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1.
Health Serv Res ; 58 Suppl 2: 218-228, 2023 08.
Article in English | MEDLINE | ID: covidwho-20232325

ABSTRACT

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.


Subject(s)
COVID-19 , Syphilis , Vaccines , Adult , Child , Humans , Trust , Pandemics/prevention & control , Pharmaceutical Preparations
2.
Aust J Gen Pract ; 52(6): 345-357, 2023 06.
Article in English | MEDLINE | ID: covidwho-20237045

ABSTRACT

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.


Subject(s)
COVID-19 , Garlic , Humans , Pharmaceutical Preparations , Herb-Drug Interactions , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Australia , Primary Health Care
3.
Acta Pharm ; 73(2): 157-173, 2023 Jun 01.
Article in English | MEDLINE | ID: covidwho-20235398

ABSTRACT

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.


Subject(s)
COVID-19 , Humans , SARS-CoV-2 , BNT162 Vaccine , ChAdOx1 nCoV-19 , Pandemics , Pharmaceutical Preparations
4.
Braz. J. Pharm. Sci. (Online) ; 59: e21425, 2023. tab, graf
Article in English | WHO COVID, LILACS (Americas) | ID: covidwho-2328188

ABSTRACT

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.


Subject(s)
Pharmacy/classification , Education, Pharmacy , COVID-19/classification , Patients/classification , Pharmaceutical Services/history , Teaching/ethics , Pharmaceutical Preparations/supply & distribution , Patient Care/ethics
5.
Ultrason Sonochem ; 97: 106463, 2023 Jul.
Article in English | MEDLINE | ID: covidwho-2328013

ABSTRACT

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.


Subject(s)
Water Pollutants, Chemical , Zeolites , Azithromycin , Zeolites/chemistry , Water Pollutants, Chemical/chemistry , Thermodynamics , Kinetics , Adsorption , Water , Pharmaceutical Preparations , Hydrogen-Ion Concentration
6.
Spectrochim Acta A Mol Biomol Spectrosc ; 300: 122911, 2023 Nov 05.
Article in English | MEDLINE | ID: covidwho-2327829

ABSTRACT

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.


Subject(s)
COVID-19 , Humans , SARS-CoV-2 , Spectrophotometry/methods , Pharmaceutical Preparations
7.
Sci Total Environ ; 892: 164309, 2023 Sep 20.
Article in English | MEDLINE | ID: covidwho-2324753

ABSTRACT

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.


Subject(s)
COVID-19 , Chlorella vulgaris , Microalgae , Water Pollutants, Chemical , Humans , Ecosystem , COVID-19 Drug Treatment , Hydroxychloroquine/analysis , Hydroxychloroquine/pharmacology , Azithromycin/toxicity , Pharmaceutical Preparations , Water , Water Pollutants, Chemical/analysis
8.
Pharmazie ; 78(5): 63-66, 2023 05 01.
Article in English | MEDLINE | ID: covidwho-2317853

ABSTRACT

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.


Subject(s)
COVID-19 , Drug-Related Side Effects and Adverse Reactions , Influenza Vaccines , Influenza, Human , Oral Ulcer , Female , Humans , Male , Pharmaceutical Preparations , COVID-19 Vaccines/adverse effects , Oral Ulcer/chemically induced , Oral Ulcer/epidemiology , East Asian People , COVID-19/prevention & control , RNA, Messenger/genetics , mRNA Vaccines , Adverse Drug Reaction Reporting Systems
9.
Molecules ; 28(9)2023 May 05.
Article in English | MEDLINE | ID: covidwho-2312914

ABSTRACT

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.


Subject(s)
Computer-Aided Design , Drug Design , Drug Discovery/methods , Computers , Pharmaceutical Preparations
10.
Int J Biol Macromol ; 235: 123784, 2023 Apr 30.
Article in English | MEDLINE | ID: covidwho-2312488

ABSTRACT

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.


