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Background: Donor interventions, including medications, protocols, and medical devices administered to donors, can enhance transplantable organ quality and quantity and maximize transplantation success. However, there is paucity of high-quality evidence about their effectiveness, in part because of ethical, practical, and regulatory challenges, and lack of guidance about conduct of donor intervention randomized controlled trials (RCTs)., Methods: With the vision to develop authoritative guidance for conduct of donor intervention RCTs, we convened a workshop of Canadian-United Kingdom experts in organ donation and transplantation ethics, research, and policy to identify stakeholders, explore unique challenges, and develop research agenda to inform future work in this promising field., Results: Donor intervention trials should consider perspectives of broad group of stakeholders including donors, transplant recipients, and their families; researchers in donation and transplantation; research ethics boards; and healthcare providers and administrators involved in donation and transplantation. Unique challenges include (1) research ethics (living versus deceased status of the donor at the time of intervention, intervention versus outcomes assessment in different individuals, harm-benefit analysis in donors versus recipients, consent, and impact on research bystanders); (2) outcome data standardization and linkage; and (3) regulatory and governance considerations., Conclusions: Donor intervention RCTs hold potential to benefit organ transplantation outcomes but face unique research ethics, outcome data, and regulatory challenges. By developing research agenda to address these challenges, our workshop was an important first step toward developing Canada-United Kingdom guidance for donor intervention RCTs that are poised to improve the quality and availability of transplantable organs., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Child sexual abuse (CSA) is an issue of epidemic proportions in the United Kingdom (UK) and an international public health problem. Evidence suggests that in the UK one in 20 children have been sexually abused, with one in three not telling anyone about it at the time of the abuse. Conservative estimates suggest that around one in six men have experienced sexual abuse before the age of 18. CSA has been correlated with the development of numerous mental health problems, abused men often displaying externalizing behaviours, including substance misuse, 'risky' sexual behaviours, anti-social behaviour, and offending. This article reports on one aspect of a research study focusing specifically on male survivors of CSA and its effect on their mental health. Using narrative research, face-to-face interviews were used to collect the stories of four men who participated in the research. Interviews were audio-recorded and transcribed verbatim. Analysis used a two-phase approach; initially, each narrative was analysed as a whole, with an across transcripts analysis then being carried out identifying shared themes emerging from the individual stories. Whilst findings from the second phase of the analysis identify four themes, it is the theme of 'Blocking the Memories' that is the focus for this article. Making a valuable contribution to existent knowledge regarding the experiences of men who were sexually abused as children, this article will help to inform mental health practitioners who are likely to deliver care to male survivors of CSA., (© 2022 The Authors. International Journal of Mental Health Nursing published by John Wiley & Sons Australia, Ltd.)

Importance: Plant-based diets have gained popularity for both environmental and health reasons, but a comprehensive assessment of their quality in relation to risk of mortality and major chronic diseases is lacking., Objective: To examine whether healthful vs unhealthful plant-based dietary patterns are associated with mortality and major chronic diseases among UK adults., Design, Setting, and Participants: This prospective cohort study used data from adults in the UK Biobank, a large-scale population-based study. Participants were recruited between 2006 and 2010 and followed up using record linkage data until 2021; follow-up for different outcomes ranged between 10.6 and 12.2 years. Data analysis was conducted from November 2021 to October 2022., Exposures: Adherence to a healthful vs unhealthful plant-based diet index (hPDI vs uPDI) derived from 24-hour dietary assessments., Main Outcomes and Measures: The main outcomes were hazard ratios (HRs) and 95% CIs of mortality (overall and cause specific), cardiovascular disease (CVD [total, myocardial infarction, ischemic stroke, and hemorrhagic stroke]), cancer (total, breast, prostate, and colorectal), and fracture (total, vertebrae, and hip) across quartiles of hPDI and uPDI adherence., Results: This study included 126 394 UK Biobank participants. They had a mean (SD) age of 56.1 (7.8) years; 70 618 (55.9%) were women. The majority of participants (115 371 [91.3%]) were White. Greater adherence to the hPDI was associated with lower risks of total mortality, cancer, and CVD, with HRs (95% CIs) of 0.84 (0.78-0.91), 0.93 (0.88-0.99), and 0.92 (0.86-0.99), respectively, for participants in the highest hPDI quartile compared with the lowest. The hPDI was also associated with lower risks of myocardial infarction and ischemic stroke, with HRs (95% CIs) of 0.86 (0.78-0.95) and 0.84 (0.71-0.99), respectively. By contrast, higher uPDI scores were associated with higher risks of mortality, CVD, and cancer. The associations observed did not show heterogeneity across strata of sex, smoking status, body mass index, or socioeconomic status or with polygenic risk scores (specifically with regard to CVD end points)., Conclusions and Relevance: The findings of this cohort study of middle-aged UK adults suggest that a diet characterized by high-quality plant-based foods and lower intakes of animal products may be beneficial for health, irrespective of established chronic disease risk factors and genetic predisposition.

