Generation of H7N9-Specific Human Polyclonal Antibodies from a Transchromosomic Goat (caprine) System

To address the unmet needs for human polyclonal antibodies both as therapeutics and diagnostic reagents, building upon our previously established transchromosomic (Tc) cattle platform, we report herein the development of a Tc goat system expressing human polyclonal antibodies in their sera. In the Tc goat system, a human artificial chromosome (HAC) comprising the entire human immunoglobulin (Ig) gene repertoire in the germline configuration was introduced into the genetic makeup of the domestic goat. We achieved this by transferring the HAC into goat fetal fibroblast cells followed by somatic cell nuclear transfer for Tc goat production. Gene and protein expression analyses in the peripheral blood mononuclear cells (PBMC) and the sera, respectively, of Tc caprine demonstrated the successful expression of human Ig genes and antibodies. Furthermore, immunization of Tc caprine with inactivated influenza A (H7N9) viruses followed by H7N9 Hemagglutinin 1 (HA1) boosting elicited human antibodies with high neutralizing activities against H7N9 viruses in vitro. As a small ungulate, Tc caprine offers the advantages of low cost and quick establishment of herds, therefore complementing the Tc cattle platform in responses to a range of medical needs and diagnostic applications where small volumes of human antibody products are needed

Internationally trained pharmacists in Great Britain: what do registration data tell us about their recruitment?

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It's powerful to gather : a community-driven study of drug users' and illicit drinkers' priorities for harm reduction and health promotion in British Columbia, Canada

It is essential that the autonomy and dignity of people who use illicit substances be respected by meaningfully involving them in research into their needs and priorities. This dissertation reports on two projects in which substance users were involved in planning and conducting qualitative research in British Columbia, Canada. In the first phase of the research, a province-wide series of 17 workshops, facilitated by drug users, was held to identify health and harm reduction priorities for this population. I found that drug users in British Columbia identified clear priorities to improve their well-being: improving interactions with health professionals, promoting access to a range of housing options, improving treatment by police, ensuring harm reduction best practices are followed everywhere, improving social assistance, supporting drug users' organizations, and engaging new and existing allies. These were based on the values of collectivity, activity, freedom from surveillance, and accountability. An unexpected finding of this research was identifying a need and opportunity for drug users to collaborate with illicit drinkers (defined as people who consume non-beverage alcohol (e.g. mouthwash) and people who consume beverage alcohol in highly criminalized ways (e.g. homeless drinkers)) based on their shared priorities, values, and polysubstance use. In response to this conclusion, the second phase of this research involved a series of 14 town hall meetings with illicit drinkers in Vancouver’s Downtown Eastside to research their perceptions of the harms they face from illicit drinking, the strategies they currently use to reduce these harms, and their ideas for additional harm reduction initiatives. These meetings were planned and facilitated with a steering committee of drug users and illicit drinkers. I found that the harms illicit drinkers experience and some of the strategies they suggest (particularly safe spaces and managed alcohol programs) can usefully be interpreted as examples of structural, everyday, and symbolic violence. This work has led to several positive outcomes for drug users and illicit drinkers, including deeper involvement of substance users in planning provincial harm reduction services and the formation of an activist group for illicit drinkers.Medicine, Faculty ofPopulation and Public Health (SPPH), School ofGraduat

Environmental justice in the therapeutic inner city

Vancouver’s Downtown Eastside (DTES) has long been characterized as Canada’s skid row within public narratives that raise concerns about communicable diseases, open drug use, survival sex work, and homelessness. This stigmatizing gaze has bolstered a deficit-oriented philosophy that emphasizes measures to mitigate these threats, ostensibly by erasing the moral and environmental depravity from the landscape. However, such measures threaten to further marginalize DTES residents by perpetuating public sentiments of fear and disgust toward the inner city. In this paper, we challenge this orientation by reporting the results of a research process in which DTES residents chronicled their impressions of the neighbourhood. Our findings reveal a paradoxical therapeutic response to environmental injustice in the inner city, one that enables society’s most marginalized people to find support, solidarity, and acceptance in their everyday struggles to survive, even thrive, amidst the structural and physical violence of the urban margins.Medicine, Faculty ofNon UBCPopulation and Public Health (SPPH), School ofReviewedFacultyGraduat

Naloxone urban legends and the opioid crisis: what is the role of public health?

