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Raphaël Porcher

Publications and source records attributed to Raphaël Porcher.

At least 19 recordsLinked to original sources
PubMed2006

Analysing multicentre competing risks data with a mixed proportional hazards model for the subdistribution.

In the competing-risks setting, to test the effect of a covariate on the probability of one particular cause of failure, the Fine and Gray model for the subdistribution hazard can be used. However, sometimes, competing risks data cannot be considered as independent because of a clustered design, for instance in registry cohorts or multicentre clinical trials. Frailty models have been shown useful to analyse such clustered data in a classical survival setting, where only one risk acts on the population. Inclusion of random effects in the subdistribution hazard has not been assessed yet. In this work, we propose a frailty model for the subdistribution hazard. This allows first to assess the heterogeneity across clusters, then to incorporate such an effect when testing the effect of a covariate of interest. Based on simulation study, the effect of the presence of heterogeneity on testing for covariate effects was studied. Finally, the model was illustrated on a data set from a registry cohort of patients with acute myeloid leukaemia who underwent bone marrow transplantation.

Bone Marrow Transplantation↗
PubMed2006

Quadriceps strength predicts mortality in patients with moderate to severe chronic obstructive pulmonary disease.

BACKGROUND: Prognosis in chronic obstructive pulmonary disease (COPD) is poorly predicted by indices of air flow obstruction, because other factors that reflect the systemic nature of the disease also influence prognosis. OBJECTIVE: To test the hypothesis that a reduction in quadriceps maximal voluntary contraction force (QMVC) is a useful predictor of mortality in patients with COPD. METHODS: A mortality questionnaire was sent to the primary care physician of 184 patients with COPD who had undergone quadriceps strength measurement over the past 5 years. QMVC was expressed as a percentage of the patient's body mass index. The end point measured was death or lung transplantation, and median (range) follow-up was 38 (1-54) months. RESULTS: Data were obtained for 162 patients (108 men and 54 women) with a mean (SD) percentage of forced expiratory volume in 1 s (FEV1) predicted of 35.6 (16.2), giving a response rate of 88%. Transplant-free survival of the cohort was 93.5% at 1 year and 87.1% at 2 years. Cox regression models showed that the mortality risk increased with increasing age and with reducing QMVC. Only age (HR 1.72 (95% CI 1.14 to 2.6); p = 0.01) and QMVC (HR 0.91 (95% CI 0.83 to 0.99); p = 0.036) continued to be significant predictors of mortality when controlled for other variables in the multivariate analysis. CONCLUSION: QMVC is simple and provides more powerful prognostic information on COPD than that provided by age, body mass index and forced expiratory volume in 1 s.

Disease-Free Survival↗
PubMed2006

Passive properties of the diaphragm in COPD.

Structural adaptations that occur in the diaphragm muscle of patients with chronic obstructive pulmonary disease (COPD), namely an increase in type I fibers and a decrease in type II fibers, have been explored in terms of the active contractile properties of the diaphragm. The aim of this study was to test the passive properties of the diaphragm by measuring the force response of relaxed diaphragm muscle fibers to stretching to determine the effect of COPD on these properties. Costal diaphragm biopsies were taken from patients with COPD and from controls with normal pulmonary function. From these biopsies, titin expression was assessed in diaphragm homogenates by gel electrophoresis, and the restoring force was measured by incremental stretching of single fibers in the relaxed state and measuring the force response to stretching. A quadratic model was used to illustrate the relationship between restoring force and muscle fiber length, and it revealed that COPD fibers generate significantly lower restoring forces than control fibers as judged by the area under the force-length curve. Furthermore, this finding applies to both type I and type II fibers. Gel electrophoresis revealed different titin isoforms in COPD and controls, consistent with the conclusion that COPD results not only in a change in muscle fiber-type distribution but in a structural change in the titin molecule in all muscle fiber types within the diaphragm. This may assist the muscle with the energetic changes in the length of the diaphragm required during breathing in COPD.

Adaptation, Physiological↗
PubMed2006

Long-term management of breast cancer-related lymphedema after intensive decongestive physiotherapy.

