ABSTRACT
Background. Five SARS-CoV-2 vaccines are approved in North America and/or Europe: Pfizer/BioNTech, Moderna, Janssen, Oxford-AstraZeneca and Novavax. Other vaccines have been developed, including Sinopharm, SinoVac, QazVac, Covaxin, Soberana, Corbevac, Medicago, Clover and Cansino, but are not approved in high income countries. This meta-analysis compared the efficacy of approved and unapproved vaccines in randomised clinical trials (RCTs). Methods. A systematic review of clinical trial registries, PUBMED and EMBASE identified placebo-controlled RCTs of SARS-CoV-2 vaccines prospectively evaluating risks of symptomatic or severe infection with clearly defined endpoints. For each trial, risk of bias was assessed using Cochrane tool 2.0 and the CONSORT checklist. In the pre-defined meta-analysis, relative risks of symptomatic infection and severe disease were compared for each vaccine versus placebo, using Cochrane-Mantel Haenszel Tests (random effects method). Results. There were 21 RCTs assessing efficacy of the COVID-19 vaccines identified. One RCT was excluded for high risk of bias. Ten RCTs in 206,667 participants evaluated 5 approved vaccines;10 RCTs in 158,599 participants evaluated 8 unapproved vaccines. In the meta-analysis, prevention of symptomatic infection was 84% (95% C.I. 68-92%) for approved vaccines versus 72% (95% C.I. 65-77%) for unapproved vaccines, with no significant difference between vaccine types (p=0.13). Prevention of severe SARS-CoV-2 infection was 95% (95% C.I. 78-99%) for approved vaccines versus 84% (95% C.I. 72-91%) for unapproved vaccines (p=0.12). In addition, the risk of serious adverse events was similar between vaccine types (p=0.49). Efficacy of approved and unapproved SARS-CoV-2 vaccines Percentage efficacy of approved and unapproved SARS-CoV-2 vaccines against symptomatic infection (Panel A) and severe disease (Panel B). Vaccines are arranged by approval-status (approved vaccines to the left and unapproved vaccines to the right of discontinuous line) and colour-coded by vaccine type. Error bars represent 95% confidence intervals. RIBSP, Research Institute for Biological Safety Problems;IFV, Instituto Finlay de Vacunas. Conclusion. This meta-analysis of 20 RCTs in 365,266 participants, showed no significant difference in efficacy between the approved and unapproved SARS-CoV-2 vaccines for endpoints of either symptomatic or severe infection. Differences in study design, end-point definitions, variants and prevalence of infection may have influenced the results. Head-to-head RCTs will be required to make definitive conclusions. If efficacy is proved definitively, new patent-free vaccines could lower costs of worldwide SARS-CoV-2 vaccination campaigns significantly.
ABSTRACT
Introduction The COVID-19 pandemic precipitated widespread implementation of telemedicine. Initial evaluation of our telemedicine service found high satisfaction rates [1]. Anticipating continuing demand for remote services we undertook a further patient survey, gauging shifting attitudes towards telemedicine. Methods We sent an anonymised, on-line survey to all patients who received telephone consultations in a six-week period (08/02/22- 22/3/22). We collected demographic data, reasons for consultation and patient satisfaction, using the standardised telemedicine satisfaction questionnaire [2]. Results 275 responses were received (∼10% response rate). 80.4% of respondents were female. 50.5% of consultations were for contraception. 60.3% of GUM consultation respondents were female. The modal age group was 30-44 years in both categories. 65.5% of patients chose an initial telephone consultation as their preferred modality, compared to 22.9% preferring walk-in-clinics. 44% of all patients surveyed would prefer not to share genital images for remote assessment in theory, however only 16.7% of the subgroup actually asked to send an image (n=18) expressed the same. Only 22% preferred video consultations. 80% reported that they were 'overall happy' with their telemedicine consultation (agree/strongly agree). Discussion Telemedicine is more convenient for many patients, cost effective, clinically efficient and aligned to the NHS global impact agenda. It is fast becoming an integral part of modern healthcare. Survey data may disproportionately represent more engaged and technologically literate patients. However, it also has the potential to engage previously unreached patient groups. This survey supports a permanent role for telemedicine. We will continue to integrate patient feedback to build a high quality, sustainable service.(Table Presented).
