Publications by authors named "Elsa Parot-Schinkel"

15 Publications

  • Page 1 of 1

Delivery Mode After Manual Rotation of Occiput Posterior Fetal Positions: A Randomized Controlled Trial.

Obstet Gynecol 2021 06;137(6):999-1006

Department of Obstetrics, the Department of Biostatistics and Methodology, the Department of Neonatal Medicine, the Department of Reproductive Medicine, Angers University Hospital, and the MITOVASC Institute, CNRS 6015, INSERM U1083, Angers University, Angers, and CESP-INSERM, U1018, Team 7, Reproductive and Sexual Health, Paris-Sud University, Kremlin-Bicêtre, France.

Objective: To evaluate whether manual rotation of fetuses in occiput posterior positions at full dilation increases the rate of spontaneous vaginal delivery.

Methods: In an open, single-center, randomized controlled trial, patients with a term, singleton gestation, epidural analgesia, and ultrasonogram-confirmed occiput posterior position at the start of the second stage of labor were randomized to either manual rotation or expectant management. Our primary endpoint was the rate of spontaneous vaginal delivery. Secondary endpoints were operative vaginal delivery, cesarean delivery, and maternal and neonatal morbidity. Analyses were based on an intention-to-treat method. A sample size of 107 patients per group (n=214) was planned to detect a 20% increase in the percent of patients with a spontaneous vaginal delivery (assuming 60% without manual rotation vs 80% with manual rotation) with 90% power and alpha of 0.05.

Results: Between February 2017 and January 2020, 236 patients were randomized to either manual rotation (n=117) or expectant management (n=119). The success rate of the manual rotation maneuver, defined by conversion to an anterior position as confirmed by ultrasonogram, was 68%. The rate of the primary endpoint did not differ between the groups (58.1% in manual rotation group vs 59.7% in expectant management group (risk difference -1.6; 95% CI -14.1 to 11.0). Manual rotation did not decrease the rate of operative vaginal delivery (29.9% in manual rotation group vs 33.6% in expectant management group (risk difference -3.7; 95% CI -16.6 to 8.2) nor the rate of cesarean delivery (12.0% in manual rotation group vs 6.7% in expectant management group (risk difference 5.3; 95% CI -2.2 to 12.6). Maternal and neonatal morbidity was also similar across the two groups.

Conclusion: Manual rotation of occiput posterior positions at the start of second stage of labor does not increase the rate of vaginal delivery without instrumental assistance.

Clinical Trial Registration: ClinicalTrials.gov, NCT03009435.
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http://dx.doi.org/10.1097/AOG.0000000000004386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132900PMC
June 2021

Hydroxychloroquine in mild-to-moderate coronavirus disease 2019: a placebo-controlled double blind trial.

Clin Microbiol Infect 2021 Apr 1. Epub 2021 Apr 1.

Département de Médecine Intensive-Réanimation, CHU d'Angers, Université d'Angers, Angers, France.

Objectives: To determine whether hydroxychloroquine decreases the risk of adverse outcome in patients with mild to moderate coronavirus disease 2019 (COVID-19) at high risk of worsening.

Methods: We conducted a multicentre randomized double-blind placebo-controlled trial evaluating hydroxychloroquine in COVID-19 patients with at least one of the following risk factors for worsening: need for supplemental oxygen, age ≥75 years, age between 60 and 74 years and presence of at least one co-morbidity. Severely ill patients requiring oxygen therapy >3 L/min or intensive care were excluded. Eligible patients were randomized in a 1:1 ratio to receive either 800 mg hydroxychloroquine on day 0 followed by 400 mg per day for 8 days or a placebo. The primary end point was a composite of death or start of invasive mechanical ventilation within 14 days following randomization. Secondary end points included mortality and clinical evolution at days 14 and 28, and viral shedding at days 5 and 10.

Results: The trial was stopped after 250 patients were included because of a slowing down of the pandemic in France. The intention-to-treat population comprised 123 and 124 patients in the placebo and hydroxychloroquine groups, respectively. The median age was 77 years (interquartile range 58-86 years) and 151/250 (60.4%) patients required oxygen therapy. The primary end point occurred in 9/124 (7.3%) patients in the hydroxychloroquine group and 8/123 (6.5%) patients in the placebo group (relative risk 1.12; 95% CI 0.45-2.80). The rates of positive SARS-CoV-2 RT-PCR tests at days 5 and 10 were 72.8% (75/103) and 57.1% (52/91) in the hydroxychloroquine group, versus 73.0% (73/100) and 56.6% (47/83) in the placebo group, respectively. No difference was observed between the two groups in any of the other secondary end points.

