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1.
Zhongguo Yufang Shouyi Xuebao / Chinese Journal of Preventive Veterinary Medicine ; 44(3):345-345, 2022.
Article in English, Chinese | CAB Abstracts | ID: covidwho-2034497

ABSTRACT

Since the outbreak of the new crown pneumonia, the new coronavirus (SARSCoV-2) has been mutating continuously, and it has now become prevalent in more than 200 countries. The cumulative number of confirmed cases in the world has exceeded 460 million, and the number of deaths has exceeded 6 million. The rapid mutation of SARS-CoV-2 highlights the importance of preventive and therapeutic drugs, however, effective therapeutic drugs for new coronary pneumonia are still very scarce. It is still the common goal of scientists from all over the world to develop a safe and effective drug for the treatment of new coronary pneumonia that can inhibit the infection of multiple SARS-CoV-2 mutant strains.

2.
Zhongguo Yufang Shouyi Xuebao / Chinese Journal of Preventive Veterinary Medicine ; 44(3):346-346, 2022.
Article in English, Chinese | CAB Abstracts | ID: covidwho-2034493

ABSTRACT

The new coronavirus (SARS-CoV-2) is raging around the world, infecting more than 460 million people and killing more than 6 million people, posing a serious threat to human health. Analyzing the pathogenic mechanism of the virus and discovering new drug targets are the keys to the development of antiviral drugs. Similar to the envelope proteins of many important viruses such as Ebola virus and Marburg virus, the spike (S) protein of SARS-CoV-2 relies on the cleavage and processing of cellular furin to mature during infection, and then make the virus infective, so furin is an important potential target for antiviral therapy. However, the regulation mechanism of furin enzyme activity in cells under physiological and infection conditions is not yet very clear.

3.
Acta Pharmaceutica Hungarica ; 91(3-4):120, 2021.
Article in English | EMBASE | ID: covidwho-2033589

ABSTRACT

A drawback of the current mRNA-lipid nanoparticle (LNP) COVID-19 vaccines is that they have to be stored at (ultra)low temperatures (2). Understanding the root cause of the instability of these vaccines may help to rationally improve mRNALNP product stability and thereby ease the temperature conditions for storage. In this presentation we discuss proposed structures of mRNALNPs, factors that impact mRNA-LNP stability and strategies to optimize mRNA-LNP product stability. Analysis of mRNA-LNP structures reveals that mRNA, the ionizable cationic lipid and water are present in the LNP core. The neutral helper lipids are mainly positioned in the outer, encapsulating, wall. mRNA hydrolysis is an important driver for mRNA-LNP instability. It is currently a matter of debate whether water in the LNP core can freely interact with the mRNA and to what extent the degradation prone sites of mRNA are protected through a coat of ionizable cationic lipids. To improve the stability of mRNALNP vaccines, optimization of the mRNA nucleotide composition should be prioritized. Secondly, a better understanding of the milieu the mRNA is exposed to in the core of LNPs may help to rationalize adjustments to the LNP structure to preserve mRNA integrity. Moreover, drying techniques, such as lyophilization, are promising options still to be explored. As vaccines turn out to be the major weapon against the COVID-19 viral attack, the urge to develop more stable formulations is still growing and alternative, not-mRNA based products, may come to the forefront in situations where the (ultra) cold chain cannot be guaranteed. (Table Presented).

4.
Asia-Pacific Journal of Clinical Oncology ; 18:101-102, 2022.
Article in English | EMBASE | ID: covidwho-2032336

ABSTRACT

Objectives:Nylon fiber is a synthetic polymer that possesses outstanding physical and chemical properties such as good strength, flexibility, and air permeability. Nylon fiber has been widely used worldwide for various products including bedding, wipes, clothing, surgical gowns, wig, etc. The outbreak of COVID-19 boosts a surge in consumer demand for antibacterial fabrics that have the ability of resistance to bacteria attack because textile materials are good medium for microorganism growth and breeding. The present study thus aims to develop a durable antibacterial nylon fabric that could be used as wig against householdwashing. Thiswig would provide a solution for patients need chemotherapy to increase their self-confidence. Methods: The method of pad-dry-cure process was used to treat the nylon fabric samples. The N1 finishing formulation was prepared by adding binder and cationic antibacterial agent to deionized water. N2 finishing solution was prepared by mixing binder and inorganic antibacterial agent in deionized water. The sample was first padded with the pre-prepared finishing formulation. Afterwards, the sample was dried in an oven at 100oC for 2 min and then cured at 150oC for 1 min. After antibacterial finishing, the samples were washed with shampoo for different cycles at room temperature. Each cycle lasts 1 min. Finally, the antibacterial property of treated samples was qualitatively conducted against gram-positive S. aureus and gram-negative K. pneumoniae according to AATCC TM 147-2011. Results: The antibacterial results demonstrate that both samples treated with N1 and N2 have excellent antibacterial activities, particularly against S. aureus. However, after washing with shampoo, N1 samples show a distinct decrease in the inhibition zone and the samples fail to kill bacteria. By contrast, N2 samples show satisfactory antibacterial properties after 52 washing cycles. Moreover, there is no significant change in the antibacterial activity of N2 samples after 52 washing cycles. This suggests that the inorganic antibacterial agent has stronger affinity to nylon fiber than cationic antibacterial agent treated nylon fabric presents durable antibacterial activity. Conclusions: The inorganic antibacterial agent shows strong affinity to nylon fiber and can be used for developing durable antibacterial nylon fabrics against washing.

