Clinical Practice Recommendations for the Management and Prevention of Cisplatin-Induced Hearing Loss Using Pharmacogenetic Markers

Currently no pharmacogenomics-based criteria exist to guide clinicians in identifying individuals who are at risk of hearing loss from cisplatin-based chemotherapy. This review summarizes findings from pharmacogenomic studies that report genetic polymorphisms associated with cisplatin-induced hearing loss and aims to (1) provide up-to-date information on new developments in the field, (2) provide recommendations for the use of pharmacogenetic testing in the prevention, assessment, and management of cisplatin-induced hearing loss in children and adults, and (3) identify knowledge gaps to direct and prioritize future research. These practice recommendations for pharmacogenetic testing in the context of cisplatin-induced hearing loss reflect a review and evaluation of recent literature, and are designed to assist clinicians in providing optimal clinical care for patients receiving cisplatin-based chemotherapy

The pharmacogenomics of cisplatin-induced hearing loss

Cisplatin is a widely used chemotherapeutic agent for the treatment of solid tumours. A serious complication of cisplatin treatment is permanent hearing loss. The study hypothesis is that genetic variants in genes involved in drug metabolism and transport can contribute to increased susceptibility to hearing loss in pediatric oncology patients treated with cisplatin. Patients were recruited from across Canada through the Canadian Pharmacogenomics Network for Drug Safety (CPNDS). Recently, our group identified several predictive genetic variants that were highly associated with cisplatin-induced hearing loss in children. We evaluated whether we could replicate these findings in a new independent cohort of 155 pediatric patients. Associations were replicated for genetic variants in TPMT (rs12201199, P=0.0013, Odds Ratio, OR 6.1) and ABCC3 (rs1051640, P=0.036, OR 1.8). A predictive model combining variants in TPMT, ABCC3 and COMT with clinical variables significantly improved the prediction of risk of developing hearing loss compared to clinical risk factors alone (P=0.00048). We next evaluated whether we could identify additional genetic variants that confer susceptibility to cisplatin-induced hearing loss. We identified novel variants in ABCB5 (rs10950831, P=1.06×10⁻⁶, OR 2.0) and DPYD (rs6667550, P=0.0047, OR 1.9) that were significantly associated with cisplatin-induced hearing loss. We included these variants into the initial genetic model that consists of variants in TPMT, ABCC3 and COMT to evaluate whether we could improve the prediction of risk. We demonstrate that the risk of prediction of hearing loss significantly improves by including genetic variants in ABCB5 and DPYD (P=0.0023). We also demonstrate that by combining the clinical and genetic factors we can significantly improve the prediction of risk of hearing loss compared to clinical factors alone (P=2.63x10⁻⁷). We were able to replicate previously described findings and also provide evidence for novel genetic variants in the prediction of cisplatin-induced hearing loss in children. Furthermore, this study demonstrates that predictive models can classify patients based on predicted risk of cisplatin-induced hearing loss. These findings have the potential to influence treatment modifications for cisplatin therapy and may improve safety in children.Medicine, Faculty ofMedical Genetics, Department ofGraduat

A scoping review of human pathogens detected in untreated human wastewater and sludge

Wastewater monitoring is an approach to identify the presence or abundance of pathogens within a population. The objective of this scoping review (ScR) was to identify and characterize research on human pathogens and antimicrobial resistance detected in untreated human wastewater and sludge. A search was conducted up to March 2023 and standard ScR methodology was followed. This ScR included 1,722 articles, of which 56.5% were published after the emergence of COVID-19. Viruses and bacteria were commonly investigated, while research on protozoa, helminths, and fungi was infrequent. Articles prior to 2019 were dominated by research on pathogens transmitted through fecal–oral or waterborne pathways, whereas more recent articles have explored the detection of pathogens transmitted through other pathways such as respiratory and vector-borne. There was variation in sampling, samples, and sample processing across studies. The current evidence suggests that wastewater monitoring could be applied to a range of pathogens as a public health tool to detect an emerging pathogen and understand the burden and spread of disease to inform decision-making. Further development and refinement of the methods to identify and interpret wastewater signals for different prioritized pathogens are needed to develop standards on when, why, and how to monitor effectively. HIGHLIGHTS A wide range of pathogens can be detected in wastewater.; 56.5% of studies were published since 2020.; Viruses were the most commonly investigated pathogen type followed by bacteria.; Earlier studies focused on pathogens transmitted through fecal–oral or waterborne pathways.; Additional research is needed to determine which pathogens are conducive to wastewater monitoring and where, when, and how it should be implemented.

Relation of the completeness of reporting of rapid reviews to journal publication status: protocol for a comparative, cross-sectional methodological study

This project will compare the completeness of reporting of journal-published rapid reviews with those not published in journals according to four reporting tools: PRISMA, PRISMA-P, Cochrane MECIR reporting standards, and IOM reporting standard

Screening and treatment for esophageal adenocarcinoma and precancerous conditions: an evidence synthesis to inform the Canadian Task Force on Preventive Health Care

The aim of the evidence syntheses is to identify evidence on the: 1) The benefits and harms of screening for esophageal cancer and precancerous conditions (systematic review); 2) The patient preferences and values about undergoing screening (systematic review); 3) The benefits and harms of treatment options for esophageal adenocarcinoma and precancerous conditions (overview of reviews). The information will be used by the Canadian Task Force on Preventive Health Care (CTFPHC) and their esophageal cancer screening guideline for primary care providers

Publication

The aim of the evidence syntheses is to identify evidence on the: 1) The benefits and harms of screening for esophageal cancer and precancerous conditions (systematic review); 2) The patient preferences and values about undergoing screening (systematic review); 3) The benefits and harms of treatment options for esophageal adenocarcinoma and precancerous conditions (overview of reviews). The information will be used by the Canadian Task Force on Preventive Health Care (CTFPHC) and their esophageal cancer screening guideline for primary care providers

Protocol

The aim of the evidence syntheses is to identify evidence on the: 1) The benefits and harms of screening for esophageal cancer and precancerous conditions (systematic review); 2) The patient preferences and values about undergoing screening (systematic review); 3) The benefits and harms of treatment options for esophageal adenocarcinoma and precancerous conditions (overview of reviews). The information will be used by the Canadian Task Force on Preventive Health Care (CTFPHC) and their esophageal cancer screening guideline for primary care providers

Taking a close look at the layout and content structure of journal published and non-journal published rapid review reports: protocol for a cross-sectional, methodological study.

This project will determine what rapid review report formats exist based on an international sample of rapid reviews, and will compare the layout features and content structure of journal-published rapid reviews with those not published in journals