Search

Einleitung: Das inzidentelle Prostatakarzinom tritt in ca. 10% der BPS-Operationen auf. Für das Festlegen einer individuellen Therapiestrategie ist eine Risikoeinschätzung des zugrundeliegenden Prostatakarzinoms entscheidend. Da keine Leitlinienempfehlung für dieses Scenario existiert, [zum vollständigen Text gelangen Sie über die oben angegebene URL]

Esclerosis múltiple; Brote; Resonancia magnética Esclerosi múltiple; Brot; Imatge per ressonància magnètica Multiple sclerosis; Outbreak; Magnetic resonance imaging Objective To study the clinico-radiological paradox in multiple sclerosis (MS) relapse by analyzing the number and location of gadolinium-enhanced (Gd+) lesions on brain MRI before methylprednisolone (MP) treatment. Methods We analyzed brain MRI from 90 relapsed MS patients in two Phase IV multicenter double-blind randomized clinical trials that showed the noninferiority of different routes and doses of MP administration. A 1.5- or 3-T brain MRI was performed at baseline before MP treatment and within 15 days of symptom onset. The number and location of Gd+ lesions were analyzed. Associations were studied using univariate analysis. Results Sixty-two percent of patients had at least 1 Gd+ brain lesion; the median number was 1 (interquartile range 0–4), and 41% of patients had 2 or more lesions. The most frequent location of Gd+ lesions was subcortical (41.4%). Gd+ brain lesions were found in 71.4% of patients with brainstem-cerebellum symptoms, 57.1% with spinal cord symptoms and 55.5% with optic neuritis (ON). Thirty percent of patients with brain symptoms did not have Gd+ lesions, and only 43.6% of patients had symptomatic Gd+ lesions. The univariate analysis showed a negative correlation between age and the number of Gd+ lesions (p = 0.002). Conclusion Most patients with relapse showed several Gd+ lesions on brain MRI, even when the clinical manifestation was outside of the brain. Our findings illustrate the clinico-radiological paradox in MS relapse and support the value of brain MRI in this scenario. Objetivo Estudiar la paradoja clínico-radiológica en el brote de la esclerosis múltiple (EM) mediante el análisis de lesiones captantes de gadolinio (Gd+) en la RM cerebral antes del tratamiento con metilprednisolona (MP). Métodos Analizamos la RM cerebral basal de 90 pacientes con EM en brote de 2 ensayos clínicos aleatorizados multicéntricos fase IV que demostraron la no inferioridad de diferentes vías y dosis de MP, realizadas antes del tratamiento con MP y en los 15 días siguientes a la aparición de los síntomas. Se analizaron el número y la localización de las lesiones Gd+. Se estudiaron las asociaciones mediante análisis univariado. Resultados El 62% de los pacientes tenía al menos una lesión Gd+ cerebral y el 41% de los pacientes tenía 2 o más lesiones. La localización más frecuente fue la subcortical (41,4%). Se encontraron lesiones Gd+ cerebrales en el 71,4% de los pacientes con síntomas de tronco cerebral o cerebelo, en el 57,1% con síntomas medulares y en el 55,5% con neuritis óptica. El 30% de los pacientes con síntomas cerebrales no tenían lesiones Gd+ y sólo el 4,.6% de los pacientes tenían lesiones Gd+ sintomáticas. El análisis univariante mostró una correlación negativa entre la edad y el número de lesiones Gd+ (p = 0,002). Conclusiones La mayoría de los pacientes en brote mostraron varias lesiones Gd+ en la RM cerebral, incluso cuando la manifestación clínica fue medular u óptica. Nuestros hallazgos ilustran la paradoja clínico-radiológica en el brote de la EM y apoyan el valor de la RM cerebral en este escenario. This work was supported in part by the Ministry of Health of Spain (grant numbers EC07/90278 and EC11/132) and personal grant Rio Hortega CM19/00042 to LMA.

The recent development of highly effective treatments for multiple sclerosis (MS) and the potential risk of infectious complications require the development of prevention and risk minimisation strategies. Vaccination is an essential element of the management of these patients. This consensus statement includes a series of recommendations and practical scenarios for the vaccination of adult patients with MS who are eligible for highly effective immunosuppressive treatments. A formal consensus procedure was followed. Having defined the scope of the statement, we conducted a literature search on recommendations for the vaccination of patients with MS and specific vaccination guidelines for immunosuppressed patients receiving biological therapy for other conditions. The modified nominal group technique methodology was used to formulate the recommendations. Vaccination in patients who are candidates for immunosuppressive therapy should be considered before starting immunosuppressive treatment providing the patient's clinical situation allows. Vaccines included in the routine adult vaccination schedule, as well as some specific ones, are recommended depending on the pre-existing immunity status. If immunosuppressive treatment is already established, live attenuated vaccines are contraindicated. For vaccines with a correlate of protection, it is recommended to monitor the serological response in an optimal interval of 1-2 months from the last dose.

