Pharmaceutical approaches for COVID-19: An update on current therapeutic opportunities.

SARS-CoV-2, a newly discovered coronavirus, has been linked to the COVID-19 pandemic and is currently an important public health issue. Despite all the work done to date around the world, there is still no viable treatment for COVID-19. This study examined the most recent evidence on the efficacy and safety of several therapeutic options available including natural substances, synthetic drugs and vaccines in the treatment of COVID-19. Various natural compounds such as sarsapogenin, lycorine, biscoclaurine, vitamin B12, glycyrrhizic acid, riboflavin, resveratrol and kaempferol, various vaccines and drugs such as AZD1222, mRNA-1273, BNT162b2, Sputnik V, and remdesivir, lopinavir, favipiravir, darunavir, oseltamivir, and umifenovir, resp., have been discussed comprehensively. We attempted to provide exhaustive information regarding the various prospective therapeutic approaches available in order to assist researchers and physicians in treating COVID-19 patients.

Interactions between complementary medicines and drugs used in primary care and oral COVID-19 antiviral drugs.

BACKGROUND: Patient harm resulting from drug interactions between conventional and traditional or complementary medicines (CM) are avoidable. OBJECTIVE: To provide a clinical overview of a selection of CM interactions with drugs commonly used in Australian general practice or in the management of COVID-19. DISCUSSION: Many herb constituents are substrates for cytochrome P450 enzymes, and inducers and/or inhibitors of transporters such as P-glycoprotein. Hypericum perforatum (St John's Wort), Hydrastis canadensis (golden seal), Ginkgo biloba (ginkgo) and Allium sativum (garlic) are reported to interact with many drugs. Simultaneous administration of certain anti-viral drugs with zinc compounds and several herbs should also be avoided. Preventing and identifying unwanted CM-drug interactions in primary care requires vigilance, access to CM-drug interaction checkers and excellent communication skills. Potential risks from interactions should be balanced against the potential benefits of continuing the drug and/or CM and involve shared decision making.

Public trust is earned: Historical discrimination, carceral violence, and the COVID-19 pandemic.

OBJECTIVE: To assess whether knowledge of Tuskegee, the U.S. Immigration and Customs Enforcement (ICE) agency's detainment of children, and satisfaction with the George Floyd death investigation were associated with trust in actors involved in the development and distribution of coronavirus vaccines. DATA SOURCES AND STUDY SETTING: National survey with a convenience sample of Black (n = 1019) and Hispanic (n = 994) adults between July 1 and 26, 2021. STUDY DESIGN: Observational study using stratified adjusted logistic regression models to measure the association between ratings of the trustworthiness of actors involved in the development and distribution of coronavirus vaccines. PRINCIPAL FINDINGS: Among Black respondents, lower satisfaction with the George Floyd death investigation was associated with lower trustworthiness ratings of pharmaceutical companies (ME: -0.09; CI: -0.15, 0.02), the FDA (ME: -0.07; CI: -0.14, -0.00), the Trump Administration (ME: -0.09; CI: -0.16, -0.02), the Biden Administration (ME: -0.07, CI: -0.10, 0.04), and elected officials (ME: -0.10, CI: -0.18, -0.03). Among Hispanic respondents, lower satisfaction was associated with lower trustworthiness ratings of the Trump Administration (ME: -0.14, CI: -0.22, -0.06) and elected officials (ME: -0.11; CI: -0.19, -0.02). Greater knowledge of ICE's detainment of children and families among Hispanic respondents was associated with lower trustworthiness ratings of state elected officials (ME: -0.09, CI: -0.16, 0.01). Greater knowledge of the US Public Health Service Study of Syphilis in Tuskegee was associated with higher trustworthiness ratings of their usual source of care (ME: 0.09; CI: 0.28, 0.15) among Black respondents (ME: 0.09; CI: 0.01, 0.16). CONCLUSIONS: Among Black respondents, lower satisfaction with the George Floyd death investigation was associated with lowered levels of trust in pharmaceutical companies, some government officials, and administrators; it was not associated with the erosion of trust in direct sources of health care delivery, information, or regulation. Among Hispanic respondents, greater knowledge of the ICE detainments was associated with lower trustworthiness ratings of elected state officials. Paradoxically, higher knowledge of the Study of Syphilis in Tuskegee was associated with higher trustworthiness ratings in usual sources of care.

