National service evaluation of the quality of care for children and young people with congenital adrenal hyperplasia in the United Kingdom: survey responses from patients and clinicians.

INTRODUCTION: Quantifying differences in service provision for children and young people (CYP) living with Congenital Adrenal Hyperplasia (CAH) across the United Kingdom. METHODS: A national service evaluation using online questionnaires circulated to patients and clinicians from secondary and tertiary UK centres managing CYP with CAH, and via the "Living with CAH" support group mailing list. RESULTS: Total of 195 responses relating to patients aged 0-20 years attending 33 clinics (43 patients, 152 carers), as well as 34 clinicians from 18 trusts working across the 33 clinics. Only 12% of clinicians were 'completely satisfied' with the service provided, compared to 68% of carers and 76% of patients. Whilst 94% of clinicians reported providing formal training to families with CAH, over 80% of both patients and carers reported not attending what they considered formal training. Appetite for further training was higher in carers (86%) than patients (55%), although further 'unsure' responses suggested formal training sessions would likely be well attended. Access to psychological services was difficult for 44% of clinicians. Biochemical monitoring of treatment was broadly in keeping with international guidelines, with 67% of clinicians reporting regular use of dried blood spots, and 12% regular urinary steroid metabolites. CONCLUSION: While there is overall good satisfaction with care provision among patients and carers with CAH in the UK, extra resources addressing the psychological and educational needs about the disease and its management would benefit patients and carers. Improved access to allied health professionals and psychologists will help support families and improve patient outcomes.

Type 1 diabetes incidence in Scotland between 2006 and 2019.

AIMS: To describe type 1 diabetes incidence in Scotland between 2006 and 2019. METHODS: Repeated annual cross-sectional studies of type 1 diabetes incidence were conducted. Incident cases were identified from the Scottish Care Information-Diabetes Collaboration (SCI-DC), a population-based register of people with diagnosed diabetes derived from primary and secondary care data. Mid-year population estimates for Scotland were used as the denominator to calculate annual incidence with stratification by age and sex. Joinpoint regression was used to investigate whether incidence changed during the study period. Age and sex-specific type 1 diabetes incidence over the whole time period was estimated by quintile of the Scottish Index of Multiple Deprivation (SIMD), an area-based measure, in which Q1 and Q5 denote the most and least deprived fifths of the population, respectively, with quasi-Poisson regression used to compare incidence for Q5 compared to Q1. RESULTS: The median (IQR) age of the study population of 14,564 individuals with incident type 1 diabetes was 24.1 (12.3-42.4) years, 56% were men, 23% were in Q1 and 16% were in Q5. Incidence of T1DM was higher in men than women overall (at around 22 and 17 per 100,000, respectively) and in under 15 year olds (approximately 40 per 100,000 in both sexes) than other age groups and was similar across the study period in all strata. There was an inverse association between socio-economic status and type 1 diabetes incidence for 15-29, 30-49 and 50+ year olds [incidence rate ratio (IRR) for Q5 compared to Q1; IRR (95% CI) 0.52 (0.47-0.58), 0.68 (0.61-0.76) and 0.53(0.46-0.61), respectively] but not for under 15 year olds [1.02 (0.92-1.12)]. CONCLUSION: Incidence of type 1 diabetes varies by age, sex and socio-economic status and has remained approximately stable from 2006 to 2019 in Scotland.

Relation of Incident Type 1 Diabetes to Recent COVID-19 Infection: Cohort Study Using e-Health Record Linkage in Scotland.