Jose M García-Domínguez,1 María L Martínez-Ginés,1 Olga Carmona,2 Ana B Caminero,3 Daniel Prefasi,4 Jorge Maurino,4 Javier Ballesteros5 On behalf of the W-IMPACT Clinical Investigators 1Department of Neurology, Hospital Universitario Gregorio Marañón, Madrid, Spain; 2Department of Neurology, Hospital de Figueres, Figueres, Spain; 3Department of Neurology, Hospital Nuestra Señora de Sonsoles, Complejo Asistencial de Ávila, Ávila, Spain; 4Medical Department, Roche Farma, Madrid, Spain; 5Department of Neurosciences and CIBERSAM, Universidad del País Vasco, Leioa, Spain Background: Understanding caregiver strain may be crucial to determine which interventions are most needed to mitigate the negative impact of caring for people with multiple sclerosis (MS). The Caregiver Strain Index (CSI) is a brief self-assessment tool for measuring the caregivers’ perceived level of burden. Limited information is available on the psychometric performance of the CSI in MS.Objective: The objective of this study was to assess the factor structure and construct validity of the CSI in MS.Methods: A multicenter, cross-sectional study in adults with relapsing-remitting and primary-progressive MS (McDonald 2010 criteria) was conducted. A non-parametric item response theory (IRT) procedure, Mokken analysis, was conducted to assess the dimensional structure of the CSI. A parametric IRT model for dichotomous responses, Rasch model, was conducted to assess item characteristics. Discriminative validity was assessed comparing the distribution of its overall score between people with mild and moderate-severe disability according to the Expanded Disability Status Scale.Results: A total of 72 MS caregivers were studied. The prevalence of a high level of strain was 23.6% (n=17). Internal reliability was high (Cronbach’s alpha =0.91). According to Mokken analysis, CSI represented a unidimensional construct of caregiver burden although two of the total 13 items (#1 and #13) could not be assigned to any factor by an automatic item selection procedure. Without these items, the scalability moved from a weak (Hi =0.37) to a medium scale (Hi =0.44). However, the item characteristic curve of the Rasch model showed a range of appropriate difficulty and the item and person parameters showed good fit (Andersen likelihood ratio test =18.40, df =11; P-value =0.07; all item values for the infit). The CSI score showed a good discriminative validity between the levels of disability of the care recipient.Conclusion: The CSI questionnaire shows appropriate psychometric characteristics being a useful instrument to assess different aspects of burden in MS caregivers in clinical practice. Keywords: caregivers, multiple sclerosis, psychometrics, caregiver burden, strain

BackgroundIn multiple sclerosis (MS), half of affected people are unemployed within 10years of diagnosis. The aim of this study was to assess the economic impact of MS in adult subjects with relapsing-remitting MS (RRMS) and primary progressive MS (PPMS).MethodsA multicenter, non-interventional, cross-sectional study was conducted. The Expanded Disability Status Scale (EDSS) and the 23-item Multiple Sclerosis Work Difficulties Questionnaire (MSWDQ-23) were used to assess disability and work performance, respectively. Only indirect costs were considered using the human capital method, including work costs. Professional support costs and informal caregivers' costs were also estimated.ResultsA total of 199 subjects were studied (mean age: 43.910.5years, 60.8% female, 86.4% with RRMS). Median EDSS score was 2.0 (interquartile range: 1.0-3.5) and median MSWDQ-23 total score was 31.5 (15.2, 50.0). The number of employed subjects decreased after MS diagnosis from 70.6 to 47.2%, and the number of retired people increased (23.6%). Mean age of retirement was 43.6 +/- 10.5years. Ten percent of the population had sick leaves (absenteeism was seen in 90.9% of the student population and 30.9% of the employed population). Professional support in their daily life activities was needed in 28.1% of subjects. Costs for sick leave, work absenteeism, premature retirement and premature work disability/pensioner were Euro416.6 +/- 2030.2, Euro763.4 +/- 3161.8, Euro5810.1 +/- 13,159.0 and Euro1816.8 +/- 9630.7, respectively. Costs for professional support and informal caregiving activities were Euro1026.93 +/- 4622.0 and Euro1328.72, respectively.Conclusions p id=Par4 MS is responsible for a substantial economic burden due to indirect and informal care costs, even in a population with low physical disability.

129 páginas. Maestría en Diseño. El presente trabajo analizará el cuadrante de Regina mediante instrumentos cuantitativos y cualitativos que permitan identificar los efectos relacionados con el auge en la creación de espacios artísticos y culturales, y se relacionarán con las categorías teóricas urbanas que fundamentan la investigación. Dichas categorías se definirán más adelante en función de las observaciones preliminares realizadas en la zona, y con el estudio de casos análogos alrededor del mundo. Para efectos de esta investigación, el área de estudio será delimitada por las calles de 16 de Septiembre al Norte, 20 de Noviembre al Oriente, Izazaga al Sur y Eje Central al Poniente. Se ha delimitado de esta manera el área de estudio ya que es en este cuadrante donde han proliferado la mayoría de espacios artísticos y culturales del Centro Histórico a raíz de su revitalización.

Background/aim - There are several reports that claim anticipation in complex or polygenic diseases such as multiple sclerosis (MS), Crohn disease or schizophrenia. The aim of the present study was to assess age at onset of MS during the last 60 years in the region of Costa de Ponent (Barcelona, Spain) showing how apparent changes in age at onset between generations can be an artefact of analysis based on cohorts that have not been followed enough time. Methods - The study comprised 1100 patients diagnosed of MS. The method used to correct for follow-up time bias involves constructing comparison cohorts that had been observed for the same amount of time. To ensure equal follow-up times, we restricted our analysis to patients whose onset was by 37 years of age (percentile 75) and were at least 37 years old. We analysed differences in age at onset using log-rank test to compare survival curves estimated by Kaplan-Meier method. Results - Age at onset decreases progressively from older to younger generations. However, when adjustment to equal follow-up time was done, anticipation in age at onset was not found. Conclusion - Anticipation of age at onset is undetectable when adjusted for follow-up time.

