Search

Aims: Hybrid closed-loop (HCL) systems are characterised by integrating continuous glucose monitoring (CGM) with insulin pumps that automate insulin delivery via specific algorithms and user-initiated insulin delivery. The aim of the study was to evaluate effectiveness of HCLs on HbA1c, time-in-range (TIR), hypoglycaemia frequency and quality of life measures in children and young people (CYP) with T1D, and their carers., Methods: Patients were recruited prospectively into the National Health Service (NHS) England real-world HCL observational study from the 1st of August 2021 to the 10th of December 2022 from eight paediatric diabetes centres in England., Results: There were 251 CYP (147 males, 58%) with T1DM recruited with a mean age at recruitment of 12.3 (SD 3.5) (range 2-19) years. Eighty nine per cent of the CYP were of white ethnicity, 3% Asian, 4% black and 3% mixed ethnicity, and 1% were recorded as others. The HCL systems used in the study were: (1) Tandem Control-IQ AP system, which uses the Tandem t:slim X2 insulin pump (Tandem Diabetes Care, San Diego, CA) with the Dexcom G6® CGM (Dexcom, San Diego, CA) sensor; (2) Medtronic MiniMed™ 780G (Medtronic, Northridge, CA) and (3) CamAPS FX (CamDiab, Cambridge, UK.) All systems were fully funded by the national health service., Conclusions: The results of the NHS England Closed Loop Study in Children and Young People showed improvements in glycaemic control, TIR, frequency of hypoglycaemia, hypoglycaemia fear and quality of sleep for children and young people when using HCL for 6 months. Hypoglycaemia fear and quality of sleep were also improved for their parents and carers at 6 months., (© 2022 Diabetes UK.)

Context: Recurrent hypoglycemia can result in significant neurological impairments in children and continuous glucose monitoring (CGM) technology has been shown to reduce recurrent hypoglycemia in conditions such as type 1 diabetes. In the United Kingdom, CGM devices are currently only recommended by the National Institute of Clinical Excellence (NICE) for patients with diabetes and not for other diagnoses., Objective: To examine access to CGM technology for children and young people with recurrent hypoglycemia in the United Kingdom., Methods: In 2021, the British Society of Paediatric Endocrinology and Diabetes (BSPED) conducted a national health professional survey in England, Wales, Scotland, and Northern Ireland looking at CGM access to funding for children and young people with recurrent hypoglycemia, without the diagnosis of diabetes. The UK Children's Hyperinsulinism Charity (UK CHC) also conducted a national patient survey., Results: Responses from BSPED were received from 55 units while the UK CHC received 69 responses from individual families, the largest response to a survey carried out by the charity. The results of the BSPED and UK CHC surveys found that funding streams for CGM were highly variable. Only 29% were able to access CGM for recurrent hypoglycemia and from these, 65% were self-funding CGM. Quality of life benefits were evident from the UK CHC survey on the utility of CGM in reducing worry, improving sleep, lessening the burden of frequently finger-pricking and reducing out-of-hours appointments as a result of hypoglycemia. Patient-reported utilization rates of blood glucose test strips per week were significantly reduced., Conclusion: BSPED and UK CHC national surveys support a call and a consideration for CGM access to be widened to patients who suffer from recurrent hypoglycemia such as those with hyperinsulinism or metabolic conditions. The prevention of recurrent hypoglycemia and improving quality of life for patients and carers remain a cornerstone management for people who suffer from frequent hypoglycemia. CGM education is critical to support its use and understand its limitations. Further research is warranted to determine the safety and efficacy of CGM in detection and reduction of hypoglycemic events, impact of hospital stay, and long-term neurological outcomes in those who suffer from recurrent hypoglceamia., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Objective: There is limited knowledge on the onset of comorbidities in congenital adrenal hyperplasia (CAH) during childhood. We aimed to establish the health status of children with CAH in the UK., Design and Methods: This cross-sectional multicentre study involved 14 tertiary endocrine UK units, recruiting 101 patients aged 8-18 years with classic 21-hydroxylase deficiency and 83 controls. We analysed demographic, clinical and metabolic data, as well as psychological questionnaires (Strengths and Difficulties (SDQ), Paediatric Quality of Life (PedsQL))., Results: Patient height SDS in relation to mid-parental height decreased with age, indicating the discrepancy between height achieved and genetic potential height. Bone age was advanced in 40.5% patients, with a mean difference from the chronological age of 1.8 (±2.3) years. Patients were more frequently overweight (27%) or obese (22%) compared to controls (10.8% and 10.8%, respectively, P < 0.001). No consistent relationship between glucocorticoid dose and anthropometric measurements or hormonal biomarkers was detected. A small number of patients had raised total cholesterol (3.0%), low HDL (3.0%), raised LDL (7.0%) and triglycerides (5.0%). SDQ scores were within the 'high' and 'very high' categories of concern for 16.3% of patients. 'School functioning' was the lowest PedsQL scoring dimension with a median (interquartile range) of 70 (55-80), followed by 'emotional functioning' with a median of 75 (65-85)., Conclusions: Our results show an increased prevalence of problems with growth and weight gain in CAH children and suggest reduced quality of life. This highlights the urgent need to optimise management and monitoring strategies to improve long-term health outcomes.

Background: Whether improved glucose control with hybrid closed-loop therapy can preserve C-peptide secretion as compared with standard insulin therapy in persons with new-onset type 1 diabetes is unclear., Methods: In a multicenter, open-label, parallel-group, randomized trial, we assigned youths 10.0 to 16.9 years of age within 21 days after a diagnosis of type 1 diabetes to receive hybrid closed-loop therapy or standard insulin therapy (control) for 24 months. The primary end point was the area under the curve (AUC) for the plasma C-peptide level (after a mixed-meal tolerance test) at 12 months after diagnosis. The analysis was performed on an intention-to-treat basis., Results: A total of 97 participants (mean [±SD] age, 12±2 years) underwent randomization: 51 were assigned to receive closed-loop therapy and 46 to receive control therapy. The AUC for the C-peptide level at 12 months (primary end point) did not differ significantly between the two groups (geometric mean, 0.35 pmol per milliliter [interquartile range, 0.16 to 0.49] with closed-loop therapy and 0.46 pmol per milliliter [interquartile range, 0.22 to 0.69] with control therapy; mean adjusted difference, -0.06 pmol per milliliter [95% confidence interval {CI}, -0.14 to 0.03]). There was not a substantial between-group difference in the AUC for the C-peptide level at 24 months (geometric mean, 0.18 pmol per milliliter [interquartile range, 0.06 to 0.22] with closed-loop therapy and 0.24 pmol per milliliter [interquartile range, 0.05 to 0.30] with control therapy; mean adjusted difference, -0.04 pmol per milliliter [95% CI, -0.14 to 0.06]). The arithmetic mean glycated hemoglobin level was lower in the closed-loop group than in the control group by 4 mmol per mole (0.4 percentage points; 95% CI, 0 to 8 mmol per mole [0.0 to 0.7 percentage points]) at 12 months and by 11 mmol per mole (1.0 percentage points; 95% CI, 7 to 15 mmol per mole [0.5 to 1.5 percentage points]) at 24 months. Five cases of severe hypoglycemia occurred in the closed-loop group (in 3 participants), and one occurred in the control group; one case of diabetic ketoacidosis occurred in the closed-loop group., Conclusions: In youths with new-onset type 1 diabetes, intensive glucose control for 24 months did not appear to prevent the decline in residual C-peptide secretion. (Funded by the National Institute for Health and Care Research and others; CLOuD ClinicalTrials.gov number, NCT02871089.)., (Copyright © 2022 Massachusetts Medical Society.)

Type 1 diabetes (T1D) is a chronic autoimmune disease of childhood affecting 1:500 children aged under 15 years, with around 25% presenting with life-threatening diabetic ketoacidosis (DKA). While first-degree relatives have the highest risk of T1D, more than 85% of children who develop T1D do not have a family history. Despite public health awareness campaigns, DKA rates have not fallen over the last decade. T1D has a long prodrome, and it is now possible to identify children who go on to develop T1D with a high degree of certainty. The reasons for identifying children presymptomatically include prevention of DKA and related morbidities and mortality, reducing the need for hospitalisation, time to provide emotional support and education to ensure a smooth transition to insulin treatment, and opportunities for new treatments to prevent or delay progression. Research studies of population-based screening strategies include using islet autoantibodies alone or in combination with genetic risk factors, both of which can be measured from a capillary sample. If found during screening, the presence of two or more islet autoantibodies has a high positive predictive value for future T1D in childhood (under 18 years), offering an opportunity for DKA prevention. However, a single time-point test will not identify all children who go on to develop T1D, and so combining with genetic risk factors for T1D may be an alternative approach. Here we discuss the pros and cons of T1D screening in the UK, the different strategies available, the knowledge gaps and why a T1D screening strategy is needed., Competing Interests: Competing interests: REJB reports receiving speaking honoraria from Springer Healthcare and Eli Lilly, and reports sitting on the NovoNordisk UK Foundation Research Selection Committee on a voluntary basis. TR reports receiving consultancy fees from Abbott Diabetes Care (specifically for Libre evidence reviews) and lecture/programme organiser fees from Novo Nordisk. CMD reports having been an advisor giving honorarium lectures to NovoNordisk, Sanofi-genzyme, Janssen, Servier, Lilly, AstraZeneca, Provention Bio, UCB, MSD and Vielo Bio. CMD holds a joint patent with Midatech. JWG chairs the NovoNordisk UK Foundation Research Selection Committee and is a Foundation Trustee. TB reports receiving speaking honoraria from AstraZeneca, Servier and Novo Nordisk, and has received consultancy fees from Novo Nordisk and is an NN Global Expert Panel., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

The cartilage aggrecan proteoglycan is crucial for both skeletal growth and articular cartilage function. A number of aggrecan (ACAN) gene variants have been linked to skeletal disorders, ranging from short stature to severe chondrodyplasias. Osteochondritis dissecans is a disorder where articular cartilage and subchondral bone fragments come loose from the articular surface. We previously reported a missense ACAN variant linked to familial osteochondritis dissecans, with short stature and early onset osteoarthritis, and now describe three novel ACAN gene variants from additional families with this disorder. Like the previously described variant, these are autosomal dominant missense variants, resulting in single amino acid residue substitutions in the C-type lectin repeat of the aggrecan G3 domain. Functional studies showed that neither recombinant variant proteins, nor full-length variant aggrecan proteoglycan from heterozygous patient cartilage, were secreted to the same level as wild-type aggrecan. The variant proteins also showed decreased binding to known cartilage extracellular matrix ligands. Mapping these and other ACAN variants linked to hereditary skeletal disorders showed a clustering of osteochondritis dissecans-linked variants to the G3 domain. Taken together, this supports a link between missense ACAN variants affecting the aggrecan G3 domain and hereditary osteochondritis dissecans., (© 2022. The Author(s).)

