Cancer in general practice research priorities in Australia.

BACKGROUND AND OBJECTIVES: The Primary Care Collaborative Cancer Clinical Trials Group (PC4) is funded by Cancer Australia to support the development of new cancer in primary care research. We undertook a research prioritisation exercise to identify cancer research priorities in Australian general practice. METHOD: We adapted the nominal group technique, including a literature search and stakeholder survey. An expert group from the Primary Care Collaborative Cancer Clinical Trials Group consolidated and ranked priorities. A second stakeholder survey reviewing the top 50 priorities informed a final prioritisation workshop. RESULTS: Overall, 311 priorities were identified across the cancer continuum. Nearly one-third of priorities were related to cancer survivorship and included strategies to detect recurrence, behavioural interventions and tools to assess physical and psychosocial aspects of survivorship. Prevention/early detection comprised 43.4% of priorities. Palliative care produced the least priorities (9.6%). Cross cutting research priorities (15.1%) included quality and models of care. DISCUSSION: This is the first study to identify cancer research priorities for general practice in Australia. It could be used to inform the development of targeted research and funding to improve the care and outcomes for Australians affected by cancer.

Semaglutide treatment for children with obesity: an observational study.

OBJECTIVE: To assess efficacy and tolerability of semaglutide as a weight loss treatment for children living with comorbid obesity. DESIGN: Retrospective observational study of the first 50 children from a weight management service treated with semaglutide for at least 6 months. SETTING: A tertiary paediatric multidisciplinary weight management clinic in a UK hospital. PATIENTS: Aged 10-18 years old with a body mass index (BMI) SD score (SDS) >2 with a weight-related comorbidity (including insulin resistance (defined as homeostatic model assessment for insulin resistance >4), type 2 diabetes, metabolic-associated fatty liver disease, obstructive sleep apnoea or hypertension). INTERVENTIONS: Once-weekly injectable semaglutide titrated over 8 weeks to a final dose of 1 mg in addition to dietary and lifestyle advice. MAIN OUTCOME MEASURES: Primary outcome measures were change in weight, BMI SDS and percentage body weight. Secondary outcomes were side effects and cessation of treatment. RESULTS: After 6 months of treatment, statistically significant decreases in BMI SDS (0.32±0.27, p<0.001) and body weight (7.03±7.50 kg, p<0.001) were seen. Mean percentage total weight loss was 6.4±6.3% (p<0.001). For the 14 patients for whom 12-month data were available, statistically significant decreases were seen in mean BMI SDS (0.54±0.52, p<0.001). Mean body weight decreased by 9.7±10.8 kg (p<0.001). Percentage total weight loss at 12 months was 8.9±10.0% (p<0.001). Mild gastrointestinal side effects were common. One patient developed gallstones. Five patients discontinued treatment due to side effects. CONCLUSION: Semaglutide appears to be a safe and effective weight loss adjunct when used in a multidisciplinary weight management clinic.

Cost-Effectiveness of Closed-Loop Automated Insulin Delivery Using the Cambridge Hybrid Algorithm in Children and Adolescents with Type 1 Diabetes: Results from a Multicenter 6-Month Randomized Trial.

BACKGROUND/OBJECTIVE: The main objective of this study is to evaluate the incremental cost-effectiveness (ICER) of the Cambridge hybrid closed-loop automated insulin delivery (AID) algorithm versus usual care for children and adolescents with type 1 diabetes (T1D). METHODS: This multicenter, binational, parallel-controlled trial randomized 133 insulin pump using participants aged 6 to 18 years to either AID (n = 65) or usual care (n = 68) for 6 months. Both within-trial and lifetime cost-effectiveness were analyzed. Analysis focused on the treatment subgroup (n = 21) who received the much more reliable CamAPS FX hardware iteration and their contemporaneous control group (n = 24). Lifetime complications and costs were simulated via an updated Sheffield T1D policy model. RESULTS: Within-trial, both groups had indistinguishable and statistically unchanged health-related quality of life, and statistically similar hypoglycemia, severe hypoglycemia, and diabetic ketoacidosis (DKA) event rates. Total health care utilization was higher in the treatment group. Both the overall treatment group and CamAPS FX subgroup exhibited improved HbA1C (-0.32%, 95% CI: -0.59 to -0.04; P = .02, and -1.05%, 95% CI: -1.43 to -0.67; P < .001, respectively). Modeling projected increased expected lifespan of 5.36 years and discounted quality-adjusted life years (QALYs) of 1.16 (U.K. tariffs) and 1.52 (U.S. tariffs) in the CamAPS FX subgroup. Estimated ICERs for the subgroup were £19 324/QALY (United Kingdom) and -$3917/QALY (United States). For subgroup patients already using continuous glucose monitors (CGM), ICERs were £10 096/QALY (United Kingdom) and -$33 616/QALY (United States). Probabilistic sensitivity analysis generated mean ICERs of £19 342/QALY (95% CI: £15 903/QALY to £22 929/QALY) (United Kingdom) and -$28 283/QALY (95% CI: -$59 607/QALY to $1858/QALY) (United States). CONCLUSIONS: For children and adolescents with T1D on insulin pump therapy, AID using the Cambridge algorithm appears cost-effective below a £20 000/QALY threshold (United Kingdom) and cost saving (United States).

