Prediction of 18-month survival in patients with primary myelodysplastic syndrome. A regression model and scoring system based on the combination of chromosome findings and the Bournemouth score.

The predictive potential of six selected factors was assessed in 72 patients with primary myelodysplastic syndrome using univariate and multivariate logistic regression analysis of survival at 18 months. Factors were age (above median of 69 years), dysplastic features in the three myeloid bone marrow cell lineages, presence of chromosome defects, all metaphases abnormal, double or complex chromosome defects (C23), and a Bournemouth score of 2, 3, or 4 (B234). In the multivariate approach, B234 and C23 proved to be significantly associated with a reduction in the survival probability. The similarity of the regression coefficients associated with these two factors means that they have about the same weight. Consequently, the model was simplified by counting the number of factors (0, 1, or 2) present in each patient, thus generating a scoring system called the Lausanne-Bournemouth score (LB score). The LB score combines the well-recognized and easy-to-use Bournemouth score (B score) with the chromosome defect complexity, C23 constituting an additional indicator of patient outcome. The predicted risk of death within 18 months calculated from the model is as follows: 7.1% (confidence interval: 1.7-24.8) for patients with an LB score of 0, 60.1% (44.7-73.8) for an LB score of 1, and 96.8% (84.5-99.4) for an LB score of 2. The scoring system presented here has several interesting features. The LB score may improve the predictive value of the B score, as it is able to recognize two prognostic groups in the intermediate risk category of patients with B scores of 2 or 3. It has also the ability to identify two distinct prognostic subclasses among RAEB and possibly CMML patients. In addition to its above-described usefulness in the prognostic evaluation, the LB score may bring new insights into the understanding of evolution patterns in MDS. We used the combination of the B score and chromosome complexity to define four classes which may be considered four possible states of myelodysplasia and which describe two distinct evolutional pathways.

Predicting stroke through genetic risk functions: the CHARGE Risk Score Project.

BACKGROUND AND PURPOSE: Beyond the Framingham Stroke Risk Score, prediction of future stroke may improve with a genetic risk score (GRS) based on single-nucleotide polymorphisms associated with stroke and its risk factors. METHODS: The study includes 4 population-based cohorts with 2047 first incident strokes from 22,720 initially stroke-free European origin participants aged ≥55 years, who were followed for up to 20 years. GRSs were constructed with 324 single-nucleotide polymorphisms implicated in stroke and 9 risk factors. The association of the GRS to first incident stroke was tested using Cox regression; the GRS predictive properties were assessed with area under the curve statistics comparing the GRS with age and sex, Framingham Stroke Risk Score models, and reclassification statistics. These analyses were performed per cohort and in a meta-analysis of pooled data. Replication was sought in a case-control study of ischemic stroke. RESULTS: In the meta-analysis, adding the GRS to the Framingham Stroke Risk Score, age and sex model resulted in a significant improvement in discrimination (all stroke: Δjoint area under the curve=0.016, P=2.3×10(-6); ischemic stroke: Δjoint area under the curve=0.021, P=3.7×10(-7)), although the overall area under the curve remained low. In all the studies, there was a highly significantly improved net reclassification index (P<10(-4)). CONCLUSIONS: The single-nucleotide polymorphisms associated with stroke and its risk factors result only in a small improvement in prediction of future stroke compared with the classical epidemiological risk factors for stroke.

Effects of zoledronate versus placebo on spine bone mineral density and microarchitecture assessed by the trabecular bone score in postmenopausal women with osteoporosis: A three-year study.

