Seasonal variation in month of diagnosis in children with type 1 diabetes registered in 23 EURODIAB centres during 1989-2008

Objectives: To investigate seasonal variation in month of diagnosis in children with type 1 diabetes registered in EURODIAB centres during 1989-2008.
Methods: 23 population-based registers recorded date of diagnosis in new cases of clinically diagnosed type 1 diabetes in children aged under 15 years. Completeness of ascertainment was assessed through capture-recapture methodology and was high in most centres. A general test for seasonal variation (11df) and Edward's test for sinusoidal (sine wave) variation (2df) were employed. Time series methods were also used to investigate if meteorological data were predictive of monthly counts after taking account of seasonality and long term trends.
Results: Significant seasonal variation was apparent in all but two small centres, with an excess of cases apparent in the winter quarter. Significant sinusoidal pattern was also evident in all but two small centres with peaks in December (14 centres), January (5 centres) or February (2 centres). Relative amplitude varied from ±11% to ±39% (median ±18%). There was no relationship across the centres between relative amplitude and incidence level. However there was evidence of significant deviation from the sinusoidal pattern in the majority of centres. Pooling results over centres, there was significant seasonal variation in each age-group at diagnosis, but with significantly less variation in those aged under 5 years. Boys showed marginally greater seasonal variation than girls. There were no differences in seasonal pattern between four sub-periods of the 20 year period. In most centres monthly counts of cases were not associated with deviations from normal monthly average temperature or sunshine hours; short term meteorological variations do not explain numbers of cases diagnosed.
Conclusions: Seasonality with a winter excess is apparent in all age-groups and both sexes, but girls and the under 5s show less marked variation. The seasonal pattern changed little in the 20 year period.

EURODIAB childhood type 1 diabetes incidence registers - results from the first 20 years. Oral presentation at the 47th EASD Annual Meeting, Lisbon, Portugal.

Background and aims: In 1989 a number of registers in Europe began recording new cases of type 1 diabetes diagnosed in children aged under 15 years using a common protocol. Trends in incidence rate during the 20 year period 1989-2008 are described.
Materials and methods: All registers operate in geographically defined regions and are based on a clinical diagnosis. When possible, completeness of registration in each register is assessed using capture-recapture methodology by identifying primary and secondary sources of ascertainment. The completeness estimate is obtained by identifying the numbers of cases identified by the primary source only, by the secondary source only and by both the primary and the secondary sources.
Results: Other registers have joined the Group since 1989, and 21 registers in 15 countries continue to submit registration data. In the first five years (1989-93) incidence rates varied from 3.2 per 100,000 in the Former Yugoslav Republic of Macedonia to 25.8 per 100,000 in the Stockholm area of Sweden. In the last five years (2004-2008) these same two registers again had the lowest and highest incidence, but rates had increased to 5.8 per 100,000 and 36.6 per 100,000, respectively. During the 20 year period all but two of the 21 registers showed statistically significant rates of increase (median rate of increase 4% per annum), and similar figures were obtained when this median rate of increase was estimated for the first half of the period (1989-98) and for the second half (1999-2008) . However, rates of increase differed significantly between the first half and the second half of the period for eight of the 17 registers with adequate coverage of both periods; four registers showing significantly higher rates of increase in the first half and four significantly higher rates in the second half.
Conclusion: The childhood type 1 diabetes incidence rate continues to rise across Europe by approximately 4% per annum, but the increase within a register is not necessarily uniform with periods of less rapid and more rapid increase in incidence occurring in some registers. This pattern of change suggests that important risk exposures differ over time in different European countries. Further time trend analysis and comparison of the patterns in defined regions are warranted.

