Canadian COVID-19 host genetics cohort replicates known severity associations.

The HostSeq initiative recruited 10,059 Canadians infected with SARS-CoV-2 between March 2020 and March 2023, obtained clinical information on their disease experience and whole genome sequenced (WGS) their DNA. We analyzed the WGS data for genetic contributors to severe COVID-19 (considering 3,499 hospitalized cases and 4,975 non-hospitalized after quality control). We investigated the evidence for replication of loci reported by the International Host Genetics Initiative (HGI); analyzed the X chromosome; conducted rare variant gene-based analysis and polygenic risk score testing. Population stratification was adjusted for using meta-analysis across ancestry groups. We replicated two loci identified by the HGI for COVID-19 severity: the LZTFL1/SLC6A20 locus on chromosome 3 and the FOXP4 locus on chromosome 6 (the latter with a variant significant at P < 5E-8). We found novel significant associations with MRAS and WDR89 in gene-based analyses, and constructed a polygenic risk score that explained 1.01% of the variance in severe COVID-19. This study provides independent evidence confirming the robustness of previously identified COVID-19 severity loci by the HGI and identifies novel genes for further investigation.

Breast and bowel cancers diagnosed in people 'too young to have cancer': A blueprint for research using family and twin studies.

Young breast and bowel cancers (e.g., those diagnosed before age 40 or 50 years) have far greater morbidity and mortality in terms of years of life lost, and are increasing in incidence, but have been less studied. For breast and bowel cancers, the familial relative risks, and therefore the familial variances in age-specific log(incidence), are much greater at younger ages, but little of these familial variances has been explained. Studies of families and twins can address questions not easily answered by studies of unrelated individuals alone. We describe existing and emerging family and twin data that can provide special opportunities for discovery. We present designs and statistical analyses, including novel ideas such as the VALID (Variance in Age-specific Log Incidence Decomposition) model for causes of variation in risk, the DEPTH (DEPendency of association on the number of Top Hits) and other approaches to analyse genome-wide association study data, and the within-pair, ICE FALCON (Inference about Causation from Examining FAmiliaL CONfounding) and ICE CRISTAL (Inference about Causation from Examining Changes in Regression coefficients and Innovative STatistical AnaLysis) approaches to causation and familial confounding. Example applications to breast and colorectal cancer are presented. Motivated by the availability of the resources of the Breast and Colon Cancer Family Registries, we also present some ideas for future studies that could be applied to, and compared with, cancers diagnosed at older ages and address the challenges posed by young breast and bowel cancers.

The Relationship between Vaping Cannabis and Frequency of Cannabis Use and Cannabis-Related Problems among Urban High School Students.

Background: Vaping, including vaping cannabis, is increasing among adolescents. In this longitudinal study, we examined the relationship between vaping cannabis and frequency of cannabis use and related problems over 6 months among adolescents. Material and Methods: Data were from 233 participants (46.8% male, 93.1% African American, mean age = 16.4 years) reporting cannabis use. The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) assessed frequency of past 30-day cannabis use and cannabis-related problems at baseline, 3- and 6-months post-baseline. We used latent growth curve modeling to compare vaping to non-vaping adolescents on trends in cannabis use frequency and ASSIST cannabis scores. Results: Adolescents who vaped cannabis (11.7%) had higher past 30-day frequency (mean = 17.89 days, SD = 10.49) of cannabis use at baseline compared to adolescents who had not vaped (mean = 12.1 days, SD = 10.93), but reported a significantly sharper decline in frequency of cannabis use (b = -0.34, p = 0.017). A significantly steeper decrease existed in the mean cannabis ASSIST scores for the vaping group than for the non-vaping group (b = -0.34, p = 0.014). Mean ASSIST scores on the cannabis subscale between the two groups were significantly different at 6-month follow-up (Vape mean = 6.00, SD = 8.12 vs. Non-vape mean = 9.6, SD = 9.39; p < 0.021). Conclusions: In a sample of cannabis-using adolescents, adolescents with experience vaping cannabis, compared to adolescents without vaping experience, on average reported sharper decreases in frequency of cannabis use and cannabis-related problems such as health or social problems.

