Non-dits méthodologiques dans la recherche en psychiatrie

Modern psychiatric practice must ground itself in evidence-based medicine, but what is evidence in medicine? For certain philosophers, to have evidence, you must have beliefs: What are the consequences for medicine, and, in particular, psychiatric research? Why randomize the administration of treatments in clinical trials? Is it to make it possible to compare groups? But, if you’re unlucky, the lack of balance can be significant. This article addresses several concepts often used by methodologists: causality, evidence, belief, risk, randomness, models, observation, experimentation and measurement. The objective is to challenge the dominant discourse, often a little forced, in order to shed light on methodological omissions.     

Préparations magistrales en radiopharmacie : contraintes liées à la mise en place

Use of radiopharmaceuticals in French nuclear medicine departments depends on marketing authorization and their development may be compromised by a limited return on investment. As an alternative, radiopharmaceuticals may also be prepared in the form of a magistral preparation, like in some European countries. In this case, these preparations are subjected to restrictions and requirements for radiopharmacies relating to quality assurance, facilities and equipment, quality of starting materials and final radiopharmaceutical products defined in French good preparation practice. Labelled tracers used as magistral preparations have to be prepared under the full responsibility of a radiopharmacist and used under the responsibility of the prescribing physician. Conditions of sufficient guarantees for the safety of the patient and adherence to pharmaceutical rules must be evaluated individually. However, this form of preparation intends to supply specific medical needs for an individual patient and is not an answer in the framework of development of radiopharmaceuticals.     

Étude de la variabilité de la clairance hépatique de la mébrofénine-99mTc en scintigraphie hépatobiliaire

AimThe purpose of this study was to investigate some of the parameters likely to influence mebrofenin-^99mTc hepatic clearance calculation and inter-and intra-observers reproducibility.Materials and methodsHepatic clearance (%/min m²) of 30 scintigraphies was calculated from the values of hepatic, cardiac, and total activities, according to the method recommended in the literature. We studied: 1) impact of injection–acquisition delay variations; 2) acquisition type: anterior face only (FA) or geometric mean (GM); 3) clearances calculated according to four different body surface area (BSA) formulas; 4) intra-and inter-observers reproducibility for three observers (two evaluations for each observer).Results1) Clearance differences between different studied intervals were statistically significant, more important if the studied interval was far from reference interval (150–350 secondes) and even more when the interval studied was too early (110–310 secondes). 2) There was a statistically significant difference between clearance calculated using either FA or GM datasets (0.85 %/min m²). 3) There were small but statistically significant differences for four of the clearance comparisons using different BSA formulas. 4) Despite differences in size of cardiac and hepatic regions of interest (ROI), intra-observer reproducibility of hepatic clearance was excellent for each observer. Inter-observers reproducibility was also excellent (r = 0.982).ConclusionHepatic clearance of mebrofenin-^99mTc appears to be a highly reproducible method provided that acquisition and clearance calculation are standardized. It provides additionnal functional information to morphological and biological data usually performed before major hepatectomy. Thereby, the definition of a standardized protocol would enable realization of multicentric studies.     

