Self-injecting non-prescribed substances into vascular access devices: a case study of one health system's ongoing journey from clinical concern to practice and policy response.

BACKGROUND: Overdose-associated deaths and morbidity related to substance use is a global public health emergency with devastating social and economic costs. Complications of substance use are most pronounced among people who inject drugs (PWID), particularly infections, resulting in increased risk of hospitalization. PWID often require intravenous access for medical treatments such as antibiotics; however, vascular access may be limited due to the impacts of long-term self-venipuncture. While vascular access devices including peripherally inserted central catheters (PICCs) allow reliable and sustained routes of administration for indicated therapies, the use of PICCs among PWID presents unique challenges. The incidence and risks associated with self-injecting non-prescribed substances into vascular access devices (SIVAD) is one such concern for which there is limited evidence and absence of formal practice guidance. CASE PRESENTATION: We report the experience of a multidisciplinary team at a health organization in Vancouver, Canada, working to characterize the incidence, patient and healthcare provider perspectives, and overall impact of SIVAD. The case study of SIVAD begins with a patient's perspective, including patient rationale for SIVAD, understanding of risks and the varying responses given by healthcare providers following disclosure of SIVAD. Using the limited literature available on the subject, we summarize the intersection of SIVAD and substance use and outline known and anticipated health risks. The case study is further contextualized by experience from a Vancouver in-hospital Overdose Prevention Site (OPS), where 37% of all individual visits involve SIVAD. The case study concludes by describing the systematic process by which local clinical guidance for SIVAD harm reduction was developed with stakeholder engagement, medical ethics consultation, expert consensus guideline development and implementation with staff education and planned research evaluation. CONCLUSION: SIVAD is encountered with enough frequency in an urban healthcare setting in Vancouver, Canada, to warrant an organizational approach. This case study aims to enhance appreciation of SIVAD as a common and complex clinical issue with anticipated health risks. The authors conclude that using a harm reduction lens for SIVAD policy and research can provide benefit to clinicians and patients by offering a clear and a consistent healthcare response to this common issue.

Low awareness of risk mitigation prescribing in response to dual crises of COVID-19 and overdose deaths among people who use unregulated drugs in Vancouver, Canada.

BACKGROUND: When the novel coronavirus pandemic emerged in March 2020, many settings across Canada and the USA were already contending with an existing crisis of drug overdoses due to the toxic unregulated drug supply. In response, the Canadian province of British Columbia (BC) released innovative risk mitigation prescribing (RMP) guidelines for medical professionals to prescribe pharmaceutical alternatives to unregulated drugs in an effort to support the self-isolation of people who use unregulated drugs (PWUD) in preventing both SARS-CoV-2 virus infection and overdoses. We sought to assess the level of awareness of RMP and identify factors associated with this awareness among PWUD in Vancouver, BC. METHODS: Cross-sectional data were derived from participants enrolled in three community-recruited prospective cohort studies of PWUD in Vancouver, interviewed between July and November 2020. Multivariable logistic regression analysis was used to identify factors associated with awareness of RMP. RESULTS: Among 633 participants, 302 (47.7%) had heard of RMP. Of those 302 participants, 199 (65.9%) had never tried to access RMP services, ten (3.3%) made an unsuccessful attempt to access RMP, and 93 (30.8%) received RMP. In the multivariable analysis, participants who had awareness of RMP guidelines were more likely to self-identify as white (adjusted odds ratio [AOR] = 1.47; 95% confidence interval [CI]: 1.01, 2.13), to have completed secondary school education or higher (AOR = 1.67; 95% CI: 1.16, 2.39), to have used drugs at a supervised consumption or overdose prevention site in the past six months (AOR = 1.66; 95% CI: 1.10, 2.52), and to have received opioid agonist therapy as treatment for opioid use disorder in the past six months (AOR = 1.51; 95% CI: 1.02, 2.24). CONCLUSION: At least four months after the release of the guidelines, RMP was known to less than half of our study participants, warranting urgent educational efforts for PWUD, particularly among racialized groups and those who were not accessing other harm reduction services. Furthermore, the majority of participants who were aware of RMP guidelines had never tried to access the service, suggesting the need to improve perceived accessibility and knowledge of eligibility criteria.

