Quality of life and health status in older adults (≥65 years) up to five years following colorectal cancer treatment: Findings from the ColoREctal Wellbeing (CREW) cohort study.

OBJECTIVE: Colorectal cancer (CRC) is common in older adults, with more than 70% of diagnoses in people aged ≥65 years. Despite this, there is a knowledge gap regarding longer-term outcomes in this population. Here, we identify those older people most at risk of poor quality of life (QoL) and health status in the five years following CRC treatment. MATERIALS AND METHODS: CREW is a UK longitudinal cohort study investigating factors associated with health and wellbeing recovery following curative-intent CRC surgery. Participants completed self-report questionnaires pre-surgery, then at least annually up to five years. Longitudinal analyses explored the prevalence and pre-surgery risk factors of poor QoL (QLACS-GSS) and health status (EQ-5D: presence/absence of problems in five domains) in older (≥65 years) participants over five years. RESULTS: 501 participants aged ≥65years completed questionnaires pre-surgery; 45% completed questionnaires five years later. Oldest-old participants (≥80 years) reported poorer QoL (18% higher QLACS-GSS) and 2-4 times higher odds of having problems with mobility or usual activities, compared with the youngest-old (65-69 years) over follow-up. Baseline higher self-efficacy was significantly associated with better QoL (10-30% lower QLACS-GSS scores compared to those with low self-efficacy) and lower odds of problems in all EQ-5D domains. Adequate social support was significantly associated with better QoL (8% lower QLACS-GSS) and lower odds of problems with usual activities (OR = 0.62) and anxiety/depression (OR = 0.56). CONCLUSION: There are important differences in QoL and health status outcomes for the oldest-old during CRC recovery. CREW reveals pre-surgery risk factors that are amenable to intervention including self-efficacy and social support.

Prevalence and determinants of depression up to 5 years after colorectal cancer surgery: results from the ColoREctal Wellbeing (CREW) study.

AIM: Depression experienced by people with colorectal cancer (CRC) is an important clinical problem affecting quality of life. Recognition of depression at key points in the pathway enables timely referral to support. This study aimed to examine depression before and 5 years after surgery to examine its prevalence and identify determinants. METHOD: The ColoREctal Wellbeing (CREW) study is a prospective UK cohort study involving 872 adults with nonmetastatic CRC recruited before surgery with curative intent. Questionnaires completed before surgery and 3, 9, 15, 24, 36, 48 and 60 months after surgery captured socio-demographics and assessed depression (Centre for Epidemiologic Studies Depression Scale, CES-D) and other psychosocial factors. Clinical details were also gathered. We present the prevalence of clinically significant depression (CES-D ≥ 20) over time and its predictors assessed before and 2 years after surgery. RESULTS: Before surgery, 21.0% of the cohort reported CES-D ≥ 20 reducing to 14.7% 5 years after surgery. Presurgery risk factors predicting subsequent depression were clinically significant depression and anxiety, previous mental health service use, low self-efficacy, poor health, having neoadjuvant treatment and low social support. Postsurgery risk factors at 2 years predicting subsequent depression were clinically significant depression, negative affect, cognitive dysfunction, accommodation type and poor health. CONCLUSION: Depression is highly pervasive in people with CRC, exceeding prevalence in the general population across follow-up. Our findings emphasize the need to screen and treat depression across the pathway. Our novel data highlight key risk factors of later depression at important and opportune time points: before surgery and at the end of routine surveillance. Early recognition and timely referral to appropriate support is vital to improve long-term psychological outcomes.

Prevalence and predictors of poor sexual well-being over 5 years following treatment for colorectal cancer: results from the ColoREctal Wellbeing (CREW) prospective longitudinal study.

