The effect of aspirin and eicosapentaenoic acid on urinary biomarkers of prostaglandin E2 synthesis and platelet activation in participants of the seAFOod polyp prevention trial.

Urinary prostaglandin (PG) E metabolite (PGE-M) and 11-dehydro (d)-thromboxane (TX) B2 are biomarkers of cyclooxygenase-dependent prostanoid synthesis. We investigated (1) the effect of aspirin 300 mg daily and eicosapentaenoic acid (EPA) 2000 mg daily, alone and in combination, on urinary biomarker levels and, (2) whether urinary biomarker levels predicted colorectal polyp risk, during participation in the seAFOod polyp prevention trial. Urinary PGE-M and 11-d-TXB2 were measured by liquid chromatography-tandem mass spectrometry. The relationship between urinary biomarker levels and colorectal polyp outcomes was investigated using negative binomial (polyp number) and logistic (% with one or more polyps) regression models. Despite wide temporal variability in PGE-M and 11-d-TXB2 levels within individuals, both aspirin and, to a lesser extent, EPA decreased levels of both biomarkers (74% [P ≤ .001] and 8% [P ≤ .05] reduction in median 11-d-TXB2 values, respectively). In the placebo group, a high (quartile [Q] 2-4) baseline 11-d-TXB2 level predicted increased polyp number (incidence rate ratio [IRR] [95% CI] 2.26 [1.11,4.58]) and risk (odds ratio [95% CI] 3.56 [1.09,11.63]). A low (Q1) on-treatment 11-d-TXB2 level predicted reduced colorectal polyp number compared to placebo (IRR 0.34 [0.12,0.93] for combination aspirin and EPA treatment) compared to high on-treatment 11-d-TXB2 values (0.61 [0.34,1.11]). Aspirin and EPA both inhibit PGE-M and 11-d-TXB2 synthesis in keeping with shared in vivo cyclooxygenase inhibition. Colorectal polyp risk and treatment response prediction by 11-d-TXB2 is consistent with a role for platelet activation during early colorectal carcinogenesis. The use of urinary 11-d-TXB2 measurement for a precision approach to colorectal cancer risk prediction and chemoprevention requires prospective evaluation.

Health-related quality of life after a diagnosis of bladder cancer: a longitudinal survey over the first year.

OBJECTIVES: To describe the health-related quality of life (HRQoL) of patients in a prospective 12-month observational cohort study of new bladder cancer diagnoses and compare with national cancer and general population surveys. PATIENTS AND METHODS: A prospective UK study in patients with new bladder cancer diagnoses at 13 NHS Trusts. The HRQoL data were collected at 3, 6, 9 and 12 months. Questionnaires used included: the EuroQoL five Dimensions (EQ-5D), European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ)-30-item core, EORTC QLQ-24-item non-muscle-invasive bladder cancer, and EORTC QLQ-30-item muscle-invasive bladder cancer. Results were compared with the Cancer Quality of Life Survey and Health Survey for England. RESULTS: A total of 349 patients were recruited, 296 (85%) completed the first (baseline) and 233 (67%) the final survey. The patients underwent transurethral resection of bladder tumour (TURBT) ± intravesical therapy (238 patients, 80%), radical cystectomy/radiotherapy (51, 17%) or palliation (seven, 2%). At baseline, patients needing radical treatment reported worse HRQoL including lower social function (74.2 vs 83.8, P = 0.002), increased fatigue (31.5 vs 26.1, P = 0.03) and more future worries (39.2 vs 29.4, P = 0.005) than patients who underwent TURBT. Post-treatment surveys showed no change/improvements for patients who underwent TURBT but deterioration for the radically treated cohort. At final survey, reports were similar to baseline, regardless of treatment. Radically treated patients continued to report poorer HRQoL including issues with body image (23.4 vs 12.5, P = 0.007) and male sexual function (75.8 vs 40.4, P < 0.001) compared to those who underwent TURBT. Radically treated patients reported lower EQ-5D utility scores and more problems with usual activities than the general population. DISCUSSION: Patients undergoing TURBT can be reassured regarding HRQoL following treatment. However, those requiring radical treatment report greater changes in HRQoL with the need for appropriate clinical and supportive care to minimise the impact of treatments.