5.
Drug Development and Delivery ; 22(4):18-23, 2022.
Article in English | Scopus | ID: covidwho-2012508
6.
Annals of the Rheumatic Diseases ; 81:1807, 2022.
Article in English | EMBASE | ID: covidwho-2008998

ABSTRACT

Background: Treatment of patients with osteoporosis was inadequate even before the COVID-19 pandemic. Not only patients without fracture, but only a small proportion of patients with osteoporotic fracture have treated. In Hungary only 30% of patients with osteoporosis received adequate antiporotic treatment before the pandemic. Almost 90% of whom were women, less than 10% of men. The incidence of fractures is increasing dramatically worldwide. In 2010, the vertebral fracture rate was 3.5 million in Europe but it is expected to reach 4.5 million by 2025. In 1990, osteoporosis caused 1.26 million hip fractures and by 2025 this is estimated at 2.6 million worldwide. The care for patients with osteoporosis was further aggravated by the restrictions necessarily imposed due to the coronavirus. Objectives: The aim of the study was to explore the extent and consequences of diagnostic and therapeutic failure in patients with osteoporosis. Methods: I determined the number of osteoporosis examinations performed in our centre in 2019-2021 from the medical database. I surveyed how many patients were discontinued the antiporotic treatment during the pandemic according to the different drug groups in Hungary and also in our centre as well as the prevalence of wrist and hip fractures due to minor trauma in our county in the pre-and post-pandemic period. Results: In our centre an average of 30 DEXA examinations were performed daily in the pre-pandemic period. From the end of October 2021 to the end of May 2021 there was not perform any ODM examinations. It means 3.980 missed exams and at least 1.000 missed osteoporosis diagnoses and therapy starts. More than 20% of patient were lost from the antiporotic care in Hungary. Drop-out was mainly seen in patients treated with bisphosphonates. There were 20730 bisphosphonate-treated patient in 2019, 19813 in 2020 and 17315 in 2021. Antiporotic treatment was discontinued in 30% of patients treated with bisphosphonate+vitamin-D (7849 in 2019, 6950 in 2020, 5484 in 2021) or bisphosphonate+calcium+vitamin-D fxed combination products (3256-2876-2289). In our centre, the prescribing of bisphosphonates has also decreased more than half. Patients treated with iv. bisphosphonates were interrupted or switched to oral formulations. Denosumab therapy was continuous: 581 injections were prescribed in the 12 months before and 579 during the pandemic. However, no new treatment started. In case of teriparatide, the initiated therapies were continued and even the number of prescriptions increased. As a consequence, an increase in the occurrence of fractures due to minor trauma is expected. Although epidemiological restrictions in this regard, the curfew has had some positive effects. According to international data, the number of wrist fractures has almost halved, while the data for hip fractures are controversial. The decrease of wrist fractures can also be verifed in our county. The number of wrist fractures was 598 in April-May 2019, 393 in the same period in 2020, and 372 in 2021. After a signifcant reduction in hip fractures in 2020, there is already an upward trend in 2021 (470 in 2019, 358 in 2020, 393 in 2021). The real consequences of failure to treat osteoporosis are expected only after years. Conclusion: Missed doctor-patient appointments were associated with missed diagnoses and interruptions of ongoing treatments. Fear of the virus, immobilisation due to home office and curfews, lack of exercise, sun exposure, caused depressive symptoms, increased alcohol consumption and caloric intake are all increase the risk of osteoporosis. Thus, traditional risk factors for osteoporosis expanded with the direct effects and the introduced restrictions because of the pandemic.