BACKGROUND: Treatment of lymphedema is based on intensive decongestive physiotherapy followed by a long-term maintenance treatment. We analyzed the factors influencing lymphedema volume during maintenance treatment. METHOD: Prospective cohort of 537 patients with secondary arm lymphedema were recruited in a single lymphology unit and followed for 12 months. Lymphedema volume was recorded prior to and at the end of intensive treatment, and at month 6 and month 12 follow-up visits. Multivariate models were fitted to analyze the respective role of the three components of complete decongestive therapy, i.e. manual lymph drainage, low stretch bandage, and elastic sleeve, on lymphedema volume during the 1-year maintenance phase therapy. RESULTS: Mean volume of lymphedema was 1,054 +/- 633 ml prior and 647 +/- 351 ml after intensive decongestive physiotherapy. During the 1-year maintenance phase therapy, the mean lymphedema volume slightly increased (84 ml-95% confidence interval [CI]: 56-113). Fifty-two percent of patients had their lymphedema volume increased above 10% from their value at the end of the intensive decongestive physiotherapy treatment phase. Non-compliance to low stretch bandage and elastic sleeve were risk factors for an increased lymphedema after 1-year of maintenance treatment (RR: 1.55 [95% CI: 1.3-1.76]; P < 0.0001 and RR: 1.61 (95% CI: 1.25-1.82); P = 0.002, respectively). Non-compliance to MLD was not a risk factor (RR: 0.99 [95% CI: 0.77-1.2]; P = 0.91). CONCLUSION: During maintenance phase after intensive decongestive physiotherapy, compliance to the use of elastic sleeve and low stretch bandage should be required to stabilize lymphedema volume.

Adult↗
PubMed2006

Experimental study of the effects of probiotics on Cryptosporidium parvum infection in neonatal rats.

To date, there is no efficient treatment for cryptosporidiosis and parasite eradication relies on innate and acquired immunity. In this study, we investigated the effect of administration of probiotic bacteria on the development and progression of the experimental infection in suckling rats. Rats were fed daily with 2.10(7) CFU of Lactobacillus casei-containing mixture, starting 2 days before the infection until the spontaneous clearance of the parasite. Effects on weight gain, parasite burden, mucosal histology and production of mucosal cytokines (IFNgamma, IL10 and TNFalpha) were studied. Although a trend to a more rapid clearance of parasites was noted in rats treated with probiotics, no significant effect of probiotics administration was observed in terms of weight gain, parasite burden, mucosal damage, or kinetics of mucosal cytokines during the course of infection. Overall, our results showed that the daily administration of L. casei-containing mixtures was unable to eradicate the parasite in our model.

Animals↗
PubMed2006

Brief communication: sirolimus-associated pneumonitis: 24 cases in renal transplant recipients.

BACKGROUND: Interstitial pneumonitis is an ill-defined side effect of sirolimus, a new immunosuppressant drug recently introduced for patients having organ transplantation. OBJECTIVE: To evaluate clinical and laboratory features of sirolimus-associated pneumonitis. DESIGN: Case series. SETTING: 1 transplantation center in Paris, France. PATIENTS: 24 patients who had renal transplantation and developed sirolimus-associated pneumonitis, including 8 patients previously reported. MEASUREMENTS: Symptoms; laboratory tests, including bronchoalveolar fluid analysis; and computed tomography (CT) of the chest. INTERVENTION: Withdrawal or dose reduction of sirolimus. RESULTS: Clinical symptoms included cough (23 patients), fatigue (20 patients), fever (16 patients), and dyspnea (8 patients). Computed tomography of the chest showed reticular and ground-glass opacities (4 patients), bronchiolitis obliterans-organizing pneumonia (19 patients), and lobar consolidation (1 patient). Bronchoalveolar lavage showed lymphocytic (19 patients) or eosinophilic (3 patients) alveolitis or pulmonary hemorrhage (2 patients). A reduction in the sirolimus dose resulted in transient clinical improvement in 2 patients, but discontinuation of drug therapy was eventually necessary in all patients. All patients recovered completely within 6 months. LIMITATIONS: The sirolimus trough level in patients from this single center was higher than that usually used in patients having renal transplantation. CONCLUSION: Lymphocytic alveolitis and radiologic bronchiolitis obliterans-organizing pneumonia are the key findings in sirolimus-associated pneumonitis. Sirolimus withdrawal was associated with recovery within 6 months.

Adult↗
PubMed2006

Diagnosis of vertebral fractures by vertebral fracture assessment.

