RESUMEN
BACKGROUND: The paucity of licensed monoclonal antibodies (mAbs) in the infectious diseases arena strongly contrasts with the ready availability of these therapeutics for use in other conditions. AIMS: This narrative review aims to assess the potential of monoclonal antibody-based interventions for infectious diseases. SOURCES: A review of the literature via the Medline database was performed and complemented by published official documents on licensed anti-infective mAbs. In addition, ongoing trials were identified through a search of the clinical trial registration platform ClinicalTrials.gov. CONTENT: We identified the few infections for which mAbs have been added to the therapeutic armamentarium and stressed their potential in representing a readily available protection tool against biothreats and newly emerging and reemerging infectious agents. In reviewing the historical context and main features of mAbs, we assert a potentially wider applicability and cite relevant examples of ongoing therapeutic developments. Factors hindering successful introduction of mAbs on a larger scale are outlined and thoughts are offered on how to possibly address some of these limitations. IMPLICATIONS: mAbs may represent important tools in treating or preventing infections occurring with reasonably sufficient prevalence to justify demand and for which existing alternatives are not deemed fully adequate. Future initiatives need to address the prohibitive costs encountered in the development process. The feasibility of more large-scale administration of alternative modalities merits further exploration. In order to ensure optimal prospect of regulatory success, an early dialogue with competent authorities is encouraged.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Enfermedades Transmisibles/terapia , Inmunoterapia/tendencias , Antiinfecciosos/uso terapéutico , Anticuerpos Monoclonales/efectos adversos , Ensayos Clínicos como Asunto , Control de Enfermedades Transmisibles/métodos , Aprobación de Drogas , Resistencia a Múltiples Medicamentos , Humanos , Concesión de LicenciasRESUMEN
Despite urgent need, the development, approval and availability of child-friendly anti-tuberculosis drugs lag significantly behind that of adults, with children having been ignored in anti-tuberculosis drug development research. This paper outlines possible strategies for accelerating and better integrating the development of drugs and regimens for pediatric tuberculosis (TB) into existing drug development pathways for adults: initiation of pediatric studies of new treatments as soon as promising efficacy data have been generated in adults following successful phase II studies, shifting from the current age de-escalated approach to concomitant enrollment of children from the various age groups in studies, and leveraging the concepts of both the Unified Pathway and regimen development that have helped speed the study and development of novel regimens in adults.
Asunto(s)
Antituberculosos/administración & dosificación , Química Farmacéutica/economía , Tuberculosis/tratamiento farmacológico , Niño , Ensayos Clínicos Fase II como Asunto , Humanos , PediatríaRESUMEN
BACKGROUND: Over the last 20 years stress at work has been found to be predictive of several conditions such as coronary heart disease, high blood pressure and non-specific sick leave. The Karasek demand/control/strain concept has been the most widely used in prospective epidemiological studies. OBJECTIVES: To describe distribution in Karasek's demand/control (DC) dimensions as well as prevalence of strain in samples from different parts of Europe grouped into three regions (South, Middle, Sweden), adjusting for occupation. To describe gender differences in Karasek's DC dimensions along with strain prevalence and assess the regional stability of those differences in different occupational groups. DESIGN: The Job stress, Absenteeism and Coronary heart disease in Europe (JACE) study, a Concerted Action (Biomed I) of the European Union, is a multicentre prospective cohort epidemiological study: 38,019 subjects at work aged 35-59 years were surveyed at baseline. Standardised techniques were used for occupation coding (International Standardised Classification of Occupations) and for the DC model (Karasek scale): five items for the psychological demand and nine items for the control or decision latitude dimensions, respectively. RESULTS: A total of 34,972 subjects had a complete data set. There were important regional differences in the Karasek scales and in prevalence of strain even after adjustment for occupational class. Mean demand and control were higher in the Swedish centres when compared to two centres in Milano and Barcelona (Southern region) and values observed in four centres (Ghent, Brussels, Lille and Hoofddorp) in Middle Europe were closer to those observed in the Southern cities than to those obtained in the Swedish cities. Clerks (ISCO 4) and, more specifically, office clerks (ISCO 41) exhibited the smallest regional variation. In a multivariate model, the factor 'region' explained a small fraction of total variance. In the two Southern centres as well as in the four Middle European centres, men perceived marginally less job-demand as compared to women whereas the reverse was observed in the two Swedish centres. Differences were larger for control: men appeared to perceive more control at work than did women. In a multivariate model, gender explained a small fraction whereas occupational level explained a large fraction of the variance. CONCLUSIONS: In this standardised multicentre European study Karasek's DC model showed large gender and occupational differences whereas geographic region explained a small fraction of the total DC variance, notwithstanding large differences in labour market and working conditions as pointed out by the European Commission as recently as 2000.
