Background In spite of high risk of mortality due to drug-induced QT interval prolongation (QTcP) usage among end stage renal disease patients (ESRD), no previous studies were conducted to assess medication safety of this drugs category among this vulnerable patients group. Objectives This study aimed to investigate the appropriateness and potential drug-drug interactions of QTcP-inducing drugs among ESRD patients in Jordan. Method This study was a cross-sectional retrospective study conducted in the outpatient clinics of 200 Jordanian healthcare facilities over three years (2017, 2018, and 2019) using Hakeem© database for data collection. CredibleMeds© was used to identify and categorise QTcP-inducing drugs. Drug-drug interactions and appropriateness of prescribing were assessed by Micromedex Drug Reax© software and a multidisciplinary committee, respectively. Results Of the 407 patients included, 954 drugs with risk of QTcP were dispensed; 618 (64.8%) had interactions with other drugs; 10.4% were major, 29.3% were moderate, and 60.3% were minor drug-drug interactions. Absence of major polypharmacy and co-morbidity decreased the odds of major drug-drug interactions by 61% (OR 0.61; 95% CI 0.23-0.97; p=0.02), and 72% (OR 0.72; 95% CI 0.44-1.23; p=0.04), respectively. After clinical evaluation, 17.6% of the dispensed drugs were considered inappropriate application, 12.9% were classified as inappropriate choice, and 26.4% were judged as inappropriate decision. Urology clinics were more likely to prescribe QTcP-inducing drugs based on inappropriate decision. Conclusion Major drug-drug interactions and dispensing medications with risk of QTcP based on inappropriate prescribing decisions for patients with ESRD were reported to be high in outpatient clinics in Jordan.

SARS COV-2 and its related disease COVID 19 has led to a major global pandemic and in absence of no known effective therapeutic agents against it, virus is having a free run. Sequence analyses, homology modelling and docking have suggested potential drugs which can be used against this virus. Sofosubivir is a direct-acting antiviral agent with NS5B RNA-dependent RNA polymerase (RdRp) inhibitory activity used in management of Hepatitis-C infection. This drug has potential role in managing this viral disease. Safety and efficacy of this drug is already established in patients of Hepatitis-C where it is given for long periods of time. Favourable pharmacokinetic profile of this drug also favors it use in this infection. This report summarises information available which can be explored further in clinical trials.

Aim: Till date, no proven treatment exists for coronavirus disease (COVID-19), though different types of treatment modalities are being practiced around the world. Small-scale convalescent plasma (CP) therapies from COVID-19 recovered donors have shown favorable results with fewer adverse consequences. In this systematic review, we aimed to determine the safety and efficacy of CP as a therapy for COVID-19. Methods: The English language databases of PubMed, Google Scholar, and ScienceDirect were searched upto 22 May 2020. Eligibility for inclusion, risk of bias assessment, and data extraction from the included studies was determined and a narrative synthesis was conducted. Results: A total of 12 studies were selected for review. The overall risks of bias was high. The results revealed that the initiation of CP therapy during the early stages of viremia was significant in a safety and efficacy viewpoint. The patients were also receiving concomitant drugs and other supportive therapies in 10 studies. Viral loads were documented to decrease and become negative in 8 studies within 3-26 days post-transfusion. The improvement in clinical symptoms following CP therapy was demonstrated in 9 studies. Most of the patients experienced very few adverse effects. There were a total of 622 mortalities out of 5079 patients in total studies. Conclusions: The rational practice of CP therapy based on a risk-benefit judgment can prove to be an efficacious therapeutic option until the approval of any therapeutic and/or prophylactic agent(s), though substantial randomized controlled trials (RCTs) are necessary to validate the effectiveness of such therapy.

