Remdesivir for the treatment of patients in hospital with COVID-19 in Canada: a randomized controlled trial.

BACKGROUND: The role of remdesivir in the treatment of patients in hospital with COVID-19 remains ill defined in a global context. The World Health Organization Solidarity randomized controlled trial (RCT) evaluated remdesivir in patients across many countries, with Canada enrolling patients using an expanded data collection format in the Canadian Treatments for COVID-19 (CATCO) trial. We report on the Canadian findings, with additional demographics, characteristics and clinical outcomes, to explore the potential for differential effects across different health care systems. METHODS: We performed an open-label, pragmatic RCT in Canadian hospitals, in conjunction with the Solidarity trial. We randomized patients to 10 days of remdesivir (200 mg intravenously [IV] on day 0, followed by 100 mg IV daily), plus standard care, or standard care alone. The primary outcome was in-hospital mortality. Secondary outcomes included changes in clinical severity, oxygen- and ventilator-free days (at 28 d), incidence of new oxygen or mechanical ventilation use, duration of hospital stay, and adverse event rates. We performed a priori subgroup analyses according to duration of symptoms before enrolment, age, sex and severity of symptoms on presentation. RESULTS: Across 52 Canadian hospitals, we randomized 1282 patients between Aug. 14, 2020, and Apr. 1, 2021, to remdesivir (n = 634) or standard of care (n = 648). Of these, 15 withdrew consent or were still in hospital, for a total sample of 1267 patients. Among patients assigned to receive remdesivir, in-hospital mortality was 18.7%, compared with 22.6% in the standard-of-care arm (relative risk [RR] 0.83 (95% confidence interval [CI] 0.67 to 1.03), and 60-day mortality was 24.8% and 28.2%, respectively (95% CI 0.72 to 1.07). For patients not mechanically ventilated at baseline, the need for mechanical ventilation was 8.0% in those assigned remdesivir, and 15.0% in those receiving standard of care (RR 0.53, 95% CI 0.38 to 0.75). Mean oxygen-free and ventilator-free days at day 28 were 15.9 (± standard deviation [SD] 10.5) and 21.4 (± SD 11.3) in those receiving remdesivir and 14.2 (± SD 11) and 19.5 (± SD 12.3) in those receiving standard of care (p = 0.006 and 0.007, respectively). There was no difference in safety events of new dialysis, change in creatinine, or new hepatic dysfunction between the 2 groups. INTERPRETATION: Remdesivir, when compared with standard of care, has a modest but significant effect on outcomes important to patients and health systems, such as the need for mechanical ventilation. Trial registration: ClinicalTrials.gov, no. NCT04330690.

Field associations of first generation densities of the pest mites Halotydeus destructor and Penthaleus major in pasture.

Halotydeus destructor and Penthaleus major are species of earth mite commonly found at high densities in agricultural fields in Australia and other parts of the world. These mites pose a risk to a range of winter crops and pastures when seedlings emerge in autumn. In order to predict likely mite pressure, we investigated whether autumn densities in pastures can be determined from agronomic and environmental field variables. For H. destructor, field densities showed little association with a range of vegetation variables but could largely be explained using the variable field type, with high densities present when fields had mixtures of grass, clover and weeds. For P. major, we found a regional effect. In the region where most data were available, P. major field densities were associated with grass abundance, whereas an association with field type was significant but different to that found for H. destructor. For both species, densities were not associated with rainfall, but there was a weak association with soil moisture capacity. We discuss how these results can help in managing these important pest mites.

Penicillin de-labelling in vancouver, British Columbia, Canada: comparison of approaches, outcomes and future directions.

BACKGROUND: Inaccurate penicillin allergy labels lead to inappropriate antibiotic prescriptions and harmful patient consequences. System-wide efforts are needed to remove incorrect penicillin allergy labels, but more health services research is required on how to best deliver these services. METHODS: Data was extracted from five hospitals in Vancouver, British Columbia, Canada from October 2018-May 2022. The primary outcomes of this study were to outline de-labelling protocol designs, identify the roles of various healthcare professionals in de-labelling protocols and identify rates of de-labelling penicillin allergies and associated adverse events at various institutions. Our secondary outcome was to describe de-labelling rates for special populations, including pediatric, obstetric and immunocompromised subpopulations. To achieve these outcomes, participating institutions provided their de-labelling protocol designs and data on program participants. Protocols were then compared to find common themes and differences. Furthermore, adverse events were reviewed and percentages of patients de-labelled at each institution and in total were calculated. RESULTS: Protocols demonstrated a high level of variability, including different methods of participant identification, risk-stratification and roles of providers. All protocols used oral and direct oral challenges, heavily involved pharmacists and had physician oversight. Despite the differences, of the 711 patients enrolled in all programs, 697 (98.0%) were de-labelled. There were 9 adverse events (1.3%) with oral challenges with mainly minor symptoms. CONCLUSIONS: Our data demonstrates that de-labelling programs effectively and safely remove penicillin allergy labels, including pediatric, obstetric and immunocompromised patients. Consistent with current literature, most patients with a penicillin allergy label are not allergic. De-labelling programs could benefit from increasing clinician engagement by increasing accessibility of resources to providers, including guidance for de-labelling of special populations.

Factors Influencing Damage by the Portuguese Millipede, Ommatoiulus moreleti (Julida: Julidae), to Crop Seedlings.

In different parts of the world, the increasing agricultural practice of retaining crop stubble in fields across seasons has led to population increases of soil-dwelling arthropods, primarily detritivorous species. These species typically play a beneficial role in the ecosystem, but some, including the Portuguese millipede (Ommatoiulus moreleti (Lucas)) can be sporadic pests. To assist in better understanding of pest risk, this study examines why O. moreleti feeds on crop seedlings. For lupin, seedling susceptibility appears to be related to plant properties, with greatly different levels of damage caused to the two cultivated species (Lupinus angustinus and Lupinus albus) and particularly between cultivated and wild-type L. angustinus seedlings. Millipedes feeding on lupin (cultivated L. angustinus), but not lucerne (Medicago sativa), gained a similar amount of weight to those feeding on other foods known to be readily consumed. The life-stage and sex of O. moreleti was found to be related to seedling damage. The presence of crop stubbles (as alternate food sources) did not limit the damage O. moreleti caused to lupin, suggesting that the presence of stubble in a field situation may not preclude feeding on crop seedlings. We discuss how results from these controlled environment trials can build a basis for understanding variable crop damage by O. moreleti in the field.

Crop Seedling Susceptibility to Armadillidium vulgare (Isopoda: Armadillidiidae) and Ommatoiulus moreletii (Diplopoda: Iulidae).

The isopod, Armadillidium vulgare (Latreille) (Isopoda: Armadillidiidae), and the millipede, Ommatoiulus moreletii (Lucas) (Diplopoda: Iulidae), are increasingly being reported as pests of emerging broadacre crop seedlings in southern Australia. This is thought to be due to the increased adoption of stubble retention practices, leading to increased abundance of these soil-dwelling organisms. Here, we evaluate the propensity of A. vulgare and O. moreletii to damage a range of crop seedlings. Through the combined analysis of a controlled feeding trial and field reports, we show A. vulgare is able to feed on and damage a range of pulses, legumes, cereals, and oilseeds, as emerging seedlings. O. moreletii had a more restricted range of feeding, being limited to lupin, lucerne, and canola in the feeding trial. These results are discussed in the context of developing pest management guidelines for these species.