OBJECTIVES: To describe prevalence and predictors of poor sexual well-being for men and women over 5 years following treatment for colorectal cancer. DESIGN: Prospective longitudinal study, from presurgery to 5 years postsurgery, with eight assessment points. Logistic regression models predicted sexual well-being from presurgery to 24 months and 24 months to 60 months; time-adjusted then fully adjusted models were constructed at each stage. SETTING: Twenty-nine hospitals in the UK. PARTICIPANTS: Patients with Dukes' stage A-C, treated with curative intent, aged ≥18 years and able to complete questionnaires were eligible. OUTCOME MEASURES: The dependent variable was the Quality of Life in Adult Cancer Survivors sexual function score. Independent variables included sociodemographic, clinical and psychosocial characteristics. RESULTS: Seven hundred and ninety participants provided a sexual well-being score for at least one time point. Thirty-seven per cent of men and 14% of women reported poor sexual well-being at 5 years. Baseline predictors for men at 24 months included having a stoma (OR 1.5, 95% CI 1.02 to 2.20) and high levels of depression (OR 2.69/2.01, 95% CI 1.68 to 4.32/1.12 to 3.61); men with high self-efficacy (OR confident 0.33/0.48, 95% CI 0.18 to 0.61/0.24 to 1.00; very confident 0.25/0.42, 95% CI 0.13 to 0.49/0.19 to 0.94) and social support (OR 0.52/0.56, 95% CI 0.33 to 0.81/0.35 to 0.91) were less likely to report poor sexual well-being. Predictors at 60 months included having a stoma (OR 2.30/2.67, 95% CI 1.22 to 4.34/1.11 to 6.40) and high levels of depression (OR 5.61/2.58, 95% CI 2.58 to 12.21/0.81 to 8.25); men with high self-efficacy (very confident 0.14, 95% CI 0.047 to 0.44), full social support (OR 0.26; 95% CI 0.13 to 0.53) and higher quality of life (OR 0.97, 95% CI 0.95 to 0.98) were less likely to report poor sexual well-being. It was not possible to construct models for women due to low numbers reporting poor sexual well-being. CONCLUSIONS: Several psychosocial variables were identified as predictors of poor sexual well-being among men. Interventions targeting low self-efficacy may be helpful. More research is needed to understand women's sexual well-being.

Does quality of life return to pre-treatment levels five years after curative intent surgery for colorectal cancer? Evidence from the ColoREctal Wellbeing (CREW) study.

BACKGROUND: The ColoREctal Wellbeing (CREW) study is the first study to prospectively recruit colorectal cancer (CRC) patients, carry out the baseline assessment pre-treatment and follow patients up over five years to delineate the impact of treatment on health and wellbeing. METHODS: CRC patients received questionnaires at baseline (pre-surgery), 3, 9, 15, 24, 36, 48 and 60 months. The primary outcome was Quality of Life in Adult Cancer Survivors (QLACS); self-efficacy, mental health, social support, affect, socio-demographics, clinical and treatment characteristics were also assessed. Representativeness was evaluated. Predictors at baseline and at 24 months of subsequent worsened quality of life (QOL) were identified using multivariable regression models. RESULTS: A representative cohort of 1017 non-metastatic CRC patients were recruited from 29 UK cancer centres. Around one third did not return to pre-surgery levels of QOL five years after treatment. Baseline factors associated with worsened QOL included >2 comorbidities, neoadjuvant treatment, high negative affect and low levels of self-efficacy, social support and positive affect. Predictors at 24 months included older age, low positive affect, high negative affect, fatigue and poor cognitive functioning. CONCLUSIONS: Some risk factors for poor outcome up to five years following CRC surgery, such as self-efficacy, social support and comorbidity management, are amenable to change. Assessment of these factors from diagnosis to identify those most likely to need support in their recovery is warranted. Early intervention has the potential to improve outcomes.

Health and Social Care Diversity Among Individuals with Longstanding Physical and Psychological Health Problems: Pooled Repeated Cross Sectional Analyses.

This paper examines differences in health-and-social care utilisation for individuals with physical and/or mental health problems. Logistic regression models are used to determine disparity in the percentage of General Household/Lifestyle Survey participants with physical compared to mental health problems receiving disability benefits or health care services between 2000 and 2011. Our findings of a relative underutilisation of secondary health care combined with a relative overutilization of out-of-work benefits by individuals with mental health problems is novel to the field of rehabilitative health care. These results provide evidence for the previously suspected disparity in health care utilisation of individuals with mental health problems and indicate problems in labour force integration. The findings support the political call for a 'parity of esteem', which, in Britain, was enshrined in the Health and Social Care Act of 2012.

A modular and divergent approach to spirocyclic pyrrolidines.