7.
Annals of the Rheumatic Diseases ; 81:590, 2022.
Article in English | EMBASE | ID: covidwho-2008867

ABSTRACT

Background: SB5, an adalimumab (ADL) biosimilar, was developed in a low-concentration (40 mg/0.8 mL, SB5-LC) aligned with the reference ADL product. Pharmacokinetics (PK) equivalence of SB5 and reference ADL was demonstrated in a Phase I study conducted in healthy subjects1. Equivalent efficacy and comparable safety between 40 mg/0.8 mL SB5 and 40 mg/0.8 mL reference ADL were demonstrated in a Phase III study conducted in patients with rheumatoid arthritis2. High-concentration, low-volume, citrate-free SB5 (40 mg/0.4 mL, SB5-HC) has been developed as a part of life cycle management in line with the reference ADL formulation. Objectives: To compare the PK, safety, and tolerability of the newly developed SB5-HC (40 mg/0.4 mL) to prior SB5-LC (40 mg/0.8 mL) in healthy male subjects. Methods: This study was a randomised, single-blind, two-arm, parallel group, single-dose study in healthy male subjects. Subjects were randomised in a ratio of 1:1 to receive a single dose of either SB5-HC or SB5-LC by subcutaneous injection on Day 1 and then observed for 57 days during which the PK, safety, and immunogenicity were evaluated. The serum concentration of ADL was measured using an enzyme-linked immunosorbent assay. The primary PK parameters were area under the concentration-time curve from time zero to infnity (AUCinf) and maximum serum concentration (Cmax). Equivalence for the primary PK parameters was to be concluded if the 90% confdence intervals (CIs) for the ratio of geometric least squares means (LSMeans) of the treatment groups compared were completely contained within the pre-defned equivalence margin of 0.80 to 1.25 using an analysis of variance. Results: Of 188 randomised subjects, 187 subjects were analysed as PK Analysis Set (PKS) (n=93 in SB5-HC and n=94 in SB5-LC). One subject was excluded from the PKS in SB5-HC group (major protocol deviation for not being withdrawn in the event of confrmed COVID-19). The geometric LSMeans ratios for the comparison of SB5-HC and SB5-LC for AUCinf and Cmax were 0.920 and 0.984, respectively, and the corresponding 90% CIs were within the pre-defned equivalence margin of 0.80 to 1.25 (Table 1), indicating the two treatment groups are bioequivalent. There were no deaths, serious adverse events or discontinuation of the study due to treatment-emergent adverse events (TEAEs) during the study. The proportions of subjects who experienced TEAEs were comparable between the two treatment groups (44.7% in SB5-HC vs 51.1% in SB5-LC). The most frequent TEAEs were headache (10.6% in SB5-HC vs 12.8% in SB5-LC). Conclusion: This study demonstrated PK equivalence between SB5-HC and SB5-LC in healthy subjects. Both SB5-HC and SB5-LC were generally well tolerated with similar safety profiles.

8.
Pharmaceutical Technology ; 2022:s30-s32, 2022.
Article in English | EMBASE | ID: covidwho-2006922
9.
Journal of Public Health in Africa ; 13:62-63, 2022.
Article in English | EMBASE | ID: covidwho-2006857

ABSTRACT

Introduction/ Background: In March 2020, the South African National Essential Medicines List Committee established a multidisciplinary expert panel to review emerging evidence for COVID-19 medicines quickly and systematically. Recommendations inform National Department of Health COVID-19 guidelines. We describe implementation of this rapid review mechanism and the impact of recommendations on medicines utilisation. Methods: A protocol was developed for conducting rapid reviews, including the formulation of pre-specified review question, search of at least 2 databases, data extraction and synthesis, evidence appraisal, and summarising key findings and recommendations (PROSPERO registration: CRD42021286710). The COVID-nma initiative was engaged, using global evidence syntheses, adapted to local context. National Surveillance Centre medicines procurement data were analysed, monitoring the impact of the guidelines on medicine use. Pre-pandemic medicine use (2019) was compared to pandemic use (2020), as a ratio of utilisation per 1000 uninsured population for corticosteroids, azithromycin, colchicine, and vitamin C. Results: To date the committee have reviewed 26 medicines (for treatment and prevention of COVID-19) by conducting 52 rapid reviews (including updates and evidence summaries). Review of aggregate procurement data showed that utilisation of corticosteroids (that is recommended for hospitalised COVID-19 patients on oxygen), increased 1.6-fold across all 9 South African provinces. Colchicine and azithromycin (not recommended to treat COVID-19) use did not change. However, use of vitamin C (not recommended) increased 2.2-fold. Impact: A generic rapid review protocol using GRADE principles and an explicit evidence-to-decision framework promoted adaptation of global evidence to develop robust and transparent guidelines. Medicines utilisation data, though, suggests that investment is needed to strengthen guideline implementation. Conclusion: Through extensive collaboration, the Department of Health managed therapeutic uncertainty by developing and implementing a rapid, robust, and transparent evidence-informed approach. However, the impact on clinical practice is uncertain, highlighting the need for more intensive investigation of patient-level prescribing data and engagement with healthcare providers.

