Publications by authors named "Benjamin Riche"

35 Publications

A Nurse-Led Bridging Program to Reduce 30-Day Readmissions of Older Patients Discharged From Acute Care Units.

J Am Med Dir Assoc 2020 Nov 20. Epub 2020 Nov 20.

Service de médecine gériatrique, Hospices Civils de Lyon, Groupement Hospitalier Sud, CHU de Lyon, Bénite-Pierre Cedex, France; Université de Lyon, F-69000, Lyon, France; Université Lyon 1, Villeurbanne, France; CarMeN, U1060 INSERM, Oullins Cedex, France.

Objectives: Older hospitalized patients are at high risk of early readmissions, requiring the implementation of enhanced coordinated transition programs on discharge. The objective of this study was to evaluate the impact of a nurse-led transition bridging program on the rate of unscheduled readmissions of older patients within 30 days from discharge from geriatric acute care units.

Design: A stepped-wedge cluster randomized trial.

Setting And Participants: Seven hundred five patients aged ≥75 years hospitalized in one of 10 acute geriatric units, with at least 2 readmission risk-screening criteria (derived from the Triage Risk Screening Tool), were included from July 2015 to August 2016.

Methods: The intervention condition consisted in a nurse-led hospital-to-home bridging program with 4 weeks postdischarge follow-up (2 home visits and 2 telephone calls). Unscheduled hospital readmission or emergency department (ED) visits were compared in intervention and control condition within 30 days from discharge.

Results: The rate of 30-day readmission or ED visit was 15.5% in the intervention condition vs 17.6% in the control condition [hazard ratio stratified on clusters: 0.61 (upper limit unilateral 95% confidence interval = 1.11), P = .09]. Rate of presence of professional caregivers was increased in the intervention condition (P < .001).

Conclusions And Implications: Although the intervention resulted in an increase in the rate of implementation of a package of care at the 4-week of follow-up, we could not demonstrate a reduction in the rate of 30-day readmissions or ED visits of older patients at risk of readmission. These findings support the evaluation of this type of program on the longer term.
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November 2020

MRI Monitoring of Residual Vestibular Schwannomas: Modeling and Predictors of Growth.

Otol Neurotol 2020 Sep;41(8):1131-1139

Department of Otolaryngology and Otoneurosurgery, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Claude Bernard University Lyon 1, Lyon, France.

Objectives: The aim was to model residual Vestibular Schwannoma (VS) over time to identify prognostic factors of postsurgical growth.

Study Design: Multicenter retrospective study.

Setting: Tertiary referral centers.

Patients: A group of 135 patients who underwent incomplete resection for VS between January 2010 and December 2018. On magnetic resonance imaging (MRI) examinations at baseline (1 year after surgery), patients included were divided into two groups: near-total resection (NTR, <25 mm × 2 mm) and subtotal resection (STR, greater volume).

Intervention: Monitoring of residual VS volume.

Main Outcome Measures: 3D volumetric segmentation of residual tumors was performed on every MRI examination at baseline and during follow-up to model volume changes over time using the Lambda-Mu-Sigma method.

Results: The study followed-up 127 patients (median age: 56 yr) over a median follow-up of 39 months. Most VS residues (76.7%; 89/116) showed no growth at 5 years. Only 27 (23.3%) residues showed signs of regrowth (increase in volume >0.05 cm). The extent of resection is a predictor of tumor growth (odds ratio [OR] = 4.85; for STR over NTR; p = 0.003), but the growth rate was significantly different between STR and NTR residues (p < 0.001). At first, over 2 years after surgery, STR residues decreased (-1.0% volume per year), whereas NTR ones grew (+8% per year). Then, both residues showed sign of regrowth.

Conclusion: Postoperative recommendations should now include the natural history of VS residue after resection: even though the growth rate differs between STR and NTR residues, most VS residues showed no growth.
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September 2020

Usefulness of Thoracic Aortic Calcium to Predict 1-Year Mortality After Transcatheter Aortic Valve Implantation.

Am J Cardiol 2021 02 2;140:103-109. Epub 2020 Nov 2.

Service de Cardiologie, Hôpital Croix-Rousse and Hôpital Lyon Sud, Hospices Civils de Lyon, Lyon, France; CREATIS UMR5220; INSERM U1044; INSA-15, Université de Lyon, Lyon, France.

In patients who underwent transcatheter aortic valve implantation (TAVI), vascular disease is associated with increased risk of mortality. Thoracic aortic calcification (TAC), an objective surrogate of vascular disease, could be a predictor of mortality after TAVI. We aimed to analyze the association between TAC burden and 1-year all-cause mortality in patients who underwent TAVI in a US population. From July 2015 through July 2017, a retrospective review of TAVI procedures was performed at Baylor Scott & White-The Heart Hospital, Plano, Texas. Patients were analyzed for comorbidities, cardiac risk factors, and 30-day and 1-year all-cause mortality. Restricted cubic splines analysis was used to define low, moderate, and high TAC categories. The association between TAC and survival was evaluated using unadjusted and adjusted Cox models. A total of 431 TAVI procedures were performed, of which TAC was measured in 374 (81%) patients. Median (interquartile range) age was 82 (77, 87) years, and 51% were male. Median (interquartile range) STS PROM was 5.6 (4.1, 8.2) %. Overall 30-day and 1-year all-cause mortality was 1% and 10%, respectively. TAC was categorized as low (<1.6 cm), moderate (1.6 to 2.9 cm), and high (>2.9 cm). At 1 year, all-cause mortality was 16% in patients with high TAC compared with 6% in the low and moderate TAC categories (p = 0.008). Unadjusted and adjusted Cox regression analysis showed a significant increase in mortality for patients with high TAC compared with low TAC (hazard ratio 2.98, 95% confidence interval [1.34-6.63]), but not significant compared with moderate TAC group. TAC is a predictor of late mortality after TAVI. In conclusion, adding TAC to preoperative evaluation may provide an objective, reproducible, and potentially widely available tool that can help in shared decision-making.
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February 2021

A beat-by-beat cardiovascular index, CARDEAN, to titrate opioid administration in the setting of orthopaedic surgery: a prospective randomized trial.

J Clin Monit Comput 2020 Oct 6. Epub 2020 Oct 6.

Anaesthesia, Hôpital D'Instruction Des Armées Desgenettes, Lyon, France.