OBJECTIVE: Studies using claims databases reported that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection >30 days earlier was associated with an increase in the incidence of type 1 diabetes. Using exact dates of diabetes diagnosis from the national register in Scotland linked to virology laboratory data, we sought to replicate this finding. RESEARCH DESIGN AND METHODS: A cohort of 1,849,411 individuals aged <35 years without diabetes, including all those in Scotland who subsequently tested positive for SARS-CoV-2, was followed from 1 March 2020 to 22 November 2021. Incident type 1 diabetes was ascertained from the national registry. Using Cox regression, we tested the association of time-updated infection with incident diabetes. Trends in incidence of type 1 diabetes in the population from 2015 through 2021 were also estimated in a generalized additive model. RESULTS: There were 365,080 individuals who had at least one detected SARS-CoV-2 infection during follow-up and 1,074 who developed type 1 diabetes. The rate ratio for incident type 1 diabetes associated with first positive test for SARS-CoV-2 (reference category: no previous infection) was 0.86 (95% CI 0.62, 1.21) for infection >30 days earlier and 2.62 (95% CI 1.81, 3.78) for infection in the previous 30 days. However, negative and positive SARS-CoV-2 tests were more frequent in the days surrounding diabetes presentation. In those aged 0-14 years, incidence of type 1 diabetes during 2020-2021 was 20% higher than the 7-year average. CONCLUSIONS: Type 1 diabetes incidence in children increased during the pandemic. However, the cohort analysis suggests that SARS-CoV-2 infection itself was not the cause of this increase.

Diazoxide-induced pulmonary hypertension in hyperinsulinaemic hypoglycaemia: Recommendations from a multicentre study in the United Kingdom.

OBJECTIVE: Diazoxide is first-line treatment for hyperinsulinaemic hypoglycaemia (HH) but diazoxide-induced pulmonary hypertension (PH) can occur. We aim to characterize the incidence and risk factors of diazoxide-induced PH in a large HH cohort to provide recommendations for anticipating and preventing PH in diazoxide-treated patients with HH. DESIGN AND PATIENTS: Retrospective cohort study involving four UK regional HH centres; review of case notes of HH patients on diazoxide. MEASUREMENTS: The diagnosis of PH was based on clinical and echocardiography evidence. Patient and treatment-related risk factors were analysed for association. RESULTS: Thirteen (6 men) of 177 HH diazoxide-treated patients developed PH, an incidence of 7%. In the PH group, HH was diagnosed at median (range) of 9 (1,180) days, with diazoxide commenced 4 (0,76) days from diagnosis and reaching a maximum dose of 7 (2.5,20) mg/kg/d. The majority (8 of 13 patients) developed PH within 2 weeks of diazoxide. Complete diazoxide withdrawal, but not dose reduction, led to PH resolution at 41 (3,959) days. In three patients, PH continued beyond 12 months. Risk factors for the development of PH included the presence of congenital heart disease (CHD) (P = .008), and total fluid volume exceeding 130 mL/kg/d in the immediate 24 hours preceding diazoxide (P = .019). CONCLUSION: Pulmonary hypertension can occur in 7% of diazoxide-treated HH patients. Risk factors include the presence of congenital heart disease and fluid overload. Recommendations include echocardiography and fluid restriction to 130 mL/kg/d prior to diazoxide treatment and immediate discontinuation of diazoxide if PH develops.

Glycaemic control trends in people with type 1 diabetes in Scotland 2004-2016.

AIMS/HYPOTHESIS: The aim of this work was to examine whether glycaemic control has improved in those with type 1 diabetes in Scotland between 2004 and 2016, and whether any trends differed by sociodemographic factors. METHODS: We analysed records from 30,717 people with type 1 diabetes, registered anytime between 2004 and 2016 in the national diabetes database, which contained repeated measures of HbA1c. An additive mixed regression model was used to estimate calendar time and other effects on HbA1c. RESULTS: Overall, median (IQR) HbA1c decreased from 72 (21) mmol/mol [8.7 (4.1)%] in 2004 to 68 (21) mmol/mol (8.4 [4.1]%) in 2016. However, all of the improvement across the period occurred in the latter 4 years: the regression model showed that the only period of significant change in HbA1c was 2012-2016 where there was a fall of 3 (95% CI 1.82, 3.43) mmol/mol. The largest reductions in HbA1c in this period were seen in children, from 69 (16) mmol/mol (8.5 [3.6]%) to 63 (14) mmol/mol (7.9 [3.4]%), and adolescents, from 75 (25) mmol/mol (9.0 [4.4]%) to 70 (23) mmol/mol (8.6 [4.3]%). Socioeconomic status (according to Scottish Index of Multiple Deprivation) affected the HbA1c values: from the regression model, the 20% of people living in the most-deprived areas had HbA1c levels on average 8.0 (95% CI 7.4, 8.9) mmol/mol higher than those of the 20% of people living in the least-deprived areas. However this difference did not change significantly over time. From the regression model HbA1c was on average 1.7 (95% CI 1.6, 1.8) mmol/mol higher in women than in men. This sex difference did not narrow over time. CONCLUSIONS/INTERPRETATION: In this high-income country, we identified a modest but important improvement in HbA1c since 2012 that was most marked in children and adolescents. These changes coincided with national initiatives to reduce HbA1c including an expansion of pump therapy. However, in most people, overall glycaemic control remains far from target levels and further improvement is badly needed, particularly in those from more-deprived areas.