Inability to access primary care clinics among people who inject drugs in a Canadian health care setting.

OBJECTIVE: To examine the prevalence and correlation of self-reported inability to access community primary care clinics among people who inject drugs (PWID). DESIGN: Self-report questionnaire data. SETTING: Vancouver, BC. PARTICIPANTS: Data were derived from 3 prospective cohort studies of PWID between 2013 and 2016. MAIN OUTCOME MEASURES: Multivariable generalized estimating equations were used to determine prevalence of and reasons for self-reported inability to access primary care, as well as factors associated with inability to access care. RESULTS: Of 1396 eligible participants, including 525 (37.6%) women, 209 (15.0%) persons were unable to access a primary care clinic at some point during the study period. In the multivariable analysis, factors independently associated with inability to access clinics included ever being diagnosed with a mental health disorder (adjusted odds ratio [AOR] = 1.63, 95% CI 1.14 to 2.35), dealing drugs (AOR = 1.60, 95% CI 1.15 to 2.22), using emergency services (AOR = 1.51, 95% CI 1.13 to 2.02), being female (AOR = 1.49, 95% CI 1.08 to 2.08), and testing positive for HIV (AOR = 0.47, 95% CI 0.30 to 0.72) (for all factors, P < .05). CONCLUSION: Specific exposures were linked to challenges in accessing primary care among the sample of PWID, even in a publicly funded health care setting. Notably, models designed for care of people with HIV appear to increase access to primary care among PWID. Further research is needed to determine how to effectively treat accompanying mental illness, how to provide women-centred services, and how to connect people with primary care who would likely otherwise go to the emergency department.

Rare, risky, recurrent: An enigmatic cutaneous polyp.

Myxofibrosarcomas (MFSs) are sarcomas most commonly seen in older patients. These are tumors of deep soft tissue seen in subcutaneous tissue and deep fascia, with frequent muscle involvement. These sarcomas are notorious for recurrences and progression to a higher grade with notable metastatic potential. They are very often under-diagnosed owing to their inherent morphological variability. A case of MFS is presented as a cutaneous, exophytic, polypoidal mass because of its rarity and importance of timely diagnosis, as under-diagnosis may lead to inadequate clearance of tumor, recurrences, metastases and increased mortality.

Risk mitigation guidance and safer supply prescribing among young people who use drugs in the context of COVID-19 and overdose emergencies.

Across North America, overlapping overdose and COVID-19 emergencies have had a substantial impact on young people who use drugs (YPWUD). New risk mitigation guidance (RMG) prescribing practices were introduced in British Columbia, Canada, in 2020 to allow people to decrease risk of overdose and withdrawal and better self-isolate. We examined how the prescribing of hydromorphone tablets specifically impacted YPWUD's substance use and care trajectories. Between April 2020 and July 2021, we conducted virtual interviews with 30 YPWUD who had accessed an RMG prescription of hydromorphone in the previous six months and 10 addiction medicine physicians working in Vancouver. A thematic analysis was conducted. YPWUD participants highlighted a disjuncture between RMG prescriptions and the safe supply of unadulterated substances such as fentanyl, underscoring that having access to the latter is critical to reducing their reliance on street-based drug markets and overdose-related risks. They described re-appropriating these prescriptions to meet their needs, stockpiling hydromorphone so that it could be used as an "emergency backup" when they were unable to procure unregulated, illicit opioids. In the context of entrenched poverty, hydromorphone was also used to generate income for the purchase of drugs and various necessities. For some YPWUD, hydromorphone prescriptions could be used alongside opioid agonist therapy (OAT) to reduce withdrawal and cravings and improve adherence to OAT. However, some physicians were wary of prescribing hydromorphone due to the lack of evidence for this new approach. Our findings underscore the importance of providing YPWUD with a safe supply of the substances they are actively using alongside a continuum of substance use treatment and care, and the need for both medical and community-based safe and safer supply models.