University Pharmacy: from the foundation to the Pandemic times of Covid-19

Abstract The University Pharmacy Program (FU), from the Federal University of Rio de Janeiro (UFRJ), was created based on the need to offer a curricular internship to students of the Undergraduate Course at the Faculty of Pharmacy. Currently, it is responsible for the care of about 200 patients/day, offering vacancies for curricular internships for students in the Pharmacy course, it has become a reference in the manipulation of many drugs neglected by the pharmaceutical industry and provides access to medicines for low-income users playing an important social function. Research is one of the pillars of FU-UFRJ and several master and doctoral students use the FU research laboratory in the development of dissertations and theses. As of 2002, the Pharmaceutical Care extension projects started to guarantee a rational and safe pharmacotherapy for the medicine users. From its beginning in 1982 until the current quarantine due to the COVID-19 pandemic, FU-UFRJ has been adapting to the new reality and continued to provide patient care services, maintaining its teaching, research, and extension activities. The FU plays a relevant social role in guaranteeing the low-income population access to special and neglected medicines, and to pharmaceutical and education services in health promotion.

Sonocrystallization of a novel ZIF/zeolite composite adsorbent with high chemical stability for removal of the pharmaceutical pollutant azithromycin from contaminated water.

Water pollution management, reduction, and elimination are critical challenges of the current era that threaten millions of lives. By spreading the coronavirus in December 2019, the use of antibiotics, such as azithromycin increased. This drug was not metabolized, and entered the surface waters. ZIF-8/Zeolit composite was made by the sonochemical method. Furthermore, the effect of pH, the regeneration of adsorbents, kinetics, isotherms, and thermodynamics were attended. The adsorption capacity of zeolite, ZIF-8, and the composite ZIF-8/Zeolite were 22.37, 235.3, and 131 mg/g, respectively. The adsorbent reaches the equilibrium in 60 min, and at pH = 8. The adsorption process was spontaneous, endothermic associated with increased entropy. The results of the experiment were analyzed using Langmuir isotherms and pseudo-second order kinetic models with a R2 of 0.99, and successfully removing the composite by 85% in 10 cycles. It indicated that the maximum amount of drug could be removed with a small amount of composite.

Sustainable Stability-Indicating spectra manipulations for the concurrent quantification of a novel Anti-COVID-19 drug and its active Metabolite: Green profile assessment.

Millions of individuals have lost their lives and changed their routines as a direct consequence of exposure to the coronavirus (Covid-19). Molnupiravir (MOL) is an orally bioavailable tiny molecule antiviral prodrug that is effective for curing the coronavirus that produces serious acute respiratory disorder (SARS-CoV-2). Fully green-assessed stability-indicating simple spectrophotometric methods have been developed and fully validated as per ICH criteria. The potential impact of degradation products of drug components on the safety and efficacy of a medication's shelf life is likely to be negligible. The field of pharmaceutical analysis necessitates various stability testing under different conditions. The conduct of such inquiries affords the prospect of predicting the most probable routes of degradation and ascertaining the inherent stability characteristics of the active drugs. Consequently, a surge in demand arose for the creation of an analytical methodology that could consistently measure the degradation products and/or impurities that may be present in pharmaceuticals. Herein, five smart and simple spectrophotometric data manipulation techniques have been produced for the concurrent estimation of MOL and its active metabolite as its possible acid degradation product namely; N-hydroxycytidine (NHC). Structure confirmation of NHC build-up through IR, MS and NMR analyses. All current techniques verified linearity ranging from 10 to 150 µg/ml and 10-60 µg/ml for MOL and NHC, respectively. The limit of quantitation (LOQ) values were in the range of 4.21-9.59 µg/ml, while the limit of detection (LOD) values were ranging from 1.38 - 3.16 µg/ml. The current methods were evaluated in terms of greenness by four assessing methods and confirmed to be green. The significant novelty of these methods depends on their being the first environmentally soundness stability-indicating spectrophotometric approaches for the concurrent estimation of MOL and its active metabolite, NHC. Also, the preparation of purified NHC delivers significant cost savings, instead of purchasing an expensive ingredient. These smart methods were utilized for analyzing the pharmaceutical dosage form which may be of great benefit to the pharmaceutical market.