To determine whether a beat-by-beat cardiovascular index (CARDEAN: cardiovascular depth of analgesia, Alpha-2 Ltd, Lyon, France) reduces the incidence of tachycardia in ASA I-III patients undergoing orthopaedic surgery. A total of 76 patients were prospectively randomized into (1) a control group or (2) the CARDEAN group, in which the nurse anaesthetist was blinded to CARDEAN application. In addition to conventional signs, an external observer instructed the nurse anaesthetist to administer sufentanil 0.1 µg kg when the CARDEAN crossed a threshold (≥ 60). The primary outcome was the incidence of tachycardia (> 120% of reference heart rate, HR). Non-invasive blood pressure (BP), electrocardiogram (ECG), O saturation-photoplethysmography and the bispectral index (40 < BIS < 60) were monitored. HR and an estimation of beat-by-beat BP changes acquired from photoplethysmography and ECG were combined in an algorithm that detected hypertension followed by tachycardia (index scaled 0-100). Sufentanil 0.1 µg kg was administered when tachycardia, hypertension or movement ("conventional signs") was observed. Data for 66 patients (27 with known hypertension) were analysed. In the CARDEAN group, (a) the dose of sufentanil was higher (control: 0.46 µg kg 100 min, CARDEAN: 0.57 µg kg 100 min, p = 0.016), (b) the incidence rates of tachycardia and untoward events were lower (respectively: - 44%; control: 2.52 events 100 min [1.98-3.22]; CARDEAN: 1.42 [1.03-1.96], p = 0.005, hazard ratio: 0.56; movement, muscular contraction, or coughing: control: 0.74 events 100 min [0.47-1.16]; CARDEAN: 0.31 [0.15-0.62], p = 0.038), and (c) extubation occurred more often in the operating room (control: 76.5%, CARDEAN: 97%, p = 0.016). CARDEAN-titrated opioid administration was associated with a higher dose of sufentanil, a reduction in tachycardia and earlier emergence in ASA I-III patients undergoing major orthopaedic surgery.
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October 2020

Epidemiology of paraneoplastic neurologic syndromes and autoimmune encephalitides in France.

Neurol Neuroimmunol Neuroinflamm 2020 11 26;7(6). Epub 2020 Aug 26.

From the Centre de Référence National pour les Syndromes Neurologiques Paranéoplasique (J. Hébert, A.V., S.M.-C., B.J., G.P., V.R., V.D., J. Honnorat), Hospices Civils de Lyon, Lyon, France; SynatAc Team (J. Hébert, A.V., S.M.-C., B.J., G.P., V.R., V.D., J. Honnorat), NeuroMyoGene Institute, INSERM U1217-CNRS UMR5310, Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France; Université de Lyon (J. Hébert, B.R., M.R.), Lyon, France; Université Lyon 1, Villeurbanne, France; CNRS UMR, Laboratoire de Biométrie et Biologie Évolutive, Équipe Biostatistique-Santé, Villeurbanne, France; Service de Biostatistique-Bioinformatique, Pôle Santé Publique, Hospices Civils de Lyon, Lyon, France; Institut Pierre Louis d'Épidémiologie et de Santé Publique (J. Hébert), Faculté de Médecine, Sorbonne Université, Paris, France; AP-HP (D.P., G.B.), Groupe Hospitalier Pitié-Salpêtrière, Service de Neurologie 2-Mazarin et Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière (CRICM), UMRS, Paris, France; Inserm U 975 (D.P., G.B.), CNRS, UMR, Paris, France; and Centre de Compétence des Syndromes Neurologiques Paraneoplasiques et Encéphalites Autoimmunes (D.P., G.B.), Groupe Hospitalier Pitié-Salpêtrière, Paris, France.

Objective: To determine the observed and expected incidence rates of paraneoplastic neurologic syndromes (PNSs) and autoimmune encephalitides (AEs) diagnosed in France between 2016 and 2018, we conducted a population-based epidemiologic study.

Methods: Observed incidence rates were stratified by sex, age groups, region of care, year of diagnosis, and disease subgroups. National expected incidence rates were calculated based on rates obtained in the area directly adjacent to the Reference Center using a mixed Poisson model and compared with observed incidence rates.

Results: Six hundred thirty-two patients with definite PNS or AE met the inclusion criteria. The observed incidence rate of definite PNS and AE in France was 3.2 per million person-years (CI: 2.9-3.4) compared with an expected incidence rate of 7.1 per million person-years (CI: 3.9-11.4). The national observed incidence rate for the antibody-positive AE subgroup increased from 1.4 per million person-years (CI: 1.2-1.7) in 2016 to 2.1 per million person-years (CI: 1.7-2.4) in 2018, thus surpassing the incidence rate of classical PNS (1.2 per million person-years [CI: 1.0-1.5]) of 2018.

Conclusions: There was a significant widespread year-to-year increase in the incidence of diagnoses registered with the Reference Center for all subgroups of PNS and AE studied. The national observed incidence rate is likely underestimated due to underdiagnosis and underreporting.
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November 2020

Role for Vascular Factors in Long-Term Outcomes After Transcatheter Aortic Valve Implantation.

Am J Cardiol 2020 06 2;125(12):1884-1889. Epub 2020 Apr 2.

Service de cardiologie, Hôpital Croix-Rousse and Hôpital Lyon Sud, Hospices Civils de Lyon, Lyon, France; Université de Lyon; CREATIS UMR5220; INSERM U1044; INSA-15 Lyon, France. Electronic address:

Despite major technological advances, 1-year morbi-mortality after transcatheter aortic valve implantation (TAVI) is still high. Further outcome improvements may be obtained provided proper identification of prognostic factors. A change of prognostic value over time should be the hallmark of an outcome-implicated factor. In 1,425 patients treated by TAVI, the examined prognostic factors were: demographic factors and co-morbidities (age, male gender, glomerular filtration rate, and chronic obstructive pulmonary disease), cardiac function (left ventricular ejection fraction, pulmonary pressure, aortic gradient, dyspnea, and mitral regurgitation), and vascular factors (coronary artery disease, peripheral vascular disease (PVD), previous stroke, and thoracic aortic calcium-TAC-as assessed by CT scan). Cox models were used to analyze cardiovascular and all-cause mortalities over 3 years of follow-up. The time-dependent effects of the factors were analyzed using the distribution of Schoenfeld residuals. During the study period, 375 (26.3%) deaths occurred of whom 248 (17.4%) from cardiovascular causes. Only 2 factors associated with cardiovascular or all-cause mortality showed significant changes over time: dyspnea and PVD. The effect of dyspnea on cardiovascular mortality decreased over time (first- and third-year hazard ratios [95% confidence intervals]: 1.47 [1.10; 1.96] and 0.94 [0.55; 1.63], respectively), whereas the effect of PVD increased (first- and third-year hazard ratios: 0.87 [0.56; 1.35] and 2.58 [1.25; 5.33], respectively). TAC had a stable effect. In conclusion, the detrimental effects of vascular factors remained stable (TAC) or increased (PVD) over time. These factors should be targeted by specific measures to improve post-TAVI outcomes.
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June 2020

Vascular Events and Carotid Atherosclerosis: A 5-Year Prospective Cohort Study in Patients with Type 2 Diabetes and a Contemporary Cardiovascular Prevention Treatment.

J Diabetes Res 2019 22;2019:9059761. Epub 2019 Dec 22.

Hospices Civils de Lyon, Department of Vascular Medicine, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France.

Background And Aims: European recommendations on cardiovascular prevention suggest that carotid atherosclerosis assessment by duplex ultrasonography could help in some cases to better assess CV risk. We investigated whether the presence of carotid atherosclerosis determined by duplex ultrasonography is associated with cardiovascular events in patients with type 2 diabetes and could therefore help to reclassify cardiovascular risk.