Sex-specific threat responding and neuronal engagement in carbon dioxide associated fear and extinction: Noradrenergic involvement in female mice.

Difficulty in appropriately responding to threats is a key feature of psychiatric disorders, especially fear-related conditions such as panic disorder (PD) and posttraumatic stress disorder (PTSD). Most prior work on threat and fear regulation involves exposure to external threatful cues. However, fear can also be triggered by aversive, within-the-body, sensations. This interoceptive signaling of fear is highly relevant to PD and PTSD but is not well understood, especially in the context of sex. Using female and male mice, the current study investigated fear-associated spontaneous and conditioned behaviors to carbon dioxide (CO2) inhalation, a potent interoceptive threat that induces fear and panic. We also investigated whether behavioral sensitivity to CO2 is associated with delayed PTSD-relevant behaviors. CO2 evoked heterogenous freezing behaviors in both male and female animals. However, active, rearing behavior was significantly reduced in CO2-exposed male but not female mice. Interestingly, behavioral sensitivity to CO2 was associated with compromised fear extinction, independent of sex. However, in comparison to CO2-exposed males, females elicited less freezing and higher rearing during extinction suggesting an engagement of active versus passive defensive coping. Persistent neuronal activation marker ΔFosB immuno-mapping revealed attenuated engagement of infralimbic-prefrontal areas in both sexes but higher activation of brain stem locus coeruleus (LC) area in females. Inter-regional co-activation mapping revealed sex-independent disruptions in the infralimbic-amygdala associations but altered LC associations only in CO2-exposed female mice. Lastly, dopamine ß hydroxylase positive (DßH + ve) noradrenergic neuronal cell counts in the LC correlated with freezing and rearing behaviors during CO2 inhalation and extinction only in female but not male mice. Collectively, these data provide evidence for higher active defensive responding to interoceptive threat CO2-associated fear in females that may stem from increased recruitment of the brainstem noradrenergic system. Our findings reveal distinct contributory mechanisms that may promote sex differences in fear and panic associated pathologies.

Time Spent in Hypoglycemia According to Age and Time of Day: Observations During Closed-Loop Insulin Delivery.

Objective: We aimed to assess whether percentage of time spent in hypoglycemia during closed-loop insulin delivery differs by age group and time of day. Methods: We retrospectively analyzed data from hybrid closed-loop studies involving young children (2-7 years), children and adolescents (8-18 years), adults (19-59 years), and older adults (≥60 years) with type 1 diabetes. Main outcome was time spent in hypoglycemia <3.9 mmol/L (<70 mg/dL). Eight weeks of data for 88 participants were analyzed. Results: Median time spent in hypoglycemia over the 24-h period was highest in children and adolescents (4.4% [interquartile range 2.4-5.0]) and very young children (4.0% [3.4-5.2]), followed by adults (2.7% [1.7-4.0]), and older adults (1.8% [1.2-2.2]); P < 0.001 for difference between age groups. Time spent in hypoglycemia during nighttime (midnight-05:59) was lower than during daytime (06:00-23:59) across all age groups. Conclusion: Time in hypoglycemia was highest in the pediatric age group during closed-loop insulin delivery. Hypoglycemia burden was lowest overnight across all age groups.

The nature and impact of patient and public involvement in cancer prevention, screening and early detection research: A systematic review.

