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1.
Clin Infect Dis ; 73(2): 283-290, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32447366

RESUMO

BACKGROUND: Pneumonia is a common, serious illness in the elderly, with a poorly characterized long-term impact on health-related quality of life (HRQoL). The Japanese Goto Epidemiology Study is a prospective, active, population-based surveillance study of adults with X-ray/CT scan-confirmed community-onset pneumonia, assessing the HRQoL outcome quality-adjusted life-years (QALYs). We report QALY scores and losses among a subset of participants in this study. METHODS: QALYs were derived from responses to the Japanese version of the EuroQol-5D-5L health-state classification instrument at days 0, 7, 15, 30, 90, 180, and 365 after pneumonia diagnosis from participants enrolled from June 2017 to May 2018. We used patients as their own controls, calculating comparison QALYs by extrapolating EuroQol-5D-5L scores for day -30, accounting for mortality and changes in scores with age. RESULTS: Of 405 participants, 85% were aged ≥65 years, 58% were male, and 69% were hospitalized for clinically and radiologically confirmed pneumonia. Compliance with interviews by patients or proxies was 100%. Adjusted EuroQol-5D-5L scores were 0.759, 0.561, 0.702, and 0.689 at days -30, 0 (diagnosis), 180, and 365, respectively. Average scores at all time points remained below the average day -30 scores (P ≤ .001). Pneumonia resulted in a 1-year adjusted loss of 0.13 QALYs (~47.5 quality-adjusted days) (P < .001). CONCLUSIONS: Substantial QALY losses were observed among Japanese adults following pneumonia diagnosis, and scores had not returned to prediagnosis levels at 1 year postdiagnosis. QALY scores and cumulative losses were comparable to those in US adults with chronic heart failure, stroke, or renal failure.


Assuntos
Pneumonia , Qualidade de Vida , Adulto , Idoso , Humanos , Japão/epidemiologia , Masculino , Pneumonia/diagnóstico , Pneumonia/epidemiologia , Estudos Prospectivos , Anos de Vida Ajustados por Qualidade de Vida , Inquéritos e Questionários
2.
J Infect Chemother ; 23(7): 498-501, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28108098

RESUMO

Enterococci have become increasingly important pathogens for nosocomial infection (e.g. bacteremia, intra-abdominal infection, endocarditis, etc.), related to their intrinsic resistance to many antibiotics. Although the in vitro susceptibility of daptomycin (DAP) against Enterococci is well established, the Food and Drug Administration has only approved its use for complicated skin and skin structure infections induced by Enterococcus faecalis. In this study we evaluated the potential therapeutic application of DAP in a murine model of enterococcal experimental peritonitis. Mice were injected intraperitoneally with 4 × 1010 colony-forming units of Enterococcus faecium. DAP alone, DAP combined with ampicillin, vancomycin, or linezolid were administered 2 h after enterococcal inoculation and examined the survival, viable bacteria counts, the level of KC/CXCL1 in the peritoneal fluid. The viable bacteria counts in the peritoneal fluid of the DAP- or DAP plus ampicillin-treated groups were decreased significantly compared to those of the vancomycin- and linezolid-treated groups (P < 0.05) at 6 and 12 h after the inoculation of Enterococcus. The level of neutrophil chemoattractants KC in the peritoneal fluid at 12 h after enterococcal inoculation was significantly decreased in the DAP plus ampicillin-treated group (P < 0.05). In addition DAP showed the inhibitory effect of enterococcal biofilm formation dose-dependently by a microtiter biofilm assay. These results indicate that DAP, particularly with ß-lactams, is a possible alternative agent to treat severe enterococcal infection such as peritonitis.


Assuntos
Antibacterianos/uso terapêutico , Daptomicina/uso terapêutico , Enterococcus , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Linezolida/uso terapêutico , Peritonite/tratamento farmacológico , Vancomicina/uso terapêutico , Animais , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Daptomicina/farmacologia , Modelos Animais de Doenças , Feminino , Infecções por Bactérias Gram-Positivas/mortalidade , Linezolida/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Vancomicina/farmacologia
3.
Med Mycol ; 54(2): 120-7, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26531100

RESUMO

Patients with chronic pulmonary aspergillosis (CPA) have a poor prognosis and CPA occurs in patients with various underlying diseases. Recently, the number of patients with CPA complicated by nontuberculous mycobacteria (NTM) has increased. Additionally, complications of both diseases have several problems like drug interactions. Since the impact of NTM on the outcome of CPA is not well understood, we investigated the risk factors for developing CPA and the clinical characteristics of CPA patients with or without NTM. We retrospectively investigated the medical records of NTM and CPA patients who were admitted to Nagasaki University Hospital between April 2008 and September 2013. Comorbid diseases, causative microorganisms, radiological findings, and outcomes were evaluated. During the study period, 82 and 41 patients were diagnosed as having NTM and CPA, respectively. Nine patients were coinfected with NTM and CPA, and cavitary type NTM and steroid usage were independent risk factors of development of CPA. Mortality rates in the coinfection group were significantly higher than those of the NTM without CPA group (P = .003, log-rank test). The rate of treatment initiation in the co-infection group (33.3%) was significantly lower than in the CPA without NTM group (84.4%) (P = .006). However, there were no significant differences in cumulative survival rate between both groups (P = .760, log-rank test). Cavity formation and steroid usage were the independent risk factors for NTM patients to develop CPA within long observation period, and development of CPA made outcomes poor. It is important to diagnose the development of CPA early and initiate treatment for CPA.


