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IntroductionAn increase in crystal methamphetamine (methamphetamine) use during the overdose epidemic is being observed in British Columbia (BC), Canada, and across North America. Concurrent use (ie, using uppers and downers one after the other or together) can increase the risk of fatal and non-fatal opioid overdose.ObjectivesWe investigated motivations for concurrent use of uppers and downers, specifically how (eg, in what order) and why people use concurrently, to identify potential interventions to prevent overdose and other harms.Setting and participantsThe 2019 Harm Reduction Client Survey was administered across 22 harm reduction supply distribution sites in BC (n=621). This thematic analysis examined 307 responses by people who affirmed concurrent use to classify order and reasons for using uppers and downers concurrently.ResultsOf the 307 people who responded ‘yes’ to concurrent use, 179 (58.3%) used downers then uppers, 76 (24.8%) used uppers then downers and 184 (59.9%) mixed uppers and downers together. Four main reasons for concurrent use emerged: self-medication, availability and preference, drug effects/properties, and financial and life situation. People who mixed drugs together predominantly wanted to achieve desired drug effects/properties, such as a specific high or balancing stimulating and sedating effects.ConclusionsThe ongoing rise in overdoses in BC is multifactorial, and the recent parallel increases in methamphetamine use and concurrent use with opioids may contribute. Qualitative interviews may further elucidate reasons for concurrent use. Addressing reasons for concurrent use identified in this study through harm reduction strategies and education may affect the rates of overdose morbidity and mortality.

Background The incidence of syphilis has been increasing worldwide in the last 20 years, disproportionately impacting those living with human immunodeficiency virus (HIV). Alongside this increase, several jurisdictions have reported increasing incidences of syphilis-related complications, including ocular syphilis. We sought to characterize ocular syphilis cases in British Columbia (BC), Canada. Methods This case-control study compared ocular syphilis cases, matched (1:4) to syphilis controls, that were diagnosed in BC between January 2010 and December 2018. Multivariable logistic regression was used to identify potential correlates of ocular syphilis, where variables were included in the final model if significant (P ≤ .05). Results During the study period, there were 6716 syphilis diagnoses, including 66 (0.98%) ocular syphilis cases. The median age of cases was 49.5 years (interquartile range 39–59). Most (87.8%) patients were male, where 54.6% identified as men who have sex with men. The most common ophthalmologic diagnosis was panuveitis (42.4%). Of ocular syphilis patients, 48.5% were living with HIV at the time of their syphilis diagnosis, compared to 26.4% of controls (P = .001). The proportion of syphilis cases with ocular syphilis increased from 0.48% in 2010 to 0.83% in 2018. The final multivariable model demonstrated correlates between ocular syphilis and early syphilis stage, including primary/secondary (odds ratio [OR] 4.96, 95% confidence interval [CI] 1.86–13.24) and early latent (OR 4.29, 95% CI 1.62–11.34) stages, and HIV serostatus (OR 2.16, 95% CI 1.14–4.09). Conclusions Ocular syphilis increased over the study period, both in absolute numbers and as a proportion of all syphilis cases, a finding consistent with other jurisdictions. These findings highlight the importance of vigilance for ocular syphilis, to avoid diagnostic and treatment delays.

Background Syphilis testing, treatment, and partner notification (PN) are centrally coordinated in British Columbia (BC), Canada. Public health (PH) nurses (PHNs) contact almost all syphilis patients and either notify partners of syphilis exposure (PH-initiated PN), or support patients to notify their own partners (patient-initiated PN). In the context of an ongoing syphilis epidemic among gay, bisexual, and other men who report sex with men (gbMSM), we measured population-level yields and compared PN approaches to inform prevention and control efforts. Methods All gbMSM diagnosed with infectious syphilis in 2016 in BC were included. We calculated indicators of engagement with PN among patients and PN outcomes among notifiable partners using a cascade-of-care framework. Chi-square tests compared indicators between PN approaches. Results Of the 759 syphilis diagnoses, 85.4% (648/759) were among gbMSM and 94.7% (614/648) were treated within 30 days of testing (mean 5.5, standard deviation [SD] 5.2 days). Among patients, 87.7% (568/648) discussed PN with PHNs and 49.5% (281/568) named at least one notifiable partner for a total of 1,094 partners (mean 3.9, SD 5.5 partners/patient). Compared to PH-initiated PN, patient-initiated PN resulted in a greater proportion of partners notified (70.1%, 573/817 versus 89.8%, 211/235; P = 1.88x10-9), but there was no difference in the proportion of partners tested and/or treated (90.2%, 517/573 versus 86.7% 183/211; P = 0.203), and diagnosed (12.8%, 66/517 versus 16.4%, 30/183; P > 0.271). Conclusion PH- and patient-initiated PN had similarly high yields of partners tested and/or treated, and diagnosed, demonstrating that gbMSM can contribute to syphilis PN when supported by resource-equipped PHNs.

