Vitamin D status is associated with early markers of cardiovascular disease in prepubertal children

Background: The associations of 25-hydroxyvitamin D [25(OH)D], non-high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL), and related markers of early cardiovascular disease (CVD) are unclear in prepubertal children. Objective: To investigate the association of 25(OH)D with markers of CVD. The hypothesis was that 25(OH)D would vary inversely with non-HDL-C. Subjects and methods: A prospective cross-sectional study of children (n=45; 26 males, 19 females) of mean age 8.3 ± 2.5 years to investigate the relationships between 25(OH)D and glucose, insulin, high-sensitivity C-reactive protein, and lipids. Vitamin D deficiency was defined as 25(OH)D/mL; overweight as body mass index (BMI) ≥ 85 th but \u3c95th \u3epercentile; and obesity as BMI \u3e95th percentile. Results: Twenty subjects (44.4%) had BMI30 ng/mL. Patients with 25(OH)D of/mL had significantly elevated non-HDL-C (136.08 ± 44.66 vs. 109.88 ± 28.25, p=0.025), total cholesterol (TC)/HDL ratio (3.89 ± 1.20 vs. 3.21 ± 0.83, p=0.042), and triglycerides (TG) (117.09 ± 71.27 vs. 73.39 ± 46.53, p=0.024), while those with 25(OH)D of \u3e30 ng/mL had significantly lower non-HDL-C, TC/HDL, TG, and LDL (82.40 ± 18.03 vs. 105.15 ± 28.38, p=0.006). Multivariate analysis showed significant inverse correlations between 25(OH)D and non-HDL cholesterol (β=-0.337, p=0.043), and TC/HDL ratio (β=-0.339, p=0.028), and LDL (β=-0.359, p=0.016), after adjusting for age, race, sex, BMI, and seasonality. Conclusions: Vitamin D varied inversely with non-HDL, TC/HDL, and LDL. A 25(OH)D level of 30 ng/mL is associated with optimal cardioprotection in children

A potential role for adjunctive vitamin D therapy in the management of weight gain and metabolic side effects of second-generation antipsychotics

Second-generation antipsychotic (SGA) medications introduced about 20 years ago are increasingly used to treat psychiatric illnesses in children and adolescents. There has been a five-fold increase in the use of these medications in U.S. children and adolescents in the past decade. However, there has also been a parallel rise in the incidence of side effects associated with these medications, such as obesity, dyslipidemia, insulin resistance, and diabetes mellitus. Despite the severity of these complications and their financial impact on the national healthcare budget, there is neither a clear understanding of the mechanisms contributing to these side effects nor the best ways to address them. Studies that examined lifestyle modification and pharmaceutical agents have yielded mixed results. Therefore, clinical studies using agents, such as vitamin D, which are inexpensive, readily available, with low side effects profile, and have mechanisms to counteract the metabolic side effects of SGA agents, are warranted. Vitamin D is a prohormone with skeletal and extraskeletal properties that could potentially reduce the severity of these metabolic side effects. Its role as an adjunctive therapy for the management of metabolic side effects of SGA agents has not been adequately studied. Effective strategies to curb these side effects will improve the overall health of youths with psychiatric illnesses who receive SGAs. Herein we present a pilot study on the use of vitamin D in patients on treatment with SGAs

Prevention of Morbidity in sickle cell disease - qualitative outcomes, pain and quality of life in a randomised cross-over pilot trial of overnight supplementary oxygen and auto-adjusting continuous positive airways pressure (POMS2a):Study protocol for a randomised controlled trial