Background: Amino acid metabolism is dysregulated in colorectal cancer patients; however, it is not clear whether pre-diagnostic levels of amino acids are associated with subsequent risk of colorectal cancer. We investigated circulating levels of amino acids in relation to colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) and UK Biobank cohorts., Methods: Concentrations of 13-21 amino acids were determined in baseline fasting plasma or serum samples in 654 incident colorectal cancer cases and 654 matched controls in EPIC. Amino acids associated with colorectal cancer risk following adjustment for the false discovery rate (FDR) were then tested for associations in the UK Biobank, for which measurements of 9 amino acids were available in 111,323 participants, of which 1221 were incident colorectal cancer cases., Results: Histidine levels were inversely associated with colorectal cancer risk in EPIC (odds ratio [OR] 0.80 per standard deviation [SD], 95% confidence interval [CI] 0.69-0.92, FDR P-value=0.03) and in UK Biobank (HR 0.93 per SD, 95% CI 0.87-0.99, P-value=0.03). Glutamine levels were borderline inversely associated with colorectal cancer risk in EPIC (OR 0.85 per SD, 95% CI 0.75-0.97, FDR P-value=0.08) and similarly in UK Biobank (HR 0.95, 95% CI 0.89-1.01, P=0.09) In both cohorts, associations changed only minimally when cases diagnosed within 2 or 5 years of follow-up were excluded., Conclusions: Higher circulating levels of histidine were associated with a lower risk of colorectal cancer in two large prospective cohorts. Further research to ascertain the role of histidine metabolism and potentially that of glutamine in colorectal cancer development is warranted., (© 2023. The Author(s).)

Background: Mildly elevated bilirubin, a by-product of hemoglobin breakdown, might mitigate cardiometabolic risk factors including adiposity, dyslipidemia, and high blood pressure (BP). We investigated the cross-sectional relationship between (total) bilirubin and baseline cardiometabolic risk factors in 467,519 UK Biobank study participants., Methods: We used multivariable-adjusted linear regression to estimate associations between bilirubin levels and risk factors of cardiometabolic diseases including body mass index (BMI), waist and hip circumferences (WC, HC), waist-to-hip ratio (WHR), fat mass (FM), and trunk FM, and the blood lipids: apolipoprotein A-I (apoA-I), apolipoprotein B (apoB), apoB/apoA-I, lipoprotein (a), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), LDL/HDL, TC/HDL, triglycerides (TG). Log-transformed bilirubin was modelled with restricted cubic splines and predicted mean values with 99% confidence intervals (CI) for each risk marker were estimated, separately. Second, we applied principal component analysis (PCA) for dimension reduction to in turn six anthropometric traits (height, weight, BMI, WC, HC, and WHR) and all above lipids. Last, we estimated associations (99%CI) between bilirubin and three components of the metabolic syndrome, i.e. WC, TG, and BP using logistic regression., Results: After multivariable adjustments, higher levels of bilirubin were inversely associated with indicators of general adiposity (BMI and FM) and of body fat distribution (WC, HC, WHR, and trunk FM) in both men and women. For example, women with mildly elevated bilirubin (95 th percentile equal to 15.0 µmol/L), compared to women with low bilirubin (5 th percentile equal to 4.5 µmol/L), had on average a 2.0 kg/m 2 (99% CI 1.9-2.1) lower BMI. Inverse associations were also observed with dyslipidemia among men and women. For example, mildly elevated bilirubin among men (95 th percentile equal to 19.4 µmol/L) compared to low levels of bilirubin (5 th percentile equal to 5.5 µmol/L) were associated with approx. 0.55 mmol/L (99% CI 0.53-0.56) lower TG levels, with similar inverse associations among women. Multiple-trait analyses using PCA confirmed single-trait analyses. Men and women with mildly elevated bilirubin levels ≥ 17.1 µmol/L, compared to low-normal bilirubin < 10 µmol/L had 13% (99% CI 8%-18%) and 11% (99% CI 4%-17%) lower odds of exceeding systolic BP levels of ≥ 130 mm Hg, respectively., Conclusions: Higher levels of bilirubin were inversely associated with cardiometabolic risk factors including adiposity, dyslipidemia, and hypertension., (© 2022. The Author(s).)

