[Show abstract][Hide abstract] ABSTRACT: Background
The month of diagnosis in childhood type 1 diabetes shows seasonal variation.Objective
We describe the pattern and investigate if year-to-year irregularities are associated with meteorological factors using data from 50 000 children diagnosed under the age of 15 yr in 23 population-based European registries during 1989–2008.Methods
Tests for seasonal variation in monthly counts aggregated over the 20 yr period were performed. Time series regression was used to investigate if sunshine hour and average temperature data were predictive of the 240 monthly diagnosis counts after taking account of seasonality and long term trends.ResultsSignificant sinusoidal pattern was evident in all but two small centers with peaks in November to February and relative amplitudes ranging from ±11 to ±38% (median ±17%). However, most centers showed significant departures from a sinusoidal pattern. Pooling results over centers, there was significant seasonal variation in each age-group at diagnosis, with least seasonal variation in those under 5 yr. Boys showed greater seasonal variation than girls, particularly those aged 10–14 yr. There were no differences in seasonal pattern between four 5-yr sub-periods. Departures from the sinusoidal trend in monthly diagnoses in the period were significantly associated with deviations from the norm in average temperature (0.8% reduction in diagnoses per 1 °C excess) but not with sunshine hours.Conclusions
Seasonality was consistently apparent throughout the period in all age-groups and both sexes, but girls and the under 5 s showed less marked variation. Neither sunshine hour nor average temperature data contributed in any substantial way to explaining departures from the sinusoidal pattern.
[Show abstract][Hide abstract] ABSTRACT: Increased newborn adiposity is associated with later adverse metabolic outcomes. Previous genome-wide association studies (GWAS) demonstrated strong association of a locus on chromosome 3 (3q25.31) with newborn sum of skinfolds, a measure of overall adiposity. Whether this locus is associated with childhood adiposity is unknown. Genotype and sum of skinfolds data were available for 293 children at birth and age 2, and for 350 children at birth and age 6 from a European cohort (Belfast, UK) who participated in the Hyperglycemia and Adverse Pregnancy Outcome GWAS. We examined single nucleotide polymorphisms (SNPs) at the 3q25.31 locus associated with newborn adiposity. Linear regression analyses under an additive genetic model adjusting for maternal body mass index were performed. In both cohorts, a positive association was observed between all SNPs and sum of skinfolds at birth (P=2.3 × 10(-4), β=0.026 and P=4.8 × 10(-4), β=0.025). At the age of 2 years, a non-significant negative association was observed with sum of skinfolds (P=0.06; β =-0.015). At the age of 6 years, there was no evidence of association (P=0.86; β=0.002). The 3q25.31 locus strongly associated with newborn adiposity had no significant association with childhood adiposity suggesting that its impact may largely be limited to fetal fat accretion.
[Show abstract][Hide abstract] ABSTRACT: Objective:
To investigate associations between known periodontal disease pathogens and increased levels of systemic inflammation measured by C-reactive protein (CRP).
A representative sample of dentate 60-70 year-old men in Northern Ireland had a comprehensive periodontal examination. Men taking statins were excluded. Subgingival plaque samples were analysed by quantitative real time PCR to identify and quantify the presence of Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Treponema denticola (Td), and Tannerella forsythia (Tf). High-sensitivity CRP was measured from fasting blood samples. Multiple linear regression analysis was completed with log transformed CRP concentration as the outcome variable and the presence of the bacterial pathogens as predictor variables with adjustment for various confounders.
A total of 511 men (Mean age 63.6 SD 3.0 years) were included in the analysis. Aa was identified in 22.1% of the cohort, whereas Td and Tf were identified in 90.8% and 90.7% respectively. Pg was present in 45.2% and in these cases the relative % abundance was low (median <0.00001%, IQR=0.096). Linear regression showed a significant association between the presence of Pg and increasing CRP concentration (p=0.005). Multivariate analysis showed that body mass index (p<0.001), smoking (p=0.006), hypertension (p=0.013), and presence of Pg (p=0.016) were independent predictors of CRP. There were no associations between the presence of other bacteria and CRP.
There was evidence in the 60-70 year-old dentate men investigated that the presence of Porphyromonas gingivalis in subgingival plaque (even at a relatively low abundance) significantly associated with a raised level of C-reactive protein.
[Show abstract][Hide abstract] ABSTRACT: Introduction: The chromosome 9p21 locus has been identified as a marker of coronary artery disease. In this locus studies have focused on variations in the ANRIL gene that has also been identified as a strong candidate for association with aggressive periodontitis (AgP).
Objective: To investigate possible associations between gene variants of ANRIL and AgP in European and African populations.
