Immunosuppressant drugs like Etanercept, Mycophenolate mofetil, Sirolimus, Cyclosporine and Rituximab can weaken the immune system and make patients susceptible to SARS nCoV-2 virus. These drugs make immunocompromised persons more vulnerable to complications associated with COVID-19. Moreover, it can also increase the mortality and morbidity, as a weakened immune system can lead to longer duration of infection. This study discusses the guidelines on immunosuppressant drugs and its associated risk factors with COVID-19, issued by the U.S CDC (Centers for Disease Control and Prevention), WHO (World Health Organisation), U.S FDA (Food and Drug Administration) and other accredited global health organisations. Moreover, it also includes information about pharmaceutical properties, mechanism of action, COVID-19 associated risk factors, adverse drug reactions, contraindications and drug-drug interactions. Our study will help government partners and international health organisations to better understand COVID-19 health risks associated with immunosuppressants. Increased public awareness about effective drug therapy for autoimmune diseases, cancer treatment, immunocompromised and organ transplant patients will help lower the mortality and morbidity associated with the disease amid COVID-19 pandemic.

Herein we report a case of a ten years old boy with rare clinical manifestations associated with COVID-19, in which the first clinical symptoms were urticaria and fever, and then he developed arthritis. The possibility of post-COVID-19, reactive arthritis, or postinfectious arthritis can be expected from this virus.

5 Key points: • As an aerosol-generating procedure (AGP), tracheostomy poses significant viral transmissions risks to health care workers • The decision about tracheostomy method and optimal setting depends on a multitude of local factors with no available studies to suggest the superior option • We describe our effective, safe and swift approach to bedside open tracheostomy during the COVID-19 pandemic • A key approach in performing an effective bedside tracheostomy is to ensure that the procedure is standardised and performed by highly experienced surgeons, anaesthetist and scrub team. • Our experience with bedside open tracheostomy demonstrated a short mean procedural time, with no tracheostomy-related complications and no reported viral transmission amongst the healthcare members involved.

There is evidence of increased incidence, rapid progression, and poor prognosis of Covid-19 in patients with underlying comorbidities such as diabetes and epilepsy. It is crucial to develop effective treatment regimens for these patients. Multiple organ failure is the most common cause of death in Covid-19 patients.

Acute epibulbar infections are one of the most frequently diagnosed ophthalmologic infections. They are usually self-limiting but can lead to a viral preseptal cellulitis mimicking a severe bacterial infection. Early diagnosis is important to shorten the course of recovery.

Coronavirus can lead to overcoagulation, blood stasis, and endothelial damage resulting in thromboembolic disorders. We report a 22-year-old pregnant woman with coronavirus admitted due to the pulmonary emboli. This case highlights the importance of considering a new category for COVID-19 pregnant patients with venous and arterial thromboembolic disorders.

Acute transverse myelitis is a rare disease that can behave either in a benign course where it may end up in full neurologic recovery, or permanent neurologic sequelae and death. This report describes a 52-year-old male who presented with features of acute transverse myelitis associated with COVID-19.

Coronavirus disease (COVID-19) is an emerging infectious disease. There may be a correlation between heatstroke and severity of COVID-19. In cases where heat stress caused by COVID-19 promotes organ failure, the proactive regulation of body temperature may be considered as an effective treatment option.

Aim COVID-19 outbreak spread all over the world and created a public health catastrophe. Here, we have aimed to conduct a systematic review and meta-analysis on remdesivir use for COVID-19. Methods We searched Pubmed, Pubmed Central, Scopus, Embase, clinicaltrials.gov, and preprint sites and identified ten studies for qualitative and four studies for quantitative analysis using PRISMA guidelines. The quantitative synthesis was performed using fixed and random effect models in RevMan 5.4. Heterogeneity was assessed using the I-squared (I2) test. Results Comparing remdesivir group with placebo or standard of care (SOC) group, remdesivir reduces 14 days mortality (OR 0.61, CI 0.41- 0.91), need of mechanical ventilation (OR 0.73, CI 0.54-0.97), and overall severe adverse effects (OR 0.69, 95% CI 0.54 to 0.88). There is better clinical improvement on day 28 (OR 1.59, CI 1.06- 2.39); day 14 clinical recovery (OR 1.48, CI 1.19-1.84); day 14 discharge rate (OR 1.41, CI 1.15-1.73) among remdesivir groups. Earlier clinical improvement (MD -2.51, CI -4.16 to -0.85); and clinical recovery (MD -4.69, CI -5.11 to -4.28) seen among remdesivir group. While no difference on 28 days mortality rate; discharge rate; overall adverse effect. Longer course (10 days) of remdesivir showed higher discharge rate at day 14 (OR 2.11, CI 1.50-2.97), but there are significantly higher rates of serious adverse effects, and drug discontinuation than the shorter course. Conclusion Remdesivir showed a better 14 days mortality profile, clinical recovery, and discharge rate. Overall clinical improvement and clinical recovery were earlier among remdesivir group.

