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With population growth and aging, the number of people with dementia and related disorders will grow substantially in the years ahead, bringing with it significant societal, health-care, and economic challenges. Here, we analyze dementia policies of seven major countries in Asia/Pacific, Europe, and North America to identify opportunities for early actions to mitigate disease burden. We find that most countries are addressing this need by including a specific focus on early action in their national dementia strategies (five of seven countries), implementing public health initiatives for risk reduction, prevention, and early detection and diagnosis (six of seven countries); supporting enabling research for early detection and risk reduction (six of seven countries); and enacting a system for early, regular brain health screening (one of seven). We discuss risks and opportunities for integrating early action policies and conducting additional systematic research to understand the potential benefits and impacts of these policies.
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Atención a la Salud , Demencia , Humanos , Costo de Enfermedad , Salud Pública , Políticas , Demencia/diagnóstico , Demencia/epidemiología , Demencia/prevención & controlRESUMEN
Background: Dialysis guidelines in Japan recommend more frequent measurement of mineral metabolism markers than the Kidney Disease: Improving Global Outcomes guidelines. However, the extent to which frequent marker measurement contributes to achievement of target ranges and to therapy adjustment is unknown. Methods: This multicenter cohort study involved 3276 hemodialysis patients with secondary hyperparathyroidism. Data on laboratory measurements and drug prescriptions were collected every 3 months. Main exposures were frequencies of measuring serum calcium and phosphorus [weekly/biweekly/monthly (reference)] and serum parathyroid hormone (PTH) [monthly/bimonthly/trimonthly (reference)] levels. Outcomes were achievement of guideline-specified ranges of mineral metabolism markers when serum levels were over, and maintenance of ranges when levels were already within, respective specified ranges, use of intravenous vitamin D receptor activator (VDRA) and initiation of cinacalcet use. Associations were examined via generalized estimating equations. Results: When serum marker levels exceeded the target range, weekly measurement of calcium and phosphorus was positively associated with achievement of the guideline-specified calcium range [adjusted odds ratio (AOR): 1.57, 95% confidence interval (CI) 1.09-2.26] but not phosphorus range (AOR: 0.99, 95% CI 0.74-1.33). Monthly measurement of PTH was positively associated with achievement of the guideline-specified PTH range (AOR: 1.14, 95% CI 1.01-1.27). When serum marker levels were within the guideline-specified range, increased frequency of measurements was not associated with in-range maintenance of marker levels for any of the three mineral markers assessed. Regarding treatment regimen, relatively frequent measurement of serum calcium and phosphorus was positively associated with cinacalcet initiation and relatively frequent measurement of serum PTH with cinacalcet initiation and intravenous VDRA use. Conclusions: Our results suggest that increasing frequency of measurements is helpful when serum marker levels exceed the target range, partially via adjustment in the therapeutic regimen. We found no evidence that frequent measurements are helpful when mineral levels are already within target ranges.
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Calcimiméticos/uso terapéutico , Cinacalcet/uso terapéutico , Hiperparatiroidismo Secundario/tratamiento farmacológico , Fallo Renal Crónico/terapia , Vitaminas/uso terapéutico , Anciano , Biomarcadores/sangre , Calcitriol/análogos & derivados , Calcitriol/uso terapéutico , Calcio/sangre , Estudios de Cohortes , Femenino , Humanos , Hiperparatiroidismo Secundario/sangre , Hiperparatiroidismo Secundario/etiología , Japón , Fallo Renal Crónico/sangre , Fallo Renal Crónico/complicaciones , Masculino , Persona de Mediana Edad , Minerales , Hormona Paratiroidea/sangre , Planificación de Atención al Paciente , Fósforo/sangre , Diálisis RenalRESUMEN
BACKGROUND: In elderly hemodialysis (HD) patients, the risk of medication-related problems is particularly high. Thus, certain medications should generally not be prescribed to those patients. The Beers criteria for potentially inappropriate medications (PIMs) have been publicized. Still, with regard to elderly HD patients, the prevalence and risk factors for prescription of PIMs are unknown. METHODS: This was a cross-sectional study of data from the Japan Dialysis Outcomes and Practice Patterns Study (2002-08). Patients were included if they were 65 years old or older and were currently receiving HD treatment at a hospital or clinic. We counted the number of patients who were prescribed at least one PIM, as defined by the modified Beers criteria. We used multiple logistic regression analysis to determine which patient characteristics and facility characteristics were associated with prescription of PIMs. RESULTS: Data from 1367 elderly patients were analyzed. More than half of the patients (57%) had been prescribed a PIM. The three most frequently prescribed PIMs were H2 blockers (33%), antiplatelet agents (19%) and α-blockers (13%). PIM prescriptions were less likely at facilities that conducted multidisciplinary rounds {adjusted odds ratio (AOR): 0.67 [95% confidence interval (CI): 0.48-0.93]} and at teaching hospitals [AOR: 0.59 (95% CI, 0.39-0.90)]. PIM prescriptions are more likely if more than one physician has clearance to alter the HD regimen [AOR: 1.65 (95% CI, 1.12-2.44)]. CONCLUSIONS: PIMs were prescribed to many elderly HD patients in Japan. Nephrologists should become more aware of PIMs. Multidisciplinary rounds could benefit patients by reducing the prescription of PIMs.