Assuntos
Coinfecção/patologia , Infecções por Mycobacterium não Tuberculosas/complicações , Infecções por Mycobacterium não Tuberculosas/patologia , Aspergilose Pulmonar/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Coinfecção/epidemiologia , Coinfecção/mortalidade , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Infecções por Mycobacterium não Tuberculosas/mortalidade , Aspergilose Pulmonar/epidemiologia , Aspergilose Pulmonar/mortalidade , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida
4.
Multidiscip Respir Med ; 7(1): 48, 2012 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-23174134

RESUMO

BACKGROUND: Imatinibmesylate (imatinib) is a small molecule tyrosine kinase inhibitor administered to patients with chronic myelogenous leukemia and gastrointestinal stromal tumor. Although imatinib-associated interstitial lung disease is uncommon, a few cases have been reported so far. However, in all these cases interstitial lung disease developed during the use of imatinib. The present case is the first report of imatinib-induced interstitial lung disease developing after discontinuation of the drug. CASE PRESENTATION: A 51-year-old woman was administered oral imatinib for gastrointestinal stromal tumor. Ten weeks later, imatinib was discontinued because of facial edema. On this occasion, chest radiography showed no abnormal findings. However, 2 weeks after discontinuation of imatinib, she developed fever, dry cough, and dyspnea. Chest radiography and computed tomography showed diffuse interstitial infiltrates in both lungs. Examination of bronchoalveolar lavage fluid showed an increased proportion of lymphocytes. Imatinib-induced interstitial lung disease was suspected, because no other cause was evident. After administration of corticosteroids, her clinical condition and chest radiographic findings improved. CONCLUSION: We report a unique case of imatinib-induced interstitial lung disease that developed 2 weeks after discontinuation of the drug. Physicians should consider occurrence of imatinib-induced interstitial lung disease even after discontinuation of the drug.

5.
Am J Hum Genet ; 91(4): 721-8, 2012 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-23000144

RESUMO

For the identification of susceptibility loci for primary biliary cirrhosis (PBC), a genome-wide association study (GWAS) was performed in 963 Japanese individuals (487 PBC cases and 476 healthy controls) and in a subsequent replication study that included 1,402 other Japanese individuals (787 cases and 615 controls). In addition to the most significant susceptibility region, human leukocyte antigen (HLA), we identified two significant susceptibility loci, TNFSF15 (rs4979462) and POU2AF1 (rs4938534) (combined odds ratio [OR] = 1.56, p = 2.84 × 10(-14) for rs4979462, and combined OR = 1.39, p = 2.38 × 10(-8) for rs4938534). Among 21 non-HLA susceptibility loci for PBC identified in GWASs of individuals of European descent, three loci (IL7R, IKZF3, and CD80) showed significant associations (combined p = 3.66 × 10(-8), 3.66 × 10(-9), and 3.04 × 10(-9), respectively) and STAT4 and NFKB1 loci showed suggestive association with PBC (combined p = 1.11 × 10(-6) and 1.42 × 10(-7), respectively) in the Japanese population. These observations indicated the existence of ethnic differences in genetic susceptibility loci to PBC and the importance of TNF signaling and B cell differentiation for the development of PBC in individuals of European descent and Japanese individuals.


Assuntos
Cirrose Hepática Biliar/genética , Transativadores/genética , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Linfócitos B , Estudos de Casos e Controles , Diferenciação Celular/genética , Feminino , Loci Gênicos/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/métodos , Antígenos HLA/genética , Humanos , Masculino , Pessoa de Meia-Idade , Subunidade p50 de NF-kappa B/genética , Polimorfismo Genético , Fator de Transcrição STAT4/genética , Fator de Necrose Tumoral alfa/genética , População Branca/genética , Adulto Jovem
6.
Antimicrob Agents Chemother ; 56(9): 4870-5, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22751542