Conclusion: In this underpowered trial involving mainly older patients with mild to moderate COVID-19, patients treated with hydroxychloroquine did not experience better clinical or virological outcomes than those receiving the placebo.

Trial Registration: ClinicalTrials.gov Identifier: NCT04325893 (https://clinicaltrials.gov/ct2/show/NCT04325893).
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http://dx.doi.org/10.1016/j.cmi.2021.03.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015393PMC
April 2021

Study protocol for a multicentre, 2×2 factorial, randomised, controlled trial evaluating the interest of intravenous iron and tranexamic acid to reduce blood transfusion in hip fracture patients (the HiFIT study).

BMJ Open 2021 01 17;11(1):e040273. Epub 2021 Jan 17.

Département Anesthésie Réanimation, Centre Hospitalier Universitaire d'Angers, Angers, France.

Introduction: Blood transfusion and anaemia are frequent and are associated with poor outcomes in patients with hip fracture (HF). We hypothesised that preoperative intravenous iron and tranexamic acid (TXA) may reduce the transfusion rate in these patients.

Methods And Analysis: The HiFIT study is a multicentre, 2×2 factorial, randomised, double-blinded, controlled trial evaluating the effect of iron isomaltoside (IIM) (20 mg/kg) vs placebo and of TXA (intravenously at inclusion and topically during surgery) versus placebo on transfusion rate during hospitalisation, in patients undergoing emergency surgery for HF and having a preoperative haemoglobin between 95 and 130 g/L. 780 patients are expected. The primary endpoint is the proportion of patients receiving an allogenic blood transfusion of packed red blood cells from the day of surgery until hospital discharge (or until D30 if patient is still hospitalised). Enrolment started on March 2017 in 11 French hospitals. The study was stopped between July 2017 and August 2018 (because of investigation of serious AEs with IIM in Spain) and slowed down since March 2020 (COVID-19 crisis). The expected date of final follow-up is May 2022. Analyses of the intent-to-treat and per-protocol populations are planned.

Ethics And Dissemination: The HiFIT trial protocol has been approved by the Ethics Committee of Comité de Protection des Personnes Ouest II and the French authorities (ANSM). It will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals. The HiFIT trial will be the largest study evaluating iron and TXA in patients with HF.

Trial Registration Number: clinicalTrials.gov identifier: NCT02972294; EudraCT Number 2016-003087-40.
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http://dx.doi.org/10.1136/bmjopen-2020-040273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813351PMC
January 2021

COvid-19 and high-dose VITamin D supplementation TRIAL in high-risk older patients (COVIT-TRIAL): study protocol for a randomized controlled trial.

Trials 2020 Dec 28;21(1):1031. Epub 2020 Dec 28.

Delegation for clinical research and innovation, Angers University Hospital, Angers, France.

Background: With the lack of effective therapy, chemoprevention, and vaccination against SARS-CoV-2, focusing on the immediate repurposing of existing drugs gives hope of curbing the COVID-19 pandemic. A recent unbiased genomics-guided tracing of the SARS-CoV-2 targets in human cells identified vitamin D among the three top-scoring molecules manifesting potential infection mitigation patterns. Growing pre-clinical and epidemiological observational data support this assumption. We hypothesized that vitamin D supplementation may improve the prognosis of COVID-19. The aim of this trial is to compare the effect of a single oral high dose of cholecalciferol versus a single oral standard dose on all-cause 14-day mortality rate in COVID-19 older adults at higher risk of worsening.

Methods: The COVIT-TRIAL study is an open-label, multicenter, randomized controlled superiority trial. Patients aged ≥ 65 years with COVID-19 (diagnosed within the preceding 3 days with RT-PCR and/or chest CT scan) and at least one worsening risk factor at the time of inclusion (i.e., age ≥ 75 years, or SpO2 ≤ 94% in room air, or PaO2/FiO2 ≤ 300 mmHg), having no contraindications to vitamin D supplementation, and having received no vitamin D supplementation > 800 IU/day during the preceding month are recruited. Participants are randomized either to high-dose cholecalciferol (two 200,000 IU drinking vials at once on the day of inclusion) or to standard-dose cholecalciferol (one 50,000 IU drinking vial on the day of inclusion). Two hundred sixty participants are recruited and followed up for 28 days. The primary outcome measure is all-cause mortality within 14 days of inclusion. Secondary outcomes are the score changes on the World Health Organization Ordinal Scale for Clinical Improvement (OSCI) scale for COVID-19, and the between-group comparison of safety. These outcomes are assessed at baseline, day 14, and day 28, together with the serum concentrations of 25(OH)D, creatinine, calcium, and albumin at baseline and day 7.

Discussion: COVIT-TRIAL is to our knowledge the first randomized controlled trial testing the effect of vitamin D supplementation on the prognosis of COVID-19 in high-risk older patients. High-dose vitamin D supplementation may be an effective, well-tolerated, and easily and immediately accessible treatment for COVID-19, the incidence of which increases dramatically and for which there are currently no scientifically validated treatments.

Trial Registration: ClinicalTrials.gov NCT04344041 . Registered on 14 April 2020 TRIAL STATUS: Recruiting. Recruitment is expected to be completed in April 2021.
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http://dx.doi.org/10.1186/s13063-020-04928-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768266PMC
December 2020

Physical activity prescription for general practice patients with cardiovascular risk factors-the PEPPER randomised controlled trial protocol.

BMC Public Health 2019 Jun 3;19(1):688. Epub 2019 Jun 3.

Faculté de Médecine d'Angers, Angers, France.

Background: The health benefits of physical exercise have been shown to be important in the prevention of cardiovascular diseases in patients with hypertension, dyslipidaemia or diabetes. However, few strategies have demonstrated efficacy and practicality in the promotion of physical exercise among this group of patients in general practice.

Methods: The PEPPER clinical study is a randomised controlled trial to evaluate the efficacy over a period of 12 months, in terms of physical activity level, of an intervention based on structured information delivery, a personalised written physical activity prescription in number of steps per day, a pedometer and a pedometer logbook, in 35 to 74-year-old patients with cardiovascular risk factors. 140 patients will be recruited in 15 GP practices and randomised in the intervention group or in the control group where patients will receive verbal advice of physical exercise. The primary outcome is the change at three months in total energy expenditure measured by an accelerometer over a 7-day period. Secondary outcomes include changes at 3 and 12 months in physical activity levels (accelerometer and International Physical Activity Questionnaire), quality of life (SF-36), blood pressure, weight, waist circumference, perceived obstacles to physical activity and patient compliance with the recommended strategy. Both groups will be compared using mixed models.

Discussion: The results are expected at the end of 2019. If the intervention proves effective in durably increasing the level of physical activity, this strategy could be tested in a larger trial to examine its impact on cardiovascular diseases.

Trial Registration: US National Institutes of Health Clinical Trials Registry NCT02317003 , December 15, 2014.
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http://dx.doi.org/10.1186/s12889-019-7048-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547598PMC
June 2019

ConFIRM trial - conversion of in vitro fertilization cycles to intrauterine inseminations in patients with a poor ovarian response to stimulation: a protocol for a multicentric, prospective randomized trial.

Trials 2018 Oct 17;19(1):565. Epub 2018 Oct 17.

Department of Reproductive Medicine, Angers University Hospital, 4 rue Larrey, 49000, Angers, France.

Background: To date, there is no consensus on the ideal management strategy of patients with poor ovarian response (POR) to controlled ovarian stimulation (COS) for in vitro fertilization (IVF). Currently, these patients are given the choice of: (1) canceling the cycle; (2) proceeding with COS regardless of the poor response, and performing the oocyte retrieval and transfer of embryos when available; or (3) conversion to an intrauterine insemination (IUI). When the decision to proceed with the COS cycle is taken, it is not clear whether IVF or conversion to IUI is the best choice. If live birth rates were comparable between the two strategies, conversion to IUI would be the better option for poor responders, since it is less invasive and is associated with a lower cost.

Methods: We designed a non-inferiority, multicentric, randomized controlled trial that will be conducted in 18 French Reproductive Medicine centers. We defined POR as the presence of only two or four mature follicles ≥ 14 mm on ovulation trigger day. Patients with POR will be randomized into two parallel arms: "IVF" and "conversion to IUI." Our main objective is to compare the efficiency of IVF and conversion to IUI in patients with POR to COS. The primary outcome is the live birth rate, defined as the birth of a living infant after 22 weeks' gestational age, or weighing ≥ 500 g. One of the secondary objectives is to compare the cost-efficiency of both strategies at 12 months. We will need to include 940 patients (470 in each arm), and the duration of the inclusion period is estimated to be 36 months.

Discussion: This is the first randomized controlled trial to compare the outcomes of IVF and embryo transfer to conversion to IUI in patients with POR to COS. If our study shows that conversion to IUI is non-inferior to IVF in terms of clinical efficiency and live birth rate, it would confirm IUI as a better alternative for patients, both individually (less invasive and more patient-friendly) and collectively (lower cost).

Trials Registration: ClinicalTrials.gov, ID: NCT03362489 . Registered on January 10th, 2018.
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http://dx.doi.org/10.1186/s13063-018-2936-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192099PMC
October 2018

High-Fidelity Simulation Nurse Training Reduces Unplanned Interruption of Continuous Renal Replacement Therapy Sessions in Critically Ill Patients: The SimHeR Randomized Controlled Trial.

Anesth Analg 2019 07;129(1):121-128

From the Département d'Anesthésie-Réanimation, L'UBL, Université d'Angers, CHU d'Angers, Angers, France.

Background: Although continuous renal replacement therapy (CRRT) is common, unplanned interruptions (UI) often limit its usefulness. In many units, nurses are responsible for CRRT management. We hypothesized that a nurse training program based on high-fidelity simulation would reduce the rate of interrupted sessions.

Methods: We performed a 2-phase (training and evaluation), randomized, single-center, open study: During the training phase, intensive care unit nurses underwent a 6-hour training program and were randomized to receive (intervention) or not (control) an additional high-fidelity simulation training (6 hours). During the evaluation phase, management of CRRT sessions was randomized to either intervention or control nurses. Sessions were defined as UI if they were interrupted and the interruption was not prescribed in writing more than 3 hours before.

Results: Study nurses had experience with hemodialysis, but no experience with CRRT before training. Intervention nurses had higher scores than control nurses on the knowledge tests (grade, median [Q1-Q3], 14 [10.5-15] vs 11 [10-12]/20; P = .044). During a 13-month period, 106 sessions were randomized (n = 53/group) among 50 patients (mean age 70 ± 13 years, mean simplified acute physiology II score 69 [54-96]). Twenty-one sessions were not analyzed (4 were not performed and 17 patients died during sessions). Among the 42 intervention and 43 control sessions analyzed, 25 (59%) and 38 (88%) were labeled as UI (relative risk [95% CI], 0.67 [0.51-0.88]; P = .002). Intervention nurses required help significantly less frequently (0 [0-1] vs 3 [1-4] times/session; P < .0001). The 2 factors associated with UI in multilevel mixed-effects logistic regression were Sequential Organ Failure Assessment score (odds ratio [95% CI], 0.81 [0.65-99]; P = .047) and the intervention group (odds ratio, 0.19 [0.05-0.73]; P = .015).

Conclusions: High-fidelity simulation nurse training reduced the rate of UI of CRRT sessions and the need for nurses to request assistance. This intervention may be particularly useful in the context of frequent nursing staff turnover.
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http://dx.doi.org/10.1213/ANE.0000000000003581DOI Listing
July 2019

Personal, biomechanical, organizational and psychosocial risk factors for neck disorders in a working population.

J Occup Health 2014 19;56(2):134-40. Epub 2014 Feb 19.

LUNAM University, Laboratory of Ergonomics and Epidemiology in Occupational health, (LEEST), University of Angers, Faculty of Medicine.

Objectives: The aim of the study was to assess both personal and occupational risk factors for non-specific neck disorder (ND) in a representative working population characterized by various levels of exposure to work-related constraints. ND during the preceding 7 days was assessed in 3,710 workers surveyed by 83 occupational physicians between 2002 and 2005. Personal risk factors and work exposure were assessed by a standardized examination and a self-administered questionnaire. Associations between ND and personal and occupational factors were analyzed using logistic regression modeling separately in men and in women.

