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.

Fish oil supplement use modifies the relationship between dietary oily fish intake and plasma n-3 PUFA levels: an analysis of the UK Biobank.

Observational evidence linking dietary n-3 PUFA intake and health outcomes is limited by a lack of robust validation of dietary intake using blood n-3 PUFA levels and potential confounding by fish oil supplement (FOS) use. We investigated the relationship between oily fish intake, FOS use and plasma n-3 PUFA levels in 121 650 UK Biobank (UKBB) participants. Ordinal logistic regression models, adjusted for clinical and lifestyle factors, were used to quantify the contribution of dietary oily fish intake and FOS use to plasma n-3 PUFA levels (measured by NMR spectroscopy). Oily fish intake and FOS use were reported by 38 % and 31 % of participants, respectively. Increasing oily fish intake was associated with a higher likelihood of FOS use (P < 0·001). Oily fish intake ≥ twice a week was the strongest predictor of high total n-3 PUFA (OR 6·7 (95 % CI 6·3, 7·1)) and DHA levels (6·6 (6·3, 7·1). FOS use was an independent predictor of high plasma n-3 PUFA levels (2·0 (2·0, 2·1)) with a similar OR to that associated with eating oily fish < once a week (1·9 (1·8, 2·0)). FOS use was associated with plasma n-3 PUFA levels that were similar to individuals in the next highest oily fish intake category. In conclusion, FOS use is more common in frequent fish consumers and modifies the relationship between oily fish intake and plasma n-3 PUFA levels in UKBB participants. If unaccounted for, FOS use may confound the relationship between dietary n-3 PUFA intake, blood levels of n-3 PUFAs and health outcomes.

Attitudes of Gay, Bisexual, and Other Men Who Have Sex with Men (GBM) toward Their Use of Amphetamine-Type Stimulants and Relation to Reducing Use in Three Canadian Cities.

BACKGROUND: We explored attitudes of gay, bisexual, and other men who have sex with men (GBM) toward their amphetamine-use and associations with reduced use over time. METHODS: We recruited sexually-active GBM aged 16+ years in Montreal, Toronto, and Vancouver, Canada, from 02-2017 to 08-2019, with follow-up visits every 6-12 months until November 2020. Among participants who reported past-six-month (P6M) amphetamine-use at enrollment, we used logistic regression to identify demographic, psychological, social, mental health, other substance-use, and behavioral factors associated with reporting needing help reducing their substance-use. We used mixed-effects logistic regression to model reduced P6M amphetamine-use with perceived problematic-use as our primary explanatory variable. RESULTS: We enrolled 2,449 GBM across sites. 15.5-24.7% reported P6M amphetamine-use at enrollment and 82.6 - 85.7% reported needing no help or only a little help in reducing their substance use. Reporting needing a lot/of help or completely needing help in reducing substance-use was associated with group sex participation (AOR = 2.35, 95%CI:1.25-4.44), greater anxiety symptomatology (AOR = 2.11, 95%CI:1.16-3.83), greater financial strain (AOR = 1.35, 95%CI:1.21-1.50), and greater Escape Motive scores (AOR = 1.07, 95%CI:1.03-1.10). Reductions in P6M amphetamine-use were less likely among GBM who perceived their amphetamine-use as problematic (AOR = 0.17 95% CI 0.10 - 0.29). CONCLUSIONS: Most amphetamine-using GBM did not feel they needed help reducing their substance use, and many reported reduced amphetamine-use at subsequent visits. Those who perceived their use as problematic were less likely to reduce their use. Further interventions to assist GBM in reducing their use are needed to assist those who perceive their use as problematic.

People With Human Immunodeficiency Virus Receiving Suppressive Antiretroviral Therapy Show Typical Antibody Durability After Dual Coronavirus Disease 2019 Vaccination and Strong Third Dose Responses.

