[Show abstract][Hide abstract] ABSTRACT: Aims/hypothesis:
The aim of this study was to investigate the association between routine vaccinations and the risk of childhood type 1 diabetes mellitus by systematically reviewing the published literature and performing meta-analyses where possible.
A comprehensive literature search was performed of MEDLINE and EMBASE to identify all studies that compared vaccination rates in children who subsequently developed type 1 diabetes mellitus and in control children. ORs and 95% CIs were obtained from published reports or derived from individual patient data and then combined using a random effects meta-analysis.
In total, 23 studies investigating 16 vaccinations met the inclusion criteria. Eleven of these contributed to meta-analyses which included data from between 359 and 11,828 childhood diabetes cases. Overall, there was no evidence to suggest an association between any of the childhood vaccinations investigated and type 1 diabetes mellitus. The pooled ORs ranged from 0.58 (95% CI 0.24, 1.40) for the measles, mumps and rubella (MMR) vaccination in five studies up to 1.04 (95% CI 0.94, 1.14) for the haemophilus influenza B (HiB) vaccination in 11 studies. Significant heterogeneity was present in most of the pooled analyses, but was markedly reduced when analyses were restricted to study reports with high methodology quality scores. Neither this restriction by quality nor the original authors' adjustments for potential confounding made a substantial difference to the pooled ORs.
This study provides no evidence of an association between routine vaccinations and childhood type 1 diabetes.
[Show abstract][Hide abstract] ABSTRACT: Objective To determine the prevalence of systemic corticosteroid-induced morbidity in severe asthma.
Design Cross-sectional observational study.
Setting The primary care Optimum Patient Care Research Database and the British Thoracic Society Difficult Asthma Registry.
Participants Optimum Patient Care Research Database (7195 subjects in three age- and gender-matched groups)—severe asthma (Global Initiative for Asthma (GINA) treatment step 5 with four or more prescriptions/year of oral corticosteroids, n=808), mild/moderate asthma (GINA treatment step 2/3, n=3975) and non-asthma controls (n=2412). 770 subjects with severe asthma from the British Thoracic Society Difficult Asthma Registry (442 receiving daily oral corticosteroids to maintain disease control).
Main outcome measures Prevalence rates of morbidities associated with systemic steroid exposure were evaluated and reported separately for each group.
Results 748/808 (93%) subjects with severe asthma had one or more condition linked to systemic corticosteroid exposure (mild/moderate asthma 3109/3975 (78%), non-asthma controls 1548/2412 (64%); p<0.001 for severe asthma versus non-asthma controls). Compared with mild/moderate asthma, morbidity rates for severe asthma were significantly higher for conditions associated with systemic steroid exposure (type II diabetes 10% vs 7%, OR=1.46 (95% CI 1.11 to 1.91), p<0.01; osteoporosis 16% vs 4%, OR=5.23, (95% CI 3.97 to 6.89), p<0.001; dyspeptic disorders (including gastric/duodenal ulceration) 65% vs 34%, OR=3.99, (95% CI 3.37 to 4.72), p<0.001; cataracts 9% vs 5%, OR=1.89, (95% CI 1.39 to 2.56), p<0.001). In the British Thoracic Society Difficult Asthma Registry similar prevalence rates were found, although, additionally, high rates of osteopenia (35%) and obstructive sleep apnoea (11%) were identified.
Conclusions Oral corticosteroid-related adverse events are common in severe asthma. New treatments which reduce exposure to oral corticosteroids may reduce the prevalence of these conditions and this should be considered in cost-effectiveness analyses of these new treatments.
[Show abstract][Hide abstract] ABSTRACT: Retinal vessel abnormalities are associated with cardiovascular disease (CVD) risk. To date, there are no trials investigating the effect of dietary factors on the retinal microvasculature. This study examined the dose response effect of fruit and vegetable (FV) intake on retinal vessel caliber in overweight adults at high CVD risk.
[Show abstract][Hide abstract] ABSTRACT: Objectives: Mendelian randomization (MR) uses a genetic variant which is associated with an exposure as an instrumental variable to determine whether the exposure is causally related to an outcome. MR exploits the random assignment of genes as a means of reducing confounding in examining exposure-outcome associations. The aim was to investigate whether abdominal adiposity (waist circumference) is causally related to periodontitis in a group of 60-70 year old men.
Methods: The study was based on 1271 dentate men in Northern Ireland who had a comprehensive periodontal examination and provided a DNA sample. The adiposity-associated variant rs17782313 in MC4R
(melanocortin-4 receptor) was used as an instrumental variable for waist circumference in a MR design. Periodontitis was classified by mean clinical attachment level (CAL). Age and smoking adjusted regression analysis was used to test for associations.
