Clinical and economic burden of community-onset multidrug-resistant infections requiring hospitalization.

OBJECTIVES: To analyze the clinical and economic burden of community-acquired (CA) or community-onset healthcare-associated (COHCA) multidrug-resistant (MDR) infections requiring hospitalization. METHODS: Case-control study. Adults admitted with CA or COHCA MDR infections were considered cases, while those admitted in the same period with non-MDR infections were controls. The matching criteria were source of infection and/or microorganism. Primary outcome was 30-day clinical failure. Secondary outcomes were 90-day and 1-year mortality, hospitalization costs and resource consumption. RESULTS: 194 patients (97 cases and 97 controls) were included. Multivariate analysis identified age (odds ratio [OR], 1.07, 95% confidence interval [CI], 1.01-1.14) and SOFA score (OR, 1.45, CI95%, 1.15-1.84) as independent predictors of 30-day clinical failure. Age (hazard ratio [HR] 1.09, 95%CI, 1.03-1.16) was the only factor associated with 90-day mortality, whereas age (HR 1.06, 95%CI, 1.03-1.09) and Charlson Index (HR 1.2, 95%CI, 1.07-1.34) were associated with 1-year mortality. MDR group showed longer hospitalization (p<0.001) and MDR hospitalization costs almost doubled those in the non-MDR group. MDR infections were associated with higher antimicrobial costs. CONCLUSIONS: Worse economic outcomes were identified with community-onset MDR infections. MDR was associated with worse clinical outcomes but mainly due to higher comorbidity of patients in MDR group, rather than multidrug resistance.

Familial primary biliary cirrhosis: like mother, like daughter?

The reasons underlying why autoimmune diseases overwhelmingly affect women more than men are not clear. Nor are the reasons why autoimmune disease is more prevalent in families. This review uses primary biliary cirrhosis (PBC) as a model autoimmune disease to discuss the familial risk, focusing mainly on mother-daughter pairs. PBC is a chronic cholestatic liver disease characterised by an immune-mediated inflammatory destruction of the small intrahepatic bile ducts, with fibrosis progressing to cirrhosis and subsequent liver failure. Epidemiological studies have demonstrated that first degree relatives of PBC patients are at higher risk of developing PBC, as well as other autoimmune diseases. This is especially true for the mothers, daughters and sisters of PBC patients. Multiple case reports have highlighted the complexity of mother-daughter pairs in PBC, and the need for follow-up of these individuals when one member of the pair is diagnosed with PBC. It may be the case that diagnosis in one individual may lead to early diagnosis in the other, even if they are asymptomatic. Early management of PBC may improve the prognosis in these patients. This review will examine the literature surrounding PBC in mothers and daughters.

Patients with cirrhosis and ascites have false values of bone density: implications for the diagnosis of osteoporosis.

UNLABELLED: The effect of ascites on bone densitometry has been assessed in 25 patients with advanced cirrhosis, and it was concluded that ascites over 4 l causes inaccuracy of BMD measurements, particularly at the lumbar spine. This fact must be considered when assessing bone mass in patients with decompensated cirrhosis. INTRODUCTION: Bone mineral density (BMD) measured by dual-energy x-ray absorptiometry (DXA) is the best procedure for assessment of osteoporosis and fracture risk, but BMD values at the central skeleton may be influenced by changes in soft tissues. Therefore, we have studied the effect of ascites on BMD. METHODS: BMD was measured by DXA at the lumbar spine, femoral neck and total hip, just before and shortly after therapeutic paracentesis in 25 patients with advanced liver cirrhosis. Changes in BMD, lean and fat mass, abdominal diameter and weight, as well as the amount of removed ascites were measured. RESULTS: The amount of drained ascites was 6.6 ± 0.5 l (range: 3.0 to 12.7 l). After paracentesis, BMD increased at the lumbar spine (from 0.944 ± 0.035 to 0.997 ± 0.038 g/cm(2), p < 0.001) and at the total hip (from 0.913 ± 0.036 to 0.926 ± 0.036 g/cm(2), p < 0.01). Patients with a volume of drained ascites higher than 4 l showed a significant increase in lumbar BMD (7.0%), compared with patients with a lower amount (1.5%) (p < 0.03). The decrease in total soft tissue mass correlated with the amount of removed ascites (r = 0.951, p < 0.001). Diagnosis of osteoporosis or osteopenia changed after paracentesis in 12% of patients. CONCLUSION: Ascites over 4 l causes inaccuracy of BMD measurements, particularly at the lumbar spine. This fact must be considered when assessing bone mass in patients with advanced cirrhosis.