The trabecular bone score (TBS) is an index of bone microarchitectural texture calculated from anteroposterior dual-energy X-ray absorptiometry (DXA) scans of the lumbar spine (LS) that predicts fracture risk, independent of bone mineral density (BMD). The aim of this study was to compare the effects of yearly intravenous zoledronate (ZOL) versus placebo (PLB) on LS BMD and TBS in postmenopausal women with osteoporosis. Changes in TBS were assessed in the subset of 107 patients recruited at the Department of Osteoporosis of the University Hospital of Berne, Switzerland, who were included in the HORIZON trial. All subjects received adequate calcium and vitamin D3. In these patients randomly assigned to either ZOL (n = 54) or PLB (n = 53) for 3 years, BMD was measured by DXA and TBS assessed by TBS iNsight (v1.9) at baseline and 6, 12, 24, and 36 months after treatment initiation. Baseline characteristics (mean ± SD) were similar between groups in terms of age, 76.8 ± 5.0 years; body mass index (BMI), 24.5 ± 3.6 kg/m(2) ; TBS, 1.178 ± 0.1 but for LS T-score (ZOL-2.9 ± 1.5 versus PLB-2.1 ± 1.5). Changes in LS BMD were significantly greater with ZOL than with PLB at all time points (p < 0.0001 for all), reaching +9.58% versus +1.38% at month 36. Change in TBS was significantly greater with ZOL than with PLB as of month 24, reaching +1.41 versus-0.49% at month 36; p = 0.031, respectively. LS BMD and TBS were weakly correlated (r = 0.20) and there were no correlations between changes in BMD and TBS from baseline at any visit. In postmenopausal women with osteoporosis, once-yearly intravenous ZOL therapy significantly increased LS BMD relative to PLB over 3 years and TBS as of 2 years. © 2013 American Society for Bone and Mineral Research.

Glomerular filtration rate: measure creatinine and height rather than cystatin C!

AIM: Inulin clearance (Cin) is the gold standard for assessing glomerular filtration rate (GFR). Other methods are based on the plasma creatinine concentration (Pcreat), creatinine clearance (Ccreat), the Haycock-Schwartz formula and the plasma concentration of cystatin C (PcysC), a 13 kDa basic protein produced at a constant rate by all nucleated cells. The present prospective study was thus designed to evaluate the reliability of PcysC as a marker of GFR in comparison with that of Pcreat, Ccreat and the Haycock-Schwartz formula, using Cin as the gold standard. METHODS: Ninety-nine children (51 m/48 f), with a median age of 8.3 y (1.0-17.9) were studied. Using a cut-off for Cin of 100 ml/min per 1.73 m2, 54 children (54.5%) had impaired GFR. Those with normal GFR were comparable for age, height, weight and body mass index. RESULTS: Logistic regression, ROC analysis and linear regression all showed that Ccreat was the best parameter to discriminate between impaired and normal GFR, followed by the Haycock-Schwartz formula, PcysC, and finally Pcreat, each one being significantly more predictive than the next. CONCLUSION: GFR is better assessed by the Haycock-Schwartz formula than by PcysC or Pcreat alone. It is therefore concluded that when urine collection is not possible, simply measuring the child's Pcreat and height is the best, easiest and cheapest way to assess GFR.

Trends in the association between height and socioeconomic indicators in France, 1970-2003

Average physical stature has increased dramatically during the 20th century in many populations across the world with few exceptions. It remains unclear if social inequalities in height persist despite improvements in living standards in the welfare economies of Western Europe. We examined trends in the association between height and socioeconomic indicators in adults over three decades in France. The data were drawn from the French Decennial Health Surveys: a multistage, stratified, random survey of households, representative of the population, conducted in 1970, 1980, 1991, and 2003. We categorised age into 10-year bands, 25-34, 35-44, 45-54 and 55-64 years. Education and income were the two socioeconomic measures used. The slope index of inequality (SII) was used as a summary index of absolute social inequalities in height. The results show that average height increased over this period; men and women aged 25-34 years were 171.9 and 161.2 cm tall in 1970 and 177.0 and 164.0 cm in 2003, respectively. However, education-related inequalities in height remained unchanged over this period and in men were 4.48 cm (1970), 4.71 cm (1980), 5.58 cm (1991) and 4.69 cm (2003), the corresponding figures in women were 2.41, 2.37, 3.14 and 2.96 cm. Income-related inequalities in height were smaller and much attenuated after adjustment for education. These results suggest that in France, social inequalities in adult height in absolute terms have remained unchanged across the three decades under examination.

Evaluation of the potential use of trabecular bone score to complement bone mineral density in the diagnosis of osteoporosis: a preliminary spine BMD-matched, case-control study.

