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1.
Transp Res Interdiscip Perspect ; 13: 100551, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35128389

RESUMO

This paper employs regression with ARIMA errors (RegARIMA) to quantify the impacts of multiple non-pharmaceutical interventions, daily new cases, seasonal and calendar effects, and other factors on activity trends across the timeline of the ongoing COVID-19 pandemic in Japan. The discussion focuses on two controversial policy sets imposed by the Japanese government that aim to contain the pandemic and to stimulate the recovery of the economy. The containing effect was achieved by stay-at-home requests and declaring a "State of Emergency" in the combat against the first waves of infectious cases. After observing reduced cases, Go-to-travel and Go-to-eat campaigns were launched in July 2020 to encourage recreational travel and to revive the economy. To better understand the impact of the policies we utilize "Google trends" which measure how much these policies are looked up online. We suggest this reflects how much they are part of the public discussion. A case study is conducted in Kyoto, a city famous for tourism. The proposed RegARIMA model is compared with linear regression and time series models. The outperformances in measuring the magnitude of intervention impacts and forecasting the future trends are confirmed by using a total of twelve activity and mobility indices as the dependent variable. Nine indices are released by Google and Apple and three are obtained from local Wi-Fi packet sensors. The effect of the State of Emergency declaration is found to erode at the second implementation, and the second stage of the Go-to-travel campaign successfully stimulated travel demand in the autumn sighting season of 2020.

2.
Int Heart J ; 63(1): 168-175, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35095067

RESUMO

Diagnostic strategies for symptomatic transthyretin (ATTR) cardiac amyloidosis showing typical morphological features such as increased ventricular wall thickness and myocardial injury such as an elevation in serum troponin T level have been established, but those for subclinical cardiac amyloidosis are limited. In the era when effective therapies to suppress/delay progression of ATTR cardiac amyloidosis are available, early detection of cardiac involvement plays a crucial role in appropriate decision-making for treatment in TTR mutation carriers who have a family history of heart failure and death due to ATTR amyloidosis. Findings of three cases with known pathogenic transthyretin (TTR) mutations (p.Ser70Arg, p.Phe53Val, and p.Val50Met) and family histories of death for amyloidosis were presented. Two cases were asymptomatic, and a case carrying p.Phe53Val had gastrointestinal symptoms and autonomic neuropathy. Levels of plasma N-terminal fragment of pro-B-type natriuretic peptide and troponin T were within normal ranges in all cases, but results of cardiac magnetic resonance (CMR) and bone scintigraphy clearly revealed the presence of cardiac involvement in all cases, even in a case without echocardiographic abnormalities including left ventricular hypertrophy and relative apical sparing of longitudinal strain shown by two-dimensional speckle-tracking echocardiography. Electrocardiography revealed modest abnormalities including reduced R wave amplitude in V2 and a trend toward left axis deviation in all cases. In conclusion, CMR, bone scintigraphy, and electrocardiography are useful for early detection of ATTR cardiac amyloidosis in TTR mutation carriers. The role of comprehensive cardiac assessment in the early detection of cardiac amyloidosis in TTR mutation carriers is discussed.


Assuntos
Neuropatias Amiloides Familiares/diagnóstico , Neuropatias Amiloides Familiares/genética , Cardiopatias/diagnóstico , Cardiopatias/genética , Mutação/genética , Pré-Albumina/genética , Adulto , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
3.
Ann Thorac Surg ; 113(5): 1617-1623, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34139190

RESUMO

BACKGROUND: In lung cancer patients with interstitial lung disease (ILD) postoperative acute exacerbation can be fatal. However the predictive biomarkers for postoperative exacerbation of ILD have not been fully elucidated. The soluble receptor for advanced glycation end products is a lung-derived antiinflammatory protein that can prevent acute lung injury. This study aimed to elucidate its role in this fatal complication, especially focusing on the predictive potential of serum levels of soluble receptor for advanced glycation end products. METHODS: We retrospectively enrolled 152 patients with lung cancer and ILD who underwent lung resection and had blood samples collected before surgery. Independent predictors of postoperative acute exacerbation were evaluated in all patients and in subgroups based on the surgical procedure. Additionally serial changes in soluble receptor levels in these subgroups were evaluated. RESULTS: Seventeen patients (11.2%) developed postoperative acute exacerbation. Receiver operating characteristic curve analysis revealed 547.4 pg/mL as the optimal soluble receptor level cutoff value. Univariate and multivariate logistic regression analyses revealed a significant association between soluble receptor serum levels (≤547.4 pg/mL) and postoperative acute exacerbation. In the subgroup analysis this independent association was observed only in the lobectomy group. Additionally lobectomy caused a significant reduction in postoperative soluble receptor levels. CONCLUSIONS: Decreased baseline levels of circulatory soluble receptor might be a potential risk factor for postoperative acute exacerbation in patients with lung cancer and ILD. Moreover additional reduction in the levels of this antiinflammatory protein occurs because of lung resection.


