RESUMEN

Renal function significantly influences the appropriate warfarin dosage. However, studies investigating the impact of genetic factors on warfarin dosage, considering renal function, are limited. This study aimed to assess the role of genetic polymorphisms in VKORC1, CYP2C9, CYP2C19, CYP4F2, GGCX, and APOE in warfarin dosage adjustment considering renal function. A total of 108 outpatients receiving warfarin treatment with controlled prothrombin time-targeted international normalized ratio (1.5-3.0) were included. Patient data, warfarin dosage, and laboratory results were collected from electronic medical records. Each SNP [VKORC1 rs9923231, CYP2C9 rs1057910, CYP4F2 rs2108622, CYP2C19* 2 (rs4244285) and* 3 (rs4986893), GGCX rs699664 and rs12714145, and APOE rs7421] was analyzed. Multiple regression analysis revealed estimated glomerular filtration rate as the most significant factor influencing warfarin dose (p <0.001) (ß = -0.445). VKORC1 rs9923231 AA, CYP4F2 rs2108622 CT/TT, GGCX rs12714145 CT/TT, and CYP2C9 rs1057910 AC carriers were associated with warfarin dose (p <0.001, 0.015, 0.020, 0.038 and ß = -0.317, 0.191, -0.188, -0.162, respectively); however, other genes showed no significant association. In conclusion, after adjusting for renal function, genetic factors of VKORC1 rs9923231, CYP4F2 rs2108622, GGCX rs12714145, and CYP2C9 rs1057910 were found to contribute to warfarin dosage, having impact in that order. In contrast, the contribution of other genes to warfarin dosage was absent or negligible.

Asunto(s)

Anticoagulantes , Polimorfismo de Nucleótido Simple , Warfarina , Humanos , Warfarina/administración & dosificación , Femenino , Masculino , Anticoagulantes/administración & dosificación , Anciano , Persona de Mediana Edad , Pueblo Asiatico/genética , Japón , Relación Normalizada Internacional , Relación Dosis-Respuesta a Droga , Tasa de Filtración Glomerular , Vitamina K Epóxido Reductasas/genética , Anciano de 80 o más Años , Familia 4 del Citocromo P450/genética , Genotipo , Adulto , Pueblos del Este de Asia

RESUMEN

Background: As a type of welfare technology, care robotics is now widely seen as a potential aide to rehabilitation, increasing independence and enhancing the wellbeing of people with disabilities and older adults. Research into and development of care robots have both been vigorously promoted in North America, Europe and Asia, and the competition for technological advancement in robotics is becoming fierce. AI ethics and policy guidelines are being established. However, there are still differences in attitudes and perceptions, as well as national policies regarding this type of welfare technology. Moreover, despite the anticipated usefulness, it is believed that progress has been slow in the diffusion of care robots. Purpose: In order to explore how public discourses support technological innovation, such as care robots, while preparing society for potential risks and impact, we sought to ascertain whether public discourse on care robots varies from region to region. For example, what are the hopes and promises associated with care robots and what are the concerns? Methods: To address these questions, this article explored how care robots have been portrayed in five major broadsheet newspapers in five jurisdictions in Asia and Europe (France, Great Britain, Hong Kong SAR, Ireland and Japan). We obtained 545 articles for the period between January 2001 and September 2020, more than half of which originated in Japan. A thematic analysis was conducted of these articles written in four languages (Chinese, English, French and Japanese). Results: Positive and negative narratives were teased out, alongside other key prominent themes identified, such as Japan as the land of robots, the pandemic, and the impact of robots on the economy. As the number of robot-related articles grew from the year 2012 onwards, narratives became more nuanced in European newspapers, but not in Asian ones. Furthermore, recent articles began to address the social and relational impact of care robots, while providing concrete examples of improvements in the quality of life for users. Further careful examination will be necessary in the future in order to establish the impact of robotics use in rehabilitation for people with disabilities, older adults, their carers and society at large.