Methods: Among 624 consecutive patients with type 2 diabetes and carotid atherosclerosis assessment by duplex ultrasonography between January and December 2012, 583 (93%) were included and followed up prospectively. The primary endpoint was the occurrence of cardiovascular events. The rate of new cardiovascular events was compared between patients with ( = 104) and those without ( = 479) prior cardiovascular events.

Results: A total of new 104 cardiovascular events occurred in 72 patients (12.5%) during a mean ± SD follow-up period of 5.1 ± 1.6 years. At baseline, for 202 patients (34.6%), carotid evaluation was normal; 381 (65.4%) had a carotid atherosclerosis lesion. The presence of carotid atherosclerosis at baseline was not significantly associated with an increased risk of new cardiovascular events in both groups. The rate of new cardiovascular events was more than twice as high in patients with prior cardiovascular event than those without.

Conclusion: Systematic carotid atherosclerosis assessment by duplex ultrasonography in patients with type 2 diabetes and a contemporary cardiovascular prevention treatment does not offer additional information as to the risk of cardiovascular events. This trial is registered with (ID: NCT02929355).
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June 2020

Lung cancer surgical treatment after solid organ transplantation: A single center 30-year experience.

Lung Cancer 2020 01 28;139:55-59. Epub 2019 Oct 28.

Department of Thoracic Surgery, Lung and Heart-Lung Transplantation, Louis Pradel Hospital, Hospices Civils de Lyon, F-69677, Lyon, France.

Objectives: Solid organ transplantation is an accepted treatment for end-stage organ failure. Long-lasting immunosuppressive therapy may increase the risk ofde novo malignancies in transplant recipients. Increased risk of bronchogenic carcinoma in this population is controversial but prolonged transplant recipients' survival (obtained in modern transplantation era) may increase the need for lung cancer surgical resection in immunosuppressed patients. Our aim was to assess morbidity, mortality and long-term survival after lung cancer surgical treatment in this population.

Materials And Methods: In an observational study, the medical charts of all consecutive patients who had undergone surgical treatment for lung cancer after solid organ transplantation were reviewed. These medical records were extracted from the University of Lyon (France) Transplantation database and Thoracic Surgery database. From 1986-2016, 61 patients underwent a surgical treatment for lung cancer after solid organ transplantation.

Results: The surgical procedures consisted of 52 lobectomies, 7 pneumonectomies and 2 wedge-resections. 90-day post-operative complications, most of which were pneumonias, affected 31 patients (50.8 %). 90-day postoperative mortality was 9.8 %. Overall survival was 40.6 % at 5 years and 18 % at 10 years.

Conclusion: Despite a higher rate of infectious complications and 90-day postoperative mortality, surgical treatment for lung cancer must be offered to these patients as it offers a chance to cure earlier- stage disease. Long-term survival rate is satisfactory and similar to that of the general population. In transplant recipients with former smoking history, close follow-up is mandatory to increase early lung cancer diagnosis.
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January 2020

Development of a Risk Score Based on Aortic Calcification to Predict 1-Year Mortality After Transcatheter Aortic Valve Replacement.

JACC Cardiovasc Imaging 2019 01 16;12(1):123-132. Epub 2018 May 16.

Cardiology Department, Hôpital Croix-Rousse and Hôpital Lyon Sud, Hospices Civils de Lyon, Lyon, France; University of Lyon, CREATIS UMR5220, INSERM U1044, INSA-15 Lyon, France.

Objectives: The aim of this study was to develop a new scoring system based on thoracic aortic calcification (TAC) to predict 1-year cardiovascular and all-cause mortality.

Background: A calcified aorta is often associated with poor prognosis after transcatheter aortic valve replacement (TAVR). A risk score encompassing aortic calcification may be valuable in identifying poor TAVR responders.

Methods: The CCAPRI (4 Cities for Assessing CAlcification PRognostic Impact) multicenter study included a training cohort (1,425 patients treated using TAVR between 2010 and 2014) and a contemporary test cohort (311 patients treated in 2015). TAC was measured by computed tomography pre-TAVR. CAPRI risk scores were based on the linear predictors of Cox models including TAC in addition to comorbidities and demographic, atherosclerotic disease and cardiac function factors. CAPRI scores were constructed and tested in 2 independent cohorts.

Results: Cardiovascular and all-cause mortality at 1 year was 13.0% and 17.9%, respectively, in the training cohort and 8.2% and 11.8% in the test cohort. The inclusion of TAC in the model improved prediction: 1-cm increase in TAC was associated with a 6% increase in cardiovascular mortality and a 4% increase in all-cause mortality. The predicted and observed survival probabilities were highly correlated (slopes >0.9 for both cardiovascular and all-cause mortality). The model's predictive power was fair (AUC 68% [95% confidence interval [CI]: 64% to 72%]) for both cardiovascular and all-cause mortality. The model performed similarly in the training and test cohorts.

Conclusions: The CAPRI score, which combines the TAC variable with classical prognostic factors, is predictive of 1-year cardiovascular and all-cause mortality. Its predictive performance was confirmed in an independent contemporary cohort. CAPRI scores are highly relevant to current practice and strengthen the evidence base for decision making in valvular interventions. Its routine use may help prevent futile procedures.
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January 2019

Predicting thyroid nodule malignancy at several prevalence values with a combined Bethesda-molecular test.

Transl Res 2017 10 22;188:58-66.e1. Epub 2017 Jul 22.

Université Lyon 1, Lyon, France; Service de Biostatistique, Hospices Civils de Lyon, Lyon, France; CNRS UMR5558, Laboratoire de Biométrie et Biologie Évolutive, Équipe Biostatistique-Santé, Villeurbanne, France.

Investigation of thyroid nodules using fine-needle aspiration cytology (FNAC) gives indeterminate results in up to 30% of samples using the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). We present a combined Bethesda-molecular predictor of nodule malignancy to improve the accuracy of the preoperative diagnosis of thyroid nodules. To detect a molecular signature of thyroid nodule malignancy, a molecular test was performed on FNACs from 128 thyroid nodules from prospectively included patients, collected in a tertiary center. The test relied on a transcriptomic array of 20 genes selected from a previous study. An optimal set of seven genes was identified using a logistic regression model. Comparison between the combined predictor (TBSRTC + molecular) and TBSRTC alone used the area under the ROC curve (AUC). Performance of the combined predictor was calculated according to various malignancy prevalence values and benefit-to-harm ratios (B/Hr) (favoring sensitivity or specificity). In our population (36% malignancy prevalence) and with a B/Hr of 1, the combined predictor achieved 95% specificity and 76% sensitivity. The AUC was 93.5%; higher than that of TBSRTC (P = 0.004). Among indeterminate nodules (30% malignancy prevalence), sensitivity and specificity were 52.2% and 96.2%, respectively, with a B/Hr of 1, or 95.7% and 64.2% with a B/Hr of 4 (favoring sensitivity), allowing avoidance of 64% of unnecessary surgeries at the cost of only one false-positive result. In conclusion, this predictor could improve the detection of thyroid nodule malignancy, taking into account malignancy prevalence and B/Hr, and reduce the number of unnecessary thyroidectomies.
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October 2017

Combined interventions to reduce HIV incidence in KwaZulu-Natal: a modelling study.

