Clinical review: practical recommendations on the management of perioperative heart failure in cardiac surgery.

Acute cardiovascular dysfunction occurs perioperatively in more than 20% of cardiosurgical patients, yet current acute heart failure (HF) classification is not applicable to this period. Indicators of major perioperative risk include unstable coronary syndromes, decompensated HF, significant arrhythmias and valvular disease. Clinical risk factors include history of heart disease, compensated HF, cerebrovascular disease, presence of diabetes mellitus, renal insufficiency and high-risk surgery. EuroSCORE reliably predicts perioperative cardiovascular alteration in patients aged less than 80 years. Preoperative B-type natriuretic peptide level is an additional risk stratification factor. Aggressively preserving heart function during cardiosurgery is a major goal. Volatile anaesthetics and levosimendan seem to be promising cardioprotective agents, but large trials are still needed to assess the best cardioprotective agent(s) and optimal protocol(s). The aim of monitoring is early detection and assessment of mechanisms of perioperative cardiovascular dysfunction. Ideally, volume status should be assessed by 'dynamic' measurement of haemodynamic parameters. Assess heart function first by echocardiography, then using a pulmonary artery catheter (especially in right heart dysfunction). If volaemia and heart function are in the normal range, cardiovascular dysfunction is very likely related to vascular dysfunction. In treating myocardial dysfunction, consider the following options, either alone or in combination: low-to-moderate doses of dobutamine and epinephrine, milrinone or levosimendan. In vasoplegia-induced hypotension, use norepinephrine to maintain adequate perfusion pressure. Exclude hypovolaemia in patients under vasopressors, through repeated volume assessments. Optimal perioperative use of inotropes/vasopressors in cardiosurgery remains controversial, and further large multinational studies are needed. Cardiosurgical perioperative classification of cardiac impairment should be based on time of occurrence (precardiotomy, failure to wean, postcardiotomy) and haemodynamic severity of the patient's condition (crash and burn, deteriorating fast, stable but inotrope dependent). In heart dysfunction with suspected coronary hypoperfusion, an intra-aortic balloon pump is highly recommended. A ventricular assist device should be considered before end organ dysfunction becomes evident. Extra-corporeal membrane oxygenation is an elegant solution as a bridge to recovery and/or decision making. This paper offers practical recommendations for management of perioperative HF in cardiosurgery based on European experts' opinion. It also emphasizes the need for large surveys and studies to assess the optimal way to manage perioperative HF in cardiac surgery.

Prevention and treatment options for postoperative delirium in the elderly.

PURPOSE OF REVIEW: To review recent findings and developments in strategies for prevention and treatment of postoperative delirium. RECENT FINDINGS: Current advances in the field include improved knowledge about predisposing and precipitating factors, evidence for efficacy of multicomponent prevention programmes, refinement of perioperative procedures, and promising pharmacological approaches for prophylaxis and management of postoperative delirium. SUMMARY: Postoperative delirium is a common and serious complication in elderly patients. Preoperative assessment of risk profiles and tailored multimodal prevention approaches proved effective and should be integrated into clinical practice. Despite promising recent findings, at present, the routine use of pharmacological prophylaxis cannot be recommended. Validated and easy-to-use bedside diagnostic tools are available and should be regularly applied for delirium screening in the first days after surgery. In patients developing delirium, causal conditions and contributing factors need to be identified and addressed. Whereas administration of antipsychotics may represent an option for symptomatic treatment, further studies are needed to evaluate the effects of pharmacological approaches on long-term outcomes in elderly patients with delirium.

Prospective validation of the Pulmonary Embolism Severity Index. A clinical prognostic model for pulmonary embolism

Practice guidelines recommend outpatient care for selected patients with non-massive pulmonary embolism (PE), but fail to specify how these low-risk patients should be identified. Using data from U.S. patients, we previously derived the Pulmonary Embolism Severity Index (PESI), a prediction rule that risk stratifies patients with PE. We sought to validate the PESI in a European patient cohort. We prospectively validated the PESI in patients with PE diagnosed at six emergency departments in three European countries. We used baseline data for the rule's 11 prognostic variables to stratify patients into five risk classes (I-V) of increasing probability of mortality. The outcome was overall mortality at 90 days after presentation. To assess the accuracy of the PESI to predict mortality, we estimated the sensitivity, specificity, and predictive values for low- (risk classes I/II) versus higher-risk patients (risk classes III-V), and the discriminatory power using the area under the receiver operating characteristic (ROC) curve. Among 357 patients with PE, overall mortality was 5.9%, ranging from 0% in class I to 17.9% in class V. The 186 (52%) low-risk patients had an overall mortality of 1.1% (95% confidence interval [CI]: 0.1-3.8%) compared to 11.1% (95% CI: 6.8-16.8%) in the 171 (48%) higher-risk patients. The PESI had a high sensitivity (91%, 95% CI: 71-97%) and a negative predictive value (99%, 95% CI: 96-100%) for predicting mortality. The area under the ROC curve was 0.78 (95% CI: 0.70-0.86). The PESI reliably identifies patients with PE who are at low risk of death and who are potential candidates for outpatient care. The PESI may help physicians make more rational decisions about hospitalization for patients with PE.

