Socioeconomic deprivation as measured by the index of multiple deprivation and its association with low sex hormone binding globulin in women

ACKNOWLEDGEMENTS M.L., I.L. and A.H.H. participated in the study concept and design, acquisition of data, study analysis, interpretation of data, drafting of the manuscript. D.M. provided statistical expertise. R.D., A.J.H., and A.F. participated in the interpretation of data and critical revision of the manuscript.Peer reviewedPublisher PD

Pre-eclampsia is associated with a twofold increase in diabetes : a systematic review and meta-analysis

CSK and RH are funded by National Institute for Health Research Academic Clinical Fellowships. This study was supported by a grant from the North Staffs Heart Committee.Peer reviewedPublisher PD

Simultaneous identification of GSTP1 Ile105→Val105 and Ala114→Val114 substitutions using an amplification refractory mutation systempolymerase chain reactionassay: studies in patients with asthma

BACKGROUND: The glutathione S-transferase (GST) enzyme GSTP1 utilizes byproducts of oxidative stress. We previously showed that alleles of GSTP1 that encode the Ile105→Val105 substitution are associated with the asthma phenotypes of atopy and bronchial hyperresponsiveness (BHR). However, a further polymorphic site (Ala114→Val114) has been identified that results in the following alleles: GSTP1(*)A (wild-type Ile105→Ala114), GSTP1(*)B (Val105→Ala114), GSTP1(*)C (Val105→Val114) and GSTP1(*)D (Ile105→Val114). METHODS: Because full identification of GSTP1 alleles may identify stronger links with asthma phenotypes, we describe an amplification refractory mutation system (ARMS) assay that allows identification of all genotypes. We explored whether the GSTP1 substitutions influence susceptibility to asthma, atopy and BHR. RESULTS: Among 191 atopic nonasthmatic, atopic asthmatic and nonatopic nonasthmatic individuals, none had the BD, CD, or DD genotypes. GSTP1 BC was significantly associated with reduced risk for atopy (P = 0.031). Compared with AA, trend test analysis identified a significant decrease in the frequency of GSTP1 BC with increasing severity of BHR (P = 0.031). Similarly, the frequency of GSTP1 AA increased with increasing BHR. CONCLUSION: These data suggest that GSTP1(*)B and possibly GSTP1(*)C are protective against asthma and related phenotypes

Investigation of polycystic ovarian syndrome: variation in practice and impact on the speed of diagnosis

Objective Accurate diagnosis of polycystic ovarian syndrome (PCOS) enables clinical interventions/cardiometabolic risk factor management. Diagnosis can take over 2 years and multiple clinician contacts. We examined patterns of PCOS-associated biochemical investigations following initial consultation prior to pelvic ultrasound scan (USS). Methods We determined in 206 women (i) the range of different biochemical test panels used in the diagnosis of PCOS in primary/secondary care prior to USS relative to national guidance in the UK and (ii) the relation between testing patterns and time to USS to highlight potential delays introduced by inappropriate testing. Results In these 206 women, 47 different test combinations were requested at initial venepuncture; only 7 (3%) had the test panel suggested in UK guidance (follicle-stimulating hormone/luteinizing hormone/testosterone/sex hormone-binding globulin/prolactin). The number of tests performed prior to USS varied from one test to all seven tests. There was an inverse relation between the number of biochemistry tests requested at initial venepuncture episode and ‘time to scan’. Those who had <3 tests had a significantly longer time from first request to USS (median 70 days) than those with 3–7 tests (median 40 days; P = 0.002). One venepuncture episode prior to USS was associated with shorter ‘time to scan’ (median 29 days) than those with 2–4 episodes (median 255 days; P < 0.001). Conclusion There was no identifiable pattern to biochemical investigations requested as part of the initial diagnostic evaluation in women with suspected PCOS. We recommend standardization of the initial biochemical panel of analytes for PCOS workup, with incorporation into hospital/general practice ordering software systems

Adrenal lesions found incidentally: how to improve clinical and cost-effectiveness