BMC Infect Dis 2017 07 26;17(1):522. Epub 2017 Jul 26.

Service de Biostatistique, Hospices Civils de Lyon, F-69003, Lyon, France.

Background: Combined prevention interventions, including early antiretroviral therapy initiation, may substantially reduce HIV incidence in hyperendemic settings. Our aim was to assess the potential short-term impact of combined interventions on HIV spreading in the adult population of Mbongolwane and Eshowe (KwaZulu-Natal, South Africa) using sex- and age-specific scenarios, and age-targeted interventions.

Methods: A mathematical model was used with data on adults (15-59 years) from the Mbongolwane and Eshowe HIV Impact in Population Survey to compare the effects of various interventions on the HIV incidence rate. These interventions included increase in antiretroviral therapy (ART) coverage with extended eligibility criteria, increase in voluntary medical male circumcision (VMMC), and implementation of pre-exposure prophylaxis (PrEP) among women.

Results: With no additional interventions to the ones in place at the time of the survey (ART at CD4 < 350 and VMMC), incidence will decrease by 24% compared to the baseline rate. The implementation of "ART at CD4<500" or "ART for all" would reduce further the incidence rate by additional 8% and 15% respectively by 4 years and 20% and 34% by 10 years. Impacts would be higher with age-targeted scenarios than without.

Conclusions: In Mbongolwane and Eshowe, implementation of the new South African guidelines, recommending ART initiation regardless of CD4 count, would accelerate incidence reduction. In this setting, combining these guidelines, VMMC, and PrEP among young women could be an effective strategy in reducing the incidence to low levels.
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July 2017

Usefulness of a systematic screening of carotid atherosclerosis in asymptomatic people with type 2 diabetes for cardiovascular risk reclassification.

Ann Endocrinol (Paris) 2017 Feb 7;78(1):14-19. Epub 2017 Feb 7.

Department of endocrinology, diabetes and nutrition, pavillon médical, hospices civils de Lyon, centre hospitalier Lyon-Sud, 69310 Pierre-Bénite, France. Electronic address:

Aims: Routine screening of carotid atherosclerosis lesions is frequently suggested for people with type 2 diabetes, the presence of a carotid lesion being associated with a significant increase risk for vascular events. However, the impact of this strategy on medical management is not validated. We herein question the usefulness of such screening.

Methods: We assessed the prevalence and severity of carotid lesions in 337 consecutive people with type 2 diabetes without known cardiovascular disease who underwent a systematic carotid duplex ultrasonography. We analyzed whether the results of duplex ultrasonography allowed reclassification of cardiovascular risk level relative to the most recent international recommendations on diabetes and modified therapy.

Results: We found that 35.9% of people had no atherosclerotic lesion. Prevalence of carotid stenosis<20%, between 20 and 50% and ≥50% were 32.9%, 28.4% and 2.7% respectively. Regarding the use of statins and LDL-C target, the result of carotid duplex ultrasonography allowed to reclassify respectively 11.8% to 55.2% of the cohort in a higher cardiovascular risk level. For the indication of antiplatelet agent, reclassification in a higher risk level concerned 6.8% of the patients. No subject had an indication of carotid revascularization.

Conclusions: Carotid atherosclerosis is frequent in asymptomatic people with type 2 diabetes in primary cardiovascular prevention. Screening for carotid atherosclerosis by duplex ultrasonography seems useful to redefine the level of cardiovascular risk.
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February 2017

Growth curves for congenital adrenal hyperplasia from a national retrospective cohort.

J Pediatr Endocrinol Metab 2016 Dec;29(12):1379-1388

Background: In congenital adrenal hyperplasia (CAH), adjusting hydrocortisone dose during childhood avoids reduced adult height. However, there are currently no CAH-specific charts to monitor growth during treatment. Our objective was to elaborate growth reference charts and bone maturation data for CAH patients.

Methods: We conducted a retrospective observational cohort study, in 34 French CAH centers. Patients were 496 children born 1970-1991 with genetically proven 21-hydroxylase deficiency. Their growth and bone maturation data were collected until age 18 together with adult height, puberty onset, parental height, and treatment. The mean (SD) heights were modeled from birth to adulthood. The median±1 SD and ±2 SDs model-generated curves were compared with the French references. A linear model for bone maturation and a logistic regression model for the probability of short adult height were built.

Results: Growth charts were built by sex for salt wasting (SW) and simple virilizing (SV) children treated before 1 year of age. In girls and boys, growth was close to that of the general French population up to puberty onset. There was almost no pubertal spurt and the mean adult height was shorter than that of the general population in girls (-1.2 SD, 156.7 cm) and boys (-1.0 SD, 168.8 cm). Advanced bone age at 8 years had a strong impact on the risk of short adult height (OR: 4.5 per year advance).

Conclusions: The 8-year bone age is a strong predictor of adult height. It will help monitoring the growth of CAH-affected children.
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December 2016

Estimating HIV Incidence Using a Cross-Sectional Survey: Comparison of Three Approaches in a Hyperendemic Setting, Ndhiwa Subcounty, Kenya, 2012.

AIDS Res Hum Retroviruses 2017 05 13;33(5):472-481. Epub 2016 Dec 13.

1 Hospices Civils de Lyon, Service de Biostatistique , Lyon, France .

Objectives: Estimating HIV incidence is critical for identifying groups at risk for HIV infection, planning and targeting interventions, and evaluating these interventions over time. The use of reliable estimation methods for HIV incidence is thus of high importance. The aim of this study was to compare methods for estimating HIV incidence in a population-based cross-sectional survey.

Design/methods: The incidence estimation methods evaluated included assay-derived methods, a testing history-derived method, and a probability-based method applied to data from the Ndhiwa HIV Impact in Population Survey (NHIPS). Incidence rates by sex and age and cumulative incidence as a function of age were presented.

Results: HIV incidence ranged from 1.38 [95% confidence interval (CI) 0.67-2.09] to 3.30 [95% CI 2.78-3.82] per 100 person-years overall; 0.59 [95% CI 0.00-1.34] to 2.89 [95% CI 0.86-6.45] in men; and 1.62 [95% CI 0.16-6.04] to 4.03 [95% CI 3.30-4.77] per 100 person-years in women. Women had higher incidence rates than men for all methods. Incidence rates were highest among women aged 15-24 and 25-34 years and highest among men aged 25-34 years.

Conclusion: Comparison of different methods showed variations in incidence estimates, but they were in agreement to identify most-at-risk groups. The use and comparison of several distinct approaches for estimating incidence are important to provide the best-supported estimate of HIV incidence in the population.
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May 2017

Focal High Intensity Focused Ultrasound of Unilateral Localized Prostate Cancer: A Prospective Multicentric Hemiablation Study of 111 Patients.

Eur Urol 2017 02 6;71(2):267-273. Epub 2016 Oct 6.

Department of Urology and Transplantation Surgery, Edouard Herriot Hospital, Lyon, France; Department of Urology, Université de Lyon, Lyon, France; INSERM Unit 1032, LabTau, Université de Lyon, Lyon, France.

