Synthetic lethality-mediated precision oncology via the tumor transcriptome.

Precision oncology has made significant advances, mainly by targeting actionable mutations in cancer driver genes. Aiming to expand treatment opportunities, recent studies have begun to explore the utility of tumor transcriptome to guide patient treatment. Here, we introduce SELECT (synthetic lethality and rescue-mediated precision oncology via the transcriptome), a precision oncology framework harnessing genetic interactions to predict patient response to cancer therapy from the tumor transcriptome. SELECT is tested on a broad collection of 35 published targeted and immunotherapy clinical trials from 10 different cancer types. It is predictive of patients' response in 80% of these clinical trials and in the recent multi-arm WINTHER trial. The predictive signatures and the code are made publicly available for academic use, laying a basis for future prospective clinical studies.

Haploinsufficiency of phosphodiesterase 10A activates PI3K/AKT signaling independent of PTEN to induce an aggressive glioma phenotype.

Glioblastoma is universally fatal and characterized by frequent chromosomal copy number alterations harboring oncogenes and tumor suppressors. In this study, we analyzed exome-wide human glioblastoma copy number data and found that cytoband 6q27 is an independent poor prognostic marker in multiple data sets. We then combined CRISPR-Cas9 data, human spatial transcriptomic data, and human and mouse RNA sequencing data to nominate PDE10A as a potential haploinsufficient tumor suppressor in the 6q27 region. Mouse glioblastoma modeling using the RCAS/tv-a system confirmed that Pde10a suppression induced an aggressive glioma phenotype in vivo and resistance to temozolomide and radiation therapy in vitro. Cell culture analysis showed that decreased Pde10a expression led to increased PI3K/AKT signaling in a Pten-independent manner, a response blocked by selective PI3K inhibitors. Single-nucleus RNA sequencing from our mouse gliomas in vivo, in combination with cell culture validation, further showed that Pde10a suppression was associated with a proneural-to-mesenchymal transition that exhibited increased cell adhesion and decreased cell migration. Our results indicate that glioblastoma patients harboring PDE10A loss have worse outcomes and potentially increased sensitivity to PI3K inhibition.

Modeling YAP fusions: a paradigm for investigating rare cancers?

Loss of the NF2 tumor suppressor gene is a common finding in meningiomas, and more recently YAP1 fusions have been found in a subset of pediatric NF2 wild-type meningiomas. In the previous issue of Genes & Development, Szulzewsky and colleagues (pp. 857-870) showed that TEAD-dependent YAP1 activity by either the loss of the NF2 gene or YAP1-MAML2 fusion is an oncogenic process promoting meningioma tumorigenesis. Furthermore, pharmacological inhibition of YAP1-TEAD resulted in antitumor activity in both YAP1 fusion-positive and NF2 mutant meningiomas. Together, these data indicate that disruption of the YAP1-TEAD interaction raises a potential therapeutic option for these tumors that requires future investigation.

Longitudinal molecular trajectories of diffuse glioma in adults.

The evolutionary processes that drive universal therapeutic resistance in adult patients with diffuse glioma remain unclear1,2. Here we analysed temporally separated DNA-sequencing data and matched clinical annotation from 222 adult patients with glioma. By analysing mutations and copy numbers across the three major subtypes of diffuse glioma, we found that driver genes detected at the initial stage of disease were retained at recurrence, whereas there was little evidence of recurrence-specific gene alterations. Treatment with alkylating agents resulted in a hypermutator phenotype at different rates across the glioma subtypes, and hypermutation was not associated with differences in overall survival. Acquired aneuploidy was frequently detected in recurrent gliomas and was characterized by IDH mutation but without co-deletion of chromosome arms 1p/19q, and further converged with acquired alterations in the cell cycle and poor outcomes. The clonal architecture of each tumour remained similar over time, but the presence of subclonal selection was associated with decreased survival. Finally, there were no differences in the levels of immunoediting between initial and recurrent gliomas. Collectively, our results suggest that the strongest selective pressures occur during early glioma development and that current therapies shape this evolution in a largely stochastic manner.

Reach of GetCheckedOnline among gay, bisexual, transgender and queer men and Two-Spirit people and correlates of use 5 years after program launch in British Columbia, Canada.