In a 6-month, placebo-controlled trial, oral fingolimod (FTY720) 1.25 or 5.0 mg, once daily, significantly reduced MRI inflammatory activity and annualized relapse rate compared with placebo in patients with relapsing multiple sclerosis (MS). The objectives were to monitor the 36-month, interim efficacy and safety results of the ongoing extension of this study. In the extension (months 7—36), placebo-treated patients were re-randomized to either dose of fingolimod; fingolimod-treated patients continued at the same dose. During months 15—24, all patients receiving fingolimod 5.0 mg switched to 1.25 mg. Of the 250 patients who entered the extension study, 173 (69%) continued to month 36. Most patients were free from gadolinium-enhanced lesions (88—89%) or new T2 lesions (70—78%) at month 36. Patients receiving continuous fingolimod treatment had sustained low annualized relapse rates of 0.20—0.21, and 68—73% remained relapse-free at month 36. Over 36 months, nasopharyngitis (34%), headache (30%), fatigue (19%) and influenza (18%) were the most commonly reported adverse events. Pulmonary function remained stable and blood pressure was stable after an initial increase (3—5 mmHg) during the first 6 months of fingolimod treatment; serious adverse events included infections and skin cancer. The low MRI and clinical disease activity at 6 months were maintained at 36 months with fingolimod, which was generally well tolerated by most patients. The efficacy and safety of oral fingolimod are being further evaluated in a large phase III MS study programme.

Objective:: To report the results of a 24-month extension of a phase II trial assessing the efficacy, safety, and tolerability of the once-daily oral sphingosine-1-phosphate receptor modulator, fingolimod (FTY720), in relapsing multiple sclerosis (MS). METHODS:: In the randomized, double-blind, placebo-controlled core study, 281 patients received placebo or FTY720, 1.25 or 5.0 mg/day, for 6 months. During the subsequent dose-blinded extension, patients assigned to placebo were re-randomized to either dose of FTY720; those originally assigned to FTY720 continued at the same dose. Patients receiving FTY720 5.0 mg were switched to 1.25 mg during the month 15 to month 24 study visits. RESULTS:: Of 281 patients randomized in the core study, 250 (89%) entered the extension phase, and 189 (75.6%) received treatment for 24 months. During the core study, FTY720 significantly reduced gadolinium-enhanced (Gd) lesions and annualized relapse rate (ARR) compared with placebo, with no differences between doses. During the extension phase, patients who switched from placebo to FTY720 showed clear reductions in ARR and lesion counts compared with the placebo phase; ARR and lesion counts remained low in patients who continued FTY720 treatment. After 24 months, 79 to 91% of patients were free from Gd lesions and up to 77% of patients remained relapse free. FTY720 was well tolerated; no new safety concerns emerged during months 7 to 24 compared with the 6-month core study. CONCLUSIONS:: Once-daily oral treatment with FTY720, 1.25 or 5.0 mg, for up to 2 years, was well tolerated and was associated with low relapse rates and lesion activity. © 2009 AAN Enterprises, Inc.

The objective of this study is to calculate direct, indirect and intangible costs of a relapse in multiple sclerosis (MS) in our cohort of patients.Data from patient questionnaires, hospital charts, Catalan Public Healthcare System tariffs and Catalan Statistics Institute. We employed a cost-of-illness method. The human capital approach was used to estimate indirect costs, and quality-of-life measurements were used to estimate intangible costs.148 MS patients monitored in our MS-Unit consecutively answered the questionnaire elaborated. We calculated 1,498.5-1,537.9 euros for direct costs (hospital admission and outpatient, respectively) and 1,530.6 euros for indirect costs. We estimated an average total cost of 3,048.8 euros per patient/relapse. We also calculated intangible costs, 539 euros per patient and relapse, which should be added to the previous figure.The total cost of a MS relapse in our population (3,048.8 euros) is lower than the cost reported in the literature. The economic impact of MS is due to its disabling progression rather than to relapses

S. aureus es un patógeno importante en el medio hospitalario y en la comunidad. Analizamos su comportamiento frente a los antimicrobianos. Clasificamos los antimicrobianos según su uso clínico y estructura farmacológica. Estudiamos 30.344 cepas de Staphylococcus aureus procedentes de los centros de salud del Grupo Venezolano de Vigilancia de la Resistencia Bacteriana a los Antimicrobianos (GVRB) realizando antibiogramas según las normas del NCCLS, y utilizando el análisis de series cronológicas, con los siguientes resultados. Antibióticos de primera línea: oxacilina, disminuyó; la variación porcentual fue del 64%, con respecto al primer valor de la serie. Vancomicina disminuyó el 100%. El descenso de la resistencia a oxacilina y vancomicina pareciera depender de las mejoras introducidas en las técnicas de determinación de la resistencia a estos antibióticos. b-lactámicos: ampicilina-sulbactam aumentó un 66,7%; aminoglucósidos: amikacina disminuyó 50% y gentamicina 63,20%. Quinolonas: ciprofloxacina aumentó un 300% y norfloxacina 50%. Otros: todos presentaron descenso. El uso de vancomicina debe reservarse para infecciones severas por cepas de S. aureus con comprobada resistencia a oxacilina. S. aureus is an important pathogen, both in hospitalized subjects and in the community. S. aureus’ antibiotic resistance was analyzed. We grouped the anti-microbial agents according to clinical use and pharmacological structure. We studied 30.344 isolates recuperated from hospital and community infections from 23 bacteriology laboratories registered in the data-base of the Surveillance Program of Bacterial Resistance to Antimicrobials in Venezuela (GVRB). Resistance being determined by the method of disc diffusion, following the NCCLS breakpoints. Results were as follows: first line antibiotics: oxacillin shows descent of 64% of variability according to the initial series value when applying the statistical tools for the Analysis of Chronological Series; vancomycin’s resistance descended 100%. Those descent are probably due to more careful procedures: ampicillin-sulbactam’s resistance raised 66,70%; aminoglycosides: amikacin lowered resistance in 50% and gentamicin in 63,20%; for the quinolones, cyprofloxacin raised values in 300% and norfloxacin in 50%. Among other antimicrobial tested, all of the group have reduced the resistance values. We consider that vancomycin should be reserved exclusively for patients with severe infections by S. aureus isolates where it has been demonstrated resistance to oxacillin.