Background: Up to a third of patients with localized prostate cancer have unilateral disease that may be suitable for partial treatment with hemiablation.

Objective: To evaluate the ability of high intensity focused ultrasound (HIFU) to achieve local control of the tumor in patients with unilateral localized prostate cancer.

Design, Setting, And Participants: The French Urological Association initiated a prospective IDEAL multi-institutional study (2009-2015), to evaluate HIFU-hemiablation as a primary treatment.

Intervention: Multiparametric magnetic resonance imaging and biopsy were used for unilateral cancer diagnosis and control, and HIFU-hemiablation.

Outcome Measurements And Statistical Analysis: Primary: absence of clinically significant cancer (CSC) on control biopsy at 1 yr (CSC: Gleason score ≥ 7 or cancer core length>3mm regardless of grade or > 2 positive cores). Secondary: presence of any cancer on biopsy, biochemical response, radical treatment free survival, adverse events, continence (no pad), erectile function (International Index of Erectile Function-5 ≥ 16), and quality of life (European Organization for Research and Treatment of Cancer QLQ-C28) questionnaires.

Results And Limitations: One hundred and eleven patients were treated (mean age: 64.8 yr [standard deviation 6.2]; mean prostate-specific antigen: 6.2 ng/ml [standard deviation 2.6]; 68% low risk, 32% intermediate risk). Of the 101 patients with control biopsy, 96 (95%) and 94 (93%) had no CSC in the treated and contralateral lobes, respectively. Mean prostate-specific antigen at 2 yr was 2.3 ng/ml (standard deviation 1.7). The radical treatment-free survival rate at 2 years was 89% (radical treatments: six radical prostatectomies, three radiotherapies, and two HIFU). Adverse events were Grade 3 in 13%. At 12 mo continence and erectile functions were preserved in 97% and 78%. No significant decrease in quality of life score was observed at 12 mo. One limitation is the number of low-risk patients included in this study.

Conclusions: At 1 yr, HIFU-hemiablation was efficient with 95% absence of clinically significant cancer associated with low morbidity and preservation of quality of life. Radical treatment-free survival rate was 89% at 2 yr.

Patient Summary: This report shows that high intensity focused ultrasound half-gland treatment of unilateral prostate cancer provides promising results with high cancer control and low morbidity.
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February 2017

Effect of Cyclosporine in Nonshockable Out-of-Hospital Cardiac Arrest: The CYRUS Randomized Clinical Trial.

JAMA Cardiol 2016 08;1(5):557-65

Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 1060, Carmen, Equipe Cardioprotection, Lyon, France3Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France6Hospices Civils de Lyon, Hôpital Louis Pradel, Explo.

Importance: Experimental evidence suggests that cyclosporine prevents postcardiac arrest syndrome by attenuating the systemic ischemia reperfusion response.

Objective: To determine whether early administration of cyclosporine at the time of resuscitation in patients with out-of-hospital cardiac arrest (OHCA) would prevent multiple organ failure.

Design, Setting, And Participants: A multicenter, single-blind, randomized clinical trial was conducted from June 22, 2010, to March 13, 2013 (Cyclosporine A in Out-of-Hospital Cardiac Arrest Resuscitation [CYRUS]). Sixteen intensive care units in 7 university-affiliated hospitals and 9 general hospitals in France participated. A total of 6758 patients who experienced nonshockable OHCA (ie, asystole or pulseless electrical activity) were assessed for eligibility. Analyses were performed according to the intention-to-treat analysis.

Interventions: Patients received an intravenous bolus injection of cyclosporine, 2.5 mg/kg, at the onset of advanced cardiovascular life support (cyclosporine group) or no additional intervention (control group).

Main Outcomes And Measures: The primary end point was the Sequential Organ Failure Assessment (SOFA) score, assessed 24 hours after hospital admission, which ranges from 0 to 24 (with higher scores indicating more severe organ failure). Secondary end points included survival at 24 hours, hospital discharge, and favorable neurologic outcome at discharge.

Results: Of the 6758 patients screened, 794 were included in intention-to-treat analysis (cyclosporine, 400; control, 394). The median (interquartile range [IQR]) ages were 63.0 (54.0-71.8) years for the cyclosporine group and 66.0 (57.0-74.0) years for the control group. The cohorts included 293 men (73.3%) in the treatment group and 288 men (73.1%) in the control group. At 24 hours after hospital admission, the SOFA score was not significantly different between the cyclosporine (median, 10.0; IQR, 7.0-13.0) and the control (median, 11.0; IQR, 7.0-15.0) groups. Survival was not significantly different between the 98 (24.5%) cyclosporine vs 101 (25.6%) control patients at hospital admission (adjusted odds ratio [aOR], 0.94; 95% CI, 0.66-1.34), at 24 hours for 67 (16.8%) vs 62 (15.7%) patients (aOR, 1.08; 95% CI, 0.71-1.63), and at hospital discharge for 10 (2.5%) vs 5 (1.3%) patients (aOR, 2.00; 95% CI, 0.61-6.52). Favorable neurologic outcome at discharge was comparable between the cyclosporine and control groups: 7 (1.8%) vs 5 (1.3%) patients (aOR, 1.39; 95% CI, 0.39-4.91).

Conclusion And Relevance: In patients presenting with nonshockable cardiac rhythm after OHCA, cyclosporine does not prevent early multiple organ failure.

Trial Registration: Identifier: NCT01595958; EudraCT Identifier: 2009-015725-37.
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August 2016

Modeling and predicting the long-term effects of various strategies and objectives of varicella-zoster vaccination campaigns.

Expert Rev Vaccines 2016 07 10;15(7):927-36. Epub 2016 May 10.

a Service de Biostatistique , Hospices Civils de Lyon , Lyon , France.

Background: Susceptible, exposed, infected, and recovered (SEIR) models are increasingly developed and used, but their simplicity contrasts with the wide variety of scenarios before launching vaccination campaigns.

Methods: We investigated the effects of some model-building choices (targets, pace, coverage rate) on the results of SEIR models in the case of vaccination against varicella and herpes zoster.

Results: The analysis demonstrated the need for a progressive unvaccinated to vaccinated transition and a dynamic system-equilibrium before vaccination onset. When several doses are considered, new compartments are needed to account for vaccination histories. For varicella, the delay to reach the expected coverage rate and the pace until reaching this rate have significant impacts, especially on the short-term incidence. The impact of vaccination through herd immunity should be systematically investigated.

Conclusions: Graphs help understanding the progress of instantaneous incidence; however, tables of cumulative average incidence over decades should be preferred because of higher stability.
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July 2016

Potential impact of multiple interventions on HIV incidence in a hyperendemic region in Western Kenya: a modelling study.

BMC Infect Dis 2016 Apr 29;16:189. Epub 2016 Apr 29.

Epicentre, F-75011, Paris, France.

Background: Multiple prevention interventions, including early antiretroviral therapy initiation, may reduce HIV incidence in hyperendemic settings. Our aim was to predict the short-term impact of various single and combined interventions on HIV spreading in the adult population of Ndhiwa subcounty (Nyanza Province, Kenya).