OBJECTIVES: Understanding who uses internet-based sexually transmitted and blood-borne infection (STBBI) services can inform programme implementation, particularly among those most impacted by STBBIs, including gender and sexual minority (GSM) men. GetCheckedOnline, an internet-based STBBI testing service in British Columbia, Canada, launched in 2014. Our objectives were to assess reach, identify factors associated with use of GetCheckedOnline 5 years into implementation and describe reasons for using and not using GetCheckedOnline among GSM men. METHODS: The Sex Now 2019 Survey was an online, cross-sectional survey of GSM men in Canada administered from November 2019 to February 2020. Participants were asked a subset of questions related to use of GetCheckedOnline. Multivariable binary logistic regression modelling was used to estimate associations between correlates and use of GetCheckedOnline. RESULTS: Of 431 British Columbia (BC) participants aware of GetCheckedOnline, 27.6% had tested using the service. Lower odds of having used GetCheckedOnline were found among participants with non-white race/ethnicity (adjusted OR (aOR)=0.41 (95% CI 0.21 to 0.74)) and those living with HIV (aOR=0.23 (95% CI 0.05 to 0.76)). Those who usually tested at a walk-in clinic, relative to a sexual health clinic, had greater odds of using GetCheckedOnline (aOR=3.91 (95% CI 1.36 to 11.61)). The most commonly reported reason for using and not using GetCheckedOnline was convenience (78%) and only accessing the website to see how the service worked (48%), respectively. CONCLUSION: Over a quarter of GSM men in BC aware of GetCheckedOnline had used it. Findings demonstrate the importance of social/structural factors related to use of GetCheckedOnline. Service promotion strategies could highlight its convenience and privacy benefits to enhance uptake.

The Resurgence of Lymphogranuloma Venereum: Changing Presentation of Lymphogranuloma Venereum in the Era of HIV Preexposure Prophylaxis, 2004 to 2022.

BACKGROUND: Before the early 2000s, the sexually transmitted infection lymphogranuloma venereum (LGV) was rare in high-income countries. Initially, most cases in these countries were among symptomatic men who have sex with men (MSM) living with HIV. In the context of widespread HIV preexposure prophylaxis (PrEP), LGV's epidemiology may be changing. We aimed to characterize the epidemiology and clinical presentation of LGV in the PrEP era. METHODS: A retrospective chart review was performed on all LGV cases occurring between November 2004 to October 2022 in British Columbia (BC), Canada. Cases were stratified by having occurred before (2004-2017) or after widespread PrEP availability in BC (2018-2022). Annual rates and test positivity percentages were calculated. Bivariate logistic regression was performed to identify drivers of asymptomatic infection in the PrEP era. RESULTS: Among 545 cases identified, 205 (37.6%) occurred pre-PrEP and 340 (62.4%) occurred during the PrEP era. Most cases were among MSM (97.2%). The estimated rate of LGV has doubled from 2018 to 2022, reaching 1535.2 cases per 100,000 PrEP users. Most PrEP-era cases were among HIV-negative individuals (65.3%), particularly those on PrEP (72.6%). Cases in the PrEP era were often asymptomatic compared with pre-PrEP (38.6% vs. 19.3%; P < 0.001). Users of PrEP were more likely to experience asymptomatic infection compared with HIV-negative PrEP nonusers (odds ratio, 2.07; 95% confidence interval, 1.07-3.99). CONCLUSIONS: In the context of increased asymptomatic testing, LGV may be increasing in BC. Most infections now occur among HIV-negative MSM. A high proportion of infections are asymptomatic.

Virtual multi-institutional tumor board: a strategy for personalized diagnoses and management of rare CNS tumors.