Entre el 5 y el 10% de los pacientes que ingresan a hospitales de EE UU adquieren una o mas infecciones dentro del hospital. Una cuarta parte de esas infecciones nosocomiales están representadas por infecciones de la Unidad de Cuidados Intensivos (UCI). De estas últimas, el 70% son producidas por microorganismos resistentes a antimicrobianos; constituyendo este último, un problema de salud global por sí solo. El alto grado de resistencia por parte de estos microorganismos es una de las razones más relevantes que contribuyen a incrementar el número de muertes en los casos de infección nosocomial. Los bacilos Gram-negativos son los primeros responsables de infección nosocomial, y entre ellos P. aeruginosa es la primera en frecuencia. La división entre diferentes ecosistemas en el hospital refleja diferentes poblaciones con diferentes características. En este estudio presentamos comparaciones de los porcentajes de resistencia ante ß-lactámicos y aminoglicósidos en P. aeruginosa nosocomial (UCI y cirugía) y comunitaria (COM), en centros médicos de Venezuela, diferenciando los públicos (Hpu) de los privados (Hpri), para el año 2000. Se usó el método de difusión de disco, de acuerdo al NCCLS [National Committe for Clinical Laboratories Standards (Comité Nacional de Estándares para Laboratorios Clínicos)]. Se siguió el programa software WHONET (World Health Organization Net). Se incluyeron todas las cepas reportadas en los diferentes servicios. Se realizó la evaluación estadística por prueba Z (p≤ 0,05). 1. Se muestran diferencias significativas en la frecuencia de resistencia (fr) en P. aeruginosa nosocomial entre UCI/COM en Hpu (mayores diferencias: piperacilina, 44/8% y gentamicina, 39/10%), entre UCI/CI (la mayor ≠ piperac, 44/23% y la menor cefepime, 10/8%). 2. Hay diferencias significativas entre la frb de CI de Hpu/Hpri, siendo las mayores ≠ : piper, 23/15%; piper-tazob, 11/2%; tobra, 25/2%; netilm, 25/8%; genta, 37/22%. No se observaron diferencias significativas entre UCI de Hpu/Hpri. 3. No hubo diferencias en la frb ante Amg para P. aeruginosa entre UCI/Ci de Hpu, pero sí de Hpri (mayores ≠ : tobra, 40/1 y netilm, 40/9). 4. Tiene relevancia las diferencias observadas ante ß-L entre UCI/CI y entre éstos y la comunidad, tanto en Hpu como en Hpri. Estas observaciones ponen en evidencia la importancia del medio ambiente en la dinámica de la resistencia, y por tanto la necesidad de poner en práctica, y de rutina, medidas especiales de asepsia y antisepsia. Por otra parte, y debido a la gravedad y frecuencia tanto de las infecciones como de la resistencia producidas por P. aeruginosa en este medio ambiente, se impone el uso en estos pacientes de medidas farmacológicas especiales, para asegurar el éxito de la terapia antimicrobiana, tanto para curar la infección como para prevenir la aparición de cepas resistentes. Currently, between 5 and 10 percent of patients admitted to acute care hospitals acquire one or more infections in the hospital. A quarter of these nosocomial infections are originated in the intensive care unity (ICU), 20% of these are produced by antimicrobial agents resistant microorganisms; which is a global health problem by it self. This high degree of resistance is one of the reasons which contribute to increases the numbers of death by nosocomial infections. Gram-negative bacilli are the principals responsible of nosocomial infections, and among them, the first in frequency is P. aeruginosa. We compare the percentages of resistance to either ß-lactams or aminoglycosides in nosocomial (ICU and surgery=SU) and communitarian (Com) P. aeruginosa, at the Venezuelan Medical Centres, evaluating the differences between public (puC) and privates centres (priC) for the year 2000. It was used diffusion disk, according NCCLS. The software program WHONET was used. Statistical significance (p≤0,05-0,01) was determined by "Z". 1. We show significant differences in the frequency of resistance to ß-lactams (frb) in nosocomial P. aeruginosa from puC, between ICU/Com (major differences: piperacillin 44/ 8% and genta 39/ 10%), and between ICU/ Su (the major ≠ piperacillin 44/23%, and the minor ≠ cefepime 10/8%). 2. We observe a significant difference in frb, between puC and priC, in infections of patients from Su (majors ≠ : piper 23/15%, piper-tazob 11/2%, tobra 25/2%, netilm 25/8%, genta 37/22%, but not in those from ICU. 3. We did not found any difference in the P. aeruginosa resistant isolated to aminoglycosides between ICU and Su at the puC, but at the priC majors ≠ : tobra 40/1% and netilm 40/9%. 4. The differences in the fr to ß-lactams showed by P. aeruginosa infection are noteworthy between ICU and Su and between these and Com, either for puC or for priC. These observations support the implication of the environment, and specially the hospital environment in the dynamic of bacterial resistance, and then the necessity to take in account specials routine habit of asepsis and antisepsis measures. Moreover and due to the seriousness and high frequency, either for the infections or for the resistance produced by P. aeruginosa in this environment, demand the use in these patients, of specials pharmacological strategies; in order to ensure the success of the antimicrobial therapy, either to cure the infection or to prevent resistance