L'analyse et la synthèse en systématique végétale

Analysis and synthesis have been widely used in systematics since, at least, the XIXth Century. Even now, the four major authors (Cronquist, Dahlgren, Takhtajan, Thorne) of angiosperm systems use “synthetic” to qualify their classifications. This word — synthetic or synthesis — has many different meanings that can create ambiguity. Among these meanings, is there one that can be justifiably used to define biological classifications? Although much more than the following applications can be found in the botanical literature, this paper will mainly deal with six meanings which are still in use in contemporary systematics. A synthetic classification has been understood as a classification built upward, from the lower to the higher categories. If we define synthesis as the operation that starts with elements and proceeds to a whole, then upward classification could be viewed as a synthesis in which the concept of hierarchy plays a primordial role, a role that is not initially a part of synthesis. Moreover, synthesis cannot replace all classificatory processes, and other criteria of taxa must be used in addition to synthesis Historically, synthesis has replaced analysis; the latter being employed by Linnaeus in his sexual system. Indeed, Linnaeus used a divisive method in producing his classification; and since division was seen as synonymous to analysis and recognized as a method that led to artificial taxa, leading French taxonomists Adanson, Lamarck and A.-L. de Jussieu among others, rejected analysis and viewed their classifications as synthetic, i.e., based on the natural method. Therefore, a system of value took place: natural was better than artificial, synthesis better than analysis. Reinforcing the importance of synthesis was the belief in a concept widely accepted at the end of the XVIIIth Century: that of continuity. Linking groups and forming a continuum was a procedure eminently synthetic. Such a procedure, known as “chaining”, produced series or sequences of taxa. Analysis was used solely to express the idea of dichotomous or analytical keys, a Lamarckian innovation that enabled taxonomists to identify plants. But whether classifications are built from lower to higher categories (a synthesis of taxa) or from higher to lower categories (an analysis of taxa), another simultaneous, concomitant movement is implied: with the latter, a synthesis of characters, with the former, an analysis of characters. Therefore, a synthetic classification is nevertheless an analytical classification.Basing groups on resemblance instead of difference, results in yet another application of synthesis. This application is probably due to the analogy with “composition”. Already, a separation between resemblance and difference among characters is an analysis. More important, still, is that at a certain rank some characters are used to join whereas, at another rank, they separate. Thus, depending on ranks and taxa, characters are applied in a synthetic or analytical procedure. Here also, other criteria are needed to support group delimitation.In connection with the upward (synthetic) movement in classifying taxa, the use of a great number of characters was also considered to be synthesis. This has been a recurring theme in taxonomy over the last two centuries and was sometimes seen as the Gilmourian approach to classification. When would we be justified to talk about synthesis? After how many characters? In fact, it is not the number of characters that matters but how characters are handled. The use of many characters has been closely linked to the idea of natural groups and its joining with synthesis seems to derive from the association of “natural” and “synthetic”.Synthetic classifications equally imply the common idea that they must represent a résumé of information stemming from all biological fields or disciplines. If classifications portray evolution, as many systematists suggest, then it cannot be just a résumé. And one must first decide what classifications are about: a controversial subject among different schools of thought in taxonomy. This explains another meaning attached to synthesis. Biological classifications have been said to be a synthesis or résumé of two types of information: that of similarity and that of phylogeny. Anagenesis is sometimes viewed as incremental to classification and makes up for a third type of information. Even though taxonomists would (for once!) agree that a classification should be based on phenetic, cladogenetic and anagenetic data, such a classification cannot qualify as a synthesis since it is not a composition and does not meet the definition given above (an operation that starts with elements and goes on to a whole). It is impossible to represent these three types of data together in one classification scheme; they express three, sometimes irreducible, points of view. For such a classification, the word “eclectic” is preferable and closer to reality.The use of synthesis as one term of the dialectical movement has made hesitant steps in taxonomy. Indeed, the two opposed theses that evolve into the synthesis are hardly met in classification and the “dialectical” synthesis promulgated by a few taxonomists can be referred back to synthesis as a résumé.Is classification synthetic because it appears to be based on inductive procedures, as it is sometimes implied by different authors who link deduction and analysis (stemming from downward classification)? In logic, synthesis is sometimes (and questionably so) associated with deduction. Moreover, synthesis cannot follow from induction which deals, for example, with the universality of characters. In that sense, there is no composition and so no synthesis. Thus, although induction has been part of classification, it is not a synthetic method.Apart from the ambiguity originating from the multiple meanings of the word “synthesis” in the context of taxonomy, synthetic classifications do not fully express all the complexity and procedures that lead to it. Actually, a classification is as much a synthesis as an analysis. Both methods are complementary, and should not be opposed as is sometimes the case. This opposition was implicit in the debate between Linneans and Jussieans, surrounding the development of the natural method. If one wants to use “synthetic”, then one should be explicit about its meaning. Taxonomists should also be aware of the incompleteness of synthesis in constructing a classification and should be careful not to create a system of value based upon philosophical ground. They should always prefer a complementary mode of thinking when feasible, instead of an “either-or” approach.     

