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The aim of this study was to describe the mortality risk after calcaneal fractures which required internal fixation and evaluate predictors of survival. During the observed 11-year period (1995–2006), 178 consecutive patients underwent operative fixation for displaced intra-articular calcaneal fractures. Patient demographics, mechanism of injury, and social deprivation (Carstairs index) were recorded. Mortality was obtained from patient notes. Causes of mortality were obtained from the national database. Standardised mortality ratios (SMRs) were calculated. Ten patients were lost to follow-up. Of the remaining 168 patients, the mean age was 41 (range 14–77) years. Females [n = 33, 46.3 standard deviation (SD) 17.1 years] were significantly (difference 6.5 years, 95% CI 1.1–11.9, p = 0.02) older than male patients (n = 135, 39.8 SD 13.4 years). During the study period, 28 patients died. The overall unadjusted survival rate was 92.8% (95% CI 87.0–98.7) at 10 years and 81.9% (95% CI 76.2–87.6) at 15 years. The SMR at 10 years was 5.2 (95% CI 2.8–13.3) for males and 1.4 (95% CI − 4.9 to 7.8) for females. Cox regression analysis demonstrated male gender to be a significant predictor of mortality (hazard ratio 2.77, 95% 3.83–9.65, p = 0.01) adjusted for age and social deprivation. Male patients requiring internal fixation of intra-articular calcaneal fractures have a significantly increased mortality risk compared to an age- and gender-matched population. Further study is warranted to fully identify the reasons behind this, which may enable their survival to be improved. Level of evidence Retrospective Cohort study, Level 4. [ABSTRACT FROM AUTHOR]

We have developed a new approach to determine the threshold of a biomarker that maximizes the classification accuracy of a disease. We consider a Bayesian estimation procedure for this purpose and illustrate the method using a real data set. In particular, we determine the threshold for Apolipoprotein B (ApoB), Apolipoprotein A1 (ApoA1) and the ratio for the classification of myocardial infarction (MI). We first conduct a literature review and construct prior distributions. We then develop classification rules based on the posterior distribution of the location and scale parameters for these biomarkers. We identify the threshold for ApoB and ApoA1, and the ratio as 0.908 (gram/liter), 1.138 (gram/liter) and 0.808, respectively. We also observe that the threshold for disease classification varies substantially across different age and ethnic groups. Next, we identify the most informative predictor for MI among the three biomarkers. Based on this analysis, ApoA1 appeared to be a stronger predictor than ApoB for MI classification. Given that we have used this data set for illustration only, the results will require further investigation for use in clinical applications. However, the approach developed in this article can be used to determine the threshold of any continuous biomarker for a binary disease classification. [ABSTRACT FROM PUBLISHER]

Purpose: The aim of this study in adult patients with a distal radial fracture was to determine whether socioeconomic status influenced the epidemiology, mechanism of injury, fracture severity, or the outcome according to function, radiographic assessment, and rate of associated complications. Methods: We identified 3983 distal radial fractures over a 7-year period. Socioeconomic status was assigned using the Carstairs score, and the population was divided into quintiles depending on deprivation. Patient demographics, mechanism of injury, fracture severity, and radiographic assessment at time of injury were assessed for epidemiological differences according to social quintile. Functional outcome was assessed using grip strength, Moberg pickup test, return to normal use of the hand, and range of movement. Radiographs were assessed at 1 week, 6 weeks, and 1 year. Complications were defined as malunion, carpal tunnel syndrome, complex regional pain syndrome (CRPS), persistent pain, and subjective cosmetic deformity of the wrist. Results: Socioeconomically deprived patients were significantly younger ( p < 0.001) and more likely to be male ( p = 0.017); after adjusting for confounding factors, deprived patients were 3.1 (95% CI 1.4-4.7) years younger than the most affluent patients ( p < 0.001). Deprived patients were more likely to sustain their fracture by a high-energy mechanism ( p = 0.004). There were no significant differences between quintiles in outcome. There was a significantly greater prevalence of CRPS in more affluent patients ( p = 0.004). Conclusions: Socioeconomically deprived patients sustaining a distal radial fracture are more likely to be younger and male. Outcome is not influenced by socioeconomic status, but the prevalence of CRPS is greater in more affluent patients. [ABSTRACT FROM AUTHOR]