EURODIAB childhood type 1 diabetes incidence registers - results from the first 20 years

Background and aims: In 1989 a number of registers in Europe began recording new cases of type 1 diabetes diagnosed in children aged under 15 years using a common protocol. Trends in incidence rate during the 20 year period 1989-2008 are described.
Materials and methods: All registers operate in geographically defined regions and are based on a clinical diagnosis. When possible, completeness of registration in each register is assessed using capture-recapture methodology by identifying primary and secondary sources of ascertainment. The completeness estimate is obtained by identifying the numbers of cases identified by the primary source only, by the secondary source only and by both the primary and the secondary sources.
Results: Other registers have joined the Group since 1989, and 21 registers in 15 countries continue to submit registration data. In the first five years (1989-93) incidence rates varied from 3.2 per 100,000 in the Former Yugoslav Republic of Macedonia to 25.8 per 100,000 in the Stockholm area of Sweden. In the last five years (2004-2008) these same two registers again had the lowest and highest incidence, but rates had increased to 5.8 per 100,000 and 36.6 per 100,000, respectively. During the 20 year period all but two of the 21 registers showed statistically significant rates of increase (median rate of increase 4% per annum), and similar figures were obtained when this median rate of increase was estimated for the first half of the period (1989-98) and for the second half (1999-2008) . However, rates of increase differed significantly between the first half and the second half of the period for eight of the 17 registers with adequate coverage of both periods; four registers showing significantly higher rates of increase in the first half and four significantly higher rates in the second half.
Conclusion: The childhood type 1 diabetes incidence rate continues to rise across Europe by approximately 4% per annum, but the increase within a register is not necessarily uniform with periods of less rapid and more rapid increase in incidence occurring in some registers. This pattern of change suggests that important risk exposures differ over time in different European countries. Further time trend analysis and comparison of the patterns in defined regions are warranted.

Iris cysts in children:Classification, incidence, and management. The 1998 Torrence A Makley Jr Lecture

Background - Iris cysts in children are uncommon and there is relatively little information on their classification, incidence, and management. Methods - The records of all children under age 20 years who were diagnosed with iris cyst were reviewed and the types and incidence of iris cysts of childhood determined. Based on these observations recommendations were made regarding management of iris cysts in children. Results - Of 57 iris cysts in children, 53 were primary and four were secondary. There were 44 primary cysts of the iris pigment epithelium, 34 of which were of the peripheral or iridociliary type, accounting for 59% of all childhood iris cysts. It was most commonly diagnosed in the teenage years, more common in girls (68%), was not recognised in infancy, remained stationary or regressed, and required no treatment. The five mid-zonal pigment epithelial cysts were diagnosed at a mean age of 14 years, were more common in boys (83%), remained stationary, and required no treatment. The pupillary type of pigment epithelial cyst was generally recognised in infancy and, despite involvement of the pupillary aperture, also required no treatment. There were nine cases of primary iris stromal cysts, accounting for 16% of all childhood iris cysts. This cyst was usually diagnosed in infancy, was generally progressive, and required treatment in eight of the nine cases, usually by aspiration and cryotherapy or surgical resection. Among the secondary iris cysts, two were post-traumatic epithelial ingrowth cysts and two were tumour induced cysts, one arising from an intraocular lacrimal gland choristoma and one adjacent to a peripheral iris naevus. Conclusions - Most iris cysts of childhood are primary pigment epithelial cysts and require no treatment. However, the iris stromal cyst, usually recognised in infancy, is generally an aggressive lesion that requires treatment by aspiration or surgical excision.

Growth hormone (GH) responsiveness to GHRH in normal adults is not affected by short-term gonadal blockade

The effects of changes in circulating gonadal steroids on GH secretion elicited by GHRH challenge (1µg/kg) in normal adults volunteers (aged 18-24 years), were evaluated in 10 women and 10 men before and after gonadal blockade was achieved by a GnRH agonist (1500 µg/day by nasal spray for 40 days). To see if the effect of testosterone on GH secretion was dependent on its aromatization to estradiol (E), GHRH tests were performed in 7 normal men prior to administration of testosterone enanthate (250 mg im), 8 days after this treatment had began, and again after E receptor blockade with tamoxifen (30 mg for 2 days plus 10 mg on the third day 2 h before the GHRH test, po) administered 8 days after testosterone enanthate. The study of the functional status of the somatotropes at the time of GHRH testing was made according to our previous postulate. Short-term gonadal blockade did not affect the parameters of GH response to GHRH in neither women nor men. Thus, the functional blockade of the gonads may be advisable as an adjunct therapy in the treatment of hypothalamic GH deficiency during the prepubertal stage. In the other group of men, administration of testosterone enanthate significantly increased GHRH-elicited GH release, but this was reverted after E receptor blockade. Since the hypothalamic-somatotrope rhythm was altered by both these farmacological manipulations, it appears that testosterone acts on GH release mainly at the suprapituitary level, and that this action is secondary to its aromatization to E.