RESUMEN

A triple antiemetic therapy combining aprepitant (APR) with conventional double antiemetic therapy, including 5-hydroxytryptamine 3 receptor antagonist (5-HT3-RA) and dexamethasone (DEX), is recommended for preventing chemotherapy-induced nausea and vomiting induced by a carboplatin (CBDCA) regimen. However, consensus on the additive effects of APR for gynecological patients on a combined regimen of paclitaxel and CBDCA (TC regimen) has yet to be reached. This retrospective study investigated the antiemetic effects of palonosetron and DEX (PD therapy) and granisetron and DEX with APR (GDA therapy) in patients with gynecologic cancer and who underwent their first TC regimen cycle between April 2017 and March 2020 at the Gunma University Hospital Outpatient Chemotherapy Center. The results showed that the complete response rate of the 92 patients who underwent PD therapy (PD group) and the 46 patients who underwent GDA therapy (GDA group) were both 80.4% (p = 1.000), and the complete control rates of the PD and GDA groups were 78.3% and 80.4%, respectively (p = 0.828), resulting in no significant difference. Furthermore, we observed no significant difference between the PD and GDA groups in the incidence of grade ≥2 nausea, vomiting, and anorexia (nausea: 7.6% vs. 0%, p = 0.095; vomiting: 4.3% vs. 0%, p = 0.301; and anorexia: 9.8% vs. 2.2%, p = 0.164). Concerning adverse events, compared to the PD group, the GDA group showed significantly higher incidence of grade ≥2 malaise (7.6% vs. 19.6%, p = 0.039). Given the lack of difference in the antiemetic effects of PD and GDA therapies, antiemetic therapy should be selected carefully for individual patients by accounting for the incidence of adverse reactions and interactions with APR.

Asunto(s)

Antieméticos , Neoplasias , Anorexia , Antieméticos/uso terapéutico , Aprepitant , Carboplatino/efectos adversos , Dexametasona/uso terapéutico , Femenino , Granisetrón/uso terapéutico , Humanos , Náusea/inducido químicamente , Náusea/prevención & control , Paclitaxel/efectos adversos , Palonosetrón , Estudios Retrospectivos , Vómitos/inducido químicamente , Vómitos/prevención & control

RESUMEN

OBJECTIVE: Breakfast skipping is reported to be associated with obesity in children and younger populations; however, few studies report the association among elderly. The purpose of this study was to investigate the relationships between breakfast skipping and obesity prevalence among elderly. DESIGN: Cross-sectional study. SETTING: Community-dwelling elderly in Nara, Japan. PARTICIPANTS: 1052 elderly participants (mean age: 71.6 years). MEASUREMENTS: Obesity and breakfast skipping were defined as body mass index of ≥25 kg/m2 and skipping breakfast one or more times per week, respectively. RESULTS: Two hundred and seventy-two participants (25.9%) were classified as obese and forty-one (3.9%) were as breakfast skippers. Obesity prevalence was significantly higher in breakfast skippers than in breakfast eaters (43.9% vs. 25.1%, P = 0.007). In multivariable logistic regression analysis adjusted for potential confounders (age, sex and alcohol consumption), breakfast skippers showed significantly higher odds ratio (OR) for obesity than breakfast eaters (OR, 2.23; 95% confidence interval, 1.17-4.27; P = 0.015), which continued to be significant after further adjustment for socioeconomic status. In addition, breakfast skippers showed significantly lower daily potassium (P <0.001) and dietary fibre intakes (P = 0.001) and lower subjective physical activity (P = 0.035) than breakfast eaters. CONCLUSIONS: Breakfast skipping was significantly associated with obesity among elderly. Poor diet quality and physical inactivity may be potential intermediators underlying the association between breakfast skipping and obesity.

Asunto(s)

Desayuno , Conducta Alimentaria , Obesidad/etiología , Anciano , Consumo de Bebidas Alcohólicas , Índice de Masa Corporal , Estudios Transversales , Dieta , Ejercicio Físico , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Oportunidad Relativa , Prevalencia

RESUMEN

AIM: To investigate whether Aδ and C fibre pain threshold values, measured using intra-epidermal electrical stimulation (IES), in people with and without Type 2 diabetes are useful in evaluating diabetic polyneuropathy (DPN) severity. METHODS: Aδ and C fibre pain threshold values were measured in Japanese people with (n = 120) and without (n = 76) Type 2 diabetes by IES. Nerve conduction studies and other tests were performed to evaluate diabetic complications. RESULTS: Aδ and C fibre pain threshold values were high in people with diabetes compared with control subjects (Aδ fibre: 0.050 vs. 0.030 mA, P < 0.01; C fibre: 0.180 vs. 0.070 mA, P < 0.01). Participants with diabetes and neuropathy had significantly higher Aδ and C fibre pain threshold values than participants without neuropathy (Aδ fibres 0.063 vs. 0.039 mA, P < 0.01; C fibres 0.202 vs. 0.098 mA, P < 0.05). C fibre pain threshold values were significantly higher in participants with diabetes and diabetic microvascular complications than in participants without complications. Threshold values increased with complication progression. When DPN was diagnosed according to the Diabetic Neuropathy Study Group in Japan criteria, the cut-off for the C fibre pain threshold values was 0.125 mA (area under the curve 0.758, sensitivity 81.5%, specificity 61.5%). The IES test took less time (P < 0.01) and was less invasive (P < 0.01) than the nerve conduction studies. CONCLUSIONS: Intra-epidermal electrical stimulation is a non-invasive and easy measurement of small fibre pain threshold values. It may be clinically useful for C fibre measurement to diagnose early DPN as defined by the Diabetic Neuropathy Study Group in Japan criteria.

Asunto(s)

Diabetes Mellitus Tipo 2/complicaciones , Angiopatías Diabéticas/diagnóstico , Neuropatías Diabéticas/diagnóstico , Eritromelalgia/diagnóstico , Fibras Nerviosas Amielínicas/metabolismo , Umbral del Dolor , Polineuropatías/diagnóstico , Angiopatías Diabéticas/complicaciones , Angiopatías Diabéticas/metabolismo , Angiopatías Diabéticas/fisiopatología , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/fisiopatología , Neuropatías Diabéticas/complicaciones , Neuropatías Diabéticas/metabolismo , Neuropatías Diabéticas/fisiopatología , Retinopatía Diabética/complicaciones , Retinopatía Diabética/fisiopatología , Dislipidemias/complicaciones , Dislipidemias/epidemiología , Diagnóstico Precoz , Estimulación Eléctrica/instrumentación , Epidermis , Eritromelalgia/complicaciones , Eritromelalgia/metabolismo , Eritromelalgia/fisiopatología , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/epidemiología , Japón/epidemiología , Masculino , Persona de Mediana Edad , Pruebas en el Punto de Atención , Polineuropatías/complicaciones , Polineuropatías/metabolismo , Polineuropatías/fisiopatología , Prevalencia , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad

RESUMEN

WHAT IS KNOWN AND OBJECTIVE: Carbamazepine is known to interact with warfarin. We report on a case of this interaction and on its management using the patient's genetic information. CASE SUMMARY: The case concerns a 74-year-old Japanese woman with a mood disorder and a central retinal vein occlusion. She was on therapy that included carbamazepine and had started to take warfarin. However, the patient's prothrombin time expressed as the international normalized ratio (PT-INR) was 1·40 despite taking a dose three times higher than the average. The patient's S-warfarin concentration was 0·15 µg/mL and R-warfarin was 0·52 µg/mL. Her cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex, subunit 1 (VKORC1), genotypes were *1/*1 and -1639GA, respectively. The VKORC1 genotype indicated that she would require an even higher dose. We proposed a further increase in dose and the patient's PT-INR rose to 1·99. WHAT IS NEW AND CONCLUSION: The patient required a high warfarin dose because of the VKORC1 genotype, and induction of CYP2C9 by carbamazepine. We improved the patient's pharmacotherapy based on her genetic information.