Aims: The purpose of the present research was to evaluate the cost-effectiveness of oral alendronate for individuals with osteoporosis. We also assessed the impact of medication compliance and persistence on economic outcomes of alendronate, and potential economic evaluations of persistence-enhancing interventions. Methods: We constructed an individual-level state-transition model to project health outcomes and costs of oral alendronate for Chinese postmenopausal osteoporotic women. The impact of medication compliance and persistence on economic evaluation was addressed in various scenario analyses. Model inputs were derived from clinical trials and published sources where available. Deterministic and probabilistic sensitivity analyses were conducted to explore the impact of uncertainties and assumptions on the cost-effectiveness results. Results: Compared to no treatment, alendronate treatment was associated with an additional 0.052 QALYs at an additional cost of USD 738, which yielded an ICER of USD 14,192.308/QALY. The ICER for the different scenarios (full compliance, full persistence, both full persistence and full compliance) were USD 4933.333/QALY, USD 3006.84/QALY and USD 2019.822/QALY, respectively. One-way sensitivity analysis showed the ICER was most sensitive to variations in time horizon and residual effect. Probabilistic sensitivity analysis demonstrated that, at a willingness-to-pay of USD 29,340/QALY, the probability that oral alendronate therapy will be cost-effective is approximate 80%. Conclusions: The findings support the view that oral alendronate is cost-effective for the treatment of osteoporotic fractures in Chinese postmenopausal women. Medication persistence is found to have a greater impact on cost-effectiveness than compliance, and interventions to improve persistence to be an efficient use of resources.

A peer-reviewed article of this Preprint also exists. Journal: InflammopharmacologyDOI:  https://doi.org/10.1007/s10787-020-00755-x This article discusses from a pharmacological point of view, the points of weakness in a correspondence published at the Lancet Respiratory Medicine that has suggested a hypothesis relating ACEIs, ARBs and ibuprofen to be associated with a higher risk for COVID-19 infection and complications. This article also explains some unfortunate mistakes that have been made by some who have adopted this hypothesis and decided to unwisely recommend against these important drugs.

Antibiotic concentration in pancreas tissue is very important for the treatment of severe acute pancreatitis (SAP) with infection. We report a case of a 44-year-old female with SAP on treatment of vancomycin. The time courses of vancomycin concentration in serum and pancreas tissue of the patient was described. This case demonstrated that it took about 30 minutes for vancomycin to get through from serum to pancreas tissue and about 76% of vancomycin could move into pancreas tissue for SAP patients.

Aim To identify common drug-related problems (DRPs) during pharmaceutical intervention and consultation in an intensive care unit (ICU); to explore the gap between physicians and pharmacists on their understanding of each other’s capabilities and needs. Method A single-center prospective study was conducted in the ICU of a tertiary academic hospital for 21 months. A pharmaceutical care (PC) model was implemented by pharmacy care team, and data was collected during pharmaceutical intervention and consultation. Data analysis was performed on identified DRPs, causes and their relationships. DRPs’ frequency during intervention and consultation was compared. Problem-level descriptive analysis and network analysis were conducted using R 3.6.3. Result Implementation of PC model greatly improved the efficacy of pharmacists in both interventions proposed to solve DRPs (from 13.6 to 20.1 cases per month) and number of patients being closely monitored (from 7.7 to 16.9 per month). Pharmacists identified 427 DRPs during pharmaceutical intervention with primarily adverse drug events (ADEs, 34.7%) and effect of treatment not optimal (25.5%), and 245 DRPs during consultation (mainly ADEs, 58.4%). About three-fifths DRPs were caused by antibiotics. Comparing DRPs identified during pharmaceutical intervention and consultation, physicians consulted pharmacists more on questions related to medication safety, while pharmacists also paid attention to treatment effectiveness being consulted less commonly. Conclusion Implementation of PC model is beneficial in guiding pharmacy practice and improving efficacy especially under limited human resources. Physicians and pharmacists shall continue ensuring drug safety and be familiar with the scope of PC and clinical need for a better cooperation.

