[Pervasive refusal syndrome: study of a clinical case]. / Syndrome de refus global : étude d'un cas clinique.

The clinical presentation of pervasive refusal syndrome is marked by a refusal to eat, walk, talk, firm resistance and an aggressive refusal to accept help and care. The management of patients with this syndrome is physically and emotionally draining for caregivers. The quality of the relationship can be quickly affected as it is so unusual and singular. Training, communication and support from the team are essential to be able to continue to provide compassionate care.

Common Risk Factors Add to Inherited Thrombophilia to Predict Venous Thromboembolism Risk in Families.

The clinical venous thromboembolism (VTE) pattern often shows wide heterogeneity within relatives of a VTE-affected family, although they carry the same thrombophilia defect. It is then mandatory to develop additional tools for assessing VTE risk in families with thrombophilia. This study aims to assess whether common environmental and genetic risk factors for VTE contribute to explain this heterogeneity. A total of 2,214 relatives from 651 families with known inherited thrombophilia were recruited at the referral center for thrombophilia in Marseilles, France, from 1986 to 2013. A thrombophilia screening was systematically performed in all included relatives. According to the severity of the thrombophilia defect, individuals were split into three groups: no familial defect, mild thrombophilia, and severe thrombophilia. In addition, common genetic factors (ABO blood group and 11 polymorphisms selected on the basis of their association with VTE in the general population) were genotyped. Furthermore, body mass index and smoking were collected. VTE incidence was 1.74, 3.64, and 6.40 per 1,000 person-years in individuals with no familial defect, mild thrombophilia, and severe thrombophilia, respectively. Five common risk factors were associated with VTE in this population: obesity, smoking, ABO blood group, and F11 _rs2036914 and FGG _rs2066865 polymorphisms. These common factors were then included into a three-level risk score. The score was highly efficient for assessing VTE risk in mild thrombophilia patients by identifying two groups with different VTE risk; individuals with low score had the same risk as individuals with no familial defect whereas individuals with high score had the same risk as individuals with severe thrombophilia. An overall score including the five items plus the thrombophilia status was built and displayed an area under the receiver operating characteristic curve of 0.702 for discriminating VTE and non-VTE relatives. In conclusion, integrating common environmental and genetic risk factors improved VTE risk assessment in relatives from families with thrombophilia.

Betaine anhydrous in homocystinuria: results from the RoCH registry.

BACKGROUND: The Registry of Adult and Paediatric Patients Treated with Cystadane® - Homocystinuria (RoCH) is a non-interventional, observational, multi-centre, post-authorization safety study that aimed to identify safety of betaine anhydrous (Cystadane®) in the treatment of patients with inborn errors of homocysteine metabolism (homocystinuria) in order to minimise the treatment associated risks and establish better knowledge on its clinical use. The registry included patients of all ages with homocystinuria who were treated with betaine anhydrous in conjunction with other therapies. Clinical data were collected retrospectively from 2007 to 2013, then prospectively up to February 2014. All adverse events (AEs) reported during the study were recorded. The clinical and biological status of patients was monitored at least once a year. RESULTS: A total of 125 patients with homocystinuria (adults [> 18 years]: 50; paediatric [≤18 years]: 75) were enrolled at 29 centres in France and Spain. Patients were treated with betaine anhydrous for a mean duration of 7.4 ± 4.3 years. The median total daily dose of betaine anhydrous at the first and last study visits was 6 g/day for cystathionine ß-synthase (CBS)-deficient vitamin B6 responders and 9 g/day for methylenetetrahydrofolate reductase-deficient patients, while the median daily dose increased in CBS-deficient B6 non-responders (from 6 to 9 g/day) and cobalamin metabolism-defective patients (from 3 to 6 g/day) between the first and last visits. Treatment caused a mean overall reduction of 29% in plasma homocysteine levels in the study population. A total of 277 AEs were reported during the study, of which two non-serious AEs (bad taste and headache) and one serious AE (interstitial lung disease) were considered to be drug related. Overall, betaine anhydrous was well tolerated with no major safety concerns. CONCLUSIONS: Data from the RoCH registry provided real-world evidence on the clinical safety and efficacy of betaine anhydrous in the management of homocystinuria in paediatric and adult patients.