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Quimioterapia/normas , Utilización de Medicamentos/estadística & datos numéricos , Hospitales de Enseñanza/organización & administración , Prescripción Inadecuada/estadística & datos numéricos , Lista de Medicamentos Potencialmente Inapropiados , Pautas de la Práctica en Medicina , Diálisis Renal , Anciano , Anciano de 80 o más Años , Instituciones de Atención Ambulatoria , Ensayos Clínicos Fase II como Asunto , Ensayos Clínicos Fase III como Asunto , Estudios Transversales , Femenino , Geriatría , Hospitalización , Humanos , Japón , Masculino , Prevalencia , Factores de RiesgoRESUMEN
BACKGROUND: Vascular access (VA) guidelines recommend the native arteriovenous fistula (AVF) as VA of first choice for chronic hemodialysis patients. AVF management is important in hemodialysis patient care. AVF survival is associated with various physical factors, but the effects of dialysis treatment factors upon AVF survival are still not clear. METHODS: Study patients were treated at 498 dialysis facilities participating in the Dialysis Outcomes and Practice Patterns Study (DOPPS) 2 or 3 (2002-2007). Analyses included 1,183 incident hemodialysis patients (on dialysis ≤7 days and using an AVF at study entry) and 949 prevalent patients (on dialysis >7 days at DOPPS entry and using a new AVF created during study observation). AVF survival was modeled from the study entry date for incident patients and date of first AVF use for prevalent patients. Predictors of primary and final AVF survival were compared across Japan, North America and Europe/Australia/New Zealand (EUR/ANZ) with adjustments for patient characteristics. RESULTS: No meaningful relationship was seen between AVF survival and various physician and staff practices. However, patients with prior catheter use displayed higher rates of primary and final AVF failure. Final AVF failure rates were higher in facilities with higher median blood flow rates (BFR). They were also greater in North America and EUR/ANZ than in Japan, but this difference was substantially attenuated after accounting for regional differences in facility median BFR. CONCLUSION: AVF longevity differed according to the DOPPS region, and was related to prior patient catheter use and facility BFR practice. Further longitudinal studies may help demonstrate meaningful associations between VA-handling skill and patency.
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Derivación Arteriovenosa Quirúrgica/mortalidad , Derivación Arteriovenosa Quirúrgica/estadística & datos numéricos , Pautas de la Práctica en Medicina , Diálisis Renal/mortalidad , Diálisis Renal/estadística & datos numéricos , Insuficiencia Renal Crónica/mortalidad , Insuficiencia Renal Crónica/terapia , Femenino , Humanos , Incidencia , Internacionalidad , Masculino , Persona de Mediana Edad , Factores de Riesgo , Análisis de Supervivencia , Tasa de Supervivencia , Resultado del Tratamiento , Dispositivos de Acceso VascularRESUMEN
Adult neurogenesis in the subgranular zone of the hippocampus (SGZ) is enhanced by excess as well as mild neuronal excitation, such as chemoconvulsant-induced brief seizures. Because most studies of neurogenesis after seizures have focused on the SGZ, the threshold of neuronal excitation required to enhance neurogenesis in the subventricular zone (SVZ) is not clear. Therefore, we examined the responses of SVZ precursors to brief generalized clonic seizures induced by a single administration of the chemoconvulsant pentylenetetrazole (PTZ). Cell cycle progression of precursors was analysed by systemic administration of thymidine analogues. We found that brief seizures immediately resulted in cell cycle retardation in the SVZ. However, the same effect was not seen in the SGZ. This initial cell cycle retardation in the SVZ was followed by enhanced cell cycle re-entry after the first round of mitosis, leading to precursor pool expansion, but the cell cycle retardation and expansion of the precursor pool were transient. Cell cycle progression in the PTZ-treated group returned to normal after one cell cycle. The numbers of precursors in the SVZ and new neurons in the olfactory bulb, which are descendants of SVZ precursors, were not significantly different from those in control mice more than 2 days after seizures. Because similar effects were observed following electroconvulsive seizures, these responses are likely to be general effects of brief seizures. These results suggest that neurogenesis in the SVZ is more tightly regulated and requires stronger stimuli to be modified than that in the SGZ.
