Evaluation of Clinical Trials in Onco-haematology: A New Method Based on Risk Analysis and Multidisciplinarity.

BACKGROUND: European member states are increasingly vying with one another to recruit patients for clinical trials (CTs). The French national agency for medicines (ANSM) now receives an ever-growing number of CTs, extending response times. The aim of the new methodology presented herein is to reduce assessment times below the national mandatory timeframe of 60 days and to improve patient safety. MATERIALS AND METHODS: Based on an analysis of the criteria defining CTs, 4 key points were identified (safety, fragile population, loss of opportunity, design complexity) to build a criticality score which would determine evaluation type. This score also determines the resources needed (complete evaluation, multidisciplinary advice, ad hoc evaluation) and the timeframe required for appropriate analysis. All post-phase I CTs were analysed from the implementation of the new assessment method, on 01/02/2018 through to 31/12/2019. RESULTS: 447 CTs were analysed (63% industry and 37% academic sponsors). Based on a criticality scale, 27% of the CTs received a type A evaluation (complete), 37% a type B (multidisciplinary evaluation), 23% a type C evaluation (ad hoc evaluation) and 13% a type D evaluation (fast evaluation). From 2014 to 2017, 37% of the CTs were analysed within the mandatory timeframe, with a mean of 68 days, reaching a maximum of 102 days in 2017. Using this new assessment method, 92% of CTs respected the mandatory timeframe in 2019; the mean time in 2018-2019 was 34 days; Grounds for Non-Acceptance (GNA) were raised for 66% of the CTs (69% from academic sponsors and 65% from industrial firms). 3 CTs were refused. CONCLUSION: Here, we demonstrate the feasibility of risk analysis and multidisciplinarity method, which resulted in a dramatic improvement of assessment times.

Surgical treatment of patent ductus arteriosus (PDA). Analysis of 145 cases operated on in Abidjan (Cote D'Ivoire).

This retrospective study aims to analyse our surgical procedures and our results after surgery of patent ductus arteriosus (P.D.A.) in children. Since 1978 to 1992 we have reported Abidjan Cardiology Institute 145 children operated cases. The average age was 4.7 years, the average weight 16 kg. There was female predominance with a sex ratio of 2.3/1. All patent ductus arteriosus had been confirmed by two dimensional echocardiography (2D echocardiography) and cardiac catheterization. Type 11a of NADAS' Classification was the most frequent (50%). Double or triple ligation supported on teflon felt was the most frequent technique used (86 times ie 59.3%). This technique gave good results in view of the absence of hospital mortality, only 4 cases of ductus "recanalization" supervened, a low rate of ductus arteriosus recurrence patency at long follow up of all patients from one to 10 years (mean 5 years). Double or triple ligation on teflon felt according to Wright procedure seems to be a securising technique alternative in our countries.

[Left auricular myxoma and myocardial infarction]. / Myxome auriculaire gauche et infarctus du myocarde.

The authors report the case of a 40 year old man with a postero-inferior myocardial infarction. Echocardiography showed a large left atrial myxoma. Coronary angiography performed 20 days after the onset of infarction was completely normal. The tumour was successfully removed surgically. The authors review the literature of this rare association (20 reported cases) which were commonly observed since the widespread use of echocardiography and coronary angiography. These investigations have improved the understanding of the physiopathology of this association. One of the possible hypotheses of diastolic mitral obstruction by the tumour was the probable mechanism of infarction in this case due to prolonged impaired coronary filling due to low cardiac output.

Closure of the ductus arteriosus: determinant factor in the appearance of transient peripheral pulmonary stenosis of the neonate.

We speculated that a relationship may exist between transient peripheral pulmonary stenosis and the closure of the ductus arteriosus. Fifty preterm infants had pulmonary artery and ductal color Doppler flow velocity assessments performed before and after closure of the ductus arteriosus. No flow turbulence or increase in velocity was observed immediately after birth, although a significant discrepancy in size was observed between the main pulmonary artery and its two branches. After closure of the ductus, 15 infants had signs of transient peripheral pulmonary stenosis of the left pulmonary artery in association with a significant decrease of diameter at the origin of the same artery. In all 50 infants, no significant gradient was observed in the right pulmonary artery. We conclude that, at least in the preterm infant, transient peripheral pulmonary stenosis is not present at birth but is an acquired phenomenon closely related to closure of the ductus arteriosus.

In utero sonographic diagnosis of diaphragmatic hernia with hepatic protrusion into the pericardium mimicking an intrapericardial tumour.

