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1.
Int J Gen Med ; 14: 7017-7024, 2021.
Article in English | MEDLINE | ID: mdl-34707393

ABSTRACT

PURPOSE: Seroprevalence against SARS-CoV-2 within university systems is poorly studied, making evidence-based discussions of educational system reopening difficult. Moreover, few studies evaluate how antibodies against SARS-CoV-2 are maintained over time. We assessed serological response against the SARS-CoV-2 virus among our university students and staff. PATIENTS AND METHODS: In this prospective cohort study, seroprevalence was determined in 705 randomly selected volunteers, members of the Faculty of Medicine and Health Sciences of the University of Alcalá, using a chemiluminescent Siemens' SARS-CoV-2 immunoassay for total antibodies. Positive samples were tested for IgG and IgM/IgA using VIRCLIA® MONOTEST (Vircell). A first analysis took place during June 2020, and in those testing positive, a determination of secondary outcomes was performed in November 2020. RESULTS: A total of 130 subjects showed anti-SARS-CoV-2 antibodies (18.5%, 95% CI, 15.8-21.5%). Of these, IgM/IgA was positive in 27 and indeterminate in 19; IgG was positive in 118, indeterminate in 1. After 23 weeks, among 102 volunteers remeasured, IgG became undetectable in 6. Presence of antibodies was associated, in multivariable logistic regression, with exposure to infected patients (31.3%) [OR 1.84, 95% CI, 1.14-2.96; P = 0.012], presence of COVID-19 symptoms (52.4%) [OR 6.88, 95% CI, 4.28-11.06; P < 0.001], and confirmed earlier infection (82.9%) [OR 11.87, 95% CI, 4.26-33.07; P < 0.001]. CONCLUSIONS: The faculty of medicine and health sciences personnel and students of our university showed a high infection rate for SARS-CoV-2 during 2020 associated with providing clinical care to infected patients. This emphasizes the importance of the performance of continuous surveillance methods of the most exposed health personnel, including health science students.

2.
Educ. med. (Ed. impr.) ; 20(6): 360-367, nov.-dic. 2019. ilus, tab, graf
Article in Spanish | IBECS | ID: ibc-191843

ABSTRACT

INTRODUCCIÓN: Durante el curso académico 2015-16 se implantó el 6.o curso del Grado de Medicina en la Facultad de Medicina y Ciencias de la Salud de la Universidad de Alcalá. Comprende prácticas clínicas tuteladas y trabajo fin de grado/máster. La Facultad de Medicina y Ciencias de la Salud quería que el programa formativo fuera integral e integrador centrado en la adquisición y potenciación de competencias clínicas, de comunicación e investigación, con una estructura de coordinación que permitiera una evaluación y detección continua de desviaciones, y por supuesto establecer una evaluación de los resultados a medio y largo plazo. El objetivo de este trabajo es presentar el programa formativo desarrollado. MATERIALES Y MÉTODOS: Se formó un equipo de docente y estudiantes para diseñar el curso, con un calendario de reuniones y un programa de acciones a llevar a cabo, siempre intentando que todas las decisiones fueran consensuadas, se tuvieran en cuenta los diferentes escenarios, con herramientas comunes didácticas y de evaluación, flexibles y adaptadas a los diferentes entornos. RESULTADOS: El curso tiene diversidad de entornos y actividades docentes. Las rotaciones integran al estudiante en los servicios y unidades asistenciales. Además, se realizan actividades innovadoras transversales en la Facultad. Se ha diseñado una estructura de coordinación del programa y para su valoración los instrumentos tanto de evaluación del estudiante como del programa son variados y complejos. Se han diseñado numerosas encuestas de opinión que reflejan una satisfacción muy elevada y los resultados académicos son excelentes. CONCLUSIONES: Se ha conseguido desarrollar un programa formativo integral e integrador, con una estructura de coordinación y unos instrumentos de evaluación adecuados. Los indicadores académicos y de opinión son muy positivos e indican que los objetivos de aprendizaje se cumplen con éxito. La coordinación es eficaz y homogeniza la docencia en entornos diferentes, facilitando la detección y subsanación de deficiencias