Methods: A mathematical model was used with data on adults (15-59 years) from the Ndhiwa HIV Impact in Population Survey to compare the impacts on HIV prevalence, HIV incidence rate, and population viral load suppression of various interventions. These interventions included: improving the cascade of care (use of three guidelines), increasing voluntary medical male circumcision (VMMC), and implementing pre-exposure prophylaxis (PrEP) use among HIV-uninfected women.

Results: After four years, improving separately the cascade of care under the WHO 2013 guidelines and under the treat-all strategy would reduce the overall HIV incidence rate by 46 and 58 %, respectively, vs. the baseline rate, and by 35 and 49 %, respectively, vs. the implementation of the current Kenyan guidelines. With conservative and optimistic scenarios, VMMC and PrEP would reduce the HIV incidence rate by 15-25 % and 22-28 % vs. the baseline, respectively. Combining the WHO 2013 guidelines with VMMC would reduce the HIV incidence rate by 35-56 % and combining the treat-all strategy with VMMC would reduce it by 49-65 %. Combining the WHO 2013 guidelines, VMMC, and PrEP would reduce the HIV incidence rate by 46-67 %.

Conclusions: The impacts of the WHO 2013 guidelines and the treat-all strategy were relatively close; their implementation is desirable to reduce HIV spread. Combining several strategies is promising in adult populations of hyperendemic areas but requires regular, reliable, and costly monitoring.
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April 2016

Carotid atherosclerosis progression and cerebrovascular events in patients with diabetes.

J Diabetes Complications 2016 May-Jun;30(4):638-43. Epub 2016 Jan 29.

Department of Vascular Medicine, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre Bénite, France.

Aim: Carotid atherosclerosis progression is associated with a higher risk of cerebrovascular events but there is no specific data for diabetes. We assessed in a cohort of patients with diabetes the rate of atherosclerosis progression by Doppler ultrasonography and the association with cerebrovascular events.

Methods: We analyzed a retrospective cohort of 342 patients with a mean duration of diabetes of 13.6 ± 10.6 years. The mean delay between the first and last Doppler ultrasonography was 6.4 ± 4.6 years, with a mean of 3.4 examinations per person. Cerebrovascular events were noted.

Results: A progression of carotid atherosclerosis was observed in 20.1% of cases. No factor was significantly associated with progression. A prophylactic carotid endarterectomy was performed on 6 of the 27 patients with a stenosis ≥50%. A cerebrovascular event occurred in 1.2% of patients; none of them had carotid atherosclerosis progression.

Conclusions: Carotid atherosclerosis progression in patients with diabetes is frequent but surgical treatment and cerebrovascular events are low. The benefit of a systematic follow-up of carotid atherosclerosis seems limited.
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January 2017

Closer to 90-90-90. The cascade of care after 10 years of ART scale-up in rural Malawi: a population study.

J Int AIDS Soc 2016 15;19(1):20673. Epub 2016 Feb 15.

Epicentre, Paris, France.

Introduction: The antiretroviral therapy (ART) programme supported by Médecins Sans Frontières in the rural Malawian district of Chiradzulu was one of the first in sub-Saharan Africa to scale up ART delivery in 2002. After more than a decade of continuous involvement, we conducted a population survey to evaluate the cascade of care, including population viral load, in the district.

Methods: A cross-sectional household-based survey was conducted between February and May 2013. Using a multistage cluster sampling method, we recruited all individuals aged 15 to 59 years living in 4125 randomly selected households. Each consenting individual was interviewed and tested for HIV at home. All participants who tested positive had their CD4 count and viral load measured. The LAg-Avidity assay was used to distinguish recent from long-term infections. Viral suppression was defined as a viral load below 1000 copies/mL.

Results: Of 8271 individuals eligible for the study, 7269 agreed to participate and were tested for HIV (94.1% inclusion for women and 80.3% for men). Overall HIV prevalence and incidence were 17.0% (95% CI 16.1 to 17.9) and 0.39 new cases per 100 person-years (95% CI 0.0 to 0.77), respectively. Coverage at the other steps along the HIV care cascade was as follows: 76.7% (95% CI 74.4 to 79.1) had been previously diagnosed, 71.2% (95% CI 68.6 to 73.6) were under care and 65.8% (95% CI 62.8 to 68.2) were receiving ART. Finally, the proportion of participants who were HIV positive with a viral load ≤ 1000 copies/mL reached 61.8% (95% CI 59.0 to 64.5).

Conclusions: This study demonstrates that a high level of population viral suppression and low incidence can be achieved in high HIV prevalence and resource-limited settings.
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September 2016

Management of adolescents with very poorly controlled type 1 diabetes by nurses: a parallel group randomized controlled trial.

Trials 2015 Sep 8;16:399. Epub 2015 Sep 8.

Endocrinologie, Diabétologie, Nutrition Pédiatriques, Hôpital Femme-Mère-Enfant, Hospices Civils de Lyon, F-69677, Bron, France.

Backgrounds: Fluctuation in glycemia due to hormonal changes, growth periods, physical activity, and emotions make diabetes management difficult during adolescence. Our objective was to show that a close control of patients' self-management of diabetes by nurse-counseling could probably improve metabolic control in adolescents with type 1 diabetes.

Methods: We designed a multicenter, randomized controlled, parallel group, clinical trial. Seventy seven adolescents aged 12-17 years with A1C >8% were assigned to either an intervention group (pediatrician visit every 3 months + nurse visit and phone calls) or to the control group (pediatrician visit every 3 months). The primary outcome was the evolution of the rate of A1C during the 12 months of follow-up. Secondary outcomes include patient's acceptance of the disease (evaluated by visual analog scale), the number of hypoglycemic or ketoacidosis episodes requiring hospitalization, and evaluation of A1C rate over time in each group.

Results: Seventy-seven patients were enrolled by 10 clinical centers. Seventy (89.6%) completed the study, the evolution of A1C and participants satisfaction over the follow-up period was not significantly influenced by the nurse intervention.

Conclusion: Nurse-led intervention to improve A1C did not show a significant benefit in adolescents with type 1 diabetes because of lack of power. Only psychological management and continuous glucose monitoring have shown, so far, a slight but significant benefit on A1C. We did not show improvements in A1C control in teenagers by nurse-led intervention.

Trial Registration: Clinical registration number: NCT00308256, 28 March 2006.
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September 2015

Cascade of HIV care and population viral suppression in a high-burden region of Kenya.

AIDS 2015 Jul;29(12):1557-65

aEpicentre, Paris, France bCenters for Disease Control and Prevention, Kisumu cNational AIDS & STI Control Programme dMédecins Sans Frontières, Nairobi eCenter for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya fMédecins sans Frontières, Paris gService de biostatistique, Hospices Civils de Lyon, Lyon hUMI 233 TransVIHMI, Institut de Recherche pour le Développement, Montpellier 1 University, Montpellier, France.

Introduction: Direct measurement of antiretroviral treatment (ART) program indicators essential for evidence-based planning and evaluation - especially HIV incidence, population viral load, and ART eligibility - is rare in sub-Saharan Africa.

