Host sex and ectoparasites choice: preference for, and higher survival on female hosts.

1. Sex differences in levels of parasite infection are a common rule in a wide range of mammals, with males usually more susceptible than females. Sex-specific exposure to parasites, e.g. mediated through distinct modes of social aggregation between and within genders, as well as negative relationships between androgen levels and immune defences are thought to play a major role in this pattern. 2. Reproductive female bats live in close association within clusters at maternity roosts, whereas nonbreeding females and males generally occupy solitary roosts. Bats represent therefore an ideal model to study the consequences of sex-specific social and spatial aggregation on parasites' infection strategies. 3. We first compared prevalence and parasite intensities in a host-parasite system comprising closely related species of ectoparasitic mites (Spinturnix spp.) and their hosts, five European bat species. We then compared the level of parasitism between juvenile males and females in mixed colonies of greater and lesser mouse-eared bats Myotis myotis and M. blythii. Prevalence was higher in adult females than in adult males stemming from colonial aggregations in all five studied species. Parasite intensity was significantly higher in females in three of the five species studied. No difference in prevalence and mite numbers was found between male and female juveniles in colonial roosts. 4. To assess whether observed sex-biased parasitism results from differences in host exposure only, or, alternatively, from an active, selected choice made by the parasite, we performed lab experiments on short-term preferences and long-term survival of parasites on male and female Myotis daubentoni. When confronted with adult males and females, parasites preferentially selected female hosts, whereas no choice differences were observed between adult females and subadult males. Finally, we found significantly higher parasite survival on adult females compared with adult males. 5. Our study shows that social and spatial aggregation favours sex-biased parasitism that could be a mere consequence of an active and adaptive parasite choice for the more profitable host.

The impact of personality characteristics on the clinical expression in neurodegenerative disorders--a review.

Clinical experience suggests that longstanding personality characteristics as a person's most distinctive features of all are likely to play a role in how someone with dementia copes with his increasing deficiencies. Personality characteristics may have a pathoplastic effect on both behavioral and psychological symptoms (BPS) or on cognition as well as cognitive decline. Cognitive disorders accompanied by BPS are a tremendous burden for both the patient and their proxies. This review suggests that premorbid personality characteristics are co-determinants of BPS in cognitive disorders, but much effort is needed to clarify whether or not specific premorbid personality traits are associated with specific BPS as no strong links have so far emerged. This review further shows that a growing field of research is interested in the links not only between quite short-lived emotional states and cognitive processes, but also between longstanding personality traits and cognition in both healthy individuals and patients with neurodegenerative disorders. Furthermore, a few studies found that specific premorbid personality traits may be risk factors for neurodegenerative diseases. However, research findings in this area remain scarce despite a huge literature on personality and cognitive disorders in general. An important shortcoming that hampers so far the progress of our understanding in these domains is the confusion in the literature between longstanding premorbid personality traits and transient personality changes observed in neurodegenerative diseases. Few studies have based their assessments on accepted personality theories and carefully investigated premorbid personality traits in patients with cognitive disorders, although assessing personality may be complicated in these patients. Studying the impact of personality characteristics in cognitive disorders is an especially promising field of research in particular when concomitantly using neurobiological approaches, in particular structural brain imaging and genetic studies as suggested by as yet rare studies. Improved understanding of premorbid personality characteristics as determinants of both BPS or cognitive capacities or decline is likely to influence our attitudes towards the treatment of demented patients and ultimately to help in alleviating a patient's and their proxies' burden.

A role for the endocrine and pro-inflammatory mediator MIF in the control of insulin secretion during stress.

The systemic response to injury or infection is often accompanied by significant alterations in host metabolism and glucose homeostasis. Within the liver, these changes include a decrease in glycogenesis and an increase in gluconeogenesis, and in peripheral tissues, the development of insulin resistance and the increased utilization of glucose by non-insulin-dependent pathways. Depending on the severity and the duration of the response, both hyper- and hypoglycemia can ensue and each can become a clinically important manifestation of the systemic inflammatory response. The protein known as macrophage migration inhibitory factor (MIF) has been identified recently to play a central role in host immunity and to regulate glucocorticoid effects on the immune and inflammatory systems. MIF is released in vivo from activated immune cells as well as by the anterior pituitary gland upon stimulation of the hypothalamic-pituitary-adrenal axis. MIF also has been found to be secreted together with insulin from the pancreatic beta-cells and to act as an autocrine factor to stimulate insulin release. Since circulating MIF levels are elevated during stress or systemic inflammatory processes, this protein may play a central role in the control of insulin secretion during various disease states.