Aim: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that has no approved treatment. There are some medications which may be prescribed for COVID-19 patients as investigational treatments. Drug-drug interactions (DDIs) of medications used in treating COVID-19 is an important issue to be studied. Current study aimed to evaluate potential DDIs (pDDIs) and their predictors in hospitalized COVID-19 patients. Methods: A retrospective chart review study was conducted in a tertiary respiratory hospital dedicated for COVID-19 patients. Interacting drug combinations, severity, reliability, mechanism, and clinical management of pDDIs in confirmed COVID-19 cases were identified using the Lexi-Interact database. Logistic regression was applied to assess the correlation between occurrence of severe interactions and probable risk factors. Results: Two hundred and twenty-seven patients’ medical charts were evaluated. About 68% of the patients had at least one comorbidity. The most common comorbidity was hypertension (30.4%), followed by obesity (27.8%) and diabetes (23.8%). At least one major or contraindicated interaction was detected in 37.9% of the patients. Above 50% of the interactions were between lopinavir/ritonavir (protease inhibitor) and commonly prescribed medications (e.g. atorvastatin, alprazolam, salmeterol, and tamsulosin) for management of comorbidities or COVID-19 symptoms. Logistic regression analysis demonstrated that two comorbidities (IHD and CRDs) and ICU admission are significantly associated with occurrence of major or contraindicated pDDIs. Conclusion: The frequency of pDDIs is relatively high in COVID-19 patients. Patients receiving a protease inhibitor and having comorbidity or critical conditions should be monitored carefully in terms of DDIs.

Mitotane is the only drug approved for treating adrenocortical carcinoma (ACC) by the FDA since 1959, despite the controversy regarding its efficacy in prolonging patient survival. This drug has cytotoxic effects on tumor tissue by inducing cell death and antisecretory effects on adrenal cells by inhibiting the synthesis of adrenocortical steroids involved in the pathogenesis of ACC. To reach the therapeutic plasma concentration, high doses of mitotane are usually necessary, which may result in several adverse effects. This suggests that important pharmacological features are involved in the mechanisms of action of this drug, such as first pass metabolism, tissue accumulation, and extensive time needed for drug elimination. However, few studies have reported the pharmacological aspects of mitotane, and they did not provide sufficient evidence regarding monitoring mitotane’s therapeutic effects. Therefore, this review summarized the chemistry, pharmacokinetics and pharmacodynamics, therapeutic effects, toxic effects, and new perspectives of mitotane treatment that are currently under investigation. Understanding the pharmacological profile of mitotane can improve the monitoring and efficacy of this drug in ACC treatment and can further provide useful information for the development of new drugs with specific action against ACC with fewer adverse effects.

Aim To observe the clinical effect of small splint fixation and Gukangling-Fluid in the treatment of patients with closed trauma fractures. Materials and Methods Methods: the patients were divided into two groups: 350 cases of Gukangling-Fluid treatment group and 84 cases of conventional western medicine plaster control group. Results Results statistically significant difference was found between the two groups (P<0.001). The total effective rate of the experimental treatment group was 92 %, and that of the conventional western medicine control group was 72 %. Conclusion Gukangling-Fluid has a good effect on the treatment of closed fracture.

Aim To observe the clinical efficacy and healing time of small splint fixation and Gukangling-Flquid in the treatment of patients with closed traumatic fracture treated with conventional western medicine plaster fixation. Methods The patients were divided into two groups:Gukangling-Flquid treatment group and western medicine conventional plaster control group. Results The total effective rate of the experimental treatment group was higher than that of the conventional western medicine control group. Conclusion Gukangling-Flquid has a good curative effect on the treatment of closed fractures. The clinical healing time of Gukangling-Flquid is one third earlier than that of conventional western medicine.

Nowadays the prescription of off-label in psychiatric practice is very common, exclusively in the pregnant women, pediatric and geriatric groups due to the lack of available standards and alternatives, that elevate the safety issue in the vulnerable groups. This observational study performed in a Tertiary Care Teaching Hospital for six months prospectively and retrospectively. It involved 549 patients with a mean age of 37.13 ± 12.62 years (range 9–81 years) and male: female ratio was 1:1.3, showing a higher incidence of the female population as compared to previous Indian studies which reported a higher population of males. We found approximately 1550 drugs prescriptions in which the 44% were antipsychotic and antidepressants. The indication of drugs was found to be 560 in numbers, in which 31.5% of drugs prescription not found any distinguish indication. Amitriptyline 19.51% was the most commonly prescribed drug followed by the Escitalopram 17.0%, Clonazepam 12.1%, Fluoxetine 11.2%, Sertraline 6.5%, etc. Also the various adverse effect association recorded with this prescribing pattern. The off-label prescription was ascertaining with the application of drug package insert (US-FDA) and National formulary of India 2011 and 2016 was used as a reference basis to ascertain the off-label prescribing. Wide variability was noticed in prescribing practices among clinicians, however it is not limited to psychiatric only. The conclusion of the study underlined a prerequisite accountability of healthcare professional on the way to safe medication practices through a lot of scientific evidence for the risks and benefits profiling of off-label medication

