Mobile supervised consumption services in Rural British Columbia: lessons learned.

BACKGROUND: In 2016, a public health emergency was declared in British Columbia due to an unprecedented number of illicit drug overdose deaths. Injection drug use was implicated in approximately one third of overdose deaths. An innovative delivery model using mobile supervised consumption services (SCS) was piloted in a rural health authority in BC with the goals of preventing overdose deaths, reducing public drug use, and connecting clients to health services. METHODS: Two mobile SCS created from retrofitted recreational vehicles were used to serve the populations of two mid-sized cities: Kelowna and Kamloops. Service utilization was tracked, and surveys and interviews were completed to capture clients', service providers', and community stakeholders' attitudes towards the mobile SCS. RESULTS: Over 90% of surveyed clients reported positive experiences in terms of access to services and physical safety of the mobile SCS. However, hours of operation met the needs of less than half of clients. Service providers were generally dissatisfied with the size of the space on the mobile SCS, noting constraints in the ability to respond to overdose events and meaningfully engage with clients in private conversations. Additional challenges included frequent operational interruptions as well as poor temperature control inside the mobile units. Winter weather conditions resulted in cancelled shifts and disrupted services. Among community members, there was variable support of the mobile SCS. CONCLUSIONS: Overall, the mobile SCS were a viable alternative to a permanent site but presented many challenges that undermined the continuity and quality of the service. A mobile site may be best suited to temporarily provide services while bridging towards a permanent location. A needs assessment should guide the stop locations, hours of operation, and scope of services provided. Finally, the importance of community engagement for successful implementation should not be overlooked.

Drug checking at an electronic dance music festival during the public health overdose emergency in British Columbia.

SETTING: Shambhala is a 5-day electronic dance music (EDM) festival held in rural British Columbia that annually hosts between 15,000 and 18,000 people on a 500-acre ranch. The AIDS Network Outreach & Support Society (ANKORS) has provided harm reduction services throughout the duration of the festival since 2003, including point-of-care drug checking, which allows real-time testing of illicit substances to assess their composition. Drug checking results are provided directly to clients and displayed in aggregate on a screen for all attendees to see. INTERVENTION: In 2017, ANKORS added fentanyl checking to their repertoire of drug checking technologies for festivalgoers. Volunteers used a brief survey to collect information on what clients expected the samples to contain. Volunteers carried out drug checks and subsequently logged test results. ANKORS provided an amnesty bin at the tent for clients who chose to discard their substances. OUTCOMES: Of the 2683 surveys, 2387 included data on both the client's belief and the actual test result. Clients were more likely to discard when the test result differed from their belief (5.16%) than when their belief was confirmed (0.69%). Discarding increased to 15.54% when the test could not clearly identify a substance and to 30.77% if the client did not have a prior belief of the substance. Of 1971 samples tested for fentanyl, 31 tested positive and 16.13% of clients discarded compared to 2.63% in the negative group. IMPLICATIONS: Drug checking services appeal to festivalgoers who, when faced with uncertainty, may discard their substances. This innovative harm reduction service allows for a personalized risk discussion, potentially reaching others via word-of-mouth and early warning systems.

Expanding harm reduction to include fentanyl urine testing: results from a pilot in rural British Columbia.

BACKGROUND: Harm reduction has been at the forefront of the response to the opioid overdose public health emergency in British Columbia (BC). The unprecedented number of opioid overdose deaths in the province calls for an expansion of harm reduction services. The purpose of this study was to determine the acceptability of a fentanyl urine drug test among people who use drugs (PWUD) and explore whether testing introduced any changes in participants' attitudes and behaviors towards their drug use. METHODS: A pilot of fentanyl urine testing was implemented in partnership with an outreach harm reduction program in rural BC. Participants were PWUD who had consumed within the last 3 days prior to the test. Participants filled out a semi-structured questionnaire at the time of the test and were invited for a follow-up interview 2 to 4 weeks after the test. Urine samples were tested with BNTX Rapid Response™ fentanyl urine strip test at a detection level of 20 ng/ml norfentanyl. RESULTS: Of the 24 participants who completed the urine test and first interview, 4 had a positive fentanyl urine test. Fifteen clients completed the second questionnaire, 10 of whom reported introducing a behavior change after testing and the remaining 5 indicated being already engaged in harm reduction practices. All four clients who tested positive completed the second questionnaire; all but one indicated adopting behaviors towards overdose prevention. DISCUSSION: Fentanyl urine testing appealed to illicit opioid users and may have contributed to adopting behaviors towards safer drug use. A relationship of trust between tester and client seemed important for clients who expressed concerns with privacy of the urine test results. Post-consumption urine testing could complement the use of pre-consumption drug checking in the context of harm reduction services.