Summary: Data were gathered with regard to mortality after fractures in 1006 younger patients. Results revealed that major osteoporotic fractures of the hip and humerus and drinking alcohol to excess were related to an increased risk of mortality. Introduction: Major osteoporotic fractures are known to be associated with increased mortality in older individuals. It is less clear whether this also applies to younger patients. Methods: Date were gathered regarding patient demographics, fracture pattern, mechanism of injury, as well as smoking and alcohol intake at the time of injury in consecutive patients aged between 40 and 55 who presented to a UK trauma centre over a 12-month period. Mortality data was taken from the electronic patient records and was cross referenced with data from the General Registrar Office of Scotland. Cox regression analysis was used to identify independent predictors of mortality after adjusting for confounding factors. Results: The study cohort consisted of 1006 patients, of which 53% were male. The commonest mechanism of injury was a fall. We obtained complete data regarding mortality for all patients at a median of 5.4 years (inter-quartile range 5.1 to 5.6). During this period, 46 patients were identified as being deceased. The overall standardised mortality ratio for the cohort was substantially increased relative to the age and sex matched general population with a ratio of 3.89 (95% confidence intervals (CI) 1.59 to 6.19). Alcohol excess and fractures involving the humerus and the neck of femur were independent predictors of mortality. Conclusions: Young individuals with hip and humerus fractures have a significantly increased mortality risk after their injury relative to the general population. The results of our study suggest that this may be in part due to a high prevalence of alcohol excess. [ABSTRACT FROM AUTHOR]

Delay in the diagnosis of acute compartment syndrome (ACS) has serious and sometimes catastrophic consequences for the outcome of injury, and has been recognised as one of the primary causes of a poor outcome. This article reviews the evidence for the use of clinical findings and intra-compartmental pressure (ICP) monitoring in making a prompt diagnosis of ACS. Clinical findings have poor sensitivities (13-64 %) compared to ICP monitoring (94 %) using a differential pressure threshold of less than 30 mmHg for more than 2 h. The specificities of clinical findings range from 63 to 98 % compared to a value of 98 % for ICP monitoring. Patients at risk of ACS or at risk of a delayed diagnosis are defined, and it is recommended that these patients undergo ICP monitoring. It is recommended that decompression is carried out primarily on the basis of the differential pressure being less than 30 mmHg for more than 2 h as this results in a reduced time to definitive treatment when compared to waiting for the development of clinical symptoms and signs. [ABSTRACT FROM AUTHOR]

We present the epidemiology and incidence of proximal humeral fractures over a 17-year period for a defined urban population that represents approximately 13 % of the population in Scotland, and functional outcome in relation to the socio-economic status of the patient. The incidence of proximal humeral fractures significantly increased during the study period from 47.9/10/year to 98.7/10/year in 2008 ( p < 0.0001), which was greatest for the most socially deprived patients reaching 274.2/10/year in 2008 ( p < 0.0001). The most deprived patients sustained their fracture 4 years earlier than the most affluent patients ( p = 0.026). Social deprivation was an independent predictor, after adjusting for other confounding variables using multivariable regression analysis, of a significantly worse functional outcome according to the Constant score at 1 year ( p = 0.046). Preventative measures, especially for the most socially deprived patients within society, need to be instigated urgently to address the increasing incidence of proximal humeral fractures and alleviate the burden of these morbid fractures in the future. Whether the observed increased incidence is generalisable to a national population would need to be confirmed in future studies. [ABSTRACT FROM AUTHOR]

Superelderly patients (≥80 years old) account for 20% of all distal radial fractures and are at an increased risk of malunion. The primary aim of this study was to identify predictors of malunion and the degree of improvement in the fracture position offered by closed manipulation of displaced distal radial fractures in the superelderly. We retrospectively identified 228 displaced distal radial fractures in superelderly patients from a prospective database of 4024 distal radial fractures. The inclusion criterion was a patient that underwent closed manipulation as their primary intervention. The majority of patients (P = 196, 86%) were defined as having a malunion. A premanipulation dorsal angulation of greater than 25 degrees (P = 0.047) and an ulnar variance of 6mm or more (P = 0.02) significantly increased the risk ofmalunion. The premanipulation dorsal angulation was a significant independent predictor of the degree of improvement in the final dorsal angulation (P < 0.001) and ulnar variance (P = 0.01). Patients with a high risk of malunion or poor improvement in the fracture position can be identified before manipulation and these patients may benefit from primary surgical intervention. [ABSTRACT FROM AUTHOR]

