Transition Readiness in Adolescents and Young Adults Living With Congenital Adrenal Hyperplasia.

OBJECTIVE: Congenital adrenal hyperplasia (CAH) refers to a group of genetic disorders that affect cortisol biosynthesis and the need for glucocorticoid treatment is lifelong. The complexities of CAH can greatly affect teenage life and the transition from pediatric to adult care. The aim was to assess transition readiness and the impact on quality of life (QoL) as well as medication adherence rates in adolescents and young adults with CAH. METHODS: Prospective assessment of transition readiness was conducted through standardized questionnaires for adolescents and young adults (aged 16-35 years). Four open-ended questions on self-care were summarized in adolescents (aged 18-19 years) and their parents. Transition readiness was assessed using a modified CAH specific questionnaire: "Transition preparation and readiness to transfer from pediatric to adult care" with a cutoff level of >25 defined as good transition readiness. Measurement of QoL was performed using Rand 36. Medication adherence rate was measured using the self-reported questionnaire Adherence Starts with Knowledge. RESULTS: Thirty-eight adolescents and young adults with CAH were included in the study. Transition readiness was classified as good in 26 (68%) of the participants. Good transition readiness was more frequent in participants with good medication adherence rates. A general linear model analysis showed a good transition readiness affected QoL by increasing QoL scores. CONCLUSION: Self-reported transition readiness was found in the majority of adolescents and young adults with CAH. A good medication adherence rate was associated with a better transition readiness and a good transition readiness was associated with increased QoL scores.

The impact of adherence and therapy regimens on quality of life in patients with congenital adrenal hyperplasia.

OBJECTIVE: Varying outcomes regarding the quality of life (QoL) have been reported in patients with congenital adrenal hyperplasia (CAH). To assess the impact of adherence rate to medical therapy regimens on QoL in patients with CAH. PATIENTS: Adolescents and adults aged 15-72 years with CAH due to 21-hydroxylase deficiency at Karolinska University Hospital, Stockholm, Sweden. MEASUREMENTS: QoL was assessed using the Addison QoL (n = 72) and RAND 36 questionnaires (n = 75). Adherence to therapy regimens was measured using the Adherence Starts with Knowledge questionnaire (ASK-12). Associations between QoL, type of glucocorticoid therapy prescribed and ASK-12 results were examined. Results were compared to reference RAND 36 data obtained from a representative sample from the general Swedish population. RESULTS: A good adherence rate to therapy regimens and a younger age were key factors for a better QoL in study participants with CAH. Younger patients on hydrocortisone and with good adherence had higher RAND 36 scores than older patients on prednisolone independently adherence. Participants with classic CAH (both the salt-wasting and simple virilizing form) reported higher QoL than those with nonclassic CAH. Patients with CAH, especially nonclassic, more frequently reported an impaired QoL than the general population, especially regarding limitations related to body pain, vitality and mental health. CONCLUSION: A poor adherence rate to therapy regimens, rather than type of glucocorticoid was associated with impaired QoL in adolescents and adults with CAH.

Assessment of medication adherence in children and adults with congenital adrenal hyperplasia and the impact of knowledge and self-management.

BACKGROUND: Congenital adrenal hyperplasia (CAH) is caused by a deficiency of one of the enzymes required for cortisol biosynthesis. The disease is classified as either classic (severe phenotype), subdivided into simple virilizing (SV) and salt-wasting (SW), or non-classic (NC) CAH. The treatment regime involves life-long glucocorticoid replacement, especially in classic phenotype. OBJECTIVES: We aimed to assess medication adherence, endocrine knowledge and self-management in patients with CAH and to compare patients' and physicians' assessments of medication adherence. METHODS: A prospective cross-sectional study of 108 patients with CAH (52 children and 56 adults) and 45 parents/caregivers. Two adherence measures were used, a self-reported questionnaire named Adherence Starts with Knowledge (ASK-12) with a cut-off level > 22 defined as poor adherence rate, and an assessment by a physician based on growth rate, 17-hydroxyprogesterone profile, and medical history, ranked using a five-point Likert scale. Measurements of the patients'/parents' knowledge and self-management were performed using Endocrine Society Clinical Practice Guidelines. RESULTS: Self-reported medication adherence was good with 74% of the participants reported good adherence with higher adherence in patients with the SW form. The highest endocrine knowledge and self-management were found in parents compared with children and adults with classic CAH. There was 30% discordance between the assessments by a physician and the self-reported ASK-12 scores independent of the severity of CAH. CONCLUSION: Patients and endocrinologists reported high medication adherence, however, discordance was found in 30% of the studied patients. Patients with the more severe form of CAH had higher adherence rates and demonstrated good endocrine knowledge/self-management.