Patient and public involvement can produce high-quality, relevant research that better addresses the needs of patients and their families. This systematic review investigated the nature and impact of patient and public involvement in cancer prevention, screening and early detection research. Two patient representatives were involved as members of the review team. Databases (Medline, EMBASE, Emcare, Involve Evidence Library) were searched for English-language studies published 1995-March 2022. Titles/abstracts were screened by two reviewers independently. For eligible studies, data were extracted on study characteristics, patient and public involvement (who, when, how, and impact on research outcomes), and reporting quality using the Guidance for Reporting Involvement of Patients and the Public 2-Short Form. Of 4095 articles screened, 58 were eligible. Most research was from the United States (81%) and examined cancer screening or prevention (82%). Community members/organisations/public were the most involved (71%); fewer studies involved patients and/or carers (14%). Over half reported a high-level of involvement (i.e. partner and/or expert involvement), although this declined in later stages of the research cycle, e.g. data analysis. Common positive impacts included improved study design, research methods and recruitment, although most papers (62%) did not describe methods to determine impact. Reporting quality was sub-optimal, largely due to failure to consider challenges. This review found that high-level involvement of patients and the public in cancer prevention, screening and early detection research is feasible and has several advantages. However, improvements are needed to encourage involvement across the research cycle, and in evaluating and reporting its impact.

Evaluating the Impact of Applying Personal Glucose Targets in a Closed-Loop System for People With Type 1 Diabetes.

BACKGROUND: CamAPS FX is a hybrid closed-loop smartphone app used to manage type one diabetes. The closed-loop algorithm has a default target glucose of 5.8 mmol/L (104.5 mg/dL), but users can select personal glucose targets (adjustable between 4.4 mmol/L and 11.0 mmol/L [79 mg/dL and 198 mg/dL, respectively]). METHOD: In this post-hoc analysis, we evaluated the impact of personal glucose targets on glycemic control using data from participants in five randomized controlled trials. RESULTS: Personal glucose targets were widely used, with 20.3% of all days in the data set having a target outside the default target bin (5.5-6.0 mmol/L [99-108 mg/dL]). Personal glucose targets >6.5 mmol/L (117 mg/dL) were associated with significantly less time in target range (3.9-10.0 mmol/L [70-180 mg/dL]; 6.5-7.0 mmol/L [117-126 mg/dL]: mean difference = -3.2 percentage points [95% CI: -5.3 to -1.2; P < .001]; 7.0-7.5 mmol/L [126-135 mg/dL]: -10.8 percentage points [95% CI: -14.1 to -7.6; P < .001]). Personal targets >6.5 mmol/L (117 mg/dL) were associated with significantly lower time (<3.9 mmol/L [<70 mg/dL]; 6.5-7.0 mmol/L [117-126 mg/dL]: -1.85 percentage points [95% CI: -2.37 to -1.34; P < .001]; 7.0-7.5 mmol/L [126-135 mg/dL]: -2.68 percentage points [95% CI: -3.49 to -1.86; P < .001]). CONCLUSIONS: Discrete study populations showed differences in glucose control when applying similar personal targets.

Lived experience of CamAPS FX closed loop system in youth with type 1 diabetes and their parents.

AIM: To examine changes in the lived experience of type 1 diabetes after use of hybrid closed loop (CL), including the CamAPS FX CL system. MATERIALS AND METHODS: The primary study was conducted as an open-label, single-period, randomized, parallel design contrasting CL versus insulin pump (with or without continuous glucose monitoring). Participants were asked to complete patient-reported outcomes before starting CL and 3 and 6 months later. Surveys assessed diabetes distress, hypoglycaemia concerns and quality of life. Qualitative focus group data were collected at the completion of the study. RESULTS: In this sample of 98 youth (age range 6-18, mean age 12.7 ± 2.8 years) and their parents, CL use was not associated with psychosocial benefits overall. However, the subgroup (n = 12) using the CamAPS FX system showed modest improvements in quality of life and parent distress, reinforced by both survey (p < .05) and focus group responses. There were no negative effects of CL use reported by study participants. CONCLUSIONS: Closed loop use via the CamAPS FX system was associated with modest improvements in aspects of the lived experience of managing type 1 diabetes in youth and their families. Further refinements of the system may optimize the user experience.