BACKGROUND: Sickle cell anaemia (SCA) is an inherited disorder of haemoglobin. Patients experience long-term health care problems, affecting quality of life (QOL) including frequent acute pain, which is difficult to document in trials except as hospital admissions. Pilot data suggests that overnight respiratory support, either supplementary oxygen or auto-adjusting continuous positive airways pressure (APAP), is safe and may have clinical benefit. This pilot trial aims to determine which intervention is more acceptable to participants and whether there are other advantages of one over the other, e.g. in respiratory function or haematological parameters, before conducting the Phase 2 trial of overnight respiratory support funded by the National Institutes of Health Research.METHODS/DESIGN: This is a pilot cross-over interventional trial with the order of interventions decided by simple randomization. Ten adults (age over 18 years) and 10 children (aged between 8 and 18 years) with homozygous sickle cell disease (haemoglobin SS, HbSS), recruited regardless of symptoms of sleep-disordered breathing, will undergo overnight pulse oximetry and will have two interventions, overnight oxygen and APAP, for a week each in randomised order with a washout week between interventions. Participants will complete online diaries via an iPad throughout the 29 days of the study and will complete QOL questionnaires and have measurement of haematology, biochemistry, spirometry and lung volumes (adults only) at 3 time points, at baseline and after each intervention, as well as in-depth semi-structured qualitative interviews after each intervention, carried out by an experienced psychologist. Both qualitative and statistical methods will be used to analyze the data. The primary outcome is qualitative data looking at participant experience from the transcribed interviews after each intervention. The participant's view on feasibility, acceptability and preference will specifically be explored. The QOL, laboratory and lung function data will be compared with baseline for each arm.DISCUSSION: Patient and public involvement is an integral part of this trial and the key outcome is the qualitative result, which is dependent on obtaining good quality data to advise on participant feasibility, acceptability and preference. This is being addressed by using a standard interview. The development of a pain endpoint is another important outcome and collecting daily measurements is likely to be challenging. Research results will be used to inform design of the Phase 2 trial.TRIAL REGISTRATION: ISRCTN46078697 18 July 2014

Prevention of morbidity in sickle cell disease phase II (Improvement of cognition in children with Sickle Cell Disease with auto-adjusting Continuous Positive Airways Pressure: Phase II) (POMS 2b paediatric cohort)

Background: Complications in sickle cell anemia (SCA, HbSS) include neurocognitive difficulties in attention and processing speed associated with low daytime and night-time oxygen saturation. These effects can be compounded by obstructive sleep apnea (OSA).However, there is concern that oxygen supplementation in SCA may lead to bone marrow suppression. Continuous Positive Airways Pressure (CPAP) is an accepted treatment for OSA in the general population and prevents dips in oxygen saturation.. The aim of this single-blind, randomised, controlled phase II trial is to compare Auto-adjusting CPAP (APAP) with standard care to standard care alone in subjects with HbSS to determine whether the intervention is safe and improves Cancellation, a measure of selective attention and processing speed. Methods: Eligibility criteria included ability to provide informed consent, age >8 and <16 years, diagnosis of HbSS and mean overnight saturation of <90% for <30% of the night. Key exclusion criteria were overnight respiratory support, respiratory or decompensated cardiac failure, chronic transfusion or contra-indications to APAP therapy or MRI. Minimisation/stratification factors were age group (8-11, 12-15 years), silent infarction on MRI, minimum overnight oxygen saturation >90% or <90%, and hydroxyurea (HU) use. APAP adherence was defined as using APAP for an average of 4 hours a night for >50% of the time and was recorded using software documenting hours of use each night. Participant support in terms of appropriate facemask and facilitating adherence were provided by an unblinded sleep physiologist. Full blood counts were obtained at baseline, 2 weeks, 3 months and 6 months. Data were analysed by intention-to-treat. The primary outcome is change in the Cancellation subtest from the Wechsler scales, and secondary outcomes include general cognitive functioning, assessed at baseline and after 6 months of treatment by assessors blind to treatment assignment. Analysis of Covariance (ANCOVA) models, adjusted for minimisation factors, were used to calculate least-square mean changes from baseline to 6 months. Results: 30 children (18 boys; median age 12.5; range 7.9-16 years) with SCA were randomised to standard care + APAP (n=15) or standard care alone (n=15) for 6 months. One child in the standard care alone arm withdrew after 6 weeks, and 8 children in the APAP arm were not adherent to treatment. Increase in cancellation score was numerically greater in the APAP arm (mean 1.46, SE 0.59 vs 1.01, SE 0.61) but this was not significant (mean difference 0.44, 95% CI: -1.42; 2.31; p=0.626). Increase in Cancellation score was greater (mean 2.63; 95%CI: 0.95, 4.30) in those whose adherence was in the highest quartile (> 2.4 hours/night) compared with the other 3 quartiles (mean 0.71, 95%CI: -0.32, 1.75; mean difference 1.91, 95%CI: -0.06, 3.88; p=0.057). In subjects assigned to APAP, cancellation scores were significantly higher with hydroxyurea use (p=0.01). There was no evidence of decline in haemoglobin in either group; hydroxyurea use was associated with an increase in haemoglobin (p=0.01). There were 7 subjects with serious adverse events in the standard care alone arm, compared to 3 in the APAP + standard care arm, all related to hospital admission for pain. Discussion: APAP for 6 months is feasible and safe in children with SCA. Alhough >50% were not adherent by the pre-defined definition, those who were compliant appeared to have more benefit in terms of improvement in attention/processing speed. There appears to be an interaction with HU use, consistent with the importance of oxygen supply and carriage for brain function. If delivery of the intervention can be improved, avoidance of oxygen desaturation with overnight respiratory support alongside HU use may play a role in improving cognition in SCD. Disclosures: No relevant conflicts of interest to declare