COVID-19 pharmaceuticals in aquatic matrices: The threatening effects over cyanobacteria and microalgae.

Water contamination by pharmaceuticals is a global concern due to their potential negative effects on aquatic ecosystems and human health. This study examined the presence of three repositioned drugs used for COVID-19 treatment: azithromycin (AZI), ivermectin (IVE) and hydroxychloroquine (HCQ) in water samples collected from three urban rivers in Curitiba, Brazil, during August and September 2020. We conducted a risk assessment and evaluated the individual (0, 2, 4, 20, 100 and 200 µg.L-1) and combined (mix of the drugs at 2 µg.L-1) effects of the antimicrobials on the cyanobacterium Synechococcus elongatus and microalga Chlorella vulgaris. The liquid chromatography coupled to mass spectrometry results showed that AZI and IVE were present in all collected samples, while HCQ occurred in 78 % of them. In all the studied sites, the concentrations found of AZI (up to 2.85 µg.L-1) and HCQ (up to 2.97 µg.L-1) represent environmental risks for the studied species, while IVE (up to 3.2 µg.L-1) was a risk only for Chlorella vulgaris. The hazard quotients (HQ) indices demonstrated that the microalga was less sensitive to the drugs than the cyanobacteria. HCQ and IVE had the highest values of HQ for the cyanobacteria and microalga, respectively, being the most toxic drugs for each species. Interactive effects of drugs were observed on growth, photosynthesis and antioxidant activity. The treatment with AZI + IVE resulted in cyanobacteria death, while exposure to the mixture of all three drugs led to decreased growth and photosynthesis in the cells. On the other hand, no effect on growth was observed for C. vulgaris, although photosynthesis has been negatively affected by all treatments. The use of AZI, IVE and HCQ for COVID-19 treatment may have generated surface water contamination, which could increased their potential ecotoxicological effects. This raises the need to further investigation into their effects on aquatic ecosystems.

Past, Present, and Future Perspectives on Computer-Aided Drug Design Methodologies.

The application of computational approaches in drug discovery has been consolidated in the last decades. These families of techniques are usually grouped under the common name of "computer-aided drug design" (CADD), and they now constitute one of the pillars in the pharmaceutical discovery pipelines in many academic and industrial environments. Their implementation has been demonstrated to tremendously improve the speed of the early discovery steps, allowing for the proficient and rational choice of proper compounds for a desired therapeutic need among the extreme vastness of the drug-like chemical space. Moreover, the application of CADD approaches allows the rationalization of biochemical and interactive processes of pharmaceutical interest at the molecular level. Because of this, computational tools are now extensively used also in the field of rational 3D design and optimization of chemical entities starting from the structural information of the targets, which can be experimentally resolved or can also be obtained with other computer-based techniques. In this work, we revised the state-of-the-art computer-aided drug design methods, focusing on their application in different scenarios of pharmaceutical and biological interest, not only highlighting their great potential and their benefits, but also discussing their actual limitations and eventual weaknesses. This work can be considered a brief overview of computational methods for drug discovery.

Microfluidic devices for the detection of disease-specific proteins and other macromolecules, disease modelling and drug development: A review.