Assuntos
Lesão Pulmonar Aguda , Doenças Pulmonares Intersticiais , Neoplasias Pulmonares , Lesão Pulmonar Aguda/etiologia , Produtos Finais de Glicação Avançada , Humanos , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/cirurgia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/cirurgia , Receptor para Produtos Finais de Glicação Avançada , Estudos Retrospectivos
4.
Inquiry ; 58: 469580211059281, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34851754

RESUMO

The environment and personnel are both exposed to powdered pharmaceuticals inside pharmacies. This makes developing new methods for rapidly determining such contaminants an important objective. In this study, we developed a liquid-chromatography tandem-mass-spectrometry (LC-MS/MS) method for the simultaneous qualitative and quantitative determination of powdered medicinal drugs, such as famotidine, risperidone, lansoprazole, olanzapine, haloperidol, clarithromycin, promethazine, levomepromazine, and chlorpromazine. The method involves the use of acetaminophen as the internal standard, an LC-MS/MS method with a core-shell column, and a 10 mM ammonium formate/acetonitrile gradient mobile phase. The analytes were separated within 14 min, and MS with an electrospray ionization source in positive-ion mode was used. The limits of detection for the 9 drugs were .1-8.4 ng/mL. Linear calibration curves in the 10-50 000 ng/mL range were constructed, and inter-day accuracies of 92.6-113.8% were determined for the 9 drugs. The coefficients of variation were less than 14.6%. These data suggest that the proposed method is applicable for the routine assaying of powdered-medicine contamination in pharmacies.


Assuntos
Preparações Farmacêuticas , Farmácias , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Humanos , Reprodutibilidade dos Testes , Extração em Fase Sólida , Espectrometria de Massas em Tandem
5.
Br J Neurosurg ; : 1-6, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34553665

RESUMO

BACKGROUND: Postoperative intracranial complications are rare in spine surgery not including cranial procedures. We describe an uncommon case of pseudohypoxic brain swelling (PHBS) and secondary hydrocephalus after transforaminal lumbar interbody fusion (TLIF) presenting as impaired consciousness and repeated seizures. CASE PRESENTATION: A 65-year-old man underwent L4-5 TLIF for lumbar spondylolisthesis and began experiencing generalized seizures immediately postoperatively. Computed tomography (CT) revealed diffuse cerebral edema-like hypoxic ischemic encephalopathy. He was transported to our hospital, at which time epidural drainage was halted and anti-edema therapy was commenced. His impaired consciousness improved. However, he suffered secondary hydrocephalus due to continuous bleeding from a dural defect and spinal epidural fluid collection 3 months later. Following the completion of dural repair and insertion of a ventriculoperitoneal shunt, his neurologic symptoms and neuroimaging findings improved significantly. CONCLUSIONS: PHBS can be considered in patients with unexpected neurological deterioration following lumbar spine surgery even with the absence of documented durotomy. This might be due to postoperative intracranial hypotension-associated venous congestion, and to be distinguished from the more common postoperative cerebral ischemic events-caused by arterial or venous occlusions-or anesthetics complications.

6.
Cancer Chemother Pharmacol ; 88(5): 857-865, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34350479

RESUMO

PURPOSE: Cytotoxic chemotherapy-induced lung injury is a fatal complication in patients with lung cancer and interstitial lung disease (ILD). We aimed to evaluate the association between hyperglycemia and this form of lung injury in patients with lung cancer concomitant with ILD. METHODS: From 1147 patients with advanced lung cancer, we retrospectively enrolled 98 patients with ILD whose hemoglobin A1c (HbA1c) levels were measured, and investigated the association between HbA1c levels and cytotoxic chemotherapy-induced lung injury. In 73 patients whose serum samples were retained, we measured serum levels of advanced glycation end products (AGE) and assessed the association of AGE levels with HbA1c levels and cytotoxic chemotherapy-induced lung injury. RESULTS: The incidence of cytotoxic chemotherapy-induced lung injury was significantly higher in patients with HbA1c levels ≥ 5.8% than in those with HbA1c levels < 5.8%, but not in those with HbA1c levels ≥ 6.5% than in those with HbA1c levels < 6.5%. The multivariate logistic regression model revealed that HbA1c level ≥ 5.8% was a significant risk factor for this complication [odds ratio 3.178 (95% confidence interval 1.057-9.556), P = 0.040]. In addition, serum AGE levels were significantly higher in patients with HbA1c levels ≥ 5.8% than in those with HbA1c levels < 5.8% [median (interquartile range); 0.129 (0.023-0.290) and 0.474 (0.213-1.109) µg/mL, P = 0.001]. CONCLUSION: Glucose intolerance (e.g., HbA1c level ≥ 5.8%) may be a risk factor of cytotoxic chemotherapy-induced lung injury, which might be associated with elevated AGE production due to hyperglycemia.


