Structure-toxicity relationships of saturated and unsaturated free fatty acids for elucidating the lipotoxic effects in human EndoC-ßH1 beta-cells.

Lipotoxicity has been considered a major cause for beta-cell dysfunction in type 2 diabetes mellitus. However, the underlying mechanisms are still unclear. To achieve a better understanding of the toxicity a wide range of structurally different free fatty acids (FFAs) has been analyzed in human EndoC-ßH1 beta-cells. Exposure of human EndoC-ßH1 beta-cells to physiological saturated and monounsaturated long-chain FFAs induced apoptosis. Particularly noteworthy was that the toxicity increased more rapidly with increasing chain length of saturated than of unsaturated FFAs. The highest toxicity was observed in the presence of very long-chain FFAs (C20-C22), whereas polyunsaturated FFAs were not toxic. Long-chain FFAs increased peroxisomal hydrogen peroxide generation slightly, while very long-chain FFAs increased hydrogen peroxide generation more potently in both peroxisomes and mitochondria. The greater toxicity of very long-chain FFAs was accompanied by hydroxyl radical formation, along with cardiolipin peroxidation and ATP depletion. Intriguingly, only saturated very long-chain FFAs activated ER stress. On the other hand saturated very long-chain FFAs did not induce lipid droplet formation in contrast to long-chain FFAs and unsaturated very long-chain FFAs. The present data highlight the importance of structure-activity relationship analyses for the understanding of the mechanisms of lipotoxicity. Chain length and degree of saturation of FFAs are crucial factors for the toxicity of FFAs, with peroxisomal, mitochondrial, and ER stress representing the major pathogenic factors for induction of lipotoxicity. The results might provide a guide for the composition of a healthy beta-cell protective diet.

The monounsaturated fatty acid oleate is the major physiological toxic free fatty acid for human beta cells.

Free fatty acids (FFAs) can cause glucose intolerance and diabetes. Lipotoxicity to the pancreatic beta cells is considered to be a major underlying cause for this phenomenon. The aim of this study was to analyse the toxicity profile of FFAs in the human EndoC-ßH1 beta-cell line and to compare the results with isolated rat and human islets with special reference to the physiologically most prevalent FFAs palmitic acid (PA) and oleic acid (OA). Toxicity after a 2-day incubation with the different FFAs was analysed by the caspase-3 assay and confirmed by the propidium iodide and annexin V staining tests. The long-chain saturated PA (C16:0) and the monounsaturated OA (C18:1) were both toxic to human EndoC-ßH1 beta cells and pseudoislets, as well as to rat islets, and, as confirmed in a pilot experiment, also to human islets. Furthermore, OA provided no protection against the toxicity of PA. Likewise, elaidic acid (EA, the trans isomer of OA; trans-OA) was significantly toxic, in contrast to the non-metabolisable analogues methylated PA (MePA) and methylated OA (MeOA). Fatty acids with a chain length < C16 were not toxic in EndoC-ßH1 beta cells. Caspase-3 was also activated by linoleic acid (LA)(C18:2) but not by γ-linolenic acid (γ-LNA)(C18:3). Overall, only long-chain FFAs with chain lengths > C14, which generate hydrogen peroxide in the peroxisomal beta-oxidation, were toxic. This conclusion is also supported by the toxicity of the branched-chain FFA pristanic acid, which is exclusively metabolised in the peroxisomal beta-oxidation. The lack of a protective effect of the monounsaturated fatty acid OA has important consequences for a beta-cell protective lipid composition of a diet. A cardioprotective diet with a high OA content does not fulfil this requirement.

[Specialized home care of medical diseases in an urban tertiary university hospital. Coordination between the medical services of the hospital and the primary health care]. / Atención especializada domiciliaria de patologías médicas desde un hospital universitario terciario urbano. Coordinación entre los servicios médicos del hospital y la Atención Primaria de salud del territorio.