Polymorphisms in Cyclooxygenase, Lipoxygenase, and TP53 Genes Predict Colorectal Polyp Risk Reduction by Aspirin in the seAFOod Polyp Prevention Trial.

Aspirin and eicosapentaenoic acid (EPA) reduce colorectal adenomatous polyp risk and affect synthesis of oxylipins including prostaglandin E2. We investigated whether 35 SNPs in oxylipin metabolism genes such as cyclooxygenase (PTGS) and lipoxygenase (ALOX), as well as 7 SNPs already associated with colorectal cancer risk reduction by aspirin (e.g., TP53; rs104522), modified the effects of aspirin and EPA on colorectal polyp recurrence in the randomized 2 × 2 factorial seAFOod trial. Treatment effects were reported as the incidence rate ratio (IRR) and 95% confidence interval (CI) by stratifying negative binomial and Poisson regression analyses of colorectal polyp risk on SNP genotype. Statistical significance was reported with adjustment for the false discovery rate as the P and q value. 542 (of 707) trial participants had both genotype and colonoscopy outcome data. Reduction in colorectal polyp risk in aspirin users compared with nonaspirin users was restricted to rs4837960 (PTGS1) common homozygotes [IRR, 0.69; 95% confidence interval (CI), 0.53-0.90); q = 0.06], rs2745557 (PTGS2) compound heterozygote-rare homozygotes [IRR, 0.60 (0.41-0.88); q = 0.06], rs7090328 (ALOX5) rare homozygotes [IRR 0.27 (0.11-0.64); q = 0.05], rs2073438 (ALOX12) common homozygotes [IRR, 0.57 (0.41-0.80); q = 0.05], and rs104522 (TP53) rare homozygotes [IRR, 0.37 (0.17-0.79); q = 0.06]. No modification of colorectal polyp risk in EPA users was observed. In conclusion, genetic variants relevant to the proposed mechanism of action on oxylipins are associated with differential colorectal polyp risk reduction by aspirin in individuals who develop multiple colorectal polyps. SNP genotypes should be considered during development of personalized, predictive models of colorectal cancer chemoprevention by aspirin. PREVENTION RELEVANCE: Single-nucleotide polymorphisms in genes controlling lipid mediator signaling may modify the colorectal polyp prevention activity of aspirin. Further investigation is required to determine whether testing for genetic variants can be used to target cancer chemoprevention by aspirin to those who will benefit most.

Contrasting socio-economic influences on colorectal cancer incidence and survival in England and Wales.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the world and second most common cause of cancer death. The relationship between socio-economic deprivation and CRC incidence is unclear and previous findings have been inconsistent. There is stronger evidence of an association between area-level deprivation and CRC survival; however, few studies have investigated the association between individual-level socio-economic status (SES) and CRC survival. Data from the Office for National Statistics Longitudinal Study (LS) in England and Wales was used. LS members aged 50+ were stratified by individual-level educational attainment, social class, housing tenure and area deprivation quintile, measured at the 2001 Census. Time-to-event analysis examined associations between indicators of SES and CRC incidence and survival (all-cause and CRC death), over a 15-year follow-up period. Among 178116 LS members, incidence of CRC was lower among those with a degree, compared to those with no degree and higher among those employed in manual occupations compared to non-manual occupations. No clear relationship was observed between CRC incidence and the area-based measure of deprivation. Disparities were greater for survival. Among 5016 patients diagnosed with CRC aged 50+, probability of death from all-causes was lower among those with a degree, compared to no degree and higher among those employed in manual occupations, compared to non-manual occupations and among those living in social-rented housing, compared to owner-occupiers. Individual indicators of SES were also associated with probability of death from CRC. Those living in the most deprived areas had a higher probability of death (from all-causes and CRC) compared to those in the least deprived areas. Both individual and area-based indicators of SES were associated with CRC survival, and the relationships were stronger than those observed for CRC incidence. These findings could help inform more effective targeting of public health interventions for CRC.

Colorectal polyp outcomes after participation in the seAFOod polyp prevention trial: Evidence of rebound elevated colorectal polyp risk after short-term aspirin use.

