Chloroquine (CQ) exhibited promising in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the optimal dosage regimens remain unknown. Our objective was to explore the optimal chloroquine phosphate (CQP) dosage regimens for early achievement of virological clearance within 48-72 hours to diminish in-hospital transmission to front-line healthcare workers. A 10,000-subject Monte Carlo simulation was performed to calculate both probability of efficacy and safety attainment (PTA) using pharmacokinetic (PK) parameters obtained from the published population PK study. Dosage regimens that early achieved PTA of efficacy (PTAeff) ≥90% within 48-72 hours, while maintained PTA of toxicity (PTAtox) ≤1% were considered optimal. For the previously proposed regimens in published guidelines and clinical studies, all dosage regimens could not achieve ≥90% PTAeff, except one with the highest dosage regimen. Our simulations suggested that large amount of loading dose was required for the early achievement. We designed three dosage regimens containing high loading dose (2-3 gram per day), which early achieved ≥90% PTAeff within 48-72 hours, while also maintained ≤1% PTAtox throughout the treatment course. Further clinical studies are needed to prove the efficacy and safety of our designed regimens.
Coronavirus disease 2019 (COVID-19) is an infectious disease that causes acute respiratory illness. It was first reported in Wuhan, China. The virus has spread rapidly around the world. Epidemiological studies performed in children found that most children infected with COVID-19 were asymptomatic or had mild symptoms. However, about 10% developed severe symptoms, needed oxygen support, and were admitted to critical care units 1 . The most common route of coronavirus transmission to children is via household contact 2 . No specific drugs have been approved to treat COVID-19 infections in children. Many clinical trials of drugs for the treatment of COVID-19 have been conducted. Some drugs were proven their efficacy for adult patients, but none as yet demonstrated satisfactory outcomes for children [3][4][5][6][7][8][9] . Analyses of in vitro data for hydroxychloroquine, an analogue of chloroquine, showed that it effectively inhibited coronavirus replication [10][11][12] . Hydroxychloroquine blocks coronaviral entry by obstructing glycosylation in the host receptor, thereby viral replication is inhibited by increasing endosomal pH. Hydroxychloroquine also has an immunomodulatory effect by decreasing
BackgroundA comparative study was conducted to evaluate prescribed antibiotic (AB) use in surgical patients with the Transtheoretical Model of Behavior (TTM) and Theory of Planned Behavior (TPB).MethodsA survey was conducted at Thammasat University Hospital from January 1 to 31, 2019. We evaluated the appropriateness of AB uses in the surgical department reported per the hospital’s Drug Use Evaluation (DUE) form. After review of the DUE, in-depth interviews were conducted to all prescribers to explore antibiotic prescribing behavior based on TTM vs. TPB, using a standardized data collection tool. Data collected included demographics, indications, appropriateness of AB uses, the individual prescriber’s behavior based on TTM and TPB. The five TTM stages of change were categorized precontemplation, contemplation, preparation, action, and maintenance. In TPB assessment, we evaluated attitude toward AB uses, subjective norm to AB uses behavior, and perceived behavior control of AB uses behavior.ResultsThere were 92 AB uses from 64 prescribers; 70 (70/92; 76%) used antibiotics appropriately. The majority of AB uses (62/92; 67%) were for treatment of infections. The most common reasons for inappropriate AB uses included inappropriate AB choices for treatment and prophylaxis of SSIs (n = 11, 50%) and inappropriate duration (n = 8, 36%). Physicians categorized in higher stages of TTM (action and maintenance) were strongly correlated with appropriate AB uses, while there was no correlation between the total TPB score and appropriateness of AB uses. By multivariate analysis, the TTM action and maintenance (aOR = 7.95; P = 0.02) and self-reported prescribers who considered patients as first priority (aOR = 4.02; P = 0.04) were associated with appropriate AB uses, while neurosurgical procedures (aOR = 0.13; P = 0.003) and antibiotic prescriptions for surgical prophylaxis (aOR = 0.15; P = 0.04) were associated with inappropriate AB uses.ConclusionAntibiotic prescribers categorized by TTM stages strongly correlated with appropriate AB uses. Additional studies to assess appropriate AB prescribing behavior, based on TTM stages of change, offer an opportunity to optimize surgical care.Disclosures All authors: No reported disclosures.
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