10.
South African Medical Journal ; 112(8):522-525, 2022.
Article in English | EMBASE | ID: covidwho-2006465

ABSTRACT

Background. Ivermectin is an antiparasitic drug that has shown in vitro activity against COVID-19. Clinical studies supporting ivermectin for COVID-19 prevention and treatment are conflicting, with important limitations. Public support for ivermectin is significant, with extensive off-label use despite the conflicting views on its efficacy. Ivermectin tablets and injectable formulations are not registered in South Africa for human use by the South African Health Products Regulatory Authority. The National Department of Health does not currently recommend the use of ivermectin for COVID-19. Objectives. To describe cases of ivermectin exposure reported to the Poisons Information Helpline of the Western Cape (PIHWC) before and after publication of the drug’s in vitro activity against SARS-CoV-2. Methods. In a retrospective review, ivermectin-related calls reported to the PIHWC from 1 June 2015 to 30 June 2020 (period 1) were compared with calls received from 1 July 2020 to 31 July 2021 (period 2), dichotomised according to the first publication indicating ivermectin activity against SARS-CoV-2. Results. Seventy-one cases were screened, and 65 were included for analysis;19 cases were reported during period 1 and 46 during period 2. During period 2, 25 ivermectin cases (54.3%) were related to COVID-19 use. Of these, 24 cases (52.2%) involved veterinary preparations, 3 (6.5%) human preparations and 19 (41.3%) unknown preparations. Fourteen cases (73.7%) during period 1 and 30 (65.2%) during period 2 were reported to be symptomatic. The most common organ systems involved were the central nervous (n=26 cases;40.0%), gastrointestinal (n=18;27.7%), ocular (n=9;13.8%) and dermatological (n=5;7.7%) systems. Conclusion. Ivermectin-related exposure calls increased during study period 2, probably as a result of ivermectin being used as preventive and definitive therapy for COVID-19 in the absence of robust evidence on efficacy, dosing recommendations or appropriate formulations.

11.
Journal of Clinical Oncology ; 40(16), 2022.
Article in English | EMBASE | ID: covidwho-2005689

ABSTRACT

Background: Rituximab (anti-CD20 Ab) is the cornerstone of the treatment of non-Hodgkin B lymphomas. Infusion-related reactions (IRR) are the most common adverse effects. To reduce them, intravenous premedication with antihistamine and acetaminophen is administered prior to rituximab. If no IRR after first infusion, subsequent infusions time takes 3-6 hours. Many centers use the rapid 90-minute infusion (off-label). Since 2017 subcutaneous rituximab formulation is available, that takes 5 minutes of administration. Nevertheless, in order to reduce cost, due to approval of biosimilars, some health providers continue using intravenous rituximab. On the other hand, with COVID pandemic, an effort to reduce visits and day-care hospitals stays has been made. In the current situation, it would be convenient to reduce day-care stay and the nursing care burden. We wanted to evaluate the safety of an ultrarapid infusion of biosimilar rituximab in a total time of 30 minutes by analyzing IRR and adverse events (AE). Methods: Since November 2021, 3 cohorts of ultrafast infusion have been studied as follows: One cohort (Cohort 1) with intravenous premedication with dexchlorpheniramine and acetaminophen, followed by rituximab infusion over 1 hour, and 2 cohorts with rituximab infusion over 30 minutes: Cohort 2: with intravenous premedication, and cohort 3 with oral premedication. IRR and adverse events have been independently reviewed and graded using Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 (November 27, 2017). Results: 34 patients have been included receiving 48 rituximab infusions (16 infusions in each cohort). Median age was 64 years old (range: 51-91). Diagnostic of NHL were as follows: large b cell: 10;follicular: 13;marginal: 7;mantle cell: 1, Waldeström: 1;Ritcher transformation: 2. Rituximab infusion was in monotherapy (21), and in combination (27) with: bendamustine: 9, CHOP: 17, GEMOX: 1. Considering safety, no IRR has been observed in cohort 1 (1 hour infusion), and 1 IRR grade II in cohort 3 (30 minutes, oral premedication). Other AE were: hypertension grade I and hypotension grade I, both in cohort 2. Conclusions: Ultrarapid rituximab infusion is safe. Oral premedication is feasibly allowing a total infusion time of 30 minutes. This infusion rate alleviates day-care burden saving between 75-90% of time in each rituximab infusion, reduce day-care stay and is comfortable for the patients.

