Integrated supervised consumption services and hepatitis C testing and treatment among people who inject drugs in Toronto, Canada: A cross-sectional analysis.

Despite the availability of publicly funded hepatitis C (HCV) treatment in Canada, treatment gaps persist, particularly among people who inject drugs. We estimate correlates of HCV care cascade engagement (testing, diagnosis, and treatment) among people who inject drugs in Toronto, Canada and examine the effect of accessing differing supervised consumption service (SCS) models on self-reported HCV testing and treatment. This is a cross-sectional baseline analysis of 701 people who inject drugs surveyed in the Toronto, Ontario integrated Supervised Injection Services (OiSIS-Toronto) study between November 2018 and March 2020. We examine correlates of self-reported HCV care cascade outcomes including SCS model, demographic, socio-structural, drug use, and harm reduction characteristics. Overall, 647 participants (92%) reported ever receiving HCV testing, of whom 336 (52%) had been diagnosed with HCV. Among participants who reported ever being diagnosed with HCV, 281 (84%) reported chronic HCV, of whom 130 (46%) reported HCV treatment uptake and 151 (54%) remained untreated. Compared to those with no SCS use, participants who had ever injected at an integrated SCS model with co-located HCV care had greater prevalence of both ever receiving HCV testing (adjusted prevalence ratio [aPR]: 1.12, 95% confidence interval [CI]: 1.02-1.24) and ever receiving HCV treatment (aPR: 1.67, 95% CI: 1.04-2.69). Over half of participants diagnosed with chronic HCV reported remaining untreated. Our findings suggest that integrated SCS models with co-located HCV care represent key strategies for linkage to HCV care, but that more is needed to support scale-up.

Service utilization patterns and characteristics among clients of integrated supervised consumption sites in Toronto, Canada.

INTRODUCTION: Supervised consumption services (SCS), intended to reduce morbidity and mortality among people who inject drugs, have been implemented in a variety of delivery models. We describe and compare access to and uptake of co-located and external services among clients accessing harm reduction-embedded (HR-embedded) and community health center-embedded (CHC-embedded) SCS models. METHODS: Cross-sectional baseline data were collected between November 2018 and March 2020 as part of a cohort of people who inject drugs in Toronto, Canada designed to evaluate one HR-embedded and two CHC-embedded SCS. This analysis was restricted to clients who reported accessing these SCS more than once in the previous 6 months. Participants were classified as HR-embedded or CHC-embedded SCS clients based on self-reported usage patterns. Client characteristics, as well as access to onsite services and referral and uptake of external services, were compared by SCS model. RESULTS: Among 469 SCS clients, 305 (65.0%) primarily used HR-embedded SCS and 164 (35.0%) primarily used CHC-embedded SCS. Compared to clients accessing CHC-embedded SCS, clients accessing HR-embedded SCS were somewhat younger (37.6 vs. 41.4, p < 0.001), more likely to report fentanyl as their primary injected drug (62.6% vs. 42.7%, p < 0.001), and visited SCS more often (49.5% vs. 25.6% ≥ daily, p < 0.001). HR-embedded SCS clients were more likely to access harm reduction services onsite compared to CHC-embedded SCS clients (94.8% vs. 89.6%, p = 0.04), while CHC-embedded SCS clients were more likely to access non-harm reduction services onsite (57.3% vs. 26.6%, p < 0.001). For external services, HR-embedded SCS clients were more likely to receive a referral (p = 0.03) but less likely to report referral uptake (p = 0.009). CONCLUSIONS: Clients accessing HR-embedded and CHC-embedded SCS were largely demographically similar but had different drug and SCS use patterns, with CHC-embedded SCS clients using the site less frequently. While clients of CHC-embedded SCS reported greater access to ancillary health services onsite, external service use remained moderate overall, underscoring the importance of co-location and support for clients with system navigation. Importantly, lack of capacity in services across the system may impact ability of staff to make referrals and/or the ability of clients to take up a referral.

The Ontario Integrated Supervised Injection Services Cohort Study of People Who Inject Drugs in Toronto, Canada (OiSIS-Toronto): Cohort Profile.