Correlates of Circulating Osteoprotegerin in Women with a Pathogenic or Likely Pathogenic Variant in the BRCA1 Gene.

BACKGROUND: Lower levels of osteoprotegerin (OPG), the decoy receptor for receptor activator of NFκB (RANK)-ligand, have been reported among women with a BRCA1 mutation, suggesting OPG may be marker of cancer risk. Whether various reproductive, hormonal, or lifestyle factors impact OPG levels in these women is unknown. METHODS: BRCA1 mutation carriers enrolled in a longitudinal study, no history of cancer, and a serum sample for OPG quantification, were included. Exposure information was collected through self-reported questionnaire at study enrollment and every 2 years thereafter. Serum OPG levels (pg/mL) were measured using an ELISA, and generalized linear models were used to assess the associations between reproductive, hormonal, and lifestyle exposures at the time of blood collection with serum OPG. Adjusted means were estimated using the fully adjusted model. RESULTS: A total of 701 women with a median age at blood collection of 39.0 years (18.0-82.0) were included. Older age (Spearman r = 0.24; P < 0.001) and current versus never smoking (98.82 vs. 86.24 pg/mL; Pcat < 0.001) were associated with significantly higher OPG, whereas ever versus never coffee consumption was associated with significantly lower OPG (85.92 vs. 94.05 pg/mL; Pcat = 0.03). There were no other significant associations for other exposures (P ≥ 0.06). The evaluated factors accounted for 7.5% of the variability in OPG. CONCLUSIONS: OPG is minimally influenced by hormonal and lifestyle factors among BRCA1 mutation carriers. IMPACT: These findings suggest that circulating OPG levels are not impacted by non-genetic factors in high-risk women.

Sense of community belonging and influenza vaccine uptake in Canada.

OBJECTIVES: The objectives of this study are to determine the prevalence of influenza vaccine uptake across Canadians aged 18 to 64 years with different sense of community belonging (SoCB) and whether SoCB is associated with uptake of the seasonal influenza vaccine. METHODS: We combined the 2007 to 2014 cycles of the nationally representative Canadian Community Health Survey (N = 301,802). The main exposure, SoCB, was measured as "strong" vs "weak." The outcome of interest was receipt of the influenza vaccine within the preceding 12 months. We used robust Poisson regression to estimate prevalence ratios. Normalized weights were utilized to account for the unequal probability of sample selection. RESULTS: The adjusted prevalence of uptake of seasonal influenza vaccines was modestly greater for individuals with a strong SoCB compared to those with a weak SoCB (PR, 1.12; 95% CI, 1.11, 1.13). Older individuals, females, those with post-secondary education, non-immigrants, those who are married, those with at least one chronic condition, and those residing in a jurisdiction where pharmacists are authorized to administer influenza vaccine and/or where influenza vaccine is universally funded for all residents were more likely to have received an influenza vaccine within the past year. CONCLUSION: Canadians with a strong SoCB had modestly higher uptake of seasonal influenza vaccines. While the association is modest, findings suggest that SoCB may be an important component to investigate further and to consider in efforts aimed to increase the uptake of seasonal influenza vaccines.