Barriers and facilitators to taking on diabetes self-management tasks in pre-adolescent children with type 1 diabetes: a qualitative study.

BACKGROUND: When children with type 1 diabetes approach adolescence, they are encouraged to become more involved in diabetes self-management. This study explored the challenges pre-adolescent children encounter when self-managing diabetes and the factors which motivate and enable them to take on new diabetes-related tasks. A key objective was to inform the support offered to pre-adolescent children. METHODS: In-depth interviews using age-appropriate questioning with 24 children (aged 9-12 years) with type 1 diabetes. Data were analysed using an inductive, thematic approach. RESULTS: Children reported several barriers to taking on self-management tasks. As well as seeking respite from managing diabetes, children described relying on their parents to: perform the complex maths involved in working out carbohydrate content in food; calculate insulin doses if they did not use a bolus advisor; and administer injections or insert a cannula in hard-to-reach locations. Children described being motivated to take on diabetes tasks in order to: minimise the pain experienced when others administered injections; alleviate the burden on their parents; and participate independently in activities with their peers. Several also discussed being motivated to take on diabetes-management responsibilities when they started secondary school. Children described being enabled to take on new responsibilities by using strategies which limited the need to perform complex maths. These included using labels on food packaging to determine carbohydrate contents, or choosing foods with carbohydrate values they could remember. Many children discussed using bolus advisors with pre-programmed ratios and entering carbohydrate on food labels or values provided by their parents to calculate insulin doses. Several also described using mobile phones to seek advice about carbohydrate contents in food. CONCLUSIONS: Our findings highlight several barriers which deter children from taking on diabetes self-management tasks, motivators which encourage them to take on new responsibilities, and strategies and technologies which enable them to become more autonomous. To limit the need to perform complex maths, children may benefit from using bolus advisors provided they receive regular review from healthcare professionals to determine and adjust pre-programmed insulin-to-carbohydrate ratios. Education and support should be age-specific to reflect children's changing involvement in self-managing diabetes.

Hormone supplementation for pubertal induction in girls.

Pubertal induction in girls with ovarian insufficiency aims to mimic normal puberty, a highly complex process. Here we amalgamate the sparse global evidence and propose three options for pubertal induction regimens including oral ethinyloestradiol, and oral and transdermal 17ß-oestradiol. The introduction of progestogens is discussed and the transition to hormone supplementation for adult women. The merits and disadvantages of the different options are detailed. The available evidence indicates that transdermal 17ß-oestradiol has the most favourable efficacy, safety and cost profile but randomised controlled trials are urgently required to determine which regimen provides the best clinical outcomes.

A Validated Normative Model for Human Uterine Volume from Birth to Age 40 Years.

