Réseau de prise en charge de la lombalgie chronique

ObjectifsIls sont d’étudier l’efficience d’un réseau de santé de maintien dans l’emploi pour les patients lombalgiques chroniques, d’appréhender la réalisation des aménagements du poste de travail des lombalgiques ayant une inadéquation santé/travail et également d’apprécier la communication interprofessionnelle entre le médecin du travail et les autres intervenants du réseau. Méthodes Étude descriptive et rétrospective, réalisée par questionnaires envoyés aux 53 médecins du travail de 88 patients inclus dans le réseau Lombaction. Étaient inclus dans l’étude tous les lombalgiques chroniques adressés initialement à la consultation pluridisciplinaire du réseau par leur médecin du travail, leur médecin traitant ou leur médecin rééducateur, et ayant ensuite bénéficié d’un programme de réentraînement à l’effort dans le cadre du réseau en 2006. Résultats Soixante cinq questionnaires ont été remplis par 43 médecins du travail (soit 73,9 % de réponses). Les indicateurs de santé au travail montrent le caractère handicapant des lombalgies présentées par les patients. Le maintien dans l’emploi est majoritairement obtenu grâce soit à une amélioration clinique liée au programme Lombaction de réentraînement à l’effort, soit à un aménagement du poste de travail ou à la combinaison des deux. Une intervention ergonomique, afin de contribuer à l’effort de maintien dans l’emploi, est vivement souhaitée par les médecins du travail. Toutefois le réseau Lombaction souffre d’un manque de communication entre les différents intervenants, qui nuit à l’interdisciplinarité requise à tout réseau de santé. Conclusion La prise en charge des lombalgiques chroniques par le réseau Lombaction se doit d’être interdisciplinaire au-delà de la consultation pluridisciplinaire d’inclusion. Cela nécessite du temps et une confiance partagée entre les différents acteurs de ce réseau de santé. L’information au sein du réseau promue par le coordinateur du réseau, en particulier sur les missions de chacun des intervenants, doit contribuer à décloisonner le programme Lombaction et à parfaire l’interdisciplinarité au profit des patients

Effectiveness of three treatment strategies on occupational limitations and quality of life for patients with non-specific chronic low back pain: Is a multidisciplinary approach the key feature to success: study protocol for a randomized controlled trial

BACKGROUND: Chronic low back pain (cLBP) is a significant public health problem, being the primary cause of work absenteeism, as well as affecting sufferers\u27 quality of life, in industrialized society. International guidelines recommend intensive multidisciplinary approaches for patients with cLBP. However, these costly and time-consuming programs can only be offered to a minority of the most heavily affected patients and therefore do not seem likely to respond to public health requirements. Lighter programs may be an alternative to full time hospital-based programs with valuable results in terms of disability and occupational activity for cLBP patients. It is therefore important to define both what the determining components of management to improve activity restriction are and how to treat a larger number of patients more effectively at a lower cost. The aim of this study is to compare three programs with various levels of intensity and multidisciplinary. METHODS/DESIGN: This paper describes the protocol for a prospective, randomized, controlled, clinical trial in working aged patients with cLBP. Three treatment strategies are compared: (1) intensive and multidisciplinary program conducted in a rehabilitation center; (2) less intensive outpatient program conducted by a private physiotherapist; (3) mixed strategy combining the same out program with a multidisciplinary intervention. The primary outcome of the trial is the impact of the mixed strategy on being able to work compared to hospital centered-program and out program. The secondary outcome is the impact of the mixed strategy on quality of life and social ability compared to the two others programs. The intervention part of the trial programs will take 5 weeks and observational follow-up will take 12 months. The sample size will be 180 participants (60 for each arm). The project has been approved by the Ethical Committee of Angers Hospital, France. DISCUSSION: On the hypothesis that a multidisciplinary approach is the key feature to programs success in reducing social and occupational impairment in cLBP patients, we suggest that it is possible to achieve the same results with less intensive strategies if a multidisciplinary approach is maintained. TRIAL REGISTRATION: Current Controlled Trials NCT02030171

Multidisciplinary intensive functional restoration versus outpatient active physiotherapy in chronic low back pain: a randomized controlled trial.

