Impact of preeclampsia on cardiovascular events: an analysis of the Generation Scotland: Scottish Family Health Study

Preeclampsia is a recognised cause of an increased risk of major adverse cardiovascular events when compared to the background risk in women who did not have hypertensive disorders during pregnancy. The Generation Scotland: Scottish Family Health Study (GS:SFHS) is a population cohort of more than 20,000 members of the Scottish population. Using the Scottish Morbidity Records, we linked the women in the GS:SFHS cohort to validated maternity and inpatient admission data. This allowed us to robustly identify cardiovascular outcomes in the form of inpatient admission for cardiovascular events, We also aimed to explore the risk of pregnancy on future cardiovascular events, using data from nulliparous and parous women.In total, 9732 women were selected. 3693 women were nulliparous, and after study exclusion, 5253 women with 9583 pregnancies remained. Pregnancies from 1980 until the end of the study period of 1st of July 2013 were included. Cardiovascular events occurred in 9.0% of nulliparous women, 4.2% of women with pregnancies and in 7.6% of women with a history of preeclampsia. A total of 218 parous women experienced cardiovascular events, 25 in the preeclampsia group and 193 in the normotensive group.Survival analysis was undertaken, with index pregnancy taken as first pregnancy in normotensive controls and first preeclampsia pregnancy in cases. Endpoint of interest was admission to hospital with first cardiovascular event. After further exclusions a total of 169 cardiovascular events occurred in the normotensive pregnancy group and 20 in the preeclampsia group. Women with a history of preeclampsia were more likely to have cardiovascular events later in life than women with normotensive deliveries., This was statistically significantly different on Kaplan Meier survival analysis, (log rank Mantel-Cox p-value < 0.001). The women in our study were middle-aged, within 33 years of pregnancy, with a mean age of 53 years in the preeclampsia cardiovascular events group.Our study supports the urgent need for uniform guidelines and implementation to improve the health in women with this medical history. Increased awareness among the public of the cardiovascular risk associated with PE is vital to aid uptake of cardiovascular prevention programmes

Factors Influencing Men's Choice of and Adherence to Active Surveillance for Low-risk Prostate Cancer:A Mixed-method Systematic Review

Context: Despite support for active surveillance (AS) as a first treatment choice for men with low-risk prostate cancer (PC), this strategy is largely underutilised. Objective: To systematically review barriers and facilitators to selecting and adhering to AS for low-risk PC. Evidence acquisition: We searched PsychINFO, PubMed, Medline 2000-now, Embase, CINAHL, and Cochrane Central databases between 2002 and 2017 using the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. The Purpose, Respondents, Explanation, Findings and Significance (PREFS) and Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) quality criteria were applied. Forty-seven studies were identified. Evidence synthesis: Key themes emerged as factors influencing both choice and adherence to AS: (1) patient and tumour factors (age, comorbidities, knowledge, education, socioeconomic status, family history, grade, tumour volume, and fear of progression/side effects); (2) family and social support; (3) provider (speciality, communication, and attitudes); (4) healthcare organisation (geography and type of practice); and (5) health policy (guidelines, year, and awareness). Conclusions: Many factors influence men's choice and adherence to AS on multiple levels. It is important to learn from the experience of other chronic health conditions as well as from institutions/countries that are making significant headway in appropriately recruiting men to AS protocols, through standardised patient information, clinician education, and nationally agreed guidelines, to ultimately decrease heterogeneity in AS practice. Patient summary: We reviewed the scientific literature for factors affecting men's choice and adherence to active surveillance (AS) for low-risk prostate cancer. Our findings suggest that the use of AS could be increased by addressing a variety of factors such as information, psychosocial support, clinician education, and standardised guidelines. (C) 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved

Screening and brief intervention for obesity in primary care:cost-effectiveness analysis in the BWeL trial