Prevention of Morbidity in Sickle Cell Disease Phase II (Improvement of Cognition in children with Sickle Cell Disease with Auto-adjusting Continuous Positive Airways Pressure: Phase II) (POMS 2b paediatric cohort)

Background: Complications in sickle cell anemia (SCA, HbSS) include neurocognitive difficulties in attention and processing speed associated with low daytime and night-time oxygen saturation. These effects can be compounded by obstructive sleep apnea (OSA).However, there is concern that oxygen supplementation in SCA may lead to bone marrow suppression. Continuous Positive Airways Pressure (CPAP) is an accepted treatment for OSA in the general population and prevents dips in oxygen saturation.. The aim of this single-blind, randomised, controlled phase II trial is to compare Auto-adjusting CPAP (APAP) with standard care to standard care alone in subjects with HbSS to determine whether the intervention is safe and improves Cancellation, a measure of selective attention and processing speed. Methods: Eligibility criteria included ability to provide informed consent, age >8 and <16 years, diagnosis of HbSS and mean overnight saturation of <90% for <30% of the night. Key exclusion criteria were overnight respiratory support, respiratory or decompensated cardiac failure, chronic transfusion or contra-indications to APAP therapy or MRI. Minimisation/stratification factors were age group (8-11, 12-15 years), silent infarction on MRI, minimum overnight oxygen saturation >90% or <90%, and hydroxyurea (HU) use. APAP adherence was defined as using APAP for an average of 4 hours a night for >50% of the time and was recorded using software documenting hours of use each night. Participant support in terms of appropriate facemask and facilitating adherence were provided by an unblinded sleep physiologist. Full blood counts were obtained at baseline, 2 weeks, 3 months and 6 months. Data were analysed by intention-to-treat. The primary outcome is change in the Cancellation subtest from the Wechsler scales, and secondary outcomes include general cognitive functioning, assessed at baseline and after 6 months of treatment by assessors blind to treatment assignment. Analysis of Covariance (ANCOVA) models, adjusted for minimisation factors, were used to calculate least-square mean changes from baseline to 6 months. Results: 30 children (18 boys; median age 12.5; range 7.9-16 years) with SCA were randomised to standard care + APAP (n=15) or standard care alone (n=15) for 6 months. One child in the standard care alone arm withdrew after 6 weeks, and 8 children in the APAP arm were not adherent to treatment. Increase in cancellation score was numerically greater in the APAP arm (mean 1.46, SE 0.59 vs 1.01, SE 0.61) but this was not significant (mean difference 0.44, 95% CI: -1.42; 2.31; p=0.626). Increase in Cancellation score was greater (mean 2.63; 95%CI: 0.95, 4.30) in those whose adherence was in the highest quartile (> 2.4 hours/night) compared with the other 3 quartiles (mean 0.71, 95%CI: -0.32, 1.75; mean difference 1.91, 95%CI: -0.06, 3.88; p=0.057). In subjects assigned to APAP, cancellation scores were significantly higher with hydroxyurea use (p=0.01). There was no evidence of decline in haemoglobin in either group; hydroxyurea use was associated with an increase in haemoglobin (p=0.01). There were 7 subjects with serious adverse events in the standard care alone arm, compared to 3 in the APAP + standard care arm, all related to hospital admission for pain. Discussion: APAP for 6 months is feasible and safe in children with SCA. Alhough >50% were not adherent by the pre-defined definition, those who were compliant appeared to have more benefit in terms of improvement in attention/processing speed. There appears to be an interaction with HU use, consistent with the importance of oxygen supply and carriage for brain function. If delivery of the intervention can be improved, avoidance of oxygen desaturation with overnight respiratory support alongside HU use may play a role in improving cognition in SCD. Disclosures: No relevant conflicts of interest to declare

Whose voice?: an exploration of the current policy interest in pupil involvement in school decision-making

Personal cover image 1: Study logo. (DOC 21 kb

Overnight auto-adjusting continuous airway pressure + standard care compared with standard care alone in the prevention of morbidity in sickle cell disease phase II (POMS2b): study protocol for a randomised controlled trial