Oral intake of mesoporous silica is safe and well tolerated in male humans.

BACKGROUND: Precisely engineered mesoporous silica has been shown to induce weight loss in mice, but whether it is safe to use in humans have not investigated. OBJECTIVE: The aim was to determine whether oral dosing, up to 9 grams/day, of precisely engineered mesoporous silica as a food additive can be used safely in male humans. DESIGN: This single blinded safety study consisted of two study arms including 10 males each (18-35 years). One arm consisted of participants with normal weight and one with obesity. After a placebo run-in period, all subjects were given porous silica three times daily, with increasing dose up to 9 grams/day (Phase 1). Subjects with obesity continued the study with highest dose for additional 10 weeks (Phase 2). RESULTS: All participants completed Phase 1 and 90% completed Phase 2, with approximately 1% missed doses. Participants reported no abdominal discomfort, and changes in bowel habits were minor and inconsistent. The side effects observed were mild and tolerable, biomarkers did not give any safety concern, and no severe adverse events occurred. CONCLUSION: Mesoporous silica intake of up to 9 grams/day can be consumed by males without any major adverse events or safety concerns.

Adherence to Vitamin Supplementation Recommendations in Youth Who Have Undergone Bariatric Surgery as Teenagers: a Mixed Methods Study.

PURPOSE: Adherence to vitamin supplementation recommendations after bariatric surgery is generally poor, which is associated with nutritional deficiencies. Patients' own perspectives and reasons for poor adherence to vitamin supplementation recommendations have not yet been studied in depth. The purpose of this study was first to measure the accuracy of self-reported adherence to supplementation recommendations by using objective measures of vitamin D levels in blood and thereafter to explore perceptions of barriers and facilitators to participants' adherence to supplementation recommendations. MATERIAL AND METHOD: Participants were recruited from a prospective study investigating the outcome of bariatric surgery in adolescents with severe obesity. Mixed methods were used, including a quantitative part where vitamin D levels were analysed through 25(OH)D levels in blood and/or a questionnaire on adherence to supplementation programmes 5 years after surgery (n = 40) plus a qualitative part with semi-structured interviews (n = 20). RESULTS: We found a convergence between self-reported adherence to vitamin supplementation and vitamin D 25(OH)D levels in blood indicating honestly in self-reported responses. The qualitative evaluations resulted in the categories awareness and personal capability and external factors. In the analysis, an overall theme emerged; capacity is crucial for adherence in youth who have undergone bariatric surgery. CONCLUSION: Bariatric surgery is a comprehensive procedure that requires lifelong treatment afterwards. There is coherence between what adolescents actually do and what they say they do. Capacity is crucial for adherence and social support has been shown to be important.

A randomized controlled trial comparing intensive non-surgical treatment with bariatric surgery in adolescents aged 13-16 years (AMOS2): Rationale, study design, and patient recruitment.