El objetivo de este trabajo fue estudiar los cambios en la resistencia a los antimicrobianos de aislados de Staphylococcus aureus (SA) provenientes de muestras clínicas recuperadas en tres centros de salud del área metropolitana de Caracas durante el período 1995-2002. Los datos se obtuvieron de los Servicios de Bacteriología del Hospital Vargas (HV), Hospital Clínico Universitario (HCU) y Centro Médico (CM), participantes del Grupo Venezolano de Vigilancia de la Resistencia Bacteriana a los Antimicrobianos (GVRB). Analizamos 6.291 cepas de S. aureus mediante pruebas de sensibilidad a los antimicrobianos por el método de difusión en agar. Los rangos de resistencia registrados fueron: HV: oxacilina (Ox) 9 a 33%, vancomicina (Van) 0 a 1%, gentamicina (Gen) 2 a 16%, ciprofloxacina (Cip) 1 a 13%, eritromicina (E)10 a 25% y trimetoprim-sulfametoxazol (SXT) 2 a 13%. HUC: Ox 3 a 18%, Van 0 a 2%, Gen 5 a 33%, Cip 3 a 14%, E 10 a 30% y SXT 1 a 10%. CM: Ox 4 a 20%, Van 0%, Gen 5 a 10, Cip 2 a 14%, E 16 a 29% y SXT 1 a 6%. Los porcentajes de resistencia de este patógeno en estos centros, en general, reflejan una tendencia al aumento, especialmente ciprofloxacina, eritromicina y trimetoprim-sulfametoxazol. Sin embargo, los valores reportados para oxacilina son inferiores a los hallados en países asiáticos, Europa, EE UU y otros países de América Latina. We studied the changes in antimicrobial resistance of Staphylococcus aureus (SA) isolates from three Health Institutions from the metropolitan area of Caracas during the period between 1995-2002. SA isolates were recuperated from the Bacteriology Services from Hospital Vargas (HV), Hospital Clínico Universitario (HCU) and Centro Médico (CM) participants of the venezuelan group for the surveillance of bacterial antimicrobial resistance (GVRB). The sensibility to antimicrobials of 6,291 isolates of SA was analyzed by the agar diffusion method. Percentages of resistance found were as follows: HV: oxacillin (Ox) reported values between 9 and 33%, vancomycin (Van) 0 to 1%, gentamicin (Gen) 2 to 16%, ciprofloxacin (Cip) 1 to 13%, erytromycin (E) 10 to 25% and trimethoprim-sulfamethoxazole (SXT) 2 to 13%. HUC: Ox 3 to 18%, Van 0 to 2%, Gen 5 to 33%, Cip 3 to 14%, E 10 to 30% and SXT 1 to 10%, and in CM: Ox 4 to 20%, Van 0%, Gen 5 to 10, Cip 2 to 14%, E 16 to 29% and SXT 1 to 6%. The percentages of antimicrobial resistance for these isolates, in general, show tendency to increase, specially for Cip, E and SXT. Notwithstanding, the values found are lower than those reported in countries of Asia, Europe, USA and other Latinamerican countries.

Al abordar el tema de la infección producida por bacterias resistentes, es conveniente considerar al hospital y a la comunidad como ecosistemas separados. Esta división refleja diferentes poblaciones, presiones de selección, reservorios y otros factores que son importantes en la aparición, persistencia y transmisión de organismos resistentes a antimicrobianos. En este ecosistema hospitalario tiene especial relevancia la infección y resistencia de bacilos Gram-negativos. Actualmente son ellos los primeros responsables de infección nosocomial y en especial Pseudomonas aeruginosa. El problema de la resistencia bacteriana existe en todo el mundo, y está relacionado con infecciones nosocomiales y comunitarias en los países en desarrollo, donde el problema reviste dimensiones preocupantes. En este estudio presentamos las tendencias de la resistencia de P. aeruginosa nosocomial y comunitaria en hospitales de Venezuela, diferenciando los públicos de los privados. Desde 1988, el Grupo Venezolano de Vigilancia de la Resistencia Bacteriana a los Antimicrobianos, que agrupa a 29 instituciones de salud de siete estados, está a cargo de analizar y publicar resultados de resistencia bacteriana a los antimicrobianos (entre los que se encuentran ß-lactámicos, aminoglicósidos, quinolonas), en bacterias aisladas de pacientes con infecciones hospitalarias y de la comunidad. Se usó el método de difusión con discos, de acuerdo a NCCLS. Se siguió el programa software WHONET (World Health Organization Net). Se realizó la evaluación estadística por análisis de las diferencias entre dos porcentajes. Se muestran diferencias importantes entre la resistencia de P. aeruginosa nosocomial y comunitaria. También hay diferencias entre los resultados provenientes de hospitales públicos y privados. Se muestra la tendencia, a partir de 1998, a disminuir el porcentaje de la resistencia; esto es más evidente en centros privados. Nuevos antibióticos con nuevos mecanismos de acción y, a más largo plazo, las nuevas tecnologías, podrían solucionar la situación actual. Sin embargo, las herramientas más importantes con las que contamos son la prevención y los antimicrobianos, por lo que debemos usarlos adecuadamente. In order to approach the infection produced by resistant bacteria, it is convenient to consider the hospital and the community as two separate ecosystems. This division reflect different population, selection pressure, reservoirs and others factors which are important in the development, persistence and transmission of resistant organism to antimicrobials. This hospital ecosystem has special relevance in the infection and resistance of gramnegative aerobic bacilli. Today they are the main responsible of nosocomial infection, with special reference to Pseudomonas aeruginosa. The problem of infection by resistant bacteria occur in the whole world; related to nosocomial as well as communitarian infection in developing countries, where the problem has important dimension. In this study we present the tendencies of resistance in P. aeruginosa, nosocomial and communitarian in Venezuelan medical centres, at the same time we make difference between publics and private hospitals. Since 1988, The Venezuelan Group of Bacterial Resistance to antimicrobials, with 29 health institution in the country; identify, analyses and publish data on bacterial resistance of isolates from patients with bacterial infection coming from hospitals and the community. It was used diffusion disk, according NCCLS. The software program WHONET (WORLD HEALTH ORGANIZATION NET) was used. Statistical analyses was made by evaluating the difference among percentages of resistance. We show important differences in the resistance of P. aeruginosa nosocomial and communitarian. We also established differences between the resistance arising in public hospitals and private hospitals. Since 1998, we show the tendency in decreasing of resistance; this tendency is more evident in private hospitals. New antimicrobials and new mechanism of action, and in the future the new technology will solve today’s problem. However, the most important tools we have today are prevention and antimicrobials, and we must make them suitable.