Etablissement de l’empreinte parentale dans la lignée germinale. Conséquences pour la prise en charge en AMP

Genomic imprinting is an epigenetic phenomenon in eutherian mammals that results in the differential expression of the paternally and maternally inherited alleles of a gene. Imprinted genes are necessary for normal mammalian development. Parental specific epigenetic modifications are imprinted on a subset of genes in the mammalian genome during germ cell maturation. Imprinting involves both cytosine methylation within CpG islands and changes in chromatin structure. All such epigenetic modifications are potentially reversible and can be erased. After the erasure step, new parental imprints are initiated, resulting in reintroduction of sex-specific imprints in the male and female germ line. Although the function of genomic imprinting is not clear, it has been proposed that it evolved in mammals to regulate intrauterine growth and mammalian development. If the epigenotype of individual gametes is directly correlated with their later developmental capacities, genomic imprinting would have important practical implications in reproductive medicine for the use of embryos derived from assisted reproduction.     

Imagerie de la néoangiogenèse en médecine nucléaire

The formation of new vessels, a process referred to as neoangiogenesis, is one of the key pathophysiological mechanisms in the development and progression of cancer. It contributes to tumour growth and dissemination of neoplastic cells and can determine response or resistance to anticancer therapies. It involves different signaling pathways including the vascular endothelial growth factor (VEGF) pathway and integrins, which are also preferred targets for the development of antiangiogenic therapies. Changes in the microvasculature induced by antiangiogenic treatments occur before morphological changes can be detected with conventional imaging approaches. The development of molecular tools enabling an assessment of these targets before initiating therapy, or early detection of response or recurrence during or following treatment is essential for the close monitoring of antiangiogenic treatments. These outstanding needs call for the development of specific probes enabling the characterization of the molecules and pathways involved. This review summarizes the major signaling pathway involved in promoting tumor neoangiogenes is, the different radiotracers recently developed in preclinical and clinical settings, as well as their potential use in humans in order to improve the management of patients treated with antiangiogenic treatments.     

Réduction des effets de la respiration en imagerie TEP pulmonaire par une acquisition synchronisée à la respiration associée à une TDM en apnée

Respiratory motion causes a spread of lesion uptake over a larger area in Positron Emission Tomography (PET) images for moving structures. When CT images are used for attenuation correction of emission data, this motion may alter the quantization of PET images. We present the clinical results of a respiratory-gated PET processing “CT-based” method, which aims to improve PET-CT coregistration by using an additional breath-hold CT (BH-CT). The CT-based protocol consisted in a 10-min List Mode respiratory-gated PET acquisition, followed by an end-expiration BH-CT acquisition. During these two examinations, the respiratory signal was recorded continuously. Eleven pulmonary lesions were studied. Patients underwent both a standard clinical PET protocol (free breathing) and the CT-based protocol. The respective performances of the CT-based and clinical PET methods were evaluated by comparing the distances between the lesions’ centroids on PET and CT images. SUV_MAX (Standardized Uptake Value) and volume variations were also investigated. The CT-based method showed a significant reduction (p = 0.049) of centroid distances (mean relative change versus standard method: 49%). We also noted a higher SUV_MAX (mean change: 39%). Lesion volumes were significantly lower (p = 0.026) in CT-based PET volumes (mean change: 43%) compared with standard ones. The CT-based method improves PET-CT coregistration of pulmonary lesions. This protocol should lead to more accurate attenuation correction and thus improve SUV measurement.     