Background: GNAS encodes the Gα s (stimulatory G-protein alpha subunit) protein, which mediates G protein-coupled receptor (GPCR) signaling. GNAS mutations cause developmental delay, short stature, and skeletal abnormalities in a syndrome called Albright's hereditary osteodystrophy. Because of imprinting, mutations on the maternal allele also cause obesity and hormone resistance (pseudohypoparathyroidism)., Methods: We performed exome sequencing and targeted resequencing in 2548 children who presented with severe obesity, and we unexpectedly identified 22 GNAS mutation carriers. We investigated whether the effect of GNAS mutations on melanocortin 4 receptor (MC4R) signaling explains the obesity and whether the variable clinical spectrum in patients might be explained by the results of molecular assays., Results: Almost all GNAS mutations impaired MC4R signaling. A total of 6 of 11 patients who were 12 to 18 years of age had reduced growth. In these patients, mutations disrupted growth hormone-releasing hormone receptor signaling, but growth was unaffected in carriers of mutations that did not affect this signaling pathway (mean standard-deviation score for height, -0.90 vs. 0.75, respectively; P = 0.02). Only 1 of 10 patients who reached final height before or during the study had short stature. GNAS mutations that impaired thyrotropin receptor signaling were associated with developmental delay and with higher thyrotropin levels (mean [±SD], 8.4±4.7 mIU per liter) than those in 340 severely obese children who did not have GNAS mutations (3.9±2.6 mIU per liter; P = 0.004)., Conclusions: Because pathogenic mutations may manifest with obesity alone, screening of children with severe obesity for GNAS deficiency may allow early diagnosis, improving clinical outcomes, and melanocortin agonists may aid in weight loss. GNAS mutations that are identified by means of unbiased genetic testing differentially affect GPCR signaling pathways that contribute to clinical heterogeneity. Monogenic diseases are clinically more variable than their classic descriptions suggest. (Funded by Wellcome and others.)., (Copyright © 2021 Massachusetts Medical Society.)

Introduction: X-linked hypophosphataemia (XLH) is conventionally managed with oral phosphate and active vitamin D analogues., Objectives: To evaluate long term treatment response by assessing biochemical disease activity [serum alkaline phosphatase (ALP)], radiological rickets severity score (RSS), growth and morbidity in patients with XLH on conventional therapy and assess the correlation between serum ALP and RSS., Methods: XLH patients from 3 UK tertiary centres with ≥3 radiographs one year apart were included. Data was collected retrospectively. The RSS was assessed from routine hand and knee radiographs and ALP z scores were calculated using age-specific reference data., Results: Thirty-eight (male = 12) patients met the inclusion criteria. The mean ± SD knee, wrist and total RSS at baseline (median age 1.2 years) were 2.0 ± 1.2, 1.9 ± 1.2 and 3.6 ± 1.3 respectively; and at the most recent clinic visit (median age 9.0 years, range 3.3-18.9) were 1.6 ± 1.0, 1.0 ± 1.0 and 2.5 ± 1.5 respectively. The mean ± SD serum ALP z scores at baseline and the most recent visit were 4.2 ± 2.3 and 4.0 ± 3.3. Median height SDS at baseline and most recent visit were -1.2 and -2.1 (p = 0.05). Dental abscess, craniosynostosis, limb deformity requiring orthopaedic intervention and nephrocalcinosis were present in 31.5%, 7.9%, 31.6% and 42.1% of the cohort respectively. There was no statistically significant (p > 0.05) correlation between ALP z scores and knee (r = 0.07) or total (r = 0.12) RSS., Conclusions: Conventional therapy was not effective in significantly improving biochemical and radiological features of disease. The lack of association between serum ALP and rickets severity on radiographs limits the value of ALP as the sole indicator of rickets activity in patients receiving conventional therapy., (Copyright © 2021. Published by Elsevier Inc.)

Background: Closed-loop technology may help address health disparities experienced by adolescents, who are more likely to have suboptimal glycemic control than other age groups and, because of their age, find diabetes self-management particularly challenging. The CamAPS FX closed-loop has sought to address accessibility and usability issues reported by users of previous prototype systems. It comprises small components and a smartphone app used to: announce meal-time boluses, adjust ("boost" or "ease-off") closed-loop insulin delivery, customize alarms, and review/share data. We explored how using the CamAPS FX platform influences adolescents' self-management practices and everyday lives., Methods: Eighteen adolescents were interviewed after having ≥6 months experience using the closed-loop platform. Data were analyzed thematically., Results: Participants reported feeling less burdened and shackled by diabetes because closed-loop components were easier to carry/wear, finger-pricks were not required, the smartphone app provided a discreet and less stigmatizing way of managing diabetes in public, and they were able to customize alarms. Participants also reported checking and reviewing data more regularly, because they did so when using the smartphone for other reasons. Some reported challenges in school settings where use of personal phones was restricted. Participants highlighted how self-management practices were improved because they could easily review glucose data and adjust closed-loop insulin delivery using the "boost" and "ease-off" functions. Some described how using the system resulted in them forgetting about diabetes and neglecting certain tasks., Conclusions: A closed-loop system with small components and control algorithm on a smartphone app can enhance usability and acceptability for adolescents and may help address the health-related disparities experienced by this age group. However, challenges can arise from using a medical app on a device which doubles as a smartphone., Trial Registration: Closed Loop From Onset in Type 1 Diabetes (CLOuD); NCT02871089; https://clinicaltrials.gov/ct2/show/NCT02871089.

Objective: To understand and explore data sharing practices among adolescents and their parents using a closed-loop system. Methods: Eighteen adolescents (aged 11-18 years) and 19 parents were interviewed after adolescents had ∼6 months experience of using a closed-loop system, which permitted them to share glucose and insulin data with parents/caregivers. Data were analyzed thematically. Results: There was considerable variability in how parent-child dyads perceived, valued, and undertook data sharing. Parents of early adolescents (11-13 years) reported making extensive use of "real time" data to remotely manage their child's diabetes and early adolescents described needing and wanting this input. Parents of middle adolescents (14-16 years) described making greater use of retrospective data. To avoid conflict and encourage and support their son/daughter's autonomy, these individuals reported practicing watchful waiting and only intervening after concerns about a pattern of problematic behavior or their child's safety arose. Middle adolescents indicated that data sharing had been done primarily for the benefit of their parents, although they also noted quality of life benefits for themselves. Among late adolescents (17+ years), parents were simply remote because their son/daughter had not permitted access to their data. Participants recommended clear ground rules be put in place about when, and how, data sharing should be used. Conclusions: To help parent-child dyads use data sharing in ways which minimize conflict and optimize constructive parental support, we recommend tailored input and support, which takes account of family dynamics, the young person's developmental maturity, and the different ways in which data are used across the adolescent age range.

