Ten-year review of trends in children with type 1 diabetes in England and Wales.

This review describes the prevalence, incidence, and demographics of children and young people (CYP) with type 1 diabetes in England and Wales using data from the United Kingdom National Paediatric Diabetes Audit (NPDA) and has almost 100% submission from all paediatric diabetes centres annually. It is a powerful benchmarking tool and is an essential part of a long-term quality improvement programme for CYP with diabetes. Clinical characteristics of this population by age, insulin regimen, complication rates, health inequalities, access to diabetes technology, socioeconomic deprivation and glycaemic outcomes over the past decade is described in the review. The NPDA for England and Wales is commissioned by the United Kingdom Healthcare Quality Improvement Partnership as part of the National Clinical Audit for the United Kingdom National Service Framework for Diabetes. The rising incidence of Type 1 diabetes is evidenced in the past decade. Reduction in national median glycated hemoglobin for CYP with diabetes is observed over the last 10 years and the improvement sustained by various initiatives and quality improvement pro-grammes implemented with universal health coverage.

Association of British Clinical Diabetologists, Diabetes Technology Network UK and Association of Children's Diabetes Clinicians Survey of UK Healthcare Professional Attitudes Towards Open-Source Automated Insulin Delivery Systems.

INTRODUCTION: Automated insulin delivery (AID) systems can enable improved glycaemic outcomes with reduced mental burden. Open-source AID (OS-AID) systems overcome some of the developmental and access barriers enabling a wider use of these systems. Limited data are available on healthcare professional (HCP) opinions and current practice regarding these systems. The aim of this survey was to gain insight into HCP perceptions and practices around OS-AID. METHODS: This survey was developed collaboratively with OS-AID users and distributed to adult and children's teams, using an online survey tool. Results were received between February and April 2019. Responses were assessed using simple descriptive statistics with analyses stratified by respondent characteristics. RESULTS: 317 responses were obtained from a range of HCPs in both adult and paediatric services. Key results include: HCP perception of OS-AID as "risky in the wrong hands" (43%); 91% felt uncomfortable initiating discussions around OS-AID because of lack of regulation (67%) and/or their own lack of knowledge (63%). Half of HCPs (47%) reported that they would choose OS-AID if they themselves had type 1 diabetes. CONCLUSIONS: HCPs are generally supportive of OS-AID users but many feel uncomfortable with the technicalities of the systems given the lack of approval. Knowledge around the use of these systems was limited. Re-assessment of HCP perceptions should be performed in the future given the evolving landscape of diabetes technology, recent consensus statements and emerging ethical and legal perspectives.

Open-source automated insulin delivery systems are an increasingly encountered diabetes technology. These involve a small glucose sensor and an insulin delivery device called an insulin pump. These two devices interact to allow adjustment of insulin delivery to maintain glucose levels in a desirable range. The computer codes which drive these systems are developed by people with diabetes or their families rather than by device companies; as such, they have not been through formal approval processes and therefore there is limited formal evidence concerning whether they are safe or beneficial to use. Users report high satisfaction with these devices and improvements in their diabetes management. This survey was performed to assess the opinions of UK healthcare professionals and their usual practice. Key results include: UK healthcare professionals would not routinely recommend the use of these devices and there was concern about the medicolegal implications of use. However, UK healthcare professionals were generally supportive of those who chose to use the devices. Interestingly, almost half of the healthcare professionals would use the systems if they had diabetes.

A Solution Focused Approach of Delivering Virtual Paediatric Diabetes Consultations During the COVID-19 Pandemic.