BACKGROUND: Longer-term humoral responses to 2-dose coronavirus disease 2019 (COVID-19) vaccines remain incompletely characterized in people living with human immunodeficiency virus (HIV) (PLWH), as do initial responses to a third dose. METHODS: We measured antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor-binding domain, angiotensin-converting enzyme 2 (ACE2) displacement, and viral neutralization against wild-type and Omicron strains up to 6 months after 2-dose vaccination, and 1 month after the third dose, in 99 PLWH receiving suppressive antiretroviral therapy and 152 controls. RESULTS: Although humoral responses naturally decline after 2-dose vaccination, we found no evidence of lower antibody concentrations or faster rates of antibody decline in PLWH compared with controls after accounting for sociodemographic, health, and vaccine-related factors. We also found no evidence of poorer viral neutralization in PLWH after 2 doses, nor evidence that a low nadir CD4+ T-cell count compromised responses. Post-third-dose humoral responses substantially exceeded post-second-dose levels, though Omicron-specific responses were consistently weaker than responses against wild-type virus. Nevertheless, post-third-dose responses in PLWH were comparable to or higher than controls. An mRNA-1273 third dose was the strongest consistent correlate of higher post-third-dose responses. CONCLUSION: PLWH receiving suppressive antiretroviral therapy mount strong antibody responses after 2- and 3-dose COVID-19 vaccination. Results underscore the immune benefits of third doses in light of Omicron.

Can we achieve better trial recruitment by presenting patient information through multimedia? Meta-analysis of 'studies within a trial' (SWATs).

BACKGROUND: People need high-quality information to make decisions about research participation. Providing information in written format alone is conventional but may not be the most effective and acceptable approach. We developed a structure for the presentation of information using multimedia which included generic and trial-specific content. Our aim was to embed 'Studies Within A Trial' (SWATs) across multiple ongoing trials to test whether multimedia presentation of patient information led to better rates of recruitment. METHODS: Five trials included a SWAT and randomised their participants to receive a multimedia presentation alongside standard information, or standard written information alone. We collected data on trial recruitment, acceptance and retention and analysed the pooled results using random effects meta-analysis, with the primary outcome defined as the proportion of participants randomised following an invitation to take part. RESULTS: Five SWATs provided data on the primary outcome of proportion of participants randomised. Multimedia alongside written information results in little or no difference in recruitment rates (pooled odds ratio = 0.96, 95% CI: 0.79 to 1.17, p-value = 0.671, I2 = 0%). There was no effect on any other outcomes. CONCLUSIONS: Multimedia alongside written information did not improve trial recruitment rates. TRIAL REGISTRATION: ISRCTN71952900, ISRCTN 06710391, ISRCTN 17160087, ISRCTN05926847, ISRCTN62869767.

Preventative behaviours and COVID-19 infection in a Canadian cohort of people living with HIV.

Few studies have examined preventative behaviour practices with respect to COVID-19 among people living with HIV (human immunodeficiency virus). Using a cross-sectional survey from a Canadian Institutes of Health Research Canadian HIV Trials Network study (CTN 328) of people living with HIV on vaccine immunogenicity, we examined the relationships between participant characteristics and behavioural practices intended to prevent COVID-19 infection. Participants living in four Canadian urban centers were enrolled between April 2021-January 2022, at which time they responded to a questionnaire on preventative behaviour practices. Questionnaire and clinical data were combined to explore relationships between preventive behaviours and (1) known COVID-19 infection pre-enrolment, (2) multimorbidity, (3) developing symptomatic COVID-19 infection, and (4) developing symptomatic COVID-19 infection during the Omicron wave. Among 375 participants, 49 had COVID-19 infection pre-enrolment and 88 post-enrolment. The proportion of participants reporting always engaging in preventative behaviours included 87% masking, 79% physical distancing, 70% limiting social gatherings, 65% limiting contact with at-risk individuals, 33% self-isolating due to symptoms, and 26% self-quarantining after possible exposure. Participants with known COVID-19 infection pre-enrolment were more likely to self-quarantine after possible exposure although asymptomatic (65.0% vs 23.4%, p < 0.001; Chi-square test). Participants with multiple comorbidities more likely endorsed physical distancing (85.7% vs 75.5%, p = 0.044; Chi-square test), although this was not significant in logistic regression analysis adjusted for age, sex, race, number of household members, number of bedrooms/bathrooms in the household per person, influenza immunization, and working in close physical proximity to others. Overall, participants reported frequent practice of preventative behaviours.

Disjuncture between self-perceived and clinically assessed risk of HIV among gay, bisexual, and other men who have sex with men in Ontario and British Columbia, Canada.