Subject(s)
High-Throughput Screening Assays , Microfluidics , Reproducibility of Results , Pharmaceutical Preparations , Lab-On-A-Chip Devices
11.
Eur J Pharm Biopharm ; 187: 141-155, 2023 Jun.
Article in English | MEDLINE | ID: covidwho-2306002

ABSTRACT

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.


Subject(s)
Clofazimine , Nanoparticles , Drug Delivery Systems , Solubility , Pharmaceutical Preparations , Administration, Oral , Biological Availability , Nanoparticles/chemistry , Emulsions/chemistry , Particle Size
12.
Chemosphere ; 331: 138775, 2023 Aug.
Article in English | MEDLINE | ID: covidwho-2305489

ABSTRACT

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.


Subject(s)
COVID-19 , Wastewater , Humans , Pandemics , COVID-19/epidemiology , Research , Pharmaceutical Preparations
13.
Ann Behav Med ; 57(6): 472-482, 2023 05 23.
Article in English | MEDLINE | ID: covidwho-2292055

ABSTRACT

BACKGROUND: People who inject drugs (PWID) have low rates of COVID-19 testing yet are vulnerable to severe disease. In partnership with a mobile syringe service program (SSP) in San Diego County, CA, we developed the evidence-, community-, and Social Cognitive Theory-informed "LinkUP" intervention (tailored education, motivational interviewing, problem-solving, and planning) to increase COVID-19 testing uptake among PWID. PURPOSE: To assess preliminary efficacy of LinkUP in increasing PWID COVID-19 testing in a pilot randomized controlled trial (RCT). METHODS: We referred participants (PWID, ≥18 years old, San Diego County residents who had not recently undergone voluntary COVID-19 testing) to mobile SSP sites that had been randomized (by week) to offer the active LinkUP intervention or didactic attention-control conditions delivered by trained peer counselors. Following either condition, counselors offered on-site rapid COVID-19 antigen testing. Analyses estimated preliminary intervention efficacy and explored potential moderation. RESULTS: Among 150 participants, median age was 40.5 years, 33.3% identified as Hispanic/Latinx, 64.7% were male, 73.3% were experiencing homelessness, and 44.7% had prior mandatory COVID-19 testing. The LinkUP intervention was significantly associated with higher COVID-19 testing uptake (p < .0001). Homelessness moderated intervention effects; LinkUP increased COVID-19 testing uptake more among participants experiencing homelessness (adjusted risk ratio [aRR]: 1.80; 95% CI: 1.56-2.09; p < .0001) than those not experiencing homelessness (aRR: 1.20; 95% CI: 1.01-1.43; p = .04). CONCLUSIONS: Findings from this pilot RCT support the preliminary efficacy of the "LinkUP" intervention to increase COVID-19 testing among PWID and underscore the importance of academic-community partnerships and prevention service delivery through SSPs and other community-based organizations serving vulnerable populations.


People who inject drugs (PWID) are vulnerable to severe COVID-19 disease yet have low rates of COVID-19 testing. We partnered with a syringe service program (SSP) in San Diego County, CA, to develop "LinkUP," an evidence- and community-informed intervention. Specifically, LinkUP used tailored education, motivational interviewing, and problem-solving and planning strategies to increase COVID-19 testing uptake among PWID. This study was a pilot randomized controlled trial (RCT) designed to assess the preliminary efficacy of LinkUP in increasing PWID COVID-19 testing. We referred participants (PWID, ≥18 years old, San Diego residents without recent voluntary COVID-19 testing) to mobile SSP sites that had been randomized (by week). Trained peer counselors then offered LinkUP or an educational control condition lasting the same length (~30 minutes). After either condition, counselors offered on-site rapid COVID-19 antigen testing. Among 150 participants, our analyses found that the LinkUP intervention was associated with higher COVID-19 testing uptake, especially for participants experiencing homelessness. In summary, our findings from this pilot RCT support the preliminary efficacy of the "LinkUP" intervention in increasing COVID-19 testing among PWID. This study also underscores the importance of academic-community partnerships and prevention service delivery through SSPs and other community-based organizations serving vulnerable populations.


