The incidence of type 1 diabetes in children under 15 years of age is rising again-a nationwide study.

International incidence rates (IRs) and trends of childhood type 1 diabetes (T1D) vary. Recent data from Ireland and other high incidence countries suggested a stabilisation in IRs of T1D in children aged under 15 years. Our primary objective was to report the IR of T1D in children in Ireland from 2019 to 2021 and evaluate if age, sex and season of diagnosis had changed. Incident cases of T1D in those aged under 15 years were identified prospectively by clinicians nationally and reported to the Irish Childhood Diabetes National Register (ICDNR). Following case verification, capture-recapture methodology was applied, and IRs calculated. Numbers of children including age, sex and season of diagnosis per year were evaluated. There were 1027 cases, 542 males (53%). The direct standardised incidence rates (SIRs) increased by 21% overall and were 31.1, 32.2 and 37.6/100,000/year, respectively, with no significant sex difference. The highest IRs were in the 10-14-year category until 2021, then changed to the 5-9-year category (40% of cases). Whilst autumn and winter remain dominant diagnostic seasons, seasonality differed in 2021 with a greater number presenting in spring. CONCLUSION: The incidence of childhood T1D in Ireland is increasing, observed prior to the COVID-19 pandemic, and shifting to an earlier age at diagnosis for the first time. The pattern of seasonality also appears to have changed. This may reflect an increased severity of diabetes with important implications for healthcare providers. WHAT IS KNOWN: • Ireland has a very high incidence of T1D in childhood, which had stabilised following a rapid rise, similar to other high incidence countries. • The incidence rate is consistently highest in older children (10-14 years). WHAT IS NEW: • Irish IR is no longer stable and has increased again, with the highest incidence occurring in the younger 5-9 age category for the first time. • The seasonality of diagnosis has changed during the COVID-19 pandemic years of 2020-2021.

Incidence of childhood type 1 diabetes mellitus in Ireland remains high but no longer rising.

AIM: The global incidence of type 1 diabetes mellitus (T1DM) varies considerably geographically. Ireland has a high incidence of T1DM. Incidence accelerated between 1997 and 2008, although more recent data (2008-2013) suggested stabilisation in the incidence rate (IR). This study sought to determine IRs for 2014 to 2018. METHODS: Incident cases were prospectively recorded through the established Irish Childhood Diabetes National Register (ICDNR). Cases were verified, and IRs were calculated. Capture-recapture methodology was identical to previous studies. Age and seasonality data were compared. RESULTS: A total of 1429 cases were reported (age range 0.45-14.98 years), with significantly more males (772, 54%) and male-to-female ratio of 1.17 (95% CI 1.05, 1.29). Standardised IRs for T1DM in the period were 28.0; 29.6; 30.9; 27.0; and 27.1/100,000/year, respectively. There was a slight reduction in standardised IR, more marked in females than males (9.9% v 1.6%). The highest IR remains in the 10- to 14-year-old age group (44% of total cases). Seasonality of diagnosis is persistently higher in autumn and winter. CONCLUSION: Ireland remains a high incidence country, despite a minor reduction in incidence rates. Ongoing incidence monitoring through national registers is vital to inform healthcare services, research relating to aetiology and paediatric diabetes management.

Is the incidence of type 1 diabetes in children and adolescents stabilising? The first 6 years of a National Register.

The Irish Childhood Diabetes National Register (ICDNR) was established in 2008 to define accurately the incidence and monitor the epidemiology of type 1 diabetes (T1D) in the Irish population. Here, we report data from the first 6 years of the National Register and compare with previous national data. Prospective national incident data regarding T1D in those under 15 years resident in Ireland were collected from 2008 to 2013 and national incidence rates (IRs) calculated. Ascertainment completeness was assessed using capture-recapture methodology. The period identified 1566 new cases of T1D, ascertainment reached 96.8 % in 2013. The standardised incidence rate was 27.5 in 2008 stabilising at 28.7 and 28.8 cases /100,000/year in 2012 and 2013. There was no evidence that the incidence changed significantly in the 6-year period either overall or for each age group and gender. There was evidence of a difference in the incidence of T1D across the age groups with the overall incidence highest in the 10-14 year age category. A strong seasonal association was demonstrated. CONCLUSIONS: This study confirms Ireland as a high-incidence country for type 1 diabetes whilst demonstrating that the previous marked increase in IR from 16.3 cases/100,000/year in 1997 has not continued. Ongoing monitoring through the robust mechanism of the ICDNR is required to clarify whether this is a fluctuation or if the incidence of T1D diabetes has stopped rising in our population. Alternatively, this apparent stabilisation may reflect a shift to a later age at diagnosis. "What is known :" • The incidence of Type 1 diabetes (T1D) is increasing in most populations worldwide although in certain high-incidence populations, it may be stabilising • There was a marked increase in T1D in Ireland between 1997 and 2008 • T1D incidence increases with affluence "What is New:" • The high incidence of T1D in Ireland has been confirmed at 28.8 cases/100,000/year in 2013 and has been effectively stable in the period 2008-2013 • Incidence is highest in Irish 10-14 year olds • Changes in incidence possibly reflecting life style and economic climate • Marked seasonality of diagnosis confirmed.