BACKGROUND: Self-perceived and clinically assessed HIV risk do not always align. We compared self-perceived and clinically assessed risk of HIV and the reasons for self-perceived low risk of HIV among gay, bisexual, and other men who have sex with men (GBM) from large urban centers in Ontario and British Columbia, Canada. METHODS: Never PrEP users recruited from sexual health clinics or online, completed a cross-sectional survey between July/2019 and August/2020. We contrasted self-perceived HIV risk against criteria from the Canadian PrEP guidelines and participants were categorized as concordant or discordant. We used content analysis to categorize participants' free-text explanations for perceived low HIV risk. These were compared with answers to quantitative responses about condomless sex acts and number of partners. RESULTS: Of 315 GBM who self-perceived low risk of HIV, 146 (46%) were considered at high risk according to the guidelines. Participants with discordant assessment were younger, had less years of formal education, were more often in an open relationship and were more likely to self-identify as gay. Reasons for self-perceived low HIV risk in the discordant group were condom use (27%), being in a committed relationship/having one main partner (15%), having no or infrequent anal sex (12%) and having few partners (10%). CONCLUSIONS: There is a disjuncture between self-perceived and clinically assessed risk of HIV. Some GBM may underestimate their HIV risk and clinical criteria may overestimate risk. Bridging these gaps requires efforts to increase HIV risk awareness in the community, and refinement of clinical assessments based on individualized discussions between the provider and the user.

Gay, bisexual, and queer men's confidence in the Undetectable equals Untransmittable HIV prevention message: longitudinal qualitative analysis of the sexual decision-making of pre-exposure prophylaxis users over time.

BACKGROUND: Our objective was to understand what gay, bisexual, and queer men (GBQM) who had experience using pre-exposure prophylaxis (PrEP) thought about the 'Undetectable equals Untransmittable' (U=U) message and how it informed their sexual decision-making over time. METHODS: We conducted annual longitudinal qualitative interviews (2020-22) with 17 current or former PrEP users as part of a mixed-methods implementation science study examining barriers and facilitators to PrEP awareness, access, and adherence. Over 3years, 47 interviews were conducted with GBQM in Ontario, Canada. Interviews were transcribed verbatim and coded in NVivo following reflexive thematic analysis. RESULTS: Participants' sexual health decision-making was informed by their confidence in biomedical HIV prevention and the person taking medication (i.e. themselves using PrEP versus a real/imagined person living with HIV (PLHIV)). Longitudinal narratives of U=U clustered around four overarching themes: (1) U=U confidence (i.e. increasing trust in U=U irrespective of their PrEP use); (2) PrEP confidence (i.e. accounts of self-reliance and PrEP as sufficient HIV protection); (3) combination confidence (i.e. trusting U=U and PrEP as a package); and (4) partner confidence (i.e. potential 'distrust' of U=U due to uncertainties about partners' medication adherence). Overall, men described increased sex with PLHIV over time, including some participants who, during earlier interviews, said they would 'never be comfortable' with serodifferent sexual partners. CONCLUSIONS: GBQM's use of PrEP shaped how they thought about U=U and sex with PLHIV. Although many GBQM embraced treatment as prevention/U=U as significant to their sexual lives, longitudinal analysis revealed its varied and uneven adoption across participants and time.

Omega-3 polyunsaturated fatty acids: moving towards precision use for prevention and treatment of colorectal cancer.

Data from experimental studies have demonstrated that marine omega-3 polyunsaturated fatty acids (O3FAs) have anti-inflammatory and anticancer properties. In the last decade, large-scale randomised controlled trials of pharmacological delivery of O3FAs and prospective cohort studies of dietary O3FA intake have continued to investigate the relationship between O3FA intake and colorectal cancer (CRC) risk and mortality. Clinical data suggest that O3FAs have differential anti-CRC activity depending on several host factors (including pretreatment blood O3FA level, ethnicity and systemic inflammatory response) and tumour characteristics (including location in the colorectum, histological phenotype (eg, conventional adenoma or serrated polyp) and molecular features (eg, microsatellite instability, cyclooxygenase expression)). Recent data also highlight the need for further investigation of the effect of O3FAs on the gut microbiota as a possible anti-CRC mechanism, when used either alone or in combination with other anti-CRC therapies. Overall, these data point towards a precision approach to using O3FAs for optimal prevention and treatment of CRC based on mechanistic understanding of host, tumour and gut microbiota factors that predict anticancer activity of O3FAs.

