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This study introduces a comparative performance analysis of the technological solutions that have been used to build distal active articulations for minimally invasive medical procedures. The aim is to provide a practical and concise database and classification tool for anyone that wants to learn more about the technologies involved in minimally invasive medical devices, or for any designer interested in further improving these devices. A review of the different articulations developed in this field is therefore performed and organized by both actuation technology and structural architecture. Details are presented concerning the mechanical structures as well as the actuation and the mechanical transmission technologies available. The solutions are evaluated keeping as a reference some chosen required performances and characteristics for minimally invasive surgical procedures. Finally, a quantified comparison chart of these devices is given regarding selected criteria of interest for minimally invasive surgical application.

In the present subanalysis of a cross-sectional study showing the favorable effect of prior transient ischemia, leisure-time physical activity, and lipid-lowering drug therapy on stroke severity, we aimed to evaluate whether previous physical activity was dose dependently associated to minor stroke (NIHSS 0–3) and to identify possible underlying factors. Among 362 consecutive patients, less severe stroke was related to weekly exercise duration prior to stroke (no exercise: 36.1%; 5 hours: 64.0%; 𝑃=0.003). Only weak and moderate exercise practices were protective (weak: 50.0%; moderate: 79.3%; heavy: 22.2%; 𝑃

Background & aimsRecent studies reported a role for more than 70 genes or loci in the susceptibility to Crohn's disease (CD). However, the impact of these associations in clinical practice remains to be defined. The aim of the study was to analyse the relationship between genotypes and phenotypes for the main 53 CD-associated polymorphisms.MethodA cohort of 798 CD patients with a median follow up of 7 years was recruited by tertiary adult and paediatric gastroenterological centres. A detailed phenotypic description of the disease was recorded, including clinical presentation, response to treatments and complications. The participants were genotyped for 53 CD-associated variants previously reported in the literature and correlations with clinical sub-phenotypes were searched for. A replication cohort consisting of 722 CD patients was used to further explore the putative associations.ResultsThe NOD2 rare variants were associated with an earlier age at diagnosis (p = 0.0001) and an ileal involvement (OR = 2.25[1.49-3.41] and 2.77 [1.71-4.50] for rs2066844 and rs2066847, respectively). Colonic lesions were positively associated with the risk alleles of IL23R rs11209026 (OR = 2.25 [1.13-4.51]) and 6q21 rs7746082 (OR = 1.60 [1.10-2.34] and negatively associated with the risk alleles of IRGM rs13361189 (OR = 0.29 [0.11-0.74]) and DEFB1 rs11362 (OR = 0.50 [0.30-0.80]). The ATG16L1 and IRGM variants were associated with a non-inflammatory behaviour (OR = 1.75 [1.22-2.53] and OR = 1.50 [1.04-2.16] respectively). However, these associations lost significance after multiple testing corrections. The protective effect of the IRGM risk allele on colonic lesions was the only association replicated in the second cohort (p = 0.03).ConclusionsIt is not recommended to genotype the studied polymorphisms in routine practice.