Background: Dysregulation of endocrine pathways related to steroid and growth hormones may modify endometrial cancer risk; however, prospective data on testosterone, sex hormone-binding globulin (SHBG) and insulin-like growth factor (IGF)-1 are limited. To elucidate the role of these hormones in endometrial cancer risk we conducted complementary observational and Mendelian randomization (MR) analyses., Methods: The observational analyses included 159,702 women (80% postmenopausal) enrolled in the UK Biobank. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. For MR analyses, genetic variants associated with hormone levels were identified and their association with endometrial cancer (12,906 cases/108,979 controls) was examined using two-sample MR., Results: In the observational analysis, higher circulating concentrations of total (HR per unit inverse normal scale = 1.38, 95% CI = 1.22-1.57) and free testosterone (HR per unit log scale = 2.07, 95% CI = 1.66-2.58) were associated with higher endometrial cancer risk. An inverse association was found for SHBG (HR per unit inverse normal scale = 0.76, 95% CI = 0.67-0.86). Results for testosterone and SHBG were supported by the MR analyses. No association was found between genetically predicted IGF-1 concentration and endometrial cancer risk., Conclusions: Our results support probable causal associations between circulating concentrations of testosterone and SHBG with endometrial cancer risk., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: To estimate whether thigh-administered intermittent pneumatic compression (IPC) could potentially afford the UK's National Health Service (NHS) a cost-effective intervention for the management of hard-to-heal venous leg ulcers (VLUs)., Method: A Markov model was constructed depicting the management of hard-to-heal VLUs with IPC plus standard care or standard care alone over a period of 24 weeks. The model estimated the cost-effectiveness of the two interventions in terms of the incremental cost per quality-adjusted life year (QALY) gained at 2019/20 prices., Results: Treatment of hard-to-heal VLUs with IPC plus standard care instead of standard care alone is expected to increase the probability of healing by 58% (from 0.24 to 0.38) at 24 weeks and increase health-related quality of life over 24 weeks from 0.32 to 0.34 QALYs per patient. Additionally, the cost of treating with IPC plus standard care (£3,020 per patient) instead of standard care alone (£3,037 per patient) has the potential to be cost-neutral if use of this device is stopped after 6 weeks in non-improving wounds. Sensitivity analysis showed that the relative cost-effectiveness of IPC plus standard care remains <£20,000 per QALY with plausible variations in costs and effectiveness., Conclusion: Within the limitations of this study, the addition of IPC to standard care potentially affords a cost-effective treatment to the NHS for managing hard-to-heal VLUs. However, a controlled study is required to validate the outcomes of this analysis.

Background: Epidemiologic studies evaluating associations between sex steroid hormones and colorectal cancer risk have yielded inconsistent results. To elucidate the role of circulating levels of testosterone, and sex hormone-binding globulin (SHBG) in colorectal cancer risk, we conducted observational and Mendelian randomization (MR) analyses., Methods: The observational analyses included 333,530 participants enrolled in the UK Biobank with testosterone and SHBG measured. HRs and 95% confidence intervals (CI) were estimated using multivariable Cox proportional hazards models. For MR analyses, genetic variants robustly associated with hormone levels were identified and their association with colorectal cancer (42,866 cases/42,752 controls) was examined using two-sample MR., Results: In the observational analysis, there was little evidence that circulating levels of total testosterone were associated with colorectal cancer risk; the MR analyses showed a greater risk for women (OR per 1-SD = 1.09; 95% CI, 1.01-1.17), although pleiotropy may have biased this result. Higher SHBG concentrations were associated with greater colorectal cancer risk for women (HR per 1-SD = 1.16; 95% CI, 1.05-1.29), but was unsupported by the MR analysis. There was little evidence of associations between free testosterone and colorectal cancer in observational and MR analyses., Conclusions: Circulating concentrations of sex hormones are unlikely to be causally associated with colorectal cancer. Additional experimental studies are required to better understand the possible role of androgens in colorectal cancer development., Impact: Our results from large-scale analyses provide little evidence for sex hormone pathways playing a causal role in colorectal cancer development. See related commentary by Hang and Shen, p. 1302 ., (©2021 American Association for Cancer Research.)