Laparoscopic and open colorectal surgery in everyday practice : retrospective study

Résumé Introduction: La plupart des études disponibles sur la chirurgie colorectale par laparoscopie concernent des patients hautement sélectionnés. Le but de cette étude est d'analyser les résultats à court et à long terme de l'ensemble des patients traités dans un service de chirurgie générale. Méthodes: Il s'agit d'une analyse rétrospective d'un registre prospectif interne au service, dans lequel tous les patients consécutifs opérés pour la première fois du colon et du rectum entre mars 1993 et décembre 1997 ont été enregistrés. Les informations concernant le suivi ont été collectées par questionnaire. Résultats: Un total de 187 patients ont été opérés par laparoscopie et 215 patients par chirurgie ouverte durant la période d'étude. Les informations concernant le suivi ont pu être collectées dans 95% des cas avec une évolution de 1-107 mois (médiane 59 mois), respectivement de 1-104 mois (médiane 53 mois). Une conversion fut nécessaire dans 28 cas (15%) mais ceux-ci restent inclus dans le groupe laparoscopie pour l'analyse par intention de traitement. Dans le groupe laparoscopie, les opérations ont duré plus longtemps (205 vs 150 min, p<0.001) mais l'hospitalisation a été plus courte (8 vs 13 jours, p<0.001). La reprise du transit a été plus rapide après laparoscopie, mais uniquement après intervention sur le colon gauche (3 vs 4 jours, p<0.01). Cependant, la sélection préopératoire (nombre plus élevé d'urgences et de patients avec un risque anesthésiologique élevé dans le groupe de la chirurgie ouverte) a été favorable à la laparoscopie. Le taux de complications (global ainsi que pour chaque complication chirurgicale) a été similaire dans les deux groupes, avec un taux global de 20% environ. Conclusions: Malgré une sélection favorable des cas, uniquement très peu d'avantages à la laparoscopie sur la chirurgie ouverte ont pu être observés. Abstract Background: Most studies available on laparoscopic colorectal surgery focus on highly selected patient groups. The aim of the present study was to review short- and long-term outcome of everyday patients treated in a general surgery department. Methods: Retrospective review was carried out of a prospective database of all consecutive patients having undergone primary laparoscopic (LAP) or open colorectal surgery between March 1993 and December 1997. Follow-up data were completed via questionnaire. Results: A total of 187 patients underwent LAP resection and 215 patients underwent open surgery. Follow up was complete in 95% with a median of 59 months (range, 1-107 months) and 53 months (range, 1-104 months), respectively. There were 28 conversions (15%) in the LAP group and these remained in the LAP group in an intention-to-treat analysis. The LAP operations lasted significantly longer for all types of resections (205 vs 150 min, P<0.001) and hospital stay was shorter (8 vs 13 days, P<0.001). Recovery of intestinal function was faster in the LAP group, but only after left-sided procedures (3 vs 4days, P<0.01). However, preoperative patient selection (more emergency operations and patients with higher American Society of Anesthesiologists (ASA) score in the open group) had a major influence on these elements and favours the LAP group. Surprisingly, the overall surgical complication rate (including long-term complications such as wound hernia) was 20% in both groups with rates of individual complications also being comparable in both groups. Conclusion: Despite a patient selection favourable to the laparoscopy group, only little advantage in postoperative outcome could be shown for the minimally invasive over the open approach in the everyday patient.

Use of high-frequency jet ventilation for percutaneous tumor ablation.