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Ciclo Celular/efectos de los fármacos , Hipocampo/citología , Células-Madre Neurales/citología , Animales , Movimiento Celular/efectos de los fármacos , Convulsivantes , Masculino , Ratones , Ratones Endogámicos ICR , Mitosis/efectos de los fármacos , Células-Madre Neurales/efectos de los fármacos , Neurogénesis/efectos de los fármacos , Neuronas/citología , Bulbo Olfatorio/citología , Bulbo Olfatorio/metabolismo , Pentilenotetrazol , Convulsiones/inducido químicamenteRESUMEN
Over the past 50 years, Japan has successfully developed and maintained an increasingly equitable system of universal health coverage in addition to achieving the world's highest life expectancy and one of the lowest infant mortality rates. Against this backdrop, Japan is potentially in a position to become a leading advocate for and supporter of global health. Nevertheless, Japan's engagement with global health has not been outstanding relative to its substantial potential, in part because of government fragmentation, a weak civil society, and lack of transparency and assessment. Japan's development assistance for health, from both governmental and non-governmental sectors, has remained low and Japanese global health leadership has been weak. New challenges arising from changes in governance and global and domestic health needs, including the recent Great East Japan Earthquake, now provide Japan with an opportunity to review past approaches to health policy and develop a new strategy for addressing global and national health. The fragmented functioning of the government with regards to global health policy needs to be reconfigured and should be accompanied by further financial commitment to global health priorities, innovative non-governmental sector initiatives, increased research capacity, and investments in good leadership development as witnessed at the G8 Hokkaido Toyako Summit. Should this strategy development and commitment be achieved, Japan has the potential to make substantial contributions to the health of the world as many countries move toward universal coverage and as Japan itself faces the challenge of maintaining its own health system.
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Programas Nacionales de Salud , Dinámica Poblacional , Cobertura Universal del Seguro de Salud , HumanosRESUMEN
We previously demonstrated that anemia was not associated with mortality in hemodialysis patients with cardiovascular disease (CVD). Since diabetes mellitus (DM) accelerates CVD, the influence of DM on the relationship between anemia and mortality was examined using the data obtained from 1,385 DM patients and 2,583 non-DM hemodialysis patients recruited into the Dialysis Outcomes Practice Pattern Study in Japan (J-DOPPS). When all patients were stratified into four groups on their hematocrit levels, mortality rate was significantly and steadily lower in the subgroups with the higher levels of hematocrit by the Kaplan-Meier method (p = 0.0003 by log-rank test). When DM and non-DM patients were analyzed separately, a significant association of lower hematocrit levels with higher mortality disappeared in DM patients (p = 0.6280), in contrast with its retention in non-DM counterparts (p < 0.0001). Multivariable-adjusted Cox proportional hazards models demonstrated a significant association between hematocrit with all-cause mortality in non-DM patients after adjustment for age, gender, BMI, hemodialysis duration, SBP, DBP, albumin, total cholesterol, calcium, phosphorus, and intact PTH (p = 0.046), whereas this association disappeared in DM patients in the same model (p = 0.583). In conclusion, these results suggested that the association between anemia and higher mortality disappeared in DM hemodialysis patients, in contrast with non-DM counterparts.