Assuntos
Antineoplásicos/efeitos adversos , Intolerância à Glucose/induzido quimicamente , Doenças Pulmonares Intersticiais/tratamento farmacológico , Lesão Pulmonar/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Feminino , Hemoglobina A Glicada/análise , Produtos Finais de Glicação Avançada/sangue , Humanos , Hiperglicemia/induzido quimicamente , Hiperglicemia/fisiopatologia , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/fisiopatologia , Neoplasias Pulmonares/fisiopatologia , Masculino , Estudos Retrospectivos , Capacidade Vital
7.
BMC Pharmacol Toxicol ; 22(1): 47, 2021 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-34462002

RESUMO

BACKGROUND: Acute kidney injury (AKI) is associated with significant increases in short- and long-term morbidity and mortality. Drug-induced AKI is a major concern in the present healthcare system. Our spontaneous reporting system (SRS) analysis assessed links between AKI, along with patients' age, as healthcare-associated risks and administered anti-infectives. We also generated anti-infective-related AKI-onset profiles. METHOD: We calculated reporting odds ratios (RORs) for reports of anti-infective-related AKI (per Medical Dictionary for Regulatory Activities) in the Japanese Adverse Drug Event Report database and evaluated the effect of anti-infective combination therapy. The background factors of cases with anti-infective monotherapy and combination therapy (≥ 2 anti-infectives) were matched using propensity score. We evaluated time-to-onset data and hazard types using the Weibull parameter. RESULTS: Among 534,688 reports (submission period: April 2004-June 2018), there were 21,727 AKI events. The reported number of AKI associated with glycopeptide antibacterials, fluoroquinolones, third-generation cephalosporins, triazole derivatives, and carbapenems were 596, 494, 341, 315, and 313, respectively. Crude RORs of anti-infective-related AKI increased among older patients and were higher in anti-infective combination therapies [anti-infectives, ≥ 2; ROR, 1.94 (1.80-2.09)] than in monotherapies [ROR, 1.29 (1.22-1.36)]. After propensity score matching, the adjusted RORs of anti-infective monotherapy and combination therapy (≥ 2 anti-infectives) were 0.67 (0.58-0.77) and 1.49 (1.29-1.71), respectively. Moreover, 48.1% of AKI occurred within 5 days (median, 5.0 days) of anti-infective therapy initiation. CONCLUSION: RORs derived from our new SRS analysis indicate potential AKI risks and number of administered anti-infectives.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Anti-Infecciosos/efeitos adversos , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Razão de Chances , Farmacovigilância , Adulto Jovem
8.
Sci Total Environ ; 795: 148873, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34247072

RESUMO

The fate of microplastics (MPs) in the sewage treatment process has been investigated worldwide, and novel results have been reported; few studies have also clarified the fate of MPs in the sewage sludge treatment process. Although most MPs in sewage are transferred to sludge, some flow back from the sludge treatment process to the sewage treatment process. Therefore, throughout the sewage treatment plant, the removal rate of MPs may increase via a countermeasure during the sludge treatment process. In this study, samples obtained from sewage and sewage sludge treatments were used to degrade organic matter with hydrogen peroxide. Water sample particles were trapped on Ni filters with 20-µm-sized pores, dried at room temperature and then the MPs were detected and identified by FTIR microscopy. Note that sludge samples were treated with hydrogen peroxide and separated by specific gravity using NaI solution. The concentration of MPs per unit volume was then calculated and the MPs load was estimated using flow rates of water and sludge. Subsequently, we clarified the fate of MPs with sizes of 20 µm or greater in a sewage treatment plant. When the MPs load in the influent sewage is 100%, 12% of the MPs were found to return to the sewage treatment process via the sidestream of the sludge treatment process. Per this observation, it was made evident that MPs are in fact circulating throughout the sewage and sludge treatment processes. MPs in the sidestream mainly consisted of the effluent from the sludge concentration process, and most MPs were thought to be fibrous polyethylene terephthalate (fibrous MPs, i.e. microfibers [MFs]). The results show that MFs circulate throughout the sewage and sludge treatment processes, and for effectively increasing the removal rate of MPs, the removal of MFs proves correspondingly effective during the sludge treatment process.