BACKGROUND: The seAFOod polyp prevention trial was a randomised, placebo-controlled, 2 × 2 factorial trial of aspirin 300 mg and eicosapentaenoic acid (EPA) 2000 mg daily in individuals who had a screening colonoscopy in the English Bowel Cancer Screening Programme (BCSP). Aspirin treatment was associated with a 20% reduction in colorectal polyp number at BCSP surveillance colonoscopy 12 months later. It is unclear what happens to colorectal polyp risk after short-term aspirin use. AIM: To investigate colorectal polyp risk according to the original trial treatment allocation, up to 6 years after trial participation. METHODS: All seAFOod trial participants were scheduled for further BCSP surveillance and provided informed consent for the collection of colonoscopy outcomes. We linked BCSP colonoscopy data to trial outcomes data. RESULTS: In total, 507 individuals underwent one or more colonoscopies after trial participation. Individuals grouped by treatment allocation were well matched for clinical characteristics, follow-up duration and number of surveillance colonoscopies. The polyp detection rate (PDR; the number of individuals who had ≥1 colorectal polyp detected) after randomization to placebo aspirin was 71.1%. The PDR was 80.1% for individuals who had received aspirin (odds ratio [OR] 1.13 [95% confidence interval 1.02, 1.24]; p = 0.02). There was no difference in colorectal polyp outcomes between individuals who had been allocated to EPA compared with its placebo (OR for PDR 1.00 [0.91, 1.10]; p = 0.92). CONCLUSION: Individuals who received aspirin in the seAFOod trial demonstrated increased colorectal polyp risk during post-trial surveillance. Rebound elevated neoplastic risk after short-term aspirin use has important implications for aspirin cessation driven by age-related bleeding risk. ISRCTN05926847.

Lifestyle Factors in Patients with Bladder Cancer: A Contemporary Picture of Tobacco Smoking, Electronic Cigarette Use, Body Mass Index, and Levels of Physical Activity.

BACKGROUND: Little is known about contemporary lifestyle choices in patients with bladder cancer (BC). These choices include carcinogenic risk factors and could affect fitness to receive treatments. OBJECTIVE: To evaluate the contemporary lifestyle choices in BC patients. DESIGN, SETTING, AND PARTICIPANTS: Self-reported surveys from participants diagnosed with BC in the previous 10 yr captured smoking patterns, e-cigarette use, physical activity using the GODIN Leisure-Time Exercise Questionnaire, long-term conditions (LTCs), relationship status, sociodemographics, and body mass index (BMI; height and weight). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Findings were compared with the general population and men with prostate cancer. RESULTS AND LIMITATIONS: Completed surveys were received from 2092 participants. Most respondents were ex-smokers (61% vs 10% current vs 29% never). The use of e-cigarettes was uncommon (9%) and at lower rates than the age-equivalent general population. Passive smoke exposure was frequent (48%). Most participants (68%) were "insufficiently active" using the GODIN criteria and less physically active than the age-equivalent general population. Most respondents (44%) were classified as overweight (BMI 25-29.99) or obese (22%, BMI >30). Lifestyle factors varied with age, sex, socioeconomic deprivation, and LTCs. Younger participants were less likely to smoke (p < 0.001), more likely to have used e-cigarettes (p < 0.001), but more likely to have had passive smoke exposure (p = 0.008). Those from less affluent areas were more likely to smoke (p < 0.001), have used e-cigarettes (p < 0.001), and have had passive smoke exposure (p = 0.02). Females were less likely to be smokers (p < 0.001) but more likely to have been exposed to passive smoke (p < 0.001). CONCLUSIONS: Persons affected by BC often have smoking exposures and high BMI, and are insufficiently active. Rates of e-cigarette use were lower than in the general population. Efforts to improve quality of life in this cohort should include wider advocation of smoking cessation, perhaps including the use of e-cigarettes, and programmes to increase exercise and reduce BMI. PATIENT SUMMARY: We looked at the lifestyle choices, such as smoking, e-cigarette use, physical activity levels, and obesity, of patients following a bladder cancer diagnosis. We conclude that this population would benefit from healthy lifestyle interventions.

The risk of colorectal cancer in individuals with mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene: An English population-based study.