Purpose. The management of unstable distal radial fractures in the superelderly (≥80 years old) remains controversial. The aim of this study was to compare the functional outcome of super-elderly patients with and without malunion after a distal radial fracture. Methods. We identified 51 superelderly patients living independently with displaced fractures from a prospective database of 4024 patients with distal radial fractures. Activities of daily living, presence of wrist pain, whether the wrist had returned to its normal level function, grip strength and ROM were recorded. The dorsal angulation was measured radiographically. Results. There were 17 (33.3%) patients defined to have a malunion. The outcomes of the independent patients with and without malunion were compared at a mean follow-up of 15 months. No difference was observed in activities of daily living (P = 0.28), wrist pain (P = 0.14), whether the wrist had returned to its normal level function (P = 0.25), grip strength (P = 0.31), or ROM (P = 0.41). An increasing degree of dorsal angulation correlated with diminished ROM (P = 0.038), but did not correlate with activities of daily living (P = 0.10). Conclusions. Malunion of the distal radius does not influence the functional outcome of independent superelderly patients. [ABSTRACT FROM AUTHOR]

Purpose. The management of unstable distal radial fractures in the superelderly (>80 years old) remains controversial. The aim of this study was to compare the functional outcome of super-elderly patients with and without malunion after a distal radial fracture. Methods. We identified 51 superelderly patients living independently with displaced fractures from a prospective database of 4024 patients with distal radial fractures. Activities of daily living, presence of wrist pain, whether the wrist had returned to its normal level function, grip strength and ROM were recorded. The dorsal angulation was measured radiographically. Results. There were 17 (33.3%) patients defined to have a malunion. The outcomes of the independent patients with and without malunion were compared at a mean follow-up of 15 months. No difference was observed in activities of daily living (P = 0.28), wrist pain (P = 0.14), whether the wrist had returned to its normal level function (P = 0.25), grip strength (P = 0.31), or ROM (P = 0.41). An increasing degree of dorsal angulation correlated with diminished ROM (P = 0.038), but did not correlate with activities of daily living (P = 0.10). Conclusions. Malunion of the distal radius does not influence the functional outcome of independent superelderly patients. [ABSTRACT FROM AUTHOR]

Purpose. The management of unstable distal radial fractures in the superelderly (>80 years old) remains controversial. The aim of this study was to compare the functional outcome of super-elderly patients with and without malunion after a distal radial fracture. Methods. We identified 51 superelderly patients living independently with displaced fractures from a prospective database of 4024 patients with distal radial fractures. Activities of daily living, presence of wrist pain, whether the wrist had returned to its normal level function, grip strength and ROM were recorded. The dorsal angulation was measured radiographically. Results. There were 17 (33.3%) patients defined to have a malunion. The outcomes of the independent patients with and without malunion were compared at a mean follow-up of 15 months. No difference was observed in activities of daily living (P = 0.28), wrist pain (P = 0.14), whether the wrist had returned to its normal level function (P = 0.25), grip strength (P = 0.31), or ROM (P = 0.41). An increasing degree of dorsal angulation correlated with diminished ROM (P = 0.038), but did not correlate with activities of daily living (P = 0.10). Conclusions. Malunion of the distal radius does not influence the functional outcome of independent superelderly patients. [ABSTRACT FROM AUTHOR]

Nicotine binds to nicotinic acetylcholine receptors and studies in animal models have shown that α4β2 receptors mediate many behavioral effects of nicotine. Human genetics studies have provided support that variation in the gene that codes for the α4 subunit influences nicotine dependence ( ND), but the evidence for the involvement of the β2 subunit gene is less convincing. In this study, we examined the genetic association between variation in the genes that code for the α4 ( CHRNA4) and β2 ( CHRNB2) subunits of the nicotinic acetylcholine receptor and a quantitative measure of lifetime DSM-IV ND symptom counts. We performed this analysis in two longitudinal family-based studies focused on adolescent antisocial drug abuse: the Center on Antisocial Drug Dependence (CADD, N = 313 families) and Genetics of Antisocial Drug Dependence (GADD, N = 111 families). Family-based association tests were used to examine associations between 14 single nucleotide polymorphisms ( SNPs) in CHRNA4 and CHRNB2 and ND symptoms. Symptom counts were corrected for age, sex and clinical status prior to the association analysis. Results, when the samples were combined, provided modest evidence that SNPs in CHRNA4 are associated with ND. The minor allele at both rs1044394 (A; Z = 1.988, P = 0.047, unadjusted P-value) and rs1044396 (G; Z = 2.398, P = 0.017, unadjusted P-value) was associated with increased risk of ND symptoms. These data provide suggestive evidence that variation in the α4 subunit of the nicotinic acetylcholine receptor may influence ND liability. [ABSTRACT FROM AUTHOR]