An efficient three-step sequence to afford a valuable class of spirocyclic pyrrolidines is reported. A reductive cleavage/Horner-Wadsworth-Emmons cascade facilitates the spirocyclisation of a range of isoxazolines bearing a distal ß-ketophosphonate. The spirocyclisation precursors are elaborated in a facile and modular fashion, via a [3 + 2]-cycloaddition followed by the condensation of a phosphonate ester, introducing multiple points of divergence. The synthetic utility of this protocol has been demonstrated in the synthesis of a broad family of 1-azaspiro[4,4]nonanes and in a concise formal synthesis of the natural product (±)-cephalotaxine.

Implication of the knowledge and perceptions of veterinary students of antimicrobial resistance for future prescription of antimicrobials in animal health, South Africa.

Understanding the knowledge and perceptions of veterinary students of antimicrobial resistance (AMR) as potential future prescribers of antimicrobials may serve as an opportunity to improve stewardship of AMR. Pre-final (n = 42) and final (n = 29) year veterinary students of the University of Pretoria completed questionnaires to determine their knowledge and perceptions of AMR. Of the 71 respondents, mixed practice (48%) and small animal practice (45%) were the most preferred career choices post-graduation, with the field of gross pathology being the least preferred. Over 80% of the respondents believed that veterinary practitioners' misuse of antimicrobials contributes to AMR and a higher percentage (98.6%) believed that farmers' misuse of antimicrobials encourages the development of AMR, in particular, in food animals (60.6%) compared to companion animals (50.7%). Agreement in the ranking of abuse of antimicrobials between pre-final and final year students was fair (36.4%; kappa 0.3), and the most abused antimicrobials in descending order listed by the students were tetracyclines, penicillins, sulphonamides and aminoglycosides. There was wide disparity between training and potential field application, as well as variations in the correct matching of antimicrobials to their respective antibiotic classes. Responses to the clinical application of antimicrobials also varied widely. Despite the apparent teaching of AMR to veterinary students, gaps may exist in the translation of theoretical concepts to clinical applications, hence the need for focused and targeted antimicrobial prescription and stewardship training to bridge these potential identified gaps.

HORIZONS protocol: a UK prospective cohort study to explore recovery of health and well-being in adults diagnosed with cancer.

INTRODUCTION: Understanding the impact of cancer and its treatment on people's everyday lives will help prepare people for what to expect, enable health professionals to predict likely recovery trajectories and shape care management according to needs. HORIZONS will recruit people awaiting treatment and follow them up at regular intervals to assess recovery of health and well-being. RESEARCH QUESTIONS: What impact does cancer diagnosis and treatment have on people's lives in the short, medium and long term? What are people's health and well-being outcomes, experiences and self-management activities over time across different cancer types and what influences these? How do people connect with and relate to others in mobilising resources that enable them to self-manage the consequences of cancer and treatment? METHODS AND ANALYSIS: HORIZONS is a multicentre, prospective cohort study exploring recovery of health and well-being in 3000 people diagnosed with breast cancer (<50 years), non-Hodgkin's lymphoma or gynaecological cancer. Recruitment will take place across National Health Service (NHS) sites in the UK between September 2016 and March 2019, before primary treatment starts. Participants will be identified through clinical teams and invited to complete questionnaires including assessments of quality of life, symptoms and functioning (Quality of Life in Adult Cancer Survivors; European Organisation for Research and Treatment Consortium Core quality of life questionnaire, EORTC-QLQ-C30), health status (EuroQol-5 dimensions, EQ-5D), self-efficacy, social support, social networks and lifestyle. Clinical data will also be collected. Descriptive statistics will characterise outcomes. Changes over time will be investigated. Factors that may influence recovery and self-management will be included in regression models to determine which influence health and well-being and self-management. ETHICS AND DISSEMINATION: Ethics and Health Research Authority approvals granted (IRAS Project ID: 202342, REC reference number 16/NW/0425). Adopted onto the National Institute for Health Research Clinical Research Network portfolio. We will engage with our Scientific Advisory Board, Tumour Specific Expert Panels, User Reference Group, Macmillan and the University of Southampton to ensure maximum publicity and benefit.

Comorbidities are associated with poorer quality of life and functioning and worse symptoms in the 5 years following colorectal cancer surgery: Results from the ColoREctal Well-being (CREW) cohort study.