Clinical and pharmacogenetic study on smoking and smoking cessation

Currently, smoking cessation represents one of the main strategies to reduce the incidence of tobacco-related diseases in the population. Smoking can also influence pharmacotherapy through several pharmacokinetic or pharmacodynamic interactions. Some of the most concerned drugs are those metabolized by the cytochrome P450 (CYP) 1A2 enzyme (e.g. caffeine, theophylline, clozapine, olanzapine, duloxetine), whose activity is induced by the polycyclic aromatic hydrocarbons found in tobacco smoke. This can result in a clinically significant decrease in the pharmacological effect of the drugs and the need of higher doses in smokers. Conversely, upon smoking cessation, toxic plasma levels of the drugs can be reached. The main objective of this thesis was to study the interindividual variability in CYP1A2 induction in a large cohort of smokers, by measuring CYP1A2 activity before smoking cessation and one month later in continuously abstinent subjects. For this purpose, a clinical study was conducted, including 194 smokers from the general population who wished to participate in a smoking cessation program and therefore received medical counseling and substitution therapy (nicotine or varenicline). An analytical method for the simultaneous quantification of nicotine, its metabolites and varenicline in plasma was developed and validated using ultra performance liquid chromatography coupled with tandem mass spectrometry. This method was used to confirm abstinence at different time points during the follow-up. Moreover, it was used to determine plasma levels of the smoking cessation drugs, to be used in the study of their pharmacogenetics, which was the secondary objective of this thesis. High interindividual variability in CYP1A2 induction by smoking was observed, ranging from no change to approximately 7 times decreased CYP1A2 activity after smoking cessation. Several clinical and genetic factors were investigated in an attempt to explain this variability. Firstly, a significant influence of CYP1A2*1F and *1D alleles, of contraceptive use and of the number of cigarettes smoked per day on CYP1A2 induced activity was observed, and of CYP1A2*1F and the use of contraceptives on the basal activity. But no influence of these factors was found on CYP1A2 inducibility. Given that known genetic polymorphisms in CYP1A2 gene were shown to explain only poorly the observed variations in activity, additional genetic factors were studied. SNPs in the CYP oxidoreductase (POR) gene were found to influence CYP1A2 basal activity, but not the induction. Finally, a pathway-based approach allowed to identify SNPs in genes coding for nuclear receptors (CAR, RXRa, VDR, PXR) and induction-mediating receptors (AhR), which significantly influenced CYP1A2 inducibility and basal activity (SNPs in the gene coding for CAR and RXRa). As secondary objective of the study, the pharmacogenetics of nicotine and varenicline is being investigated. Therefore, the nicotine metabolite ratio is used in the attempt to better explain nicotine dependence and the failure/success of quitting smoking. A population pharmacokinetic model is being developed for varenicline, integrating clinical and genetic factors (genes coding for its metabolizing enzymes and transporters), with the purpose of trying to predict efficacy and side effects. These findings suggest that the influence of smoking on pharmacotherapy could be better managed by including clinical and possibly in the future genetic factors, in the assessment of the adaptations needed when a person starts or stops smoking.  - L'arrêt du tabac représente une des principales stratégies pour diminuer l'incidence des maladies causées par celui-ci. Le tabagisme peut influencer la thérapie médicamenteuse par des interactions pharmacocinétiques ou pharmacodynamiques. Parmi les médicaments concernés, il y a ceux métabolisés par le cytochrome P450 (CYP) 1A2 (caféine, théophylline, clozapine, olanzapine, duloxétine, etc), dont l'activité enzymatique est induite par les hydrocarbures aromatiques polycycliques présents dans la fumée de cigarette. Ceci peut se traduire par une diminution de l'effet pharmacologique du traitement et la nécessité d'augmenter les doses d'entretien chez les fumeurs. Au contraire, à l'arrêt de la cigarette, les taux plasmatiques des médicaments peuvent devenir toxiques. L'objectif principal de cette thèse était d'étudier la variabilité interindividuelle dans l'induction du CYP1A2 dans une large cohorte de fumeurs, par la mesure de l'activité du CYP1A2 avant l'arrêt de la cigarette, ainsi qu'un mois après chez les sujets abstinents. Pour ce faire, une étude clinique a été conduite, incluant 194 fumeurs de la population générale dans un programme d'arrêt du tabac offrant des consultations spécifiques et un traitement pharmacologique (nicotine ou varénicline). Une méthode analytique pour la quantification simultanée de la nicotine, ses métabolites et la varénicline dans le plasma par chromatographie liquide couplée à la spectrométrie de masse en tandem à été développée et validée. Cette méthode a été utilisée pour confirmer l'abstinence pendant l'étude et déterminer les taux plasmatiques des médicaments, dans le but d'étudier leur