Impacts of the COVID-19 pandemic on enrollment in medications for opioid use disorder (MOUD) in Vancouver, Canada: An interrupted time series analysis.

BACKGROUND: In anticipation of COVID-19 related disruptions to opioid use disorder (OUD) care, new provincial and federal guidance for the management of OUD and risk mitigation guidance (RMG) for prescription of pharmaceutical opioids were introduced in British Columbia, Canada, in March 2020. This study evaluated the combined impacts of the COVID-19 pandemic and counteracting OUD policies on enrollment in medications for OUD (MOUD). METHODS: Using data from three cohorts of people with presumed OUD in Vancouver, we conducted an interrupted time series analysis to estimate the combined effects impact of the COVID-19 pandemic and counteracting OUD policies on the prevalence of enrollment in MOUD overall, as well as in individual MOUDs (methadone, buprenorphine/naloxone, slow-release oral morphine) between November 2018 and November 2021, controlling for pre-existing trends. In sub-analysis we considered RMG opioids together with MOUD. RESULTS: We included 760 participants with presumed OUD. In the post-COVID-19 period, MOUD and slow-release oral morphine prevalence rates showed an estimated immediate increase in level (+7.6%, 95% CI: 0.6%, 14.6% and 1.8%, 95% CI: 0.3%, 3.3%, respectively), followed by a decline in the monthly trend (-0.8% per month, 95% CI: -1.4%, -0.2% and -0.2% per month, 95% CI: -0.4, -0.1, respectively). There were no significant changes in the prevalence trends of enrollment in methadone, buprenorphine/naloxone, or when RMG opioids were considered together with MOUD. CONCLUSIONS: Despite immediate improvements in MOUD enrollment in the post-COVID-19 period, this beneficial trend reversed over time. RMG opioids appeared to have provided additional benefits to sustain retention in OUD care.

Correlates of nonfatal overdose among treatment-seeking individuals with non-heroin opioid use disorder: Findings from a pragmatic, pan-Canadian, randomized control trial.

INTRODUCTION: Misuse of prescription and synthetic opioids is a primary contributor to the escalating overdose crisis in North America. However, factors associated with nonfatal overdose (NFO) in this context are poorly understood. We examined individual and socio-structural level correlates of NFO among treatment-seeking adults with an opioid use disorder (OUD) not attributed to heroin (nonheroin opioid use disorder [NH-OUD]). METHODS: The study drew data from OPTIMA, a pan-Canadian, multicenter, pragmatic, two-arm randomized control trial comparing supervised methadone and flexible take-home dosing buprenorphine/naloxone models of care among adults with NH-OUD conducted between 2017 and 2020. We used bivariable and multivariable logistic regression to determine factors associated with a lifetime history of NFO among participants enrolled in the trial. RESULTS: Of 267 included participants, 154 (58%) reported a NFO in their lifetime, of whom 83 (55 %) had an NFO in the last 6 months. In multivariable analyses, positive urine drug test (UDT) for methamphetamine/amphetamine (Adjusted Odds Ratio [AOR] = 2.59; 95 % confidence interval [CI]: 1.17-5.80), positive UDT for fentanyl (AOR = 2.31; 95 % CI: 1.01-5.30), receiving income assistance (AOR = 2.17; 95 % CI: 1.18-4.09) and homelessness (AOR = 2.40; 95 % CI: 1.25-4.68) were positively associated with a lifetime history of NFO. CONCLUSIONS: We found a high prevalence of NFO history in treatment-seeking adults with NH-OUD, particularly among participants with certain drug use patterns and markers of socio-structural marginalization at the time of enrollment. Given the known impact of prior NFO on future harms, these findings highlight the need for comprehensive care approaches that address polysubstance use and social determinants of health to mitigate future overdose risk.

Diagnostic yield and repeat biopsies in rectal and nonrectal colorectal adenocarcinoma: Are we hedging on rectal biopsies?