Treatment of urinary schistosomiasis by chemotherapy remains challenging due to rapid re-infection and possibly to limited susceptibility to praziquantel treatment. Therefore, therapeutic vaccines represent an attractive alternative control strategy. The objectives of this study were to assess the safety and tolerability profile of the recombinant 28 kDa glutathione S-transferase of Schistosoma haematobium (rSh28GST) in healthy volunteers, and to determine its immunogenicity.Volunteers randomly received 100 µg rSh28GST together with aluminium hydroxide (Alum) as adjuvant (n = 8), or Alum alone as a comparator (n = 8), twice with a 28-day interval between doses. A third dose of rSh28GST or Alum alone was administered to this group at day 150. In view of the results obtained, another group of healthy volunteers (n = 8) received two doses of 300 µg of rSh28GST, again with a 28-day interval. A six-month follow-up was performed with both clinical and biological evaluations. Immunogenicity of the vaccine candidate was evaluated in terms of specific antibody production, the capacity of sera to inhibit enzymatic activity of the antigen, and in vitro cytokine production.Among the 24 healthy male participants no serious adverse events were reported in the days or weeks after administration. Four subjects under rSh28GST reported mild reactions at the injection site while a clinically insignificant increase in bilirubin was observed in 8/24 subjects. No hematological nor biochemical evidence of toxicity was detected. Immunological analysis showed that rSh28GST was immunogenic. The induced Th2-type response was characterized by antibodies capable of inhibiting the enzymatic activity of rSh28GST.rSh28GST in Alum did not induce any significant toxicity in healthy adults and generated a Th2-type immune response. Together with previous preclinical results, the data of safety, tolerability and quality of the specific immune response provide evidence that clinical trials with rSh28GST could be continued in humans as a potential vaccine candidate against urinary schistosomiasis.

Abstract Background To identify motivational factors linked to child health status that affected the likelihood of parents’ allowing their child to participate in pediatric research. Methods Parents were invited to return their completed questionnaires anonymously to assess motivational factors and factors that might improve participation in pediatric research. Results Of 573 eligible parents, 261 returned the completed questionnaires. Of these, 126 were parents of healthy children (group 1), whereas 135 were parents of sick children who were divided into two groups according to the severity of their pathology, i.e., 99 ambulatory children (group 2) and 36 nonambulatory children (group 3). The main factor motivating participation in a pediatric clinical research study was “direct benefits for their child” (87.7%, 100%, and 100% for groups 1, 2, and 3, respectively). The other factors differed significantly between the three groups, depending on the child’s health status (all p 2 test, all p ≤ 0.04), depending on the child’s health status. The main factor was “a better understanding of the study and its regulation” for the healthy children and ambulatory sick children groups (31.2% and 82.1%, respectively), whereas this was the third factor for the nonambulatory sick children group (50%). Conclusions Innovative strategies should be developed based on a child’s health status to improve information provision when seeking a child’s participation in pediatric research. Parents would like to spend more time in discussions with investigators.

Abstract Background In order to facilitate multinational clinical research, regulatory requirements need to become international and harmonised. The EU introduced the Directive 2001/20/EC in 2004, regulating investigational medicinal products in Europe. Methods We conducted a survey in order to identify the national regulatory requirements for major categories of clinical research in ten European Clinical Research Infrastructures Network (ECRIN) countries-Austria, Denmark, France, Germany, Hungary, Ireland, Italy, Spain, Sweden, and United Kingdom-covering approximately 70% of the EU population. Here we describe the results for regulatory requirements for typical investigational medicinal products, in the ten countries. Results Our results show that the ten countries have fairly harmonised definitions of typical investigational medicinal products. Clinical trials assessing typical investigational medicinal products require authorisation from a national competent authority in each of the countries surveyed. The opinion of the competent authorities is communicated to the trial sponsor within the same timelines, i.e., no more than 60 days, in all ten countries. The authority to which the application has to be sent to in the different countries is not fully harmonised. Conclusion The Directive 2001/20/EC defined the term 'investigational medicinal product' and all regulatory requirements described therein are applicable to investigational medicinal products. Our survey showed, however, that those requirements had been adopted in ten European countries, not for investigational medicinal products overall, but rather a narrower category which we term 'typical' investigational medicinal products. The result is partial EU harmonisation of requirements and a relatively navigable landscape for the sponsor regarding typical investigational medicinal products.

