The Japanese Journal of Antibiotics (JJA) is a peer-reviewed academic journal with a 78-year history that publishes papers, articles, and case reports on pharmaceuticals for infectious diseases, infection control, and microbiological testing. In addition to newly published papers, most past issues—except for some early publications—are available on J-STAGE, a highly reliable and internationally recognized electronic journal platform.

Regarding open access, the editorial board discussed this initiative in 2024, and starting with the current issue (Vol. 78, No. 1), the journal has transitioned to immediate full open access. As a result, all articles are now freely accessible upon publication without an embargo period (restricted access period). This change is expected to lead to faster recognition of published papers and increase their citation frequency.

Furthermore, even as an open-access journal, JJA does not impose high article processing charges (APCs); authors are only required to pay the traditional excess page fees.

With this transition to open access, JJA is becoming an even more appealing academic journal. We encourage you to make full use of the journal and look forward to receiving your submissions.

This critical appraisal is focused on three published case series of 119 COVID-19 patients with hypoxemia who were successfully treated in the United States, Zimbabwe, and Nigeria with similar off-label ivermectin-based multidrug treatments that may include ivermectin, nebulized nanosilver, doxycycline, zinc, Vitamins C, and Vitamin D, resulting in rapid recovery of oxygen levels. We used a simplified self-controlled case series method to investigate the association between treatment and the existence of hospitalization rate reduction. External controls of hospitalized patients were compared against the subgroup of patients with baseline room air SpO₂ ≤ 90% to investigate the association between treatment and the existence of mortality rate reduction. No deaths were reported in any of the three case series. One case series reported 5 hospitalization equivalent events (2 ventilations and 3 uses of supplemental oxygen). Combined, the three case series comprised 119 patients of which 61 patients presented with baseline room air SpO₂ ≤ 90%. All appropriate external controls were lower-bounded by 12% case fatality rate for hospitalized patients. The existence of hospitalization rate reduction was statistically significant and resilient against both random and systemic selection bias for two out of three case series with the most aggressive treatments. The existence of mortality rate reduction was statistically significant when at least the two case series with the most aggressive treatments were combined. It is more likely than not that random selection bias alone cannot explain this reduction in mortality. These results established an association between the two most aggressive ivermectin-based multidrug treatment protocols and reduction in hospitalization and mortality for hypoxemic COVID-19 patients.

We continue the critical appraisal of three published case series of 119 COVID-19 patients with hypoxemia, treated in the United States, Zimbabwe, and Nigeria with similar ivermectin-based multidrug treatments, to assess the available evidence supporting a causal relationship between treatment and reduction in hospitalizations and mortality. A narrative review was conducted to assess the Bradford Hill criteria for a causal association. We used a previously proposed refinement of the Bradford Hill criteria that reorganized them into three categories of direct, mechanistic, and parallel evidence. The efficacy of the two most aggressive ivermectin-based multidrug protocols is supported by the Bradford Hill criteria for temporality, strength of association, biological gradient, biological plausibility, coherence, consistency, and analogy. The causal relation between the treatment of hypoxemic COVID-19 patients using these protocols and the reduction in hospitalizations and mortality is supported as an inference to the best explanation.