Estimation of contribution of changes in classic risk factors to trends in coronary-event rates across the WHO MONICA Project populations

Background. From the mid-1980s to mid-1990s, the WHO MONICA Project monitored coronary events and classic risk factors for coronary heart disease (CHD) in 38 populations from 21 countries. We assessed the extent to which changes in these risk factors explain the variation in the trends in coronary-event rates, across the populations. Methods. In men and women aged 35-64 years, non-fatal myocardial infarction and coronary deaths were registered continuously to assess trends in rates of coronary events. We carried out population surveys to estimate trends in risk factors. Trends in event rates were regressed on trends in risk score and in individual risk factors. Findings. Smoking rates decreased in most male populations but trends were mixed in women; mean blood pressures and cholesterol concentrations decreased, body-mass index increased, and overall risk scores and coronary-event rates decreased. The model of trends in 10-year coronary-event rates against risk scores and single risk factors showed a poor fit, but this was improved with a 4-year time lag for coronary events. The explanatory power of the analyses was limited by imprecision of the estimates and homogeneity of trends in the study populations. Interpretation. Changes in the classic risk factors seem to partly explain the variation in population trends in CHD. Residual variance is attributable to difficulties in measurement and analysis, including time lag, and to factors that were not included, such as medical interventions. The results support prevention policies based on the classic risk factors but suggest potential for prevention beyond these.

Association of retinal arteriolar dilatation with lower verbal memory::The Edinburgh Type 2 Diabetes Study

Abstract


AIMS/HYPOTHESIS:

Retinal vascular calibre changes may reflect early subclinical microvascular disease in diabetes. Because of the considerable homology between retinal and cerebral microcirculation, we examined whether retinal vascular calibre, as a proxy of cerebral microvascular disease, was associated with cognitive function in older people with type 2 diabetes.

METHODS:

A cross-sectional analysis of 954 people aged 60-75 years with type 2 diabetes from the population-based Edinburgh Type 2 Diabetes Study was performed. Participants underwent standard seven-field binocular digital retinal photography and a battery of seven cognitive function tests. The Mill Hill Vocabulary Scale was used to estimate pre-morbid cognitive ability. Retinal vascular calibre was measured from an image field with the optic disc in the centre using a validated computer-based program.

RESULTS:

After age and sex adjustment, larger retinal arteriolar and venular calibres were significantly associated with lower scores for the Wechsler Logical Memory test, with standardised regression coefficients -0.119 and -0.084, respectively (p?<?0.01), but not with other cognitive tests. There was a significant interaction between sex and retinal vascular calibre for logical memory. In male participants, the association of increased retinal arteriolar calibre with logical memory persisted (p?<?0.05) when further adjusted for vocabulary, venular calibre, depression, cardiovascular risk factors and macrovascular disease. In female participants, this association was weaker and not significant.

CONCLUSIONS/INTERPRETATION:

Retinal arteriolar dilatation was associated with poorer memory, independent of estimated prior cognitive ability in older men with type 2 diabetes. The sex interaction with stronger findings in men requires confirmation. Nevertheless, these data suggest that impaired cerebral arteriolar autoregulation in smooth muscle cells, leading to arteriolar dilatation, may be a possible pathogenic mechanism in verbal declarative memory decrements in people with diabetes.

The effects of the Omagh bomb on adolescent mental health: a school-based study

Background: The main objective of this study was to assess psychiatric morbidity among adolescentsfollowing the Omagh car bombing in Northern Ireland in 1998.

Methods: Data was collected within schools from adolescents aged between 14 and 18 years via a selfcompletionbooklet comprised of established predictors of PTSD; type of exposure, initialemotional response, long-term adverse physical problems, predictors derived from Ehlers andClark’s (2000) cognitive model, a PTSD symptoms measure (PDS) and the General HealthQuestionnaire (GHQ).