Asunto(s)

Anticoagulantes/administración & dosificación , Anticoagulantes/farmacocinética , Carbamazepina/farmacología , Inductores del Citocromo P-450 CYP2C9/farmacología , Warfarina/administración & dosificación , Warfarina/farmacocinética , Anciano , Antagonismo de Drogas , Femenino , Genotipo , Humanos , Relación Normalizada Internacional , Farmacogenética , Vitamina K Epóxido Reductasas/genética

RESUMEN

Higher morning blood pressure (BP) surge is a risk factor for cardiovascular disease independent of 24-h mean BP. Although low outdoor temperatures are associated with higher morning BP surges (MBPSs), the influence of indoor temperature and ambient temperatures (temperature while indoors or temperature while outdoors) on MBPS remains unclear. Such information may help prevent excess winter mortality. We simultaneously measured indoor temperatures (living room and bedroom), ambulatory BP and physical activity using wrist actigraphy for 768 person-days during winter and spring/fall in 192 participants (mean age, 69.9 years). Although the indoor and outdoor temperatures showed a strong correlation during periods of moderate temperature (range: 9.8 to 27.7 °C, rp=0.84), the correlation decreased during periods of lower outdoor temperatures (range: -3.37 to 9.73 °C, rp=0.28). In univariate and multivariate analyses, models with ambient temperatures showed the best goodness of fit (lowest Akaike's information criterion (AIC)) followed by models with indoor temperatures and those with outdoor temperatures (AIC: ambient

Asunto(s)

Hipertensión/etiología , Estaciones del Año , Temperatura , Anciano , Monitoreo Ambulatorio de la Presión Arterial , Estudios Transversales , Ejercicio Físico , Femenino , Humanos , Masculino , Persona de Mediana Edad

RESUMEN

OBJECTIVE: Familial amyloid polyneuropathy (FAP), which is a fatal disorder inherited in an autosomal dominant fashion, is characterized by systemic accumulation of polymerized transthyretin (TTR) in the peripheral nerves and systemic organs. Liver transplantation has become an accepted treatment of this disorder because it stops the major production of amyloidogenic TTR. However, improved survival of transplant patients compared with that of nontransplant patients has not been sufficiently demonstrated. This study investigated whether transplantation improved the long-term outcome of patients by comparing the survival of patients who had transplantations with that of patients who had not had transplantations. METHODS: Eighty consecutive patients with FAP Val30Met who visited Kumamoto University Hospital between January 1990 and December 2010 were studied. The transplant group consisted of 37 patients who had a partial hepatic graft via living donor transplantation in Japan or who underwent liver transplantation in Sweden, Australia, or the United States. The nontransplant group consisted of 43 patients with FAP. Survival was evaluated by using Kaplan-Meier analysis, and the difference in survival was examined via the log-rank test. RESULTS: The transplant group had prolonged survival (p < 0.001) compared with the nontransplant group. The estimated probability of survival at 10 years was 56.1% for the nontransplant group vs 100% for the transplant group. CONCLUSION: Liver transplantation should be considered as an effective treatment in clinical management of patients with FAP Val30Met. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that liver transplantation prolongs survival in patients with FAP Val30Met.

Asunto(s)

Neuropatías Amiloides Familiares/mortalidad , Neuropatías Amiloides Familiares/cirugía , Trasplante de Hígado/mortalidad , Adulto , Anciano , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Sobrevivientes , Resultado del Tratamiento

