Was Virtual Care as Safe as In-Person Care? Analyzing Patient Outcomes at Seven and Thirty Days in Ontario during the COVID-19 Pandemic.

In 2020, almost overnight, the paradigm for healthcare interactions changed in Ontario. To limit person-to-person transmission of COVID-19, the norm of in-person interactions shifted to virtual care. While this shift was part of broader public health measures and an acknowledgment of patient and societal concerns, it also represented a change in care modalities that had the potential to affect the quality of care provided, as well as short- and long-term patient outcomes. While public policy decisions were being made to moderate the use of virtual care at the end of the declared pandemic, a thorough analysis of short-term patient outcomes was needed to quantify the impact of virtual care on the population of Ontario.

Mass homicide by firearm in Canada: Effects of legislation.

Canada implemented a series of laws regulating firearms including background checks and licensing, references, psychological questionnaires, prohibition of paramilitary style rifles, and magazine capacity restrictions in order to decrease the incidences and deaths from mass shootings. The associated effects of these laws were examined over the years 1974 to 2020. A model was constructed using difference-in-differences analysis of firearms and non-firearms mass homicide incidences and death rates. Mass homicides were defined as a homicide due to one event involving three or more deaths. Incidence rates of mass homicide by firearm were found to be 0.11 (95%CI 0.08, 0.14) per million compared to a non-firearm mass homicide rate of 0.12 (95% CI 0.10, 0.15) per million. Mass homicide death rates by firearm were found to be 0.39 (95% CI 0.29, 0.49) per million compared to a non-firearm mass homicide rate of 0.47 (95% CI 0.34, 0.61) per million. Overall, there is a gradual declining trend in the incidence of mass homicide by firearm (IRR 0.97 (95% CI 0.96, 0.98)) and by non-firearm (IRR 0.97 (95% CI 0.97, 0.98)). The decline in mass homicide death rate by firearm and non-firearm is IRR 0.96 (95% CI 0.95, 0.97), and IRR 0.97 (95% CI 0.96, 0.98) respectively. No specific associated decrease in mass homicide incidence rates or death rates with firearms legislation was found after the implementation of background checks and prohibition of full auto firearms in 1980, by the implementation of references and psychological questionnaires in 1994, by the restriction of magazine capacity in 1994, the prohibition of paramilitary rifles in 1994, or licensing in 2001.

Suicide, firearms, and legislation: A review of the Canadian evidence.

Suicide accounts for approximately 4000 deaths a year in Canada, of which about 16% of those are suicide using a firearm. Canada has undertaken legislative efforts to regulate and control firearms, Bill C-51 in 1977 and Bills C-17 and C-68 in 1991 and 1995. Regulatory approaches that decrease the availability of firearms are hypothesized to reduce suicide by firearm however the substitution effect suggests it is possible that people may substitute other methods of suicide in place. Canadian studies on associations between legislation, regulation, and suicide rates have been published over the last three decades, and a search revealed thirteen that met the criteria. Seven studies examined the association between Bill C-51 and suicide rates and found that while rates of suicide by firearm appeared to have declined in association with regulations, there appears to be a substitution effect into other methods and no overall change in suicide rates. Six studies examining the effects of Bill C-17 and C-68 revealed a decrease in the rates of suicide by firearms, with a corresponding increase in non-firearms suicide rates and no decrease in overall suicide rates. One study even suggested no associated decrease in firearm suicide rates with an increasing rate of suicide by hanging possibly due to changes in preferences. These results suggest legislation has mixed effects on firearm suicide rates and may not alone reduce overall suicide in Canada.

Effect of firearms legislation on suicide and homicide in Canada from 1981 to 2016.

Canada implemented a series of laws regulating firearms including background and psychological screening, licensing, and training in the years 1991, 1994, and 2001. The effects of this legislation on suicide and homicide rates were examined over the years 1981 to 2016. Models were constructed using difference-in-difference analysis of firearms and non firearms death rates from 1981 to 2016. In addition, negative binomial regression was used to test for an association between rates of suicide by Canadian Province and firearms prevalence, using licensing rates as a proxy for prevalence. No associated benefit from firearms legislation on aggregate rates of male suicide was found. In men aged 45 to 59 an associated shift from firearms suicide after 1991 and 1994 to an increase in hanging resulted in overall rate ratios of 0.994 (95%CI, 0.978,1.010) and 0.993 (95%CI, 0.980,1.005) respectively. In men 60 and older a similar effect was seen after 1991, 1994, and 2001, that resulted in rate ratios of 0.989 (95%CI, 0.971,1.008), 0.994 (95%CI, 0.979,1.010), and 1.010 (95%CI, 0.998,1.022) respectively. In females a similar effect was only seen after 1991, rate ratio 0.983 (95%CI, 0.956,1.010). No beneficial association was found between legislation and female or male homicide rates. There was no association found with firearm prevalence rates per province and provincial suicide rates, but an increased association with suicide rates was found with rates of low income, increased unemployment, and the percentage of aboriginals in the population. In conclusion, firearms legislation had no associated beneficial effect on overall suicide and homicide rates. Prevalence of firearms ownership was not associated with suicide rates. Multifaceted strategies to reduce mortality associated with firearms may be required such as steps to reduce youth gang membership and violence, community-based suicide prevention programs, and outreach to groups for which access to care may be a particular issue, such as Aboriginals.

