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Ceftriaxone is a third-generation cephalosporin used to treat infants with community-acquired pneumonia. Currently, there is a large variability in the amount of ceftriaxone used for this purpose in this particular age group, and an evidence-based optimal dose is still unavailable. Therefore, we investigated the population pharmacokinetics of ceftriaxone in infants and performed a developmental pharmacokinetic-pharmacodynamic analysis to determine the optimal dose of ceftriaxone for the treatment of infants with community-acquired pneumonia. A prospective, open-label pharmacokinetic study of ceftriaxone was conducted in infants (between 1 month and 2 years of age), adopting an opportunistic sampling strategy to collect blood samples and applying high-performance liquid chromatography to quantify ceftriaxone concentrations. Developmental population pharmacokinetic-pharmacodynamic analysis was conducted using nonlinear mixed effects modeling (NONMEM) software. Sixty-six infants were included, and 169 samples were available for pharmacokinetic analysis. A one-compartment model with first-order elimination matched the data best. Covariate analysis elucidated that age and weight significantly affected ceftriaxone pharmacokinetics. According to the results of a Monte Carlo simulation, with a pharmacokinetic-pharmacodynamic target of a free drug concentration above the MIC during 70% of the dosing interval (70% fT>MIC), regimens of 20 mg/kg of body weight twice daily for infants under 1 year of age and 30 mg/kg twice daily for those older than 1 year of age were suggested. The population pharmacokinetics of ceftriaxone were established in infants, and evidence-based dosing regimens for community-acquired pneumonia were suggested based on developmental pharmacokinetics-pharmacodynamics.
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Ceftriaxona , Infecciones Comunitarias Adquiridas , Adulto , Antibacterianos/uso terapéutico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Humanos , Lactante , Pruebas de Sensibilidad Microbiana , Método de Montecarlo , Estudios ProspectivosRESUMEN
PURPOSE: To assess ceftriaxone population pharmacokinetics in a large pediatric population and describe the proper dose for establishing an optimized antibiotic regimen. METHODS: From pediatric patients using ceftriaxone, blood samples were obtained and the concentration was measured using high-performance liquid chromatography ultraviolet detection. The NONMEM software program was used for population pharmacokinetic analysis, for which data from 99 pediatric patients (2 to 12 years old) was collected and 175 blood concentrations were obtained. RESULTS: The best fit with the data was shown by the one-compartment model with first-order elimination. According to covariate analysis, weight had a significant impact on the clearance of ceftriaxone. Using Monte Carlo simulation, in a pediatric population with community-acquired pneumonia, a dose regimen of 100 mg/kg every 24 h produced satisfactory target attainment rates while remaining within the required minimum inhibitory concentration (2 mg/L). CONCLUSION: Population pharmacokinetics of ceftriaxone was evaluated in children and an optimum dosing regimen was constructed on the basis of the pharmacokinetics-pharmacodynamics model-based approach.
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Ceftriaxona/farmacocinética , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Neumonía/tratamiento farmacológico , Ceftriaxona/administración & dosificación , Niño , Preescolar , Humanos , Modelos Biológicos , Método de MontecarloRESUMEN
Newborns with congenital cytomegalovirus (CMV) infection are at high risk for developing permanent sequelae. Intravenous ganciclovir therapy is frequently used for the treatment of congenital CMV infection. A target area under the concentration-time curve from 0 to 24 h (AUC0-24) of 40 to 50 µg · h/ml is recommended. The standard dose has resulted in a large variability in ganciclovir exposure in newborns, indicating the unmet need of dosage individualization for this vulnerable population, but the implementation of this strategy remains challenging in clinical practice. We aim to evaluate the clinical utility of model-based dosage individualization of ganciclovir in newborns using an opportunistic sampling approach. The predictive performance of a published ganciclovir population pharmacokinetic model was evaluated using an independent patient cohort. The individual dose was adjusted based on the target AUC0-24 to ensure its efficacy. A total of 26 newborns with congenital CMV infection were included in the present study. Only 11 (42.3%) patients achieved the target AUC0-24 after being given the standard dose. For all the subtherapeutic patients (achieving <80% of the target AUC) (n = 5), a model-based dosage adjustment was performed using the Bayesian estimation method combined with the opportunistic sampling strategy. The adjusted doses were increased by 28.6% to 60.0% in these five patients, and all adapted AUC0-24 values achieved the target (range, 48.6 to 66.1 µg · h/ml). The clinical utility of model-based dosing individualization of ganciclovir was demonstrated in newborns with congenital CMV infection. The population pharmacokinetic model combined with the opportunistic sampling strategy provides a clinically feasible method to adapt the ganciclovir dose in neonatal clinical practice. (This study has been registered at ClinicalTrials.gov under registration no. NCT03113344.).
