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OBJECTIVES: This study aimed to investigate whether inflammation affects the outcome of swallowing ability to improve treatment for sarcopenic dysphagia. DESIGN: A retrospective observational cohort study was performed using data from the Japanese sarcopenic dysphagia database. SETTING: The database was constructed using data from 19 hospitals and one home visiting rehabilitation team. PARTICIPANTS: Patients with sarcopenic dysphagia with measurements of C-reactive protein (CRP) and serum albumin (Alb) were included. MEASUREMENTS: Patients were assigned to two groups using CRP, Alb, and the Japanese modified Glasgow Prognostic Score (mGPS). The Food Intake LEVEL Scale (FILS) was measured at the times of admission and follow-up (FILS follow-up) to assess swallowing function. RESULTS: A total of 197 patients were included. Mean or median values of each parameter were as follows: age: 83.8±8.7, Alb: 3.2 ± 0.6 g/dL, CRP: 8.0 [3.0, 29.0] mg/L, mGPS: 1 [1-2], FILS: 7 [6-8], FILS follow-up: 8 [7-8], and duration of follow-up: 57.0 [27.0, 85.0] days. The FILS score at follow-up was significantly lower in the high CRP group (≥ 5.0 mg/L) than in the low CRP group (< 5.0 mg/L) (p = 0.01). Further, the FILS score at follow-up was significantly lower in the high mGPS group (class; 2) than in the low mGPS group (class; 0 and 1) (p = 0.03). In the multiple linear regression analyses without FILS at baseline, CRP and mGPS were independent risk factors for FILS follow-up. When FILS at baseline was entered, CRP and mGPS were not an independent risk factors for FILS follow-up. CONCLUSIONS: Inflammation could modify the outcome of the patients with sarcopenic dysphagia. Inflammation may be an important risk factor in evaluating patients with sarcopenic dysphagia.
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Trastornos de Deglución , Sarcopenia , Anciano , Anciano de 80 o más Años , Proteína C-Reactiva/análisis , Deglución , Trastornos de Deglución/complicaciones , Trastornos de Deglución/rehabilitación , Humanos , Inflamación/complicaciones , Pronóstico , Estudios Retrospectivos , Sarcopenia/complicacionesRESUMEN
OBJECTIVES: To investigate the prevalence of hoarseness and its association with the severity of dysphagia in patients with sarcopenic dysphagia. DESIGN: Cross-sectional study using the Japanese sarcopenic dysphagia database. SETTING: 19 hospitals including 9 acute care hospitals, 8 rehabilitation hospitals, 2 long-term care hospitals, and 1 home visit rehabilitation team. PARTICIPANTS: 287 patients with sarcopenic dysphagia, aged 20 years and older. MEASUREMENTS: Sarcopenic dysphagia was diagnosed using a reliable and validated diagnostic algorithm for the condition. The presence and characteristics of hoarseness classified as breathy, rough, asthenic, and strained were assessed. The prevalence of hoarseness and the relationship between hoarseness and Food Intake LEVEL Scale (FILS) were examined. Order logistic regression analysis adjusted for age, sex, naso-gastric tube, and handgrip strength was used to examine the relationship between hoarseness and FILS at baseline and at follow-up. RESULTS: The mean age was 83 ± 10 years. Seventy-four (26%) patients had hoarseness, while 32 (11%), 20 (7%), 22 (8%), and 0 (0%) patients had breathy, rough, asthenic, and strained hoarseness, respectively. Median FILS at the initial evaluation was 7 (interquartile range, 5-8). Hoarseness (ß=0.747, 95% confidence intervals= 0.229, 1.265, p=0.005), age, sex, naso-gastric tube, and handgrip strength were associated independently with baseline FILS, while hoarseness (ß=0.213, 95% confidence intervals= -0.324, 0.750, p=0.438) was not associated independently with the FILS at follow-up. CONCLUSIONS: Hoarseness was associated with the severity of dysphagia at baseline, however not a prognostic factor for sarcopenic dysphagia. Resistance training of swallowing and respiratory muscles and voice training as part of rehabilitation nutrition might be useful for treating sarcopenic dysphagia.