Abstract Background Suicide attempts (SA) constitute a serious clinical problem. People who attempt suicide are at high risk of further repetition. However, no interventions have been shown to be effective in reducing repetition in this group of patients. Methods/Design Multicentre randomized controlled trial. We examine the effectiveness of «ALGOS algorithm»: an intervention based in a decisional tree of contact type which aims at reducing the incidence of repeated suicide attempt during 6 months. This algorithm of case management comprises the two strategies of intervention that showed a significant reduction in the number of SA repeaters: systematic telephone contact (ineffective in first-attempters) and «Crisis card» (effective only in first-attempters). Participants who are lost from contact and those refusing healthcare, can then benefit from «short letters» or «postcards». Discussion ALGOS algorithm is easily reproducible and inexpensive intervention that will supply the guidelines for assessment and management of a population sometimes in difficulties with healthcare compliance. Furthermore, it will target some of these subgroups of patients by providing specific interventions for optimizing the benefits of case management strategy. Trial Registration The study was registered with the ClinicalTrials.gov Registry; number: NCT01123174.

Abstract Background 'Compassionate use' programmes allow medicinal products that are not authorised, but are in the development process, to be made available to patients with a severe disease who have no other satisfactory treatment available to them. We sought to understand how such programmes are regulated in ten European Union countries. Methods The European Clinical Research Infrastructures Network (ECRIN) conducted a comprehensive survey on clinical research regulatory requirements, including questions on regulations of 'compassionate use' programmes. Ten European countries, covering approximately 70% of the EU population, were included in the survey (Austria, Denmark, France, Germany, Hungary, Ireland, Italy, Spain, Sweden, and the UK). Results European Regulation 726/2004/EC is clear on the intentions of 'compassionate use' programmes and aimed to harmonise them in the European Union. The survey reveals that different countries have adopted different requirements and that 'compassionate use' is not interpreted in the same way across Europe. Four of the ten countries surveyed have no formal regulatory system for the programmes. We discuss the need for 'compassionate use' programmes and their regulation where protection of patients is paramount. Conclusions 'Compassionate use' is a misleading term and should be replaced with 'expanded access'. There is a need for expanded access programmes in order to serve the interests of seriously ill patients who have no other treatment options. To protect these patients, European legislation needs to be more explicit and informative with regard to the regulatory requirements, restrictions, and responsibilities in expanded access programmes.

Abstract Background Thorough knowledge of the regulatory requirements is a challenging prerequisite for conducting multinational clinical studies in Europe given their complexity and heterogeneity in regulation and perception across the EU member states. Methods In order to summarise the current situation in relation to the wide spectrum of clinical research, the European Clinical Research Infrastructures Network (ECRIN) developed a multinational survey in ten European countries. However a lack of common classification framework for major categories of clinical research was identified, and therefore reaching an agreement on a common classification was the initial step in the development of the survey. Results The ECRIN transnational working group on regulation, composed of experts in the field of clinical research from ten European countries, defined seven major categories of clinical research that seem relevant from both the regulatory and the scientific points of view, and correspond to congruent definitions in all countries: clinical trials on medicinal products; clinical trials on medical devices; other therapeutic trials (including surgery trials, transplantation trials, transfusion trials, trials with cell therapy, etc.); diagnostic studies; clinical research on nutrition; other interventional clinical research (including trials in complementary and alternative medicine, trials with collection of blood or tissue samples, physiology studies, etc.); and epidemiology studies. Our classification was essential to develop a survey focused on protocol submission to ethics committees and competent authorities, procedures for amendments, requirements for sponsor and insurance, and adverse event reporting following five main phases: drafting, consensus, data collection, validation, and finalising. Conclusion The list of clinical research categories as used for the survey could serve as a contribution to the, much needed, task of harmonisation and simplification of the regulatory requirements for clinical research in Europe.

