Assessment of drug-induced hepatotoxicity in clinical practice: a challenge for gastroenterologists.

Currently, pharmaceutical preparations are serious contributors to liver disease; hepatotoxicity ranking as the most frequent cause for acute liver failure and post-commercialization regulatory decisions. The diagnosis of hepatotoxicity remains a difficult task because of the lack of reliable markers for use in general clinical practice. To incriminate any given drug in an episode of liver dysfunction is a step-by-step process that requires a high degree of suspicion, compatible chronology, awareness of the drug's hepatotoxic potential, the exclusion of alternative causes of liver damage and the ability to detect the presence of subtle data that favors a toxic etiology. This process is time-consuming and the final result is frequently inaccurate. Diagnostic algorithms may add consistency to the diagnostic process by translating the suspicion into a quantitative score. Such scales are useful since they provide a framework that emphasizes the features that merit attention in cases of suspected hepatic adverse reaction as well. Current efforts in collecting bona fide cases of drug-induced hepatotoxicity will make refinements of existing scales feasible. It is now relatively easy to accommodate relevant data within the scoring system and to delete low-impact items. Efforts should also be directed toward the development of an abridged instrument for use in evaluating suspected drug-induced hepatotoxicity at the very beginning of the diagnosis and treatment process when clinical decisions need to be made. The instrument chosen would enable a confident diagnosis to be made on admission of the patient and treatment to be fine-tuned as further information is collected.

Optimising translational oncology in clinical practice: Strategies to accelerate progress in drug development.

Despite intense efforts, the socioeconomic burden of cancer remains unacceptably high and treatment advances for many common cancers have been limited, suggesting a need for a new approach to drug development. One issue central to this lack of progress is the heterogeneity and genetic complexity of many tumours. This results in considerable variability in therapeutic response and requires knowledge of the molecular profile of the tumour to guide appropriate treatment selection for individual patients. While recent advances in the molecular characterisation of different cancer types have the potential to transform cancer treatment through precision medicine, such an approach presents a major economic challenge for drug development, since novel targeted agents may only be suitable for a small cohort of patients. Identifying the patients who would benefit from individual therapies and recruiting sufficient numbers of patients with particular cancer subtypes into clinical trials is challenging, and will require collaborative efforts from research groups and industry in order to accelerate progress. A number of molecular screening platforms have already been initiated across Europe, and it is hoped that these networks, along with future collaborations, will benefit not only patients but also society through cost reductions as a result of more efficient use of resources. This review discusses how current developments in translational oncology may be applied in clinical practice in the future, assesses current programmes for the molecular characterisation of cancer and describes possible collaborative approaches designed to maximise the benefits of translational science for patients with cancer.

L'examen neuropsychologique en pratique quotidienne [Neuropsychological test in daily practice]

Neuropsychology is a scientific discipline, born in the XIX century, and bridges the fields of neurology and psychology. Neuropsychologists apply scientific knowledge about the relationship between brain function and mental performances. The major clinical role of a neuropsychological evaluation is to help to establish medical and functional diagnosis in patients (adults or infants) with different neurological pathologies such as stroke, traumatic brain injury, dementia, epilepsy.... Such analysis necessitates accurate observation of behaviour and administration of tests of mental abilities (e.g. language, memory...). Test results can also help to clarify the nature of cognitive difficulties and to support the formulation of plans for neuropsychological therapy and functional adjustment in every day life.

Evaluation of email alerts in practice: Part 2. Validation of the information assessment method.

RATIONALE AND OBJECTIVE:. The information assessment method (IAM) permits health professionals to systematically document the relevance, cognitive impact, use and health outcomes of information objects delivered by or retrieved from electronic knowledge resources. The companion review paper (Part 1) critically examined the literature, and proposed a 'Push-Pull-Acquisition-Cognition-Application' evaluation framework, which is operationalized by IAM. The purpose of the present paper (Part 2) is to examine the content validity of the IAM cognitive checklist when linked to email alerts. METHODS: A qualitative component of a mixed methods study was conducted with 46 doctors reading and rating research-based synopses sent on email. The unit of analysis was a doctor's explanation of a rating of one item regarding one synopsis. Interviews with participants provided 253 units that were analysed to assess concordance with item definitions. RESULTS AND CONCLUSION: The content relevance of seven items was supported. For three items, revisions were needed. Interviews suggested one new item. This study has yielded a 2008 version of IAM.