PURPOSE: To report feasibility and potential benefits of high-frequency jet ventilation (HFJV) in tumor ablations techniques in liver, kidney, and lung lesions. METHODS: This prospective study included 51 patients (14 women, mean age 66 years) bearing 66 tumors (56 hepatic, 5 pulmonary, 5 renal tumors) with a median size of 16 ± 8.7 mm, referred for tumor ablation in an intention-to-treat fashion before preoperative anesthesiology visit. Cancellation and complications of HFJV were prospectively recorded. Anesthesia and procedure duration, as well as mean CO2 capnea, were recorded. When computed tomography guidance was used, 3D spacial coordinates of an anatomical target <2 mm in diameter on 8 slabs of 4 slices of 3.75-mm slice thickness were registered. RESULTS: HFJV was used in 41 of 51 patients. Of the ten patients who were not candidate for HFJV, two patients had contraindication to HFJV (severe COPD), three had lesions invisible under HFJV requiring deep inspiration apnea for tumor targeting, and five patients could not have HFJV because of unavailability of a trained anesthetic team. No specific complication or hypercapnia related to HFJV were observed despite a mean anesthetic duration of 2 h and ventilation performed in procubitus (n = 4) or lateral decubitus (n = 6). Measured internal target movement was 0.3 mm in x- and y-axis and below the slice thickness of 3.75 mm in the z-axis in 11 patients. CONCLUSIONS: HFJV is feasible in 80 % of patients allowing for near immobility of internal organs during liver, kidney, and lung tumor ablation.

Multiple prisoner's dilemma games with (out) an outside option: An experimental study

Experiments in which subjects play simultaneously several finite prisoner's dilemma supergames with and without an outside optionreveal that: (i) subjects use probabilistic start and endeffect behaviour, (ii) the freedom to choose whether to play the prisoner's dilemma game enhances cooperation, (iii) if the payoff for simultaneous defection is negative, subjects' tendency to avoid losses leads them to cooperate; while this tendency makes them stick to mutual defection if its payoff is positive.

The rise and fall in menopausal hormone therapy and breast cancer incidence.

Studies conducted in different areas of North America and Europe showed a 5-10% decline in the incidence of breast cancer following reductions up to 70% in menopause hormone therapy (HT) use after 2002. The observation that the decline was larger in (or limited to) women aged > or =50 years weighs in favour of an effect of reduced HT use on breast cancer incidence. However, changes in screening are also likely to play a role in the decreasing incidence of breast cancer observed in several countries. In particular, the technical improvements and the increased effectiveness of breast cancer screening and detection during the 1990s led to a decreased number of pre-clinical cases found by screening in subsequent years. Further, disentangling the effects of HT use and screening is difficult, as women who stop using HT may also undergo mammography screening less frequently. Thus, the reasons of the falls in incidence remain open to discussion.

Do Jardim-de-Infância ao Centro de Actividades de Tempos Livres: Representações das Crianças sobre o Brincar

A investigação “Do Jardim-de-infância ao Centro de Actividades de Tempos Livres: Representações das Crianças sobre o Brincar” reconhece as crianças como actores sociais, sujeitos de direitos, entre eles, o direito à participação em assuntos que lhes digam directamente respeito, a assuntos de seu interesse, nomeadamente o direito ao brincar. O brincar é uma actividade lúdica, assim como o jogar, importante no processo de crescimento e desenvolvimento da criança e, nos tempos que correm, a sociedade, de uma forma geral, e particularmente as famílias, preocupam-se muito com o trabalho e colocam as necessidades básicas das crianças em segundo plano ao valorizarem acima de tudo o sucesso e o desempenho das mesmas. Assim, se participar significa “tomar parte em”, reconhece-se a necessidade de ouvir as crianças e o que elas têm a dizer sobre essa actividade lúdica, sobre a forma como organizam o seu dia e o tempo que despendem para brincar e sobre a forma como gostariam de ver os seus dias ocupados. É neste pressuposto, de que é através da acção e da voz das crianças, que é possível a construção de um conhecimento teórico e válido que contribua para uma melhor intervenção educativa com as crianças. Esta investigação, que decorreu numa instituição com várias vertentes, entre elas a vertente da Animação Infantil, enquadra-se no paradigma qualitativo de natureza participativa, e procura interpretar os significados atribuídos pelas crianças, que frequentam o Jardim-deinfância da rede pública e a mesma instituição, na condição de Componente de Apoio à Família, ao brincar, às suas vivências no que concerne à gestão do seu quotidiano, quer no que refere ao tempo que passam no Jardim-de-infância, quer no que passam no Prolongamento de Horário/Actividades de Tempos Livres. Neste trabalho de investigação que decorreu numa instituição situada numa freguesia pertencente ao Distrito de Viana do Castelo e que disponibiliza os serviços de ATL, participaram como protagonistas as crianças da faixa etária entre os três e os seis anos de idade e que frequentam dois contextos: educacional e lúdico. Este trabalho é sustentado por um referencial teórico que engloba o brincar na sociedade actual e a sua importância, a educação pré-escolar e as suas funções, a natureza da componente de apoio à família, a animação sócio-educativa e os contextos de vida das crianças, que permitiram questionar a participação infantil em assuntos de seu interesse. Ainda que este estudo não permita generalizações, reflecte-se sobre a realidade existente, dá voz às crianças e indica aspectos que, de uma forma geral, precisam de mais atenção. Afinal o brincar na infância é um assunto sério…