Patients with rectal cancer undergo more repeat biopsies compared to those with nonrectal colon cancer prior to management. We investigated the factors driving the higher frequency of repeat biopsies in patients with rectal cancer. We compared clinicopathologic features of diagnostic and nondiagnostic (in regard to invasion) rectal (n = 64) and colonic (n = 57) biopsies from colorectal cancer patients and characterized corresponding resections. Despite similar diagnostic yield, repeat biopsy was more common in rectal carcinoma, especially in patients receiving neoadjuvant therapy (p < 0.05). The presence of desmoplasia (odds ratio 12.9, p < 0.05) was a strong predictor of making a diagnosis of invasion in both rectal and nonrectal colon cancer biopsies. Diagnostic biopsies had more desmoplasia, intramucosal carcinoma component and marked inflammation, and less low-grade dysplasia component (p < 0.05). Diagnostic yield of biopsy was higher for tumors with high-grade tumor budding, mucosal involvement by high-grade dysplasia/intramucosal carcinoma without low-grade dysplasia and diffuse surface desmoplasia irrespective of tumor location. Sample size, amount of benign tissue, appearance, and T stage did not affect diagnostic yield. Repeat biopsy of rectal cancer is primarily driven by management implications. Diagnostic yield in colorectal cancer biopsies is multifactorial and is not due to differing pathologists' diagnostic approach per tumor site. For rectal tumors, a multidisciplinary strategic approach is warranted to avoid repeat biopsy when unnecessary.

Supporting Self-isolation for COVID-19 With "Risk Mitigation" Prescribing and Housing Supports for People Who Use Drugs: A Case Report.

BACKGROUND: Self-isolation is critical in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. However, people who use drugs face significant barriers in adhering to the regulations. As a response, several supportive measures have been introduced in British Columbia, including temporary housing access and "risk mitigation" prescribing, in which health care providers prescribe pharmaceutical alternatives to the unregulated drug supply to prevent withdrawal and reduce overdose risk. CASE SUMMARY: We present a case of a 39-year-old male with a history of polysubstance use and frequent overdoses, who had tested positive for SARS-CoV-2 and was able to successfully self-isolate. "Risk mitigation" prescribing, supportive housing, and harm reduction services were initiated for his self-isolation and connection to community outreach teams for ongoing support. DISCUSSION: This case illustrates how "risk mitigation" prescribing supported patient's self-isolation, reduced his illicit drug use, and offered an opportunity for healthcare engagement. Access to safer alternatives to the toxic drug supply should continue beyond COVID-19 pandemic to address the persistent issues of contaminated drug supply and the overdose crisis in North America.

Challenges with buprenorphine inductions in the context of the fentanyl overdose crisis: A case series.

INTRODUCTION AND AIMS: North America is currently experiencing an epidemic of opioid overdose deaths, driven by the proliferation of fentanyl in the street drug market. Although buprenorphine/naloxone (BUP/NX) is an evidence-based, first-line opioid agonist for the management of opioid use disorder, a key challenge in its prescribing lies in the fact that it can precipitate opioid withdrawal during its initial induction process. At this time, there is minimal literature on the BUP/NX induction process in individuals who use illicit fentanyl regularly. DESIGN, METHODS AND RESULTS: A case series from a Vancouver, Canada addiction medicine clinic of three fentanyl-exposed patients who experienced unexpected, precipitated withdrawal when initiating BUP/NX. DISCUSSION AND CONCLUSION: These cases describe incidents of precipitated opioid withdrawal occurring after unusually long periods of fentanyl abstention. Although fentanyl is experienced as a short-acting opioid, the drug persists much longer in the body's peripheral tissues. Here, we highlight the new challenges fentanyl may pose to current BUP/NX induction strategies, and explore the possibility of a long-acting pharmacokinetic effect of fentanyl in the setting of repeated illicit use.

Histologic Findings and Tissue B-Cell Depletion in Endoscopic Mucosal Biopsy Specimens of the Gastrointestinal Tract After Treatment With Rituximab.