Microfluidics is a revolutionary technology that has promising applications in the biomedical field.Integrating microfluidic technology with the traditional assays unravels the innumerable possibilities for translational biomedical research. Microfluidics has the potential to build up a novel platform for diagnosis and therapy through precise manipulation of fluids and enhanced throughput functions. The developments in microfluidics-based devices for diagnostics have evolved in the last decade and have been established for their rapid, effective, accurate and economic advantages. The efficiency and sensitivity of such devices to detect disease-specific macromolecules like proteins and nucleic acids have made crucial impacts in disease diagnosis. The disease modelling using microfluidic systems provides a more prominent replication of the in vivo microenvironment and can be a better alternative for the existing disease models. These models can replicate critical microphysiology like the dynamic microenvironment, cellular interactions, and biophysical and biochemical cues. Microfluidics also provides a promising system for high throughput drug screening and delivery applications. However, microfluidics-based diagnostics still encounter related challenges in the reliability, real-time monitoring and reproducibility that circumvents this technology from being impacted in the healthcare industry. This review highlights the recent microfluidics developments for modelling and diagnosing common diseases, including cancer, neurological, cardiovascular, respiratory and autoimmune disorders, and its applications in drug development.

Analysis of COVID-19 mRNA Vaccine-induced Mouth Ulcers Using the Japanese Adverse Drug Event Report Database.

There are case reports of mouth ulcers caused by the coronavirus disease 2019 (COVID-19) messenger ribonucleic acid (mRNA) vaccine; however, the actual number and characteristics of cases are unknown. Therefore, we examined this issue using the Japanese Adverse Drug Event Report (JADER), a large Japanese database. We calculated the reported odds ratio (ROR) of drugs that may be specifically associated with mouth ulcers and assumed that a signal was present if the lower limit of the calculated ROR's 95% confidence interval (CI) was > 1. In addition, the time to symptom onset after administration of the COVID-19 mRNA and influenza HA vaccines was investigated. We found that the JADER database contained 4,661 mouth ulcer cases between April 2004 and March 2022. The COVID-19 mRNA vaccine was the eighth most common causative drug for mouth ulcers, with 204 reported cases. The ROR was 1.6 (95% CI, 1.4-1.9) and a signal was detected. There were 172 mouthulcer cases associated with the Pfizer-BioNTech's COVID-19 mRNA vaccine, 76.2% of which were female. The outcome was no unrecovered cases with the influenza HA vaccine, whereas the COVID-19 mRNA vaccine showed unrecovered cases (Pfizer-BioNTech: 12.2%, Moderna: 11.1%). The median time-to-onset of the mouth ulcers was two days for the COVID-19 mRNA vaccine and one day for the influenza HA vaccine, indicating that mouth ulcers caused by the COVID-19 mRNA vaccine were delayed adverse events. In this study, the COVID-19 mRNA vaccine was shown to cause mouth ulcers in a Japanese population.

Anesthetic drug shortages in Pakistan: a multicentre nationwide survey.

PURPOSE: There is a paucity of literature on anesthetic drug shortages and their impact on patient safety in lower-middle-income countries. We sought to determine the magnitude of the problem, the effect on patient care and safety, and the adverse patient outcomes witnessed by anesthesiologists in Pakistan METHODS: We conducted a nationwide, multicentre, cross-sectional survey of a representative sample of anesthesiologists in Pakistan (January 2021 to June 2021). The survey questionnaire was adapted from the American Society of Anesthesiologists (ASA) survey on drug shortages and was modified based on the national essential medication list 2018 of Pakistan. It was distributed through Google Forms to anesthesiologists practicing in both the private and government sector. The names of hospitals or the identity of anesthesiologists was not required. The questionnaire consisted of 20 items and focused on the anesthesiologists' experience of drug shortages, the availability of drugs, and the impact of drug shortages on their individual practice. RESULTS: Two hundred and forty-six responses were received. Approximately 50% (122/246) of anesthesia practitioners in Pakistan reported anesthetic drug shortages. Fifty-seven percent of respondents mentioned using an inferior drug that may have significantly affected the delivery of anesthetic care. Four participants mentioned severe morbidity and another four mentioned observing a mortality associated with drug shortage. CONCLUSION: Anesthetic drug shortages are common in anesthetic practice in Pakistan and they appear to affect patient care and outcomes.