Enhancing access to cervical and colorectal cancer screening for women in rural and remote northern Alberta: a pilot study.

BACKGROUND: Women in rural and remote northern Alberta access breast cancer screening through a mobile mammogram program (Screen Test). The Enhanced Access to Cervical and Colorectal Cancer Screening (EACS) project was a 2-year pilot that aimed to integrate cervical and colorectal cancer screening with the Screen Test program. This study compares cervical and colorectal cancer screening uptake among women screened through the pilot (Screen Test-EACS) versus Screen Test. METHODS: Screen Test-EACS was offered between 2013 and 2015 in selected rural and remote sites, with a focus on hard-to-reach women living in First Nations, Métis and Hutterite communities. Participation in cervical and colorectal cancer screening was analyzed for Screen Test and Screen Test-EACS participants 6 weeks before clients received their mammogram and then again 3 months after. RESULTS: A total of 8390 and 1312 women participated in Screen Test and Screen Test-EACS, respectively. Screen Test-EACS significantly increased uptake of cervical (10.1% v. 27.5%) and colorectal (10.9% v. 22.5%) cancer screening, increasing the prevalence of women up to date with screening from 52.5% to 62.9% for cervical cancer screening and from 37.3% to 48.7% for colorectal cancer screening. INTERPRETATION: Screen Test-EACS increased participation in and the overall prevalence of cervical and colorectal cancer screening among hard-to-reach clients in northern Alberta, probably through removal of barriers to access and increased awareness. Further research should focus on balancing the benefits of increased participation with the costs and potential risks of over-screening.

Screening History in 313 Cases of Invasive Cancer: A Retrospective Review of Cervical Cancer Screening in Alberta, Canada.

OBJECTIVE: To examine the screening history of invasive cervical cancer (ICC) cases in Alberta, Canada to identify areas for improvement of the population-based cervical cancer screening program. METHODS: Retrospective review of ICC cases diagnosed in 2 cities in Alberta between 2007 and 2012. Cancer morphology and staging were elicited from the Alberta Cancer Registry; cancer screening history and Pap test results were extracted from the Provincial Cervical Cancer Screening database. Women were classified as adequately screened, underscreened, and unscreened depending on time from last screening Pap test to diagnosis. RESULTS: Of the 280 cases that occurred in women eligible for screening, 125 (44.6%) were adequately screened, 18 (6.4%) were underscreened, and 137 (49%) were unscreened. Among the adequately screened, 71 (56.8%) had normal Pap test results, but 48 (38%) had less than 3 previous Pap tests (p = .003). Cancer stages I to II were diagnosed in 48.8% and 44.1% of adequately screened and unscreened women and cancer stages III to IV in 30.6% and 66.1% in each group, respectively (p = .0058). Squamous cell carcinoma (SCC) was diagnosed in 189 women (67.5%). The proportion of SCCs was similar in adequately screened and unscreened women. CONCLUSIONS: The proportion of SCCs and advanced stages of ICC seems to be decreased. The results of quality improvement initiatives such as enhanced surveillance of high-grade Pap test results and histology-cytology correlation will be monitored and are expected to result in better outcomes for adequately screened women.

Integrated Cancer Screening Performance Indicators: A Systematic Review.

Cancer screening guidelines recommend that women over 50 years regularly be screened for breast, cervical and colorectal cancers. Population-based screening programs use performance indicators to monitor uptake for each type of cancer screening, but integrated measures of adherence across multiple screenings are rarely reported. Integrated measures of adherence that combine the three cancers cannot be inferred from measures of screening uptake of each cancer alone; nevertheless, they can help discern the proportion of women who, having received one or two types of screening, may be more amenable to receiving one additional screen, compared to those who haven't had any screening and may experience barriers to access screening such as distance, language, and so on. The focus of our search was to identify indicators of participation in the three cancers, therefore our search strategy included synonyms of integrated screening, cervical, breast and colorectal cancer screening. Additionally, we limited our search to studies published between 2000 and 2015, written in English, and pertaining to females over 50 years of age. The following databases were searched: MEDLINE, EMBASE, EBM Reviews, PubMed, PubMed Central, CINAHL, and Nursing Reference Center, as well as grey literature resources. Of the 78 initially retrieved articles, only 7 reported summary measures of screening across the three cancers. Overall, adherence to cervical, breast and colorectal cancer screening ranged from around 8% to 43%. Our review confirms that reports of screening adherence across breast, cervical and colorectal cancers are rare. This is surprising, as integrated cancer screening measures can provide additional insight into the needs of the target population that can help craft strategies to improve adherence to all three screenings.

Childhood vision screening in Canada: public health evidence and practice.