OBJECTIVE: More people are living with the consequences of cancer and comorbidity. We describe frequencies of comorbidities in a colorectal cancer cohort and associations with health and well-being outcomes up to 5 years following surgery. METHODS: Prospective cohort study of 872 colorectal cancer patients recruited 2010 to 2012 from 29 UK centres, awaiting curative intent surgery. Questionnaires administered at baseline (pre-surgery), 3, 9, 15, 24 months, and annually up to 5 years. Comorbidities (and whether they limit activities) were self-reported by participants from 3 months. The EORTC QLQ-C30 and QLQ-CR29 assessed global health/quality of life (QoL), symptoms, and functioning. Longitudinal analyses investigated associations between comorbidities and health and well-being outcomes. RESULTS: At baseline, the mean age of participants was 68 years, with 60% male and 65% colon cancer. Thirty-two per cent had 1 and 40% had ≥2 comorbidities. The most common comorbidities were high blood pressure (43%), arthritis/rheumatism (32%), and anxiety/depression (18%). Of those with comorbidities, 37% reported at least 1 that limited their daily activities. Reporting any limiting comorbidities was associated with poorer global health/QoL, worse symptoms, and poorer functioning on all domains over 5-year follow-up. Controlling for the most common individual comorbidities, depression/anxiety had the greatest deleterious effect on outcomes. CONCLUSIONS: Clinical assessment should prioritise patient-reported comorbidities and whether these comorbidities limit daily activities, as important determinants of recovery of QoL, symptoms, and functioning following colorectal cancer. Targeted interventions and support services, including multiprofessional management and tailored assessment and follow-up, may aid recovery of health and well-being in these individuals.

Assessment of Multiple Membership Multilevel Models: An Application to Interviewer Effects on Nonresponse.

Multilevel multiple membership models account for situations where lower level units are nested within multiple higher level units from the same classification. Not accounting correctly for such multiple membership structures leads to biased results. The use of a multiple membership model requires selection of weights reflecting the hypothesized contribution of each level two unit and their relationship to the level one outcome. The Deviance Information Criterion (DIC) has been proposed to identify such weights. For the case of logistic regression, this study assesses, through simulation, the model identification rates of the DIC to detect the correct multiple membership weights, and the properties of model variance estimators for different weight specifications across a range of scenarios. The study is motivated by analyzing interviewer effects across waves in a longitudinal study. Interviewers can substantially influence the behavior of sample survey respondents, including their decision to participate in the survey. In the case of a longitudinal survey several interviewers may contact sample members to participate across different waves. Multilevel multiple membership models are suitable to account for the inclusion of higher-level random effects for interviewers at various waves, and to assess, for example, the relative importance of previous and current wave interviewers on current wave nonresponse. To illustrate the application, multiple membership models are applied to the UK Family and Children Survey to identify interviewer effects in a longitudinal study. The paper takes a critical view on the substantive interpretation of the model weights and provides practical guidance to statistical modelers. The main recommendation is that it is best to specify the weights in a multiple membership model by exploring different weight specifications based on the DIC, rather than prespecifying the weights.

Cost analysis of open radical cystectomy versus robot-assisted radical cystectomy.

OBJECTIVES: To perform a cost analysis comparing the cost of robot-assisted radical cystectomy (RARC) with open RC (ORC) in a UK tertiary referral centre and to identify the key cost drivers. PATIENTS AND METHODS: Data on hospital length of stay (LOS), operative time (OT), transfusion rate, and volume and complication rate were obtained from a prospectively updated institutional database for patients undergoing RARC or ORC. A cost decision tree model was created. Sensitivity analysis was performed to find key drivers of overall cost and to find breakeven points with ORC. Monte Carlo analysis was performed to quantify the variability in the dataset. RESULTS: One RARC procedure costs £12 449.87, or £12 106.12 if the robot was donated via charitable funds. In comparison, one ORC procedure costs £10 474.54. RARC is 18.9% more expensive than ORC. The key cost drivers were OT, LOS, and the number of cases performed per annum. CONCLUSION: High ongoing equipment costs remain a large barrier to the cost of RARC falling. However, minimal improvements in patient quality of life would be required to offset this difference.

Social support following diagnosis and treatment for colorectal cancer and associations with health-related quality of life: Results from the UK ColoREctal Wellbeing (CREW) cohort study.