Lithocholic acid downregulates vitamin D effects in human osteoblasts.

BACKGROUND: Osteoporosis is a common complication in chronic cholestasis. It has been proposed that retained substances such as bile acids may produce a damaging effect on bone cells. This study analyses the effects of lithocholic acid (LCA) on cell survival and vitamin D metabolism in human osteoblasts (hOB). MATERIALS AND METHODS: Human osteoblasts cultures were performed with or without foetal bovine serum (FBS) or human albumin (HA) at different LCA concentrations and times with or without vitamin D. RESULTS: Lithocholic acid at concentrations higher than 10(-5 )M decreased cell survival. This effect was partially prevented by the presence of FBS or HA. Vitamin D stimulated CYP24A, BGLAP and TNFSF11 expression in hOB and these effects were modified by nontoxic LCA concentrations. LCA significantly decreased vitamin D stimulation of CYP24A, BGLAP and TNFSF11 gene expression at 72%, 79% and 56% (respectively). LCA alone has an agonistic effect, as has vitamin D, thus partially increasing CYP24A and BGLAP expression, but with no changes on TNFRSF11B expression. Equivalent effects of the LCA were observed by performing gene reporter assays using MG-63 cells transfected with constructs containing CYP24A1 promoter regions. CONCLUSIONS: Lithocholic acid decreases the stimulatory effect of vitamin D on CYP24A, BGLAP and TNFSF11 expression in hOB. This effect is produced through vitamin D response elements (VDREs), located in the promoter regions of these genes, suggesting that LCA acts as a mild analogous of vitamin D, interacting with the vitamin D receptor. These results may explain the potential deleterious effects of retained bile acids on hOB.

Tratamiento de la hepatitis alcohólica / No disponible

No disponible

Antimitochondrial antibodies in patients with chronic hepatitis C virus infection: description of 18 cases and review of the literature.

To describe the clinical and immunologic patterns of disease expression of patients with chronic hepatitis C virus (HCV) infection and positive antimitochondrial antibodies (AMA). We investigated the presence of AMA in 237 consecutive HCV patients with extrahepatic manifestations from an International Registry. AMA were detected by indirect immunofluorescence in triple rat tissue (liver, stomach and kidney), aceton-fixed criosections and FITC-conjugated rabbit anti-human immunoglobulins. We found positive AMA in 18 (8%) out of 237 HCV patients. All patients were female with a mean age at protocol inclusion of 65.8 years (ranging from 37 to 87 years). Twelve (67%) patients fulfilled classification criteria for systemic autoimmune diseases (SAD), including Sjögren's syndrome (n = 7), systemic sclerosis (n = 3) and systemic lupus erythematosus (n = 2). Fourteen (78%) of the HCV-AMA patients presented at least one of the highly suggestive characteristics of primary biliary cirrhosis (PBC): 9 (50%) had a specific M2 pattern, 6 (33%) had more than twice normal levels of alkaline phosphatase, 5 (28%) had raised IgM levels and 4 (22%) a histological pattern compatible with PBC. Five (28%) patients developed neoplasia after detection of AMA. Seven (39%) patients died, due to neoplasia (n = 4), cirrhotic complications (n = 2) and hepatopulmonary syndrome (n = 1). We describe a subset of HCV patients with positive AMA who presented a broad spectrum of clinical features, including liver, autoimmune and neoplasic manifestations. Two-thirds of these patients presented an associated SAD, mainly Sjögren's syndrome or systemic sclerosis, together with a high frequency of multiple autoantibodies and an increased prevalence of cirrhosis and neoplasia.

Prevalence and clinical significance of isotype specific antinuclear antibodies in primary biliary cirrhosis.

BACKGROUND: Antinuclear antibodies (ANA) giving a rim-like/membranous (RL/M) or a multiple nuclear dot (MND) pattern are highly specific for primary biliary cirrhosis (PBC). Aim and SUBJECTS: To assess the prevalence of PBC specific ANAs, their Ig isotype, and their clinical significance in 90 PBC patients from Greece and Spain. Twenty eight patients with chronic hepatitis C, 23 patients with systemic lupus erythematosus, and 17 healthy subjects were studied as controls. METHODS: PBC specific ANA reactivity was tested by indirect immunofluorescence using HEp2 cells as substrate and individual Ig class (IgG, IgA, IgM) and IgG subclass (IgG1, IgG2, IgG3, IgG4) specific antisera as revealing reagents. RESULTS: Fourteen of 90 (15.6%) PBC patients had PBC specific ANA reactivity when an anti-IgG (total) antiserum was used as the revealing reagent while 58 (64.4%) were positive when specific antisera to each of the four IgG isotypes were used. The prevailing isotype was IgG3 for MND and IgG1 for RL/M. PBC patients with specific ANA, in particular of the IgG3 isotype, had significantly more severe biochemical and histological disease compared with those who were seronegative. None of the controls was positive. CONCLUSIONS: Disease specific ANA are present in the majority of patients with PBC when investigated at the level of immunoglobulin isotype. PBC specific ANA, in particular of the IgG3 isotype, are associated with a more severe disease course, possibly reflecting the peculiar ability of this isotype to engage mediators of damage.