RéSUMé: OBJECTIFS: Cette étude vise à déterminer la prévalence de la vaccination antigrippale chez les Canadiens âgés de 18 à 64 ans ayant un sentiment d'appartenance à la communauté différent et de déterminer si ce sentiment est associé à la vaccination contre la grippe saisonnière. MéTHODES: Nous avons combiné les cycles 2007 à 2014 de l'Enquête sur la santé dans les collectivités canadiennes représentative sur le plan national (N = 301 802). L'exposition principale, à savoir le sentiment d'appartenance à la communauté, a été mesurée comme « forte ¼ ou « faible ¼. Le résultat recherché était la réception du vaccin antigrippal au cours des douze derniers mois. Nous avons utilisé une régression de Poisson robuste pour estimer les rapports de prévalence (RP). Des poids normalisés ont été utilisés pour tenir compte de la probabilité inégale de l'échantillonnage. RéSULTATS: La prévalence ajustée de la vaccination contre la grippe saisonnière était légèrement plus élevée chez les personnes ayant un sentiment fort d'appartenance à la communauté par rapport à celles dont ce sentiment était faible (RP : 1,12; IC de 95 % : 1,11, 1,13). Les personnes plus âgées, les femmes, les personnes ayant fait des études supérieures, les non-immigrants, les personnes mariées, les personnes souffrant d'au moins une maladie chronique et les personnes résidant dans une juridiction où les pharmaciens sont autorisés à administrer le vaccin antigrippal et/ou où le vaccin antigrippal est financé de manière universelle pour tous les résidents, étaient plus susceptibles d'avoir reçu un vaccin antigrippal au cours de l'année écoulée. CONCLUSION: Les Canadiens ayant un sentiment fort d'appartenance à la communauté étaient légèrement plus nombreux à s'être fait vacciner contre la grippe saisonnière. Bien que l'association soit modeste, les résultats suggèrent que le sentiment d'appartenance à la communauté pourrait être un élément important à étudier davantage et à prendre en compte dans les efforts visant à augmenter la vaccination contre la grippe saisonnière.

Isoquercetin for thromboinflammation in sickle cell disease: a randomized double-blind placebo-controlled trial.

ABSTRACT: Data from a small trial in patients with cancer suggest that isoquercetin (IQ) treatment lowered thrombosis biomarkers and prevented clinical thrombosis, but, to our knowledge, no studies of IQ have been conducted to target thromboinflammation in adults with sickle cell disease (SCD). We conducted a randomized, double-blind, placebo-controlled trial in adults with steady-state SCD (hemoglobin SS [HbSS], HbSß0thal, HbSß+thal, or HbSC). The primary outcome was the change in plasma soluble P-selectin (sP-selectin) after treatment compared with baseline, analyzed in the intention-to-treat population. Between November 2019 and July 2022, 46 patients (aged 40 ± 11 years, 56% female, 75% under hydroxyurea treatment) were randomized to receive IQ (n = 23) or placebo (n = 23). IQ was well tolerated and all the adverse events (AEs; n = 21) or serious AEs (n = 14) recorded were not attributable to the study drug. The mean posttreatment change for sP-selectin showed no significant difference between the treatment groups (IQ, 0.10 ± 6.53 vs placebo, 0.74 ± 4.54; P = .64). In patients treated with IQ, whole-blood coagulation (P = .03) and collagen-induced platelet aggregation (P = .03) were significantly reduced from the baseline. Inducible mononuclear cell tissue factor gene expression and plasma protein disulfide isomerase reductase activity were also significantly inhibited (P = .003 and P = .02, respectively). Short-term fixed-dose IQ in patients with SCD was safe with no off-target bleeding and was associated with changes from the baseline in the appropriate direction for several biomarkers of thromboinflammation. The trial was registered at www.clinicaltrials.gov as #NCT04514510.

Trends in infection-related and infection-unrelated cancer incidence among people with and without HIV infection in Ontario, Canada, 1996-2020: a population-based matched cohort study using health administrative data.

