Classifying insulin regimens--difficulties and proposal for comprehensive new definitions.

Modern insulin regimens for the treatment of type 1 diabetes are highly individualized. The concept of an individually tailored medicine accounts for a broad variety of different insulin regimens applied. Despite clear recommendations for insulin management in children and adolescents with type 1 diabetes there is little distinctiveness about concepts and the nomenclature is confusing. Even among experts similar terms are used for different strategies. The aim of our review--based on the experiences of the Hvidoere Study Group (HSG)--is to propose comprehensive definitions for current insulin regimens reflecting current diabetes management in childhood and adolescence. The HSG--founded in 1994--is an international group representing 24 highly experienced pediatric diabetes centers, from Europe, Japan, North America and Australia. Different benchmarking studies of the HSG revealed a broad variety of insulin regimens applied in each center, respectively. Furthermore, the understanding of insulin regimens has been persistently different between the centers since more than 20 yr. Not even the terms 'conventional' and 'intensified therapy' were used consistently among all members. Besides the concepts 'conventional' and 'intensified', several other terms for the characterization of insulin regimens are in use: Basal Bolus Concept (BBC), multiple daily injections (MDI), and flexible insulin therapy (FIT) are most frequently used, although none of these expressions is clearly or consistently defined. The proposed new classification for insulin management will be comprehensive, simple, and catchy. Currently available terms were included. This classification may offer the opportunity to compare therapeutic strategies without the currently existing confusion on the insulin regimen.

The incidence of childhood type 1 diabetes in Ireland and the National Childhood Diabetes Register.

The incidence of Type 1 diabetes (T1D) in childhood and adolescence is increasing globally with few exceptions. To date limited conflicting data has been available regarding diabetes epidemiology in Ireland. We sought to determine the incidence of T1D in those aged under 15 years in the ROI by establishing a prospective national register of incident cases (Irish Childhood Diabetes National Registry (ICDNR)) using a standardised protocol which includes a measure of case ascertainment using capture-recapture methodology. In the period, 489 new cases were identified. All paediatric centres nationally participated. The directly standardised incidence rate was 27.5 per 100,000 per year (95% CIs: 24.0, 30.9) and 26.0 (95% CIs: 22.7, 29.3) in 2008 and 2009 respectively. The ICDNR is widely acceptable, it has confirmed a high incidence of T1D and is vital to monitor changes in disease incidence, optimise resource utilisation and diabetes management in the Irish population.

Target setting in intensive insulin management is associated with metabolic control: the Hvidoere childhood diabetes study group centre differences study 2005.

OBJECTIVE: To evaluate glycaemic targets set by diabetes teams, their perception by adolescents and parents, and their influence on metabolic control. METHODS: Clinical data and questionnaires were completed by adolescents, parents/carers and diabetes teams in 21 international centres. HbA1c was measured centrally. RESULTS: A total of 2062 adolescents completed questionnaires (age 14.4 +/- 2.3 yr; diabetes duration 6.1 +/- 3.5 yr). Mean HbA 1c = 8.2 +/- 1.4% with significant differences between centres (F = 12.3; p < 0.001) range from 7.4 to 9.1%. There was a significant correlation between parent (r = 0.20) and adolescent (r = 0.21) reports of their perceived ideal HbA1c and their actual HbA1c result (p < 0.001), and a stronger association between parents' (r = 0.39) and adolescents' (r = 0.4) reports of the HbA1c they would be happy with and their actual HbA1c result. There were significant differences between centres on parent and adolescent reports of ideal and happy with HbA1c (8.1 < F > 17.4;p < 0.001). A lower target HbA1c and greater consistency between members of teams within centres were associated with lower centre HbA1c (F = 16.0; df = 15; p < 0.001). CONCLUSIONS: Clear and consistent setting of glycaemic targets by diabetes teams is strongly associated with HbA1c outcome in adolescents. Target setting appears to play a significant role in explaining the differences in metabolic outcomes between centres.

Oral health of children born small for gestational age.

We sought to evaluate the oral health status of children born small for gestational age (SGA). Children now aged 4-8 years who were born SGA (birth weight < -2 SDS) were examined using standardised criteria. The parents completed a structured oral health questionnaire. Twenty females and 25 males, mean age 72.1 months, and mean birth weight 2.1 kg, participated in the study. Poor appetite was a concern; 32 (71%) children snacked between meals and 14 (30%) used carbonated beverages more than 3 times daily. Erosion was present in 9 (20%) children. Dental decay occurred in 22 (47%) children with 92% being untreated. Eight children had more than 5 decayed teeth. It is essential that clinicians working with children born SGA include oral health within the general health surveillance and refer these children for a dental assessment within the first 2 years to support parents in establishing safe feeding patterns for their children.

