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Infecções Assintomáticas , COVID-19/transmissão , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
In 2018, dosing regimens of the two most prescribed immune check point inhibitors (ICI), nivolumab (Opdivo®) and pembrolizumab (Keytruda®), in the treatment of lung cancer were changed from weight-based dosing to fixed dosing. The aim of this study was to compare the economic impact of this change in our university hospital group and then across Ile-de-France, the most inhabited French region. A budget impact analysis (BIA) has been performed on the French public health insurance data. The duration of treatment and the weight of the patients were calculated using data from the patients treated at our health facility and from clinical studies. The cost of treatment was calculated at the local level of our health facility and then for Ile-de-France. Our model demonstrates an additional cost of 550,115 in our hospital and 9,704,778 in Ile-de-France for a fixed dose prescription in 2018. In 2019, the BIA concluded an additional cost, according to the respective low and high assumptions, of 556,969 and 756,544 locally and 10,201,027 to 14,486,141 for Ile-de-France for an equivalent efficacy between the two different drug dosing regimens of nivolumab and pembrolizumab. The adoption of the fixed dose regimen would lead, according to the least expensive hypothesis, to an additional cost of 26% for the ICI. These results encourage reflection on the strict adoption of this dosage modification. The option of maintaining the free choice between a prescription adapted to weight or in a fixed dose seems a relevant option and should be considered.
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Background Our hospital organization raised the possibilities of outsourcing their sterile pediatric chemotherapy preparations to another hospital conditional on analyzing the potential hazardous events that need to be anticipated. Methods The study was conducted by a multidisciplinary working group from September 2015 to January 2016 with the support of a risk manager. A list of hazardous situations that could occur during outsourcing process was assessed. First, a map of hazardous situations was developed by crossing outsourcing processes divided into phases classified as critical or not. Second, a map of risk was established by crossing potential consequences of these hazardous situations and elaborating corrective actions to reduce the initial risks. Results The map of hazardous situations identified 183 relevant hazardous situations, 78 of which were considered high priority and 154 scenarios were developed. Slightly more than half of these hazardous situations concerned information system (30%), human resources (14%), and management (11%). The generic hazards of information system and human generated 37 (24%) and 41 (27%) scenarios, respectively. To reduce critical risks, 33 corrective actions were proposed. Working time required was estimated at 35 days. The subcontractor personnel for this new organization included an estimated extra time of 0.7-pharmacist working day and 1.4-pharmacy dispenser working day. Conclusions The preliminary hazard analysis method appeared to apply to our system of outsourcing sterile cytotoxic preparations in another hospital. Regardless, this analysis is complex and requires time and expertise.
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Because the magnitude of spontaneous bacterial clearance can be similar or even higher than treatment effect, depending upon experimental model and bacterial strain used, this work investigated the value of rendering rats immunosuppressed to facilitate bacterial implantation and reduce spontaneous bacterial clearance. In a first step, rats received a single intravenous cyclophosphamide dose 4 days before infection. Three different doses were tested: 10, 20, and 40 mg/kg. After modeling with NONMEM V, the cyclophosphamide dose required to maintain white blood cell count <1.0 × 10(3)/µL from day 4 to day 5 was 30 mg/kg. In a second step, influence of immunosuppression on lung bacterial titers was characterized. Rats were given one of the three intravenous cyclophosphamide doses (0, 10, 30 mg/kg), and after 4 days, they were infected by tracheal injection of 8.9 ± 0.1 log10 cfu Enterobacter cloacae before being sacrificed at different times. Bacteria in homogenized lungs were quantitatively cultured on Drigalski agar. Bacterial lung count was closely influenced by the grade of induced leukopenia. A single intravenous 30 mg/kg cyclophosphamide dose 4 days before infection suppressed the spontaneous clearance of E. cloacae for at least 30 h without significantly increasing animal mortality; this result seems to be linked to a white blood cell count maintained lower than 1.0 × 10(3)/µL for all the time. This modified animal model could be contributive in the evaluation of antibacterial agents, especially to simulate the behavior of intensive care unit immunocompromised patients.
Assuntos
Ciclofosfamida/farmacologia , Enterobacter cloacae/metabolismo , Infecções por Enterobacteriaceae/metabolismo , Hospedeiro Imunocomprometido , Animais , Antibacterianos/farmacologia , Cefalosporinase/metabolismo , Contagem de Colônia Microbiana , Ciclofosfamida/administração & dosagem , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Enterobacter cloacae/enzimologia , Infecções por Enterobacteriaceae/tratamento farmacológico , Imunossupressores/administração & dosagem , Imunossupressores/farmacologia , Contagem de Leucócitos , Leucopenia/metabolismo , Masculino , Dinâmica não Linear , Pneumonia Bacteriana/tratamento farmacológico , Ratos , Ratos Wistar , Fatores de TempoRESUMO
BACKGROUND: The aim of this study was to compare the bactericidal activity of cefepime plus amikacin against experimental pneumonia induced by a stably derepressed cephalosporinase-producing Enterobacter cloacae strain in immunocompetent and leucopenic rats. METHODS: Sixty Wistar rats were used. Leucopenia was induced in half of them by a single intravenous administration of 30 mg/kg cyclophosphamide, while the remaining rats received the same volume of saline. All rats were infected 96 h later by tracheal instillation of 8 log(10) colony-forming units of E. cloacae. Twelve rats (6 immunocompetent and 6 leucopenic) were sacrificed 6 h later to assess the initial bacterial burden to the lungs. Then, the remaining 48 rats received a combination of 60 mg/kg cefepime twice a day and 25 mg/kg amikacin once a day given intraperitoneally or the same volume of saline. Six rats per group (leucopenic or not, treated or not) were sacrificed 12 and 30 h after therapy started. RESULTS: Spontaneous bacterial clearance with time was observed only in immunocompetent rats. Compared to untreated animals, antibiotic administration induced a decrease in lung bacterial titres in immunocompetent and leucopenic rats. The difference was statistically significant only in leucopenic rats. CONCLUSIONS: The use of leucopenic rats reduced spontaneous bacterial clearance in the lungs and increased the bactericidal effect of the antibiotic combination and ultimately the confidence in the reliability of the results.
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Cefalosporinase/metabolismo , Enterobacter cloacae/enzimologia , Modelos Animais , Pneumonia Bacteriana/tratamento farmacológico , Amicacina/uso terapêutico , Animais , Antibacterianos/uso terapêutico , Cefepima , Cefalosporinas/uso terapêutico , Ciclofosfamida/toxicidade , Quimioterapia Combinada , Enterobacter cloacae/patogenicidade , Hospedeiro Imunocomprometido , Injeções Intraperitoneais , Leucopenia/induzido quimicamente , Masculino , Ratos , Ratos WistarRESUMO
A rat pneumonia model was established with a Pseudomonas aeruginosa strain that produced the plasmid-encoded metallocarbapenemase VIM-2. A significant decrease in lung bacterial titers was observed when imipenem, cefepime, ceftazidime, and piperacillin-tazobactam were given at the highest doses recommended for humans, despite their high MICs. Aztreonam at high doses produced a similar decrease in bacterial titers.