Physiotherapists in private practice in France

In France, most of the physiotherapists providing ambulatory care are in private practice: they are paid on a fee-for-service basis by the patients who are reimbursed by the Sickness Insurance Fund. A survey on a sample of 2000 (out of 40,000) private practitioners was undertaken in early 2004. As concerns their workload, only 4% think that it is "not sufficient" whereas 66% estimate it "certainly sufficient". Such a feature is noteworthy, as private practitioners are most often fearful of lack of work. In the coming years, one physiotherapist out of 10 envisages to increase his workload, whereas 27% are in favour of a reduction. Furthermore, the survey shows that more than one third of private physiotherapists plan to offer to patients services which are not listed in the contractual agreement document signed by their profession and the Sickness Insurance Fund. The trend is most noticeable among the young practitioners. As the feeling of medical doctors shortage is currently widespread in France, the public debates are focused on the issue of task delegation. After the survey, 54% private physiotherapists are in favour of task delegation, 24% have an opposite opinion and 22% do not express a clear-cut position. However, an in-depth analysis of the written answers to the question shows that a large majority do not accept to replace medical doctors for performing the tasks which are of a subordinate level, are not significant or are time-consuming (e.g. filling out the administrative forms). The question of vocabulary is fundamental in the matter. Moreover, a process of task delegation implies that certain tasks carried out by an overburdened profession are transferred to an other profession less heavily surcharged. Is it the case of French private physiotherapists whose two thirds declare that "their workload is certainly sufficient"?     

Methylazoxymethanol acetate does not fully block cell genesis in the young and aged dentate gyrus

During adulthood, new neurons are continuously added to the mammalian dentate gyrus (DG). An increasing number of studies have correlated changes in rates of dentate neurogenesis with memory abilities. One study based on subchronic treatment with the toxin methylazoxymethanol acetate (MAM) has provided causal evidence that neurogenesis is involved in hippocampal-dependent trace conditioning. In contrast, spatial learning is not impaired following MAM treatment. We hypothesized that this was due to the small residual number of new cells produced following MAM treatment. In the present experiment, we attempted to achieve a higher level of reduction of adult-generated cells following MAM treatment in young and aged rats. We found only a partial reduction of adult-generated cells in the DG. More importantly, independently of the age of the animals, MAM treatment at a dose necessary to reduce neurogenesis altered the overall health of the animals. In conclusion, the behavioural results obtained following subchronic treatment with high doses of MAM in adulthood must be interpreted with extreme caution.     

Chronic psychosocial stress down-regulates central cytokines mRNA

Brain cytokines have been implicated in brain plasticity and mood alterations. We present here the first evidence of a chronic stress-induced modulation of central cytokines, in absence of experimentally induced inflammatory processes. Several brain areas were extracted from stressed and control mice and cytokines mRNA analyzed with semi-quantitative RT-PCR. Mice subjected to chronic psychosocial stress showed decreased interleukin (IL)-1beta mRNA levels in the hippocampus, decreased IL-1Receptor antagonist in the striatum and pituitary, decreased tumor necrosis factor (TNF)-alpha in the striatum and hippocampus, and decreased glucocorticoid receptor (GR) in the striatum and hippocampus compared to group housed sibling mice. An independent group of mice subjected to chronic psychosocial stress also showed increased plasma corticosterone. These findings may open new perspectives for understanding the pathophysiological basis of chronic stress-induced disorders.     

Dietary fish oil increases lipid mobilization but does not decrease lipid storage-related enzyme activities in adipose tissue of insulin-resistant,sucrose-fed rats

Fish oil feeding has been shown to limit visceral fat accumulation in insulin-resistant rats. Our goal was to determine whether this finding is due to increased fat mobilization or decreased lipid storage. Adipocytes were isolated from rats fed for 3 wk a diet containing 57.5 g/100 g sucrose and 14 g/100 g lipids as either fish oil (SF) or a mixture of standard oils (SC); there was also a reference group (R). Substituting fish oil for standard oils protected rats from visceral fat hypertrophy, hypertriglyceridemia and hyperglycemia. The stimulation of lipolysis was greater in adipocytes isolated from SF-fed rats than in those from SC-fed rats. Fatty acid synthase (FAS) activity was markedly lower in the liver but not in the adipose tissues of rats fed SF. Lipoprotein lipase (LPL) activity was 2.2-fold higher in the adipose tissues but not in the muscle in rats fed the SF diet than in those fed the SC diet. The decrease in visceral fat in rats fed fish oil could be attributed to decreased plasma triacylglycerol concentration and/or increased lipid mobilization rather than to reduced lipid storage.     