Abstract Background In addition to pain, sickle cell anaemia (HbSS) complications include neurocognitive difficulties in attention and processing speed associated with low daytime and night-time oxygen saturation compounded by obstructive sleep apnoea (OSA). In the general population OSA is treated with continuous positive airways pressure (CPAP). The aim of this single-blind, randomised, controlled phase II trial is to compare auto-adjusting CPAP (APAP) with standard care to standard care alone in individuals with HbSS to determine whether the intervention improves attention and processing speed, brain structure, pain and quality of life. Methods/Design Eligibility criteria include: ability to provide informed consent; age > 8 years; diagnosis of HbSS; and mean overnight saturation of  23 years); silent infarction on MRI; minimum overnight oxygen saturation > 90% or < 90%; and hydroxyurea use. For APAP individuals, the intervention is administered at home. Adherence and effectiveness are recorded using software documenting hours of use each night and overnight oximetry. Participant support in terms of appropriate facemask and facilitating adherence are provided by an unblinded sleep physiologist. The primary outcome is change in the cancellation subtest from the Wechsler scales. Secondary outcomes include general cognitive functioning, quantitative brain MRI, blood and urine chemistry, quality of life and daily pain via a smartphone App (GoMedSolutions, Inc) and, where possible MRI heart, echocardiography, and 6-min walk. These outcomes will be assessed at baseline and after six months of treatment by assessors blind to treatment assignment. Discussion Altering oxygen saturation in HbSS may lead to bone marrow suppression. This risk will be reduced by monitoring full blood counts at baseline, two weeks, three months and six months, providing treatment as appropriate and reporting as safety events. Trial registration ISRCTN46012373 . Registered on 10 July 2015. Protocol Version: 6.0 Date: 24th December 2015 Sponsor: University Hospital Southampton. Sponsor’s protocol code: RHMCHIOT5

Overnight auto-adjusting continuous airway pressure + standard care compared with standard care alone in the prevention of morbidity in sickle cell disease phase II (POMS2b): study protocol for a randomised controlled trial

Background: in addition to pain, sickle cell anaemia (HbSS) complications include neurocognitive difficulties in attention and processing speed associated with low daytime and night-time oxygen saturation compounded by obstructive sleep apnoea (OSA). In the general population OSA is treated with continuous positive airways pressure (CPAP). The aim of this single-blind, randomised, controlled phase II trial is to compare auto-adjusting CPAP (APAP) with standard care to standard care alone in individuals with HbSS to determine whether the intervention improves attention and processing speed, brain structure, pain and quality of life.Methods/desigh: eligibility criteria include: ability to provide informed consent; age &gt; 8 years; diagnosis of HbSS; and mean overnight saturation of &lt; 90% for &lt; 30% of the night (i.e. not meeting current criteria for overnight oxygen therapy). Key exclusion criteria are: overnight respiratory support; respiratory or decompensated cardiac failure; chronic transfusion; or contraindications to APAP therapy or magnetic resonance imaging (MRI). Sixty individuals with HbSS (30 children and 30 adults) will be randomised to standard care + APAP or standard care alone for six months. Minimisation factors are: age group (8-11, 12-15, 16-22 and &gt; 23 years); silent infarction on MRI; minimum overnight oxygen saturation &gt; 90% or &lt; 90%; and hydroxyurea use. For APAP individuals, the intervention is administered at home. Adherence and effectiveness are recorded using software documenting hours of use each night and overnight oximetry. Participant support in terms of appropriate facemask and facilitating adherence are provided by an unblinded sleep physiologist. The primary outcome is change in the cancellation subtest from the Wechsler scales. Secondary outcomes include general cognitive functioning, quantitative brain MRI, blood and urine chemistry, quality of life and daily pain via a smartphone App (GoMedSolutions, Inc) and, where possible MRI heart, echocardiography, and 6-min walk. These outcomes will be assessed at baseline and after six months of treatment by assessors blind to treatment assignment.Discussion: altering oxygen saturation in HbSS may lead to bone marrow suppression. This risk will be reduced by monitoring full blood counts at baseline, two weeks, three months and six months, providing treatment as appropriate and reporting as safety events.Trial registration: ISRCTN46012373 . Registered on 10 July 2015. Protocol Version: 6.0 Date: 24th December 2015 Sponsor: University Hospital Southampton. Sponsor's protocol code: RHMCHIOT53.</p