Methods: European AgP cases (n= 213) and age-matched periodontally healthy controls (n= 81) were recruited from centres in the United Kingdom (Belfast, Glasgow, Newcastle and London). African AgP cases (n= 95) and controls (n= 105) were recruited in Khartoum, Sudan. Five single nucleotide polymorphisms (SNPs) in ANRIL were genotyped using Sequenom and analysed using Haploview with permutation testing to correct for multiple candidates. Odds ratios (OR) and 95% confidence intervals (95%CI) were calculated.
Results: In the European subjects there was a significant association between rs518394 (p=0.0013; OR = 1.81, 95%CI 1.26-2.61) and rs1333049 (p=0.0028; OR = 1.75, 95%CI 1.21-2.52) and AgP. These associations remained significant after permutation testing. In addition there was an association between rs 1360590 (p=0.035) and AgP in females. In the African subjects there was a significant association between only one SNP rs1537415 and AgP (p=0.036; OR = 1.59, 95%CI 1.04-2.43), however, this was not significant following permutation testing. There were no significant associations with rs3217992 in either population.
Conclusions: SNP variants in the ANRIL locus were shown to be significantly associated with AgP in a European population and for the first time in an African population confirming this as the best replicated locus for aggressive periodontitis.
[Show abstract][Hide abstract] ABSTRACT: Severe refractory asthma poses a substantial burden in terms of healthcare costs but relatively little is known about the factors which drive these costs. This study uses data from the British Thoracic Society Difficult Asthma Registry (n=596) to estimate direct healthcare treatment costs from an National Health Service perspective and examines factors that explain variations in costs. Annual mean treatment costs among severe refractory asthma patients were £2912 (SD £2212) to £4217 (SD £2449). Significant predictors of costs were FEV1% predicted, location of care, maintenance oral corticosteroid treatment and body mass index. Treating individuals with severe refractory asthma presents a substantial cost to the health service.
[Show abstract][Hide abstract] ABSTRACT: Rationale
Daily low dose oral corticosteroids (OCS) are an effective anti-inflammatory drug in refractory asthma but can be associated with
significant side-effects. There is clear evidence to show adverse events in other clinical populations, but little data is available in severe
refractory asthma. This issue is important in defining the potential benefits of novel biologic steroid-sparing therapies. We wished to
examine the adverse effects of regular daily OCS use compared to frequent rescues courses in a severe asthma population using data from
the BTS Difficult Asthma Registry.
Cross sectional analysis of patients from the BTS Difficult Asthma Registry attending 7 UK Specialist Difficult Asthma Centres following
detailed systematic assessment, was performed to evaluate the prevalence of steroid-related morbidities in patients prescribed daily OCS
compared to prevalence rates in patients with severe asthma who did not receive daily OCS and/or infrequent rescue courses of OCS.
We examined 771 patients with severe asthma (mean age 50±15 years, 65% females, 90% Caucasian). Of these 443 patients were receiving
high dose inhaled steroids (median BDP equivalent daily dose 2000μg[range1600-2000μg]) plus daily maintenance OCS (median daily
dose of prednisolone 15mg [10-20mg]) as well as frequent rescue OCS courses in the previous 12 months (median 5[range 2-8]). 328
patients were on high dose inhaled steroids (median BDP equivalent daily dose 2000μg[range1000-2000μg]), were not prescribed
maintenance OCS but received frequent rescue courses in the previous 12 months (median 4 [range 1-6]). High prevalence rates for
conditions associated with systemic steroid exposure were identified (Table 1) and were statistically significantly higher than prevalence
rates compared to patients taking frequent rescue courses of OCS only.
Severe asthmatics receiving maintenance OCS have significantly higher prevalence rates of OCS related morbidity compared to severe
asthma patients receiving rescue courses of OCS only. The lifetime healthcare cost associated with progression to regular OCS treatment is
likely to be significant and warrants further investigation.
This abstract is funded by: GSK, HSC R&D
Am J Respir Crit Care Med 189;2014:A2426
Internet address: www.atsjournals.org Online Abstracts Issue
Cardiovascular disease 6%[4-9%] 8%[5-11%] ns
Cataracts 6%[4-8%] 0%[0-1%] p<0.001
Glaucoma 2%[1-4%] 2[1-4%] ns
3%[1-5%] 0.3%[0-2%] p<0.05
[Show abstract][Hide abstract] ABSTRACT: Asthma management guidelines advocate a stepwise approach to asthma therapy, including the addition of a long-acting bronchodilator to inhaled steroid therapy at step 3. This is almost exclusively prescribed as inhaled combination therapy.