Background: Brown adipose tissue (BAT) is essential to maintain body temperature. Its ability to convert chemical energy in glucose and free fatty acids to heat is conferred by a unique protein, UCP-1. BAT activity is greatest in children and adolescents, declining through adulthood. Blood glucose concentrations outside the normal nondiabetic range are common in type 1 diabetes and hyperglycaemia leads to insulin resistance in muscle and white adipose tissue, but whether this applies to BAT, is not known., Method: To investigate the effect of type 1 diabetes on BAT activity, we measured the supraclavicular temperature of 20 children with type 1 diabetes and compared them to 20 age-matched controls, using infrared thermography., Results: The diabetes group had lower stimulated supraclavicular temperatures (diabetes group: 35.03 (34.76-35.30)°C; control group: 35.42 (35.16-35.69)°C; p = 0.037) and a reduced response in relative temperature following cold stimulation, after adjusting for BMI (diabetes group: 0.11 (0.03-0.18)°C; control group: 0.22 (0.15-0.29)°C; p = 0.034). In the diabetes group, there was no association between glycaemic measures and supraclavicular temperatures, but the method of insulin delivery may significantly affect the change in supraclavicular temperature with stimulation (injections: 0.01 (-0.07-0.09)°C; pump: 0.15 (0.04-0.26)°C; p = 0.028)., Conclusions: While further work is needed to better understand the glucose-insulin-BAT relationship, one possible explanation for the reduced supraclavicular temperature is that exogenous, unlike endogenous, insulin, is not suppressed by the activity of the sympathetic nervous system, preventing lipolysis-driven activation of BAT., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Young drivers ages 15-24 continue to constitute a high-risk population for fatal motor vehicle collisions (MVCs) compared to all other age groups. Driving under the influence of cannabis is an important contributor to the high rates of MVCs among youth. Understanding the specific impact of cannabis on the driving performance outcomes of young drivers can inform injury prevention, education, and intervention strategies., Objectives: This systematic literature review (SLR) aims to determine the Class (I- highest to IV-lowest) of evidence and level of confidence (A-high to U-insufficient) in the effects of cannabis on the driving performance of young drivers., Methods: Registered in PROSPERO (#CRD42020180541), this SLR searched seven data bases and appraised the quality and confidence in the evidence using an established research methodology., Results: Class II evidence suggests that THC is likely to reduce mean speed, headway distance, and reaction time; and increase lane and steering wheel position variability among young drivers (Level B, moderate confidence)., Conclusions: This study shows that there is a moderate to low level of confidence on the impact of cannabis on the specific driving performance outcomes of young drivers. A need remains for Class I and II studies that focus on the specific effects on young drivers, distinguish between the biological and socially constructed variables of sex and gender, and includes larger and more representative samples., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: This study aimed to evaluate the proportion of patients with seizures and electroencephalography (EEG) abnormalities in autoimmune encephalitis (AE) and its most common subtypes., Methods: This systematic review followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) standards and was registered with the International Prospective Register of Systematic Reviews (PROSPERO). We searched Medline All, Embase, and PsychINFO in Ovid from inception to June 2019 for articles pertaining to AE and seizure. Included studies reported seizure and/or EEG data in cohorts of ≥10 AE patients. Patient demographics, antibody type, seizure incidence, and EEG findings were extracted. Review of studies and data extraction were performed in duplicate. In addition to descriptive analysis, quantitative synthesis stratified by autoantibody subtype was performed with logistic regression and chi-square analyses., Results: Our search yielded 3856 abstracts: 1616 were selected for full-text review and 118 studies met eligibility criteria. Of 3722 antibody-positive AE patients, 2601 (69.9%) had clinical seizures during the course of their illness. Of the 2025 patients with antibody-positive AE and available EEG data, 1718 (84.8%) had some EEG abnormality (eg, epileptiform discharges, slowing, and so on). Anti- N-methyl-d-aspartate (NMDA) receptor encephalitis (anti-NMDARE) was the most commonly reported type of AE (1985/3722, 53.3%). Of the anti-NMDARE patients with available seizure or EEG data, 71.8% (n = 1425/1985) had clinical seizures during their illness, and 89.7% (n = 1172/1306) had EEG abnormalities. For all AE patients and in the anti-NMDARE subpopulation, seizures were more common in younger patients (p < .05)., Significance: This systematic review provides an estimate of the proportion of AE patients with seizures, confirming the magnitude of seizure burden in this population. Prospective studies are needed to understand population-based prevalence of seizures, identify factors associated with seizures, and evaluate particular EEG findings as biomarkers of seizures and outcomes in AE., (© 2021 International League Against Epilepsy.)

Objective : We evaluated cognitive, emotional, and social function after encephalitis, as perceived and reported by individuals post-encephalitis and their relatives. Hypothesis : There will be differential effects on various domains as self-reported by individuals post-encephalitis. Outcomes will be worse than in prior studies of other forms of acute brain injury. Post-encephalitis relative-report will demonstrate worse outcomes than self-report. Methods and Procedures : Members of The Encephalitis Society residing in the United Kingdom and Ireland were recruited to complete a demographic questionnaire and the European Brain Injury Questionnaire (EBIQ). Results : 266 individuals affected by encephalitis and 140 relatives participated in this study. The three domains with the highest (worst) mean scores were somatic, cognitive , and communication ( p < .001). Individuals post-encephalitis self-reported worse outcomes than individuals post-stroke in seven of nine domains ( p < .005), but there were no differences compared to individuals post-traumatic brain injury (TBI). Relatives reported worse encephalitis outcomes in seven of nine domains than did individuals directly affected by encephalitis ( p < .005). Conclusions : Individuals affected by encephalitis experience the most significant symptoms in the somatic, cognitive , and communication domains. Outcomes as assessed by relatives were notably worse than those assessed by individuals themselves in nearly all domains.

Objective: To review domestic and family violence (DFV) and non-lethal strangulation (NLS) presentations to an ED with 24-h social work., Methods: Retrospective cohort study of 12 months of DFV presentations comparing demographics, perpetrator relationship, social work review, injuries and NLS incidence and assessment., Results: Women represent 90% of DFV presentations. In 26% of DFV presentations NLS was identified, with 47.5% clinically assessed appropriately. Social work did not review 34% of DFV presentations, 64% due to no referral., Conclusions: Social work referral for DFV is regularly missed despite 24-h access. Assessment of NLS in ED requires improvement and standardised national guidelines., (© 2020 Australasian College for Emergency Medicine.)

Aim: To explore health professionals' views about who would benefit from using a closed-loop system and who should be prioritized for access to the technology in routine clinical care., Methods: Health professionals (n = 22) delivering the Closed Loop from Onset in type 1 Diabetes (CLOuD) trial were interviewed after they had ≥ 6 months' experience supporting participants using a closed-loop system. Data were analysed thematically., Results: Interviewees described holding strong assumptions about the types of people who would use the technology effectively prior to the trial. Interviewees described changing their views as a result of observing individuals engaging with the closed-loop system in ways they had not anticipated. This included educated, technologically competent individuals who over-interacted with the system in ways which could compromise glycaemic control. Other individuals, who health professionals assumed would struggle to understand and use the technology, were reported to have benefitted from it because they stood back and allowed the system to operate without interference. Interviewees concluded that individual, family and psychological attributes cannot be used as pre-selection criteria and, ideally, all individuals should be given the chance to try the technology. However, it was recognized that clinical guidelines will be needed to inform difficult decisions about treatment allocation (and withdrawal), with young children and infants being considered priority groups., Conclusions: To ensure fair and equitable access to closed-loop systems, prejudicial assumptions held by health professionals may need to be addressed. To support their decision-making, clinical guidelines need to be made available in a timely manner., (© 2020 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Background: We explored health professionals' views about the training, support, and resourcing needed to support people using closed-loop technology in routine clinical care to help inform the development of formal guidance. Methods: Interviews were conducted with health professionals ( n  = 22) delivering the Closed Loop from Onset in Type 1 Diabetes (CLOuD) trial after they had ≥6 months' experience of supporting participants using a closed-loop system. Data were analyzed descriptively. Results: Interviewees described how, compared with other insulin regimens, teaching and supporting individuals to use a closed-loop system could be initially more time-consuming. However, they also noted that after an initial adjustment period, users had less need for initiating contact with the clinical team compared with people using pumps or multiple daily injections. Interviewees highlighted how a lessened need for ad hoc clinical input could result in new challenges; specifically, they had fewer opportunities to reinforce users' diabetes knowledge and skills and detect potential psychosocial problems. They also observed heightened anxiety among some parents due to the constant availability of data and unrealistic expectations about the system's capabilities. Interviewees noted that all local diabetes teams should be empowered to deliver closed-loop system care, but stressed that health professionals supporting closed-loop users in routine care will need comprehensive technology training and standardized clinical guidance. Conclusion: These findings constitute an important starting point for the development of formal guidance to support the rollout of closed-loop technology. Our recommendations, if actioned, will help limit the potential additional burden of introducing closed-loop systems in routine clinical care and help inform appropriate user education and support.

Introduction: Management of newly diagnosed type 1 diabetes (T1D) in children and adolescents is challenging for patients, families and healthcare professionals. The objective of this study is to determine whether continued intensive metabolic control using hybrid closed-loop (CL) insulin delivery following diagnosis of T1D can preserve C-peptide secretion, a marker of residual beta-cell function, compared with standard multiple daily injections (MDI) therapy., Methods and Analysis: The study adopts an open-label, multicentre, randomised, parallel design, and aims to randomise 96 participants aged 10-16.9 years, recruited within 21 days of diagnosis with T1D. Following a baseline mixed meal tolerance test (MMTT), participants will be randomised to receive 24 months treatment with conventional MDI therapy or with CL insulin delivery. A further 24-month optional extension phase will be offered to all participants to continue with the allocated treatment. The primary outcome is the between group difference in area under the stimulated C-peptide curve (AUC) of the MMTT at 12 months post diagnosis. Analyses will be conducted on an intention-to-treat basis. Key secondary outcomes are between group differences in time spent in target glucose range (3.9-10 mmol/L), glycated haemoglobin (HbA1c) and time spent in hypoglycaemia (<3.9 mmol/L) at 12 months. Secondary efficacy outcomes include between group differences in stimulated C-peptide AUC at 24 months, time spent in target glucose range, glucose variability, hypoglycaemia and hyperglycaemia as recorded by periodically applied masked continuous glucose monitoring devices, total, basal and bolus insulin dose, and change in body weight. Cognitive, emotional and behavioural characteristics of participants and parents will be evaluated, and a cost-utility analysis performed to support adoption of CL as a standard treatment modality following diagnosis of T1D., Ethics and Dissemination: Ethics approval has been obtained from Cambridge East Research Ethics Committee. The results will be disseminated by peer-reviewed publications and conference presentations., Trial Registration Number: NCT02871089; Pre-results., Competing Interests: Competing interests: RH reports having received speaker honoraria from Eli Lilly and Novo Nordisk, serving on advisory panel for Eli Lilly and Novo Nordisk, receiving licence fees from BBraun and Medtronic. RH and MEW report patient patents and patent applications. MT has received speaker honoraria from Medtronic and Novo Nordisk. SH is a member of Sigma (Dexcom) advisory board and reports having received training honoraria from Medtronic and Sanofi. TLR has received speaker honoraria from Novo Nordisk and serves as a consultant for Abbott Diabetes Care. KH has received research support from Dexcom, Inc for an investigator-initiated project; he has received consultant fees from Lilly Innovation Center, Bigfoot Biomedical, and Insulet, Inc., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Congenital hyperinsulinism (CHI) is a significant cause of hypoglycaemia in neonates and infants with the potential for permanent neurologic injury. Accurate calculations of the incidence of rare diseases such as CHI are important as they inform health care planning and can aid interpretation of genetic testing results when assessing the frequency of variants in large-scale, unselected sequencing databases. Whilst minimal incidence rates have been calculated for four European countries, the incidence of CHI in the UK is not known. In this study we have used referral rates to a central laboratory for genetic testing and annual birth rates from census data to calculate the minimal incidence of CHI within the UK from 2007 to 2016. CHI was diagnosed in 278 individuals based on inappropriately detectable insulin and/or C-peptide measurements at the time of hypoglycaemia which persisted beyond 6 months of age. From these data, we have calculated a minimum incidence of 1 in 28,389 live births for CHI in the UK. This is comparable to estimates from other outbred populations and provides an accurate estimate that will aid both health care provision and interpretation of genetic results, which will help advance our understanding of CHI., Competing Interests: The authors have declared that no competing interests exist.