This paper is closed access until 31 July 2019.Background: The Brief Intervention for Weight Loss Trial enrolled 1882 consecutively attending primary care patients who were obese and participants were randomised to physicians opportunistically endorsing, offering, and facilitating a referral to a weight loss programme (support) or recommending weight loss (advice). After one year, the support group lost 1.4 kg more (95%CI 0.9 to 2.0): 2.4 kg versus 1.0 kg. We use a cohort simulation to predict effects on disease incidence, quality of life, and healthcare costs over 20 years. Methods: Randomly sampling from the trial population, we created a virtual cohort of 20 million adults and assigned baseline morbidity. We applied the weight loss observed in the trial and assumed weight regain over four years. Using epidemiological data, we assigned the incidence of 12 weight-related diseases depending on baseline disease status, age, gender, body mass index. From a healthcare perspective, we calculated the quality adjusted life years (QALYs) accruing and calculated the incremental difference between trial arms in costs expended in delivering the intervention and healthcare costs accruing. We discounted future costs and benefits at 1.5% over 20 years. Results: Compared with advice, the support intervention reduced the cumulative incidence of weight-related disease by 722/100,000 people, 0.33% of all weight-related disease. The incremental cost of support over advice was £2.01million/100,000. However, the support intervention reduced health service costs by £5.86 million/100,000 leading to a net saving of £3.85 million/100,000. The support intervention produced 992 QALYs/100,000 people relative to advice. Conclusions: A brief intervention in which physicians opportunistically endorse, offer, and facilitate a referral to a behavioural weight management service to patients with a BMI of at least 30 kg/m2 reduces healthcare costs and improves health more than advising weight loss

Less than 10 percent of star formation in z=0.6 massive galaxies is triggered by major interactions

Both observations and simulations show that major tidal interactions or mergers between gas-rich galaxies can lead to intense bursts of starformation. Yet, the average enhancement in star formation rate (SFR) in major mergers and the contribution of such events to the cosmic SFR are not well estimated. Here we use photometric redshifts, stellar masses and UV SFRs from COMBO-17, 24 micron SFRs from Spitzer and morphologies from two deep HST cosmological survey fields (ECDFS/GEMS and A901/STAGES) to study the enhancement in SFR as a function of projected galaxy separation. We apply two-point projected correlation function techniques, which we augment with morphologically-selected very close pairs (separation <2 arcsec) and merger remnants from the HST imaging. Our analysis confirms that the most intensely star-forming systems are indeed interacting or merging. Yet, for massive (M* > 10^10 Msun) star-forming galaxies at 0.4<z<0.8, we find that the SFRs of galaxies undergoing a major interaction (mass ratios <1:4 and separations < 40 kpc) are only 1.80 +/- 0.30 times higher than the SFRs of non-interacting galaxies when averaged over all interactions and all stages of the interaction, in good agreement with other observational works. We demonstrate that these results imply that <10% of star formation at 0.4 < z < 0.8 is triggered directly by major mergers and interactions; these events are not important factors in the build-up of stellar mass since z=1.Comment: Submitted to ApJ. 41 pages, 11 figure

Molecular Monitoring after Autologous Stem Cell Transplantation and Preemptive Rituximab Treatment of Molecular Relapse; Results from the Nordic Mantle Cell Lymphoma Studies (MCL2 and MCL3) with Median Follow-Up of 8.5 Years

The main objectives of the present study were to monitor minimal residual disease (MRD) in the bone marrow of patients with mantle cell lymphoma (MCL) to predict clinical relapse and guide preemptive treatment with rituximab. Among the patients enrolled in 2 prospective trials by the Nordic Lymphoma Group, 183 who had completed autologous stem cell transplantation (ASCT) and in whom an MRD marker had been obtained were included in our analysis. Fresh samples of bone marrow were analyzed for MRD by a combined standard nested and quantitative real-time PCR assay for Bcl-1/immunoglobulin heavy chain gene (IgH) and clonal IgH rear-rangements. Significantly shorter progression-free survival (PFS) and overall survival (OS) was demonstrated for patients who were MRD positive pre-ASCT (54 patients) or in the first analysis post-ASCT (23 patients). The median PFS was only 20 months in those who were MRD-positive in the first sample post-ASCT, compared with 142 months in the MRD-negative group (PPeer reviewe

Screening and brief intervention for obesity in primary care: a parallel, two-arm, randomised trial