SummaryBackgroundAngiotensin converting enzyme 2 (ACE2) serves as the host receptor for SARS-CoV-2, with a critical role in viral infection. We aim to understand population level variation of nasopharyngealACE2expression in people tested for COVID-19 and the relationship betweenACE2expression and SARS-CoV-2 viral RNA load, while adjusting for expression of the complementary protease, Transmembrane serine protease 2 (TMPRSS2), solubleACE2, age, and biological sex.MethodsA cross-sectional study of n=424 participants aged 1-104 years referred for COVID-19 testing was performed in British Columbia, Canada. Participants who tested negative or positive for COVID-19 were matched by age and biological sex. Viral and host gene expression was measured by quantitative reverse-transcriptase polymerase chain reaction. Bivariate analysis and multiple linear regression were performed to understand the role of nasopharyngealACE2expression in SARS-CoV-2 infection. TheACE2gene was targeted to measure expression of transmembrane and soluble transcripts.FindingsAnalysis shows no association between age and nasopharyngealACE2expression in those who tested negative for COVID-19 (P=0·092). Mean expression of transmembrane (P=1·2e-4), solubleACE2(PTMPRSS2(PACE2positively correlated with SARS-CoV-2 RNA viral load (PACE2negatively correlated (PTMPRSS2 (P=0·694). Multivariable analysis showed that the greatest viral RNA loads were observed in participants with high transmembraneACE2expression (B=0·886, 95%CI:[0·596 to 1·18]), while expression of solubleACE2may protect against high viral RNA load in the upper respiratory tract (B= −0·0990, 95%CI:[−0·176 to −0·0224]).InterpretationNasopharyngealACE2expression plays a dual, contrasting role in SARS-CoV-2 infection of the upper respiratory tract. TransmembraneACE2positively correlates, while solubleACE2negatively correlates with viral RNA load after adjusting for age, biological sex and expression of TMPRSS2.FundingThis project (COV-55) was funded by Genome British Columbia as part of their COVID-19 rapid response initiative.

Background In 2008, British Columbia (BC) implemented a school-based quadrivalent human papillomavirus (HPV-4) immunization program for girls born in 1994 or later. In 2015, an expanded clinic-based program included men who report sex with men (MSM) born in 1989 or later. To evaluate the impacts of HPV-4 programs on anogenital warts (AGWs), diagnosis rates were measured among women who report sex with men (WSM), men who report sex with women (MSW), and MSM. Methods Diagnoses of AGW were ascertained from 16 sexually transmitted infection clinics. Rates were calculated as new AGW diagnoses over person-years (py) at risk and stratified by age group, calendar period, and birth cohort. Adjusted relative rates (aRR) were estimated using multivariable Poisson regression. Results There were 204,832 clinic visits by 85,158 individuals: 28,366 (33%) WSM, 35,688 (42%) MSW, and 14,534 (17%) MSM. After adjusting for age and period, AGW rates in the 1994-1996 birth cohort decreased by 56% overall (1.21 vs. 2.72 cases/100 py; aRR, 0.44; 95% confidence interval [CI], 0.34-0.59), 65% among WSM (0.97 vs. 2.77 cases/100 py; aRR, 0.35; 95% CI, 0.22-0.57), 58% among MSW (1.60 vs. 3.78 cases/100 py; aRR, 0.42; 95% CI, 0.28-0.65), and 41% among MSM (1.14 vs. 1.19 cases/100 py; aRR, 0.59; 95% CI, 0.38-0.91) versus the 1991-1993 birth cohort. Conclusions The HPV-4 programs had significant impacts on lowering AGW rates in BC. The greatest decrease was among WSM eligible for the school-based program, followed by birth cohorts of men who likely have sex with HPV-4 eligible women. The smallest decrease among MSM may reflect the later introduction of the clinic-based program.