STUDY DESIGN: Randomized parallel group comparative trial with a 1-year follow-up period. OBJECTIVE: To compare in a population of patients with chronic low back pain, the effectiveness of a functional restoration program (FRP), including intensive physical training and a multidisciplinary approach, with an outpatient active physiotherapy program at 1-year follow-up. SUMMARY OF BACKGROUND DATA: Controlled studies conducted in the United States and in Northern Europe showed a benefit of FRPs, especially on return to work. Randomized studies have compared these programs with standard care. A previously reported study presented the effectiveness at 6 months of both functional restoration and active physiotherapy, with a significantly greater reduction of sick-leave days for functional restoration. METHODS: A total of 132 patients with low back pain were randomized to either FRP (68 patients) or active individual therapy (64 patients). One patient did not complete the FRP; 19 patients were lost to follow-up (4 in the FRP group and 15 in the active individual treatment group). The number of sick-leave days in 2 years before the program was similar in both groups (180 ± 135.1 days in active individual treatment vs. 185 ± 149.8 days in FRP, P = 0.847). RESULTS: In both groups, at 1-year follow-up, intensity of pain, flexibility, trunk muscle endurance, Dallas daily activities and work and leisure scores, and number of sick-leave days were significantly improved compared with baseline. The number of sick-leave days was significantly lower in the FRP group. CONCLUSION: Both programs are efficient in reducing disability and sick-leave days. The FRP is significantly more effective in reducing sick-leave days. Further analysis is required to determine if this overweighs the difference in costs of both programs

HUWE1 E3 ligase promotes PINK1/PARKINindependent mitophagy by regulating AMBRA1 activation via IKKa

The selective removal of undesired or damaged mitochondria by autophagy, known as mitophagy, is crucial for cellular homoeostasis, and prevents tumour diffusion, neurodegeneration and ageing. The pro-autophagic molecule AMBRA1 (autophagy/beclin-1 regulator-1) has been defined as a novel regulator of mitophagy in both PINK1/PARKIN-dependent and -independent systems. Here, we identified the E3 ubiquitin ligase HUWE1 as a key inducing factor in AMBRA1-mediated mitophagy, a process that takes place independently of the main mitophagy receptors. Furthermore, we show that mitophagy function of AMBRA1 is post-translationally controlled, upon HUWE1 activity, by a positive phosphorylation on its serine 1014. This modification is mediated by the IKKα kinase and induces structural changes in AMBRA1, thus promoting its interaction with LC3/GABARAP (mATG8) proteins and its mitophagic activity. Altogether, these results demonstrate that AMBRA1 regulates mitophagy through a novel pathway, in which HUWE1 and IKKα are key factors, shedding new lights on the regulation of mitochondrial quality control and homoeostasis in mammalian cells

HER2 Oncogenic Function Escapes EGFR Tyrosine Kinase Inhibitors via Activation of Alternative HER Receptors in Breast Cancer Cells