Expression of Angiogenic Factors in Patients With Sporadic Small Bowel Angiodysplasia.

GOALS: To identify putative angiogenic factors associated with sporadic small bowel angiodysplasia (SBA). BACKGROUND: SBAs account for 50% of obscure gastrointestinal bleeding and due to delays in diagnosis and ineffective treatments, are associated with high levels of morbidity and mortality. Treatment development is impeded by a limited knowledge of the pathophysiology behind SBA formation. STUDY: We identified patients with definite sporadic SBA, and fecal immunochemical-negative controls were recruited from our institution's colorectal cancer screening program. Serum levels of VEGF, endoglin, Angiopoietin-2 (Ang-2), PDGF, Angiopoietin-1 (Ang-1), and TNF-α were measured using commercially available enzyme-linked immunosorbent assay kits. On the basis of serum results, we measured gene expression of target angiogenic factors in small bowel biopsy samples from angiodysplasias and unaffected tissue by quantitative PCR assessment. RESULTS: Serum samples were analyzed from 40 SBA patients and 40 controls. Median serum levels of Ang-2 were significantly higher in patients than controls with levels of Ang-1 and TNF-α significantly lower. There were no differences in serum levels of VEGF, endoglin, or PDGF. Gene expression levels of Ang-1, Ang-2, and their receptor Tie2 were all significantly higher in biopsies from areas of angiodysplasia compared with normal small bowel. CONCLUSIONS: This study, the first to explore the role of angiogenic factors in SBA, has identified a positive association between SBA and the Angiopoietin pathway, with increased serum and mucosal expression of Ang-2, which could potentially be used as a serum biomarker and future therapeutic target to improve outcome in affected patients.

Periocular triamcinolone for prevention of macular edema after plaque radiotherapy of uveal melanoma: a randomized controlled trial.

OBJECTIVE: To determine the efficacy and safety of periocular triamcinolone acetonide (40 mg) for the prevention of macular edema in patients undergoing plaque radiotherapy for uveal melanoma. DESIGN: Prospective, randomized, controlled clinical trial. PARTICIPANTS AND CONTROLS: One-hundred sixty-three patients with newly diagnosed uveal melanoma undergoing iodine 125 plaque radiotherapy were entered into the study. Fifty-five patients were randomized to the control group and 108 to the triamcinolone group. Eighteen-month data were available for 143 (88%) of the 163 patients. INTERVENTION: Periocular injection of triamcinolone acetonide (40 mg in 1 ml) at the time of plaque radiotherapy and 4 months and 8 months later. Optical coherence tomography was performed at each patient evaluation. MAIN OUTCOME MEASURES: Optical coherence tomography-evident macular edema, moderate vision loss, and poor final visual acuity. RESULTS: Optical coherence tomography-evident macular edema occurred significantly less often in the triamcinolone group compared with the control group up to 18 months after plaque radiotherapy (hazard estimate, 0.45; 95% confidence interval, 0.19-0.70; P = 0.001). At the 18-month follow-up, moderate vision loss (loss of 3 lines or more of best-corrected visual acuity [BCVA]) and severe vision loss (BCVA <5/200 Snellen) occurred significantly less frequently in the triamcinolone group than in the control group (31% vs. 48% [P = 0.039] and 5% vs. 15% [P = 0.048], respectively). Rates of elevated intraocular pressure and cataract progression were similar in both groups. CONCLUSIONS: Periocular triamcinolone is beneficial in reducing the risk of macular edema up to 18 months after plaque radiotherapy for uveal melanoma and significantly reduces the risk of moderate vision loss and poor visual acuity in these patients.

