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In this study we evaluated the outcomes of non-clinical toxicity studies of various SARS-CoV-2 vaccines produced with different manufacturing technologies, with focus on Repeated Dose Toxicity (RDT) and Developmental and Reproductive Toxicity (DART) studies. We found that RDT and DART studies at doses relevant for human treatment showed no adverse effects while remaining observations were expected findings including local reactogenicity, immune response and macroscopic findings at the injection site. We have also reviewed the European Medicines Agency (EMA) nonclinical assessment reports for market authorization. Regardless of utilized vaccine manufacturing technology EMA assessment of the non-clinical studies consisted most frequently of comments related to study design, species selection and missing data. Sponsors have often submitted platform studies (vaccine studies with the same technology/construct but using other antigens) as supplementary data. Animal model-based toxicity testing has shown rather small effects, which have been never serious adverse effects. The translational value to support clinical development is mainly to inflammatory effects, indicative of the primary action of the vaccines. From a 3R perspective supportive platform technology data consisting of previously executed RDT and DART studies from the same platform technology are encouraged to be implemented in the vaccine assessment process.
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Vacunas contra la COVID-19 , COVID-19 , Animales , Humanos , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/toxicidad , SARS-CoV-2 , Pruebas de Toxicidad , VacunasRESUMEN
Endoscopic resection (ER) is an important diagnostic step in management of patients with early Barrett's esophagus (BE) neoplasia. Based on ER specimens, an accurate histological diagnosis can be made, which guides further treatment. Based on depth of tumor invasion, differentiation grade, lymphovascular invasion, and margin status, the risk of lymph node metastases and local recurrence is judged to be low enough to justify endoscopic management, or high enough to warrant invasive surgical esophagectomy. Adequate assessment of these histological risk factors is therefore of the utmost importance. Aim of this study was to assess pathologist concordance on these histological features on ER specimens and evaluate causes of discrepancy. Of 62 challenging ER cases, one representative H&E slide and matching desmin and endothelial marker were digitalized and independently assessed by 13 dedicated GI pathologists from 8 Dutch BE expert centers, using an online assessment module. For each histological feature, concordance and discordance were calculated. Clinically relevant discordances were observed for all criteria. Grouping depth of invasion categories according to expanded endoscopic treatment criteria (T1a and T1sm1 vs. T1sm2/3), ≥1 pathologist was discrepant in 21% of cases, increasing to 45% when grouping diagnoses according to the traditional T1a versus T1b classification. For differentiation grade, lymphovascular invasion, and margin status, discordances were substantial with 27%, 42%, and 32% of cases having ≥1 discrepant pathologist, respectively. In conclusion, histological assessment of ER specimens of early BE cancer by dedicated GI pathologists shows significant discordances for all relevant histological features. We present propositions to improve definitions of diagnostic criteria.
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Adenocarcinoma , Esófago de Barrett , Neoplasias Esofágicas , Esófago de Barrett/cirugía , Consenso , Neoplasias Esofágicas/cirugía , Esofagoscopía , HumanosRESUMEN
We studied the use of the 3 commonly used reproductive hormones, namely prostaglandins, GnRH, and progesterone, and associated herd-level factors on 760 Dutch dairy farms from 5 veterinary clinics. From 2017 to 2019 we collected data on the sales of reproductive hormones, converted this data into the number of reproductive hormone doses conducted, and expressed this as the annual number of reproductive hormone doses per 100 adult dairy cows. Additional herd-level information was available for 2019. Due to the excess of zeros in the data set (i.e., a substantial number of farms did not use any hormones), we used a zero-inflated negative binomial model to identify related herd-level factors for the use of reproductive hormones. In the entire study period of 2017 to 2019, 5.8% of the dairy farms did not use any reproductive hormones, with the proportion of nonusers varying between 0.0 and 10.3% per veterinary clinic. This proportion was around 13.5% on an annual basis. Prostaglandins were the most frequently used reproductive hormone in Dutch dairy cows (62.9%), followed by GnRH (33.1%) and progesterone (4.0%). Furthermore, participating in a veterinary herd health management program had a significant effect on reproductive hormone use. These farms used more reproductive hormones than farms that did not participate in a herd health management program and were less represented in the group of nonuser farms. Technologies, such as pedometers and automatic milking systems, also had an effect on reproductive hormone use. The presence of pedometers or activity monitors did not reduce the use of the reproductive hormones but was associated with a greater frequency of users. Farms with an automatic milking system used more reproductive hormones than farms with a conventional milking system. With this study, we have made a first step in achieving transparency in the Dutch dairy industry by providing an objective overview of reproductive hormone use on Dutch dairy farms and identifying associations with some herd-level factors.