BACKGROUND: Previous non-randomized studies show similar outcomes in adolescents and adults after bariatric surgery. We describe the study protocol, recruitment, and selected baseline data of patients in a randomized multi-center study, the Adolescent Morbid Obesity Surgery 2 (AMOS2). METHODS: Three clinics in Sweden collaborated in designing the study and recruitment of patients from August 1, 2014 to June 30, 2017. Patients were selected among adolescents 13-16 years of age attending third-level obesity care for at least one year. Patients were randomized 1:1 to bariatric surgery (predominantly Roux-en-Y gastric bypass) or intensive non-surgical treatment starting with an eight-week low-calorie-diet. RESULTS: Fifty adolescents (37 girls) were randomized, 25 (19 girls) to bariatric surgery. Mean age was 15.7 years (range 13.3-16.9), weight 122.6 kg (range 95-183.3), Body Mass Index (BMI) 42.6 kg/m2 (range 35.7-54.9) and BMI-SDS 3.45 (range 2.9-4.1). One patient had type 2 diabetes mellitus, and 12/45 (27%) had elevated liver enzymes. There were no significant differences between the groups. For the 39 eligible patients who were offered but declined inclusion, BMI was not different from included patients. However, patients who declined were younger, 15.2 years (p = 0.021). A sex difference was also noted with more of eligible girls, 37/53 (69.8%), than boys, 13/36 (36.1%), wanting to participate in the study (p = 0.002). CONCLUSIONS: This clinical trial, randomizing adolescents with severe obesity to bariatric surgery or intensive non-surgical treatment, aims at informing about whether it is beneficial to undergo bariatric surgery in early adolescence. It will also enlighten the outcome of comprehensive non-surgical treatment. The study was registered at www.clinicalTrials.gov number NCT02378259.

Development of sleep patterns in children with obese and normal-weight parents.

AIM: To study the sleep development and sleep characteristics in children at different obesity risks, based on parental weight, and also to explore their weekday-weekend sleep variations and associated family factors. METHODS: A total of 145 children participating in a longitudinal obesity prevention project were included, of which 37 had normal-weight parents (low obesity risk), and 108 had overweight/obese parents (high obesity risk). Sleep diaries at ages 1 and 2 years were used to study sleep development in children at different obesity risks. Objectively assessed sleep using an accelerometer at 2 years of age was used to analyse weekday-weekend sleep variations. RESULTS: There was no difference in sleep development from age 1 to age 2 among children at different obesity risks, but more children in the high-risk group had prolonged sleep onset latency and low sleep efficiency. At 2 years of age, children in the high-risk group had more weekday-weekend variation in sleep offset (mean difference 18 min, 95% confidence interval (CI) 4-33 min), midpoint of sleep (mean difference 14 min, 95% CI 3-25 min) and nap onset (mean difference 42 min, 95% CI 10-74 min) than children in the low-risk group, after adjusting for other family factors. However, no difference could be detected between groups in weekday-weekend variation in sleep duration. CONCLUSIONS: Unfavourable sleep characteristics, as well as more variation in sleep schedules, have been observed in children at high obesity risk. While the differences were relatively small, they may reflect the unfavourable sleep hygiene in families at high obesity risk.

Adolescents' experiences of obesity surgery: a qualitative study.

BACKGROUND: The positive effects of behavioural treatment and weight management in adolescents with severe obesity are modest. Obesity surgery can be an option for adolescents, but is not the first-hand choice of treatment. The knowledge about adolescents' own experiences of having undergone surgery and their thoughts and feelings of the follow-up period are limited. OBJECTIVES: To describe adolescents' decision to go through obesity surgery as teenager and their experiences of the follow-up period. SETTING: National Childhood Obesity Centre at Karolinska University Hospital in Stockholm, Sweden. METHODS: Phone interviews with 20 young adults that went through obesity surgery as teenagers. Interviews were analysed with qualitative systematic text condensation. RESULTS: "Lost in the healthcare system" and "A rough but well worth journey to a healthier life" were the categories that appeared in our analysis. The participant had a feeling of uncertainty about contacts with the healthcare system and the transition to primary care was confusing. Most of the participants were happy with the decision to go through obesity surgery as teenager, despite it had been a difficult time. CONCLUSIONS: Our results show implications for improving the clinical care of adolescents undergoing obesity surgery, which should be offered as a last choice. Information and individualized supports should be offered more often during first year postsurgery and should be given by a multidisciplinary team. This multifaceted population should be given priority for a successful transition.

Thyroid-Stimulating Hormone, Degree of Obesity, and Metabolic Risk Markers in a Cohort of Swedish Children with Obesity.