To examine whether asthma prescribing practice for inhaled combination therapy (inhaled corticosteroid/long-acting β2-agonist (ICS/LABA)) in primary care in Northern Ireland is in line with national asthma management guidelines.
Using data from the Northern Ireland Enhanced Prescribing Database, we examined initiation of ICS/LABA in subjects aged 5-35 years in 2010.
A total of 2,640 subjects (67%) had no inhaled corticosteroid monotherapy (ICS) in the study year or six months of the preceding year (lead-in period) and, extending this to a 12-month lead-in period, 52% had no prior ICS. 41% of first prescriptions for ICS/LABA were dispensed in January to March. Prior to ICS/LABA prescription, in the previous six months only 17% had a short-acting β2-agonist (SABA) dispensed, 5% received oral steroids, and 17% received an antibiotic.
ICS/LABA therapy was initiated in the majority of young subjects with asthma without prior inhaled steroid therapy. Most prescriptions were initiated in the January to March period. However, the prescribing of ICS/LABA did not appear to be driven by asthma symptoms (17% received SABA in the previous 6 months) or severe asthma exacerbation (only 5% received oral steroids). Significant reductions in ICS/LABA, with associated cost savings, would occur if the asthma prescribing guidelines were followed in primary care.
Primary care respiratory journal: journal of the General Practice Airways Group 02/2014; 23(1). DOI:10.4104/pcrj.2014.00007
[Show abstract][Hide abstract] ABSTRACT: This paper describes the methodology, results and limitations of the 2013 International Diabetes Federation (IDF) Atlas (6th edition) estimates of the worldwide numbers of prevalent cases of type 1 diabetes in children (<15 years). The majority of relevant information in the published literature is in the form of incidence rates derived from registers of newly diagnosed cases. Studies were graded on quality criteria and, if no information was available in the published literature, extrapolation was used to assign a country the rate from an adjacent country with similar characteristics. Prevalence rates were then derived from these incidence rates and applied to United Nations 2012 Revision population estimates for 2013 for each country to obtain estimates of the number of prevalent cases. Data availability was highest for the countries in Europe (76%) and lowest for the countries in sub-Saharan Africa (8%). The prevalence estimates indicate that there are almost 500,000 children aged under 15 years with type 1 diabetes worldwide, the largest numbers being in Europe (129,000) and North America (108,700). Countries with the highest estimated numbers of new cases annually were the United States (13,000), India (10,900) and Brazil (5000). Compared with the prevalence estimates made in previous editions of the IDF Diabetes Atlas, the numbers have increased in most of the IDF Regions, often reflecting the incidence rate increases that have been well-documented in many countries. Monogenic diabetes is increasingly being recognised among those with clinical features of type 1 or type 2 diabetes as genetic studies become available, but population-based data on incidence and prevalence show wide variation due to lack of standardisation in the studies. Similarly, studies on type 2 diabetes in childhood suggest increased incidence and prevalence in many countries, especially in Indigenous peoples and ethnic minorities, but detailed population-based studies remain limited.
Diabetes research and clinical practice 12/2013; 103(2). DOI:10.1016/j.diabres.2013.11.005 · 2.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE
The purpose of this randomized controlled trial was to investigate the dose-response effect of fruit and vegetable (F&V) intake on insulin resistance (IR) in people who are overweight and at high risk of cardiovascular disease (CVD).RESEARCH DESIGN AND METHODSA total of 105 participants (mean age 56 years) followed a 4-week washout diet (one to two portions of F&Vs per day). Ninety-two participants completed the washout and were randomized to receive one to two, four, or seven portions of F&Vs per day for 12 weeks. IR was assessed at the start and end of this 12-week period by the two-step euglycemic-hyperinsulinemic clamp. Compliance was monitored using a combination of 4-day food diaries and plasma biomarkers of F&V intake.RESULTSA total of 89 participants completed the study. Participants attained self-reported F&V intakes of 1.8, 3.8, and 7.0 portions per day (P < 0.001) per group. There was a significant linear increase in serum lutein status across the groups, indicating good compliance (P < 0.001), and body weight was maintained (P = 0.77). No significant difference was found between groups in terms of a change in measures of whole-body, peripheral, or hepatic IR or adiponectin multimers.CONCLUSIONS
Increased consumption of F&Vs, as advocated in public-health advice, has no effect on IR in overweight individuals who are at high risk of CVD when body weight is maintained. Recent evidence from systematic reviews indicates that particular classes or types of F&Vs may have particular antidiabetic properties; hence, it is possible that benefits may only be observed in response to a more specific fruit or vegetable intervention.
