The Japanese Journal of Antibiotics（JJA）は，感染症に対する医薬品，感染制御，又は微生物検査に関する論文，記事及び感染症に関する症例報告を掲載する，創刊78年を迎える歴史ある査読付学術誌です。

本誌は，新たに発行される論文はもちろん，過去の発行分についても，創刊早期の一部を除き，国際的にもよく知られた信頼度の高い電子ジャーナルプラットフォームであるJ-STAGEで公開されています。

オープンアクセス化については，2024年に編集委員会にて検討を行い，本号（Vol. 78, No. 1）より即時フルオープンアクセス誌に移行いたしました。これにより，エンバーゴ期間（閲覧制限期間）を設けず，出版と同時に誰もが無償で閲覧可能となるため，迅速に掲載論文が認知され，被引用数の上昇が期待できます。

また，本誌は，オープンアクセス誌となっても，高額な投稿手数料（APC）はかからず，費用は従来のページ超過料のみとしています。

オープンアクセス化により，本誌は，より魅力的な学術誌に生まれ変わります。この機に，これまで以上に本誌をご活用いただけますよう，お願い申し上げます。皆様からの投稿をお待ちしています。

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.