BACKGROUND: People with HIV infection are at higher risk for certain cancers than the general population. We compared trends in infection-related and infection-unrelated cancers among people with and without HIV infection. METHODS: We conducted a retrospective population-based matched cohort study of adults with and without HIV infection using linked health administrative databases in Ontario, Canada. Participants were matched on birth year, sex, census division (rurality), neighbourhood income quintile and region of birth. We followed participants from cohort entry until the earliest of date of cancer diagnosis, date of death, Nov. 1, 2020, or date of loss to follow-up. Incident cancers identified from Jan. 1, 1996, to Nov. 1, 2020, were categorized as infection-related or-unrelated. We examined calendar periods 1996-2003, 2004-2011 and 2012-2020, corresponding to the early combination antiretroviral therapy (cART), established cART and contemporary cART eras, respectively. We used competing risk analyses to examine trends in cumulative incidence by calendar period, age and sex, and cause-specific hazard ratios (HRs). RESULTS: We matched 20 304 people with HIV infection to 20 304 people without HIV infection. A total of 2437 cancers were diagnosed, 1534 (62.9%) among infected people and 903 (37.0%) among uninfected people. The risk of infection-related cancer by age 65 years for people with HIV infection decreased from 19.0% (95% confidence interval [CI] 15.6%-22.3%) in 1996-2011 to 10.0% (95% CI 7.9%-12.1%) in 2012-2020. Compared to uninfected people, those with HIV infection had similar HRs of infection-unrelated cancer but increased rates of infection-related cancer, particularly among younger age groups (25.1 [95% CI 13.2-47.4] v. 1.9 [95% CI 1.0-3.7] for age 18-39 yr v. ≥ 70 yr); these trends were consistent when examined by sex.Interpretation: We observed significantly higher rates of infection-related, but not infection-unrelated, cancer among people with HIV infection than among uninfected people. The elevated rate of infection-related cancer in 2012-2020 highlights the importance of early and sustained antiretroviral therapy along with cancer screening and prevention measures.

Linkage of whole genome sequencing and administrative health data in autism: A proof of concept study.

Whether genetic testing in autism can help understand longitudinal health outcomes and health service needs is unclear. The objective of this study was to determine whether carrying an autism-associated rare genetic variant is associated with differences in health system utilization by autistic children and youth. This retrospective cohort study examined 415 autistic children/youth who underwent genome sequencing and data collection through a translational neuroscience program (Province of Ontario Neurodevelopmental Disorders Network). Participant data were linked to provincial health administrative databases to identify historical health service utilization, health care costs, and complex chronic medical conditions during a 3-year period. Health administrative data were compared between participants with and without a rare genetic variant in at least 1 of 74 genes associated with autism. Participants with a rare variant impacting an autism-associated gene (n = 83, 20%) were less likely to have received psychiatric care (at least one psychiatrist visit: 19.3% vs. 34.3%, p = 0.01; outpatient mental health visit: 66% vs. 77%, p = 0.04). Health care costs were similar between groups (median: $5589 vs. $4938, p = 0.4) and genetic status was not associated with odds of being a high-cost participant (top 20%) in this cohort. There were no differences in the proportion with complex chronic medical conditions between those with and without an autism-associated genetic variant. Our study highlights the feasibility and potential value of genomic and health system data linkage to understand health service needs, disparities, and health trajectories in individuals with neurodevelopmental conditions.

Canadian Healthcare Professionals' Views and Attitudes toward Risk-Stratified Breast Cancer Screening.

Given the controversy over the effectiveness of age-based breast cancer (BC) screening, offering risk-stratified screening to women may be a way to improve patient outcomes with detection of earlier-stage disease. While this approach seems promising, its integration requires the buy-in of many stakeholders. In this cross-sectional study, we surveyed Canadian healthcare professionals about their views and attitudes toward a risk-stratified BC screening approach. An anonymous online questionnaire was disseminated through Canadian healthcare professional associations between November 2020 and May 2021. Information collected included attitudes toward BC screening recommendations based on individual risk, comfort and perceived readiness related to the possible implementation of this approach. Close to 90% of the 593 respondents agreed with increased frequency and earlier initiation of BC screening for women at high risk. However, only 9% agreed with the idea of not offering BC screening to women at very low risk. Respondents indicated that primary care physicians and nurse practitioners should play a leading role in the risk-stratified BC screening approach. This survey identifies health services and policy enhancements that would be needed to support future implementation of a risk-stratified BC screening approach in healthcare systems in Canada and other countries.

Association between estimated cardiorespiratory fitness and breast cancer: a prospective cohort study.