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Anemia/mortalidad , Anemia/rehabilitación , Diabetes Mellitus/mortalidad , Diabetes Mellitus/rehabilitación , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/rehabilitación , Diálisis Renal/mortalidad , Comorbilidad , Femenino , Humanos , Japón/epidemiología , Masculino , Pautas de la Práctica en Medicina , Prevalencia , Medición de Riesgo , Estadística como Asunto , Análisis de Supervivencia , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND/AIMS: Resistance to erythropoiesis-stimulating agent (ESA) is associated with mortality in hemodialysis (HD) patients. Time-dependent variability of ESA resistance has been not investigated adequately, although consistently high ESA resistance is expected to be a high risk for mortality. Our aim, therefore, was to investigate consistently high ESA resistance as an independent predictor of mortality in HD patients. METHODS: This study evaluated 2,104 Japanese HD patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS) III. ESA resistance index (ERI) was defined as the weekly weight-adjusted dose of ESA divided by hemoglobin concentration. The average ERI was calculated from ERI levels every 4 months throughout the observation period for each patient. To assess the size of the fluctuation in average ERI during the observation periods according to ERI quartiles at the enrollment periods, six patient groups were defined on the basis of patterns of ERI level fluctuation: low-low (Low), intermediate-intermediate (Intermediate), high-high (High), low-intermediate, intermediate-high, and low-high. RESULTS: The number of deaths among the patients was 227 (10.8%), which included 113 (5.4%) cases of cardiovascular disease (CVD). In multivariate analysis after adjustment for age, albumin, C-reactive protein, comorbidities, etc., the High group was independently and significantly related to all-cause and CVD-related mortality (OR = 2.33, 95% CI: 1.33-4.07, p = 0.002, and OR = 2.09, 95% CI: 1.05-4.14, p = 0.035, respectively). CONCLUSION: Factoring out fluctuating ERI increases the ability of consistently high ERI levels as an independent risk factor for all-cause and CVD mortality in HD patients.
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Enfermedades Cardiovasculares/mortalidad , Hematínicos/uso terapéutico , Diálisis Renal/mortalidad , Resistencia a Medicamentos , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Factores de Riesgo , Factores de TiempoRESUMEN
Importance: Real-world evidence of SARS-CoV-2 transmission is needed to understand the prevalence of infection in the Japanese population. Objective: To conduct sentinel screening of the Japanese population to determine the prevalence of SARS-CoV-2 infection in asymptomatic individuals, with complementary analysis for symptomatic patients as reported by active epidemiologic surveillance used by the government. Design, Setting, and Participants: This cross-sectional study of a sentinel screening program investigated approximately 1 million asymptomatic individuals with polymerase chain reaction (PCR) testing for SARS-CoV-2 infection between February 22 and December 8, 2021. Participants included children, students, employed adults, and older individuals, as well as volunteers to broadly reflect the general Japanese population in the 14 prefectures of Japan that declared a state of emergency. Saliva samples and a cycle threshold (Ct) value of approximately 40 as standard in Japan were used. Polymerase chain reaction testing for symptomatic patients was separately done by public health authorities, and the results were obtained from the Ministry of Health, Labour, and Welfare of Japan to complement data on asymptomatic infections from the present study. Main Outcomes and Measures: Temporal trends in positivity and prevalence (including surges of different variants) and demographic associations (eg, age, geographic location, and vaccination status) were assessed. Results: The positive rate of SARS-CoV-2 infection in 1â¯082â¯976 asymptomatic individuals (52.08% males; mean [SD] age 39.4 [15.7] years) was 0.03% (95% CI, 0.02%-0.05%) during periods without surges and a maximum of 0.33% (95% CI, 0.25%-0.43%) during peak surges at the Japanese standard Ct value of approximately 40; however, the positive rate would have been 10-fold less at a Ct value of 25 as used elsewhere in the world (eg, UK). There was an increase in patients with a positive PCR test result with a Ct value of 25 or 30 preceding surges in infection and hotspots of asymptomatic infections. Conclusions and Relevance: In this cross-sectional study of asymptomatic SARS-CoV-2 infection in the general population of Japan in 2021, as investigated by sentinel surveillance, a low rate of infection was seen in the Japanese population compared with reported levels elsewhere in the world. This finding provides real-world data on the state of infection in Japan.