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.

Risk of HCC With Hepatitis B Viremia Among HIV/HBV-Coinfected Persons in North America.

BACKGROUND AND AIMS: Chronic HBV is the predominant cause of HCC worldwide. Although HBV coinfection is common in HIV, the determinants of HCC in HIV/HBV coinfection are poorly characterized. We examined the predictors of HCC in a multicohort study of individuals coinfected with HIV/HBV. APPROACH AND RESULTS: We included persons coinfected with HIV/HBV within 22 cohorts of the North American AIDS Cohort Collaboration on Research and Design (1995-2016). First occurrence of HCC was verified by medical record review and/or cancer registry. We used multivariable Cox regression to determine adjusted HRs (aHRs [95% CIs]) of factors assessed at cohort entry (age, sex, race, body mass index), ever during observation (heavy alcohol use, HCV), or time-updated (HIV RNA, CD4+ percentage, diabetes mellitus, HBV DNA). Among 8,354 individuals coinfected with HIV/HBV (median age, 43 years; 93% male; 52.4% non-White), 115 HCC cases were diagnosed over 65,392 person-years (incidence rate, 1.8 [95% CI, 1.5-2.1] events/1,000 person-years). Risk factors for HCC included age 40-49 years (aHR, 1.97 [1.22-3.17]), age ≥50 years (aHR, 2.55 [1.49-4.35]), HCV coinfection (aHR, 1.61 [1.07-2.40]), and heavy alcohol use (aHR, 1.52 [1.04-2.23]), while time-updated HIV RNA >500 copies/mL (aHR, 0.90 [0.56-1.43]) and time-updated CD4+ percentage <14% (aHR, 1.03 [0.56-1.90]) were not. The risk of HCC was increased with time-updated HBV DNA >200 IU/mL (aHR, 2.22 [1.42-3.47]) and was higher with each 1.0 log10 IU/mL increase in time-updated HBV DNA (aHR, 1.18 [1.05-1.34]). HBV suppression with HBV-active antiretroviral therapy (ART) for ≥1 year significantly reduced HCC risk (aHR, 0.42 [0.24-0.73]). CONCLUSION: Individuals coinfected with HIV/HBV on ART with detectable HBV viremia remain at risk for HCC. To gain maximal benefit from ART for HCC prevention, sustained HBV suppression is necessary.

Prevalence and incidence of hepatitis C infection amongst men who have sex with men in a population-based pre-exposure prophylaxis program in British Columbia, Canada.

BACKGROUND: Men who have sex with men (MSM) are at risk for sexually-transmitted hepatitis C (HCV). Evidence for HCV infection in the context of pre-exposure prophylaxis (PrEP) use in North America is limited. We sought to characterize baseline HCV prevalence and incidence in MSM receiving PrEP in British Columbia (BC), Canada. METHODS: We followed individuals in the BC PrEP program from January 2018 to August 2019. We evaluated baseline prevalence and incident seroconversions (newly positive HCV antibody). A multivariable logistic regression model was performed in MSM for factors associated with HCV prevalence at enrollment, including reported prior sexually transmitted infection (STI), HIV Incidence Risk Index for MSM score, PrEP use because of a partner living with HIV, and location of residence. RESULTS: The median age of the cohort was 33 years, 98.3% male, with 3058 person years (PY) of follow-up. Baseline HCV prevalence was 0.82% (31/3907 MSM enrollees) and HCV incidence (n = 3) was 0.15 per 100 PY (95% confidence interval [CI] 0.03-0.45). In multivariable analysis, initiating PrEP because of a partner living with HIV (adjusted odds ratio [aOR] 5.02; 95% CI 1.87-13.47) and prior STI (aOR 2.34; 95% CI 1.04-5.24) were associated with positive HCV status. CONCLUSIONS: Baseline HCV prevalence and incidence was low amongst MSM in a population-based PrEP program in BC, Canada. HCV was associated with bridging from populations living with HIV and evidence of a reported prior STI as a PrEP indicator condition amongst MSM. PrEP initiation may be an opportunity for linkage to HCV screening and treatment.