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Empleo/psicología , Factores Sexuales , Estrés Psicológico , Adulto , Empleo/clasificación , Europa (Continente) , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
Psychosocial characteristics have been linked to coronary heart disease. In the Belgian Job Stress Project (1994-1999), the authors examined the independent role of perceived job stress on the short-term incidence of clinical manifest coronary events in a large occupational cohort. A total of 14,337 middle-aged men completed the Job Content Questionnaire to determine the dimensions of the extended job strain model, job demands, decision latitude, and social support. Jobs were categorized into high strain, low strain, active jobs, and passive jobs. During the 3-year follow-up, 87 coronary events were registered. At baseline, 17% of workers experienced high strain. Job demands and decision latitude were not significantly related to the development of coronary heart disease after adjustment for covariates. The 38% risk excess among subjects classified in the high-strain category did not reach statistical significance. However, coronary heart disease incidence was substantially associated with the social support scale independently of other risk factors, with an adjusted hazard ratio of 2.4 (95% confidence interval: 1.4, 4.0) between extreme tertiles. No convincing evidence for an association of job demands, decision latitude, or job strain with the short-term incidence of coronary heart disease was found. However, our study underscores the importance of a supportive social work environment in the prevention of coronary heart disease.
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Enfermedad Coronaria/epidemiología , Apoyo Social , Estrés Psicológico/epidemiología , Lugar de Trabajo , Bélgica/epidemiología , Distribución de Chi-Cuadrado , Toma de Decisiones , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
CONTEXT: Sick leave is a major problem in public health. The Karasek demands/control/social support/strain (JDCS) model has been largely used to predict a wide range of health outcomes and to a lesser extent sickness absence. STUDY OBJECTIVE: The aim of the study was to test the predictive power of the JDCS model in relation with one year incidence of sick leave in a large cohort of workers. DESIGN AND SETTING: Cohort study conducted between 1994 and 1998 in 25 companies across Belgium. PARTICIPANTS: A total of 20 463 workers aged 35 to 59 years were followed up for sick leave during one year after the baseline survey. OUTCOMES: The outcomes were a high sick leave incidence, short spells (>/=7 days), long spells (>/=28 days), and repetitive spells of sickness absence (>/=3 spells/year). MAIN RESULTS: Independently from baseline confounding variables, a significant association between high strained jobs with low social support and repetitive spells of sickness absence was observed in both sexes with odds ratios of 1.32 (99% CI, 1.04 to 1.68) in men and 1.61 (99% CI, 1.13 to 2.33) in women. In men, high strained jobs with low social support was also significantly associated with high sick leave incidence, and short spells of sick leave with odds ratios of 1.38 (99% CI, 1.16 to 1.64) and 1.22 (99% CI, 1.05 to 1.44) respectively. CONCLUSIONS: Perceived high strain at work especially combined with low social support is predictive of sick leave in both sexes of a large cohort of the Belgian workforce.