Are family factors universally related to metabolic outcomes in adolescents with Type 1 diabetes?

AIMS: To assess the importance of family factors in determining metabolic outcomes in adolescents with Type 1 diabetes in 19 countries. METHODS: Adolescents with Type 1 diabetes aged 11-18 years, from 21 paediatric diabetes care centres, in 19 countries, and their parents were invited to participate. Questionnaires were administered recording demographic data, details of insulin regimens, severe hypoglycaemic events and number of episodes of diabetic ketoacidosis. Adolescents completed the parental involvement scale from the Diabetes Quality of Life for Youth--Short Form (DQOLY-SF) and the Diabetes Family Responsibility Questionnaire (DFRQ). Parents completed the DFRQ and a Parental Burden of Diabetes score. Glycated haemoglobin (HbA(1c)) was analysed centrally on capillary blood. RESULTS: A total of 2062 adolescents completed a questionnaire, with 2036 providing a blood sample; 1994 parents also completed a questionnaire. Family demographic factors that were associated with metabolic outcomes included: parents living together (t = 4.1; P < 0.001), paternal employment status (F = 7.2; d.f. = 3; P < 0.001), parents perceived to be over-involved in diabetes care (r = 0.11; P < 0.001) and adolescent-parent disagreement on responsibility for diabetes care practices (F = 8.46; d.f. = 2; P < 0.001). Although these factors differed between centres, they did not account for centre differences in metabolic outcomes, but were stronger predictors of metabolic control than age, gender or insulin treatment regimen. CONCLUSIONS: Family factors, particularly dynamic and communication factors such as parental over-involvement and adolescent-parent concordance on responsibility for diabetes care appear be important determinants of metabolic outcomes in adolescents with diabetes. However, family dynamic factors do not account for the substantial differences in metabolic outcomes between centres.

Thyroid dysfunction in Down's syndrome and screening for hypothyroidism in children and adolescents using capillary TSH measurement.

UNLABELLED: Thyroid dysfunction is more common in individuals with Down's syndrome (DS) than in the general population, whose clinical features can mask the presenting signs and symptoms of hypothyroidism. Biochemical screening is necessary; however, venepuncture may be difficult. AIMS: To assess the prevalence of thyroid dysfunction in children and adolescents with DS and the feasibility of screening for hypothyroidism using capillary dried blood spot thyroid stimulating hormone (TSH) from infancy. METHODS: 394 children (217 boys, 177 girls) were clinically assessed for thyroid dysfunction and 305 children (aged 4 months to 18.9 years) were screened for hypothyroidism by capillary whole blood TSH sample. RESULTS: Thyroid dysfunction was detected in 4.6%, with 50% unscreened since neonatal screening. Parents reported minimal distress by fingerprick screening. CONCLUSION: DS is associated with an increased prevalence of thyroid dysfunction, particularly in preschool children. Biochemical screening is essential and capillary whole blood TSH sampling for hypothyroidism is feasible, less invasive and acceptable.

A retrospective cohort analysis of hypoglycaemic and cardiovascular agent use in young adults in the Irish primary care setting.

AIM: The prevalence of type 2 diabetes in young adults is increasing, yet little is known about medication use in this population. This study aimed to describe hypoglycaemic and cardiovascular treatment patterns in young adults newly treated with oral hypoglycaemic agents. METHODS: A retrospective cohort study from 2008-2011 was conducted using the Irish national pharmacy claims database. Subjects aged 15-39 years were analysed for use of hypoglycaemic therapy, subsequent regimen changes, and any co-prescription of cardiovascular agents 1 year after treatment initiation. Cox-proportional-hazards regression and logistic regression were used to examine factors associated with non-persistence to initial hypoglycaemic therapy (in males only), insulin use as a regimen change, and use of cardiovascular agents. Hazard ratios (HR), odds ratios (OR), and 95 % confidence intervals (CI) are presented. RESULTS: There were 5284 individuals initiated on hypoglycaemic agents. Most were initiated on metformin (88 %); 13 % of subjects received a hypoglycaemic agent regimen change, with insulin being used in 26 % of these cases. A total of 38 % of males were non-persistent with their initial hypoglycaemic agent, with males aged 15-29 years and those on sulphonylureas significantly more likely to be non-persistent with therapy. Over 40 % of subjects were initiated on cardiovascular agents. Females were less likely to receive cardiovascular agents [OR 0.50 (95 % CI 0.42-0.83)]. CONCLUSIONS: Treatment patterns were found to be associated with high levels of non-persistence, substantial use of insulin, and a low use of cardiovascular agents. This may pose problems for the management of the long-term complications associated with type 2 diabetes.

