Severe acute respiratory syndrome coronavirus 2 (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 has infected millions of people of which more than half a million succumbed to the viral disease, COVID-19. The urgent need for an effective treatment together with a lack of small animal infection models has led to clinical trials using repurposed drugs without preclinical evidence of their in vivo efficacy. We established an infection model in Syrian hamsters to evaluate the efficacy of small molecules on both infection and transmission. Treatment of SARS-CoV-2−infected hamsters with a low dose of favipiravir or hydroxychloroquine with(out) azithromycin resulted in, respectively, a mild or no reduction in virus levels. However, high doses of favipiravir significantly reduced infectious virus titers in the lungs and markedly improved lung histopathology. Moreover, a high dose of favipiravir decreased virus transmission by direct contact, whereas hydroxychloroquine failed as prophylaxis. Pharmacokinetic modeling of hydroxychloroquine suggested that the total lung exposure to the drug did not cause the failure. Our data on hydroxychloroquine (together with previous reports in macaques and ferrets) thus provide no scientific basis for the use of this drug in COVID-19 patients. In contrast, the results with favipiravir demonstrate that an antiviral drug at nontoxic doses exhibits a marked protective effect against SARS-CoV-2 in a small animal model. Clinical studies are required to assess whether a similar antiviral effect is achievable in humans without toxic effects.

Utilizing equipment standard available in the clinical laboratory, the use of home-sampled dried VAMS and DBS is not a reliable tool for the monitoring of HbA1c. However, perfect agreement between HbA1c measured on wet VAMS and capillary microsamples was obtained.

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27SARS-CoV-2 rapidly spread around the globe after its emergence in Wuhan in December 28 2019. With no specific therapeutic and prophylactic options available, the virus was able to 29 infect millions of people. To date, close to half a million patients succumbed to the viral disease, 30 COVID-19. The high need for treatment options, together with the lack of small animal models 31 of infection has led to clinical trials with repurposed drugs before any preclinical in vivo 32 evidence attesting their efficacy was available. We used Syrian hamsters to establish a model 33 to evaluate antiviral activity of small molecules in both an infection and a transmission setting. 34Upon intranasal infection, the animals developed high titers of SARS-CoV-2 in the lungs and 35 pathology similar to that observed in mild COVID-19 patients. Treatment of SARS-CoV-2-36 infected hamsters with favipiravir or hydroxychloroquine (with and without azithromycin) 37 resulted in respectively a mild or no reduction in viral RNA and infectious virus. Micro-CT scan 38 analysis of the lungs showed no improvement compared to non-treated animals, which was 39 confirmed by histopathology. In addition, both compounds did not prevent virus transmission 40 through direct contact and thus failed as prophylactic treatments. By modelling the PK profile 41 of hydroxychloroquine based on the trough plasma concentrations, we show that the total lung 42 exposure to the drug was not the limiting factor. In conclusion, we here characterized a hamster 43 infection and transmission model to be a robust model for studying in vivo efficacy of antiviral 44 compounds. The information acquired using hydroxychloroquine and favipiravir in this model 45 is of critical value to those designing (current and) future clinical trials. At this point, the data 46 here presented on hydroxychloroquine either alone or combined with azithromycin (together 47 with previously reported in vivo data in macaques and ferrets) provide no scientific basis for 48 further use of the drug in humans. 49

