Identifying social distress: a cross-sectional survey of social outcomes 12 to 36 months after colorectal cancer diagnosis

Purpose: To establish the prevalence and determinants of poor social outcomes after a diagnosis of colorectal cancer (CRC). Patients and Methods: All 12- to 36-month survivors of CRC (International Classification of Diseases [10th revision] codes C18 to C20) diagnosed in 2010 or 2011 and treated in the English National Health Service were identified and sent a questionnaire from their treating cancer hospital. This included the Social Difficulties Inventory, a 16-item scale of social distress (SD) comprising everyday living, money matters, and self and others subscales, plus five single items. Sociodemographic and clinical data were also collected. Analyses using descriptive statistics, 2 tests, and logistic regression models were conducted. Results: Response rate was 63.3% (21,802 of 34,467). Of the 21,802 participants, 17,830 (81.8%) completed all SD items; 2,688 (15.1%) of these 17,830 respondents were classified as experiencing SD (everyday living, 19.5%; money matters, 15.6%; self and others, 18.1%). Multivariable analysis demonstrated having three long-term conditions was the strongest predictor of SD (odds ratio [OR], 6.64; 95% CI, 5.67 to 7.77 compared with no long-term conditions), followed by unemployment (OR, 5.11; 95% CI, 4.21 to 6.20 compared with being employed), having recurrent or nontreatable disease (OR, 2.75; 95% CI, 2.49 to 3.04 compared with being in remission), and having a stoma (OR, 2.10; 95% CI, 1.86 to 2.36 compared with no stoma). Additional predictors of SD were young age (< 55 years), living in a more deprived area, nonwhite ethnicity, having advanced-stage disease, having undergone radiotherapy, and being a carer. Conclusion: Although it is reassuring a majority do not experience social difficulties, a minority reported significant SD 12 to 36 months after diagnosis of CRC. The identified clinical and social risk factors are easy to establish and should be used to target support

Obesity surgery and risk of colorectal and other obesity-related cancers: An English population-based cohort study

Background: The association between obesity surgery (OS) and cancer risk remains unclear. We investigated this association across the English National Health Service. A population-based Swedish study has previously suggested that OS may increase the risk of developing colorectal cancer (CRC). Methods: A retrospective observational study of individuals who underwent OS (surgery cohort) or diagnosed with obesity, but had no OS (no-surgery cohort) (1997–2013) were identified using Hospital Episode Statistics. Subsequent diagnosis of CRC, breast, endometrial, kidney and lung cancer, as well as time ‘at risk’, were determined by linkage to National Cancer Registration & Analysis Service and Office of National Statistics data, respectively. Standardised incidence ratios (SIR) in relation to OS were calculated. Results: 1 002 607 obese patients were identified, of whom 3.9% (n = 39 747) underwent OS. In the no-surgery obese population, 3 237 developed CRC (SIR 1.12 [95% CI 1.08–1.16]). In those who underwent OS, 43 developed CRC (SIR 1.26 [95% CI 0.92–1.71]). The OS cohort demonstrated decreased breast cancer risk (SIR 0.76 [95% CI 0.62–0.92]), unlike the no surgery cohort (SIR 1.08 [95% CI 1.04–1.11]). Increased risk of endometrial and kidney cancer was observed in surgery and no-surgery cohorts. Conclusions: CRC risk is increased in individuals diagnosed as obese. Prior obesity surgery was not associated with an increased CRC risk. However, the OS population was small, with limited follow-up. Risk of breast cancer after OS is reduced compared with the obese no-surgery population, while the risk of endometrial and kidney cancers remained elevated after OS

Unequal impact of the Covid-19 pandemic on excess deaths, life expectancy, and premature mortality across Spanish regions in 2020 and 2021

Spain is one of the most heavily affected countries by the Covid-19 pandemic. In this study, we estimated the regional inequalities in excess deaths and premature mortality in Spain. Between January 2020 and June 2021, an estimated 89,200 (men: 48,000; women: 41,200) excess deaths occurred in the 17 Spanish regions with a substantial variability (highest in Madrid: 22,000, lowest in Canary Islands: -210). Highest reductions in life expectancy at birth (e0) in 2020 were observed in Madrid (men: -3.48 years, women: -2.15), Castile La Mancha (men: -2.67, women: -2.30), and Castile and León (men: -2.00, women: -1.32). In the first six months of 2021, the highest reduction in e0 was observed in Valencian Community (men: -2.04, women: -1.63), Madrid (men: - 2.37), and Andalusia (men: -1.75; women: -1.43). In some Spanish regions, life expectancy at age 65 during the Covid-19 pandemic in 2020 was comparable to that observed as far back as 20 years ago

Socioeconomic inequalities in risk of infection with SARS-CoV-2 delta and omicron variants in the UK, 2020-22: analysis of the longitudinal COVID-19 Infection Survey