pharmacogénétique. Une grande variabilité interindividuelle dans l'induction du CYP1A2 par la fumée a été observée, parfois sans changement et pouvant aller jusqu'à une diminution d'environ 7 fois l'activité du CYP1A2 après l'arrêt de la cigarette. Plusieurs facteurs cliniques et génétiques ont été étudiés pour essayer d'expliquer cette variabilité. Tout d'abord, on a observé une influence significative: des allèles CYP1A2*1F et *1D, des contraceptifs et du nombre de cigarettes fumées par jour sur l'activité induite du CYP1A2, ainsi que l'influence de l'allèle *1F et des contraceptifs sur l'activité basale. Cependant, aucune influence de ces facteurs n'a été démontrée sur l'inductibilité du CYP1A2. Étant donné que les polymorphismes génétiques du CYP1A2 apportent peu de renseignements sur la variabilité de son activité, des facteurs génétiques supplémentaires ont été étudiés. Des polymorphismes dans le gène POR (CYP oxidoreductase) ont été associés à l'activité basale du CYP1A2, mais pas à l'induction. Finalement, une approche basée sur la voie de signalisation du CYP1A2 a permis d'identifier des polymorphismes dans des gènes codant pour des récepteurs nucléaires (CAR, RXRa, VDR, PXR) et d'autres liés à l'induction (AhR) qui influencent significativement l'inductibilité et l'activité basale (les SNPs du CAR et RXRa). L'objectif secondaire de cette étude était d'investiguer la pharmacogénétique de la nicotine et de la varénicline. Le ratio métabolique de la nicotine est utilisé pour mieux expliquer la dépendance à la nicotine et le succès/échec de l'arrêt de la cigarette. Un modèle pharmacocinétique de population est en cours de développement pour la varénicline, intégrant des facteurs cliniques et génétiques (gènes codant pour ses enzymes de métabolisme et transporteurs), pour tenter de prédire son efficacité et ses effets secondaires. Les résultats de cette thèse suggèrent que l'influence du tabagisme sur la pharmacothérapie serait mieux gérée par l'inclusion des facteurs cliniques et peut-être, dans le futur, génétiques, dans l'évaluation des adaptations nécessaires lorsqu'une personne fume ou arrête de fumer.  - l'arrêt du tabac représente une des principales stratégies pour diminuer l'incidence des maladies causées par celui-ci dans la population. Le tabagisme peut influencer les traitements médicamenteux, soit en modifiant leur élimination par l'organisme, soit en agissant sur leur mode d'action. Parmi les médicaments les plus concernés, on retrouve par exemple: la caféine, la théophylline, la clozapine, l'olanzapine, la duloxétine, dont l'élimination est accélérée par la fumée de cigarette (induction enzymatique). Ceci peut se traduire par une diminution de l'effet du traitement et la nécessité d'en augmenter les doses chez les fumeurs. Au contraire, à l'arrêt de la cigarette, on observe un ralentissement de la fonction enzymatique, qui a pour conséquence une augmentation du taux de médicament dans le sang, pouvant devenir toxique. L'objectif principal de cette thèse était d'étudier comment cette induction par le tabac varie dans une population de fumeurs, par la mesure de l'activité de l'enzyme avant l'arrêt de la cigarette, ainsi qu'un mois après chez les sujets abstinents. Pour ce faire, une étude clinique a été conduite, incluant 194 fumeurs de la population générale dans un programme d'arrêt du tabac offrant des consultations spécifiques et un traitement médicamenteux (nicotine ou varénicline). Une méthode analytique a été mise au point pour mesurer la quantité de nicotine, de ses produits de dégradation et de la varénicline dans le sang des participants à l'étude. De plus, cette méthode a été utilisée pour confirmer l'abstinence pendant l'étude. Une grande variabilité interindividuelle a été observée dans l'induction de l'enzyme par la fumée; il en résulte aucun changement d'activité chez certains sujets après l'arrêt de la cigarette, alors que pour d'autres elle peut être diminuée jusqu'à 7 fois. Plusieurs facteurs cliniques et génétiques ont été étudiés pour essayer d'expliquer cette variabilité. Premièrement, une influence sur l'activité de l'enzyme a été observée pour les contraceptifs hormonaux et le nombre de cigarettes fumées par jour, ainsi que pour certaines variations génétiques dans le gène codant pour l'enzyme d'intérêt, mais il η y a pas eu d'influence sur l'induction. Par la suite, des variations génétiques dans d'autres gènes influençant le fonctionnement de l'enzyme ont été associées soit avec son activité, soit avec son induction par le tabac. Finalement, l'étude propose également d'investiguer si le métabolisme de la nicotine a une influence sur la dépendance, les symptômes de sevrage et le succès/échec de l'arrêt de la cigarette. Des variations génétiques dans les gènes du métabolisme de la varénicline sont également étudiées en lien avec les quantités de varénicline mesurées dans le sang ainsi que les effets du médicament. Ceci permettra peut-être de prédire son efficacité et ses effets secondaires. Les résultats de cette thèse suggèrent que l'influence du tabagisme sur la thérapie médicamenteuse serait mieux gérée en tenant compte des facteurs cliniques et peut-être, dans le futur, de la génétique dans l'adaptation des traitements, que la personne soit fumeuse ou en phase d'arrêt.