OBJECTIVES: Best practice guidelines recommend vision testing in children 3 to 5 years of age for the prevention of amblyopia; however, universal vision screening is controversial. In Canada, amblyopia screening can be the responsibility of physicians, optometrists, and/or Public Health. We review the evidence underlying preschool vision screening for amblyopia using an Evidence-based Public Health (EBPH) approach, and consider implications for the Public Health provision of universal screening programs for amblyopia in Canadian jurisdictions in light of present practices. METHODS: We searched the literature to address each major screening criterion (disease, test, treatment, program requirements) necessary to support preschool vision screening for amblyopia. We also reappraised papers cited in two systematic reviews related to the impact of vision screening. The Chief Medical Officer of Health of each province/territory was sent a short survey asking whether there currently was a Public Health preschool vision screening program in place and if so, for specifics about the program. RESULTS: An EBPH approach to the literature with respect to the criteria for screening and available intervention studies support amblyopia screening by Public Health. There is a public health divide in amblyopia screening practice in Canada; while some provinces maintain organized programs, others have chosen to delegate the task to other professionals, without a concurrent surveillance function to monitor disparities in uptake. CONCLUSIONS: Amblyopia deserves attention from Public Health. Efforts should be made to maintain existing programs, and provinces without organized screening programs should reconsider their role in the prevention of inequities with regard to preventable blindness in Canadian children.

Inner retina remodeling in a mouse model of stargardt-like macular dystrophy (STGD3).

Purpose. To investigate the impact of progressive age-related photoreceptor degeneration on retinal integrity in Stargardt-like macular dystrophy (STGD3). Methods. The structural design of the inner retina of the ELOVL4 transgenic mouse model of STGD3 was compared with that of age-matched littermate wild-type (WT) mice from 1 to 24 months of age by using immunohistofluorescence and confocal microscopy and by relying on antibodies against cell-type-specific markers, synapse-associated proteins, and neurotransmitters. Results. Müller cell reactivity occurred at the earliest age studied, before photoreceptor loss. This finding is perhaps not surprising, considering the cell's ubiquitous roles in retina homeostasis. Second-order neurons displayed salient morphologic changes as a function of photoreceptoral input loss. Age-related sprouting of dendritic fibers from rod bipolar and horizontal cells into the ONL did not occur. In contrast, with the loss of photoreceptor sensory input, these second-order neurons progressively bore fewer synapses. After rod loss, the few remaining cones showed abnormal opsin expression, revealing tortuous branched axons. After complete ONL loss (beyond 18 months of age), localized areas of extreme retinal disruptions were observed in the central retina. RPE cell invasion, dense networks of strongly reactive Müller cell processes, and invagination of axons and blood vessels were distinctive features of these regions. In addition, otherwise unaffected cholinergic amacrine cells displayed severe perturbation of their cell bodies and synaptic plexi in these areas. Conclusions. Remodeling in ELOVL4 transgenic mice follows a pattern similar to that reported after other types of hereditary retinopathies in animals and humans, pointing to a potentially common pathophysiologic mechanism.

Incomplete penetrance and phenotypic variability characterize Gdf6-attributable oculo-skeletal phenotypes.

Proteins of the bone morphogenetic protein (BMP) family are known to have a role in ocular and skeletal development; however, because of their widespread expression and functional redundancy, less progress has been made identifying the roles of individual BMPs in human disease. We identified seven heterozygous mutations in growth differentiation factor 6 (GDF6), a member of the BMP family, in patients with both ocular and vertebral anomalies, characterized their effects with a SOX9-reporter assay and western analysis, and demonstrated comparable phenotypes in model organisms with reduced Gdf6 function. We observed a spectrum of ocular and skeletal anomalies in morphant zebrafish, the latter encompassing defective tail formation and altered expression of somite markers noggin1 and noggin2. Gdf6(+/-) mice exhibited variable ocular phenotypes compatible with phenotypes observed in patients and zebrafish. Key differences evident between patients and animal models included pleiotropic effects, variable expressivity and incomplete penetrance. These data establish the important role of this determinant in ocular and vertebral development, demonstrate the complex genetic inheritance of these phenotypes, and further understanding of BMP function and its contributions to human disease.

The electroretinogram (ERG) of a diurnal cone-rich laboratory rodent, the Nile grass rat (Arvicanthis niloticus).

The most widespread models to study blindness, rats and mice, have retinas containing less than 3% cones. The diurnal rodent Arvicanthis niloticus retina has around 35% cones. Using ERG recordings, we studied retina function in this species. Several features differed from that reported in rats and mice: (a) fivefold larger photopic a-wave amplitudes; (b) photopic hill effect in Nile grass rats only; and (c) flicker amplitude plateau between 5 to 35 Hz with fusion beyond 60 Hz in Nile grass rats only. We conclude that A. niloticus might complement rats and mice for studying retinal function and pathologies involving cones.