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Industria Lechera , Leche , Animales , Bovinos , Granjas , Femenino , Hormonas , ReproducciónRESUMEN
AIMS: The effects of biologics on reproduction/lactation are mostly unknown although many patients that receive biologics are women of reproductive age. The first objective of this study was to investigate the publicly available data on pregnancy/lactation before and after marketing authorization in Europe of biologics for the indications of rheumatologic inflammatory autoimmune diseases and inflammatory bowel disease. Secondary objectives included the assessment of the clinical relevance of the provided data and comparison of initial and post-authorization data. METHODS: Initial and post-authorization data were extracted from the European Public Assessment Reports and the latest versions of Summary of Product Characteristics using publicly available documents on the European Medicines Agency's website. Four sections were categorized regarding pregnancy outcomes: pre-clinical/animal studies, human female fertility, pregnancy-related outcomes and congenital malformations in the human fetus. Three sections were categorized regarding lactation outcomes: pre-clinical/animal studies, excretion in human breast milk and absorption in children through breastfeeding. The clinical applicability of each category was scored by specified criteria, based on scientific literature, and further as defined by the authors. RESULTS: For the 16 included biologics, post-authorization data were delivered only for adalimumab, certolizumab pegol, etanercept and infliximab. For the 12 remaining biologics limited data on pregnancy and lactation during the post-marketing period of 2-21 years were available. CONCLUSIONS: In this article several suggestions are provided for improving a multidisciplinary approach to these issues. The initiation of suitable registries by marketing authorization holders and data transparency for clinicians and academics are highly endorsed.
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Productos Biológicos , Lactancia Materna , Adalimumab , Animales , Niño , Europa (Continente) , Femenino , Humanos , Lactancia , EmbarazoRESUMEN
Pluripotent stem cells offer the potential for an unlimited source for cell therapy products. However, there is concern regarding the tumorigenicity of these products in humans, mainly due to the possible unintended contamination of undifferentiated cells or transformed cells. Because of the complex nature of these new therapies and the lack of a globally accepted consensus on the strategy for tumorigenicity evaluation, a case-by-case approach is recommended for the risk assessment of each cell therapy product. In general, therapeutic products need to be qualified using available technologies, which ideally should be fully validated. In such circumstances, the developers of cell therapy products may have conducted various tumorigenicity tests and consulted with regulators in respective countries. Here, we critically review currently available in vivo and in vitro testing methods for tumorigenicity evaluation against expectations in international regulatory guidelines. We discuss the value of those approaches, in particular the limitations of in vivo methods, and comment on challenges and future directions. In addition, we note the need for an internationally harmonized procedure for tumorigenicity assessment of cell therapy products from both regulatory and technological perspectives.
