Second Primary Cancer Risks After Breast Cancer in and Pathogenic Variant Carriers.

Purpose: Second primary cancer (SPC) risks after breast cancer (BC) in pathogenic variant (PV) carriers are uncertain. We estimated relative and absolute risks using a novel linkage of genetic testing data to population-scale National Disease Registration Service and Hospital Episode Statistics electronic health records.

Methods: We followed 25,811 females and 480 males diagnosed with BC and tested for germline PVs in NHS Clinical Genetics centers in England between 1995 and 2019 until SPC diagnosis, death, migration, contralateral breast/ovarian surgery plus 1 year, or the 31st of December 2020.

Factors associated with receipt of systemic anticancer treatment for locally advanced or metastatic urothelial carcinoma in England: a population-based study.

Introduction: Systemic anticancer therapy for locally advanced or metastatic urothelial carcinoma (la/mUC) is associated with efficacy benefits, including longer overall survival (OS), but many patients remain untreated. This observational, real-world, national study aimed to investigate factors associated with receiving systemic anticancer therapy for la/mUC in England.

Patients And Methods: Adults diagnosed with la/mUC between 2013 and 2019 were identified in the National Cancer Registration Dataset and followed until March 2021.

Risks of second primary cancers among 584,965 female and male breast cancer survivors in England: a 25-year retrospective cohort study.

Background: Second primary cancers (SPCs) after breast cancer (BC) present an increasing public health burden, with little existing research on socio-demographic, tumour, and treatment effects. We addressed this in the largest BC survivor cohort to date, using a novel linkage of National Disease Registration Service datasets.

Methods: The cohort included 581,403 female and 3562 male BC survivors diagnosed between 1995 and 2019.

Cohort study to assess geographical variation in cholangiocarcinoma treatment in England.

Background: Outcomes for cholangiocarcinoma (CCA) are extremely poor owing to the complexities in diagnosing and managing a rare disease with heterogenous sub-types. Beyond curative surgery, which is only an option for a minority of patients diagnosed at an early stage, few systemic therapy options are currently recommended to relieve symptoms and prolong life. Stent insertion to manage disease complications requires highly specialised expertise.

Outcomes of dostarlimab versus chemotherapy in post-platinum patients with recurrent/advanced endometrial cancer: data from the GARNET trial and the National Cancer Registration Service in England.

Objectives: Immune checkpoint inhibitors have emerged as novel treatment options in patients with endometrial cancer. In this study we aimed to compare the survival outcomes of patients with recurrent or advanced endometrial cancer. These patients had received dostarlimab after platinum-based chemotherapy in the single-arm, Phase I GARNET trial.

Regional variation in routes to diagnosis of cholangiocarcinoma in England from 2006 to 2017.

Background: Incidence of cholangiocarcinoma (CCA) is rising, with overall prognosis re-maining very poor. Reasons for the high mortality of CCA include its late presentation in most patients, when curative options are no longer feasible, and poor response to systemic therapies for advanced disease. Late presentation presents a large barrier to improving outcomes and is often associated with diagnosis mergency presentation (EP).

Trends in incidence, treatment and survival of Merkel cell carcinoma in England 2004-2018: a cohort study.

Background: Merkel cell carcinoma (MCC) is a rare tumour with neuroendocrine differentiation and high associated mortality. Studies that describe the epidemiology of MCC are often limited by small sample size, short duration of follow-up, absence of nationwide data and paucity of data on different risk factors.

Objectives: To determine the incidence, demographics and survival for MCC in England between 2004 and 2018.

An Adjusted Treatment Comparison Comparing Amivantamab Versus Real-World Clinical Practice in Europe and the United States for Patients with Advanced Non-Small Cell Lung Cancer with Activating Epidermal Growth Factor Receptor Exon 20 Insertion Mutations.

Introduction: Patients with advanced, epidermal growth factor receptor (EGFR)-mutated, non-small cell lung cancer (NSCLC) with Exon 20 insertion mutations (Exon20ins) have poor prognoses, exacerbated by a previous lack of specific treatment guidelines and unmet need for targeted therapies. Amivantamab, an EGFR and MET bispecific antibody, demonstrated efficacy and tolerability in patients with advanced EGFR-mutated NSCLC with Exon20ins following platinum-based therapy in CHRYSALIS (NCT02609776; Cohort D+). Since CHRYSALIS was single-arm, individual patient data (IPD)-based adjusted analyses versus similar patients in real-world clinical practice (RWCP) were conducted to generate comparative evidence.

A registry study of relapsed or refractory multiple myeloma pre-exposed to three or more prior therapies including a proteasome inhibitor, an immunomodulatory agent and CD38-targeted monoclonal antibody therapy in England.

Some patients with multiple myeloma are receiving treatment in clinical practice in England after prior exposure to a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. We investigated the characteristics of these patients, their outcomes, and the salvage therapies they received using the national cancer registry for England and linked healthcare data. After a median follow-up time of 6.

Previously treated recurrent or advanced endometrial cancer in England: A real-world observational analysis.

Objectives: In patients with recurrent/advanced endometrial cancer who have progressed after first-line treatment, there are a lack of real-world data on treatment patterns, characteristics, and survival outcomes. A novel study was conducted to determine real-world treatment patterns and outcomes in England.

Methods: This non-interventional study used routine, administrative health data from the National Cancer Registration and Analysis Service in England to identify patients diagnosed with recurrent/advanced endometrial cancer between 1 January 2013 and 31 December 2018, inclusive.

Changes in workplace car parking and commute mode: a natural experimental study.

Background: The use of private motor vehicles places a considerable burden on public health. Changes in workplace car parking policies may be effective in shifting behaviour. We use a natural experimental design to assess whether changes in policy were associated with differences in commute mode.