12.
Production Planning & Control ; 2022.
Article in English | Web of Science | ID: covidwho-2004874

ABSTRACT

This study presents an optimisation model for scheduling homebound vaccination in a more efficient way to address the existing workforce management challenge. We consider a home healthcare routeing challenge for people to be vaccinated at home based on limited resources. There are different types of patients that are categorised based on the services they require and should be served by appropriate workforce teams or a single medical staff, where teams are transported by rental vehicles. In this context, our goal is to minimise the total cost of transportation while considering patient requirements and workforce qualifications, as well as resource constraints and the time limit within which the vaccine must be administered. To pursue this goal, a mathematical formulation, based on the vehicle routeing dynamics is proposed, along with an algorithm to address the challenge. A case study with a Physician who administers vaccinations at home in southeastern Italy is analysed. Driving and working times are subject to uncertainty and are defined by empirical data. Our approach allows the physician to identify the most promising solutions and thus the best one in terms of reducing work time and risk. The resulting schedule maximises the vaccine delivery rate.

13.
World Journal of Clinical Cases ; 10(23):8170-8185, 2022.
Article in English | EMBASE | ID: covidwho-1998047

ABSTRACT

BACKGROUND Coronavirus disease 2019 (COVID-19) is a global pandemic putting the population at a high risk of infection-related health hazards, mortality and a potential failure of proper medical therapies. Therefore, it is necessary to evaluate the potential use of the existing drugs that could be used as options for the medical management of COVID-19 patients. AIM To evaluate the role of the H2 receptor blocker “famotidine” in COVID-19 illness. METHODS This study was done on seriously ill COVID-19 patients admitted to the intensive care unit (ICU) from different institutes in Bangladesh. Patients were divided into famotidine treatment group “A” (famotidine 40 mg to 60 mg oral formulation every 8 h with other treatment as given), and control group “B” (treatment as given). National early warning score (NEWS)-2, and sequential organ failure assessment day-1 score was calculated to evaluate the outcome. Outcomes were evaluated by the time required for clinical improvement, characterized as duration required from enrollment to the achievement of NEWS-2 of ≤ 2 maintained for 24 h;time to symptomatic recovery, defined as the duration in days (from randomization) required for the recovery of the COVID-19 symptoms;mortality rate;duration of ICU and hospital stay;total period of hospitalization;the rate of supplementary oxygen requirement;the computed tomography (CT) chest recovery (%), the time required for the viral clearance and “NEWS-2” on discharge. RESULTS A total of 208 patients were enrolled in this study with 104 patients in each group. The famotidine treatment group had comparatively better recovery of 75% and a low mortality of 25% than the control with a recovery of 70% and a mortality of 30%. Duration of clinical improvement (group A 9.53 d, group B 14.21 d);hospitalization period among the recovered patients (group A 13.04 d, group B 16.31 d), pulmonary improvement in chest CT (group A 21.7%, group B 13.2%), and the time for viral clearance (group A 20.7 d, group B 23.8 d) were found to be statistically significant P ≤ 0.05. However, the Kaplan Meier survival test was not significant among the two study groups, P = 0.989. CONCLUSION According to our study, treatment with famotidine achieved a better clinical outcome compared to the control group in severe COVID-19 illness, although no significant survival benefit was found.

14.
American Journal of Kidney Diseases ; 79(4):S88, 2022.
Article in English | EMBASE | ID: covidwho-1996899

ABSTRACT

Immune dysregulation has been postulated as a pathogenetic mechanism for minimal change disease (MCD) and several vaccines have been reported to act as a trigger for relapse. While cases of both de-novo MCD and MCD relapse have been reported following severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) mRNA vaccinations, we report, to the best of our knowledge, the first case of MCD relapse following booster dose of Pfizer-BioNTech SARS-CoV-2 vaccine. 63-year-old Italian male, with history of nephrotic syndrome secondary to kidney biopsy proven MCD, who had achieved complete remission with steroid therapy, had follow up labs done that showed spot urine protein: creatinine of 10.1 and albumin of 3.0g/dL. He had received the booster dose of Pfizer-BioNTech SARS-CoV-2 vaccine 2 weeks ago, and endorsed generalized weakness, puffiness over face, edema over upper extremities that appeared within a week after administration of the vaccine, and weight gain of 10 lbs over past week. Blood pressure was elevated (152/78 mmHg). He denied any recent infections, use of Nonsteroidal Anti-Inflammatory Drugs, or antibiotics. Other diagnostic work up revealed hypertriglyceridemia, normal serum creatinine. Serological work up for secondary causes of glomerular diseases was negative. He was initiated on oral prednisone therapy. Spot urine protein:creatinine decreased to 1.1, 2 weeks after initiation of steroids. Vaccination is a recognized trigger for relapse of nephrotic syndrome. mRNA vaccines are expected to produce a higher antibody response as well as increased production of cytokines and chemokines. This can lead to dysregulation in permeability factors that can result in relapsing glomerulonephritis. As data on adverse effects of SARS-CoV-2 vaccines continue to evolve, we suggest to closely monitor patients with history of nephrotic syndrome for relapse after receipt of the SARS-CoV-2 vaccine, including the booster dose. Further studies are needed to determine whether relapse of MCD is specific for SARS-CoV-2 mRNA vaccination and to decipher mechanisms for possible immune dysregulation in those patients. This may help in formulation of protocol for vaccination in patients with nephrotic syndrome and contribute to informed decision making.