Transabdominal pelvic ultrasound and/or pelvic Magnetic Resonance Imaging are safe, accurate and non-invasive means of determining the size and configuration of the internal female genitalia. The assessment of uterine size and volume is helpful in the assessment of many conditions including disorders of sex development, precocious or delayed puberty, infertility and menstrual disorders. Using our own data from the assessment of MRI scans in healthy young females and data extracted from four studies that assessed uterine volume using transabdominal ultrasound in healthy females we have derived and validated a normative model of uterine volume from birth to age 40 years. This shows that uterine volume increases across childhood, with a faster increase in adolescence reflecting the influence of puberty, followed by a slow but progressive rise during adult life. The model suggests that around 84% of the variation in uterine volumes in the healthy population up to age 40 is due to age alone. The derivation of a validated normative model for uterine volume from birth to age 40 years has important clinical applications by providing age-related reference values for uterine volume.

Improving communication and recall of information in paediatric diabetes consultations: a qualitative study of parents' experiences and views.

BACKGROUND: Parents of non-adolescent children with type 1 diabetes are responsible for most of their child's diabetes management tasks. Consultations are used to provide diabetes education, review clinical progress and promote diabetes management tasks. This study explored parents' experiences of, and views about, their child's diabetes consultations. The objective was to identify ways in which consultations could be improved to aid communication, understanding and knowledge retention. METHODS: In-depth interviews with 54 parents of children (aged ≤12 years) with type 1 diabetes. Data were analysed using an inductive thematic approach. RESULTS: Parents' accounts revealed structural and contextual factors which could hinder effective communication and knowledge acquisition during consultations. Most reported feeling anxious going into consultations and worrying about being reprimanded by health professionals if their child's glycaemic control had not improved. As a consequence, many parents highlighted problems concentrating and assimilating information during consultations. In extreme cases, worries about being reprimanded led parents to omit or fabricate information when discussing their child's treatment or even to their cancelling appointments. Many parents described wanting opportunities to speak to health professionals alone because young children could be distracting and/or they did not want to raise distressing issues in front of their child. Parents described the benefits of receiving clinical advice from health professionals familiar with their family circumstances and disliking attending busy clinics and seeing different health professionals on each occasion. Parents also highlighted the benefits of receiving treatment recommendations in a written form after the consultation. DISCUSSION AND CONCLUSIONS: This study has highlighted unrecognised and undocumented aspects of the consultation which may result in parents leaving uncertain about the main issues discussed and with questions unanswered and support needs unaddressed. Structural and contextual changes to consultations are recommended to improve concentration, knowledge acquisition and retention. These include: sending letters/written summaries after consultations highlighting key decisions, providing opportunities for parents to consult health professionals without their child being present, encouraging parents to ask more questions during consultations, having procedures in place to promote continuity of care and providing parents with consistent and non-contradictory advice.

Pathways to diagnosis: a qualitative study of the experiences and emotional reactions of parents of children diagnosed with type 1 diabetes.

OBJECTIVE: The aim of this study was to explore from parents' perspectives the circumstances and events which led to their child being diagnosed with type 1 diabetes (T1D). The objective was to understand reasons for delays in seeking treatment and parents' emotional reactions to diagnosis so others can be better informed and supported in future. METHODS: In-depth interviews with 54 parents of children (aged ≤12 yr) with T1D were conducted. Data analysis used an inductive, thematic approach. RESULTS: Parents described a 'prompt' and a 'delayed' pathway to their child being diagnosed. Parents who considered the diagnosis to be 'prompt' reported how they, or other people, had recognized their child had developed symptoms of T1D which resulted in a rapid presentation to health care professionals. In contrast, parents who perceived their child's diagnosis to be 'delayed' did not recognize signs of T1D and attributed their child's deteriorating health to other conditions, being out of routines and/or their stage of development. These parents often only sought medical help when symptoms became extreme. All parents were distressed by their child's diagnosis; however, parents in the 'delayed' pathway expressed unresolved feelings of guilt, particularly when their child was diagnosed with diabetic ketoacidosis. DISCUSSION: Parents' and other people's knowledge about T1D can affect the duration between onset of their child's symptoms and diagnosis. Campaigns to raise awareness should ensure that parents are made aware of symptoms and that T1D can develop during childhood. Health care professionals could discuss with parents the events preceding their child's diagnosis to better determine their emotional support needs.

