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A letter to the editor is presented in response to the article "Association of Childhood Type 1 Diabetes Mellitus With a Variant of PAX4; Possible Link to Beta Cell Regeneration Capacity," by A. Biason-Lauber and colleagues in the 2005 issue.

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. [ABSTRACT FROM AUTHOR]

Aims To assess the effect of pregnancy planning on maternal and neonatal outcomes in women with Type 1 diabetes. Methods Pregnancy planning was assessed retrospectively in a cohort of women who participated in the Diabetes and Pre-eclampsia Intervention Trial ( DAPIT). Pregnancy planning was determined based on self-report as to whether pregnancy was planned or unplanned. The effect of pregnancy planning on maternal and neonatal outcomes was examined, controlling for confounding variables. Results A total of 747 women were included in the study, of whom 39% considered their pregnancy unplanned. Characteristics associated with unplanned pregnancy included being younger ( P<0.001), being a current smoker ( P<0.001), being from a lower social class ( P<0.001) and having higher HbA1c values prior to and throughout pregnancy ( P≤0.005). Significantly fewer women with unplanned vs planned pregnancies received pre-pregnancy counselling (24% vs 64%; P<0.001). Infants of women with unplanned pregnancies were more likely to be small for gestational age (<5th centile; P=0.004), to be admitted to the neonatal care unit ( P=0.001) and to have a longer stay in hospital ( P=0.01). Outcomes did not differ between the groups in relation to pre-eclampsia, congenital malformations or a composite adverse outcome. Conclusions Risks associated with diabetes in pregnancy need to be highlighted to all women, their partners and families, and healthcare professionals. Further research is required to determine if these groups are fully aware of the risks associated with diabetes in pregnancy. [ABSTRACT FROM AUTHOR]

Diabet. Med. 29, 950-956 (2012) Abstract Aims To determine if an educational DVD increases knowledge and changes attitudes of women with diabetes towards preconception care. Methods Ninety-seven women with diabetes (Type 1, n = 89; Type 2, n = 8), aged 18-40 years, completed a pre-DVD and post-DVD intervention study by postal questionnaire. Beliefs and attitudes associated with preventing an unplanned pregnancy and seeking preconception care were assessed using a validated questionnaire; scales included benefits, barriers, personal attitudes and self-efficacy. Knowledge of pregnancy planning and pregnancy-related risks were assessed by a 22-item questionnaire. Results After viewing the DVD there was significant positive change in women's perceived benefits of, and their personal attitudes to, receiving preconception care and using contraception: change in score post-DVD viewing 0.7 (95% confidence interval 0.3, 1.2), P = 0.003, and 0.8 (0.3, 1.2), P = 0.001, respectively. The DVD significantly improved self-efficacy, that is, self-confidence to use contraception for prevention of an unplanned pregnancy and to access preconception care [3.3 (1.9, 4.7), P < 0.001], and significantly reduced perceived barriers to preconception care [−0.7 (−1.2, −0.2), P = 0.01]. Knowledge of pregnancy planning and pregnancy-related risks increased significantly after viewing the DVD: mean increase was 37.6 ± 20.0%, P < 0.001, and 16.9 ± 21.2%, P < 0.001, respectively. Conclusions This study demonstrates the effectiveness of a DVD in increasing knowledge and enhancing attitudes of women with diabetes to preconception care. This DVD could be used as a prepregnancy counselling resource to prepare women with diabetes for pregnancy. [ABSTRACT FROM AUTHOR]