INTRODUCTION: During 2015-16 academic implanted the 6th course of medicine degree in the Faculty of Medicine and Health Sciences of the Universidad de Alcalá. Includes clinical practices and master's dissertation. The Faculty of Medicine and Health Sciences wanted the training program to be integral and integrator focused on the acquisition and promotion of clinical skills, communication and research, with a coordination structure that would enable an assessment and continuous detection of deviations, and of course establish an assessment of results in the medium and long term. The objective of this work is to present the developed training programme. MATERIALS AND METHODS: A team of teachers and students was formed to design the course, with a calendar of meetings and a program of actions to be carried out, always trying to that all decisions were consensual, the different took into account scenarios, with common teaching tools and assessment, flexible and adapted to the different environments. RESULTS: The course has diversity of environments and teaching activities. Rotations integrated student services and healthcare units. In addition, are cross-cutting innovative activities at the Faculty. A coordination of the program structure is designed and for their evaluation, both of student assessment and program, instruments are varied and complex. Numerous opinion tests that reflect a very high satisfaction and academic results are excellent have been designed. CONCLUSIONS: We have managed to develop a training program comprehensive and inclusive, with a coordination structure and appropriate assessment tools. Academic and opinion indicators are very positive and indicate that the learning objectives are met with success. He has been established very effective coordination to homogenize the teaching in different environments, and facilitates the detection and correction of deficiencies


Subject(s)
Humans , Clinical Competence , Research/education , Students, Premedical , Education, Premedical/methods , Communication , Faculty , Curriculum , Surveys and Questionnaires
3.
Rev Esp Salud Publica ; 90: E13, 2016 02 05.
Article in Spanish | MEDLINE | ID: mdl-26847950

ABSTRACT

OBJECTIVE: The aim of this study was to establish the prevalence of Chronic obstructive pulmonary disease [COPD] in a rural health area and its stratification according different risk factors. METHODS: A cross-sectional, observational study was performed in Yunquera de Henares (Guadalajara, Spain) in the year 2014. A questionnaire on sociodemographic factors, tobacco consumption, age, education level and occupation was used in a randomized, stratified sample in different stages. The sample was proportional in age, sex and population centers. A total of 749 persons were included. Data were analyzed using descriptive, analytical, and multivariant statistical procedures and logistical regression. RESULTS: The prevalence of COPD was 15.8% (CI95%: 13.2-18.4) and was statistically significantly higher in elderly (64.6±11 years vs 58.9±11,7 years); males (83.2%;CI95%:85.9-80.5),smokers (40.3%;CI95%:43.8-36.8) and people with primary education (66.4%;CI95%:69.7-63). People with COPD had higher BMI (28.2%;IC95%:29.5-26.9). People working in the field was 28.6% (IC95%:20,5-36,7%). CONCLUSIONS: A high prevalence of Chronic Obstructive Pulmonary Disease was found. Occupational exposure may be an important factor in rural areas.


OBJETIVO: El objetivo de este estudio fue establecer la prevalencia de enfermedad pulmonar obstructiva crónica en una zona básica de salud de ámbito rural y el análisis según diferentes factores de riesgo. METODOS: Estudio transversal realizado en Yunquera de Henares (Guadalajara) durante 2014. Para la recogida de información se utilizó un cuestionario que recogió datos sociodemograficos, consumo de tabaco, edad, nivel de estudios y ocupación en una muestra de sujetos seleccionada de manera aleatoria y estratificada según edad, sexo y núcleos de población. El tamaño muestral fue de 749 personas. Se realizó análisis estadístico descriptivo con medias y porcentajes, analítico: chi2, t de Student, ANOVA y multivariante por regresión logística. RESULTADOS: La prevalencia de enfermedad pulmonar obstructiva crónica fue del 15,8% (IC95%: 13,2-18,4).Las personas con enfermedad pulmonar obstructiva crónica tenían una edad media de 64,6±11 años vs 58,9±11,7 de quienes no la padecían. Eran hombres el 83,2% (IC95%: 85,9-80,5), fue más frecuente en personas con estudios primarios: 66,4% (IC95%: 69,7-63) y entre quienes consumían tabaco: 40,3% (IC 95%: 43,8-36,8). De manera no estadísticamente significativa, también presentaban mayor índice de masa corporal:28,2% (IC95%: 29,5-26,9).Trabajababan en el campo el 28,6% (IC95%: 20,5-36,7). CONCLUSIONES: La prevalencia de enfermedad pulmonar obstructiva crónica encontrada fue alta. La exposición laboral puede ser un factor importante en el medio rural.