During a public health overdose emergency driven by fentanyl in British Columbia (BC), Canada, a parallel increase in concurrent use of methamphetamines may be contributing to the risk of overdose. Concurrent use refers to the use of stimulants and opioids one after the other, or together. Describing substance use practices and elucidating correlates of concurrent use can inform harm reduction service provision and prevent overdose events.This cross-sectional study analyzed the 2019 Harm Reduction Client Survey administered at 22 harm reduction sites across BC and sampled individuals aged 19 and older. Bivariable and multivariable logistic regression models identified correlates of concurrent use of stimulants and opioids in the last three days.The study sample was composed of 574 individuals who used stimulants and/or opioids, among whom 307 (53.5%) reported concurrent use. Compared with individuals who used stimulants and/or opioids separately, the odds of concurrent use were significantly increased (OR=2.74, 95%CI 1.71-4.51) while the adjusted odds were increased (aOR=1.79, 95%CI 0.98-3.34) among individuals who experienced an opioid overdose. Further, the adjusted odds of concurrent use decreased with every one-year increase in age (aOR=0.97, 95%CI 0.95-0.99), among individuals with paid work (aOR=0.58, 95%CI 0.33-0.99), and stable housing (aOR=0.61, 95%CI 0.37-1.02). The adjusted odds of concurrent use increased among individuals who used drugs daily (aOR=3.78, 95%CI 2.28-6.40), used tobacco (aOR=2.03, 95%CI 1.09-3.87), used benzodiazepines (aOR=3.72, 95%CI 1.76-8.41), owned a naloxone kit (aOR=1.94, 95%CI 1.15-3.31), used observed consumption sites (aOR=2.51, 95%CI 1.57-4.07), and were prescribed opioid agonist therapy (aOR=2.92, 95%CI 1.81-4.77).Individuals who used stimulants and opioids concurrently tend to be younger, without paid work or housing. They were engaged in harm reduction and treatment services, yet used illicit drugs with unknown concentration daily. Improving access to age-appropriate services and expanding the availability of both legal and regulated stimulants and opioids may further reduce harms of concurrent use.

CONTEXT MD/PhD programmes provide structured paths for physician-scientist training. However, considerable proportions of graduates of these programmes do not pursue careers in research consistent with their training. OBJECTIVES We sought to identify factors associated with sustained involvement in research after completion of all postgraduate training. METHODS Anonymised data from a national survey of Canadian MD/PhD programme graduates who had completed all physician-scientist training (n = 70) were analysed. Multivariable logistic regression was used to measure the associations between characteristics of graduates and five indicators of sustained research involvement following postgraduate training: (i) protected research time in the current appointment; (ii) percentage of time dedicated to research; (iii) planned future involvement in research; (iv) role as a principal investigator on a recent funded project, and (v) receipt of funding from a federal granting agency since graduation. RESULTS The majority of graduates were significantly involved in research on the basis of at least one outcome. Completion of a research fellowship, number of first-authored or co-authored manuscripts published during MD/PhD training, and duration of MD/PhD training were positively associated with continued research involvement. Completion of a Masters degree prior to MD/PhD training, female gender, debt greater than CAD$50 000 at completion of training, and pursuit of a clinical specialty other than internal medicine, paediatrics, neurology, pathology and the surgical specialties were negatively associated with sustained research involvement. CONCLUSIONS Most MD/PhD programme graduates remain significantly involved in research, but this involvement often does not correspond to traditional physician-scientist roles, in which a majority of time is dedicated to research. To minimise loss of investment in physician-scientist training, MD/PhD programmes should prioritise research productivity during training and the pursuit of additional research training during residency, and policymakers should establish stable sources of funding to reduce debt among graduates. Our data suggest further study is warranted to identify interventions to reduce attrition among female MD/PhD programme graduates.

BACKGROUND Spatial clusters of syphilis have been observed within several jurisdictions globally; however, the degree to which they are predicted by the spatial distributions of gay, bisexual, and other men who have sex with men (GBM) and testing remains unknown. We sought to describe the spatial-temporal epidemiology of infectious syphilis and identify associations between neighborhood-level factors and rates of syphilis, in British Columbia, Canada. METHODS We used ArcGIS to map infectious syphilis cases among men (2005 to 2016), SaTScan to detect areas with significantly elevated rates of syphilis, and spatial regression to identify associations between neighborhood-level factors and rates of syphilis. RESULTS Five clusters were identified: a core in downtown Vancouver (incidence rate ratio [IRR], 18.0; 2007-2016), 2 clusters adjacent to the core (IRR, 3.3; 2012-2016; and IRR, 2.2; 2013-2016), 1 cluster east of Vancouver (IRR, 2.1; 2013-2016), and 1 cluster in Victoria (IRR, 4.3; 2015-2016). Epidemic curves were synchronized across cluster and noncluster regions. Neighborhood-level GBM population estimates and testing rates were both associated with syphilis rates; however, the spatial distribution of syphilis was not fully explained by either of these factors. CONCLUSIONS We identified two novel ecologic correlates of the spatial distribution of infectious syphilis-density of GBM and rates of syphilis testing-and found that these factors partially, though not entirely, explained the spatial distribution of clusters. Residual spatial autocorrelation suggests that greater syphilis testing coverage may be needed and low-barrier GBM-affirming testing should be expanded to regions outside the core.