A Qualitative Study Exploring Feasibility and Acceptability of Acupuncture, Yoga, and Mindfulness Meditation for Managing Weight After Breast Cancer.

INTRODUCTION: Weight gain is common after breast cancer. Yoga, mindfulness meditation, and acupuncture may assist with managing weight. However, evidence on effectiveness is limited. This study assessed the feasibility and acceptability of recruiting for and implementing a randomized controlled trial (RCT) evaluating these interventions as adjuncts to lifestyle interventions (diet and exercise) for weight management in women with breast cancer. METHODS: Qualitative study involving virtual focus groups or semi-structured interviews. Participants were recruited via email invitation from a breast cancer consumer organization and breast cancer center in Australia. Eligible participants had received treatment for breast cancer, and were fluent in English. A purposive sample of culturally and linguistically diverse (CALD) participants was also recruited. Focus groups and interviews were audio-recorded, transcribed verbatim and analyzed using thematic analysis with the constant comparison method. RESULTS: Emails were sent to 1415 women of which 37 provided data in 5 focus groups and 1 semi-structured interview, including 1 focus group (n = 6) with only women from CALD backgrounds. Yoga and mindfulness meditation were perceived as feasible and acceptable for weight management, but acupuncture was seen to be too invasive to be acceptable. A focus on wellness rather than weight reduction, flexible program delivery, trusted advice, consideration of participant burden and benefit, and peer-support were key factors perceived to increase feasibility and acceptability. CONCLUSIONS: Yoga and mindfulness meditation are acceptable and useful adjuncts to lifestyle interventions for weight management after breast cancer. This research places end-users at the forefront of trial design, and will inform future trials using these interventions for weight management and improving health and wellbeing after breast cancer.

Cambridge hybrid closed-loop algorithm in children and adolescents with type 1 diabetes: a multicentre 6-month randomised controlled trial.

BACKGROUND: Closed-loop insulin delivery systems have the potential to address suboptimal glucose control in children and adolescents with type 1 diabetes. We compared safety and efficacy of the Cambridge hybrid closed-loop algorithm with usual care over 6 months in this population. METHODS: In a multicentre, multinational, parallel randomised controlled trial, participants aged 6-18 years using insulin pump therapy were recruited at seven UK and five US paediatric diabetes centres. Key inclusion criteria were diagnosis of type 1 diabetes for at least 12 months, insulin pump therapy for at least 3 months, and screening HbA1c levels between 53 and 86 mmol/mol (7·0-10·0%). Using block randomisation and central randomisation software, we randomly assigned participants to either closed-loop insulin delivery (closed-loop group) or to usual care with insulin pump therapy (control group) for 6 months. Randomisation was stratified at each centre by local baseline HbA1c. The Cambridge closed-loop algorithm running on a smartphone was used with either (1) a modified Medtronic 640G pump, Medtronic Guardian 3 sensor, and Medtronic prototype phone enclosure (FlorenceM configuration), or (2) a Sooil Dana RS pump and Dexcom G6 sensor (CamAPS FX configuration). The primary endpoint was change in HbA1c at 6 months combining data from both configurations. The primary analysis was done in all randomised patients (intention to treat). Trial registration ClinicalTrials.gov, NCT02925299. FINDINGS: Of 147 people initially screened, 133 participants (mean age 13·0 years [SD 2·8]; 57% female, 43% male) were randomly assigned to either the closed-loop group (n=65) or the control group (n=68). Mean baseline HbA1c was 8·2% (SD 0·7) in the closed-loop group and 8·3% (0·7) in the control group. At 6 months, HbA1c was lower in the closed-loop group than in the control group (between-group difference -3·5 mmol/mol (95% CI -6·5 to -0·5 [-0·32 percentage points, -0·59 to -0·04]; p=0·023). Closed-loop usage was low with FlorenceM due to failing phone enclosures (median 40% [IQR 26-53]), but consistently high with CamAPS FX (93% [88-96]), impacting efficacy. A total of 155 adverse events occurred after randomisation (67 in the closed-loop group, 88 in the control group), including seven severe hypoglycaemia events (four in the closed-loop group, three in the control group), two diabetic ketoacidosis events (both in the closed-loop group), and two non-treatment-related serious adverse events. There were 23 reportable hyperglycaemia events (11 in the closed-loop group, 12 in the control group), which did not meet criteria for diabetic ketoacidosis. INTERPRETATION: The Cambridge hybrid closed-loop algorithm had an acceptable safety profile, and improved glycaemic control in children and adolescents with type 1 diabetes. To ensure optimal efficacy of the closed-loop system, usage needs to be consistently high, as demonstrated with CamAPS FX. FUNDING: National Institute of Diabetes and Digestive and Kidney Diseases.