Subject(s)
Pulmonary Disease, Chronic Obstructive/epidemiology , Rural Health/statistics & numerical data , Adult , Age Distribution , Aged , Analysis of Variance , Cross-Sectional Studies , Female , Humans , Logistic Models , Male , Middle Aged , Occupational Exposure , Prevalence , Pulmonary Disease, Chronic Obstructive/etiology , Risk Factors , Sex Distribution , Smoking/epidemiology , Spain/epidemiology , Surveys and Questionnaires
4.
Rev. esp. salud pública ; 90: 0-0, 2016. tab
Article in Spanish | IBECS | ID: ibc-152938

ABSTRACT

Fundamentos: La enfermedad pulmonar obstructiva crónica es un problema sanitario mundial debido a su elevada prevalencia, alta morbilidad y cuantioso coste económico. En España su prevalencia varía considerablemente entre las diferentes áreas geográfica estudiadas. El objetivo de este estudio fue establecer la prevalencia de enfermedad pulmonar obstructiva crónica en una zona básica de salud de ámbito rural y el análisis según diferentes factores de riesgo. Métodos: Estudio transversal realizado en Yunquera de Henares (Guadalajara) durante 2014. Para la recogida de información se utilizó un cuestionario que recogió datos sociodemograficos, consumo de tabaco, edad y profesión a una muestra de sujetos seleccionada de manera aleatoria y estratificada según edad, sexo y núcleos de población. El tamaño muestral fue de 749 personas. Se realizó análisis estadístico descriptivo con medias y porcentajes, analítico: chi2, t de Student, ANOVA y multivariante por regresión logística. Resultados: La prevalencia de enfermedad pulmonar obstructiva crónica fue del 15,8% (IC 95%: 13,2-18,4). Las personas con enfermedad pulmonar obstructiva crónica tenían una edad media de 64,6±11años vs 58,9±11,7 de quienes no la padecían (p<0,05), eran hombres el 83,2% (IC95%: 85,9-80,5; p<0,001), fue más frecuente en personas con estudios primarios: 66,4% (IC95%: 69,7-63; p<0,01) y entre quienes consumían tabaco: 40,3% (IC 95%: 43,8-36,8 ; p<0,001). De manera no estadísticamente significativa, también presentaban mayor índice de masa corporal:28,2% (IC95%: 29,5-26,9). Trabajababan en el campo el 28,6% (IC95%: 20,5-36,7). Conclusiones: La prevalencia de enfermedad pulmonar obstructiva crónica encontrada fue alta. La exposición laboral puede ser un factor importante en el medio rural (AU)


Background: Chronic obstructive pulmonary disease (COPD) is a global health problem due its elevated prevalence, high morbimortality, and substantial socioeconomic cost. In Spain its prevalence varies considerably among the different geographical areas studied. The aim of this study was to establish the prevalence of COPD in a rural area health and its stratification according different risk factors. Methods: A cross-sectional, observational study was perfomed in Yunquera de Henares (Guadalajara, Spain) in the year 2014. A questionnaire on sociodemographic, consumption tobacco age and profession was used to a randomized, stratified sample in different stages. The sample was proportional in age, sex and population centers. A total of 749 persons were included. Data were analyzed using descriptive, analytical, and multivariant statistical procedures and logistical regression. Results: The prevalence of COPD was 15.8% (CI 95%: 13.2-18.4) and was statistically significantly higher in elderly (64.6±11 years vs 58.9±11,7 years); males (83.2%; CI95%: 85.9-80.5), smokers (40.3%, CI95%: 43.8-36.8) and people with primary education (66.4% ; CI95%: 69.7-63). People with COPD had higher BMI (28.2%; IC95%: 29.5-26.9). People working in the field was 28.6% (IC95%: 20,5-36,7%). Conclusions: High prevalence of Chronic Obstructive Pulmonary Disease was found. Occupational exposure may be an important factor in rural areas (AU)