INTRODUCTION: The experience of an urban Tertiary University Hospital in the design and implementation of Hospital at Home Program (HaHP) integrated in a Department of Internal Medicine and highly coordinated with Medical Services of the Hospital and the Primary Health Care, that contemplates the like main objectives of the promotion of specialized home care medical diseases and the improvement of the coordination with the primary health care. PATIENTS AND METHOD: Systematic collection in all the patients admitted between April 2006 and March 2007 in the HaHP of the following variables: age, gender, service of origin, main diagnosis, Barthel and Charlson index, number of visits per day to doctors and nurses, destination on discharge and medical team. The descriptive statistical analysis was made in April 2007. The results are presented globally and differentiated by teams (internal medicine, respiratory and nutritional support teams). RESULTS: 506 admissions in 390 patients with a mean age of 66.5 (18) years, 53% being women. The Charlson index was 2 (2.2) and the Barthel index 63.5 (40,4). Average stay was 7.9 (8.2) days. The main reasons for admission were the infections and domiciliary intravenous antibiotic therapy in 153 (30.5%) cases, followed by patients with chronic obstructive pulmonary disease or cardiac failure in 107 (21%) cases, and home enteral and parenteral nutrition in 102 (20%) cases. Two hundred (39.5) patients were subsequently controlled by their primary care team after discharger, 241 (47.5) patients were followed-up in the hospital consultations, and 45 (9%) of the patients had to return directly to the hospital. CONCLUSIONS: The creation of a HaHP, for medical diseases, in internal medicine department that is highly coordinated with medical services of the hospital, especially with emergency, respiratory, and nutritional support teams, and with the primary health care, facilitates specialized home care of medical diseases and improves coordination with the primary health care.

Safety and efficacy of home intravenous antimicrobial infusion therapy in older patients: a comparative study with younger patients.

BACKGROUND: Home intravenous antimicrobial infusion therapy has proved its safety and efficacy in a great number of infections. Despite this there are few published studies about this way of managing in the elderly patient. OBJECTIVE: To study the safety and efficacy of home intravenous antimicrobial infusion therapy in elderly patients. STUDY DESIGN: A prospective and comparative study of an elderly group of patients > or =70 years old vs. a cohort of younger adult patients as a control group. All patients were followed until 3 months after discharge. SETTING: Hospital at Home Programme (HHP) as part of the Internal Medicine Department at Valle de Hebrón Hospital, Barcelona, Spain. PATIENTS: All patients admitted to HHP diagnosed of infections requiring intravenous antibiotic therapy between March 2006 and March 2007. RESULTS: We included 145 patients, 90 of whom were 70 years or older. Diabetes mellitus, heart failure and respiratory tract infection were more frequent in these elderly patients. In this group 14 (12%) developed some type of adverse event during treatment, phlebitis being the most common. The majority of those in the elderly patients group were discharged because of satisfactory clinical evolution and only 7 (7%) were re-admitted to hospital. Another 13 (14%) were re-admitted to hospital 3 months after discharge from HHP, mostly for chronic diseases. There were no significant differences between these results and those obtained from the control group. CONCLUSION: Home intravenous antimicrobial infusion therapy in elderly patients is safe and effective.

Atención especializada domiciliaria de patologías médicas desde un hospital universitario terciario urbano. Coordinación entre los servicios médicos del hospital y la Atención Primaria de salud del territorio / Specialized home care of medical diseases in an urban tertiary university hospital. Coordination between the medical services of the hospital and the primary health care

Introducción. Se presenta la experiencia de un hospital universitario terciario urbano en el diseño e implementación de una unidad de hospitalización a domicilio (UHaD) integrada en un Servicio de Medicina Interna y altamente coordinada con los servicios médicos del hospital y la Atención Primaria de salud del entorno hospitalario, que contempla como principales objetivos la promoción de la atención especializada domiciliaria de patologías médicas y la mejora de la coordinación con la Atención Primaria de salud. Pacientes y métodos. Recogida sistemática en todos los pacientes ingresados entre abril 2006 y marzo 2007 en la UHaD de las siguientes variables: edad, sexo, lugar y servicio de procedencia, diagnóstico principal, índice de Barthel y de Charlson, número de visitas al día de enfermería y médicas, destino al alta y equipo médico responsable. El análisis estadístico descriptivo se realizó en abril de 2007. Los resultados se presentan de forma global y diferenciados por equipos (Medicina Interna, Neumología y soporte nutricional). Resultados. Quinientos seis ingresos que correspondían a 390 pacientes con una edad media de 66,5 (18) años, y un 53% mujeres. El índice de Charlson fue de 2 (2,2) y el índice de Barthel de 63,5 (40,4). La estancia media fue de 7,9 (8,2) días. Los principales motivos de ingreso fueron las infecciones y tratamiento antibiótico por vía intravenosa en 153 (30,5%) casos, las agudizaciones de enfermedad pulmonar obstructiva crónica o insuficiencia cardíaca en 107 (21%) casos y la nutrición enteral o parenteral domiciliaria en 102 (20%) casos. Doscientos (39,5%) pacientes al finalizar el ingreso fueron controlados por sus equipos de Atención Primaria, 241 (47,5%) fueron seguidos en consultas del hospital y 45 (9%) retornaron directamente al hospital. Conclusión. La creación de una UHaD para patologías médicas desde el Servicio de Medicina Interna, altamente coordinada con servicios médicos del hospital, especialmente con Urgencias, Neumología y Soporte Nutricional y con la Atención Primaria del entorno hospitalario, facilita la atención especializada domiciliaria de patologías médicas y mejora la coordinación con la Atención Primaria de salud

Introduction. The experience of an urban Tertiary University Hospital in the design and implementation of Hospital at Home Program (HaHP) integrated in a Department of Internal Medicine and highly coordinated with Medical Services of the Hospital and the Primary Health Care, that contemplates the like main objectives of the promotion of specialized home care medical diseases and the improvement of the coordination with the primary health care. Patients and method. Systematic collection in all the patients admitted between April 2006 and March 2007 in the HaHP of the following variables: age, gender, service of origin, main diagnosis, Barthel and Charlson index, number of visits per day to doctors and nurses, destination on discharge and medical team. The descriptive statistical analysis was made in April 2007. The results are presented globally and differentiated by teams (internal medicine, respiratory and nutritional support teams). Results. 506 admissions in 390 patients with a mean age of 66.5 (18) years, 53% being women. The Charlson index was 2 (2.2) and the Barthel index 63.5 (40,4). Average stay was 7.9 (8.2) days. The main reasons for admission were the infections and domiciliary intravenous antibiotic therapy in 153 (30.5%) cases, followed by patients with chronic obstructive pulmonary disease or cardiac failure in 107 (21%) cases, and home enteral and parenteral nutrition in 102 (20%) cases. Two hundred (39.5) patients were subsequently controlled by their primary care team after discharger, 241 (47.5) patients were followed-up in the hospital consultations, and 45 (9%) of the patients had to return directly to the hospital. Conclusions. The creation of a HaHP, for medical diseases, in internal medicine department that is highly coordinated with medical services of the hospital, especially with emergency, respiratory, and nutritional support teams, and with the primary health care, facilitates specialized home care of medical diseases and improves coordination with the primary health care

[Fast specialized ambulatory care of medical disease in an urban tertiary university hospital. Fast care consultation]. / Atención especializada ambulatoria rápidade patologías médicas desde un hospital universitario terciario. Consulta de atención inmediata.