The trabecular bone score (TBS) is a new parameter that is determined from gray-level analysis of dual-energy X-ray absorptiometry (DXA) images. It relies on the mean thickness and volume fraction of trabecular bone microarchitecture. This was a preliminary case-control study to evaluate the potential diagnostic value of TBS as a complement to bone mineral density (BMD), by comparing postmenopausal women with and without fractures. The sample consisted of 45 women with osteoporotic fractures (5 hip fractures, 20 vertebral fractures, and 20 other types of fracture) and 155 women without a fracture. Stratification was performed, taking into account each type of fracture (except hip), and women with and without fractures were matched for age and spine BMD. BMD and TBS were measured at the total spine. TBS measured at the total spine revealed a significant difference between the fracture and age- and spine BMD-matched nonfracture group, when considering all types of fractures and vertebral fractures. In these cases, the diagnostic value of the combination of BMD and TBS likely will be higher compared with that of BMD alone. TBS, as evaluated from standard DXA scans directly, potentially complements BMD in the detection of osteoporotic fractures. Prospective studies are necessary to fully evaluate the potential role of TBS as a complementary risk factor for fracture.

Value of clinical factors in selecting postmenopausal women with rheumatoid arthritis for bone densitometry.

Criteria to decide which patients with rheumatoid arthritis (RA) should be examined by dual energy x ray absorptiometry (DXA) are currently not available. The rheumatologists from Amsterdam have proposed preliminary criteria based on clinical risk factors (age, disease activity, and functional status). These criteria are preliminary and not widely accepted but might be helpful in practice. The value of the proposal in a group of Spanish postmenopausal women with RA is analysed. METHODS DXA (lumbar spine and femoral neck) was performed in 128 patients recruited from a clinical setting, and the proposed criteria were applied. T and Z scores were established for a Spanish reference population. RESULTS The mean (SD) age of the patients was 61.3 (10.7) and mean duration of the postmenopausal period 14.5 (10.1) years. Mean duration of RA was 13.7 (7.7) years. Mean C reactive protein was 22 (21) mg/l; mean erythrocyte sedimentation rate 26 (18) mm/1st h; and mean Health Assessment Questionnaire score 1.25 (0.79). Ninety (70%) patients fulfilled the proposed criteria. Their sensitivity for the diagnosis of osteoporosis (T score ¿¿2.5 SD) was 86% and their specificity, 43%. Positive predictive value was 54% and negative predictive value, 79%. CONCLUSIONS The proposed criteria seem a good screening method for the selection of those patients with RA whose bone mineral density should be assessed as the sensitivity and negative predictive value are acceptable.

Management of fragility fractures in Switzerland: results of a nationwide survey.

A nationwide survey was conducted in Switzerland to assess the quality level of osteoporosis management in patients aged 50 years or older presenting with a fragility fracture to the emergency ward of the participating hospitals. Eight centres recruited 4966 consecutive patients who presented with one or more fractures between 2004 and 2006. Of these, 3667 (2797 women, 73.8 years old and 870 men, 73.0 years old in average) were considered as having a fragility fracture and included in the survey. Included patients presented with a fracture of the upper limbs (30.7%), lower limbs (26.4%), axial skeleton (19.5%) or another localisation, including malleolar fractures (23.4%). Thirty-two percent reported one or more previous fractures during adulthood. Of the 2941 (80.2%) hospitalised women and men, only half returned home after discharge. During diagnostic workup, dual x-ray absorptiometry (DXA) measurement was performed in 31.4% of the patients only. Of those 46.0% had a T-score < or =-2.5 SD and 81.1% < or =-1.0 SD. Osteoporosis treatment rate increased from 26.3% before fracture to 46.9% after fracture in women and from 13.0% to 30.3% in men. However, only 24.0% of the women and 13.8% of the men were finally adequately treated with a bone active substance, generally an oral bisphosphonate, with or without calcium / vitamin D supplements. A positive history of previous fracture vs none increased the likelihood of getting treatment with a bone active substance (36.6 vs 17.9%, ? 18.7%, 95% CI 15.1 to 22.3, and 22.6 vs 9.9%, ? 12.7%, CI 7.3 to 18.5, in women and men, respectively). In Switzerland, osteoporosis remains underdiagnosed and undertreated in patients aged 50 years and older presenting with a fragility fracture.