Assuntos
Esgotos , Poluentes Químicos da Água , Peróxido de Hidrogênio , Microplásticos , Plásticos , Eliminação de Resíduos Líquidos , Águas Residuárias , Poluentes Químicos da Água/análise
9.
Sci Rep ; 11(1): 10105, 2021 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-33980944

RESUMO

Postoperative acute exacerbation of interstitial lung disease (AE-ILD) can be fatal in patients with lung cancer concomitant with ILD. We aimed to elucidate the predictive potential of high-mobility group box 1 (HMGB1), which is associated with the development and severity of lung injury, for evaluating the risk of this complication. We included 152 patients with lung cancer and ILD who underwent radical surgery between January 2011 and August 2019. We evaluated the preoperative levels of serum HMGB1 and its predictive potential for postoperative AE-ILD. Postoperative AE-ILD developed in 17 patients. Serum levels of HMGB1 were significantly higher in patients with postoperative AE-ILD than in those without (median [interquartile range]: 5.39 [3.29-11.70] ng/mL vs. 3.55 [2.07-5.62] ng/mL). Univariate and multivariate logistic regression analyses revealed that higher HMGB1 levels were significantly associated with the development of postoperative AE-ILD in entire studied patients (n = 152). In the subgroup analysis, higher HMGB1 levels were associated with a significantly increased risk of this complication in patients who underwent lobectomy (n = 77) than in those who underwent sublobar resection (n = 75). Serum HMGB1 could be a promising marker for evaluating the risk of postoperative AE-ILD, specifically in patients who underwent lobectomy.


Assuntos
Proteína HMGB1/sangue , Doenças Pulmonares Intersticiais/sangue , Neoplasias Pulmonares/cirurgia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Progressão da Doença , Feminino , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/complicações , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Retrospectivos
10.
Anticancer Res ; 41(3): 1497-1506, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33788742

RESUMO

BACKGROUND: No study has yet investigated the incidence of chemotherapy-induced acute exacerbation of interstitial pneumonia (AE-IP) in patients with autoantibody-positive IP and lung cancer. Herein, we retrospectively compared the incidence of chemotherapy-induced AE-IP in patients with lung cancer between those with autoantibody-positive and -negative IP. PATIENTS AND METHODS: Between October 2003 and December 2018, patients with lung cancer who received chemotherapy, underwent serological test of antinuclear antibody or rheumatoid factor, and were diagnosed with IP were enrolled. RESULTS: A total of 81 patients were enrolled; autoantibody-positive cases were observed in 23.5%. Autoantibody positivity was an independent risk factor for chemotherapy-induced AE-IP at 6 months after initiation of chemotherapy for lung cancer. The time to onset of AE-IP was significantly shorter in autoantibody-positive patients than in the seronegative patients. CONCLUSION: Chemotherapy-induced AE-IP developed earlier in patients with autoantibody than in those without. Therefore, the potential development of AE-IP in autoantibody-positive patients warrants monitoring.


Assuntos
Autoanticorpos/imunologia , Quimioterapia de Indução/efeitos adversos , Doenças Pulmonares Intersticiais/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Quimioterapia de Indução/métodos , Estimativa de Kaplan-Meier , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/imunologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco
11.
SAGE Open Med ; 8: 2050312120974176, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33282307

RESUMO

OBJECTIVES: Reye's syndrome is a rare and potentially fatal illness that is defined as encephalopathy accompanied by liver failure. The aim of this study was to assess Reye's syndrome profiles by analyzing data from the spontaneous reporting system database. METHODS: We analyzed reports of Reye's syndrome using the US Food and Drug Administration Adverse Event Reporting System and the Japanese Adverse Drug Event Report databases. The reporting odds ratio and proportional reporting rate were used to detect the pharmacovigilance signal. RESULTS: The US Food and Drug Administration Adverse Event Reporting System contains 12,201,620 reports from January 2004 to June 2020, of which 186 are on Reye's syndrome. The Japanese Adverse Drug Event Report contains 646,779 reports from April 2004 to September 2020, of which 30 are on Reye's syndrome. In the US Food and Drug Administration Adverse Event Reporting System database, the reporting odds ratios (95% confidence interval, number of cases) of aspirin, diclofenac, ibuprofen, acetaminophen, and valproate sodium were 404.6 (302.6-541.0, n = 80), 15.1 (6.7-34.1, n = 6), 26.2 (16.1-42.6, n = 18), 10.7 (5.5-20.9, n = 9), and 47.1 (26.2-84.6, n = 12), respectively. In the Japanese Adverse Drug Event Report database, the reporting odds ratios (95% confidence interval, number of cases) of aspirin, diclofenac, ibuprofen, loxoprofen, acetaminophen, and valproate sodium were 14.1 (5.4-36.8, n = 5), 51.7 (22.2-120.5, n = 7), 135.0 (40.8-446.2, n = 3), 17.6 (6.7-46.0, n = 5), 24.0 (9.2-62.6, n = 5), and 13.8 (3.3-57.9, n = 2), respectively. The reported number of female patients aged 30-39 years was the highest in the Japanese Adverse Drug Event Report. CONCLUSION: Although the frequency of the occurrence of Reye's syndrome is low, the possible risk of the disease occurring in adult females should be considered.