Enjeux de la biologie délocalisée en milieu hospitalier et contractualisation

La réussite d’une délocalisation des analyses de biologie médicale est la résultante d’une volonté de coopération entre les trois partenaires que sont le clinicien, le biologiste et les services administratifs. Elle s’appuie sur la répartition clairement définie des responsabilités en termes d’utilisation de résultats et de management, la mise en place de procédures de fonctionnement et un suivi continu de la totalité du processus. Elle ne peut se passer d’une liaison informatique en temps réel avec le laboratoire qui permet de respecter les règles de l’assurance qualité et du GBEA. Bien ma?trisée, et appliquée à bon escient, elle peut représenter une solution pour améliorer la prise en charge du patient.     

La radiothérapie interne vectorisée par les analogues de la somatostatine,en pratique,en 2019

Somatostatin receptors are overexpressed in differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NET). Radiolabeled somatostatin analogs have been used for a few decades for imaging and more recently for peptide receptor radionuclide therapy (PRRT) in a theranostic approach. Medical access to PRRT has long been limited to a few European specialized medical centers despite promising results in large cohorts of patients. NETTER-1, a phase 3 randomized trial, has demonstrated a drastic improvement of midgut NET patients progression-free survival in PRRT arm as compared to somatostatin analogs, leading to marketing authorizations in USA and Europe. PRRT clinical availability is growing in France, with around 20 medical centers offering this innovative treatment for GEP-NET patients care in 2019. PPRT success-story should lead to improvements of radionuclide therapy developments, which will reshape our medical specialty to a more “clinically” practice. This review aims to detail PRRT in clinical practice in France in 2019, with emphasize on treatment indications, planning and practical aspects. Radioprotection aspects and future optimization perspectives will also be discussed.     

Efficacité comparée de l'antibioprophylaxie par la céfoxitine en une ou trois doses dans la césarienne.

To compare the effectiveness of three doses and of a single dose of cefoxitin, a second-generation cephalosporin, in preventing infection after nonelective cesarean section, we carried out a prospective study in 255 women who underwent the procedure between March 1983 and February 1985. The rate of postoperative infection was 7% in the group that received three doses and 8% in the one-dose group. The sensitivity and specificity of perioperative cultures were low. The rate of asymptomatic bacteriuria was high, at 20%, but few symptomatic urinary tract infections were found. Routine antibiotic prophylaxis with a single dose is suggested for all nonelective cesarean sections.     

Réflexions sur la place des médecins spécialistes en médecine nucléaire dans le dispositif d’annonce en cancérologie

Nuclear medicine physicians are very involved in French's oncology announcement procedure. However, their role needs to be analysed and evaluated. Before diagnosis’ announcement, information provided by nuclear medicine physicians are never neutral for patients. Information must not increase patient's anxiety or false patient's sense of reassurance. In this context, it seems necessary to engage in ethical reflexions about nuclear medicine physicians communication challenges.     

Impact de la méthode de segmentation dans la caractérisation des adénocarcinomes pulmonaires en TEP-TDM au 18FDG

ObjectiveThe treatment of lung adenocarcinomas is conditioned by the presence of certain genetic abnormalities. Certain quantitative parameters obtained from FDG PET-CT, at the voxel scale, provide tumour shape and texture characteristics and might predict their mutational status. Our objective was to determine the impact of the segmentation method in the characterization of lung adenocarcinomas in FDG PET-CT.MethodsForty-nine patients with pulmonary adenocarcinomas were retrospectively included, with their initial FDG PET-CT image. The studied tumours were big, heterogeneous and difficult to segment automatically. The automatic FLAB algorithm was used with and without manual adjustment. The parameters were extracted and compared to the ALK, PDL1, and KRAS status, in order to compare the performances of the two segmentation methods. Their performance was determined by the ROC curve method.ResultsSeveral parameters were significant to predict genetic status (AUC > 0.65). The best performing parameters were different according to the genes studied and according to the resampling methods used. The results were less dependent on resampling in automatic segmentation without manual adjustment. The best performing parameters were volume dependent parameters for segmentation with manual adjustment, and texture parameters for automatic segmentation without adjustment.ConclusionThe study of texture parameters is more efficient in automatic segmentation that is not manually adjusted, and it is advantageous to use a manual adjustment when studying volume-dependent parameters in the case of very heterogeneous tumors.     