The onset of the COVID-19 global pandemic rapidly accelerated the use of virtual consultations into everyday practice. A solution focused approach (SFA) has been established in paediatric diabetes care, resulting in positive clinical outcomes and communication. The aim of this study was to assess feedback from paediatric diabetes patients and their parents or carers regarding virtual consultations, using a solution focused approach, in a hospital setting. An electronic survey was sent to patients following their virtual consultation. Of those surveyed, 86% recommended video consultations to be part of their diabetes care. Qualitative data showed reduced travel time, comfort, reduced need for parking and convenience as the highest areas improved through video consultations. Clinical care was shown to be positive and addressed patients concerns, the majority of respondents (84%) reported that the appointment was about what they wanted it to be about. Using the solution focused model helped overcome the challenges faced with virtual consultations particularly with concerns surrounding safeguarding issues, confidentiality, audio/video difficulties and also helped to support the patient journey.

Fluid and electrolyte therapy in childhood diabetic ketoacidosis management: A rationale for new national guideline.

Fluid and electrolyte therapy in childhood diabetic ketoacidosis (DKA) management has been controversial. Previous National Institute for Health and Care Excellence (NICE) 2015 guidance advocated a restricted fluid regimen while more recent guidelines have advocated a more liberal approach to fluid replacement in DKA. At the core of the debate is the need to avoid developing cerebral oedema as a complication. Although subtle asymptomatic cerebral oedema is common in children presenting in DKA, clinically apparent cerebral oedema is rare and has been reported in approximately 0.5%-1% of DKA cases in children. Recent research evidence has shown that there was no clear evidence of a difference in rates of clinically apparent cerebral injury in children in DKA managed with a range of fluid volumes and rates of rehydration. In view of this, NICE has updated its guideline. In this paper, we review literature evidence underpinning the current understanding of the pathophysiology of cerebral oedema in children and discuss the rationale for the new NICE guidance.

Hybrid closed-loop therapy: Where are we in 2021?

Hybrid closed-loop systems are characterized by the coexistence of algorithm-driven automated insulin delivery combined with manual mealtime boluses. Used correctly, these insulin delivery systems offer better glucose control and reduced risk of hypoglycaemia and represent the most advanced form of insulin delivery available for people with type 1 diabetes. The aim of this paper was to compare the currently available commercial hybrid closed-loop systems in the UK: the Medtronic 670G/780G, Tandem t:slim X2 Control IQ and CamAPS FX systems. The Medtronic 670G/780G systems use Guardian 3 sensor (7-day use, two to four calibrations per day), while Tandem and CamAPS systems use the calibration-free Dexcom G6 sensor (10 days). The CamAPS system is available as an android app, whereas the other two systems have the algorithm embedded in the insulin pump. During pivotal studies, depending on the study population and baseline glycated haemoglobin level, these systems achieve a time spent in the target range 3.9 to 10 mmol/L (70 to 180 mg/dL) of 65% to 76% with low burden of hypoglycaemia. All three systems allow a higher glucose target for announced exercise, while the Tandem system offers an additional night-time tighter target. The CamAPS system offers fully customizable glucose targets and is the only system licensed for use during pregnancy. Additional education is required for both users and healthcare professionals to harness the best performance from these systems as well as to troubleshoot when "automode exits" occur. We provide consensus recommendations to develop pragmatic pathways to guide patients, clinicians and commissioners in making informed decisions on the appropriate use of the diabetes technology.

Vaginal Bleeding in Pre-pubertal Females.

STUDY OBJECTIVE: Puberty is a normal process for adolescents, and the first signs may include change in body odor, breast development, or pubic hair growth. This is then followed by menarche approximately 2 years later. Vaginal bleeding in pre-pubertal female individuals is rare. The aim of this study was to investigate causes of pre-pubertal bleeding in a group of patients. DESIGN, SETTING, METHOD, AND MAIN OUTCOME MEASURES: Seventeen patients who presented with pre-pubertal recurrent vaginal bleeding with no other signs of precocious puberty were investigated, to determine the cause of this symptom. RESULTS: The mean age for the onset of vaginal bleeding was 7.4 years, ranging from 4 to 9.67 years. Gonadotrophin-releasing hormone (GnRH) stimulation tests showed a pre-pubertal response in all cases. Pelvic ultrasound scans showed a pre-pubertal uterus in all patients. Two patients were found to have foreign bodies identified during a genital examination under anesthetic, and in both cases removal of the foreign bodies terminated the vaginal bleeding. CONCLUSION: In conclusion, recurrent vaginal bleeding was not associated with GnRH response, raised estradiol levels, or abnormal pelvic ultrasound findings. In cases of recurrent vaginal bleeding with normal hormonal investigations in pre-pubertal girls, it is recommended that a genital examination under anesthetic be undertaken to rule out undiagnosed causes of the presenting symptom.