Subject(s)
Humans , Male , Female , Pulmonary Disease, Chronic Obstructive/epidemiology , Risk Factors , Smoking/epidemiology , Rural Population/statistics & numerical data , Cross-Sectional Studies/methods , Cross-Sectional Studies/statistics & numerical data , Surveys and Questionnaires , Analysis of Variance , Multivariate Analysis , Logistic Models , Primary Health Care/methods
6.
Crit Care ; 17(3): R105, 2013 May 30.
Article in English | MEDLINE | ID: mdl-23721745

ABSTRACT

INTRODUCTION: It has recently been proposed that B lymphocytes are involved in sepsis pathogenesis. The goal of this study is to investigate potential abnormalities in a subset distribution and activation of circulating B lymphocytes in patients with septic shock. METHODS: This observational prospective study was conducted in a medical-surgical ICU. All patients with septic shock were eligible for inclusion. B-cell phenotypes (CD19+CD69+, CD19+CD23+, CD19+CD5+, CD19+CD80, CD19+CD86+, CD19+CD40 and CD19+CD95+) were assessed by quantitative flow cytometry upon admission to the ICU and 3, 7, 14 and 28 d later. RESULTS: Fifty-two patients were included. Thirty-six healthy volunteers matched for age and sex were used as controls. The patients had lymphopenia that was maintained during 28 d of follow-up. In patients with septic shock who died, the percentage of CD19+CD23+ was lower during the 7 d of follow-up than it was in survival patients. Moreover, the percentage of CD80+ and CD95+ expression on B cells was higher in patients who died than in survivors. Receiver operating characteristic curve analysis showed that a CD19+CD23+ value of 64.6% at ICU admission enabled discrimination between survivors and nonsurvivors with a sensitivity of 90.9% and a specificity of 80.0% (P=0.0001). CONCLUSIONS: Patients with septic shock who survive and those who don't have different patterns of abnormalities in circulating B lymphocytes. At ICU admission, a low percentage of CD23+ and a high of CD80+ and CD95+ on B cells were associated with increased mortality of patients with septic shock. Moreover, a drop in circulating B cells persisted during 28 d of ICU follow-up.


Subject(s)
B-Lymphocytes/metabolism , Shock, Septic/blood , Shock, Septic/diagnosis , Aged , Female , Humans , Male , Middle Aged , Prospective Studies , Shock, Septic/mortality , Survival Rate/trends , Time Factors
7.
Eur J Intern Med ; 24(2): 132-8, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23352000

ABSTRACT

BACKGROUND: Vascular endothelium activation is a key pathogenic step in systemic inflammatory response syndrome (SIRS) that can be triggered by both microbial and sterile proinflammatory stimuli. The relevance of soluble adhesion molecules as clinical biomarkers to discriminate between infectious and non-infectious SIRS, and the individual patient prognosis, has not been established. METHODS: We prospectively measured by sandwich ELISA, serum levels of soluble E-Selectin (sE-Selectin), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble intercellular adhesion molecule-2 (sICAM-2) at ICU admission and at days 3, 7, 14 and 28 in patients with sepsis and at days 3 and 7 in patients with non-infectious SIRS. RESULTS: At ICU admission, sE-Selectin, sVCAM-1 and sICAM-1 in patients with infectious SIRS were significantly higher than those found in patients with non-infectious SIRS. ROC analysis revealed that the AUC for infection identification was best for sICAM-1 (0.900±0.041; 95% CI 0.819-0.981; p<0.0001). Moreover, multivariate analysis showed that 4 variables were significantly and independently associated with mortality at 28 days: male gender (OR 15.90; 95% CI, 2.54-99.32), MODS score (OR 5.60; 95% CI, 1.67-18.74), circulating sE-Selectin levels (OR 4.81; 95% CI, 1.34-17.19) and sVCAM-1 concentrations (OR 4.80; 95% CI, 1.34-17.14). CONCLUSIONS: Patients with SIRS secondary to infectious or non-infectious etiology show distinctive patterns of disturbance in serum soluble adhesion molecules. Serum ICAM-1 is a reliable biomarker for classifying patients with infectious SIRS from those with non-infectious SIRS. In addition, soluble E-Selectin is a prognostic biomarker with higher levels in patients with SIRS and fatal outcome.


