Safety and Efficacy of Ivermectin and Doxycycline Monotherapy and in Combination in the Treatment of COVID-19: A Scoping Review.

INTRODUCTION AND OBJECTIVE: Ivermectin (IVM) and doxycycline (DOXY) have demonstrated in-vitro activity against SARS-CoV-2, and have a reasonable safety profile. The objective of this systematic review was to explore the evidence in the literature on the safety and efficacy of their use as monotherapy and combination therapy in COVID-19 management. METHODS: After prospectively registering the study protocol with the Open Science Framework, we searched PubMed, Google Scholar, clinicaltrials.gov, various pre-print servers and reference lists for relevant records published until 16 February, 2021 using appropriate search strategies. Baseline features and data pertaining to efficacy and safety outcomes were extracted separately for IVM monotherapy, DOXY monotherapy, and IVM + DOXY combination therapy. Methodological quality was assessed based on the study design. RESULTS: Out of 200 articles screened, 19 studies (six retrospective cohort studies, seven randomised controlled trials, five non-randomised trials, one case series) with 8754 unique patients with multiple stages of COVID-19 were included; four were pre-prints and one was an unpublished clinicaltrials.gov document. The comparator was standard care and 'hydroxychloroquine + azithromycin' in seven and three studies respectively, and two studies were placebo controlled; six studies did not have a comparator. IVM monotherapy, DOXY monotherapy and IVM + DOXY were explored in eight, five and five studies, respectively; one study compared IVM monotherapy and IVM + DOXY with placebo. While all studies described efficacy, the safety profile was described in only six studies. Efficacy outcomes were mixed with some studies concluding in favour of the intervention and some studies displaying no significant benefit; barring one study that described 9/183 patients with erosive esophagitis and non-ulcer dyspepsia with IVM + DOXY (without causality assessment details), there were no new safety signals of concern with any of the three interventions considered. The quality of studies varied widely, with five studies having a 'good' methodological quality. CONCLUSIONS: Evidence is not sufficiently strong to either promote or refute the efficacy of IVM, DOXY, or their combination in COVID-19 management. SYSTEMATIC REVIEW PROTOCOL REGISTRATION DETAILS: Open Science Framework: https://osf.io/n7r2j .

Efficacy and Safety of EGFR Inhibitors in the Treatment of EGFRPositive NSCLC Patients: A Meta-Analysis.

BACKGROUND: We compared the response rates, survival rates, and safety profile of epidermal growth factor receptor (EGFR) inhibitors with non-targeted chemotherapy and older EGFR inhibitors when used to treat advanced non-small cell lung cancer (NSCLC) patients with activating EGFR mutations. METHODS: We searched PubMed, Cochrane Central Register of Controlled Trials, and clinicaltrial.- gov for randomized controlled trials published until 11-Feb-2020. Treatment outcomes were compared between EGFR inhibitor and pooled comparator; a subgroup analysis compared outcomes between EGFR inhibitor and non-targeted chemotherapy, and between newer and older EGFR inhibitors. RESULTS: Twenty-one studies with 4,250 unique patients were included. Significantly higher objective response rate (ORR) (odds ratio (OR) 2.28; 95% CI 2.00-2.61), higher disease control rate (DCR) (OR 2.3; 95% CI 1.88-3.06), and longer progression-free survival (PFS) (Hazard ratio (HR) 0.56; 95% CI 0.52-0.60) were observed in the EGFR inhibitor group compared to the pooled comparator group. Subgroup analysis revealed that the ORR, DCR, and PFS were significantly higher with EGFR inhibitors than non-targeted chemotherapy, and only PFS (and not ORR and DCR) was significantly longer with newer EGFR inhibitors than the older EGFR inhibitors. Overall survival (OS) was not significantly different between EGFR inhibitors and pooled comparator (HR 0.91; 95% CI 0.83-1.00) as well as in either of the subgroup analyses. Adverse events ≥ grade 3 and treatment discontinuation were significantly higher with non-targeted chemotherapy compared to the EGFR inhibitors. CONCLUSION: The benefits of prolongation of ORR, DCR, and PFS might not imply significantly improved OS after therapy with EGFR inhibitors when compared with non-targeted chemotherapy or older EGFR inhibitors.

Hydroxychloroquine and Remdesivir in COVID-19: A critical analysis of recent events.

The world is going through an unprecedented medical emergency with no effective remedy for the SARS-CoV2 virus causing Covid-19. Two drugs used for other indications in the past, hydroxychloroquine (HCQ) and remdesivir (RDV), are sought to be repurposed to treat Covid-19. Both these drugs have received emergency use authorisation by the US Food and Drug Administration. In this review, we critically analyse the identification of and subsequent events concerning these two drugs as potential treatment options for Covid-19, and conclude by raising some ethical issues that require serious thought from the global scientific community concerned with using these two drugs against Covid-19.

Key Words: Covid-19, hydroxychloroquine, remdesivir, USFDA, emergency use authorisation

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Recurrent cellulitis in a case of Aagenaes syndrome.

Aagenaes syndrome, also called Lymphedema Cholestasis Syndrome (LSC 1), is a form of idiopathic familial intrahepatic cholestasis associated with lymphedema of the lower extremities. It is named after the Norwegian pediatrician Oyestein Aagenaes, who described the syndrome in 1968. The presence of lymphedema is likely the predisposing factor for development of recurrent infections in such patients.1 Recurrent cellulitis as such has never been described in the literature with Aagenaes syndrome. This case highlights recurrent cellulitis as one of the potential complications of Aagenaes syndrome.