Amorphous formulations of indomethacin and griseofulvin prepared by electrospinning

Following an array of optimization experiments, two series of electrospun polyvinylpyrrolidone (PVP) fibers were prepared. One set of fibers contained various loadings of indomethacin, known to form stable glasses, and the other griseofulvin (a poor glass former). Drug loadings of up to 33% w/w were achieved. Electron microscopy data showed the fibers largely to comprise smooth and uniform cylinders, with evidence for solvent droplets in some samples. In all cases, the drug was found to exist in the amorphous physical state in the fibers on the basis of X-ray diffraction and differential scanning calorimetry (DSC) measurements. Modulated temperature DSC showed that the relationship between a formulation’s glass transition temperature (<i>T</i>_g) and the drug loading follows the Gordon–Taylor equation, but not the Fox equation. The results of Gordon–Taylor analysis indicated that the drug/polymer interactions were stronger with indomethacin. The interactions between drug and polymer were explored in more detail using molecular modeling simulations and again found to be stronger with indomethacin; the presence of significant intermolecular forces was further confirmed using IR spectroscopy. The amorphous form of both drugs was found to be stable after storage of the fibers for 8 months in a desiccator (relative humidity <25%). Finally, the functional performance of the fibers was studied; in all cases, the drug-loaded fibers released their drug cargo very rapidly, offering accelerated dissolution over the pure drug

One Health drivers of antibacterial resistance: Quantifying the relative impacts of human, animal and environmental use and transmission

This is the final version. Available on open access from Elsevier via the DOI in this recordData accessibility statement: All model code is open source and available for download on GitHub https://github.com/rdbooton/OHDARTmodelObjectives Antibacterial resistance (ABR) is a major global health security threat, with a disproportionate burden on lower-and middle-income countries (LMICs). It is not understood how ‘One Health’, where human health is co-dependent on animal health and the environment, might impact the burden of ABR in LMICs. Thailand's 2017 “National Strategic Plan on Antimicrobial Resistance” (NSP-AMR) aims to reduce AMR morbidity by 50% through 20% reductions in human and 30% in animal antibacterial use (ABU). There is a need to understand the implications of such a plan within a One Health perspective. Methods A model of ABU, gut colonisation with extended-spectrum beta-lactamase (ESBL)-producing bacteria and transmission was calibrated using estimates of the prevalence of ESBL-producing bacteria in Thailand. This model was used to project the reduction in human ABR over 20 years (2020–2040) for each One Health driver, including individual transmission rates between humans, animals and the environment, and to estimate the long-term impact of the NSP-AMR intervention. Results The model predicts that human ABU was the most important factor in reducing the colonisation of humans with resistant bacteria (maximum 65.7–99.7% reduction). The NSP-AMR is projected to reduce human colonisation by 6.0–18.8%, with more ambitious targets (30% reductions in human ABU) increasing this to 8.5–24.9%. Conclusions Our model provides a simple framework to explain the mechanisms underpinning ABR, suggesting that future interventions targeting the simultaneous reduction of transmission and ABU would help to control ABR more effectively in Thailand.Antimicrobial Resistance Cross Council Initiativ

Effective and rapid treatment of wound botulism, a case report

Abstract Background The latest news shows several cases of contaminated heroin that is found in different parts all over Europe. This information can be helpful for the emergency doctors to find the correct diagnosis of wound botulism in patients who are intravenous drug users. Case presentation We describe a case of a 40-year-old man who presented to the emergency department in 2016. He suffered from mild dysarthria, diplopia, dysphagia and ptosis since two days. The CT-scan of the cerebrum and the liquor were without any pathological results. We found out that the patient is an intravenous drug user and the clinical examination showed an abscess in the left groin. So we treated him with the suspected diagnosis of wound botulism. In the emergency operation we split the abscess, made a radical debridement and complementary treated him with a high dose of penicillin g and two units of botulism antitoxin. The suspected diagnosis was confirmed a few days later by finding the Toxin B in the abscess and in the patient’s serum. In the following days the neurological symptoms decreased and the wound healing was without any complications. The patient left the hospital after nine days; the antibiotic therapy with penicillin g was continued for several days. In a following examination, 14 days after the patient’s discharge of the hospital, no further symptoms were found and the abscess was treated successfully without any problems. Conclusion Because wound botulism is a very rare disease it can be challenging to the attending physician. This case shows a fast treatment with full recovery of the patient without any further disabilities, which can be used for the future

Are older deafblind people being left behind? A narrative review of literature on deafblindness through the lens of the United Nations Principles for Older People

Underpinned by the United Nations Convention on the Rights of Persons with Disabilities (CRDP), Agenda 2030 and the Sustainable Development Goals (SDGs) is the international goal to ‘leave no one behind’. However, the World Federation of the Deafblind have argued that deafblind people have been excluded from international welfare and disability development programmes. Despite making up the majority of the deafblind population, it appears that older deafblind people are particularly invisible. This paper builds on the work of Overbury et al. (2005), who translated the UN Principles for Older Persons into the language of older visually impaired adults, by using them here as the lens for a narrative review of the literature on older deafblind people. It argues that existing research demonstrates that older deafblind people are not only being ‘left behind’ in benefiting from implementation of the UN Principles, but also that the focus of the UN Principles themselves risks maintaining or enhancing their exclusion. Further research and policy development with older deafblind people is required to ensure that international and national social welfare policies and provision are not nugatory to the older deafblind population