Background: There is evidence that the intermediate filament protein, nestin, may play a role in tissue regeneration and nestin expression has been detected in coronary atherosclerotic plaques. However, to date, no population-based studies concerning the role of the nestin gene in coronary heart disease (CHD) have been reported. Methods: We evaluated 3 SNPs in the nestin gene amongst 1494 individuals in 580 Irish families with at least one member prematurely affected with coronary heart disease. Genotypes were determined by multiplex SNaPshot technology. Results: Using the TDT/S-TDT test, we found that rs11582300 and rs3748570 were associated with early-onset CHD (P=0.04 and P=0.02). Conclusion: We found that nestin gene variants were associated with early-onset CHD. These findings emphasise the importance of further research to explore the role of nestin in atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: Genome-wide association studies have been successful in identifying susceptibility loci for common diseases. DNA pooling is a practical way to reduce the huge cost of large-scale genotyping. Methods: In the first stage, our work focused on the use of 330k / 550k SNP chips, using pooled DNA samples from up to 50 cases or controls. The cases were male patients with early-onset (<55yr) coronary heart disease. The control individuals (age > 68yr) were identified from the PRIME study. We then selected SNPs with differences of allele frequencies between 5% and 13%, combined with a 'cluster' method. In the second stage, replication was undertaken using independent DNA samples from a family-based study (1494 individuals from 580 families with probands having early-onset coronary heart disease). Results: Among 9 regions, SNPs in 2 chromosomal regions were successfully replicated in the second stage. The P values for SNPs in the DNAJC6 gene, rs501691, rs1325607, rs4325172 were 0.03, 0.03, and 0.004, respectively. Another SNP on chromosome 15, rs3825877 was also positive (P=0.009). Conclusion: Genome-wide association studies using pooled DNA samples are feasible and may be a cost-effective way to detect genes for complex diseases. DNAJC6 gene may be associated with early-onset coronary heart disease. [ABSTRACT FROM AUTHOR]

Aims: Specific patterns in incidence may reveal environmental explanations for type 1 diabetes incidence. We aimed to study type 1 diabetes incidence in European childhood populations to assess whether an increase could be attributed to either period or cohort effects. Methods: Nineteen EURODIAB centres provided single year incidence data for ages 0–14 in the 25-year period 1989–2013. Case counts and person years were classified by age, period and cohort (APC) in 1-year classes. APC Poisson regression models of rates were fitted using restricted cubic splines for age, period and cohort per centre and sex. Joint models were fitted for all centres and sexes, to find a parsimonious model. Results: A total of 57,487 cases were included. In ten and seven of the 19 centres the APC models showed evidence of nonlinear cohort effects or period effects, respectively, in one or both sexes and indications of sex-specific age effects. Models showed a positive linear increase ranging from approximately 0.6 to 6.6%/year. Centres with low incidence rates showed the highest overall increase. A final joint model showed incidence peak at age 11.6 and 12.6 for girls and boys, respectively, and the rate-ratio was according to sex below 1 in ages 5–12. Conclusion: There was reasonable evidence for similar age-specific type 1 diabetes incidence rates across the EURODIAB population and peaks at a younger age for girls than boys. Cohort effects showed nonlinearity but varied between centres and the model did not contribute convincingly to identification of environmental causes of the increase. [ABSTRACT FROM AUTHOR]

Aims 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. Methods 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. Results 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. Conclusions 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. [ABSTRACT FROM AUTHOR]

Diabet. Med. 27, 1188–1194 (2010) Background Polymorphisms in ACE and AGTR1 genes have been assessed in multiple studies for association with diabetic nephropathy; however, results are conflicting. The ACE2 gene has not been studied extensively for association with diabetic nephropathy. Methods We investigated variants in ACE, ACE2 and AGTR1 for association with nephropathy in a case–control group (1467 participants with Type 1 diabetes, case subjects n = 718; control subjects n = 749) of white descent with grandparents born in the British Isles. All recruited individuals were carefully phenotyped and genotyping was performed using Sequenom, Taqman and gel electrophoresis methods. The χ2-test for contingency tables was used to compare genotype and allele frequencies in case and control groups. Results No departure from Hardy–Weinberg equilibrium was observed in cases or controls. Two variants within the ACE gene (rs4293, Pallelic = 0.02, Pgenotypic = 0.008; rs4309, Pallelic = 0.02, Pgenotypic = 0.01) were significantly associated with nephropathy at the 5% level. No variant remained statistically significant following adjustment for multiple comparisons. No single nucleotide polymorphisms in the ACE2 or AGTR1 genes were significantly associated with nephropathy when analysed either by genotype or allele frequencies. Conclusions Our independent case–control study provides no evidence that common variants in ACE, ACE2 and AGTR1 play a major role in genetic susceptibility to diabetic nephropathy in a white population with Type 1 diabetes. [ABSTRACT FROM AUTHOR]