OBJECTIVE: Social support is acknowledged as important in cancer survivorship, but little is known about change in support after cancer diagnosis and factors associated with this, particularly in colorectal cancer. The CREW cohort study investigated social support up to 2 years following curative intent surgery for colorectal cancer. METHODS: A total of 871 adults recruited pre-treatment from 29 UK centres 2010 to 2012 consented to follow-up. Questionnaires at baseline, 3, 9, 15, and 24 months post-surgery included assessments of social support (Medical Outcomes Study-Social Support Survey, MOS-SSS) and health-related quality of life (HRQoL). Socio-demographic, clinical and treatment details were collected. Longitudinal analyses assessed social support over follow-up, associations with participant characteristics, and HRQoL. RESULTS: Around 20% were living alone and 30% without a partner. Perceived social support declined in around 29% of participants, with 8% of these reporting very low levels overall from baseline to 2 years (mean MOS-SSS overall score < 40 on a scale from 0 to 100). Older age, female gender, greater neighbourhood deprivation, presence of co-morbidities, and rectal cancer site were significantly associated with reductions in perceived support. Poorer HRQoL outcomes (generic health/QoL, reduced wellbeing, anxiety, and depression) were significantly associated with lower levels of social support. CONCLUSIONS: Levels of social support decline following colorectal cancer diagnosis and treatment in nearly a third of patients and are an important risk factor for recovery of HRQoL. Assessment of support early on and throughout follow-up would enable targeted interventions to improve recovery, particularly in the more vulnerable patient groups at risk of poorer social support.

Colorectal cancer patient's self-efficacy for managing illness-related problems in the first 2 years after diagnosis, results from the ColoREctal Well-being (CREW) study.

PURPOSE: There is a growing emphasis on self-management of cancer aftercare. Little is known about patient's self-efficacy (confidence) to manage illness-related problems and how this changes over time. This paper describes the patterns of self-efficacy for managing illness-related problems amongst colorectal cancer patients in the 2 years following diagnosis. METHODS: In this prospective cohort study, questionnaires were administered at baseline (pre-surgery), 3, 9, 15 and 24 months to 872 colorectal cancer patients. Self-efficacy (confidence to manage illness-related problems), anxiety, social support, affect, socio-demographics, physical symptoms and clinical and treatment characteristics were assessed. Group-based trajectory analysis identified trajectories of self-efficacy up to 24 months and predictors. RESULTS: Four trajectories of self-efficacy were identified: group 1 (very confident) 16.0% (95% confidence interval (CI) 10.7-21.3%), group 2 (confident) 45.6% (95% CI 40.3-51.0%), group 3 (moderately confident) 29.5% (95% CI 25.1-33.8%) and group 4 (low confidence) 8.9% (95% CI 6.4-11.4%). Greater deprivation, domestic status, more co-morbidities, worse fatigue and pain, lower positivity and greater negativity were significantly associated with lower self-efficacy. There was an increase in mean scores for self-efficacy over time for the whole sample, but this did not reach the cut-off for minimally important differences. At 2 years, the lowest level of confidence to manage was for symptoms or health problems. CONCLUSION: Around 40% of patients had suboptimal levels of confidence to manage illness-related problems with little change from the time of diagnosis across the four groups. IMPLICATIONS FOR CANCER SURVIVORS: Screening for self-efficacy at diagnosis would enable targeted, early intervention which could in turn enhance health-related quality of life.

Integrated modelling of age and sex patterns of European migration.

Age and sex patterns of migration are essential for understanding drivers of population change and heterogeneity of migrant groups. We develop a hierarchical Bayesian model to estimate such patterns for international migration in the European Union and European Free Trade Association from 2002 to 2008, which was a period of time when the number of members expanded from 19 to 31 countries. Our model corrects for the inadequacies and inconsistencies in the available data and estimates the missing patterns. The posterior distributions of the age and sex profiles are then combined with a matrix of origin-destination flows, resulting in a synthetic database with measures of uncertainty for migration flows and other model parameters.

An internet-based intervention with brief nurse support to manage obesity in primary care (POWeR+): a pragmatic, parallel-group, randomised controlled trial.