15.
Journal of Hepatology ; 77:S551, 2022.
Article in English | EMBASE | ID: covidwho-1996642

ABSTRACT

Background and aims: Hepatitis C virus (HCV) infection is a major global health problem in adults & children. The recent efficacy of Direct Acting Anti-viral therapy (DAA) has cure rates of 99% in adults and adolescents. These drugs were licensed for children 3–12 yrs during the recent coronavirus pandemic. To ensure equitable access, safe & convenient supply during lockdown, we established a virtual national treatment pathway for children with HCV in England & evaluated its feasibility, efficacy & treatment outcomes. Method: A paediatric Multidisciplinary Team Operational Delivery Network (pMDT ODN), supported by NHS England (NHSE), was established with relevant paediatric specialists to provide a single point of contact for referrals & information. Referral & treatment protocolswere agreed for HCV therapy approved byMHRA& EMA. On referral the pMDT ODN agreed the most appropriate DAA therapy based on clinical presentation & patient preferences, including ability to swallow tablets. Treatment was prescribed in association with the local paediatrician & pharmacist, without the need for children & families to travel to national centres. All children were eligible for NHS funded therapy;referral centres were approved by the pMDT ODN to dispense medication;funding was reimbursed via a national NHSE agreement. Demographic & clinical data, treatment outcomes & SVR 12 were collected. Feedback on feasibility & satisfaction on the pathway was sought from referrers. Results: In the first 6 months, 34 childrenwere referred;30- England;4-Wales;median (range) age 10 (3.9–14.5) yrs;15M;19F: Most were genotype type 1 (17) & 3 (12);2 (1);4 (4). Co-morbidities included: obesity (2);cardiac anomaly (1);Cystic Fibrosis (1);Juvenile Arthritis (1). No child had cirrhosis. DAA therapy prescribed: Harvoni (21);Epclusa (11);Maviret (2). 27/34 could swallow tablets;3/7 received training to swallowtablets;4/7 are awaiting release of granules.11/27 have completed treatment and cleared virus;of these 7/11 to date achieved SVR 12. 30 children requiring DAA granule formulation are awaiting referral and treatment. Referrers found the virtual process easy to access, valuing opportunity to discuss their patient’s therapy with the MDT & many found it educational. There were difficulties in providing the medication through the local pharmacy. However there are manufacturing delays in providing granule formulations because suppliers focused on treatments for COVID, leading to delays in referring and treating children unable to swallow tablets. Conclusion: The National HCV pMDT ODN delivers high quality treatment & equity of access for children & young people, 3–18 yrs with HCV in England, ensuring they receive care close to home with 100% cure rates.