[Schizophrenia in primary health care centers: the SASPE study (alert signs and prodromic symptoms of schizophrenia in primary health care)]. / La esquizofrenia en atención primaria: el estudio SASPE (señales de alerta y síntomas prodrómicos de la esquizofrenia en atención primaria).

OBJECTIVES: To contribute to the knowledge of the alert signs and precursors of the schizophrenia, just as they can appear in the childhood, and of the prodromic signs other ages. DESIGN: Five descriptive studies: three retrospective, one transversal and one longitudinal study, based in the revision of clinical histories of an Community Mental Health Unit closely linked with the APS, additional revisions of the clinical histories of Family Doctors and Peadiatrics of Primary Care, and structured interviews with patients, patient's offspring, and PHC professionals. Two prospective studies: one, with schizophrenic's children; other, of children with alert signs detected in the first childhood. LOCATION OF THE PROJECT: USM-MHU of Sant Martí-La Mina, 5 Sanitary Basic Areas of Barcelona and Sant Adriá (Barcelona), besides the Functional Unit of Attention to the First Childhood of Sant Martí (Barcelona). PARTICIPANTS: Schizophrenic patients and relatives detected by the USM-MHU. Schizophrenic patients and relatives not detected by the USM. MHU-USM assistance staff and assistance staff of 5 ABS and of the Functional Unit of Attention to the First Childhood (UFAPI). Children with alert signs detected in the UFAPI and children with alert signs or risk factors detected in the EAP and in the Pediatric Teams of PC. METHODOLOGY AND INSTRUMENTS: Diagnoses DSM-IV. Structured interviews SCAN and IRAOS. Scales of positive and negative symptoms. Scales or screenings for the first childhood: ARBB, CBCL, and LISMEP. Structured interviews to determine precursory and prodromic signs: FETZ (Colony), ERIE-IRAOS (Hamburg-Barcelona), ERIE-red (reduced version of the IRAOS, adapted by the investigating team).

La esquizofrenia en atención primaria: el estudio SASPE (señales de alerta y síntomas prodrómicos de la esquizofrenia en atención primaria) / Schizophrenia in primary health care centers: the SASPE study (alert signs and prodromic symptoms of schizophrenia in primary health care)

Objetivos. Contribuir al conocimiento de las señales de alerta y precursores de la esquizofrenia, tal como pueden aparecer en la infancia, y de los signos prodrómicos en otras edades. Diseño. Un total de 5 estudios descriptivos, 1 transversal, 1 longitudinal y 3 retrospectivos, basados en el vaciado de historias clínicas de una unidad de salud mental comunitaria estrechamente vinculada con la atención primaria (APS), en la consulta de las historias clínicas de los equipos de APS y de pediatría de AP y en entrevistas con profesionales de APS y con hijos de pacientes. Dos de los estudios se realizaron con hijos de esquizofrénicos y con niños con señales de alerta detectadas en la primera infancia. Emplazamiento del proyecto. Unidad de Salud Mental (USM) de Sant Martí-La Mina, 5 áreas básicas de salud (ABS) de Barcelona y Sant Adrià (provincia de Barcelona), además de la Unidad Funcional de Atención a la Primera Infancia de Sant Martí (Institut Català de la Salut). Sujetos participantes. Pacientes esquizofrénicos y con "otras psicosis" detectados por la USM. Pacientes esquizofrénicos y con "otras psicosis" no detectados por la USM. Personal asistencial de la USM, 5 ABS y de la Unidad Funcional de Atención a la Primera Infancia (UFAPI). Niños con señales de alerta detectadas en la UFAPI y niños con señales de alerta o factores de riesgo detectados en los equipos de atención primaria (EAP) y en los Equipos de Pediatría de APS. Metodología e instrumentos. Diagnósticos DSM-IV. Entrevistas estructuradas SCAN e IRAOS. Escalas de "síntomas en negativo" y "síntomas en positivo". Escalas o sistemas de cribado en la primera infancia: cribados ARBB, CBCL y LISMEP. Entrevistas estructuradas para determinar los signos precursores y prodrómicos: FETZ (Colonia), ERIE-IRAOS (HamburgBarcelona), ERIE-red (versión reducida del IRAOS, adaptada por el equipo investigador) (AU)

Health inequalities in Seville, Spain: use of indicators of social deprivation and mortality in small areas.