A 13-month-old healthy patient without COVID-compatible symptoms and no known sick contacts presented to the emergency department with an esophageal coin. New institutional policy requiring pre-operative SARS-CoV-2 testing was positive for the virus. Additional precautions were taken in the operating room to successfully prevent transmission of the virus.

Abiotrophia defectiva (A defectiva), a rare cause of bacterial infective endocarditis(IE) often presents with pyrexia and florid sepsis. This case highlights that A defectiva IE can present non-specifically in older frail patients without classical clinical findings. A. defectiva may be associated with a high proportion of culture-negative IE.

Aim Patients on anti-tuberculosis (anti-TB) therapy are at risk of drug-induced liver injury (DILI). MicroRNA-122 (miR-122) and cytokeratin-18 (K18) are exploratory DILI biomarkers. To explore their utility in this global context, circulating miR-122 and K18 concentrations were measured in UK and Ugandan populations on anti-TB therapy for mycobacterial infection. Methods European patients receiving anti-TB therapy were recruited at the Royal Infirmary of Edinburgh, UK (ALISTER-ClinicalTrials.gov Identifier: NCT03211208). African patients with HIV-TB coinfection, receiving anti-TB and anti-retroviral therapy (ART), were recruited at the Infectious Diseases Institute, Kampala, Uganda (SAEFRIF-NCT03982277). Serial blood samples, demographic and clinical data were collected. MiR-122 was quantified using PCR. K18 was quantified using the M65 ELISA. Results The study had 235 participants (healthy volunteers (n=28); ALISTER: active TB (n=30), latent TB (n=88), non-tuberculous mycobacterial infection (n=25); SAEFRIF: HIV-TB coinfection (n=64)). In the absence of DILI, there was no difference in miR-122 and K18 across the groups. Both miR-122 and K18 correlated with alanine transaminase activity (ALT) (miR-122: r=0.52, 95%CI=0.42-0.61, P<0.0001. K18: r=0.42, 95%CI=0.34-0.49, P<0.0001). There were two DILI cases: baseline ALT was 18 and 28 IU/L, peak ALT 431 and 194 IU/L; baseline K18 58 and 219 U/L, peak K18 1247 and 3490 U/L; baseline miR-122 4 and 17 fM, peak miR-122 60 and 336 fM, respectively. Conclusion In European and African patients treated with anti-TB therapy miR-122 and K18 correlated with ALT and increased with DILI. Further work should determine the diagnostic and prognostic utility of miR-122 and K18 in this global context-of-use.

Kikuchi–Fujimoto disease (KFD) is a rare disease characterized by cervical lymphadenopathy, fever, and skin rash. The KFD can be confused with other conditions including lymphoma, autoimmune, and hematological diseases, which can lead to misdiagnosis of KFD as a clinical identity. Another condition can be novel coronavirus disease 2019 (COVID-19).

Timely intravenous (IV) to oral antimicrobial switch (IV-oral-switch) is a key antimicrobial stewardship (AMS) strategy. A retrospective audit was undertaken to determine concordance with IV-oral-switch guidelines in the context of a long-standing, tightly regulated AMS program. Data from 107 general medical and surgical patients in an Australian hospital were analysed. Median duration of IV antimicrobial courses before switching to oral therapy was 3 days (interquartile range, 2.25-5.00). Timely IV-oral-switch occurred in 57% (n=61) of patients. The median delay to switching was 0 days (IQR 0 to 1.25). In most courses (92/106, 86.8%), the choice of oral alternative after switching was appropriate. In 45% (47/105) of courses, total duration of therapy (IV plus oral) exceeded the recommended duration by >1.0 day. Excessive IV antimicrobial duration was uncommon at a hospital with a tightly regulated AMS program. Total duration of therapy was identified as an AMS target for improvement.