16.
Bioengineered ; 13(6): 14681-14718, 2022 06.
Article in English | MEDLINE | ID: covidwho-1984964

ABSTRACT

Arthrospira platensis (A. platensis) aqueous extract has massive amounts of natural products that can be used as future drugs, such as C-phycocyanin, allophycocyanin, etc. This extract was chosen because of its high adaptability, which reflects its resolute genetic composition. The proactive roles of cyanobacteria, particularly in the medical field, have been discussed in this review, including the history, previous food and drug administration (FDA) reports, health benefits and the various dose-dependent therapeutic functions that A. platensis possesses, including its role in fighting against lethal diseases such as cancer, SARS-CoV-2/COVID-19, etc. However, the remedy will not present its maximal effect without the proper delivery to the targeted place for deposition. The goal of this research is to maximize the bioavailability and delivery efficiency of A. platensis constituents through selected sites for effective therapeutic outcomes. The solutions reviewed are mainly on parenteral and tablet formulations. Moreover, suggested enteric polymers were discussed with minor composition variations applied for better storage in high humid countries alongside minor variations in the polymer design were suggested to enhance the premature release hindrance of basic drugs in low pH environments. In addition, it will open doors for research in delivering active pharmaceutical ingredients (APIs) in femtoscale with the use of various existing and new formulations.Abbrevations: SDGs; Sustainable Development Goals, IL-4; Interleukin-4, HDL; High-Density Lipoprotein, LDL; Low-Density Lipoprotein, VLDL; Very Low-Density Lipoprotein, C-PC; C-Phycocyanin, APC; Allophycocyanin, PE; Phycoerythrin, COX-2; Cyclooxygenase-2, RCTs; Randomized Control Trials, TNF-α; Tumour Necrosis Factor-alpha, γ-LFA; Gamma-Linolenic Fatty Acid, PGs; Polyglycans, PUFAs: Polyunsaturated Fatty Acids, NK-cell; Natural Killer Cell, FDA; Food and Drug Administration, GRAS; Generally Recognized as Safe, SD; Standard Deviation, API; Active Pharmaceutical Ingredient, DW; Dry Weight, IM; Intramuscular, IV; Intravenous, ID; Intradermal, SC; Subcutaneous, AERs; Adverse Event Reports, DSI-EC; Dietary Supplement Information Executive Committee, cGMP; Current Good Manufacturing Process, A. platensis; Arthrospira platensis, A. maxima; Arthrospira maxima, Spirulina sp.; Spirulina species, Arthrospira; Spirulina, Tecuitlatl; Spirulina, CRC; Colorectal Cancer, HDI; Human Development Index, Tf; Transferrin, TfR; Transferrin Receptor, FR; Flow Rate, CPP; Cell Penetrating Peptide, SUV; Small Unilamenar Vesicle, LUV; Large Unilamenar Vesicle, GUV; Giant Unilamenar Vesicle, MLV; Multilamenar Vesicle, COVID-19; Coronavirus-19, PEGylated; Stealth, PEG; Polyethylene Glycol, OSCEs; Objective Structured Clinical Examinations, GI; Gastrointestinal Tract, CAP; Cellulose Acetate Phthalate, HPMCP, Hydroxypropyl Methyl-Cellulose Phthalate, SR; Sustained Release, DR; Delay Release, Poly(MA-EA); Polymethyl Acrylic Co-Ethyl Acrylate, f-DR L-30 D-55; Femto-Delay Release Methyl Acrylic Acid Co-Ethyl Acrylate Polymer, MW; Molecular Weight, Tg; Glass Transition Temperature, SN2; Nucleophilic Substitution 2, EPR; Enhance Permeability and Retention, VEGF; Vascular Endothelial Growth Factor, RGD; Arginine-Glycine-Aspartic Acid, VCAM-1; Vascular Cell Adhesion Molecule-1, P; Coefficient of Permeability, PES; Polyether Sulfone, pHe; Extracellular pH, ζ-potential; Zeta potential, NTA; Nanoparticle Tracking Analysis, PB; Phosphate Buffer, DLS; Dynamic Light Scattering, AFM; Atomic Force Microscope, Log P; Partition Coefficient, MR; Molar Refractivity, tPSA; Topological Polar Surface Area, C log P; Calculated Partition Coefficient, CMR; Calculated Molar Refractivity, Log S; Solubility Coefficient, pka; Acid Dissociation Constant, DDAB; Dimethyl Dioctadecyl Ammonium Bromide, DOPE; Dioleoylphosphatidylethanolamine, GDP; Good Distribution Practice, RES; Reticuloendothelial System, PKU; Phenylketonuria, MS; Multiple Sclerosis, SLE; Systemic Lupus Erythematous, NASA; National Aeronautics and Space Administration, DOX; Doxorubicin, ADRs; Adverse Drug Reactions, SVM; Support Vector Machine, MDA; Malondialdehyde, TBARS; Thiobarbituric Acid Reactive Substances, CRP; C-Reactive Protein, CK; Creatine Kinase, LDH; Lactated Dehydrogenase, T2D; Type 2 Diabetes, PCB; Phycocyanobilin, PBP; Phycobiliproteins, PEB; Phycoerythrobilin, DPP-4; Dipeptidyl Peptidase-4, MTT; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide, IL-2; Interleukin-2, IL-6; Interleukin-6, PRISMA; Preferred Reporting Items for Systematic Reviews and Meta-Analyses, STATA; Statistics, HepG2; Hepatoblastoma, HCT116; Colon Cancer Carcinoma, Kasumi-1; Acute Leukaemia, K562; Chronic Leukaemia, Se-PC; Selenium-Phycocyanin, MCF-7; Breast Cancer Adenocarcinoma, A375; Human Melanoma, RAS; Renin-Angiotensin System, IQP; Ile-Gln-Pro, VEP; Val-Glu-Pro, Mpro; Main Protease, PLpro; Papin-Like Protease, BMI; Body Mass Index, IC50; Inhibitory Concentration by 50%, LD50; Lethal Dose by 50%, PC12 Adh; Rat Pheochromocytoma Cells, RNS; Reactive Nitrogen Species, Hb1Ac; hemoglobin A1c.