Design/methods: To measure key indicators in rural western Kenya, an area with high HIV burden, we conducted a population survey in September to November 2012 via multistage cluster sampling, recruiting everyone aged 15-59 years living in 3330 randomly selected households. Consenting individuals were interviewed and tested for HIV at home. Participants testing positive were assessed for CD4 cell count and viral load, and their infections classified as either recent or long term based on Limiting Antigen Avidity assays. HIV-negative participants were tested by nucleic acid amplification to detect acute infections.

Results: Of 6833 household members eligible for the study, 6076 (94.7% of all women and 81.0% of men) agreed to participate. HIV prevalence and incidence were 24.1% [95% confidence interval [CI] 23.0-25.2] and 1.9 new cases/100 person-years (95% CI 1.1-2.7), respectively. Among HIV-positive participants, 59.4% (95% CI 56.8-61.9) were previously diagnosed, 53.1% (95% CI 50.5-55.7) were receiving care, and 39.7% (95% CI 37.1-42.4) had viral load less than 1000 copies/ml. Applying 2013 WHO recommendations for ART initiation increased the proportion of ART-eligible people from 60.0% (based on national guidelines in place during the survey; 95% CI 57.3-62.7) to 82.0% (95% CI 79.5-84.5). Among HIV-positive people not receiving ART, viral load increased with decreasing CD4 cell count (500-749 vs. ≥750 cells/μl, adjusted mean difference, 0.40 log10 copies/ml, 95% CI 0.20-0.60, P < 0.01).

Conclusion: This study demonstrates how population-level data can help optimize HIV programs. Based on these results, new regional programs are prioritizing diagnosis and expanding ART eligibility, key steps to reach undetectable viral load.
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July 2015

Estimation and Short-Term Prediction of the Course of the HIV Epidemic Using Demographic and Health Survey Methodology-Like Data.

PLoS One 2015 19;10(6):e0130387. Epub 2015 Jun 19.

Service de Biostatistique, Hospices Civils de Lyon, F-69003, Lyon, France; Université de Lyon, F-69000, Lyon, France; Université Lyon 1, F-69100, Villeurbanne, France; CNRS UMR 5558, Equipe Biostatistique-Santé, Laboratoire de Biométrie et Biologie Evolutive, F-69100, Villeurbanne, France.

Background: Mathematical models have played important roles in the understanding of epidemics and in the study of the impacts of various behavioral or medical measures. However, modeling accurately the future spread of an epidemic requires context-specific parameters that are difficult to estimate because of lack of data. Our objective is to propose a methodology to estimate context-specific parameters using Demographic and Health Survey (DHS)-like data that can be used in mathematical modeling of short-term HIV spreading.

Methods And Findings: The model splits the population according to sex, age, HIV status, and antiretroviral treatment status. To estimate context-specific parameters, we used individuals' histories included in DHS-like data and a statistical analysis that used decomposition of the Poisson likelihood. To predict the course of the HIV epidemic, sex- and age-specific differential equations were used. This approach was applied to recent data from Kenya. The approach allowed the estimation of several key epidemiological parameters. Women had a higher infection rate than men and the highest infection rate in the youngest age groups (15-24 and 25-34 years) whereas men had the highest infection rate in age group 25-34 years. The immunosuppression rates were similar between age groups. The treatment rate was the highest in age group 35-59 years in both sexes. The results showed that, within the 15-24 year age group, increasing male circumcision coverage and antiretroviral therapy coverage at CD4 ≤ 350/mm3 over the current 70% could have short-term impacts.

Conclusions: The study succeeded in estimating the model parameters using DHS-like data rather than literature data. The analysis provides a framework for using the same data for estimation and prediction, which can improve the validity of context-specific predictions and help designing HIV prevention campaigns.
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April 2016

Spatial distribution of Toxoplasma gondii oocysts in soil in a rural area: Influence of cats and land use.

Vet Parasitol 2014 Oct 20;205(3-4):629-37. Epub 2014 Aug 20.

Université de Reims Champagne-Ardenne, Laboratoire de Parasitologie-Mycologie, EA 3800, UFR de Médecine, SFR Cap Santé FED 4231, 51 rue Cognacq-Jay, F-51096 Reims, France.

Toxoplasma gondii is the protozoan parasite responsible for toxoplasmosis, one of the most prevalent zoonoses worldwide. T. gondii infects humans through the ingestion of meat containing bradyzoites or through soil, food or water contaminated with oocysts. Soil contamination with oocysts is increasingly recognized as a major source of infection for humans, but has rarely been quantified directly. In this study, we investigated the spatial pattern of soil contamination with T. gondii over an area of 2.25 km(2) in a rural area of eastern France. The frequency and spatial distribution of T. gondii in soil was analyzed in relation with the factors that could influence the pattern of contamination: cats' frequency and spatial distribution and land use. According to a stratified random sampling Scheme 243 soil samples were collected. The detection of T. gondii oocysts was performed using a recent sensitive method based on concentration and quantitative PCR. Sensitivity was improved by analyzing four replicates at each sampling point. T. gondii was detected in 29.2% of samples. Soil contamination decreased with increasing distance from the core areas of cat home ranges (households and farms). However, it remained high at the periphery of the study site, beyond the boundaries of the largest cat home ranges, and was not related to land use. This pattern of contamination strongly supports the role of inhabited areas which concentrate cat populations as sources of risk for oocyst-induced infection for both humans and animals. Moreover, soil contamination was not restricted to areas of high cat density suggesting a large spatial scale of environmental contamination, which could result from T. gondii oocysts dissemination through rain washing or other mechanisms.
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October 2014

Specific vs general cognitive remediation for executive functioning in schizophrenia: a multicenter randomized trial.

Schizophr Res 2013 Jun 9;147(1):68-74. Epub 2013 Apr 9.

Departement de psychiatrie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

Background: This study assesses the benefits of an individualized therapy (RECOS program) compared with the more general cognitive remediation therapy (CRT).

Methods: 138 participants took part with 65 randomized to CRT and 73 to RECOS. In the RECOS group, participants were directed towards one of five training modules (verbal memory, visuo-spatial memory and attention, working memory, selective attention or reasoning) corresponding to their key cognitive concern whereas the CRT group received a standard program. The main outcome was the total score on BADS (Behavioural Assessment of Dysexecutive Syndrome) and the secondary outcomes were: cognition (executive functions; selective attention; visuospatial memory and attention; verbal memory; working memory) and clinical measures (symptoms; insight; neurocognitive complaints; self-esteem). All outcomes were assessed at baseline (T1), week 12 (posttherapy, T2), and follow-up (week 36, i.e., 6months posttherapy, T3).

Results: No difference was shown for the main outcome. A significant improvement was found for BADS' profile score for RECOS at T2 and T3, and for CRT at T3. Change in BADS in the RECOS and CRT arms were not significantly different between T1 and T2 (+0.86, p=0.108), or between T1 and T3 (+0.36, p=0.540). Significant improvements were found in several secondary outcomes including cognition (executive functions, selective attention, verbal memory, and visuospatial abilities) and clinician measures (symptoms and awareness to be hampered by cognitive deficits in everyday) in both treatment arms following treatment. Self-esteem improved only in RECOS arm at T3, and working memory improved only in CRT arm at T2 and T3, but there were no differences in changes between arms.