12.
Biol Pharm Bull ; 43(12): 1831-1838, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33268700

RESUMO

Hemorrhoids are a common anorectal disease. Epidemiological studies on medication trends and risk factors using information from real-world databases are rare. Our objective was to analyze the relationship between hemorrhoid treatment prescription trends and several risk factors using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) Open Data Japan and related medical information datasets. We calculated the standardized prescription ratio (SPR) based on the 2nd NDB Open Data Japan from 2015. The correlation coefficients between the SPR of antihemorrhoidals and those of "antispasmodics," "antiarrhythmic agents," "antidiarrheals, intestinal regulators," "purgatives and clysters," "hypnotics and sedatives, antianxietics," "psychotropic agents," and "opium alkaloids preparations" were 0.7474, 0.7366, 0.7184, 0.6501, 0.6320, 0.4571, and 0.4542, respectively. The correlation coefficient between the SPR of antihemorrhoidals and those of "average annual temperature," "percentage of people who were smokers," and "percentage of people who drank regularly" were -0.7204, 0.6002, and 0.3537, respectively. The results of cluster analysis revealed that Hokkaido and Tohoku regions tended to have low average annual temperature values and high percentage of people who were smokers and had comparatively high SPRs of "antispasmodics," "antiarrhythmic agents," "antidiarrheals, intestinal regulators," "purgatives and clysters," "hypnotics and sedatives, antianxietics," "psychotropic agents," and "opium alkaloids preparations." Antihemorrhoidals are frequently used in Hokkaido and Tohoku, Japan; thus, it is important for these prefectural governments to focus on these factors when taking measures regarding health promotion.


Assuntos
Mineração de Dados/métodos , Bases de Dados Factuais/tendências , Hemorroidas/epidemiologia , Revisão da Utilização de Seguros/tendências , Seguro Saúde/tendências , Informática Médica/tendências , Análise por Conglomerados , Registros Eletrônicos de Saúde/tendências , Feminino , Hemorroidas/diagnóstico , Hemorroidas/tratamento farmacológico , Humanos , Japão/epidemiologia , Masculino , Informática Médica/métodos , Medicamentos sem Prescrição/uso terapêutico
13.
Pharmacoepidemiol Drug Saf ; 29(10): 1279-1294, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32869941

RESUMO

PURPOSE: The aim of our study was to characterize the clinical features of immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs) in a real-world setting using the Japanese Adverse Drug Event Report (JADER) database. METHODS: The irAEs were defined using the preferred terms of the Medical Dictionary for Regulatory Activities. irAEs were categorized as follows: adrenal insufficiency, colitis, eye diseases, hematological disorder, hepatitis, hyperthyroidism, hypopituitarism, hypothyroidism, myasthenia gravis, myocarditis, nephritis/renal dysfunction, pneumonitis, rash, and type 1 diabetes mellitus. We used several indices such as reporting odds ratio (ROR) to assess disproportionality in pharmacovigilance data, time-to-onset analysis using Weibull shape parameters, and the association rule mining technique to evaluate possible risk factors between variables in the spontaneous reporting system database. RESULTS: The JADER database contained 534 688 reports from April 2004 to June 2018. The RORs of pneumonitis including interstitial lung disease for nivolumab, pembrolizumab, and ipilimumab were 7.02 (95% confidence interval: 6.55-7.52), 9.08 (8.28-9.97), and 1.74 (1.27-2.38), respectively. The median onsets (quartiles, 25-75%) of myocarditis caused by nivolumab and pembrolizumab were 28.0 (15.5-60.5) and 18.0 (13.0-44.5) days, respectively. Co-therapy with nivolumab and ipilimumab may be associated with irAEs in several categories as per the association rule mining analysis. CONCLUSION: Our results demonstrated a potential risk of irAEs associated with ICIs, based on RORs and time-to-onset analysis. Furthermore, our findings indicated that patients receiving nivolumab and ipilimumab as co-therapy should be carefully monitored.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Inibidores de Checkpoint Imunológico/efeitos adversos , Farmacovigilância , Bases de Dados Factuais/estatística & dados numéricos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Humanos , Inibidores de Checkpoint Imunológico/administração & dosagem , Ipilimumab/administração & dosagem , Ipilimumab/efeitos adversos , Japão/epidemiologia , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos
14.
Respir Med ; 172: 106131, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32911136