BACKGROUND/AIMS: Thyroid-stimulating hormone (TSH) is affected in obesity and might influence metabolic risk. It is unclear what mechanisms cause elevated TSH in obesity. We aimed to investigate TSH status within the normal range and the association of TSH with degree of obesity and metabolic parameters in children with obesity. METHODS: A total of 3,459 children, aged 3.0-17.9 years, were identified in the Swedish Childhood Obesity Treatment Registry, BORIS. Age, gender, TSH, free triiodothyronine (fT3), free thyroxine (fT4), body mass index standard deviation scores (BMI SDS), as well as variables of lipid and glucose metabolism were examined. RESULTS: Children with high-normal TSH (>3.0 mU/L) (28.8%) had higher BMI SDS compared to children with low-normal TSH (<3.0 mU/L) (p < 0.001). Multivariable regression analysis adjusted for age and gender showed that TSH levels were associated with BMI SDS (ß: 0.21, 95% CI: 0.14-0.28, p < 0.001). Associations of thyroid hormones with markers of lipid and glucose metabolism were observed, where TSH was associated with fasting insulin, HOMA (homeostatic model assessment of insulin resistance), total cholesterol, and triglycerides. CONCLUSIONS: A positive association between TSH levels and BMI SDS was seen in children with obesity. Associations of TSH and free thyroid hormones with glucose metabolism indicated that TSH might be one of several factors acting to determine body weight and obesity co-morbidities, although the underlying mechanism remains unclear.

Laparoscopic Roux-en-Y gastric bypass in adolescents with severe obesity (AMOS): a prospective, 5-year, Swedish nationwide study.

BACKGROUND: Severe obesity in adolescence is associated with reduced life expectancy and impaired quality of life. Long-term benefits of conservative treatments in adolescents are known to be modest, whereas short-term outcomes of adolescent bariatric surgery are promising. We aimed to compare 5-year outcomes of adolescent surgical patients after Roux-en-Y gastric bypass with those of conservatively treated adolescents and of adults undergoing Roux-en-Y gastric bypass, in the Adolescent Morbid Obesity Surgery (AMOS) study. METHODS: We did a nationwide, prospective, non-randomised controlled study of adolescents (aged 13-18 years) with severe obesity undergoing Roux-en-Y gastric bypass at three specialised paediatric obesity treatment centres in Sweden. We compared clinical outcomes in adolescent surgical patients with those of matched adolescent controls undergoing conservative treatment and of adult controls undergoing Roux-en-Y gastric bypass. The primary outcome measure was change in BMI over 5 years. We used multilevel mixed-effect regression models to assess longitudinal changes. This trial is registered with ClinicalTrials.gov, number NCT00289705. FINDINGS: Between April, 2006, and May, 2009, 100 adolescents were recruited to the study, of whom 81 underwent Roux-en-Y gastric bypass (mean age 16·5 years [SD 1·2], bodyweight 132·8 kg [22·1], and BMI 45·5 kg/m2 [SD 6·1]). 80 matched adolescent controls and 81 matched adult controls were enrolled for comparison of outcomes. The change in bodyweight in adolescent surgical patients over 5 years was -36·8 kg (95% CI -40·9 to -32·8), resulting in a reduction in BMI of -13·1 kg/m2 (95% CI -14·5 to -11·8), although weight loss less than 10% occurred in nine (11%). Mean BMI rose in adolescent controls (3·3 kg/m2, 95% CI 1·1-4·8) over the 5-year study period, whereas the BMI change in adult controls was similar to that in adolescent surgical patients (mean change -12·3 kg/m2, 95% CI -13·7 to -10·9). Comorbidities and cardiovascular risk factors in adolescent surgical patients showed improvement over 5 years and compared favourably with those in adolescent controls. 20 (25%) of 81 adolescent surgical patients underwent additional abdominal surgery for complications of surgery or rapid weight loss and 58 (72%) showed some type of nutritional deficiency; health-care consumption (hospital attendances and admissions) was higher in adolescent surgical patients compared with adolescent controls. 20 (25%) of 81 adolescent controls underwent bariatric surgery during the 5-year follow-up. INTERPRETATION: Adolescents with severe obesity undergoing Roux-en-Y gastric bypass had substantial weight loss over 5 years, alongside improvements in comorbidities and risk factors. However, gastric bypass was associated with additional surgical interventions and nutritional deficiencies. Conventional non-surgical treatment was associated with weight gain and a quarter of patients had bariatric surgery within 5 years. FUNDING: Swedish Research Council; Swedish Governmental Agency for Innovation Systems; National Board of Health and Welfare; Swedish Heart and Lung Foundation; Swedish Childhood Diabetes Foundation; Swedish Order of Freemasons Children's Foundation; Stockholm County Council; Västra Götaland Region; Mrs Mary von Sydow Foundation; Stiftelsen Göteborgs Barnhus; Stiftelsen Allmänna Barnhuset; and the US National Institute of Diabetes, Digestive, and Kidney Diseases (National Institutes of Health).