ESPEN endorsed recommendations: nutritional therapy in major burns.

BACKGROUND & AIMS: Nutrition therapy is a cornerstone of burn care from the early resuscitation phase until the end of rehabilitation. While several aspects of nutrition therapy are similar in major burns and other critical care conditions, the patho-physiology of burn injury with its major endocrine, inflammatory, metabolic and immune alterations requires some specific nutritional interventions. The present text developed by the French speaking societies, is updated to provide evidenced-based recommendations for clinical practice. METHODS: A group of burn specialists used the GRADE methodology (Grade of Recommendation, Assessment, Development and Evaluation) to evaluate human burn clinical trials between 1979 and 2011. The resulting recommendations, strong suggestions or suggestions were then rated by the non-burn specialized experts according to their agreement (strong, moderate or weak). RESULTS: Eight major recommendations were made. Strong recommendations were made regarding, 1) early enteral feeding, 2) the elevated protein requirements (1.5-2 g/kg in adults, 3 g/kg in children), 3) the limitation of glucose delivery to a maximum of 55% of energy and 5 mg/kg/h associated with moderate blood glucose (target ≤ 8 mmol/l) control by means of continuous infusion, 4) to associated trace element and vitamin substitution early on, and 5) to use non-nutritional strategies to attenuate hypermetabolism by pharmacological (propranolol, oxandrolone) and physical tools (early surgery and thermo-neutral room) during the first weeks after injury. Suggestion were made in absence of indirect calorimetry, to use of the Toronto equation (Schoffield in children) for energy requirement determination (risk of overfeeding), and to maintain fat administration ≤ 30% of total energy delivery. CONCLUSION: The nutritional therapy in major burns has evidence-based specificities that contribute to improve clinical outcome.

Clinical significance of the CCR5delta32 allele in hepatitis C.

BACKGROUND: The CCR5 receptor, expressed on Th1 cells, may influence clinical outcomes of HCV infection. We explored a possible link between a CCR5 32-base deletion (CCR5delta32), resulting in the expression of a non-functioning receptor, and clinical outcomes of HCV infection. METHODS: CCR5 and HCV-related phenotypes were analysed in 1,290 chronically infected patients and 160 patients with spontaneous clearance. RESULTS: Carriage of the CCR5delta32 allele was observed in 11% of spontaneous clearers compared to 17% of chronically infected patients (OR = 0.59, 95% CI interval 0.35-0.99, P = 0.047). Carriage of this allele also tended to be observed more frequently among patients with liver inflammation (19%) compared to those without inflammation (15%, OR = 1.38, 95% CI interval 0.99-1.95, P = 0.06). The CCR5delta32 was not associated with sustained virological response (P = 0.6), fibrosis stage (P = 0.8), or fibrosis progression rate (P = 0.4). CONCLUSIONS: The CCR5delta32 allele appears to be associated with a decreased rate of spontaneous HCV eradication, but not with hepatitis progression or response to antiviral therapy.

Molecular detection and identification of zygomycetes species from paraffin-embedded tissues in a murine model of disseminated zygomycosis: a collaborative European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Fungal Infection Study Group (EFISG) evaluation.

The present study was performed to assess the interlaboratory reproducibility of the molecular detection and identification of species of Zygomycetes from formalin-fixed paraffin-embedded kidney and brain tissues obtained from experimentally infected mice. Animals were infected with one of five species (Rhizopus oryzae, Rhizopus microsporus, Lichtheimia corymbifera, Rhizomucor pusillus, and Mucor circinelloides). Samples with 1, 10, or 30 slide cuts of the tissues were prepared from each paraffin block, the sample identities were blinded for analysis, and the samples were mailed to each of seven laboratories for the assessment of sensitivity. A protocol describing the extraction method and the PCR amplification procedure was provided. The internal transcribed spacer 1 (ITS1) region was amplified by PCR with the fungal universal primers ITS1 and ITS2 and sequenced. As negative results were obtained for 93% of the tissue specimens infected by M. circinelloides, the data for this species were excluded from the analysis. Positive PCR results were obtained for 93% (52/56), 89% (50/56), and 27% (15/56) of the samples with 30, 10, and 1 slide cuts, respectively. There were minor differences, depending on the organ tissue, fungal species, and laboratory. Correct species identification was possible for 100% (30 cuts), 98% (10 cuts), and 93% (1 cut) of the cases. With the protocol used in the present study, the interlaboratory reproducibility of ITS sequencing for the identification of major Zygomycetes species from formalin-fixed paraffin-embedded tissues can reach 100%, when enough material is available.