Freestyle libre flash glucose monitoring improves patient quality of life measures in children with Type 1 diabetes mellitus (T1DM) with appropriate provision of education and support by healthcare professionals.

BACKGROUND: In 2017 the UK's Association of Children's Diabetes Clinicians (ACDC) launched a national educational package to provide training in the use of Freestyle Flash glucose monitoring (GM) to healthcare professionals. OBJECTIVE: To evaluate metabolic outcomes and quality of life (QoL) of children with T1DM trained in the use of the Freestyle Flash GM system adopting the ACDC guidelines. METHODS: Prospective study conducted at a single UK children's diabetes unit from 2017 to 2018.52 children with T1DM (age 5-18 yrs) were commenced on the Freestyle Flash GM system, received education and were followed up for 12 months. The Peds QL 3.2 diabetes questionnaire was used to assess QoL before and after the use of the system. HbA1c was measured at 3, 6 and 12 months pre and post use of Freestyle. RESULTS: 52 children (33 M,19 F) with a mean age of 11.6 yrs (range 4 m-17.2 yrs) were evaluated. Mean HbA1c 3 months post Freestyle Flash GM showed a significant improvement when compared with HbA1c values at 12, 6 and 3 months pre Freestyle (p-value 0.040, 0.040, 0.012 respectively). This improvement was not sustained at 6 and 12 months (p-value 0.15, 0.50). The PedsQL3.2 diabetes scores demonstrated significant improvement in patient QoL, reduction of diabetes symptoms and treatment barriers following the use of the new technology (p-values 0.014; 0.018; 0.035 respectively). CONCLUSIONS: Freestyle Flash GM technology associated with appropriate education and regular support by healthcare professionals improves patient quality of life measures in children with T1DM.

Adrenal function of extremely premature infants in the first 5 days after birth.

Background There is limited data on adrenal function in the early days after birth in extremely premature infants. The relationship between plasma adrenocorticotrophic (ACTH) and cortisol hormone is central to the integrity of the hypothalamic-pituitary-adrenal (HPA) axis yet there are no studies examining this relationship in prematurity. Methods The aim of this study was to examine the relationship between early morning plasma cortisol and ACTH concentrations during the first 5 days after birth in infants born at less than 28 weeks' gestation and to identify any independent factors that determine plasma cortisol levels in these infants during extreme prematurity. We prospectively studied early morning plasma ACTH and cortisol concentrations in infants born below 28 weeks' gestation during the first 5 days of birth. Plasma cortisol was measured without extraction, using DPC Immulite® 2000 using a solid phase 2 site chemiluminescent immunometric assay. ACTH was measured using a radioimmunoassay. Spearman's correlation was used to examine the relationship between cortisol and ACTH. Multiple regression analysis was used to examine the relationship between plasma cortisol and clinical risk index for babies (CRIB) score, antenatal dexamethasone, mode of delivery and gestation. Results There were 95 infants (53 males) of mean gestation 25.3 ± 1.3 standard deviation (SD) (range 23-27 + 6) weeks. The mean birth weight was 809 ± 17.0 g. The mean plasma cortisol was 400.5 ± 42.6 nmol/L and the mean plasma ACTH was 4.5 ± 0.9 pmol/L. Early morning plasma cortisol correlated significantly with gestation (R = 0.4, p = 0.005). Early morning plasma ACTH did not correlate with early morning plasma cortisol (R = -0.12, p = 0.7). Multiple regression analysis showed that gestation was the only independent determinant of early morning plasma cortisol concentration (beta coefficient = -0.4, p = 0.04). Conclusions The relationship between early morning plasma ACTH and plasma cortisol is either not established or is impaired in infants of less than 28 weeks' gestation in the first 5 days after birth. The plasma cortisol level is mainly determined by gestation and is not directly related to illness severity, antenatal steroids or plasma ACTH in these infants in the first 5 days after birth.