New psychoactive substances (NPS) continue to appear on the drug market. Until recently, new synthetic opioids, which are amongst the most dangerous NPS, primarily encompassed analogues of the potent analgesic fentanyl. Lately, also other new synthetic opioids have increasingly started to surface. This is the first report on the identification and full chemical characterization of brorphine, a novel potent synthetic opioid with a piperidine benzimidazolone structure. Brorphine was identified in a powder and in the serum of a patient seeking medical help for detoxification. Liquid chromatography–high resolution mass spectrometry (LC–HRMS) identified an exact mass of m/z 400.1020 and 402.1005 for the compound, corresponding to both bromine isotopes. Further chemical characterization was performed by gas chromatography–mass spectrometry (GC–MS), LC–diode array detection (DAD) and Fourier-transform infrared (FT-IR) spectroscopy analyses. Finally, the structure was confirmed by performing 1H- and 13C-NMR spectroscopy. In vitro biological activity of brorphine was determined by a cell-based µ-opioid receptor (MOR) activation assay, resulting in an EC50 of 30.9 nM (13.5 ng/mL) and an Emax of 209% relative to hydromorphone, confirming the high potency and efficacy of this compound. In a serum sample of the patient, brorphine and a hydroxy-metabolite were found using the LC–HRMS screening method. The presence of opioid activity in the serum was also confirmed via the activity-based opioid screening assay. The occurrence of brorphine is yet another example of how the illicit drug market is continuously evolving in an attempt to escape international legislation. Its high potency poses a serious and imminent health threat for any user.

ObjectivesAs Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are the most commonly reported STIs in Belgium and the majority of women infected are asymptomatic, targeted screening of patients in specified risk groups is indicated. To prevent long-term complications and interrupt transmission, extragenital samples should be included. As this comes with a substantial extra cost, analysis of a pooled sample from vaginal and extragenital sites could be a solution. In this study, we evaluated the feasibility of molecular testing for CT and NG in pooled versus single-site samples in a large cohort of female sex workers.MethodsWomen were sampled from three anatomical sites: a pharyngeal, a vaginal and a rectal swab. Each sample was vortexed, and 400 µL of transport medium from each sample site was pooled into an empty tube. NAAT was performed using the Abbott RealTime CT/NG assay on the m2000sp/rt system.ResultsWe included 489 patients: 5.1% were positive for CT; 2.0% were positive for NG and 1.4% were coinfected, resulting in an overall prevalence of 6.5% (95% CI 4.5% to 9.1%) for CT and 3.5% (95% CI 2.0% to 5.5%) for NG. From the 42 patients positive on at least one non-pooled sample, only 5 gave a negative result on the pooled sample, resulting in a sensitivity of 94% (95% CI 79% to 99%) for CT and 82% (95% CI 57% to 96%) for NG. The missed pooled samples were all derived from single-site infections with low bacterial loads. The possibility of inadequate self-sampling as a cause of false negativity was excluded, as 4/5 were collected by the physician. Testing only vaginal samples would have led to missing 40% of CT infections and 60% of NG infections.ConclusionsPooling of samples is a cost-saving strategy for the detection of CT and NG in women, with minimal decrease in sensitivity. By reducing costs, more patients and more extragenital samples can be tested, resulting in higher detection rates.

There are few fields of medicine in which the individualisation of medicines is more important than in the area of oncology. Under‐dosing can have significant ramifications due to the potential for therapeutic failure and cancer progression; by contrast, over‐dosing may lead to severe treatment‐limiting side effects, such as agranulocytosis and neutropenia. Both circumstances lead to poor patient prognosis and contribute to the high mortality rates still seen in oncology. The concept of dose individualisation tailors dosing for each individual patient to ensure optimal drug exposure and best clinical outcomes. While the value of this strategy is well recognised, it has seen little translation to clinical application. However, it is important to recognise that the clinical setting of oncology is unlike that for which therapeutic drug monitoring (TDM) is currently the cornerstone of therapy (e.g. antimicrobials). Whilst there is much to learn from these established TDM settings, the challenges presented in the treatment of cancer must be considered to ensure the implementation of TDM in clinical practice. Recent advancements in a range of scientific disciplines have the capacity to address the current system limitations and significantly enhance the use of anticancer medicines to improve patient health. This review examines opportunities presented by these innovative scientific methodologies, specifically sampling strategies, bioanalytics and dosing decision support, to enable optimal practice and facilitate the clinical implementation of TDM in oncology.

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