Results:Those with more direct physical exposure were significantly more likely to meet caseness onthe GHQ and the PDS. The combined pre and peri trauma risk factors highlighted in previousmeta-analyses accounted for 20% of the variance in PDS scores but the amount of varianceaccounted for increased to 56% when the variables highlighted in Ehlers and Clark’scognitive model for PTSD were added.

Conclusions: High rates of chronic PTSD were observed in adolescents exposed to the bombing. Whilstincreased exposure was associated with increased psychiatric morbidity, the best predictors ofPTSD were specific aspects of the trauma (‘seeing someone you think is dying’), what youare thinking during the event (‘think you are going to die’) and the cognitive mechanismsemployed after the trauma. As these variables are in principle amenable to treatment theresults have implications for teams planning treatment interventions after future traumas.

Predicting the need for insulin therapy in late onset (40-69 years) diabetes mellitus

A six-year prospective study of 144 newly diagnosed, symptomatic diabetic patients aged 40-69 years showed that 21 (15%) required insulin therapy, commencing 1-61 months after diagnosis. The plasma insulin response to oral glucose was assessed at the time of diagnosis. All 12 patients with very low peak insulin response (less than or equal to 6 mU/l) required insulin therapy. Thirty-six patients had an intermediate insulin response (greater than 6 less than or equal to 18 mU/l); of these, 7 with a mean weight 88% (range 73-96%) of average body weight required insulin, while 29 with a mean weight 117% (range 98-158%) of average body weight, did not. Ninety-six patients had a peak insulin response (greater than 18 mU/l); 2 patients whose weights were 96% and 100% of average body weight, required insulin, while the remainder did not. Consideration of initial body weight and peak insulin response provides a useful prediction of the eventual need for insulin.

The effect of socioeconomic deprivation on corneal graft survival in the United Kingdom

Objective: To investigate the effect of socioeconomic deprivation on cornea graft survival in the United Kingdom.

Design: Retrospective cohort study.

Participants: All the recipients (n = 13?644) undergoing their first penetrating keratoplasty (PK) registered on the United Kingdom Transplant Registry between April 1999 and March 2011 were included.

Methods: Data of patients' demographic details, indications, graft size, corneal vascularization, surgical complication, rejection episodes, and postoperative medication were collected at the time of surgery and 1, 2, and 5 years postoperatively. Patients with endophthalmitis were excluded from the study. Patients' home postcodes were used to determine the socioeconomic status using a well-validated deprivation index in the United Kingdom: A Classification of Residential Neighborhoods (ACORN). Kaplan–Meier survival and Cox proportional hazards regression were used to evaluate the influence of ACORN categories on 5-year graft survival, and the Bonferroni method was used to adjust for multiple comparisons.

Main Outcome Measures: Patients' socioeconomic deprivation status and corneal graft failure.

Results: A total of 13?644 patients received their first PK during the study periods. A total of 1685 patients (13.36%) were lost to follow-up, leaving 11?821 patients (86.64%) for analysis. A total of 138 of the 11?821 patients (1.17%) developed endophthalmitis. The risk of graft failure within 5 years for the patients classified as hard-pressed was 1.3 times that of the least deprived (hazard ratio, 1.3; 95% confidence interval, 1.1–1.5; P = 0.003) after adjusting for confounding factors and indications. There were no statistically significant differences between the causes of graft failure and the level of deprivation (P = 0.14).

Conclusions: Patients classified as hard-pressed had an increased risk of graft failure within 5 years compared with the least deprived patients.

Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article

First steps: study protocol for a randomized controlled trial of the effectiveness of the Group Family Nurse Partnership (gFNP) program compared to routine care in improving outcomes for high-risk mothers and their children and preventing abuse

Background: Evidence from the USA suggests that the home-based Family Nurse Partnership program (FNP), extending from early pregnancy until infants are 24 months, can reduce the risk of child abuse and neglect throughout childhood. FNP is now widely available in the UK. A new variant, Group Family Nurse Partnership (gFNP) offers similar content but in a group context and for a shorter time, until infants are 12 months old. Each group comprises 8 to 12 women with similar expected delivery dates and their partners. Its implementation has been established but there is no evidence of its effectiveness.