Risk factors for venous thromboembolism in women under combined oral contraceptive. The PILl Genetic RIsk Monitoring (PILGRIM) Study.

Identifying women at risk of venous thromboembolism (VTE) is a major public health issue. The objective of this study was to identify environmental and genetic determinants of VTE risk in a large sample of women under combined oral contraceptives (COC). A total of 968 women who had had one event of VTE during COC use were compared to 874 women under COC but with no personal history of VTE. Clinical data were collected and a systematic thrombophilia screening was performed together with ABO blood group assessment. After adjusting for age, family history, and type and duration of COC use, main environmental determinants of VTE were smoking (odds ratio [OR] =1.65, 95% confidence interval [1.30-2.10]) and a body mass index higher than 35 kg.m⁻² (OR=3.46 [1.81-7.03]). In addition, severe inherited thrombophilia (OR=2.13 [1.32-3.51]) and non-O blood groups (OR=1.98 [1.57-2.49]) were strong genetic risk factors for VTE. Family history poorly predicted thrombophilia as its prevalence was similar in patients with or without first degree family history of VTE (29.3% vs 23.9%, p=0.09). In conclusion, this study confirms the influence of smoking and obesity and shows for the first time the impact of ABO blood group on the risk of VTE in women under COC. It also confirms the inaccuracy of the family history of VTE to detect inherited thrombophilia.

TFPI resistance related to inherited or acquired protein S deficiency.

BACKGROUND: Protein S (PS) is an essential component of the protein C pathway and PS deficiency can explain a poor response to activated protein C. It has recently been shown that PS also acts as a cofactor of Tissue Factor Pathway Inhibitor (TFPI). OBJECTIVES: In the present study, we investigated whether PS deficiency could be responsible for a poor response to TFPI. PATIENTS/METHODS: Thirty-one patients with inherited PS deficiency, seven pregnant women and 36 controls were enrolled in the study. We measured the plasma response to added TFPI using a two-step diluted prothrombin time (dPT) assay. The response of the different plasmas to the anticoagulant activity of TFPI was expressed as TFPI Normalised Ratio (TFPI NR). RESULTS: The median TFPI NR was statistically significantly lower in patients with inherited PS deficiency (0.5) than in controls (1.0) (p<0.0001). It was statistically significantly lower in patients with type I inherited PS deficiency (0.47) compared to patients with type III inherited PS deficiency (0.58) (p=0.018). In contrast, it did not differ between patients with and without thrombosis. Median TFPI NR values were statistically significantly lower during pregnancy (0.54) than 3 months after delivery (0.71) (p=0.016). TFPI NR values correlated well with PS activity values (R(2)=0.681) whatever the nature of the PS deficiency. CONCLUSIONS: Our findings confirm that PS deficiency results in a poor anticoagulant response to TFPI, demonstrating again the cofactor role of PS in TFPI activity.

ABO blood group and von Willebrand factor levels partially explained the incomplete penetrance of congenital thrombophilia.

OBJECTIVE: We aimed to study the association among ABO blood group, von Willebrand factor, factor VIII plasma levels, and the risk of venous thrombosis (VT) in a cohort of 1774 relatives from 500 families with inherited thrombophilia. METHODS AND RESULTS: One hundred sixty-one of the 1774 relatives had a VT. Different risk groups were formed: no, low-(factor V Leiden or F2G20210A heterozygous carriers), and high-risk thrombophilia (antithrombin, protein C, protein S, factor V Leiden, or F2G20210A homozygous carriers and combined defects). Compared with group O, AB blood group was associated with increased risk of VT: hazard ratio (HR)=3.8 (2.0-7.2). The effect of blood group A and B was milder (HR=1.6 [1.1-2.5] and 1.8 [1.0-3.3], respectively). An increased risk of VT was observed with increasing levels of von Willebrand factor and factor VIII plasma levels (HR=2.96 [1.92-4.56] and HR=2.60 [1.92-4.56] for third versus first tertile of von Willebrand factor and factor VIII plasma levels, respectively). In multivariate analysis, AB group (HR=2.3 [1.1-4.8]), high-risk thrombophilia (HR=2.8 [1.6-4.6]), and high von Willebrand factor levels (HR=2.3 [1.3-4.0]) were significantly associated with increased risk of VT. The risk of VT in individuals with high-risk thrombophilia and AB group was 14.4× higher than in those without thrombophilia and O group (5.0-41.4). CONCLUSIONS: ABO blood group modifies the risk of VT in families with hereditary thrombophilia. Phenotyping of the ABO blood group should be performed to better assess the risk of VT in asymptomatic individuals from thrombophilic families.

