Analysing Time to Event Data in Dementia Prevention Trials: The Example of the GuidAge Study of EGb761.

Time-to-event analysis is frequently used in medical research to investigate potential disease-modifying treatments in neurodegenerative diseases. Potential treatment effects are generally evaluated using the logrank test, which has optimal power and sensitivity when the treatment effect (hazard ratio) is constant over time. However, there is generally no prior information as to how the hazard ratio for the event of interest actually evolves. In these cases, the logrank test is not necessarily the most appropriate to use. When the hazard ratio is expected to decrease or increase over time, alternative statistical tests such as the Fleming-Harrington test, provide a better sensitivity. An example of this comes from a large, five-year randomised, placebo-controlled prevention trial (GuidAge) in 2854 community-based subjects making spontaneous memory complaints to their family physicians, which evaluated whether treatment with EGb761 can modify the risk of developing AD. The primary outcome measure was the time to conversion from memory complaint to Alzheimer's type dementia. Although there was no significant difference in the hazard function of conversion between the two treatment groups according to the preplanned logrank test, a significant treatment-by-time interaction for the incidence of AD was observed in a protocol-specified subgroup analysis, suggesting that the hazard ratio is not constant over time. For this reason, additional post hoc analyses were performed using the Fleming-Harrington test to evaluate whether there was a signal of a late effect of EGb761. Applying the Fleming-Harrington test, the hazard function for conversion to dementia in the placebo group was significantly different from that in the EGb761 treatment group (p = 0.0054), suggesting a late effect of EGb761. Since this was a post hoc analysis, no definitive conclusions can be drawn as to the effectiveness of the treatment. This post hoc analysis illustrates the interest of performing another randomised clinical trial of EGb761 explicitly testing the hypothesis of a late treatment effect, as well as of using of better adapted statistical approaches for long term preventive trials when it is expected that prevention cannot have an immediate effect but rather a delayed effect that increases over time.

Practical experience with the implementation of an athlete's biological profile in athletics, cycling, football and swimming.

The introduction of the athlete's biological passport (ABP) has been a milestone in the fight against doping. The ABP is a collection of measurements of different biological parameters influenced by the administration of doping agents through the time and for each athlete. Two different modules have been developed and validated so far: the haematological module, which aims to identify enhancement of oxygen transport, including use of erythropoiesis-stimulating agents and any form of blood transfusion or manipulation, which became effective in 2010; and the steroidal module, which intends to detect the use of endogenous anabolic androgenic steroids when administered exogenously and other anabolic agents, which was introduced in 2014. Prior to the implementation of the haematological module, it is important to define an athlete's testing pool on whom to collect blood and/or urine in-competition and out-of-competition (for the steroidal module, this is irrelevant because all collected urine samples will be subjected to analysis for the steroidal variables) and to be compliant with the strict requirements of the World Anti-Doping Agency ABP Operating Guidelines. The established individual profile can be used either to target traditional antidoping tests (recombinant erythropoietins, or homologous blood transfusion tests for the haematological module; isotope ratio mass spectrometry (IRMS) for the steroidal module) or to support an antidoping rule violation due to the use of a forbidden substance or method. In this article, we present the experience of four major International Federations which have implemented an ABP programme, focusing on the haematological module. They constitute examples which could be followed by other antidoping organisations wishing to introduce this new, efficient and innovative antidoping tool.

Complete resolution of cerebral air embolism secondary to a transbronchial needle aspiration.

Air embolism following transbronchial needle aspiration (TBNA) is extremely rare. To date, only 1 case has been described (estimated incidence: 0.02-0.07%). Here, a 70-year-old patient developed a left upper-lobe alveolar syndrome with no response to well-conducted antibiotic treatments. Conventional bronchoscopy was normal, but virtual bronchoscopy showed that the tumor was contiguous to the left B3-B4 division. During a second bronchoscopy, a TBNA was performed without bleeding, and pathology later revealed primitive lung adenocarcinoma. Immediately after the puncture, an epileptic seizure occurred with right rotation of the head and a tonic seizure of the left arm followed by left hemiplegia. A brain CT scan performed almost immediately showed no abnormalities and a chest radiography did not show any pleural or mediastinal aeric image. A few hours later, clonic seizures occurred and brain MRI showed lesions compatible with air embolisms (right gyral cortical location). Several hyperbaric therapy sessions successfully cured the neurological deficit. Despite its rarity, each practitioner of TBNA has to be aware of this side effect and its early treatment. The mechanism of such accidents remains unclear, but probably involves high bronchial pressure and venous trauma. © 2013 S. Karger AG, Basel.

[A baobab solution for the prevention and treatment of acute dehydration in infantile diarrhea]. / Une solution de pain de singe pour la prévention et le traitement de la déshydratation aiguë due aux diarrhées infantiles.

OBJECTIVE: The purpose of this study was to compare the clinical efficacy of a local solution based on "pain de singe", fruit of baobab (Adansonia digitata), and the WHO standard solution in the treatment of children with acute diarrhea and resulting mild to moderate dehydration. METHODOLOGY: A prospective clinical trial comparing the local solution to the standard WHO solution was conducted; in children of 6 months or older (mean age = 16.6 +/- 8.8 months), 79 received the WHO solution and 82 the local solution, and were followed for a period ranging from 4 to 48 hours. Evolution of diarrhea and weight gain were evaluated as variables of interest. RESULTS: WHO solution was found to be superior, but not statistically significant in term of duration of diarrhea and weight gain. DISCUSSION: The pain de singe based solution presents additional advantages: nutritional, economic and cultural; we recommend it to promote use of TRO at home.

[Use of hormonal parameters of phospho-calcium metabolism as a means of discriminating bone and joint disorders in patients with renal insufficiency]. / Utilisation des paramètres hormonaux du métabolisme phospho-calcique comme moyen de discrimination des troubles ostéo-articulaires chez les patients insuffisants rénaux.

Serum carboxyterminal parathyroid hormone (PTH) concentration (homologous measurement of the 53-84 fragment and heterologous bovine measurement) has been measured and correlated with both clinical and radiological findings of secondary hyperparathyroidism (HPT), studied quantitatively according to a score published in literature, in 95 patients with chronic renal failure on maintenance hemodialysis. Mean serum PTH concentration (53.84) is statistically higher in patients with severe clinical and radiological evaluation of HPT than in patients with moderate or slight manifestations of HPT (M +/- DS: 515.8 +/- 243.7 pg/ml VS 271.3 +/- 166.1 pg/ml p less than 0.001). However, even with high serum concentration, serum PTH level does not allow to predict HPT severity, suggesting a retention of PTH fragments in serum without biologic activity probably.