Socioeconomic Deprivation, Household Education, and Employment are Associated With Increased Hospital Admissions and Poor Glycemic Control in Children With Type 1 Diabetes Mellitus.

BACKGROUND: Socioeconomic deprivation, obesity, and emotional discomfort are important determinants of health inequalities and poor glycemic control in children and young people with type 1 diabetes mellitus (T1D). OBJECTIVES: The aims of this study were to evaluate the incidence of hospital admissions of T1D children in relation to socioeconomic deprivation, and to determine the effects of social deprivation, body mass index (BMI), and patient-reported emotional well-being on glycemic control. METHODS: All hospital admissions of T1D patients aged 1-18 years were identified during 2007 and 2012. Admission cause and glycemic control were related to social deprivation, BMI, and psychological, emotional well-being. Indices of Multiple Deprivation (IMD) 2010 were applied to the United Kingdom data. The associations were calculated using the Spearman's rank correlation coefficient. RESULTS: A significant correlation was found between hospital admission rates and overall deprivation scores (r = -0.18, p = 0.04). Patients living in deprived areas were more likely to selfpresent to the accident and emergency department (r = -0.24, p = 0.02). Poor glycemic control (n = 124) was significantly associated with lower levels of education (r = -0.22, p = 0.02) and unemployment (r = -0.19, p = 0.04). Significance was not reached for level of income (r = -0.16, p = 0.07) and overall deprivation (r = -0.17, p = 0.06). Glycemic control was not found to be associated with BMI, standard deviation scores (SDS), or emotional well-being. CONCLUSION: Early intervention and education from primary care and specialist diabetes teams within the community in deprived areas may be effective in reducing hospital admissions for diabetes-related problems and improving glycemic control.

Do maternal factors influence neonatal thyroid status in the extreme premature infant?

BACKGROUND: In early pregnancy, maternal transfer of thyroxine (T4) significantly contributes to the foetal T4 requirements. Interruption of the maternal transfer of T4 may lead to inadequate T4 exposure, potentially leading to neurodevelopmental deficits. AIM: To determine if maternal factors are associated with the thyroid hormone status of extremely premature infants during the first five days of life. METHOD: This prospective study looked at 117 mothers and their extremely premature babies (born before 28 weeks' gestation). The relationship between neonatal thyroid hormone status and maternal factors (gestation, route of delivery, exogenous maternal glucocorticoid administration, maternal free T4 (FT4), presence or absence of maternal chorioamnionitis, maternal smoking status, maternal body mass index (BMI) index, maternal thyroid peroxidase antibody status (TPO) and maternal haemoglobin levels) were evaluated. Multiple linear regression was used to study independent factors affecting neonatal thyroid function. RESULTS: Mean gestational age was 25(+5) ± 1.3 weeks (range 22(+0) to 27(+6)). Neonatal FT4 strongly correlated with gestation, with a greater severity of hypothyroxinaemia associated with lower gestation (r = 0.6, p < 0.0001). Multiple regression found gestation to be the only independent factors affecting thyroid status (beta coefficient = 0.08, p = 0.01), and no maternal factors were found to be associated with neonatal thyroid status. CONCLUSION: Neonatal thyroid status in extreme preterm infants is independently affected by gestation and not maternal factors such as route of delivery, exogenous maternal glucocorticoid administration, third trimester maternal FT4, presence or absence of chorioamnionitis, smoking status, BMI, TPO status or haemoglobin levels. The severity of neonatal hypothyroxinaemia increases with lower gestational age.