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Trastornos de Deglución , Sarcopenia , Anciano , Anciano de 80 o más Años , Astenia/complicaciones , Estudios Transversales , Trastornos de Deglución/complicaciones , Trastornos de Deglución/epidemiología , Fuerza de la Mano , Ronquera/complicaciones , Ronquera/epidemiología , Humanos , Prevalencia , Sarcopenia/complicaciones , Sarcopenia/diagnóstico , Sarcopenia/epidemiologíaRESUMEN
Risk of fracture due to glucocorticoid-induced osteoporosis (GIO) can be reduced by anti-osteoporosis (OP) medications. The proportion of patients on long-term glucocorticoid therapy who received anti-OP medications according to the GIO management guidelines has increased in recent years, but is still suboptimal. INTRODUCTION: Adherence of physicians to guidelines for glucocorticoid (GC)-induced osteoporosis (GIO) management is currently unclear. This study aimed to clarify the state of guideline adherence by physicians in Japan and identify factors associated with guideline adherence using a nationwide health insurance claims database (NDBJ). METHODS: Patients aged ≥ 50 years who were prescribed GC for ≥ 90 days after 180 days without a GC prescription and who were followed up for osteoporosis (OP) management for the subsequent 360 days during the period spanning 2012-2018 were selected from the NDBJ. Guideline adherence was evaluated with the proportion of patients who received OP management as recommended by the Japanese guidelines. Information on previous vertebral and hip fractures, dementia, and polypharmacy was obtained. Factors associated with OP management were evaluated by logistic regression analysis. RESULTS: A total of 512,296 patients were considered to be at high risk of fracture according to the guidelines. Proportions of patients receiving OP management (BMD testing or anti-OP medications) have increased in recent years. In 2017, 33.7% of men and 55.3% of women received OP management in the initial 90 days of GC therapy. Female sex, previous anti-OP medications, polypharmacy, and higher GC dose were significantly associated with receiving OP management, while dementia showed an inverse association. A prior history of hip fracture, a strong risk factor for future fracture, was not significantly associated with receiving OP management. CONCLUSIONS: Although guideline adherence by physicians has increased in recent years, it remains suboptimal. Further efforts to improve guideline adherence are necessary. TRIAL REGISTRATION NUMBER: The present study is not registered.
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Conservadores de la Densidad Ósea , Demencia , Fracturas de Cadera , Osteoporosis , Médicos , Conservadores de la Densidad Ósea/efectos adversos , Femenino , Glucocorticoides/efectos adversos , Adhesión a Directriz , Humanos , Seguro de Salud , Japón/epidemiología , Masculino , Osteoporosis/inducido químicamente , Osteoporosis/tratamiento farmacológico , Osteoporosis/epidemiologíaRESUMEN
BACKGROUND/OBJECTIVES: The Japan-multimodal intervention trial for prevention of dementia (J-MINT) is intended to verify the effectiveness of multi-domain interventions and to clarify the mechanism of cognitive improvement and deterioration by carrying out assessment of dementia-related biomarkers, omics analysis and brain imaging analysis among older adults at high risk of dementia. Moreover, the J-MINT trial collaborates with partnering private enterprises in the implementation of relevant interventional measures. This manuscript describes the study protocol. DESIGN/SETTING: Eighteen-month, multi-centered, randomized controlled trial. PARTICIPANTS: We plan to recruit 500 older adults aged 65-85 years with mild cognitive impairment. Subjects will be centrally randomized into intervention and control groups at a 1:1 allocation ratio using the dynamic allocation method with all subjects stratified by age, sex, and cognition. INTERVENTION: The multi-domain intervention program includes: (1) management of vascular risk factors; (2) group-based physical exercise and self-monitoring of physical activity; (3) nutritional counseling; and (4) cognitive training. Health-related information will be provided to the control group every two months. MEASUREMENTS: The primary and secondary outcomes will be assessed at baseline, 6-, 12-, and 18-month follow-up. The primary outcome is the change from baseline to 18 months in a global composite score combining several neuropsychological domains. Secondary outcomes include: cognitive change in each neuropsychological test, incident dementia, changes in blood and dementia-related biomarkers, changes in geriatric assessment including activities of daily living, frailty status and neuroimaging, and number of medications taken. CONCLUSIONS: This trial that enlist the support of private enterprises will lead to the creation of new services for dementia prevention as well as to verify the effectiveness of multi-domain interventions for dementia prevention.
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Cognición/fisiología , Disfunción Cognitiva/terapia , Demencia/prevención & control , Ejercicio Físico , Evaluación Geriátrica , Actividades Cotidianas , Anciano , Anciano de 80 o más Años , Ejercicio Físico/fisiología , Femenino , Humanos , Japón , Masculino , Pruebas Neuropsicológicas/estadística & datos numéricos , Evaluación Nutricional , Factores de RiesgoRESUMEN
BACKGROUND: high recurrence rates of up to 75% within 2 years in pancreatic ductal adenocarcinoma (PDAC) patients resected for cure indicate a high medical need for clinical prediction tools and patient specific treatment approaches. Addition of the EGFR inhibitor erlotinib to adjuvant chemotherapy failed to improve outcome but its efficacy in some patients warrants predictors of responsiveness. PATIENTS AND METHODS: we analysed tumour samples from 293 R0-resected patients from the randomized, multicentre phase III CONKO-005 trial (gemcitabine ± erlotinib) with targeted sequencing, copy number, and RNA expression analyses. FINDINGS: a total of 1086 mutations and 4157 copy-number aberrations (CNAs) with a mean of 17.9 /tumour were identified. Main pathways affected by genetic aberrations were the MAPK-pathway (99%), cell cycle control (92%), TGFß signalling (77%), chromatin remodelling (71%), and the PI3K/AKT pathway (65%). Based on genetic signatures extracted with non-negative matrix factorization we could define five patient clusters, which differed in mutation patterns, gene expression profiles, and survival. In multivariable Cox regression analysis, SMAD4 aberrations were identified as a negative prognostic marker in the gemcitabine arm, an effect that was counteracted when treated with erlotinib (DFS: HR=1.59, p = 0.016, and OS: HR = 1.67, p = 0.014). Integration of differential gene expression analysis established SMAD4 alterations with low MAPK9 expression (n = 91) as a predictive biomarker for longer DFS (HR=0.49; test for interaction, p = 0.02) and OS (HR = 0.32; test for interaction, p = 0.001). INTERPRETATION: this study identified five biologically distinct patient clusters with different actionable lesions and unravelled a previously unappreciated association of SMAD4 alteration status with erlotinib effectiveness. Confirmatory studies and mechanistic experiments are warranted to challenge the hypothesis that SMAD4 status might guide addition of erlotinib treatment in early-stage PDAC patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biomarcadores de Tumor , Variaciones en el Número de Copia de ADN , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Clorhidrato de Erlotinib/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida , Mutación , Estadificación de Neoplasias , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Polimorfismo de Nucleótido Simple , Pronóstico , Modelos de Riesgos Proporcionales , Transducción de Señal , Resultado del Tratamiento , Adulto Joven , GemcitabinaRESUMEN
OBJECTIVES: We investigated the associations about the mass of geniohyoid and tongue muscle and the maximum tongue pressure in patients with sarcopenic dysphagia using ultrasonography. DESIGN: Cross sectional study. SETTING: 5 hospitals including 3 acute and 2 rehabilitation hospitals and 1 older facility. PARTICIPANTS: 36 inpatients with sarcopenic dysphagia. MEASUREMENTS: Ultrasonography was performed for geniohyoid muscle and tongue. The area for geniohyoid and tongue muscles in sagittal plane and the mean brightness level (0-255) in the muscle area were calculated. Maximum tongue pressure as strength of swallowing muscle were investigated. Partial correlation coefficient and multiple regression analysis adjusting for age and sex were performed. RESULTS: The mean age was 81.1 ± 7.9. Men were 23. The mean BMI was 19.0 ± 4.1. The mean maximum tongue pressure was 21.3 ± 9.3 kPa. The mean cross sectional area for geniohyoid muscles was 140 ± 47 mm2. The mean brightness for geniohyoid muscle was 18.6 ± 9.0. The mean cross sectional area for tongue muscles was 1664.1 ± 386.0 mm2. The mean brightness for tongue muscles was 34.1 ± 10.6. There was a significant positive correlation between area of geniohyoid muscle and maximum tongue pressure (r = 0.38, p = 0.04). Geniohyoid muscle area was an explanatory factor for maximum tongue pressure (p = 0.012) and tongue muscle area (p = 0.031) in multivariate analysis. CONCLUSIONS: Geniohyoid muscle mass was an independent explanatory factor for maximum tongue pressure and tongue muscle mass.
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Trastornos de Deglución/complicaciones , Fuerza Muscular/fisiología , Sarcopenia/complicaciones , Lengua/anatomía & histología , Anciano de 80 o más Años , Estudios Transversales , Trastornos de Deglución/diagnóstico por imagen , Femenino , Humanos , Masculino , Lengua/fisiopatologíaRESUMEN
Using the nationwide health insurance claims database, we found that the age-standardized hip fracture incidence rates in Japan indicated significant increase in males but no significant change in females during 2012-2015. The fracture risk in subjects aged 75-84 years indicated decrease in females but no change in males. INTRODUCTION: Nationwide registry data on hip fractures have not yet been established in Japan. Using the newly developed National Database of Health Insurance Claims (NDB), which covers the entire Japanese population, we investigated the incidence rates of hip fractures and the associated regional differences. We also assessed the frequency of osteoporosis prescriptions, bone turnover marker (BTM) level, and bone mineral density (BMD) measurements. METHODS: The annual numbers of hip fractures, osteoporosis prescriptions, and BTM level and BMD measurements by prefecture from 2012 to 2015 were obtained from NDB data. We calculated the standardized claims-data ratio (SCR) in each prefecture. RESULTS: The age-standardized incidence rates from 2012 to 2015 indicated no significant change in females and significant increase in males (p value for trend; 0.920, 0.002, respectively). The fracture risk decreased in females aged 75-84 years and indicated no increase in females aged 85-89 years during 2012-2015, while the fracture risk indicated no change in males aged 75-84 years and increased in males aged 85-89 years. The frequency of osteoporosis prescriptions, BTM level measurements, and BMD measurements in the general population in the corresponding period increased with statistical or marginal significance in females and males. West-east regional differences were observed in the incidence rates; the highest SCR values in the western prefectures were approximately double the lowest values in the eastern prefectures. CONCLUSIONS: The age-standardized hip fracture incidence rates indicated no significant change in females and significant increase in males in Japan from 2012 to 2015.
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Fracturas de Cadera/epidemiología , Fracturas Osteoporóticas/epidemiología , Distribución por Edad , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Densidad Ósea/fisiología , Conservadores de la Densidad Ósea/uso terapéutico , Remodelación Ósea/fisiología , Bases de Datos Factuales , Prescripciones de Medicamentos/estadística & datos numéricos , Femenino , Fracturas de Cadera/fisiopatología , Fracturas de Cadera/prevención & control , Humanos , Incidencia , Japón/epidemiología , Masculino , Osteoporosis/tratamiento farmacológico , Osteoporosis/epidemiología , Fracturas Osteoporóticas/fisiopatología , Fracturas Osteoporóticas/prevención & control , Distribución por SexoRESUMEN
BACKGROUND: This study assessed whether a combined intervention of omega-3 polyunsaturated fatty acids (PUFAs) and psychoeducation better improved mild to moderate depression in workers compared to psychoeducation alone. METHODS: This study was a double-blinded, parallel group, randomized controlled trial that compared the intervention group, receiving omega-3 fatty acids, with a control group, receiving a placebo supplement. Participants receiving omega-3 fatty acids took 15â¯×â¯300â¯mg capsules per day for 12 weeks. The total daily dose of omega-3 PUFAs was 500â¯mg docosahexaenoic acid and 1000â¯mg eicosapentaenoic acid (EPA). The Beck Depression Inventory®-II (BDI-II) was used to assess the severity of depression after treatment. RESULTS: After 12 weeks of treatment, BDI-II scores were significantly lower in the placebo and omega-3 group, when compared to their respective baseline scores (Placebo: tâ¯=â¯-â¯4.6, pâ¯<â¯0.01; Omega-3: tâ¯=â¯-â¯7.3, pâ¯<â¯0.01). However, after 12 weeks of treatment, we found no significant difference between both groups with respect to changes in the BDI-II scores (0.7; 95% CI,â¯-â¯0.7 to 2.1; pâ¯=â¯0.30). LIMITATIONS: This study did not measure blood omega-3 fatty acid concentration and presented a high-dropout rate. Moreover, our results may not be generalizable to other regions. CONCLUSIONS: The results show that a combination of omega-3 fatty acids and psychoeducation and psychoeducation alone can contribute to an improvement in symptoms in people with mild to moderate depression. However, there is no difference between the interventions in ameliorating symptoms of depression.
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Trastorno Depresivo/terapia , Ácidos Grasos Omega-3/uso terapéutico , Psicoterapia/educación , Adulto , Terapia Combinada , Depresión , Suplementos Dietéticos , Ácidos Docosahexaenoicos/uso terapéutico , Método Doble Ciego , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración PsiquiátricaRESUMEN
BACKGROUND: Attention bias modification normalizes electroencephalographic abnormalities in alpha and beta power percentages related to attention in patients with irritable bowel syndrome (IBS). Yet, it is unknown whether ABM contributes to the normalization of event-related potentials (ERP) in these patients. We hypothesized that ERP related to attention deficit would be normalized after ABM implementation in individuals with IBS. METHODS: Thirteen patients with IBS and 10 control subjects completed a 2-month intervention that included five ABM sessions. Each session included 128 trials, resulting in a total of 640 trials during the study period. Event-related potentials were measured at the first and fifth sessions. As per the international 10-20 system for electroencephalographic electrode placement, right parietal P4 was evaluated to measure the attention component of facial expression processing. KEY RESULTS: A group comparison of P100 latency at P4 revealed that latencies were significantly different between groups in session 1 (IBS vs control, 108 ± 8 vs 97 ± 14; t = -2.51, P = .0203). This difference was absent in session 5 (94 ± 11 vs 93 ± 11, respectively; t = -0.397, P = .6954, r = .09), indicating an effect of ABM in the IBS group. CONCLUSIONS AND INFERENCES: Attention bias modification may have clinical utility for normalizing brain function and specifically attentional abnormalities in patients with IBS.
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Sesgo Atencional/fisiología , Terapia Cognitivo-Conductual/métodos , Potenciales Evocados/fisiología , Síndrome del Colon Irritable/psicología , Síndrome del Colon Irritable/terapia , Femenino , Humanos , Síndrome del Colon Irritable/fisiopatología , Masculino , Adulto JovenRESUMEN
BACKGROUND: New-onset diabetes mellitus after transplantation (NODAT) is a risk factor for both cardiovascular disease and poor graft survival after kidney transplantation (KTx). In this study, we identified single-nucleotide polymorphisms (SNPs) in genes involved in glucose metabolism and examined the correlation between these SNPs and glucose intolerance after KTx. METHODS: Thirty-eight patients with normal glucose tolerance before KTx were included in this study. Patients with plasma glucose levels of >140 mg/dL at 120 minutes on the 75-g oral glucose tolerance test at 1 year after KTx were classified as having new-onset impaired glucose tolerance (NIGT). We identified 8 SNPs in 7 genes that are involved in glucose metabolism among the patients included in this study, and compared the prevalence rate of NIGT among SNPs in each gene. RESULTS: Of the 38 patients, 11 (28.9%) were diagnosed with NIGT. For rs4982856 in the PCK2 gene, the distribution of genotypes among the total patient population was as follows: T/T, 12 (31.6%); T/C, 22 (57.9%); and C/C, 4 (10.5%). Seven of 11 patients with NIGT had the T/T genotype of rs4982856, whereas only 5 of 27 patients with normal glucose tolerance had this genotype. The T allele frequency of the rs4982856 was significantly higher in the NIGT group than in the normal group (81.8 vs 52.8%, respectively; P = .015). CONCLUSION: Our study indicates that the T allele of the rs4982856 SNP in the PCK2 gene may be a risk factor for glucose intolerance after KTx.
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Diabetes Mellitus/genética , Intolerancia a la Glucosa/genética , Trasplante de Riñón/efectos adversos , Fosfoenolpiruvato Carboxiquinasa (ATP)/genética , Adulto , Femenino , Frecuencia de los Genes , Genotipo , Supervivencia de Injerto/genética , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Factores de RiesgoRESUMEN
BACKGROUND: Whether direct-acting anti-viral therapy can reduce liver fibrosis and steatosis in patients with chronic hepatitis C virus (HCV) infection is unclear. AIMS: To evaluate changes in liver stiffness and steatosis in patients with HCV who received direct-acting anti-viral therapy and achieved sustained virological response (SVR). METHODS: A total of 198 patients infected with HCV genotype 1 or 2 who achieved SVR after direct-acting anti-viral therapy were analysed. Liver stiffness as evaluated by magnetic resonance elastography, steatosis as evaluated by magnetic resonance imaging-determined proton density fat fraction (PDFF), insulin resistance, and laboratory data were assessed before treatment (baseline) and at 24 weeks after the end of treatment (SVR24). RESULTS: Alanine aminotransferase and homeostatic model assessment-insulin resistance levels decreased significantly from baseline to SVR24. Conversely, platelet count, which is inversely associated with liver fibrosis, increased significantly from baseline to SVR24. In patients with high triglyceride levels (≥150 mg/dL), triglyceride levels significantly decreased from baseline to SVR24 (P = 0.004). The median (interquartile range) liver stiffness values at baseline and SVR24 were 3.10 (2.70-4.18) kPa and 2.80 (2.40-3.77) kPa respectively (P < 0.001). The PDFF values at baseline and SVR 24 were 2.4 (1.7-3.4)% and 1.9 (1.3-2.8)% respectively (P < 0.001). In addition, 68% (19/28) of patients with fatty liver at baseline (PDFF ≥5.2%; n = 28) no longer had fatty liver (PDFF <5.2%) at SVR24. CONCLUSION: Viral eradication reduces both liver stiffness and steatosis in patients with chronic HCV who received direct-acting anti-viral therapy (UMIN000017020).
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Antivirales/uso terapéutico , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/tratamiento farmacológico , Cirrosis Hepática/tratamiento farmacológico , Hígado/patología , Respuesta Virológica Sostenida , Anciano , Estudios de Cohortes , Elasticidad , Diagnóstico por Imagen de Elasticidad , Femenino , Estudios de Seguimiento , Hepacivirus/genética , Hepatitis C Crónica/patología , Hepatitis C Crónica/virología , Humanos , Hígado/diagnóstico por imagen , Hígado/virología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/patología , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Inducción de Remisión , Carga Viral/efectos de los fármacosRESUMEN
OBJECTIVES: To clarify the status of home care massage services provided to patients. This will help in understanding how many patients utilize this service and the circumstances under which treatment is provided. DESIGN: A retrospective study. SETTING: Fifty-four acupuncture, moxibustion, and massage clinics. Participants were patients who had received home care massage for six months or more. We collected a total of 1587 responses from these 54 massage clinics; of these, 1415 responses (mean ageâ¯=â¯79.1⯱â¯11.5â¯years) were valid (valid response rate 89.2%). MAIN OUTCOME MEASURES: Actual patients and actual care services. RESULTS: The most common disorder observed among patients who utilized home care massage services was cerebrovascular disease (at approximately 36%), while the second most common were arthropathy-related disorders (16.3%). Although most patients received massage, approximately 30% received manual therapy (e.g. manual correction) and hot fomentation as part of thermotherapy. Notably, only around 10% of patients received massage alone; the majority received treatment in combination with range of motion and muscle-strengthening exercises. CONCLUSIONS: This study helped to clarify the actual state of patients receiving home care massage and the details of the massage services provided. This study clearly showed the treatment effectiveness of massage, which can be used by home medical care stakeholders to develop more effective interventions.
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Trastornos Cerebrovasculares/rehabilitación , Terapia por Ejercicio , Servicios de Atención de Salud a Domicilio , Seguro de Salud , Masaje , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Japón , Masculino , Rango del Movimiento Articular/fisiología , Estudios RetrospectivosRESUMEN
Somatic G17V RHOA mutations were found in 50-70% of angioimmunoblastic T-cell lymphoma (AITL). The mutant RHOA lacks GTP binding capacity, suggesting defects in the classical RHOA signaling. Here, we discovered the novel function of the G17V RHOA: VAV1 was identified as a G17V RHOA-specific binding partner via high-throughput screening. We found that binding of G17V RHOA to VAV1 augmented its adaptor function through phosphorylation of 174Tyr, resulting in acceleration of T-cell receptor (TCR) signaling. Enrichment of cytokine and chemokine-related pathways was also evident by the expression of G17V RHOA. We further identified VAV1 mutations and a new translocation, VAV1-STAP2, in seven of the 85 RHOA mutation-negative samples (8.2%), whereas none of the 41 RHOA mutation-positive samples exhibited VAV1 mutations. Augmentation of 174Tyr phosphorylation was also demonstrated in VAV1-STAP2. Dasatinib, a multikinase inhibitor, efficiently blocked the accelerated VAV1 phosphorylation and the associating TCR signaling by both G17V RHOA and VAV1-STAP2 expression. Phospho-VAV1 staining was demonstrated in the clinical specimens harboring G17V RHOA and VAV1 mutations at a higher frequency than those without. Our findings indicate that the G17V RHOA-VAV1 axis may provide a new therapeutic target in AITL.
