Clinical utility of ultrasonography-measured visceral adipose tissue depth as a tool in early pregnancy screening for gestational diabetes: a proof-of-concept study.

AIM: To examine, in a proof-of-concept study, the ability of visceral adipose tissue depth and subcutaneous fat depth measured in early pregnancy to predict subsequent gestational diabetes, and to assess the performance of these measures as screening tests for gestational diabetes compared with use of the current UK criteria. METHODS: A total of 100 women in early pregnancy were recruited from a maternity hospital in Belfast, UK. Visceral adipose tissue depth and subcutaneous fat depth were measured, and each participant underwent a 75-g oral glucose tolerance test at 28 weeks' gestation for the diagnosis of gestational diabetes using WHO 2013 criteria. RESULTS: Eighty women completed the study, of whom 15 (19%) developed gestational diabetes. Increasing visceral adipose tissue depth, but not subcutaneous fat depth, was associated with greater gestational diabetes risk after adjusting for confounding factors (odds ratio for a 1-sd rise 2.09, 95% CI 1.06-4.12; P=0.03). Visceral adipose tissue depth ≥4.27 cm had greater sensitivity compared with current National Institute of Health and Care Excellence criteria (87% vs 40%, respectively; P=0.02) and similar specificity (62% vs 74%, respectively; P=0.15) for identifying gestational diabetes. CONCLUSIONS: Ultrasonography-measured visceral adipose tissue in early pregnancy is a potential clinical tool for improving sensitivity of selective screening for gestational diabetes, which, compared with universal oral glucose tolerance testing, is likely to reduce by half the numbers requiring this test. Further larger studies are now required for confirmation, including investigation into impact on clinical outcomes.

Development of a Core Outcome Set for studies evaluating the effects of anaesthesia on perioperative morbidity and mortality following hip fracture surgery.

BACKGROUND: Perioperative studies of patients following hip fracture have large heterogeneity within their reported outcomes. This study aimed to develop a core outcome set for use in perioperative studies comparing the types of anaesthesia for hip fracture surgery. METHODS: The consensus process consisted of a systematic review of the literature, three rounds of a Delphi survey, two consensus webinars, and face-to-face patient meetings. RESULTS: The Delphi participants represented nine stakeholder groups. The numbers of participants completing Rounds 1-3 were 242, 186, and 169, respectively. Seventeen outcomes that met the predefined consensus criteria were considered at two consensus meetings. A final set of 10 core outcomes was agreed: mortality, time from injury to surgery, acute coronary syndrome, hypotension, acute kidney injury, delirium, pneumonia, orthogeriatric input, being out of bed at day 1, and pain. CONCLUSIONS: We generated a consensus-based set of core outcomes recommended for use in all perioperative trials evaluating the effects of anaesthesia for hip fracture surgery. An important next step is developing consensus-based consistency on how they should be measured. CLINICAL TRIAL REGISTRATION: http://www.comet-initiative.org/studies/details/757.

Perioperative outcomes in the context of mode of anaesthesia for patients undergoing hip fracture surgery: systematic review and meta-analysis.