Methods/Design: The study comprises a multi-site randomized controlled trial designed to identify the benefits of gFNP compared to standard care. Participants (not eligible for FNP) must be either aged <20 years at their last menstrual period (LMP) with one or more previous live births, or aged 20 to 24 at LMP with low educational qualifications and no previous live births. 'Low educational qualifications' is defined as not having both Maths and English Language GCSE at grade C or higher or, if they have both, no more than four in total at grade C or higher. Exclusions are: under 20 years and previously received home-based FNP and, in either age group, severe psychotic mental illness or not able to communicate in English. Consenting women are randomly allocated (minimized by site and maternal age group) when between 10 and 16 weeks pregnant to either to the 44 session gFNP program or to standard care after the collection of baseline information. Researchers are blind to group assignment. The primary outcomes at 12 months are child abuse potential based on the revised Adult-Adolescent Parenting Inventory and parent/infant interaction coded using the CARE Index based on a video-taped interaction. Secondary outcomes are maternal depression, parenting stress, health related quality of life, social support, and use of services.

Discussion: This is the first study of the effectiveness of gFNP in the UK. Results should inform decision-making about its delivery alongside universal services, potentially enabling a wider range of families to benefit from the FNP curriculum and approach to supporting parenting.

Prevalence of human papillomavirus in women attending cervical screening in the UK and Ireland:New data from northern Ireland and a systematic review and meta-analysis

There is substantial international variation in human papillomavirus (HPV) prevalence; this study details the first report from Northern Ireland and additionally provides a systematic review and meta-analysis pooling the prevalence of high-risk (HR-HPV) subtypes among women with normal cytology in the UK and Ireland. Between February and December 2009, routine liquid based cytology (LBC) samples were collected for HPV detection (Roche Cobas® 4800 [PCR]) among unselected women attending for cervical cytology testing. Four electronic databases, including MEDLINE, were then searched from their inception till April 2011. A random effects meta-analysis was used to calculate a pooled HR-HPV prevalence and associated 95% confidence intervals (CI). 5,712 women, mean age 39 years (±SD 11.9 years; range 20-64 years), were included in the analysis, of which 5,068 (88.7%), 417 (7.3%) and 72 (1.3%) had normal, low, and high-grade cytological findings, respectively. Crude HR-HPV prevalence was 13.2% (95% CI, 12.7-13.7) among women with normal cytology and increased with cytological grade. In meta-analysis the pooled HR-HPV prevalence among those with normal cytology was 0.12 (95% CIs, 0.10-0.14; 21 studies) with the highest prevalence in younger women. HPV 16 and HPV 18 specific estimates were 0.03 (95% CI, 0.02-0.05) and 0.01 (95% CI, 0.01-0.02), respectively. The findings of this Northern Ireland study and meta-analysis verify the prevalent nature of HPV infection among younger women. Reporting of the type-specific prevalence of HPV infection is relevant for evaluating the impact of future HPV immunization initiatives, particularly against HR-HPV types other than HPV 16 and 18. J. Med. Virol. 85:295-308, 2013. © 2012 Wiley Periodicals, Inc. Copyright © 2012 Wiley Periodicals, Inc.

Early Holocene M similar to 6 explosive eruption from Plosky volcanic massif (Kamchatka) and its tephra as a link between terrestrial and marine paleoenvironmental records