Task force IV: Clinical use of ambulatory blood pressure monitoring. Participants of the 1999 Consensus Conference on Ambulatory Blood Pressure Monitoring

OBJECTIVE: To reach a consensus on the clinical use of ambulatory blood pressure monitoring (ABPM). METHODS: A task force on the clinical use of ABPM wrote this overview in preparation for the Seventh International Consensus Conference (23-25 September 1999, Leuven, Belgium). This article was amended to account for opinions aired at the conference and to reflect the common ground reached in the discussions. POINTS OF CONSENSUS: The Riva Rocci/Korotkoff technique, although it is prone to error, is easy and cheap to perform and remains worldwide the standard procedure for measuring blood pressure. ABPM should be performed only with properly validated devices as an accessory to conventional measurement of blood pressure. Ambulatory recording of blood pressure requires considerable investment in equipment and training and its use for screening purposes cannot be recommended. ABPM is most useful for identifying patients with white-coat hypertension (WCH), also known as isolated clinic hypertension, which is arbitrarily defined as a clinic blood pressure of more than 140 mmHg systolic or 90 mmHg diastolic in a patient with daytime ambulatory blood pressure below 135 mmHg systolic and 85 mmHg diastolic. Some experts consider a daytime blood pressure below 130 mmHg systolic and 80 mmHg diastolic optimal. Whether WCH predisposes subjects to sustained hypertension remains debated. However, outcome is better correlated to the ambulatory blood pressure than it is to the conventional blood pressure. Antihypertensive drugs lower the clinic blood pressure in patients with WCH but not the ambulatory blood pressure, and also do not improve prognosis. Nevertheless, WCH should not be left unattended. If no previous cardiovascular complications are present, treatment could be limited to follow-up and hygienic measures, which should also account for risk factors other than hypertension. ABPM is superior to conventional measurement of blood pressure not only for selecting patients for antihypertensive drug treatment but also for assessing the effects both of non-pharmacological and of pharmacological therapy. The ambulatory blood pressure should be reduced by treatment to below the thresholds applied for diagnosing sustained hypertension. ABPM makes the diagnosis and treatment of nocturnal hypertension possible and is especially indicated for patients with borderline hypertension, the elderly, pregnant women, patients with treatment-resistant hypertension and patients with symptoms suggestive of hypotension. In centres with sufficient financial resources, ABPM could become part of the routine assessment of patients with clinic hypertension. For patients with WCH, it should be repeated at annual or 6-monthly intervals. Variation of blood pressure throughout the day can be monitored only by ABPM, but several advantages of the latter technique can also be obtained by self-measurement of blood pressure, a less expensive method that is probably better suited to primary practice and use in developing countries. CONCLUSIONS: ABPM or equivalent methods for tracing the white-coat effect should become part of the routine diagnostic and therapeutic procedures applied to treated and untreated patients with elevated clinic blood pressures. Results of long-term outcome trials should better establish the advantage of further integrating ABPM as an accessory to conventional sphygmomanometry into the routine care of hypertensive patients and should provide more definite information on the long-term cost-effectiveness. Because such trials are not likely to be funded by the pharmaceutical industry, governments and health insurance companies should take responsibility in this regard.

Rapid bacterial genome sequencing: methods and applications in clinical microbiology.

The recent advances in sequencing technologies have given all microbiology laboratories access to whole genome sequencing. Providing that tools for the automated analysis of sequence data and databases for associated meta-data are developed, whole genome sequencing will become a routine tool for large clinical microbiology laboratories. Indeed, the continuing reduction in sequencing costs and the shortening of the 'time to result' makes it an attractive strategy in both research and diagnostics. Here, we review how high-throughput sequencing is revolutionizing clinical microbiology and the promise that it still holds. We discuss major applications, which include: (i) identification of target DNA sequences and antigens to rapidly develop diagnostic tools; (ii) precise strain identification for epidemiological typing and pathogen monitoring during outbreaks; and (iii) investigation of strain properties, such as the presence of antibiotic resistance or virulence factors. In addition, recent developments in comparative metagenomics and single-cell sequencing offer the prospect of a better understanding of complex microbial communities at the global and individual levels, providing a new perspective for understanding host-pathogen interactions. Being a high-resolution tool, high-throughput sequencing will increasingly influence diagnostics, epidemiology, risk management, and patient care.

A novel tool for the assessment of pain: validation in low back pain.

BACKGROUND: Adequate pain assessment is critical for evaluating the efficacy of analgesic treatment in clinical practice and during the development of new therapies. Yet the currently used scores of global pain intensity fail to reflect the diversity of pain manifestations and the complexity of underlying biological mechanisms. We have developed a tool for a standardized assessment of pain-related symptoms and signs that differentiates pain phenotypes independent of etiology. METHODS AND FINDINGS: Using a structured interview (16 questions) and a standardized bedside examination (23 tests), we prospectively assessed symptoms and signs in 130 patients with peripheral neuropathic pain caused by diabetic polyneuropathy, postherpetic neuralgia, or radicular low back pain (LBP), and in 57 patients with non-neuropathic (axial) LBP. A hierarchical cluster analysis revealed distinct association patterns of symptoms and signs (pain subtypes) that characterized six subgroups of patients with neuropathic pain and two subgroups of patients with non-neuropathic pain. Using a classification tree analysis, we identified the most discriminatory assessment items for the identification of pain subtypes. We combined these six interview questions and ten physical tests in a pain assessment tool that we named Standardized Evaluation of Pain (StEP). We validated StEP for the distinction between radicular and axial LBP in an independent group of 137 patients. StEP identified patients with radicular pain with high sensitivity (92%; 95% confidence interval [CI] 83%-97%) and specificity (97%; 95% CI 89%-100%). The diagnostic accuracy of StEP exceeded that of a dedicated screening tool for neuropathic pain and spinal magnetic resonance imaging. In addition, we were able to reproduce subtypes of radicular and axial LBP, underscoring the utility of StEP for discerning distinct constellations of symptoms and signs. CONCLUSIONS: We present a novel method of identifying pain subtypes that we believe reflect underlying pain mechanisms. We demonstrate that this new approach to pain assessment helps separate radicular from axial back pain. Beyond diagnostic utility, a standardized differentiation of pain subtypes that is independent of disease etiology may offer a unique opportunity to improve targeted analgesic treatment.