Objective: To determine whether, in children with newly diagnosed type 1 diabetes who were not acutely unwell, management at home for initiation of insulin treatment and education of the child and family, would result in improved clinical and psychological outcomes at 2 years postdiagnosis., Design: A multicentre randomised controlled trial (January 2008/October 2013)., Setting: Eight paediatric diabetes centres in England, Wales and Northern Ireland., Participants: 203 clinically well children aged under 17 years, with newly diagnosed type 1 diabetes and their carers., Intervention: Management of the initiation period from diagnosis at home, for a minimum of 3 days, to include at least six supervised injections and delivery of pragmatic educational care., Main Outcome Measures: Primary outcome was glycosylated haemoglobin (HbA1c) concentration at 24 months postdiagnosis. Secondary outcomes included coping, anxiety, quality of life and use of NHS resources., Results: 203 children, newly diagnosed, were randomised to commence management at home (n=101) or in hospital (n=102). At the 24 month primary end point, there was one withdrawal and a follow-up rate of 194/202 (96%). Mean HbA1c in the home treatment arm was 72.1 mmol/mol and in the hospital treated arm 72.6 mmol/mol. There was a negligible difference between the mean HbA1c levels in the two arms adjusted for baseline (1.01, 95% CI 0.93 to 1.09). There were mostly no differences in secondary outcomes at 24 months, apart from better child self-esteem in the home-arm. No home-arm children were admitted to hospital during initiation and there were no adverse events at that time. The number of investigations was higher in hospital patients during the follow-up period. There were no differences in insulin regimens between the two arms., Conclusions: There is no evidence of a difference between home-based and hospital-based initiation of care in children newly diagnosed with type 1 diabetes across relevant outcomes., Trial Registration Number: ISRCTN78114042., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: A retrospective audit of presentations to a tertiary trauma centre reviewing the demographics of electric scooter injuries in the first 2 months of the scooter-share scheme, which was commenced in Brisbane in November 2018., Methods: Electric scooter-associated presentations to the Royal Brisbane and Women's Hospital Emergency and Trauma Centre from November 2018 to January 2019 were identified. Data collected included patient demographics, type and location of injuries, helmet use, alcohol consumption, length of stay and disposition. Estimates of costs associated with electric scooter presentation were also obtained., Results: Fifty-four electric scooter encounters were included during the 2-month period. Helmets were worn in 46% and was associated with reduced risk of head injury (odds ratio (OR) 0.18, P = 0.029). Alcohol was involved in 27% although this did not impact on admission rates (OR 1.25, P = 0.83) or operative management (OR 2.14, P = 0.42). Contusions/abrasions and fractures/dislocations were the most common types of injury, whereas upper limb and minor head injuries were the most common sites of injury. Most patients were discharged home (87%), with 74% completing their emergency visit in under 4 h. Six patients required operative management and 15 patients needed outpatient follow-up. There were no deaths. Average patient cost per presentation was $542 and ranged from $285 to $1345., Conclusions: The findings characterised injury patterns and costs associated with electric scooters in our ED. Given the increasing popularity of electric scooters as an alternate form of transportation, our study may help to inform public policy for future injury prevention., (© 2019 Australasian College for Emergency Medicine.)

Background: Monitoring of hormonal control represents a key part of the management of congenital adrenal hyperplasia (CAH). Monitoring strategies remain suboptimal because they rely on frequent blood tests and are not specific for adrenal-derived hormones. Recent evidence suggests the crucial role of adrenal-specific 11-oxygenated-C19 androgens in the pathogenesis of CAH., Objective: To establish a correlation between plasma and salivary adrenal-specific androgens in CAH as a noninvasive monitoring strategy., Design: This prospective cross-sectional study recruited patients between 2015 and 2018., Setting: Multicenter study including 13 tertiary centers in the United Kingdom., Participants: Seventy-eight children with CAH and 62 matched healthy controls., Methods: Using liquid chromatography-tandem mass spectrometry, plasma and salivary concentrations of five steroids were measured: 17-hydroxyprogesterone (17OHP), androstenedione (A4), testosterone (T), 11-hydroxyandrostenedione (11OHA4), and 11-ketotestosterone (11KT). The correlation between plasma and salivary steroids was analyzed to assess their use in clinical practice., Results: Strong correlations between plasma and salivary steroid concentrations in patients with CAH were detected: 17OHP (rs = 0.871; P < 0.001), A4 (rs = 0.931; P < 0.001), T (rs = 0.867; P < 0.001), 11OH4A (rs = 0.876; P < 0.001), and 11KT (rs = 0.944; P < 0.001). These results were consistent for patient subgroups based on sex and age. Analysis of patient subgroups based on 17OHP concentrations established clear correlations between plasma and salivary concentrations of the adrenal-specific androgen 11KT., Conclusions: The current study identified tight correlations between plasma and saliva for the adrenal-derived 11-oxygenated C19 androgen 11KT, as well as 17OHP and A4, which are widely used for monitoring treatment in CAH. This combination of steroid hormones will serve as an improved noninvasive salivary test for disease monitoring in patients with CAH., (Copyright © 2019 Endocrine Society.)

Objective: The interaction between thyroid status and brown adipose tissue (BAT) activation is complex. We assessed the effect of autoimmune hypothyroidism (ATD) in female children on BAT activation, measured using infrared thermography., Design: Twenty-six female participants (14 with ATD and 12 healthy controls) between 5 and 17 years of age attended a single study session. Thermal images were taken of the supraclavicular region before, and after, the introduction of a cool stimulus., Results: Participants with ATD had lower resting (hypothyroid, 34.9 ± 0.7°C; control, 35.4 ± 0.5°C; P = 0.03) and stimulated (hypothyroid, 35.0 ± 0.6°C; control, 35.5 ± 0.5°C; P = 0.04) supraclavicular temperatures compared with controls, but there was no difference between groups in the temperature increase with stimulation. BAT activation, calculated as the relative temperature change comparing the supraclavicular temperature to a sternal reference region, was reduced in participants with ATD (hypothyroid, 0.1 ± 0.1°C; control, 0.2 ± 0.2°C; P = 0.04). Children with ATD were frequently biochemically euthyroid due to replacement therapy, but, despite this, increased relative supraclavicular temperature was closely associated with increased TSH ( r = 0.7, P = 0.01) concentrations., Conclusions: Girls with ATD had an attenuated thermogenic response to cold stimulation compared with healthy controls, but, contrary to expectation, those with suboptimal biochemical control (with higher TSH) showed increased BAT activation. This suggests that the underlying disease process may have a negative effect on BAT response, but high levels of TSH can mitigate, and even stimulate, BAT activity. In summary, thyroid status is a complex determinant of BAT activity in girls with ATD., (Copyright © 2019 Endocrine Society.)

Objectives: Hypophosphataemic rickets (HR) is usually secondary to renal phosphate wasting but may occur secondary to reduced intake or absorption of phosphate. We describe a series of cases of HR associated with the use of Neocate ® , an amino-acid based formula (AAF)., Methods: A retrospective review of cases with HR associated with AAF use presenting to centres across the United Kingdom., Results: 10 cases were identified, over a 9 month period, all associated with Neocate ® use. The age at presentation was 5 months to 3 years. The majority (8/10) were born prematurely. Gastro oesophageal reflux disease (6/10) was the most frequent indication for AAF use. Radiologically apparent rickets was observed after a median of 8 months (range 3-15 months) of exclusive Neocate ® feed. The majority (7/10) were diagnosed on the basis of incidental findings on radiographs: rickets (6/10) or fracture with osteopenia (5/10). All patients had typical biochemical features of HR with low serum phosphate, high alkaline phosphatase, normal serum calcium and 25 hydroxyvitamin D. However, in all cases the tubular reabsorption of phosphate (TRP) was ≥96%. Phosphate supplementation resulted in normalisation of serum phosphate within 1-16 weeks, and levels remained normal only after Neocate ® cessation. In patients with sufficient follow up duration (4/10), normalisation of phosphate and radiological healing of rickets was noted after 6 months (range: 6-8 months) following discontinuation of Neocate ® ., Conclusion: The presence of a normal TRP and resolution of hypophosphataemia and rickets following discontinuation of Neocate ® indicates this is a reversible cause likely mediated by poor phosphate absorption. Close biochemical surveillance is recommended for children on Neocate ® , especially in those with gastrointestinal co-morbidities, with consideration of a change in feed or phosphate supplementation in affected children., (Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.)