Background Obesity is a common cause of non-communicable disease. Guidelines recommend that physicians screen and offer brief advice to motivate weight loss through referral to behavioural weight loss programmes. However, physicians rarely intervene and no trials have been done on the subject. We did this trial to establish whether physician brief intervention is acceptable and effective for reducing bodyweight in patients with obesity. Methods In this parallel, two-arm, randomised trial, patients who consulted 137 primary care physicians in England were screened for obesity. Individuals could be enrolled if they were aged at least 18 years, had a body-mass index of at least 30 kg/m² (or at least 25 kg/m² if of Asian ethnicity), and had a raised body fat percentage. At the end of the consultation, the physician randomly assigned participants (1:1) to one of two 30 s interventions. Randomisation was done via preprepared randomisation cards labelled with a code representing the allocation, which were placed in opaque sealed envelopes and given to physicians to open at the time of treatment assignment. In the active intervention, the physician offered referral to a weight management group (12 sessions of 1 h each, once per week) and, if the referral was accepted, the physician ensured the patient made an appointment and offered follow-up. In the control intervention, the physician advised the patient that their health would benefit from weight loss. The primary outcome was weight change at 12 months in the intention-to-treat population, which was assessed blinded to treatment allocation. We also assessed asked patients’ about their feelings on discussing their weight when they have visited their general practitioner for other reasons. Given the nature of the intervention, we did not anticipate any adverse events in the usual sense, so safety outcomes were not assessed. This trial is registered with the ISRCTN Registry, number ISRCTN26563137. Findings Between June 4, 2013, and Dec 23, 2014, we screened 8403 patients, of whom 2728 (32%) were obese. Of these obese patients, 2256 (83%) agreed to participate and 1882 were eligible, enrolled, and included in the intention-to-treat analysis, with 940 individuals in the support group and 942 individuals in the advice group. 722 (77%) individuals assigned to the support intervention agreed to attend the weight management group and 379 (40%) of these individuals attended, compared with 82 (9%) participants who were allocated the advice intervention. In the entire study population, mean weight change at 12 months was 2·43 kg with the support intervention and 1·04 kg with the advice intervention, giving an adjusted difference of 1·43 kg (95% CI 0·89–1·97). The reactions of the patients to the general practitioners’ brief interventions did not differ significantly between the study groups in terms of appropriateness (adjusted odds ratio 0·89, 95% CI 0·75–1·07, p=0·21) or helpfulness (1·05, 0·89–1·26, p=0·54); overall, four ( Interpretation A behaviourally-informed, very brief, physician-delivered opportunistic intervention is acceptable to patients and an effective way to reduce population mean weight.</p

Genome-wide scan identifies CDH13 as a novel susceptibility locus contributing to blood pressure determination in two European populations

Hypertension is a complex disease that affects a large proportion of adult population. Although approximately half of the inter-individual variance in blood pressure (BP) level is heritable, identification of genes responsible for its regulation has remained challenging. Genome-wide association study (GWAS) is a novel approach to search for genetic variants contributing to complex diseases. We conducted GWAS for three BP traits [systolic and diastolic blood pressure (SBP and DBP); hypertension (HYP)] in the Kooperative Gesundheitsforschung in der Region Augsburg (KORA) S3 cohort (n = 1644) recruited from general population in Southern Germany. GWAS with 395 912 single nucleotide polymorphisms (SNPs) identified an association between BP traits and a common variant rs11646213 (T/A) upstream of the CDH13 gene at 16q23.3. The initial associations with HYP and DBP were confirmed in two other European population-based cohorts: KORA S4 (Germans) and HYPEST (Estonians). The associations between rs11646213 and three BP traits were replicated in combined analyses (dominant model: DBP, P = 5.55 × 10–5, effect –1.40 mmHg; SBP, P = 0.007, effect –1.56 mmHg; HYP, P = 5.30 × 10−8, OR = 0.67). Carriers of the minor allele A had a decreased risk of hypertension. A non-significant trend for association was also detected with severe family based hypertension in the BRIGHT sample (British). The novel susceptibility locus, CDH13, encodes for an adhesion glycoprotein T-cadherin, a regulator of vascular wall remodeling and angiogenesis. Its function is compatible with the BP biology and may improve the understanding of the pathogenesis of hypertension

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis