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Four incorrect figure citations in this Letter have been corrected online.
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The inversion of inhomogeneous physical states has great technological importance; for example, active noise reduction relies on the emission of an inverted sound wave that interferes destructively with the noise of the emitter1, and inverting the evolution of a spin system by using a magnetic-field pulse enables magnetic resonance tomography2. In contrast to these examples, inversion of a distribution of ferromagnetic or ferroelectric domains within a material is surprisingly difficult: field poling creates a single-domain state, and piece-by-piece inversion using a scanning tip is impractical. Here we report inversion of entire ferromagnetic and ferroelectric domain patterns in the magnetoelectric material Co3TeO6 and the multiferroic material Mn2GeO4, respectively. In these materials, an applied magnetic field reverses the magnetization or polarization, respectively, of each domain, but leaves the domain pattern intact. Landau theory indicates that this type of magnetoelectric inversion is universal across materials that exhibit complex ordering, with one order parameter holding the memory of the domain structure and another setting its overall sign. Domain-pattern inversion is only one example of a previously unnoticed effect in systems such as multiferroics, in which several order parameters are available for combination. Exploring these effects could therefore advance multiferroics towards new levels of functionality.
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Optical absorption spectra in the visible and near-infrared light were measured for magnetoelectric spin glass Ni_{0.4}Mn_{0.6}TiO_{3} under various field-cooled conditions. Despite the absence of long-range magnetic-dipole order, this spin-glass system exhibits nonreciprocal directional dichroism (NDD) at zero external field after a magnetoelectric field-cooled procedure. This result is distinct from previous studies on NDD in systems with magnetic toroidal moments induced either by long-range magnetic-dipole order or by applying crossed electric and magnetic fields. The present Letter conclusively demonstrates that the observed NDD originates from magnetoelectrically induced ferroic order of magnetic toroidal moments without conventional magnetic-dipole order.
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Clostridioides (Clostridium) difficile infection (CDI) is the leading cause of infectious diarrhoea in hospitalised patients, representing a substantial economic burden driven mainly by increased length of hospital stay (LoS). Currently in Japan, limited evidence on CDI-associated excess LoS is available. We conducted a retrospective, matched-cohort study using a large, Japanese, hospital-based administrative database. CDI was defined as CDI treatment plus either CDI diagnosis or positive enzyme immunoassay result. Propensity score matching at the time of CDI or recurrent CDI (rCDI) onset was applied to adjust baseline confounding and immortal time bias. The analysis included 5 994 054 hospitalisation records during 2008-2017, of which 11 823 were identified as CDI and 1359 as rCDI. The median excess LoS attributable to CDI and rCDI was 3 days and 6.5 days, respectively. The excess mortality attributable to CDI was 6.9%; there was no excess mortality attributable to rCDI (-1.9%). The median difference in costs attributable to CDI and rCDI during the residual stay was JPY 130 296 (USD 1185) and JPY 81 054 (USD 737) per hospitalisation, respectively. By adjusting the biases, the burden of CDI in Japan was evaluated. The findings could support decision making and resource allocation for CDI management in Japanese hospitals.
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Infecções por Clostridium/epidemiologia , Tempo de Internação/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Clostridioides difficile , Infecções por Clostridium/economia , Infecções por Clostridium/mortalidade , Comorbidade , Feminino , Custos Hospitalares , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
AIM: To evaluate the diagnostic accuracy of magnetic resonance imaging (MRI) for the antenatal diagnosis of placenta accreta spectrum (PAS). MATERIALS AND METHODS: Data from 95 patients with placenta previa or low-lying placenta who underwent MRI at Osaka University Hospital for the antenatal diagnosis of PAS between January 2013 and December 2018 were reviewed retrospectively. The antenatal MRI signs suggesting PAS were assessed. Patients were divided into two groups depending on whether they were diagnosed with PAS. Factors that affected PAS diagnosis were identified using multivariate analysis. RESULTS: The diagnostic accuracy of MRI for detecting PAS was as follows: 71.4% sensitivity, 96.4% specificity, and area under the curve (AUC) of 0.839 (95% confidence interval [CI]: 0.73-0.91). The diagnostic accuracy was lower in patients with in-vitro fertilisation with embryo transfer (IVF-ET): 22.2% sensitivity, 93.3% specificity, and AUC=0.578 (95% CI: 0.417-0.724). On multivariate analysis, only IVF-ET showed a significant association with false-positive or -negative MRI diagnosis of PAS (adjusted odds ratio: 26.5; 95% CI: 2.42-289.4; p=0.007). CONCLUSION: IVF-ET affects the antenatal diagnosis of PAS using MRI.
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Transferência Embrionária/efeitos adversos , Fertilização in vitro/efeitos adversos , Imageamento por Ressonância Magnética/métodos , Placenta Acreta/diagnóstico por imagem , Diagnóstico Pré-Natal/métodos , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Previous studies of guselkumab have demonstrated clinical benefits in patients with plaque-type psoriasis, generalized pustular psoriasis, erythrodermic psoriasis and palmoplantar pustulosis (PPP). OBJECTIVE: The aim of this exploratory analysis of a double-blind, multicenter, placebo-controlled, phase 3 study in Japanese patients with PPP was to evaluate the efficacy of guselkumab in the subset of patients with pustulotic arthro-osteitis (PAO). METHODS: Patients were randomized to receive guselkumab 100 or 200 mg at weeks 0, 4, 12 and every 8 weeks, or placebo with cross-over to guselkumab 100 or 200 mg at week 16 (placebo group). Efficacy endpoints were changes from baseline in magnetic resonance imaging (MRI) score, EuroQOL-5 dimensions (EQ-5D) index score, EQ-5D pain/discomfort dimension score and C-reactive protein (CRP, mg/L) level in all PAO patients through week 52. Data from both guselkumab groups were combined and presented as results for a single overall guselkumab group. RESULTS: Among 159 patients with PPP, 66 with PAO were randomized across treatment groups. For patients with MRI data for all regions assessed, the proportion of patients in the guselkumab group with PAO characterized as severe decreased from 23.8% (10/42) at baseline to 5.4% (2/42) at week 52. The mean (SD) change from baseline at week 52 in EQ-5D index score was 0.20 (0.17) among PPP patients with PAO and 0.15 (0.17) among those without PAO in the guselkumab group. Among all PAO patients, the proportions with an EQ-5D pain/discomfort dimension score of no or slight pain/discomfort in the guselkumab group increased from baseline to week 52 [33.3% (7/21) vs. 87.5% (35/40)]. The mean (SD) CRP levels decreased in all PAO patients in the guselkumab group at week 52 compared to baseline [-1.71 (8.16) mg/L]. CONCLUSION: Guselkumab treatment showed beneficial outcomes for PAO signs and symptoms in Japanese patients with PPP.
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Osteíte , Psoríase , Anticorpos Monoclonais Humanizados , Método Duplo-Cego , Humanos , Japão , Psoríase/tratamento farmacológico , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: To examine the association between maternal alcohol consumption during pregnancy and the risk of preterm delivery. DESIGN: Prospective cohort study. SETTING: The Japan Environment and Children's Study (JECS). POPULATION: A total of 94 349 singleton pregnancies. METHODS: Participants completed questionnaires detailing alcohol consumption during the first trimester and during the second and third trimesters. Participants were divided into four categories according to alcohol consumption (non-drinkers, consumers of 1-149 g, 150-299 g and ≥300 g ethanol/week). We examined the effect of alcohol consumption during different stages of pregnancy on the risk of preterm delivery. Odds ratios (OR) and 95% CI were calculated relative to non-drinkers using logistic regression. MAIN OUTCOME MEASURES: Medical record-based preterm delivery. RESULTS: Alcohol consumption during the second and third trimesters, but not during the first trimester, was associated with increased risk of preterm delivery. Heavy alcohol consumption (≥300 g ethanol/week) during the second and third trimesters was associated with a four-fold higher risk compared with non-drinkers (multivariable OR 4.52; 95% CI 1.68-12.2). Light alcohol consumption (1-149 g ethanol/week) tended to be associated with lower risk of preterm delivery (multivariable OR 0.78; 95% CI 0.60-1.00). CONCLUSIONS: Heavy alcohol consumption during the second and third trimesters was associated with increased risk of preterm delivery among pregnant women. TWEETABLE ABSTRACT: Heavy drinking during pregnancy may increase the risk of preterm delivery.
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Consumo de Bebidas Alcoólicas/efeitos adversos , Nascimento Prematuro/epidemiologia , Adulto , Estudos de Coortes , Feminino , Humanos , Japão/epidemiologia , Serviços de Saúde Materno-Infantil , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Nascimento Prematuro/etiologia , Estudos Prospectivos , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: Several studies have reported that single nucleotide polymorphisms (SNPs) in the gene encoding NF-E2-related factor 2 (Nrf2) contribute to airflow limitations in smokers without COPD. Although small airway lesions and emphysema contribute cooperatively to airflow limitation, the relationship between Nrf2 SNPs and the development of emphysema in smokers without COPD is not well understood. METHODS: Healthy subjects who underwent an annual health checkup with computed tomography (CT) of the chest at Osaka City University Hospital were prospectively recruited. The percentage of low-attenuation area (%LAA) on chest CT was quantified, and correlations between %LAA, Nrf2 SNP [rs6726395 (G/A)] genotypes, and clinical characteristics were examined. RESULTS: A total of 245 subjects without COPD [non-/light-smoker: 153 (62.4%) and smoker: 92 (37.6%)] were enrolled. The %LAA in the upper lung field was higher than that in the lower lung field (p < 0.001). The %LAA in smokers was significantly higher than that in non-/light-smokers (p = 0.021). The %LAA showed significant but weak correlation with age in all subjects (r = 0.141, p = 0.028). Divided by genotype, the %LAA of the upper lung field was significantly correlated with age in smokers with genotype GG (wild type) (r = 0.333, p = 0.022), but was not significantly correlated with age in smokers with genotype AG/AA. These correlations were not observed in non-/light smokers. CONCLUSION: A polymorphism rs6726395 in Nrf2 can contribute to the development of emphysema-associated aging in smokers. The Nrf2 SNP may be a predictive factor for smoking-induced emphysema, and genotyping of Nrf2 SNP may serve as biomarker for emphysema prevention.
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Fator 2 Relacionado a NF-E2/genética , Polimorfismo de Nucleotídeo Único , Enfisema Pulmonar/genética , Fumantes , Fumar/efeitos adversos , Adulto , Fatores Etários , Idoso , Feminino , Predisposição Genética para Doença , Heterozigoto , Homozigoto , Humanos , Japão , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , não Fumantes , Fenótipo , Estudos Prospectivos , Enfisema Pulmonar/diagnóstico por imagem , Enfisema Pulmonar/fisiopatologia , Medição de Risco , Fatores de Risco , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: FGFR3 chondrodysplasia is caused by a gain-of-function mutation of the FGFR3 gene. The disease causes abnormal growth plate cartilage and lacks effective drug treatment. We sought to establish an in vivo model for the study of FGFR3 chondrodysplasia pathology and drug testing. DESIGN: We created cartilage from human induced pluripotent stem cells (hiPSCs) and transplanted the cartilage into the subcutaneous spaces of immunodeficient mice. We then created cartilage from the hiPSCs of patients with FGFR3 chondrodysplasia and transplanted them into immunodeficient mice. We treated some mice with a FGFR inhibitor after the transplantation. RESULTS: Xenografting the hiPSC-derived cartilage reproduced human growth plate cartilage consisting of zones of resting, proliferating, prehypertrophic and hypertrophic chondrocytes and bone in immunodeficient mice. Immunohistochemistry of xenografts using anti-human nuclear antigen antibody indicated that all chondrocytes in growth plate cartilage were human, whereas bone was composed of human and mouse cells. The pathology of small hypertrophic chondrocytes due to up-regulated FGFR3 signaling in FGFR3 skeletal dysplasia was recapitulated in growth plate cartilage formed in the xenografts of patient-specific hiPSC-derived cartilage. The mean diameters of hypertrophic chondrocytes between wild type and thanatophoric dysplasia were significantly different (95% CI: 13.2-26.9; n = 4 mice, one-way analysis of variance (ANOVA)). The pathology was corrected by systemic administration of a FGFR inhibitor to the mice. CONCLUSION: The patient-specific growth plate cartilage xenograft model for FGFR3 skeletal dysplasia indicated recapitulation of pathology and effectiveness of a FGFR inhibitor for treatment and warrants more study for its usefulness to study disease pathology and drug testing.
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Cartilagem/patologia , Lâmina de Crescimento/patologia , Mutação , Osteocondrodisplasias/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Animais , Cartilagem/metabolismo , Ciclo Celular , Diferenciação Celular , Proliferação de Células , Modelos Animais de Doenças , Lâmina de Crescimento/metabolismo , Xenoenxertos , Camundongos , Osteocondrodisplasias/metabolismo , Osteocondrodisplasias/patologia , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismo , Transdução de SinaisRESUMO
BACKGROUND: Liver fibrosis is a risk factor for hepatectomy but cannot be determined accurately before hepatectomy because diagnostic procedures are too invasive. Magnetic resonance elastography (MRE) can determine liver stiffness (LS), a surrogate marker for assessing liver fibrosis, non-invasively. The aim of this study was to investigate whether the LS value determined by MRE is predictive of major complications after hepatectomy. METHODS: This prospective study enrolled consecutive patients who underwent hepatic resection between April 2013 and August 2016. LS values were measured by imaging shear waves by MRE in the liver before hepatectomy. The primary endpoint was major complications, defined as Clavien-Dindo grade IIIa or above. Logistic regression analysis identified independent predictive factors, from which a logistic model to estimate the probability of major complications was constructed. RESULTS: A total of 96 patients were included in the study. Major complications were observed in 15 patients (16 per cent). Multivariable logistic analysis confirmed that higher LS value (P = 0·021) and serum albumin level (P = 0·009) were independent predictive factors for major complications after hepatectomy. Receiver operating characteristic (ROC) analysis showed that the best LS cut-off value was 4·3 kPa for detecting major complications, comparable to liver fibrosis grade F4, with a sensitivity of 80 per cent and specificity of 82 per cent. A logistic model using the LS value and serum albumin level to estimate the probability of major complications was constructed; the area under the ROC curve for predicting major complications was 0·84. CONCLUSION: The LS value determined by MRE in patients undergoing hepatectomy was an independent predictive factor for major complications.
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Técnicas de Imagem por Elasticidade/métodos , Hepatectomia/efeitos adversos , Cirrose Hepática/cirurgia , Fígado/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico , Idoso , Fenômenos Biomecânicos , Feminino , Seguimentos , Humanos , Incidência , Japão/epidemiologia , Fígado/fisiopatologia , Fígado/cirurgia , Cirrose Hepática/diagnóstico , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Valor Preditivo dos Testes , Estudos ProspectivosRESUMO
OBJECTIVES: The aim of this study was to evaluate the applicability of genotyping of the ABCG2 gene using MALDI-TOF MS and to estimate the allele frequency in the Japanese population. BACKGROUND: Jr (a-) phenotype has a prevalence of approximately 0·05% among Japanese blood donors; DNA-based genotyping was conducted to investigate the molecular basis of the Jr (a-) phenotype along with serological typing. To detect all SNPs of the ABCG2 gene, a high-throughput SNP genotyping platform is needed. METHODS: Overall, 1004 Jr (a-) blood samples were collected from blood donors in Japan and pre-genotyped. To detect the SNPs of the ABCG2 gene using MALDI-TOF MS, polymerase chain reaction and unextend primer were designed. In total, 205 Jr (a-) samples were genotyped using MALDI-TOF MS analysis. RESULTS: The SNPs of 1004 Jr (a-) samples were identified using the HRM analysis and DNA sequencing, and 799 of 1004 (80%) Jr (a-) samples had the homozygous for c.376 T. The designed primers for MALDI-TOF MS perfectly detected the SNPs of the ABCG2 gene. A total of 205 Jr (a-) samples were genotyped using MALDI-TOF MS. Calling failures occurred in only two samples with the mutations c.736CT to c.376C and c.421C to c.421CA. The concordance rate between the pre-genotyped and MALDI-TOF MS-based genotyping results was very high (99·02%) for all ABCG2 alleles. CONCLUSIONS: Jr (a-) Japanese donors had almost the homozygous for c.376 T. However, detections of more than 20 SNPs of the ABCG2 gene for the JR blood group genotyping are needed. MALDI-TOF MS-based genotyping was highly concordant with the pre-genotyped results for all ABCG2 alleles.
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Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Técnicas de Genotipagem/métodos , Proteínas de Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Povo Asiático , Feminino , Técnicas de Genotipagem/instrumentação , Humanos , Japão , MasculinoRESUMO
INTRODUCTION: The aim of this study was to assess the effectiveness of improving the attitude of dental students towards the use of a full-body patient simulation system (SIMROID) compared to the traditional mannequin (CLINSIM) for dental clinical education. MATERIALS AND METHODS: The participants were 10 male undergraduate dental students who had finished clinical training in the university hospital 1 year before this study started. They performed a crown preparation on an upper pre-molar tooth using SIMROID and CLINSIM as the practical clinical trials. The elapsed time for preparation was recorded. The taper of the abutment teeth was measured using a 3-dimensional shape-measuring device after this trial. In addition, a self-reported questionnaire was collected that included physical pain, treatment safety and maintaining a clean area for each simulator. Qualitative data analysis of a free format report about SIMROID was performed using text mining analysis. This trial was performed twice at 1-month intervals. RESULTS: The students considered physical pain, treatment safety and a clean area for SIMROID significantly better than that for CLINSIM (P < .01). The elapsed time of preparation in the second practical clinical trial was significantly lower than in the first for SIMROID and CLINSIM (P < .01). However, there were no significant differences between the abutment tapers for both systems. For the text mining analysis, most of the students wrote that SIMROID was similar to real patients. CONCLUSION: The use of SIMROID was proven to be effective in improving the attitude of students towards patients, thereby giving importance to considerations for actual patients during dental treatment.
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Atitude do Pessoal de Saúde , Assistência Odontológica , Manequins , Robótica , Treinamento por Simulação , Competência Clínica , Coroas , Relações Dentista-Paciente , Humanos , Japão , Masculino , Segurança do Paciente , Autorrelato , Estudantes de Odontologia , Inquéritos e Questionários , Adulto JovemRESUMO
OBJECTIVES: The cerebrospinal fluid tap test for idiopathic normal pressure hydrocephalus (iNPH) is one of the good predictors of the shunt treatment, although this test has a low sensitivity. We aimed to identify key parameters that could be used to improve this sensitivity. MATERIALS & METHODS: During 2010-2011, we recruited and then followed 93 patients with possible iNPH for 12 months after shunt. Among them, 82 patients were finally enrolled in this study. The modified Rankin Scale, iNPH grading scale, and several quantitative measurements were evaluated at entry, after the tap test, before and after shunt. Area under the receiver-operating characteristic curves (AUCs), sensitivities, and specificities of the tap test for predicting shunt effectiveness were calculated for each measurement. They were additionally assessed after stratification by disease duration since the initial presentation of iNPH symptoms. RESULTS: The gait disturbance on the iNPH grading scale had the highest accurate scale at the tap test for predicting effectiveness 12 months after shunt: AUC 0.74, sensitivity 56.5%, specificity 91.7%. This AUC increased to 0.76, 0.91 and 0.94 in the subgroup of disease duration <24, <12, and <6 months, respectively. The sensitivity and specificity of the gait disturbance on the iNPH grading scale in the subgroup of <12 months' duration were 92.3% and 90.0%. CONCLUSIONS: The shorter period of clinical symptoms, for example, <12 months, made the tap test sufficiently accurate examination for predicting improvement 12 months after shunt surgery. The findings imply that the tap test should be applied to patients being considered for shunt surgery as soon as possible.
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Derivações do Líquido Cefalorraquidiano/normas , Hidrocefalia de Pressão Normal/diagnóstico , Hidrocefalia de Pressão Normal/cirurgia , Punção Espinal/normas , Idoso , Idoso de 80 Anos ou mais , Derivações do Líquido Cefalorraquidiano/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Punção Espinal/métodos , Fatores de TempoRESUMO
WHAT IS KNOWN AND OBJECTIVES: The Screening Tool of Older Persons' Potentially Inappropriate Prescriptions (stopp) criteria were updated in 2014 (stopp criteria ver.2), but few studies have evaluated the usefulness of stopp criteria in elderly patients. This prospective observational study evaluated the prevalence of potentially inappropriate medications (PIMs), and the efficacy of hospital pharmacists' assessment and intervention based on stopp criteria ver.2. METHODS: The study was conducted at three medical units of Kobe University Hospital between April 2015 and March 2016. Pharmacists assessed and detected PIMs based on stopp criteria ver.2 and considered the patient's intention to change the prescription at the time of admission of each patient. If the pharmacists judged that benefits outweighed risks of prescription change and the patients consented to change the medications, they recommended the doctor to change the prescription. If there was a risk of exacerbation of disease by the change of medications and the pharmacists judged it to be difficult to adjust medications during hospitalization or the patients did not consent to change the medications, they did not recommend to change it. The pharmacists and the doctors discussed and finally decided whether to change the PIMs or not. The number of patients prescribed PIMs, the number and contents of PIMs, and the number of medications changed after pharmacists' intervention were calculated. RESULTS: Totally, 822 new inpatients aged ≥65 years prescribed ≥1 daily medicine were included. Their median (interquartile range) age was 75·0 (71·0-80·0) years, and 54·9% were male. According to the criteria, 346 patients (42·1%) were prescribed ≥1 PIMs. Patients prescribed PIMs took significantly more medications than others: 10·0 (7·0-13·0) vs. 6·0 (4·0-9·0), P < 0·001. The total number of PIMs was 651%, 47·6% of which (n = 310) were recommended the doctors to change, and 292 of 651 PIMs (44·9%) were finally discontinued/changed after pharmacists' assessment and intervention. PIMs related to benzodiazepines, including Z-drugs, were most frequent, with a detailed classifications as follows (changed/total): (i) benzodiazepines for 4 or more weeks (75/205), (ii) drugs that predictably increase the risk of falls in older people (benzodiazepines) (30/67) and (iii) drugs that predictably increase the risk of falls in older people (hypnotic Z-drugs) (15/31). CONCLUSION: Over 40% elderly patients were prescribed PIMs, and pharmacists' assessments and interventions based on stopp criteria ver.2 were useful in detecting and correcting prescription of PIMs.
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Prescrição Inadequada/estatística & dados numéricos , Farmacêuticos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Estudos ProspectivosRESUMO
The efficacy of thiopurines, including azathioprine (AZA) and 6-mercaptopurine (6MP), has been demonstrated for the treatment of inflammatory bowel disease (IBD). The most common and serious adverse event of treatment with thiopurines altered by doctors is leukopenia. Hair loss is also a serious event that could be a critical reason for patients to decline thiopurine treatment. Thiopurine-induced severe hair loss causes cosmetic problems, and it takes a long time to recover. In a recent study, NUDT15 R139C was strongly associated with thiopurine-induced leukopenia in Korean and Caucasian populations. In this study, we performed an association study to investigate and replicate the association of R139C with adverse events of thiopurines in Japanese patients. A total of 142 Japanese patients with IBD, with histories of thiopurine treatment, were examined. NUDT15 R139C was genotyped using a custom TaqMan genotyping assay. Adverse events including leukopenia were reviewed from medical records. The 6MP dose was adjusted to AZA equivalents by multiplying with 2 as a thiopurine dose. Five patients developed severe hair loss and all of them were risk homozygous (T/T) for R139C. No early severe hair loss was observed in patients with the C/T or C/C genotype (P=3.82 × 10(-16), odds ratio=212). The association of R139C with early (<8 weeks) leukopenia (white blood cells<3000 mm(-3)), which was previously reported in Korean patients, was replicated in our Japanese IBD cohort (P=1.92 × 10(-16), odds ratio=28.4). However, we could not confirm the association with late leukopenia in the Japanese subjects. Patients with the C/T genotype discontinued treatment or required thiopurine dose reduction significantly earlier than patients with the C/C genotype (P=1.45 × 10(-4)); however, on manipulating the doses, there was no significant difference in the thiopurine continuation rates between the groups. In the maintenance period, the frequencies of 6MP usage were higher, and the doses of thiopurines were significantly lower in patients with the C/T genotype than in those with the C/C genotype (0.574±0.316 mg kg(-1) per day vs 1.03±0.425 mg kg(-1) per day, P=6.21 × 10(-4)). NUDT R139C was significantly associated with early severe hair loss in Japanese patients with IBD. We also verified the previously reported association of R139C with early leukopenia in a different East Asian population. It is recommended that treatment with thiopurines should be avoided for patients with the T/T genotype. Low-dose 6MP (0.2-0.3 mg kg(-1) per day) could be used rather than AZA for the patients with C/T genotype to continue thiopurine treatments. However, late leukopenia and other several adverse events could not be completely predicted by R139C genotypes.
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Alopecia/induzido quimicamente , Alopecia/genética , Anti-Inflamatórios/efeitos adversos , Azatioprina/efeitos adversos , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/efeitos adversos , Leucopenia/induzido quimicamente , Leucopenia/genética , Mercaptopurina/efeitos adversos , Pirofosfatases/genética , Adulto , Alopecia/enzimologia , Alopecia/etnologia , Anti-Inflamatórios/administração & dosagem , Povo Asiático/genética , Azatioprina/administração & dosagem , Distribuição de Qui-Quadrado , Colite Ulcerativa/etnologia , Doença de Crohn/etnologia , Relação Dose-Resposta a Droga , Feminino , Fármacos Gastrointestinais/administração & dosagem , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Japão , Estimativa de Kaplan-Meier , Leucopenia/enzimologia , Leucopenia/etnologia , Modelos Logísticos , Masculino , Mercaptopurina/administração & dosagem , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Fenótipo , Pirofosfatases/metabolismo , Fatores de Risco , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto JovemRESUMO
We evaluated the clinical efficacy and safety of teicoplanin according to the pharmacokinetics (PK) therapeutic level achieved in patients with renal dysfunction. Target trough concentration (Cmin) was ≥15-30 µg/ml which has been recommended in patients with normal renal function. Adult patients (estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2)) who were treated by teicoplanin were included in the study. We adopted two types of regimen for the initial 3 days: the conventional regimen, and the enhanced loading regimen (10 mg/kg twice daily on the 1st day, followed by 6.7-10 mg/kg once daily for the 2nd and 3rd days]. Two hundred and eighty-eight patients were evaluated for safety, and 106 patients with methicillin-resistant Staphylococcus aureus (MRSA) infections were evaluated for clinical efficacy. A significantly higher success rate was obtained in patients who achieved the target initial Cmin compared with those that did not (75.0 % vs 50.0 %, p = 0.008). In a multivariate analysis, initial Cmin ≥15 µg/ml was an independent factor for clinical success (adjusted odds ratio: 4.20, 95 % confidence interval: 1.34-13.15). In patients with 15-30 µg/ml of maximal Cmin during therapy, nephrotoxicity occurred in 13.1 %, and hepatotoxicity in 2.6 %, and these incidences were not significantly higher compared with those patients with <15 µg/ml. In conclusion, achievement of Cmin of 15-30 µg/ml without delay was necessary to improve clinical outcomes for the treatment by teicoplanin in patients with renal dysfunction. Further investigation is required regarding the optimal loading regimen to achieve the therapeutic levels in those patients.
Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Insuficiência Renal , Infecções Estafilocócicas/tratamento farmacológico , Teicoplanina/administração & dosagem , Teicoplanina/farmacocinética , Injúria Renal Aguda/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Teicoplanina/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Urinary tract infection caused by human adenovirus (HAdV) after renal transplantation (RT) results in graft loss because of concomitant nephropathy and acute rejection and may result in death because of systemic dissemination. METHODS: We assessed the time period between RT and disease onset, symptoms, treatment details, disease duration, renal graft function, outcomes, and complications. RESULTS: HAdV infection of the urinary tract occurred in 8 of 170 renal transplant recipients. Symptoms were macrohematuria in all 8 patients, dysuria in 7, and fever in 5. The median period from RT to disease onset was 367 (range, 7-1763) days, and the median disease duration was 15 (range, 8-42) days. The mean serum creatinine (sCr) level prior to onset was 1.35 ± 0.48 mg/dL and the mean maximum sCr level during disease was 2.34 ± 1.95 mg/dL. These values were increased by ≥25% in 5 patients. The mean sCr levels when symptoms resolved was 1.54 ± 0.67 mg/dL, and no significant difference was seen before, during, or after disease onset (P = 0.069). Two patients were diagnosed with HAdV viremia and 1 with acute tubulointerstitial nephritis revealed on biopsy. In addition to a reduction in immunosuppressant dosage, 2 patients received gammaglobulins and 5 received ganciclovir. CONCLUSION: Symptoms of all patients were alleviated, although some patients developed nephritis or viremia. Hence, the possibility of exacerbation should always be considered. Adequate follow-up observation should be conducted, and diligent and aggressive therapeutic intervention is required to prevent the condition from worsening.
Assuntos
Infecções por Adenovirus Humanos/complicações , Infecções por Adenovirus Humanos/virologia , Adenovírus Humanos/isolamento & purificação , Rejeição de Enxerto , Transplante de Rim/efeitos adversos , Infecções Urinárias/virologia , Adulto , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Feminino , Ganciclovir/administração & dosagem , Ganciclovir/uso terapêutico , Humanos , Hospedeiro Imunocomprometido , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Pessoa de Meia-Idade , Infecções Urinárias/complicaçõesRESUMO
PURPOSE: To present a case report on the successful management of a low-lying placenta and aplastic anemia. Aplastic anemia is a rare but serious disorder that is often characterized by severe pancytopenia. Because of the rarity of aplastic anemia, a pregnancy complicated by it is rarely encountered by obstetricians. Moreover, placenta previa (low-lying placenta) complicated by aplastic anemia has not been previously reported. MATERIALS AND METHODS: The authors present the first reported case of placenta previa with aplastic anemia in a patient who had undergone a previous cesarean delivery. RESULTS: They successfully managed this case by making a transverse uterine fundal incision during an elective cesarean delivery. This incision minimized blood loss and enabled good visualization of the source of bleeding in the lower uterine segment. Bleeding was stemmed by suturing the source of bleeding. CONCLUSION: The authors propose that this procedure should be considered for patients with low platelet counts and abnormal placentation.
Assuntos
Anemia Aplástica , Cesárea/métodos , Placenta Prévia/cirurgia , Complicações Hematológicas na Gravidez , Útero/cirurgia , Adulto , Perda Sanguínea Cirúrgica/prevenção & controle , Gerenciamento Clínico , Feminino , Humanos , Placentação , Gravidez , SuturasRESUMO
PURPOSE: The influence of the B-Lynch suture technique on subsequent fertility and pregnancy outcomes is not clear. In the present report, the authors describe the case of a very short interpregnancy interval following the successful placement of a B-lynch suture and discuss the associated problems. MATERIALS AND METHODS: A 33-year-old-woman underwent cesarean section after undergoing artificial induction of labor and subsequent atonic postpartum hemorrhage. Placement of a B-Lynch brace suture successfully stopped the bleeding and preserved the uterus. The patient became unexpectedly pregnant only four months later, making the present case the shortest reported interpregnancy interval after a surgery involving the B-Lynch suture. CONCLUSION: In the present case, fertility was not affected, and obstetric complications (abortion, fetal growth restriction, preterm delivery, and placenta previa) were not observed. Adhesions between the abdominal wall and the surface of the uterus along the previous B-Lynch suture line were observed and irregular, large blood vessels were observed on the surface of the uterus. Further reports are expected to determine the influence of the B-Lynch brace suture technique on the subsequent pregnancy.