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Enfermedades Profesionales/epidemiología , Ausencia por Enfermedad/estadística & datos numéricos , Estrés Psicológico/epidemiología , Adulto , Bélgica/epidemiología , Métodos Epidemiológicos , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: In many studies, obesity has been associated with morbidity or mortality, but only a few have studied the relation between obesity and sick leave. Our aim is to analyse the independent effects of both adiposity and body fat distribution in relation to the 1-y incidence of sick leave in a large cohort of male and female workers covering a variety of occupations, taking into account a wide range of socio-demographic, behavioural and bioclinical variables. DESIGN AND SETTING: The baseline survey of the Belstress study was conducted in 25 companies across Belgium between 1994 and 1998. A cohort of 20 463 workers (15 557 males and 4906 females) aged 35-59 y was followed for absenteeism during 1 y. The 75th percentile of the distribution of the total annual sickness days was used as a cutoff to classify the workers with a high 1-y incidence rate of sick leave. The relation between sick leave and both obesity and body fat distribution assessed by the body mass index (BMI) and the waist circumference, respectively, was analysed by multivariate logistic regression models. RESULTS: Using a backward procedure based on the likelihood ratio, we found central abdominal fatness to be an independent predictor of sick leave in both genders (high sick-leave incidence and long spells), but not BMI. In men, the odds ratios was 1.31 (99% CI 1.12-1.52, P<0.0001) and in women it ranged from 1.32 (99% CI 1.03-1.70, P=0.005) to 1.47 (99% CI 1.14-1.90, P<0.0001). Two baseline covariables, respiratory problems and perceived health, are confounders or mediators. CONCLUSIONS: In this study, body fat distribution was associated with a high annual sick-leave incidence and long spells of sickness absence. If this link is reversible, employers may benefit from programs aiming at the prevention and treatment of central obesity.
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Tejido Adiposo/patología , Obesidad/complicaciones , Ausencia por Enfermedad/estadística & datos numéricos , Adulto , Análisis de Varianza , Bélgica/epidemiología , Constitución Corporal , Índice de Masa Corporal , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad/patología , Salud Laboral/estadística & datos numéricos , Estudios Prospectivos , Factores de RiesgoRESUMEN
In 1992, a population-based breast cancer screening programme was initiated in the municipality of Ghent: all women aged 40-69 years were personally invited to attend a local radiology unit for a mammogram, after being examined by a general practitioner or gynaecologist of their choice. The results of history taking, clinical breast examination, first and second reading, further investigation and primary treatment were registered. In total, 24.3% of the eligible population was screened in the period 1992-1994. The recall and biopsy rates were 2.9% and 1.4%, respectively. The cancer detection rate was 8.1 per 1000 women screened. Of all cancers detected, 88.0% (66/75) were invasive. Of these, 35.9% (23/64) measured 10 mm or less in diameter. The benign to malignant biopsy ratio was 0.7. Apart from the low participation, these results suggest that the programme is effective, compared with reference standards and the results of other studies.
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Neoplasias de la Mama/prevención & control , Mamografía/métodos , Tamizaje Masivo/métodos , Adulto , Anciano , Bélgica/epidemiología , Biopsia/métodos , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Femenino , Humanos , Persona de Mediana Edad , Aceptación de la Atención de Salud , Servicios Preventivos de Salud/organización & administración , Evaluación de Programas y Proyectos de SaludRESUMEN
OBJECTIVE: To answer the question if their is a difference between cimetidine versus ranitidine on the gastric emptying rate. DESIGN: Prospective, blinded, randomised controlled study. SETTING: A mixed intensive care unit at the University Hospital. PATIENTS: Twenty-four patients sustained on artificial respiration. INTERVENTIONS: Blinded and randomised either cimetidine 200 mg or ranitidine 50 mg were administered IV, after administration of 500 ml of enteral nutrition. MAIN OUTCOME MEASURES: The gastric emptying rate (gastric filling index) was measured over 120 minutes by an ultrasonographic method. In both groups t/2 was very long, there was no statistical difference between the two groups concerning the mean gastric filling index values at successive measurements (time 0 to 120 minutes). Neither was there a difference between the young and the elderly, female and male patients. CONCLUSION: Following administration of either ranitidine or cimetidine in bolus, no difference in the gastric emptying of gastric liquid feeding could be observed in critically ill intubated, ventilated patients.