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Antivirales/administración & dosificación , Antivirales/farmacocinética , Infecciones por Citomegalovirus/tratamiento farmacológico , Ganciclovir/administración & dosificación , Ganciclovir/farmacocinética , Antivirales/uso terapéutico , Teorema de Bayes , Femenino , Ganciclovir/uso terapéutico , Humanos , Lactante , Recién Nacido , Masculino , Proyectos PilotoRESUMEN
Traditional medicines are composed of herbal formulations and their active ingredients and constituents which play a crucial role in the treatment of various human ailments. Astragalus eremophilus and Melilotus indicus (L.) All. (syn. Melilotus parviflora Desf.) are used traditionally as antiperspirant, tonic, diuretic, laxative and narcotic agents. The current study was designed to investigate the Astragalus eremophilus and Melilotus indicus (L.) All. (syn. Melilotus parviflora Desf.) methanol extracts for their antioxidant, antibacterial and antifungal activities. Fine powder of A. eremophilus and M. parviflora was extracted with 70% methanol to get crude methanol extract. Extract was characterized for antioxidant, antibacterial and antifungal activities. Antioxidant activity of various concentrations (3 mg/ml, 1.5 mg/ ml, 0.75 mg/ml, and 0.38 mg/ml) of both plant extracts was analyzed using 2,2-Diphenyl-1-picrylhydrazyl (DPPH) free radical. Salmonella typhemorium, Klebsiella pneumoniae (gram-negative) and Staphylococcus aureus, Enterococcus faecalis (gram-positive) bacterial strains were used for assessment of antibacterial activities. Antifungal activities of 7.5 mg/ml, 5.0 mg/ml, 2.5 mg/ml (A. eremophilus and M. parviflora) were conducted using Aspergillus niger, Aspergillus flavus, Aspergillus fumigatus and Candida albicons. At high concentration (3 mg/ml), all the tested fractions of A. eremophilus and M. parviflora methanol extracts showed potent antioxidant activities, ranging between 83.8 and 63.33%. Antibacterial activities revealed that A. eremophilus showed a maximum zone of inhibition (8.1 ± 0.1) on Salmonella typhenorium followed by Enterococcus faecalis (7.2 ± 0.1), Klebsellesa pneumonia (6.1 ± 0.6), and Staphylococcus aureus (5.1 ± 0.4), and at highest concentration (7.5 mg/ml), however, maximum zone of inhibition of Melilotus parviflora was at 7.5 mg/ml followed by 5.0 mg/ml and 2.5 mg/ml against Klebsiella pneumonia, Staphylococcus aureus, Salmonella typhemorium and Enterococcus faecalis. Antifungal assessment of both plant extracts showed that the higher concentration (7.5 mg/ml) has significant inhibitory effect as compared to control. The results can lead to the conclusion that A. eremophilus and M. parviflora methanol extracts are indeed sources of potential therapeutic compounds against antibacterial, antifungal and free radical associated disorders.
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Antibacterianos/farmacología , Antifúngicos/farmacología , Antioxidantes/farmacología , Planta del Astrágalo , Melilotus , Extractos Vegetales/farmacología , Antibacterianos/aislamiento & purificación , Antifúngicos/aislamiento & purificación , Antioxidantes/aislamiento & purificación , Aspergillus/efectos de los fármacos , Aspergillus/crecimiento & desarrollo , Planta del Astrágalo/química , Compuestos de Bifenilo/química , Candida albicans/efectos de los fármacos , Candida albicans/crecimiento & desarrollo , Pruebas Antimicrobianas de Difusión por Disco , Relación Dosis-Respuesta a Droga , Enterococcus faecalis/efectos de los fármacos , Enterococcus faecalis/crecimiento & desarrollo , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/crecimiento & desarrollo , Melilotus/química , Picratos/química , Extractos Vegetales/aislamiento & purificación , Plantas Medicinales , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/crecimiento & desarrollo , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrolloRESUMEN
Researchers in the field of sustainable management have recently dedicated significant efforts to understand why organizations exhibit diverse responses to environmental responsibilities. Ethical scholars assert that internal management plays a pivotal role in promoting sustainability because of its attitude toward sustainable issues. In alignment with this perspective, our study formulates a framework for internal monitoring that underscores the significance of independent, female, international, and politically connected directors. We investigate how these internal monitors influence a company's commitment to promote sustainable investments for pollution prevention. By employing fixed effect model and generalized method of moments (GMM) on a dataset obtained from the largest emerging market-China over the period 2012 to 2019, our findings indicate that the mentioned monitors demonstrate a stronger commitment to pollution prevention by promoting corporate sustainable investments. In addition, our analysis reveals that when the government withdraws its involvement in enterprises, it has a notable negative impact on the connection between internal monitors and a company's efforts in pollution prevention. Our results imply that implementation of sustainable policies for pollution prevention fundamentally result from not only internal management, but also from powerful stakeholders (like government involvement). Moreover, our study educates the policy makers regarding the social consequences of governmental withdrawal.