OBJECTIVES: Rituximab (RTX) is associated with variable adverse gastrointestinal (GI) events. However, the histologic correlate in affected patients is not well defined. METHODS: Patients (n = 93) who had received RTX and undergone endoscopic biopsies were identified. CD20 and PAX5 immunostains were performed on biopsy specimens showing inflammatory pathology (group A, 36 patients) and 35 of 57 noninflammatory biopsies (group B) that were taken within 1 year from the last RTX infusion. Histologic findings were correlated with tissue B-cell depletion (CD20/PAX5-/-). RESULTS: B cells were depleted in 12 (33%) of 36 group A biopsy specimens. After excluding biopsies taken more than 1 year from the last RTX infusion, the frequencies of tissue B-cell depletion were similar between group A (12/26; 46.2%) and group B (17/35; 48.6%) (P > .05). Also, the frequencies of inflammatory pathology were not statistically different whether B cells were depleted or not (P > .05). In group A with tissue B-cell depletion (n = 12), causality was indicated in two (17%) cases showing lymphocytic colitis pattern of injury (LCPI). CONCLUSIONS: In RTX-treated patients, tissue B-cell depletion does not appear to be the main cause of inflammatory pathology in the GI tract. A minor subset, however, develops histologic evidence of potential RTX-induced effect, notably in the form of LCPI.

Primary care embedded within permanent supportive housing for people who use substances: A qualitative study examining healthcare access in Vancouver, Canada.

Marginally housed people who use drugs and alcohol (PWUD/A) face barriers in accessing healthcare services, which may be improved by providing healthcare in housing settings. This case study examines the experiences of healthcare access amongst PWUD/A who live in a permanent supportive housing model in Vancouver, Canada. This model has an embedded multidisciplinary clinic providing in-reach services. Thirty participants were recruited via posters placed throughout the building and semi-structured qualitative interviews were conducted remotely. Interviews were conducted with participants who accessed onsite care regularly (n = 15) and those who do not (n = 15). Data were analysed to identify both a priori and emerging themes. Participants who accessed the onsite clinic reported benefiting from stigma-free care. Close proximity and convenience of drop-in appointments enabled participants to engage with healthcare services more consistently, though hours of operation and privacy concerns were barriers for others. Participants who did not use the onsite clinic highlighted the importance of continuity of care with their pre-existing primary care team, particularly if their clinic was in close geographic proximity. However, they also described utilising these services for urgent health needs or as an occasional alternative source of care. Shared perspectives across all participants emphasised the importance of low-barrier services, including medication delivery, convenience and positive therapeutic relationships. Our findings suggest that embedding access to primary care within supportive housing benefits PWUD/A who have previously encountered barriers to healthcare access. This model could be implemented to prevent utilisation of acute healthcare resources and improve health outcomes amongst PWUD/A.

PSMA Immunohistochemistry in Hepatic Neoplasms: A Promising Diagnostic Marker With Potential Theranostic Applications.

Accurate classification of well-differentiated hepatocellular neoplasms can be challenging especially in core biopsies. Prostate-specific membrane antigen (PSMA) has been shown to highlight tumor-associated neovasculature in many nonprostatic solid tumors including hepatocellular carcinoma (HCC). Archived 164 hepatectomies and explants with 68 HCCs, 31 hepatocellular adenoma (HA), 24 dysplastic nodules (DN), and 42 metastases were retrieved, and pathologic parameters were evaluated. Sensitivity, specificity, accuracy, positive, and negative predictive values for correct diagnosis of HCC were calculated for PSMA and CD34 immunostains in tissue sections and HCC tissue microarrays. PSMA positivity was defined as capillarized sinusoidal/tumor-associated vessel staining involving ≥5% of the tumor area. In all, 55/68 (80.9%) HCC and 37/42 (88.1%) of liver metastasis were PSMA positive. PSMA was negative in HA, DN, and background liver (100% specificity). CD34 had a 98.5% sensitivity but a 65.5% specificity in identifying HCC. PSMA sensitivity remained high in the HCC tissue microarray (89.7%). PSMA was more accurate than CD34 (95.5% vs. 69.7%) in distinguishing grade 1 HCC from HA and high-grade DN while retaining high sensitivity (80%). The degree of PSMA positivity in HCC was greater in older, male, and human immunodeficiency virus patients ( P <0.05). No associations were found between PSMA staining and other tumor parameters ( P >0.05). PSMA is a marker of neoangiogenesis with increased expression in both primary and metastatic hepatic malignancies. Neovascular PSMA expression is more specific and accurate than CD34 for differentiating HCC from benign and precursor hepatic lesions. Diagnostic and therapeutic utility of PSMA radioligands in malignant liver neoplasms warrant further clinical investigations.