OBJECTIVE: To examine the association between cardiorespiratory fitness (CRF) and the risk of breast cancer in postmenopausal women. METHODS: This study used data from 17 840 cancer-free postmenopausal women with a CRF assessment from the UK Biobank. High estimated CRF (eCRF) was categorised as being >80th percentile within 10-year age bands. Fine and Gray regression was used to examine the association between eCRF and breast cancer risk, accounting for both non-breast cancer diagnoses and all-cause mortality as competing risks. Age was used as the time scale. Several different models were produced, including those adjusting for known breast cancer risk factors, and stratified by measures of body fat (body mass index and per cent body fat). RESULTS: Over a median follow-up of 11.0 years there were 529 cases of invasive breast cancer, 1623 cases of non-breast cancer disease and 241 deaths. With adjustment for breast cancer risk factors, high eCRF was associated with a 24% (subdistribution HR (SDHR) 0.76, 95% CI 0.60 to 0.97) lower risk of breast cancer. When stratified by measures of body fat, we found evidence of effect measure modification. Mainly, having high eCRF was only associated with a lower risk of breast cancer among those classified as having overweight/obesity (SDHR 0.33, 95% CI 0.11 to 1.01) or percentage body fat above the 1st quintile (SDHR 0.65, 95% CI 0.45 to 0.94). CONCLUSION: Having higher CRF may be a protective factor against breast cancer in postmenopausal women but only for women with elevated body fat.

Mapping prescription drug monitoring program data to self-report measures of non-medical prescription opioid use in community pharmacy settings.

BACKGROUND: Community pharmacists are well-positioned to identify patients engaged in non-medical prescription opioid use (NMPOU) through Prescription Drug Monitoring Program (PDMP) databases. Integrating patient-reported outcomes with PDMP data may improve the interpretability of PDMP information to support clinical decision-making. OBJECTIVE: This study linked patient-reported clinical measures of substance use with PDMP data to examine relationships between average daily opioid dose in morphine milligram equivalents (MME) and visits to multiple pharmacies/prescribers with self-reported NMPOU. METHODS: Data from a cross-sectional health assessment given to patients aged ≥18 years filling opioid prescriptions were linked to PDMP records. NMPOU in the past three months was assessed on a continuous scale (range 0-39) using an adapted version of the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST). PDMP measures included average daily MME and number of distinct pharmacies/prescribers visited in the past 180 days. Univariable and multivariable zero-inflated negative binomial models estimated associations between PDMP measures and any NMPOU and severity of use. RESULTS: The sample included 1421 participants. In multivariable models adjusted for sociodemographic, mental health, and physical health characteristics, any NMPOU was associated with higher average daily MME (adjusted OR = 1.22, 95% CI = 1.05-1.39) and number of distinct prescribers visited (adjusted OR = 1.15, 95% CI = 1.01-1.30). Higher average daily MME (adjusted mean ratio (MR) = 1.12, 95% CI = 1.08-1.15), number of distinct pharmacies visited (adjusted MR = 1.11, 95% CI = 1.04-1.18), and number of distinct prescribers visited (adjusted MR = 1.07, 95% CI = 1.02-1.11) were associated with increased NMPOU severity. CONCLUSIONS: We observed significant, positive associations between average daily MME and visits to multiple pharmacies/prescribers with any NMPOU and severity of use. This study demonstrates self-report clinical measures of substance use can be cross-walked to PDMP data and translated into clinically interpretable information.

Validation of the International Breast Cancer Intervention Study (IBIS) model in the High Risk Ontario Breast Screening Program: A retrospective cohort study.