PURPOSE: Multidisciplinary tumor boards (MTBs) integrate clinical, molecular, and radiological information and facilitate coordination of neuro-oncology care. During the COVID-19 pandemic, our MTB transitioned to a virtual and multi-institutional format. We hypothesized that this expansion would allow expert review of challenging neuro-oncology cases and contribute to the care of patients with limited access to specialized centers. METHODS: We retrospectively reviewed records from virtual MTBs held between 04/2020-03/2021. Data collected included measures of potential clinical impact, including referrals to observational or therapeutic studies, referrals for specialized neuropathology analysis, and whether molecular findings led to a change in diagnosis and/or guided management suggestions. RESULTS: During 25 meetings, 32 presenters discussed 44 cases. Approximately half (n = 20; 48%) involved a rare central nervous system (CNS) tumor. In 21% (n = 9) the diagnosis was changed or refined based on molecular profiling obtained at the NIH and in 36% (n = 15) molecular findings guided management. Clinical trial suggestions were offered to 31% (n = 13), enrollment in the observational NCI Natural History Study to 21% (n = 9), neuropathology review and molecular testing at the NIH to 17% (n = 7), and all received management suggestions. CONCLUSION: Virtual multi-institutional MTBs enable remote expert review of CNS tumors. We propose them as a strategy to facilitate expert opinions from specialized centers, especially for rare CNS tumors, helping mitigate geographic barriers to patient care and serving as a pre-screening tool for studies. Advanced molecular testing is key to obtaining a precise diagnosis, discovering potentially actionable targets, and guiding management.

Patterns of Socioeconomic Marginalization among People Who Use Drugs: A Gender-Stratified Repeated Measures Latent Class Analysis.

Socioeconomic factors are important correlates of drug use behaviors and health-related outcomes in people who use drugs (PWUD) residing in urban areas. However, less is known about the complex overlapping nature of socioeconomic conditions and their association with a range of individual, drug use, and health-related factors in men and women who use drugs. Data were obtained from two community-recruited prospective cohorts of PWUD. Using a gender-stratified approach, we conducted repeated measures latent class analyses (RMLCA) to identify discrete latent socioeconomic subgroups. Multivariable generalized estimating equations were then used to identify correlates of class membership. Between June 2014 and December 2018, RMLCA of 9844 observations from 1654 participants revealed five distinct patterns of socioeconomic status for both men and women. These patterns were primarily distinguished by variations in income, material and housing security, income generation activity, exposure to violence, criminal justice involvement, and police contact. Across gender, progressive increases in exposure to multiple dimensions of socioeconomic disadvantage were found to be associated with frequent use of opioids and stimulants, accessing social services, and being hepatitis C virus antibody-positive. Similar but less congruent trends across gender were observed for age, binge drug use, engagement with opioid agonist therapy, and living with HIV. Gendered patterns of multiple and overlapping dimensions of socioeconomic adversity aligned with patterns of frequent drug use and health-related concerns, highlighting priority areas for gender-inclusive, multilevel responses to mitigate health disparities and meet the diverse socioeconomic needs of urban-dwelling men and women who use drugs.

Perspectives on digital testing services for sexually transmitted and blood-borne infections from Two-Spirit, gay, bisexual, transgender, and other queer Black, Indigenous, people of colour living in Ontario, Canada.

OBJECTIVES: Increased sexually transmitted and blood-borne infections (STBBI) testing can reduce the burden of disease among Two-Spirit, gay, bisexual, transgender, and other queer Black, Indigenous, people of colour (2SGBTQ+ BIPOC). However, this population encounters barriers, such as discrimination, when accessing in-person STBBI testing services. Digital STBBI testing, such as self-testing/collection kits ordered online and digital requisitions, may address some of these barriers. Our aim was to understand acceptability of free digital STBBI testing among 2SGBTQ+ BIPOC living in Ontario, Canada. DESIGN: We approached this analysis using Implementation Science and Critical Race Theory. We conducted interviews and focus groups with 21 2SGBTQ + BIPOC individuals from 2020-2021. Participants were asked about their perceptions of the benefits and drawbacks of digital STBBI testing, populations that would benefit from using these services, and recommendations for how these services may be implemented in Ontario. Interviews and focus groups were transcribed verbatim and analyzed using reflexive thematic analysis. RESULTS: Six themes emerged. Digital STBBI testing services: (1) May reduce oppression experienced by 2SGBTQ + BIPOC when testing in-person; (2) Should address the unique needs that 2SGBTQ + BIPOC experience due to other intersecting identities they possess; (3) Should adapt their services to suit the varying cultural contexts and living circumstances of 2SGBTQ + BIPOC; (4) Should be accessible to 2SGBTQ + BIPOC who hold diverse or no documentation; (5) Should be offered in multiple languages; (6) May be inaccessible to those without Internet access or devices. CONCLUSION: Digital STBBI testing is one strategy that may reduce discrimination experienced by 2SGBTQ + BIPOC when getting tested in-person. However, digital STBBI testing services may not address all the needs of 2SGBTQ + BIPOC. Racism and other forms of oppression embedded into in-person and digital testing services will need to be addressed to meet the needs of this diverse population.