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the global pandemic and caused hundreds of thousands of people died in the world, which is in urgent need to develop new drug therapy and pathogen progressive information. Although abundant anti-viral drugs has been directly practiced in some patients, there are no specific drug treatment due to the new SARS-CoV-2 virus, which cause great disaster and panic all over the world. Remdesivir has been recently a strong candidate for the treatment of COVID-19. Recently, due to the support of antiviral experiments in vitro and a case report by compassionate use of the drug, remdesivir has been a promising candidate treatment for the treatment of COVID-19. As a broad-spectrum anti-viral compound targeting the viral RNA dependent RNA polymerase, remdesivir has been shown to suppress the coronavirus, such as SARS-CoV and MERS-CoV. However, is remdesivir really a magic bullet for COVID-19, also a coronavirus? In this article, we first overview the general information about SARS-CoV-2 and its potential suppressing drug remdesivir. Then, we carefully discussed the limitation with the remdesivir antiviral study, including the case report by compassionate use of remdesivir. Finally, from the pharmaceutical perspective we explored the anti-virus capability of remdesivir against different viruses to see whether it’s a magic bullet for COVID-19. Therefore, this paper provides crucial evidence and objective theoretical basis on remdesivir to cure COVID-19 infections.

Background The aim of the present theoretical essay is to evaluate evidence published on the characteristics of the transcription of SARS-CoV-2 and explain the mechanism of action of ivermectin that may justify its therapeutic use in clinical practice for the treatment of COVID-19. Methods Laboratory studies, narratives, editorials and expert opinions on the subject were identified through a systematic search of the literature in the Medline/PubMed, Cochrane Library, Web of Science and Embase databases. Two blinded, independent reviewers selected studies published up to May 17, 2020 based on the eligibility criteria. Results The search of the databases led to the retrieval of 25 articles. After the different phases of the selection process, eight articles were included in the present review for the extraction of relevant data. The results suggest that ivermectin inhibits the viral replication of SARS-CoV-2 through the action of the hypoxia-inducible factor (HIF-1α) and consequent destabilization of importin α/β1 proteins. Conclusions Ivermectin inhibits the viral replication of SARS-CoV-2. Laboratory and clinical studies are needed to provide more evidence in terms of the best posology and possible associations with other drugs for combatting COVID-19.

Diffuse Large B-Cell Lymphoma is the most common type of Non-Hodgkin’s Lymphoma. The disease exhibits significant clinical and biologic heterogeneity. Treatment with standard first line therapy results in cure in about 60% of patients while 30-40%of patients either are refractory to therapy or relapse. Current prognostic scores and biomarkers are unable to accurately predict patients who would relapse or would have refractory disease. A part of the heterogeneity in the behavior of DLBCL is explained by the cell of origin of the tumor. Germinal center type (GCB) DLBCL which is derived from centroblasts are associated with better prognosis compared with activated B-cell type (ABC), which is derived from a B-cell committed to secretory differentiation. While the gold standard for cell of origin determination is gene expression profiling, immunohistochemical methods are routinely used because of more readily available fixed tissue and expertise. Immunohistochemical methods are however associated with a significant degree of discordance with GEP. Within the ABC and GCB types of DLBCL, subgroups of prognostic significance have been identified using various multiple approaches which do not inure themselves to routine practice partly because of limitation of diagnostic material or expertise. Exosomes are a class of membrane bound extracellular vesicles of endosomal origin, produced by multiple cell types. They are involved in intercellular communication and present in abundance in various bodily fluids. Exosomal cargo which includes nucleic acids and proteins can be analyzed, yielding diagnostic and prognostic information in management of DLBCL.