Canadian firearms legislation and effects on homicide 1974 to 2008.

Canada has implemented legislation covering all firearms since 1977 and presents a model to examine incremental firearms control. The effect of legislation on homicide by firearm and the subcategory, spousal homicide, is controversial and has not been well studied to date. Legislative effects on homicide and spousal homicide were analyzed using data obtained from Statistics Canada from 1974 to 2008. Three statistical methods were applied to search for any associated effects of firearms legislation. Interrupted time series regression, ARIMA, and Joinpoint analysis were performed. Neither were any significant beneficial associations between firearms legislation and homicide or spousal homicide rates found after the passage of three Acts by the Canadian Parliament--Bill C-51 (1977), C-17 (1991), and C-68 (1995)--nor were effects found after the implementation of licensing in 2001 and the registration of rifles and shotguns in 2003. After the passage of C-68, a decrease in the rate of the decline of homicide by firearm was found by interrupted regression. Joinpoint analysis also found an increasing trend in homicide by firearm rate post the enactment of the licensing portion of C-68. Other factors found to be associated with homicide rates were median age, unemployment, immigration rates, percentage of population in low-income bracket, Gini index of income equality, population per police officer, and incarceration rate. This study failed to demonstrate a beneficial association between legislation and firearm homicide rates between 1974 and 2008.

Multiplying the serum aminotransferase by the acetaminophen concentration to predict toxicity following overdose.

CONTEXT: The first available predictors of hepatic injury following acetaminophen (APAP) overdose are the serum APAP and aminotransferases [AT, i.e., aspartate (AST) aminotransferase or alanine (ALT) aminotransferase]. OBJECTIVE: We describe the initial value, rate of change, and interrelationship between these biomarkers in patients who develop hepatotoxicity despite treatment following acute overdose. A new parameter, the APAP × AT multiplication product, is proposed for early risk stratification. METHODS: We conducted a descriptive study of individuals selected from a multicenter retrospective cohort of patients hospitalized for APAP poisoning. We selected those acute APAP overdose patients who subsequently developed AT > 1,000 IU/L. Rising serum AT values were compared to simultaneously measured (or estimated) falling serum APAP. The APAP × AT was expressed relative to initiation of acetylcysteine therapy and grouped by time to meeting hepatotoxicity criteria. RESULTS: In the 94 cases studied, serum APAP concentrations were still appreciable [median 570 (interquartile range (IQR) 314-983) µmol/L] at the time of the first measured AT [211 (77-511) IU/L at 15.3 (12.1-19.2) h post-ingestion], yielding an initial APAP × AT of 99,000 (52,000-240,000) µmol × IU/L(2). Because serum AT rose rapidly (doubling time 9.5 h ) and APAP fell slowly (half-life 4.8 h), the multiplication product remained elevated during the first 12-24 h of antidotal therapy, especially among patients who developed earlier hepatotoxicity (AT > 1,000 IU/L). DISCUSSION AND CONCLUSIONS: The APAP × AT multiplication product, calculated at the time of presentation and after several h of antidotal therapy, holds promise as a new risk predictor following APAP overdose. It requires neither graphical interpretation nor accurate time of ingestion, two limitations to current risk stratification.

When do the aminotransferases rise after acute acetaminophen overdose?

CONTEXT: Rising aminotransferases (ATs) [either aspartate aminotransferase (AST) or alanine aminotransferase (ALT) are one of the first signs of hepatotoxicity following acetaminophen (APAP)] overdose (OD). However, the timing and speed of such rises are not well characterized, hampering early risk prediction. OBJECTIVE: To describe the kinetics of AT release in acute APAP OD patients who develop hepatotoxicity despite treatment. METHODS: A descriptive study of acute APAP OD patients with peak AT > 1,000 IU/L taken from the derivation subset of the Canadian Acetaminophen Overdose Study (CAOS), a large, multicenter retrospective cohort of patients hospitalized for APAP poisoning. RESULTS: Of 2,488 hospital admissions for acute APAP OD, 94 met inclusion criteria. Treatment with acetylcysteine, mostly intravenously, was begun in all cases within 24 h of ingestion. The initial AT concentration was already elevated in most patients at presentation [median 211 (IQR 77-511) IU/L obtained at 15.3 (12.1-19.2) h postingestion], and exceeded 100 IU/L in almost all patients within 24 h of ingestion. Serum AT concentrations rose rapidly [doubling time 9.5 h (95% CI: 8.7-10.4 h)], especially in patients who developed AT > 1,000 IU/L within 48 h of ingestion. Coagulopathy was worse in these patients and in those with an AT > 250 IU/L during the first 12 h of treatment with acetylcysteine. DISCUSSION AND CONCLUSIONS: An abnormal and rapidly doubling AT at presentation is more typical in severely poisoned patients, as judged by the effects on clotting. These data suggest that risk prediction instruments may be improved by incorporating both the serum AT concentration at initiation of antidotal therapy and its rate of change. Further studies using such an approach are warranted.