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Gobierno , Organizaciones , Femenino , Humanos , Contaminación Ambiental/prevención & control , China , PolíticasRESUMEN
Achalasia is a rare esophageal motility disorder that leads to dysphagia, regurgitation, and several other symptoms. While the etiology of achalasia is not completely understood, studies have suggested an immune reaction to viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as a potential cause. Here, we present a case report of a previously healthy 38-year-old male who presented to the emergency room with severe shortness of breath, recurrent vomiting, and dry cough, that had progressively worsened over five days. The patient was diagnosed with coronavirus disease 2019 (COVID-19), and a chest CT also revealed prominent features of achalasia with a markedly dilated esophagus and areas of narrowing at the distal esophagus. The initial management of the patient included IV fluids, antibiotics, anticholinergics, and corticosteroid inhalers which improved his symptoms. This case report highlights the importance of considering the acute-onset of achalasia in COVID-19 patients and the need for further research on the potential association between SARS-CoV-2 and achalasia.
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Purpose SARS-CoV-2 has been a diagnostic challenge for healthcare setups worldwide since 2019 due to its proximity to a myriad of pathological processes. Although reverse transcription - polymerase chain reaction (RT-PCR) and high-resolution computed tomography (HRCT) have helped in the diagnosis of the disease, they are not as widely available as chest X-rays. This study aims to investigate the diagnostic accuracy of right bronchial infiltration in chest X-ray in diagnosing COVID-19. Material and methods This was a validation study conducted in a single center in Riyadh, Saudi Arabia. A total of 114 patients were enrolled according to the selection criteria of the study. Consent was waived off on the condition of confidentiality maintenance as per the ethical review board. X-rays of suspected patients were viewed and analyzed by two blinded consultant radiologists. Patients were followed for their RT-PCR reports. Data were entered and analyzed in SPSS Statistics v.23.0 (IBM Corp., Armonk, USA). Results Among the 114 patients, the mean age was 46.2±17.3 years and 85 (74.6%) were males. The total number of COVID-19-positive patients were 82 (71.9%) while the patients presenting with right bronchial infiltration (RBI) were 94 (82.5%). RBI was significantly associated with the presence and absence of COVID-19 on PCR (p<0.001) and the presence of comorbidities (p<0.001). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the sign were 84.04%, 85.00%, 96.34%, 53.12%, and 84.21%, respectively. Conclusions RBI can be used as a diagnostic sign in X-rays for early identification of COVID-19 positive patients. This feature can be used in the triage of patients. This would decrease the spread of disease by providing early time to intervene to isolate patients.
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The blood-brain barrier (BBB) restricts the transport of potential therapeutic moieties to the brain. Direct targeting the brain via olfactory and trigeminal neural pathways by passing the BBB has gained an important consideration for delivery of wide range of therapeutics to brain. Intranasal route of transportation directly delivers the drugs to brain without systemic absorption, thus avoiding the side effects and enhancing the efficacy of neurotherapeutics. Over the last several decades, different drug delivery systems (DDSs) have been studied for targeting the brain by the nasal route. Novel DDSs such as nanoparticles (NPs), liposomes and polymeric micelles have gained potential as useful tools for targeting the brain without toxicity in nasal mucosa and central nervous system (CNS). Complex geometry of the nasal cavity presented a big challenge to effective delivery of drugs beyond the nasal valve. Recently, pharmaceutical firms utilized latest and emerging nasal drug delivery technologies to overcome these barriers. This review aims to describe the latest development of brain targeted DDSs via nasal administration. CHEMICAL COMPOUNDS STUDIED IN THIS ARTICLE: Carbopol 934p (PubChem CID: 6581) Carboxy methylcellulose (PubChem CID: 24748) Penetratin (PubChem CID: 101111470) Poly lactic-co-glycolic acid (PubChem CID: 23111554) Tween 80 (PubChem CID: 5284448).