Exercise tolerance and physical activity levels in children referred to a weight reduction clinic.

The aim of this study was to investigate exercise tolerance and physical activity levels in children with exogenous obesity. Measures included BMI, waist circumference, exercise tolerance and self reported physical activity. Exercise tolerance was measured by the Modified Balke Treadmill Protocol and results were compared to normal values. Physical activity levels were assessed by measuring energy expended in regular activities each week over the past year and number of hours spent watching TV/video using an adaptation of the 'Modifiable Activity Questionnaire for Adolescents'. Details on transport to school were also obtained. Forty five children between September 2002 and June 2004 were assessed. This group comprised of 25 girls and 20 boys with mean ages (standard deviation) of 11.9 +/- 3.0 years and 13.7 +/- 2.5 years respectively. Exercise tolerance as a percentage of normal was below minimal levels in 64% girls and 75% boys. Energy expended in regular activity was less than the minimal recommendation in 80% girls and 65% boys. Seventy six percent of girls and 70% of boys spent 2 hours or more per day watching television and 40% of girls and 70% of boys walked to school. The low levels of activity and exercise tolerance need to be addressed in the managemeni of children with obesity

Guidelines for the medical management of Irish children and adolescents with Down syndrome.

Down syndrome (DS) is the most common chromosomal cause of developmental disability in Ireland. Children with DS have a high incidence of associated treatable medical disorders where early intervention carries a better outcome. Currently there are no agreed protocols for the screening and management of children and adults with DS in Ireland. A cross-sectional study of 394 children and adolescents was undertaken in the Eastern Regional Health Authority (ERHA) to assess the medical needs of children and adolescents with DS, in order to develop medical management guidelines. This study provides evidence-based data that children and adolescents with DS have a high incidence of treatable medical disorders, which supports the need for the medical management guidelines presented.

Good metabolic control is associated with better quality of life in 2,101 adolescents with type 1 diabetes.

OBJECTIVE: It is unclear whether the demands of good metabolic control or the consequences of poor control have a greater influence on quality of life (QOL) for adolescents with diabetes. This study aimed to assess these relations in a large international cohort of adolescents with diabetes and their families. RESEARCH DESIGN AND METHODS: The study involved 2,101 adolescents, aged 10-18 years, from 21 centers in 17 countries in Europe, Japan, and North America. Clinical and demographic data were collected from March through August 1998. HbA(1c) was analyzed centrally (normal range 4.4-6.3%; mean 5.4%). Adolescent QOL was assessed by a previously developed Diabetes Quality of Life (DQOL) questionnaire for adolescents, measuring the impact of diabetes, worries about diabetes, satisfaction with life, and health perception. Parents and health professionals assessed family burden using newly constructed questionnaires. RESULTS: Mean HbA(1c) was 8.7% (range 4.8-17.4). Lower HbA(1c) was associated with lower impact (P < 0.0001), fewer worries (P < 0.05), greater satisfaction (P < 0.0001), and better health perception (P < 0.0001) for adolescents. Girls showed increased worries (P < 0.01), less satisfaction, and poorer health perception (P < 0.01) earlier than boys. Parent and health professional perceptions of burden decreased with age of adolescent (P < 0.0001). Patients from ethnic minorities had poorer scores for impact (P < 0.0001), worries (P < 0.05), and health perception (P < 0.01). There was no correlation between adolescent and parent or between adolescent and professional scores. CONCLUSIONS: In a multiple regression model, lower HbA(1c) was significantly associated with better adolescent-rated QOL on all four subscales and with lower perceived family burden as assessed by parents and health professionals.

Persistent differences among centers over 3 years in glycemic control and hypoglycemia in a study of 3,805 children and adolescents with type 1 diabetes from the Hvidøre Study Group.