Subject(s)
E-Selectin/blood , Intercellular Adhesion Molecule-1/blood , Systemic Inflammatory Response Syndrome/blood , Biomarkers/blood , Diagnosis, Differential , Enzyme-Linked Immunosorbent Assay , Female , Humans , Incidence , Male , Middle Aged , Prognosis , Prospective Studies , ROC Curve , Severity of Illness Index , Spain/epidemiology , Survival Rate/trends , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/epidemiology
8.
Eur J Intern Med ; 23(4): 358-62, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22560386

ABSTRACT

BACKGROUND: TGF-ß1 is a promoter of pulmonary fibrosis in many chronic inflammatory diseases. TGF-ß1 circulating levels in patients with sepsis-induced Acute Respiratory Distress Syndrome (ARDS) have not been established. METHODS: In this prospective pilot cohort study, serum bioactive TGF-ß1 concentration, determined by sandwich ELISA, was analyzed in 52 patients who fulfilled criteria for septic shock at admission and on days 3 and 7. RESULTS: Of the 52 patients enrolled in the study, 46.1% fulfilled the criteria for ARDS on admission. At ICU admission, there were not statistical differences in TGF-ß1 concentrations between septic shock patients with or without ARDS. After 7 days of follow-up in ICU, circulating TGF-ß1 levels were significantly higher in patients with sepsis and ARDS than in those without ARDS [55.47 (35.04-79.48 pg/ml) versus 31.65 (22.89-45.63 pg/ml), respectively] (p = 0.002). Furthermore, in septic shock associated ARDS patients, TGF-ß1 levels were significantly higher in nonsurvivors than in survivors [85.23 (78.19-96.30 pg/ml) versus 36.41 (30.21-55.47 pg/ml), respectively] (p = 0.006) on day 7 of ICU follow-up. CONCLUSIONS: In patients with septic shock, persistent ARDS is accompanied with increased circulating TGF-ß1 levels. Furthermore, ARDS patients with fatal outcome show higher TGF-ß1 concentrations than survivors. These results suggest the relevance of TGF-ß1 levels found in the pathogenesis of persistent sepsis-induced ARDS.


Subject(s)
Respiratory Distress Syndrome/blood , Transforming Growth Factor beta1/blood , Adult , Aged , Disease Progression , Female , Humans , Intensive Care Units , Male , Middle Aged , Prospective Studies , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/mortality , Shock, Septic/blood , Shock, Septic/complications , Shock, Septic/mortality
10.
J Intensive Care Med ; 26(2): 125-32, 2011.
Article in English | MEDLINE | ID: mdl-21464065