PURPOSE: Women with a remaining lifetime risk of breast cancer of ≥25%, estimated using the International Breast Cancer Intervention Study (IBIS) model, were eligible for the High Risk Ontario Breast Screening Program. This study examined the performance of IBIS 10-year risk estimates in the program. METHODS: This retrospective study included 7487 women aged 30 to 69 years referred to the High Risk Ontario Breast Screening Program between July 1, 2011, and December 31, 2016, with follow-up until December 31, 2018. Model calibration and discrimination were assessed. Analyses were conducted overall and stratified by age (< or ≥50 years). Different 10-year risk thresholds were compared with the current eligibility criteria. RESULTS: Overall, IBIS overestimated the risk of breast cancer with an expected vs observed case ratio of 1.17 (95% CI = 1.04-1.35). Overestimation was highest in women aged 50 to 69 years (expected vs observed case ratio = 1.29, 95% CI = 1.03-1.69) and for those in the top quartile of risk. Overall discrimination was fair with a concordance statistic of 0.66 (95% CI = 0.63-0.70). Furthermore, when using different 10-year risk eligibility thresholds, most cases would have been missed in the 30 to 49 age group using the 8% 10-year risk threshold, whereas relatively few women aged 50 to 69 would have been ineligible at any of the thresholds examined. CONCLUSION: We found that IBIS overestimated the risk of breast cancer in this screening cohort but had adequate discrimination. Age-specific risk thresholds should be considered to optimize the program eligibility criteria.

Screening behaviours, demographics, and stage at diagnosis in the publicly funded Ontario Breast Screening Program.

PURPOSE: The Ontario Breast Screening Program (OBSP) offers free screening mammograms every 2 years, to women aged 50-74. Study objectives were to determine demographic characteristics associated with the adherence to OBSP and if women screened in the OBSP have a lower stage at diagnosis than non-screened eligible women. METHODS: We used the Ontario cancer registry (OCR) to identify 48,927 women, aged 51-74 years, diagnosed with breast cancer between 2010 and 2017. These women were assigned as having undergone adherent screening (N = 26,108), non-adherent screening (N = 6546) or not-screened (N = 16,273) in the OBSP. We used multinomial logistic regression to investigate the demographic characteristics associated with screening behaviour, as well as the association between screening status and stage at diagnosis. RESULTS: Among women with breast cancer, those living in rural areas (versus the largest urban areas) had a lower odds of not being screened (odds ratio [OR] 0.73, 95% confidence interval [CI] 0.68, 0.78). Women in low-income (versus high-income) communities were more likely not to be screened (OR 1.42, 95% CI 1.33, 1.51). When stratified, the association between income and screening status only held in urban areas. Non-screened women were more likely to be diagnosed with stage II (OR 1.91, 95% CI 1.82, 2.01), III (OR 2.96, 95% CI 2.76, 3.17), or IV (OR 8.96, 95% CI 7.94, 10.12) disease compared to stage I and were less likely to be diagnosed with ductal carcinoma in situ (DCIS) (OR 0.91, 95% CI 0.84-0.98). CONCLUSIONS: This study suggests that targeting OBSP recruitment efforts to lower income urban communities could increase screening rates. OBSP adherent women were more likely to be diagnosed with earlier stage disease, supporting the value of this initiative and those like it.

Maternal acetaminophen use and cognitive development at 4 years: the Ontario Birth Study.

BACKGROUND: Studies have suggested a link between prenatal maternal acetaminophen use and adverse developmental outcomes in children. However, there exists a knowledge gap regarding overall cognitive development and use of acetaminophen, especially concerning the timing of use in pregnancy. This study aimed to characterize the relationship between maternal acetaminophen use and cognitive development at 4 years. METHODS: This analysis included data collected throughout pregnancy and delivery from women in the Ontario Birth Study prospective cohort from 2013 to 2019 and from the NIH Toolbox Early Childhood Cognition battery administered to 4-year-old children between 2018 and 2021 (n = 436). The exposure was maternal acetaminophen use and the primary outcome was a cognition composite score. The relationship between exposure and outcome was determined using Poisson regression with a robust error variance. RESULTS: We did not observe any association between maternal acetaminophen intake any time before or during pregnancy and low cognition composite score of offspring. The IRR of suboptimal overall cognition was 1.38 (0.78-2.45), 1.22 (0.67-2.22), 0.80 (0.44-1.47), and 1.56 (0.74-3.29) for maternal use of acetaminophen before, in early, late, or overall pregnancy, respectively. CONCLUSION: Current data do not provide evidence to support a relationship of maternal acetaminophen use during pregnancy with adverse cognitive effects at 4 years. IMPACT: Acetaminophen use during pregnancy may influence the risk of child neurocognitive disorders, but there is conflicting evidence of its relationship to sub-clinical measures of cognitive development such as executive function. The study design allowed us to examine the role of timing of acetaminophen use in its relationship with cognitive development, based on a validated and standardized tablet-administered instrument for children, instead of a teacher or parent report. We did not observe a clear relationship between maternal acetaminophen use at different timepoints during pregnancy and child cognitive development.