Diabetes care 10/2013; 36(12). DOI:10.2337/dc13-0718 · 8.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate whether young people with Type 1 diabetes have an increased rate of depression and antidepressant use and whether their risk varies by age group, time from diabetes diagnosis, calendar period of diagnosis or complications status.
A cohort of incident cases of patients with Type 1 diabetes diagnosed before 35 years of age (n = 5548) was identified within the Clinical Practice Research Datalink and individually age and sex matched with up to two control subjects without diabetes (n = 10 657). Patients with depression were identified through general practice-recorded depression codes and antidepressant prescriptions. Cox regression models gave hazard ratios for depression in people with Type 1 diabetes compared with control subjects.
People with Type 1 diabetes were twice as likely to have a record of antidepressant use and general practice-diagnosed depression as their matched control subjects (hazard ratio 2.08, 95% CI 1.73-2.50, P < 0.001). These associations varied by time from diagnosis, with marked increases observed within the first 5 years of diagnosis (hazard ratio 2.14, 95% CI 1.51-3.03, P < 0.001), and by age at diabetes diagnosis, with excesses noted even in the 10- to 19-year age group (hazard ratio 1.45, 95% CI 1.06-1.98, P = 0.02).
This population-based study shows that people with Type 1 diabetes have higher rates of general practice-recorded depression and antidepressant use. The excess is present within 5 years of diabetes diagnosis, suggesting psychological input for patients is warranted in the early years of their condition. This article is protected by copyright. All rights reserved.
Diabetic Medicine 09/2013; 31(2). DOI:10.1111/dme.12330 · 3.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We investigated the prevalence of chronic kidney disease and attainment of therapeutic targets for HbA1c and blood pressure in a large UK-based diabetes population.
The UK National Diabetes Audit provided data from 1 January 2007 to 31 March 2008. Inclusion criteria were a documented urinary albumin:creatinine ratio and serum creatinine. Patients were stratified according to chronic kidney disease stage and albuminuria status. Chronic kidney disease was defined as an estimated glomerular filtration rate < 60 ml min(-1) 1.73 m(-2) , albuminuria or both. The proportions of patients achieving nationally defined glycaemic and systolic blood pressure targets were determined.
The cohort comprised 1 423 669 patients, of whom 868 616 (61%) met inclusion criteria. Of the patients analysed, 92.2% had Type 2 diabetes. A higher proportion of people with Type 2 diabetes (42.3%) had renal dysfunction compared with those with Type 1 diabetes (32.4%). Achievement of systolic blood pressure and HbA1c targets was poor. Among people with Type 1 diabetes, 67.8% failed to achieve an HbA1c < 58 mmol/mol (7.5%). Of all people with diabetes, 37.8% failed to achieve a systolic blood pressure < 140 mmHg. Blood pressure control was poor in advanced chronic kidney disease. For example, mean (standard deviation) systolic blood pressure rose from 128.6 (15.4) mmHg among people with Type 1 diabetes and normal renal function to 141.0 (23.6) mmHg in those with chronic kidney disease stage 5 and macroalbuminuria.
The high prevalence of chronic kidney disease and poor attainment of treatment targets highlights a large subset of the diabetes population at increased risk of cardiovascular mortality or progressive kidney disease.
Diabetic Medicine 09/2013; 31(4). DOI:10.1111/dme.12312 · 3.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective
The phenotype of the antioxidant and pro-angiogenic protein haptoglobin (Hp) predicts cardiovascular disease risk and treatment response to antioxidant vitamins in individuals with diabetes. Our objective was to determine whether Hp phenotype influences pre-eclampsia risk, or the efficacy of vitamins C and E in preventing pre-eclampsia, in women with type-1 diabetes. DesignThis is a secondary analysis of a randomised controlled trial in which women with diabetes received daily vitamins C and E, or placebo, from 8 to 22 weeks of gestation until delivery. SettingTwenty-five antenatal metabolic clinics across the UK (in north-west England, Scotland, and Northern Ireland). PopulationPregnant women with type-1 diabetes. Methods
Hp phenotype was determined in white women who completed the study and had plasma samples available (n = 685). Main outcome measurePre-eclampsia. ResultsCompared with Hp 2-1, Hp 1-1 (OR 0.59, 95% CI 0.30–1.16) and Hp 2-2 (OR 0.93, 95% CI 0.60–1.45) were not associated with significantly decreased pre-eclampsia risk after adjusting for treatment group and HbA1c at randomisation. Our study was not powered to detect an interaction between Hp phenotype and treatment response; however, our preliminary analysis suggests that vitamins C and E did not prevent pre-eclampsia in women of any Hp phenotype (Hp 1-1, OR 0.77, 95% CI 0.22–2.71; Hp 2-1, OR 0.81, 95% CI 0.46–1.43; Hp 2-2, 0.67, 95% CI 0.34–1.33), after adjusting for HbA1c at randomisation. Conclusions
The Hp phenotype did not significantly affect pre-eclampsia risk in women with type-1 diabetes.