Diabet. Med. 27, 624–630 (2010) Aims Diabetic nephropathy is a leading cause of end-stage renal disease. The transforming growth factor β–bone morphogenic protein (BMP) pathway is implicated in the pathogenesis of diabetic nephropathy. The BMP2, BMP4 and BMP7 genes are located near linkage peaks for renal dysfunction, and we hypothesize that genetic polymorphisms in these biological and positional candidate genes may be risk factors for diabetic kidney disease. Methods The BMP7 gene was screened, variants identified and allele frequencies determined by bidirectionally sequencing 46 individuals to facilitate selection of tag SNPs ( n = 4). For BMP2 and BMP4 genes, data were downloaded for 19 single nucleotide polymorphisms (SNPs) from the International HapMap project and six tag SNPs selected. Results The BMP7 gene was screened for novel genetic polymorphisms, haplotypes were identified, an appropriate subset of variants selected for the investigation of common genetic risk factors, and BMP2, BMP4 and BMP7 genes assessed for association with diabetic nephropathy in 1808 individuals. Thirty-two SNPs were identified, of which 11 were novel, including an amino-acid changing SNP (+63639C>T). No significant differences ( P > 0.2) were observed when comparing genotype or allele or haplotype frequencies between 864 individuals with Type 1 diabetes and nephropathy compared with 944 individuals with Type 1 diabetes without nephropathy, stratified by recruitment centre. Conclusions Common polymorphisms in these BMP genes do not strongly influence genetic susceptibility to diabetic nephropathy in White individuals with Type 1 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Aims To determine whether children with infections in early life (recorded routinely in general practice) have a reduced risk of Type 1 diabetes, as would be expected from the hygiene hypothesis. Methods Children with Type 1 diabetes and up to 20 matched (on year of birth, sex and region) control subjects were selected from a cohort of children born in the UK at General Practice Research Database practices. For each child, the frequency of general practitioner consultations for infections and prescriptions for antibiotics in the first year of life were determined. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated using conditional logistic regression. Results The main analysis included 367 case and 4579 matched control subjects. There was no evidence of any reduction in the subsequent risk of Type 1 diabetes in children with at least one infection in the first year of life (OR = 1.03, 95%CI 0.79, 1.34) or in children prescribed antibiotics in the first year of life (OR = 1.03, 95%CI 0.82, 1.29). Further analyses also revealed little evidence of a difference in subsequent risk of Type 1 diabetes after different types of infection in the first year of life (including gastrointestinal, conjunctivitis, otitis media and upper and lower respiratory tract). Analyses of infections in the first 2 years of life reached similar conclusions. Conclusions This study provides no evidence of an association between infections in early life and subsequent risk of childhood-onset Type 1 diabetes and therefore does not support the hygiene hypothesis. [ABSTRACT FROM AUTHOR]

Aims To investigate secular trends in the incidence of Type 1 diabetes in Northern Ireland over the period 1989–2003. To highlight geographical variations in the incidence of Type 1 diabetes by producing disease maps and to compare incidence rates by relevant area characteristics. Methods New cases of Type 1 diabetes in children aged 0–14 years in Northern Ireland were prospectively registered from 1989 to 2003. Standardized incidence rates were calculated and secular trends investigated. Bayesian methodology was used to produce maps of disease incidence using small geographical areas (582 electoral wards). Ecological analyses were conducted using Poisson regression to investigate incidence rates by area characteristics at a finer geographical subdivision (5022 census output areas). Results In Northern Ireland during 1989–2003, there were 1433 new cases, giving a directly standardized incidence rate of 24.7 per 100 000 person-years. This incidence rate increased by a mean of 4.2% per annum. Disease maps highlighted higher incidence rates in the predominately rural north-east of the province and lower incidence rates in the urban areas around Belfast in the east and Derry in the north-west of the province. Ecological analysis identified higher incidence in rural areas ( P < 0.001), areas with low migration rates ( P = 0.002), affluent areas ( P < 0.0001), sparsely populated areas ( P = 0.0001) and remote areas ( P = 0.005). Conclusions In Northern Ireland the incidence of Type 1 diabetes is increasing. The observed higher incidence in rural, affluent, sparsely populated and remote areas may reflect a reduced or delayed exposure to infections in these areas. [ABSTRACT FROM AUTHOR]