Insulin-like growth factor-I (IGF-I) and testosterone have been implicated in prostate cancer aetiology. Using data from a large prospective full-cohort with standardised assays and repeat blood measurements, and genetic data from an international consortium, we investigated the associations of circulating IGF-I, sex hormone-binding globulin (SHBG), and total and calculated free testosterone concentrations with prostate cancer incidence and mortality. For prospective analyses, risk was estimated using multivariable-adjusted Cox regression in 199 698 male UK Biobank participants. Hazard ratios (HRs) were corrected for regression dilution bias using repeat hormone measurements from a subsample. Two-sample Mendelian randomisation (MR) analysis of IGF-I and risk used genetic instruments identified from UK Biobank men and genetic outcome data from the PRACTICAL consortium (79 148 cases and 61 106 controls). We used cis- and all (cis and trans) SNP MR approaches. A total of 5402 men were diagnosed with and 295 died from prostate cancer (mean follow-up 6.9 years). Higher circulating IGF-I was associated with elevated prostate cancer diagnosis (HR per 5 nmol/L increment = 1.09, 95% CI 1.05-1.12) and mortality (HR per 5 nmol/L increment = 1.15, 1.02-1.29). MR analyses also supported the role of IGF-I in prostate cancer diagnosis (cis-MR odds ratio per 5 nmol/L increment = 1.34, 1.07-1.68). In observational analyses, higher free testosterone was associated with a higher risk of prostate cancer (HR per 50 pmol/L increment = 1.10, 1.05-1.15). Higher SHBG was associated with a lower risk (HR per 10 nmol/L increment = 0.95, 0.94-0.97), neither was associated with prostate cancer mortality. Total testosterone was not associated with prostate cancer. These findings implicate IGF-I and free testosterone in prostate cancer development and/or progression., (© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: Obesity has been positively associated with upper gastrointestinal cancers, but prospective data by subtype/subsite are limited. Obesity influences hormonal factors, which may play a role in these cancers. We examined anthropometry, body fat and reproductive factors in relation to oesophageal and gastric cancer by subtype/subsite in the UK Biobank cohort., Methods: Among 458,713 UK Biobank participants, 339 oesophageal adenocarcinomas, 124 oesophageal squamous cell carcinomas, 137 gastric cardia and 92 gastric non-cardia cancers were diagnosed during a mean of 6.5 years follow-up. Cox models estimated multivariable hazard ratios (HRs) and 95% confidence intervals (CIs)., Results: Body mass index (BMI), hip circumference, waist circumference, waist-to-hip ratio, waist-to-height ratio, total body fat and trunk fat were positively associated with oesophageal adenocarcinoma (highest vs lowest category: HR = 2.33, 95%-CI:1.65-3.28; HR = 1.56, 95%-CI:1.15-2.13; HR = 2.30, 95%-CI:1.47-3.57; HR = 1.71, 95%-CI:1.01-2.90; HR = 2.87, 95%-CI:1.88-4.38; HR = 1.96, 95%-CI:1.30-2.96; HR = 2.34, 95%-CI:1.70-3.22, respectively). Although there were no statistically significant associations in combined sex analyses, BMI (HR = 1.83, 95%-CI:1.00-3.37), waist circumference (HR = 2.21, 95%-CI:1.27-3.84) and waist-to-hip ratio (HR = 1.92, 95%-CI:1.11-3.29) were associated with gastric cardia cancer in men; however, mutual adjustment attenuated the associations for BMI and waist-to-hip ratio. For oesophageal squamous cell carcinoma, statistically significant inverse associations were observed among women for BMI, hip circumference, waist circumference, waist-to-height ratio, total body fat and trunk fat, although they were based on small numbers. In addition, older age at first (HR = 0.44, 95%-CI:0.22-0.88) and last live birth (HR = 0.44, 95%-CI:0.22-0.87) were inversely associated with oesophageal squamous cell carcinoma and having a stillbirth/miscarriage/termination was positively associated (HR = 1.84, 95%-CI:1.10-3.07)., Conclusions: Obesity and abdominal obesity specifically may be a risk factor for oesophageal adenocarcinoma and gastric cardia cancer in men. Some reproductive factors may be associated with oesophageal squamous cell carcinoma in women., Competing Interests: The authors have declared that no competing interests exist.