The Ontario Integrated Supervised Injection Services cohort in Toronto, Canada (OiSIS-Toronto) is an open prospective cohort of people who inject drugs (PWID). OiSIS-Toronto was established to evaluate the impacts of supervised consumption services (SCS) integrated within three community health agencies on health status and service use. The cohort includes PWID who do and do not use SCS, recruited via self-referral, snowball sampling, and community/street outreach. From 5 November 2018 to 19 March 2020, we enrolled 701 eligible PWID aged 18+ who lived in Toronto. Participants complete interviewer-administered questionnaires at baseline and semi-annually thereafter and are asked to consent to linkages with provincial healthcare administrative databases (90.2% consented; of whom 82.4% were successfully linked) and SCS client databases. At baseline, 86.5% of participants (64.0% cisgender men, median ([IQR] age= 39 [33-49]) had used SCS in the previous 6 months, of whom most (69.7%) used SCS for <75% of their injections. A majority (56.8%) injected daily, and approximately half (48.0%) reported fentanyl as their most frequently injected drug. As of 23 April 2021, 291 (41.5%) participants had returned for follow-up. Administrative and self-report data are being used to (1) evaluate the impact of integrated SCS on healthcare use, uptake of community health agency services, and health outcomes; (2) identify barriers and facilitators to SCS use; and (3) identify potential enhancements to SCS delivery. Nested sub-studies include evaluation of "safer opioid supply" programs and impacts of COVID-19.

Supervised consumption service use and recent non-fatal overdose among people who inject drugs in Toronto, Canada.

BACKGROUND: Aiming to reducing overdose mortality, over 40 supervised drug consumption services (SCS) presently operate in Canada. Arguments against SCS include the potential for increased non-fatal overdoses mediated by risk compensation. This study estimates associations between SCS use and recent non-fatal overdose among people who inject drugs (PWID). METHODS: We analyzed cross-sectional baseline data collected between November 2018 and March 2020 from a cohort of adult PWID in Toronto, Canada. Recent non-fatal overdose was self-reported over the previous six months. The primary exposure was frequency of SCS use, self-reported as the proportion of injections performed at an SCS (all or most [75-100%], some [26-74%], few [≤25%], or none) in the previous six months. The prevalence of recent overdose was compared between all unique pairs of groups based on their frequency of SCS use and expressed as covariate-adjusted prevalence ratios (PR) estimated using modified Poisson regression. RESULTS: Among 701 PWID (median [IQR] age, 40 [33 to 49]; 64.3% cisgender men; 56.8% injecting daily), most reported SCS use (all/most, 26.2%; some, 30.9%; few, 29.4%) versus no use (13.5%), with 38.6% reporting a recent overdose. From adjusted regression analyses, more frequent SCS use was not statistically significantly associated with overdose when compared to either no SCS use or less frequent use. Associations between SCS use frequency and overdose were notably smaller among SCS clients compared to associations between SCS clients and non-users (e.g., all/most versus none: PR, 1.43 [95% CI, 0.93 to 2.21]; all/most versus some: PR, 0.94 [95% CI, 0.75 to 1.17]; all/most versus few: PR, 1.15 [95% CI, 0.89 to 1.48]). CONCLUSION: Findings did not indicate statistically significant associations between SCS use frequency and recent non-fatal overdose, particularly among SCS clients who may be more comparable. Nevertheless, overdose was common, underscoring the need to prevent non-fatal overdose and associated morbidity.

Seeing the whole elephant - How lobstermen's local ecological knowledge can inform fisheries management.

Lobstermen in Southern New England come from a longstanding intergenerational fishing tradition. Their local ecological knowledge (LEK) on the American lobster, Homarus americanus can be an important source of information for management. This paper examines lobstermen's LEK as it relates to stock assessment and the overlap to science based ecological knowledge (SEK). Although in recent years, using vent-less trap assessments and conducting young of the year surveys, has set the stage for more cooperative research, in our opinion, lobstermen's LEK remains underutilized in fisheries management. There has been a steady decline in the lobster stocks over the years, raising concerns regarding fisheries management. For this reason, we turn to lobstermen's knowledge as an important source that could inform fisheries management. Using a semi-structured approach, the stakeholders' LEK and open discussions were recorded during three meetings where lobstermen participated with managers and scientists. LEK was transcribed and categorized and matched to the corresponding SEK described in the literature. Results generally found that the lobstermen's LEK corresponded with the best available SEK. LEK is compatible with an ecosystem view of the fishery that integrates the complexities of interacting systems. The lobstermen explained that they viewed their fishing grounds as "managed landscapes", areas used productively, maintained and protected by them. These results are a starting point to broaden the base of the knowledge used in fisheries management enabling us to see the whole picture. Topics of LEK and SEK convergence are promising common ground, while topics where lobstermen and managers' views differ, can serve as points of entry to enable research and cooperative management. Both can be the basis for cooperative hypothesis testing.

Acute Bone Pain: An Analysis of Symptom Management Interventions After Administration of Granulocyte-Colony-Stimulating Factors for Myelosuppression.