BACKGROUND: Previous meta-analyses on the anaesthetic management of patients undergoing surgery for hip fracture have focused on randomized trials. Furthermore, heterogeneity in outcome reporting across the studies has made it difficult to inform best practice guidelines for patient care. METHODS: This systematic review examined how perioperative outcomes were reported and defined in the context of comparing modes of anaesthesia for hip fracture surgery. Outcomes were included from randomised and non-randomised studies published between January 2000 and July 2017. Meta-analyses were performed for regional versus general anaesthesia, with sensitivity analyses performed for spinal versus general anaesthesia. RESULTS: By including data from 15 large observational studies in this meta-analysis, we have increased the number of patients for whom outcomes were assessed from approximately 3000 to 202 000. There was no significant difference in 30-day mortality (OR 1.02; 95% CI 0.96, 1.07, I2 31%; n=200 616), prevalence of pneumonia (OR 1.07; 95% CI 0.94, 1.23, I2 34%; n=65 011), acute myocardial infarction (OR 0.96; 95% CI 0.88, 1.04, I2 0%, n=64 904), delirium (OR 1.07; 95% CI 0.72, 1.58, I2 93%, n=19 923), or renal failure (OR 0.94; 95% CI 0.54, 1.64, I2 0%, n=27 873) for regional compared with general anaesthesia [corrected]. There was a small statistically significant difference for length of stay (standardized mean difference -0.03; 95% CI -0.05, -0.02; I2 0%; n=78 711) favouring regional anaesthesia, which is unlikely to be clinically significant. Sensitivity analyses for the same outcomes examining spinal only vs general anaesthesia showed minor statistical significance for length of stay favouring spinal. We also present data highlighting the scale of the inconsistencies in reported outcomes across 32 studies, making evaluation in a standardized manner very difficult. As an example, mortality was reported in nine different ways throughout the studies. CONCLUSIONS: We highlight the need for agreement on outcome definitions and for a minimum core outcome set to be measured and reported in hip fracture studies. This would strengthen the evidence-based approach to delivering optimal care.

A Role for Behavior in the Relationships Between Depression and Hostility and Cardiovascular Disease Incidence, Mortality, and All-Cause Mortality: the Prime Study.

BACKGROUND: Behavioral factors are important in disease incidence and mortality and may explain associations between mortality and various psychological traits. PURPOSE: These analyses investigated the impact of behavioral factors on the associations between depression, hostility and cardiovascular disease(CVD) incidence, CVD mortality, and all-cause mortality. METHODS: Data from the PRIME Study (N = 6953 men) were analyzed using Cox proportional hazards models, following adjustment for demographic and biological CVD risk factors, and other psychological traits, including social support. RESULTS: Following initial adjustment, both depression and hostility were significantly associated with both mortality outcomes (smallest SHR = 1.24, p < 0.001). Following adjustment for behavioral factors, all relationships were attenuated both when accounting for and not accounting for other psychological variables. Associations with all-cause mortality remained significant (smallest SHR = 1.14, p = 0.04). Of the behaviors included, the most significant contribution to outcomes was found for smoking, but a role was also found for fruit and vegetable intakes and high alcohol consumption. CONCLUSIONS: These findings demonstrate well-known associations between depression, hostility, and mortality and suggest the potential importance of behaviors in explaining these relationships.

Depression and mortality: artifact of measurement and analysis?

BACKGROUND: 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. METHODS: Data from the PRIME Study (N=9798 men) on depression and 10-year CVD incidence and mortality were analysed using Cox proportional hazards models. RESULTS: 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. LIMITATIONS: 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. CONCLUSIONS: 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.

Do lifestyle behaviours explain socioeconomic differences in all-cause mortality, and fatal and non-fatal cardiovascular events? Evidence from middle aged men in France and Northern Ireland in the PRIME Study.

OBJECTIVE: To examine the contribution of lifestyle behaviours to the socioeconomic gradient in all-cause mortality, and fatal and non-fatal cardiovascular events. METHOD: 10,600 men aged 50-59 years examined in 1991-1994 in Northern Ireland (NI) and France and followed annually for deaths and cardiovascular events for 10 years. Baseline smoking habit, physical activity, and fruit, vegetable, and alcohol consumption were assessed. RESULTS: All lifestyle behaviours showed marked socioeconomic gradients for most indicators in NI and France, with the exception of percentage of alcohol consumers in NI and frequency of alcohol consumption in NI and France. At 10 years, there were 544 deaths from any cause and 440 fatal and non-fatal cardiovascular events. After adjustment for country and age, socioeconomic gradients were further adjusted for lifestyle behaviours. For total mortality, the median residual contribution of lifestyle behaviours was 28% and for cardiovascular incidence, 41%. When cardiovascular risk factors were considered in conjunction with lifestyle behaviours these percentages increased to 38% and 67% respectively. CONCLUSION: Lifestyle behaviours contribute to the gradient in mortality and cardiovascular incidence between socioeconomic groups, particularly for cardiovascular incidence, but a substantial proportion of these differentials was not explained by lifestyle behaviours and cardiovascular risk factors.