Autism symptoms in Attention-Deficit/Hyperactivity Disorder: a familial trait which correlates with conduct, oppositional defiant, language and motor disorders.

It is hypothesised that autism symptoms are present in Attention-Deficit/Hyperactivity Disorder (ADHD), are familial and index subtypes of ADHD. Autism symptoms were compared in 821 ADHD probands, 1050 siblings and 149 controls. Shared familiality of autism symptoms and ADHD was calculated using DeFries-Fulker analysis. Autism symptoms were higher in probands than siblings or controls, and higher in male siblings than male controls. Autism symptoms were familial, partly shared with familiality of ADHD in males. Latent class analysis using SCQ-score yielded five classes; Class 1(31%) had few autism symptoms and low comorbidity; Classes 2-4 were intermediate; Class 5(7%) had high autism symptoms and comorbidity. Thus autism symptoms in ADHD represent a familial trait associated with increased neurodevelopmental and oppositional/conduct disorders.

Recovery after stroke: a 1-year profile.

PURPOSE: To document the course of recovery in a group of first stroke patients, with stroke of moderate severity, over a 1-year period. Evaluation of recovery is important for estimating rehabilitation needs. METHOD: One-year observational study of 23 acute first stroke patients. Recovery was assessed at 15 specific intervals using measures of impairment, activity, social participation and quality of life. RESULTS: There were significant changes in impairment (p < 0.05) and motor disability over 1 year (F ratio = 75.627, d.f. = 4, p < or = 0.0001) including the period between 6 and 12 months though recovery did appear to slow down after a 9-week 'turning point'. Significant improvements in social participation were also seen between 6 and 12 months (p = 0.0021). Quality of life did not change and patients' quality of life scores indicated levels of 'severe distress' at 6 (57.8 [8.8]) and 12 months (58.9 [8.6]). CONCLUSIONS: Recovery after stroke was detectable beyond 6 months using detailed measures. This demonstration of late recovery has therapeutic implications. An increased understanding of the course of recovery following stroke could provide a basis for evaluating the varied aspects of therapeutic intervention in stroke rehabilitation.

Chronic hepatitis C infection and sicca syndrome: a clear association with HLA DQB1*02.

BACKGROUND: Hepatitis C virus infection is a major cause of nonA, nonB hepatitis worldwide. A high prevalence of immunological abnormalities has been shown to occur in patients with chronic hepatitis C virus infection. AIM: The aim of this study was to assess the development of sicca syndrome in a cohort of patients infected with a single strain of hepatitis C virus, namely genotype 1b, and correlate this with viral persistence and human leukocyte antigen type of the patients. METHODS: Ninety-five patients infected with the single strain hepatitis C virus were used in this study, 32 of whom were polymerase chain reaction-negative and 63 polymerase chain reaction-positive. Patient details were reviewed for symptoms consistent with sicca syndrome. Human leukocyte antigen class I (A, B and C) and class II (DRB and DQB1) typing was performed on all patients. Auto-antibodies were also measured. RESULTS: DQB1*02 was highly significantly associated with viral persistence (P<0.0001). Nineteen of 21 patients with sicca syndrome were hepatitis C virus-polymerase chain reaction-positive demonstrating a strong association with viral persistence and the development of the syndrome. Human leukocyte antigen DQB1*02 was significantly associated with the development of sicca syndrome, P=0.02. CONCLUSION: The development of autoimmune disease in patients with chronic hepatitis C virus infection depends on the interaction of multiple factors. This study suggests that important factors in this process are viral persistence and human leukocyte antigen type of the patients.

Sudden unexplained death in childhood (1-4 years) in Ireland: an epidemiological profile and comparison with SIDS.