Imagerie hybride,TEP-TDM et TEMP-TDM. En quoi peut-elle influencer la formation et la pratique en médecine nucléaire en France ?

To define the policy of our specialty with a consensus opinion, a questionnaire entitled “hybrid imaging” was sent to practicing nuclear medicine specialist physicians in France to obtain their opinion on the impact of this recent method in training and in the practice of nuclear medicine and on the relations between nuclear medicine specialists and other medical imaging specialists. This questionnaire, written by the office of the French Society of Nuclear Medicine (FSNM) and molecular imaging , was divided into four parts: Profile and experience in hybrid imaging, Relations with radiologists, Practice of CT scans with hybrid equipment, and the Future of the specialty and of training in nuclear medicine. The response rate was 60%, i.e. 374 completed questionnaires. Overall, the responses were uniform, whatever the respondent's experience, type and place of practice. Regular participation in hybrid imaging practice was the reply provided by the majority of respondents. In terms of relations with radiologists, such contacts existed in over 85% of cases and are considered as being of high quality in over 90% of cases. The vast majority of practitioners believe that hybrid imaging will become the standard. Opinions on the diagnostic use of CT scans are divided, as well as their interpretation by a radiologist, a nuclear medicine specialist or by both. In the opinion of the vast majority, hybrid equipment systems should be managed by nuclear medicine specialists. With regard to the future, nuclear medicine should remain an independent specialty with enhanced training in morphological imaging and a residency training program whose length should be increased to 5 years.     

Variations du taux d'adsorption du bactériophageϕ80 en rapport avec la résistance à la colicine B

Various mutants ofEscherichia coli selected by colicine B show a wide range of resistance spectra towards colicines B, I and V, phages T₁ andq 80, by mutation in locusbt ₁. Such relations of specificity of resistance seem to result from quantitative variations in the adsorption rate. Indeed, the ability to fix the phage 80, or its derivative the plaque-forming transducing phage 80pt ₁, decreases in correlation with the extent of the spectrum of cross-resistance in the mutants studied. It is never completely abolished even in mutants apparently resistant to this phage, as shown either directly by titration of infective centers or indirectly by the rate of transduction.     

Nouvelles données sur la présence d'Orthotrichum philibertii Vent. dans le bassin méditerranéen

The occurrence of Orthotrichum philibertii Vent. in the Iberian Peninsula, Balearic islands and northern Morocco is reported, extending its area to the westernmost Mediterranean basin. The new populations supply some new elements that enlarge the variability range of this species.     

Innovations technologiques récentes en détection pour la Tomographie par Emission de Positons

Since the recognition of the clinical value of Positron Emission Tomography (PET) for the diagnosis and staging of several cancers, the PET systems have evolved to systems associating PET and Computed Tomography (CT). The main constraint for clinical imaging is to reduce the acquisition duration. As a consequence, PET detectors are faster and emit more light than the BGO crystal used previously. These detectors allow an improvement of the count rate performance of the PET systems, reducing the scattered and the random events while increasing the true events at high activity concentration. Among the new crystals, some allow measuring the time of flight of the annihilation photons. This measurement further improves the performance of the systems. The spatial resolution of clinical PET systems is still equal to 5 mm at best. High spatial resolution PET systems dedicated to small animal imaging have been developed. These systems use similar crystal materials as the clinical systems. However, in order to permit spatial resolution close to 1 mm, the crystal elements have much smaller transverse dimensions than that of clinical systems. The detectors are compact using position sensitive photomultipliers or photodiodes. In order to preserve the uniformity of the spatial resolution over the transverse field of view of the tomographs, solutions allowing the measurement of the depth of interaction of the photons in the crystal have been designed. New compact detectors based on semi conductors are currently investigated.