Vertebral fractures are independent risk factors for both vertebral and peripheral fractures and only one-third of these fractures come to clinical attention. Vertebral fracture assessment (VFA) is a radiographic method using dual X-ray absorptiometry (DXA) to assess vertebral deformities during bone density measurement. We performed VFA of the spine from T4 to L5 on a Delphi W device (Hologic, Bedford, MA) in 136 postmenopausal patients (69+/-10 yr). These patients also had X-rays of the thoracic and lumbar spine. VFA was independently compared with X-rays by two rheumatologists, for the diagnosis of vertebral fractures at both the patient and vertebral levels. Using X-rays, 61 patients (45%) had at least one vertebral fracture. The percentage of unreadable vertebrae was 1% and 12.4% on X-rays and VFA, respectively (p<0.0001). At the patient level, VFA allowed to diagnose if the patient had no fracture or had at least one fracture in 74% of patients. In 11.2% of cases, VFA misclassified the patients. At the vertebral level, diagnostic efficacy of VFA as compared with X-rays was 97%. Concordance between both observers was good (kappa-score=0.69). We designed an algorithm for decision of performing X-rays in postmenopausal women: Using results of VFA would avoid X-rays in 32% of our patients. VFA is a reliable technique with low radiation, and is easily and rapidly applicable during bone density measurement by DXA, which could improve management of osteoporotic patients.

Absorptiometry, Photon↗
PubMed2006

MRI of clot in cerebral venous thrombosis: high diagnostic value of susceptibility-weighted images.

BACKGROUND AND PURPOSE: In cerebral venous thrombosis (CVT), the sensitivity of conventional MRI sequences to detect clot in the sinuses or veins is incomplete and largely depends on the time elapsed since thrombus formation. Little is known concerning the corresponding diagnostic value of fluid-attenuated inversion recovery (FLAIR), echo-planar T2* susceptibility-weighted imaging (T2*SW) or diffusion-weighted images (DWI). METHODS: We performed a retrospective analysis of 114 MRI examinations from 39 patients with CVT using a structured assessment. The time course of sensitivity in the detection of clot (n=166 clots) was analyzed for different MR sequences using a multilevel logistic model. The sensitivity of different MR sequences for diagnosis of cortical venous thrombosis was tested separately (n=38 clots). RESULTS: The sensitivity of T2*SW and T1-weighted spin echo image (T1SE) sequences to detect clot in the sinuses or veins was estimated at 90% and 71% between day 1 and day 3, which was much higher than that of T2SE, FLAIR or DWI during the first week of clinical onset. The sensitivity of T2*SW was stable in the first week. After this period, the sensitivity of T2*SW decreased less than that of T1SE. Thrombosed cortical veins, even in the absence of visible occlusion on magnetic resonance venography, were detected more frequently with T2*SW (97%) and T1SE (78%) than with FLAIR or DWI (<40%). CONCLUSIONS: T2*SW imaging appears to be of additional diagnostic value in CVT. The T2*SW sequence may be particularly useful during the acute phase of CVT when the sensitivity of the other sequences is incomplete and for the diagnosis of isolated cortical venous thrombosis.

Adolescent↗
PubMed2006

Predictive factors of response to intensive decongestive physiotherapy in upper limb lymphedema after breast cancer treatment: a cohort study.

BACKGROUND: Lymphedema is a frequent complication after breast cancer treatment. Reduction of lymphedema volume is obtained during an intensive phase with daily physiotherapy. Response to treatment remains unknown prior treatment. We purposed to analyze predictors of response of lymphedema treatment throughout the first course of physiotherapy. DESIGN: Patients with secondary arm lymphedema were recruited in a single lymphology unit between 2001 and 2004. For each patient, the following data were recorded: characteristics of breast cancer treatment, patient characteristics, body mass index and lymphedema volume prior and at the end of treatment. RESULTS: Three hundred and fifty-seven women (mean age: 53+/-11 years) were included. Initial excess volume of lymphedema was correlated to body mass index and duration of lymphedema. Mean duration of intensive decongestive therapy was 11.8+/-3.3 days. Mean excess volume of lymphedema was 1067+/-622 ml prior treatment and 663+/-366 ml after treatment (p<0.001), percentage of excess volume of lymphedema was 59+/-34% and 36+/-19%, respectively. Absolute volume reduction was 404+/-33 ml (p<0.001). Body mass index and duration of lymphedema before treatment were the two predictors of absolute reduction of lymphedema volume. Higher was the body mass index or the duration of lymphedema, more important was the absolute reduction of lymphedema volume. Mean relative percentage of volume reduction was 36+/-14% whatever mass index or the duration of lymphedema was. CONCLUSION: Duration of lymphedema from cancer treatment and body mass index were the only two predictors of absolute reduction of lymphedema volume after intensive decongestive physiotherapy. For all patients this latter treatment is highly effective in management of secondary upper limb lymphedema after breast cancer.

Adult↗
PubMed2006

Clinical and electrophysiological predictors of respiratory failure in Guillain-Barré syndrome: a prospective study.