Contribution of lifetime smoking habit in France and Northern Ireland to country and socioeconomic differentials in mortality and cardiovascular incidence: the PRIME Study.

BACKGROUND: This study examines the contribution of lifetime smoking habit to the socioeconomic gradient in all-cause and smoking-related mortality and in cardiovascular incidence in two countries. METHODS: 10,600 men aged 50-59 years were examined in 1991-4 in centres in Northern Ireland and France and followed annually for 10 years. Deaths and cardiovascular events were documented. Current smoking habit, lifetime smoking (pack-years) and other health behaviours were evaluated at baseline. As socio-occupational coding schemes differ between the countries seven proxy socioeconomic indicators were used. RESULTS: Lifetime smoking habit showed marked associations with most socioeconomic indicators in both countries, but lifetime smoking was more than 10 pack-years greater overall in Northern Ireland and smoking patterns differed. Total mortality was 49% higher in Northern Ireland than in France, and smoking-related mortality and cardiovascular incidence were 93% and 92% higher, respectively. Both lifetime smoking and fibrinogen contributed independently to these differentials, but together explained only 42% of the difference in total mortality between countries, adjusted for both biological and lifestyle confounders. Socioeconomic gradients were steeper for total and smoking-related mortality than for cardiovascular incidence. Residual contributions of lifetime smoking habit ranged from 6% to 34% for the seven proxy indicators of socioeconomic position for total and smoking-related mortality. Socioeconomic gradients in cardiovascular incidence were minimal following adjustment for confounders. CONCLUSION: In Northern Ireland and France lifetime smoking appeared to explain a significant part of the gradients in total and smoking-related mortality between socioeconomic groups, but the contribution of smoking was generally small for cardiovascular incidence.

An investigation of susceptibility loci in benign, aggressive and primary progressive multiple sclerosis in Northern Irish population.

OBJECTIVE: To investigate the possibility that susceptibility loci in multiple sclerosis (MS) have a role in determining the disease outcome in Northern Ireland population. BACKGROUND: The Genetic Analysis of Multiple Sclerosis in Europeans (GAMES) initiative and follow-up refined analysis identified 15 candidate susceptibility loci within the Northern Irish population for MS. We aimed to investigate the 12 most significant markers for their role in disease outcome. METHODS: Cases with probable or definite MS (Poser criteria) were classified as benign onset (Kurtzke Expanded Disability Status Scale [EDSS]or=6.0 by 10 years), or primary progressive MS. All cases were Caucasian of Northern Irish origin. DNA was extracted from venous blood, microsatellite markers were amplified using polymerase chain reaction and typed using fluorescent fragment analysis. Allele frequencies were compared statistically using a chi-squared test with allowance for multiple comparisons (critical P<0.0042); significant markers were further analyzed by CLUMP (critical P<0.0014). RESULTS: Two microsatellite markers were significant: D3S1278 (Chr 3q13, P<0.001) and tumor necrosis factor (TNF)-alpha (Chr 6p21, P<0.001). A further three markers were significant in our preliminary analysis suggesting a trend toward impact on disease outcome; D4S432 (Chr 4p16, P=0.001), D2S347 (Chr 2q14, P=0.003), and D19S903 (Chr 19p13, P=0.003). CONCLUSIONS: This is the first study to suggest a role for TNF-alpha in the disease outcome in MS. Larger replication studies need to be performed to assess the role of markers D4S432, D2S347, and D19S903.

Genetic polymorphisms in platelet-related proteins and coronary artery disease: investigation of candidate genes, including N-acetylgalactosaminyltransferase 4 (GALNT4) and sulphotransferase 1A1/2 (SULT1A1/2).