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Carcinogénesis/patología , Tratamiento Basado en Trasplante de Células y Tejidos/efectos adversos , Tratamiento Basado en Trasplante de Células y Tejidos/normas , Guías de Práctica Clínica como Asunto , Animales , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Consenso , Necesidades y Demandas de Servicios de Salud , Humanos , Técnicas In Vitro , Pruebas de Mutagenicidad/métodos , Pruebas de Mutagenicidad/normas , Células Madre Pluripotentes/fisiología , Guías de Práctica Clínica como Asunto/normasRESUMEN
We present simulation results quantitatively showing that circularly polarized light persists in transmission through several real-world and model fog environments better than linearly polarized light over broad wavelength ranges from the visible through the infrared. We present results for polydisperse particle distributions from realistic and measured fog environments, comparing the polarization persistence of linear and circular polarization. Using a polarization-tracking Monte Carlo program, we simulate polarized light propagation through four MODTRAN fog models (moderate and heavy radiation fog and moderate and heavy advection fog) and four real-world measured fog particle distributions (Garland measured radiation and advection fogs, Kunkel measured advection fog, and Sandia National Laboratories' Fog Facility's fog). Simulations were performed for each fog environment with wavelengths ranging from 0.4 to 12 µm for increasing optical thicknesses of 5, 10, and 15 (increasing fog density or sensing range). Circular polarization persists superiorly for all optical wavelength bands from the visible to the long-wave infrared in nearly all fog types for all optical thicknesses. Throughout our analysis, we show that if even a small percentage of a fog's particle size distribution is made up of large particles, those particles dominate the scattering process. In nearly all real-world fog situations, these large particles and their dominant scattering characteristics are present. Larger particles are predominantly forward-scattering and contribute to circular polarization's persistence superiority over broad wavelength ranges and optical thicknesses/range. Circularly polarized light can transmit over 30% more signal in its intended state compared to linearly polarized light through real-world fog environments. This work broadens the understanding of how circular polarization persists through natural fog particle distributions with natural variations in mode particle radius and single or bimodal characteristics.
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We find for infrared wavelengths that there are broad ranges of particle sizes and refractive indices that represent fog and rain, where circular polarization can persist to longer ranges than linear polarization. Using polarization tracking Monte Carlo simulations for varying particle size, wavelength, and refractive index, we show that, for specific scene parameters, circular polarization outperforms linear polarization in maintaining the illuminating polarization state for large optical depths. This enhancement with circular polarization can be exploited to improve range and target detection in obscurant environments that are important in many critical sensing applications. Initially, researchers employed polarization-discriminating schemes, often using linearly polarized active illumination, to further distinguish target signals from the background noise. More recently, researchers have investigated circular polarization as a means to separate signal from noise even more. Specifically, we quantify both linearly and circularly polarized active illumination and show here that circular polarization persists better than linear for radiation fog in the short-wave infrared, for advection fog in the short-wave and long-wave infrared, and large particle sizes of Sahara dust around the 4 µm wavelength. Conversely, we quantify where linear polarization persists better than circular polarization for some limited particle sizes of radiation fog in the long-wave infrared, small particle sizes of Sahara dust for wavelengths of 9-10.5 µm, and large particle sizes of Sahara dust through the 8-11 µm wavelength range in the long-wave infrared.
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Insulin analogues are widely used in clinical practice. Modifications on the insulin molecular structure can affect the affinity and activation towards two closely related receptor tyrosine kinases: the insulin receptor (INSR) and the insulin-like growth factor 1 receptor (IGF1R). A switch towards higher IGF1R affinity is likely to emphasize mitogenesis rather than glucose metabolism. Relevant well-validated experimental tools to address the insulin analogue activation of either INSR or IGF1R are missing. We have established a panel of human MCF-7 breast cancer cell lines either ectopically expressing the INSR (A or B isoform) in conjunction with a stable knockdown of the IGF1R or ectopically expressing the IGF1R in conjunction with a stable knockdown of the INSR. In these cell lines, we systematically evaluated the INSR and IGF1R receptor activation and downstream mitogenic signalling of all major clinical relevant insulin analogues in comparison with insulin and IGF1R. While most insulin analogues primarily activated the INSR, the mitogenic activation pattern of glargine was highly similar to IGF1 and insulin AspB10, known to bind IGF1R and induce carcinogenesis. Yet, in a long-term proliferation assay, the proliferative effect of glargine was not much different from regular insulin or other insulin analogues. This was caused by the rapid enzymatic conversion into its two metabolic active metabolites M1 and M2, with reduced mitogenic signalling through the IGF1R. In summary, based on our new cell models, we identified a similar mitogenic potency of insulin glargine and AspB10. However, rapid enzymatic conversion of glargine precludes a sustained activation of the IGF1R signalling pathway.