Tratamento do erro na produção escrita: análise das estratégias de correcção dos erros

Sabemos que no dia-a-dia, um dos trabalhos do professor consiste em corrigir os textos produzidos pelos alunos com vista a detectar os erros cometidos. É evidente, que esta função envolve o conhecimento de princípios orientadores, razão pela qual, entendemos ser importante que o professor tenha uma visão de como processar esta tarefa. Deste modo, reveste-se de particular importância a atenção sobre o assunto de correcção dos erros na produção escrita, para que seja possível por parte do professor também uma reflexão sobre metodologias a adoptar para obtenção de melhores resultados na gestão dos erros. Focalizamos o nosso estudo nesta temática, pela importância que pode assumir na formação inicial e contínua dos professores de Língua Portuguesa em Cabo Verde. Uma das questões que colocamos e que atravessa toda a tese é a seguinte: que estratégias utilizam para corrigir os textos produzidos? Concretamente, constitui nossa intenção, olhar um pouco para o contexto da população alvo (alguns professores de Língua Portuguesa), em Cabo Verde, com o intuito de por um lado, conhecer as estratégias que utilizam para corrigir os textos produzidos pelos seus alunos e, por outro lado, verificar se as estratégias são ou não eficazes de modo a ajudar o aluno a compreender e a corrigir o seu erro. O corpus analisado é constituído por 40 (quarenta) composições produzidas por alunos do 7º ano de escolaridade, pertencentes a 4 (quatro) escolas secundárias, localizadas na ilha de Santiago – Praia - Cabo Verde

Will endoscopists soon replace pathologists in the diagnosis of (pre-)neoplastic and inflammatory mucosal lesions?

This short review addresses the question whether pathologists will continue to play a central role in the diagnosis of mucosal lesions of the gastrointestinal tract or whether their role will soon be assumed by clinical colleagues equipped with modern high-resolution endoscopes. In order to support the raison d'etre of the pathologist - at least for the time being and the near future - the author lists three arguments, related to (i) the differences in the orientation of the plane of view (histology: perpendicular to the mucosal surface vs. endoscopy: parallel to the mucosal surface), (ii) the advantages of staining and immunostaining tissue sections, and (iii) the possibility to perform deeper sections and to consul with colleagues in the case of difficult diagnoses.

The role of SGLT1 and GLUT2 in intestinal glucose transport and sensing.

