Oxaliplatin desensitization for ovarian cancer in pregnancy: A case report.

•Incidence of cancer in pregnancy is rising and successful treatment of these patients requires expert multidisciplinary care.•Platinum hypersensitivity reactions in ovarian cancer are commonly treated with desensitization protocols.•To our knowledge, chemotherapy desensitization in pregnant patients has not been previously reported.•Oxaliplatin desensitization during pregnancy may be safe and feasible.

ß-catenin and PD-L1 expression in mismatch repair deficient endometrial carcinomas.

INTRODUCTION: Predictors of non-response in mismatch repair deficiency cancers are poorly understood. Upregulation of the canonical Wnt pathway has been associated with decreased immune cell infiltration in many cancer types. The relationship between Wnt/ß-catenin pathway activation and the programmed death-ligand 1 axis in endometrial cancer remains poorly characterized. This study evaluates ß-catenin expression in a well characterized cohort of endometrial cancers by mismatch repair status and programmed death-ligand 1 expression. METHODS: Whole sections of formalin-fixed, paraffin embedded tissue from 23 Lynch syndrome-associated carcinomas, 20 mutL homolog-1 (MLH1) promoter hypermethylated carcinomas, and 19 mismatch repair intact carcinomas were evaluated. Immunohistochemistry staining for ß-catenin and programmed death-ligand 1 was performed on all cases. Programmed death-ligand 1 expression was scored in both the tumor and the peri-tumoral immune compartment. Tumor staining was classified as positive when membranous (programmed death-ligand 1) staining was present in ≥1% of tumor cells. Immune stromal staining was scored as positive when ≥5% of peritumoral and intratumoral immune cells (including lymphocytes and macrophages) showed reactivity. RESULTS: Six tumors (6/62, 9.7%) demonstrated nuclear expression of ß-catenin (4 were Lynch syndrome-associated, 1 was MLH1 methylated, 1 was mismatch repair intact). The majority of tumors with nuclear ß-catenin expression demonstrated concomitant tumoral programmed death-ligand 1 expression (5/6, 83.3%) and were more likely to demonstrate tumoral programmed death-ligand 1 expression compared to tumors without nuclear ß-catenin expression (83.3% vs 39.3%, p=0.04). Both tumoral and immune cell expression of programmed death-ligand 1 was statistically significantly associated with mismatch repair deficient tumors. DISCUSSION: Tumors demonstrating nuclear ß-catenin expression were more likely to express tumoral programmed death-ligand 1 staining than tumors without nuclear ß-catenin expression. Nuclear ß-catenin expression could be a potential predictive biomarker for non-response to immune checkpoint inhibition in mismatch repair deficient tumors. Nuclear ß-catenin expression status should be considered as a translational endpoint in future clinical trials of immune checkpoint inhibition in endometrial cancer.

Translating evidence into practice with the National Advisory Committee on Sexually Transmitted and Blood-Borne Infections.

For over 30 years, the Government of Canada has developed guidelines on sexually transmitted and blood-borne infections (STBBI) with a group of subject matter experts. This expert group provided advice to the Public Health Agency of Canada (PHAC) from 2004 to 2019; transitioning to the National Advisory Committee on STBBI (NAC-STBBI) in 2019. NAC-STBBI supports PHAC's mandate to prevent and control infectious diseases by providing advice for the development of STBBI guidelines. The methodology for developing the NAC-STBBI recommendations is evolving to a more rigorous, systematic and transparent process that is consistent with current standards in guideline development. It is also informed by-and aligned with-the methods of several other major guideline developers. The methodology incorporates the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, as appropriate, when conducting evidence reviews and developing recommendations. Recommendations will be published on the canada.ca website with the supporting NAC-STBBI Statement detailing the methodology and evidence used to develop them. This process will ensure that PHAC provides trustworthy evidence-based STBBI recommendations to primary care providers and public health professionals.

Canadian physicians' knowledge and counseling practices related to antibiotic use and antimicrobial resistance: Two-cycle national survey.

