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.

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.

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.

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.

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.

Beta blocker prescribing differences in patients with and without diabetes following a first myocardial infarction.

AIMS: To document the prescribed usage of beta blockers in patients with and without diabetes mellitus discharged from hospital following a first myocardial infarction. METHODS: All patients with diabetes and a group of patients matched for age and sex without diabetes, admitted with a documented first myocardial infarction during the period 1995-1999 at the Royal Liverpool University Hospital, Liverpool, UK were audited. RESULTS: Data were available on 201 patients with diabetes and 199 patients without diabetes. No significant differences existed between the diabetic and non-diabetic groups for age and sex. Twenty-three per cent of patients with diabetes were prescribed a beta blocker compared to 52% of non-diabetic patients (P < 0.01). Patients with diabetes had a higher frequency of perceived contraindications than patients without diabetes (36 vs. 27%, P < 0.001). Thirty-five per cent of patients with diabetes and 18% of non-diabetic patients had no contraindication to the use of beta blocker but were not prescribed one (P < 0.001). CONCLUSIONS: Although beta blockers can provide useful benefits in patients with diabetes following a myocardial infarction, this study suggests that a significant proportion of patients with diabetes and without a contraindication to treatment are still not receiving beta blockers after myocardial infarction.

The effect of selenium supplementation on outcome in very low birth weight infants: a randomized controlled trial. The New Zealand Neonatal Study Group.

BACKGROUND: Low selenium (SE) status has been documented in preterm infants and has been suggested to be a risk factor for chronic lung disease. METHODS: A total of 534 infants with birth weight <1500 g were enrolled in 8 New Zealand centers in a double-blind placebo-controlled randomized trial of SE supplementation from week 1 of life until 36 weeks' postmenstrual age or discharge home. Supplemented infants received 7 microg/kg/d of SE when fed parenterally and 5 microg/kg/d when fed orally. Plasma SE and glutathione peroxidase concentrations were measured in mothers after delivery and in infants before randomization and at 28 days and 36 weeks' postmenstrual age. Primary outcome measures were oxygen dependency at 28 days and total days oxygen dependency. RESULTS: No significant differences were seen between the groups with respect to primary or secondary outcome measures, with the exception that fewer supplemented infants had an episode of sepsis after the first week of life (P <.038). Mean plasma SE concentrations were 0.33 micromol/L before randomization in both groups and at 28 days had risen in the supplemented group (0.56 micromol/L) but fallen in the control group (0.29 micromol/L) (P <.0001). There was no association between outcome measures and SE concentrations at 28 days or 36 weeks' postmenstrual age. However, lower maternal and infant prerandomization SE concentrations were associated with increased respiratory morbidity. CONCLUSIONS: Postnatal SE supplementation in very low birth weight infants did not improve neonatal outcome. Further investigation of SE supplementation of mothers from the second half of pregnancy is warranted.

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.

Older subjects show no age-related decrease in cardiac baroreceptor sensitivity.

OBJECTIVE: To examine the relationship between age, blood pressure and cardiac baroreceptor sensitivity derived from spectral analysis, the Valsalva manoeuvre and impulse response function. METHODS: We studied 70 healthy normotensive volunteers who were free from disease and not taking medication with cardiovascular or autonomic effects. We measured beat-to-beat arterial blood pressure and used standard surface electrocardiography to record pulse interval under standardized conditions with subjects resting supine as well as during three Valsalva manoeuvres. We performed single, multiple and stepwise regression of patient characteristics against cardiac baroreceptor sensitivity results. RESULTS: There is a non-linear decline in cardiac baroreceptor sensitivity with advancing age, increasing systolic blood pressure and heart rate values (except for the Valsalva-derived result), but little further decline after the fourth decade. Only age significantly influenced values derived using the Valsalva manoeuvre and impulse response analysis. Using spectral analysis, age, systolic and diastolic blood pressure and heart rate influenced cardiac baroreceptor sensitivity, age contributing to 50% of the variability. Age also influenced the relationship between pulse interval and blood pressure, possibly indicating more non-baroreceptor-mediated changes with advancing age. CONCLUSIONS: Although age is the dominant factor influencing cardiac baroreceptor sensitivity in this normotensive population, there is little change in mean values after 40 years of age. The differences in the relationship between pulse interval and blood pressure with advancing age have implications for the calculation of cardiac baroreceptor sensitivity using spectral analysis.

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.

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.

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.

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.

Is impaired baroreflex sensitivity a predictor or cause of sudden death in insulin-dependent diabetes mellitus?

Sudden death at night is known to occur in young patients with insulin-dependent (Type 1) diabetes mellitus (IDDM) but the aetiology is uncertain. A cardiac arrhythmia has been postulated, but there has been little evidence to support this. We present the case of a 31-year-old man with IDDM of 17 years duration, who died suddenly while asleep. Over preceding months, he had had strict glycaemic control (HbA1 8.9%), normal 24 h blood pressure (mean 131 +/- 2.1/76 +/- 2.2 mmHg), no evidence of microangiopathy or endothelial dysfunction and normal standard clinical tests of autonomic function. An electrocardiogram was similarly unremarkable, with a QTc interval of 0.414 s, and an echocardiogram had demonstrated normal left ventricular mass index (96.4 g m-2). However, there was no nocturnal dip in heart rate (daytime 74 +/- 2.7, and nocturnal 68 +/- 1.6 beats min-1), and he had grossly impaired baroreflex sensitivity during Phase 4 of the valsalva manoeuvre (0.5 ms mmHg-1), with power spectral analysis studies suggesting an abnormality of parasympathetic function. The coroner's autopsy demonstrated no structural abnormalities. We hypothesize that abnormal baroreflex sensitivity could either predict a risk of or account for some of the unexplained deaths in IDDM, in that relative overactivity of the sympathetic nervous system could cause ventricular arrhythmias.