OBJECTIVES: To analyse the spatial distribution of social structure and mortality in Seville, and to examine the association between various social indicators and mortality. METHODS: Small areas of the city were typified on the basis of four social indicators, which were used to derive a social index. Overall mortality and cause of death were studied in two age groups (1+years and 1-64 years). Pearson's correlation coefficient was used to examine the relationship between the social indicators and mortality. RESULTS: Significant social and mortality differences, particularly in premature mortality of males, were found between the areas studied. However, when the basic health zones are grouped together by social level, these differences in mortality are not so clear. The social indicators that correlate most closely with mortality are unemployment and illiteracy. When the social index is used, the correlations are weaker. Premature death from trauma in males presents the highest coefficient of correlation with unemployment and illiteracy. CONCLUSIONS: The social index used in the present study places less emphasis on material differences than those used by Townsend et al. and Carstairs and Morris. Also, it was not possible to study mortality by individual neighbourhoods in this study. Both factors could have influenced the finding that the correlations between both types of indicator are weaker with the social index than with unemployment and illiteracy.

[Clinical management units in primary care: a question under debate]. / Las unidades clínicas de gestión en la atención primaria. Un tema en debate.

OBJECTIVE: To find the views of health professionals on how the terms of the new management agreement with clinical units affect the quality of health delivery. DESIGN: Qualitative study to find professionals' views. Individual opinions of key informers were obtained, secondary sources were analysed and a discussion group rounded off the study. The categories for the analysis were established on the basis of the results obtained. SETTING: Primary care districts in the provinces of Sevilla and Cádiz, in the Autonomous Community of Andalusia. Health districts of differing social-economic and geographical characteristics were chosen. PARTICIPANTS: 9 professionals involved in the new system of management. The selection criteria refer to the kind of professional, the unit or work team and the characteristics of the health district. METHOD: The semi-structured interview with key informers and a discussion group were the basic techniques for gathering information. RESULTS: A view that the clinical management units were designed as a savings strategy was detected. There were differences about primary care teams. CONCLUSIONS: Professionals think there is too much rigidity and adding-up in the measurement of targets and objectives. This creates unfavourable working conditions, which affects the quality of health service delivery.

Las unidades clínicas de gestión en la atención primaria. Un tema en debate / Clinical management units in primary care: a question under debate

Objetivo. Considerar las opiniones de los profesionales sanitarios acerca de cómo afectan a la calidad de las prestaciones sanitarias los términos en que se establece el acuerdo de gestión con las unidades clínicas. Diseño. Estudio cualitativo para conocer las opiniones de los profesionales. Se obtuvieron opiniones individuales de informadores clave, se analizaron fuentes secundarias y se finalizó con un grupo de discusión. Las categorías del análisis se establecieron a partir de los resultados obtenidos. Emplazamiento. Distritos de atención primaria de la comunidad autónoma andaluza, en las provincias de Sevilla y Cádiz. Se han elegido zonas básicas de salud con características socioeconómicas y geográficas diferentes. Participantes. Nueve profesionales implicados en la nueva forma de gestión. Los criterios de selección se refieren al tipo de profesional, la unidad o equipo de trabajo y las características de la zona básica de salud. Método. La entrevista semiestructurada a informadores clave y grupo de discusión cómo técnicas básicas para la obtención de la información. Resultados. Se ha detectado una visión de las unidades clínicas de gestión como estrategia dirigida al ahorro. Se manifiestan diferencias respecto a los equipos básicos de atención primaria. Conclusiones. Los profesionales opinan que hay excesiva rigidez y cuantificación en la medición de servicios y objetivos, lo que genera unas condiciones de trabajo desfavorables que influyen en la calidad de las prestaciones (AU)

Consulta diaria. Qué haría usted ante... un enfermo ictérico

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Cholangiocarcinoma in primary sclerosing cholangitis: risk factors and clinical presentation.