Con la aparición de los antimicrobianos, hace más de 60 años, cambió el curso de la historia de las enfermedades infecciosas; es así como la tasa de mortalidad disminuyó de 797 por cada 100.000 habitantes en 1900 a 36 por cada 100.000 habitantes para 1980. Sin embargo, a pesar de los éxitos alcanzados por las medidas sanitarias preventivas y por el uso de fármacos antimicrobianos, siempre hubo preocupación, debido a que la introducción de un nuevo fármaco antimicrobiano iba seguida de resistencia bacteriana (RB) al mismo. De esta forma se plantean estrategias para la prevención de la RB, tanto en el ecosistema hospitalario como en el comunitario. Algunas de las estrategias que deben ser tomadas en consideración en la comunidad son: control sobre el libre expendio de antimicrobianos, políticas sanitarias gubernamentales relacionadas con las medidas higiénicas, control de epidemias, vacunaciones y control del uso de antimicrobianos en veterinaria, entre otros. En cuanto a las estrategias para el control de la RB en el medio hospitalario se hace énfasis en las medidas de asepsia y antisepsia que deben practicarse a diario en los hospitales por el equipo de salud. Además, se mencionan seis puntos importantes a tener en consideración en ambos ecosistemas. Por último, se dan recomendaciones, de manera de poner en práctica algunos conceptos farmacológicos: 1) En lo posible usar antimicrobianos de espectro reducido; 2) Usar combinaciones de antimicrobianos sólo cuando se justifique; 3) Usar antimicrobianos bactericidas; 4) Evitar la selección de terapia antimicrobiana empírica; 5) Restringir el uso profiláctico de los antimicrobianos; 6) Conocer y evaluar el concepto PK/PD en sus diferentes expresiones, de manera de asegurar el uso de dosis y tiempos adecuados, que repercutirá con mayor probabilidad de cura del paciente y menor posibilidad de aparición de resistencia; 7) Estar actualizado en los avances quimioterapéuticos. Conclusiones: Las herramientas más importantes con las que contamos para controlar la RB son: la prevención de las infecciones y el uso adecuado de antimicrobianos. Sólo a través de una comisión de control de infecciones nosocomiales se podrá prevenir y controlar el problema, particularmente el relacionado con la RB a los antimicrobianos, el cual es considerado un "problema de Salud Pública" en todo el mundo.

Los ß-lactámicos, primeros antibióticos introducidos para uso en clínica, siguen siendo los más usados. También es frecuente el desarrollo de resistencia a ellos, la cual fue identificada inmediatamente después de la introducción de la penicilina. El mecanismo de resistencia más frecuente en bacilos Gram-negativos a los ß-lactámicos es la producción de ß-lactamasas, y su forma de transmisión es a través de plásmidos y cromosomas. Los bacilos Gram-negativos aeróbicos son los principales responsables de infección nosocomial. Hemos publicado los valores de resistencia de éstos ante ß-lactámicos, haciendo un diagnóstico de la situación a nivel nacional. Además de seguir su evolución durante la década 1988-1998, estudiamos los cambios producidos sobre la evolución de la resistencia, en presencia de inhibidores de ß-lactamasas. Desde 1988, el Grupo Venezolano de Vigilancia de la Resistencia Bacteriana, cuyos miembros pertenecen a 29 instituciones de salud de siete estados, está a cargo de analizar y publicar resultados de resistencia bacteriana a antimicrobianos de bacterias aisladas de pacientes con infecciones hospitalarias y de la comunidad. Se usó el método de difusión de disco, de acuerdo a las normas de la NCCLS. Se siguió el programa software WHONET (World Health Organization Net). Las diferencias de sensibilidad entre el ß-lactámico y el ß-lactámico más el inhibidor de ß-lactamasas son: 1. Piperacilina versus piperacilina/tazobactam: entre el 10 y el 30% para la mayoría de los gérmenes estudiados, excepto para E. coli (45%) y Serratia sp. (60%). 2. Ampicilina versus ampicilina/sulbactam: entre el 10 y el 30%. 3. Cefoperazona versus cefoperazona/sulbactam: entre el 5 y el 25%. Como era de esperar, la resistencia de bacilos Gram-negativos aeróbicos a betalactámicos en presencia del inhibidor de ß-lactamasas es menor que ante el ß-lactámico solo; además, esta diferencia se hace mayor con el tiempo. Las diferencias entre las dos series durante el primer año (1988) son menores que las encontradas entre las series durante el último año (1998) en muchas de las bacterias estudias. Estos resultados son relevantes especialmente si recordamos el mecanismo de inductores de betalactamasas que se les ha atribuido. The ß-lactams antimicrobial were the first to be used, and today they still are the most frequently used. Among the bacteria responsible of high resistance to ß-lactams are gramnegative rods; the most frequent mechanism is the production of ß-lactamase We follow the trends of resistance of Gram-negative rods to ß-lactams alone and with ß-lactamase-inhibitors during the decade 1988-1998. Since 1988, The Venezuelan Group of Vigilance of the Bacterial Resistance, with 29 health institution in the country; they identify, analyze and publish data on bacteria resistance of isolates from patients with bacterial infection coming from hospitals and the community. It was used diffusion disk, according NCCLS. The software program WHONET (World Health Organization Net) was used. The difference in sensitivity among ß-lactam and ß-lactam/ß-lactamase-inhibitor are: 1. Piperacillin versus piperacillin/tazobactam: between 10 and 30% of resistance for most isolated, except for E. coli (45%) and Serratia sp. (60%). 2. Ampicillin versus ampicillin/sulbactam: between 10 and 30%. 3. Cefoperazone versus Cefoperazone/sulbactam: between 5 and 25%. How is expected gramnegative rods resistance to ß-lactams with a betalactamase-inhibitor (ß-L-I), is lower than the ß-lactam alone; furthermore the difference between them, grows higher with time. This results are relevant, since ß-L-I are described as ß-lactamase inductors.