Prevalence of impaired awareness of hypoglycemia and identification of predictive symptoms in children and adolescents with type 1 diabetes.

BACKGROUND: In children with type 1 diabetes mellitus (T1DM) the prevalence of impaired awareness of hypoglycemia (IAH) is uncertain. This study aimed to ascertain this with greater precision. Secondary aims were to assess symptoms of hypoglycemia and which of these best predict awareness of hypoglycemia in children. METHODS: Questionnaires were completed by 98 children with T1DM (mean age 10.6 yr) and their parent(s); hospital admission data for the previous year were collected. Awareness of hypoglycemia was assessed using two questionnaire-based methods that have been validated in adults. For 4 wk, participants performed routine blood glucose measurements and completed questionnaires after each episode of hypoglycemia. Principal components analysis determined how symptoms correlate; multinomial logistic regression models identified which symptom aggregate best predicted awareness status. RESULTS: The 'Gold' questionnaire classified a greater proportion of the participants as having IAH than the 'Clarke' questionnaire (68.4 vs. 22.4%). Using the 'Clarke' method, but not the 'Gold' method, children with IAH were younger and more likely to require external assistance or hospital admission. Most aged ≥9 yr (98.6%) were able to self-assess awareness status accurately. Puberty and increasing age, augmented symptom scores; duration of diabetes and glycemic control had no effect. In contrast to adults, behavioral symptoms were the best predictors of awareness status. CONCLUSIONS: IAH affects a substantial minority of children and impending hypoglycemia may be heralded by behavioral symptoms. The 'Clarke' method was more effective at identifying those at increased risk and could be used as a screening tool.

Quantification of human urinary exosomes by nanoparticle tracking analysis.

Exosomes are vesicles that are released from the kidney into urine. They contain protein and RNA from the glomerulus and all sections of the nephron and represent a reservoir for biomarker discovery. Current methods for the identification and quantification of urinary exosomes are time consuming and only semi-quantitative. Nanoparticle tracking analysis (NTA) counts and sizes particles by measuring their Brownian motion in solution. In this study, we applied NTA to human urine and identified particles with a range of sizes. Using antibodies against the exosomal proteins CD24 and aquaporin 2 (AQP2), conjugated to a fluorophore, we could identify a subpopulation of CD24- and AQP2-positive particles of characteristic exosomal size. Extensive pre-NTA processing of urine was not necessary. However, the intra-assay variability in the measurement of exosome concentration was significantly reduced when an ultracentrifugation step preceded NTA. Without any sample processing, NTA tracked exosomal AQP2 upregulation induced by desmopressin stimulation of kidney collecting duct cells. Nanoparticle tracking analysis was also able to track changes in exosomal AQP2 concentration that followed desmopressin treatment of mice and a patient with central diabetes insipidus. When urine was stored at room temperature, 4°C or frozen, nanoparticle concentration was reduced; freezing at -80°C with the addition of protease inhibitors produced the least reduction. In conclusion, with appropriate sample storage, NTA has potential as a tool for the characterization and quantification of extracellular vesicles in human urine.

Assessing and addressing cardiovascular risk in adults with Turner syndrome.

UNLABELLED: Turner syndrome (TS), the result of a structurally abnormal or absent X chromosome, occurs in one in 2 000 live born females. The phenotype is highly variable, but short stature and gonadal dysgenesis are usually present. The main objective in adults with TS is health surveillance, but TS still causes a reduction in life expectancy of up to 13 years, with cardiovascular disease, congenital or acquired, as the major cause of an early death. While it has been established that all women with TS should undergo in-depth cardiovascular examination at diagnosis, advice on the cardiovascular management of women with TS is limited. Here, we provide a summary of our current practice within a multidisciplinary team, supported by our expertise in various aspects of cardiovascular risk management, and the evidence from research where it is available, with the aim of providing optimal support to our patients with TS. BACKGROUND: A dedicated Adult Turner Clinic was established in South East Scotland in 2002. This gynaecology-led clinic serves a population of roughly 1·2 million and, currently, reviews around 50 women with TS annually. Referrals for adult care come from paediatrics or general practice. Following a series of individual case discussions regarding the management of more complex cardiovascular problems, we have assembled a dedicated multidisciplinary group to determine a timely cardiovascular screening strategy, a basis for specialist referral, and appropriate hypertension management. This team now includes a paediatric endocrinologist, gynaecologist, cardiologist (with an interest in inherited disorders), vascular radiologist and hypertension specialist. Here, we review the literature on cardiovascular disease in women with TS and, make recommendations, based on relatively limited high-quality evidence, together with our experience, on the optimal timing of cardiovascular screening.