RéSUMé: OBJECTIF: Il existe peu de littérature sur les pénuries de médicaments anesthésiques et leur impact sur la sécurité des patients dans les pays à revenu intermédiaire ou faible. Nous avons cherché à déterminer l'ampleur du problème, l'effet sur les soins et la sécurité des patients ainsi que les issues indésirables observées par les anesthésiologistes au Pakistan. MéTHODE: Nous avons mené une enquête transversale multicentrique à l'échelle nationale auprès d'un échantillon représentatif d'anesthésiologistes au Pakistan (janvier 2021 à juin 2021). Le questionnaire de l'enquête a été adapté de l'enquête de l'American Society of Anesthesiologists (ASA) sur les pénuries de médicaments et a été modifié en fonction de la liste nationale des médicaments essentiels 2018 du Pakistan. Il a été distribué via Google Forms aux anesthésiologistes exerçant dans les secteurs privé et gouvernemental. Les noms des hôpitaux et l'identité des anesthésiologistes n'étaient pas demandés. Le questionnaire comprenait 20 éléments et portait sur l'expérience des anesthésiologistes en matière de pénuries de médicaments, la disponibilité des médicaments et l'impact des pénuries de médicaments sur leur pratique individuelle. RéSULTATS: Deux cent quarante-six réponses ont été reçues. Environ 50 % (122/246) des praticiens anesthésistes au Pakistan ont signalé des pénuries de médicaments anesthésiques. Cinquante-sept pour cent des répondants ont mentionné avoir utilisé un médicament de qualité inférieure qui pourrait avoir eu une incidence significative sur la prestation des soins anesthésiques. Quatre participants ont mentionné une morbidité grave et quatre autres ont mentionné avoir observé une mortalité associée à une pénurie de médicaments. CONCLUSION: Les pénuries de médicaments anesthésiques sont courantes dans la pratique anesthésique au Pakistan et semblent affecter les soins aux patients et les devenirs.

Role of Cytochrome P450 2C9 in COVID-19 Treatment: Current Status and Future Directions.

The major human liver drug metabolising cytochrome P450 (CYP) enzymes are downregulated during inflammation and infectious disease state, especially during coronavirus disease 2019 (COVID-19) infection. The influx of proinflammatory cytokines, known as a 'cytokine storm', during severe COVID-19 leads to the downregulation of CYPs and triggers new cytokine release, which further dampens CYP expression. Impaired drug metabolism, along with the inevitable co-administration of drugs or 'combination therapy' in patients with COVID-19 with various comorbidities, could cause drug-drug interactions, thus worsening the disease condition. Genetic variability or polymorphism in CYP2C9 across different ethnicities could contribute to COVID-19 susceptibility. A number of drugs used in patients with COVID-19 are inducers or inhibitors of, or are metabolised by, CYP2C9, and co-administration might cause pharmacokinetic and pharmacodynamic interactions. It is also worth mentioning that some of the COVID-19 drug interactions are due to altered activity of other CYPs including CYP3A4. Isoniazid/rifampin for COVID-19 and tuberculosis co-infection; lopinavir/ritonavir and cobicistat/remdesivir combination therapy; or multi-drug therapy including ivermectin, azithromycin, montelukast and acetylsalicylic acid, known as TNR4 therapy, all improved recovery in patients with COVID-19. However, a combination of CYP2C9 inducers, inhibitors or both, and plausibly different CYP isoforms could lead to treatment failure, hepatotoxicity or serious side effects including thromboembolism or bleeding, as observed in the combined use of azithromycin/warfarin. Further, herbs that are CYP2C9 inducers and inhibitors, showed anti-COVID-19 properties, and in silico predictions postulated that phytochemical compounds could inhibit SARS-CoV-2 virus particles. COVID-19 vaccines elicit immune responses that activate cytokine release, which in turn suppresses CYP expression that could be the source of compromised CYP2C9 drug metabolism and the subsequent drug-drug interaction. Future studies are recommended to determine CYP regulation in COVID-19, while recognising the involvement of CYP2C9 and possibly utilising CYP2C9 as a target gene to tackle the ever-mutating SARS-CoV-2.