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Linfadenopatía Inmunoblástica/metabolismo , Linfoma de Células T/metabolismo , Proteínas Proto-Oncogénicas c-vav/metabolismo , Transducción de Señal , Proteína de Unión al GTP rhoA/metabolismo , Biomarcadores de Tumor , Línea Celular Tumoral , Citocinas/metabolismo , Análisis Mutacional de ADN , Humanos , Linfadenopatía Inmunoblástica/genética , Linfoma de Células T/genética , Mutación , Factores de Transcripción NFATC/metabolismo , Fosforilación , Unión Proteica , Proteínas Proto-Oncogénicas c-vav/genética , Receptores de Antígenos de Linfocitos T/metabolismo , Proteína de Unión al GTP rhoA/genéticaRESUMEN
OBJECTIVE: To examine the relationship of fear of fear and broad dimensions of psychopathology in panic disorder with agoraphobia over the course of cognitive behavioural therapy in Japan. METHODS: A total of 177 Japanese patients with panic disorder with agoraphobia were treated with group cognitive behavioural therapy between 2001 and 2015. We examined associations between the change scores in Agoraphobic Cognitions Questionnaire or Body Sensations Questionnaire and the changes in subscales of Symptom Checklist-90 Revised during cognitive behavioural therapy controlling the change in panic disorder severity using multiple regression analysis. RESULTS: Reduction in Agoraphobic Cognitions Questionnaire score was related to a decrease in all Symptom Checklist-90 Revised (SCL-90-R) subscale scores. Reduction in Body Sensations Questionnaire score was associated with a decrease in anxiety. Reduction in Panic Disorder Severity Scale score was not related to any SCL-90-R subscale changes. CONCLUSIONS: Changes in fear of fear, especially maladaptive cognitions, may predict broad dimensions of psychopathology reductions in patients of panic disorder with agoraphobia over the course of cognitive behavioural therapy. For the sake of improving a broader range of psychiatric symptoms in patients of panic disorder with agoraphobia, more attention to maladaptive cognition changes during cognitive behavioural therapy is warranted.
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Agorafobia/complicaciones , Agorafobia/terapia , Terapia Cognitivo-Conductual , Miedo/psicología , Trastorno de Pánico/complicaciones , Trastorno de Pánico/terapia , Psicopatología/estadística & datos numéricos , Adulto , Agorafobia/psicología , Ansiedad/psicología , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Trastorno de Pánico/psicología , Psicoterapia de Grupo , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
Background: Anucleate platelets can undergo apoptosis in response to various stimuli, as do nucleated cells. Cardiopulmonary bypass (CPB) causes platelet dysfunction and can also activate platelet apoptotic pathways. We therefore evaluated time-dependent changes in blood platelet Bax (a pro-apoptotic molecule) levels and platelet dysfunction after cardiac surgery. Methods: We assessed blood samples obtained from subjects having on-pump or off-pump coronary artery bypass graft surgery ( n =20 each). We also evaluated the in vitro effects of platelet Bax increase in eight healthy volunteers. Results: Thrombin-induced platelet calcium mobilisation and platelet-surface glycoprotein Ib (GPIb) expression were lowest at weaning from CPB and did not recover on postoperative day one. On-pump surgery increased platelet expression of Bax, especially the oligomerised form, along with translocation of Bax from the cytosol to mitochondria and platelet-surface tumour necrosis factor-alpha (TNF-α)-converting enzyme (TACE) expression. In contrast, mitochondrial cytochrome c expression was reduced. While similar in direction, the magnitude of the observed changes was smaller in patients having off-pump surgery. In vitro , a cell-permeable Bax peptide increased platelet Bax expression to the same extent seen during bypass and produced similar platelet changes. These apoptotic-like changes were largely reversed by Bcl-xL pre-administration, and were completely reversed by combined application of inhibitors that stabilise outer mitochondrial membrane permeability and TACE. Conclusions: CPB increases platelet Bax expression, which contributes to reduced platelet-surface GPIb expression and thrombin-induced platelet calcium changes. These changes in platelet apoptotic signalling might contribute to platelet dysfunction after CPB. Clinical trial registration: UMIN Clinical Trials Registry (number UMIN000006033).