"It Just Depends on Their Stability": A Qualitative Examination of Patient Factors Influencing Providers' Contraceptive Counseling Approaches for Persons With Substance Use Disorders.

OBJECTIVES: This qualitative study examined how patient-related factors influence providers' contraceptive counseling for persons with substance use disorders (SUDs). Specifically, we explored individual behavior and social factors that contribute to providers modifying their contraceptive counseling approaches and described how providers alter their counseling recommendations and communication strategies in the presence of such factors. METHODS: In 2019, we purposively recruited a national sample of contraceptive providers (N = 24) and conducted semistructured phone interviews to inquire about their contraceptive counseling practices for women with SUDs. Interviews were audio recorded, transcribed verbatim, and analyzed using thematic analysis with inductive codes. RESULTS: Participants included 10 medical doctors, 8 nurse practitioners, and 6 certified nurse-midwives. We found that providers modify their contraceptive counseling provision when their patients are actively using substances or have unstable living conditions, such as intimate partner violence or homelessness. With patients experiencing these instabilities, providers reported postponing contraceptive discussions until patients are stabilized in treatment, recommending long-active reversible contraceptive methods, and varying communication styles according to their own perceptions of patients' communication needs. Providers perceived that individuals in long-term recovery have increased stability and fewer barriers to contraceptive access and adherence and therefore reported increased willingness to provide greater autonomy during contraceptive decision making and shift the counseling focus to short-acting contraceptive methods. CONCLUSIONS: This study highlights that substance use and social "stability" of patients contributes to how providers approach their contraceptive counseling and make methods recommendations for their patients with SUDs. More research is needed to understand strategies that individuals with SUDs use to overcome barriers to contraceptive access and adherence in the context of active substance use and social instability.

Polygenic risk scores and risk-stratified breast cancer screening: Familiarity and perspectives of health care professionals.

PURPOSE: Health care professionals are expected to take on an active role in the implementation of risk-based cancer prevention strategies. This study aimed to explore health care professionals' (1) self-reported familiarity with the concept of polygenic risk score (PRS), (2) perceived level of knowledge regarding risk-stratified breast cancer (BC) screening, and (3) preferences for continuing professional development. METHODS: A cross-sectional survey was conducted using a bilingual-English/French-online questionnaire disseminated by health care professional associations across Canada between November 2020 and May 2021. RESULTS: A total of 593 professionals completed more than 2 items and 453 responded to all questions. A total of 432 (94%) participants were female, 103 (22%) were physicians, and 323 (70%) were nurses. Participants reported to be unfamiliar with (20%), very unfamiliar (32%) with, or did not know (41%) the concept of PRS. Most participants reported not having enough knowledge about risk-stratified BC screening (61%) and that they would require more training (77%). Online courses and webinar conferences were the preferred continuing professional development modalities. CONCLUSION: The study indicates that health care professionals are currently not familiar with the concept of PRS or a risk-stratified approach for BC screening. Online information and training seem to be an essential knowledge transfer modality.

Considerations of biomarker application for cancer continuum in the era of precision medicine.