'Sometimes white doctors are not very friendly or inclusive': a Critical Race Theory analysis of racism within and beyond sexual health settings.

Many Two-Spirit, gay, bisexual, transgender, and other queer Black, Indigenous, people of colour in Canada encounter racism when testing for sexually transmitted and blood-borne infections. Our objective in this study was to understand how racism shapes testing experiences for these communities in Ontario, Canada. Four peer researchers conducted recruitment and data collection in consultation with a community advisory board. Focus groups and interviews took place with 21 participants and their narrative accounts were analysed using reflexive thematic analysis. Participants identified three interrelated issues when testing: (1) experiencing judgement and discomfort due to racism; (2) lack of community and cultural indicators in testing spaces; and (3) barriers to accessing testing centres and services. Systemic racism was linked to each of these barriers, including increased distance to testing centres due to racial segregation. Participant accounts signal the need for antiracist testing spaces and practices. Key implications include the need for antiracism training for health service providers and others working with Two-Spirit, gay, bisexual, transgender, and other queer Black, Indigenous, people of colour, and the organisations that serve them, in order to make testing spaces safer. Dismantling systemic racism is imperative to achieve health equity for members of these communities.

Healthcare Utilization After Respiratory Tuberculosis: A Controlled Interrupted Time Series Analysis.

BACKGROUND: Despite data suggesting elevated morbidity and mortality among people who have survived tuberculosis disease, the impact of respiratory tuberculosis on healthcare utilization in the years following diagnosis and treatment remains unclear. METHODS: Using linked health administrative data from British Columbia, Canada, we identified foreign-born individuals treated for respiratory tuberculosis between 1990 and 2019. We matched each person with up to four people without a tuberculosis diagnosis from the same source cohort using propensity score matching. Then, using a controlled interrupted time series analysis, we measured outpatient physician encounters and inpatient hospital admissions in the 5 years following respiratory tuberculosis diagnosis and treatment. RESULTS: We matched 1216 individuals treated for respiratory tuberculosis to 4864 non-tuberculosis controls. Immediately following the tuberculosis diagnostic and treatment period, the monthly rate of outpatient encounters in the tuberculosis group was 34.0% (95% confidence interval [CI]: 30.7%, 37.2%) higher than expected, and this trend was sustained for the duration of the post-tuberculosis period. The excess utilization represented an additional 12.2 (95% CI: 10.6, 14.9) outpatient encounters per person over the post-tuberculosis period, with respiratory morbidity a large contributor to the excess healthcare utilization. Results were similar for hospital admissions, with an additional 0.4 (95% CI: .3, .5) hospital admissions per person over the post-tuberculosis period. CONCLUSIONS: Respiratory tuberculosis appears to have long-term impacts on healthcare utilization beyond treatment. These findings underscore the need for screening, assessment, and treatment of post-tuberculosis sequelae, as it may provide an opportunity to improve health and reduce resource use.

Clinical impact of molecular profiling in rare brain tumors.

PURPOSE OF REVIEW: The purpose of this review is to describe the commonly used molecular diagnostics and illustrate the prognostic importance to the more accurate diagnosis that also may uncover therapeutic targets. RECENT FINDINGS: The most recent WHO Classification of Central Nervous System Tumours (2021) lists over 100 distinct tumor types. While traditional histology continues to be an important component, molecular testing is increasingly being incorporated as requisite diagnostic criteria. Specific molecular findings such as co-deletion of the short arm of chromosome 1 (1p) and long arm of chromosome 19 (19q) now define IDH-mutant gliomas as oligodendroglioma. In recent years, DNA methylation profiling has emerged as a dynamic tool with high diagnostic accuracy. The integration of specific genetic (mutations, fusions) and epigenetic (CpG methylation) alterations has led to diagnostic refinement and the discovery of rare brain tumor types with distinct clinical outcomes. Molecular profiling is anticipated to play an increasing role in routine surgical neuropathology, although costs, access, and logistical concerns remain challenging. SUMMARY: This review summarizes the current state of molecular testing in neuro-oncology highlighting commonly used and developing technologies, while also providing examples of new tumor types/subtypes that have emerged as a result of improved diagnostic precision.