INTRODUCTION: The experience of an urban tertiary university hospital in the design and establishment of Specialized Ambulatory Consultation (SAC) of Internal Medicine is presented. The purpose of this consultation is fast specialized ambulatory care of medical diseases, decrease of inappropriate hospitalizations and improvement of coordination with primary health care. PATIENTS AND METHOD: Systematic collection of the following variables in all the patients who visited the SAC between March 2006 and February 2007: origin, syndromic diagnosis and reason for consultation, age and gender, number of visits, examinations made, and destination on discharge. The descriptive statistical analysis was made in March 2007. RESULTS: A total of 744 patients with 1248 visits were seen (successive/first ratio of 0.67). Mean age was 62.56 (18.6) years and 50.6% were women. The hospital origin/primary origin went from 3.5 - 4 in the first quarter to between 2.6 - 2.8 in the last quarter. The main reasons for consultation due to patient with constitutional or anemic syndromes with suspicion of serious disease and patients with decompensation of chronic diseases or infectious disease. Half of the patients returned to primary care and the rest were distributed among different hospital resources. It stands out that 30% were sent to the hospital consultations and 10% required hospitalization or transfer to the emergency room. CONCLUSIONS: The SAC is a Fast Consultation Care (diagnosis and treatment) of general internal medicine located in a tertiary university hospital with a good capacity of resolution. It facilitates Specialized Ambulatory Care of medical diseases, decreasing inappropriate hospitalization and improving coordination with the Primary Health Care.

Atención especializada ambulatoria rápidade patologías médicas desde un hospital universitario terciario. Consulta de atención inmediata / Fast specialized ambulatory care of medical disease in an urban tertiary university hospital. Fast care consultation

Introducción. Se presenta la experiencia de un hospital universitario terciario urbano en el diseño e implementación de una consulta de atención inmediata (CAI) de medicina interna que tiene como objetivo la atención especializada ambulatoria rápida de patologías médicas, la disminución de ingresos inadecuados y la mejora de la coordinación con la Atención Primaria de salud. Material y métodos. Recogida sistemática en todos los pacientes visitados en la CAI entre marzo de 2006 y febrero de 2007 de las siguientes variables: procedencia, orientación sindrómica y motivo de consulta, edad y sexo, número de visitas, exploraciones realizadas y destino al alta. El análisis estadístico descriptivo se realizó en marzo de 2007. Resultados. Se han visitado 744 pacientes, realizándose un total de 1.248 vistas (ratio sucesivas/primeras de 0,67). La edad media fue de 62,56 (18,6) años y un 50,6% fueron mujeres. La ratio procedencia hospital/procedencia primaria pasó de 3,5 a 4 en el primer trimestre a 2,6-2,8 en el último trimestre. Los principales motivos de consulta fueron pacientes con síndromes constitucionales o anémicos con sospecha de enfermedad grave y pacientes con agudizaciones de procesos crónicos o infecciones. La mitad de los pacientes volvieron a la primaria y el resto se distribuyó entre diferentes recursos hospitalarios, destacando un 30% que fueron remitidos a las consultas del hospital y un 10% que precisó ingreso hospitalario o traslado a Urgencias. Discusión. La CAI es una consulta de atención (diagnóstico y tratamiento) inmediata de medicina interna general ubicada en un hospital universitario terciario con una buena capacidad de resolución, facilitando la atención especializada ambulatoria de patologías médicas, disminuyendo los ingresos inadecuados y mejorando la coordinación con la Atención Primaria de salud (AU)

Introduction. The experience of an urban tertiary university hospital in the design and establishment of Specialized Ambulatory Consultation (SAC) of Internal Medicine is presented. The purpose of this consultation is fast specialized ambulatory care of medical diseases, decrease of inappropriate hospitalizations and improvement of coordination with primary health care. Patients and method. Systematic collection of the following variables in all the patients who visited the SAC between March 2006 and February 2007: origin, syndromic diagnosis and reason for consultation, age and gender, number of visits, examinations made, and destination on discharge. The descriptive statistical analysis was made in March 2007. Results. A total of 744 patients with 1248 visits were seen (successive/first ratio of 0.67). Mean age was 62.56 (18.6) years and 50.6% were women. The hospital origin/primary origin went from 3.5 - 4 in the first quarter to between 2.6 - 2.8 in the last quarter. The main reasons for consultation due to patient with constitutional or anemic syndromes with suspicion of serious disease and patients with decompensation of chronic diseases or infectious disease. Half of the patients returned to primary care and the rest were distributed among different hospital resources. It stands out that 30% were sent to the hospital consultations and 10% required hospitalization or transfer to the emergency room. Conclusions. The SAC is a Fast Consultation Care (diagnosis and treatment) of general internal medicine located in a tertiary university hospital with a good capacity of resolution. It facilitates Specialized Ambulatory Care of medical diseases, decreasing inappropriate hospitalization and improving coordination with the Primary Health Care (AU)

Policy brief: How can the settings used to provide care to older people be balanced?