BACKGROUND: The obesity epidemic has major public health consequences. Expert dietetic and behavioural counselling with intensive follow-up is effective, but resource requirements severely restrict widespread implementation in primary care, where most patients are managed. We aimed to estimate the effectiveness and cost-effectiveness of an internet-based behavioural intervention (POWeR+) combined with brief practice nurse support in primary care. METHODS: We did this pragmatic, parallel-group, randomised controlled trial at 56 primary care practices in central and south England. Eligible adults aged 18 years or older with a BMI of 30 kg/m(2) or more (or ≥28 kg/m(2) with hypertension, hypercholesterolaemia, or diabetes) registered online with POWeR+-a 24 session, web-based, weight management intervention lasting 6 months. After registration, the website automatically randomly assigned patients (1:1:1), via computer-generated random numbers, to receive evidence-based dietetic advice to swap foods for similar, but healthier, choices and increase fruit and vegetable intake, in addition to 6 monthly nurse follow-up (control group); web-based intervention and face-to-face nurse support (POWeR+Face-to-face [POWeR+F]; up to seven nurse contacts over 6 months); or web-based intervention and remote nurse support (POWeR+Remote [POWeR+R]; up to five emails or brief phone calls over 6 months). Participants and investigators were masked to group allocation at the point of randomisation; masking of participants was not possible after randomisation. The primary outcome was weight loss averaged over 12 months. We did a secondary analysis of weight to measure maintenance of 5% weight loss at months 6 and 12. We modelled the cost-effectiveness of each intervention. We did analysis by intention to treat, with multiple imputation for missing data. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN21244703. FINDINGS: Between Jan 30, 2013, and March 20, 2014, 818 participants were randomly assigned to the control group (n=279), the POWeR+F group (n=269), or the POWeR+R group (n=270). Weight loss averaged over 12 months was recorded in 666 (81%) participants. The control group lost almost 3 kg over 12 months (crude mean weight: baseline 104·38 kg [SD 21·11; n=279], 6 months 101·91 kg [19·35; n=136], 12 months 101·74 kg [19·57; n=227]). The primary imputed analysis showed that compared with the control group, patients in the POWeR+F group achieved an additional weight reduction of 1·5 kg (95% CI 0·6-2·4; p=0·001) averaged over 12 months, and patients in the POWeR+R group achieved an additional 1·3 kg (0·34-2·2; p=0·007). 21% of patients in the control group had maintained a clinically important 5% weight reduction at month 12, compared with 29% of patients in the POWeR+F group (risk ratio 1·56, 0·96-2·51; p=0·070) and 32% of patients in the POWeR+R group (1·82, 1·31-2·74; p=0·004). The incremental overall cost to the health service per kg weight lost with the POWeR+ interventions versus the control strategy was £18 (95% CI -129 to 195) for POWeR+F and -£25 (-268 to 157) for POWeR+R; the probability of being cost-effective at a threshold of £100 per kg lost was 88% and 98%, respectively. No adverse events were reported. INTERPRETATION: Weight loss can be maintained in some individuals by use of novel written material with occasional brief nurse follow-up. However, more people can maintain clinically important weight reductions with a web-based behavioural program and brief remote follow-up, with no increase in health service costs. Future research should assess the extent to which clinically important weight loss can be maintained beyond 1 year. FUNDING: Health Technology Assessment Programme of the National Institute for Health Research.

Properties of bootstrap tests for N-of-1 studies.

N-of-1 study designs involve the collection and analysis of repeated measures data from an individual not using an intervention and using an intervention. This study explores the use of semi-parametric and parametric bootstrap tests in the analysis of N-of-1 studies under a single time series framework in the presence of autocorrelation. When the Type I error rates of bootstrap tests are compared to Wald tests, our results show that the bootstrap tests have more desirable properties. We compare the results for normally distributed errors with those for contaminated normally distributed errors and find that, except when there is relatively large autocorrelation, there is little difference between the power of the parametric and semi-parametric bootstrap tests. We also experiment with two intervention designs: ABAB and AB, and show the ABAB design has more power. The results provide guidelines for designing N-of-1 studies, in the sense of how many observations and how many intervention changes are needed to achieve a certain level of power and which test should be performed.

Pre-Surgery Depression and Confidence to Manage Problems Predict Recovery Trajectories of Health and Wellbeing in the First Two Years following Colorectal Cancer: Results from the CREW Cohort Study.