Fatal drug use in the COVID-19 pandemic response: Changing trends in drug-involved deaths before and after stay-at-home orders in Louisiana.

The effect of disaster events on increasing drug-involved deaths has been clearly shown in previous literature. As the COVID-19 pandemic led to stay-at-home orders throughout the United States, there was a simultaneous spike in drug-involved deaths around the country. The landscape of a preexisting epidemic of drug-involved deaths in the United States is one which is not geographically homogenous. Given this unequal distribution of mortality, state-specific analysis of changing trends in drug use and drug-involved deaths is vital to inform both care for people who use drugs and local policy. An analysis of public health surveillance data from the state of Louisiana, both before and after the initial stay-at-home order of the COVID-19 pandemic, was used to determine the effect the pandemic may have had on the drug-involved deaths within this state. Using the linear regression analysis of total drug-involved deaths, as well as drug-specific subgroups, trends were measured based on quarterly (Qly) deaths. With the initial stay-at-home order as the change point, trends measured through quarter 1 (Q1) of 2020 were compared to trends measured from quarter 2 (Q2) of 2020 through quarter 3 (Q3) of 2021. The significantly increased rate of change in Qly drug-involved deaths, synthetic opioid-involved deaths, stimulant-involved deaths, and psychostimulant-involved deaths indicates a long-term change following the initial response to the COVID-19 pandemic. Changes in the delivery of mental health services, harm reduction services, medication for opioid use disorder (MOUD), treatment services, withdrawal management services, addiction counseling, shelters, housing, and food supplies further limited drug-involved prevention support, all of which were exacerbated by the new stress of living in a pandemic and economic uncertainty.

Improvement and characterization of oral absorption behavior of clofazimine by SNEDDS: Quantitative evaluation of extensive lymphatic transport.

Clofazimine, an anti-leprosy drug, has been anticipated for a candidate to treat tuberculosis, cryptosporidiosis, and coronavirus infection, but its low oral bioavailability is considered a reason for its limited activity. In the current study, we have tried to improve the oral bioavailability of clofazimine by several SNEDDS formulations and characterized the absorption behavior from various aspects. Among four SNEDDS formulations prepared, SNEDDS A, prepared with castor oil as an oil component, provided the highest bioavailability (around 61%) and SNEDDS D, prepared with Capryol 90, gave the second highest bioavailability. SNEDDS A formed the finest nanoparticles, which were maintained under gastric and intestinal luminal conditions. The comparison in oral bioavailability between the SNEDDS formulation and its corresponding preformed nanoemulsion suggested that SNEDDS A would efficiently form nanoemulsion in the gastrointestinal tract after oral administration. AUC of mesenteric lymph node concentration was the highest for SNEDDS A, which would be one of the reasons for SNEDDS A to reveal the highest oral bioavailability. A cycloheximide-treated oral absorption study and single-pass perfusion study by utilizing a vascular-luminal perfused small intestine-liver preparation clearly indicated that over 90% of clofazimine absorbed to systemic circulation should be derived from lymphatic transport for both SNEDDS A and D. Furthermore, the fraction of dose absorbed was around 65% for SNEDDS D, but SNEDDS A achieved around 94%, indicating the excellent performance of SNEDDS A.

Global trends in the research and development of medical/pharmaceutical wastewater treatment over the half-century.

The COVID-19 pandemic has severely impacted public health and the worldwide economy. The overstretched operation of health systems around the world is accompanied by potential and ongoing environmental threats. At present, comprehensive scientific assessments of research on temporal changes in medical/pharmaceutical wastewater (MPWW), as well as estimations of researcher networks and scientific productivity are lacking. Therefore, we conducted a thorough literature study, using bibliometrics to reproduce research on medical wastewater over nearly half a century. Our primary goal is systematically to map the evolution of keyword clusters over time, and to obtain the structure and credibility of clusters. Our secondary objective was to measure research network performance (country, institution, and author) using CiteSpace and VOSviewer. We extracted 2306 papers published between 1981 and 2022. The co-cited reference network identified 16 clusters with well-structured networks (Q = 0.7716, S = 0.896). The main trends were as follows: 1) Early MPWW research prioritized sources of wastewater, and this cluster was considered to be the mainstream research frontier and direction, representing an important source and priority research area. 2) Mid-term research focused on characteristic contaminants and detection technologies. Particularly during 2000-2010, a period of rapid developments in global medical systems, pharmaceutical compounds (PhCs) in MPWW were recognized as a major threat to human health and the environment. 3) Recent research has focused on novel degradation technologies for PhC-containing MPWW, with high scores for research on biological methods. Wastewater-based epidemiology has emerged as being consistent with or predictive of the number of confirmed COVID-19 cases. Therefore, the application of MPWW in COVID-19 tracing will be of great interest to environmentalists. These results could guide the future direction of funding agencies and research groups.