Non-alcoholic fatty liver disease and childhood obesity.

Non-alcoholic fatty liver disease (NAFLD) in children and adolescents has an estimated prevalence of 36.1% in the context of obesity. This figure is anticipated to increase in conjunction with the global obesity epidemic. Worryingly, NAFLD in childhood persisting into adulthood is likely to be harmful, contributing to significant hepatic and extrahepatic morbidities. Early disease detection is required, although the optimum timing, frequency and mode of screening remains undetermined. While the efficacy of several medications, antioxidants, fatty acid supplements and probiotics has been investigated in children, healthy eating and physical activity remain the only prevention and treatment strategies for paediatric NAFLD. This short review discusses the epidemiology, diagnosis, pathogenesis and management of NAFLD in childhood obesity.

Combined resistance and aerobic exercise intervention improves fitness, insulin resistance and quality of life in survivors of childhood haemopoietic stem cell transplantation with total body irradiation.

PURPOSE: To investigate the effects of a supervised combined resistance and aerobic training programme on cardiorespiratory fitness, body composition, insulin resistance and quality of life (QoL) in survivors of childhood haematopoietic stem cell transplantation (HSCT) with total body irradiation (TBI). PARTICIPANTS: HSCT/TBI survivors (n = 20; 8 females). Mean (range) for age at study and time since HSCT/TBI was 16.7 (10.9-24.5) and 8.4 (2.3-16.0) years, respectively. METHODS: After a 6-month run-in, participants undertook supervised 45- to 60-minute resistance and aerobic training twice weekly for 6 months, with a 6-month follow-up. The following assessments were made at 0, 6 (start of exercise programme), 12 (end of exercise programme) and 18 months: Body composition via dual energy X-ray absorptiometry, homeostatic model assessment of insulin resistance (HOMA-IR), cardiorespiratory fitness (treadmill-based peak rate of oxygen uptake (VO2 peak) test), QoL questionnaires (36-Item Short Form Health Survey (SF-36) and Minneapolis-Manchester Quality of Life Instrument (MMQL). RESULTS: Results expressed as mean (standard deviation) or geometric mean (range). There were significant improvements in VO2 peak (35.7 (8.9) vs 41.7 (16.1) mL/min/kg, P = 0.05), fasted plasma insulin (16.56 (1.48-72.8) vs 12.62 (1.04-54.97) mIU/L, P = 0.03) and HOMA-IR (3.65 (0.30-17.26) vs 2.72 (0.22-12.89), P = 0.02) after the exercise intervention. There were also significant improvements in the SF-36 QoL general health domain (69.7 (14.3) vs 72.7 (16.0), P = 0.001) and the MMQL school domain (69.1 (25.2) vs (79.3 (21.6), P = 0.03) during the exercise intervention. No significant changes were observed in percentage body fat, fat mass or lean mass. CONCLUSION: The supervised 6-month combined resistance and aerobic exercise programme significantly improved cardiorespiratory fitness, insulin resistance and QoL in childhood HSCT/TBI survivors, with no change in body composition, suggesting a metabolic training effect on muscle. These data support a role for targeted physical rehabilitation services in this group at high risk of diabetes and cardiovascular disease.

Mental health among Ebola survivors in Liberia, Sierra Leone and Guinea: results from a cross-sectional study.