Results: There was an association between variants in rs17782313 and waist circumference (P trend=0.02). After adjustment for age and smoking each extra C allele was associated with a 1.2 (95% confidence interval 0.3 to 2.1) cm increase in waist circumference, P=0.01. Abdominal adiposity was significantly associated with CAL, P=0.007: each 1 cm increase in WC was associated with 0.01 (95% CI 0.00 to 0.02) mm increase in CAL. However, when the instrumental variable was applied to investigate the effect of WC on CAL the association was not significant, P=0.44: each 1 cm increase in WC mediated through genotype was associated with -0.04 (95% CI -0.14 to 0.06) mm increase in CAL.
Conclusions: Mendelian randomisation did not support a causal relationship between abdominal adiposity and periodontitis via the instrumental variable method applied.
[Show abstract][Hide abstract] ABSTRACT: Objectives: Whilst an association between periodontitis and obesity has been described, a possible association between subgingival periodontal pathogens and obesity is less clear. This study investigated associations between the presence of periodontal disease pathogens and various measures of adiposity in a group of 60-70 year old men.
Methods: A cross-sectional analysis was performed on 642 dentate men enrolled on a longitudinal study of cardiovascular disease in Northern Ireland. A comprehensive periodontal examination, including subgingival plaque sampling, was performed. Body mass index, waist circumference, waist-to-height ratio and waist-to-hip ratio were analysed as dependent outcome variables in multiple linear regression models. The detectable presence of four subgingival periodontal pathogens (Aggregatibacter Actinomycetemcomitans,
Porphyromonas gingivalis, Treponema denticola, and Tannerella Forsythia) at different detection thresholds were entered as predictive variables with adjustment for the various confounders.
Results: The mean age of the men studied was 63.7 (SD 3.0) years. Of the 642 men, 347 (54%) were classified as being overweight (BMI 25-29.9 kg/m2), and 144 (22.4%) as obese (BMI ≥30 kg/m2). At a detection threshold of 1x10^3 bacteria, the mean BMI of the 178 men that had Porphyromonas gingivalis was 28.0 (SD 3.6) kg/m2 compared to 27.3 (SD 3.6) kg/m2 for men that did not, p=0.03. Multiple linear regression analysis showed the
detectable presence of Porphyromonas gingivalis was significantly associated with an increased BMI
p=0.03, waist circumference p=0.04, and waist-to-height ratio p=0.02, after adjustment for age, CRP, smoking, socio-economic status, cholesterol and diabetes. There were no associations between the presence of the other bacteria and measures of adiposity.
Conclusions: In these 60-70 year old dentate men, the presence of Porphyromonas gingivalis in subgingival plaque was significantly associated with an increased BMI, waist circumference, and waist-to-height ratio after adjustment for known confounders.
[Show abstract][Hide abstract] ABSTRACT: Aim:
To investigate the association between periodontal disease, periodontal pathogens and incident diabetes in a homogeneous group of 60–70 year old Western European men.
Material and Methods:
A representative sample of dentate males in Northern Ireland underwent a detailed periodontal examination between 2001 and 2003. Examination included subgingival plaque sampling, which was subsequently analysed
by quantitative real time PCR, to determine presence of periodontal pathogens. Men were followed up by annual questionnaire and for those reporting diabetes their practitioner was contacted to validate diabetes type, treatment and diagnosis date. Cox proportional hazard models were used to estimate the effect
of periodontitis and the presence of the various periodontal pathogens on incident diabetes. Multivariate analysis included adjustment for age, smoking, hypertension, BMI, baseline cholesterol level, baseline C-reactive protein level, marital status and socioeconomic status.
A total of 496 men (Mean age 63.5 SD 3.0 years) were included in the analysis. 37 cases (7.5%) of incident diabetes were identified and 49 men (9.9%) died during follow up. The median follow up period was 9.3 years. Multivariate effect estimation through Cox proportional hazard models showed that low threshold periodontitis was significantly associated with an increased risk of diabetes HR=2.23, 95% CI=1.07–4.62, p=0.03. The effect of high threshold periodontitis was not significant HR=1.85, 95% CI=0.63–5.48, p=0.26. There were
no notable associations between presence of periodontal pathogens and incident diabetes.
There was evidence in this homogeneous group of dentate 60–70 year old men that low threshold periodontal disease was significantly associated with an increased risk of incident diabetes.
[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.
Full-text · Article · Oct 2014 · Pediatric Diabetes
[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