The optimal balance between institutional, home-based and community care for older adults requires an effective mix of organizational, funding and delivery mechanisms for target populations. This spans health and social care, and the coordination of care must respect older people's care preferences and that of their families and friends as well as limits on the available resources to support and fund service provision. Care settings used to provide long-term care for older people and how they are defined vary greatly across Europe. This policy brief addresses the appropriate balance between three main components of long-term care: home care services; institutional care (formal and informal sectors); and care provided by family and friends (informal care). The dramatic upward trend in the cost and use of long-term care, the projected impact of ageing populations and the prevalence of age-related chronic disease and dependency ratios have catalysed proposals to redesign the funding, organization and delivery of affordable, effective and equitable health and social care for older people.

Impact of a harm-reduction policy on HIV and hepatitis C virus transmission among drug users: recent French data--the ANRS-Coquelicot Study.

In France a harm-reduction policy was implemented in the late 1980s with the aim of reducing the prevalence of HIV and hepatitis C virus (HCV) infection among drug users. The ANRS-Coquelicot survey was designed to measure the prevalence of HIV and HCV infection among drug users and to examine determinants of at-risk behaviors. In 2002, information was collected from 166 drug users recruited in all types of services specializing in drug use intervention and harm reduction in Marseille, France. Self-reported HIV and HCV serostatus was compared with the results of serological tests done on capillary blood collected on filter paper. The self-reported and biologically documented prevalence rates of HIV infection were identical (22%). In contrast, the self-reported prevalence of HCV infection was 52%, whereas the biologically documented prevalence was 73%. Overall, 30% of HCV-infected drug users were unaware of their status. Forty-four percent of drug users under 30 years of age were HCV seropositive, suggesting that they had been infected early during drug use. The harm-reduction policy seems to have had a marked impact on HIV transmission among drug users but a much more limited impact on HCV transmission. The limitations and implications of the study are discussed.

Geriatrización de los Servicios de Urgencias / Geriatrization of Emergency Services

No disponible

The economic burden of disabling hip and knee osteoarthritis (OA) from the perspective of individuals living with this condition.

OBJECTIVE: To estimate the direct and indirect arthritis-attributable costs to individuals with disabling hip and/or knee osteoarthritis (OA). METHODS: An established population cohort with disabling hip and/or knee OA from two regions of Ontario, Canada was surveyed to determine participant and caregiver costs related to OA, and the predictors of these costs. RESULTS: The response rate was 87.2%. Of 1378 respondents, 1258 had OA (mean age 73.1 yr, range 59-100). Sixty per cent (n = 758) reported OA-related costs. Among these individuals, the average annual cost was 12,200 dollars(CDN dollars in 2002, where 1.00 CDN dollar approximately 0.81 US dollar). Time lost from employment and leisure by participants and their unpaid caregivers accounted for 80% of the total. Men were less likely than women to report costs (adjusted odds ratio 0.54, P < 0.0001), but when they did their expenditures were significantly higher (P = 0.004). Greater disability was associated with higher costs: compared with individuals with WOMAC total scores <15, those with scores > or = 55 were 15 times more likely to report costs, and their costs were 3 times greater (both P < 0.0001). Both the young (<65 yr) and very old were more likely to incur costs (P < 0.0001), and when they did their costs were higher (P < 0.001). CONCLUSION: Costs incurred were mainly for time lost from employment and leisure, and for unpaid informal caregivers. Failure to value such indirect costs significantly underestimates the true burden of OA. Costs increased with worsening health status and greater OA severity. After adjustment, men were less likely to incur costs, possibly due to greater social resources.