We present a non-consanguineous family of three siblings who presented with diabetes mellitus (DM), two of whom had genetically confirmed cystic fibrosis (CF), with one pancreatic-sufficient mutation in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene (ΔF508/R117H;IVS8-5T). A detailed history revealed family members from three successive generations diagnosed with 'type 1' or 'type 2' diabetes, leading to genetic investigations for monogenic DM. A heterozygous frameshift mutation in the hepatocyte nuclear factor 1 homeobox alpha ( HNF1A ) gene (c.404delA) was subsequently confirmed in all three siblings, which is known to cause monogenic diabetes and is exquisitely sensitive to sulfonylurea therapy. Following this diagnosis, both siblings with CF and HNF1A monogenic diabetes were started on gliclazide therapy, while their older brother who had been wrongly diagnosed with type 1 diabetes was switched from insulin to gliclazide, all with excellent therapeutic responses., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Physical activity and self-monitoring are important for children with type 1 diabetes mellitus (T1DM) but it is unclear whether interventions delivered online are feasible, acceptable to patients and efficacious. The aim was to assess the feasibility and acceptability of an internet-based physical activity and self-monitoring programme for children with T1DM, and of a randomised controlled trial (RCT) to evaluate efficacy., Methods: A total of 49 children aged 9-12 with T1DM were randomly assigned to usual care only or to an interactive intervention group combining a website (STAK-D) and a PolarActive activity watch (PAW; Polar Electro (UK) Ltd.), alongside usual care. Participants completed self-report measures on their health, self-efficacy and physical activity at baseline (T0), eight weeks (T1) and six months (T2). They also wore a PAW to measure physical activity for one week at the end of T0, T1 and T2. Intervention participants were interviewed about their experiences at T2. Explanatory variables were examined using multi-level modelling and examination of change scores, 95% confidence intervals and p-values with alpha set at 0.95. Descriptive analysis was undertaken of the 'end-of-study questionnaire'. Qualitative analysis followed a framework approach., Results: Completion rates for all self-report items and objective physical activity data were above 85% for the majority of measures. HbA1c data was obtained for 100% of participants, although complete clinical data was available for 63.3% to 63.5% of participants at each data collection time-point. Recruitment and data collection processes were reported to be acceptable to participants and healthcare professionals. Self-reported sedentary behaviour (-2.28, p=0.04, 95% CI=-4.40, -0.16; p = 0.04; d ppc2 = 0.72) and parent-reported physical health of the child (6.15, p=0.01, 95%CI=1.75, 10.55; p = 0.01; d ppc2 = 0.75) improved at eight weeks in the intervention group., Conclusions: The trial design was feasible and acceptable to participants and healthcare providers. Intervention engagement was low and technical challenges were evident in both online and activity watch elements, although enjoyment was high among users. Reported outcome improvements were observed at 8 weeks but were not sustained., Trial Registration: ISRCTN 48994721 (prospectively registered). Date of registration: 28.09.2016.

Background: Left ventricular assist devices (LVADs) improve quality of life in end-stage heart failure but can cause serious complications such as infections with driveline infection causing significant morbidity and mortality., Objectives: The purpose of this systematic literature review is to synthesize the literature to determine variables associated with driveline infection and seek opportunities to improve nursing management of LVAD drivelines., Methods: A systematic literature review was performed. The evidence was synthesized using the Johns Hopkins Nursing Evidence-Based Practice tools and the Chain of Infection epidemiological framework., Results: Thirty-four studies focused on vulnerable host, portal of entry, and causative organism aspects of the Chain of Infection. Increased BMI, younger age, exposed driveline velour showed increased risk of infection and driveline dressing protocol change showed lower risk of infection., Conclusions: Although some risk factors for infection were identified, evidence is still limited. Nurses are uniquely positioned to improve driveline management, disrupting the chain of infection., (Copyright © 2018. Published by Elsevier Inc.)

Background: The role of technology in the self-management of type 1 diabetes mellitus (T1DM) among children and young people is not well understood. Interventions should aim to improve key diabetes self-management behaviours (self-management of blood glucose, insulin administration, physical activity and dietary behaviours) and prerequisites (psychological outcomes and HbA1c) highlighted in the UK guidelines of the National Institute for Health and Care Excellence (NICE) for management of T1DM. The purpose was to identify evidence to assess the effectiveness of technological tools in promoting aspects of these guidelines amongst children and young people., Methods: A systematic review of English language articles was conducted using the following databases: Web of Science, PubMed, Scopus, NUSearch, SAGE Journals, SpringerLink, Google Scholar, Science Direct, Sport Discus, Embase, Psychinfo and Cochrane Trials. Search terms included paediatric, type one diabetes, technology, intervention and various synonyms. Included studies examined interventions which supplemented usual care with a health care strategy primarily delivered through a technology-based medium (e.g. mobile phone, website, activity monitor) with the aim of engaging children and young people with T1DM directly in their diabetes healthcare. Studies did not need to include a comparator condition and could be randomised, non-randomised or cohort studies but not single-case studies., Results: Of 30 included studies (21 RCTs), the majority measured self-monitoring of blood glucose monitoring (SMBG) frequency, clinical indicators of diabetes self-management (e.g. HbA1c) and/or psychological or cognitive outcomes. The most positive findings were associated with technology-based health interventions targeting SMBG as a behavioural outcome, with some benefits found for clinical and/or psychological diabetes self-management outcomes. Technological interventions were well accepted by children and young people. For the majority of included outcomes, clinical relevance was deemed to be little or none., Conclusions: More research is required to assess which elements of interventions are most likely to produce beneficial behavioural outcomes. To produce clinically relevant outcomes, interventions may need to be delivered for at least 1 year and should consider targeting individuals with poorly managed diabetes. It is not possible to determine the impact of technology-based interventions on insulin administration, dietary habits and/or physical activity behaviour due to lack of evidence.

Introduction: Almost 20 years after the first international guidelines on the diagnosis and treatment of GHD have been published, clinical practice varies significantly. The low accuracy of endocrine tests for GHD and the burden caused by ineffective treatment of individual patients were strong motives for national endocrine societies to set up national guidelines regarding how to diagnose GHD in childhood. This audit aims to review the current state and identify common changes, which may improve the diagnostic procedure., Methods: A group of eight German pediatric endocrinologists contacted eight pediatric endocrinologists from Spain, France, Poland, the UK, the Netherlands, Denmark, Italy, and the US. Each colleague responded as a representative for the own country to a detailed questionnaire containing 22 open questions about national rules, guidelines, and practice with respect to GHD diagnostics and GH prescription. The results were presented and discussed in a workshop and then documented in this study which was reviewed by all participants., Results: National guidelines are available in 7 of 9 countries. GH is prescribed by pediatric endocrinologists in most countries. Some countries have established boards that review and monitor prescriptions. Preferred GH stimulation tests and chosen cutoffs vary substantially. Overall, a trend to lowering the GH cutoff was identified. Priming is becoming more popular and now recommended in 5 out of 9 countries; however, with different protocols. The definition of pretest-conditions that qualify the patient to undergo GH testing varies substantially in content and strictness. The most frequently used clinical sign is low height velocity, but definition varies. Height, IGF-1, and bone age are additional parameters recommended in some countries., Conclusions: GHD diagnostics varies substantially in eight European countries and in the US. It seems appropriate to undertake further efforts to harmonize endocrine diagnostics in Europe and the US based on available scientific evidence., (© 2019 S. Karger AG, Basel.)

Objective: To determine accuracy, safety and acceptability of the FreeStyle Libre Flash Glucose Monitoring System in the paediatric population., Design, Setting and Patients: Eighty-nine study participants, aged 4-17 years, with type 1 diabetes were enrolled across 9 diabetes centres in the UK. A factory calibrated sensor was inserted on the back of the upper arm and used for up to 14 days. Sensor glucose measurements were compared with capillary blood glucose (BG) measurements. Sensor results were masked to participants., Results: Clinical accuracy of sensor results versus BG results was demonstrated, with 83.8% of results in zone A and 99.4% of results in zones A and B of the consensus error grid. Overall mean absolute relative difference (MARD) was 13.9%. Sensor accuracy was unaffected by patient factors such as age, body weight, sex, method of insulin administration or time of use (day vs night). Participants were in the target glucose range (3.9-10.0 mmol/L) ∼50% of the time (mean 12.1 hours/day), with an average of 2.2 hours/day and 9.5 hours/day in hypoglycaemia and hyperglycaemia, respectively. Sensor application, wear/use of the device and comparison to self-monitoring of blood glucose were rated favourably by most participants/caregivers (84.3-100%). Five device related adverse events were reported across a range of participant ages., Conclusions: Accuracy, safety and user acceptability of the FreeStyle Libre System were demonstrated for the paediatric population. Accuracy of the system was unaffected by subject characteristics, making it suitable for a broad range of children and young people with diabetes., Trial Registration Number: NCT02388815., Competing Interests: Competing interests: All authors' institutions received financial support from Abbott Diabetes Care to conduct the clinical trial. TR received honoraria/fees for consulting from Abbott Diabetes Care outside of the submitted work. The study sponsor (Abbott Diabetes Care) designed the study protocol in collaboration with the principal investigator and provided all study materials. The sponsor was involved in collecting data and reporting results. The sponsor also gave approval to submit for publication. The corresponding author had full access to all the data in the study and, together with all authors, had final responsibility for the decision to submit for publication., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objective: Neurosurgery in general anesthesia exposes patients to hemodynamic alterations in both the prone and the sitting position. We aimed to evaluate the hemodynamic profile during stroke volume-directed fluid administration in patients undergoing neurosurgery either in the sitting or the prone position., Methods: In 2 separate prospective trials, 30 patients in prone and 28 patients in sitting position were randomly assigned to receive either Ringer acetate (RAC) or hydroxyethyl starch (HES; 130 kDa/0.4) for optimization of stroke volume. After combining data from these 2 trials, 2-way analysis of variance was performed to compare patients' hemodynamic profile between the 2 positions and to evaluate differences between RAC and HES consumption., Results: To achieve comparable hemodynamics during surgery, a higher mean cumulative dose of RAC than HES was needed (679 mL ± 390 vs. 455 mL ± 253; P < 0.05). When fluid consumption was adjusted with weight, statistical difference was lost. Fluid administration did not differ between the prone and sitting position. Mean arterial pressure was lower and cardiac index and stroke volume index were higher over time in patients in the sitting position., Conclusions: The sitting position does not require excess fluid treatment compared with the prone position. HES is slightly more effective than RAC in achieving comparable hemodynamics, but the difference might be explained by patient weight. With goal-directed fluid administration and moderate use of vasoactive drugs, it is possible to achieve stable hemodynamics in both positions., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Regular physical activity has important health benefits for children with type 1 diabetes mellitus (T1DM), yet children and their parents face barriers to participation such as lack of self-efficacy or concerns around hypoglycaemia. Multimedia interventions are useful for educating children about their health and demonstrate potential to improve children's health-related self-efficacy, but few paediatric clinics offer web-based resources as part of routine care. The Steps to Active Kids with Diabetes (STAK-D) programme is an online intervention grounded in psychological theory (social cognitive theory) and informed by extensive preliminary research. The aim of the programme is to encourage and support safe engagement with physical activity for children with T1DM. The aim of this research is to explore the feasibility of delivering the STAK-D programme to children aged 9-12 years with T1DM, and to assess the feasibility of further research to demonstrate its clinical and cost-effectiveness., Methods: Up to 50 children aged 9-12 years with T1DM and their parents will be recruited from two paediatric diabetes clinics in the UK. Child-parent dyads randomised to the intervention group will have access to the intervention website (STAK-D) and a wrist-worn activity monitor for 6 months. The feasibility of intervention and further research will be assessed by rate of recruitment, adherence, retention, data completion and adverse events. Qualitative interviews will be undertaken with a subsample of children and parents (up to 25 dyads) and health care professionals (up to 10). Health outcomes and the feasibility of outcome measurement tools will be assessed. These include self-efficacy (CSAPPA), objective physical activity, self-reported physical activity (PAQ), fear of hypoglycaemia (CHFS; PHFS), glycaemic control (HbA1c), insulin dose, Body Mass Index (BMI), health-related quality of life (CHU9D; CHQ-PF28), health service use and patient-clinician communication. Assessments will be taken at baseline (T0), 8 weeks (T1) and at 6-month follow-up (T2)., Discussion: The goal of this feasibility trial is to assess the delivery of STAK-D to promote physical activity among children with T1DM, and to assess the potential for further, definitive research to demonstrate its effectiveness. Results will provide the information necessary to design a larger randomised controlled trial and maximise the recruitment rate, intervention delivery and trial retention., Trial Registration: ISRCTN, ISRCTN48994721 . Registered on 28 October 2016.