BACKGROUND: Studies have demonstrated a higher risk of developing colorectal cancer (CRC) in individuals with Cystic Fibrosis (CF), and also a potentially increased risk in carriers of cystic fibrosis transmembrane conductance regulator (CFTR) mutations. Life expectancy for those with CF is rising, increasing the number at risk of developing CRC. METHODS: The incidence of CRC amongst individuals with CF was calculated using data from CORECT-R and linked UK CF Registry and Secondary User Services (SUS) data. Crude, age-specific and age-standardised rates were compared to those without CF. The presence of CFTR mutations in individuals with CRC was assessed using 100,000 Genomes Project data. FINDINGS: The crude incidence rate of CRC in the CF population was 0.29 per 1,000 person-years (28 cases). The CF population were significantly younger than those without (median age at CRC diagnosis 52 years versus 73 years; p<0·01). When age-adjusted, there was a 5-fold increased CRC incidence amongst individuals with CF compared to those without (SIR 5.0 95%CI 3.2-6.9). When compared to other population studies the overall prevalence of CFTR mutations in the CRC population was significantly higher than expected (p<0·01). INTERPRETATION: CF is linked to an increased risk of CRC. The incidence of CFTR mutations in the CRC population is higher than would be expected, suggesting an association between CFTR function and CRC risk. Further research is needed to develop effective screening strategies for these populations. FUNDING: Cancer Research UK (grants C23434/A23706 & C10674/A27140).

Inflammatory Bowel Disease-Associated Colorectal Cancer Epidemiology and Outcomes: An English Population-Based Study.

INTRODUCTION: Patients with inflammatory bowel diseases (IBDs) of the colon are at an increased risk of colorectal cancer (CRC). This study investigates the epidemiology of IBD-CRC and its outcomes. METHODS: Using population data from the English National Health Service held in the CRC data repository, all CRCs with and without prior diagnosis of IBD (Crohn's, ulcerative colitis, IBD unclassified, and IBD with cholangitis) between 2005 and 2018 were identified. Descriptive analyses and logistic regression models were used to compare the characteristics of the 2 groups and their outcomes up to 2 years. RESULTS: Three hundred ninety thousand six hundred fourteen patients diagnosed with CRC were included, of whom 5,141 (1.3%) also had a previous diagnosis of IBD. IBD-CRC cases were younger (median age at CRC diagnosis [interquartile range] 66 [54-76] vs 72 [63-79] years [ P < 0.01]), more likely to be diagnosed with CRC as an emergency (25.1% vs 16.7% [ P < 0.01]), and more likely to have a right-sided colonic tumor (37.4% vs 31.5% [ P < 0.01]). Total colectomy was performed in 36.3% of those with IBD (15.4% of Crohn's, 44.1% of ulcerative colitis, 44.5% of IBD unclassified, and 67.7% of IBD with cholangitis). Synchronous (3.2% vs 1.6% P < 0.01) and metachronous tumors (1.7% vs 0.9% P < 0.01) occurred twice as frequently in patients with IBD compared with those without IBD. Stage-specific survival up to 2 years was worse for IBD-associated cancers. DISCUSSION: IBD-associated CRCs occur in younger patients and have worse outcomes than sporadic CRCs. There is an urgent need to find reasons for these differences to inform screening, surveillance, and treatment strategies for CRC and its precursors in this high-risk group.

Sexual Activity, Function and Dysfunction After a Diagnosis of Bladder Cancer.