RESUMO

BACKGROUND: High-mobility group box 1 (HMGB1) is a pro-inflammatory protein, that is associated with tumorigenesis, interstitial lung disease (ILD), and acute lung injury. Chemotherapy-induced lung injury is a common and serious adverse event in patients with lung cancer and ILD, but its pathogenesis and predictive biomarkers are not known. This study aimed to investigate the predictive potential of serum HMGB1 levels for cytotoxic chemotherapy-induced lung injury in these patients. METHODS: From 743 patients with advanced lung cancer, we enrolled 83 consecutive patients with ILD and background-matched 83 patients without ILD. Additionally, 83 healthy subjects were included. After measuring baseline levels of serum HMGB1 in three groups, we evaluated the predictive values of baseline HMGB1 levels for cytotoxic chemotherapy-induced lung injury in patients with lung cancer and ILD. RESULTS: Higher levels of serum HMGB1 were independently associated with higher tumor burden, as assessed by total tumor size, and the presence of ILD. Twenty-five (30.1%) of patients with lung cancer and ILD experienced cytotoxic chemotherapy-induced lung injury within one year. Univariate Cox proportional hazards model showed that higher levels of HMGB1 and higher tumor burden were associated with disease onset. Moreover, multivariate analysis revealed that only HMGB1 was independently associated with this severe complication in patients with lung cancer and ILD. CONCLUSIONS: HMGB1 is a potential predictive blood biomarker for cytotoxic chemotherapy-induced lung injury in patients with lung cancer and ILD. This study also suggests a potential pathogenesis of this serious adverse event that tumor- and ILD-derived HMGB1 accelerates lung injury.


Assuntos
Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/diagnóstico , Antineoplásicos/efeitos adversos , Citotoxinas/efeitos adversos , Proteínas de Grupo de Alta Mobilidade/sangue , Doenças Pulmonares Intersticiais/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Lesão Pulmonar Aguda/etiologia , Idoso , Biomarcadores/sangue , Feminino , Humanos , Doenças Pulmonares Intersticiais/complicações , Neoplasias Pulmonares/complicações , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes
15.
SAGE Open Med ; 8: 2050312120918264, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32528682

RESUMO

OBJECTIVES: Drug-induced interstitial lung disease occurs when exposure to a drug causes inflammation and, eventually, fibrosis of the lung interstitium. Drug-induced interstitial lung disease is associated with substantial morbidity and mortality. The aim of this retrospective study was to obtain new information on the time-to-onset profiles of drug-induced interstitial lung disease by consideration of other associated clinical factors using the Japanese Adverse Drug Event Report database. METHODS: We identified and analyzed reports of drug-induced interstitial lung disease between 2004 and 2018 from the Japanese Adverse Drug Event Report database. The reporting odds ratio and 95% confidence interval was used to detect the signal for each drug-induced interstitial lung disease incidence. We evaluated the time-to-onset profile of drug-induced interstitial lung disease and used the applied association rule mining technique to uncover undetected relationships, such as possible risk factors. RESULTS: The reporting odds ratios (95% confidence intervals) of drug-induced interstitial lung disease due to temsirolimus, gefitinib, sho-saiko-to, sai-rei-to, osimertinib, amiodarone, alectinib, erlotinib, everolimus, and bicalutamide were 18.3 (15.6-21.3), 17.8 (16.5-19.2), 16.3 (11.8-22.4), 14.5 (11.7-18.2), 12.5 (10.7-14.7), 10.9 (9.9-11.9), 10.6 (8.1-13.9), 9.6 (8.8-10.4), 9.4 (8.7-10.0), and 9.2 (7.9-10.6), respectively. The median durations (day (interquartile range)) for drug-induced interstitial lung disease were as follows: amiodarone (123.0 (27.0-400.5)), methotrexate (145.5 (67.8-475.8)), fluorouracil (86.0 (35.5-181.3)), gemcitabine (53.0 (20.0-83.0)), paclitaxel (52.0 (28.5-77.5)), docetaxel (47.0 (18.8-78.3)), bleomycin (92.0 (38.0-130.5)), oxaliplatin (45.0 (11.0-180.0)), nivolumab (56.0 (21.0-135.0)), gefitinib (24.0 (11.0-55.0)), erlotinib (21.0 (9.0-49.0)), temsirolimus (38.0 (14.0-68.5)), everolimus (56.0 (35.0-90.0)), osimertinib (51.5 (21.0-84.8)), alectinib (78.5 (44.3-145.8)), bicalutamide (50.0 (28.0-147.0)), pegylated interferon-2α (140.0 (75.8-233.0)), sai-rei-to (35.0 (20.0-54.5)), and sho-saiko-to (33.0 (13.5-74.0)) days. Association rule mining suggested that the risk of drug-induced interstitial lung disease was increased by a combination of amiodarone or sho-saiko-to and aging. CONCLUSION: Our results showed that patients who receive gefitinib or erlotinib should be closely monitored for the development of drug-induced interstitial lung disease within a short duration (4 weeks). In addition, elderly people who receive amiodarone or sho-saiko-to should be carefully monitored for the development of drug-induced interstitial lung disease.