Compliance with guidelines-recommended processes in pneumonia: impact of health status and initial signs

Initial care has been associated with improved survival of community-acquired pneumonia (CAP). We aimed to investigate patient comorbidities and health status measured by the Charlson index and clinical signs at diagnosis associated with adherence to recommended processes of care in CAP. We studied 3844 patients hospitalized with CAP. The evaluated recommendations were antibiotic adherence to Spanish guidelines, first antibiotic dose <6 hours and oxygen assessment. Antibiotic adherence was 72.6%, first dose <6 h was 73.4% and oxygen assessment was 90.2%. Antibiotic adherence was negatively associated with a high Charlson score (Odds ratio [OR], 0.91), confusion (OR, 0.66) and tachycardia ≥100 bpm (OR, 0.77). Delayed first dose was significantly lower in those with tachycardia (OR, 0.75). Initial oxygen assessment was negatively associated with fever (OR, 0.61), whereas tachypnea ≥30 (OR, 1.58), tachycardia (OR, 1.39), age >65 (OR, 1.51) and COPD (OR, 1.80) were protective factors. The combination of antibiotic adherence and timing <6 hours was negatively associated with confusion (OR, 0.69) and a high Charlson score (OR, 0.92) adjusting for severity and hospital effect, whereas age was not an independent factor. Deficient health status and confusion, rather than age, are associated with lower compliance with antibiotic therapy recommendations and timing, thus identifying a subpopulation more prone to receiving lower quality care.

Clinical audit of COPD patients requiring hospital admissions in Spain: AUDIPOC study.

BACKGROUNDS AUDIPOC is a nationwide clinical audit that describes the characteristics, interventions and outcomes of patients admitted to Spanish hospitals because of an exacerbation of chronic obstructive pulmonary disease (ECOPD), assessing the compliance of these parameters with current international guidelines. The present study describes hospital resources, hospital factors related to case recruitment variability, patients' characteristics, and adherence to guidelines. METHODOLOGY/PRINCIPAL FINDINGS An organisational database was completed by all participant hospitals recording resources and organisation. Over an 8-week period 11,564 consecutive ECOPD admissions to 129 Spanish hospitals covering 70% of the Spanish population were prospectively identified. At hospital discharge, 5,178 patients (45% of eligible) were finally included, and thus constituted the audited population. Audited patients were reassessed 90 days after admission for survival and readmission rates. A wide variability was observed in relation to most variables, hospital adherence to guidelines, and readmissions and death. Median inpatient mortality was 5% (across-hospital range 0-35%). Among discharged patients, 37% required readmission (0-62%) and 6.5% died (0-35%). The overall mortality rate was 11.6% (0-50%). Hospital size and complexity and aspects related to hospital COPD awareness were significantly associated with case recruitment. Clinical management most often complied with diagnosis and treatment recommendations but rarely (<50%) addressed guidance on healthy life-styles. CONCLUSIONS/SIGNIFICANCE The AUDIPOC study highlights the large across-hospital variability in resources and organization of hospitals, patient characteristics, process of care, and outcomes. The study also identifies resources and organizational characteristics associated with the admission of COPD cases, as well as aspects of daily clinical care amenable to improvement.

Patients presenting with somatic complaints in general practice : dépression, anxiety and somatoform disorders are frequent and associated with psychosocial stressors

