No abstract

Background: Repurposed medicines may have a role against the SARS-CoV-2 virus. The antiparasitic ivermectin, with antiviral and anti-inflammatory properties, has now been tested in numerous clinical trials. Areas of uncertainty: We assessed the efficacy of ivermectin treatment in reducing mortality, in secondary outcomes, and in chemoprophylaxis, among people with, or at high risk of, COVID-19 infection. Data sources: We searched bibliographic databases up to April 25, 2021. Two review authors sifted for studies, extracted data, and assessed risk of bias. Meta-analyses were conducted and certainty of the evidence was assessed using the GRADE approach and additionally in trial sequential analyses for mortality. Twenty-four randomized controlled trials involving 3406 participants met review inclusion. Therapeutic Advances: Meta-analysis of 15 trials found that ivermectin reduced risk of death compared with no ivermectin (average risk ratio 0.38, 95% confidence interval 0.19–0.73; n = 2438; I 2 = 49%; moderate-certainty evidence). This result was confirmed in a trial sequential analysis using the same DerSimonian–Laird method that underpinned the unadjusted analysis. This was also robust against a trial sequential analysis using the Biggerstaff–Tweedie method. Low-certainty evidence found that ivermectin prophylaxis reduced COVID-19 infection by an average 86% (95% confidence interval 79%–91%). Secondary outcomes provided less certain evidence. Low-certainty evidence suggested that there may be no benefit with ivermectin for “need for mechanical ventilation,” whereas effect estimates for “improvement” and “deterioration” clearly favored ivermectin use. Severe adverse events were rare among treatment trials and evidence of no difference was assessed as low certainty. Evidence on other secondary outcomes was very low certainty. Conclusions: Moderate-certainty evidence finds that large reductions in COVID-19 deaths are possible using ivermectin. Using ivermectin early in the clinical course may reduce numbers progressing to severe disease. The apparent safety and low cost suggest that ivermectin is likely to have a significant impact on the SARS-CoV-2 pandemic globally.

Background Re-purposed medicines may have a role against the SARS-CoV-2 virus. The antiparasitic ivermectin, with anti-viral and anti-inflammatory properties, has now been tested in numerous clinical trials.Areas of uncertainty We assessed the efficacy of ivermectin treatment in reducing mortality, in secondary outcomes, and in chemo-prophylaxis, among people with, or at high risk of, covid-19 infection. Data sourcesWe searched bibliographic databases up to April 25 2021. Two review authors sifted for studies, extracted data and assessed risk of bias. Meta-analyses were conducted and certainty of the evidence was assessed using the GRADE approach and additionally in trial sequential analyses for mortality.Twenty-four RCTs involving 3406 participants met review inclusion. Therapeutic Advances Meta-analysis of 15 trials found ivermectin reduced risk of death compared with no ivermectin (average Risk Ratio 0.38, 95% confidence interval (CI) 0.19 to 0.73; n=2438; I2=49%; moderate-certainty evidence). This result was confirmed in a trial sequential analysis (TSA) using the same DerSimonian-Laird method that underpinned the unadjusted analysis. This was also robust against a TSA using the Biggerstaff-Tweedie method. Low-certainty evidence found ivermectin prophylaxis reduced covid-19 infection by an average 86% (95% CI 79% to 91%). Secondary outcomes provided less certain evidence. Low certainty evidence suggested that that there may be no benefit with ivermectin for ‘need for mechanical ventilation’, whereas effect estimates for ‘improvement’ and ‘deterioration’ clearly favoured ivermectin use. Severe adverse events were rare among treatment trials and evidence of no difference was assessed as low certainty. Evidence on other secondary outcomes was very low certainty.Conclusions Moderate-certainty evidence finds that large reductions in covid-19 deaths are possible using ivermectin. Employing ivermectin early in the clinical course may reduce numbers progressing to severe disease. The apparent safety and low cost suggest that ivermectin is likely to have a significant impact on the SARS-CoV-2 pandemic globally.

It is known that internal magnetic field gradients in porous materials, caused by susceptibility differences at the solid-fluid interfaces, alter the observed effective Nuclear Magnetic Resonance transverse relaxation times T2,eff. The internal gradients scale with the strength of the static background magnetic field B0. Here, we acquire data at various magnitudes of B0 to observe the influence of internal gradients on T2-T2 exchange measurements; the theory discussed and observations made are applicable to any T2-T2 analysis of heterogeneous materials. At high magnetic field strengths, it is possible to observe diffusive exchange between regions of local internal gradient extrema within individual pores. Therefore, the observed exchange pathways are not associated with pore-to-pore exchange. Understanding the significance of internal gradients in transverse relaxation measurements is critical to interpreting these results. We present the example of water in porous sandstone rock and offer a guideline to determine whether an observed T2,eff relaxation time distribution reflects the pore size distribution for a given susceptibility contrast (magnetic field strength) and spin echo separation. More generally, we confirm that for porous materials T1 provides a better indication of the pore size distribution than T2,eff at high magnetic field strengths (B0>1 T), and demonstrate the data analysis necessary to validate pore size interpretations of T2,eff measurements.

No abstract