BACKGROUND: Sexual dysfunction is common in those affected by cancer and local and radical treatments for Bladder Cancer (BC) can affect sexual function directly. AIM: To evaluate sexual function following a bladder cancer (BC) diagnosis. METHODS: Self-reported sexual function was collected 10 years after a diagnosis of BC as part of a cross-sectional patient reported outcome measure (PROM) survey exploring life after BC diagnosis and treatment. OUTCOMES: Participants completed a combined EORTC QLQ-BLM30 and QLQ-NMIBC24 questionnaire, including questions on sexual activity, intimacy, erectile/ejaculatory function and vaginal dryness. RESULTS: A total of 1796 participants returned a completed survey out of 3279 eligible participants (55%). Of the participants who returned a completed survey, a total of 1530 (85%) participants answered sexual function questions. The median (IQR) age was 75 (70-81). Participants were predominantly men (78%) and married/in civil partnerships (66%). In total, 31% were sexually active. Vaginal dryness was common (66%) in women. Erectile and ejaculatory dysfunction (80% and 58% respectively) were common in men. Compared to TURBT +/- intravesical treatments, those who had radical treatment were less likely to be sexually active (adjusted OR 0.56, 95% CI: 0.44-0.72, P<0.001) and had worse mean scores for intimacy problems (29.1 [radical treatment] vs 12.1, P<0.001), male sexual problems (72.2 [radical treatment] vs 45.7, P<0.001) and overall sexual function (17.1 [radical treatment] vs 20.3, P=0.01). CLINICAL IMPLICATIONS: These findings highlight the magnitude of sexual dysfunction in the BC patient cohort and can help inform patients during the pre-op counselling process and shared decision making prior to BC treatments. STRENGTHS AND LIMITATIONS: This study provides the largest in-depth analysis of sexual activity and function after BC diagnosis and treatment, to date. Limitations include the lack of data on participants' sexual function prior to BC treatment and the heterogeneity with respect to time passed since last BC treatment. CONCLUSION: Sexual dysfunction in BC patients is common and rates appear higher following radical treatments compared to endoscopic. It is important to elicit these problems in clinics to enable counselling and treatment. Jubber I, Rogers Z, Catto JWF, et al. Sexual Activity, Function and Dysfunction After a Diagnosis of Bladder Cancer. J Sex Med 2022;19:1431-1441.

Quality of life profiles and their association with clinical and demographic characteristics and physical activity in people with a stoma: a latent profile analysis.

PURPOSE: Quality of life can be negatively impacted by the formation of a stoma and is influenced by a number of factors. Research to date treats people with a stoma as a homogenous group based on their quality of life. We attempted to identify subgroups based upon self-reported quality of life and explored variables associated with group membership. METHODS: The present study is a secondary analysis of a cross-sectional sample of 1419 people with a stoma. Participants completed validated questionnaires for quality of life, physical activity and clinical and demographic characteristics. Latent profile analysis was used to identify the optimal number of subgroups (profiles) and multinomial regression modelling was conducted to identify variables associated with profile membership. RESULTS: The analysis revealed 4 distinct profiles of people with a stoma: 'consistently good quality of life' [N = 891 (62.8%)], 'some quality of life concerns' [N = 184 (13.0%)], 'low quality of life' [N = 181 (12.8%)] and 'financial concerns' [N = 163 (11.5%)]. Modelling revealed that people with a recent stoma (formed < 2 years previously), who have a hernia and are less physically active were more likely to belong to the 'low quality of life' profile. Furthermore, those aged 16-55 were more likely to have financial concerns. CONCLUSION: This study was the first to identify latent profiles within this population and assess whether certain variables are associated with membership. Future research should build upon this to identify additional variables associated with these profiles, which can help to provide the basis for targeting and tailoring future interventions to specific subgroups of people with a stoma.

The long and the short of it: Mechanisms of synchronous and compensatory dynamics across temporal scales.

Synchronous dynamics (fluctuations that occur in unison) are universal phenomena with widespread implications for ecological stability. Synchronous dynamics can amplify the destabilizing effect of environmental variability on ecosystem functions such as productivity, whereas the inverse, compensatory dynamics, can stabilize function. Here we combine simulation and empirical analyses to elucidate mechanisms that underlie patterns of synchronous versus compensatory dynamics. In both simulated and empirical communities, we show that synchronous and compensatory dynamics are not mutually exclusive but instead can vary by timescale. Our simulations identify multiple mechanisms that can generate timescale-specific patterns, including different environmental drivers, diverse life histories, dispersal, and non-stationary dynamics. We find that traditional metrics for quantifying synchronous dynamics are often biased toward long-term drivers and may miss the importance of short-term drivers. Our findings indicate key mechanisms to consider when assessing synchronous versus compensatory dynamics and our approach provides a pathway for disentangling these dynamics in natural systems.

Current water quality guidelines across North America and Europe do not protect lakes from salinization.