Aim Plasminogen activator inhibitor 1 (PAI1) plays a key role in the regulation of extracellular matrix (ECM) degradation. The PAI1 gene is therefore an excellent candidate gene for diabetic nephropathy. The aim of this study was to employ gene resequencing to identify common DNA polymorphisms in the PAI1 gene, and subsequently assess haplotype tagged single nucleotide polymorphisms (htSNPs) using a case control design. Methods All nine exons, exon–intron boundaries, introns 1, 4 and 7 and approximately 3 kb upstream and 5 kb downstream of the PAI1 gene were screened for DNA polymorphisms in 15 case and 15 control subjects using WAVE® denaturing high-performance liquid chromatography technology and confirmed by DNA sequencing. Polymorphisms were genotyped in 86 healthy individuals using direct sequencing and haplotype tagged single nucleotide polymorphisms (htSNPs) identified. Genotyping of the htSNPs was performed in 583 Type 1 diabetic patients (222 with nephropathy, 361 without nephropathy) using Pyrosequencing. Results Twenty-one polymorphisms with a minor allele frequency (MAF) > 1% were identified; 14 had a MAF ≥ 10%. Five htSNPs [c.-1968_69insG, c.43 G→A (Ala15Thr), c.1092-105 A→G, c.*1737 G→A, c.*3711 C→T] were identified. Haplotype frequencies were similar in case and control groups (likelihood ratio χ2 test, P = 0.66). Conclusion It is unlikely that common polymorphisms of the PAI1 gene strongly influence susceptibility to diabetic nephropathy in the White Type 1 diabetic population. [ABSTRACT FROM AUTHOR]

Using a before and after study design, we compared protocolised weaning from mechanical ventilation with usual non-protocolised practice in intensive care. Outcomes (duration of mechanical ventilation, duration of intubation, intensive care stay) and complications (re-intubations, tracheostomy, mortality) were compared between baseline (Phase I) and following implementation of protocolised weaning (Phase II). Over the same period, we collected data in a second (reference) unit to monitor practice changes over time. In the intervention unit, outcomes were longer in Phase II compared with Phase I (all p < 0.005). When adjusted for admission APACHE II score and diagnostic category, only intensive care stay remained significantly longer (p = 0.002). There were significantly more tracheostomies in Phase II (p = 0.004). The reference unit demonstrated no statistically significant differences in study outcomes or complications between Phases. Protocolised weaning did not reduce the duration of mechanical ventilation and was not associated with an increased rate of re-intubation or intensive care unit mortality. [ABSTRACT FROM AUTHOR]

To investigate perinatal risk factors for childhood Type 1 diabetes in a UK population cohort.Perinatal data have been routinely recorded in Northern Ireland for all births in the period 1971–86 (n = 447 663). Diabetes status at the age of 15 years was ascertained in this cohort by identifying 991 children from 1079 registered with Type 1 diabetes diagnosed from 1971 to 2001 and date of birth in the period 1971–86.Increased Type 1 diabetes risk was associated with higher maternal age, paternal age, birth weight and birth weight for gestational and lower gestational age. After adjustment for maternal age, the association between Type 1 diabetes and paternal age remained significant[relative risk (RR) = 1.52 (1.10, 2.09) comparing father's age 35 years or more to less than 25 years] but not vice versa[RR= 1.11 (0.80, 1.54) comparing mother's age 35 years or more to less than 25 years]. Increased birth order was associated with a significant decrease in the risk of Type 1 diabetes[adjusted RR = 0.75 (0.62, 0.90) comparing birth order three or more with firstborn], but this only became apparent when adjustment was made for maternal age. Furthermore this association with birth order was significant only for diabetes diagnosed under the age of 5 years.Our analysis demonstrates, for the first time in a UK regional cohort setting, that maternal age and paternal age at delivery, birth order, birth weight and gestational age are significantly associated with Type 1 diabetes risk.Diabet. Med. 22, 200–206 (2005) [ABSTRACT FROM AUTHOR]

