Introduction to Bayesian statistics: a practical framework for clinical pharmacists.

OBJECTIVES: Most pharmaceutical investigations have relied on p values to infer conclusions from their study findings. Central to this paradigm is the concept of null hypothesis significance testing. This approach is however fraught with overuse and misinterpretations. Several alternatives have already been proposed, yet uptake remains low. In this study, we aimed to discuss the pitfalls of p value-based testing and to provide readers with the basics to apply Bayesian statistics. METHODS: Jeffreys's Amazing Statistical Package (JASP) was used to evaluate the effect of a clinical pharmacy (CP) intervention (opposed to usual care) on the number of emergency department (ED) visits without hospital admission. Basic Bayesian terminology was explained and compared with classical p value-based testing. In the study example, a Cauchy prior distribution was used to determine the effect size with a scale parameter r=0.707 at location=0 and Bayes factors (BF) were subsequently estimated. A robustness analysis was then performed to visualise the impact of different r values on the BF value. RESULTS: A BF of 4.082 was determined, indicating that the observed data were about four times more likely to occur under the alternative hypothesis that the CP intervention was effective. The median effect size of the CP intervention on ED visits was found to be 0.337 with a 95% credible interval of 0.074 to 0.635. A robustness check was performed and all BF values were in favour of the CP intervention. CONCLUSION: Bayesian inference can be an important addition to the statistical armamentarium of pharmacists, who should become more acquainted with the basic terminology and rationale of such testing. To prove our point, Jeffreys' approach was applied to a CP study example, using an easy-to-use software program JASP.

Antiviral treatment of SARS-CoV-2-infected hamsters reveals a weak effect of favipiravir and a complete lack of effect for hydroxychloroquine

SARS-CoV-2 rapidly spread around the globe after its emergence in Wuhan in December 2019. With no specific therapeutic and prophylactic options available, the virus was able to infect millions of people. To date, close to half a million patients succumbed to the viral disease, COVID-19. The high need for treatment options, together with the lack of small animal models of infection has led to clinical trials with repurposed drugs before any preclinical in vivo evidence attesting their efficacy was available. We used Syrian hamsters to establish a model to evaluate antiviral activity of small molecules in both an infection and a transmission setting. Upon intranasal infection, the animals developed high titers of SARS-CoV-2 in the lungs and pathology similar to that observed in mild COVID-19 patients. Treatment of SARS-CoV-2-infected hamsters with favipiravir or hydroxychloroquine (with and without azithromycin) resulted in respectively a mild or no reduction in viral RNA and infectious virus. Micro-CT scan analysis of the lungs showed no improvement compared to non-treated animals, which was confirmed by histopathology. In addition, both compounds did not prevent virus transmission through direct contact and thus failed as prophylactic treatments. By modelling the PK profile of hydroxychloroquine based on the trough plasma concentrations, we show that the total lung exposure to the drug was not the limiting factor. In conclusion, we here characterized a hamster infection and transmission model to be a robust model for studying in vivo efficacy of antiviral compounds. The information acquired using hydroxychloroquine and favipiravir in this model is of critical value to those designing (current and) future clinical trials. At this point, the data here presented on hydroxychloroquine either alone or combined with azithromycin (together with previously reported in vivo data in macaques and ferrets) provide no scientific basis for further use of the drug in humans.

Reduced length of stay in radical cystectomy patients with oral versus parenteral post-operative nutrition protocol.

BACKGROUND: In Europe, parenteral nutrition is often used after radical cystectomy to avoid postoperative malnourishment. To the best of our knowledge, however, there is a paucity of data to conclude on the best modality for delivering nutritional support to this patient group. OBJECTIVE: The parenteral nutrition policy was reconsidered and an oral nutrition protocol was implemented by the clinical pharmacist and evaluated in terms of length of stay, number and type of postoperative complications and parenteral nutrition avoided costs. SETTING: A prospective interventional non-randomized before-after study was conducted. Regular radical cystectomy patients presenting without preoperative contra-indications for enteral nutrition were eligible. METHODS: Postoperatively, in the control group, the parenteral nutrition policy from the ward was applied. Parenteral nutrition was initiated systematically and continued until the patient was able to tolerate solid food. In the interventional group, an oral nutrition protocol was implemented. Parenteral nutrition could be initiated if oral intake remained insufficient after 5 days. Main outcome measure The primary end point was postoperative length of stay. Secondary endpoints included the number of patients in whom the oral nutrition protocol was implemented successfully, as well as the number and type of postoperative complications. RESULTS: A total of 94 eligible patients was assigned consecutively to the control (n = 48) and to the interventional group (n = 46). Baseline demographics were comparable. A significant reduction in median length of stay was associated with the oral nutrition protocol [18 days (IQR 15-22) in the control group vs. 14 days (IQR 13-18) in the interventional group (p < 0.001)]. In 40 out of 46 patients from the interventional group, the oral nutrition protocol was implemented successfully. The number and type of postoperative complications did not differ significantly. Implementing the oral nutrition protocol resulted in a direct parenteral nutrition infusion bag cost saving of approximately €512 and a reduction in hospitalization cost of €2,608 per patient. CONCLUSION: The findings of our study showed that an oral nutrition protocol, when compared to the systematic postoperative use of parenteral nutrition, was associated with a decreased length of stay and costs in a regular radical cystectomy patient population.