OBJECTIVE: To examine the incidence of sudden unexplained death in children 1-4 years old (SUDC) in Ireland and to compare the epidemiological profile of SUDC with that of SIDS. DESIGN: All cases of sudden unexplained death in children <5 years in Ireland between 1994 and 2008 were reviewed. Epidemiological information obtained from parental questionnaires and post-mortem reports was examined, and data on cases ≥52 weeks compared with cases <52 weeks. RESULTS: SUDC accounted for 5% (n=44) of deaths in children aged 1-4 years during 1994-2008. During this period, the SIDS rate dropped from 0.71 to 0.34 per 1000 live births, while the SUDC rate increased from 0.08 to 0.18 deaths per 10 000 population aged 1-4 years. The median age of SUDC cases was 71.5 weeks, and the male/female ratio was 1.3:1. All died during a sleep period, 71% between 10pm and 8am, and more than two-thirds were found prone. Fewest cases occurred during July-September (11%), and a greater proportion occurred at weekends (55%). 52% (17/33) had symptoms (any) in the 48 h before death, and 35% (11/31) visited their general practitioner because of illness in the week preceding death. SUDC differed from SIDS in prevalence of maternal smoking (38% vs 72%, p<0.001), bed-sharing (17% vs 49%, p<0.001), and whether found prone (72% vs 23%, p<0.001). CONCLUSION: While SUDC shares some characteristics with SIDS, there are also some important differences. Further data collection will help determine whether SIDS and SUDC represent the same pathophysiological entity. Standardisation of protocols for investigating sudden deaths is urgently required for accurate diagnosis of cases.

Psychometric evaluation of the functional walking test for children with cerebral palsy.

PURPOSE: This study examined the psychometric properties of the functional walking test (FWT). METHOD: Fifty-six subjects with cerebral palsy (CP) (21 females and 35 males, mean age 9 years 6 months, SD 3 years 9 months, range 4-17 years) were assessed on two occasions, 6 months apart, using both the FWT and the gross motor function measure (GMFM). RESULTS: Generalisability correlation coefficients (GCC) for all 11 items were high (0.91-0.99). Inter-rater reliability was also high with excellent consensus in the scores given by the eight raters (intra-class correlation coefficient and GCC 0.99). Intra-rater reliability was equally high (GCC 0.99). The internal consistency of the FWT was estimated using Cronbach's α as 0.95 and 0.94 at Time 1 and 2, respectively. The FWT had a high degree of correlation with the GMFM, when total scores were compared at Time 1 and 2 (Pearson's r = 0.86 and 0.87, n = 56, p < 0.01). The FWT also found statistically significant differences in total scores between the three Gross Motor Function Classification System (GMFCS) levels. The correlation between the FWT scores and GMFCS was -0.70 at Time 1 and -0.76 Time 2 (p < 0.01) indicating the construct validity of the FWT. CONCLUSIONS: This study has demonstrated that the FWT has sound psychometric properties and is valid and reliable in a sample population of ambulant children with CP.

Periocular triamcinolone for prevention of macular edema after iodine 125 plaque radiotherapy of uveal melanoma.

OBJECTIVE: To investigate the potential benefit of periocular depot triamcinolone in the prevention of macular edema after iodine 125 plaque radiotherapy for uveal melanoma. METHODS: This comparative, nonrandomized, interventional study included 87 patients with uveal melanoma who underwent plaque radiotherapy. The triamcinolone group included 55 consecutive patients who were treated with 40 mg of periocular triamcinolone at the time of plaque application and 4 months and 8 months later. The comparison group comprised 32 consecutive patients treated with plaque radiotherapy without triamcinolone. Patients were evaluated at 4 months, 8 months, 12 months, 18 months, and 24 months after plaque application with clinical examination, fundus photography, and optical coherence tomography (OCT). The associations of clinical variables with the development of OCT-evident macular edema (the main outcome measure) were investigated using Cox proportional hazards analysis. RESULTS: By multivariate analysis, eyes treated with periocular triamcinolone had a significant reduction in the risk of radiation-induced macular edema (P = 0.002; hazard estimate = 0.49; 95% confidence interval, 0.17- 0.80). Adverse effects associated with periocular triamcinolone treatment included elevation of intraocular pressure (7% of cases) and blepharoptosis (5% of cases). CONCLUSIONS: Periocular triamcinolone treatment significantly lowered the risk of macular edema after plaque radiotherapy for uveal melanoma in this series but did not significantly alter the rate of vision loss at 24 months of follow-up.

Sleep disorders in children with cerebral palsy.