OBJECTIVES: To describe the prevalence and correlates of depression and anxiety among adult Ebola virus disease (EVD) survivors in Liberia, Sierra Leone and Guinea. DESIGN: Cross-sectional. SETTING: One-on-one surveys were conducted in EVD-affected communities in Liberia, Sierra Leone and Guinea in early 2018. PARTICIPANTS: 1495 adult EVD survivors (726 male, 769 female). PRIMARY AND SECONDARY OUTCOME MEASURES: Patient Health Questionnaire-9 (PHQ-9) depression scores and Generalised Anxiety Disorder-7 (GAD-7) scores. RESULTS: Prevalence and severity of depression and anxiety varied across the three countries. Sierra Leone had the highest prevalence of depression, with 22.0% of participants meeting the criteria for a tentative diagnosis of depression, compared with 20.2% in Liberia and 13.0% in Guinea. Sierra Leone also showed the highest prevalence of anxiety, with 10.7% of participants meeting criteria for generalized anxiety disorder (GAD-7 score ≥10), compared with 9.9% in Liberia and 4.2% in Guinea. Between one-third and one-half of respondents reported little interest or pleasure in doing things in the previous 2 weeks (range: 47.0% in Liberia to 37.6% in Sierra Leone), and more than 1 in 10 respondents reported ideation of self-harm or suicide (range: 19.4% in Sierra Leone to 10.4% in Guinea). Higher depression and anxiety scores were statistically significantly associated with each other and with experiences of health facility-based stigma in all three countries. Other associations between mental health scores and respondent characteristics varied across countries. CONCLUSIONS: Our results indicate that both depression and anxiety are common among EVD survivors in Liberia, Sierra Leone and Guinea, but that there is country-level heterogeneity in prevalence, severity and correlates of these conditions. All three countries should work to make mental health services available for survivors, and governments and organisations should consider the intersection between EVD-related stigma and mental health when designing programmes and training healthcare providers.

PLIN1 Haploinsufficiency Is Not Associated With Lipodystrophy.

Context: Monogenic partial lipodystrophy is a genetically heterogeneous disease where only variants with specific genetic mechanisms are causative. Three heterozygous protein extending frameshift variants in PLIN1 have been reported to cause a phenotype of partial lipodystrophy and insulin resistance. Objective: We investigated if null variants in PLIN1 cause lipodystrophy. Methods: As part of a targeted sequencing panel test, we sequenced PLIN1 in 2208 individuals. We also investigated the frequency of PLIN1 variants in the gnomAD database, and the type 2 diabetes knowledge portal. Results: We identified 6/2208 (1 in 368) individuals with a PLIN1 null variant. None of these individuals had clinical or biochemical evidence of overt lipodystrophy. Additionally, 14/17,000 (1 in 1214) individuals with PLIN1 null variants in the type 2 diabetes knowledge portal showed no association with biomarkers of lipodystrophy. PLIN1 null variants occur too frequently in gnomAD (126/138,632; 1 in 1100) to be a cause of rare overt monogenic partial lipodystrophy. Conclusions: Our study suggests that heterozygous variants that are predicted to result in PLIN1 haploinsufficiency are not a cause of familial partial lipodystrophy and should not be reported as disease-causing variants by diagnostic genetic testing laboratories. This finding is in keeping with other known monogenic causes of lipodystrophy, such as PPARG and LMNA, where only variants with specific genetic mechanisms cause lipodystrophy.

Bone Mineral Density Corrected for Size in Childhood Leukaemia Survivors Treated with Haematopoietic Stem Cell Transplantation and Total Body Irradiation.

BACKGROUND: Childhood leukaemia survivors treated with haematopoietic stem cell transplantation and total body irradiation (HSCT-TBI) have multiple risk factors for reduced bone mineral density (BMD) and growth failure; hence, BMD assessment must take body size into consideration. This study aimed to evaluate size-corrected BMD in leukaemia survivors treated with and without HSCT-TBI. METHODS: Childhood leukaemia survivors treated with HSCT-TBI (n = 35), aged 17.3 (10.5-20.9) years, were compared with those treated with chemotherapy only, (n = 16) aged 18.5 (16.1-20.9) years, and population references. Outcome measures included anthropometric measurements and BMD by dual-energy X-ray absorptiometry. BMD was corrected for size as bone mineral apparent density (BMAD). Statistical analysis was performed by 1- and 2-sample t tests as well as regression analysis (5% significance). RESULTS: HSCT-TBI survivors were lighter and shorter with reduced spinal heights compared with chemotherapy-only subjects and population references. Compared with population references, HSCT-TBI survivors showed lower BMD standard deviation scores (SDS) (p = 0.008), but no difference in BMAD-SDS, and chemotherapy-only survivors showed no differences in neither BMD-SDS nor BMAD-SDS. All HSCT-TBI participants with BMD-SDS <-2 had BMAD-SDS >-2. BMAD-SDS was negatively associated with age (r = -0.38, p = 0.029) in HSCT-TBI survivors. CONCLUSIONS: Size-corrected BMD are normal in HSCT-TBI survivors in young adulthood, but may reduce overtime. BMD measurements should be corrected for size in these patients to be clinically meaningful.