BACKGROUND: Primary sclerosing cholangitis (PSC) confers a high risk of cholangiocarcinoma (CC) development. Since patients at risk of CC may be selected for early liver transplantation, it is a challenge to identify any predisposing factors. We compared the presentation and natural history of a large number of PSC patients with and without later CC development to identify features associated with risk of CC. METHODS: Clinical and laboratory data from presentation and follow-up were collected from 394 PSC patients from five European countries. The cohort included 48 (12.2%) patients with CC. RESULTS: CC was diagnosed within the first year after diagnosis of PSC in 24 (50%) cases and in 13 (27%) patients at intended liver transplantation. Jaundice, pruritus, abdominal pain and fatigue were significantly more frequent at diagnosis of PSC in the group that developed CC, but not after exclusion of cases diagnosed within the first year. Inflammatory bowel disease was diagnosed at least 1 year before PSC more often among patients with CC development than among those without (90% and 65%, respectively: P = 0.001). The duration of inflammatory bowel disease before diagnosis of PSC was significantly longer in patients who developed CC than in the remaining group (17.4 years and 9.0 years, respectively: P=0.009 in multivariate analysis). CONCLUSIONS: A high proportion of CC cases is diagnosed within the first year after diagnosis of PSC. A long history of inflammatory bowel disease is a risk factor for CC development.

Patología orgánica / Somatic pathology

El consumo crónico de alcohol se acompaña de un amplio espectro de trastornos orgánicos, derivados de la acción directa de la oxidación del alcohol y de la producción de acetaldehído, o bien de las deficiencias nutricionales asociadas. La enfermedad hepática alcohólica es una de las alteraciones más frecuentes en los alcohólicos crónicos y se caracteriza por presentar desde lesiones leves como esteatosis hasta una cirrosis hepática. También son importantes las alteraciones neurológicas, de patogenia menos clara, pero relacionadas con la acción directa del alcohol y las deficiencias nutricionales. Asimismo, es frecuente que el alcohólico crónico tenga manifestaciones del tracto gastrointestinal y páncreas, asi como trastornos hematológicos, metabólicos y endocrinos. El alcoholismo crónico también se asocia a osteoporosis y osteopenia, al desarrollo de ciertos tipos de cáncer y a la fetopatía alcohólica (AU)

Chronic alcohol intake results in a wide spectrum of organic disturbances derived from the alcohol oxidation and the subsequent generation of acetaldehyde, as well as from the nutritional deficiencies associated with alcohol intake. Alcoholic liver disease is the most prevalent organic abnormality observed in chronic alcoholic, ranging from fatty liver to established cirrhosis. Neurologic diseases are also frequent. Its pathogenesis is less clear, but it probably results from the direct toxic effect of alcohol as well as nutritional deficiencies. Moreover, alcoholic patients also may experience other diseases of the gastrointestinal tract and pancreas, as well as hematological, metabolic and endocrine disturbances. Chronic alcoholism is also associated with osteopenia and osteoporosis, the development of cancer and the fetal alcoholic syndrome (AU)

The HLA-DR3,DQ2 heterozygous genotype is associated with an accelerated progression of primary sclerosing cholangitis.

BACKGROUND: An improvement of prognostic models in primary sclerosing cholangitis (PSC) is needed. In particular, inclusion of prognostic markers that are independent of the disease stage would be advantageous. We investigated whether HLA class II genes associated with PSC are also related to disease progression. METHODS: The study included 265 PSC patients from five European countries with a median follow-up of 9.1 years. The end-points were death (n = 38) or liver transplantation (n = 52). Thirty patients developed cholangiocarcinoma during follow-up. RESULTS: The DRB1*03,DQA1*0501, DQB1*02 (i.e. DR3,DQ2) heterozygous genotype was associated with an increased risk of death or liver transplantation (hazard ratio = 1.63; 95% confidence interval (CI) = 1.06-2.52). The presence of a DQ6 encoding haplotype (DQB1*0603 or DQB1*0602) in DR3,DQ2 negative individuals was associated with a reduced risk of death or liver transplantation (hazard ratio = 0.57; 95% CI = 0.36-0.88). There was a trend towards an increased risk of developing cholangiocarcinoma among DR4,DQ8 positive patients, but this did not reach significance (odds ratio = 2.27; 95% CI = 0.78-6.62). CONCLUSION: The DR3,DQ2 heterozygous genotype is associated with a more rapid progression of PSC, whereas HLA-DQ6 is associated with a retarded disease progression. It is possible that the DR4,DQ8 haplotype is related to cholangiocarcinoma development.