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COVID-19 , Masculino , Adulto , Niño , Humanos , Femenino , COVID-19/diagnóstico , COVID-19/epidemiología , SARS-CoV-2 , Infecciones Asintomáticas/epidemiología , Prevalencia , Japón/epidemiología , Estudios TransversalesRESUMEN
In April 2006, Japan's health insurance system instituted a bundling policy that included recombinant human erythropoietin (rHuEPO) in outpatient hemodialysis therapy. To evaluate outcomes of this, we analyzed a prospective cohort of hemodialysis patients in the Japan Dialysis Outcomes and Practice Patterns Study, in 53 facilities using prevalent cross-sections of 1584 patients before and 1622 patients after the rHuEPO reimbursement change. Patient data included hemoglobin levels, iron management profiles, and anemia treatment with rHuEPO and intravenous iron. No significant differences were found in pre- or post-policy cross-sections for hemoglobin distributions or the percentage of patients prescribed rHuEPO. Among patients receiving rHuEPO, the mean dose significantly decreased by 11.8 percent. The percentage of patients prescribed intravenous iron over 4 months significantly increased; however, the mean dose of iron did not significantly change. Thus, this bundling policy was associated with reduced rHuEPO doses, increased intravenous iron use, and stable hemoglobin levels in Japanese patients receiving hemodialysis.
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Anemia/tratamiento farmacológico , Eritropoyetina/administración & dosificación , Política de Salud , Hematínicos/administración & dosificación , Hemoglobinas/metabolismo , Fallo Renal Crónico/terapia , Programas Nacionales de Salud/legislación & jurisprudencia , Evaluación de Procesos y Resultados en Atención de Salud , Pautas de la Práctica en Medicina/legislación & jurisprudencia , Diálisis Renal , Anciano , Atención Ambulatoria/legislación & jurisprudencia , Anemia/sangre , Biomarcadores/sangre , Costos de los Medicamentos , Utilización de Medicamentos/legislación & jurisprudencia , Eritropoyetina/economía , Femenino , Gastos en Salud/legislación & jurisprudencia , Política de Salud/economía , Hematínicos/economía , Humanos , Reembolso de Seguro de Salud/legislación & jurisprudencia , Hierro/administración & dosificación , Japón , Fallo Renal Crónico/sangre , Fallo Renal Crónico/economía , Masculino , Persona de Mediana Edad , Programas Nacionales de Salud/economía , Evaluación de Procesos y Resultados en Atención de Salud/economía , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina/economía , Estudios Prospectivos , Proteínas Recombinantes , Diálisis Renal/economía , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND/AIMS: The Mineral and Bone Disorder Outcomes Study for Japanese CKD Stage 5D Patients (MBD-5D) is a multicenter, prospective observational study of hemodialysis patients with secondary hyperparathyroidism (SHPT) in Japan, where the national guideline recommends targets for serum calcium (8.4-10.0 mg/dl), phosphorus (3.5-6.0 mg/dl), and intact parathyroid hormone (PTH) (60-180 pg/ml). METHODS: The MBD-5D involved patients who were receiving hemodialysis for more than 3 months and met at least one of the following conditions: having intact PTH levels >180 pg/ml, or receiving intravenous vitamin D receptor activators (VDRAs) or oral VDRA analog. This report describes the baseline characteristics of the study participants and examines factors associated with mineral metabolism controllability. RESULTS: A total of 8,229 patients were registered from 86 facilities as the whole cohort, and 3,276 patients were randomly selected as the subcohort. The severity of SHPT was associated with a lower likelihood of achieving the targets for calcium and phosphorus, whereas patients with a history of parathyroidectomy were more likely to achieve these targets as compared with those who had not undergone surgery despite high PTH levels. The use of 2.5 mEq/l calcium dialysate was also associated with a higher likelihood of achieving the targets compared with the use of 3.0 mEq/l calcium dialysate. CONCLUSION: The severity of SHPT and the use of dialysate with higher calcium concentration are associated with practical difficulty in managing mineral metabolism in dialysis patients. Further prospective follow-up is needed to confirm our findings and to examine their impact on patient-level outcomes.