Results: The personal risk factors for ND were age (OR for 1-year increment 1.02, 95% CI 1.01 to 1.03 in men and 1.03 [1.01-1.04] in women) and previous history of arthritis disease (OR 2.39 [1.17-4.91] in men and 3.95 [1.92-8.12] in women). The risk of ND increased with previous history or upper limb musculoskeletal disorders in men (OR 1.58 [1.17-2.13]) and decreased with BMI in women (OR for 1-kg/m(2) increment 0.96, [0.93-0.99]). The work-related risk factors of ND were sustained or repeated arm abduction (OR 2.08 [1.35-3.21] in men and 2.22 [1.27-3.86] in women) and neck flexion (OR 1.64 [1.26-2.12] in women). Work pace dependent on customers (OR 1.42 [1.10-1.83]) and psychological demand of the task (OR 1.49 [1.15-1.92]) increased the risk of ND in men. Work pace dependent on quantified targets (OR 1.37 [1.05-1.79]) and low supervisor support (OR 1.68 [1.30-2.17]) increased the risk of ND in women. This study highlighted the multifactorial nature of ND.
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http://dx.doi.org/10.1539/joh.13-0186-oaDOI Listing
June 2015

Biomechanical constraints remain major risk factors for low back pain. Results from a prospective cohort study in French male employees.

Spine J 2015 Apr 12;15(4):559-69. Epub 2013 Jul 12.

Laboratory of Ergonomics and Epidemiology in Occupational Health, Faculty of Medicine, University of Angers, Rue Haute de Reculée, 49045 Angers Cedex 01, France; Department of Occupational Health, Faculty of Medicine, University Hospital of Angers, 4, rue Larrey, 49933 Angers Cédex, France.

Background Context: Low back pain (LBP) is a major public health problem, with a considerable impact on workers.

Purpose: To model the risk of LBP in the male general working population.

Study Design/setting: Repeated cross-sectional surveys in a wide occupational setting.

Patient Sample: A random sample of 2,161 men working in various occupations in a French region participated in a first survey in 2002, and 1,313 of these (60.8%) participated in a second survey in 2007.

Outcome Measure: The self-reported prevalence of LBP during the previous week in the second survey.

Methods: Twenty-one biomechanical, organizational, psychosocial, and individual factors were assessed in the first survey. The association between these potential risk factors and the prevalence of later LBP (in the second survey) was studied, using multistep logistic regression models.

Results: Three hundred ninety-four men reported LBP in the second survey (prevalence 30.0%). The final multivariate model highlighted four risk factors: frequent bending (odds ratio [OR], 1.45, 95% confidence interval [CI], 1.07-1.97 for bending forward only; and OR, 2.13, 95% CI, 1.52-3.00 for bending both forward and sideways), driving industrial vehicles (OR, 1.35; 95% CI, 1.00-1.81), working more hours than officially planned (OR, 1.38; 95% CI, 1.05-1.81), and reported low support from supervisors (OR, 1.35; 95% CI, 1.02-1.79).

Conclusions: These results emphasize that biomechanical factors remain worth considering, even when psychosocial factors are taken into account, and provide a significant contribution to preventive strategies.
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http://dx.doi.org/10.1016/j.spinee.2013.05.040DOI Listing
April 2015

Prevalence of multisite musculoskeletal symptoms: a French cross-sectional working population-based study.

BMC Musculoskelet Disord 2012 Jul 20;13:122. Epub 2012 Jul 20.

LUNAM Université, Université d'Angers, Laboratoire d'ergonomie et d'épidémiologie en santé au travail (LEEST), 49045, Angers, France.

Background: The musculoskeletal disorders in working population represent one of the most worrying work-related health issues at the present time and although the very great majority of available data on the subject focus on musculoskeletal disorders defined by anatomical site, a growing number of studies indicate the low prevalence of disorders strictly confined to a specific anatomical site. The objective of this study was to describe the prevalence and characteristics of multisite musculoskeletal symptoms (multisite MS) in a large French working population.

Methods: This study was performed on surveillance data of the cross-sectional survey (2002-2005) conducted by a network of occupational physicians in the working population of the Loire Valley region (from 20 to 59 years old). Data concerning MS were collected in the waiting room of the occupational physicians by means of the self-administrated standardized NORDIC questionnaire.

