In the absence of a parenteral drug, oral oseltamivir is currently recommended by the WHO for treating H5N1 influenza. Whether oseltamivir absorption is adequate in severe influenza is unknown. We measured the steady state, plasma concentrations of nasogastrically administered oseltamivir 150 mg bid and its active metabolite, oseltamivir carboxylate (OC), in three, mechanically ventilated patients with severe H5N1 (male, 30 yrs; pregnant female, 22 yrs) and severe H3N2 (female, 76 yrs). Treatments were started 6, 7 and 8 days after illness onset, respectively. Both females were sampled while on continuous venovenous haemofiltration. Admission and follow up specimens (trachea, nose, throat, rectum, blood) were tested for RNA viral load by reverse transcriptase PCR. In vitro virus susceptibility to OC was measured by a neuraminidase inhibition assay. Admission creatinine clearances were 66 (male, H5N1), 82 (female, H5N1) and 6 (H3N2) ml/min. Corresponding AUC0–12 values (5932, 10,951 and 34,670 ng.h/ml) and trough OC concentrations (376, 575 and 2730 ng/ml) were higher than previously reported in healthy volunteers; the latter exceeded 545 to 3956 fold the H5N1 IC50 (0.69 ng/ml) isolated from the H5N1 infected female. Two patients with follow-up respiratory specimens cleared their viruses after 5 (H5N1 male) and 5 (H3N2 female) days of oseltamivir. Both female patients died of respiratory failure; the male survived. 150 mg bid of oseltamivir was well absorbed and converted extensively to OC. Virus was cleared in two patients but two patients died, suggesting viral efficacy but poor clinical efficacy.
Objectives: SARS-CoV-2 is a novel and highly infectious virus. An effective response requires rapid training of healthcare workers (HCWs). We measured the change in knowledge related to COVID-19 and associated factors before and after training of HCWs in Vietnam. Methods: A quasi-experimental design was used to evaluate HCW knowledge related to prevention and control of SARS-CoV-2 before and after attending a 2-day training-of-trainers course. Between June and September 2020, 963 HCWs from 194 hospitals in 21 provinces received the training. HCW knowledge was assessed using a 20-item questionnaire consisting of multiple-choice questions at the beginning and closing of the training course. A participant received 1 point for each correct answer. He or she was considered to have improved knowledge the posttest score was higher than the pretest score with a score ≥15 on the posttest. We applied the McNemar test and logistic regression model to test the level of association between demographic factors and change in knowledge of COVID-19. Results: Overall, 100% of HCWs completed both the pretest and posttest. At baseline, only 14.7% scored ≥15. Following the training, 78.4% scored ≥15 and 64.3% had improved knowledge according to the predetermined definition. Questions related to the order of PPE donning and doffing and respiratory specimen collection procedures were identified as having the greatest improvement (44.6% and 60.7%, respectively). Being female (OR, 1.5; 95% CI, 1.1–2.0), having a postgraduate degree (OR, 2.5; 95% CI, 1.4–4.4), working in a nonmanager position (OR, 1.5; 95% CI, 1.1–2.1), previous contact with a COVID-19 patient (OR, 1.5; 95% CI, 1.1–2.0), and working in northern Vietnam (OR, 2.0; 95% CI, 1.4–2.6), were associated with greater knowledge improvement. Conclusions: Most HCWs demonstrated improved knowledge of COVID-19 prevention and control after attending the training. Particular groups may benefit from additional training: those who are male, leaders and managers, those who hold an undergraduate degree, and those who work in the southern provinces.
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