OBJECTIVE: Twenty-one international pediatric diabetes centers from 17 countries investigated the effect of simple feedback about the grand mean HbA(1c) level of all centers and the average value of each center on changes in metabolic control, rate of severe hypoglycemia, and insulin therapy over a 3-year period. RESEARCH DESIGN AND METHODS: Clinical data collection and determination of HbA(1c) levels were conducted at a central location in 1995 (n = 2,780, age 0-18 years) and 1998 (n = 2,101, age 11-18 years). RESULTS: Striking differences in average HbA(1c) concentrations were found among centers; these differences remained after adjustment for the significant confounders of sex, age, and diabetes duration. They were apparent even in patients with short diabetes duration and remained stable 3 years later (mean adjusted HbA(1c) level: 8.62 +/- 0.03 vs. 8.67 +/- 0.04 [1995 vs. 1998, respectively]). Three centers had improved significantly, four centers had deteriorated significantly in their overall adjusted HbA(1c) levels, and 14 centers had not changed in glycemic control. During the observation period, there were increases in the adjusted insulin dose by 0.076 U/kg, the adjusted number of injections by 0.23 injections per day, and the adjusted BMI by 0.95 kg/m(2). The 1995 versus 1998 difference in glycemic control for the seven centers could not be explained by prevailing insulin regimens or rates of hypoglycemia. CONCLUSIONS: This study reveals significant outcome differences among large international pediatric diabetes centers. Feedback and comparison of HbA(1c) levels led to an intensification of insulin therapy in most centers, but improved glycemic control in only a few.

Social, communicational, and behavioral deficits associated with ring X turner syndrome.

We describe the cognitive and behavioral characteristics of five individuals with a ring X chromosome. All subjects had a small active (early replicating) ring X chromosome. The X inactive specific transcript (XIST) locus was confirmed by fluorescent in situ hybridisation (FISH) to be present in all ring X chromosomes. Mental retardation was present in four individuals. All patients with or without mental retardation had a characteristic profile of aggression toward self and others, episodes of screaming, attentional problems, and impulsiveness. Autistic-like features were also present in all individuals and included limited communication, obsessive compulsive behavior, and social difficulties. In some cases the obsessive behavior was extreme and incapacitating. This characteristic behavioral profile may aid the diagnosis and future understanding of ring X.

Evaluation of intraocular pressure in the immediate period after phacoemulsification.

PURPOSE: To determine the incidence of hypotony or intraocular pressure (IOP) spikes in the early period after clear corneal phacoemulsification in normal and glaucomatous eyes. SETTING: Ambulatory surgical center. METHODS: This retrospective analysis comprised 112 eyes that had clear corneal phacoemulsification. Postoperative IOP measurements were collected 30 minutes, 1 day, and 1 month after surgery. RESULTS: Twenty-three eyes had an IOP of 5 mm Hg or below 30 minutes postoperatively. The IOP at 30 minutes was lower than at 1 day in both the normal and the glaucoma group. The mean IOP in the normal group was 10.0 mm Hg +/- 4.3 (SD) at 30 minutes and 16.9 +/- 4.4 mm Hg at 1 day (P < or = .005). The means in the glaucoma group were 9.6 +/- 3.9 mm Hg and 16.9 +/- 5.7 mm Hg, respectively (P < or = .0002). The IOPs at 30 minutes and 1 day were not significantly different between the 2 groups. CONCLUSIONS: A significant percentage of eyes having clear corneal phacoemulsification had an IOP of 5 mm Hg or less 30 minutes after surgery. Even though there were no postoperative complications from hypotony and there was a relative absence of significant IOP elevation 1 day postoperatively, the frequency of low IOP at 30 minutes suggests that consideration be given to leaving postoperative eyes with a higher IOP at the completion of phacoemulsification rather than with the estimated 10 mm Hg tactile IOP strived for in this study.

Rectal hydrocortisone during vomiting in children with adrenal insufficiency.

AIM: To evaluate rectal hydrocortisone as an emergency glucocorticoid replacement therapy in adrenal insufficient children. METHODS: A parental questionnaire evaluated preferred treatment, problems or benefits of i.m. and rectal hydrocortisone, frequency and indications for administration and who administered treatment. Admissions of children with adrenal insufficiency were monitored. RESULTS: There were 39/52 families who responded to the questionnaire. 93% (26/28) preferred rectal hydrocortisone. Parents or children who previously received emergency treatment from a doctor now self-administered rectal hydrocortisone. The cost of suppositories and i.m. hydrocortisone is similar; however, storage of suppositories was inconvenient. One girl presented with pneumonia and collapse despite rectal hydrocortisone and a hydrocortisone level at admission of >2000 nmol/l with normal electrolytes. CONCLUSIONS: Rectal hydrocortisone is an acceptable and safe emergency therapy. We still advise i.m. hydrocortisone if rectal administration is not possible or with suppository extrusion.