BACKGROUND: The administration of granulocyte-colony-stimulating factors (G-CSFs) has proven to be essential in increasing the body's immune system following treatment with chemotherapy; however, many patients have reported varying levels of acute bone pain after receiving G-CSFs. OBJECTIVES: The purpose of this study was to assess the use of pharmacologic and nonpharmacologic interventions to manage acute bone pain following G-CSF administration. METHODS: A descriptive, cross-sectional survey was administered to hospitalized patients who received G-CSFs during a four-month period to evaluate the perceived effectiveness of interventions in reducing pain. FINDINGS: The findings of this study suggest that patients employ pharmacologic and nonpharmacologic interventions for pain management, but results are inconsistent and often inadequate. Nonpharmacologic interventions received higher scores for consistency and perceived effectiveness.

Acute calcific periarthritis secondary to calcium hydroxyapatite crystal deposition in the wrist: a case report.

Acute calcific periarthritis (ACP) is an unusual cause of monoarticular pain characterised by the deposition of calcium hydroxyapatite in the peri-articular and intra-articular tissues. Although the most commonly affected joint is the shoulder, other joints may be involved, including the wrist. This case report describes a 57-year-old female presenting with wrist pain and swelling associated with amorphous calcification overlying the lunate. The patient improved with the use of non-steroidal anti-inflammatory drugs and splinting. Clinician awareness of the clinical presentation and radiographic features of ACP is important to reduce unnecessary invasive diagnostic procedures such as joint aspiration.

Priorities and recommended actions for how researchers, practitioners, policy makers, and the affected community can work together to improve access to hepatitis C care for people who use drugs.

It is estimated that 6.1 million people with recent injecting drug use (PWID) are living with hepatitis C virus (HCV). Although HCV-related morbidity and mortality among PWID continues to increase, the advent of direct acting antiviral (DAA) HCV regimens with cure rates >95% provides an opportunity to reverse the rising burden of disease. Additionally, given evidence that opioid substitution therapy and high-coverage needle and syringe programs can reduce HCV incidence by up to 80%, there is an opportunity to reduce HCV transmission with increased coverage of harm reduction services. However, there are significant patient, provider, health system, structural, and societal barriers that impede access to HCV prevention and care for PWID. The International Network on Hepatitis in Substance Users (INHSU), in collaboration with the Australasian Society for HIV, Viral Hepatitis, Sexual Health Medicine (ASHM), Harm Reduction International, the Canadian Network on Hepatitis C, Canadian Research Initiative in Substance Misuse, the National Viral Hepatitis Roundtable, Médecins du Monde and CATIE, held a roundtable discussion prior to the Harm Reduction Conference in Montreal, Canada on 13th May 2017 to discuss how to improve HCV prevention and care for PWID. Over 100 international researchers, practitioners, policy makers, advocates, and affected community members came together to discuss shared priorities for action, develop actionable next steps and to create partnerships to enable application of priorities. This paper highlights the key priority areas identified by participants including: enhancing global coverage of harm reduction services; addressing punitive drug policies; ensuring access to affordable HCV diagnostics and treatment; improving the evidence-base for HCV prevention, testing, linkage to care and treatment; implementing integrated HCV programs; advancing peer-based models of HCV care; and tackling social determinants of health inequalities for PWID. This paper also highlights the recommended actions for each priority identified by the participants from this roundtable.

Comparing fishers' and scientific estimates of size at maturity and maximum body size as indicators for overfishing.

We tested whether fishers' local ecological knowledge (LEK) of two fish life-history parameters, size at maturity (SAM) at maximum body size (MS), was comparable to scientific estimates (SEK) of the same parameters, and whether LEK influenced fishers' perceptions of sustainability. Local ecological knowledge was documented for 82 fishers from a small-scale fishery in Samaná Bay, Dominican Republic, whereas SEK was compiled from the scientific literature. Size at maturity estimates derived from LEK and SEK overlapped for most of the 15 commonly harvested species (10 of 15). In contrast, fishers' maximum size estimates were usually lower than (eight species), or overlapped with (five species) scientific estimates. Fishers' size-based estimates of catch composition indicate greater potential for overfishing than estimates based on SEK. Fishers' estimates of size at capture relative to size at maturity suggest routine inclusion of juveniles in the catch (9 of 15 species), and fishers' estimates suggest that harvested fish are substantially smaller than maximum body size for most species (11 of 15 species). Scientific estimates also suggest that harvested fish are generally smaller than maximum body size (13 of 15), but suggest that the catch is dominated by adults for most species (9 of 15 species), and that juveniles are present in the catch for fewer species (6 of 15). Most Samaná fishers characterized the current state of their fishery as poor (73%) and as having changed for the worse over the past 20 yr (60%). Fishers stated that concern about overfishing, catching small fish, and catching immature fish contributed to these perceptions, indicating a possible influence of catch-size composition on their perceptions. Future work should test this link more explicitly because we found no evidence that the minority of fishers with more positive perceptions of their fishery reported systematically different estimates of catch-size composition than those with the more negative majority view. Although fishers' and scientific estimates of size at maturity and maximum size parameters sometimes differed, the fact that fishers make routine quantitative assessments of maturity and body size suggests potential for future collaborative monitoring efforts to generate estimates usable by scientists and meaningful to fishers.