Emergency use authorization medication distribution, utilization, and monitoring in a national integrated healthcare system.

PURPOSE: The purpose of this project was to develop and optimize a dashboard and registry to manage the distribution, utilization, and monitoring of coronavirus disease 2019 (COVID-19) emergency use-authorized medications (CEUAMs). SUMMARY: CEUAMs have specific requirements that must be met for prescribing, monitoring, and compliance. When remdesivir, the first COVID-19 medication with emergency use authorization (EUA), was approved, it immediately became necessary for the Veterans Health Administration, a national integrated health system, to describe the requirements for EUA, to distribute the medication in a fair and equitable manner, and to ensure compliance with all EUA requirements. A dashboard was developed and iteratively updated as additional CEUAMs were approved. The dashboard tracked CEUAM distribution and monitoring at the national, regional, facility, and patient level. Par stock levels were initially determined at the national level. Facilities were also able to request an additional allotment of medication based on demand and allocated supplies from the Department of Health and Human Services. Providers completed a questionnaire for the CEUAM for each patient to ensure all requirements for the medication were met. If there were data integrity concerns, the entry was flagged for review at the facility level and, upon evaluation, corrections were made. CONCLUSION: Development of the dashboard was resource intensive but provided an excellent mechanism to share information among facilities and national offices. Other healthcare systems can develop similar dashboards to ensure appropriate use of CEUAMs for their patients while meeting all CEUAM requirements.

Promoting the personal importation of therapeutic goods: recent legislative amendments to advertising regulations may impact consumer access and understanding.

Objective The personal importation scheme is a legislative mechanism that allows health consumers to import unapproved medicines under certain conditions. This article analyses the legal and policy basis for the scheme and considers how reforms to advertising laws for therapeutic goods may restrict communications about it. The article represents the first published analysis of the personal importation scheme's interaction with the communications of health professionals and buyer's clubs. It considers how these communications may be affected by legal amendments, particularly where unapproved medicines may be accessed through the scheme. Methods An examination of Australian therapeutic goods law concerning the personal importation scheme was conducted, including both the historical law and recent regulatory reforms. Illustrative tables were prepared to identify scheme-related advertising that may contravene therapeutic goods law. Risk estimates were allocated to several new legal rules to indicate whether health professionals or buyer's clubs would contravene these laws when promoting the scheme to health consumers for unapproved medicines. Results Representations made directly to the public by health practitioners or on buyer's clubs websites about accessing unapproved therapeutic goods through the personal importation scheme are likely to contravene one or more advertising laws. Conclusions The Therapeutic Goods Administration has very strong powers to initiate compliance or enforcement action for advertising breaches in Australia for many promotional practices. Arguably, in the age of the internet and in the context of emerging expensive medicines, these powers should not be used to restrict health practitioners or buyer's clubs from sharing information about the lawful personal importation scheme to health consumers in need. Nevertheless, the study finds that health practitioners who promote or refer to the availability of unapproved medicines through the personal importation scheme outside of a consultation are likely to contravene the law and may be subject to disciplinary or enforcement action.

ASGARD is A Single-cell Guided Pipeline to Aid Repurposing of Drugs.