An explanatory randomised placebo controlled trial of levothyroxine supplementation for babies born <28 weeks' gestation: results of the TIPIT trial.

BACKGROUND: Babies born before 28 weeks' gestation have lower plasma thyroid hormone concentrations than more mature infants. This may contribute to their risk of poor developmental outcome. Previous studies have suggested that thyroxine supplementation for extremely preterm neonates may be beneficial. The aim of this study was to investigate the effect of administration of supplemental thyroxine to very premature babies on brain size and somatic growth at 36 weeks' corrected gestational age (CGA). METHODS: In this explanatory multicentre double blind randomised placebo controlled trial, 153 infants born below 28 weeks' gestation were randomised to levothyroxine (LT4) supplementation or placebo until 32 weeks' CGA. The primary outcome was brain size assessed by the width of the subarachnoid space measured by cranial ultrasound at 36 weeks' CGA. Lower leg length was measured by knemometry. RESULTS: Babies in the LT4-supplemented and placebo groups had similar baseline characteristics. There were no significant differences between infants given LT4 (n=78) or placebo (n=75) for width of the subarachnoid space, head circumference at 36 weeks' CGA, body weight at 36 weeks' CGA or mortality. Infants who received LT4 had significantly shorter leg lengths at 36 weeks' CGA although adjusted analysis for baseline length did not find a statistical difference. There was a significant correlation between low FT4 and wider subarachnoid space. No unexpected serious adverse events were noted and incidence of adverse events did not differ between the two groups. CONCLUSION: This is the only randomised controlled trial of thyroxine supplementation targeting extremely premature infants. Supplementing all babies below 28 weeks' gestation with LT4 had no apparent effect on brain size. These results do not support routine supplementation with LT4 for all babies born below 28 weeks' gestation. TRIAL REGISTRATION: Current Controlled Trials ISRCTN89493983EUDRACT number: 2005-003-09939.

A novel method of collection of saliva for estimation of steroid levels in extremely premature infants.

AIM: The major advantage of salivary cortisol sampling is that it is considerably less invasive than taking a blood sample. However, previous methods of obtaining saliva in premature infants have been poorly tolerated and inaccurate. We describe a simple, non-distressing technique for obtaining saliva samples to assess extremely premature infants' salivary cortisol status. METHODS: We prospectively obtained early morning saliva samples from extremely premature infants. Their gestational age ranged between 23 and 27 weeks. Saliva was obtained using four standard universal swabs by placing one swab at a time in the infant's mouth for 1-2 min. No salivary stimulants were used. RESULTS: There were 65 infants (36 males). Mean gestation was 25.3 ± 1.3 weeks. This technique had a success rate of 85% in obtaining a mean of 150 µL of saliva (range 50-350 µL) by trained staff. No adverse events were recorded. CONCLUSION: We describe a novel, safe, non-distressing and effective method of saliva collection for salivary cortisol measurement in extremely premature infants.

TIPIT: a randomised controlled trial of thyroxine in preterm infants under 28 weeks gestation: magnetic resonance imaging and magnetic resonance angiography protocol.

