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The Western Journal of Emergency... May 2020In March 2020, the World Health Organization declared the spread of SARS-CoV-2 a global pandemic. To date, coronavirus disease-2019 (COVID-19) has spread to over 200...
In March 2020, the World Health Organization declared the spread of SARS-CoV-2 a global pandemic. To date, coronavirus disease-2019 (COVID-19) has spread to over 200 countries, leading to over 1.6 million cases and over 99,000 deaths. Given that there is neither a vaccine nor proven treatment for COVID-19, there is currently an urgent need for effective pharmacotherapy. To address the need for an effective treatment of SARS-CoV-2 during the worldwide pandemic, this systematic review of intravenous (IV) remdesivir was performed. Remdesivir, an anti-viral prodrug originally developed to treat Ebola virus disease, has shown broad spectrum activity against the Coronavirus family. A recent case report reported improvement of clinical symptoms with remdesivir in a patient with COVID-19. After conducting a systematic search of 18 clinical trial registries and three large scientific databases, we identified 86 potentially eligible items. Following removal of duplicates (n = 21), eligible studies were reviewed independently by two authors. After the first round of screening, inter-rater agreement was 98.5% (κ = 0.925). After the second round of full-text screening, inter-rater agreement was 100%. A total of seven ongoing and recruiting clinical trials of remdesivir (100-200 milligrams, intravenous [IV]) were included. We identified the following primary outcomes: patients discharged (n = 2); time to clinical status improvement (n = 2); improved O2 saturation (n = 2); body temperature normalization (n = 2); and clinical status (n = 1). Secondary outcomes in all identified studies included documentation of adverse events. Phase 3 trials are expected to be completed between April 2020-2023. Therefore, despite supportive data from in vitro and in vivo studies, the clinical effectiveness of IV remdesivir for treatment of COVID-19 and potential side effects remain incompletely defined in the human population.
Topics: Adenosine Monophosphate; Administration, Intravenous; Alanine; Antiviral Agents; Betacoronavirus; COVID-19; Clinical Trials as Topic; Coronavirus Infections; Humans; Pandemics; Pneumonia, Viral; SARS-CoV-2; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 32726230
DOI: 10.5811/westjem.2020.5.47658 -
British Journal of Cancer Jul 2006Two oral fluoropyrimidine therapies have been introduced for metastatic colorectal cancer. One is a 5-fluorouracil pro-drug, capecitabine; the other is a combination of... (Comparative Study)
Comparative Study Review
Two oral fluoropyrimidine therapies have been introduced for metastatic colorectal cancer. One is a 5-fluorouracil pro-drug, capecitabine; the other is a combination of tegafur and uracil administered together with leucovorin. The purpose of this study was to compare the clinical effectiveness and cost-effectiveness of these oral therapies against standard intravenous 5-fluorouracil regimens. A systematic literature review was conducted to assess the clinical effectiveness of the therapies and costs were calculated from the UK National Health Service perspective for drug acquisition, drug administration, and the treatment of adverse events. A cost-minimisation analysis was used; this assumes that the treatments are of equal efficacy, although direct randomised controlled trial (RCT) comparisons of the oral therapies with infusional 5-fluorouracil schedules were not available. The cost-minimisation analysis showed that treatment costs for a 12-week course of capecitabine (Pounds 2132) and tegafur with uracil (Pounds 3385) were lower than costs for the intravenous Mayo regimen (Pounds 3593) and infusional regimens on the de Gramont (Pounds 6255) and Modified de Gramont (Pounds 3485) schedules over the same treatment period. Oral therapies result in lower costs to the health service than intravenous therapies. Further research is needed to determine the relative clinical effectiveness of oral therapies vs infusional regimens.
Topics: Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Colorectal Neoplasms; Cost-Benefit Analysis; Deoxycytidine; Fluorouracil; Humans; Meta-Analysis as Topic; Randomized Controlled Trials as Topic; State Medicine; Tegafur; Treatment Outcome; United Kingdom; Uracil
PubMed: 16804526
DOI: 10.1038/sj.bjc.6603215 -
South African Medical Journal =... Mar 2014There is an alarming global increase in the incidence of nosocomial infections with multidrug-resistant Gram-negative bacteria, which are often only susceptible to... (Review)
Review
BACKGROUND
There is an alarming global increase in the incidence of nosocomial infections with multidrug-resistant Gram-negative bacteria, which are often only susceptible to colistin. Colistin was developed prior to current methods of establishing dosing using pharmacokinetic-pharmacodynamic relationships. Dosing regimens differ in package inserts from different manufacturers and in different guidelines. It is imperative to avoid under-dosing with colistin in order to limit the development of resistance, as it is the last line of defence.
METHODS
We conducted a systematic review of the literature to develop guidelines for rational dosing of intravenous colistin, with a particular focus on critically ill patients.
RESULTS
Colistin is administered as the inactive pro-drug colistimethate sodium. Colistin demonstrates concentration-dependent bacterial killing, suggesting that higher doses should be administered less frequently to achieve higher peak concentrations. Dose-related nephrotoxicity occurs, making it impossible to safely achieve concentrations that prevent the selection of resistant mutants or the effective eradication of bacteria with higher minimum inhibitory concentrations. Theoretically, combination therapy should be used to reduce the risk of selection of resistant bacteria. In critically ill patients, a loading dose should be given to rapidly achieve therapeutic concentrations, followed by maintenance doses of 4.5 MU 12-hourly. Maintenance dose adjustment is necessary with renal impairment.