As the overdose crisis in North America continues to deepen, public health leaders find themselves responding to sensational media stories, many of which carry forms and themes that mark them as urban legends. This article analyzes one set of media accounts – stories of misuse of naloxone, an opioid overdose antidote distributed to people who use drugs – through the lens of social science scholarship on urban legends. We suggest that these stories have met a public need to feel a sense of safety in uncertain times, but function to reinforce societal views of people who use drugs as undeserving of support and resources. Our field has a duty to speak out in favour of evidence-based programs that support the health of people who use drugs, but the optimal communication strategies are not always clear. Drawing attention to the functions and consequences of urban legends can help frame public health communication in a way that responds to needs without reinforcing prejudices, with application beyond naloxone to the other urban legends that continue to emerge in response to this crisis.Medicine, Faculty ofNon UBCPopulation and Public Health (SPPH), School ofReviewedFacult

Toxicology and prescribed medication histories among people experiencing fatal illicit drug overdose in British Columbia, Canada.

BACKGROUND: Since 2015, illicit drug overdose has been one of British Columbia’s most pressing public health issues. Our objective was to assess prescription history in the context of postmortem toxicology among people who had a fatal illicit drug overdose in BC. METHODS: Toxicology results from drug overdose deaths involving 1 or more illicit drugs, as identified by the BC Coroners Service in 2015–2017, were linked to the prescription drug histories of individuals as recorded in BC’s PharmaNet database for a descriptive analysis. Substances identified in toxicology were considered prescribed if the individual had an active dispensation for a matching medication within 60 days before overdose. RESULTS: There were 2872 deaths from illicit drug toxicity during the study period; 1789 (62.3%) were closed cases with toxicology results available. In 85.5% of cases, 1 or more opioids were found to be relevant to death. Prescribed opioids in the absence of nonprescribed opioids were detected in only 2.0% of cases, and 6.7% had a combination of prescribed and nonprescribed opioids. Among those with 1 or more nonprescribed opioids, 78.5% had fentanyl or fentanyl analogues detected. Medications used in opioid agonist therapy (methadone and buprenorphine) were found to be relevant to death in 7.4% of cases, with methadone (130 cases) much more common than buprenorphine (< 5 cases). Stimulants were detected in 70.6% of cases. INTERPRETATION: Our data show a high prevalence of nonprescribed fentanyl and stimulants, and a low prevalence of prescribed opioids detected on toxicology in people who died from illicit drug overdose. These results suggest that strategies to address the current overdose crisis in Canada must do much more than target deprescribing of opioids

A qualitative study of the perceived effects of blue lights in washrooms on people who use injection drugs

Background: Blue lights are sometimes placed in public washrooms to discourage injection drug use. Their effectiveness has been questioned and concerns raised that they are harmful but formal research on the issue is limited to a single study. We gathered perceptions of people who use injection drugs on the effects of blue lights with the aim of informing harm reduction practice. Methods: We interviewed 18 people in two Canadian cities who currently or previously used injection drugs to better understand their perceptions of the rationale for and consequences of blue lights in public washrooms. Results: Participants described a preference for private places to use injection drugs, but explained that the need for an immediate solution would often override other considerations. While public washrooms were in many cases not preferred, their accessibility and relative privacy appear to make them reasonable compromises in situations involving urgent injecting. Participants understood the aim of blue lights to be to deter drug use. The majority had attempted to inject in a blue-lit washroom. While there was general agreement that blue lights do make injecting more difficult, a small number of participants were entirely undeterred by them, and half would use a blue-lit washroom if they needed somewhere to inject urgently. Participants perceived that, by making veins less visible, blue lights make injecting more dangerous. By dispersing public injection drug use to places where it is more visible, they also make it more stigmatizing. Despite recognizing these harms, more than half of the participants were not opposed to the continued use of blue lights. Conclusions: Blue lights are unlikely to deter injection drugs use in public washrooms, and may increase drug use-related harms. Despite recognizing these negative effects, people who use injection drugs may be reluctant to advocate against their use. We attempt to reconcile this apparent contradiction by interpreting blue lights as a form of symbolic violence and suggest a parallel with other emancipatory movements for inspiration in advocating against this and other oppressive interventions.Medicine, Faculty ofNon UBCMedicine, Department ofReviewedFacult

Improving Health Literacy for Positive Patient Outcomes

Health literacy is defined as the degree to which individuals have the capacity to obtain, process, and understand basic health information and services needed to make appropriate health decisions (Health.gov, 2017). Unfortunately, a large portion of the American population has low literacy skills coupled with low socioeconomic status, resulting in an increase of individuals experiencing poor health outcomes. The professional nurse plays an integral role in educating patients and their family members. Students will report on evidence based practice related to assessment of health literacy skills and the teaching interventions provided to patients to improve their health literacy and promote positive outcomes

Discontinuation and tapering of prescribed opioids and risk of overdose among people on long-term opioid therapy for pain with and without opioid use disorder in British Columbia, Canada: A retrospective cohort study