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Neoplasias de la Mama/patología , Proliferación Celular/efectos de los fármacos , Ingeniería Genética , Hipoglucemiantes/toxicidad , Insulina/toxicidad , Antígenos CD/genética , Antígenos CD/metabolismo , Biotransformación , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Relación Dosis-Respuesta a Droga , Activación Enzimática , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Femenino , Ingeniería Genética/métodos , Humanos , Hipoglucemiantes/metabolismo , Insulina/análogos & derivados , Insulina/metabolismo , Insulina Glargina/toxicidad , Células MCF-7 , Proteínas Proto-Oncogénicas c-akt/metabolismo , Interferencia de ARN , Receptor IGF Tipo 1 , Receptor de Insulina/agonistas , Receptor de Insulina/genética , Receptor de Insulina/metabolismo , Receptores de Somatomedina/agonistas , Receptores de Somatomedina/genética , Receptores de Somatomedina/metabolismo , Transducción de Señal/efectos de los fármacos , Factores de Tiempo , TransfecciónRESUMEN
OBJECTIVES: Statins offer significant cardiovascular benefits. Their use, however, influences immune regulation, which may potentially facilitate autoimmunity, eventually resulting in autoimmune diseases such as rheumatoid arthritis (RA).The authors studied whether statin use was associated with an increased risk of developing RA by conducting a case-control study using the Netherlands Information Network of General Practice database. METHODS: The authors identified 508 patients aged 40 years or older with a first-time diagnosis of RA in the period 2001-2006. Each RA case was matched to five controls for age, sex and index date, which was selected 1 year before the first diagnosis of RA. Odds ratios for the first-time diagnosis of RA were verified by a referral to a rheumatologist and/or at least one prescription of disease-modifying anti-rheumatic drugs and/or two prescriptions of corticosteroids after the date of first diagnosis. RESULTS: Cases were more often users of statins (15.9%) compared to controls (8.6%). After adjustment for cardiovascular risk factors and use of comedication, statin use was associated with an increased risk of incident RA (adjusted OR, 1.71 (95% CI 1.16 to 2.53); p=0.007). A consistent trend of increasing risk with increased cumulative duration, cumulative defined daily doses and number of prescriptions was not observed. However, a small trend between the potency of statin treatment and the risk of RA was found. CONCLUSIONS: Statin use seems to be associated with an increased risk of developing RA. Our findings should be replicated by additional studies.
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Artritis Reumatoide/etiología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Antirreumáticos/uso terapéutico , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Estudios de Casos y Controles , Bases de Datos Factuales , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prescripciones/estadística & datos numéricos , Factores de Riesgo , Factores de TiempoRESUMEN
Background: Dysplasia assessment of Barrett's esophagus biopsies is associated with low observer agreement; guidelines advise expert review. We have developed a web-based review panel for dysplastic Barrett's esophagus biopsies. Objective: The purpose of this study was to test if 10 gastrointestinal pathologists working at Dutch Barrett's esophagus expert centres met pre-set benchmark scores for quality criteria. Methods: Ten gastrointestinal pathologists twice assessed 60 digitalized Barrett's esophagus cases, enriched for dysplasia; then randomised (7520 assessments). We tested predefined benchmark quality criteria: (a) percentage of 'indefinite for dysplasia' diagnoses, benchmark score ≤14% for all cases, ≤16% for dysplastic subset, (b) intra-observer agreement; benchmark score ≥0.66/≥0.39, (c) percentage agreement with 'gold standard diagnosis'; benchmark score ≥82%/≥73%, (d) proportion of cases with high-grade dysplasia underdiagnosed as non-dysplastic Barrett's esophagus; benchmark score ≤1/78 (≤1.28%) assessments for dysplastic subset. Results: Gastrointestinal pathologists had seven years' Barrett's esophagus-experience, handling seven Barrett's esophagus-cases weekly. Three met stringent benchmark scores; all cases and dysplastic subset, three met extended benchmark scores. Four pathologists lacked one quality criterion to meet benchmark scores. Conclusion: Predefined benchmark scores for expert assessment of Barrett's esophagus dysplasia biopsies are stringent and met by some gastrointestinal pathologists. The majority of assessors however, only showed limited deviation from benchmark scores. We expect further training with group discussions will lead to adherence of all participating gastrointestinal pathologists to quality criteria, and therefore eligible to join the review panel.