Physical Fitness and Body Composition Two Years after Roux-En-Y Gastric Bypass in Adolescents.

BACKGROUND: We have previously shown promising results 2 years after Roux-en-Y gastric bypass surgery, within the Adolescence Morbid Obesity Surgery study (AMOS). The aim of the current study was to describe the 2-year outcome in cardiorespiratory fitness, body composition, and functional capacity in the Stockholm subset of the AMOS study. METHODS: Forty-one adolescents (10 male, 31 female, age 14-18 years, body mass index 35-69 kg·m-2) were included. In addition to anthropometric measurements, participants performed a submaximal bicycle test, 6-min walk test, dual-energy X-ray absorptiometry, and a short interview at baseline, 1 and 2 years after surgery. RESULTS: Relative improvements in maximal oxygen consumption (VO2max) per kilogram body mass (+62 %) and per kilogram fat-free mass (+21 %), as well as walking distance (+13 %) were observed after 1 year, and persisted 2 years after surgery. Despite a reduction of fat-free mass (-15 %), absolute VO2max was maintained across the full group (+8 %, p = ns) and significantly increased in non-smokers. Body mass and fat mass were significantly decreased (-45.4 and -33.3 kg, respectively). Self-reported physical activity was significantly increased, and pain associated with movement was reduced. CONCLUSIONS: In adolescents with obesity, Roux-en-Y gastric bypass improved VO2max more than could be explained by fat mass loss alone. In combination with improved functional capacity and body composition, these results suggest that surgery in adolescence might add specific benefits of importance for future health.

Sleep differences in one-year-old children were related to obesity risks based on their parents' weight according to baseline longitudinal study data.

AIM: Parental obesity is the predominant risk factor for child obesity. We compared sleep in one-year-old children with different obesity risks, based on parental weight, and explored associations with weight, parental sleep and family factors. METHODS: Baseline data from 167 families participating in a longitudinal obesity prevention programme was used. Sleep patterns were compared between groups with high and low obesity risks, based on parental weight, and associations between child sleep and weight status, family obesity risk and parental sleep were explored. Sleep was assessed using child sleep diaries and standard parental questionnaires. RESULTS: Later bedtime, longer sleep onset latency and lower sleep efficiency were observed among children in the high-risk group. Child sleep onset latency was associated with the family obesity risk (ß = 0.25, p = 0.001), child bedtime with both maternal (ß = 0.33, p < 0.01) and paternal bedtime (ß = 0.22, p < 0.05) and child sleep efficiency with maternal sleep quality (ß = 0.20, p < 0.01). The child's bedtime was weakly associated with their body mass index (ß = 0.17, p < 0.05). CONCLUSION: Sleep differed between one-year-old children with high or low obesity risks, based on their parents' body mass index, and was associated with the family obesity risk and parental sleep. The child's bedtime was weakly associated with their weight status.

Vitamin D deficiency is associated with prediabetes in obese Swedish children.

AIM: Low vitamin D levels have been associated with obesity and living in areas that lack sunshine, such as northern Europe. The aim of this study was to investigate the vitamin D status of a group of obese children in Sweden and to investigate the associations between vitamin D status and markers of glucose metabolism and metabolic risk markers. METHODS: This was a prospective cross-sectional study of 202 obese children between 4.5 and 17.9 years of age who had been referred to the National Childhood Obesity Centre at Karolinska University Hospital, Stockholm. We examined age, gender, 25-hydroxyvitamin D (25(OH)D), f-glucose, f-insulin and metabolic risk markers. Vitamin D deficiency was defined as less than 30 25(OH)D nmol/L. Children with and without a vitamin D deficiency were compared. RESULTS: Just over a third (33.2%) of our study population had vitamin D levels <30 nmol/L 25(OH)D. A significant interaction effect was found between age and 25(OH)D. An association was also found between low 25(OH)D levels and impaired fasting glycaemia (IFG) independent of age and season. CONCLUSION: Low vitamin D levels were common among obese adolescents living in Sweden and were strongly associated with age and associated with a higher risk of IFG.

Obesogenic dietary intake in families with 1-year-old infants at high and low obesity risk based on parental weight status: baseline data from a longitudinal intervention (Early STOPP).

PURPOSE: To compare dietary intake in 1-year-old infants and their parents between families with high and low obesity risk, and to explore associations between infant dietary intake and relative weight. METHODS: Baseline analyses of 1-year-old infants (n = 193) and their parents participating in a longitudinal obesity intervention (Early STOPP) were carried out. Dietary intake and diet quality indicators were compared between high- and low-risk families, where obesity risk was based on parental weight status. The odds for high diet quality in relation to parental diet quality were determined. Associations between measured infant relative weight and dietary intake were examined adjusting for obesity risk, socio-demographics, and infant feeding. RESULTS: Infant dietary intake did not differ between high- and low-risk families. The parents in high-risk families consumed soft drinks, French fries, and low-fat spread more frequently, and fish and fruits less frequently (p < 0.05) compared to parents in low-risk families. Paternal intake of vegetables and fish increased the odds for children being consumers of vegetables (OR 1.7; 95 % CI 1.0-2.9) and fish, respectively (OR 2.5; 95 % CI 1.4-4.4). Infant relative weight was weakly associated with a high intake of milk cereal drink (r = 0.15; p < 0.05), but not with any other aspect of dietary intake, obesity risk, or early feeding patterns. CONCLUSIONS: At the age of one, dietary intake in infants is not associated with family obesity risk, nor with parental obesogenic food intake. Milk cereal drink consumption but no other infant dietary marker reflects relative weight at this young age.

Laparoscopic Roux-en-Y gastric bypass in adolescents with morbid obesity--surgical aspects and clinical outcome.

In this paper, we address surgical aspects on bariatric surgery in adolescents from a nationwide Swedish study. Laparoscopic gastric bypass surgery was performed for 81 adolescents with morbid obesity (13-18 years), while 81 adolescents with obesity-matched by age, sex, and BMI received conventional care. Another comparison group was adults undergoing gastric bypass at the same institution during the same time period. This report addresses the 2-year clinical outcome and five-year surgical adverse event rate. Body weight decreased from 133 kg (SD = 22) at inclusion to 92 kg (SD = 17) after 1 year and was 89 (SD = 18) after 2 years (p < 0·001) representing a 32% (-35 to -30) weight loss after 2 years, corresponding to 76% (-81 to -71) excess weight loss. Weight loss was similar in the adult gastric bypass patients (-31%) while weight gain (+3%) was seen in the conventionally treated obese adolescents. Significant improvement in cardiovascular and metabolic risk factors and inflammation was seen after surgery. The treatment was generally well tolerated and quality of life improved significantly. The surgical adverse events included cholecystectomies (10%) and operations for internal hernia (9%) but no postoperative mortality. Adolescents undergoing laparoscopic gastric bypass surgery achieve similar weight loss to adults. Improvements in risk factors and quality of life were substantial. There were surgical complications similar to the adult group, which may be preventable.

Effects of midazolam and nitrous oxide on endocrine and metabolic measurements in children.