The investigation of children and adolescents with abnormalities of pubertal timing.

Concerns with pubertal development are common and can cause considerable distress to patients and their carers. Many presentations reflect normal variations of pubertal timing and primarily require reassurance, although patients may opt for interventions. Other presentations need active management to avoid significant adverse effects on growth and psychosocial development. All should undergo careful assessment, particularly as some children or adolescents presenting with abnormalities in pubertal timing may have serious pathology which requires urgent investigations and treatment. This review describes the appropriate investigations and their interpretation for young people presenting with disorders in pubertal timing.

Implementing transition: Ready Steady Go.

There is good evidence that morbidity and mortality increase for young persons (YP) following the move from paediatric to adult services. Studies show that effective transition between paediatric and adult care improves long-term outcomes. Many of the issues faced by young people across subspecialties with a long-term condition are generic. This article sets out some of the obstacles that have delayed the implementation of effective transition. It reports on a successful generic transition programme 'Ready Steady Go' that has been implemented within a large National Health Service teaching hospital in the UK, with secondary and tertiary paediatric services, where it is now established as part of routine care.

Body composition in children with type 1 diabetes in the first year after diagnosis: relationship to glycaemic control and cardiovascular risk.

INTRODUCTION: Rapid weight gain is often observed following initiation of insulin therapy in children with type 1 diabetes mellitus (T1DM) and girls are particularly at risk of becoming overweight. The authors evaluated body composition changes in children during the first year after diagnosis and related this to markers of cardiovascular risk. METHODS: Body mass index (BMI) and body composition measured by whole body dual energy x-ray absorptiometry (DEXA) were assessed in 30 patients (18 boys) with T1DM 3-10 days after diagnosis, 6 weeks later and at 1 year, and on two occasions 1 year apart in 14 controls (8 boys). Cardiovascular risk markers were assessed in T1DM subjects at 1 year. RESULTS: T1DM subjects had lower BMI SD scores (SDS) at diagnosis than controls (mean (SD) BMI SDS -0.67 (1.34) vs 0.20 (1.14), p<0.05) and reduced percentage body fat (20.3% (4.6) vs 24.5% (7.7), p<0.05). T1DM subjects normalised their body composition at 6 weeks and this was maintained 1 year later. Girls with diabetes were thinner than boys at diagnosis (BMI SDS -1.64 (1.02) vs -0.02 (1.17), p<0.05) and at 1 year (BMI SDS -0.58(0.9) vs 0.65 (0.98), p<0.05). Girls had higher glycated haemoglobin (HbA1c) (8.8% (1.2) vs 7.8% (1.0), p<0.05), insulin dose (1.01 (0.30) vs 0.82 (0.18) U/kg/day, p=0.04), total cholesterol (4.30 (0.45) vs 3.79 (0.50) mmol/l, p<0.05) and high-density lipoprotein (2.62 (0.53) vs 2.02 (0.37) mmol/l). High sensitivity C reactive protein and fibrinogen were in the normal range and there were no differences between genders. DISCUSSION: Insulin deficiency at diagnosis of diabetes causes a catabolic state that is predominantly lipolytic. Body composition normalises within 6 weeks of treatment, though girls remain thinner than boys both at diagnosis and 1 year thereafter, in contrast to published findings. Despite girls being prescribed a larger insulin dose, their HbA1c and cholesterol levels are higher at 1 year suggesting increased insulin resistance and cardiovascular risk.

Priapism in teenage boys following depot testosterone.

Priapism is rare in children and may result in erectile dysfunction and sexual aversion behaviours. Testosterone therapy is commonly regarded as safe in children and is widely used in constitutional delay of growth and puberty, hypogonadism, hypospadias and micropenis. We report two cases of priapism in teenage boys with constitutional delay of growth and puberty after a change in the formulation of depot testosterone. One case required surgical intervention and the other was preceded by stuttering priapism. These cases illustrate the importance of patient and/or parent counselling before testosterone administration and consideration of lower doses in at-risk patients.