Medical Detoxification for Nonopioid Substances Is Associated With Lower Likelihood of Subsequent Linkage to Substance Use Disorder Treatment.

BACKGROUND: Although factors associated with completion of medical detoxification treatment for substance use disorders (SUD) are well described, there is limited information on barriers and facilitators to subsequent linkage to SUD treatment in the community. This study aimed to evaluate correlates of successful linkage to community SUD treatment on discharge. METHODS: Data were drawn from 2 prospective cohorts of people who use unregulated drugs in Vancouver, Canada between December 2012 and May 2018. Multivariable generalized estimating equations were used to investigate factors associated with linkage to community SUD treatment in the 6-month period after attending detoxification treatment. RESULTS: Of the 264 detoxification treatment encounters contributed by 178 people who use unregulated drugs, these were most often (n = 104, 39%) related to polysubstance use, and the majority (n = 174, 66%) resulted in subsequent linkage to community treatment. In the multivariable analysis, compared to attending detoxification treatment for opioid use, attending detoxification treatment for stimulants (adjusted odds ratio [AOR] = 0.23, 95% confidence interval [CI] : 0.10-0.51) and alcohol (AOR = 0.17, 95% CI: 0.06-0.54) were associated with lower odds of subsequent linkage to community treatment. Conversely, later calendar year of detoxification treatment remained associated with higher odds (AOR = 1.23, 95% CI: 1.06-1.42). CONCLUSIONS: Only two-thirds of detoxification treatment encounters in Vancouver were subsequently linked to community SUD treatment, with those related to nonopioid substances being less likely. Findings suggest the need for tailored interventions for specific substances to improve linkage to SUD treatment in the community on discharge.

Inability to contact opioid agonist therapy prescribers during the COVID-19 pandemic in a Canadian setting: a cross-sectional analysis among people on opioid agonist therapy.

BACKGROUND: The COVID-19 pandemic and consequent public health response may have undermined key responses to the protracted drug poisoning crisis, including reduced access to opioid agonist therapy (OAT) among people with opioid use disorder. Our study objectives were to estimate the prevalence of and identify factors associated with inability to contact OAT prescribers when in need among people on OAT in a Canadian setting during the dual public health crises. METHODS: Survey data were collected from three prospective cohort studies of community-recruited people who use drugs between July and November 2020, in Vancouver, Canada. A multivariable logistic regression analysis was used to identify potential factors associated with inability to contact OAT prescribers among patients who accessed OAT in the past 6 months. RESULTS: Among 448 respondents who reported accessing OAT in the past 6 months, including 231 (54.9%) men, 85 (19.0%) reported having been unable to contact OAT prescribers when needed, whereas 268 (59.8%) reported being able to talk to their prescriber when needed, and 95 (21.2%) reported that they did not want to talk to their medication prescriber in the previous 6 months. Among those who reported inability to contact prescribers, 45 (53.6%) reported that their overall ability to contact prescribers decreased since the start of the pandemic. In multivariable analyses, factors independently associated with inability to talk to OAT prescribers included: chronic pain (Adjusted Odds Ratio [AOR] = 1.82; 95% Confidence Interval [CI] 1.02, 3.27), moderate to severe symptoms of depression or anxiety (AOR = 4.74; 95% CI 2.30, 9.76), inability to access health/social services (AOR = 2.66; 95% CI 1.41, 5.02), and inability to self-isolate or socially distance most or all of the time (AOR = 2.13; 95% CI 1.10, 4.14). CONCLUSIONS: Overall, approximately one fifth of the sample reported inability to contact their OAT prescribers when needed, and those people were more likely to have co-occurring vulnerabilities (i.e., co-morbidities, inability to access health/social services) and higher vulnerability to COVID-19. Interventions are needed to ensure optimal access to OAT and mitigate the deepening health inequities resulting from the COVID-19 pandemic and the escalating drug poisoning crisis.