ABSTRACT
Background. There is a continued and pressing need for safe and effective treatment of COVID-19. Significant survival benefits have been shown by dexamethasone, tocilizumab and sarilumab, however they are only recommended in hospitalised COVID-19 patients. Ivermectin is a well-established and readily available antiparasitic drug which may be suitable for treatment in mild and moderate disease stages. It recently demonstrated anti-viral properties in vitro and now over 80 clinical trials have been registered worldwide to test its effectiveness in COVID-19 patients. This meta-analysis aims to collect data on adverse events reported in new COVID-19 treatment trials for the use of ivermectin as a repurposed medication. Methods. Data was extracted from randomised trials of COVID-19 treatment trials identified through systematic searches of PUBMED, EMBASE, MedRxiv and trial registries. The primary outcome of this meta-analysis is the frequency of adverse events. Key safety events included serious, gastrointestinal, neurological, cardiovascular and dermatological adverse events. Results. Overall, 18 trials investigating ivermectin for COVID-19 in a total of 2496 participants reported safety data and were included. There was no significant difference in the proportion of all adverse events between ivermectin and the comparator. There were 371/1261 (29%) adverse events recorded in the ivermectin containing arms and 376/1284 (29%) in the control arms (RR 1.02 [95% CI 0.77 - 1.34];p = 0.91). There was no significant difference in the rate of serious adverse events across treatment arms (RR 1.95 [95% CI 0.75 - 5.11];p = 0.18). No significant differences between ivermectin and the control were seen across different subcategories of adverse events. Figure 1 shows a summary of the results for all adverse events. Forest plot comparing ivermectin and the control for all adverse events in COVID-19 trials, subdivided into single-day dosing trials and multi-day dosing trials. Conclusion. The results of recent COVID-19 trials show that overall, ivermectin is safe and well-tolerated. No significant difference in adverse event reporting was found across all subgroups in single and multi-day treatment regimens for the studies analysed. Safety reporting methodologies often varied across trials. Future and ongoing trials should be encouraged to collect and monitor safety data systematically.
ABSTRACT
Background: Many treatments are being assessed for repurposing to treat coronavirus disease 2019 (COVI D-19). One drug that has shown promising results in vitro is nitazoxanide. Unlike other postulated drugs, nitazoxanide shows a high ratio of maximum plasma concentration (Cmax), after 1 day of 500 mg twice daily (BD), to the concentration required to inhibit 50% replication (EC50) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Cmax: E C50 roughly equal to 14:1). As such, it is important to investigate the safety of nitazoxanide for further trials. Furthermore, treatments for COVI D-19 should be cheap to promote global access, but prices of many drugs are far higher than the costs of production. We aimed to conduct a review of the safety of nitazoxanide for any prior indication and calculate its minimum costs of production. Methods: A review of nitazoxanide clinical research was conducted using EMBASE and MEDLINE databases, supplemented by ClinicalTrials.gov. We searched for phase 2 or 3 randomised controlled trials (RCTs) comparing nitazoxanide with placebo or active control for 5-14 days in participants experiencing acute infections of any kind. Data extracted were grade 1-4 and serious adverse events (AEs). Data were also extracted on gastrointestinal (GI) AEs, as well as hepatorenal and cardiovascular effects. Active pharmaceutical ingredient cost data from 2016 to 2019 were extracted from the Panjiva database and adjusted for 5% loss during production, costs of excipients, formulation, a 10% profit margin and tax. Two dosages, at 500 mg BD and a higher dose of 1100 mg three times daily (TDS), were considered. Our estimated costs were compared with publicly available list prices from a selection of countries. Results: Nine RCTs of nitazoxanide were identified for inclusion. These RCTs accounted for 1514 participants and an estimated 95.3 person-years-of-follow-up. No significant differences were found in any of the AE endpoints assessed, across all trials or on subgroup analyses of active- or placebo-controlled trials. Mild GI AEs increased with dose. No hepatorenal or cardiovascular concerns were raised, but few appropriate metrics were reported. There were no teratogenic concerns, but the evidence base was very limited. Based on a weighted-mean cost of US $61/kg, a 14-day course of treatment with nitazoxanide 500 mg BD would cost $1.41. The daily cost would therefore be $0.10. The same 14-day course could cost $3944 in US commercial pharmacies, and $3 per course in Pakistan, India and Bangladesh. At a higher dose of 1100 mg TDS, our estimated cost was $4.08 per 14-day course, equivalent to $0.29 per day. Conclusion: Nitazoxanide demonstrates a good safety profile at approved doses. However, further evidence is required regarding hepatorenal and cardiovascular effects, as well as teratogenicity. We estimate that it would be possible to manufacture nitazoxanide as generic for $1.41 for a 14-day treatment course at 500 mg BD, up to $4.08 at 1100 mg TDS. Further trials in COVI D-19 patients should be initiated. If efficacy against SARS-CoV-2 is demonstrated in clinical studies, nitazoxanide may represent a safe and affordable treatment in the ongoing pandemic.