PURPOSE: This paper identifies predictors of recovery trajectories of quality of life (QoL), health status and personal wellbeing in the two years following colorectal cancer surgery. METHODS: 872 adults receiving curative intent surgery during November 2010 to March 2012. Questionnaires at baseline, 3, 9, 15, 24 months post-surgery assessed QoL, health status, wellbeing, confidence to manage illness-related problems (self-efficacy), social support, co-morbidities, socio-demographic, clinical and treatment characteristics. Group-based trajectory analyses identified distinct trajectories and predictors for QoL, health status and wellbeing. RESULTS: Four recovery trajectories were identified for each outcome. Groups 1 and 2 fared consistently well (scores above/within normal range); 70.5% of participants for QoL, 33.3% health status, 77.6% wellbeing. Group 3 had some problems (24.2% QoL, 59.3% health, 18.2% wellbeing); Group 4 fared consistently poorly (5.3% QoL, 7.4% health, 4.2% wellbeing). Higher pre-surgery depression and lower self-efficacy were significantly associated with poorer trajectories for all three outcomes after adjusting for other important predictors including disease characteristics, stoma, anxiety and social support. CONCLUSIONS: Psychosocial factors including self-efficacy and depression before surgery predict recovery trajectories in QoL, health status and wellbeing following colorectal cancer treatment independent of treatment or disease characteristics. This has significant implications for colorectal cancer management as appropriate support may be improved by early intervention resulting in more positive recovery experiences.

Recent applications in natural product synthesis of dihydrofuran and -pyran formation by ring-closing alkene metathesis.

In the past two decades, alkene metathesis has risen in prominence to become a significant synthetic strategy for alkene formation. Many total syntheses of natural products have used this transformation. We review the use, from 2003 to 2015, of ring-closing alkene metathesis (RCM) for the generation of dihydrofurans or -pyrans in natural product synthesis. The strategies used to assemble the RCM precursors and the subsequent use of the newly formed unsaturation will also be highlighted and placed in context.

A web-based intervention (RESTORE) to support self-management of cancer-related fatigue following primary cancer treatment: a multi-centre proof of concept randomised controlled trial.

PURPOSE: Cancer-related fatigue (CRF) is a frequent and distressing symptom experienced after cancer treatment. RESTORE is the first web-based resource designed to enhance self-efficacy to manage CRF following curative-intent treatment. The aim of this study is to test the proof of concept and inform the design of an effectiveness trial. METHODS: A multi-centre parallel-group two-armed (1:1) exploratory randomised controlled trial (RCT) with qualitative process evaluation was employed in the study. Participants (≥18 years; ≤5 years post treatment with moderate to severe fatigue) were recruited and randomly assigned to RESTORE or a leaflet. Feasibility and acceptability were measured by recruitment, attrition, intervention adherence, completion of outcome measures and process evaluation. Change in self-efficacy to manage CRF was also explored. Outcome measures were completed at baseline (T0), 6 weeks (T1) and 12 weeks (T2). Data were analysed using mixed-effects linear regression and directed content analysis. RESULTS: One hundred and sixty-three people participated in the trial and 19 in the process evaluation. The intervention was feasible (39 % of eligible patients consented) and acceptable (attrition rate 36 %). There was evidence of higher fatigue self-efficacy at T1 in the intervention group vs comparator (mean difference 0.51 [-0.08 to 1.11]), though the difference in groups decreased by 12 weeks. Time since diagnosis influenced perceived usefulness of the intervention. Modifications were suggested. CONCLUSION: Proof of concept was achieved. The RESTORE intervention should be subject to a definitive trial with some adjustments. Provision of an effective supportive resource would empower cancer survivors to manage CRF after treatment completion. TRIAL REGISTRATION: ISRCTN67521059.

Bayesian Population Forecasting: Extending the Lee-Carter Method.

In this article, we develop a fully integrated and dynamic Bayesian approach to forecast populations by age and sex. The approach embeds the Lee-Carter type models for forecasting the age patterns, with associated measures of uncertainty, of fertility, mortality, immigration, and emigration within a cohort projection model. The methodology may be adapted to handle different data types and sources of information. To illustrate, we analyze time series data for the United Kingdom and forecast the components of population change to the year 2024. We also compare the results obtained from different forecast models for age-specific fertility, mortality, and migration. In doing so, we demonstrate the flexibility and advantages of adopting the Bayesian approach for population forecasting and highlight areas where this work could be extended.