Summary: The relationship between fall-related fractures and social deprivation was studied in 3,843 patients. The incidence of fractures correlated with deprivation in all age groups although the spectrum of fractures was not affected by deprivation. The average age and the prevalence of hip fractures decreased with increasing deprivation. Introduction: This study examines the relationship between social deprivation and fall-related fractures. Social deprivation has been shown to be a predisposing factor in a number of diseases. There is evidence that it is implicated in fractures in children and young adults, but the evidence that it is associated with fragility fractures in older adults is weak. As fragility fractures are becoming progressively more common and increasingly expensive to treat, the association between social deprivation and fractures is important to define. Methods: All out-patient and in-patient fractures presenting to the Royal Infirmary of Edinburgh over a 1-year period were prospectively recorded. The fractures caused by falls from a standing height were analysed in all patients of at least 15 years of age. Social deprivation was assessed using the Carstairs score and social deprivation deciles, and the 2001 census was used to calculate fracture incidence. The data were used to analyse the relationship between social deprivation and fall-related fractures in all age groups. Results: The incidence of fall-related fractures correlated with social deprivation in all age groups including fragility fractures in the elderly. The overall spectrum of fractures was not affected by social deprivation although the prevalence of proximal femoral fractures decreased with increasing deprivation. The average age of patients with fall-related fractures also decreased with increasing social deprivation as did the requirement for in-patient treatment. Conclusions: This is the first study to show the relationship between fall-related fractures and social deprivation in older patients. We believe that the decreased incidence of proximal femoral fractures, and the lower average age of patients with fall-related fractures, in the socially deprived relates to the relative life expectancies in the different deprivation deciles. [ABSTRACT FROM AUTHOR]

ims/hypothesis: Although diabetes is an established risk factor for myocardial infarction (MI), disease control may vary. HbA is a reliable index of ambient glucose levels and may provide more information on MI risk than diabetes status. Methods: The relationship between HbA levels in MI patients and controls who participated in the 52 country INTERHEART study was analysed. Results: In 15,780 participants with a HbA value (1,993 of whom had diabetes), the mean (SD) levels for HbA were 6.15% (1.10) in the 6,761 MI patients and 5.85% (0.80) in the control participants. After adjustment for age, sex and nine major MI risk factors (including diabetes), higher HbA fifths above the lowest fifth (HbA <5.4%) were associated with progressively higher OR of MI, with OR for the highest HbA fifth (≥6.12%) being 1.55 (95% CI 1.37-1.75). When analysed as a continuous variable after adjustment for the same factors, every 1% higher HbA value was associated with 19% (95% CI 14-23) higher odds of MI, while every 0.5% higher HbA was associated with 9% higher odds of MI (95% CI 7-11). Concordant relationships were noted across subgroups, with a higher OR noted in younger people, patients without diabetes or hypertension, and those from some regions and ethnicities. Conclusions/interpretation: The HbA value provides more information on MI odds than self-reported diabetes status or many other established risk factors. Every 1% increment independently predicts a 19% higher odds of MI after accounting for other MI risk factors including diabetes. [ABSTRACT FROM AUTHOR]

The CHRNA6 and CHRNB3 genes have been associated with nicotine dependence and early subjective response to nicotine. Here we present evidence, using a nationally representative sample of adults, that this region is also associated with alcohol behaviors. Six SNPs (single nucleotide polymorphisms) spanning the CHRNB3/A6 genes were analyzed using the statistical genetics software FBAT-PC, which allows one to examine a collection of multiple phenotypes to generate a maximally heritable composite phenotype for each SNP. The six SNPs were tested using FBAT-PC including four alcohol phenotypes: average number of drinks, blackouts, total number of DSM-IV abuse and dependence symptoms endorsed, and quit attempts. Three SNPs in CHRNA6 (rs1072003, P = 0.015; rs892413, P = 0.0033 and rs2304297, P = 0.012) and one SNP in CHRNB3 (rs13280604, P = 0.0053) were associated with a composite of the alcohol phenotypes. The association was primarily driven by the average number of drinks. [ABSTRACT FROM AUTHOR]