Human-induced salinization caused by the use of road deicing salts, agricultural practices, mining operations, and climate change is a major threat to the biodiversity and functioning of freshwater ecosystems. Yet, it is unclear if freshwater ecosystems are protected from salinization by current water quality guidelines. Leveraging an experimental network of land-based and in-lake mesocosms across North America and Europe, we tested how salinization-indicated as elevated chloride (Cl-) concentration-will affect lake food webs and if two of the lowest Cl- thresholds found globally are sufficient to protect these food webs. Our results indicated that salinization will cause substantial zooplankton mortality at the lowest Cl- thresholds established in Canada (120 mg Cl-/L) and the United States (230 mg Cl-/L) and throughout Europe where Cl- thresholds are generally higher. For instance, at 73% of our study sites, Cl- concentrations that caused a ≥50% reduction in cladoceran abundance were at or below Cl- thresholds in Canada, in the United States, and throughout Europe. Similar trends occurred for copepod and rotifer zooplankton. The loss of zooplankton triggered a cascading effect causing an increase in phytoplankton biomass at 47% of study sites. Such changes in lake food webs could alter nutrient cycling and water clarity and trigger declines in fish production. Current Cl- thresholds across North America and Europe clearly do not adequately protect lake food webs. Water quality guidelines should be developed where they do not exist, and there is an urgent need to reassess existing guidelines to protect lake ecosystems from human-induced salinization.

Stability of health-related quality of life and morbidity burden from 18 months after diagnosis of prostate cancer: results of a UK-wide population-based outcome cohort.

OBJECTIVE: To evaluate the dynamic nature of self-reported health-related quality of life (HRQL) and morbidity burden in men diagnosed with prostate cancer, we performed a follow-up study of the Life After Prostate Cancer Diagnosis (LAPCD) study cohort 12 months after initial survey. METHODS: The LAPCD study collected information from 35,823 men across the UK who were 18-42 months post-diagnosis of prostate cancer. Men who were still alive 12 months later were resurveyed. Generic HRQL (EQ-5D-5L plus self-assessed health rating) and prostate cancer-specific outcomes (EPIC-26) were assessed. Treatment(s) received was self-reported. Previously defined clinically meaningful differences were used to evaluate changes in outcomes over time. RESULTS: A total of 28,450 men across all disease stages completed follow-up surveys (85.8% response). Of the 21,700 included in this study, 89.7% reported no additional treatments since the first survey. This group experienced stable urinary and bowel outcomes, with good function for most men at both time points. On-going poor (but stable) urinary issues were associated with previous surgery. Sexual function scores remained low (mean: 26.8/100). Self-assessed health ratings were stable over time. The largest declines in HRQL and functional outcomes were experienced by men reporting their first active treatment between surveys. DISCUSSION: The results suggest stability of HRQL and most specific morbidities by 18-42 months for men who report no further treatment in the subsequent 12 months. This is reassuring for those with good function and HRQL but re-enforces the need for early intervention and support for men who experience poor outcomes.

A systematic review and meta-analysis of the effectiveness of self-management interventions in people with a stoma.

AIMS: Explore the evidence from randomized controlled trials for the effect of self-management interventions on quality of life, self-management skills and self-efficacy, and to explore which intervention characteristics are associated with effectiveness. DESIGN: Systematic review. DATA SOURCES: A search of the literature was conducted in these databases: MEDLINE (OVID), EMBASE (OVID) and PsychINFO (OVID) from January 2000 to February 2020. REVIEW METHODS: Studies were included if participants had a bowel stoma, were over the age of 18 and the design was a randomized controlled trial of a self-management programme. The outcome measures for this review were quality of life, self-management skills and self-efficacy. The Behaviour Change Technique Taxonomy was used to code interventions for underlying components and alongside other intervention characteristics, associations with improvements in outcomes were explored. RESULTS: The search identified 3141 articles, 16 of which were eligible. A meta-analysis of self-efficacy scores from five studies (N = 536) found an improvement in those that received the self-management intervention at follow-up with a 12-point mean difference compared with the usual care group. Effects on quality of life and self-management skills were mixed, and meta-analyses of these data were not possible. Across 13 studies an average of 10 behaviour change techniques were used with, credible source (e.g. nurse, doctor, therapist) (n = 13), instruction on how to perform the behaviour (n = 13), demonstration of the behaviour (n = 12) used most often. The behaviour change technique of self-monitoring was associated with an improvement in quality of life. The involvement of a nurse was associated with higher self-efficacy and self-management skills. CONCLUSION: This review suggests that self-management interventions can increase peoples' self-efficacy for managing their stoma. IMPACT: A standardized approach to the reporting of interventions and the measures used is needed in future studies to better understand the effect on quality of life and self-management skills.