Objective: Appropriate use of oral anticoagulants (OACs) reduces the risk of stroke in patients with atrial fibrillation (AF). The study characterised the prescribing of OACs in people with AF in the Australian primary care setting over 10 years. Methods: We performed 10 sequential cross-sectional analyses of patients with a recorded diagnosis of AF between 2009 and 2018 using nationally representative general practice data from the NPS MedicineWise’s dataset, MedicineInsight. The proportion of patients with AF who were prescribed an OAC based on their stroke risk was examined. Results: The sample size of patients with AF ranged from 9,874 in 2009 to 41,751 in 2018. The proportion who were prescribed an OAC increased from 39.5% (95% CI 38.6%-40.5%) in 2009 to 52.0% (95% CI 51.5%-52.4%) in 2018 (p for trend <0.001). During this time, the proportion of patients with AF and high stroke risk who were prescribed an OAC rose from 41.7% (95% CI 40.7%-42.8%) to 55.2% (95% CI 54.7%-55.8%; p for trend <0.001) with the direct-acting oral anticoagulants accounting for over three-quarters of usage by 2018. There was substantial variation in OAC prescribing according to stroke risk between general practices. In 2018, the proportion of moderate to high stroke risk patients who were prescribed an OAC was 38.6% (95% CI 37.2%-40.1%) in the lowest practice site quintile and 65.6% (95% CI 64.5%-66.7%) in the highest practice site quintile. Conclusions: Over the ten years, OAC prescribing in high stroke risk patients with AF increased by one-third.

Aims: The aim of this double-blind randomized clinical trial was to determine the effects of FBX in comparison with hydroxychloroquine (HCQ) on clinical symptoms, laboratory tests and chest CT findings in patients with COVID-19-causing moderate symptomatic disease. Methods: We conducted a randomized, double blind clinical trial involving adult outpatients’ patients with COVID-19 infection, which causes the moderate respiratory illness. Sixty patients were randomly assigned to receive either FBX or HCQ for 5 days. The measured variables were clinical and laboratory data including rate of fever, cough, berating rate, C-Reactive Protein level, lymphocytes count at onset of admission and was well as at 5 days of treatments. In addition, CT lesions were evaluated on admission and 14 days of treatments in both groups. Results: Fever, cough and tachypnea significantly mitigated in both groups after five days of treatments. The lymphocytes count significantly increased in both treatment groups and the CRP values were dropped in normal range (negative) in major of patients receiving FBX or HCQ treatment. It was not observed any significantly difference between FBX and HCQ in frequency of these symptoms. The mean percentages of CT abnormality scores were significantly reduced to 7.3% and 8% after 14 days of FBX and HCQ treatments, respectively. In adult outpatients with moderate symptomatic Covid-19, the effectiveness of FBX was same to HCQ in improvement of clinical manifestations, laboratory tests and CT lesions. Conclusion: These findings suggest FBX as an alternative treatment for Covid-19 infection in patients with contraindication or precaution to HCQ.

Aims: To assess whether randomized clinical trials (RCTs) proposed to evaluate treatment of COVID-19 with HQ or chloroquine include outcome definitions and data collection plans to produce meaningful efficacy/effectiveness and safety outcomes. Methods: We searched the World Health Organization International Clinical Trials Registry Platform (WHO-ICTRP) database for registers of RCTs evaluating HQ or chloroquine, alone or in any combination, to treat patients diagnosed with COVID-19 compared with any other treatment option. The final search was performed on April 8th, 2020. Results: Among 51 registered RCTs (median sample size of 262; IQR: 100, 520), 34 (67%) reported a clinical outcome, 12 (24%) a surrogate outcome, and five (10%) a combination of clinical and surrogate outcomes as primary endpoints. Clinical status/recovery and all-cause mortality/mortality accounted for 49% of the unique domains among 20 different clinical outcome domains of efficacy. Twenty-four (47%) RCTs did not describe plans to assess safety outcomes; when assessed, safety outcomes were determined in generic terms of total, severe or serious adverse events. Conclusions: The RCTs investigating HQ or chloroquine include heterogenous and insufficient approaches to measure efficacy/effectiveness and safety that are relevant to patients and clinical practice. These findings provide important insights to inform clinical and regulatory decisions that can be drawn about the efficacy/effectiveness and safety of these agents in patients with COVID-19.

