dead in bed' syndrome revisited.

AIMS: Sudden nocturnal death in young persons with Type 1 diabetes mellitus has been recently described, and is known as the 'dead in bed' syndrome. Its aetiology is unknown, and we have therefore explored the details of all papers recording the syndrome, to formulate a hypothesis of causation. METHODS: Literature review of 'dead in bed' reports as well as of nocturnal hypoglycaemia, and autonomic dysfunction in relation to baroreceptor-cardiac reflex sensitivity. RESULTS: Clinical reports of 'dead in bed' cases strongly suggest that nocturnal hypoglycaemia is a likely precipitant, but that the death is sudden and probably arrhythmic. Ventricular dysrhythmias may occur in the context of early autonomic neuropathy, with relative sympathetic overactivity, in young Type 1 diabetic persons. CONCLUSION: We conclude that the 'dead in bed' syndrome probably occurs in Type 1 diabetic persons with early autonomic neuropathy, resulting in relative sympathetic overactivity. In such persons, risks of ventricular dysrhythmias will be compounded by nocturnal hypoglycaemia, which may be associated with an increase in the electrocardiographic Q-T interval, and Q-T dispersion. This could lead to the observed sudden death in undisturbed beds. Further research in this area is urgently needed, in particular into the possible protective use of drugs that modulate the autonomic nervous system.

The pharmacokinetics of bupivacaine following interpleural nerve block in infants of very low birthweight.

Infants of very low birthweight (VLBW) who underwent thoracotomy were given 2.0 mg.kg-1 of bupivacaine by the intrapleural route, and serial blood levels were taken to determine the pharmacokinetic profile in this group of babies. It was apparent that the half life was longer, clearance lower, and volume of distribution greater than in term infants. Although the drug did not reach toxic levels at this dose, caution should be observed when redosing as the accumulation of the drug may be unpredictable.

Immunocytochemical localization of growth hormone and growth hormone-releasing hormone immunoreactivity in the brain and pituitary of the little brown bat.

Anterior pituitary cells exhibiting growth hormone (GH) immunoreactivity and forebrain neurons containing growth hormone-releasing hormone (GHRH) immunoreactivity were identified in little brown bats (Myotis lucifugus) using light microscopic immunocytochemistry. Pituitary somatotropes appeared as ovoid or polyhedral cells that were distributed throughout most of the pars distalis, with the exception of its most rostral region where this cell type was scarce. GH-immunoreactive cells occupied approximately one-third of the total volume of the pars distalis; this proportion did not differ significantly between males and females or in bats collected at different times of year. Neuronal perikarya containing immunoreactive GHRH were observed in the hypothalamic arcuate and suprachiasmatic nuclei, as well as in the cortical and subcortical telencephalon. Fibers were most evident in the median eminence, paraventricular and periventricular nuclei, and molecular layer of the cerebral cortex. Fine fibers were also accumulated in the bed nucleus of the stria terminalis and in the amygdala.

Peripheral nerve regeneration is impeded by interleukin-1 receptor antagonist released from a polymeric guidance channel.

Interleukin-1 receptor antagonist (IL-1ra), a true antagonist of the interleukin-1 (IL-1) receptors, is released by activated macrophages and binds specifically to the IL-1 receptors without triggering IL-1 effects. Following peripheral nerve axotomy, activated macrophages release IL-1, which induces the expression of nerve growth factor (NGF) mRNA in Schwann cells. IL-1ra may therefore impede peripheral nerve regeneration by blocking the NGF-mediated effect of IL-1. Peripheral nerve regeneration occurring through polymeric guidance channels releasing IL-1ra was investigated in a 4-mm gap transected mouse sciatic nerve model. Cohorts of five animals were implanted with tubes releasing either bovine serum albumin (BSA), BSA with IL-1ra, or BSA with deactivated IL-1ra (dIL-1ra) for 4 weeks. In vitro release kinetics indicated that after an initial burst, IL-1ra release was linear for the next 3 1/2 weeks. Following implantation of a polymeric guidance channel, a regenerated cable bridged the nerve gap in all animals. The cables were similar in size and were composed of nerve microfascicles containing both unmyelinated and myelinated axons in association with their Schwann cells. Tissue regenerated in tubes releasing BSA-IL-1ra contained, however, significantly fewer myelinated and unmyelinated axons and blood vessels than did tubes releasing BSA alone or BSA-dIL-1ra. We conclude that a naturally occurring antagonist of IL-1 receptors impedes peripheral nerve regeneration, suggesting that macrophages play an essential role in controlling peripheral nerve regeneration through the release of stimulatory and/or inhibitory molecules.

An automatic device for the assessment of cardiovascular autonomic function.

Autonomic neuropathy is a common complication of diabetes mellitus and is associated with significant morbidity and possibly an increase in mortality. Despite this, however, autonomic dysfunction is not usually sought in the routine assessment of diabetic patients. We report the development and testing of a small, portable and reliable device that allows the routine testing of cardiac autonomic function in the outpatient setting with minimal inconvenience to the patient. This should facilitate the accurate assessment both of patients with symptoms suggestive of autonomic dysfunction and of autonomic function in research.