Conclusions: RECOS (specific remediation) and CRT (general remediation) globally showed similar efficacy in the present trial.
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June 2013

Is it possible to model the risk of malignancy of focal abnormalities found at prostate multiparametric MRI?

Eur Radiol 2012 May 7;22(5):1149-57. Epub 2012 Jan 7.

Hospices Civils de Lyon, Department of Urinary and Vascular Radiology, Hôpital Edouard Herriot, Lyon, France.

Objective: To evaluate whether focal abnormalities (FAs) depicted by prostate MRI could be characterised using simple semiological features.

Methods: 134 patients who underwent T2-weighted, diffusion-weighted and dynamic contrast-enhanced MRI at 1.5 T before prostate biopsy were prospectively included. FAs visible at MRI were characterised by their shape, the degree of signal abnormality (0 = normal to 3 = markedly abnormal) on individual MR sequences, and a subjective score (SS(1) = probably benign to SS(3) = probably malignant). FAs were then biopsied under US guidance.

Results: 56/233 FAs were positive at biopsy. The subjective score significantly predicted biopsy results (P < 0.01). As compared to SS(1) FAs, the odds ratios (OR) of malignancy of SS(2) and SS(3) FAs were 9.9 (1.8-55.9) and 163.8 (11.5-2331). Unlike FAs' shape, a simple combination of MR signal abnormalities (into "low-risk", "intermediate" and "high-risk" groups) significantly predicted biopsy results (P < 0.008). As compared to "low risk" FAs, the OR of malignancy of "intermediate" and "high-risk" FAs were 4.5 (1.1-18.4) and 52.7 (6.8-407) in the overall population and 5.4 (1.1-27.2) and 118.2 (6.1-2301) in PZ.

Conclusions: A simple combination of signal abnormalities of individual MR sequences can significantly stratify the risk of malignancy of FAs, holding promise of a more standardised interpretation of MRI by readers with varying experience.

Key Points: • Using multiparameter(mp)-MRI, experienced uroradiologists can stratify the malignancy risk of prostatic lesions • The shape of prostatic focal abnormalities in the peripheral zone does not help predicting malignancy. • A simple combination of findings at mp-MRI can help less-experienced radiologists.
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May 2012

DNA double-strand breaks induced by mammographic screening procedures in human mammary epithelial cells.

Int J Radiat Biol 2011 Nov 19;87(11):1103-12. Epub 2011 Sep 19.

Hospices Civils de Lyon, Service de Radiologie, Centre Hospitalier Lyon Sud, Pierre-Bénite, France.

Purpose: To assess in vitro mammographic radiation-induced DNA damage in mammary epithelial cells from 30 patients with low (LR) or high (HR) family risk of breast cancer.

Materials And Methods: Spontaneous and radiation-induced DNA double-strand breaks (DSB) were quantified by using immunofluorescence of the phosphorylated H2AX histone (γH2AX) in different conditions of mammography irradiation (2, 4, 2 + 2 mGy).

Results: HR patients showed significantly more spontaneous γH2AX foci than LR patients (p = 0.014). A significant dose-effect was observed, with an exacerbation in HR patients (p = 0.01). The dose repetition (2 + 2 mGy) provided more induced and more unrepaired DSB than 2 mGy and 4 mGy, and was exacerbated in HR (p = 0.006).

Conclusions: This study highlights the existence of DSB induced by mammography and revealed by γH2AX assay with two major radiobiological effects occurring: A low-dose effect, and a LOw and Repeated Dose (LORD) effect. All these effects were exacerbated in HR patients. These findings may lead us to re-evaluate the number of views performed in screening using a single view (oblique) in women whose mammographic benefit has not properly been proved such as HR patients.
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November 2011

Methodology of the sensitivity analysis used for modeling an infectious disease.

Vaccine 2010 Nov 13;28(51):8132-40. Epub 2010 Oct 13.

Hospices Civils de Lyon, Service de Biostatistique, F-69003 Lyon, France. claire

Mathematical models may be used to help clarify dynamics of several infectious diseases. Because of the complexity of some models and the high degree of uncertainty in estimating many parameters, the present study proposes a rigorous framework for sensitivity analyses of mathematical models using as example a model to assess varicella and herpes zoster incidence. Its main steps are to assess the uncertainty of the factors to be studied, to evaluate qualitatively and quantitatively the impacts of these factors on model results, and to conduct an univariate and multivariate sensitivity analysis. The application of this technique may have considerable utility in the analysis of a wide variety of complex biological and epidemiological models.
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November 2010

Relationship between haemagglutination-inhibiting antibody titres and clinical protection against influenza: development and application of a bayesian random-effects model.

BMC Med Res Methodol 2010 Mar 8;10:18. Epub 2010 Mar 8.

Sanofi pasteur, 2 avenue Pont Pasteur F-69367 Lyon cedex 07 France.

Background: Antibodies directed against haemagglutinin, measured by the haemagglutination inhibition (HI) assay are essential to protective immunity against influenza infection. An HI titre of 1:40 is generally accepted to correspond to a 50% reduction in the risk of contracting influenza in a susceptible population, but limited attempts have been made to further quantify the association between HI titre and protective efficacy.

Methods: We present a model, using a meta-analytical approach, that estimates the level of clinical protection against influenza at any HI titre level. Source data were derived from a systematic literature review that identified 15 studies, representing a total of 5899 adult subjects and 1304 influenza cases with interval-censored information on HI titre. The parameters of the relationship between HI titre and clinical protection were estimated using Bayesian inference with a consideration of random effects and censorship in the available information.

Results: A significant and positive relationship between HI titre and clinical protection against influenza was observed in all tested models. This relationship was found to be similar irrespective of the type of viral strain (A or B) and the vaccination status of the individuals.

Conclusion: Although limitations in the data used should not be overlooked, the relationship derived in this analysis provides a means to predict the efficacy of inactivated influenza vaccines when only immunogenicity data are available. This relationship can also be useful for comparing the efficacy of different influenza vaccines based on their immunological profile.
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March 2010

Interleukin 17 acts in synergy with B cell-activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus.

Nat Immunol 2009 Jul 31;10(7):778-85. Epub 2009 May 31.

Université de Lyon, Institut Fédératif de Recherche 128, Lyon, France.

Studies have suggested involvement of interleukin 17 (IL-17) in autoimmune diseases, although its effect on B cell biology has not been clearly established. Here we demonstrate that IL-17 alone or in combination with B cell-activating factor controlled the survival and proliferation of human B cells and their differentiation into immunoglobulin-secreting cells. This effect was mediated mainly through the nuclear factor-kappaB-regulated transcription factor Twist-1. In support of the relevance of our observations and the potential involvement of IL-17 in B cell biology, we found that the serum of patients with systemic lupus erythematosus had higher concentrations of IL-17 than did the serum of healthy people and that IL-17 abundance correlated with the disease severity of systemic lupus erythematosus.
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July 2009