Mechanisms underlying adiposity-colorectal cancer (CRC) association are incompletely understood. Using UK Biobank data, we investigated the role of C-reactive protein (CRP), hemoglobin-A1c (HbA1c) and (jointly) sex hormone-binding globulin (SHBG) and testosterone, in explaining this association. Total effect of obesity versus normal-weight (based on waist circumference, body mass index, waist-hip ratio) on CRC risk was decomposed into natural direct (NDE) and indirect (NIE) effects using sequential mediation analysis. After a median follow-up of 7.1 years, 2070 incident CRC cases (men = 1,280; postmenopausal women = 790) were recorded. For men, the adjusted risk ratio (RR) for waist circumference (≥102 vs. ≤94 cm) was 1.37 (95% confidence interval [CI], 1.19-1.58). The RRs NIE were 1.08 (95% CI: 1.01-1.16) through all biomarkers, 1.06 (95% CI: 1.01-1.11) through pathways influenced by CRP, 0.99 (95% CI: 0.97-1.01) through HbA1c beyond (the potential influence of) CRP and 1.03 (95% CI: 0.99-1.08) through SHBG and testosterone combined beyond CRP and HbA1c. The RR NDE was 1.26 (95% CI: 1.09-1.47). For women, the RR for waist circumference (≥88 vs. ≤80 cm) was 1.27 (95% CI: 1.07-1.50). The RRs NIE were 1.08 (95% CI: 0.94-1.22) through all biomarkers, 1.08 (95% CI: 0.99-1.17) through CRP, 1.00 (95% CI: 0.98-1.02) through HbA1c beyond CRP and 1.00 (95% CI: 0.92-1.09) through SHBG and testosterone combined beyond CRP and HbA1c. The RR NDE was 1.18 (95% CI: 0.96-1.45). For men and women, pathways influenced by CRP explained a small proportion of the adiposity-CRC association. Testosterone and SHBG also explained a small proportion of this association in men. These results suggest that pathways marked by these obesity-related factors may not explain a large proportion of the adiposity-CRC association., (© 2020 UICC.)

Circulating insulin-like growth factor I (IGF-I) is positively associated with the risks of colorectal, breast, and prostate cancer, but evidence for other less common cancers is limited. In this study, we investigated associations between serum IGF-I concentrations and incidence of less common cancers in the UK Biobank study. To enable comparison of effect estimates, and as positive controls, both common and less common cancer sites (total 30) were included in an outcome-wide analysis. Data from 394,388 cancer-free participants in the UK Biobank study were analyzed. Multivariable adjusted Cox proportional hazards models were used to determine associations between baseline serum IGF-I concentrations and cancer incidence, using repeated IGF-I measurements from up to 14,149 participants to correct for regression dilution bias. Higher IGF-I concentration was associated with increased risks of thyroid cancer [HR per 5 nmol/L higher concentration 1.18; 95% confidence interval (CI), 1.01-1.37] in addition to colorectal (HR, 1.08; 95% CI, 1.03-1.13), breast (HR, 1.11; 95% CI, 1.07-1.15), and prostate cancer (HR, 1.08; 95% CI, 1.05-1.12), and reduced risks of ovarian and liver cancer. Mean follow-up was 6.9 years and the possibility that the observed associations may be influenced by reverse causality bias cannot be excluded. Additional nominally significant associations with malignant melanoma, multiple myeloma, oral cancer, and esophageal squamous cell carcinoma did not survive correction for multiple testing. Studies with longer follow-up and pooled analyses are needed to further assess how broad the role of IGF-I is in cancer development. SIGNIFICANCE: The results from this outcome-wide analysis are consistent with a positive association of IGF-I with cancers at several sites., (©2020 American Association for Cancer Research.)