BACKGROUND: Both platelet function and heart disease show strong genetic components, many of which remain to be elucidated. MATERIALS AND METHODS: The roles of candidate polymorphisms in ten platelet-associated genes were compared between 1,237 Acute Coronary Syndrome (ACS) cases (with myocardial infarction and unstable angina) and 386 controls, from an Irish Caucasian population. Additionally, 361 stable angina patients were investigated. Two genes of interest were followed up in a separate Irish study of 1,484 individuals (577 with IHD and 907 unaffected). RESULTS: The GALNT4 (N-acetyl galactosaminyl transferase 4) 506I allele was significantly underrepresented in ACS (OR = 0.66, CI = 0.52-0.84; P = 0.001; P = 0.01 after correction for multiple testing), while the SULT1A1 (Sulphotransferase 1A1) 213H allele was associated with risk of ACS (OR = 1.37, CI = 1.08-1.74; P = 0.01; P = 0.1 after correction for multiple testing). Subsequent genotyping of further SNPs in GALNT4 in the family-based (IHD) group revealed that the 506I allele showed the same trend towards protecting against ACS but the haplotypic test over the four commonest haplotypes was not significant (P = 0.55). In contrast, the SULT1A1/SULT1A2 gene complex showed suggestive haplotypic association in the family-based study (P = 0.07), with the greatest increase in risk conferred by the SULT1A2 235T allele (P = 0.025). CONCLUSION: We have identified two risk genes for cardiovascular disease, one of whose (GALNT4) effects may be on either platelet or endothelial function through modifications of PSGL1 or other important glycosylated proteins. The role of sulphotransferases (SULT1A1/2) in cardiovascular disease requires further exploration. Further validation of cardiovascular risks conferred by both genes in other populations (including gene copy number variation) is warranted.

Infections in early life and childhood leukaemia risk: a UK case-control study of general practitioner records.

We investigated infections in early life (diagnosed in general practice) and subsequent risk of childhood leukaemia in the UK General Practice Research Database (GPRD). All children born at GPRD practices and subsequently diagnosed with leukaemia were identified as cases and were individually matched (on year of birth, sex and practice) to up to 20 controls. The final analysis included 162 leukaemia cases and 2215 matched controls. Conditional logistic regression demonstrated no evidence that children with one or more recorded infection in the first year of life had a reduced risk of leukaemia (OR=1.05, 95%CI 0.69, 1.59; P=0.83) or acute lymphoblastic leukaemia (ALL; OR=1.05, 95%CI 0.64-1.74; P=0.84). Our study provides no support for the Greaves hypothesis, which proposes that reduced or delayed exposure to infections in early life increases the risk of childhood ALL.

A rapid rise in circulating pancreastatin in response to somatostatin analogue therapy is associated with poor survival in patients with neuroendocrine tumours.

AIM: To assess the value of pancreastatin as a predictive factor for identifying patients with neuroendocrine tumours (NETs) who respond poorly to somatostatin analogues. METHODS: A retrospective study of patients with NETs. Patient records from the Northern Ireland Neuroendocrine Tumour Register were interrogated. Those who had pancreastatin concentrations measured on two or more occasions, before and during somatostatin analogue therapy (within the set time-limits) were selected. Data relating to diagnosis, surgery, somatostatin analogue therapy and survival outcome were noted. Data were subjected to univariate and multivariate analysis using Cox proportional hazard model. RESULTS: Fifty-nine patients with gastroenteropancreatic NETs fulfilled the inclusion criteria. Factors associated with a poor survival outcome on univariate analysis were primary tumour site (P = 0.006) and rapid rise in pancreastatin during somatostatin analogue treatment (P < 0.001). In multivariate analysis, highly significant clinical prognostic indicators were: tumour location (P < 0.001), pre-treatment pancreastatin (P < 0.001) and pancreastatin change (P < 0.001). CONCLUSIONS: This study endorses the finding that pancreastatin is a useful prognostic indicator of neuroendocrine disease. On commencement of treatment, one-third of the subjects showed an immediate negative pancreastatin response to somatostatin analogues, which was associated with poor survival. This is the first study to document such an association. These findings have significant therapeutic consequences. In the presence of a rapidly rising pancreastatin alternative, treatment modalities should be sought.