RESUMEN

WHAT IS KNOWN AND OBJECTIVE: Polymorphisms in the gene encoding CYP4F2 may partly explain the variability in warfarin maintenance dose by altering the metabolism of vitamin K. To determine the genetic factors that cause large inter-patient variability in warfarin efficacy, we investigated the relationship between serum warfarin concentration and CYP4F2 V433M (1347C>T, rs2108622) polymorphism in Japanese subjects. METHODS: Gene variations in VKORC1, CYP2C9 and CYP4F2 were analysed in 126 Japanese patients treated with warfarin. The daily dosage of warfarin, concentration of S- and R-warfarin in plasma, and prothrombin time international normalized ratio (PT-INR) was used as the pharmacokinetic and pharmacodynamic indices. RESULTS AND DISCUSSION: The maintenance dose of warfarin was larger in the CYP4F2 1347 CT genotype group (3·59±1·80 mg/day, P=0·027) than in the CYP4F2 CC genotype group (2·88±1·00 mg/day). CYP4F2 1347C>T polymorphism significantly affected serum R-warfarin concentration when the VKORC1-1639 genotypes are AG and GG. WHAT IS NEW AND CONCLUSION: Although a significant inter-patient difference in warfarin maintenance dose was observed between the CYP4F2 CC and CT genotypes, serum S-warfarin concentration was not significantly different between them. An effect of CYP4F2 V433M polymorphism on warfarin maintenance dose was observed but was relatively small when compared to the effects of CYP2C9 and VKOR polymorphism.

Asunto(s)

Anticoagulantes/administración & dosificación , Pueblo Asiatico/genética , Sistema Enzimático del Citocromo P-450/genética , Warfarina/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Anticoagulantes/farmacocinética , Anticoagulantes/farmacología , Hidrocarburo de Aril Hidroxilasas/genética , Citocromo P-450 CYP2C9 , Familia 4 del Citocromo P450 , Relación Dosis-Respuesta a Droga , Femenino , Variación Genética , Genotipo , Humanos , Relación Normalizada Internacional , Japón , Masculino , Persona de Mediana Edad , Oxigenasas de Función Mixta/genética , Polimorfismo Genético , Estereoisomerismo , Vitamina K Epóxido Reductasas , Warfarina/farmacocinética , Warfarina/farmacología , Adulto Joven

Asunto(s)

Envejecimiento , Prealbúmina/metabolismo , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Compuestos de Sulfhidrilo/metabolismo , Anciano , Anciano de 80 o más Años , Humanos , Prealbúmina/química , Propiedades de Superficie

Asunto(s)

Albúminas/farmacología , Amiloide/biosíntesis , Amiloidosis/metabolismo , Antioxidantes/farmacología , Prealbúmina/fisiología , Amiloidosis/fisiopatología , Animales , Humanos , Ratas

Asunto(s)

Neuropatías Amiloides Familiares/metabolismo , Amiloide/biosíntesis , Membrana Basal/metabolismo , Línea Celular , Humanos , Inmunohistoquímica

Asunto(s)

Amiloidosis/inmunología , Interleucina-1beta/inmunología , Animales , Secuencia de Bases , Cartilla de ADN , Ensayo de Inmunoadsorción Enzimática , Masculino , Ratones , Ratones Endogámicos C3H

Asunto(s)

Amiloide/biosíntesis , Amiloidosis/metabolismo , Ciclodextrinas/farmacología , Prealbúmina/biosíntesis , Humanos

Asunto(s)

Amiloidosis/patología , Enfermedades Musculoesqueléticas/patología , Prealbúmina/fisiología , Humanos , Inmunohistoquímica

Asunto(s)

Neuropatías Amiloides Familiares/fisiopatología , Hemodinámica , Anciano , Humanos , Masculino , Persona de Mediana Edad

Asunto(s)

Neuropatías Amiloides Familiares/genética , Homocigoto , Metionina/genética , Prealbúmina/genética , Valina/genética , Anciano , Femenino , Humanos , Prealbúmina/química

Asunto(s)

Amiloide/metabolismo , Miocardio/metabolismo , Prealbúmina/metabolismo , Anciano , Anciano de 80 o más Años , Amiloidosis/metabolismo , Humanos , Inmunohistoquímica , Japón

Asunto(s)

Neuropatías Amiloides Familiares/cirugía , Análisis de Supervivencia , Adulto , Neuropatías Amiloides Familiares/mortalidad , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad

Asunto(s)

Neuropatías Amiloides Familiares/cirugía , Amiloide/metabolismo , Trasplante de Hígado , Neuropatías Amiloides Familiares/genética , Neuropatías Amiloides Familiares/metabolismo , Humanos , Prealbúmina/genética