Background & Aims: Human studies examining associations between circulating levels of insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein 3 (IGFBP3) and colorectal cancer risk have reported inconsistent results. We conducted complementary serologic and Mendelian randomization (MR) analyses to determine whether alterations in circulating levels of IGF1 or IGFBP3 are associated with colorectal cancer development., Methods: Serum levels of IGF1 were measured in blood samples collected from 397,380 participants from the UK Biobank, from 2006 through 2010. Incident cancer cases and cancer cases recorded first in death certificates were identified through linkage to national cancer and death registries. Complete follow-up was available through March 31, 2016. For the MR analyses, we identified genetic variants associated with circulating levels of IGF1 and IGFBP3. The association of these genetic variants with colorectal cancer was examined with 2-sample MR methods using genome-wide association study consortia data (52,865 cases with colorectal cancer and 46,287 individuals without [controls]) RESULTS: After a median follow-up period of 7.1 years, 2665 cases of colorectal cancer were recorded. In a multivariable-adjusted model, circulating level of IGF1 associated with colorectal cancer risk (hazard ratio per 1 standard deviation increment of IGF1, 1.11; 95% confidence interval [CI] 1.05-1.17). Similar associations were found by sex, follow-up time, and tumor subsite. In the MR analyses, a 1 standard deviation increment in IGF1 level, predicted based on genetic factors, was associated with a higher risk of colorectal cancer risk (odds ratio 1.08; 95% CI 1.03-1.12; P = 3.3 × 10 -4 ). Level of IGFBP3, predicted based on genetic factors, was associated with colorectal cancer risk (odds ratio per 1 standard deviation increment, 1.12; 95% CI 1.06-1.18; P = 4.2 × 10 -5 ). Colorectal cancer risk was associated with only 1 variant in the IGFBP3 gene region (rs11977526), which also associated with anthropometric traits and circulating level of IGF2., Conclusions: In an analysis of blood samples from almost 400,000 participants in the UK Biobank, we found an association between circulating level of IGF1 and colorectal cancer. Using genetic data from 52,865 cases with colorectal cancer and 46,287 controls, a higher level of IGF1, determined by genetic factors, was associated with colorectal cancer. Further studies are needed to determine how this signaling pathway might contribute to colorectal carcinogenesis., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

BACKGROUND Organ donation-rates using deceased donors and organizational approaches to organ donation differ drastically between countries at a similar level of health care as measured by the Euro Health Consumer Index (EHCI). MATERIAL AND METHODS Expert opinions from intensive care nurses, physicians, transplant coordinators and transplant surgeons from Austria, Germany, Spain, and the U.K. were obtained in semi-structured interviews followed by qualitative content analysis. Results were reported back to all interview partners to identify potential controversies and consensus recommendations. RESULTS No controversies could be detected. On a variety of beneficial factors an interprofessional consensus between interview partners could be reached: A) The relevance of standardization of the screening for potential donors, the family approach and training; B) standards and best-practice procedures should be regulated and supervised by state authorities; C) full transparency and the prevention of scandals is essential; D) overburdened intensive care unit (ICU) doctors need to be supported by full-time in-house special nurses who organize donor evaluation, transport logistics and pastoral care, if required; E) public awareness campaigns are helpful; F) a broad public consensus on the concept of donation after brain and cardiac death is essential; G) incentives for the reporting of potential organ donors are inappropriate; H) an opt-out system alone is not sufficient. CONCLUSIONS Expert opinions from different professional backgrounds from different European health care systems reach a broad consensus on the most relevant issues for the improvement of organ donation.