Drosophila RhoGAP68F is a putative GTPase activating protein for RhoA participating in gastrulation.

The Rho family small GTPases Rho, Rac, and Cdc42 regulate cell shape and motility through the actin cytoskeleton. These proteins cycle between a GTP-bound "on" state and a GDP-bound "off" state and are negatively regulated by GTPase-activating proteins (GAPs), which accelerate the small GTPase's intrinsic hydrolysis of bound GTP to GDP. Drosophila RhoGAP68F is similar to the mammalian protein p50RhoGAP/Cdc42GAP, which exhibits strong GAP activity toward Cdc42. We find that, despite the strong similarities between RhoGAP68F and p50RhoGAP/Cdc42GAP, RhoGAP68F is most effective as a GAP for RhoA. These in vitro data are supported by the in vivo analysis of mutants in RhoGAP68F. We demonstrate through the characterization of two alleles of the RhoGAP68F gene that RhoGAP68F participates in gastrulation of the embryo, a morphogenetic event driven by cell constriction that involves RhoA signaling. We propose that RhoGAP68F functions as a regulator of RhoA signaling during gastrulation.

The RING-finger scaffold protein Plenty of SH3s targets TAK1 to control immunity signalling in Drosophila.

Imd-mediated innate immunity is activated in response to infection by Gram-negative bacteria and leads to the activation of Jun amino-terminal kinase (JNK) and Relish, a nuclear factor-kappaB transcription factor responsible for the expression of antimicrobial peptides. Plenty of SH3s (POSH) has been shown to function as a scaffold protein for JNK activation, leading to apoptosis in mammals. Here, we report that POSH controls Imd-mediated immunity signalling in Drosophila. In POSH-deficient flies, JNK activation and Relish induction were delayed and sustained, which indicated that POSH is required for properly timed activation and termination of the cascade. The RING finger of POSH, possessing ubiquitin-ligase activity, was essential for termination of JNK activation. We show that POSH binds to and degrades TAK1, a crucial activator of both the JNK and the Relish signalling pathways. These results establish a novel role for POSH in the Drosophila immune system.

CYFIP/Sra-1 controls neuronal connectivity in Drosophila and links the Rac1 GTPase pathway to the fragile X protein.

Neuronal plasticity requires actin cytoskeleton remodeling and local protein translation in response to extracellular signals. Rho GTPase pathways control actin reorganization, while the fragile X mental retardation protein (FMRP) regulates the synthesis of specific proteins. Mutations affecting either pathway produce neuronal connectivity defects in model organisms and mental retardation in humans. We show that CYFIP, the fly ortholog of vertebrate FMRP interactors CYFIP1 and CYFIP2, is specifically expressed in the nervous system. CYFIP mutations affect axons and synapses, much like mutations in dFMR1 (the Drosophila FMR1 ortholog) and in Rho GTPase dRac1. CYFIP interacts biochemically and genetically with dFMR1 and dRac1. Finally, CYFIP acts as a dRac1 effector that antagonizes FMR1 function, providing a bridge between signal-dependent cytoskeleton remodeling and translation.

Drac1 and Crumbs participate in amnioserosa morphogenesis during dorsal closure in Drosophila.

Dorsal closure of the Drosophila embryo involves morphological changes in two epithelia, the epidermis and the amnioserosa, and is a popular system for studying the regulation of epithelial morphogenesis. We previously implicated the small GTPase Drac1 in the assembly of an actomyosin contractile apparatus, contributing to cell shape change in the epidermis during dorsal closure. We now present evidence that Drac1 and Crumbs, a determinant of epithelial polarity, are involved in setting up an actomyosin contractile apparatus that drives amnioserosa morphogenesis by inducing apical cell constriction. Expression of constitutively active Drac1 causes excessive constriction of amnioserosa cells and contraction of the tissue, whereas expression of dominant-negative Drac1 impairs amnioserosa morphogenesis. These Drac1 transgenes may be acting through their effects on the amnioserosa cytoskeleton, as constitutively active Drac1 causes increased staining for F-actin and myosin, whereas dominant-negative Drac1 reduces F-actin levels. Overexpression of Crumbs causes premature cell constriction in the amnioserosa, and dorsal closure defects are seen in embryos homozygous for hypomorphic crumbs alleles. The ability of constitutively active Drac1 to cause contraction of the amnioserosa is impaired in a crumbs mutant background. We propose that amnioserosa morphogenesis is a useful system for studying the regulation of epithelial morphogenesis by Drac1.