Predicting the presence of depressive symptoms in the HIV-HCV co-infected population in Canada using supervised machine learning.

BACKGROUND: Depression is common in the human immunodeficiency virus (HIV)-hepatitis C virus (HCV) co-infected population. Demographic, behavioural, and clinical data collected in research settings may be of help in identifying those at risk for clinical depression. We aimed to predict the presence of depressive symptoms indicative of a risk of depression and identify important classification predictors using supervised machine learning. METHODS: We used data from the Canadian Co-infection Cohort, a multicentre prospective cohort, and its associated sub-study on Food Security (FS). The Center for Epidemiologic Studies Depression Scale-10 (CES-D-10) was administered in the FS sub-study; participants were classified as being at risk for clinical depression if scores ≥ 10. We developed two random forest algorithms using the training data (80%) and tenfold cross validation to predict the CES-D-10 classes-1. Full algorithm with all candidate predictors (137 predictors) and 2. Reduced algorithm using a subset of predictors based on expert opinion (46 predictors). We evaluated the algorithm performances in the testing data using area under the receiver operating characteristic curves (AUC) and generated predictor importance plots. RESULTS: We included 1,934 FS sub-study visits from 717 participants who were predominantly male (73%), white (76%), unemployed (73%), and high school educated (52%). At the first visit, median age was 49 years (IQR:43-54) and 53% reported presence of depressive symptoms with CES-D-10 scores ≥ 10. The full algorithm had an AUC of 0.82 (95% CI:0.78-0.86) and the reduced algorithm of 0.76 (95% CI:0.71-0.81). Employment, HIV clinical stage, revenue source, body mass index, and education were the five most important predictors. CONCLUSION: We developed a prediction algorithm that could be instrumental in identifying individuals at risk for depression in the HIV-HCV co-infected population in research settings. Development of such machine learning algorithms using research data with rich predictor information can be useful for retrospective analyses of unanswered questions regarding impact of depressive symptoms on clinical and patient-centred outcomes among vulnerable populations.

Tobacco smoking and HIV-related immunologic and virologic response among individuals of the Canadian HIV Observational Cohort (CANOC).

We assessed the relationship between tobacco smoking and immunologic and virologic response among people living with HIV (PLWH) initiating combination antiretroviral therapy (cART) in the Canadian HIV Observational Cohort (CANOC). Positive immunologic and virologic response, respectively, were defined as ≥50 cells/mm3 CD4 count increase (CD4+) and viral suppression ≤50 copies/mL (VL+) within 6 months of cART initiation. Using multinomial regression, we examined the relationship between smoking, immunologic, and virologic response category. Model A adjusted for birth sex, baseline age, enrolling province, and era of cohort entry; models B and C further adjusted for neighbourhood level material deprivation and history of injection drug use (IDU), respectively. Among 4267 individuals (32.7%) with smoking status data, concordant positive (CD4+/VL+) response was achieved by 64.2% never, 66.9% former, and 59.4% current smokers. In the unadjusted analysis, current smoking was significantly associated with concordant negative response (odds ratio [OR] 1.85, 95% confidence interval [CI] 1.40-2.45). Similarly, models A and B showed an increased odds of concordant negative response in current smokers (adjusted OR [aOR] 1.78, 95% CI 1.32-2.39 and 1.74, 95% CI 1.29-2.34, respectively). The association between current smoking and concordant negative response was no longer significant in model C (aOR 1.18, 95%CI 0.85-1.65).

Systematic review and meta-analysis: Associations between metabolic syndrome and colorectal neoplasia outcomes.