OBJECTIVE: To establish a baseline for physicians' knowledge of and counseling practices on the use of antibiotics and antimicrobial resistance (AMR), and to determine potential changes in these measures after the implementation of a national AMR awareness campaign. DESIGN: Cross-sectional design. SETTING: Canada. PARTICIPANTS: A total of 1600 physicians. MAIN OUTCOME MEASURES: Physicians' knowledge of and counseling practices on antibiotic use and AMR at baseline and after implementation of the AMR awareness campaign. RESULTS: A total of 336 physicians responded to the first-cycle survey (before the campaign), and 351 physicians responded to the second-cycle survey (after the campaign). Overall, physicians' knowledge of appropriate antibiotic use and AMR was high and their counseling practices in relation to antibiotics were appropriate in both surveys. Counseling levels about topics related to infection prevention and control (eg, food handling, household hygiene) were slightly lower. Counseling levels were also lower for certain antibiotic-use practices (eg, proper disposal of antibiotics). In addition, physicians with less than 10 years of practice experience had significantly lower odds of counseling their patients on topics related to preventing antibiotic resistance and infection prevention than those with 15 or more years of practice experience (adjusted odds ratio = 0.27, 95% CI 0.10 to 0.74). Significantly more physicians from the second-cycle survey counseled patients on the appropriate disposal of antibiotics (P = .03), as well as on some of the infection prevention topics (eg, using antibacterial hand soap [P = .02] and cleaning supplies [P = .01]). Most respondents in both surveys reported feeling confident with respect to counseling their patients on the appropriate use of antibiotics and AMR. CONCLUSION: Physicians' knowledge of and levels of counseling on the use of antibiotics and AMR were high and fairly stable in both survey results. This shows that Canadian physicians are demonstrating behaviour patterns of AMR stewardship. Existing gaps in counseling practices might be a result of physicians believing that pharmacists or nurses are addressing these issues with patients. Future national surveys conducted among pharmacists and nurses would contribute to the evidence base for AMR stewardship activities.

Management of gonococcal infection among adults and youth: New key recommendations.

OBJECTIVE: To provide recommendations on the management of gonococcal infection among adults and youth. QUALITY OF EVIDENCE: Treatment recommendations in the Canadian guidelines on sexually transmitted infections are based on review of the literature, as well as the grades of recommendations and the levels of evidence quality determined by a minimum of 2 reviewers. The recommendations are peer-reviewed and require approval by the expert working group. MAIN MESSAGE: The new key recommendations for managing gonococcal infection among adults and youth include using culture as a diagnostic tool when practical, providing treatment with combination antibiotic therapy (ceftriaxone combined with azithromycin), and promptly reporting all cases with treatment failure to public health. CONCLUSION: Following these new key recommendations might reduce treatment failure, contribute to better surveillance of antibiotic-resistance trends in Neisseria gonorrhoeae, and contribute to the prevention of transmission of multidrug-resistant gonorrhea.

Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries.

Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of <100 per 100 000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing and treatment of LTBI is conditionally recommended, according to TB epidemiology and resource availability. Either commercial interferon-gamma release assays or Mantoux tuberculin skin testing could be used to test for LTBI. Chest radiography should be performed before LTBI treatment to rule out active TB disease. Recommended treatment regimens for LTBI include: 6 or 9 month isoniazid; 12 week rifapentine plus isoniazid; 3-4 month isoniazid plus rifampicin; or 3-4 month rifampicin alone.

A systematic review of HIV testing among Canadian populations.

OBJECTIVE: Regular HIV testing and early detection leads to timely treatment. Appropriate treatment and care can prevent disease progression in the individual and prevent onwards transmission within the community. This review describes HIV testing coverage in populations disproportionately affected by HIV and in the general population in Canada. METHODS: A search of published and grey literature on HIV testing uptake in Canada was conducted. Studies reporting quantitative data on testing practices (ever tested, recent testing, and regular testing), published in either English or French from 2008-2012, were included. Studies that involved testing for immigration or prenatal purposes, and post-intervention studies, were excluded. Included studies were assessed using a modified version of the Public Health Agency of Canada's Descriptive Study Critical Appraisal Tool. Pooled prevalence for percent ever tested was calculated for subpopulations and heterogeneity was estimated using the I2 statistic. SYNTHESIS: A total of 26 studies were included in the review. The highest rates of ever having been tested were among people who inject drugs (90.6%) and inmates (90.4%); followed by men who have sex with men (83.0%); Aboriginal peoples (55.5%); and the general population (32.8%). Limited information was available on regular and recent testing. CONCLUSION: HIV testing can reduce the number of undiagnosed cases in Canada. Future research should focus on testing coverage in certain populations, and on the extent to which populations engage in regular testing.

The impact of HIV treatment as prevention in the presence of other prevention strategies: lessons learned from a review of mathematical models set in resource-rich countries.

OBJECTIVE: We aimed to assess the potential prevention benefits of HIV treatment as prevention (TasP) in resource-rich countries and examine the potential interactions between TasP and other prevention strategies by reviewing mathematical models of TasP. METHOD: Multiple databases were searched for mathematical models published in the previous 5 years (from July 2007 to July 2012). The nine models located were set in Canada, Australia and the United States. RESULTS: These models' predictions suggested that the impact of expanding treatment rates on expected new infections could range widely, from no decrease to a decrease of 76%, depending on the time horizon, assumptions and the form of TasP modeled. Increased testing, reducing sexually transmitted infections and reducing risky practices were also predicted to be important strategies for decreasing expected new infections. Sensitivity analysis suggests that current uncertainties such as the effectiveness of highly active antiretroviral therapy outside of heterosexual transmission, less than ideal adherence, and risk compensation, could impact on the success of TasP at the population level. CONCLUSION: The results from large scale pilots and community randomized controlled trials will be useful in demonstrating how well this prevention approach works in real world settings, and in identifying the factors that are needed to support its effectiveness.