16.
Int J Med Sci ; 17(7): 921-930, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32308545

RESUMO

Clostridium difficile-associated colitis (CDAC) may cause gastrointestinal illness, ranging in severity from mild diarrhea to fulminant colitis and even mortality. The purpose of this study was to evaluate anti-infective-related CDAC profiles using the Japanese Adverse Drug Event Report (JADER) database. Methods: We selected case reports of adverse events of CDAC as specified in the Medical Dictionary for Regulatory Activities. The association between the number of administered anti-infectives and aging was evaluated using reporting odds ratio (ROR) and adjusted for covariates using multiple-logistic regression. We also evaluated anti-infective-related CDAC-onset profiles using Weibull shape parameter. Results: The JADER database contained 534 688 reports from April 2004 to June 2018. There were 1222 anti-infective related CDAC events. The top five anti-infectives were as follows: third-generation cephalosporins (Anatomical Therapeutic Chemical (ATC) code: J01DD, 313 cases), fluoroquinolones (ATC code: J01MA, 201 cases), macrolides (ATC code: J01FA, 146 cases), carbapenems (ATC code: J01DH, 143 cases), and penicillins with extended spectrum (ATC code: J01CA, 103 cases). The adjusted RORs (95% confidence interval) in individuals using 1, 2, and ≥ 3 anti-infectives were 8.88 (7.05-11.18), 9.77 (6.89-13.86), and 18.39 (11.85-28.54), respectively. Moreover, 47.2% of CDACs occurred within 7 days of anti-infective therapy initiation. The adjusted ROR of interaction terms of ≥ 70 years × 1 drug was 21.81 (14.56-32.68). Conclusion: Our results suggest that the number of administered anti-infectives and patient age are associated with CDAC. These data may be particularly beneficial to prescribers and would contribute to improving the management of CDAC.


Assuntos
Anti-Infecciosos/efeitos adversos , Clostridioides difficile , Bases de Dados de Produtos Farmacêuticos , Enterocolite Pseudomembranosa/induzido quimicamente , Idoso , Cefalosporinas/efeitos adversos , Enterocolite Pseudomembranosa/epidemiologia , Fluoroquinolonas/efeitos adversos , Humanos , Japão/epidemiologia , Macrolídeos/efeitos adversos , Razão de Chances
17.
Case Rep Oncol ; 13(3): 1495-1500, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33564289

RESUMO

The incidence of central nervous system metastasis is known to be high among patients with lung cancer. The frequency of brain metastasis and carcinomatous meningitis during the entire clinical course of non-small cell lung cancer is reported to be about 40% and 5%, respectively. In contrast, the incidence of cranial nerve metastasis is extremely rare, and detailed reports of its clinical course remain limited. Herein, we report 2 patients diagnosed with cranial nerve metastasis of lung adenocarcinoma and treated with radiotherapy and systemic chemotherapy. Both patients had cranial nerve symptoms, and brain magnetic resonance imaging showed cranial nerve enhancement. However, no evidence of carcinomatous meningitis was noted on magnetic resonance imaging and cerebrospinal fluid cytology. Based on these observations, these patients were diagnosed with cranial nerve metastasis of lung adenocarcinoma. Radiotherapy and chemotherapy were performed in both cases. In both cases, neurological symptoms had not worsened and imaging findings did not indicate any deteriorations. Therefore, radiotherapy and systemic chemotherapy should be considered when treating cranial nerve metastasis of lung adenocarcinoma. Early therapeutic intervention may lead to attenuation of the cranial nerve dysfunction resulting from cranial nerve metastasis.

18.
Anticancer Res ; 39(10): 5725-5731, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570474

RESUMO

BACKGROUND/AIM: In lung cancer (LC) patients, pre-existing interstitial lung disease (ILD) is a risk of chemotherapy-associated acute exacerbation of ILD (AE-ILD). AE-ILD shows a diverse clinical course varying from fatal respiratory failure to asymptomatic event, and the prognostic impact is still unclear. MATERIALS AND METHODS: We retrospectively evaluated the association between the prognosis and AE-ILD in 86 LC patients with pre-existing ILD who were treated with cytotoxic chemotherapy, especially focusing on histological types of LC. RESULTS: Thirty (34.9%) patients had AE-ILD, that was significantly associated with a poor prognosis in LC patients with ILD. When analyzed by histological types, a significant association of AE-ILD with shorter survival was observed only in the small cell LC (SCLC) group, but not in the non-small cell LC group. CONCLUSION: The development of AE-ILD by cytotoxic chemotherapy is associated with poor prognosis in LC patients with ILD, especially in patients with SCLC.


Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Doenças Pulmonares Intersticiais/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/mortalidade , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Doenças Pulmonares Intersticiais/mortalidade , Doenças Pulmonares Intersticiais/patologia , Masculino , Prognóstico , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/patologia
19.
Int J Med Sci ; 16(9): 1295-1303, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588196

RESUMO

Direct oral anticoagulants (DOACs) are used in anticoagulant therapy. The purpose of this study was to evaluate the association of DOAC-induced gastrointestinal (GI) and nervous system hemorrhage using the FDA's Adverse Event Reporting System (FAERS) database and the Japanese Adverse Drug Event Report (JADER) database. We identified and analyzed the reports of hemorrhagic reactions between 2004 and 2016 from the FAERS and JADER databases, and calculated the adjusted reported odds ratio (ROR) using the multiple logistic regression method. Additionally, we used the time-to-onset analysis. In the FAERS database, the adjusted ROR of apixaban, rivaroxaban, and dabigatran for GI hemorrhage was 6.79 (5.84-7.91), 19.58 (18.85-20.34), and 14.51 (13.58-15.51), respectively. In the JADER database, the adjusted ROR of apixaban, rivaroxaban, edoxaban, and dabigatran for GI hemorrhage was 11.80 (9.50-14.64), 11.03 (9.18-13.26), 10.17 (6.95-14.88), and 9.85 (7.23-13.42), respectively. We found that the association of GI hemorrhage with DOACs was affected by sex (female). Additionally, 30% of GI hemorrhage was observed after 30 days. Hemorrhagic reactions of both GI and nervous systems were observed in both the spontaneous reporting system databases. We recommend that female patients who experience symptoms related to GI hemorrhage should be closely monitored and advised to adhere to an appropriate care plan. Additionally, our results show that patients should be closely monitored for hemorrhage even after a month.


Assuntos
Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Administração Oral , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/epidemiologia , Humanos , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/epidemiologia , Japão/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estados Unidos/epidemiologia , United States Food and Drug Administration
20.
PLoS One ; 14(10): e0217951, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31593579

RESUMO

Many drugs can cause hearing loss, leading to sensorineural deafness. The aim of this study was to evaluate the risk of drug-induced hearing loss (DIHL) by using the Japanese Adverse Drug Event Report (JADER) database and to obtain profiles of DIHL onset in clinical settings. We relied on the Medical Dictionary for Regulatory Activities preferred terms and standardized queries, and calculated the reporting odds ratios (RORs). Furthermore, we applied multivariate logistic regression analysis, association rule mining, and time-to-onset analysis using Weibull proportional hazard models. Of 534688 reports recorded in the JADER database from April 2004 to June 2018, adverse event signals were detected for platinum compounds, sulfonamides (plain) (loop diuretics), interferons, ribavirin, other aminoglycosides, papillomavirus vaccines, drugs used in erectile dysfunction, vancomycin, erythromycin, and pancuronium by determining RORs. The RORs of other aminoglycosides, other quaternary ammonium compounds, drugs used in erectile dysfunction, and sulfonamides (plain) were 29.4 (22.4-38.6), 18.5 (11.2-30.6), 15.4 (10.6-22.5), and 12.6 (10.0-16.0), respectively. High lift score was observed for patients with congenital diaphragmatic hernia treated with pancuronium using association rule mining. The median durations (interquartile range) for DIHL due to platinum compounds, sulfonamides (plain), interferons, antivirals for treatment of hepatitis C virus (HCV) infections, other aminoglycosides, carboxamide derivatives, macrolides, and pneumococcal vaccines were 25.5 (7.5-111.3), 80.5 (4.5-143.0), 64.0 (14.0-132.0), 53.0 (9.0-121.0), 11.0 (3.0-26.8), 1.5 (0.3-11.5), 3.5 (1.3-6.8), and 2.0 (1.0-4.5), respectively. Our results demonstrated potential risks associated with several drugs based on their RORs. We recommend to closely monitor patients treated with aminoglycosides for DIHL for at least two weeks. Moreover, individuals receiving platinum compounds, sulfonamides (plain), interferons, and antivirals for HCV infection therapy should be carefully observed for DIHL for at least several months.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Bases de Dados Factuais , Perda Auditiva/induzido quimicamente , Perda Auditiva/epidemiologia , Autorrelato , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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