RESUMO

This is the first report of a detailed relationship between triazole treatment history and triazole MICs for 154 Aspergillus fumigatus clinical isolates. The duration of itraconazole dosage increased as the itraconazole MIC increased, and a positive correlation was observed (r = 0.5700, P < 0.0001). The number of itraconazole-naïve isolates dramatically decreased as the itraconazole MIC increased, particularly for MICs exceeding 2 µg/ml (0.5 µg/ml versus 2 µg/ml, P = 0.03). We also examined the relationship between cumulative itraconazole usage and the MICs of other azoles. A positive correlation existed between itraconazole dosage period and posaconazole MIC (r = 0.5237, P < 0.0001). The number of itraconazole-naïve isolates also decreased as the posaconazole MIC increased, particularly for MICs exceeding 0.5 µg/ml (0.25 µg/ml versus 0.5 µg/ml, P = 0.004). Conversely, the correlation coefficient obtained from the scattergram of itraconazole usage and voriconazole MICs was small (r = -0.2627, P = 0.001). Susceptibility to three triazole agents did not change as the duration of voriconazole exposure changed. In addition, we carried out detailed analysis, including microsatellite genotyping, for isolates obtained from patients infected with azole-resistant A. fumigatus. We confirmed the presence of acquired resistance to itraconazole and posaconazole due to a G54 substitution in the cyp51A gene for a patient with chronic pulmonary aspergillosis after oral itraconazole therapy. We should consider the possible appearance of azole-resistant A. fumigatus if itraconazole is used for extended periods.


Assuntos
Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/genética , Sistema Enzimático do Citocromo P-450/genética , Farmacorresistência Fúngica/efeitos dos fármacos , Proteínas Fúngicas/genética , Aspergilose Pulmonar/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Aspergillus fumigatus/enzimologia , Aspergillus fumigatus/isolamento & purificação , Sistema Enzimático do Citocromo P-450/metabolismo , Farmacorresistência Fúngica/genética , Feminino , Proteínas Fúngicas/metabolismo , Humanos , Itraconazol/administração & dosagem , Itraconazol/efeitos adversos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mutação , Aspergilose Pulmonar/microbiologia , Fatores de Tempo , Triazóis/administração & dosagem , Triazóis/efeitos adversos
7.
Antimicrob Agents Chemother ; 56(1): 584-7, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22024829

RESUMO

We investigated the triazole, amphotericin B, and micafungin susceptibilities of 196 A. fumigatus clinical isolates in Nagasaki, Japan. The percentages of non-wild-type (non-WT) isolates for which MICs of itraconazole, posaconazole, and voriconazole were above the ECV were 7.1%, 2.6%, and 4.1%, respectively. A G54 mutation in cyp51A was detected in 64.2% (9/14 isolates) and 100% (5/5 isolates) of non-WT isolates for itraconazole and posaconazole, respectively. Amphotericin B MICs of ≥2 µg/ml and micafungin minimum effective concentrations (MECs) of ≥16 µg/ml were recorded for two and one isolates, respectively.


Assuntos
Antifúngicos/administração & dosagem , Aspergilose/tratamento farmacológico , Aspergillus fumigatus/efeitos dos fármacos , Sistema Enzimático do Citocromo P-450/genética , Proteínas Fúngicas/genética , Substituição de Aminoácidos , Anfotericina B/administração & dosagem , Aspergilose/microbiologia , Aspergillus fumigatus/genética , Aspergillus fumigatus/isolamento & purificação , Farmacorresistência Fúngica/efeitos dos fármacos , Equinocandinas/administração & dosagem , Feminino , Humanos , Itraconazol/administração & dosagem , Japão , Lipopeptídeos/administração & dosagem , Masculino , Micafungina , Testes de Sensibilidade Microbiana , Mutação , Pirimidinas/administração & dosagem , Análise de Sequência de DNA , Triazóis/administração & dosagem , Voriconazol
9.
Nihon Kokyuki Gakkai Zasshi ; 49(6): 458-64, 2011 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-21735749

RESUMO

Three cases of organizing pneumonia (OP) that occurred after planned radiation therapy for postoperative breast cancer are reported. All patients received tangential radiation therapy and adjuvant tamoxifen (TAM) for postoperative breast cancer. Two patients developed fever and cough; one was asymptomatic. Chest radiography and computed tomography demonstrated peripheral alveolar opacities outside the radiation field. Bronchoalveolar lavage showed an elevated total cell count with a high percentage of lymphocytes, as well as elevated eosinophil levels in two cases. Transbronchial lung biopsy revealed a histologic pattern consistent with organizing pneumonia. For the two symptomatic cases, treatment with corticosteroids reduced clinical symptoms promptly and improved imaging findings. The single asymptomatic case improved without treatment. The number of such reported cases has increased in recent years, but the etiology is unclear. In the three cases presented, TAM combined with radiation therapy may have been the cause of the OP.


Assuntos
Neoplasias da Mama/radioterapia , Pneumonite por Radiação/etiologia , Adulto , Antineoplásicos Hormonais/efeitos adversos , Terapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Tamoxifeno/efeitos adversos
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