A case of right-sided congenital diaphragmatic hernia was detected at 33 weeks of gestation. Fetal echocardiography revealed the presence of an intrapericardial mass (3.5 x 3 cm) localized at the right of the heart and surrounded by a massive pericardial effusion. This mass had the same echogenicity as the liver, with which it shared vascular channels. The diagnosis of right diaphragmatic hernia with protrusion of hepatic tissue into the pericardial sac and secondary pericardial effusion was made and confirmed after birth. In utero diagnosis of this anomaly enabled correct assessment of perinatal risk, and optimal fetal and infant management.

[Transposition of the great vessels in western Africa. Apropos of 17 cases observed at the Institute of Cardiology in Abidjan]. / La transposition des gros vaisseaux en Afrique noire. A propos de 17 cas observés à l'institut de cardiologie d'Abidjan.

During the last 10 years, 17 children with transposition of the great arteries (TGA) were admitted to the Cardiology Institute of Abidjan: 1 case between March 1978 and December 1985, 16 cases between January 1986 and December 1989. The average age was 58 days (range 5 to 270 days) at the first consultation, and 90 days (5 to 270 days) at the time of admission. The diagnosis was confirmed by echocardiography and hemodynamic investigation in 12 cases. There were 9 simple forms of TGA, 7 with ventricular septal defects (VSD) and 1 with VSD and pulmonary stenosis. Two children were taken back by their parents before any treatment was given. A Rashkind atrial septostomy was carried out in 11 children which increased aortic oxygen saturation from 35 +/- 18 percent to 57 +/- 19 percent; there were 3 unsuccessful procedures in children aged 2, 3 and 5 months with 2 deaths. Five patients later underwent surgical correction by a Senning procedure in 4 cases and anatomical correction in 1 case with VSD. All are well after an average 15 months follow-up (1 to 48 months). One of the 8 children awaiting surgery died. Therefore, TGA is not a rare abnormality in Black Africa; it represents 2 percent of the 887 cases of congenital heart disease observed during the same period. The inadequacy of means of diagnosis is certainly the cause of the relatively low incidence of this malformation, of the considerable delay in under specialist care and, as a consequence, of the greater difficulties in treatment, especially with regards to atrial septostomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary heart disease in the diabetic African: frequency clinical and angiographic features.

The frequency and clinical and coronarographic features of coronary heart disease (CHD) in black African diabetic patients were assessed in a two-part study. The aim of part I was to determine the frequency of CHD in 50 diabetic patients selected by the following criteria: male, age between 40 and 60 years, diabetes history less than 20 years, no history of CHD and normal E.K.G. All 50 of these patients underwent a stress test and those who failed or for whom results were inconclusive were submitted to coronary arteriography. Part II was a retrospective study of 104 patients with CHD. Its aim was to compare the clinical and coronarographic features of CHD patients with (27 cases) and without (77 cases) diabetes mellitus. The frequency of CHD in the 50 diabetics selected for this study was 10% (31 negative exercise tests, 19 inconclusive exercise tests, 5 coronary arteriographies with significant narrowing). Of these 5 diabetics with CHD, 3 had single vessel involvement (left descending artery: 2 cases, circumflex artery: 1 case), 1 patient had double vessel involvement (right coronary circumflex artery) and 1 had triple vessel involvement (left descending, circumflex, and right coronary artery). In the retrospective study the clinical profile of the diabetic and non-diabetic CHD patients was the same with respect to sex, age, angina, myocardial infarction, and death rate. As regard the risk factors, blood cholesterol level was higher in diabetics while cigarette smoking was higher in non-diabetics. The frequency of hypertension was the same in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Silent coronary artery disease in black African diabetic patients. A prospective study of 50 patients.

Silent coronary heart disease (CHD) has been researched among a sample of 50 black African diabetic patients in a prospective study. The diabetic patients were chosen on the following criteria: male sex, age ranging from 40 to 60 years, absence of history of CHD, normal EKG. A stress test was performed in all cases. A coronary arteriography was done each time the exercise test was positive, doubtful or non-conclusive. This study has shown a prevalence of 10% CHD:31 exercise test negatives, 17 exercise test non-conclusives, 2 exercise test positives, 5 coronary arteriography with significant narrowing. There were 3 patients with one vessel disease (LDA: 2 cases, CFX: 1 case), one patient with double vessel disease (CFX, RCA) while another had a triple vessel disease (RCA, LDA, CFX). Proximal lesions were encountered in 5 cases and distal lesions in 3 cases. The authors conclude that CHD exist in a silent state among black African diabetics. Its prevalence is lower than in white diabetics. The coronary lesions are mostly limited. Proximal narrowing and one vessel disease were mostly encountered.