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Purpose: The aim of this study was to evaluate mental nerve regeneration in rats after a crush lesion by using a polymeric membrane functionalized with nerve growth factor (NGF). Materials and Methods: To evaluate the regeneration 1 month after the lesion, electrophysiological recordings of afferent neurograms were associated with a histologic analysis of neurons soma in the trigeminal ganglion using a retrograde fluorescent tracer. Three animal groups were used: uninjured rats (TEM), injured control rats without membrane (CONT), and injured rats with membrane containing NGF. Results: One month after the crush injury, an early regeneration was observed independently of exogenous NGF. However, in comparison with the level recorded before the lesion, the afferent activity was decreased by 28.5% in the CONT group, whereas it was increased by 30.8% in the NGF group. In comparison with the TEM group, a decrease in the mean number of labeled neurons was observed in the CONT group, whereas no significant difference was found after 1 month of NGF treatment. Conclusion: The exogenous application of NGF using a polymeric membrane improves mental nerve regeneration after a crush lesion. [Copyright &y& Elsevier]

Based on its anatomical relationships, the lateral pterygoid muscle is strongly linked with the temporomandibular joint (TMJ). It plays a major role in mastication. Embryological, histological, and anatomical knowledge define the lateral pterygoid muscle as a single muscle with a penniform structure. The various results of electromyographic (EMG) studies describe a complex physiology with a chronological contraction of the layers during the masticatory cycle. The sequential contraction of the layers of the lateral pterygoid muscle is the result of a selective neuronal activation induced by the masticatory Central Pattern Generator (mCPG). This neurophysiological theory highlights the essential role of the reticular formation in oral motor control. The sensitivity of those neurological structures to chronic emotional stress is one of the possible explanations for the appearance of oral parafunctions accompanied by a modification of pain perception and a disorganized muscular activation, determining factors in temporomandibular disorders. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the prevalence of neurosensory disturbances (NSDs) of the inferior alveolar nerve after dental procedures. Materials and Methods: A retrospective study of patient complaints for transient and permanent NSDs was achieved by means of a 10-year follow-up of claims to a national practitioner insurance company. Claims for 3 different dental procedures were analyzed from 157,292 contracts of insurance recorded during this period. Results: Three hundred eighty-two complaints of NSDs were recorded with 75 permanent injuries (19.6%). The incidence of endodontic treatment and surgical procedures in NSDs cases were 35.3% and 61.5%, respectively, and the prevalence of third molar removals in permanent loss of sensation was 46.6%. Conclusion: Impacted third molar removal appears to be the main etiology of permanent inferior alveolar nerve sensory deficiency, but endodontic treatments are often implicated and implant placement procedures can cause severe nerve injuries. [Copyright &y& Elsevier]

A meeting was organised in Paris on 13 September 2004, to provide an in-depth description of the state of the art in institutional clinical research infrastructures and their environment in France. This meeting was scheduled within the ECRIN (European Clinical Research Infrastructures Network) project, funded by the European Union (6th Framework Programme). Ten items were addressed: (i) centres and networks; (ii) funding and sponsoring of clinical research; (iii) ethics; (iv) legislation and regulation; (v) adverse-event reporting and drug dispensing; (vi) methodology, data management and data monitoring; (vii) quality management and audits; (viii) communication with investigators, sponsors and participants; (ix) transparency and registration of clinical studies; and (x) education and careers. This description, together with parallel workshops held in other countries using a similar pattern, helped prepare a comparative analysis enabling better identification of the bottlenecks for multinational research in Europe, and define the most relevant approaches to harmonisation and the services required to support the role of sponsors in transnational studies. Keywords: clinical research, Clinical Research Centre, Clinical Trial Unit, network, sponsor, ethics, trial registry, regulation, training Résumé Un séminaire organisé à Paris le 13 septembre 2004 a permis de procéder à une description approfondie de l’état des lieux concernant les infrastructures académiques de recherche clinique en France, leurs réseaux, ainsi que leur environnement. Ce séminaire était organisé dans le cadre du projet ECRIN (European Clinical Research Infrastructures Network) financé par l’Union Européenne (6e Programme-Cadre). L’analyse a porté sur dix points : (i) centres et réseaux de recherche clinique ; (ii) financement et promotion de la recherche clinique ; (iii) éthique ; (iv) législation et réglementation ; (v) gestion des effets indésirables et dispensation du médicament ; (vi) méthodologie, traitement et monitorage des données ; (vii) gestion de la qualité et audits ; (viii) communication avec les investigateurs, les promoteurs et les participants ; (ix) transparence et registres d’essais cliniques ; et (x) éducation et carrières. Des séminaires identiques ont été organisés dans chacun des pays participants afin de préparer une analyse comparée. En précisant les obstacles à la recherche clinique multinationale en Europe, cette analyse comparée permettra de définir quelles actions d’harmonisation mener et quels services proposer aux promoteurs pour faciliter la réalisation d’études transnationales. Mots clés : recherche clinique, Centre d’Investigation Clinique, Unité d’Essai Clinique, réseau, promotion, éthique, registres, réglementation, formation [ABSTRACT FROM AUTHOR]