Differential uptake and effects of digital sexually transmitted and bloodborne infection testing interventions among equity-seeking groups: a scoping review.

BACKGROUND: Digital sexually transmitted and bloodborne infection (STBBI) testing interventions have gained popularity. However, evidence of their health equity effects remains sparse. We conducted a review of the health equity effects of these interventions on uptake of STBBI testing and explored design and implementation factors contributing to reported effects. METHODS: We followed Arksey and O'Malley's framework for scoping reviews (2005) integrating adaptations by Levac et al (2010). We searched OVID Medline, Embase, CINAHL, Scopus, Web of Science, Google Scholar and health agency websites for peer-reviewed articles and grey literature comparing uptake of digital STBBI testing with in-person models and/or comparing uptake of digital STBBI testing among sociodemographic strata, published in English between 2010 and 2022. We extracted data using the Place of residence, Race, Occupation, Gender/Sex, Religion, Education, Socioeconomic status (SES), Social capital and other disadvantaged characteristics (PROGRESS-Plus) framework, reporting differences in uptake of digital STBBI testing by these characteristics. RESULTS: We included 27 articles from 7914 titles and abstracts. Among these, 20 of 27 (74.1%) were observational studies, 23 of 27 (85.2%) described web-based interventions and 18 of 27 (66.7%) involved postal-based self-sample collection. Only three articles compared uptake of digital STBBI testing with in-person models stratified by PROGRESS-Plus factors. While most studies demonstrated increased uptake of digital STBBI testing across sociodemographic strata, uptake was higher among women, white people with higher SES, urban residents and heterosexual people. Co-design, representative user recruitment, and emphasis on privacy and security were highlighted as factors contributing to health equity in these interventions. CONCLUSION: Evidence of health equity effects of digital STBBI testing remains limited. While digital STBBI testing interventions increase testing across sociodemographic strata, increases are lower among historically disadvantaged populations with higher prevalence of STBBIs. Findings challenge assumptions about the inherent equity of digital STBBI testing interventions, emphasising the need to prioritise health equity in their design and evaluation.

Evaluating the Impact of the COVID-19-Related Public Health Restrictions on Access to Digital Sexually Transmitted and Blood-Borne Infection Testing in British Columbia, Canada: An Interrupted Time Series Analysis.

BACKGROUND: Evidence of long-term impacts of COVID-19-related public health restrictions on digital sexually transmitted and blood-borne infection (STBBI) testing utilization is limited. We assessed these impacts on GetCheckedOnline (a digital testing resource for STBBIs) relative to all STBBI tests in British Columbia (BC). METHODS: Interrupted time series analyses were conducted using GetCheckedOnline program data comparing monthly test episodes (STBBI tests per requisition) among BC residents, stratified by BC region, and testers' sociodemographic and sexual risk profiles, for the prepandemic (March 2018-February 2020) and pandemic periods (March 2020-October 2021). Trends in GetCheckedOnline testing per 100 STBBI tests in BC regions with GetCheckedOnline were analyzed. Each outcome was modeled using segmented generalized least squared regression. RESULTS: Overall, 17,215 and 22,646 test episodes were conducted in the prepandemic and pandemic periods. Monthly GetCheckedOnline test episodes reduced immediately after restrictions. By October 2021 (end of the pandemic period), monthly GetCheckedOnline testing increased by 21.24 test episodes per million BC residents (95% confidence interval, -11.88 to 54.84), and GetCheckedOnline tests per 100 tests in corresponding BC regions increased by 1.10 (95% confidence interval, 0.02 to 2.17) above baseline trends. After initial increases among users at higher STBBI risk (symptomatic testers/testers reporting sexual contacts with STBBIs), testing decreased below baseline trends later in the pandemic, whereas monthly GetCheckedOnline testing increased among people 40 years or older, men who have sex with men, racialized minorities, and first-time testers via GetCheckedOnline. CONCLUSIONS: Sustained increases in utilization of digital STBBI testing during the pandemic suggest fundamental changes in STBBI testing in BC, highlighting the need for accessible and appropriate digital testing, especially for those most affected by STBBIs.