Intestinal glucose absorption is mediated by SGLT1 whereas GLUT2 is considered to provide basolateral exit. Recently, it was proposed that GLUT2 can be recruited into the apical membrane after a high luminal glucose bolus allowing bulk absorption of glucose by facilitated diffusion. Moreover, SGLT1 and GLUT2 are suggested to play an important role in intestinal glucose sensing and incretin secretion. In mice that lack either SGLT1 or GLUT2 we re-assessed the role of these transporters in intestinal glucose uptake after radiotracer glucose gavage and performed Western blot analysis for transporter abundance in apical membrane fractions in a comparative approach. Moreover, we examined the contribution of these transporters to glucose-induced changes in plasma GIP, GLP-1 and insulin levels. In mice lacking SGLT1, tissue retention of tracer glucose was drastically reduced throughout the entire small intestine whereas GLUT2-deficient animals exhibited higher tracer contents in tissue samples than wild type animals. Deletion of SGLT1 resulted also in reduced blood glucose elevations and abolished GIP and GLP-1 secretion in response to glucose. In mice lacking GLUT2, glucose-induced insulin but not incretin secretion was impaired. Western blot analysis revealed unchanged protein levels of SGLT1 after glucose gavage. GLUT2 detected in apical membrane fractions mainly resulted from contamination with basolateral membranes but did not change in density after glucose administration. SGLT1 is unequivocally the prime intestinal glucose transporter even at high luminal glucose concentrations. Moreover, SGLT1 mediates glucose-induced incretin secretion. Our studies do not provide evidence for GLUT2 playing any role in either apical glucose influx or incretin secretion.

Genetic aspects of normal and disturbed sleep.

Sleep disorders commonly involve genetic susceptibility, environmental effects, and interactions between these factors. The heritability of sleep patterns has been shown in studies of monozygotic twins, and sleep electroencephalogram patterns offer a unique genetic fingerprint which may assist in the identification of genes involved in the regulation of sleep. Genetic factors are also thought to play a role in sleep disorders; narcolepsy is a disabling sleep condition and research has revealed the complexity of underlying genetic and environmental influences in the development of this disorder. An understanding of sleep regulation at the molecular level is essential in the identification of new targets for the treatment of sleep disorders, and genome-wide association studies for both normal sleep and sleep disorders may shed new light on the molecular architecture of mechanisms regulating these behaviours.

Evolutionary forces affect multigenomic arbuscular mycorhizal fungi : an experimental approach using Glomus intraradices

Abstract Arbuscular Mycorhizal Fungi (AMF) are important plant symbionts that can improve floristic diversity and ecosystem productivity. These important fungi are obligate biotrophs and form symbioses with roots of the majority of plant species, improving plant nutrient acquisition in exchange of photosynthates. AM fungi are successful both ecologically as they occupy a very large spectrum of environments as well as host range and evolutionarily, as this symbiosis is over 400 million years old. These fungi grow and reproduce clonally by hyphae and multinucleate spores. AMF are coenocytic and recent work has shown that they harbor genetically different nuclei and that AMF populations are genetically diverse. How AMF species diversity is maintained has been addressed theoretically and experimentally at the community level. Much less attention has been drawn to understand how genetic diversity is maintained within populations although closely related individuals are more likely to compete for the same resources and occupy similar niches. How infra-individual genetic diversity is shaped and maintained has received even less attention. In Chapter 2, we show that individuals from a field population may differ in their symbiotic efficiency under reduced phosphate availability: We show there is genetic variation in an AMF field population for fitness-related growth traits in response to different phosphate availability acid host species. Furthermore, AFLP fingerprints of the same individuals growing in contrasting environments diverged suggesting that the composition in nuclei of AMF is dynamical and affected by environmental factors. Thus environmental heterogeneity is likely to play an important role for the maintenance of genetic diversity at the population level. In Chapter 3 we show that single spores do not inherit necessarily the same genetic material. We have found genetic divergences using two different types of molecular marker, as well as phenotypic divergences among single spore lines. Our results stress the importance of considering these organisms as a multilevel hierarchical system and of better knowing their life cycle. They have important consequences for the understanding of AMF genetics, ecology and the development of commercial AMF inocculum. Résumé Les champignons endomycorhiziens arbusculaires (CEA) sont d'importants symbiontes pour les plantes, car ils augmentent la diversité et la productivité des écosystèmes. Ces importants symbiontes sont des biotrophes obligatoires et forment une symbiose avec la plupart des plantes terrestres. Ils améliorent l'acquisition de substances nutritives de leurs hôtes en échange de sucres obtenus par photosynthèse. Ces champignons ont un grand succès écologique, ils colonisent une grande rangée d'environnements ainsi que d'hôtes. Ils ont aussi un succès évolutif certain de part le fait que cette symbiose existe depuis plus de 400 millions d'années. Les CEA sont asexués et croissent clonalement en formant des hyphes et des spores multinuclées. Les CEA sont des coenocytes et des travaux de recherche récents ont montré qu'ils possèdent des noyaux génétiquement différents. D'autres travaux ont aussi révélé que les populations de CEA sont génétiquement diversifiées. Comment la diversité des CEA est maintenue a seulement été adressée par des études théoriques et expérimentalement au niveau des communautés. Très peu d'attention a été portée sur le maintien de la diversité génétique infra et inter populationnelle, or ce sont les individus les plus proches génétiquement qui vont entrer en compétition pour des ressources et niches similaires. La formation et le maintien de la diversité intra-individu des CEA a reçu très peu d'attention. Dans le chapitre 2, nous montrons que des individus CEA d'un même champ différent dans leur efficacité symbiotique lorsque la concentration en phosphoré est réduite. Nous montrons qu'il existe de la variance génétique dans une population de CEA provenant d'un même champ en réponse à différentes concentrations de phosphore, ainsi qu'en réponse à différentes espèces d'hôtes, et ceci pour des traits de croissance vraisemblablement liés au succès reproducteur. De plus grâce à des AFLP nous avons pu montrer que le génome de ces individus subissent des changements lorsqu'ils croissent dans des environnements contrastés. Ceci suggère que les noyaux génétiquement différents des CEA sont des entités dynamiques. Il est fort probable que l'hétérogénéité environnementale joue un rôle dans le maintien de la diversité génétique des populations de CEA. Dans le chapitre 3, nous montrons que toutes les spores d'un même mycélium parental de CEA ne reçoivent pas exactement le même contenu génétique. Nous avons mis en évidence des divergences entre des Lignées monosporales en utilisant deux types de marqueur moléculaires, ainsi que des différences phénotypiques. Nos résutats soulignent l'importance de considézer ces organismes comme dés systëmes hiérarchiques mufti-niveaux, ainsi que de mieux connaître leur cycle de vie. Nos résultats ont d'importantes conséquences pour la compréhension du système génétique des CEA, ainsi que de leur évolution, leur écológie, mais également des conséquences pour la production d' inoccultim commercial.

Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial.

BACKGROUND: Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. METHODS: The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. FINDINGS: The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006). Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). INTERPRETATION: Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery. FUNDING: Medical Research Council, the Stroke Association, Sanofi-Synthélabo, European Union.

Oral Antibiotics for Fever in Low-Risk Neutropenic Patients With Cancer: A Double-Blind, Randomized, Multicenter Trial Comparing Single Daily Moxifloxacin With Twice Daily Ciprofloxacin Plus Amoxicillin/Clavulanic Acid Combination Therapy--EORTC Infectious Diseases Group Trial XV.

PURPOSE This double-blind, multicenter trial compared the efficacy and safety of a single daily oral dose of moxifloxacin with oral combination therapy in low-risk febrile neutropenic patients with cancer. PATIENTS AND METHODS Inclusion criteria were cancer, febrile neutropenia, low risk of complications as predicted by a Multinational Association for Supportive Care in Cancer (MASCC) score > 20, ability to swallow, and ≤ one single intravenous dose of empiric antibiotic therapy before study drug treatment initiation. Early discharge was encouraged when a set of predefined criteria was met. Patients received either moxifloxacin (400 mg once daily) monotherapy or oral ciprofloxacin (750 mg twice daily) plus amoxicillin/clavulanic acid (1,000 mg twice daily). The trial was designed to show equivalence of the two drug regimens in terms of therapy success, defined as defervescence and improvement in clinical status during study drug treatment (< 10% difference). Results Among the 333 patients evaluated in an intention-to-treat analysis, therapy success was observed in 80% of the patients administered moxifloxacin and in 82% of the patients administered combination therapy (95% CI for the difference, -10% to 8%, consistent with equivalence). Minor differences in tolerability, safety, and reasons for failure were observed. More than 50% of the patients in the two arms were discharged on protocol therapy, with 5% readmissions among those in either arm. Survival was similar (99%) in both arms. CONCLUSION Monotherapy with once daily oral moxifloxacin is efficacious and safe in low-risk febrile neutropenic patients identified with the help of the MASCC scoring system, discharged early, and observed as outpatients.