Describimos y analizamos la evolución de la resistencia de Klebsiella pneumoniae a los antimicrobianos durante el período 1989-1998, en Venezuela. Estudiamos 14.970 aislados de K. pneumoniae procedentes de los centros de salud que conforman el GVRB, realizando antibiograma según normas del NCCLS, con los siguientes resultados: para betalactámicos clásicos, ampicilina progresa del 94% en 1989 al 97% en 1998; ampicilina-sulbactam y amoxicilina-clavulánico se mantienen entre el 30-40%; carbenicilina reporta hasta el 98%; piperacilina 40-50%; y piperacilina-tazobactam entre el 8 y el 16%. Su comportamiento frente a cefalosporinas: cefotaxima ha tenido un ascenso rápido, ubicándose cerca del 70%; ceftriaxona reportó hasta el 59%; ceftazidima llegó hasta el 53%; cefoperazona cercano al 30%; y cefoperazona-sulbactam

La resistencia a los antibióticos ß-lactámicos es debida fundamentalmente a la producción de ß-lactamasas por parte de los bacilos gramnegativos. Han sido identificadas más de 200 ß-lactamasas, de esta manera hemos tenido un aumento en la resistencia a ß-lactámicos efectivos contra los bacilos gramnegativos, los cuales han estado en uso desde 1963. Para combatir el aumento de la resistencia bacteriana a antibióticos, se requiere de un adecuado seguimiento de ésta localmente. La información debe provenir del análisis detallado de los resultados de los test de suceptibilidad que son hechos rutinariamente para guiar el tratamiento de infecciones en cada paciente. De esto se desprende la importancia de la vigilancia de la resistencia bacteriana a antibióticos. Materiales y Métodos: Desde 1988, el Grupo Venezolano de Resistencia Bacteriana (GVRB), desde 25 instituciones de salud y perteneciente a siete estados, están a cargo de realizar, analizar y publicar los resultados de la resistencia a antibióticos, proveniente de gérmenes aislados de pacientes con infecciones adquiridas en la comunidad y en los hospitales. Se usó el método de difusión de discos de acuerdo al NCCI; el programa WHONET de la Organización Mundial de la Salud; El análisis estadístico se realizó por c² . Resultados y Conclusiones: A) El aumento de resistencia ante 1) cefotaxima es: E.coli 34%, E.aerógenes 13%, E.cloacae 10%, K.pneumoniae 57%, 2) ceftazidima: E.coli 16%, K.pneumoniae 30%, P.aeruginosa 20%; 3) ceftriaxona: E.coli 17%, E.aerógenes 5%, K.pneumoniae 43%. 4) cefoperazona-sulbactam: no es significativo el aumento. B.-La resistencia ante: 5) cefepime: P.eruginosa 10-14%, Acinetobacter sp.35 %, otros alrededor de 5 %. 6) piperacilina-tazobactam: la resistencia es de 5 to10 %, excepto para el Acinetobacter sp. (40 %); 7) La resistencia de los bacilos gramnegativos aeròbicos ante los carbapenemos imipenem y meropenem es baja, excepto para P.aeruginosa (10-15 %) y Acinetobacter sp. (25-35%). Durante la década hubo un aumento de la resistencia de los bacilos gramnegativos ante la mayoría de los ß-lactámicos estudiados. Es importante implementar medidas especiales en el uso de los antibióticos y continuar los programas de vigilancia de la resistencia bacteriana ante los antibióticos. La segunda mitad del siglo XX ha sido la edad de oro para los antibióticos, sin embargo el futuro parece incierto. Resistance to ß-lactam antibiotics is mainly due to production of ß-lactamases by gramnegative bacilli. Over 200 ß-lactamases have been identified to date, therefore we have had increased resistance to ß-lactams effective against gramnegative bacilli, which have been in use since 1963. Combating the surge in antibiotic-resistant (AR) bacteria requires tracking of local resistance. The information must come from ongoing detailed analysis of the results of antimicrobial susceptibility tests that are done routinely to guide the treatment of infections in individual patients. This is the importance of AR surveillance. Materials and Methods: Since 1988 Venezuelan group of Bacterial Resistance (GVRB), in 25-health institutions from seven states are in charge of analysing and publishing AR data of bacterial isolates, proceeding from patients with infection acquired in the community and hospitals. Methods of disc diffusion according to NCCI; WHONET software program (Word Health Organisation NET); statistical analysis by c². Results and Conclusions: A.-The increase of resistance during the decade to: 1) cefotaxime is: E.coli 34%, E.aerogenes 13%, E.cloacae 10%, K.pneumoniae 57%, 2) ceftazidime: E.coli 16%, K.pneumoniae 30%, P.aeruginosa 20%; 3) ceftriaxona: E.coli 17%, E.aerógenes 5%, K.pneumoniae 43%. 4) cefoperazone-sulbactam: no significance in the increase. B.-Resistance to: 5) cefepime:P. aeruginosa 10-14%, Acinetobacter sp.35 %, others around 5 %. 6) piperaciline-tazobactam: resistance is 5 to10 %, except Acinetobacter sp. (40 %); 7) the results of GVRB to imipenem and meropenem is low except P.aeruginosa (10-15 %) and Acinetobacter sp. (25-35%). During the decade there was an increase in GVRB to most ß-lactams. The second half of the 20th century has been a golden age of antibiotics but the outlook is uncertain.