Feasibility and preliminary efficacy of a virtual reality intervention targeting distress and anxiety in primary brain tumor patients at the time of clinical evaluation: Study protocol for a phase 2 clinical trial.

BACKGROUND: Primary brain tumor (PBT) patients experience higher levels of distress and anxiety than other solid tumor patients, particularly at the time of clinical evaluation when uncertainty about disease status is high ("scanxiety"). There is promising evidence supporting use of virtual reality (VR) to target psychological symptoms in other solid tumor patients, though PBT patients have not been studied extensively in this context. The primary aim of this phase 2 clinical trial is to establish the feasibility of a remote VR-based relaxation intervention for a PBT population, with secondary aims designed to determine preliminary efficacy of improving distress and anxiety symptoms. METHODS: PBT patients (N = 120) with upcoming MRI scans and clinical appointments who meet eligibility will be recruited to participate in a single arm trial conducted remotely through the NIH. Following completion of baseline assessments, participants will complete a 5-min VR intervention via telehealth using a head-mounted immersive device while under supervision of the research team. Following the intervention, over the course of 1 month patients can use VR at their discretion with follow-up assessments done immediately post-VR intervention, as well as 1 week and 4 weeks later. Additionally, a qualitative phone interview will be conducted to assess patient satisfaction with the intervention. DISCUSSION: Use of immersive VR is an innovative interventional approach to target distress and scanxiety symptoms in PBT patients who are at high risk for experiencing these symptoms leading into their clinical appointments. Findings from this study may inform design of a future multicenter randomized VR trial for PBT patients and may aid in development of similar interventions for other oncology populations. TRIAL REGISTRATION: Clinicaltrials.gov (NCT04301089), registered 9 March 2020.

Capturing evolving definitions of 12 select rare CNS tumors: a timely report from CBTRUS and NCI-CONNECT.

PURPOSE: Incidence, prevalence, and survival are population-based statistics describing cancer burden. The National Cancer Institute's (NCI) Comprehensive Oncology Network Evaluating Rare CNS Tumors (NCI-CONNECT) specializes in tumor biology and outcomes for 12 rare CNS tumor types selected for their importance in adults, research interest, or potential for targeted treatment. The aim of this study was to update incidence, prevalence, and survival statistics for these tumors. METHODS: The Central Brain Tumor Registry of the United States (CBTRUS) database, a combined dataset of Centers for Disease Control and Prevention's (CDC) National Program of Cancer Registries (NPCR) and NCI's Surveillance, Epidemiology and End Results (SEER) data, was used to calculate average annual age-adjusted incidence rates (AAAIR) per 100,000 population overall and by sex, race-ethnicity, and age for diagnosis years 2008-2019. Incidence time trends were calculated for diagnosis years 2004-2019. NPCR data were used to calculate relative survival rates. Point prevalence on December 31, 2019 was estimated using annual age-specific incidence and survival. RESULTS: AAAIR was 1.47 per 100,000 for these tumors combined, with highest incidence in ependymomas (AAAIR = 0.41/100,000). Most tumor types were more common in males, adults (ages 40 + years) or children (ages < 15 years), and non-Hispanic White individuals. Ependymomas were the most prevalent tumor type (19,320 cases) followed by oligodendrogliomas (14,900 cases). Ependymomas had the highest five-year survival (90.6%) and primary CNS sarcomas the lowest (7.7%). CONCLUSIONS: These data provide means to measure the impact of clinical care and evaluate new therapies and the evolving histopathology definitions in rare CNS tumor types.

Feasibility of a virtual reality intervention targeting distress and anxiety symptoms in patients with primary brain tumors: Interim analysis of a phase 2 clinical trial.