Background: Patients with Congenital Hyperinsulinism (CHI) due to mutations in K-ATP channel genes (K-ATP CHI) are increasingly treated by conservative medical therapy without pancreatic surgery. However, the natural history of medically treated K-ATP CHI has not been described; it is unclear if the severity of recessively and dominantly inherited K-ATP CHI reduces over time. We aimed to review variation in severity and outcomes in patients with K-ATP CHI treated by medical therapy., Methods: Twenty-one consecutively presenting patients with K-ATP CHI with dominantly and recessively inherited mutations in ABCC8/KCNJ11 were selected in a specialised CHI treatment centre to review treatment outcomes. Medical treatment included diazoxide and somatostatin receptor agonists (SSRA), octreotide and somatuline autogel. CHI severity was assessed by glucose infusion rate (GIR), medication dosage and tendency to resolution. CHI outcome was assessed by glycaemic profile, fasting tolerance and neurodevelopment., Results: CHI presenting at median (range) age 1 (1, 240) days resolved in 15 (71%) patients at age 3.1(0.2, 13.0) years. Resolution was achieved both in patients responsive to diazoxide (n = 8, 57%) and patients responsive to SSRA (n = 7, 100%) with earlier resolution in the former [1.6 (0.2, 13.0) v 5.9 (1.6, 9.0) years, p = 0.08]. In 6 patients remaining on treatment, diazoxide dose was reduced in follow up [10.0 (8.5, 15.0) to 5.4 (0.5, 10.8) mg/kg/day, p = 0.003]. GIR at presentation did not correlate with resolved or persistent CHI [14.9 (10.0, 18.5) v 16.5 (13.0, 20.0) mg/kg/min, p = 0.6]. The type of gene mutation did not predict persistence; resolution could be achieved in recessively-inherited CHI with homozygous (n = 3), compound heterozygous (n = 2) and paternal mutations causing focal CHI (n = 2). Mild developmental delay was present in 8 (38%) patients; adaptive functioning assessed by Vineland Adaptive Behavior Scales questionnaire showed a trend towards higher standard deviation scores (SDS) in resolved than persistent CHI [-0.1 (-1.2, 1.6) v -1.2 (-1.7, 0.03), p = 0.1]., Conclusions: In K-ATP CHI patients managed by medical treatment only, severity is reduced over time in the majority, including those with compound heterozygous and homozygous mutations in ABCC8/KCNJ11. Severity and treatment requirement should be assessed periodically in all children with K-ATP CHI on medical therapy.

Background: Relatively little is known about parents' or children's attitudes toward recruitment for, and participation in, studies of new diabetes technologies immediately after diagnosis. This study investigated factors affecting recruitment of participants for studies in newly diagnosed youth with type 1 diabetes., Methods: Qualitative focus group study incorporating four recorded focus groups, conducted in four outpatient pediatric diabetes clinics in large regional hospitals in England. Participants comprised four groups of parents (n = 22) and youth (n = 17) with type 1 diabetes, purposively sampled on the basis of past involvement (either participation or nonparticipation) in an ongoing two-arm randomized trial comparing multiple daily injection with conventional continuous subcutaneous insulin infusion regimens from the onset of type 1 diabetes., Results: Stress associated with diagnosis presents significant challenges in terms of study recruitment, with parents demonstrating varied levels of willingness to be approached soon after diagnosis. Additional challenges arise regarding the following: randomization when study arms are perceived as sharply differentiated in terms of therapy effectiveness; burdens arising from study participation; and the need to surrender new technologies following the end of the study. However, these challenges were mostly insufficient to rule out study participation. Participants emphasized the benefits and reassurance arising from support provided by staff and fellow study participants., Conclusions: Recruitment to studies of new diabetes technologies immediately after diagnosis in youth presents significant challenges, but these are not insurmountable. The stress and uncertainty arising from potential participation may be alleviated by personalized discussion with staff and peer support from fellow study participants., Competing Interests: Author Disclosure Statement R.H. reports having received speaker honoraria from Eli Lilly and Novo Nordisk, serving on advisory panel for Eli Lilly and Novo Nordisk, and patent applications related to closed-loop glucose control. M.T. reports having received speaker honoraria from Novo Nordisk.

Background: Traumatic brain injury (TBI) is one of the leading causes of death and permanent disability. Emergency Medical Services (EMS) personnel are often the first healthcare providers attending patients with TBI. The level of available care varies, which may have an impact on the patient's outcome. The aim of this study was to evaluate mortality and neurological outcome of TBI patients in two regions with differently structured EMS systems., Methods: A 6-year period (2005 - 2010) observational data on pre-hospital TBI management in paramedic-staffed EMS and physician-staffed EMS systems were retrospectively analysed. Inclusion criteria for the study were severe isolated TBI presenting with unconsciousness defined as Glasgow coma scale (GCS) score ≤ 8 occurring either on-scene, during transportation or verified by an on-call neurosurgeon at admission to the hospital. For assessment of one-year neurological outcome, a modified Glasgow Outcome Score (GOS) was used., Results: During the 6-year study period a total of 458 patients met the inclusion criteria. One-year mortality was higher in the paramedic-staffed EMS group: 57 % vs. 42 %. Also good neurological outcome was less common in patients treated in the paramedic-staffed EMS group., Discussion: We found no significant difference between the study groups when considering the secondary brain injury associated vital signs on-scene. Also on arrival to ED, the proportion of hypotensive patients was similar in both groups. However, hypoxia was common in the patients treated by the paramedic-staffed EMS on arrival to the ED, while in the physician-staffed EMS almost none of the patients were hypoxic. Pre-hospital intubation by EMS physicians probably explains this finding., Conclusion: The results suggest to an outcome benefit from physician-staffed EMS treating TBI patients., Trial Registration: ClinicalTrials.gov ID NCT01454648.

We sought to identify factors associated with the prognosis and survival of burn patients by analyzing data related to the prehospital treatment of burn patients transferred directly to the burn unit from the accident site. We also aimed to assess the role of prehospital physicians and paramedics providing care to major burn patients. This study included adult burn patients with severe burns treated between 2006 and 2010. Prehospital patient records and clinical data collected during treatment were analyzed, and the Injury Severity Scale (ISS) was calculated. Patients were grouped into two cohorts based on the presence or absence of a physician during the prehospital phase. Data were analyzed with reference to survival by multivariable regression model. Specific inclusion criteria resulted in a sample of 67 patients. The groups were comparable with regard to age, gender, and injury etiology. Patients treated by prehospital physicians (group 1, n = 49) were more severely injured than patients treated by paramedics (group 2, n = 18) in terms of total burn surface area (%TBSA) (32% vs. 17%, p = 0.033), ISS (25 vs. 8, p < 0.000), and inhalation injuries (51% vs. 16%, p = 0.013), and presented with a higher pulse rate, lower systolic blood pressure, and lower median pH. Age, gender, %TBSA, and ISS were significantly associated with survival in both groups. Survival at 30 days was associated with age, gender, the amount of intravenous fluids (in liters) received during the first 24 hours, and the final %TBSA. Variables found to be independently associated by multivariable regression model with 30 day mortality were age, female gender, and final TBSA. We identified prehospital prognostic factors affecting patient outcomes. Based on the results from this study, our current EMS system is capable of identifying seriously injured burn patients who may benefit from physician attendance at the injury scene.