Le soignant face au patient lombalgique chronique: l'expérience clinique de l'Unité Rachis à l'Hôpital orthopédique [The health professional's approach to chronic lumbago: clinical experience at the Spinal Cord Unit at the orthopedic hospital]

The treatment of back pain patients refers to the biopsychosocial model of care. This model includes illness in patient's personal and relational life. In this context, it is not only the physical symptom of the patient which is focused but also his psychological distress often hidden by algic complain. Clinical interviews conducted with back pain patients have highlighted psychosocial aspects able to influence the relationship between health care user and provider. Taking account of psychosocial aspects implies an interdisciplinary approach that identify and assesses patients' needs through adequate tools. As a result, the different health care providers implied with back pain patients have to collaborate in a structured network.

Species distribution models for conservation-oriented studies in Switzerland : filling data and tools gaps

SUMMARYSpecies distribution models (SDMs) represent nowadays an essential tool in the research fields of ecology and conservation biology. By combining observations of species occurrence or abundance with information on the environmental characteristic of the observation sites, they can provide information on the ecology of species, predict their distributions across the landscape or extrapolate them to other spatial or time frames. The advent of SDMs, supported by geographic information systems (GIS), new developments in statistical models and constantly increasing computational capacities, has revolutionized the way ecologists can comprehend species distributions in their environment. SDMs have brought the tool that allows describing species realized niches across a multivariate environmental space and predict their spatial distribution. Predictions, in the form of probabilistic maps showing the potential distribution of the species, are an irreplaceable mean to inform every single unit of a territory about its biodiversity potential. SDMs and the corresponding spatial predictions can be used to plan conservation actions for particular species, to design field surveys, to assess the risks related to the spread of invasive species, to select reserve locations and design reserve networks, and ultimately, to forecast distributional changes according to scenarios of climate and/or land use change.By assessing the effect of several factors on model performance and on the accuracy of spatial predictions, this thesis aims at improving techniques and data available for distribution modelling and at providing the best possible information to conservation managers to support their decisions and action plans for the conservation of biodiversity in Switzerland and beyond. Several monitoring programs have been put in place from the national to the global scale, and different sources of data now exist and start to be available to researchers who want to model species distribution. However, because of the lack of means, data are often not gathered at an appropriate resolution, are sampled only over limited areas, are not spatially explicit or do not provide a sound biological information. A typical example of this is data on 'habitat' (sensu biota). Even though this is essential information for an effective conservation planning, it often has to be approximated from land use, the closest available information. Moreover, data are often not sampled according to an established sampling design, which can lead to biased samples and consequently to spurious modelling results. Understanding the sources of variability linked to the different phases of the modelling process and their importance is crucial in order to evaluate the final distribution maps that are to be used for conservation purposes.The research presented in this thesis was essentially conducted within the framework of the Landspot Project, a project supported by the Swiss National Science Foundation. The main goal of the project was to assess the possible contribution of pre-modelled 'habitat' units to model the distribution of animal species, in particular butterfly species, across Switzerland. While pursuing this goal, different aspects of data quality, sampling design and modelling process were addressed and improved, and implications for conservation discussed. The main 'habitat' units considered in this thesis are grassland and forest communities of natural and anthropogenic origin as defined in the typology of habitats for Switzerland. These communities are mainly defined at the phytosociological level of the alliance. For the time being, no comprehensive map of such communities is available at the national scale and at fine resolution. As a first step, it was therefore necessary to create distribution models and maps for these communities across Switzerland and thus to gather and collect the necessary data. In order to reach this first objective, several new developments were necessary such as the definition of expert models, the classification of the Swiss territory in environmental domains, the design of an environmentally stratified sampling of the target vegetation units across Switzerland, the development of a database integrating a decision-support system assisting in the classification of the relevés, and the downscaling of the land use/cover data from 100 m to 25 m resolution.The main contributions of this thesis to the discipline of species distribution modelling (SDM) are assembled in four main scientific papers. In the first, published in Journal of Riogeography different issues related to the modelling process itself are investigated. First is assessed the effect of five different stepwise selection methods on model performance, stability and parsimony, using data of the forest inventory of State of Vaud. In the same paper are also assessed: the effect of weighting absences to ensure a prevalence of 0.5 prior to model calibration; the effect of limiting absences beyond the environmental envelope defined by presences; four different methods for incorporating spatial autocorrelation; and finally, the effect of integrating predictor interactions. Results allowed to specifically enhance the GRASP tool (Generalized