Single-cell RNA sequencing technology has enabled in-depth analysis of intercellular heterogeneity in various diseases. However, its full potential for precision medicine has yet to be reached. Towards this, we propose A Single-cell Guided Pipeline to Aid Repurposing of Drugs (ASGARD) that defines a drug score to recommend drugs by considering all cell clusters to address the intercellular heterogeneity within each patient. ASGARD shows significantly better average accuracy on single-drug therapy compared to two bulk-cell-based drug repurposing methods. We also demonstrated that it performs considerably better than other cell cluster-level predicting methods. In addition, we validate ASGARD using the drug response prediction method TRANSACT with Triple-Negative-Breast-Cancer patient samples. We find that many top-ranked drugs are either approved by the Food and Drug Administration or in clinical trials treating corresponding diseases. In conclusion, ASGARD is a promising drug repurposing recommendation tool guided by single-cell RNA-seq for personalized medicine. ASGARD is free for educational use at https://github.com/lanagarmire/ASGARD .

On-site treatment of hospital wastewater in a full-scale treatment plant in Germany: SARS-CoV-2 and treatment performance.

The separate, advanced treatment of hospital wastewater might be a promising approach to prevent the dissemination of residual compounds of high environmental concern, like pharmaceuticals, viruses and pathogenic microorganisms. This study investigates the performance of a full-scale, on-site treatment plant, consisting of a membrane bioreactor and a subsequent ozonation, at a German hospital. We analysed the elimination of pharmaceutical residues, microbiological parameters and SARS-CoV-2 RNA fragments. Additionally, we conducted an orienting study on the practicability of implementing targeted wastewater monitoring at a hospital. Our results demonstrate that after 10 years of stable operation, the treatment plant works highly efficiently regarding the elimination of pharmaceuticals and bacterial indicators. Elimination rates for pharmaceutical substances were above 90%, and log reductions of up to 6 log10 units for microbiological parameters were achieved. SARS-CoV-2 RNA could be detected and quantified in the influent but not in the effluent. The RNA load in the raw wastewater showed good correspondence with COVID-19 case numbers in the hospital. We showed that the full-scale on-site treatment of hospital wastewater is technically feasible and contributes to sustainable hospital effluent management and that monitoring biological markers on the building level might be a useful complementary tool for disease surveillance.

Users' Reactions to Announced Vaccines Against COVID-19 Before Marketing in France: Analysis of Twitter Posts.

BACKGROUND: Within a few months, the COVID-19 pandemic had spread to many countries and had been a real challenge for health systems all around the world. This unprecedented crisis has led to a surge of online discussions about potential cures for the disease. Among them, vaccines have been at the heart of the debates and have faced lack of confidence before marketing in France. OBJECTIVE: This study aims to identify and investigate the opinions of French Twitter users on the announced vaccines against COVID-19 through sentiment analysis. METHODS: This study was conducted in 2 phases. First, we filtered a collection of tweets related to COVID-19 available on Twitter from February 2020 to August 2020 with a set of keywords associated with vaccine mistrust using word embeddings. Second, we performed sentiment analysis using deep learning to identify the characteristics of vaccine mistrust. The model was trained on a hand-labeled subset of 4548 tweets. RESULTS: A set of 69 relevant keywords were identified as the semantic concept of the word "vaccin" (vaccine in French) and focused mainly on conspiracies, pharmaceutical companies, and alternative treatments. Those keywords enabled us to extract nearly 350,000 tweets in French. The sentiment analysis model achieved 0.75 accuracy. The model then predicted 16% of positive tweets, 41% of negative tweets, and 43% of neutral tweets. This allowed us to explore the semantic concepts of positive and negative tweets and to plot the trends of each sentiment. The main negative rhetoric identified from users' tweets was that vaccines are perceived as having a political purpose and that COVID-19 is a commercial argument for the pharmaceutical companies. CONCLUSIONS: Twitter might be a useful tool to investigate the arguments for vaccine mistrust because it unveils political criticism contrasting with the usual concerns on adverse drug reactions. As the opposition rhetoric is more consistent and more widely spread than the positive rhetoric, we believe that this research provides effective tools to help health authorities better characterize the risk of vaccine mistrust.