Sickle cell anaemia (SCA) is a monogenic disease with a highly variable clinical course. We aimed to investigate associations between microvascular function, haemolysis markers, blood viscosity and various types of SCA-related organ damage in a multicentric sub-Saharan African cohort of patients with SCA. In a cross-sectional study, we selected seven groups of adult patients with SS phenotype in Dakar and Bamako based on the following complications: leg ulcer, priapism, osteonecrosis, retinopathy, high tricuspid regurgitant jet velocity (TRV), macro-albuminuria or none. Clinical assessment, echocardiography, peripheral arterial tonometry, laboratory tests and blood viscosity measurement were performed. We explored statistical associations between the biological parameters and the six studied complications. Among 235 patients, 58 had high TRV, 46 osteonecrosis, 43 priapism, 33 leg ulcers, 31 retinopathy and 22 macroalbuminuria, whereas 36 had none of these complications. Multiple correspondence analysis revealed no cluster of complications. Lactate dehydrogenase levels were associated with high TRV, and blood viscosity was associated with retinopathy and the absence of macroalbuminuria. Despite extensive phenotyping of patients, no specific pattern of SCA-related complications was identified. New biomarkers are needed to predict SCA clinical expression to adapt patient management, especially in Africa, where healthcare resources are scarce.

Importance:An international comparison of pediatric outpatient prescriptions (POPs) is pivotal to investigate inadequate practices at the national scale and guide corrective actions. Objective:To compare annual POP prevalence among Organisation for Economic Co-operation and Development (OECD) member countries. Evidence Review:Two independent reviewers systematically searched PubMed, Embase, and institutes of public health or drug agency websites for studies published since 2000 and reporting POP prevalence (expressed as number of patients aged <20 years with ≥1 POP per 1000 pediatric patients per year) in OECD member countries or large geographic areas within them. Risk of bias was assessed for exhaustiveness and representativeness. Prevalence ratios (PRs) were used to compare the highest and lowest POP prevalence among countries overall, by levels of Anatomical Therapeutic Chemical (ATC) classification for the overall pediatric population, and by age group (ie, ages <5-6 vs ≥5-6 years), stratifying on prescription-only drug (POD) status. Findings:Among 11 studies performed on 3 regional and 8 national medicoadministrative databases in 11 countries, 35 552 550 pediatric patients were included. The overall risk of bias was low (10 studies were representative [90.9%], and the prevalence denominator included nonusers of health care for 9 studies [81.8%]). Prevalence of 1 or more POP per year ranged from 480 to 857 pediatric patients per 1000 in Sweden and France, respectively (PR, 1.8 [95% CI, 1.8-1.8]). Overall, among 8 studies reporting ATC level 1 drugs, Denmark had the lowest POP prevalence (eg, systemic hormonal preparations: 9 pediatric patients per 1000 per year) and France the highest (eg, systemic hormonal preparation: 216 pediatric patients per 1000 per year). Among 8 studies reporting ATC level 2 drugs for PODs, the PR between France and Denmark was 108.2 (95% CI, 108.2-108.2) for systemic corticosteroids and 2.1 (95% CI, 2.1-2.1) for drugs for obstructive airway disease. The PR for antibiotics was 3.4 (95% CI, 3.4-3.4) between New Zealand and Sweden. For pediatric patients aged 5 to 6 years or older, the PR for sex hormones was 2.1 (95% CI, 2.1-2.1) between Denmark and France. Among 7 studies reporting ATC level 5 drugs, the prevalence of the 10 most prevalent PODs was less than 100 pediatric patients per 1000 per year in Scandinavian countries and the Netherlands and less than 300 pediatric patients per 1000 per year in France and New Zealand. Conclusions and Relevance:This study found large between-country variations in POPs, which may suggest substantial inappropriate prescriptions. The findings may suggest guidance for educational campaigns and regulatory decisions in some OECD member countries.