OBJECTIVE: Pain, stress as well as drugs may affect metabolic and endocrine measurements, especially in stressed children. The aim was to study how release of glucose and stress hormones are affected when procedural sedation with nitrous oxide or midazolam are used for establishing intravenous access in obese and lean children. METHODS: In a prospective, double-blind, randomized study 90 children, 60 obese and 30 growth-retarded (GR), aged 5-18 years, with reported anxiety or difficulties connected with i.v. access, were randomized to 1 of 3 groups: oral midazolam (0.3 mg/kg, max. 15 mg), 50% nitrous oxide (N(2)O), and 10% N(2)O. In addition, all children received anesthesia cream (EMLA®) locally 1 h before i.v. access. Blood samples were drawn at 4 time points during 30 min after establishing venous access and, when feasible, after 24 h. The 24-hour sample was regarded as obtained during unstressed condition. The effect of procedural sedation was analyzed. Children's evaluations of pain (Numeric Rating Scale) and procedure (Likert Scale) were correlated with mean values of cortisol and glucose after i.v. access. For the metabolic and hormone control measurements, 60 children aged 4-18 years (40 obese and 20 GR) served as controls. These children underwent a 24-hour blood sampling and did not receive sedation. The control samples were drawn 10-12 h after i.v. access. RESULTS: After midazolam, significantly lower cortisol levels were found compared to both 50% N(2)O and 10% N(2)O and to unstressed controls. The growth hormone levels decreased with time in the midazolam group compared to 50 and 10% N(2)O, where the effect of time was reversed. Glucose levels among GR children increased from 0 to 30 min, whereas the opposite was found in obese children regardless of treatment. A post hoc analysis demonstrated significant correlations between children's evaluations of the procedure and mean values of cortisol (r = -0.53), growth hormone (r = -0.52), and norepinephrine (r = -0.5) in children treated with a very low dose of N(2)O (10%). CONCLUSIONS: When sedation is insufficient during i.v. access, and blood sampling pain and stress affect hormone values, treatment with N(2)O or midazolam influence the glucose and stress hormone levels differently. These differences need to be accounted for when results are used for diagnosis and clinical decisions.

Efficient intravenous access without distress: a double-blind randomized study of midazolam and nitrous oxide in children and adolescents.

OBJECTIVE: To determine whether treatment with midazolam or with nitrous oxide is more efficient in facilitating intravenous (IV) access in lean and obese children and adolescents. DESIGN: A prospective, double-blind, randomized trial of 90 children and adolescents. SETTING: Astrid Lindgrens Children's Hospital, Karolinska University Hospital, Stockholm, Sweden. Patients A total of 60 obese children and adolescents and 30 growth-retarded children and adolescents, aged 5 to 18 years, with reported anxiety and/or difficulties with IV access. INTERVENTIONS: The patients were randomly assigned to receive midazolam (dose, 0.3 mg/kg; maximum dose, 15 mg), 50% nitrous oxide, or 10% nitrous oxide. All patients received lidocaine-prilocaine. MAIN OUTCOME MEASURES: Efficiency, measured as total procedure time and number of attempts, which was defined as the number of attempts required to succeed in setting up 2 IV lines, with a successful procedure defined as 2 attempts for 2 IV lines. Secondary end points were patients' and parents' evaluations and procedure cancellations. RESULTS: Treatment with 50% nitrous oxide was the most efficient with regard to total procedure time (P < .001). An unfavorably long procedure time was observed after treatment with midazolam, especially in obese patients. An increased number of successful IV line procedures were obtained in the group of patients who received 50% nitrous oxide compared with the midazolam group and 10% nitrous oxide group (P = .04). The patients' evaluations were significantly more positive for 50% nitrous oxide than for both midazolam and 10% nitrous oxide, whereas no such difference was observed between midazolam and 10% nitrous oxide. CONCLUSIONS: Compared with treatment with midazolam, treatment with 50% nitrous oxide during IV line procedures results in a shorter total procedure time, improved rate of IV access, and a better experience for the child or adolescent. Only under rare circumstances should obese children or adolescents be treated with midazolam because of the long procedure time. TRIAL REGISTRATIONS: isrctn.org Identifier: ISRCTN33779750 and kctr.se Identifier: KCTR CT20090023.