Inflammation and tissue remodeling contribute to fibrogenesis in stricturing Crohn's disease: image processing and analysis study.

BACKGROUND: Inflammation and structural remodeling may contribute to fibrogenesis in Crohn's disease (CD). We quantified the immunoexpression of calretinin, CD34, and calprotectin as a surrogate for mucosal innervation, telocytes (interstitial cells playing a role in networking), and inflammation, respectively, and correlated them with bowel alterations in stricturing CD. METHODS: Primary resection specimens for ileal CD (n = 44, 31 stricturing CD, 13 inflammatory CD) were identified. Left-sided ulcerative colitis and trauma cases were used as controls. Proximal and distal margin and middle (diseased) sections were stained for calretinin, CD34, and calprotectin. Microscopic images were captured from the mucosa (calretinin), submucosa (calprotectin), and myenteric plexus (CD34), and the immunostaining was quantified using image processing and analysis. Bowel thickness at the corresponding sections were measured and correlated with the amount of immunoexpression. RESULTS: A total of 2,037 images were analyzed. In stricturing CD, submucosal alteration/thickening at the stricture site correlated with calprotectin staining and inversely correlated with calretinin staining at the proximal margin. Muscularis propria alteration/thickening at the stricture site correlated with mucosal calretinin staining at the proximal margin. Submucosal alteration/thickening at the proximal margin correlated with calretinin and CD34 staining at the proximal margin and inversely correlated with CD34 staining at the stricture site. Calretinin immunostaining at the distal margin was significantly higher in stricturing CD than the controls. CONCLUSIONS: Inflammation and tissue remodeling appear to contribute to fibrogenesis in stricturing CD. Increased mucosal calretinin immunostaining distal to the diseased segment could be helpful in diagnosing CD in the right clinical context.

"COVID just kind of opened a can of whoop-ass": The rapid growth of safer supply prescribing during the pandemic documented through an environmental scan of addiction and harm reduction services in Canada.

OBJECTIVES: In the context of the ongoing overdose crisis, a stark increase in toxic drug deaths from the unregulated street supply accompanied the onset of the COVID-19 pandemic. Injectable opioid agonist treatment (iOAT - hydromorphone or medical-grade heroin), tablet-based iOAT (TiOAT), and safer supply prescribing are emerging interventions used to address this crisis in Canada. Given rapid clinical guidance and policy change to enable their local adoption, our objectives were to describe the state of these interventions before the pandemic, and to document and explain changes in implementation during the early pandemic response (March-May 2020). METHODS: Surveys and interviews with healthcare providers comprised this mixed methods national environmental scan of iOAT, TiOAT, and safer supply across Canada at two time points. Quantitative data were summarized using descriptive statistics; interview data were coded and analyzed thematically. RESULTS: 103 sites in 6 Canadian provinces included 19 iOAT, 3 TiOAT and 21 safer supply sites on March 1, 2020; 60 new safer supply sites by May 1 represented a 285% increase. Most common substances were opioids, available at all sites; most common settings were addiction treatment programs and primary care clinics, and onsite pharmacies models. 79% of safer supply services were unfunded. Diversity in service delivery models demonstrated broad adaptability. Qualitative data reinforced the COVID-19 pandemic as the driving force behind scale-up. DISCUSSION: Data confirmed the capacity for rapid scale-up of flexible, community-based safer supply prescribing during dual public health emergencies. Geographical, client demographic, and funding gaps highlight the need to target barriers to implementation, service delivery and sustainability.