AIM: We propose the use of in silico mathematical models to provide insights that optimize therapeutic interventions designed to eradicate respiratory infection during a pandemic. A modelling and simulation framework is provided using SARS-CoV-2 as an example, considering applications of both treatment and prophylaxis. METHODS: A target cell-limited model was used to quantify the viral infection dynamics of SARS-CoV-2 in a pooled population of 105 infected patients. Parameter estimates from the resulting model were used to simulate and compare the impact of various interventions against meaningful viral load endpoints. RESULTS: Robust parameter estimates were obtained for the basic reproduction number, viral release rate and infected-cell mortality from the infection model. These estimates were informed by the largest dataset currently available for SARS-CoV-2 viral time course. The utility of this model was demonstrated using simulations, which hypothetically introduced inhibitory or stimulatory drug mechanisms at various target sites within the viral life-cycle. We show that early intervention is crucial to achieving therapeutic benefit when monotherapy is administered. In contrast, combination regimens of two or three drugs may provide improved outcomes if treatment is initiated late. The latter is relevant to SARS-CoV-2, where the period between infection and symptom onset is relatively long. CONCLUSIONS: The use of in silico models can provide viral load predictions that can rationalize therapeutic strategies against an emerging viral pathogen.

Aims: This article describes the report of a rare case of fungal ball in the frontal sinus in an adult male and discuss about the variables of this condition related to the patient. Additionally, this study aims to identify the state of the art of fungal ball in paranasal sinuses, especially in the frontal sinus. Method: We performed a literature review on fungal ball in the paranasal sinuses and described a rare case of fungal ball in the frontal sinus, which is listed as the paranasal sinus most rarely affected by fungal ball. Result: All reported cases of fungus ball in the frontal sinus affected male patients, contrary to the common prevalence of females in fungal ball of the other paranasal sinuses. Of the total of 8 patients with fungal ball in the frontal sinus reported, 40% had unilateral disease and 60% bilateral, also contrary to the incidence data of the other paranasal sinuses, with unilateral prevalence. However, with the present study, this index changes, with 50% unilateral and 50% bilateral in frontal sinus involvement. The average age of cases reported in the frontal sinus is 65.29 years, with a minimum age of 61.16 and a maximum of 69 years. As for the etiologic agent, Aspergillus sp., the endonasal endoscopic therapeutic approach corresponded to 80% of cases, while frontal osteoplasty accounted for 20% of cases, reaffirming this prevalence data from other studies. Conclusion: Despite being a low incidence entity, frontal sinus fungal ball should be considered in patients with pain in the frontal region refractory to the usual clinical treatments. We hope to contribute to the knowledge of this presentation as a differential diagnosis and reinforce the importance of thorough clinical investigation.

Aims: Emodepside is an anthelmintic, originally developed for veterinary use. We investigated the safety, pharmacokinetics, relative bioavailability and dose linearity of four oral formulations of emodepside in healthy male subjects. Methods: Three randomised, parallel‐group, controlled, Phase I studies were conducted using various oral formulations, involving 79 subjects in ten cohorts in the single-ascending-dose study, 24 subjects in three ascending-dose cohorts in the multiple-ascending-dose study and 77 subjects in seven different cohorts in the relative bioavailability study. Pharmacokinetics and safety assessments were performed up to 21, 30 and 7 days, respectively. Results: As a liquid service formulation, emodepside was rapidly absorbed under fasting conditions, with dose-proportional increases in plasma concentrations at doses from 1 mg to 40 mg. The half-life during the first 24 hours after dosing was around 11 hours, followed by a terminal elimination half-life > 500 hours. Emodepside was less bioavailable in the fed state. The rate of absorption was slower and Cmax was lower with the amorphous solid dispersion tablets compared to the liquid service formulation. Emodepside was well tolerated overall with no major safety concerns. Conclusion: These Phase I studies with various dosage forms revealed a pharmacokinetic profile suggesting good tissue distribution of emodepside and a long terminal half‐life. A 15 mg dose with the gastrosoluble tablet is predicted to provide exposure that will achieve the target concentration for clinical efficacy. These data enabled us to select a field-adapted tablet formulation that will open the way for further clinical development of emodepside in individuals with onchocerchiasis.

Abstract Patients at risk of severe forms of COVID 19 share metabolic disturbances, diabetes, hypertension, among which dysregulation of antioxydant defence mechanisms and orientation toward Th17 immunological response are predisposing factors for severe cellular lesions of Covid infection. We propose to act on NrF2, so as to protect tissues from oxydative burst, and cellular lesions characteristic of hyperinflammation of Covid 19. Bardoxolone acts upon Nrf2 and represses NfKappa B. It has been evaluated in diabetic nephropathy, but some patients suffered from overhydration and cardiac failure (Beacon study). In Covid infection, benefit-risk equation is different from long term use of this drug in diabetic nephropathy, in a disease potentialy lethal in a couple of weeks, with a short term risk of overhydration which could be seen as quite negligeable with a daily monitoring of weight. We advocate for an evaluation of Bardoxolone in recently infected Covid patients, with severe-Covid19-risk, in a framework of a strict evaluation of their cardio-vascular risk.