ABSTRACT

BACKGROUND: Mortality in patients with septic shock remains unacceptably high and the attempts to antagonize certain proinflammatory cytokines based on the results of animal model studies have failed to improve survival rates. The objective of this article is to examine the pro-/anti-inflammatory cytokine balance in patients with septic shock and its connection with mortality. METHODS: Serum levels of proinflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin 1ß [IL-1ß], interferonγ [IFN-γ], and IL-6) and soluble cytokine antagonists (soluble TNF receptor I [sTNF-RI], sTNF-RII, and IL-1Ra) were determined on admission to the intensive care unit (ICU) and 3, 7, 14, and 28 days later in 52 patients with septic shock and in 36 healthy controls. Specific sandwich enzyme-linked immunosorbent assay (ELISA) was used for all determinations. RESULTS: Serum levels of most of the pro- and anti-inflammatory molecules examined (TNF-α, IL-6, sTNF-RI, sTNF-RII, and IL-1 receptor agonist [IL-1Ra]) were significantly elevated on admission and during the 28-day observation period in patients when compared to controls. Notably, the anti-inflammatory mediators sTNF-RI, sTNF-RII, and IL-1Ra were better predictors of mortality. Receiver-operating characteristic (ROC) analysis revealed that sTNF-RI or sTNF-RII concentrations over 2767 or 4619 pg/mL, respectively, determined a high risk of death (sensitivity: 100%-100%, specificity: 57.1%-71.4%, area under the curve [AUC] 0.759-0.841, respectively), whereas IL-1Ra concentrations below 7033 pg/mL determined a high probability of survival (sensitivity: 60%, specificity: 100%, AUC 0.724). In addition, IFN-γ levels were significantly higher in survivors than in controls during the initial 2 weeks of observation. CONCLUSIONS: Our data show that serum cytokine disturbance patterns have prognostic significance in patients with septic shock admitted to the ICU. The pattern, defined by an early response to continuously elevated anti-inflammatory cytokine serum levels, is associated with an enhanced risk of a fatal outcome for patients.


Subject(s)
Critical Care , Shock, Septic/blood , Shock, Septic/mortality , Aged , Female , Humans , Interferon-gamma/blood , Interleukin 1 Receptor Antagonist Protein/blood , Interleukin-1beta/blood , Interleukin-6/blood , Male , Middle Aged , Prognosis , ROC Curve , Receptors, Tumor Necrosis Factor, Type I/blood , Receptors, Tumor Necrosis Factor, Type II/blood , Sensitivity and Specificity , Shock, Septic/pathology , Tumor Necrosis Factor-alpha/blood
11.
Infect Immun ; 78(7): 3272-9, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20404074

ABSTRACT

In animal models, a defective Th1 response appears to be critical in the pathogenesis of brucellosis, but the Th1 response in human brucellosis patients remains partially undefined. Peripheral blood from 24 brucellosis patients was studied before and 45 days after antibiotherapy. Twenty-four sex- and age-matched healthy donors were analyzed in parallel. Significantly increased levels of interleukin 1beta (IL-1beta), IL-2, IL-4, IL-6, IL-12p40, gamma interferon (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha), but not of IL-10, in serum and/or significantly increased percentages of samples with detectable levels of these cytokines, measured by enzyme-linked immunosorbent assays (ELISA), were found for untreated brucellosis patients, but these levels were reduced and/or normalized after treatment. Flow cytometry studies showed that the intracytoplasmic expression of IFN-gamma, IL-2, and TNF-alpha, but not that of IL-4, by phorbol myristate-activated CD4(+) CD3(+) and CD8(+) CD3(+) T lymphocytes was significantly increased in untreated brucellosis patients and was also partially normalized after antibiotherapy. The percentage of phagocytic cells, the mean phagocytic activity per cell, and the phagocytic indices for monocytes at baseline were defective and had only partially reverted at follow-up. T lymphocytes from untreated brucellosis patients are activated in vivo and show Th1 cytokine production polarization, with strikingly high serum IFN-gamma levels. In spite of this Th1 environment, we found deficient effector phagocytic activity in peripheral blood monocytes.


Subject(s)
Brucellosis/immunology , Monocytes/immunology , Th1 Cells/immunology , Adult , Aged , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Enzyme-Linked Immunosorbent Assay , Female , Flow Cytometry , Humans , Interferon-gamma/blood , Interleukin-10/blood , Interleukin-12/blood , Interleukin-1beta/blood , Interleukin-2/blood , Interleukin-4/blood , Interleukin-6/blood , Lymphocyte Activation/immunology , Male , Middle Aged , Tumor Necrosis Factor-alpha/blood , Young Adult
12.
Diagn Microbiol Infect Dis ; 58(4): 481-5, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17509788