Cardiovascular risk factor profiles and their social gradient from adolescence to age 74 in a Swiss region.

BACKGROUND: Few European studies have investigated how cardiovascular risk factors (CRF) in adults relate to those observed in younger generations. OBJECTIVE: To explore this issue in a Swiss region using two population health surveys of 3636 adolescents ages 9-19 years and 3299 adults ages 25-74 years. METHODS: Age patterns of continuous CRF were estimated by robust locally weighted regression and those of high-risk groups were calculated using adult criteria with appropriate adjustment for children. RESULTS: Gender differences in height, weight, blood pressure, and HDL cholesterol observed in adults were found to emerge in adolescents. Overweight, affecting 10-12% of adolescents, was increasing steeply in young adults (three times among males and twice among females) in parallel with inactivity. Median age at smoking initiation was decreasing rapidly from 18 to 20 years in young adults to 15 in adolescents. A statistically significant social gradient in disfavor of the lower education level was observed for overweight in all age groups of women above 16 (odds ratios (ORs) 2.4 to 3.3, P < 0.01), for inactivity in adult males (ORs 1.6 to 2.0, P < 0.05), and for regular smoking in older adolescents (OR 1.9 for males, 2.7 for females, P < 0.005), but not for elevated blood pressure. CONCLUSION: Discontinuities in the cross-sectional age patterns of CRF indicated the emergence of a social gradient and the need for preventive actions against the early adoption of persistent unhealthy behaviors, to which low-educated girls and women are particularly exposed.

The prognostic value of semi-quantitative i-123 mibg scintigraphy at diagnosis in high risk neuroblastoma: validation of the siopen score method

Purpose: SIOPEN scoring of 123I mIBG imaging has been shown to predict response to induction chemotherapy and outcome at diagnosis in children with HRN.Method: Patterns of skeletal 123I mIBG uptake were assigned numerical scores (Mscore) ranging from 0 (no metastasis) to 72 (diffuse metastases) within 12 body areas as described previously. 271 anonymised, paired image data sets acquired at diagnosis and on completion of Rapid COJEC induction chemotherapy were reviewed, constituting a representative sample of 1602 children treated prospectively within the HR-NBL1/SIOPEN trial. Pre-and post-treatment Mscores were compared with bone marrow cytology (BM) and 3 year event free survival (EFS).Results: Results 224/271 patients showed skeletal MIBG-uptake at diagnosis and were evaluable forMIBG-response. Complete response (CR) on MIBG to Rapid COJEC induction was achieved by 66%, 34% and 15% of patients who had pre-treatment Mscores of <18 (n¼65, 29%), 18-44 (n¼95,42%) and Y ´ 45 (n¼64, 28.5%) respectively (chi squared test p<.0001). Mscore at diagnosis and on completion of Rapid COJEC correlated strongly with BM involvement (p<0.0001). The correlation of pre score with post scores and response was highly significant (p<0.001). Most importantly, the 3 year EFS in 47 children with Mscore 0 at diagnosis was 0.68 (A ` 0.07), by comparison with 0.42 (A` 0.06), 0.35 (A` 0.05) and 0.25 (A` 0.06) for patients in pre-treatment score groups <18, 18-44 and Y ´ 45, respectively (p<0.001). AnMscore threshold ofY ´ 45 at diagnosis was associated with significantly worse outcome by comparison with all other Mscore groups (p¼0.029). The 3 year EFS of 0.53 (A` 0.07) of patients in metastatic CR (mIBG and BM) after Rapid Cojec (33%) is clearly superior to patients not achieving metastatic CR (0.24 (A ` 0.04), p¼0.005).Conclusion: SIOPEN scoring of 123I mIBG imaging has been shown to predict response to induction chemotherapy and outcome at diagnosis in children with HRN.

New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.

Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.

Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity.