An open-label acceptability study of Norditropin SimpleXx--a new liquid growth hormone formulation.

A new liquid formulation of hGH (Norditropin SimpleXx) has been developed to avoid the need for reconstitution before administration. In addition, the liquid GH formulation has been combined with an advanced pen delivery system, either with or without a needle auto-insertion mechanism. This study was designed to assess the acceptability of the new system compared with the patient's previous system. A total of 103 children with GH deficiency received a daily injection of Norditropin liquid GH for 12 weeks with a choice of a pen/auto-insertion system. Acceptability was determined by nurse-supervised questionnaires administered to the patients and parents. Following treatment, 94% of patients preferred the Norditropin liquid GH system. This preference was irrespective of the previous system in use, patient age or length of GH therapy. More patients found it the less painful system (50% vs 13%), 92% of patients found it more convenient, and the formulation was well tolerated. In conclusion, Norditropin liquid GH was very well accepted and preferred by the majority of patients. It avoided reconstitution which had been a major cause of dissatisfaction with the patients' previous systems, and resulted in greater convenience and reduced levels of pain associated with injection.

Sibling incest in a clergy family: a case study.

A case study is presented of a female adult survivor of childhood sexual abuse where the perpetrator was her older brother. The children belonged to a clergy family where the father was a clergyman in a mainstream Christian church. The family dynamics are described, emphasizing the physically absent father, the emotionally distant mother, and the surrogate parent status of the perpetrator. The victim's adult years are described, revealing recurrent failures both socially and in the workplace, and a general dissatisfaction with life. Her several attempts to seek appropriate help are described. Eventually, one of these proved successful, and the victim's emotional outlook was transformed into that of a survivor. She is now able to view the world from a contented and achieving aspect. Her experiences of disclosing the abuse to her parents and confronting the church hierarchy are described. Concern is expressed at the perceived inappropriateness of some of the professional assistance the victim was offered as she came to terms with her experience of sibling incest.

The age of menarche in Irish girls.

PIP: Age at menarche in Ireland is analyzed using data from a representative sample of 2,940 girls aged 9 to 17 drawn from schools in Dublin, Dundalk, Navan, and Portlaoise, of whom some half were urban and half rural residents. The mean age at menarche was 13.52 years. The authors note that this is the latest mean age at menarche recorded for a contemporary European population. No significant differences in age at menarche by place of residence or social class were noted.^ieng

National incidence of type 1 diabetes in childhood and adolescence.

The Republic of Ireland is considered a region of low type 1 diabetes incidence compared with the British Isles and the rest of Europe. To establish a baseline national incidence of type 1 diabetes, in those under 15 years, with a measure of case ascertainment. Prospective active monthly reporting of incident cases by paediatricians was undertaken, with survey of adult physicians, endocrinologists and nurse specialists nationally. A secondary source of case ascertainment was employed. The crude incidence rate of type 1 diabetes was 16.6 per 100,000 per year and the directly standardised incidence rate was 16.3 per 100,000 per year. The Republic has a high incidence of type 1 diabetes. Services should be planned and resources allocated accordingly. A register should be established to monitor changes in this important disease. Further study is required to explore differing incidence in Northern and Southern Ireland.

Treatment outcome in Turner syndrome.

Short stature is an almost universal feature of Turner Syndrome (TS) with patients having a mean adult height up to 20 cm less than that of the general female population. As a result a significant focus of medical management in TS is on growth promoting strategies. The aim of this study was to assess factors influencing final height in those with TS and evaluate the response to various treatments. A retrospective study was performed in 2 Dublin centres. The age of commencement, cessation, dose and duration of treatment was calculated for growth hormone, oestrogen and oxandrolone, either alone or in combination. Additional factors known to influence growth in TS were also examined. The mean final height achieved was 147.31 cm (SD 4.77), the mean predicted height was 142.81 (SD 5.63). Height gain was 4.28 cm (SD 4.93). All patients received growth hormone. 75% of patients received oestrogen and 35% received oxandrolone. The maximal height gain of 6.71 cm (SD 2.43) in the triple therapy group. Parental height was found to have a significant correlation with final height (r=0.591). Spontaneous menarche in TS was associated with a poor adult height (r=-0.522), mean height 144.03 cm (SD 3.23) whereas those with induced menarche had a mean height of 148.43 cm (SD 4.67). Growth hormone therapy improves the mean final height in TS. However, the degree of height gain is influenced by confounding variables of parental height and age and tempo of puberty and treatment variables.