Background: The use of blood products after subarachnoid hemorrhage (SAH) is common, but not without controversy. The optimal hemoglobin level in patients with SAH is unknown, and data on perioperative need for red blood cell (RBC), fresh frozen plasma (FFP), or platelet transfusions are limited. We studied perioperative administration of RBCs, FFP, and platelets and the impact of red blood cell transfusions (RBCTs) on outcome in patients undergoing surgery for ruptured a cerebral arterial aneurysm., Methods: A retrospective analysis was performed of 488 patients with aneurysmal SAH during the years 2006-2009 at Helsinki University Central Hospital. Patients who received RBC, FFP, or platelet concentrates perioperatively were compared with a cohort of patients from the Helsinki database of aneurysmal SAH who did not receive transfusions. A multiple regression model was created to identify factors related to transfusion and outcome., Results: RBC, FFP, or platelet concentrates were given in 7.6% (37 of 488), 3.1% (15 of 488), and 1.2% (6 of 488) of patients intraoperatively and in 3.5% (17 of 486), 1.6% (8 of 488), and 0.9% (4 of 488) of patients postoperatively. Of 37 intraoperative RBCTs, 26 were related to intraoperative rupture of the aneurysm. Intraoperative RBCTs were associated with lower preoperative hemoglobin concentration, higher World Federation of Neurosurgical Societies classification, and intraoperative rupture of an aneurysm. In multivariate analysis, intraoperative RBCT (odds ratio = 5.13, 95% confidence interval = 1.53-17.15), worse World Federation of Neurosurgical Societies classification and Fisher grade (odds ratio = 1.97, confidence interval = 1.64-2.36 and odds ratio = 1.89, confidence interval = 1.23-2.92, respectively), and increasing age (odds ratio = 1.07, confidence interval = 1.04-1.10) independently increased the risk of poor neurologic outcome at 3 months., Conclusions: Transfusion frequencies of RBCs, FFP, and platelets were relatively low. Intraoperative RBCT was strongly related to intraoperative rupture of the aneurysm in patients with poor-grade SAH. The observed association between poor outcome and RBCT in patients with SAH warrants further study., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The aim of physician staffed emergency medical services (EMS) is to supplement other EMS units in the care of prehospital patients. The need for advanced airway management in critical prehospital patients can be considered as one indicator of the severity of the patient's condition. Our primary aim was to study the long-term outcome of critically ill patients (excluding cardiac arrest) who were intubated by EMS physicians in the prehospital setting., Methods: Data of 845 patients, whose airways were secured by the EMS physicians during a 5-year (2007-2011) period, were retrospectively evaluated. After exclusions, the outcome of 483 patients (8.9% of all patients treated by EMS) was studied. Evaluation was based on hospital patient records 1 year after the incident. For assessment of neurological outcome, a modified Glasgow Outcome Score (GOS) was used. Time and cause of death were recorded., Results: 55.3% of the study patients had a good neurological recovery (GOS 4-5) with independent life 1 year after the event. The overall 1-year mortality (GOS 1) was 35.0%. Poor neurological outcome (GOS 2-3) was found in 9.7% of the patients. Patients with intoxication or convulsions survived best, while those with suspected intracranial pathology had the worst prognosis. Of all survivors, 85% recovered well., Conclusion: The majority of the study patients had a favourable neurological recovery with independent life at 1 year after the incident. More than 80% of all deaths occurred within 30 days of the incident., (© 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Aims: To synthesize evidence from randomized and non-randomized studies of physical activity interventions in children and young people with Type 1 diabetes so as to explore clinically relevant health outcomes and inform the promotion of physical activity., Method: We conducted a search of CINAHL Plus, the Cochrane Library, EMBASE, MEDLINE, PsycINFO, SCOPUS, SportDiscus and Web of Science between October and December 2012. Eligible articles included subjects aged ≤18 years with Type 1 diabetes and a physical activity intervention that was more than a one-off activity session. Physiological, psychological, behavioural or social outcomes were those of interest., Results: A total of 26 articles (10 randomized and 16 non-randomized studies), published in the period 1964-2012, were reviewed. Although there was heterogeneity in study design, methods and reporting, 23 articles reported at least one significant beneficial health outcome at follow-up. Meta-analyses of these studies showed potential benefits of physical activity on HbA1c (11 studies, 345 participants, standardized mean difference -0.52, 95% CI -0.97 to -0.07; P = 0.02), BMI (four studies, 195 participants, standardized mean difference -0.41, 95% CI -0.70 to -0.12; P = 0.006) and triglycerides (five studies, 206 participants, standardized mean difference -0.70, 95% CI -1.25 to -0.14; P = 0.01).The largest effect size was for total cholesterol (five studies, 206 participants, standardized mean difference -0.91, 95% CI -1.66 to -0.17; P = 0.02)., Conclusions: Physical activity is important for diabetes management and has the potential to delay cardiovascular disease, but there is a lack of studies that are underpinned by psychological behaviour change theory, promoting sustained physical activity and exploring psychological outcomes. There remains a lack of knowledge of how to promote physical activity in people with Type 1 diabetes., (© 2014 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Purpose: General anesthesia in the prone position is associated with hypotension. We studied stroke volume (SV)-directed administration of hydroxyethyl starch (HES 130 kDa/0.4) and Ringer’s acetate (RAC) in neurosurgical patients operated on in a prone position to determine the volumes required for stable hemodynamics and possible coagulatory effects., Methods: Thirty elective neurosurgical patients received either HES (n = 15) or RAC (n = 15). Before positioning, SV measured by arterial pressure waveform analysis was maximized by fluid boluses until SV did not increase more than 10 %. SV was maintained by repeated administration of fluid. RAC 3 ml/kg/h was infused in both groups. Thromboelastometry assessed coagulation. Mann–Whitney U test, Wilcoxon signed-rank test, ANOVA on ranks, and a linear mixed model were applied., Results: Comparable hemodynamics were achieved with the mean cumulative (SD) boluses of HES or RAC 240 (51) or 267 (62) ml (P = 0.207) before positioning, 340 (124) or 453 (160) ml (P = 0.039) 30 min after positioning, and 440 (229) or 653 (368) ml at the end of surgery (P = 0.067). The mean dose of basal RAC infusion was 813 (235) and 868 (354) ml (P = 0.620) in the HES and RAC group, respectively. Formation and maximum strength of the fibrin clot were decreased in the HES group. Intraoperative blood loss was comparable between groups (P = 0.861)., Conclusion: The amount of RAC needed in the prone position was 25 % greater. The cumulative dose of 440 ml HES induced a slight disturbance in fibrin formation and clot strength. We suggest cautious administration of HES during neurosurgery.

Expansion of CAG/CTG trinucleotide repeats causes numerous inherited neurological disorders, including Huntington's disease (HD), several spinocerebellar ataxias and myotonic dystrophy type 1. Expanded repeats are genetically unstable with a propensity to further expand when transmitted from parents to offspring. For many alleles with expanded repeats, extensive somatic mosaicism has been documented. For CAG repeat diseases, dramatic instability has been documented in the striatum, with larger expansions noted with advancing age. In contrast, only modest instability occurs in the cerebellum. Using microarray expression analysis, we sought to identify the genetic basis of these regional instability differences by comparing gene expression in the striatum and cerebellum of aged wild-type C57BL/6J mice. We identified eight candidate genes enriched in cerebellum, and validated four--Pcna, Rpa1, Msh6 and Fen1--along with a highly associated interactor, Lig1. We also explored whether expression levels of mismatch repair (MMR) proteins are altered in a line of HD transgenic mice, R6/2, that is known to show pronounced regional repeat instability. Compared with wild-type littermates, MMR expression levels were not significantly altered in R6/2 mice regardless of age. Interestingly, expression levels of these candidates were significantly increased in the cerebellum of control and HD human samples in comparison to striatum. Together, our data suggest that elevated expression levels of DNA replication and repair proteins in cerebellum may act as a safeguard against repeat instability, and may account for the dramatically reduced somatic instability present in this brain region, compared with the marked instability observed in the striatum.

Background: Femoral neck fractures (FNFs) comprise 50% of geriatric hip fractures. Appropriate management requires surgeons to balance potential risks and associated healthcare costs with surgical treatment. Treatment complications can lead to reoperation resulting in increased patient risks and costs. Understanding etiologies of treatment failure and the population at risk may decrease reoperation rates., Questions/purposes: We therefore (1) determined if treatment modality and/or displacement affected reoperation rates after FNF; and (2) identified factors associated with increased reoperation and timing and reasons for reoperation., Methods: We reviewed 1411 records of patients older than 60 years treated for FNF with internal fixation or hemiarthroplasty between 1998 and 2009. We extracted patient age, sex, fracture classification, treatment modality and date, occurrence of and reasons for reoperation, comorbid conditions at the time of each surgery, and dates of death or last contact. Minimum followup was 12 months (median, 45 months; range, 12-157 months)., Results: Internal fixation (hazard ratio [HR], 6.38) and displacement (HR, 2.92) were independently associated with increased reoperation rates. The reoperation rate for nondisplaced fractures treated with fixation was 15% and for displaced fractures 38% after fixation and 7% after hemiarthroplasty. Most fractures treated with fixation underwent reoperation within 1 year primarily for nonunion. Most fractures treated with hemiarthroplasty underwent reoperation within 3 months, primarily for infection., Conclusions: Overall, hemiarthroplasty resulted in fewer reoperations versus internal fixation and displaced fractures underwent reoperation more than nondisplaced. Our data suggest there are fewer reoperations when treating elderly patients with displaced FNFs with hemiarthroplasty than with internal fixation.