Changes in the mode of travel to work and the severity of depressive symptoms: a longitudinal analysis of UK Biobank.

Although commuting provides an opportunity for incorporating physical activity into daily routines, little is known about the effect of active commuting upon depressive symptoms. This study aimed to determine whether changes in commute mode are associated with differences in the severity of depressive symptoms in working adults. Commuters were selected from the UK Biobank cohort if they completed ≥2 assessment centre visits between 2006 and 2016.

Trajectories of alcohol consumption prior to the diagnosis of type 2 diabetes: a longitudinal case-cohort study.

Background: Non-linear associations have been reported between baseline measures of alcohol consumption and type 2 diabetes (T2DM). However, given that drinking varies over the adult life course, we investigated whether differences existed in the longitudinal trajectory of alcohol consumption according to T2DM status.

Methods: For a case-cohort (916 incident cases; 7376 controls) of British civil servants nested within the Whitehall II cohort, the self-reported weekly volume of alcohol consumption was traced backwards from the date of diagnosis or censoring to the beginning of the study, covering a period of up to 28 years.

The stability of baseline-defined categories of alcohol consumption during the adult life-course: a 28-year prospective cohort study.

Background And Aims: Studies that report the relationship between alcohol consumption and disease risk have predominantly operationalized drinking according to a single baseline measure. The resulting assumption of longitudinal stability may be simplistic and complicate interpretation of risk estimates. This study aims to describe changes to the volume of consumption during the adult life-course according to baseline categories of drinking.

Alcohol Consumption and the Risk of Type 2 Diabetes: A Systematic Review and Dose-Response Meta-analysis of More Than 1.9 Million Individuals From 38 Observational Studies.

Objective: Observational studies indicate that moderate levels of alcohol consumption may reduce the risk of type 2 diabetes. In addition to providing an updated summary of the existing literature, this meta-analysis explored whether reductions in risk may be the product of misclassification bias.

Research Design And Methods: A systematic search was undertaken, identifying studies that reported a temporal association between alcohol consumption and the risk of type 2 diabetes.

All cause mortality and the case for age specific alcohol consumption guidelines: pooled analyses of up to 10 population based cohorts.

Objectives: To examine the suitability of age specific limits for alcohol consumption and to explore the association between alcohol consumption and mortality in different age groups.

Design: Population based data from Health Survey for England 1998-2008, linked to national mortality registration data and pooled for analysis using proportional hazards regression. Analyses were stratified by sex and age group (50-64 and ≥ 65 years).

Hypertension management in England: a serial cross-sectional study from 1994 to 2011.

Background: Hypertension is the leading risk factor contributing to the global burden of disease. We aimed to assess the change in blood pressure management between 1994 and 2011 in England with a series of annual surveys.

Methods: We did a serial cross-sectional study of five Health Survey for England surveys based on nationally representative samples of non-institutionalised adults (aged ≥16 years).

Association between alcohol calorie intake and overweight and obesity in English adults.

We investigated the contribution of alcohol-derived calories to the alcohol-obesity relation. Adult alcohol calorie intake was derived from consumption volume and drink type in the Health Survey for England 2006 (n = 8864). We calculated the odds of obesity with survey-adjusted logistic regression.

Could more than three million older people in England be at risk of alcohol-related harm? A cross-sectional analysis of proposed age-specific drinking limits.

Objective: to determine the impact of recently proposed age-specific alcohol consumption limits on the proportion and number of older people classified at risk of alcohol-related harm.

Design: nationally representative cross-sectional population data from the Health Survey for England (HSE).

Participants: adults with valid alcohol consumption data, comprising 14,718 participants from 2003 and 14,939 from 2008.

Ergocalciferol supplementation in children with CKD delays the onset of secondary hyperparathyroidism: a randomized trial.

Background And Objectives: Vitamin D deficiency is an important contributor to the development of hyperparathyroidism and is independently associated with cardiovascular and bone disease. The hypothesis was that nutritional vitamin D (ergocalciferol) supplementation in children with CKD stages 2-4 delays the onset of secondary hyperparathyroidism.

Design, Setting, Participants, & Measurements: A randomized, double-blinded, placebo-controlled study in children with CKD2-4 who had 25-hydroxyvitamin D [25(OH)D] deficiency was conducted.

Urinary and dialysate losses of vitamin D-binding protein in children on chronic peritoneal dialysis.

Background: Vitamin D deficiency is widely prevalent in chronic kidney disease [CKD] patients. The aim of our study was to determine whether losses of vitamin D binding protein [VDBP] in urine and dialysate contribute to circulating 25-hydroxyvitamin D [25OHD] levels in chronic peritoneal dialysis [PD] patients.

Methods: Dialysate, serum, and urine VDBP levels were measured in 16 children on PD and compared with serum and urine VDBP in ten CKD4-5 patients.

Vitamin D deficiency is associated with short stature and may influence blood pressure control in paediatric renal transplant recipients.

Vitamin D deficiency is common in adult renal transplant recipients, but data in children are scarce. Vitamin D is shown to have multiple effects on the cardiovascular system, renal function, and maintenance of bone health. We hypothesized that 25(OH)D deficiency is common in pediatric renal transplant recipients, and may be associated with hyperparathyroidism, short stature, renal function, and blood pressure control.

The virtues of vitamin D--but how much is too much?

Vitamin D deficiency is common in healthy adults and children as well as in the chronic kidney disease (CKD) population. What was once a disease of malnourished children in the developing world has re-emerged and reached pandemic proportions. In parallel with this development, there is a growing awareness that vitamin D is not simply a 'calcaemic hormone' but plays an important role in the prevention of cardiovascular disease, infectious and auto-immune conditions, renoprotection, glycaemic control and prevention of some common cancers.