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Antiulcerosos/farmacología , Cimetidina/farmacología , Vaciamiento Gástrico/efectos de los fármacos , Ranitidina/farmacología , Respiración Artificial , Adulto , Anciano , Antiulcerosos/uso terapéutico , Cimetidina/uso terapéutico , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Úlcera Péptica/etiología , Úlcera Péptica/prevención & control , Estudios Prospectivos , Ranitidina/uso terapéutico , Estrés Fisiológico/complicacionesRESUMEN
Imported malaria is increasing in Western countries, which results in considerable morbidity and mortality, the latter mainly due to delayed diagnosis and treatment. Partial exchange transfusion has been proposed as a therapy for very severe falciparum malaria, but the utility of this procedure has not been proven. We report on 12 patients with severe Plasmodium falciparum malaria, treated with exchange transfusion in 5 Belgian hospitals between 1987 and 1991. The mean parasitaemia before exchange was 17.2% (range 6-35%). An average of 3.1 l was exchanged within 3 to 7 hours. Ten of the 12 patients survived. One patient recovered initially, but died as a consequence of a cascade of complications of dialysis. Three patients developed the adult respiratory distress syndrome (ARDS), two had less serious pulmonary involvement, and five had temporary renal failure; none of the survivors had sequelae. A formula is proposed to calculate the expected reduction in parasitized erythrocytes by exchange transfusion in function of the initial parasitaemia, the initial haemoglobin level and the volume of blood exchanged. Comparison between the mathematically predicted and the observed decline in parasitaemia shows on average a 25% excess of observed over predicted efficacy per unit of blood exchanged. After introducing this correction the formula enables the clinician to estimate roughly the volume of blood that has to be exchanged in order to bring the initial parasitaemia down to a desired level.
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Recambio Total de Sangre , Malaria Falciparum/terapia , Parasitemia/prevención & control , Adulto , Anciano , Volumen Sanguíneo , Recuento de Eritrocitos , Femenino , Humanos , Malaria Falciparum/complicaciones , Malaria Falciparum/parasitología , Masculino , Persona de Mediana Edad , Parasitemia/parasitología , Valor Predictivo de las Pruebas , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
A patient with neurosyphilis, presenting with severe ocular impairment due to optic neuropathy, is described. In such a case, a low index of clinical suspicion and improper use of syphilitic serologic tests may delay diagnosis. However, specific tests of serum and cerebrospinal fluid are mandatory for the diagnosis. Treatment evaluation necessitates the follow-up of serology and cerebrospinal fluid cell count. Recent changes of therapy recommendations in subjects with neurosyphilis and in those syphilitic patients co-infected with HIV are mentioned.
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Neurosífilis/complicaciones , Enfermedades del Nervio Óptico/etiología , Anciano , Antibacterianos , Quimioterapia Combinada/uso terapéutico , Femenino , Humanos , Neurosífilis/diagnóstico , Neurosífilis/tratamiento farmacológico , Atrofia Óptica/etiología , Enfermedades del Nervio Óptico/diagnóstico , Penicilinas/administración & dosificación , Serodiagnóstico de la SífilisRESUMEN
Belgium, with its pluralistic health care system, has many small-sized maternity units staffed almost exclusively with obstetricians. The maternal and perinatal mortality and morbidity rates are still higher than in some of the neighboring countries. The new regulations with regard to the accreditation of maternity units might improve the figures. Other measures must be taken, however, to ensure that only low-risk patients are taken into small maternity units and that all high-risk cases and all those developing complications are cared for in large, well-equipped and well-staffed hospitals. Some form of peer review would also be beneficial.