Genomic Scans across Three Eucalypts Suggest that Adaptation to Aridity is a Genome-Wide Phenomenon.

Widespread species spanning strong environmental (e.g., climatic) gradients frequently display morphological and physiological adaptations to local conditions. Some adaptations are common to different species that occupy similar environments. However, the genomic architecture underlying such convergent traits may not be the same between species. Using genomic data from previous studies of three widespread eucalypt species that grow along rainfall gradients in southern Australia, our probabilistic approach provides evidence that adaptation to aridity is a genome-wide phenomenon, likely to involve multiple and diverse genes, gene families and regulatory regions that affect a multitude of complex genetic and biochemical processes.

Taking knowledge for health the extra mile: participatory evaluation of a mobile phone intervention for community health workers in Malawi.

In Malawi, where the majority of the population resides in rural areas, community health workers (CHWs) are the first, and often only, providers of health services. An assessment of health information needs, however, found that these frontline workers often lacked essential health information. A pilot project, implemented in 2 rural districts of Malawi between 2010 and 2011, introduced a mobile phone system to strengthen knowledge exchange within networks of CHWs and district staff. To evaluate the mobile phone intervention, a participatory evaluation method called Net-Map was used, an approach built on traditional social network analysis. Together, CHWs and district personnel discussed information needs and gaps and the roles of different actors in their information networks. They then used drawings and 3-dimensional objects to create baseline and endline maps showing the linkages and levels of influence among members of the information network. Net-Map provided them with powerful evidence of differences before and after the mobile phone initiative. At baseline, CHWs were not mentioned as actors in the information network, while at endline they were seen to have significant connections with colleagues, beneficiaries, supervisors, and district health facilities, as both recipients and providers of information. Focus groups with CHWs complemented the Net-Map findings with reports of increased self-confidence and greater trust by their communities. These qualitative results were bolstered by surveys that showed decreases in stockouts of essential medicines, lower communication costs, wider service coverage, and more efficient referrals. As an innovative, participatory form of social network analysis, Net-Map yielded important visual, quantitative, and qualitative information at reasonable cost.

Genome-wide scans detect adaptation to aridity in a widespread forest tree species.

Patterns of adaptive variation within plant species are best studied through common garden experiments, but these are costly and time-consuming, especially for trees that have long generation times. We explored whether genome-wide scanning technology combined with outlier marker detection could be used to detect adaptation to climate and provide an alternative to common garden experiments. As a case study, we sampled nine provenances of the widespread forest tree species, Eucalyptus tricarpa, across an aridity gradient in southeastern Australia. Using a Bayesian analysis, we identified a suite of 94 putatively adaptive (outlying) sequence-tagged markers across the genome. Population-level allele frequencies of these outlier markers were strongly correlated with temperature and moisture availability at the site of origin, and with population differences in functional traits measured in two common gardens. Using the output from a canonical analysis of principal coordinates, we devised a metric that provides a holistic measure of genomic adaptation to aridity that could be used to guide assisted migration or genetic augmentation.

Soybean SAT1 (Symbiotic Ammonium Transporter 1) encodes a bHLH transcription factor involved in nodule growth and NH4+ transport.

Glycine max symbiotic ammonium transporter 1 was first documented as a putative ammonium (NH4(+)) channel localized to the symbiosome membrane of soybean root nodules. We show that Glycine max symbiotic ammonium transporter 1 is actually a membrane-localized basic helix-loop-helix (bHLH) DNA-binding transcription factor now renamed Glycine max bHLH membrane 1 (GmbHLHm1). In yeast, GmbHLHm1 enters the nucleus and transcriptionally activates a unique plasma membrane NH4(+) channel Saccharomyces cerevisiae ammonium facilitator 1. Ammonium facilitator 1 homologs are present in soybean and other plant species, where they often share chromosomal microsynteny with bHLHm1 loci. GmbHLHm1 is important to the soybean rhizobium symbiosis because loss of activity results in a reduction of nodule fitness and growth. Transcriptional changes in nodules highlight downstream signaling pathways involving circadian clock regulation, nutrient transport, hormone signaling, and cell wall modification. Collectively, these results show that GmbHLHm1 influences nodule development and activity and is linked to a novel mechanism for NH4(+) transport common to both yeast and plants.