Radiotherapy Plus Procarbazine,Lomustine, and Vincristine Versus Radiotherapy Plus Temozolomide for IDH-Mutant Anaplastic Astrocytoma: A Retrospective Multicenter Analysis of the French POLA Cohort

Background IDH‐mutant anaplastic astrocytomas (AAs) are chemosensitive tumors for which the best choice of adjuvant chemotherapy between procarbazine, lomustine, and vincristine (PCV) or temozolomide (TMZ) after radiotherapy (RT) remains unclear.MethodsIn a large cohort of patients with histologically proven 2016 World Health Organization classification AA with IDH1/2 mutations included in the French national POLA cohort (n = 355), the primary objective was to compare progression‐free survival (PFS) between the two treatment regimens (n = 311). Secondary endpoints were overall survival (OS), progression type, pseudoprogression rate, and toxicity.ResultsThe 4‐year PFS in the RT + PCV arm was 70.8% versus 53.5% in the RT + TMZ arm, with a hazard ratio (HR) of 0.58 (95% confidence interval [CI], 0.38–0.87; p = .0074) in univariable analysis and 0.63 (95% CI, 0.41–0.97; p = .0348) in multivariable analysis. The 4‐year OS in the RT + PCV arm was 84.3% versus 76.6% in the RT + TMZ arm, with an HR of 0.57 (95% CI, 0.30–1.05; p = .0675) in univariable analysis. Toxicity was significantly higher in the RT + PCV arm with more grade ≥3 toxicity (46.7% vs. 8.6%, p < .0001).ConclusionRT + PCV significantly improved PFS compared with RT + TMZ for IDH‐mutant AA. However, RT + TMZ was better tolerated.Implications for PracticeIn the absence of fully conducted randomized trials comparing procarbazine, lomustine, and vincristine (PCV) with temozolomide (TMZ) in adjuvant treatment after radiotherapy (RT) for the management of IDH‐mutant anaplastic astrocytoma (AA) and a similar level of evidence, these two chemotherapies are both equally recommended in international guidelines. This study in a national cohort of IDH‐mutant AA defined according the 2016 World Health Organization (WHO) classification shows for the first time that the RT + PCV regimen significantly improves progression‐free survival in comparison with the RT + TMZ regimen. Even if at the time of analysis the difference in overall survival was not significant, this result provides new evidence for the debate about the chemotherapy regimen to prescribe in adjuvant treatment to RT for WHO 2016 IDH‐mutant AA.     

Performance Comparison of Various Maximum Likelihood Nonlinear Mixed-Effects Estimation Methods for Dose–Response Models

Estimation methods for nonlinear mixed-effects modelling have considerably improved over the last decades. Nowadays, several algorithms implemented in different software are used. The present study aimed at comparing their performance for dose-response models. Eight scenarios were considered using a sigmoid E(max) model, with varying sigmoidicity and residual error models. One hundred simulated datasets for each scenario were generated. One hundred individuals with observations at four doses constituted the rich design and at two doses, the sparse design. Nine parametric approaches for maximum likelihood estimation were studied: first-order conditional estimation (FOCE) in NONMEM and R, LAPLACE in NONMEM and SAS, adaptive Gaussian quadrature (AGQ) in SAS, and stochastic approximation expectation maximization (SAEM) in NONMEM and MONOLIX (both SAEM approaches with default and modified settings). All approaches started first from initial estimates set to the true values and second, using altered values. Results were examined through relative root mean squared error (RRMSE) of the estimates. With true initial conditions, full completion rate was obtained with all approaches except FOCE in R. Runtimes were shortest with FOCE and LAPLACE and longest with AGQ. Under the rich design, all approaches performed well except FOCE in R. When starting from altered initial conditions, AGQ, and then FOCE in NONMEM, LAPLACE in SAS, and SAEM in NONMEM and MONOLIX with tuned settings, consistently displayed lower RRMSE than the other approaches. For standard dose-response models analyzed through mixed-effects models, differences were identified in the performance of estimation methods available in current software, giving material to modellers to identify suitable approaches based on an accuracy-versus-runtime trade-off.     