The possible role of the K469E polymorphism in the intercellular adhesion molecule-1 (ICAM-1) gene in the susceptibility to ischaemic heart disease (IHD) was investigated in a well-defined Irish population using two recently described family-based tests of association. One thousand and twelve individuals from 386 families with at least one member prematurely affected with IHD were genotyped for the ICAM-1 K469E polymorphism. Using the combined transmission disequilibrium test (TDT)/sib-TDT and the pedigree disequilibrium test (PDT), no association between the ICAM-1 K469E polymorphism and IHD was found. Our data demonstrate that, in an Irish population, the ICAM-1 K469E polymorphism is not associated with IHD. [ABSTRACT FROM AUTHOR]

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.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.One thousand three hundred and twenty-six patients with invasive primary cutaneous melanoma were included in the study.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.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. [ABSTRACT FROM AUTHOR]

EURODIAB ACE is a collaborative European study that was set up to assess incidence of childhood insulin-dependent diabetes mellitus (IDDM) in Europe, test the proposal of a south-north gradient, and to gather information to determine the causes and pathogenesis of the disease. Here, the basic epidemiological results are reported. Newly diagnosed cases of IDDM in children aged up to 15 years were identified prospectively in twenty-four geographically well-defined study regions in Europe and Israel (a total of 16.8 million children) during 1989 and 1990. 3060 cases were identified with estimated ascertainment rates exceeding 90% in all study regions. Age-standardised and sex-standardised incidence rates varied widely, ranging from 4.6 (northern Greece) to 42.9 (two regions in Finland) cases per 100,000 per year. Rates in southern Europe were generally higher than previously assumed, and there was an unexpectedly high incidence in Sardinia, which had the second highest rate (30.2 cases per 100,000 per year) recorded in Europe. Eastern European regions had generally low rates. The collaborative network now established provides a framework for further studies to examine the complex interaction between genetic and environmental factors in the cause and pathogenesis of IDDM. [ABSTRACT FROM AUTHOR]