The pubertal height growth spurt is a distinctive feature of childhood growth reflecting both the central onset of puberty and local growth factors. Although little is known about the underlying genetics, growth variability during puberty correlates with adult risks for hormone-dependent cancer and adverse cardiometabolic health. The only gene so far associated with pubertal height growth, LIN28B, pleiotropically influences childhood growth, puberty and cancer progression, pointing to shared underlying mechanisms. To discover genetic loci influencing pubertal height and growth and to place them in context of overall growth and maturation, we performed genome-wide association meta-analyses in 18 737 European samples utilizing longitudinally collected height measurements. We found significant associations (P < 1.67 × 10(-8)) at 10 loci, including LIN28B. Five loci associated with pubertal timing, all impacting multiple aspects of growth. In particular, a novel variant correlated with expression of MAPK3, and associated both with increased prepubertal growth and earlier menarche. Another variant near ADCY3-POMC associated with increased body mass index, reduced pubertal growth and earlier puberty. Whereas epidemiological correlations suggest that early puberty marks a pathway from rapid prepubertal growth to reduced final height and adult obesity, our study shows that individual loci associating with pubertal growth have variable longitudinal growth patterns that may differ from epidemiological observations. Overall, this study uncovers part of the complex genetic architecture linking pubertal height growth, the timing of puberty and childhood obesity and provides new information to pinpoint processes linking these traits.

Validation of a clinical prediction score for ruling out coronary heart disease in primary care patients with chest pain.

Background: A patient's chest pain raises concern for the possibility of coronary heart disease (CHD). An easy to use clinical prediction rule has been derived from the TOPIC study in Lausanne. Our objective is to validate this clinical score for ruling out CHD in primary care patients with chest pain. Methods: This secondary analysis used data collected from a oneyear follow-up cohort study attending 76 GPs in Germany. Patients attending their GP with chest pain were questioned on their age, gender, duration of chest pain (1-60 min), sternal pain location, pain increases with exertion, absence of tenderness point at palpation, cardiovascular risks factors, and personal history of cardiovascular disease. Area under the curve (ROC), sensitivity and specificity of the Lausanne CHD score were calculated for patients with full data. Results: 1190 patients were included. Full data was available for 509 patients (42.8%). Missing data was not related to having CHD (p = 0.397) or having a cardiovascular risk factor (p = 0.275). 76 (14.9%) were diagnosed with a CHD. Prevalence of CHD were respectively of 68/344 (19.8%), 2/62 (3.2%), 6/103 (5.8%) in the high, intermediate and low risk category. ROC was of 72.9 (CI95% 66.8; 78.9). Ruling out patients with low risk has a sensitivity of 92.1% (CI95% 83.0; 96.7) and a specificity of 22.4% (CI95% 18.6%; 26.7%). Conclusion: The Lausanne CHD score shows reasonably good sensitivity and can be used to rule out coronary events in patients with chest pain. Patients at risk of CHD for other rarer reasons should nevertheless also be investigated.

Intravitreal ranibizumab for age-related macular degeneration - optical coherence tomography guided retreatment intervals and their intra- and inter-individual variability

PURPOSE:To determine whether the need for retreatment after an initial loading phase of 3 monthly intravitreal injections of ranibizumab shows an intra-individual regular rhythm and to what degree it varies between different patients.SETTING:Prospective mono-centre cohort study.METHODS:Prospective study with 42 patients with exudative age-related macular degeneration (AMD), treatment na?ve, giving informed consent. Loading dose of 3 monthly doses of ranibizumab (0,5mg), followed by a 12 months pro re nata (PRN) regimen according to early exudative signs on spectral domain optical coherence tomography (HD-OCT Cirrus Zeiss?, cube 512x126). The follow-up visits were intensified (week 4, 5, 6, 7, 8, 10, 12, 14, 16, 20, 24, etc after each injection) in order to detect exudative recurrences early, and injection followed within 3 days in cases of subretinal fluid, or intraretinal cysts, or central thickness increase of >50?m. Intervals were calculated between injections and the following recurrence was calculated for the 12 month follow-up with PRN treatment. Variability was expressed as standard deviation (SD). RESULTS Visual acuity (VA) improved from a mean ETDRS letter score of 61.6 (SD 10.8) at baseline to 68.0 (SD 10.2, +6.4 letters) at month 3 and increased further to 74.7 (SD 9.0, +13.1 letters from baseline) at month 12. The 15 patients who have completed the study by October 2010 showed maintenance of the VA improvement. Retinal thickness of the central foveal subfield improved from a mean value of 366?m(baseline) to 253?m(month 3), well maintained thereafter. Mean number of injections was 8.8 (SD 3.5) per 12 months of follow-up (after 3 loading doses), ranging from 0 to 12, with mean individual treatment-recurrence intervals ranging from 28 to >365 days (mean 58 days). Intraindividual variability of treatment-recurrence intervals, measured as SD of the individual intervals, was 7.1days as a mean value(range 1.7 ? 22.6 days) for the 33 patients with more than 1 injection during follow-up. SD was higher for longer intervals of an individual patient. It ranged within 20% of the mean intra-individual interval for 30 patients(91%) and within 15% for 21 patients(64%). The first interval was within 1 week of the mean intra-individual interval in 64% of patients and within 2 weeks in 89% of patients.CONCLUSIONS:The majority of AMD patients showed a relatively stable rhythm for PRN injections of intravitreal ranibizumab after initial loading phase, associated with excellent functional and anatomical results. The initial interval between last loading dose and first recurrence may have a predictive value for further need of treatment, therefore potentially facilitating follow-up and patient care.