Retinal anatomy and visual performance in a diurnal cone-rich laboratory rodent, the Nile grass rat (Arvicanthis niloticus).

Unlike laboratory rats and mice, muridae of the Arvicanthis family (A. ansorgei and A. niloticus) are adapted to functioning best in daylight. To date, they have been used as experimental models mainly in studies of circadian rhythms. However, recent work aimed at optimizing photoreceptor-directed gene delivery vectors (Khani et al. [2007] Invest Ophthalmol Vis Sci 48:3954-3961) suggests their potential usefulness for studying retinal pathologies and therapies. In the present study we analyzed the retinal anatomy and visual performance of the Nile grass rat (A. niloticus) using immunohistofluorescence and the optokinetic response (OKR). We found that approximately 35-40% of photoreceptors are cones; that many neural features of the inner retina are similar to those in other diurnal mammals; and that spatial acuity, measured by the OKR, is more than two times that of the usual laboratory rodents. These observations are consistent with the known diurnal habits of this animal, and further support its pertinence as a complementary model for studies of structure, function, and pathology in cone-rich mammalian retinae.

Modified Ca(v)1.4 expression in the Cacna1f(nob2) mouse due to alternative splicing of an ETn inserted in exon 2.

The Cacna1f(nob2) mouse is reported to be a naturally occurring null mutation for the Ca(v)1.4 calcium channel gene and the phenotype of this mouse is not identical to that of the targeted gene knockout model. We found two mRNA species in the Cacna1f(nob2) mouse: approximately 90% of the mRNA represents a transcript with an in-frame stop codon within exon 2 of CACNA1F, while approximately 10% of the mRNA represents a transcript in which alternative splicing within the ETn element has removed the stop codon. This latter mRNA codes for full length Ca(v)1.4 protein, detectable by Western blot analysis that is predicted to differ from wild type Ca(v)1.4 protein in a region of approximately 22 amino acids in the N-terminal portion of the protein. Electrophysiological analysis with either mouse Ca(v)1.4(wt) or Ca(v)1.4(nob2) cDNA revealed that the alternatively spliced protein does not differ from wild type with respect to activation and inactivation characteristics; however, while the wild type N-terminus interacted with filamin proteins in a biochemical pull-down experiment, the alternatively spliced N-terminus did not. The Cacna1f(nob2) mouse electroretinogram displayed reduced b-wave and oscillatory potential amplitudes, and the retina was morphologically disorganized, with substantial reduction in thickness of the outer plexiform layer and sprouting of bipolar cell dendrites ectopically into the outer nuclear layer. Nevertheless, the spatial contrast sensitivity (optokinetic response) of Cacna1f(nob2) mice was generally similar to that of wild type mice. These results suggest the Cacna1f(nob2) mouse is not a CACNA1F knockout model. Rather, alternative splicing within the ETn element can lead to full-length Ca(v)1.4 protein, albeit at reduced levels, and the functional Ca(v)1.4 mutant may be incapable of interacting with cytoskeletal filamin proteins. These changes, do not alter the ability of the Cacna1f(nob2) mouse to detect and follow moving sine-wave gratings compared to their wild type counterparts.

Blindness caused by deficiency in AE3 chloride/bicarbonate exchanger.

BACKGROUND: Vision is initiated by phototransduction in the outer retina by photoreceptors, whose high metabolic rate generates large CO2 loads. Inner retina cells then process the visual signal and CO2. The anion exchanger 3 gene (AE3/Slc4a3) encodes full-length AE3 (AE3fl) and cardiac AE3 (AE3c) isoforms, catalyzing plasma membrane Cl-/HCO3- exchange in Müller (AE3fl) and horizontal (AE3c) cells. AE3 thus maintains acid-balance by removing photoreceptor-generated CO2 waste. METHODOLOGY/PRINCIPAL FINDINGS: We report that Slc4a3-/- null mice have inner retina defects (electroretinogram b-wave reduction, optic nerve and retinal vessel anomalies). These pathologic features are common to most human vitreoretinal degenerations. Immunobloting analysis revealed that Na+/HCO3- co-transporter (NBC1), and carbonic anhydrase II and CAXIV, protein expression were elevated in Slc4a3-/- mouse retinas, suggesting compensation for loss of AE3. TUNEL staining showed increased numbers of apoptotic nuclei from 4-6 months of age, in Slc4a3-/- mice, indicating late onset photoreceptor death. CONCLUSIONS/SIGNIFICANCE: Identification of Slc4a3 as underlying a previously unrecognized cause of blindness suggests this gene as a new candidate for a subset of hereditary vitreoretinal retinal degeneration.