Motivations for concurrent use of uppers and downers among people who access harm reduction services in British Columbia, Canada: findings from the 2019 Harm Reduction Client Survey.

INTRODUCTION: An 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. OBJECTIVES: We 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 PARTICIPANTS: The 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. RESULTS: Of 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. CONCLUSIONS: The 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.

Correlates of concurrent use of stimulants and opioids among people who access harm reduction services in British Columbia, Canada: Findings from the 2019 Harm Reduction Client Survey.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Population-Level Outcomes of Partner Notification Among Gay, Bisexual, and Other Men Who Report Sex With Men Diagnosed With Infectious Syphilis in British Columbia, Canada.

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. χ2 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 [SD], 5.5 [5.2] days). Among patients, 87.7% (568/648) discussed PN with PHNs and 49.5% (281/568) named at least 1 notifiable partner, for a total of 1094 partners (mean [SD], 3.9 [5.5] partners/patient). Compared with PH-initiated PN, patient-initiated PN resulted in a greater proportion of partners notified (70.1% [573/817] vs. 89.8% [211/235]; P = 1.88 × 10-9), but there was no difference in the proportion of partners tested and/or treated (90.2% [517/573] vs. 86.7% [183/211]; P = 0.203), and diagnosed (12.8% [66/517] vs. 16.4% [30/183]; P > 0.271). CONCLUSIONS: Public health- 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.

The contrasting role of nasopharyngeal angiotensin converting enzyme 2 (ACE2) transcription in SARS-CoV-2 infection: A cross-sectional study of people tested for COVID-19 in British Columbia, Canada.

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<0•0001) ACE2 isoforms, as well as TMPRSS2 (P<0•0001) was higher in COVID-19-negative participants than COVID--19 positive ones, yielding a negative correlation between targeted host gene expression and positive COVID-19 diagnosis. In bivariate analysis of COVID-19-positive participants, transcription of transmembrane ACE2 positively correlated with SARS-CoV-2 viral RNA load (B = 0•49, R2=0•14, P<0•0001), transcription of soluble ACE2 negatively correlated (B= -0•85, R2= 0•26, P<0•0001), and no correlation was found with TMPRSS2 transcription (B= -0•042, R2=<0•10, P = 0•69). Multivariable analysis showed that the greatest viral RNA loads were observed in participants with high transmembrane ACE2 transcription (Β= 0•89, 95%CI: [0•59 to 1•18]), while transcription of the soluble isoform appears to protect against high viral RNA load in the upper respiratory tract (Β= -0•099, 95%CI: [-0•18 to -0•022]). INTERPRETATION: Nasopharyngeal ACE2 transcription plays a dual, contrasting role in SARS-CoV-2 infection of the upper respiratory tract. Transcription of the transmembrane ACE2 isoform positively correlates, while transcription of the soluble isoform negatively correlates with viral RNA load after adjusting for age, biological sex, and transcription of TMPRSS2. FUNDING: This project (COV-55) was funded by Genome British Columbia as part of their COVID-19 rapid response initiative.

Impacts of Human Papillomavirus Immunization Programs on Rates of Anogenital Warts in British Columbia, Canada, 2000 to 2017.

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.

Predictors of sustained research involvement among MD/PhD programme graduates.

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.

Incidence and Natural Progression of Neurogenic Shock after Traumatic Spinal Cord Injury.

Neurogenic shock, a distributive type of circulatory shock after spinal cord injury (SCI), results in profound hypotension. The consequent hemodynamic instability complicates clinical management, delays surgical intervention, and impacts neurological outcome. Moreover, the reported incidence of this condition varies significantly. We establish the true incidence of neurogenic shock by comparing the most common clinical definitions used to diagnose the condition. Further, we characterize the acute progression and recovery of neurogenic shock. Daily blood pressure, heart rate, and fluid management as well as vasopressor therapy and neurologic status were collected over 30 days from 84 adults admitted to our tertiary trauma center after cervical (n = 56) and thoracic (n = 28) SCI. We found that the reported incidence of neurogenic shock varied greatly depending on which clinical definition was applied. By using a novel combination of hemodynamic and laboratory criteria to define neurogenic shock, the calculated incidence (29% cervical SCI) in our sample most appropriately reflects the true incidence, finding that hypovolemia was the primary factor responsible for the inconsistency in incidence reports between studies. In addition, we found a characteristic decline in blood pressure after the first week post-injury and that fluid management is not currently an integral aspect of clinical management (all persons were treated at a net fluid intake ≤ zero). The results demonstrate the need for accurate identification of neurogenic shock through consistent and appropriate criteria, which is not only important from a clinical point of view, but also in establishing accurate epidemiology to responsibly allocate resources to its management.

Cross-sectional-derived determinants of satisfaction with physician-scientist training among Canadian MD/PhD graduates.

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.