Since the advent of COVID-19 as a pandemic, multiple therapeutic options have been looked into as possible options for the management of COVID-19 disease. Remdesivir, a broad-spectrum anti-viral, has since been given Emergency Use Authorization by the US Food and Drug Agency (FDA). While cohort studies have shown benefit in the use of Remdesivir, the only Randomized Controlled Trial showed no statistically significant clinical benefit, and the other results from a trial by the NIH has only shown some benefit in reducing hospital admission in early results prior to peer review. In this scenario, with data lacking, is it justified for Remdesivir to be given Emergency Use Authorization?

Aim To assess clinical outcomes and adverse drug events in patients hospitalised with COVID -19 treated with off- label hydroxychloroquine and azithromycin. Methods We performed a retrospective analysis of hospitalised COVID-19+ patients who received hydroxychloroquine plus azithromycin over a 2 week period. The primary end point was clinical improvement on day 7 defined as either hospital discharge or an improvement of two points on a six-category ordinal scale. Secondary outcomes evaluated included mortality at day 28, ICU admission, requirement for mechanical ventilation and incidence of adverse drug events. Results Data from a total of 82 patients with laboratory confirmed SARS-CoV-2 infection was evaluated. Clinical improvement was seen in 26.8% of patients at Day 7. 31% of patients were admitted to ICU, 16 (19.5%) underwent mechanical ventilation and Day 28 mortality was 28%. Age over 70, history of cardiovascular disease and 3 or more comorbidities were risk factors for mortality. The incidence of adverse drug events was 42%. No patient experienced a Grade 4 or 5 toxicity. Over a fifth of patients (23) had raised LFTs (65% had raised LFTs at baseline), 11 patients experienced prolonged QT and 1 patient experienced grade 1 hypoglycaemia. Treatment was stopped early in 6(7.3%) patients due to prolonged QT interval or LFT elevations. Conclusion This descriptive study details the clinical outcomes of COVID-19 positive patients treated with these agents and highlights the importance of monitoring all repurposed agents for adverse drug events.

Aims This study aimed to develop a parent-metabolite joint population pharmacokinetic model to characterize the pharmacokinetic (PK) profile for phosphocreatine (PCr) and its metabolite creatine (Cr) in children with myocarditis, and to use this model to study the PK profile of different dosing schemes. Methods One hundred pediatric patients with myocarditis were enrolled. Blood samples were collected at baseline and, approximately 30, 40 or 50, 75 and 180 min after a single dose of phosphocreatine sodium. Plasma PCr and Cr concentrations were determined using a HPLC-MS/MS method. A nonlinear mixed-effects model approach was used to build the population pharmacokinetic model. After validation, the model was used for simulations to evaluate the PK profile of different dosing schemes. Results A total of 997 plasma concentrations (498 for PCr and 499 for Cr) were included in the analysis. A four-compartment chain model (central and peripheral compartments for both PCr and Cr) with first-order elimination adequately characterized the in vivo process of PCr and Cr. Allometric scaling based on bodyweight was applied to the PK parameters. The covariate analysis identified that the glomerular filtration rate (GFR) was strongly associated with the Cr clearance. Bootstrap and visual predictive check suggested a robust and reliable pharmacokinetic model was developed. The simulation results showed that the PCr had no accumulation in vivo. With the infusion of PCr, the concentration of Cr increased rapidly. Conclusion The joint population pharmacokinetic model for PCr and Cr in pediatric patients with myocarditis was successfully developed for the first time.