ABSTRACT

Prosthetic joint infection (PJI) due to Brucella spp. is extremely rare. We report the case of a prosthetic hip infection due to Brucella melitensis in a 51-year-old male patient. The initial presentation was a gluteal abscess. There was radiographic evidence of implant loosening. The patient was cured after prolonged treatment with streptomycin, rifampicin, and doxycycline, followed by 2-stage exchange of the prosthesis. Brucella spp. should be considered in the differential diagnosis of PJI in countries where brucellosis is endemic. The review of all cases previously reported shows that a conservative approach using antibiotics alone can be followed in patients without signs of implant loosening. In contrast, prolonged antibiotic treatment and prosthetic joint revision should be considered in patients with evidence of implant loosening.


Subject(s)
Arthroplasty, Replacement, Hip/adverse effects , Brucella melitensis/isolation & purification , Brucellosis/microbiology , Prosthesis-Related Infections/microbiology , Anti-Bacterial Agents/therapeutic use , Brucellosis/diagnosis , Humans , Male , Middle Aged , Prosthesis-Related Infections/drug therapy , Prosthesis-Related Infections/surgery
17.
Clin Infect Dis ; 39(12): 1776-82, 2004 Dec 15.
Article in English | MEDLINE | ID: mdl-15578399

ABSTRACT

BACKGROUND: Human brucellosis is usually treated with a combination of tetracyclines and aminoglycosides. However, the optimal duration of therapy has not been clearly determined. METHODS: We conducted a prospective, double-blind, randomized, multicenter study comparing treatment with doxycycline (100 mg po b.i.d.) for 30 days (30-day group) with the same dosage of doxycycline for 45 days (45-day group) in patients with brucellosis without endocarditis, spondylitis, or neurobrucellosis. All patients were treated with gentamicin (240 mg im once daily) for the first 7 days. Therapeutic outcome was evaluated by measuring relapse rates and drug safety. RESULTS: Seventy-three patients were included in each group. During the first 45 days after treatment, the percentage of patients with relapse was significantly higher in the 30-day group than in the 45-day group (12.3% vs. 1.37%; relative risk, 9.00; 95% confidence interval [CI], 1.17-69.2; P=.017). Between day 45 after treatment and 12 months after treatment, no further significant differences were found in relapse rates between groups (9.38% in the 30-day group vs. 11.11% in the 45-day group; relative risk, 0.84; 95% CI, 0.31-2.30; P=.78). Overall, relapses occurred in 15 (20.55%) of 73 patients in the 30-day group and in 9 (12.33%) of 73 patients in the 45-day group (relative risk, 1.67; 95% CI, 0.78-3.56; P=.264). Compliance and adverse effects were comparable in the 2 groups. CONCLUSIONS: Doxycycline treatment for 45 days significantly decreased early relapse rates among adults with brucellosis without increasing adverse effects.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Brucellosis/drug therapy , Doxycycline/therapeutic use , Adolescent , Adult , Aged , Anti-Bacterial Agents/adverse effects , Double-Blind Method , Doxycycline/adverse effects , Female , Humans , Male , Middle Aged , Prospective Studies , Recurrence , Risk Factors , Treatment Outcome
18.
J Exp Med ; 200(4): 541-7, 2004 Aug 16.
Article in English | MEDLINE | ID: mdl-15314078

ABSTRACT

Human immunodeficiency virus (HIV)-1 infectivity requires actin-dependent clustering of host lipid raft-associated receptors, a process that might be linked to Rho guanosine triphosphatase (GTPase) activation. Rho GTPase activity can be negatively regulated by statins, a family of drugs used to treat hypercholesterolemia in man. Statins mediate inhibition of Rho GTPases by impeding prenylation of small G proteins through blockade of 3-hydroxy-3-methylglutaryl coenzyme A reductase. We show that statins decreased viral load and increased CD4+ cell counts in acute infection models and in chronically HIV-1-infected patients. Viral entry and exit was reduced in statin-treated cells, and inhibition was blocked by the addition of l-mevalonate or of geranylgeranylpyrophosphate, but not by cholesterol. Cell treatment with a geranylgeranyl transferase inhibitor, but not a farnesyl transferase inhibitor, specifically inhibited entry of HIV-1-pseudotyped viruses. Statins blocked Rho-A activation induced by HIV-1 binding to target cells, and expression of the dominant negative mutant RhoN19 inhibited HIV-1 envelope fusion with target cell membranes, reducing cell infection rates. We suggest that statins have direct anti-HIV-1 effects by targeting Rho.