AIM: Metabolic syndrome (MetS) is a cluster of factors including obesity, hypertension, diabetes, hypercholesterolemia and hyperlipidaemia. It has been associated with an increased risk of colorectal neoplasia. This systematic review and meta-analysis assessed the association between MetS and (i) recurrence of adenomas or occurrence of CRC in patients with prior adenomas, and (ii) survival in patients with CRC. METHOD: MEDLINE, Embase, Scopus and Web of Science were searched up to 22 November 2019. Two authors independently conducted title and abstract screening; full text of eligible studies was evaluated. Where ≥3 studies reported effect measures for a specific outcome, meta-analysis using random effects model was conducted. I2 was used to assess between-study heterogeneity. Quality appraisal was undertaken with the Newcastle-Ottawa Score. RESULTS: The search identified 1,764 articles, 55 underwent full text screening, resulting in a total of 15 eligible studies. Five studies reported on metachronous neoplasia, with differing outcomes precluded a meta-analysis. No consistent relationship between MetS and metachronous neoplasia was found. Ten studies reported on survival outcomes. MetS was associated with poorer CRC-specific survival (HR = 1.8, 95% CI: 1.04-3.12, I2  = 92.7%, n = 3). Progression-free survival was also worse but this did not reach statistical significance (HR = 1.12, 95% CI: 0.89-1.42, I2  = 85.6%, n = 3). There was no association with overall survival (HR = 1.04, 95% CI: 0.94-1.15, I2  = 43.7%, n = 7). Significant heterogeneity was present but subgroup analysis did not account for this. CONCLUSION: MetS is associated with poorer CRC-specific survival, but evidence is inconsistent on metachronous neoplasia. Further research is warranted to better understand the impact of MetS on the adenoma-carcinoma pathway.

The COLO-COHORT (Colorectal Cancer Cohort) study: Protocol for a multi-centre, observational research study and development of a consent-for-contact research platform.

AIM: The COLO-COHORT study aims to produce a multi-factorial risk prediction model for colorectal neoplasia that can be used to target colonoscopy to those at greatest risk of colorectal neoplasia, ensuring that people are not investigated unnecessarily and maximizing the use of limited endoscopy resources. The study will also explore the link between neoplasia and the human gut microbiome. Additionally, the study aims to generate a cohort of colonoscopy patients who are 'research ready' through the development of a consent-for-contact (C4C) platform, to facilitate a range of colorectal cancer prevention studies to be conducted at scale and speed. METHODS AND ANALYSIS: This is a multi-centre observational study involving sites across the UK. Recruitment is over a 6-year period (2019-2025). Patients recruited to the study are those attending for colonoscopy. Patients are recruited into two groups, namely observational group A (10 000 patients) and C4C group B (10 000 patients), known as COLO-SPEED (Colorectal Cancer Screening Prevention Endoscopy and Early Diagnosis; https://colospeed.uk). Patients complete a health questionnaire, provide anthropometric measurements and submit biosamples (blood and stool-depending on the part of the study they are recruited into). Patients' colonoscopy and histology findings are also recorded. Models of factors associated with the presence of neoplasia at colonoscopy will be developed using logistic or multinomial regression. For internal validation, model discrimination and calibration will be assessed and bootstrapping and cross-validation approaches used. To enable long-term follow-up for outcomes related to colorectal cancer and polyps, patients are asked to consent to follow-up through data linkage with national databases. DISSEMINATION: In keeping with good research practice, following analysis by the study team the study investigators will make the anonymized dataset available to other researchers. The C4C platform will also be accessible to other researchers. The study findings will be submitted for publication in peer-reviewed journals and lay summaries will be disseminated to participants and the wider public.

PrEP-related stigma and PrEP use among gay, bisexual and other men who have sex with men in Ontario and British Columbia, Canada.

BACKGROUND: We aimed to explore the association between PrEP-related stereotypes and perceived disapproval (hereafter PrEP-related stigma), and PrEP use. METHODS: We used data from a cross-sectional online survey among adult gay, bisexual, other men who have sex with men in Ontario and British Columbia, Canada. Participants were recruited 2019-2020 in-person from sexual health clinics and outreach programs, and online through dating mobile applications and websites. We used logistic regression models to explore the relationship between PrEP-related stigma and: 1-being a 'never' versus 'current' PrEP user, and 2-being a 'former' versus 'current' user. RESULTS: The median age of the sample was 32 (Q1-Q3 = 27-40), most were white born in Canada (48%), 45% had never used PrEP, 16% were former PrEP users and 39% were current PrEP users. Of 1527 individuals who started the survey, 1190 participants answered questions about PrEP-related stigma: 254 (21.3%) were classified as having low level of PrEP-related stigma, 776 (65.2%) intermediate, and 160 (13.5%) high. No significant association was found when never PrEP users and current PrEP users were compared: adjusted OR = 1.44 (95%-CI: 0.8-2.5). High PrEP-related stigma was positively associated with being a former PrEP user compared to being a current PrEP user: adjusted OR = 2.5 (95%-CI: 1.3-4.9). CONCLUSION: PrEP-related stigma is associated with not using PrEP, particularly with PrEP discontinuation. Our findings indicate that stigma persists as a barrier to PrEP use.