A partir d’une revue de la littérature et des observations de la base de données nationale française de pharmacovigilance pour la période de 1984 à avril 2003, sont présentés les principaux médicaments responsables ou révélateurs d’une insuffisance cardiaque. Plusieurs grandes classes pharmacologiques se distinguent : outre certains antimitotiques dont les anthracyclines, de nombreux médicaments tels que les immunomodulateurs, les anti-inflammatoires (y compris les coxibs), les antiarhythmiques, les anesthésiques, les antipsychotiques, les médicaments antidiabétiques (dont les glitazones) sont impliqués dans la survenue de décompensations cardiaques. Il est habituel de les classer en trois catégories : (i) médicaments susceptibles de provoquer des insuffisances cardiaques de novo (tels que cyclophosphamide, paclitaxel, mitoxantrone, interférons, interleukine-2..) ; (ii) médicaments susceptibles d’aggraver une insuffisance cardiaque préexistante (tels que antiarhythmiques, β-bloquants, antagonistes du calcium, anti-inflammatoires non stéroïdiens et stéroïdiens, sympathomimétiques..) ; et (iii) médicaments provoquant exceptionnellement une insuffisance cardiaque. Cette revue montre que cette classification est en fait artificielle et que si la préoccupation d’une toxicité cardiaque doit être constante lors du maniement des anticancéreux et de certains immunomodulateurs, il convient d’être attentif au maniement de nombreux médicaments chez le sujet insuffisant cardiaque, y compris lorsque la situation clinique est bien équilibrée, en tenant compte, en particulier, du terrain et des interactions médicamenteuses potentielles. Mots clés : insuffisance cardiaque, effet indésirable Abstract The principal drugs implicated in or disclosing cardiac insufficiency are drawn from a review of the literature and observations by the French national pharmacovigilance database, from 1984 to April 2003. Several pharmacological classes are identified: in addition to antimitotic drugs, such as anthracyclines, many drugs are implicated in cardiac insufficiency, e.g. immunomodulators, anti-inflammatory drugs (including coxibs), antiarrhythmic drugs, anaesthetic drugs, antipsychotic drugs, and antidiabetic drugs (including glitazones). It is usual to classify these drugs according to three categories: (i) drugs likely to cause cardiac insufficiency de novo (such as cyclophosphamide, paclitaxel, mitoxantrone, interferons, interleukin-2 etc.); (ii) drugs likely to worsen pre-existing cardiac insufficiency (such as antiarrhythmics, β-blockers, calcium antagonists, nonsteroidal and steroidal anti-inflammatory drugs, sympathomimetic drugs etc.); and (iii) drugs only occasionally causing cardiac insufficiency. This review shows that this classification is, in fact, artificial. If cardiac toxicity is a constant concern when using antimitotic drugs or some immunomodulator drugs, it is advisable to exercise caution in the use of many other drugs when treating patients with cardiac insufficiency, even if the clinical situation is well controlled. In particular, drug-drug interactions and patient medical history must be taken into account. Keywords: heart failure, adverse drug effect Texte reçu le 13 janvier 2004 ; accepté le 19 janvier 2004 [ABSTRACT FROM AUTHOR]