Background In 2008, British Columbia (BC), Canada, implemented a provincially-funded school-based quadrivalent human papillomavirus (HPV-4) vaccine program for girls born in 1994 or later. In 2015, the program was expanded to include men who have sex with men (MSM) born in 1989 or later. To determine the impact of the vaccine on anogenital warts (AGW), diagnosis rates were measured among women who have sex with men (WSM), men who have sex with women (MSW), and MSM. Methods AGW diagnoses were ascertained from an electronic medical record system used at 16 geographically dispersed high volume sexually transmitted infection (STI) clinics across BC. Clients aged 14–46 years, born between 1970–1999 who accessed services from 2000–2017 were included. Rates were calculated as new AGW diagnoses over person-years (PY) at risk, and stratified by age group, period of clinic visit, and birth cohort. Age-period-cohort Poisson modeling produced adjusted relative rates (aRR). Results There were 204,832 clinic visits by 85,158 unique individuals: 28,366 (33%) WSM, 35,688 (42%) MSW and 14,534 (17%) MSM. After adjusting for age and period, overall AGW rates were 56% lower among the birth cohorts 1994–1996 compared to 1991–1993 (1.21 vs 2.72 cases/100PY, aRR: 0.44, 95%CI: 0.34, 0.59). AGW rates in the 1994–1996 cohort were 65% lower among WSM (0.97 vs 2.77 cases/100PY, aRR: 0.35, 95%CI: 0.22, 0.57), 58% lower among MSW (1.60 vs 3.78 cases/100PY, aRR: 0.42, 95%CI: 0.28, 0.65) and 41% lower among MSM (1.14 vs 1.19 cases/100PY, aRR: 0.59, 95%CI: 0.38, 0.91) versus the 1991–1993 cohort. Conclusion The HPV-4 vaccine program had a significant impact on lowering AGW rates in BC, specifically among WSM born after 1994 who had access to the school-based program, and MSW born after 1994 likely from herd immunity. A smaller reduction in AGW rates among MSM may reflect delayed access to provincially-funded HPV-4 vaccine. Disclosure No significant relationships.

Background The incidence of syphilis has been increasing worldwide in the last 20 years, and disproportionately affecting people living with HIV. Additionally, several jurisdictions have reported increasing incidence of ocular syphilis (OS). If untreated or treatment is delayed, OS can lead to permanent blindness. We assessed characteristics of OS cases in British Columbia (BC), and sought to identify risk factors that may be associated with OS diagnosis, including factors related to HIV co-infection (e.g. CD4 count. viral load). Methods This case-control study matched OS cases to syphilis controls (1:4) diagnosed in BC between January 2010 – March 2018. Demographic and clinical data were extracted from the provincial sexually transmitted infection database and analyzed using the chi-squared test. A multivariate logistic model was developed to assess factors associated with OS. Results Between 2010–2018, 5681 syphilis cases were diagnosed in BC, including 61 (1.1%) diagnosed with OS. The proportion of syphilis cases with OS increased from 0.48% in 2010 to 2.99% in 2018 (P≤0.05). Among OS cases, median age was 47 years, 88.5% were male and the most common ophthalmologic diagnosis was panuveitis (44.3%). At the time of syphilis diagnosis, 50.8% of OS cases were HIV-positive compared to 25.8% of controls (P≤0.001). Among individuals with HIV co-infection, OS cases had higher viral loads (42.9% vs 79.7% were suppressed; P≤0.001) and lower median CD4 counts (470 vs 615 cells/mm3;P≤0.05) than controls. Factors associated with OS were primary/secondary stage of syphilis (adjusted odds ratio [aOR] 4.06; 95% confidence interval [CI] 1.52–10.8), early latent stage of syphilis (aOR 3.71; 95%CI 1.39–9.95), and HIV-positive serostatus (aOR 2.49; 95%CI 1.27–4.88). Conclusion OS incidence and proportion increased over the study period in BC. These findings highlight the importance of vigilance for OS, particularly those in the early stages of syphilis and those living with HIV, to avoid diagnostic and treatment delays. Disclosure No significant relationships.

