To Push or To Pull? In a Post-COVID World, Supporting and Incentivizing Antimicrobial Drug Development Must Become a Governmental Priority.

The COVID-19 pandemic has refocused attention worldwide on the dangers of infectious diseases, in terms of both global health and the effects on the world economy. Even in high income countries, health systems have been found wanting in dealing with the new infectious agent. However, the even greater long-term danger of antimicrobial resistance in pathogenic bacteria and fungi is still under-appreciated, especially among the general public. Although antimicrobial drug development faces significant scientific challenges, the gravest challenge at the moment appears to be economic, where the lack of a viable market has led to a collapse in drug development pipelines. There is therefore a critical need for governments across the world to further incentivize the development of antimicrobials. Most incentive strategies over the past decade have focused on so-called "push" incentives that bridge the costs of antimicrobial research and development, but these have been insufficient for reviving the pipeline. In this Perspective, we analyze the current incentive strategies in place for antimicrobial drug development, and focus on "pull" incentives, which instead aim to improve revenue generation and thereby resolve the antimicrobial market failure challenge. We further analyze these incentives in a broader "One Health" context and stress the importance of developing and enforcing strict protocols to ensure appropriate manufacturing practices and responsible use. Our analysis reiterates the importance of international cooperation, coordination across antimicrobial research, and sustained funding in tackling this significant global challenge. A failure to invest wisely and continuously to incentivize antimicrobial pipelines will have catastrophic consequences for global health and wellbeing in the years to come.

Pharmacological assessment of ibuprofen arginate on platelet aggregation and colon cancer cell killing.

Nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen, are amongst the most commonly used medications and produce their anti-inflammatory and analgesic benefits by blocking cyclooxygenase (COX)-2. These drugs also have the potential to prevent and treat cancer and some members of the class including ibuprofen can produce anti-platelet effects. Despite their utility, all NSAIDs are associated with increased risk of cardiovascular side effects which our recent work suggests could be mediated by increased levels of the endogenous NO synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) leading to reduced endothelial NOS activity and associated endothelial cell dysfunction. ADMA is a cardiotoxic hormone and biomarker of cardiovascular risk whose effects can be prevented by l-arginine. The ibuprofen salt, ibuprofen arginate (Spididol®) was created to increase drug solubility but we have previously established that it not only effectively blocks COX-2 but also provides an arginine source able to reverse the effects of ADMA in vitro and in vivo. Here we have gone on to explore whether the formulation of ibuprofen with arginine influences the potency and efficacy of the parent molecule using a range of simple in vitro assays designed to test the effects of NSAIDs on (i) platelet aggregation and (iii) colon cancer cell killing. Our findings demonstrate that ibuprofen arginate retains these key functional effects of NSAIDs with similar or increased potency compared to ibuprofen sodium, further illustrating the potential of ibuprofen arginate as an efficacious drug with the possibility of improved cardiovascular safety.

[Use of a diode laser for glaucoma in children and adolescents]. / Zastosowanie lasera diodowego w jaskrze u dzieci i mlodziezy.

OBJECTIVE: To present the results of the use of diode laser in the treatment of secondary glaucoma in children. MATERIAL AND METHODS: The study was performed on 15 eyes in 14 children (7 males and 7 females) with glaucoma resistant to pharmacotherapy. Transscleral contact cyclophotocoagulation (TSCPC) was performed using SLx diode laser (Iris Medical Instrument). The number of photocoagulations performed within the circumference of 270 degrees ranged from 18 to 30 and the energy depended on "pop sound". RESULTS: In one child visual acuity decreased from 0.5/50 to light perception, while in the remaining children it did not change. Prior to coagulation, the mean intraocular pressure was 37.67 +/- 3.2 mm Hg, and 6 months after coagulation it was 22 +/- 3.74 mm Hg. CONCLUSIONS: TSPC is a well tolerated method of treatment in children with pharmacotherapy-resistant glaucoma. In order to assess the late outcomes of the therapy, prolonged observation of the patients is required.

[Eye with implanted keratoprosthesis in ultrasound biomicroscopy]. / Oko z wszczepiona keratoproteza--w obrazie biomikroskopii ultradzwiekowej.

OBJECTIVE: Of the study is to assess the possibility of the ultrasound biomicroscopy (UBM) in diagnosis of the eyes with implanted Fiodorov-Zujev's keratoprosthesis. MATERIAL: We examined 10 eyes of 10 patients, 3 females and 7 males. The patients were 12 to 17 years after the second stage of keratoprosthesis implantation (mean 14.9 +/- 1.37). METHODS: The examinations were performed with the use of ultrasound biomicroscope (Humphrey Instruments model 840). RESULTS: UBM made it possible to visualise keratoprosthesis and many complications: decentration of keratoprosthesis, thinning of anterior part of leucoma, shallowing of anterior chamber, very narrow angle of filtration, retroprosthetic membrane-like structures.

[Use of Nd:YAG laser for disruption of retrocorneal membranes in eyes with implanted keratoprosthesis]. / Zastosowanie lasera Nd:YAG do rozbicia blon pozarogówkowych w oczach z wszczepiona keratoproteza.

PURPOSE: Presentation of some problems connected with the occurrence of retroprosthetic membranes following successful keratoprosthetic surgery, and of early results of the Q-switch Nd:YAG laser use in the disruption of these membranes. METHODS: Disruption of retroprosthetic membranes with the use of Nd:YAG laser was performed on 12 aphakic eyes in 12 patients. The age of patients ranged from 34 to 64 years. Ten eyes had implanted Fiodorow-Zujew keratoprosthesis and two had keratoprosthesis with their haptic parts made of carbo-carbonic compound. RESULTS: Improvement of visual acuity was observed in 9 patients (75%). The effect was not stable. It let us postpone the surgery in 7 cases. Further follow-up is necessary to evaluate the use of Nd:YAG laser in the disruption of retroprosthetic membranes.