BACKGROUND: Infants born at extreme prematurity are at high risk of developmental disability. A major risk factor for disability is having a low level of thyroid hormone described as hypothyroxinaemia, which is recognised to be a frequent phenomenon in these infants. Derangements of critical thyroid function during the sensitive window in prematurity when early development occurs, may have a range of long term effects for brain development. Further research in preterm infants using neuroimaging techniques will increase our understanding of the specificity of the effects of hypothyroxinaemia on the developing foetal brain. This is an explanatory double blinded randomised controlled trial which is aimed to assess the effect of thyroid hormone supplementation on brain size, key brain structures, extent of myelination, white matter integrity and vessel morphology, somatic growth and the hypothalamic-pituitary-adrenal axis. METHODS: The study is a multi-centred double blinded randomised controlled trial of thyroid hormone supplementation in babies born below 28 weeks' gestation. All infants will receive either levothyroxine or placebo until 32 weeks corrected gestational age. The primary outcomes will be width of the sub-arachnoid space measured using cranial ultrasound and head circumference at 36 weeks corrected gestational age. The secondary outcomes will be thyroid hormone concentrations, the hypothalamic pituitary axis status and auxological data between birth and expected date of delivery; thyroid gland volume, brain size, volumes of key brain structures, extent of myelination and brain vessel morphology at expected date of delivery and markers of morbidity which include duration of mechanical ventilation and/or oxygen requirement and chronic lung disease. Trial registration Current Controlled Trials ISRCTN89493983.

TIPIT: A randomised controlled trial of thyroxine in preterm infants under 28 weeks' gestation.

BACKGROUND: Infants born at extreme prematurity (below 28 weeks' gestation) are at high risk of developmental disability. A major risk factor for disability is having a low level of thyroid hormone which is recognised to be a frequent phenomenon in these infants. At present it is unclear whether low levels of thyroid hormone are a cause of disability, or a consequence of concurrent adversity. METHODS: We propose an explanatory multi-centre double blind randomised controlled trial of thyroid hormone supplementation in babies born below 28 weeks' gestation. All infants will receive either levothyroxine or placebo until 32 weeks' corrected gestational age. The primary outcome will be brain growth. This will be assessed by the width of the sub-arachnoid space measured using cranial ultrasound and head circumference at 36 weeks' corrected gestational. The secondary outcomes will be (a) thyroid hormone concentrations measured at increasing postnatal age, (b) status of the hypothalamic pituitary axis, (c) auxological data between birth and 36 weeks' corrected gestational age, (d) thyroid gland volume, (e) volumes of brain structures (measured by magnetic resonance imaging), (f) determination of the extent of myelination and white matter integrity (measured by diffusion weighted MRI) and brain vessel morphology (measured by magnetic resonance angiography) at expected date of delivery and (g) markers of morbidity including duration of mechanical ventilation and chronic lung disease.We will also examine how activity of the hypothalamic-pituitary-adrenal axis modulates the effects of thyroid supplementation. This will contribute to decisions about which confounding variables to assess in large-scale studies. TRIAL REGISTRATION: Current Controlled Trials ISRCTN89493983.

Selecting girls with precocious puberty for brain imaging: validation of European evidence-based diagnosis rule.

OBJECTIVES: To test the sensitivities of recently published American recommendations predicting occult intracranial lesion (OICL) in girls with central precocious puberty (CPP), and to validate a previously derived diagnosis rule predicting OICL based on age at puberty onset and estradiol (E2) level. STUDY DESIGN: A retrospective, multicenter, hospital-based, cohort study was performed, including all girls with CPP seen in 7 centers in 6 European countries during given periods. American recommendations and the previously derived diagnosis rule were tested. RESULTS: Girls with CPP (n=443), including 35 with OICL, were recruited. American recommendations did not identify all OICL. Previously identified independent risk factors for OICL were confirmed: age <6 years (adjusted odds ratio 20.5; 95% CI, 8.1-52.1) and E2 >45th percentile (3.0; 95% CI, 1.3-7.1). The previously derived diagnosis rule had 100% sensitivity (95% CI, 90-100): all girls with OICL had either an age <6 years or an E2 level >45th percentile. The specificity was 39% (95% CI, 34-44). CONCLUSIONS: American recommendations do not seem safe to select European girls with CPP who require brain imaging. In settings where systematic brain imaging is not possible, the proposed diagnosis rule could safely help to avoid more than one third of unnecessary brain imaging.