Experiences of Support for Sexual Dysfunction in Men With Prostate Cancer: Findings From a U.K.-Wide Mixed Methods Study.

BACKGROUND: Men with prostate cancer (PCa) often experience sexual dysfunction following diagnosis and treatment, yet little is known about the support they receive to deal with this. AIM: To explore men's experiences of support for sexual dysfunction following PCa diagnosis. METHODS: This study included a U.K.-wide survey of men 18-42 months post-diagnosis of PCa, identified through cancer registries. The survey measured sexual function and the extent to which men perceived sexual dysfunction to be a problem (Expanded Prostate Cancer Index Composite-26), access to and experience of medications, devices, and specialist services for sexual dysfunction, and included a free-text question for further comments. Analysis focussed on men who reported poor sexual function, which they considered a moderate or big problem. Descriptive statistics explored the characteristics of men offered intervention and those that found this helpful. Free-text responses were analyzed using thematic analysis. OUTCOME: The main outcome of this study was to assess access to and experience of medications, devices, and specialist services for sexual dysfunction. RESULTS: 39.0% of all survey respondents (13,978/35,823) reported poor sexual function, which they considered a moderate or big problem. 51.7% of these men were not offered any intervention to aid sexual functioning. 71.9% of those offered an intervention reported trying it, of whom 48.7% found the intervention helpful. Men treated with surgery or brachytherapy were most likely to be offered an intervention. Medication was the most commonly offered intervention and 39.3% of those who tried medication found this helpful. Although offered less often, approximately half of the men who tried devices or attended specialist services found the intervention helpful. Free-text responses indicated that barriers to accessing support included inadequate information and support from healthcare professionals, embarrassment, negative views about treatment options, concerns about side effects and safety, and inconsistencies between secondary and primary care. Barriers to continuing use included limited effectiveness of treatments, inadequate ongoing support, and funding constraints. Drivers of sexual recovery included patient proactivity and persistence with trying different treatment options and ongoing support from health professionals. CLINICAL IMPLICATIONS: There is an urgent need to ensure that all men are offered, and have equal access to, sexual care support, with referral to specialist services when required. STRENGTHS & LIMITATIONS: This study presents data from a large, U.K.-wide, population-based study of men with PCa and includes quantitative and qualitative findings. The possibility of non-response bias should, however, be considered. CONCLUSION: There are significant shortcomings in the support offered to U.K. men with sexual dysfunction following diagnosis and treatment for PCa which need to be addressed. Watson E, Wilding S, Matheson L, et al. Experiences of Support for Sexual Dysfunction in Men With Prostate Cancer: Findings From a U.K.-Wide Mixed Methods Study. J Sex Med 2021;18:515-525.

Quality of Life After Bladder Cancer: A Cross-sectional Survey of Patient-reported Outcomes.

BACKGROUND: Little is known about health-related quality of life (HRQOL) following treatment for bladder cancer (BC). OBJECTIVE: To determine this, we undertook a cross-sectional survey covering 10% of the English population. DESIGN, SETTING, AND PARTICIPANTS: Participants 1-10 yr from diagnosis were identified through national cancer registration data. INTERVENTION: A postal survey was administered containing generic HRQOL and BC-specific outcome measures. Findings were compared with those of the general population and other pelvic cancer patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Generic HRQOL was measured using five-level EQ-5D (EQ-5D-5L) and European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ)-C30. BC-specific outcomes were derived from EORTC QLQ-BLM30 and EORTC QLQ-NMIBC24. RESULTS AND LIMITATIONS: A total of 1796 surveys were completed (response rate 55%), including 868 (48%) patients with non-muscle-invasive BC, 893 (50%) patients who received radiotherapy or radical cystectomy, and 35 (1.9%) patients for whom treatment was unknown. Most (69%) of the participants reported at least one problem in any EQ-5D dimension. Age/sex-adjusted generic HRQOL outcomes were similar across all stages and treatment groups, whilst problems increased with age (problems in one or more EQ-5D dimensions: <65 yr [67% {95% confidence interval or CI: 61-74}] vs 85+ yr [84% {95% CI: 81-89}], p = 0.016) and long-term conditions (no conditions [53% {95% CI: 48-58}] vs more than four conditions [94% {95% CI: 90-97}], p < 0.001). Sexual problems were reported commonly in men, increasing with younger age and radical treatment. Younger participants (under 65 yr) reported more financial difficulties (mean score 20 [95% CI: 16-25]) than those aged 85+ yr (6.8 [4.5-9.2], p < 0.001). HRQOL for BC patients (for comparison, males with problems in one or more EQ-5D dimensions 69% [95% CI: 66-72]) was significantly worse than what has been found after colorectal and prostate cancers and in the general population (51% [95% CI: 48-53], all p < 0.05). CONCLUSIONS: HRQOL following BC appears to be relatively independent of disease stage, treatment, and multimodal care. Issues are reported with sexual function and financial toxicity. HRQOL after BC is worse than that after other pelvic cancers. PATIENT SUMMARY: Patients living with bladder cancer often have reduced quality of life, which may be worse than that for other common pelvic cancer patients. Age and other illnesses appear to be more important in determining this quality of life than the treatments received. Many men complain of sexual problems. Younger patients have financial worries.