CONCLUSION
Easier access to colistin is needed in South Africa, where it is not a registered medicine. Further research is needed to better characterise colistin's pharmacokinetic-pharmacodynamic relationships in humans and to establish whether combinations of colistin with other antimicrobials result in improved clinical outcomes or a reduction in selection of resistant bacteria.
Topics: Colistin; Critical Illness; Evidence-Based Medicine; Gram-Negative Bacteria; Humans; Injections, Intravenous
PubMed: 24897820
DOI: No ID Found -
Drug Design, Development and Therapy 2022The rising outbreak of SARS-CoV-2 continues to unfold all over the world. The development of novel effective antiviral drugs to fight against SARS-CoV-2 is a time cost....
The rising outbreak of SARS-CoV-2 continues to unfold all over the world. The development of novel effective antiviral drugs to fight against SARS-CoV-2 is a time cost. As a result, some specific FDA-approved drugs have already been repurposed and authorized for COVID-19 treatment. The repurposed drugs used were either antiviral or non-antiviral drugs. Accordingly, the present review thoroughly focuses on the repurposing efficacy of these drugs including clinical trials experienced, the combination therapies used, the novel methods followed for treatment, and their future perspective. Therefore, drug repurposing was regarded as an effective avenue for COVID-19 treatment. Recently, molnupiravir is a prodrug antiviral medication that was approved in the United Kingdom in November 2021 for the treatment of COVID-19. On the other hand, PF-07321332 is an oral antiviral drug developed by Pfizer. For the treatment of COVID-19, the PF-07321332/ritonavir combination medication is used in Phase III studies and was marketed as Paxlovid. Herein, we represented the almost history of combating COVID-19 from repurposing to the recently available oral anti-SARS-CoV-2 candidates, as a new hope to end the current pandemic.
Topics: Antiviral Agents; Cytidine; Drug Approval; Drug Repositioning; Humans; Hydroxylamines; Microbial Sensitivity Tests; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35321497
DOI: 10.2147/DDDT.S354841 -
Expert Review of Pharmacoeconomics &... Apr 2010Capecitabine, an oral prodrug of 5-fluorouracil, is indicated for adjuvant treatment in patients with Dukes' C colon cancer and for subsequent lines in metastatic... (Review)
Review
Capecitabine, an oral prodrug of 5-fluorouracil, is indicated for adjuvant treatment in patients with Dukes' C colon cancer and for subsequent lines in metastatic colorectal cancer. The aim of this article is to review the literature on the economics of capecitabine for the treatment of colon cancer. A systematic review was conducted to search for articles published from January 2003 to December 2009 that met the inclusion criteria. For abstracts that were considered acceptable, full-text articles were then reviewed. Of the 42 potential studies that were identified, 13 original studies (16 publications) met the inclusion criteria. To date, the economic evaluation literature has consistently projected or found that capecitabine is not only a cost-effective treatment for adjuvant or for metastatic colorectal cancer (i.e., providing good value for money) but, furthermore, would actually be cost saving in the majority of country settings.
Topics: Antimetabolites, Antineoplastic; Capecitabine; Chemotherapy, Adjuvant; Colorectal Neoplasms; Cost Savings; Cost-Benefit Analysis; Deoxycytidine; Fluorouracil; Health Care Costs; Humans; Neoplasm Metastasis; Prodrugs
PubMed: 20384557
DOI: 10.1586/erp.10.12 -
Zeitschrift Fur Geburtshilfe Und... Apr 2020The number of diseases covered by universal neonatal screening in Germany has risen steadily from 1 (phenylketonuria) in 1968 to 17 (with hearing impairment and...
INTRODUCTION
The number of diseases covered by universal neonatal screening in Germany has risen steadily from 1 (phenylketonuria) in 1968 to 17 (with hearing impairment and congenital hip dysplasia) in 2018. Treatment, however, of disorders diagnosed by screening may harm children, as failed neuroblastoma screening has shown. There are several pilot studies to detect congenital cytomegalovirus (CMV) infection but no consensus as to the treatment of the infants identified.
METHODOLOGY
Systematic search for studies investigating therapy of congenital CMV infection, using PubMed and the WHO International Clinical Trials Registry Platform (ICTRP).
RESULTS
We found only one controlled trial that randomized infants with symptomatic congenital CMV infection (involving the central nervous system) to treatment (intravenous ganciclovir for 6 weeks) or no treatment. Treatment was associated with significantly less hearing deterioration. A second trial comparing 6 weeks vs. 6 months of treatment with valganciclovir, an oral prodrug of ganciclovir, found no benefit for hearing but modestly improved developmental outcomes associated with 6 months of treatment. In contrast, an open-label registry reported benefits for infants with congenital CMV infection and isolated hearing who received valganciclovir for 12 months, with hearing improvement in 2/3 of cases after a median follow-up of 4½ years.
CONCLUSIONS
Antiviral treatment of neonates with congenital CMV infection and few symptoms including isolated hearing loss remains controversial. A generally accepted therapy, however, is pivotal before introducing universal or targeted screening for congenital CMV infection.
Topics: Antiviral Agents; Child; Cytomegalovirus Infections; Ganciclovir; Germany; Hearing Loss, Sensorineural; Humans; Infant; Infant, Newborn; Neonatal Screening; Treatment Outcome
PubMed: 31426118
DOI: 10.1055/a-0966-9915