Effects of an integrated poultry value chain,nutrition, gender and WASH intervention (SELEVER) on hygiene and child morbidity and anthropometry in Burkina Faso: A secondary outcome analysis of a cluster randomised trial

Nutrition-sensitive agriculture programmes have the potential to improve child nutrition outcomes, but livestock intensification may pose risks related to water, sanitation and hygiene (WASH) conditions. We assessed the impact of SELEVER, a nutrition- and gender-sensitive poultry intervention, with and without added WASH focus, on hygiene practices, morbidity and anthropometric indices of nutrition in children aged 2−4 years in Burkina Faso. A 3-year cluster randomised controlled trial was implemented in 120 villages in 60 communes (districts) supported by the SELEVER project. Communes were randomly assigned using restricted randomisation to one of three groups: (1) SELEVER intervention (n = 446 households); (2) SELEVER plus WASH intervention (n = 432 households); and (3) control without intervention (n = 899 households). The study population included women aged 15−49 years with an index child aged 2−4 years. We assessed the effects 1.5-years (WASH substudy) and 3-years (endline) post-intervention on child morbidity and child anthropometry secondary trial outcomes using mixed effects regression models. Participation in intervention activities was low in the SELEVER groups, ranging from 25% at 1.5 years and 10% at endline. At endline, households in the SELEVER groups had higher caregiver knowledge of WASH-livestock risks (∆ = 0.10, 95% confidence interval [CI] [0.04−0.16]) and were more likely to keep children separated from poultry (∆ = 0.09, 95% CI [0.03−0.15]) than in the control group. No differences were found for other hygiene practices, child morbidity symptoms or anthropometry indicators. Integrating livestock WASH interventions alongside poultry and nutrition interventions can increase knowledge of livestock-related risks and improve livestock-hygiene-related practices, yet may not be sufficient to improve the morbidity and nutritional status of young children.     

Essential role of Notch signaling in apoptosis of human pancreatic tumoral cells mediated by exosomal nanoparticles

We previously reported that exosomal nanoparticles secreted by human pancreatic tumoral cell lines decrease tumoral cell proliferation through the mitochondria‐dependent apoptotic pathway, because of activation of pro‐apoptotic phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and of glucose synthase kinase‐3β (GSK‐3β). Interactions between exosomal nanoparticles and cells are thought to involve membrane lipid rafts. However, the underlying mechanism is unknown. Here, we report that the interaction of exosomal nanoparticles with pancreatic cancer cells led to decreased expression of hairy and enhancer‐of‐split homolog‐1 (Hes‐1), the intranuclear target of Notch‐1 signaling pathway, and to activation of the apoptotic pathway after a cell cycle arrest in G₀G₁ phase. Strikingly, the expression level of Notch‐1 pathway components was critical, because exosomal nanoparticles decreased the proliferation of cells in which these partners are either weakly represented, in differentiated adenocarcinoma cells, or inhibited, in poorly differentiated carcinoma cells, by blocking presenilin in the γ‐secretase complex that regulates the Notch‐1 pathway. Overexpression of Notch‐1 intracellular domain resulted in the reversion of the cell proliferation inhibition promoted by exosomal nanoparticles. Blocking presenilin unexpectedly resulted in activation of PTEN and GSK‐3β. Conversely, inhibiting either PTEN or GSK‐3β increased Hes‐1 expression and partially counteracted the inhibition of proliferation promoted by exosomal nanoparticles, highlighting reciprocal regulations between Notch signaling and PTEN/GSK‐3β. We concluded that interactions of exosomal nanoparticles with target cells, at lipid rafts where Notch‐1 pathway partners are localized, hampered the functioning of the Notch‐1 survival pathway and activated the apoptotic pathway, which determines tumoral cell fate. © 2009 UICC     

Spastic paraplegia 15: Linkage and clinical description of three Tunisian families

Hereditary spastic paraplegias (HSP) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by slowly progressive spasticity of the lower limbs. The locus designated spastic paraplegia 15 (SPG15), located in a 16‐Mb interval on chromosome 14q, is associated with a rare autosomal recessive complicated form of HSP known as Kjellin's syndrome. In this study, we describe three additional families, of Tunisian origin, linked to the SPG15 locus, one of which had a significant multipoint LOD score of 3.46. In accordance with previous reports, the phenotype of our patients consisted of early onset spastic paraparesis associated with mental impairment and severe progression. Retinal degeneration was not observed, however, but we extended the phenotype of this form to include peripheral neuropathy and white matter abnormalities on MRI. Interestingly, like retinal degeneration, thin corpus callosum is not a constant feature in this entity. © 2007 Movement Disorder Society