Acute Intermittent Porphyria as a Rare Challenging Neuro-Metabolic Disease; a Case Report.

Porphyria is a challenging metabolic disease due to its heterogeneous presentation symptoms and its difficult diagnosis. Many affected individuals can complain of recurrent neuro-visceral attacks per year, some of which may be persistent and life-threatening, which is confusing if there is no established diagnosis. Although the motor manifestations, autonomic changes and seizure are highly suggestive, the diagnosis is often overlooked and needs confirmatory genetic testing. To the best of our knowledge, the acute intermittent porphyria (AIP) reported in this case, involving severe electrolyte disturbances and rapid severe weakness is a challenging neuro-metabolic case and is extremely rare worldwide. Here, we reported a case of AIP in a young girl who presented to the emergency department of Al-Araby international Hospital, Monufia, Egypt with severe abdominal pain, constipation, and headache which had started 10 days ago. It seems that the diagnosis of porphyria should be considered particularly in those patients with abdominal complaints associated with electrolyte disturbances, seizures, and severe progressive neuropathy.

Ivermectin role in COVID-19 treatment (IRICT): single-center, adaptive, randomized, double-blind, placebo-controlled, clinical trial.

BACKGROUND: To investigate the efficacy and safety of ivermectin compared to hydroxychloroquine and placebo in hospitalized moderate to severe COVID-19 patients. RESEARCH DESIGN AND METHODS: The study was an adaptive, randomized, double-blinded, controlled, single-center trial. The study was a series of 3-arm comparisons between two different investigational therapeutic agents (ivermectin and hydroxychloroquine) and a placebo. There was interim monitoring to allow early stopping for futility, efficacy, or safety. RESULTS: Ivermectin decreased survival time from 29 to 18.3 days (HR, 9.8, 95%CI, 3.7-26.2), while it did not shorten the recovery time (HR, 1.02, 95%CI, 0.69-1.5). Subgroup analysis showed an association between ivermectin-related mortality and baseline oxygen saturation level. Moreover, stratified groups showed higher risk among patients on high flow O2. Hydroxychloroquine delayed recovery from 10.1 to 12.5 days (HR, 0.62, 95%CI, 0.4-0.95) and non-significantly decreased survival time from 29 to 26.8 days (HR, 1.47, 95%CI, 0.73-2.9). However, 3 months mortality rates were increased with hydroxychloroquine (RR, 2.05, 95%CI, 1.33-3.16). Neither ivermectin nor hydroxychloroquine increased adverse events and demonstrated safety profile compared to placebo. CONCLUSIONS: The study recommends against using either ivermectin or hydroxychloroquine for treatment of COVID-19 in hospitalized patients with any degree of severity. Clinical trial registration: www.clinicaltrials.gov identifier is: NCT04746365.

Efficacy and safety of remdesivir in hospitalized Covid-19 patients: Systematic review and meta-analysis including network meta-analysis.

Remdesivir is an antiviral agent that has shown broad-spectrum activity, including against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clinical trials investigating the role of remdesivir in coronavirus disease 2019 (Covid-19) reported conflicting results. This study aimed to systematically review the best available evidence and synthesize the results. Several electronic databases were searched for candidate studies up to 12 October 2020. Studies eligible for meta-analysis were selected based on the inclusion criteria. Primary outcomes are the recovery and mortality rates, while secondary outcomes are the safety profile of remdesivir. The main effective measures are the rate ratio (RR) and rate difference (RD). Four clinical trials and one observational study were included. Remdesivir treatment for 10 days increased the recovery rate on day 14 by 50% among severe Covid-19 patients (RR = 1.5, 95%CI = 1.33-1.7), while on day 28 it was increased by 14% among moderate and severe Covid-19 patients (RR = 1.14, 95%CI = 1.06-1.22). Additionally, remdesivir decreased the mortality rate on day 14 by 36% among all patients (RR = 0.64, 95%CI = 0.45-0.92) but not on day 28 (RR = 1.05, 95%CI = 0.56-1.97). Nonmechanically ventilated Covid-19 patients showed better response to remdesivir in the recovery (RR = 0.3, 95%CI = 0.13-0.7) and mortality (RR = 2.33, 95%CI = 1.24-4.4) rates on day 14. Remdesivir reduced serious adverse effects by absolute 6% and no significant Grade 3 or 4 adverse effects were reported. At this early stage of the pandemic, there is evidence that remdesivir can be safely administered for hospitalized Covid-19 patients. It improves the recovery rate in both moderate and severe patients but, the optimal effect is achieved for those who are severely affected but not mechanically ventilated.

Hydroxychloroquine for treatment of nonsevere COVID-19 patients: Systematic review and meta-analysis of controlled clinical trials.

Being a pandemic and having a high global case fatality rate directed us to assess the evidence strength of hydroxychloroquine efficacy in treating coronavirus disease-2019 (COVID-19) arising from clinical trials and to update the practice with the most reliable clinical evidence. A comprehensive search was started in June up to 18 July, 2020 in many databases, including PubMed, Embase, and others. Of 432 studies found, only six studies fulfilled the inclusion criteria, which includes: clinical trials, age more than 12 years with nonsevere COVID-19, polymerase chain reaction-confirmed COVID-19, hydroxychloroquine is the intervention beyond the usual care. Data extraction and bias risk assessment were done by two independent authors. Both fixed-effect and random-effect models were utilized for pooling data using risk difference as a summary measure. The primary outcomes are clinical and radiological COVID-19 progression, severe acute respiratory syndrome coronavirus-2 clearance in the pharyngeal swab, and mortality. The secondary outcomes are the adverse effects of hydroxychloroquine. Among 609 COVID-19 confirmed patients obtained from pooling six studies, 294 patients received hydroxychloroquine and 315 patients served as a control. Hydroxychloroquine significantly prevents early radiological progression relative to control with risk difference and 95% confidence interval of -0.2 (-0.36 to -0.03). On the other hand, hydroxychloroquine did not prevent clinical COVID-19 progression, reduce 5-day mortality, or enhance viral clearance on days 5, 6, and 7. Moreover, many adverse effects were reported with hydroxychloroquine therapy. Failure of hydroxychloroquine to show viral clearance or clinical benefits with additional adverse effects outweigh its protective effect from radiological progression in nonsevere COVID-19 patients. Benefit-risk balance should determine the hydroxychloroquine use in COVID-19.