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Esófago de Barrett/patología , Benchmarking , Esófago/patología , Patólogos/normas , Esófago de Barrett/diagnóstico , Biopsia , Transformación Celular Neoplásica , Adhesión a Directriz , Humanos , Internet , Microscopía/métodos , Países Bajos , Variaciones Dependientes del Observador , Factores de RiesgoRESUMEN
The first revision of the guideline 'Influenza and influenza vaccination' from the Dutch College of General Practitioners contains the new indications for influenza vaccination. The most important revisions are: the minimum age has been lowered from 65 to 60 years, the indication for furunculosis patients and their families has been removed, and vaccination is recommended to healthcare professionals who have regular and intensive contact with patients. The purpose of vaccinating healthcare professionals against influenza is to reduce the transmission of the influenza virus to patients at very high risk of complications from influenza and reduce sick leave among healthcare professionals. The use of antiviral agents should only be considered for patients with a very high risk of complications from influenza.
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Medicina Familiar y Comunitaria/normas , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/prevención & control , Pautas de la Práctica en Medicina , Factores de Edad , Antivirales/uso terapéutico , Humanos , Países Bajos , Medición de Riesgo , Sociedades MédicasRESUMEN
In general practice important health gain is obtainable by encouraging patients to stop smoking with support from the general practitioner. The practice guideline 'Smoking cessation' differentiates between smokers who are motivated to stop smoking, smokers who are considering smoking cessation, and smokers who are unmotivated to stop smoking. It is important to offer smokers, who are motivated to stop, intensive support at the right moment. Medicinal support in the way of nicotine replacement therapy, nortriptyline or bupropion is, ifpossible, recommended in motivated smokers who smoke at least 10 cigarettes daily.
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Enfermedad Crónica/prevención & control , Medicina Familiar y Comunitaria/normas , Pautas de la Práctica en Medicina , Cese del Hábito de Fumar/métodos , Cese del Hábito de Fumar/psicología , Bupropión/uso terapéutico , Femenino , Humanos , Masculino , Motivación , Países Bajos , Nicotina/uso terapéutico , Nortriptilina/uso terapéutico , Apoyo Social , Sociedades MédicasRESUMEN
A complex containing lipopolysaccharides, phospholipids and proteine separated from the medium by gelfiltration on Sephadex G-200 or by centrifugation. Electron microscopy revealed that this material is released as vesicles and membrane fragements. To determine the origin of these fragments, they were compared to outer and cytoplasmic membranes with respect to keto-deoxyoctulosonic acid, phospholipid, and protein content, phospholipid composition, fatty acid composition, protein distribution on sodium dodecyl sulfate-polyacrylamide gels, buoyant density, and content of several membrane marker enzymes. The results of this comparison indicate that the membrane fragments found in the culture supernatant of normally growing Escherichia coli consist of practically unmodified outer membrane. Possible mechanisms as to the cause of the release of outer membrane fragments, and its relationship to cell-division, are discussed.