Abstract: Aims: To measure total 25‐hydroxyvitamin D levels in women in mid‐pregnancy who participated in the Belfast centre of the Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) observational study, and to investigate the associations between levels of 25‐hydroxyvitamin D and markers of gestational diabetes mellitus and lipid biomarkers. Methods: A total of 1585 pregnant women had serum samples available for measurement. Participants were recruited from the Royal Jubilee Maternity Hospital, Belfast, Northern Ireland, at 24–32 weeks’ gestation, as part of the HAPO study. 25‐hydroxyvitamin D concentrations were measured using liquid chromatography tandem mass spectrometry. Glucose, C‐peptide and lipid levels were previously analysed in a central laboratory. Statistical analysis was performed. Results: The median (interquartile range) 25‐hydroxyvitamin D concentration during pregnancy was 38.6 (24.1–60.7) nmol/l, with 65.8% of women being vitamin D‐deficient (≤50 nmol/l). In regression analysis, the association between maternal 25‐hydroxyvitamin D and fasting plasma glucose levels approached significance [regression coefficient –0.017 (95% CI –0.034 to 0.001); P=0.06], and a significant positive association was observed between maternal 25‐hydroxyvitamin D and β‐cell function [1.013 (95% CI 1.001 to 1.024); P=0.031]. Maternal 25‐hydroxyvitamin D level was positively associated with HDL [0.047 (95% CI 0.021 to 0.073) P≤ 0.001] and total cholesterol [0.085 (95% CI 0.002 to 0.167); P=0.044] in regression analysis. Conclusions: These results indicate a high prevalence of vitamin D deficiency during pregnancy, which requires identification and treatment; however, only weak associations were observed between 25‐hydroxyvitamin D level and markers of glucose and insulin metabolism. This would suggest that these are of doubtful clinical significance. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To compare blood pressure between 50-year-old adults who were born at term (37-42 weeks of gestation) with intra-uterine growth restriction (IUGR; birth weight <10th centile) and a control group of similar age born at term without IUGR (birth weight ≥ 10th centile). Study design: Controlled comparative study. Methods: Participants included 232 men and women who were born at the Royal Maternity Hospital, Belfast, a large regional maternity hospital in Northern Ireland, between 1954 and 1956. One hundred and eight subjects who were born with IUGR were compared with 124 controls with normal birth weight for gestation. The main outcome measures were systolic and diastolic blood pressure at approximately 50 years of age, measured according to European recommendations. Results: The IUGR group had higher systolic and diastolic blood pressure than the control group: 131.5 [95% confidence interval (CI) 127.9-135.1] vs 127.1 (95% CI 124.3-129.2) mmHg and 82.3 (95% CI 79.6-85.0) vs 79.0 (95% CI 77.0-81.0) mmHg, respectively. After adjustment for gender, the differences between the groups were statistically significant: systolic blood pressure 4.5 (95% CI 0.3-8.7) mmHg and diastolic blood pressure 3.4 (95% CI 0.2-6.5) mmHg (both P < 0.05). More participants in the IUGR group were receiving treatment for high blood pressure compared with the control group [16 (15%) vs 11 (9%)], although this was not statistically significant. The proportion of subjects with blood pressure >140/90 mmHg or currently receiving antihypertensive treatment was 45% (n - 49) for the IUGR group, and 31% (n 38) for the control group (odds ratio 1.9, 95% CI 1.1-3.3). Adjustment for potential confounders made little difference. Conclusions: IUGR is associated with higher blood pressure at 50 years of age. Individuals born with IUGR should have regular blood pressure screening and early treatment as required. Hypertension remains underdiagnosed and undertreated in adult life. [ABSTRACT FROM AUTHOR]

Diabet. Med. 27, 143–149 (2010) Aims Macrophage migration inhibitory factor (MIF) is a potent pro-inflammatory cytokine whose production is transcriptionally regulated by glucose. Experimental data from both Type 1 diabetes mellitus (T1D) patients and animal models suggests a role for MIF in the development of T1D. The aim of this study was to employ gene resequencing to identify common DNA polymorphisms in the MIF gene and subsequently assess haplotype tagged single nucleotide polymorphisms (htSNPs) using a combination of case–control and family-based association analyses in order to assess the association of MIF htSNPs with the development of T1D in a white population. Methods All exons, introns and approximately 3 kb upstream and downstream of the MIF gene were screened for DNA polymorphisms in 46 individuals using DNA sequencing. Genotyping of the htSNPs was performed in 432 cases, 407 control subjects and 290 T1D parent–offspring trios, using Taqman, Sequenom, Pyrosequencing and fluorescence-based microsatellite technologies. Results Twenty-three polymorphisms (two novel) with a minor allele frequency > 10% were identified. Four MIF htSNPs (rs875643 G>A, rs7388067 C>T, rs5844572 −/CATT, rs6003941 T>G) were identified. Allele and haplotype frequencies were similar between case and control groups ( P > 0.6 by permutation test) and assessment of allele transmission distortion from informative parents to affected offspring also failed to find an association. Stratification of these analyses for age-at-onset and human leukocyte antigen (HLA)-DR risk group (DR3/DR4) did not reveal any significant associations. Conclusions It is unlikely that common polymorphisms in the MIF gene strongly influence susceptibility to T1D in the UK population. [ABSTRACT FROM AUTHOR]