Subject(s)
Acquired Immunodeficiency Syndrome/metabolism , Cytoskeleton/metabolism , Down-Regulation/drug effects , HIV-1/metabolism , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Leukocytes, Mononuclear/drug effects , rho GTP-Binding Proteins/metabolism , Acquired Immunodeficiency Syndrome/drug therapy , Animals , CD4 Lymphocyte Count , Cells, Cultured , Cholesterol/blood , Disease Models, Animal , Electrophoresis, Polyacrylamide Gel , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Mevalonic Acid , Mice , Mice, SCID , Polyisoprenyl Phosphates , Precipitin Tests , RNA/metabolism
19.
Med. clín (Ed. impr.) ; 115(5): 161-165, jul. 2000.
Article in Es | IBECS | ID: ibc-7181

ABSTRACT

Objetivo: Evaluar la cumplimentación, tolerancia y eficacia de una pauta corta de quimioprofilaxis para tuberculosis con isoniacida y rifampicina durante 3 meses frente a una pauta estándar de isoniacida durante 12 meses en pacientes con infección por el virus de la inmunodeficiencia humana (VIH). Pacientes y métodos: Ensayo clínico prospectivo, comparativo, aleatorizado y abierto realizado en cuatro hospitales generales y un centro penitenciario de Castilla-La Mancha. La profilaxis se administró en pacientes PPD positivos y pacientes anérgicos de acuerdo con las normas de los Centers for Diseases Control (CDC) de 1991. Los pacientes se distribuyeron de forma aleatoria en dos pautas: pauta de rifampicina a los que se les administraron 300 mg/día de isoniacida y 600 mg/día de rifampicina durante 3 meses, y pauta de isoniacida a los que se les administraron 300 mg/día de isoniacida durante 12 meses. Resultados: Se incluyeron 133 pacientes: 64 en la pauta isoniacida y 69 en la pauta rifampicina. Se toleró mejor la pauta de rifampicina, con un 28 por ciento de efectos adversos frente a un 55 por ciento en la pauta de isoniacida. La hepatotoxicidad fue más frecuente en la pauta de isoniacida, con un riesgo relativo (RR) de 2,2 (intervalo de confianza [IC] del 95 por ciento, 1,23-4,01). La hepatotoxicidad grave, que obligó a suspender el tratamiento, se relacionó con el tiempo de administración del fármaco, siendo más frecuente en la pauta de 12 meses. Se cumplimentó mejor la pauta corta, pero sin diferencias valorables. La incidencia de tuberculosis fue de 4,23 casos por 100 personas-año para la pauta de isoniacida y 2,08 para la pauta de rifampicina, con un riesgo relativo para desarrollar tuberculosis con la pauta de rifampicina de 0,51 (IC del 95 por ciento, 0,09-2,8) frente a la pauta de isoniacida, no estadísticamente significativo. La estancia en prisión se asoció con un riesgo significativo de tuberculosis, independientemente de la pauta de tratamiento (RR = 9,2; IC del 95 por ciento; 1,06-80,2). Conclusiones: En pacientes con infección por el VIH con PPD positivo o anérgicos, la pauta de rifampicina es al menos igual de eficaz para prevenir el desarrollo de tuberculosis que la pauta de isoniacida, y presenta menos efectos adversos (AU)


Subject(s)
Adult , Aged , Male , Female , Humans , Hospital Mortality , Rifampin , Spain , Subarachnoid Hemorrhage , Tuberculosis , Time Factors , Incidence , AIDS-Related Opportunistic Infections , Registries , Prospective Studies , Antibiotics, Antitubercular , Antitubercular Agents , Isoniazid , Liver , Tuberculin Test
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