Évaluation d'un score simplifié de bas débit cardiaque chez l'enfant.

1.1 Objectifs Le syndrome de bas débit cardiaque est une appréciation clinique (Hoffman et al.) dont les signes sont peu sensibles, peu spécifiques, souvent tardifs et dont la mesure chez l'enfant est rendue impossible en clinique pour des raisons techniques et de fiabilités des systèmes de mesures. Aucun score n'est applicable à l'heure actuelle chez l'enfant. C'est pourquoi, ces 10 dernières années, de nombreuses équipes se sont penchée activement sur ce problème afin de définir des marqueurs performants prédisant la survenue du LCOS après chirurgie cardiaque chez l'enfant. Cette étude s'est attachée à réunir ses marqueurs cardiaques, de les combiner et de les inclure dans un score de bas débit cardiaque. 1.2 Méthode Enfants et nouveau-nés ayant subit une chirurgie cardiaque au CHUV, après malformation cardiaque congénitale, entre janvier 2010 et octobre 2011 (N=48). Age : 8 jours à 13 ans (médiane : 16.3 mois). Deux scores développés. Soumission à l'aveugle de la liste des patients à un comité d'expert pour identifier les patients en LCOS à 48h post-chirurgie, puis comparaison avec le résultat du score. Les paramètres du premier score (SCORE 1), sont agendées de manière ordinales, alors que dans le deuxième score (SCORE 2) elles le sont de manière dichotomiques. Valeurs cut-off supérieures et inférieures des scores choisies selon une recherche extensive dans la littérature. Les valeurs cut-off intermédiaires (SCORE 1) ont été choisies au hasard. 1.3 Résultats La régression logistique multivariée pour la prédiction d'un LCOS à 48h, démontre que seul le score d'amine durant les 24 premières heures et un prédicteur indépendant de LCOS (OR 16.6 [2.6- 105.5] p<0.0001). Ce paramètre est bien corrélé avec le résultat des experts avec un coefficient de corrélation r=0.57 (p<0.0001). Les spécificités des deux scores (AUC=0.78 (p<0.0001) respectivement AUC=0.81 (p<0.0001)) sont de 71% respectivement 93.5%, les sensibilités de 70.6% respectivement 41.2 %, VPP de 57.1% respectivement 77.8%, VPN de 81.5 % respectivement 74.4%. Les tests du khi2 valent 7.7 (p=0.006) respectivement 8.69 (p=003), rejettent l'hypothèse nulle d'indépendance entre le résultat des experts et celui prédit par le score. 1.4 Conclusions Les scores développés dans le cadre de cette étude ne montrent pas une corrélation significative avec l'apparition d'un bas débit cardiaque. Même si le choix des paramètres permettant de quantifier l'apparition d'un bas débit cardiaque à 48h fût réalisé selon une recherche extensive dans la littérature, le design rétrospectif de l'étude, n'a pas permit de vérifier efficacement la relation entre l'apparition d'un bas débit cardiaque et le score de bas débit cardiaque.