[Geriatric physical performance assessment in an emergency department]. / Valoración geriátrica de la función física en un Servicio de Urgencias.

BASIS: Premorbid situation with regard to daily life activities is an important prognostic factor in elderly people who needs medical care. This work analyzes the way the parameter evaluation of core processes of daily life (CPDL) is made in patients over 70 years cared in an Emergency Service because of diverse medical conditions. PATIENTS AND METHODS: A prospective study, carried out in a third level medical institution, on 200 patients over 70 years cared in the Emergency medical Service, with questioning a group of 60 physicians on duty (POD) about the informal or subjective assessments of five parameters of CPDL (to get dressed, to be fed, sphincter control, walking, and transfer). POD evaluation is compared with evaluation carried out formally by the research physician. Assessments are evaluated, grouping the patients according to the degree of dependency, age, or sex. RESULTS: 82% of most dependent patients and 53% of those older than 80 years were poorly assessed, and both parameters were statistically significant. The analysis with multiple linear regression showed that the intensity of these errors is only determined by a variable: the greater degree of dependency. CONCLUSIONS: Correct performance assessment of elderly patients in emergency services, especially of those older and most dependent, requires a specific training of professionals in this regard and the use of formal instruments of evaluation.

Valoración geriátrica de la función física en un Servicio de Urgencias / Geriatric physical performance assessment in an emergency department

Fundamento. Entre la población anciana que precisa atención médica, la situación premórbida, respecto a las actividades de la vida diaria, tiene un importante factor pronóstico. Este trabajo analiza cómo se realiza la evaluación de parámetros de actividades básicas de la vida diaria en pacientes de más de 70 años que acuden por patología médica a un Servicio de Urgencias. Pacientes y métodos. Estudio prospectivo, realizado en un hospital de tercer nivel, con 200 pacientes de más de 70 años atendidos en el Servicio de Urgencias médicas, interrogando a un grupo de 60 médicos de guardia de medicina las valoraciones informales o subjetivas de 5 parámetros de actividades básicas de la vida diaria (vestirse, alimentarse, control de esfínteres, deambulación y transferencias). Se compara la evaluación de los médicos de guardia con la realizada de manera formal por el médico investigador. Se evalúan las valoraciones, agrupando a los pacientes según el grado de dependencia, edad o sexo. Resultados. El 82% de los pacientes con más dependencia y el 53% de los mayores de 80 años estaban mal valorados; ambos hallazgos eran estadísticamente significativos. El análisis con regresión lineal múltiple detecta que la gravedad de dichos errores sólo está determinada por una variable: el mayor grado de dependencia. Conclusiones. La correcta valoración funcional de los pacientes ancianos en los servicios de urgencias, especialmente de los más mayores y más dependientes, exige la formación de los profesionales en este sentido y el uso de instrumentos formales de evaluación (AU)

Basis. Premorbid situation with regard to daily life activities is an important prognostic factor in elderly people who needs medical care. This work analyzes the way the parameter evaluation of core processes of daily life (CPDL) is made in patients over 70 years cared in an Emergency Service because of diverse medical conditions. Patients and methods. A prospective study, carried out in a third level medical institution, on 200 patients over 70 years cared in the Emergency medical Service, with questioning a group of 60 physicians on duty (POD) about the informal or subjective assessments of five parameters of CPDL (to get dressed, to be fed, sphincter control, walking, and transfer). POD evaluation is compared with evaluation carried out formally by the research physician. Assessments are evaluated, grouping the patients according to the degree of dependency, age, or sex. Results. 82% of most dependent patients and 53% of those older than 80 years were poorly assessed, and both parameters were statistically significant. The analysis with multiple linear regression showed that the intensity of these errors is only determined by a variable: the greater degree of dependency. Conclusions. Correct performance assessment of elderly patients in emergency services, especially of those older and most dependent, requires a specific training of professionals in this regard and the use of formal instruments of evaluation (AU)