In times of a pandemic: limited resources and ambiguity make clinical reasoning and diagnostic skills a must for each physician. This an atypical headache scenario in a suspected case of COVID-19.The clinical outcomes, differentials, progression, and reasoning have been discussed and highlighted as possible.

Pharmacometrics is an emerging science that interprets drug, disease and trial information in a mathematical fashion to inform and facilitate efficient drug development and/or regulatory decisions. Pharmacometric study is increasingly adopted in the regulatory review of new antimicrobial agents. We summarized and reviewed the 31 antimicrobial agents approved by the US Food and Drug Administration (FDA) and the 26 antimicrobial agents approved by European Medicines Agency (EMA) from January 2001 to May 2019. Regulatory concerns in pharmacometric review of antimicrobial agents were expounded with examples, including modeling and simulation methods, effects of internal/external factors on PK parameters, safety and efficacy evaluation in terms of exposure-response analysis, refinement of the wording of product labeling and package leaflet, and possible post-marketing clinical trial. Ongoing communication among regulators, academia, and industry regarding pharmacometrics is encouraged to streamline and facilitate the development of new antimicrobial agents. The industry can maximize its benefit in drug development through continued pharmacometric education/training.

Cytomegalovirus (CMV) infection exists in 50-80% of the world’s population in clinically undetected form due to their immunocompetent status. Here we report a case of a 42-year-old COVID-19 patient with no past medical history, who received tocilizumab, which led to a massive lower gastrointestinal bleeding not responded to medical management.

Aim: To evaluate current fluconazole dosing regimens against established pharmacodynamic targets in critically ill adults. Methods: Data from critically ill adults treated with fluconazole (n=30) were used to develop a population pharmacokinetic model. Probability of target attainment (PTA) (fAUC24/MIC >100) was determined from simulations for four previously proposed dosing regimens; (i) 400 mg once daily (ii) a 800 mg loading dose followed by 400 mg once daily, (iii) 400 mg twice daily and (iv) a 12 mg/kg loading dose followed by 6 mg/kg once daily. The effect of body weight (40, 70, 120 kg) and renal function (continuous renal replacement therapy (CRRT), 20, 60, 120, 180 mL/min glomerular filtration rates) on PTA was assessed. Results: Early (0-48 h) fluconazole target attainment for patients with Minimum Inhibitory Concentrations (MIC) of 2 mg/L was highly variable. PTA was highest with an 800 mg loading dose for underweight (40 kg) patients and with a 12 mg/kg loading dose for the remainder. End-of-treatment PTA was highest with 400 mg twice daily maintenance dosing for patients who were under- or normal- weight and 6 mg/kg maintenance dosing for overweight (120 kg) patients. None of the fluconazole regimens reliably attained early targets for MICs of ≥4 mg/L. Conclusion: Current fluconazole dosing regimens do not achieve adequate early target attainment in critically ill adults, particularly in those who are overweight, have higher renal function or are undergoing CRRT. Current fluconazole dosing strategies are generally inadequate to treat organisms with an MIC of ≥4 mg/L.

Objectives To determine the perceived threats, psychological stress and economic concerns among practicing otolaryngologists in low and middle income countries facing the furry of COVID-19 pandemic, exposing the soft underbelly of healthcare systems in resource limited economies. Design A cross sectional anonymous, self-reported questionnaire-based study was carried out among otolaryngologists in India over a period of 3 weeks during the countrywide lock-down. Setting An online platform was used to host a questionnaire, publicized using various social media platforms. Participants A total of 178 participants landed on the page, 73 were excluded at the first question itself, in all 105 otolaryngologists, who were allowed to proceed, completed the questionnaire. Main Outcomes and Measures There are clear indications of psychological stress among the practicing otolaryngologists. Main reasons being anxiety about risk of infection from patients for self, staff members and family, and economic impact of the increased protective measures needed in view of pandemic. Results Out of the 105 Otolaryngologists who completed the survey, 57 (52.8%) were from private sector. Significantly (p=0.001) higher number of private doctors (66.7%) feared about escalated cost of running out-patient clinics compared to government doctors (33.3%). Majority (80.8%) were against routine surgeries during pandemic and difference between private and government doctors was not significant (p=0.765). Increased stress during this pandemic was perceived by 73.1%. Conclusions It can be safely concluded based on this survey based study that to alleviate fears of otolaryngologists in low middle income countries; a comprehensive policy intervention is the need of the hour.

Medullary thyroid carcinoma (MTC) typically manifests as a solitary thyroid nodule, and a miliary pattern on conventional chest imaging is not commonly observed. Here, we report a 58-year-old woman with constitutional symptoms, and innumerable small nodules on chest imaging, mimicking miliary tuberculosis. Pathologic findings confirmed a diagnosis of metastatic MTC.