Plasticity of functional traits varies clinally along a rainfall gradient in Eucalyptus tricarpa.

Widespread species often occur across a range of climatic conditions, through a combination of local genetic adaptations and phenotypic plasticity. Species with greater phenotypic plasticity are likely to be better positioned to cope with rapid anthropogenic climate changes, while those displaying strong local adaptations might benefit from translocations to assist the movement of adaptive genes as the climate changes. Eucalyptus tricarpa occurs across a climatic gradient in south-eastern Australia, a region of increasing aridity, and we hypothesized that this species would display local adaptation to climate. We measured morphological and physiological traits reflecting climate responses in nine provenances from sites of 460 to 1040 mm annual rainfall, in their natural habitat and in common gardens near each end of the gradient. Local adaptation was evident in functional traits and differential growth rates in the common gardens. Some traits displayed complex combinations of plasticity and genetic divergence among provenances, including clinal variation in plasticity itself. Provenances from drier locations were more plastic in leaf thickness, whereas leaf size was more plastic in provenances from higher rainfall locations. Leaf density and stomatal physiology (as indicated by δ(13)C and δ(18)O) were highly and uniformly plastic. In addition to variation in mean trait values, genetic variation in trait plasticity may play a role in climate adaptation.

Wait or escape? Contrasting submergence tolerance strategies of Rorippa amphibia, Rorippa sylvestris and their hybrid.

BACKGROUND AND AIMS: Differential responses of closely related species to submergence can provide insight into the evolution and mechanisms of submergence tolerance. Several traits of two wetland species from habitats with contrasting flooding regimes, Rorippa amphibia and Rorippa sylvestris, as well as F(1) hybrid Rorippa × anceps were analysed to unravel mechanisms underlying submergence tolerance. METHODS: In the first submergence experiment (lasting 20 d) we analysed biomass, stem elongation and carbohydrate content. In the second submergence experiment (lasting 3 months) we analysed survival and the effect of re-establishment of air contact on biomass and carbohydrate content. In a separate experiment we analysed expression of two carbohydrate catabolism genes, ADH1 and SUS1, upon re-establishment of air contact following submergence. KEY RESULTS: All plants had low mortality even after 3 months of submergence. Rorippa sylvestris was characterized by 100 % survival and higher carbohydrate levels coupled with lower ADH1 gene expression as well as reduced growth compared with R. amphibia. Rorippa amphibia and the hybrid elongated their stems but this did not pay-off in higher survival when plants remained submerged. Only R. amphibia and the hybrid benefited in terms of increased biomass and carbohydrate accumulation upon re-establishing air contact. CONCLUSIONS: Results demonstrate contrasting 'escape' and 'quiescence' strategies between Rorippa species. Being a close relative of arabidopsis, Rorippa is an excellent model for future studies on the molecular mechanism(s) controlling these strategies.

Root hydraulic conductance and aquaporin abundance respond rapidly to partial root-zone drying events in a riparian Melaleuca species.

• Drying a portion of a root system (partial root-zone drying (PRD)) can induce partial stomatal closure, but this response is not always observed. We hypothesized that some of the variation in PRD response reflects adaptations to the native environment, where plants subjected to frequent PRD events may display a greater degree of root-level compensation. • Here, we examined PRD responses of Melaleuca argentea, a tree native to intermittent waterways in which PRD events are common. Seedlings were grown with part of their root system in soil and part in an aquatic compartment, mimicking conditions often observed in the field. • The aquatic roots initially provided two-thirds of total water uptake, but draining the aquatic compartment had no effect on stomatal conductance, so long as soil moisture remained c. 80% of field capacity. Water uptake from the soil compartment increased threefold within 24 h, with a corresponding transient threefold increase in root hydraulic conductance (L(p)), an increase in plasma membrane intrinsic protein 1 (PIP1) aquaporins at 24 h, and a decrease in PIP2 aquaporins by 48 h. • Our results demonstrate that PRD can induce rapid changes in L(p) and aquaporin expression in roots, which may play a role in short-term water uptake adjustments, particularly in species adapted to heterogeneous water availability.