Results: The study population comprised 3,710 workers (2,162 men (58%) and 1,548 women (42%)) with a mean age of 38.4 years (standard deviation: 10.4 years). The prevalence of MS during the past 12 months was 83.8% with 95% confidence interval of [82.8-85.3] for men and 83.9% [82.0-85.7] for women. The prevalence of subacute MS (lasting at least 30 days) over the past 12 months was 32.8% [30.9-34.8] for men and 37.3% [34.9-39.7] for women. Two-thirds of workers reported MS in more than one anatomical site and about 20% reported MS lasting at least 30 days in more than one anatomical site. The anatomical sites most frequently associated with other MS were the upper back, hip, elbow and neck. The majority of these multisite MS were widespread, involving at least two of the three anatomical regions (upper limb, axial region and lower limb).

Conclusions: The frequency and extent of multisite MS reported by workers are considerable. Further research must be conducted in this field in order to provide a better understanding of the characteristics and determinants of these multisite MS.
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http://dx.doi.org/10.1186/1471-2474-13-122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3495201PMC
July 2012

Factors affecting return to work after carpal tunnel syndrome surgery in a large French cohort.

Arch Phys Med Rehabil 2011 Nov;92(11):1863-9

Laboratory of Ergonomics and Epidemiology in Occupational Health, University of Angers, France.

Objective: To evaluate occupational outcomes after surgical release of the median nerve in carpal tunnel syndrome (CTS).

Design: Retrospective study 12 to 24 months after surgery.

Setting: Hand centers (N=3) in 2 different areas.

Participants: Patients who had undergone surgical release of the median nerve in 2002 to 2003.

Interventions: Not applicable.

Main Outcome Measure: Duration of sick leave after surgery and associated factors were analyzed by using bivariate (log rank) and multivariate analyses of survival (Cox model).

Results: Questionnaires mailed in 2004 regarding medical condition (history and surgery), employment (occupational category codes in 1 digit), and compensation were returned (N=1248; 62%), with 253 men and 682 women stating they were employed at the time of surgery (N=935). Most were working at the time of the study (n=851; 91.0%). Median duration of sick leave before returning to work was 60 days. The main factors associated with adverse occupational outcome (long duration of sick leave) were simultaneous intervention for another upper-extremity musculoskeletal disorder, belief (by the patient) in an occupational cause, and "blue-collar worker" occupational category (the strongest determinant).

Conclusion: This study emphasizes the multifactorial nature of the occupational outcome of CTS after surgery, including occupational category. The probability of return to work for each risk factor provides a fair description of prognosis for physicians and patients.
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http://dx.doi.org/10.1016/j.apmr.2011.06.001DOI Listing
November 2011

Alzheimer's disease--input of vitamin D with mEmantine assay (AD-IDEA trial): study protocol for a randomized controlled trial.

Trials 2011 Oct 20;12:230. Epub 2011 Oct 20.

Department of Neuroscience, Angers University Hospital, France.

Background: Current treatments for Alzheimer's disease and related disorders (ADRD) are symptomatic and can only temporarily slow down ADRD. Future possibilities of care rely on multi-target drugs therapies that address simultaneously several pathophysiological processes leading to neurodegeneration. We hypothesized that the combination of memantine with vitamin D could be neuroprotective in ADRD, thereby limiting neuronal loss and cognitive decline. The aim of this trial is to compare the effect after 24 weeks of the oral intake of vitamin D3 (cholecalciferol) with the effect of a placebo on the change of cognitive performance in patients suffering from moderate ADRD and receiving memantine.

Methods: The AD-IDEA Trial is a unicentre, double-blind, randomized, placebo-controlled, intent-to-treat, superiority trial. Patients aged 60 years and older presenting with moderate ADRD (i.e., Mini-Mental State Examination [MMSE] score between 10-20), hypovitaminosis D (i.e., serum 25-hydroxyvitamin D [25OHD] < 30 ng/mL), normocalcemia (i.e., serum calcium < 2.65 mmol/L) and receiving no antidementia treatment at time of inclusion are being recruited. All participants receive memantine 20 mg once daily -titrated in 5 mg increments over 4 weeks- and each one is randomized to one of the two treatment options: either cholecalciferol (one 100,000 IU drinking vial every 4 weeks) or placebo (administered at the same pace). One hundred and twenty participants are being recruited and treatment continues for 24 weeks. Primary outcome measure is change in cognitive performance using Alzheimer's Disease Assessment Scale-cognition score. Secondary outcomes are changes in other cognitive scores (MMSE, Frontal Assessment Battery, Trail Making Test parts A and B), change in functional performance (Activities of Daily Living scale, and 4-item Instrumental Activities of Daily Living scale), posture and gait (Timed Up & Go, Five Time Sit-to-Stand, spatio-temporal analysis of walking), as well as the between-groups comparison of compliance to treatment and tolerance. These outcomes are assessed at baseline, 12 and 24 weeks, together with the serum concentrations of 25OHD, calcium and parathyroid hormone.