Subject(s)
COVID-19 , Drug Users , Substance Abuse, Intravenous , Male , Humans , Adult , Adolescent , Female , Substance Abuse, Intravenous/complications , Substance Abuse, Intravenous/psychology , Pharmaceutical Preparations , Pilot Projects , COVID-19 Testing
14.
Can J Anaesth ; 70(3): 335-342, 2023 03.
Article in English | MEDLINE | ID: covidwho-2299450

ABSTRACT

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.


Subject(s)
Anesthetics , Humans , Pakistan , Cross-Sectional Studies , Pharmaceutical Preparations , Surveys and Questionnaires
15.
Eur J Drug Metab Pharmacokinet ; 48(3): 221-240, 2023 May.
Article in English | MEDLINE | ID: covidwho-2298862

ABSTRACT

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.


Subject(s)
COVID-19 , Cytochrome P-450 CYP2C9 Inducers , Humans , Cytochrome P-450 CYP2C9/genetics , Azithromycin , COVID-19 Vaccines , SARS-CoV-2/metabolism , Cytochrome P-450 Enzyme System/metabolism , Pharmaceutical Preparations , Drug Interactions
16.
Front Public Health ; 11: 1117841, 2023.
Article in English | MEDLINE | ID: covidwho-2298665

ABSTRACT

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.


Subject(s)
COVID-19 , Drug Overdose , Humans , United States/epidemiology , COVID-19/epidemiology , Pharmaceutical Preparations , Pandemics , Drug Overdose/epidemiology , Louisiana/epidemiology
17.
Sci Rep ; 13(1): 6165, 2023 04 15.
Article in English | MEDLINE | ID: covidwho-2296870

ABSTRACT

Quantitative analysis of pharmaceutical compounds up to Nano gram levels is highly recommended to introduce feasible and sensitive tool for determination of the compounds in the pharmaceutical and biological samples. Nirmatrelvir plus ritonavir was recently approved in the US, the UK and Europe as a new co-packaged dosage form for the treatment of COVID-19. The objective of this work was to develop a more sensitive TLC method based on using ß-cyclodextrin as a chiral selector additive in the mobile phase for simultaneous determination of nirmatrelvir and ritonavir in pure form, pharmaceutical formulation and spiked human plasma. The analysis procedures were developed using TLC aluminum silica gel plates and methanol-water- 2% urea solution of ß-cyclodextrin (40:10:.5, by volume) as a mobile phase with UV detection at 215 nm. The developed method was successfully applied over a linearity range of 10-50 ng/band for both nirmatrelvir and ritonavir. The method was validated for limits of detection and quantitation, accuracy, precision, specificity, system suitability, and robustness. Furthermore, the eco-friendliness of the proposed method was assessed using the analytical eco-scale and the green analytical procedure index. The described method exhibited compliance with green analytical chemistry principles based on common green metric values.


Subject(s)
COVID-19 , Ritonavir , Humans , Chromatography, Thin Layer/methods , COVID-19 Drug Treatment , Pharmaceutical Preparations
18.
Nat Commun ; 14(1): 993, 2023 02 22.
Article in English | MEDLINE | ID: covidwho-2296306

ABSTRACT

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 .


Subject(s)
Drug Repositioning , Precision Medicine , Humans , Pharmaceutical Preparations
19.
Water Sci Technol ; 87(7): 1747-1763, 2023 Apr.
Article in English | MEDLINE | ID: covidwho-2296037

ABSTRACT

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.


Subject(s)
COVID-19 , Wastewater , Humans , SARS-CoV-2 , COVID-19/epidemiology , RNA, Viral , Hospitals , Germany , Pharmaceutical Preparations
20.
Am J Health Syst Pharm ; 80(8): 518-525, 2023 04 08.
Article in English | MEDLINE | ID: covidwho-2303744

ABSTRACT

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.


Subject(s)
COVID-19 , Delivery of Health Care, Integrated , Humans , Pharmaceutical Preparations
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