PURPOSE: Cancer patients experience distress and anxiety when undergoing imaging studies to monitor disease status, yet these symptoms are not always appropriately identified or well-managed. This interim analysis of a phase 2 clinical trial explored feasibility and acceptability of a virtual reality relaxation (VR) intervention for primary brain tumor (PBT) patients at the time of clinical evaluation. METHODS: English speaking, adult PBT patients with previous reports of distress and upcoming neuroimaging were recruited between March of 2021 and March 2022. A brief VR session was done within 2 weeks prior to neuroimaging with patient-reported outcomes (PROs) collected before and immediately post-intervention. Self-directed VR use over the next 1 month was encouraged with additional PROs assessments at 1 and 4 weeks. Feasibility metrics included enrollment, eligibility, attrition, and device-related adverse effects with satisfaction measured with qualitative phone interviews. RESULTS: Fifty-five patients were approached via email, 40 (73%) responded and 20 (50%) enrolled (9 declines, 11 screen fails). 65% of participants were ≤ 50 years, 50% were male, 90% were White/non-Hispanic, 85% had good KPS (≥ 90), and most were on active treatment. All patients completed the VR intervention, PROs questionnaires, weekly check-ins, and qualitative interview. Most (90%) reported frequent VR use and high satisfaction and only 7 mild AEs were recorded (headache, dizziness, nausea, neck pain). CONCLUSION: This interim analysis supports feasibility and acceptability of a novel VR intervention to target psychological symptoms for PBT patients. Trial enrollment will continue to assess for intervention efficacy. TRIAL REGISTRATION: NCT04301089 registered on 3/9/2020.

Using a theory-informed approach to guide the initial development of a post-tuberculosis care package in British Columbia, Canada.

BACKGROUND: The importance of addressing the long-term needs of tuberculosis (TB) survivors is gaining increasing attention. One promising approach to improving post-TB care is implementing a post-TB care package. With a specific focus on the perspectives of healthcare providers in British Columbia, Canada, this study aimed to (1) determine a set of components to be included in a post-TB care package, (2) explore barriers and facilitators influencing their implementation, and (3) propose potential solutions to overcome identified challenges. METHODS: Employing a multi-method approach guided by the Theoretical Domains Framework, we first conducted virtual workshops with TB care providers and utilized a modified Delphi process to establish a preliminary list of care package components. Then, we surveyed healthcare providers using closed-ended, Likert-scale questions to identify implementation barriers and enablers. Lastly, we mapped the identified barriers and enablers to establish behaviour change techniques to identify possible solutions to overcome the challenges identified. RESULTS: Eleven participants attended virtual workshops, and 23 of 51 (45.1%) healthcare providers completed questionnaires. Identified components of the post-TB care package included: 1. Linking people with TB to a primary care provider if they do not have one. 2. Referring people with pulmonary TB for an end-of-treatment chest x-ray and pulmonary function testing. 3. Referring people with TB who smoke to a smoking cessation specialist. 4. Sharing a one-page post-TB information sheet with the patient's primary care provider, including a summary of post-TB health concerns, complications, and recommendations to prioritize age-appropriate screening for cardiovascular disease, lung cancer, and depression. Survey results indicated that domain scores for 'environment, context, and resources' were the lowest, suggesting potential implementation barriers. Care navigation services to help individuals overcome health system barriers while transitioning from TB care, information leaflets, and checklists summarizing key post-TB health concerns for patients and healthcare providers to help facilitate discussions may help overcome the identified barriers. CONCLUSION: Healthcare providers in British Columbia acknowledge that post-TB care is integral to comprehensive health care but are limited by time and resources. Care navigation services, a post-TB checklist, and patient information leaflets may help resolve some of these barriers.

Disruptions of sexually transmitted and blood borne infections testing services during the COVID-19 pandemic: accounts of service providers in Ontario, Canada.