Discussion: The combination of memantine plus vitamin D may represent a new multi-target therapeutic class for the treatment of ADRD. The AD-IDEA Trial seeks to provide evidence on its efficacy in limiting cognitive and functional declines in ADRD.

Trial Registration: ClinicalTrials.gov number, NCT01409694.
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http://dx.doi.org/10.1186/1745-6215-12-230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3212921PMC
October 2011

Practical application and clinical impact of the WHO histopathological criteria on bone marrow biopsy for the diagnosis of essential thrombocythemia versus prefibrotic primary myelofibrosis.

Histopathology 2010 May;56(6):758-67

Département de Pathologie Cellulaire et Tissulaire, Service des Maladies du Sang, Centre Hospitalier Universitaire, Angers, France.

Aims: To evaluate the feasibility of the histopathological diagnosis of prefibrotic-early primary myelofibrosis (PM) as described in the World Health Organization (WHO) classification and to evaluate the clinical implications of prefibrotic-early PM in a series of patients previously diagnosed as having essential thrombocythemia (ET) according to the Polycythemia Vera Study Group criteria.

Methods And Results: WHO criteria were applied to bone marrow biopsy specimens by two pathologists who then reclassified 127 cases as 102 ET (80.3%), 18 prefibrotic-early PM (14.2%) and seven fibrotic PM (5.5%). In 45 cases (35%), the final diagnosis was only reached by consensus. The megakaryocytic criteria that best discriminated between ET and prefibrotic-early PM were an increased nucleo-cytoplasmic ratio, presence of cloudlike nuclei, hyperchromatic-dysplastic nuclei, paratrabecular megakaryocytes and tight clusters. A histological score discriminated between ET (score < or =3) and PM (score > or =6), but 21 cases showed an intermediate ambiguous score. No significant differences were observed at diagnosis and at follow-up (median time 93 months) for thrombosis, major haemorrhage, laboratory data, transformation into overt myeloid metaplasia and survival.

Conclusions: The distinction between ET and prefibrotic-early PM is impaired by subjectivity in pathological practice and is of questionable clinical relevance, at least when considering individual patients.
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http://dx.doi.org/10.1111/j.1365-2559.2010.03545.xDOI Listing
May 2010

Biodegradable carmustine wafers (Gliadel) alone or in combination with chemoradiotherapy: the French experience.

Ann Surg Oncol 2010 Jul 5;17(7):1740-6. Epub 2010 May 5.

Département de Neurochirurgie, INSERM U646, CHU d'Angers, Angers, France.

Background: Carmustine-releasing wafers (Gliadel have been available and reimbursed in France since 2005.

Methods: A retrospective multicenter study was conducted in 26 French Departments of Neurosurgery to analyze practices of French neurosurgeons using Gliadel, compare the adverse effects and survival with those of previous phase III trials, and assess survival in patients with newly diagnosed malignant gliomas (MG) receiving Gliadel plus radiochemotherapy with temozolomide (TMZ). A total of 163 patients who received Gliadel for MG were included in this study: 83 (51%) with newly diagnosed MG and 80 (49%) with recurrent MG. In the newly diagnosed group, 51.8% of patients received radiochemotherapy with TMZ.

Results: Adverse events (AEs) emerged in 44.6% of the population, including 6% with septic abscess. The AE rate was not statistically correlated with adjuvant use of TMZ. For the newly diagnosed group, median survival was 17 months. Total or subtotal resection appeared to have a great impact on survival (P = 0.016), as did treatment with adjuvant radiotherapy (P = 0.004). For the group with recurrent MG, median survival was 7 months. Total or subtotal resection excision appeared to have a great impact on survival (P = 0.002), as did preoperative Karnowsky Scale (PO-KPS) (P = 0.012).

Conclusions: Survival rates for newly diagnosed patients were better than those reported in previous phase III trials. The combination of Gliadel and radiochemotherapy with TMZ was well tolerated and appeared to increase survival without increasing AEs.
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http://dx.doi.org/10.1245/s10434-010-1081-5DOI Listing
July 2010