Purpose of the review: The goal of this review is to highlight emerging biomarker research by the key phases of the cancer continuum and outline the methodological considerations for biomarker application. Recent findings: While biomarkers have an established role in targeted therapy and to some extent, disease monitoring, their role in early detection and survivorship remains to be elucidated. With the advent of omics technology, the discovery of biomarkers has been accelerated exponentially, therefore careful consideration to ensure an unbiased study design and robust validity is crucial. Summary: The rigor of biomarker research holds the key to the success of precision health care. The potential clinical utility and the feasibility of implementation should be central to future biomarker research study design.

MRI background parenchymal enhancement, breast density and breast cancer risk factors: A cross-sectional study in pre- and post-menopausal women.

Breast tissue enhances on contrast MRI and is called background parenchymal enhancement (BPE). Having high BPE has been associated with an increased risk of breast cancer. We examined the relationship between BPE and the amount of fibroglandular tissue on MRI (MRI-FGT) and breast cancer risk factors. This was a cross-sectional study of 415 women without breast cancer undergoing contrast-enhanced breast MRI at Memorial Sloan Kettering Cancer Center. All women completed a questionnaire assessing exposures at the time of MRI. Prevalence ratios (PR) and 95% confidence intervals (CI) describing the relationship between breast cancer risk factors and BPE and MRI-FGT were generated using modified Poisson regression. In multivariable-adjusted models a positive association between body mass index (BMI) and BPE was observed, with a 5-unit increase in BMI associated with a 14% and 44% increase in prevalence of high BPE in pre- and post-menopausal women, respectively. Conversely, a strong inverse relationship between BMI and MRI-FGT was observed in both pre- (PR = 0.66, 95% CI 0.57, 0.76) and post-menopausal (PR = 0.66, 95% CI 0.56, 0.78) women. Use of preventive medication (e.g., tamoxifen) was associated with having low BPE, while no association was observed for MRI-FGT. BPE is an imaging marker available from standard contrast-enhanced MRI, that is influenced by endogenous and exogenous hormonal exposures in both pre- and post-menopausal women.

The burden of cancer among people living with HIV in Ontario, Canada, 1997-2020: a retrospective population-based cohort study using administrative health data.

BACKGROUND: With combination antiretroviral therapy (ART) and increased longevity, cancer is a leading cause of morbidity among people with HIV. We characterized trends in cancer burden among people with HIV in Ontario, Canada, between 1997 and 2020. METHODS: We conducted a population-based, retrospective cohort study of adults with HIV using linked administrative health databases from Jan. 1, 1997, to Nov. 1, 2020. We grouped cancers as infection-related AIDS-defining cancers (ADCs), infection-related non-ADCs (NADCs) and infection-unrelated cancers. We calculated age-standardized incidence rates per 100 000 person-years with 95% confidence intervals (CIs) using direct standardization, stratified by calendar period and sex. We also calculated limited-duration prevalence. RESULTS: Among 19 403 adults living with HIV (79% males), 1275 incident cancers were diagnosed. From 1997-2000 to 2016- 2020, we saw a decrease in the incidence of all cancers (1113.9 [95% CI 657.7-1765.6] to 683.5 [95% CI 613.4-759.4] per 100 000 person-years), ADCs (403.1 [95% CI 194.2-739.0] to 103.8 [95% CI 79.2-133.6] per 100 000 person-years) and infection-related NADCs (196.6 [95% CI 37.9-591.9] to 121.9 [95% CI 94.3-154.9] per 100 000 person-years). The incidence of infection-unrelated cancers was stable at 451.0 per 100 000 person-years (95% CI 410.3-494.7). The incidence of cancer among females increased over time but was similar to that of males in 2016-2020. INTERPRETATION: Over a 24-year period, the incidence of cancer decreased overall, largely driven by a considerable decrease in the incidence of ADC, whereas the incidence of infection-unrelated cancer remained unchanged and contributed to the greatest burden of cancer. These findings could reflect combination ART-mediated changes in infectious comorbidity and increased life expectancy; targeted cancer screening and prevention strategies are needed.