Background: To determine the volumes required for stable haemodynamics and possible effects on the coagulation, we studied stroke volume (SV)-directed administration of hydroxyethyl starch (HES 130 kDa/0.4) and Ringer's acetate (RAC) in neurosurgical patients operated on in a sitting position., Methods: Thirty craniotomy patients were randomised to receive either HES or RAC. Before positioning, SV, measured by arterial pressure waveform analysis, was maximised by boluses of fluid until SV did not increase more than 10%. SV was maintained by repeated administration of fluid. RAC 3 ml/kg/h was infused in both groups during surgery., Results: Comparable haemodynamics were achieved with the mean [standard deviation (SD)] cumulative doses of HES or RAC 271 (47) or 264 (50) ml (P = 0.699) before the sitting position. Mean (SD) doses of HES or RAC at 30 min after the positioning were 343 (94) or 450 (156) ml (P = 0.036), and at the end of surgery 464 (284) or 707 (425) ml, respectively (P = 0.087). The intraoperative fluid balance was more positive in the RAC than in the HES group [P = 0.044, 95% confidence interval (CI) -978 to -14]. Cardiac and stroke volume indexes [CI and stroke volume index (SVI)] increased in the HES group (P < 0.05) but not in the RAC group [non significant (N.S.)]. Neither coagulation profile nor blood loss differed between the groups., Conclusion: Fluid filling with HES boluses resulted in a positive response in CI and SVI during the sitting position. The 34% smaller volume of HES than crystalloid and less positive fluid balance in the HES group might be important in craniotomy patients with decreased brain compliance., (© 2013 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Although Discrete-trial Teaching (DTT) is effective in teaching a many skills to children with autism, its proper implementation requires rigorous staff training. This study used an interactive computer simulation program ("DTkid") to teach staff relevant DTT skills. Participants (N = 12) completed two sets of pre-tests either once (n = 7) or twice (n = 5) before brief DTkid training. These evaluated (a) simulated interactive teaching using DTkid and (b) in vivo teaching of three basic skills (receptive and expressive labeling; verbal imitation) to children with autism. Post-tests showed that DTkid training, rather than repeated testing, was significantly associated with improvements in staff's ability to implement DTT both within the simulation and in vivo, and that the skills acquired showed both stimulus and response generalization.

Congenital hyperinsulinism (CHI) is a rare disorder of hypoglycaemia in children due to excessive and dysregulated insulin secretion. Octreotide, a somatostatin analogue, is used in the treatment of hypoglycaemia in Diazoxide unresponsive CHI, but is associated with side effects such as gastrointestinal dysmotility and rarely, necrotising enterocolitis. It would be important to recognise rare but serious side effects from Octreotide therapy, particularly with long-term use. In this report, we have described drug-induced hepatitis with moderately high doses of Octreotide in a child with diffuse CHI. While serum alanine transaminase levels rose significantly with Octreotide therapy (maximum dose 30 μg/kg/day), hepatitis resolved following discontinuation of medical treatment. Liver enzymes should be monitored routinely in children with CHI using long-term Octreotide treatment, particularly with high doses. The presence of drug-induced hepatitis should prompt discontinuation of Octreotide treatment with likely subsequent resolution.

Study Objective: To understand the timing and factors affecting diagnosis of phenotypically female 46XY children., Design, Setting, and Participants: We studied all phenotypically female 46XY children who attended our multidisciplinary disorders of sexual differentiation (DSD) clinic in Nottingham England in a 3-year period since its inception. Case notes from a prospectively maintained database were reviewed and data were analyzed on the age at presentation, family history, findings on genital examination, and underlying endocrine abnormality., Results: Eleven children were studied, all of whom were being raised as girls. The median age of presentation was 18 months (range birth-15 years). Although the newborn examination detected the possibility of DSD in only 3 cases; 10 of 11 children had at least one significant abnormality in their external genitalia at presentation., Conclusion: Careful neonatal genital examination can identify children with DSD. However, not all children with these conditions are identified early. Early diagnosis, when possible, is important, as it has the potential to make the management of this difficult condition more straightforward., (Copyright © 2012 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.)

Context: Isolated 17,20 lyase deficiency is commonly defined by apparently normal 17α-hydroxylase activity but severely reduced 17,20 lyase activity of the bifunctional enzyme cytochrome P450 (CYP) enzyme 17A1 (CYP17A1), resulting in sex steroid deficiency but normal glucocorticoid and mineralocorticoid reserve. Cytochrome b5 (CYB5A) is thought to selectively enhance 17,20 lyase activity by facilitating the allosteric interaction of CYP17A1 with its electron donor P450 oxidoreductase (POR)., Objective: We investigated a large consanguineous family including three siblings with 46,XY disorder of sex development (DSD) presenting with isolated 17,20 lyase deficiency., Design: We investigated the clinical and biochemical phenotype, conducted genetic analyses, and functionally characterized the identified CYB5A mutation in cell-based CYP17A1 coexpression assays., Results: All three siblings presented with 46,XY DSD, sex steroid deficiency, normal mineralocorticoids and glucocorticoids, and a urine steroid metabolome suggestive of isolated 17,20 lyase deficiency. CYP17A1 and POR sequences were normal, but we detected a homozygous CYB5A missense mutation (g.28,400A→T; p.H44L). Functional in vitro analysis revealed normal CYP17A1 17α-hydroxylase activity but severely impaired 17,20 lyase activity. In silico analysis suggested the disruption of CYB5A heme binding by p.H44L., Conclusion: We have identified the first human CYB5A missense mutation as the cause of isolated 17,20 lyase deficiency in three individuals with 46,XY DSD. Detailed review of previously reported cases with apparently isolated 17,20 lyase deficiency due to mutant CYP17A1 and POR reveals impaired 17α-hydroxylase activity as assessed by steroid metabolome analysis and short cosyntropin testing. This suggests that truly isolated 17,20 lyase deficiency is observed only in individuals with inactivating CYB5A mutations.

Background: The pre-hospital assessment of a blunt trauma is difficult. Common triage tools are the mechanism of injury (MOI), vital signs, and anatomic injury (AI). Compared to the other tools, the clinical assessment of anatomic injury is more subjective than the others, and, hence, more dependent on the skills of the personnel.The aim of the study was to estimate whether the training and qualifications of the personnel are associated with the accuracy of prediction of anatomic injury and the completion of pre-hospital procedures indicated by local guidelines., Methods: Adult trauma patients met by a trauma team at Helsinki University Trauma Centre during a 12-month period (n = 422) were retrospectively analysed. To evaluate the accuracy of prediction of anatomic injury, clinically assessed pre-hospital injuries in six body regions were compared to injuries assessed at hospital in two patient groups, the patients treated by pre-hospital physicians (group 1, n = 230) and those treated by paramedics (group 2, n = 190)., Results: The groups were comparable in respect to age, sex, and MOI, but the patients treated by physicians were more severely injured than those treated by paramedics [ISS median (interquartile range) 16 (6-26) vs. 6 (2-10)], thus rendering direct comparison of the groups ineligible. The positive predictive values (95% confidence interval) of assessed injury were highest in head injury [0,91 (0,84-0,95) in group 1 and 0,86 (0,77-0,92) in group 2]. The negative predictive values were highest in abdominal injury [0,85 (0,79-0,89) in group 1 and 0,90 (0,84-0,93) in group 2]. The measurements of agreement between injuries assessed pre- and in-hospitally were moderate in thoracic and extremity injuries. Substantial kappa values (95% confidence interval) were achieved in head injury, 0,67 (0,57-0,77) in group 1 and 0,63 (0,52-0,74) in group 2. The rate of performing the pre-hospital procedures as indicated by the local instructions was 95-99%, except for decompression of tension pneumothorax., Conclusion: Accurate prediction of anatomic injury is challenging. No conclusive differences were seen in the ability of pre-hospital physicians and paramedics to predict anatomic injury in the respective patient populations.

Objective: To present a summary of anesthetic considerations for use of the sitting position in procedures to remove lesions of the occipital and suboccipital regions, with a special reference to the Helsinki experience with more than 300 operations in 1997-2007, and a retrospective study evaluating the incidence of venous air embolism (VAE) and hemodynamic stability in patients operated in the steep sitting position., Methods: Anesthesiology reports of 72 patients with a mean (± standard deviation [SD]) age of 33 years ± 18 treated by the senior author (J.H.) for pineal region tumors using the infratentorial supracerebellar approach in the sitting position during an 11-year period were retrospectively reviewed for the incidence of VAE and hemodynamic stability., Results: In the sitting position, median systolic blood pressure changed -8 (-95 to +50) mm Hg without alteration in heart rate. Based on patient records, the incidence of VAE was 19% (14 of 72 patients). In five patients, end-tidal carbon dioxide (ETCO(2)) decreased more than 0.7 kPa (5.25 mm Hg), possibly indicating VAE. Comparing patients with and without VAE, no differences in change of blood pressure, heart rate, or amount of administered vasoactive agents were observed. Postoperative duration of ventilator treatment and hospital stay were similar in patients with and without VAE. No signs of arterial embolization were seen postoperatively., Conclusions: The sitting position is associated with risk for hypotension. The same surgical approach and procedure does not exclude the occurrence of VAE. In this study, the unaltered hemodynamics in patients during VAE indicates relatively small VAE. Possible explanations for this are early recognition of air leakage and good cooperation between the surgical and anesthesia teams., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: Rupture of an intracranial aneurysm during surgical clipping may have devastating consequences. Should this happen all methods ought to be considered to stop the bleeding. A short-term cardiac arrest induced by adenosine could be a feasible method to help the surgeon. We present our experiences in the administration of adenosine during an intraoperative aneurysm rupture., Methods: Medical records of patients who underwent surgical clipping of a cerebral arterial aneurysm were reviewed from 2 university hospitals' operative database in the years 2003 to 2008. Patients were included in this study if adenosine had been administered during intraoperative rupture of an aneurysm., Results: Altogether, 16 of 1014 patients were identified with the use of adenosine during an intraoperative rupture of an aneurysm. All of the patients had sinus rhythm and normotension before the rupture of the aneurysm. Twelve patients were administered a single dose of adenosine and 4 multiple boluses for induction of cardiac arrest; the median (range) total dose was 12 (6-18) mg and 27 (18-87) mg, respectively. The clipping of the aneurysm and the recovery of circulation were uneventful in all cases. In a subgroup analysis according to patient outcome as alive/dead, the pre- and postoperative neurologic condition correlated with the outcome, whereas adenosine did not have any effect on the patient outcome., Conclusion: In a case of a sudden aneurysm rupture, adenosine-induced circulatory arrest could be a safe option to facilitate clipping of an aneurysm. However, if adenosine is used, a very close collaboration between the surgeon and the anesthesiologist is required., (Copyright © 2010 Elsevier Inc. All rights reserved.)