Resumen Se analizó la resistencia de 659 cepas de Serratia marcescens a los antimicrobianos mediante el método de difusión en agar, siguiendo las normas de eficiencia de la NCCLS, obtenidas del Proyecto de Vigilancia de la Resistencia a los Antimicrobianos en Venezuela durante los años 1995-1998. La resistencia de S. marcescens a las penicilinas presentó un porcentaje elevado para la ampicilina y sulbactam-ampicilina, siendo 84-92% y 73-80% respectivamente, correspondiéndole a la piperacilina un porcentaje menor (13-26%). A las cefalosporinas de 3era. generación S. marcescens presentó la siguiente resistencia: a ceftriaxona, 20%; a ceftazidima, 15%; a cefotaxima, 23%; a cefoperazona, 16%. La cefepima (cefalosporina de 4ta. generación) presentó un porcentaje de resistencia bajo (6%). La resistencia a la gentamicina y a la amikacina es alta, 21 y 19% respectivamente, siendo menor para la tobramicina (11%). El porcentaje de resistencia a las quinolonas es bajo, oscilando entre 2 y 5%. El incremento de la resistencia a las cefalosporinas de 3era. generación se debe a la adquisición de betalactamasas de espectro expandido Abstract We studied the resistance to antimicrobial agents of 659 strains of Serratia marcescens from the Survey Project Control of Resistance to antimicrobial agents in Venezuela during the period 1995 to 1998, following the agar diffusion method according to the NCCLS standards. Serratia marcescens showed a high percentage of resistance to ampicillin and ampicillin-sulbactam, 84-92% and 73-80% respectively; to piperacillin there was a much lower percentage (13-26%). To the third generation cephalosporins the resistance reported was as follows: ceftriaxone 20%, ceftazidime 15%, cefotaxime 23% and cefoperazone 16%. To cefepime, a fourthgeneration cephalosporin, there was reported a low percentage of resistance (6%). The resistance reported to gentamicin and amikacine is high (21 and 19%) respectively, and lower for tobramycin (11%). The resistance to quinolones is low, with values ranging from 2 to 5%. The higher percentage of resistance reported for third generation of cephalosporins it is due to the production of b-lactamases of expanded-spectrum

Resumen Se realizó una revisión de la resistencia de 20.030 cepas de Pseudomonas aeruginosa a la gentamicina (GM), tobramicina (NN) y amikacina (AN), mediante el método de difusión en agar, siguiendo las normas de eficiencia de la NCCLS, obtenidas del Proyecto de Vigilancia de la Resistencia a los Antimicrobianos en Venezuela durante los años 1988-1998. En 1988, el menor porcentaje de resistencia correspondió a AN (19%), seguido de NN (23%) y GM (27%). En 1992 se aprecia una disminución en los porcentajes de resistencia, siendo el más bajo para NN (12%). Para los años 1996 y 1997, se refleja un aumento en los porcentajes de resistencia, y para el año 1998 éstos vuelven a disminuir, manteniendo los porcentajes de resistencia similares a los del año 1988. La elevada resistencia de Pseudomonas aeruginosa a estos aminoglicosidos es parecida a la encontrada en estudios realizados en otros países Abstract We studied the resistance to antimicrobial-agents of 20.030 strains of Pseudomonas aeruginosa from The Survey Project for Control of Resistance to antimicrobial-agents in Venezuela during the period 1988-1998, to gentamicin (GM), tobramycin (NN) and amikacin (AN) by the diffusion agar technique, following the NCCLS standards. In 1988, the lower percentage of resistance was for AN (19%) followed by NN (23%) and GM (27%). In 1992 we could appreciate a reduction of the resistance and the lower corresponds to NN (12%). For the years 1996 and 1997 we can evidence a rise in resistance values and for 1998 they show a reduction with similar values as for 1988. The higher resistance reported for Pseudomonas aeruginosa to aminoglycosides it is similar to the findings in other countries

The first epidemiological studies on multiple sclerosis (MS) around the world pictured a north to south latitudinal gradient that led to the first genetic and environmental pathogenic hypothesis. MS incidence seems to be increasing during the past 20 years based on recent data from prospective studies performed in Europe, America and Asia. This phenomenon could be explained by a better case ascertainment as well as a change in causal factors. The few prospective studies in our area together with the increase in the disease in other regions, justifies an epidemiological MS project in order to describe the incidence and temporal trends of MS.A prospective multicenter MS registry has been established according to the actual requirements of an epidemiological surveillance system. Case definition is based on the fulfillment of the McDonald diagnostic criteria. The registry setting is the geographical area of Cataluna (northeastern Spain), using a wide network of hospitals specialized in MS management.Recent epidemiological studies have described an increase in MS incidence. In order to contrast this finding in our area, we consider appropriate to set up a population based registry.