Homocysteine and coronary heart disease risk in the PRIME study.

INTRODUCTION: Despite recent meta-analyses suggesting that homocysteine is an independent predictor of coronary heart disease (CHD), there is debate regarding whether elevated homocysteine may be deleterious only in the presence of other risk factors, with which it acts synergistically to exert a multiplicative effect on CHD risk, emerging only as a CHD predictor in patients with pre-existing risk factors. The Prospective Epidemiological Study of Myocardial Infarction (PRIME) Study is a multicentre prospective study of 10593 men from France and Northern Ireland, investigating cardiovascular risk factors. We investigated: (1) whether higher homocysteine is associated with increased CHD risk in the PRIME case-control cohort; (2) whether homocysteine interacts synergistically with pre-existing CHD risk factors. METHODS: Homocysteine was measured in 323 participants who had developed CHD at 5-year follow-up and in 638 matched controls. RESULTS: There was no significant difference in homocysteine between cases and controls (p=0.18). Homocysteine was significantly higher in current smokers (geometric mean mumol/l (interquartile range mumol/l) 9.45 (7.43, 11.75)) compared with non-smokers (8.90 (7.32, 10.70); p=0.007). There was a significant interaction between homocysteine, smoking and CHD risk (chi2=10.29, d.f.=2, p=0.006). CONCLUSIONS: These findings suggest that elevated homocysteine is significantly associated with CHD risk in current smokers.

Circulating markers of prognosis and response to treatment in patients with midgut carcinoid tumours.

BACKGROUND AND AIMS: Midgut carcinoid tumours are uncommon tumours with an unpredictable clinical behaviour and few useful prognostic markers. Somatostatin analogues are widely used in treatment but a survival advantage has not been proven. We analysed features associated with poor prognosis and assessed the clinical implications of the biochemical response to therapy. METHODS: Clinical and biochemical data were collected for patients with midgut carcinoid tumours attending a tertiary referral neuroendocrine clinic from 1978 to 2000. Using death as the end point, univariate and multivariate survival analyses were performed to identify prognostic indicators. The significance of altering biomarkers with therapy was also studied by including repeated measurements of the most prognostic biochemical parameter in a time dependent covariate survival analysis. RESULTS: We identified 139 patients with sufficient data for our analyses. Factors associated with a poor outcome on univariate analysis included: plasma neurokinin A (NKA), urinary 5-hydroxyindolacetic acid output, age, and >/=5 liver metastases. Plasma NKA was the strongest and only independent predictor of outcome on multivariate analysis. Patients in whom NKA continued to rise despite somatostatin analogues had a significantly worse survival than those in whom NKA stabilised or fell (one year survival rate 40% v 87%). Time dependent covariate analysis concluded that survival was better predicted by the most recent plasma NKA value rather than by the initial value. CONCLUSIONS: Plasma NKA is an accurate marker of prognosis for midgut carcinoid tumours. This is the first paper to support a survival advantage in patients in whom plasma NKA is altered by somatostatin analogues.

The CTLA4+49A/G and CT60 polymorphisms and chronic inflammatory arthropathies in Northern Ireland.

Rheumatoid and juvenile idiopathic arthritis (RA, JIA) are chronic inflammatory arthropathies with an autoimmune background. The cytotoxic T-lymphocyte antigen-4 (CTLA-4) protein plays a key role in the down-regulation of T cell activation. We analyzed the CTLA4 +49A/G and CT60 polymorphisms in cohorts of Northern Irish RA and JIA patients and healthy control subjects using restriction fragment length polymorphism methods. The +49 A allele was increased in RA (61.2%; P=0.02; OR=1.28; 95% C.I.=1.04-1.58) and JIA (61.8%; P=0.14) patients compared to the control population (55.3%). No significant association was observed for the CT60 polymorphism. Haplotype analysis revealed a significantly different distribution of +49 A/G-CT60 haplotypes in RA and JIA patients compared to controls (P value<0.00001 and 0.030 for comparison of RA and JIA patients with controls, respectively). Our results suggest that the CTLA-4 gene is involved in predisposition to inflammatory arthropathies in the Northern Irish population.