We performed a genome-wide association scan in 1461 patients with bipolar (BP) 1 disorder, 2008 controls drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder and the University College London sample collections with successful genotyping for 372 193 single nucleotide polymorphisms (SNPs). Our strongest single SNP results are found in myosin5B (MYO5B; P=1.66 × 10−7) and tetraspanin-8 (TSPAN8; P=6.11 × 10−7). Haplotype analysis further supported single SNP results highlighting MYO5B, TSPAN8 and the epidermal growth factor receptor (MYO5B; P=2.04 × 10−8, TSPAN8; P=7.57 × 10−7 and EGFR; P=8.36 × 10−8). For replication, we genotyped 304 SNPs in family-based NIMH samples (n=409 trios) and University of Edinburgh case–control samples (n=365 cases, 351 controls) that did not provide independent replication after correction for multiple testing. A comparison of our strongest associations with the genome-wide scan of 1868 patients with BP disorder and 2938 controls who completed the scan as part of the Wellcome Trust Case–Control Consortium indicates concordant signals for SNPs within the voltage-dependent calcium channel, L-type, alpha 1C subunit (CACNA1C) gene. Given the heritability of BP disorder, the lack of agreement between studies emphasizes that susceptibility alleles are likely to be modest in effect size and require even larger samples for detection.Molecular Psychiatry (2008) 13, 558–569; doi:10.1038/sj.mp.4002151; published online 4 March 2008 [ABSTRACT FROM AUTHOR]

OBJECTIVE: Impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG) are risk factors for diabetes, cardiovascular disease (CVD), and kidney disease. We determined the effects of ramipril and rosiglitazone on combined and individual CVD and renal outcomes in people with IGT and/or IFG in the Diabetes REduction Assessment With ramipril and rosiglitazone Medication (DREAM) trial. RESEARCH DESIGN AND METHODS: A total of 5,269 people aged >or=30 years, with IGT and/or IFG without known CVD or renal insufficiency, were randomized to 15 mg/day ramipril versus placebo and 8 mg/day rosiglitazone versus placebo. A composite cardiorenal outcome and its CVD and renal components were assessed during the 3-year follow-up. RESULTS: Compared with placebo, neither ramipril (15.7% [412 of 2,623] vs. 16.0% [424 of 2,646]; hazard ratio [HR] 0.98 [95% CI 0.84-1.13]; P = 0.75) nor rosiglitazone (15.0% [394 of 2,635] vs. 16.8% [442 of 2,634]; 0.87 [0.75-1.01]; P = 0.07) reduced the risk of the cardiorenal composite outcome. Ramipril had no impact on the CVD and renal components. Rosiglitazone increased heart failure (0.53 vs. 0.08%; HR 7.04 [95% CI 1.60-31.0]; P = 0.01) but reduced the risk of the renal component (0.80 [0.68-0.93]; P = 0.005); prevention of diabetes was independently associated with prevention of the renal component (P < 0.001). CONCLUSIONS: Ramipril did not alter the cardiorenal outcome or its components. Rosiglitazone, which reduced diabetes, also reduced the development of renal disease but not the cardiorenal outcome and increased the risk of heart failure. [ABSTRACT FROM AUTHOR]

The introduction of waiting list initiatives and targets has resulted in the concentration of resources in politically important medical disciplines. This has inevitably meant that other medical disciplines, many of which involve emergency or unplanned admissions, have diminished resources. We believe that both the scale of this problem and the number of emergency or unplanned admissions to Scottish hospitals are underestimated. An analysis of the surgical mortality in Scotland between April 2004 and March 2005 was undertaken and the prevalence of emergency and unplanned admissions in the different surgical disciplines in different areas of Scotland was calculated. It is apparent that about 40% of all surgical admissions in Scotland are emergency or unplanned admissions with about 70% being in general or orthopaedic surgery. About half of all admissions in neurosurgery, paediatric surgery, general surgery, orthopaedic surgery and cardiothoracic surgery are emergency or unplanned admissions. The numbers of emergency and unplanned admissions are much greater than is appreciated by many surgeons, managers and politicians. Recent changes in working hours, staffing levels and training have proved detrimental to the provision of good care for these patients. This situation is likely to worsen as the population ages and there are more emergency admissions. We believe that increasing centralisation is required in the major surgical disciplines if future problems are to be avoided. [ABSTRACT FROM AUTHOR]