"What other choices might I have made?": Sexual Minority Men, the PrEP Cascade and the Shifting Subjective Dimensions of HIV Risk.

The PrEP Cascade is a dominant framework for investigating barriers to HIV pre-exposure prophylaxis (PrEP), an HIV prevention tool. We interviewed 37 PrEP users and 8 non-PrEP users in Ontario and British Columbia, Canada, about their decision-making through the Cascade. Participants were HIV-negative gay, bisexual, and queer men (GBQM). The data were analyzed using thematic analysis. PrEP decision-making was based on pragmatic considerations (logistics, costs, and systemic barriers), biomedical considerations (efficacy, side-effects, and sexually transmitted infections), and subjective considerations (identity, politics, and changing sexual preferences). Affective attachments to established versions of "safer sex" (condoms and serosorting) made some GBQM less likely to try PrEP. Some GBQM expressed increased social expectations to use PrEP, have condomless sex, and serodifferent sex. These findings support offering PrEP at no-cost, offering individualized counseling and community-based opportunities to discuss PrEP use and changing sexual practices, and improving communication on the manageability of PrEP side-effects.

Liver Fibrosis in Human Immunodeficiency Virus (HIV)-Hepatitis C Virus (HCV) Coinfection Before and After Sustained Virologic Response: What Is the Best Noninvasive Marker for Monitoring Regression?

BACKGROUND: Noninvasive markers of liver fibrosis such as aspartate aminotransferase-to-platelet ratio (APRI) and transient elastography (TE) have largely replaced liver biopsy for staging hepatitis C virus (HCV). As there is little longitudinal data, we compared changes in these markers before and after sustained virologic response (SVR) in human immunodeficiency virus (HIV)-HCV coinfected patients. METHODS: Participants from the Canadian Coinfection Cohort study who achieved SVR after a first treatment with either interferon/ribavirin or direct acting antivirals (DAAs), with at least 1 pre- and posttreatment fibrosis measure were selected. Changes in APRI or TE (DAA era only) were modeled using a generalized additive mixed model, assuming a gamma distribution and adjusting for sex, age at HCV acquisition, duration of HCV infection, and time-dependent body mass index, binge drinking, and detectable HIV RNA. RESULTS: Of 1981 patients, 151 achieved SVR with interferon and 553 with DAAs; 94 and 382 met inclusion criteria, respectively. In the DAA era, APRI increased (0.03 units/year; 95% credible interval (CrI): -.05, .12) before, declined dramatically during, and then changed minimally (-0.03 units/year; 95% CrI: -.06, .01) after treatment. TE values, however, increased (0.74 kPa/year; 95% CrI: .36, 1.14) before treatment, changed little by the end of treatment, and then declined (-0.55 kPa/year; 95% CrI: -.80, -.31) after SVR. CONCLUSIONS: TE should be the preferred noninvasive tool for monitoring fibrosis regression following cure. Future studies should assess the risk of liver-related outcomes such as hepatocellular carcinoma according to trajectories of fibrosis regression measured using TE to determine if and when it will become safe to discontinue screening.

Interest in Hypothetical Preexposure Prophylaxis Against Herpes Simplex Virus: A Cross-Sectional Survey.

ABSTRACT: We surveyed 383 men who have sex with men attending sexual health clinics regarding interest in hypothetical preexposure prophylaxis against herpes simplex virus. Overall interest was 62.5% and was associated with the number of different sexually transmitted infections previously diagnosed (adjusted odds ratio, 1.9; 95% confidence interval, 1.5-2.6) and previous HIV preexposure prophylaxis use (adjusted odds ratio, 2.9; 95% confidence interval, 1.1-8.3).