Background: Most of the previous studies on diet and colorectal cancer were based on diets consumed during the 1990s., Methods: We used Cox-regression models to estimate adjusted hazard ratios for colorectal cancer by dietary factors in the UK Biobank study. Men and women aged 40-69 years at recruitment (2006-10) reported their diet on a short food-frequency questionnaire (n = 475 581). Dietary intakes were re-measured in a large sub-sample (n = 175 402) who completed an online 24-hour dietary assessment during follow-up. Trends in risk across the baseline categories were calculated by assigning re-measured intakes to allow for measurement error and changes in intake over time., Results: During an average of 5.7 years of follow-up, 2609 cases of colorectal cancer occurred. Participants who reported consuming an average of 76 g/day of red and processed meat compared with 21 g/day had a 20% [95% confidence interval (CI): 4-37] higher risk of colorectal cancer. Participants in the highest fifth of intake of fibre from bread and breakfast cereals had a 14% (95% CI: 2-24) lower risk of colorectal cancer. Alcohol was associated with an 8% (95% CI: 4-12) higher risk per 10 g/day higher intake. Fish, poultry, cheese, fruit, vegetables, tea and coffee were not associated with colorectal-cancer risk., Conclusions: Consumption of red and processed meat at an average level of 76 g/d that meets the current UK government recommendation (≤90 g/day) was associated with an increased risk of colorectal cancer. Alcohol was also associated with an increased risk of colorectal cancer, whereas fibre from bread and breakfast cereals was associated with a reduced risk., (© The Author(s) 2019. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: Acute-on-chronic liver failure (ACLF) is an entity comprising an acute deterioration of liver function in cirrhotic patients, associated with organ failure(s) and high short-term mortality. We aimed to identify predictive factors for short-term mortality in patients admitted with ACLF that may benefit most from liver transplantation., Methods: Retrospective analysis of patients admitted in ACLF to a tertiary intensive care unit between 2013 and 2017 was performed. The EASL-CLIF acute-on-chronic liver failure in cirrhosis (CANONIC) criteria were used to define ACLF grade. Multivariable analysis using 28-day mortality as an end-point was performed, including severity-of-disease scores and clinical parameters., Results: Seventy-seven patients were admitted in ACLF over the study period. The commonest aetiology of liver disease was alcohol related 52/77(68%) and the commonest precipitant of ACLF was variceal haemorrhage 38/77(49%). Overall 28-day mortality was 42/77(55%) [ACLF-(grade)1:3/42(7%); ACLF-2:10/42(24%); and, ACLF-3:29/42(69%);p = 0.002]. On multivariable analysis MELD ≥ 26 [odds ratio(OR) = 11.559; 95% confidence interval(CI):2.820-47.382;p = 0.001], ACLF-3 (OR = 3.287; 95%CI:1.047-10.325;p = 0.042) at admission and requirement for renal replacement therapy (OR = 5.348; 95%CI:1.385-20.645;p = 0.015) were independently associated with 28-day mortality., Conclusion: Patients admitted with ACLF to intensive care have a high mortality rate. Defined early thresholds at admission can identify patients at the highest risk that may benefit most from liver transplantation., (Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.)

Objective: To systematically identify and validate published colorectal cancer risk prediction models that do not require invasive testing in two large population-based prospective cohorts., Design: Models were identified through an update of a published systematic review and validated in the European Prospective Investigation into Cancer and Nutrition (EPIC) and the UK Biobank. The performance of the models to predict the occurrence of colorectal cancer within 5 or 10 years after study enrolment was assessed by discrimination (C-statistic) and calibration (plots of observed vs predicted probability)., Results: The systematic review and its update identified 16 models from 8 publications (8 colorectal, 5 colon and 3 rectal). The number of participants included in each model validation ranged from 41 587 to 396 515, and the number of cases ranged from 115 to 1781. Eligible and ineligible participants across the models were largely comparable. Calibration of the models, where assessable, was very good and further improved by recalibration. The C-statistics of the models were largely similar between validation cohorts with the highest values achieved being 0.70 (95% CI 0.68 to 0.72) in the UK Biobank and 0.71 (95% CI 0.67 to 0.74) in EPIC., Conclusion: Several of these non-invasive models exhibited good calibration and discrimination within both external validation populations and are therefore potentially suitable candidates for the facilitation of risk stratification in population-based colorectal screening programmes. Future work should both evaluate this potential, through modelling and impact studies, and ascertain if further enhancement in their performance can be obtained., Competing Interests: Competing interests: TS received a studentship from the Medical Research Council (MR/M501712/1). DCM is supported by a Cancer Research UK Population Research Fellowship (C57955/A24390). KJA received a research grant from the German Research Foundation (DFG) (AL 1784/3-1), KEB received research grants from Cancer Research UK (C570/A16491) and the Medical Research Council (MR/M012190/1); no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; KGMM is director of Research of a large (around 500 employees) research and teaching institute within his University Medical Center. They perform both investigator-driven and industry-driven research projects with a number of pharmaceutical and diagnostic companies. In addition, some of the members of staff receive unrestricted grants for research projects from a number of companies. It is their explicit policy to work with several companies and not to focus on one or two industrial partners. He receives no personal payment from any industrial partner., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: In various medical and surgical conditions, research has found that centers with higher patient volumes have better outcomes. This relationship has not previously been explored for status epilepticus. This study sought to examine whether centers that see higher volumes of patients with status epilepticus have lower in-hospital mortality than low-volume centers., Design: Cohort study, using 2010-2015 data from the nationwide Case Mix Programme database of the U.K.'s Intensive Care National Audit and Research Centre., Setting: Greater than 90% of ICUs in United Kingdom, Wales, and Northern Ireland., Patients: Twenty-thousand nine-hundred twenty-two adult critical care admissions with a primary or secondary diagnosis of status epilepticus or prolonged seizure., Interventions: Annual hospital status epilepticus admission volume., Measurements and Main Results: We used multiple logistic regression to evaluate the association between hospital annual status epilepticus admission volume and in-hospital mortality. Hospital volume was modeled as a nonlinear variable using restricted cubic splines, and generalized estimating equations with robust SEs were used to account for clustering by institution. There were 2,462 in-hospital deaths (11.8%). There was no significant association between treatment volume and in-hospital mortality for status epilepticus (p = 0.54). This conclusion was unchanged across a number of subgroup and sensitivity analyses, although we lacked data on seizure duration and medication use. Secondary analyses suggest that many high-risk patients were already transferred from low- to high-volume centers., Conclusions: We find no evidence that higher volume centers are associated with lower mortality in status epilepticus overall. It is likely that national guidelines and local pathways in the United Kingdom allow efficient patient transfer from smaller centers like district general hospitals to provide satisfactory patient care in status epilepticus. Future research using more granular data should explore this association for the subgroup of patients with refractory and superrefractory status epilepticus.