Background The overdose crisis in North America has prompted system-level efforts to restrict opioid prescribing for chronic pain. However, little is known about how discontinuing or tapering prescribed opioids for chronic pain shapes overdose risk, including possible differential effects among people with and without concurrent opioid use disorder (OUD). We examined associations between discontinuation and tapering of prescribed opioids and risk of overdose among people on long-term opioid therapy for pain, stratified by diagnosed OUD and prescribed opioid agonist therapy (OAT) status. Methods and findings For this retrospective cohort study, we used a 20% random sample of residents in the provincial health insurance client roster in British Columbia (BC), Canada, contained in the BC Provincial Overdose Cohort. The study sample included persons aged 14 to 74 years on long-term opioid therapy for pain (≥90 days with ≥90% of days on therapy) between October 2014 and June 2018 (n = 14,037). At baseline, 7,256 (51.7%) persons were female, the median age was 55 years (quartile 1–3: 47–63), 227 (1.6%) persons had been diagnosed with OUD (in the past 3 years) and recently (i.e., in the past 90 days) been prescribed OAT, and 483 (3.4%) had been diagnosed with OUD but not recently prescribed OAT. The median follow-up duration per person was 3.7 years (quartile 1–3: 2.6–4.0). Marginal structural Cox regression with inverse probability of treatment weighting (IPTW) was used to estimate the effect of prescribed opioid treatment for pain status (discontinuation versus tapered therapy versus continued therapy [reference]) on risk of overdose (fatal or nonfatal), stratified by the following groups: people without diagnosed OUD, people with diagnosed OUD receiving OAT, and people with diagnosed OUD not receiving OAT. In marginal structural models with IPTW adjusted for a range of demographic, prescription, comorbidity, and social-structural exposures, discontinuing opioids (i.e., ≥7-day gap[s] in therapy) was associated with increased overdose risk among people without OUD (adjusted hazard ratio [AHR] = 1.44; 95% confidence interval [CI] 1.12, 1.83; p = 0.004), people with OUD not receiving OAT (AHR = 3.18; 95% CI 1.87, 5.40; p Conclusions Discontinuing prescribed opioids was associated with increased overdose risk, particularly among people with OUD. Prescribed opioid tapering was associated with reduced overdose risk among people with OUD not receiving OAT. These findings highlight the need to avoid abrupt discontinuation of opioids for pain. Enhanced guidance is needed to support prescribers in implementing opioid therapy tapering strategies with consideration of OUD and OAT status. In a retrospective cohort study from Canada, Dr Mary Kennedy and colleagues explore the effect of discontinuation and tapering of prescribed opioids on risk of overdose among people on long-term opioid therapy for pain with and without opioid use disorder. Author summary Why was this study done? In Canada and the United States, a rise in opioid-related morbidity and mortality has prompted system-level efforts to restrict opioid prescribing for chronic pain. Guidelines implemented in Canada and the United States have recommended tapering prescribed opioids for pain to the lowest effective dose, potentially discontinuing therapy, among people receiving opioid therapy for chronic pain when risks outweigh benefits. Although there is emerging evidence to suggest that deprescribing opioid therapy for chronic pain may increase risk of opioid-related harms, most existing studies have focused on non-representative subpopulations. To our knowledge, no studies to date have examined whether the effects of discontinuing and tapering opioid therapy for pain on overdose risk might differ among people with and without concurrent opioid use disorder. What did the researchers do and find? Drawing on administrative data linked at the individual level for a random sample of residents registered in the provincial health insurance client roster in British Columbia, Canada, we identified 14,037 persons prescribed long-term opioid therapy for pain between October 2014 and June 2018. We examined associations between discontinuation and tapering of prescribed opioid therapy for pain (versus continued treatment) and risk of overdose, stratified by whether patients had been diagnosed with opioid use disorder and recently prescribed opioid agonist therapy. We found that discontinuing opioid therapy for pain was associated with increased overdose risk among people without opioid use disorder (adjusted hazard ratio [AHR] = 1.44; 95% confidence interval [CI] 1.12, 1.83; p = 0.004). However, stronger associations were observed among people with opioid use disorder, including those not receiving opioid agonist therapy (AHR = 3.18; 95% CI 1.87, 5.40; p What do these findings mean? Abrupt discontinuation of prescribed opioid treatment for pain is contraindicated given its association with increased risk of overdose. Enhanced guidance is needed to support healthcare providers in implementing safe and effective strategies for tapering opioid treatment for pain that are tailored to the unique needs of individual patients, with particular consideration of opioid use disorder and prescribed opioid agonist therapy status