Cancer incidence and mortality in patients with insulin-treated diabetes: a UK cohort study.

Raised risks of several cancers have been found in patients with type II diabetes, but there are few data on cancer risk in type I diabetes. We conducted a cohort study of 28 900 UK patients with insulin-treated diabetes followed for 520 517 person-years, and compared their cancer incidence and mortality with national expectations. To analyse by diabetes type, we examined risks separately in 23 834 patients diagnosed with diabetes under the age of 30 years, who will almost all have had type I diabetes, and 5066 patients diagnosed at ages 30-49 years, who probably mainly had type II. Relative risks of cancer overall were close to unity, but ovarian cancer risk was highly significantly raised in patients with diabetes diagnosed under age 30 years (standardised incidence ratio (SIR)=2.14; 95% confidence interval (CI) 1.22-3.48; standardised mortality ratio (SMR)=2.90; 95% CI 1.45-5.19), with greatest risks for those with diabetes diagnosed at ages 10-19 years. Risks of cancer at other major sites were not substantially raised for type I patients. The excesses of obesity- and alcohol-related cancers in type II diabetes may be due to confounding rather than diabetes per se.

Improved survival for melanoma in Northern Ireland: a comparison of two 5-year periods (1984-88 and 1994-98).

BACKGROUND: The incidence of cutaneous malignant melanoma has been rising steadily in Caucasian populations for several decades, with a doubling time of 10-14 years. An increase in incidence of about 5% per year has been reported in most Caucasian populations since the early 1960s. OBJECTIVES: This study was designed to determine the changing incidence of primary cutaneous malignant melanoma in Northern Ireland and to examine changes in survival rates from cutaneous malignant melanoma in two 5-year periods, 1984-88 and 1994-98. METHODS: One thousand three hundred and twenty-six patients with invasive primary cutaneous melanoma were included in the study. RESULTS: The age standardized rate of melanoma rose from 4.3 per 100,000 population per year in men and 8.6 per 100,000 population per year in women to 7.7 and 11.8, respectively, per 100,000 population per year in the 1994-98 period. Overall, the absolute 5-year survival for the 1984-88 period was 71.0% [95% confidence interval (CI) 66.9-75.1%] and 77.4% (95% CI 73.4-81.4%) for the 1994-98 period. Women consistently showed better survival at all ages and within almost all categories of thickness of primary tumour. Younger patients of both sexes showed better survival rates. CONCLUSIONS: When survival rates between the 1984-88 and 1994-98 periods were compared using multivariate analysis, we found that patients diagnosed in the second period had a one-third lower risk of dying than those in the earlier period. Much of this reduction was explained by changes in the number of melanomas of thin Breslow depth and ulcerated melanomas.

Smoking, atopy and certain furry pets are major determinants of respiratory symptoms in children: the International Study of Asthma and Allergies in Childhood Study (Ireland).