Increase awareness of the impact and multi-disciplinary up-to-date roles of A. platensis on human lives and the importance of having further research on microalgae.Soliciting a critical analysis study on A. platensis biocomposition for drug delivery research.Insights on the correlation between ionization and drug bioavailability in specific sites in the human body.Offering solutions for improvising an optimized 'Advanced Spirulina Dosage Forms' products to maximize A. platensis therapeutic/pharmacological outcomes.Insights on existing biomaterials for optimization.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Leukemia , Spirulina , Humans , Lipoproteins, LDL/metabolism , Peptide Hydrolases/metabolism , Pharmaceutical Preparations/metabolism , Phycocyanin/chemistry , Polymers/metabolism , SARS-CoV-2 , Spirulina/chemistry , Spirulina/metabolism , Treatment Outcome , United States , Vascular Endothelial Growth Factor A/metabolism
17.
Pharmaceutical Technology ; 46(4):36–37 and 53, 2022.
Article in English | EMBASE | ID: covidwho-1980483
18.
International Journal of Applied Metaheuristic Computing ; 13(1):25, 2022.
Article in English | Web of Science | ID: covidwho-1979479

ABSTRACT

GSK algorithm is based on the concept of how humans acquire and share knowledge through their lifespan. Discrete binary version of GSK named novel binary gaining sharing knowledge-based optimization algorithm (DBGSK) depends on mainly two binary stages: binary junior gaining sharing stage and binary senior gaining sharing stage with knowledge factor 1. These two stages enable BGSK for exploring and exploitation of the search space efficiently and effectively to solve problems in binary space. One of these practical applications is to optimally schedule the flights for residual stranded citizens due to COVID-19. The problem is defined for a decision maker who wants to schedule a multiple stepped trip for a subset of candidate airports to return the maximum number of residuals of stranded citizens remaining in listed airports while comprising the minimization of the total travelled distances for a carrying airplane. A nonlinear binary mathematical programming model for the problem is introduced with a real application case study. The case study is solved using DBGSK.

19.
J Forensic Leg Med ; 91: 102401, 2022 Jul 30.
Article in English | MEDLINE | ID: covidwho-1966843

ABSTRACT

This study investigated the problem of refusal of the COVID-19 vaccine. To solve this problem, it is necessary to develop regulations governing sanctions for refusing the COVID-19 vaccine and include these sanctions on informed consent documents. An informed consent document can be provided when health workers give a person a COVID-19 vaccine and be used as concrete evidence that a person refused to be vaccinated. This is very important considering that the COVID-19 vaccination program is expected to be able to accelerate COVID-19 management and prevention by achieving herd immunity. In this study, the researchers applied a socio-legal research method. This study investigated several aspects, the first is the issue of the refusal of the COVID-19 vaccine and the second are the legal considerations. The third aspect is a regulation model to deal with the issue of COVID-19 vaccine refusal.

20.
Medicine in Drug Discovery ; : 100141, 2022.
Article in English | ScienceDirect | ID: covidwho-1966944

ABSTRACT

Ivermectin is a well-known and widely used anti-parasitic drug. Recently, in vitro data suggest anti-viral efficacy of the drug, albeit at much higher concentrations than currently approved. Despite warnings by several governing bodies, the (uncontrolled) human use of ivermectin has significantly increased during the COVID-19 epidemic. This study thus aimed to elucidate potential neurological risk of particularly the veterinary formulation of ivermectin in comparison to pure ivermectin. Zebrafish eggs (1hpf) and larvae (4dpf) were exposed to a range of concentrations of either pure ivermectin (IVM) or a veterinary formulation (V-IVM) for a period of 24 hours. Behavioral responses to both treatments were assessed at various timepoints using the pentylenetetrazol assay, the light-dark assay and a 5-day teratogenesis protocol. In addition, dissolution rates were calculated for both treatments. Acute responses of larvae at 4 - <5dpf was similar for both treatments – a transient hyperlocomotion was followed by a general hypolocomotion (ANOVA dose effect, P<0.01). Both IVM and V-IVM-treated larvae showed significant dose-dependent (ANOVA dose effect, P<0.0001) decreases in responsiveness to repeated light-dark transitions, which again was more pronounced in IVM. These effects were maintained after 24 hours of exposure. In contrast, when ivermectin was administered prior to establishment of the blood brain-barrier in the teratogenesis protocol, V-IVM treatment was linked to more severe activity decline on <5dpf. Differences in dissolution rates cannot account for these differences. In conclusion, current data suggest significantly higher neurological risk of a veterinary formulation of ivermectin under conditions of penetration across the blood brain-barrier.

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