To determine the frequency and predictors of sleep disorders in children with cerebral palsy (CP) we analyzed the responses of 173 parents who had completed the Sleep Disturbance Scale for Children. The study population included 100 males (57.8%) and 73 females (42.2%; mean age 8y 10mo [SD 1y 11mo]; range 6y-11y 11mo). Eighty-three children (48.0%) had spastic diplegia, 59 (34.1%) congenital hemiplegia, 18 (10.4%) spastic quadriplegia, and 13 (7.5%) dystonic/dyskinetic CP. Seventy-three children (42.2%) were in Gross Motor Function Classification System Level I, 33 (19.1%) in Level II, 30 (17.3%) in Level III, 23 (13.3%) in Level IV, and 14 (8.1%) in Level V. Thirty children (17.3%) had epilepsy. A total sleep problem score and six factors indicative of the most common areas of sleep disorder in childhood were obtained. Of the children in our study, 23% had a pathological total sleep score, in comparison with 5% of children in the general population. Difficulty in initiating and maintaining sleep, sleep-wake transition, and sleep breathing disorders were the most frequently identified problems. Active epilepsy was associated with the presence of a sleep disorder (odds ratio [OR]=17.1, 95% confidence interval [CI] 2.5-115.3), as was being the child of a single-parent family (OR=3.9, 95% CI 1.3-11.6). Disorders of initiation and maintenance of sleep were more frequent in children with spastic quadriplegia (OR=12.9, 95% CI 1.9-88.0), those with dyskinetic CP (OR=20.6, 95% CI 3.1-135.0), and those with severe visual impairment (OR=12.5, 95% CI 2.5-63.1). Both medical and environmental factors seem to contribute to the increased frequency of chronic sleep disorders in children with CP.

Nasalance scores for normal-speaking Irish children.

OBJECTIVE: To obtain normal nasalance values during the production of a standardized speech sample for Irish children and determine whether significantly different scores exist for different speech stimuli for female and male speakers. DESIGN: Mean nasalance scores were obtained for normal-speaking children during the repetition of 16 test sentences that were categorized according to consonant type within the sentences (high-pressure consonants, low-pressure consonants, nasal consonants). PARTICIPANTS: Seventy children (36 girls and 34 boys, aged 4 years 11 months to 13 years) with normal articulation, resonance, and voice were included. PROCEDURES: Children repeated each of the 16 test sentences individually. The sentences were presented in groups according to consonant type, referred to as sentence categories. Data were collected and analyzed using the Kay nasometer (model 6200.3). Nasalance scores were obtained for the total speech sample and each sentence category. Data were statistically analyzed to investigate the effects of gender, sentence category, and gender by sentence category. RESULTS: Normative nasalance scores were obtained for the total speech sample (26%), high-pressure consonant sentences (14%), low-pressure consonant sentences (16%), and a nasal consonant sentence (51%). There was no significant difference in nasalance scores between male and female speakers. Significant differences were found between each sentence category (p

Recovery of the upper limb post ischaemic stroke and the predictive value of the Orpington Prognostic Score.

OBJECTIVE: To document upper limb recovery in stroke patients and investigate whether the Orpington Prognostic Score (OPS) performed within 48 hours of admission to hospital post ischaemic stroke was a predictor of upper limb function at six months and two years. DESIGN: Inception cohort design. SETTING: Teaching Hospital. SUBJECTS: One hundred and fourteen patients hospitalized with acute ischaemic stroke were stratified into three groups based on their OPS within 48 hours of admission post stroke and underwent further assessments at two weeks, six months and two years after stroke onset. MAIN MEASURES: Rivermead Arm Score (RAS), Nine Hole Peg Test (NHPT) and grip strength (GS). RESULTS: Patients with a good OPS and intermediate OPS showed significant recovery in all outcome measures for up to six months post stroke (p < 0.05), while those with a poor OPS at 48 hours showed no significant improvement (p > 0.05). The OPS score at 48 hours was the most highly correlated variable with upper limb outcome at six months (r= -0.728) and at two years (r= -0.712) compared with other variables such as age, class of stroke, sensation, grip strength and RAS. CONCLUSION: Stroke patients demonstrate differential upper limb recovery patterns which need to be taken in consideration when designing studies that investigate efficacy of rehabilitation, and the OPS is highly correlated with upper limb recovery at six months and two years.