Regression Analysis and Spatial Predictions) that now incorporates new selection methods and the possibility of dealing with interactions among predictors as well as spatial autocorrelation. The contribution of different sources of remotely sensed information to species distribution models was also assessed. The second paper (to be submitted) explores the combined effects of sample size and data post-stratification on the accuracy of models using data on grassland distribution across Switzerland collected within the framework of the Landspot project and supplemented with other important vegetation databases. For the stratification of the data, different spatial frameworks were compared. In particular, environmental stratification by Swiss Environmental Domains was compared to geographical stratification either by biogeographic regions or political states (cantons). The third paper (to be submitted) assesses the contribution of pre- modelled vegetation communities to the modelling of fauna. It is a two-steps approach that combines the disciplines of community ecology and spatial ecology and integrates their corresponding concepts of habitat. First are modelled vegetation communities per se and then these 'habitat' units are used in order to model animal species habitat. A case study is presented with grassland communities and butterfly species. Different ways of integrating vegetation information in the models of butterfly distribution were also evaluated. Finally, a glimpse to climate change is given in the fourth paper, recently published in Ecological Modelling. This paper proposes a conceptual framework for analysing range shifts, namely a catalogue of the possible patterns of change in the distribution of a species along elevational or other environmental gradients and an improved quantitative methodology to identify and objectively describe these patterns. The methodology was developed using data from the Swiss national common breeding bird survey and the article presents results concerning the observed shifts in the elevational distribution of breeding birds in Switzerland.The overall objective of this thesis is to improve species distribution models as potential inputs for different conservation tools (e.g. red lists, ecological networks, risk assessment of the spread of invasive species, vulnerability assessment in the context of climate change). While no conservation issues or tools are directly tested in this thesis, the importance of the proposed improvements made in species distribution modelling is discussed in the context of the selection of reserve networks.RESUMELes modèles de distribution d'espèces (SDMs) représentent aujourd'hui un outil essentiel dans les domaines de recherche de l'écologie et de la biologie de la conservation. En combinant les observations de la présence des espèces ou de leur abondance avec des informations sur les caractéristiques environnementales des sites d'observation, ces modèles peuvent fournir des informations sur l'écologie des espèces, prédire leur distribution à travers le paysage ou l'extrapoler dans l'espace et le temps. Le déploiement des SDMs, soutenu par les systèmes d'information géographique (SIG), les nouveaux développements dans les modèles statistiques, ainsi que la constante augmentation des capacités de calcul, a révolutionné la façon dont les écologistes peuvent comprendre la distribution des espèces dans leur environnement. Les SDMs ont apporté l'outil qui permet de décrire la niche réalisée des espèces dans un espace environnemental multivarié et prédire leur distribution spatiale. Les prédictions, sous forme de carte probabilistes montrant la distribution potentielle de l'espèce, sont un moyen irremplaçable d'informer chaque unité du territoire de sa biodiversité potentielle. Les SDMs et les prédictions spatiales correspondantes peuvent être utilisés pour planifier des mesures de conservation pour des espèces particulières, pour concevoir des plans d'échantillonnage, pour évaluer les risques liés à la propagation d'espèces envahissantes, pour choisir l'emplacement de réserves et les mettre en réseau, et finalement, pour prévoir les changements de répartition en fonction de scénarios de changement climatique et/ou d'utilisation du sol. En évaluant l'effet de plusieurs facteurs sur la performance des modèles et sur la précision des prédictions spatiales, cette thèse vise à améliorer les techniques et les données disponibles pour la modélisation de la distribution des espèces et à fournir la meilleure information possible aux gestionnaires pour appuyer leurs décisions et leurs plans d'action pour la conservation de la biodiversité en Suisse et au-delà. Plusieurs programmes de surveillance ont été mis en place de l'échelle nationale à l'échelle globale, et différentes sources de données sont désormais disponibles pour les chercheurs qui veulent modéliser la distribution des espèces. Toutefois, en raison du manque de moyens, les données sont souvent collectées à une résolution inappropriée, sont échantillonnées sur des zones limitées, ne sont pas spatialement explicites ou ne fournissent pas une information écologique suffisante. Un exemple typique est fourni par les données sur 'l'habitat' (sensu biota). Même s'il s'agit d'une information essentielle pour des mesures de conservation efficaces, elle est souvent approximée par l'utilisation du sol, l'information qui s'en approche le plus. En outre, les données ne sont souvent pas échantillonnées selon un plan d'échantillonnage établi, ce qui biaise les échantillons et par conséquent les résultats de la modélisation. Comprendre les sources de variabilité liées aux différentes phases du processus de modélisation s'avère crucial afin d'évaluer l'utilisation des cartes de distribution prédites à des fins de conservation.La recherche présentée dans cette thèse a été essentiellement menée dans le cadre du projet Landspot, un projet soutenu par le Fond National Suisse pour la Recherche. L'objectif principal de ce projet était d'évaluer la contribution d'unités 'd'habitat' pré-modélisées pour modéliser la répartition des espèces animales, notamment de papillons, à travers la Suisse. Tout en poursuivant cet objectif, différents aspects touchant à la qualité des données, au plan d'échantillonnage et au processus de modélisation sont abordés et