We report tephrochronological and geochemical data on early Holocene activity from Plosky volcanic massif in the Kliuchevskoi volcanic group, Kamchatka Peninsula. Explosive activity of this volcano lasted for similar to 1.5 kyr, produced a series of widely dispersed tephra layers, and was followed by profuse low-viscosity lava flows. This eruptive episode started a major reorganization of the volcanic structures in the western part of the Kliuchevskoi volcanic group. An explosive eruption from Plosky (M similar to 6), previously unstudied, produced tephra (coded PL2) of a volume of 10-12 km(3) (11-13 Gt), being one of the largest Holocene explosive eruptions in Kamchatka. Characteristic diagnostic features of the PL2 tephra are predominantly vitric sponge-shaped fragments with rare phenocrysts and microlites of plagioclase, olivine and pyroxenes, medium- to high-K basaltic andesitic bulk composition, high-K, high-Al and high-P trachyandesitic glass composition with SiO2 = 57.5-59.5 wt%, K2O = 2.3-2.7 wt%, Al2O3 = 15.8-16.5 wt%, and P2O5 = 0.5-0.7 wt%. Other diagnostic features include a typical subduction-related pattern of incompatible elements, high concentrations of all REE (> 10x mantle values), moderate enrichment in LREE (La/Yb similar to 5.3), and non-fractionated mantle-like pattern of LILE. Geochemical fingerprinting of the PL2 tephra with the help of EMP and LA-ICP-MS analyses allowed us to map its occurrence in terrestrial sections across Kamchatka and to identify this layer in Bering Sea sediment cores at a distance of > 600 km from the source. New high-precision C-14 dates suggest that the PL2 eruption occurred similar to 10,200 cal BP, which makes it a valuable isochrone for early Holocene climate fluctuations and permits direct links between terrestrial and marine paleoenvironmental records. The terrestrial and marine C-14 dates related to the PL2 tephra have allowed us to estimate an early Holocene reservoir age for the western Bering Sea at 1,410 +/- A 64 C-14 years. Another important tephra from the early Holocene eruptive episode of Plosky volcano, coded PL1, was dated at 11,650 cal BP. This marker is the oldest geochemically characterized and dated tephra marker layer in Kamchatka to date and is an important local marker for the Younger Dryas-early Holocene transition. One more tephra from Plosky, coded PL3, can be used as a marker northeast of the source at a distance of similar to 110 km.

Examining the Neurocognitive Validity of Commercially Available, Smartphone-Based Puzzle Games

Cognitive assessment typically involves assessing a person’s cognitive performance in unfamiliar and ar-guably unnatural clinical surroundings. User-centred approaches to assessment and monitoring, driven by issues such as enjoyability and familiarity, are largely absent. Everyday technologies, for example, smartphones represent an opportunity to obtain an objective assessment of a person’s cognitive capabili-ties in a non-threatening, discreet and familiar way, e.g. by everyday puzzle games undertaken as a leisure activity at home. We examined the strength of relationships that exist between performance on common puzzle games and standard measures of neuropsychological performance. Twenty-nine participants, aged 50 - 65 years, completed a comprehensive neuropsychological test battery and played three smart-phone-based puzzle games in triplicate: a picture puzzle [Matches Plus], a word puzzle [Jumbline] and a number puzzle [Sudoku]. As anticipated, a priori, significant correlations were observed between scores on a picture puzzle and visual memory test (r = 0.49; p = 0.007); a word puzzle and estimated verbal IQ (r = 0.53; p = 0.003) and verbal learning (r = 0.30; p = 0.039) tests; and a number puzzle and reason-ing/problem solving test (r = 0.42; p = 0.023). Further analyses making allowance for multiple compari-sons identified a significant unanticipated correlation (r = 0.49; p = 0.007) between number puzzle scores and a measure of nonverbal working memory. Performance on these smartphone-based games was in-dicative of relative cognitive ability across several cognitive domains at a fixed time point. Smart-phone-based, everyday puzzle games may offer a valid, portable measure of assessing and monitoring cognition in older adults.

Effects of continuing professional development on group work practices in Scottish primary schools

The present study investigated the effects of a continuing professional development (CPD) initiative that provided collaborative group work skills training for primary school teachers. The study collected data from 24 primary school classrooms in different schools in a variety of urban and rural settings. The sample was composed of 332 pupils, aged 9-12 years old, and 24 primary school teachers. Results indicated that the CPD initiative had a significant impact on the attainment of pupils in science. In addition, data indicated that the CPD promoted effective discourse and pupil dialogue during science lessons. Pre-test and post-test observation scores were significantly different in terms of children giving of suggestions or courses of actions, offering of explanations, and telling someone to say something or carry out an action. Increases in effective dialogue were significantly correlated to increased science attainment, and teacher evaluations of the impact of the CPD were positive. Significant correlations were found between teacher evaluation of impact upon pupil learning and increased attainment in science. The design and structure of CPD initiatives and the implications for practice, policy and future research are explored.