BACKGROUND: The response rate to EGFR tyrosine kinase inhibitors (TKIs) may be poor and unpredictable in cancer patients with EGFR expression itself being an inadequate response indicator. There is limited understanding of the mechanisms underlying this resistance. Furthermore, although TKIs suppress the growth of HER2-overexpressing breast tumor cells, they do not fully inhibit HER2 oncogenic function at physiological doses. METHODOLOGY AND PRINCIPAL FINDINGS: Here we have provided a molecular mechanism of how HER2 oncogenic function escapes TKIs' inhibition via alternative HER receptor activation as a result of autocrine ligand release. Using both Förster Resonance Energy Transfer (FRET) which monitors in situ HER receptor phosphorylation as well as classical biochemical analysis, we have shown that the specific tyrosine kinase inhibitors (TKIs) of EGFR, AG1478 and Iressa (Gefitinib) decreased EGFR and HER3 phosphorylation through the inhibition of EGFR/HER3 dimerization. Consequent to this, we demonstrate that cleavage of HER4 and dimerization of HER4/HER2 occur together with reactivation of HER3 via HER2/HER3, leading to persistent HER2 phosphorylation in the now resistant, surviving cells. These drug treatment-induced processes were found to be mediated by the release of ligands including heregulin and betacellulin that activate HER3 and HER4 via HER2. Whereas an anti-betacellulin antibody in combination with Iressa increased the anti-proliferative effect in resistant cells, ligands such as heregulin and betacellulin rendered sensitive SKBR3 cells resistant to Iressa. CONCLUSIONS AND SIGNIFICANCE: These results demonstrate the role of drug-induced autocrine events leading to the activation of alternative HER receptors in maintaining HER2 phosphorylation and in mediating resistance to EGFR tyrosine kinase inhibitors (TKIs) in breast cancer cells, and hence specify treatment opportunities to overcome resistance in patients

Precise measurement of the Ds+D^+_s lifetime at Belle II

We measure the lifetime of the $D_s^+$ meson using a data sample of 207 fb$^{-1}$ collected by the Belle II experiment running at the SuperKEKB asymmetric-energy $e^+ e^-$ collider. The lifetime is determined by fitting the decay-time distribution of a sample of $116\times 10^3$ $D_s^+\rightarrow\phi\pi^+$ decays. Our result is \tau^{}_{D^+_s} = (498.7\pm 1.7\,^{+1.1}_{-0.8}) fs, where the first uncertainty is statistical and the second is systematic. This result is significantly more precise than previous measurements.Comment: 7 pages, 4 figures, to be submitted to Physical Review Letter

Measurement of the Λc+\Lambda_c^+ lifetime

An absolute measurement of the $\Lambda^{+}_c$ lifetime is reported using $\Lambda_c^+\rightarrow pK^-\pi^+$ decays in events reconstructed from data collected by the Belle II experiment at the SuperKEKB asymmetric-energy electron-positron collider. The total integrated luminosity of the data sample, which was collected at center-of-mass energies at or near the $\Upsilon(4S)$ resonance, is 207.2~\mbox{fb}^{-1}. The result, $\tau(\Lambda^{+}_c) = 203.20 \pm 0.89 \,\mathrm{(stat)} \pm 0.77 \,\mathrm{(syst)}$ fs, is the most precise measurement to date and is consistent with previous determinations.Comment: Accepted for publication in PR

Search for an invisible Z′Z^\prime in a final state with two muons and missing energy at Belle II

The $L_{\mu}-L_{\tau}$ extension of the standard model predicts the existence of a lepton-flavor-universality-violating $Z^{\prime}$ boson that couples only to the heavier lepton families. We search for such a $Z^\prime$ through its invisible decay in the process $e^+ e^- \to \mu^+ \mu^- Z^{\prime}$. We use a sample of electron-positron collisions at a center-of-mass energy of 10.58GeV collected by the Belle II experiment in 2019-2020, corresponding to an integrated luminosity of 79.7fb$^{-1}$. We find no excess over the expected standard-model background. We set 90$\%$-confidence-level upper limits on the cross section for this process as well as on the coupling of the model, which ranges from $3 \times 10^{-3}$ at low $Z^{\prime}$ masses to 1 at $Z^{\prime}$ masses of 8$GeV/c^{2}$

Tests of light-lepton universality in angular asymmetries of B0→D∗−ℓνB^0 \to D^{*-} \ell \nu decays

We present the first comprehensive tests of light-lepton universality in the angular distributions of semileptonic \Bz-meson decays to charged spin-1 charmed mesons. We measure five angular-asymmetry observables as functions of the decay recoil that are sensitive to lepton-universality-violating contributions. We use events where one neutral \B is fully reconstructed in \PUpsilonFourS{} \to\B\overline{B} decays in data corresponding to \lumion integrated luminosity from electron-positron collisions collected with the \belletwo detector. We find no significant deviation from the standard model expectations