améliorés, et leurs implications pour la conservation des espèces discutées. Les principaux 'habitats' considérés dans cette thèse sont des communautés de prairie et de forêt d'origine naturelle et anthropique telles que définies dans la typologie des habitats de Suisse. Ces communautés sont principalement définies au niveau phytosociologique de l'alliance. Pour l'instant aucune carte de la distribution de ces communautés n'est disponible à l'échelle nationale et à résolution fine. Dans un premier temps, il a donc été nécessaire de créer des modèles de distribution de ces communautés à travers la Suisse et par conséquent de recueillir les données nécessaires. Afin d'atteindre ce premier objectif, plusieurs nouveaux développements ont été nécessaires, tels que la définition de modèles experts, la classification du territoire suisse en domaines environnementaux, la conception d'un échantillonnage environnementalement stratifié des unités de végétation cibles dans toute la Suisse, la création d'une base de données intégrant un système d'aide à la décision pour la classification des relevés, et le « downscaling » des données de couverture du sol de 100 m à 25 m de résolution. Les principales contributions de cette thèse à la discipline de la modélisation de la distribution d'espèces (SDM) sont rassemblées dans quatre articles scientifiques. Dans le premier article, publié dans le Journal of Biogeography, différentes questions liées au processus de modélisation sont étudiées en utilisant les données de l'inventaire forestier de l'Etat de Vaud. Tout d'abord sont évalués les effets de cinq méthodes de sélection pas-à-pas sur la performance, la stabilité et la parcimonie des modèles. Dans le même article sont également évalués: l'effet de la pondération des absences afin d'assurer une prévalence de 0.5 lors de la calibration du modèle; l'effet de limiter les absences au-delà de l'enveloppe définie par les présences; quatre méthodes différentes pour l'intégration de l'autocorrélation spatiale; et enfin, l'effet de l'intégration d'interactions entre facteurs. Les résultats présentés dans cet article ont permis d'améliorer l'outil GRASP qui intègre désonnais de nouvelles méthodes de sélection et la possibilité de traiter les interactions entre variables explicatives, ainsi que l'autocorrélation spatiale. La contribution de différentes sources de données issues de la télédétection a également été évaluée. Le deuxième article (en voie de soumission) explore les effets combinés de la taille de l'échantillon et de la post-stratification sur le la précision des modèles. Les données utilisées ici sont celles concernant la répartition des prairies de Suisse recueillies dans le cadre du projet Landspot et complétées par d'autres sources. Pour la stratification des données, différents cadres spatiaux ont été comparés. En particulier, la stratification environnementale par les domaines environnementaux de Suisse a été comparée à la stratification géographique par les régions biogéographiques ou par les cantons. Le troisième article (en voie de soumission) évalue la contribution de communautés végétales pré-modélisées à la modélisation de la faune. C'est une approche en deux étapes qui combine les disciplines de l'écologie des communautés et de l'écologie spatiale en intégrant leurs concepts de 'habitat' respectifs. Les communautés végétales sont modélisées d'abord, puis ces unités de 'habitat' sont utilisées pour modéliser les espèces animales. Une étude de cas est présentée avec des communautés prairiales et des espèces de papillons. Différentes façons d'intégrer l'information sur la végétation dans les modèles de répartition des papillons sont évaluées. Enfin, un clin d'oeil aux changements climatiques dans le dernier article, publié dans Ecological Modelling. Cet article propose un cadre conceptuel pour l'analyse des changements dans la distribution des espèces qui comprend notamment un catalogue des différentes formes possibles de changement le long d'un gradient d'élévation ou autre gradient environnemental, et une méthode quantitative améliorée pour identifier et décrire ces déplacements. Cette méthodologie a été développée en utilisant des données issues du monitoring des oiseaux nicheurs répandus et l'article présente les résultats concernant les déplacements observés dans la distribution altitudinale des oiseaux nicheurs en Suisse.L'objectif général de cette thèse est d'améliorer les modèles de distribution des espèces en tant que source d'information possible pour les différents outils de conservation (par exemple, listes rouges, réseaux écologiques, évaluation des risques de propagation d'espèces envahissantes, évaluation de la vulnérabilité des espèces dans le contexte de changement climatique). Bien que ces questions de conservation ne soient pas directement testées dans cette thèse, l'importance des améliorations proposées pour la modélisation de la distribution des espèces est discutée à la fin de ce travail dans le contexte de la sélection de réseaux de réserves.

Data bases for the assessment of medical technologies: examples from Europe.

The assessment of medical technologies has to answer several questions ranging from safety and effectiveness to complex economical, social, and health policy issues. The type of data needed to carry out such evaluation depends on the specific questions to be answered, as well as on the stage of development of a technology. Basically two types of data may be distinguished: (a) general demographic, administrative, or financial data which has been collected not specifically for technology assessment; (b) the data collected with respect either to a specific technology or to a disease or medical problem. On the basis of a pilot inquiry in Europe and bibliographic research, the following categories of type (b) data bases have been identified: registries, clinical data bases, banks of factual and bibliographic knowledge, and expert systems. Examples of each category are discussed briefly. The following aims for further research and practical goals are proposed: criteria for the minimal data set required, improvement to the registries and clinical data banks, and development of an international clearinghouse to enhance information diffusion on both existing data bases and available reports on medical technology assessments.