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Membrana Celular/metabolismo , Escherichia coli/metabolismo , Proteínas Bacterianas/metabolismo , División Celular , Fraccionamiento Celular , Membrana Celular/ultraestructura , Escherichia coli/ultraestructura , Ácidos Grasos/metabolismo , Lipopolisacáridos/metabolismo , Lípidos de la Membrana/metabolismo , Proteínas de la Membrana/metabolismo , Fosfolípidos/metabolismoRESUMEN
Digestion of beta c-hemocyanin yielded tubular polymers as well as so-called collars. Analysis of the collar fraction revealed that it consisted of two fragments, one having a relative molecular mass of approx. 125000 and the other a relative molecular mass of approx. 65000. They were separated using ion-exchange chromatography. The large fragment dissociated around pH 9.5 into two components having a molecular mass of approx. 65000. Both fragments bound oxygen and displayed heterotropic interactions. The large fragment bound oxygen with a Hill coefficient less than unity under certain conditions. The fragments differed also in amino acid composition, sugar content, spectral parameters, association-dissociation phenomena and ageing. by comparison with fragments obtained after limited proteolysis of tenth molecules, their location in the polypeptide chain was established.
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Caracoles Helix/análisis , Hemocianinas/análisis , Péptidos/aislamiento & purificación , Aminoácidos/análisis , Animales , Carbohidratos/análisis , Cromatografía por Intercambio Iónico , Peso Molecular , Oxígeno , EspectrofotometríaRESUMEN
Crystals of the flavin-containing enzyme p-hydroxybenzoate hydroxylase (PHBHase) complexed with its reaction product were investigated in order to obtain insight into the catalytic cycle of this enzyme involving two substrates and two cofactors. PHBHase was crystallized initially with its substrate, p-hydroxybenzoate and the substrate was then converted into the product 3,4-dihydroxybenzoate by allowing the catalytic reaction to proceed in the crystals. In addition, crystals were soaked in mother liquor containing a high concentration of this product. Data up to 2.3 A (1 A = 0.1 nm) were collected by the oscillation method and the structure of the enzyme product complex was refined by alternate restrained least-squares procedures and model building by computer graphics techniques. A total of 273 solvent molecules could be located, four of them being presumably sulfate ions. The R-factor for 14,339 reflections between 6.0 A and 2.3 A is 19.3%. The 3-hydroxyl group of the product introduced by the enzyme is clearly visible in the electron density, showing unambiguously which carbon atom of the substrate is hydroxylated. A clear picture of the hydroxylation site is obtained. The plane of the product is rotated 21 degrees with respect to the plane of the substrate in the current model of enzyme-substrate complex. The 4-hydroxyl group of the product is hydrogen bonded to the hydroxyl group of Tyr201, its carboxyl group is interacting with the side-chains of Tyr222, Arg214 and Ser212, while the newly introduced 3-hydroxyl group makes a hydrogen bond with the backbone carbonyl oxygen of Pro293.
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4-Hidroxibenzoato-3-Monooxigenasa/metabolismo , Hidroxibenzoatos/metabolismo , Oxigenasas de Función Mixta/metabolismo , Secuencia de Aminoácidos , Sitios de Unión , Gráficos por Computador , Simulación por Computador , Cristalización , Enlace de Hidrógeno , Modelos Biológicos , Modelos Moleculares , Datos de Secuencia Molecular , Conformación ProteicaRESUMEN
Single crystals of naproxen esterase from Bacillus subtilis have been obtained from PEG6000 solutions at pH 8.0 by liquid-liquid diffusion while applying a temperature gradient from 4 degrees C to room temperature over a period of four weeks. The crystals belong to the trigonal space group P3(1)21 or P3(2)21 with a = b = 47.59 A and c = 212.91 A. The asymmetric part of the unit cell contains one protein molecule with M(r) = 33,771. The crystals diffract to at least 3.0 A resolution and are suitable for an X-ray structure analysis.