This corrects the article DOI: 10.1038/bjc.2017.85.

Obesity has been consistently associated with a greater colorectal cancer risk, but this relationship is weaker among women. In the UK Biobank, we investigated the associations between body size (body mass index [BMI], height, waist circumference, and waist-to-hip ratio) and body fat composition (total body fat percentage and trunk fat percentage) measurements with colorectal cancer risk among 472,526 men and women followed for 5.6 years on average. Multivariable hazard ratios (HRs) and 95% confidence intervals (95%CI) for developing colorectal cancer (2,636 incident cases) were estimated using Cox proportional hazards models. Among men, when the highest and lowest fifths were compared, BMI (HR = 1.35, 95%CI: 1.13-1.61; P trend  < 0.0001), waist circumference (HR = 1.66, 95%CI: 1.39-1.99; P trend  < 0.0001), waist-to-hip ratio (HR = 1.58, 95%CI: 1.31-1.91; P trend  < 0.0001), total body fat percentage (HR = 1.27, 95%CI: 1.06-1.53; P trend  = 0.002), and trunk fat percentage (HR = 1.31, 95%CI: 1.09-1.58; P trend  = 0.002) were associated with greater colorectal cancer risk. For women, only waist-to-hip ratio (HR for highest versus lowest fifth = 1.33, 95%CI: 1.08-1.65; P trend  = 0.005) was positively associated with colorectal cancer risk. Greater body size (overall and abdominal adiposity) was positively associated with colorectal cancer development in men. For women, abdominal adiposity, rather than overall body size, was associated with a greater colorectal cancer risk.

'Ethnicity' is an important concept in dental health services research and in enabling general dental practitioners to gain insight into their patients values and expectations. Since more health services research is being undertaken in primary dental care settings it is becoming an important issue for dental professionals and researchers in primary care to be aware of. Ethnicity is thought to be related to dental health inequalities and access and is often used as a stratifying variable in many dental studies. The meaning and use of the term however differs among researchers and among the public. It is clear that researchers and professionals need to pause for thought when considering what this often bandied about term actually means and the impact of different definitions. This is illustrated using examples from the authors' own research and published papers in the medical and dental literature. There is also much debate about whether ethnicity--however defined--is an important predictor of differences in dental health in itself or is merely a marker for other factors such as social deprivation or the impact of 'place' on dental health. While the jury on this debate is out we suggest guidelines on the reporting of ethnicity should be outlined in the dental literature--perhaps updating those published in 1996 in the British Medical Journal.