BJOG An International Journal of Obstetrics & Gynaecology 09/2013; 120(10). DOI:10.1111/1471-0528.12288 · 3.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: More infants with bronchopulmonary dysplasia (BPD) now survive to adulthood but little is known regarding persisting respiratory impairment. We report respiratory symptoms, lung function and health-related quality of life (HRQoL) in adult BPD survivors compared with preterm (non-BPD) and full term (FT) controls.Respiratory symptoms (European Community Respiratory Health Survey) and HRQoL [EuroQol 5D (EQ-5D)] were measured in 72 adult BPD survivors [mean(SD) study age 24.1(4.0)y; mean(SD) gestational age (GA)=27.1(2.1)wk; mean(SD) birth weight (BW)=955(256)g] cared for in the Regional Neonatal Intensive Care Unit, Belfast (between 1978 and 1993) were compared with 57 non-BPD controls [mean(SD) study age 25.3(4.0)y; mean(SD) GA 31.0(2.5)wk; mean(SD) BW 1238(222)g] and 78 FT controls [mean(SD) study age 25.7(3.8)y; mean(SD) GA=39.7(1.4)wk; mean(SD) BW=3514(456)g] cared for at the same hospital. Spirometry was performed on 56 BPD, 40 non-BPD and 55 FT participants.BPD subjects were twice as likely to report wheeze and three times more likely to use asthma medication than controls. BPD adults had significantly lower FEV1 and FEF25-75 than both the preterm non-BPD and FT controls (all p<0.01). Mean EQ-5D was 6 points lower in BPD adults compared to FT controls (p<0.05).BPD survivors have significant respiratory and quality of life impairment persisting into adulthood.
European Respiratory Journal 07/2013; 43(3). DOI:10.1183/09031936.00039513 · 7.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Previous research demonstrates various associations between depression, cardiovascular disease (CVD) incidence and mortality, possibly as a result of the different methodologies used to measure depression and analyse relationships. This analysis investigated the association between depression, CVD incidence (CVDI) and mortality from CVD (MCVD), smoking related conditions (MSRC), and all causes (MALL), in a sample data set, where depression was measured using items from a validated questionnaire and using items derived from the factor analysis of a larger questionnaire, and analyses were conducted based on continuous data and grouped data.
Data from the PRIME Study (N=9798 men) on depression and 10-year CVD incidence and mortality were analysed using Cox proportional hazards models.
Using continuous data, both measures of depression resulted in the emergence of positive associations between depression and mortality (MCVD, MSRC, MALL). Using grouped data, however, associations between a validated measure of depression and MCVD, and between a measure of depression derived from factor analysis and all measures of mortality were lost.
Low levels of depression, low numbers of individuals with high depression and low numbers of outcome events may limit these analyses, but levels are usual for the population studied.
These data demonstrate a possible association between depression and mortality but detecting this association is dependent on the measurement used and method of analysis. Different findings based on methodology present clear problems for the elucidation and determination of relationships. The differences here argue for the use of validated scales where possible and suggest against over-reduction via factor analysis and grouping.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Taking antiobesity medication can be a cost effective way to lose weight. Uptake is determined in part by a General Practitioner's decision to prescribe weight loss medication and, in part, by patient preference. It is probable that the latter may indicate a patient's readiness to lose weight. METHODS: Analysis of cross-sectional data (from February 2003 to March 2011) from a population based prescribing database (∼1.75 million people) using an adjusted Poisson regression. RESULTS: The number of antiobesity medications increased from 23.4 per 1000 population in 2004 to 30.7 per 1000 population in 2010 and was three times higher in female than in male subjects. Against this background, a marked seasonal variation in the number of antiobesity medications dispensed was evident (p<0.001), peaking in June/July with a trough in December/January (±8.0% peak to trough). The seasonal component was stronger in female subjects, ±11.2% peak to trough, compared with ±3.5% for male subjects. CONCLUSIONS: Obese patients, particularly women, increase their uptake of weight loss medication in the months leading up to the summer holiday period. The period prior to the summer may represent a time that health professionals could promote increased participation of obese patients in weight loss programmes.
Journal of epidemiology and community health 01/2013; 67(6). DOI:10.1136/jech-2012-201995 · 3.29 Impact Factor