Objective: to explore the risk of a positive test result for the delta or omicron variant of the SARS-CoV-2 virus in different occupations and deprivation groups in the UK.Design: analysis of the longitudinal COVID-19 Infection Survey.Setting: COVID-19 Infection Survey, conducted by the Office for National Statistics and the University of Oxford, UK, a nationwide longitudinal survey to monitor SARS-CoV-2 infection in the community, 26 April 2020 to 31 January 2022.Participants: survey participants recruited from randomly selected households to reflect the UK population (England, Scotland, Wales, and Northern Ireland) were divided into the delta cohort (2 July 2020 to 19 December 2021) and the omicron variant (on or after 20 December 2021), the dominant variants during our study period.Main outcome measures: incidence rate and incidence rate ratio for the presence of the delta and omicron variants by area level deprivation and occupation sector. Multivariable Poisson regression models were fitted to estimate the adjusted incidence rate ratio after adjusting for age, sex, ethnic group, comorbid conditions, urban or rural residence, household size, patient or client facing job, and time (as quarters of the year).Results: 329 356 participants were included in the delta cohort and 246 061 in the omicron cohort. The crude incidence rate for the presence of the delta and omicron variants of the SARS-CoV-2 virus were higher in the most deprived group (based on the index of multiple deprivation divided by deciles; delta cohort 4.33 per 1000 person months, 95.09 to 4.58; omicron cohort 76.67 per 1000 person months, 71.60 to 82.11) than in the least deprived group (3.18, 3.05 to 3.31 and 54.52, 51.93 to 57.24, respectively); the corresponding adjusted incidence rate ratios were 1.37 (95.29 to 1.47) and 1.34 (1.24 to 1.46) during the delta and omicron variant dominant periods, respectively. The adjusted incidence rate ratios for a positive test result in the most deprived group compared with the least deprived group in the delta cohort were 1.59 (95.25 to 2.02) and 1.50 (1.19 to 1.87) in the healthcare and manufacturing or construction sectors, respectively. Corresponding values in the omicron cohort were 1.50 (1.15 to 1.95) and 1.43 (1.09 to 1.86) in the healthcare and teaching and education sectors, respectively. Associations between SARS-CoV-2 infection and other employment sectors were not significant or were not tested because of small numbers.Conclusion: in this study, the risk of a positive test result for the SARS-CoV-2 virus in the delta and omicron cohorts was higher in the most deprived than in the least deprived group in the healthcare, manufacturing or construction, and teaching and education sectors.<br/

Socioeconomic inequalities of Long COVID: a retrospective population-based cohort study in the United Kingdom

Objectives: to estimate the risk of Long COVID by socioeconomic deprivation and to further examine the inequality by sex and occupation. Design: we conducted a retrospective population-based cohort study using data from the ONS COVID-19 Infection Survey between 26 April 2020 and 31 January 2022. This is the largest nationally representative survey of COVID-19 in the UK with longitudinal data on occupation, COVID-19 exposure and Long COVID. Setting: community-based survey in the UK. Participants: a total of 201,799 participants aged 16 to 64 years and with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Main outcome measures: the risk of Long COVID at least 4 weeks after SARS-CoV-2 infection by index of multiple deprivation (IMD) and the modifying effects of socioeconomic deprivation by sex and occupation. Results: nearly 10% (n = 19,315) of participants reported having Long COVID. Multivariable logistic regression models, adjusted for a range of variables (demographic, co-morbidity and time), showed that participants in the most deprived decile had a higher risk of Long COVID (11.4% vs. 8.2%; adjusted odds ratio (aOR): 1.46; 95% confidence interval (CI): 1.34, 1.59) compared to the least deprived decile. Significantly higher inequalities (most vs. least deprived decile) in Long COVID existed in healthcare and patient-facing roles (aOR: 1.76; 95% CI: 1.27, 2.44), in the education sector (aOR: 1.68; 95% CI: 1.31, 2.16) and in women (aOR: 1.56; 95% CI: 1.40, 1.73) than men (aOR: 1.32; 95% CI: 1.15, 1.51).Conclusions: this study provides insights into the heterogeneous degree of inequality in Long COVID by deprivation, sex and occupation. These findings will help inform public health policies and interventions in incorporating a social justice and health inequality lens.</p

Novel experimental strategies to prevent the development of type 1 diabetes mellitus.

Type 1 diabetes is an autoimmune disease leading to extensive destruction of the pancreatic beta-cells. Our research focusses on the role of beta-cells during the course of the disease, aiming at finding novel strategies to enhance beta-cell resistance against the cytotoxic damage inflicted by the immune system. Special attention has been paid to the possibility that cytokines released by the immune cells infiltrating the pancreatic islets can directly suppress and kill beta-cells. Certain cytokines (interleukin-1beta, tumor necrosis factor-alpha and interferon-gamma) either alone or in combination, are able to activate signal transduction pathways in beta-cells leading to transcription factor activation and de novo gene expression. In this context, it has been found that induction of inducible nitric oxide synthase mediates an elevated production of nitric oxide, which impairs mitochondrial function and causes DNA damage eventually leading to apoptosis and necrosis. However, other induced proteins SUCH AS heat shock protein 70 and superoxide dismutase may reflect a defense reaction elicited in the beta-cells by the cytokines. Our strategy is to further seek for proteins involved in both destruction and protection of beta-cells. Based on this knowledge, we plan to apply gene therapeutic approaches to increase expression of protective genes in beta-cells. If this is feasible we will then evaluate the function and survival of such modified beta-cells in animal models of type 1 diabetes such as the NOD mouse. The long-term goal for this research line is to find novel approaches to influence beta-cell resistance in humans at risk of developing type 1 diabetes.Journal ArticleResearch Support, Non-U.S. Gov'tReviewinfo:eu-repo/semantics/publishe

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of