Proptosis as the presenting sign of giant prolactinoma in a prepubertal boy: successful resolution of hydrocephalus by use of medical therapy.

We report the case of a 13-year-old prepubertal boy who presented with a left-sided proptosis, bilateral papilloedema and hydrocephalus who was subsequently diagnosed with a giant prolactinoma invading the left orbit. He was commenced on dopamine receptor agonists in the form of quinagolide and cabergoline, and made an excellent response to medical therapy alone, with resolution of hydrocephalus, restoration of normal vision and a 98% reduction in serum prolactin. The rapid improvement achieved negated the requirement for surgery and this highlights the efficacy of the dopamine agonists in the management of giant prolactinomas, even in the presence of neurological symptoms.

Physiological versus standard sex steroid replacement in young women with premature ovarian failure: effects on bone mass acquisition and turnover.

BACKGROUND: The aim of this exploratory study was to establish whether we could improve skeletal health with a physiological regimen of SSR in young women with premature ovarian failure (POF). PATIENTS AND METHODS: In an open-label randomized controlled crossover trial, 34 women with POF were randomized to 4-week cycles of pSSR (transdermal oestradiol, 100 µg daily for week 1, 150 µg for weeks 2-4; vaginal progesterone, 200 mg twice daily for weeks 3-4) or standard hormone replacement treatment (sHRT) (oral ethinyloestradiol 30 µg and 1·5 mg norethisterone daily for weeks 1-3, week 4 'pill-free') for 12 months. Bone mineral density (BMD) was measured by DEXA at study entry and after each 12-month treatment period. Blood samples for hormones and markers of bone formation (bone alkaline phosphatase, BALP and type I collagen N-terminal propeptide, PINP) and bone resorption (CrossLaps) were collected pre-/postwashout and after 3, 6 and 12 months of each treatment. RESULTS: Eighteen women, mean 27 (range 19-39) years, completed the study. Both regimens caused similar suppression of LH and FSH. Mean baseline lumbar spine BMD z-score was -0·89 (95% CI -1·27 to -0·51) and increased by +0·17 (CI +0·07 to +0·27) in response to pSSR (P = 0·003), compared with +0·07 (CI -0·03 to +0·18) during standard HRT (P = 0·2). During pSSR, the increment in lumbar spine BMD z-score was related positively to oestradiol (r = +0·49, P = 0·04) and inversely to FSH (r = -0·65, P = 0·004). Bone formation markers, BALP and P1NP increased in the pSSR arm (anova P < 0·001) but decreased in the sHRT arm (P < 0·01). Both treatments suppressed the bone resorption marker, CrossLaps (P < 0·001). CONCLUSION: We conclude that pSSR over 12 months has a beneficial affect on bone mass acquisition on the lumbar spine in women with POF, mediated by increased bone formation and decreased bone resorption.

Cardiovascular effects of physiological and standard sex steroid replacement regimens in premature ovarian failure.

Current hormone replacement therapy may not optimize cardiovascular health in women with premature ovarian failure. We compared the effects of physiological and standard sex steroid replacement regimens on cardiovascular health in these women. In an open-label, randomized, controlled crossover trial, 34 women with premature ovarian failure were randomly assigned to 4-week cycles of physiological (transdermal estradiol and vaginal progesterone) and standard (oral ethinylestradiol and norethisterone) therapy for 12 months. Cardiovascular health was assessed by 24-hour ambulatory blood pressure, arterial stiffness, and renal and humoral factors. Eighteen women (19 to 39 years of age) completed the 28-month protocol. Both regimens caused similar suppression of luteinizing hormone and follicle-stimulating hormone and provided symptom relief. In comparison with the standard regimen, physiological sex steroid replacement caused lower mean 24-hour systolic and diastolic blood pressures throughout the 12-month treatment period (ANOVA; P

Audit of microalbumin excretion in children with type I diabetes.