BACKGROUND: Environmental, cultural and health care differences may account for variation among countries in the prevalence of asthma and respiratory symptoms in teenagers. OBJECTIVE: To examine the prevalence of respiratory symptoms and the level of diagnosis, and to compare determinants of asthma and severe wheeze in two countries. METHODS: Self-completion questionnaires based on the International Study of Asthma and Allergies in Childhood (ISAAC) protocol were provided to school children in Ireland (Republic and Northern Ireland). In the Republic of Ireland, all children in classes largely aged 13-14 years from 30 post-primary schools were selected by random sampling stratified by school size, composition and Health Board in Spring 1995. In Northern Ireland, all children largely aged 13-14 years of age from 26 post-primary schools were selected by random sampling stratified by school type, composition and Education and Library Board in Spring 1996. RESULTS: Questionnaires were completed by 2,364 children from Northern Ireland and 2,671 from the Republic, about 90% of those eligible to participate. The prevalences of wheeze at various levels of severity, of diagnosed asthma and of treated wheeze were very similar in Northern Ireland and the Republic of Ireland. A significant proportion of those reporting more severe symptomatology (four or more attacks of wheeze in the past 12 months and/or one or more nights disturbed and/or moderate or greater disruption of daily activities and/or speech restriction due to wheeze) had been neither diagnosed nor treated for asthma (20-37%). To investigate the determinants of the more severe symptomatology of asthma or treated wheeze a series of stepwise multiple regression analyses was performed. A history of atopy, cigarette smoking, the possession of a furry pet other than a dog or cat and age were each independently associated with severe wheeze, whilst atopy, a furry pet (as above) and gender were each independently associated with asthma or treated wheeze. CONCLUSIONS: Cigarette smoking is closely associated with the reporting of significant respiratory symptoms together with atopy and exposure to furry pets. Some 20-37% of severe symptoms were neither diagnosed nor treated as asthma.

Central obesity: predictive value of skinfold measurements for subsequent ischaemic heart disease at 14 years follow-up in the Caerphilly Study.

OBJECTIVE: To assess the predictive value of central obesity for risk of ischaemic heart disease (IHD) in a long-term follow-up, measured by skinfold thickness in comparison to general measures of overweight and obesity such as Quetelet's index. SUBJECTS AND DESIGN: A total of 2512 men aged 45-59 y from the general population first examined in 1979-1982. Men were re-examined at approximately 5 y intervals. All fatal and non-fatal cases of IHD during a 14 y follow-up were recorded. MEASUREMENTS: Skinfold thickness was measured at four sites. Height (m) and weight (kg) were also measured and Quetelet's index (weight/height(2)) was used as the reference body mass index (BMI). RESULTS: Data were available for 2512 men among whom 411 new cases of IHD (fatal and non-fatal) occurred during 14 y of follow-up. Increasing values of BMI showed a statistically significant trend with increasing risk of new IHD that contributed independently to risk of IHD when adjusted for age, smoking habit and social class. Skinfold thickness measures were entered singly and in combination into this model with and without the additional inclusion of BMI. All individual skinfolds were significantly associated with risk of new IHD when BMI was excluded from the regression model, as was the sum of four skinfolds and the sum of subscapular and abdominal skinfolds. Only the subscapular skinfold measure contributed independently to risk of subsequent IHD when BMI was included in the model although biceps, biceps plus triceps and total sum of skinfolds were close to achieving statistical significance. The relative odds of IHD in the upper quintile of subscapular skinfold compared to the lowest was 1.9 (95% CI 1.3-2.8) when adjusted for age, smoking habit and social class. CONCLUSIONS: In general skinfold measurements contribute only marginally to improved prediction of risk of IHD as measured by BMI, but central obesity, as measured by the subscapular skinfold, is predictive of IHD independently of BMI.

Possible association between CTLA4 DNA polymorphisms and early onset type 1 diabetes in a UK population.

Linkage and association has been reported between CTLA4 DNA markers and susceptibility to type 1 diabetes in some populations, but not others. We performed case-control and family-based association studies to assess if the CTLA4 A49G and intron 1 C/T polymorphisms were associated with development of early onset type 1 diabetes in the Northern Ireland population. The distribution of A49G and C/T alleles in cases (n = 144) was similar to those observed in controls (n = 307). In contrast, significant distortions in allele transmissions from informative parents to probands were observed for both the A49G (P = 0.02) and C/T (P = 0.01) polymorphisms employing 297 nuclear families. Our results suggest that the CTLA4 gene may play a minor role in the overall genetic predisposition to type 1 diabetes in this UK population.