Medications and dosages used in medical assistance in dying: a cross-sectional study.

BACKGROUND: There is little evidence describing the technical aspects of medical assistance in dying (MAiD) in Canada, such as medications, dosages and complications. Our objective was to describe clinical practice in providing MAiD in Ontario and Vancouver, Canada, and explore relations between medications used, time until death and complications. METHODS: We conducted a retrospective cohort study of a sample of adult (age ≥ 18 yr) patients who received MAiD in Ontario between 2016 and 2018, and patients who received MAiD in 1 of 3 Canadian academic hospitals (in Hamilton and Ottawa, Ontario, and Vancouver, British Colombia) between 2019 and 2020. We used de-identified data for 2016-2018 from the Office of the Chief Coroner for Ontario MAiD Database and chart review data for 2019-2020 from the 3 centres. We used multivariable parametric survival analysis to identify relations between medications, dosages and time from procedure start until death. RESULTS: The sample included 3557 patients (1786 men [50.2%] and 1770 women [49.8%] with a mean age of 74 [standard deviation 13] yr). The majority of patients (2519 [70.8%]) had a diagnosis of cancer. The medications most often used were propofol (3504 cases [98.5%]), midazolam (3251 [91.4%]) and rocuronium (3228 [90.8%]). The median time from the first injection until death was 9 (interquartile range 6) minutes. Standard-dose lidocaine (40-60 mg) and high-dose propofol (> 1000 mg) were associated with prolonged time until death (prolonged by a median of 1 min and 3 min, respectively). Complications occurred in 41 cases (1.2%), mostly related to venous access or need for administration of a second medication. INTERPRETATION: In a large sample of patients who died with medical assistance, certain medications were associated with small differences in time from injection to death, and complications were rare. More research is needed to identify the medication protocols that predict outcomes consistent with patient and family expectations for a medically assisted death.

Evaluation of the Ottawa 3DY as a screening tool for cognitive impairment in older emergency department patients.

OBJECTIVE: This study sought to evaluate the implementation of the Ottawa 3DY Tool, a simple screening instrument for cognitive impairment, by front-line ED clinicians. METHODS: We conducted a prospective cohort study in an academic ED. Patients ≥75 years underwent cognitive screening with the Ottawa 3DY by front-line nurses and physicians. Descriptive statistics were used to describe level of implementation and acceptability of the tool. Sensitivity and specificity was calculated using an Mini-Mental State Exam <25 as the cut-off for cognitive impairment. A weighted kappa was calculated to establish inter-rater agreement. RESULTS: Cognitive screening was completed in 260/332 eligible patients (78.3%), who were 60% female and had a mean age of 83.7 years. Facilitators to screening: perceived importance and ownership of screening and feasibility of Ottawa 3DY. Barriers to screening were: over confidence in clinical judgement and perceived lack of patient benefit. Ottawa 3DY had a sensitivity of 84.6% (64.3-95.0) and specificity of 54.2% (39.3-68.4) when completed by nurses. When completed by emergency physicians, sensitivity was 78.9% (53.9-93.0) and specificity was 70.0% (45.7-87.2). Inter-rater agreement kappa score was 0.67. DISCUSSION: This study demonstrated that incorporating the Ottawa 3DY tool into the routine evaluation of older ED patients by front-line ED clinicians is both feasible and effective. With its demonstrated good inter-rater reliability and moderate level of sensitivity and specificity when compared with the much longer MMSE, the routine adoption of this tool may help lead to improved recognition of cognitive impairment and ultimately patient and system outcomes.

Benefits of 21% Oxygen Compared with 100% Oxygen for Delivery of Isoflurane to Mice (Mus musculus) and Rats (Rattus norvegicus).

At research institutions, isoflurane delivered by precision vaporizer to a face mask is the standard for rodent surgery and for procedures with durations that exceed a few minutes. Pure oxygen is often used as the carrier gas for isoflurane anesthesia, despite documented complications from long-term 100% oxygen use in humans and known occupational safety risks. We therefore examined the effect of anesthetic delivery gas on physiologic variables in mice and rats. Rodents were anesthetized for 60 min with isoflurane delivered in either 21% or 100% oxygen by means of a nose cone. We noted no difference between carrier gasses in physiologic variables in mice, including body temperature, respiratory rate, mean arterial pressure, surgical recovery time, pH, or PaCO2. However, blood gas analysis revealed evidence of a ventilation-perfusion mismatch in the 100% oxygen group. Pressure-volume hysteresis and histomorphometric analyses confirmed the presence of increased atelectasis in mice that received 100% oxygen. Unlike mice, rats that received isoflurane in 100% oxygen had acute respiratory acidosis and elevated mean arterial pressure, but atelectasis was similar between carrier gasses. Our data suggest that both 100% and 21% oxygen are acceptable for the delivery of isoflurane to mice. However, mice anesthetized for studies focused on lung physiology or architecture would benefit from the delivery of isoflurane in 21% oxygen to reduce absorption atelectasis and the potential associated downstream inflammatory effects. For rats, delivery of isoflurane in 21% and 100% oxygen both caused perturbations in physiologic variables, and choosing a carrier gas is not straightforward.