Introduction Adrenal incidentalomas are lesions that are incidentally identified while scanning for other conditions. While most are benign and hormonally non-functional, around 20% are malignant and/or hormonally active, requiring prompt intervention. Malignant lesions can be aggressive and life-threatening, while hormonally active tumours cause various endocrine disorders, with significant morbidity and mortality. Despite this, management of patients with adrenal incidentalomas is variable, with no robust evidence base. This project aimed to establish more effective and timely management of these patients. Methods We developed a web-based, electronic Adrenal Incidentaloma Management System (eAIMS), which incorporated the evidence-based and National Health Service–aligned 2016 European guidelines. The system captures key clinical, biochemical and radiological information necessary for adrenal incidentaloma patient management and generates a pre-populated outcome letter, saving clinical and administrative time while ensuring timely management plans with enhanced safety. Furthermore, we developed a prioritisation strategy, with members of the multidisciplinary team, which prioritised high-risk individuals for detailed discussion and management. Patient focus groups informed process-mapping and multidisciplinary team process re-design and patient information leaflet development. The project was partnered by University Hospital of South Manchester to maximise generalisability. Results Implementation of eAIMS, along with improvements in the prioritisation strategy, resulted in a 49% reduction in staff hands-on time, as well as a 78% reduction in the time from adrenal incidentaloma identification to multidisciplinary team decision. A health economic analysis identified a 28% reduction in costs. Conclusions The system’s in-built data validation and the automatic generation of the multidisciplinary team outcome letter improved patient safety through a reduction in transcription errors. We are currently developing the next stage of the programme to proactively identify all new adrenal incidentaloma cases

Conservative formulations of general relativistic kinetic theory

Experience with core-collapse supernova simulations shows that accurate accounting of total particle number and 4-momentum can be a challenge for computational radiative transfer. This accurate accounting would be facilitated by the use of particle number and 4-momentum transport equations that allow transparent conversion between volume and surface integrals in both configuration and momentum space. Such conservative formulations of general relativistic kinetic theory in multiple spatial dimensions are presented in this paper, and their relevance to core-collapse supernova simulations is described.Comment: 48 page

Relationship between anemia and mortality outcomes in a national acute coronary syndrome cohort: Insights from the UK Myocardial Ischemia National Audit Project registry

Background: We aim to determine the prevalence of anemia in ACS patients and compared their clinical characteristics, management and clinical outcomes to those without anemia in an unselected national ACS cohort. Methods and Results: The Myocardial Ischemia National Audit Project (MINAP) registry collects data on all adults admitted to hospital trusts in England and Wales with diagnosis of an ACS. We conducted a retrospective cohort study by analyzing patients in this registry between January 2006 and December 2010 and followed them up until August 2011. Multiple logistic regressions were used to determine factors associated with anemia and the adjusted odds of 30-day mortality with 1 g/dl incremental hemoglobin increase and the 30-days and 1-year mortality for anemic compared to non-anemic groups. Analyses were adjusted for covariates. Our analysis of 422,855 patients with ACS showed that 27.7% of patients presenting with ACS are anemic, and that these patients are older, have a greater prevalence renal disease, peripheral vascular disease, diabetes mellitus and previous acute myocardial infarction and are less likely to receive evidence based therapies shown to improve clinical outcomes. Finally our analysis suggests that anemia is independently associated with 30-day (OR 1.28, 95%CI 1.22-1.35) and 1-year mortality (OR 1.31, 95%CI 1.27-1.35) and we observed a reverse J-shaped relationship between hemoglobin levels and mortality outcomes. Conclusion: The prevalence of anemia in a contemporary national ACS cohort is clinically significant. Patients with anemia are older and multi-morbid, and less likely to receive evidence-based therapies shown to improve clinical outcomes with the presence of anemia independently associated mortality outcomes

Monitoring drug interventions in people with bipolar disorder

'Editorial Material

Investigating cortisol excess or deficiency: a practical approach.

'No abstract

Genome-wide profiling in treatment-naive early rheumatoid arthritis reveals DNA methylome changes in T and B lymphocytes

AIM: Although aberrant DNA methylation has been described in rheumatoid arthritis (RA), no studies have interrogated this epigenetic modification in early disease. Following recent investigations of T- and B-lymphocytes in established disease, we now characterize in these cell populations genome-wide DNA methylation in treatment-naive patients with early RA. PATIENTS & METHODS: HumanMethylation450 BeadChips were used to examine genome-wide DNA methylation in lymphocyte populations from 23 early RA patients and 11 healthy individuals. RESULTS: Approximately 2000 CpGs in each cell type were differentially methylated in early RA. Clustering analysis identified a novel methylation signature in each cell type (150 sites in T-lymphocytes, 113 sites in B-lymphocytes) that clustered all patients separately from controls. A subset of sites differentially methylated in early RA displayed similar changes in established disease. CONCLUSION: Treatment-naive early RA patients display novel disease-specific DNA methylation aberrations, supporting a potential role for these changes in the development of RA