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Hiperparatiroidismo Secundario/epidemiología , Hiperparatiroidismo Secundario/terapia , Diálisis Renal/métodos , Calcio/química , Estudios de Cohortes , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Minerales/metabolismo , Oportunidad Relativa , Hormona Paratiroidea/sangre , Hormona Paratiroidea/metabolismo , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: We examined associations of C-reactive protein (CRP) levels with mortality in Japanese hemodialysis patients and trends in prevalence of CRP measurement at hemodialysis facilities internationally. To assess whether measurement of CRP may influence outcomes, we examined associations of facility prevalence of CRP measurement with mortality. METHODS: CRP measurements were from a cross-section of patients in the international Dialysis Outcomes and Practice Patterns Study (n = 610 facilities, 16,355 patients). Cox proportional hazards models assessed associations of mortality with CRP in Japan, and with a facility's frequency of measuring CRP internationally, (except in the USA and Canada). RESULTS: From 2002-2004, CRP was measured in 0-19% of patients in each country, except Japan (55%). From 2005-2007, CRP was measured in ≥ 50% of country patients except in Canada (15%) and the USA (2%). After multivariable adjustment, the hazard ratio (HR) of death was 1.6- to 2.4-fold higher (p < 0.05) for various categories of CRP levels >3 mg/l (vs. <1.0 mg/l). Cardiovascular mortality risk was lower in facilities measuring CRP for ≥ 50% of patients (HR = 0.72, p = 0.01) in multivariable-adjusted analyses. CONCLUSIONS: CRP is informative regarding mortality risk beyond that provided by other inflammatory and nutritional markers, with significantly higher risk seen at CRP >3 mg/l. Greater use of CRP may lead to improved patient care as suggested by the association of greater CRP measurement with lower cardiovascular mortality.
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Proteína C-Reactiva/análisis , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/mortalidad , Fallo Renal Crónico/sangre , Fallo Renal Crónico/mortalidad , Diálisis Renal/mortalidad , Diálisis Renal/estadística & datos numéricos , Biomarcadores/sangre , Enfermedades Cardiovasculares/diagnóstico , Comorbilidad , Femenino , Humanos , Incidencia , Internacionalidad , Fallo Renal Crónico/diagnóstico , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Medición de Riesgo , Factores de Riesgo , Sensibilidad y Especificidad , Análisis de Supervivencia , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Immediately after the Great East Japan Earthquake on March 11, 2011, the public could not receive accurate information concerning about the reality of the accident at the Fukushima Nuclear Power Plant because of communication problems with mobile phone base stations caused by power outages and the inadequate use of communication satellites between local governments. These telecommunications troubles caused not only a delay between the Japanese central government to local governments, but also a failure in conveying the seriousness of the accident to residents. The central government issued evacuation orders, but in some areas, a delay was seen in the time residents took to notice the orders. Some residents were forced to change their evacuation site several times and move to areas with higher radiation exposure. Although iodine preparations needed to be distributed to saturate the thyroid gland and reduce the uptake of iodine-131, a radioactive isotope, many municipalities were unable to secure them. Preparations were distributed on March 15, 2011 when the detectable amount of radioactive isotopes peaked, but only the Naraha and Miharu towns received them. At the time of the Fukushima Nuclear Power Plant accident, communication lines had already been interrupted by the major earthquake that struck on March 11, and information systems between local governments were not communicating well. With such a social infrastructure, residential evacuation orders were inadequate, and the delivery of medication was extremely difficult. The experience of the Fukushima Nuclear Power Plant accident suggests that the government should have distributed iodine preparations to residents living within a 30-km radius of the plant in advance, so that they could learn about the background and side effects of the drug beforehand. This distribution strategy is similar to that of targeted antivirus prophylaxis (TAP), which is an extralegal policy carried out in situations where face-to-face medical treatment is impossible because of an outbreak during a pandemic.
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Terremotos , Accidente Nuclear de Fukushima , Yodo , Preparaciones Farmacéuticas , Humanos , Japón , Plantas de Energía NuclearRESUMEN
We welcome their additional suggestion that the government should publish potential causes for and implications of the additional outbreak beyond the quarantine to the international scientific community so that similar outbreaks may be swiftly prevented. However, given the absence of government-driven publications, we published this report based on our independent investigation, which may be more reliable considering the inherently sensitive and political nature of the events.