Repeated dose (28-day) administration of silver nanoparticles of varied size and coating does not significantly alter the indigenous murine gut microbiome.

Silver nanoparticles (AgNPs) have been used as antimicrobials in a number of applications, including topical wound dressings and coatings for consumer products and biomedical devices. Ingestion is a relevant route of exposure for AgNPs, whether occurring unintentionally via Ag dissolution from consumer products, or intentionally from dietary supplements. AgNP have also been proposed as substitutes for antibiotics in animal feeds. While oral antibiotics are known to have significant effects on gut bacteria, the antimicrobial effects of ingested AgNPs on the indigenous microbiome or on gut pathogens are unknown. In addition, AgNP size and coating have been postulated as significantly influential towards their biochemical properties and the influence of these properties on antimicrobial efficacy is unknown. We evaluated murine gut microbial communities using culture-independent sequencing of 16S rRNA gene fragments following 28 days of repeated oral dosing of well-characterized AgNPs of two different sizes (20 and 110 nm) and coatings (PVP and Citrate). Irrespective of size or coating, oral administration of AgNPs at 10 mg/kg body weight/day did not alter the membership, structure or diversity of the murine gut microbiome. Thus, in contrast to effects of broad-spectrum antibiotics, repeat dosing of AgNP, at doses equivalent to 2000 times the oral reference dose and 100-400 times the effective in vitro anti-microbial concentration, does not affect the indigenous murine gut microbiome.

Prospective Validation of the Ottawa 3DY Scale by Geriatric Emergency Management Nurses to Identify Impaired Cognition in Older Emergency Department Patients.

STUDY OBJECTIVE: Assessment of older emergency department (ED) patients with cognitive impairment is challenging because few tools exist that can be quickly administered by front-line practitioners. Our objective is to validate the Ottawa 3DY Scale, a 4-question screening tool for cognitive impairment, in older ED patients and compare its performance with that of the Animal Fluency Test. METHODS: We conducted a prospective cohort study in 2 EDs and enrolled a convenience sample of patients aged 75 years or older with no history of cognitive impairment. Eligible patients were assessed by geriatric emergency management nurses who administered the Mini-Mental State Examination, ordered with the Ottawa 3DY Scale questions first, followed by the Animal Fluency Test. Mini-Mental State Examination score less than 25 was our criterion standard for cognitive impairment. RESULTS: Study patients (N=238) had a mean age of 81.9 years and were 60.1% women, and 26.5% were admitted to the hospital. The Ottawa 3DY Scale and Mini-Mental State Examination were in agreement for 75.6% of cases, with a sensitivity of 93.8% (95% confidence interval [CI] 77.8% to 98.9%) and specificity of 72.8% (95% CI 66.1% to 78.7%). The Animal Fluency Test score less than 15 and Mini-Mental State Examination score were in agreement for 46.2% of cases, with sensitivity 90.6% (95% CI 73.8% to 97.5%) and specificity 39.3% (95% CI 32.7% to 46.4%). CONCLUSION: Both the Ottawa 3DY Scale and the Animal Fluency Test demonstrated excellent sensitivity versus the Mini-Mental State Examination; however, the Animal Fluency Test exhibited poor specificity. The Ottawa 3DY Scale is an effective tool to screen for cognitive impairment in older ED patients, and its use may facilitate improved care in this vulnerable population.

Enucleation for treating rodent ocular disease.

Our standard of care for rodent corneal lesions previously included treatment of the primary lesion, application of topical NSAIDs, and systemic NSAIDs in severe cases. When intensive medical management was unsuccessful, animals were euthanized, leading to premature loss of valuable genetically modified animals and those on long-term studies. We investigated enucleation surgery as a treatment for 15 cases of rodent corneal disease that did not respond to medical management. Enucleation was performed under isoflurane anesthesia and involved removal of the globe, extensive hemostasis, and packing the orbital space with absorbable gelatin sponge. The lid margins were closed by tarsorrhaphy and tissue glue. Analgesia was provided by using buprenorphine preoperatively and carprofen chew tabs postoperatively. To date, we have a 100% success rate with this procedure (n = 20; 15 clinically affected rodents [2 rats, 13 mice], 5 healthy controls), which included a 60-d follow-up period. The single complication involved dehiscence of the tarsorrhaphy site and was repaired by trimming the lid margins to provide fresh tissue for closure. Histologic examination at both 1 and 3 mo after surgery revealed no evidence of infection of the enucleation site. Enucleation in rodents is a straightforward procedure that represents a refinement to our current standard of care for rodents, does not cause significant inflammation of remaining periocular structures, and has reduced the number of animals euthanized prior to study endpoint because of severe ocular lesions.