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COVID-19 , Secuencia de Bases , COVID-19/epidemiología , Canadá/epidemiología , Humanos , SARS-CoV-2/genéticaRESUMEN
Given the steady rise of overdose morbidity and mortality in North America, and increasing frequency of sudden clusters of non-fatal and fatal overdoses in other jurisdictions, regional preparedness plans to respond effectively to clusters of overdoses may reduce the impact of such events on the population. On the 27th of February 2017 in Kingston, Ontario, KFL&A Public Health, in collaboration with public health partners, hosted a full-day workshop involving table-top exercises and discussions for service partners on how to prepare for, respond to, and manage a mass-casualty event secondary to opioid overdose in Southeastern Ontario. The workshop assisted in identifying the various challenges faced by service partners, provided an understanding of the roles and responsibilities of partner agencies, and helped to determine next steps in preparation to address a mass opioid overdose situation at the local level. This report suggests key roles and responsibilities of partners involved in responding to a mass-casualty event secondary to opioid overdose, recommendations to address the feedback and challenges raised throughout the workshop, and a protocol to help determine when to activate an Incident Management System (IMS).
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BACKGROUND: Although income assistance is an important source of support for low income individuals, there is evidence that adverse outcomes may increase when payments are disbursed on the same day for all recipients. The objective of this study was to assess the temporal patterns and causal relation between population-level illicit drug overdose deaths and income assistance payments using daily mortality data for British Columbia over a period of five years. METHODS: Retrospective data on daily mortality due to illicit drug overdose, 2009-2013, were provided by the BC Coroners Service. These data were analyzed using regression models and time series tests for causality in relation to dates of income assistance payments. RESULTS: 1343 deaths due to illicit drug overdose were reported in BC during 2009-2013; 394 occurred during cheque weeks (n=60) and 949 occurred during non-cheque weeks (n=202). Average weekly mortality due to illicit drug overdose was 40% higher during weeks of income assistance payments compared to weeks without payments (P<0.001). Consistent increases in mortality appeared the day after cheque disbursement and were significantly higher for two days, and marginally higher after 3 days, even when controlling for other temporal trends. Granger causality testing suggests the timing of cheque issue was causally linked to increased drug overdose mortality (P<0.001). CONCLUSIONS: Our findings clarify the temporal relation and causal impact of income assistance payments on illicit drug deaths. We estimate 77 avoidable deaths were attributable to the synchronized disbursement of income assistance cheques over the five year period. An important consideration is whether varying the timing of payments among recipients could reduce this excess mortality and the related demands on health and social services.
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Sobredosis de Droga/epidemiología , Drogas Ilícitas/provisión & distribución , Asistencia Pública , Trastornos Relacionados con Sustancias/mortalidad , Colombia Británica , Causas de Muerte , Sobredosis de Droga/economía , Sobredosis de Droga/mortalidad , Humanos , Drogas Ilícitas/economía , Análisis de Regresión , Estudios Retrospectivos , Trastornos Relacionados con Sustancias/economía , Trastornos Relacionados con Sustancias/epidemiología , Factores de TiempoRESUMEN
Hypertension is a risk factor for chronic kidney disease, particularly when associated with impaired renal autoregulation and thereby increased intraglomerular pressure (Pgc). Elevated Pgc can be modeled in vitro by exposing glomerular mesangial cells to mechanical strain. We previously showed that RhoA mediates strain-induced matrix production. Here, we show that RhoA activation is dependent on an intact microtubule network. Upregulation of the profibrotic cytokine connective tissue growth factor (CTGF) by mechanical strain is dependent on RhoA activation and inhibited by microtubule disruption. We tested the effects of the microtubule depolymerizing agent colchicine in 5/6 nephrectomized rats, a model of chronic kidney disease driven by elevated Pgc. Colchicine inhibited glomerular RhoA activation and attenuated both glomerular sclerosis and interstitial fibrosis without affecting systemic blood pressure. Upregulation of the matrix proteins collagen I and fibronectin, as well as CTGF, was attenuated by colchicine. Activity of the profibrotic cytokine TGF-ß, as assessed by Smad3 phosphorylation, was also inhibited by colchicine. Microtubule disruption significantly decreased renal infiltration of lymphocytes and macrophages. Our studies thus indicate that colchicine modifies hypertensive renal fibrosis. Its protective effects are likely mediated by inhibition of RhoA signaling and renal infiltration of inflammatory cells. Already well-established in clinical practice for other indications, prevention of hypertension-associated renal fibrosis may represent a new potential use for colchicine.