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Bacillus subtilis/enzimología , Hidrolasas de Éster Carboxílico/química , Carboxilesterasa , Hidrolasas de Éster Carboxílico/aislamiento & purificación , Cristalización , Conformación Proteica , Difracción de Rayos X/métodosRESUMEN
The FAD-containing enzyme lipoamide dehydrogenase (EC 1.6.4.3. NADH: lipoamide oxidoreductase) of Azotobacter vinelandii has been crystallized from polyethylene glycol solutions. The space group is P2(1)2(1)2(1) with one dimer in the asymmetric unit. The cell dimensions are: a = 64.2, b = 83.8, c = 193 A. X-ray reflections extend to at least 2.2 A resolution.
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Azotobacter/enzimología , Dihidrolipoamida Deshidrogenasa , Cristalización , Difracción de Rayos XRESUMEN
The reported high sensitivity and specificity of impedance plethysmography (IPG) in the diagnosis of proximal vein thrombosis were evaluated in a prospective cohort follow-up study, in which IPG was performed three times over a period of seven days in 243 consecutive outpatients with clinically suspected deep venous thrombosis (DVT). The test was abnormal in 112 patients (46%). The positive predictive value of an abnormal IPG for venography-proved DVT was 90%. One hundred thirty-one patients (54%) with repeatedly normal tests were considered not to have DVT, and anticoagulants were withheld. During six months of follow-up, completed in all patients with repeatedly normal IPG, no patient died of venous thromboembolism and no patient returned with clinically suspected pulmonary embolism. One patient (0.8%) returned after two months with recurrent leg symptoms, and venous thrombosis was documented (95% confidence limits, 0.02% to 4.21%). Another patient, who was nonsymptomatic, had an abnormal IPG at the three-month follow-up visit, and venography revealed venous thrombosis. Patients sent by general practitioners to a community hospital, with clinically suspected acute DVT, can be effectively managed by serial IPG alone.
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Atención Ambulatoria , Pletismografía de Impedancia , Tromboflebitis/diagnóstico , Anticoagulantes/uso terapéutico , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Hospitales Comunitarios , Humanos , Masculino , Persona de Mediana Edad , Países Bajos , Servicio Ambulatorio en Hospital , Estudios Prospectivos , Tromboflebitis/terapia , Factores de TiempoAsunto(s)
Comunicación , Educación Médica Continua , Educación de Postgrado en Medicina , Cirugía General/educación , Internado y Residencia , Selección de Profesión , Competencia Clínica , Conducta Cooperativa , Retroalimentación , Alemania , Humanos , Comunicación Interdisciplinaria , Satisfacción en el Trabajo , Motivación , Programas Nacionales de Salud , Rol del Médico/psicología , Valores Sociales , Socialización , Sociedades Médicas , Carga de Trabajo/psicologíaRESUMEN
In the period July-September 2003, a multi-resistant Escherichia coli strain caused an outbreak on a surgical ward in the Deventer Hospital, the Netherlands. This strain produced a beta-lactamase with an extended spectrum, making it resistant to third generation cephalosporins. Furthermore, the strain was resistant to trimethoprim-sulphamethoxazole (co-trimoxazole), gentamicin and quinolones, so that only treatment with carbapenems was possible. 8 patients were colonised. Genotyping of the strains by means of amplified fragment length polymorphism indicated the spread of a single strain. A multidisciplinary crisis team coordinated the infection control measures and the communication to involved persons and the press. Control measures consisted of contact isolation of colonised patients and extra attention to hand hygiene. After this proved to be ineffective, all patients on the ward were screened and the ward was closed for several days. The outbreak was stopped by strict cohorting ofthe colonised patients. There were no indications for transmission of resistance genes by plasmids. Several months later, on visiting the outpatient clinic, 3 other patients appeared to have been colonised by the epidemic E. coli strain during their admission. They had not been screened because they had already been discharged when all patients on the ward were screened for colonisation. In a follow-up study 9 months after the outbreak, 3 of the 6 investigated patients, who had in the meantime returned home, were still found to be colonised. Such patients constitute a risk for the re-introduction of multi-resistant bacteria into the hospital and should be preventively screened and isolated on admission.