BACKGROUND: Since the onset of the COVID-19 pandemic in March 2020 in Canada, the availability of sexual health services including sexually transmitted and blood-borne infection (STBBI) testing has been negatively impacted in the province of Ontario due to their designation as "non-essential" health services. As a result, many individuals wanting to access sexual healthcare continued to have unmet sexual health needs throughout the pandemic. In response to this, sexual health service providers have adopted alternative models of testing, such as virtual interventions and self-sampling/testing. Our objective was to investigate service providers' experiences of disruptions to STBBI testing during the COVID-19 pandemic in Ontario, Canada, and their acceptability of alternative testing services. METHODS: Between October 2020-February 2021, we conducted semi-structured virtual focus groups (3) and in-depth interviews (11) with a diverse group of sexual health service providers (n = 18) including frontline workers, public health workers, sexual health nurses, physicians, and sexual health educators across Ontario. As part of a larger community-based research study, data collection and analysis were led by three Peer Researchers and a Community Advisory Board was consulted throughout the research process. Transcripts were transcribed verbatim and analysed with NVivo software following grounded theory. RESULTS: Service providers identified the reallocation of public health resources and staff toward COVID-19 management, and closures, reduced hours, and lower in-person capacities at sexual health clinics as the causes for a sharp decline in access to sexual health testing services. Virtual and self-sampling interventions for STBBI testing were adopted to increase service capacity while reducing risks of COVID-19 transmission. Participants suggested that alternative models of testing were more convenient, accessible, safe, comfortable, cost-effective, and less onerous compared to traditional clinic-based models, and that they helped fill the gaps in testing caused by the pandemic. CONCLUSIONS: Acceptability of virtual and self-sampling interventions for STBBI testing was high among service providers, and their lived experiences of implementing such services demonstrated their feasibility in the context of Ontario. There is a need to approach sexual health services as an essential part of healthcare and to sustain sexual health services that meet the needs of diverse individuals.

Community and Health Care Provider Preferences for Bacterial Sexually Transmitted Infection Testing Interventions for Gay, Bisexual, and Other Men Who Have Sex With Men: e-Delphi Study.

BACKGROUND: Canadian clinical guidelines recommend at least annual and up to quarterly bacterial sexually transmitted infection (STI) testing among sexually active gay, bisexual, and other men who have sex with men (GBM). However, testing rates are suboptimal. Innovative solutions are needed to close the gap because there is currently limited knowledge on how best to approach this issue. OBJECTIVE: Our aim was to build consensus regarding interventions with the greatest potential for improving local STI testing services for GBM communities in Toronto, Ontario, Canada, using a web-based e-Delphi process. METHODS: The e-Delphi method involves using a panel format to conduct successive rounds of prioritization, with feedback between rounds, to determine priorities among groups. We recruited experts separately from the community (GBM who sought or underwent STI testing in the preceding 18 months; conducted between October 2019 and November 2019) and health care providers (those who offered STI testing to GBM in the past 12 months; conducted between February 2020 and May 2020). The experts prioritized 6 to 8 potential interventions on a 7-point Likert scale ranging from definitely not a priority to definitely a priority over 3 survey rounds and ranked their top 3 interventions. Consensus was defined as ≥60% within a ±1 response point. Summaries of responses were provided in successive rounds. We reported the percentage of a priority (encompassing somewhat a priority, a priority, and definitely a priority responses) at the end of the final round of the survey. RESULTS: Of the community experts (CEs), 84% (43/51) completed all rounds; 19% (8/43) were living with HIV; 37% (16/43) were HIV negative and on pre-exposure prophylaxis; and 42% (18/43) were HIV negative and not on pre-exposure prophylaxis. We reached consensus on 6 interventions: client reminders (41/43, 95%), express testing (38/43, 88%), routine testing (36/43, 84%), an online booking app (36/43, 84%), online-based testing (33/43, 77%), and nurse-led testing (31/43, 72%). The CEs favored convenient interventions that also maintain a relationship with their provider. Of the provider experts (PEs), 77% (37/48) completed all rounds; 59% (22/37) were physicians. Consensus was reached on the same 6 interventions (range 25/37, 68%, to 39/39, 100%) but not for provider alerts (7/37, 19%) and provider audit and feedback (6/37, 16%). Express testing, online-based testing, and nurse-led testing were prioritized by >95% (>37/39) of the PEs by the end of round 2 because of streamlined processes and decreased need to see a provider. CONCLUSIONS: Both panels were enthusiastic about innovations that make STI testing more efficient, with express testing rating highly in both the prioritizations and top 3 rankings. However, CEs preferred convenient interventions that involved their provider, whereas PEs favored interventions that prioritized patient independence and reduced patient-provider time. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/13801.