The introduction of waiting list initiatives and targets has resulted in the concentration of resources in politically important medical disciplines. This has inevitably meant that other medical disciplines, many of which involve emergency or unplanned admissions, have diminished resources. We believe that both the scale of this problem and the number of emergency or unplanned admissions to Scottish hospitals are underestimated. An analysis of the surgical mortality in Scotland between April 2004 and March 2005 was undertaken and the prevalence of emergency and unplanned admissions in the different surgical disciplines in different areas of Scotland was calculated. It is apparent that about 40% of all surgical admissions in Scotland are emergency or unplanned admissions with about 70% being in general or orthopaedic surgery. About half of all admissions in neurosurgery, paediatric surgery, general surgery, orthopaedic surgery and cardiothoracic surgery are emergency or unplanned admissions. The numbers of emergency and unplanned admissions are much greater than is appreciated by many surgeons, managers and politicians. Recent changes in working hours, staffing levels and training have proved detrimental to the provision of good care for these patients. This situation is likely to worsen as the population ages and there are more emergency admissions. We believe that increasing centralisation is required in the major surgical disciplines if future problems are to be avoided. [ABSTRACT FROM AUTHOR]

Background: Effective methods of treating an unstable distal radial fracture are described in the literature, but there is no reliable method of identifying an unstable fracture in time to initiate appropriate treatment. The purposes of this study were to identify the predictors of fracture instability and to construct a method of prospectively predicting the radiographic outcome.Methods: Data on approximately 4000 distal radial fractures were prospectively recorded over a 5.5-year period. The database was validated by reexamining a sample of it. Demographic data on the patients and mode of injury, as well as the fracture classification and measurements, were recorded at the time of presentation. Outcome measures consisted of radiographic measurements made at one week and six weeks and assessment of carpal alignment at six weeks. Univariate and multiple logistic regression analyses were performed to identify the significance of the data obtained at presentation in the prediction of early and late instability as well as the risk of malunion and carpal malalignment.Results: The predictors of early and late instability and malunion differed according to the displacement of the fracture at presentation. Patient age, metaphyseal comminution of the fracture, and ulnar variance were the most consistent predictors of radiographic outcome. Dorsal angulation was not found to be significant in the prediction of radiographic outcome for displaced fractures. The degree to which the patient was independent was predictive of malunion in minimally displaced and displaced fractures. Formulas that are predictive of each of the seven radiographic outcome measurements were constructed.Conclusions: The study succeeded in identifying the factors that are prognostic of the radiographic outcome for distal radial fractures. Formulas to predict the radiographic outcome were constructed as the independent prognostic significance of these factors was quantified. These formulas can be used to inform the surgeon's decision about the nature of primary treatment of fractures of the distal aspect of the radius. However, they must be validated by further studies before they are used to impact the management of distal radial fractures.Level Of Evidence: Prognostic Level I. [ABSTRACT FROM AUTHOR]