BACKGROUND: Respiratory failure is the most serious short-term complication of Guillain-Barré syndrome and can require invasive mechanical ventilation in 20-30% of patients. We sought to identify clinical and electrophysiological predictors of respiratory failure in the disease. METHODS: We prospectively assessed electrophysiological data and clinical factors, including identified predictors of delay between disease onset and admission, inability to lift head, and vital capacity, in patients admitted with Guillain-Barré syndrome. We related these factors to subsequent need for ventilatory support. Neurophysiological findings were classified as demyelinating, axonal, equivocal, unexcitable, or normal. Predictive values of clinical and electrophysiological data were tested using classification trees to build up a predictive model. This model was initially built up in a two-third (fitting set) then validated in a one-third (validation set) of the total sample. The fitting and validation sets were randomly selected. We also assessed the predictive value of this model for disability at 6 months. FINDINGS: From 1998, to 2006, 154 patients with Guillain-Barré syndrome were included in the study and 34 (22%) were subsequently ventilated. Demyelinating Guillain-Barré syndrome was more common in patients who went on to be ventilated than in those who were not (85%vs 51%, p=0.0003). Vital capacity and the proximal/distal compound muscular amplitude potential (p/dCMAP) ratio of the common peroneal nerve were retained in the tree model, with a probability of needing ventilation of less than 2.5% in patients with a ratio of greater than 55.6% and a vital capacity more than 81% of predicted. A p/dCMAP ratio of the peroneal nerve less than 55.6% and age older than 40 years were retained as independent predictors of disability at 6 months. INTERPRETATION: Neurophysiological testing is helpful for assessing risk of respiratory failure, which is highest in patients with evidence of demyelination and very low in those without both 55.6% conduction block of the common peroneal nerve and a 20% reduction in vital capacity.

Action Potentials↗
PubMed2006

Guillain-Barré syndrome, greater Paris area.

We studied 263 cases of Guillain-Barré syndrome from 1996 to 2001, 40% of which were associated with a known causative agent, mainly Campylobacter jejuni (22%) or cytomegalovirus (15%). The cases with no known agent (60%) peaked in winter, and half were preceded by respiratory infection, influenza-like syndrome, or gastrointestinal illness.

Adult↗
PubMed2005

Kinetics of response to long-term treatment combining pentoxifylline and tocopherol in patients with superficial radiation-induced fibrosis.

PURPOSE: Significant regression of radiation (RT) -induced fibrosis (RIF) has been achieved after treatment combining pentoxifylline (PTX) and alpha-tocopherol (vitE). In this study, we focus on the maximum response, how long it takes to achieve response, and changes after treatment discontinuation. PATIENTS AND METHODS: Measurable superficial RIF was assessed in patients treated by RT for breast cancer in a long-treatment (24 to 48 months) PTX-vitE (LPE) group of 37 patients (47 RIFs) and in a short-treatment (6 to 12 months) PTX-vitE (SPE) group of seven patients (eight RIFs). Between April 1995 and April 2000, women were treated with a daily combination of PTX (800 mg) and VitE (1,000 IU). RESULTS: Combined PTX-vitE was continuously effective and resulted in exponential RIF surface area regression (-46% for LPE and -68% for SPE at 6 months, -58% for LPE and -69% for SPE at 12 months, -63% for LPE and -62% for SPE at 18 months, and -68% for LPE at 24 and 36 months). The mean estimated maximal treatment effect was 68% RIF surface area regression. The mean time to this effect was 24 months and was shorter (16 months) in more recent RIF (< 6 years since RT) than in older RIF (28 months; P = .0003). Symptom severity (Subjective Objective Medical Management and Analytic Evaluation score) was halved in both groups. After treatment discontinuation, mean RIF surface area at 1 year had increased by +40% in the SPE group (rebound) and +8.5% in the LPE group. CONCLUSION: Under combined PTX-vitE treatment, RIF regression was exponential, with a two-thirds maximum response after a mean of 2 years. There was a risk of a rebound effect if treatment was too short. Long treatment (>/= 3 years) is recommended in patients with severe RIF.

Adult↗
PubMed2005

Two major spondylarthropathy phenotypes are distinguished by pattern analysis in multiplex families.