OBJECTIVE: To investigate prevalence, persistence and clinical correlates of increased microalbumin excretion in random urine samples collected in a paediatric diabetes clinic. METHOD: Random urine samples were collected annually in patients >10 years attending the diabetes clinic in the Royal Hospital for Sick Children, Edinburgh. Albumin excretion is expressed as albumin:creatinine ratio (ACR) and classified as normal (10 mg/mmol), or macroalbuminuria (>47 mg/mmol in females, >35 mg/mmol in males). We analyzed retrospectively results on 421 urine samples collected from 217 patients (109 males), of a median age of 12.3 years (94% 10-16 years) over 3 years. For each sample, the corresponding mean HbA1c over the previous year was calculated. RESULTS: Prevalence of micro- and macro-albuminuria in individual samples was 1% and 0.5% respectively. ACR was equivocal in 10.1% and 4.7% in samples from females and males respectively (p=0.03). HbA1c showed borderline significant differences across ACR groups (p=0.06). Equivocal ACR excretion was associated with slightly higher mean HbA1c (9.5±1.3%) compared to normal albuminuria (9.0±1.1%, p3.5 mg/mmol. The 14-16 years age group patients were most likely to have ACR >3.5 mg/mmol (p=0.05). CONCLUSIONS: Female sex and increasing age, but not HbA1c, were independently associated with increased ACR. A robust mechanism for collection of repeat early morning urine samples from patients with increased ACR in random urine samples, and follow-up of those patients who have persistently high microalbumin excretion are important. It is also important to confirm the usefulness of ACR measurements in random urine samples as a marker of incipent nephropathy.

Hydroxybutyrate near-patient testing to evaluate a new end-point for intravenous insulin therapy in the treatment of diabetic ketoacidosis in children.

BACKGROUND: The aim of this study was to assess the clinical application of a near-patient testing (NPT) device for capillary blood hydroxybutyrate (HOB) measurement in evaluating a new end-point for intravenous insulin therapy in the treatment of diabetic ketoacidosis (DKA) in children. METHODS: Children fulfilling the criteria for DKA were treated according to an integrated care pathway (ICP) with fluid replacement and insulin infusion. We measured capillary HOB hourly by NPT (Abbott Optium meter, analytical range 0-6.0 mmol/L), venous blood gases 4 hourly, and venous HOB 4 hourly by laboratory enzymatic method and tested all urine passed for ketones. Two possible ICP end-points were compared: A, pH > 7.3 followed by two successive NPT HOB measurements <1 mmol/L, and B, pH > 7.3 and urine ketone free (our current end-point). RESULTS: In 35 patient episodes, the ICP was completed (28 to negative ketonuria) without significant variation. Before treatment, median (range) laboratory HOB was 9.5 mmol/L (4.6-15.70 mmol/L), pH 7.18 (6.98-7.38), and standard bicarbonate 11.5 mmol/L (4.3-18.6 mmol/L). ICP end-point A was reached after 17 h (4-39 h), whereas end-point B was not reached until 28 h (14-64 h) after starting treatment. The median lag was 11 h (1-36 h). For 59 paired venous samples (excluding samples with laboratory HOB >6 mmol/L), the relation between NPT (y) and laboratory (x) HOB was y = 0.92x - 0.05, r(2)= 0.94, mean bias -0.25 mmol/L. CONCLUSIONS: (i) Serial measurement of NPT HOB allows evaluation of a new, simple, earlier end-point for intravenous insulin therapy. (ii) Agreement between NPT and laboratory HOB was clinically acceptable for HOB levels within the meter's analytical range.