Aim: CQ and HCQ are currently being investigated worldwide for their clinical efficacy against COVID-19, however a major concern regarding these drugs remains their safety profile. The aim of the present study was to identify potential safety signals of CQ and HCQ use, in the period prior to their repurpose as COVID-19 treatment options analyzing safety data retrieved from the FDA Adverse Event Reporting System (FAERS) pharmacovigilance database. Methods: We performed a disproportionality analysis of all available FAERS data between the first quarter of 2004 and December 2019 using the OpenVigil2.1-MedDRA software. Disproportionality was quantified using the reporting odds ratio (ROR) and its 95% confidence interval (CIs). The reporting mortality of CQ and HCQ was also investigated Results: The dataset contained 6,635,356 reports. Based on the comparison of the RORs, significant differences were observed between CQ and HCQ for most of the adverse events: cardiomyopathy, cardiac arrhythmias, retinal disorders, corneal disorders, hearing disorders, headache, hepatic disorders, severe cutaneous reactions, musculoskeletal disorders and cytopenia. Only CQ was significantly associated with psychotic disorders, suicide and self-injury, convulsions, peripheral neuropathy and decreased appetite. In multivariable logistic regression, outcome death was more frequently associated with CQ users, generally older females, with co-reported suicide and self-injury, cardiomyopathy, cardiac arrhythmias and decreased appetite. Discussion: Our results suggest that HCQ has a safer clinical profile compared to CQ, especially regarding cardiotoxicity and thus could serve as a safer therapeutic approach in COVID-19. However, until more real-world and RCTs’ data are available, close supervision is strongly recommended.

Background: ABCB1, EPHX1 and SCN1A gene polymorphisms have been reported play important roles in individual variability carbamazepine (CBZ) metabolism and resistance, but the result of that association still remains controversial. Objective: To clarify the associations among ABCB1, EPHX1 and SCN1A gene polymorphisms and CBZ metabolism and resistance. Methods: The PubMed, EMBASE, Cochrane library, Chinese National Knowledge Infrastructure, Chinese Science and Technique Journals Database, China Biology medicine disc and Wan Fang Database were searched for appropriate studies up to April 2020. Results: A total of 18 studies involving 3293 related epilepsy patients were included. ABCB1 c.3435C>T polymorphism was significantly associated with adjusted concentrations of CBZ (CC vs. CT, P=0.004), and EPHX c.416A>G polymorphism was significantly associated with carbamazepine-10, 11-trans dihydrodiol (CBZD) (AA vs. GG, P=0.045; AG vs. GG, P=0.010). Furthermore, ABCB1 c.3435C>T polymorphism was also observed to be significantly influenced CBZ resistance (CT vs TT, P=0.01; CC+CT vs TT, P=0.006). Conclusion: ABCB1 c.3435C>T polymorphism may affect the CBZ metabolism and resistance, EPHX1 c.416A>G polymorphism may only affect CBZ metabolism. These findings provided further evidence for individualized therapy of epilepsy patients in clinics. Nevertheless further large studies are still warranted to provide conclusive evidences.

This article summarizes the effects of sivelestat on ALI/ARDS or ARDS with coagulopathy, both of which are frequently seen in patients with COVID-19. The emergence of the novel 2019-nCoV infection has been a global pandemic. The following databases were searched to identify relevant literature concerning empirical evidence: The Cochrane library, Pubmed, Medline, EMBASE from 1980 through March 2020. COVID-19 patients are more susceptible to thromboembolic diseases including DIC. In this connection, various studies have emphasized on the role of neutrophil elastase (NE) in the development of DIC in patients with ARDS and sepsis. It has been shown that NE inhibition by sivelestat mitigates ALI through amelioration of alveolar epithelium and vascular endothelium injuries as well as reversing the activated neutrophil-mediated increased vascular permeability. Sivelestat is a selective NE inhibitor has not been evaluated for its possible therapeutic effects against SARS-CoV-2 infection and/or COVID-19. Nevertheless, based on its promising beneficial effects in underlying complications of COVID-19, sivelestat could be considered as a promising treatment for the management of ALI/ARDS or coagulopathy in patients with COVID-19.