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Background: Women who engage in sex work and use drugs (WSWUD) experience disproportionate HIV risks. Substance use treatment bridge clinics offer an opportunity to increase HIV pre-exposure prophylaxis (PrEP) delivery to WSWUD, but research on best practices is lacking. Therefore, we explored facilitators and barriers to PrEP across the PrEP care continuum in these settings., Methods: Bridge clinic and affiliated harm reduction health service providers and WSWUD from Boston were recruited using passive and active outreach between December 2021 and August 2022. Participants were invited to take part in semi-structured phone or in-person interviews to explore HIV prevention and PrEP care experiences overall and within bridge clinic settings. Deductive codes were developed based on HIV risk environment frameworks and the Information-Motivation-Behavioral Skills model and inductive codes were added based on transcript review. Grounded content analysis was used to generate themes organized around the PrEP care continuum., Results: The sample included 14 providers and 25 WSWUD. Most WSWUD were aware of PrEP and more than half had initiated PrEP at some point. However, most who initiated PrEP did not report success with daily oral adherence. Providers and WSWUD described facilitators and barriers to PrEP across the steps of the care continuum: Awareness, uptake, adherence, and retention. Facilitators for WSWUD included non-stigmatizing communication with providers, rapid wraparound substance use treatment and HIV services, having a PrEP routine, and service structures to support PrEP adherence. Barriers included low HIV risk perceptions and competing drug use and survival priorities. Provider facilitators included clinical note templates prompting HIV risk assessments and training. Barriers included discomfort discussing sex work risks, competing clinical priorities, and a lack of PrEP adherence infrastructure., Conclusion: WSWUD and bridge clinic providers favored integrated HIV prevention and substance use services in harm reduction and bridge clinic settings. Harm reduction and bridge clinic programs played a key role in HIV prevention and PrEP education for WSWUD. Effective behavioral and structural interventions are still needed to improve PrEP adherence for WSWUD., (© 2024. The Author(s).)

Background: Many families and individuals do not meet criteria for a known hereditary cancer syndrome but display unusual clusters of cancers. These families may carry pathogenic variants in cancer predisposition genes and be at higher risk for developing cancer., Methods: This multi-centre prospective study recruited 195 cancer-affected participants suspected to have a hereditary cancer syndrome for whom previous clinical targeted genetic testing was either not informative or not available. To identify pathogenic disease-causing variants explaining participant presentation, germline whole-genome sequencing (WGS) and a comprehensive cancer virtual gene panel analysis were undertaken., Results: Pathogenic variants consistent with the presenting cancer(s) were identified in 5.1% (10/195) of participants and pathogenic variants considered secondary findings with potential risk management implications were identified in another 9.7% (19/195) of participants. Health economic analysis estimated the marginal cost per case with an actionable variant was significantly lower for upfront WGS with virtual panel ($8744AUD) compared to standard testing followed by WGS ($24,894AUD). Financial analysis suggests that national adoption of diagnostic WGS testing would require a ninefold increase in government annual expenditure compared to conventional testing., Conclusions: These findings make a case for replacing conventional testing with WGS to deliver clinically important benefits for cancer patients and families. The uptake of such an approach will depend on the perspectives of different payers on affordability., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Routine screening of tumors for DNA mismatch repair (MMR) deficiency (dMMR) in colorectal (CRC), endometrial (EC) and sebaceous skin (SST) tumors leads to a significant proportion of unresolved cases classified as suspected Lynch syndrome (SLS). SLS cases (n = 135) were recruited from Family Cancer Clinics across Australia and New Zealand. Targeted panel sequencing was performed on tumor (n = 137; 80×CRCs, 33×ECs and 24xSSTs) and matched blood-derived DNA to assess for microsatellite instability status, tumor mutation burden, COSMIC tumor mutational signatures and to identify germline and somatic MMR gene variants. MMR immunohistochemistry (IHC) and MLH1 promoter methylation were repeated. In total, 86.9% of the 137 SLS tumors could be resolved into established subtypes. For 22.6% of these resolved SLS cases, primary MLH1 epimutations (2.2%) as well as previously undetected germline MMR pathogenic variants (1.5%), tumor MLH1 methylation (13.1%) or false positive dMMR IHC (5.8%) results were identified. Double somatic MMR gene mutations were the major cause of dMMR identified across each tumor type (73.9% of resolved cases, 64.2% overall, 70% of CRC, 45.5% of ECs and 70.8% of SSTs). The unresolved SLS tumors (13.1%) comprised tumors with only a single somatic (7.3%) or no somatic (5.8%) MMR gene mutations. A tumor-focused testing approach reclassified 86.9% of SLS into Lynch syndrome, sporadic dMMR or MMR-proficient cases. These findings support the incorporation of tumor sequencing and alternate MLH1 methylation assays into clinical diagnostics to reduce the number of SLS patients and provide more appropriate surveillance and screening recommendations., (© 2023. The Author(s).)

Background: Infectious disease (ID) consultations have been shown to increase adherence to guidelines and decrease mortality for patients with Staphylococcus aureus bacteremia (SAB). Here, we assessed the impact of a mandatory ID consultation policy for SAB., Methods: We retrospectively reviewed all consecutive adult patients with SAB at two tertiary care teaching hospitals in Hamilton, ON, Canada. Mandatory ID consults for SAB were implemented on January 1(st) 2012. We compared SAB cases in 2011 (control group) with those in 2012 (intervention group). Outcomes included adherence to the Infectious Diseases Society of America guidelines and patient outcomes., Results: We reviewed 128 SAB cases in 2011 and 124 in 2012. The majority of S. aureus were methicillin-susceptible (97/128, 75.8 % in 2011 and 100/124, 80.6 % in 2012). ID involvement increased significantly from 93/128 (72.7 %) in 2011, to 103/124 (83.1 %) in 2012 (odds ratio [OR] 1.9, 95 % confidence interval [CI] 1.1-3.3, p = 0.047). There was also a significant decrease in the median time to ID involvement from 2 days to 1 (p = 0.001). In patients who survived the minimum treatment course (greater than 13 days), there was a significant improvement in adherence to IDSA guidelines in 2012 (65/102, 63.7 % vs. 77/96, 80.2 %; OR 2.3, 95 % CI 1.2-4.4, p = 0.01). Mortality and SAB relapse rates were similar in both groups., Conclusions: Creating an automated ID consultation for SAB led to an increase in involvement of ID, a significant decrease in time to ID involvement, and better adherence to IDSA guidelines. The study was not sufficiently powered to detect significant changes in mortality and SAB relapse rates.