RAPPORT DE SYNTHÈSE Introduction En médecine de premier recours, les plaintes physiques sont fréquemment associées à des troubles dépressifs, anxieux et somatoformes et peuvent les masquer. Il est fréquemment reporté que ces troubles mentaux ont tendance à être insuffisamment diagnostiqués. Par ailleurs, peu d'études ont été conduites en médecine de premier recours concernant la possible association entre facteurs de stress psychosociaux et troubles dépressifs, anxieux et somatoformes. Objectifs Les objectifs étaient de déterminer la prévalence des troubles dépressifs, anxieux et somatoformes chez des patients consultant avec une plainte physique en médecine de premier recours, ainsi que d'explorer la possible association entre ces troubles mentaux et des facteurs de stress psychosociaux. Méthodes Nous avons conduit une étude transversale, multicentrique parmi vingt et un cabinets médicaux en Suisse Romande et la Policlinique Médicale Universitaire de Lausanne. Les sujets étaient sélectionnés aléatoirement parmi des patients qui avaient présenté spontanément au moins une plainte physique et qui avaient consulté lors d'une demi- journée de consultation considérée pour l'étude. Les patients inclus ont rempli l'auto- questionnaire Patient Health Questionnaire (PHQ) entre novembre 2004 et juillet 2005. Nous avons utilisé la version française et validée du PHQ qui permet le diagnostic des principaux troubles mentaux selon les critères du DSM-IV et l'analyse de l'exposition aux facteurs de stress psychosociaux. Résultats Neuf cent dix-sept patients se présentant avec au moins une plainte physique ont été inclus. Le taux de troubles dépressifs, anxieux et somatoformes a été de 20,0% (intervalle de confiance [IC] à 95% = 17,4%-22,7%), 15,5% (IC 95% = 13,2%- 18,0%) et 15,1% (IC 95% = 12,8%~17,5%), respectivement. Les facteurs de stress psychosociaux ont été significativement associés aux troubles mentaux. Les patients avec une accumulation de facteurs de stress psychosociaux ont été le plus souvent déprimés, anxieux ou ont manifesté des troubles somatoformes, avec une augmentation par un facteur 2,2 (IC 95% = 2,0-2,5) pour chaque facteur additionnel. Conclusions Bien que la relation entre facteurs de stress psychosociaux et trouble dépressif soit bien établie, cette étude montre qu'il existe un lien entre ces facteurs de stress et les troubles dépressifs, anxieux et somatoformes. L'investigation de ces troubles mentaux chez des patients consultant avec un symptôme physique en médecine de premier recours est pertinente. D'autres explorations sont nécessaires pour investiguer le bénéfice potentiel d'une prise en charge intégrée des facteurs de stress psychosociaux sur la diminution des plaintes physiques et des troubles mentaux chez les patients que suivent les médecins de premier recours.

Infliximab for Crohn's disease in the Swiss IBD Cohort Study: clinical management and appropriateness.

OBJECTIVE: Antitumor necrosis factor a agents have significantly improved the management of Crohn's disease (CD), but not all patients benefit from this therapy. We used data from the Swiss Inflammatory Bowel Disease Cohort Study and predefined appropriateness criteria to examine the appropriateness of use of infliximab (IFX) in CD patients. METHODS: EPACT II (European Panel on the Appropriateness of CD Therapy, 2007; www.epact.ch) appropriateness criteria have been developed using a formal explicit panel process combining evidence from the published literature and expert opinion. Questionnaires relating to EPACT II criteria were used at enrollment and follow-up of all Swiss Inflammatory Bowel Disease Cohort Study patients. A step-by-step analysis of all possible indications for IFX therapy in a given patient allowed identification of the most appropriate indication and final classification in a single appropriateness category (appropriate, uncertain, inappropriate). RESULTS: Eight hundred and twenty-one CD patients were prospectively enrolled between November 2006 and March 2009. IFX was administered to 146 patients (18%) at enrollment and was most frequently used for complex fistulizing disease and for the maintenance of remission induced by biological therapy. IFX therapy was considered appropriate in 44%, uncertain in 44%, and inappropriate in 10% of patients. CONCLUSION: In this cohort, 9 out of 10 indications for IFX therapy were clinically generally acceptable (appropriate or uncertain) according to EPACT II criteria. Uncertain indications resulted mainly from the current more liberal use of IFX in clinical practice as compared with the EPACT II criteria.

Comment mettre en application des recommandations de pratique clinique? L'exemple des dyslipidémies [How to apply clinical guidelines in medical practice? The example of dyslipidemia]

How to summarize and facilitate the implementation of national and international guidelines in clinical practice? To adress these issues, we present a summary of dyslipidemia management for general practitioners. To achieve these aims, we adopted strategies based on international and national guidelines and focused on clinical applications which implies to choose specific options, such as the use of cardiovascular risk score and specific therapies as first options.

Coloritto ([Edition augmentée de l'appendice et des 4 pl. (2 versions supplémentaires du visage de femme, accompagnées des deux palettes de couleurs correspondantes) ]) / ; or the harmony of colouring in painting : reduced to mechanical practice, under easy precepts, and infallible rules ; together with some colour'd figures, in order to render the said precepts and rules intelligible, not only to painters, but even to all lovers of painting. By J. C. Le Blon.

Ancien possesseur : Ledoux-Lebard, Guy (1912-2003)