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Política Pública , Investigación/historia , Investigación/tendencias , Emigrantes e Inmigrantes , Financiación Gubernamental/historia , Personal Profesional Extranjero , Historia del Siglo XX , Historia del Siglo XXI , Cooperación Internacional , Japón , Investigación/economía , Recursos HumanosRESUMEN
BACKGROUND: The carbonaceous oral adsorbent AST-120 slows the deterioration of kidney function in patients with advanced chronic kidney disease (CKD). However, information about AST-120 in patients with less severe stages of CKD is lacking. STUDY DESIGN: Randomized controlled trial. SETTING & PARTICIPANTS: 75 medical facilities, 460 patients with CKD with serum creatinine (sCr) concentrations less than 5.0 mg/dL (not undergoing dialysis). INTERVENTION: Random assignment to either a low-protein diet and antihypertensive medication in the control group or that treatment combined with AST-120 (6 g/d). OUTCOMES & MEASUREMENTS: Composite primary end point: doubling of sCr level, increase in sCr level to 6.0 mg/dL or more, need for dialysis or transplantation, or death. SECONDARY OUTCOMES: adverse events and changes in estimated creatinine clearance (CCr) rate, proteinuria (protein in milligrams per day), and quality of life. RESULTS: Mean sCr level was 2.66 mg/dL and estimated CCr was 22.4 mL/min in both groups. During 56 weeks, numbers of primary end-point events (43 for control versus 42 for AST-120) and event-free survival (P = 0.9) did not differ between groups. Gastrointestinal adverse events were less common in the control group than the AST-120 group (2 versus 32 events). Estimated CCr decreased more in the control group than in the AST-120 group (-15% per year versus -12% per year, relative to the baseline value; [corrected] P = 0.001). Median proteinuria changed from protein of 1,162 to 1,167 mg/d in the control group versus 1,102 to 906 mg/d in the AST-120 group (P = 0.2). LIMITATION: Infrequent primary end-point events. CONCLUSION: AST-120 did not substantially slow the progression of kidney disease in patients with moderate to severe CKD during 1 year.
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Carbono/administración & dosificación , Progresión de la Enfermedad , Fallo Renal Crónico/sangre , Fallo Renal Crónico/tratamiento farmacológico , Óxidos/administración & dosificación , Administración Oral , Adsorción , Anciano , Carbono/farmacocinética , Creatinina/sangre , Determinación de Punto Final/tendencias , Femenino , Estudios de Seguimiento , Humanos , Fallo Renal Crónico/patología , Masculino , Persona de Mediana Edad , Óxidos/farmacocinéticaRESUMEN
OBJECTIVE: Serine protease inhibitors (serpin) play a central role in various pathological processes including coagulation, fibrinolysis, malignancy, and inflammation. Inhibition of serpins may prove therapeutic. As yet, however, only very few small molecule serpin inhibitors have been reported. For the first time, we apply a new approach of virtual screening to discover novel, orally active, small molecule serpin inhibitors and report their effectiveness. METHODS AND RESULTS: We focused on a clinically important serpin, plasminogen activator inhibitor-1 (PAI-1), whose crystal structure has been described. We identify novel, orally active molecules able to enter into the strand 4 position (s4A) of the A beta-sheet of PAI-I as a mock compound. In vitro they specifically inhibit the PAI-1 activity and enhance fibrinolysis activity. In vivo the most effective molecule (TM5007) inhibits coagulation in 2 models: a rat arteriovenous (AV) shunt model and a mouse model of ferric chloride-induced testicular artery thrombosis. It also prevents the fibrotic process initiated by bleomycin in mouse lung. CONCLUSIONS: The present study demonstrates beneficial in vitro and in vivo effects of novel PAI-1 inhibitors. Our methodology proves to be a useful tool to obtain effective inhibitors of serpin activity.
Asunto(s)
Anticoagulantes/farmacología , Inhibidor 1 de Activador Plasminogénico/fisiología , Serpinas/efectos de los fármacos , Animales , Anticoagulantes/química , Derivación Arteriovenosa Quirúrgica , Sitios de Unión , Bleomicina/toxicidad , Coagulación Sanguínea/efectos de los fármacos , Cloruros , Simulación por Computador , Evaluación Preclínica de Medicamentos/métodos , Compuestos Férricos/toxicidad , Masculino , Ratones , Ratones Endogámicos C57BL , Modelos Moleculares , Inhibidor 1 de Activador Plasminogénico/química , Conformación Proteica , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/patología , Fibrosis Pulmonar/prevención & control , Ratas , Serpina E2 , Serpinas/química , Serpinas/fisiología , Testículo/irrigación sanguínea , Trombosis/tratamiento farmacológico , Interfaz Usuario-ComputadorRESUMEN
BACKGROUND/AIMS: Given the clear benefits of mortality reduction observed for most beta-blockers in clinical trials, they are relatively underused in hemodialysis patients. Since the outcomes associated with the use of beta-blockers are not fully known, we investigated their effect on mortality among a cohort of hemodialysis patients. METHODS: Data were analyzed from the Dialysis Outcomes and Practice Patterns Study phase II for 2,286 randomly selected patients on hemodialysis in Japan. Treatment with beta-blockers was the major predictor variable. The main outcome measure was all-cause mortality. Cox regression analysis was used to assess an association between treatment with beta-blockers and the risk of death. RESULTS: 247 patients (11.9%) were administered beta-blockers and 1,828 patients (88.1%) were not. Whereas patients treated with beta-blockers had a higher prevalence of hypertension and coronary heart disease, Kaplan-Meier analysis revealed that all-cause mortality rates were significantly (p < 0.007) decreased in patients treated with beta-blockers compared to those without. In multivariable, fully adjusted models, treatment with beta-blockers was also independently associated with reduced all-cause mortality (hazard ratio = 0.48; p = 0.02). CONCLUSION: This study indicated a possible association between the use of beta-blockers and reduced risk of mortality in hemodialysis patients. These results should be confirmed in further randomized controlled trials.
Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Prescripciones de Medicamentos , Pautas de la Práctica en Medicina , Diálisis Renal/mortalidad , Estudios de Cohortes , Femenino , Humanos , Internacionalidad , Japón/epidemiología , Masculino , Persona de Mediana Edad , Pautas de la Práctica en Medicina/tendencias , Estudios Prospectivos , Diálisis Renal/tendencias , Tasa de Supervivencia/tendencias , Resultado del TratamientoRESUMEN
BACKGROUND: Pre-dialysis early referral is associated with improved survival in patients on dialysis. Here, we examined the association between pre-dialysis early referral and post-dialysis Mental Health (MH) in hemodialysis patients. METHODS: We examined data from the Dialysis Outcomes and Practice Patterns Study (DOPPS), a prospective and observational study of hemodialysis patients, by performing a cross-sectional and longitudinal analysis of DOPPS data from Japan. The outcome measure was analyzed from the MH subscale of the Medical Outcomes Study Short Form-36 Item Health Survey. Predictors of mean MH were identified using analysis of covariance. The variables evaluated in the multivariate models included age, sex, duration of dialysis and diabetes. RESULTS: A total of 552 patients under hemodialysis participated in the study, with a late referral prevalence of 34.2% (189/552). The estimated mean MH score was 60.7 (95% confidence interval (CI) 57.5-63.8) and 65.6 (95% CI 63.2-68.1) in late and early referrals, respectively. A statistically significant difference in mean MH score of 4.9 was observed between late and early referral groups (p = 0.01). The mean MH score for late referral was significantly lower than that for early referral in the 6-12 and 12-18 month groups. CONCLUSIONS: Pre-dialysis early referral is a modifiable and important factor and is associated with improved MH of post-dialysis patients.
Asunto(s)
Salud Mental , Nefrología , Médicos , Pautas de la Práctica en Medicina , Derivación y Consulta , Diálisis Renal/psicología , Anciano , Estudios de Cohortes , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Internacionalidad , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Nefrología/métodos , Estudios Prospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Bodily pain and psychiatric distress are common symptoms in patients with dialysis. However, the temporal relationships have not yet been investigated. Objective. To evaluate the longitudinal association between depressive symptoms and subsequent risk of developing severe bodily pain in dialysis patients. Design. Prospective cohort study. METHODS: We assessed bodily pain using a self-reported questionnaire and depressive symptoms using scores from the short version of Center for Epidemiological Studies Depression Screening Index (CES-D) from 531 participants showing no/mild bodily pain at baseline, based on the Japan Dialysis Outcomes and Practice Patterns Study, a cohort study of hemodialysis patients. To evaluate the relationship between depressive symptoms and development of severe bodily pain, multivariable logistic regression analysis was performed. RESULTS: The 531 patients had a mean age of 57.9 years, 61.4% were male, and 33.1% had depressive symptoms. Logistic regression analysis revealed that depressive symptoms at baseline were significantly associated with higher odds of developing severe bodily pain during a 0.5- to 2.5-year follow-up period (adjusted odds ratio [AOR] = 2.13, 95% confidence interval [CI]: 1.36-3.33, P = 0.001). Further, patients with higher CES-D scores were likely to develop severe bodily pain (AOR = 1.09, 95% CI: 1.04-1.15, P = 0.001). CONCLUSIONS: Results of this study suggest that depressive symptoms measured by CES-D predict the future risk of developing severe bodily pain in dialysis patients.