On the mathematical properties of the structural similarity index.

Since its introduction in 2004, the structural similarity (SSIM) index has gained widespread popularity as a tool to assess the quality of images and to evaluate the performance of image processing algorithms and systems. There has been also a growing interest of using SSIM as an objective function in optimization problems in a variety of image processing applications. One major issue that could strongly impede the progress of such efforts is the lack of understanding of the mathematical properties of the SSIM measure. For example, some highly desirable properties such as convexity and triangular inequality that are possessed by the mean squared error may not hold. In this paper, we first construct a series of normalized and generalized (vector-valued) metrics based on the important ingredients of SSIM. We then show that such modified measures are valid distance metrics and have many useful properties, among which the most significant ones include quasi-convexity, a region of convexity around the minimizer, and distance preservation under orthogonal or unitary transformations. The groundwork laid here extends the potentials of SSIM in both theoretical development and practical applications.

Coronary artery dissection in adult-onset homocystinuria.

The present report concerns the first case of a spontaneous arterial coronary dissection in adult onset homocystinuria leading to a premature myocardial infarct. The patient had also presented an unexplained lower limb venous thrombosis at the age of 41. A carotid artery thrombosis was found at the aged of 61 during the investigations for facial nerve palsy. The diagnosis of homocystinuria was delayed as it was only performed 20 years after the first thrombotic event. From observation, a pectus carinatum was the only clinical characteristic that could be related to homocystinuria phenotype. Cystathionine ß-synthase (CBS) gene analysis showed compound heterozygous mutations. After 3 months of pyridoxine, the plasma homocysteine level was totally normalised.

AIDS, drought, and child malnutrition in southern Africa.

OBJECTIVE: To investigate trends in child malnutrition in six countries in southern Africa, in relation to the HIV epidemic and drought in crop years 2001/2 and 2002/3. DESIGN: Epidemiological analysis of sub-national and national surveys with related data. SETTING: Data from Lesotho, Malawi, Mozambique, Swaziland, Zambia and Zimbabwe, compiled and analysed under UNICEF auspices. SUBJECTS: Secondary data: children 0-5 years for weight-for-age; HIV prevalence data from various sources especially antenatal clinic surveillance. RESULTS: Child nutritional status as measured by prevalence of underweight deteriorated from 2001 onwards in all countries except Lesotho, with very substantial increases in some provinces/districts (e.g. from 5 to 20% in Maputo (Mozambique, 1997-2002), 17 to 32% in Copperbelt (Zambia, 1999-2001/2) and 11 to 26% in Midlands province (Zimbabwe, 1999-2002)). Greater deterioration in underweight occurred in better-off areas. Areas with higher HIV/AIDS prevalences had (so far) lower malnutrition rates (and infant mortality rates), presumably because more modern areas--with greater reliance on trade and wage employment--have more HIV/AIDS. Areas with higher HIV/AIDS showed more deterioration in child nutrition. A significant area-level interaction was found of HIV/AIDS with the drought period, associated with particularly rapid deterioration in nutritional status. CONCLUSIONS: First, the most vulnerable may be households in more modern areas, nearer towns, to whom resources need to be directed. Second, the causes of this vulnerability need to be investigated. Third, HIV/AIDS amplifies the effect of drought on nutrition, so rapid and effective response will be crucial if drought strikes again. Fourth, expanded nutritional surveillance is now needed to monitor and respond to deteriorating trends. Finally, with or without drought, new means are needed of bringing help, comfort and assistance to the child population.