BACKGROUND: Angiotensin converting enzyme 2 (ACE2) protein serves as the host receptor for SARS-CoV-2, with a critical role in viral infection. We aim to understand population level variation of nasopharyngeal ACE2 transcription in people tested for COVID-19 and the relationship between ACE2 transcription and SARS-CoV-2 viral load, while adjusting for expression of: (i) the complementary protease, Transmembrane serine protease 2 (TMPRSS2), (ii) soluble ACE2, (iii) age, and (iv) biological sex. The ACE2 gene was targeted to measure expression of transmembrane and soluble transcripts. METHODS: A cross-sectional study of n = 424 "participants" aged 1-104 years referred for COVID-19 testing was performed in British Columbia, Canada. Patients who tested positive for COVID-19 were matched by age and biological sex to patients who tested negative. Viral load and host gene expression were assessed by quantitative reverse-transcriptase polymerase chain reaction. Bivariate analysis and multiple linear regression were performed to understand the role of nasopharyngeal ACE2 expression in SARS-CoV-2 infection. FINDINGS: Analysis showed no association between age and nasopharyngeal ACE2 transcription in those who tested negative for COVID-19 (P = 0•092). Mean relative transcription of transmembrane (P = 0•00012) and soluble (P

Introduction The incidence of infectious syphilis (primary, secondary, or early latent) has increased in British Columbia (BC). Identifying core groups at risk for syphilis can inform public health programming. We assessed the odds of syphilis infection among individuals with repeat Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (GC) infections in this population-based analysis. Methods Surveillance records for all BC residents diagnosed with ≥2 CT (CT reinfection) or ≥2 GC (GC reinfection) or ≥2 infections including CT and GC (CT/GC reinfection) from 1/1/2006 to 12/31/2015 were linked with all infectious syphilis cases from the same time period. Logistic regression models were used to measure the odds of acquiring syphilis with greater number of CT and/or GC reinfections, adjusted for age, ethnicity and population (e.g., men who have sex with men). Results Of 1 03 115 people having a CT infection, 11 458 (11.1%) had CT reinfection; of 14 713 people with a GC infection, 1514 (10.3%) had GC reinfection. Overall, 4989 individuals had CT/GC reinfection. Among these three re-infection groups (CT, GC, CT/GC), 80.9%/72.9%/63% had 2 infections, 14.4%/15.9%/19.5% had 3 infections, 3.2%/6.1%/8.9% had 4 infections and 1.6%/5.1%/8.6% had 5+ infections. Of all syphilis cases in BC, 7.4%/9.4%/12.3% were diagnosed among individuals with CT reinfection, GC reinfection and CT/GC reinfection. The odds of syphilis increased with greater number of infections, which persisted after adjustment in all three groups. Among the group with CT/GC reinfection, individuals with 3, 4 and 5+ infections had increased odds of syphilis compared to individuals with 2 infections (OR=2.2 (95%CI 1.6, 3.0), OR=2.5 (95%CI 1.7, 3.6) and OR=4.1 (95%CI 3.0, 5.7) respectively). Conclusion Increasing number of CT and/or GC reinfections is strongly and independently associated with a syphilis diagnosis. Targeting public health interventions to a core group of individuals with CT/GC reinfections may be an effective syphilis prevention strategy.

Although MD/PhD programs require considerable commitment on behalf of students and learning institutions, they serve as an integral means of training future physician-scientists; individuals who engage in translational medicine. As attrition from these programs has longstanding effects on the community of translational medicine and comes at substantial cost to MD/PhD programs, we aimed to identify determinants that were associated with satisfaction among MD/PhD graduates, a feature that might inform on limiting program attrition. Anonymized data from a national survey of 139 Canadian MD/PhD alumni was analyzed. Factor analysis was conducted to evaluate the reliability of three questions that measured satisfaction and logistic regression was used to assess the association of outcomes with 17 independent determinants. Eighty-one percent of graduates were satisfied with MD/PhD training. Factor analysis confirmed the reliability of the questions measuring satisfaction. Determinants of self-reported satisfaction with physician-scientist training included co-authorship of more than six manuscripts during MD/PhD training. Additionally, protected research time at the place of current appointment was strongly associated with agreement that MD/PhD training had helped career progression. Demographic variables were not associated with any satisfaction indicator. Taken together, the majority of Canadian MD/PhD graduates are satisfied with their physician-scientist training. Project collaboration leading to co-authorships and protected research time were strongly associated with training satisfaction among graduates. If the value of collaboration can be realized among current and future physician-scientist trainees who are dissatisfied with their training, this might ultimately reduce program attrition.