OBJECTIVE: To examine whether spondylarthropathy (SpA) disease manifestations would combine in any ordered pattern among patients from SpA multiplex families. METHODS: SpA patients (n = 540) belonging to 190 multiplex families were thoroughly investigated. Clinical data was collected, systematic pelvic radiographs were taken, and HLA-B27 status was determined. The patterns of SpA manifestations were examined by several methods, including multiple correspondence analysis, nonhierarchical and hierarchical clustering, and discriminant analysis. RESULTS: The nonhierarchical cluster analysis allowed us to classify patients, independent of disease duration, into 2 major groups of comparable size. Group A contained a majority of the women, whereas group B predominantly consisted of men. The 2 groups were very similar regarding axial symptoms, radiographic sacroiliitis, and uveitis. Group B was characterized by a younger age at onset and a higher frequency of clinical enthesitis, peripheral arthritis, dactylitis, psoriasis, and inflammatory bowel disease than group A. Patients belonging to those groups exhibited some degree of familial aggregation, thereby supporting their intrinsic validity. CONCLUSION: Pattern analysis of SpA manifestations among familial SpA allowed us to recognize 2 main clusters independent of disease duration. Furthermore, there was a trend toward aggregation by cluster among families, suggesting that they are determined by specific genetic factors. These clusters may indeed correspond to different severity patterns.

Adolescent↗
PubMed2005

Longitudinal diffusion changes in cerebral hemispheres after MCA infarcts.

Diffusion tensor imaging can be used in vivo to assess the longitudinal and regional microstructural changes occurring after middle cerebral artery (MCA) infarcts in humans. Nine patients were investigated 1 week (D7), 1 (M1), 3 (M3), and 6 months (M6) after the occurrence of an isolated MCA infarction. First, an overall analysis was performed using histograms of mean diffusivity (MD) and fractional anisotropy (FA) in each hemisphere. Thereafter, the regional pattern of diffusion changes was investigated voxel by voxel with statistical parametric mapping 99. In the hemisphere ipsilateral to the infarction, histogram analysis revealed a significant decrease in FA between D7 and M6 associated with a progressive increase in MD from D7 to M3. Remote from the MCA territory, the voxel by voxel analyses detected a significant increase in MD within the thalamus at M3 and M6 and a reduction in FA along the pyramidal tract at M6. In the contralateral hemisphere, between D7 and M6, a significant hemispheric atrophy was observed in association with a global reduction in anisotropy, in the absence of distinctive regional diffusion changes. These results suggest that micro- and macrostructural tissue modifications can be detected with diffusion tensor imaging in regions remote from the ischemic area in both hemispheres.

Adult↗
PubMed2004

The graft-versus-leukaemia effect after allogeneic bone-marrow transplantation: assessment through competing risks approaches.

In failure time studies involving a chronic disease such as cancer, data often focus on one or more non-fatal events, in addition to survival, to describe the course of the disease. In the example of allogeneic bone marrow transplantation in leukaemic patients, acute graft-versus host disease (aGvHD), relapse and death were taken as the reported events, and we focused on testing the existence of graft-versus-leukaemia (GvL) effect, i.e. that the occurrence of aGvHD modifies the probability of relapse. One of the weaknesses of the standard competing risks models is their inability to model secondary relapses. We thus derived, from two competing risks models, two estimators of cumulative incidence functions of primary and secondary relapses, as well as statistics to test the GvL effect. The approach is illustrated by application to a data set from a cohort of 442 children with acute leukaemia who received an unrelated transplant.

Bone Marrow Transplantation↗
PubMed2004

Sample size formula for proportional hazards modelling of competing risks.

To test the effect of a therapeutic or prognostic factor on the occurrence of a particular cause of failure in the presence of other causes, the interest has shifted in some studies from the modelling of the cause-specific hazard to that of the subdistribution hazard. We present approximate sample size formulas for the proportional hazards modelling of competing risk subdistribution, considering either independent or correlated covariates. The validity of these approximate formulas is investigated through numerical simulations. Two illustrations are provided, a randomized clinical trial, and a prospective prognostic study.

Administration, Intravaginal↗
PubMed2004

Corticospinal control of respiratory muscles in chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) face an increased respiratory load and in consequence have an elevated respiratory drive. We used transcranial magnetic stimulation (TMS) to investigate associated changes in corticospinal excitability both at rest and during voluntary facilitation at different levels of inspiratory effort. Diaphragm and abdominal motor thresholds were significantly lower in COPD than healthy controls, but the quadriceps response was the same. In patients there was a significant increase in diaphragm response from rest during 20% inspiratory efforts but no further increase with greater efforts. In controls there was a further stepwise increase at 40% and 60% of inspiratory effort. The cortical silent period was significantly shorter in COPD. Using paired stimulation to study intracortical inhibitory and excitatory circuits we found significantly less excitability of intracortical facilitatory circuits in patients at long (>7 ms) interstimulus intervals. These results suggest that there is a ceiling effect in motor control output to the respiratory muscles of patients with COPD.

Abdominal Muscles↗