Improving outcome prediction in individuals with colorectal cancer and diabetes by accurate assessment of vascular complications: Implications for clinical practice.

BACKGROUND: Diabetes is considered a risk factor for mortality following a diagnosis of cancer. We hypothesised that the risk will vary due to the heterogeneous nature of the population and accurate classification of vascular complications will improve prediction of clinical outcomes. METHODS: The COloRECTal cancer data Repository (CORECT-R) was used to identify individuals with primary colorectal cancer, who underwent surgical resection in England (2005-2016). Diabetes was recorded using ICD10 codes (E10-E14) during inpatient hospital admission in the six years preceding cancer diagnosis, complication status was determined using the adapted Diabetes Complications Severity Index (aDCSI). Survival and post-operative outcomes were compared between groups. RESULTS: Of 232,367 individuals, 28,642 (12.3%) were recorded as having diabetes, 49.2% of whom had complications according to the aDCSI. Patients with diabetes complications had increased incidence of adverse post-operative outcomes (90-day post-operative mortality (6.6% versus 3.2%) and death during the surgical episode (7.9% versus 3.6%)), compared to those without diabetes. Those without complications had rates comparable to the population without diabetes. The odds of death within a year of diagnosis were higher for those with complicated diabetes compared to those without diabetes [OR 1.58 (95%CI 1.51-1.66) p < 0.01], but no difference was observed between those with uncomplicated diabetes and those without diabetes [OR 1.05 (95%CI 0.99-1.11) p = 0.10]. CONCLUSIONS: Prediction of outcome following surgery in colorectal cancer patients with diabetes relies on the accurate assessment of complications. This study suggests that the poor post-operative outcomes in diabetes patients may be associated with diabetes complication rather than diabetes itself.

Influence of deprivation and rurality on patient-reported outcomes of men living with and beyond prostate cancer diagnosis in the UK: A population-based study.

BACKGROUND: In the UK, inequalities exist in prostate cancer incidence, survival and treatment by area deprivation and rurality. This work aimed to identify variation in patient-reported outcomes of men with prostate cancer by area type. METHODS: A population-based survey of men 18-42 months after prostate cancer diagnosis (N = 35608) measured self-assessed health (SAH) using the EQ-5D and five functional domains using the Expanded Prostate Cancer Index Composite (EPIC-26). RESULTS: Mean SAH was higher for men in least deprived areas compared to most deprived (difference 6.3 (95 %CI 5.6-7.2)). SAH scores were lower for men in most urban areas compared to most rural (difference 2.4 (95 %CI 1.8-3.0)). Equivalent estimates in the general population reported a 13 point difference by deprivation and a 4 point difference by rurality. For each EPIC-26 domain, functional outcomes were better for men in the least deprived areas, with clinically meaningful differences observed for urinary incontinence and hormonal function. There were no clinically meaningful differences in EPIC-26 outcomes by rurality with less than a three point difference in scores for each domain between urban and rural areas. CONCLUSION: In men 18-42 months post diagnosis of prostate cancer in the UK, impacts of area deprivation and rurality on self-assessed health related quality of life were not greater than would be expected in the general population. However, clinically meaningful differences were identified for some prostate functional outcomes (urinary and hormonal function) by deprivation. No impact by rurality of residence was identified.