Process integration for emerging challenges: optimal allocation of antivirals under resource constraints.

Abstract: The global scientific community has intensified efforts to develop, test, and commercialize pharmaceutical products to deal with the COVID-19 pandemic. Trials for both antivirals and vaccines are in progress; candidates include existing repurposed drugs that were originally developed for other ailments. Once these are shown to be effective, their production will need to be ramped up rapidly to keep pace with the growing demand as the pandemic progresses. It is highly likely that the drugs will be in short supply in the interim, which leaves policymakers and medical personnel with the difficult task of determining how to allocate them. Under such conditions, mathematical models can provide valuable decision support. In particular, useful models can be derived from process integration techniques that deal with tight resource constraints. In this paper, a linear programming model is developed to determine the optimal allocation of COVID-19 drugs that minimizes patient fatalities, taking into account additional hospital capacity constraints. Two hypothetical case studies are solved to illustrate the computational capability of the model, which can generate an allocation plan with outcomes that are superior to simple ad hoc allocation.

Hyperbaric oxygen therapy increases the risk of tuberculosis disease.

BACKGROUND: As Mycobacterium tuberculosis is an aerobic microbe, hyperbaric oxygen therapy (HBOT) could trigger progression from latent tuberculous infection (LTBI) to active tuberculosis (TB) disease. OBJECTIVE: To evaluate the effect of HBOT on TB reactivation. DESIGN: Our study sample was from the National Health Insurance Research Database containing one million beneficiaries. We identified a group of patients who underwent HBOT, and matched this group with individuals without HBOT. We compared the incidence of activation of TB between these two groups. RESULTS: A total of 2258 patients were identified, with each group comprising 1129 patients. One year after exposure to hyperbaric oxygen, the number of cases of active TB was significantly higher in the HBOT group than in the non-HBOT group (11 cases vs. 1 case, P = 0.006). Multiple regression analysis showed that HBOT was the only statistically significant contributor to TB activation. CONCLUSION: HBOT is likely to trigger the reactivation of TB. High-risk patients should undergo the tuberculin skin test or interferon-gamma release assays before HBOT to identify patients with LTBI.

Optimal treatment for asymptomatic neurosyphilis.

In the pre-penicillin era, patients with asymptomatic neurosyphilis (ANS) were more likely to develop long-term neurological sequelae than those patients with normal cerebrospinal fluid (CSF). Although benzathine penicillin G cannot achieve treponemicidal levels in the CSF, decreased rates of neurological complications of syphilis and non-treponemal titre serological responses are usually observed after treatment with this antibiotic. We here a homosexual man with ANS successfully treated with benzathine penicillin G. This case suggests that reconsideration on the necessity of a lumbar puncture in HIV-infected patients with ANS is warranted.

Detection of M. tuberculosis using DNA chips combined with an image analysis system.

OBJECTIVE: To develop a packaged DNA chip assay (the DR. MTBC Screen assay) for direct detection of the Mycobacterium tuberculosis complex. DESIGN: We described a DNA chip assay based on the IS6110 gene that can be used for the detection of M. tuberculosis complex. Probes were spotted onto the polystyrene strips in the wells of 96-well microtitre plates and used for hybridisation with biotin-labelled amplicon to yield a pattern of visualised positive spots. The plate image was scanned, analysed and interpreted automatically. RESULTS: The results corresponded well with those obtained by conventional culture as well as clinical diagnosis, with sensitivity and specificity rates of respectively 83.8% and 94.2%, and 84.6% and 96.3%. CONCLUSION: We conclude that the DR. MTBC Screen assay can detect M. tuberculosis complex rapidly in respiratory specimens, readily adapts to routine work and provides a flexible choice to meet different cost-effectiveness and automation needs in TB-endemic countries. The cost for reagents is around US$10 per sample.