Objectives: Several studies suggested chromosome 12 harbours an Alzheimer's disease (AD) risk factor gene. Significant association of a single nucleotide polymorphism (SNP) in the 3′ UTR of transcription factor CP2 (LBP-1c/CP2/LSF or TFCP2) at 12q1 3 was reported in three independent case-control studies, but no family based analyses have been performed to date. Methods: Genotypes for three SNPs were generated in two independent AD family samples. A meta-analysis on all published case-control studies was also performed. Results: The A allele of the 3′ UTR SNP was associated with increased risk for AD in one sample (odds ratio (OR) 2.1, 95% confidence interval (95% CI) 1.1 to 4.3), but not in the other, possibly due to low power. Haplotype analyses showed that this allele is part of a putative risk-haplotype overtransmitted to affected individuals in one sample and in bath samples combined. Meta-analysis of the previously associated 3′ UTR SNP showed a trend towards a protective effect of the A allele in AD (OR 0.73, 95% CI 0.5 to 1.1). Conclusions: This is the first study to examine LBP-1c/CP2/LSF in AD families, and the fifth to independently show significant association. While our results support a role of this gene in AD pathogenesis, the direction of the effect remains uncertain, possibly indicating linkage disequilibrium with another variant nearby. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Emerging data suggest that different indices of glycaemia are risk factors for clinical events. The aim of this analysis was to investigate the relationship between fasting plasma glucose or glycated haemoglobin (GHb) levels and incident cardiovascular (CV) outcomes, death, heart failure and overt nephropathy in diabetic and non-diabetic individuals enrolled in the Heart Outcomes Prevention Evaluation (HOPE) study. Materials and methods: The adjusted 4.5-year risk of CV events (myocardial infarction or stroke or CV death), heart failure, death and overt nephropathy was analysed in relation to baseline and updated GHb levels (in 3,529 diabetic HOPE study participants) and baseline fasting plasma glucose levels (in 1,937 non-diabetic and 1,013 diabetic participants). Results: In diabetic participants, a 1% absolute rise in the updated GHb predicted future CV events (relative risk [RR]=1.07, 95% CI 1.01–1.13; p=0.014), death (RR=1.12, 95% CI 1.05–1.19; p=0.0004), heart failure (RR=1.20, 95% CI 1.08-1.33; p=0.0008) and overt nephropathy (RR=1.26, 95% CI 1.17–1.36; p«0.0001) after adjusting for age, sex, diabetes duration, blood pressure, WHR, hyperlipidaemia and ramipril. Similarly, a 1 mmol/l rise in fasting plasma glucose was related to an increased risk of CV outcomes (RR=1.09, 95% CI 1.05–1.13; p«0.0001), death (RR=1.06, 95%CI 1.01–1.12; p=0.017), heart failure (RR=1.16, 95% CI 1.06–1.13; p=0.0007) and overt nephropathy (RR=1.34, 95% CI 1.23–1.45; p«0.0001) in the group composed of diabetic and non-diabetic individuals. The significant relationship between fasting plasma glucose and CV outcomes persisted after adjustment for diabetes status (RR=1.06, 95% CI 1.00–1.12; p=0.043). Conclusions/interpretation: There is an independent progressive relationship between indices of glycaemia and incident CV events, renal disease and death. Clinical trials of glucose lowering to prevent these outcomes in diabetic and non-diabetic individuals are indicated. [ABSTRACT FROM AUTHOR]

The HOPE study was a 19 country, prospective randomized trial in which the ACE‐inhibitor Ramipril but not Vitamin E significantly reduced the risk of future cardiovascular events in a high‐risk population of men and women, including many with diabetes. The benefits were present in all sub‐groups, independent of the presence or absence of diabetes, hypertension, evidence of cardiovascular disease, microalbuminuria, blood pressure lowering, the use of aspirin, lipid‐lowering or antihypertensive medication. It provided clear evidence that Ramipril should safely and cost‐effectively be used in individuals not known to have low ventricular ejection fraction or heart failure but at high‐risk of cardiovascular events. It was also beneficial in patients with renal insufficiency, reducing progression of proteinuria and development of new microalbuminuria. It provided micro‐ and macrovascular benefits in people with diabetes, reduced the development of new cases of diabetes and showed a positive and graded association between the waist‐to‐hip ratio and the risk of developing diabetes. Sub‐studies completed and on‐going into the predictive role of natriuretic peptides, infectious and inflammatory markers, provide insight into possible mechanisms of action of Ramipril. [ABSTRACT FROM AUTHOR]

Since the middle of the1990s the EU has vigorously pursued a policy of replacing non– reciprocal preferences for the developing countries in the Mediterranean, Latin America and with South Africa, with bilateral free–trade agreements. This article examines the content of these agreements and the empirical evidence on their likely effects and concludes that they are ‘broad’ but ‘shallow’ agreements. The static effect are likely to be very small or negative while the potential dynamic gains are problematic, especially regarding the concept of a ‘lock in’ to trade liberalisation, unless there are greater commitments to trade related issues by both sides and especially by the EU. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Anaesthetists' Society Journal is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Canadian Anaesthetists' Society Journal is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)