Background Many children with sickle cell disease living in sub-Saharan Africa die before reaching age 5 years. We estimate the child mortality associated with sickle cell anaemia using an indirect approach to overcome the absence of systematic screening at birth. Methods We did a retrospective, multicentre, case-control study in five countries in sub-Saharan Africa (Burkina Faso, Democratic Republic of the Congo, Cote d'Ivoire, Mali, and Senegal). Women with at least one child with a confirmed SS haemoglobin phenotype (sickle cell anaemia) and who had at least three (alive or deceased) children from the same father born more than 5 years ago were recruited at an outpatient consultation in a sickle cell disease care centre. Women who had children without sickle cell disease (control group) were recruited from the same area, with inclusion criteria of being a neighbour or relative of one of the mothers included in the study who had a child with sickle cell anaemia, having no child or other first-degree relative with major sickle cell syndrome, having at least three children (alive or deceased) born more than 5 years ago, and having a confirmed haemoglobin AA phenotype. During the mothers' interview, we collected data concerning the mortality of siblings from the same father of a child with sickle cell anaemia and characteristics of the family, such as age at the time of the survey and the level of education of both parents. Mortality rates were calculated for children younger than 1, 5, and 10 years using the Kaplan-Meier method after excluding the index children. We assumed, as per Mendel law, that in families who have a child with sickle cell anaemia and healthy heterozygous parents, 25% of children born on average have sickle cell anaemia. A multivariate Cox model was used to describe socioeconomic and geographical factors associated with mortality. Findings Between Sept 1, 2017, and Nov 30, 2020, 1563 women who had at least one child with sickle cell anaemia and 4972 women from the same neighbourhood who had children without sickle cell disease were assessed for eligibility. Of 1563 women, 248 were excluded because the genotype of the index child was SC or S beta-thalassaemia. 1315 families with cases of sickle cell anaemia and 1243 control families were included in the study. The median age of children (alive) was 14 years (IQR 8-20) in control families and 13 years (8-19) in families with cases of sickle cell anaemia. 5532 [50.6%] of 10 924 children were male. Mortality rates were 15.3% (95% CI 13.3-17.3) for children with sickle cell anaemia younger than 1 year, 36.4% (33.4-39.4) for those younger than 5 years, and 43.3% (39.3-47.3) for those younger than 10 years. Multivariate Cox survival analysis showed that belonging to a family with sickle cell anaemia (hazard ratio [HR] 2.23, 95% CI 1.96-2.54), living in the Democratic Republic of the Congo (HR 1.64, 1.34-2.01), having an older parent (father or mother age had similar effect; HR 1.12, 1.05-1.19 per 10 years of age), or a significantly higher global Multidimensional Poverty Index (HR 1.09, 1.03-1.14), independently increased the risk of mortality. Whereas, living in Senegal (HR 0.70, 95% CI 0.57-0.86) or having a mother with higher education (high school HR 0.66, 0.55-0.80 or advanced HR 0.41, 0.28-0.61) independently decreased the risk of mortality. Interpretation Although higher than in high-income countries and affected by non-specific socioeconomic factors, the estimated mortality in children with sickle cell anaemia living in sub-Saharan African cities was substantially lower than previous estimates, suggesting an improvement of sickle cell anaemia care in this setting. Copyright (C) 2022 Elsevier Ltd. All rights reserved.

Background: Paediatric outpatient prescription (POP) monitoring is pivotal to identify inadequate prescriptions and optimize drug use. We aimed at describing recent trends in POPs in France. Methods: All reimbursed dispensations of outpatient prescribed drugs (excluding vaccines) were prospectively collected for the paediatric population (<18 years old) in the French national health database in 2010-2011 and 2018-2019 (mean 117,356,938/year). POP prevalence (proportion of children receiving >1 drug prescriptions/year) was calculated by age groups and compared by prevalence rate ratios (PRRs). Given the large sample size, 95% confidence intervals of POP prevalences and PRRs did not differ from estimates. Findings: Among the 14,510,023 children resident in France in 2018-2019, mean POP prevalence was 857% children. Most prescribed therapeutic classes were analgesics (643%), antibiotics (405%), nasal corticosteroids (328%), nonsteroidal anti-inflammatory drugs (NSAIDs) (244%), antihistamines (246%) and systemic corticosteroids (210%). POPs decreased with age from 976% for infants to 782% for adolescents. Children <6 years old were notably more exposed to inhaled corticosteroids (PRR=3.06), non-penicillin beta-lactam antibacterial agents (PRR=3.05) and systemic corticosteroids (PRR=2.11) than older ones. The POP prevalence was slightly higher (PRR=1.04) during 2018-2019 than 2010-2011, with marked increases for anti-emetics (PRR=1.84), vitamin D (PRR=1.49), proton pump inhibitors (PRR=1.42), systemic contraceptives (PRR=1.24) and nasal corticosteroids (PRR=1.21) and decreases for propulsive/prokinetic agents (PRR=0.09), NSAIDs (PRR=0.73) and systemic antibiotics (PRR=0.88). Interpretation: POP remained highly prevalent in France throughout the 2010s, especially for children <6 years old, with only a few improvements for selected therapeutic classes. These findings should prompt clinical guidance campaigns and/or regulatory policies. (C) 2021 The Authors. Published by Elsevier Ltd.

Although most individuals with sickle cell disease (SCD) live in sub-Saharan Africa, the natural history of the disease on this continent remains largely unknown. Intravascular haemolysis results in activation of circulating blood cells and release of microparticles (MPs) that exert pro-inflammatory effects and contribute to vascular damage. We designed a case-control study nested in the CADRE cohort (Coeur-Artère-DRÉpanocytose, clinical trials.gov identifier NCTO3114137) and based on extreme phenotypes, to analyse blood cell-derived MPs in 232 adult SS patients at steady state in Bamako and Dakar. Thirty-six healthy adult controls matched by age and sex were recruited in Bamako. The MPs concentrations were higher in SS patients compared to AA controls with a predominance of erythrocyte- and reticulocyte-derived MPs. These erythroid-derived MPs were significantly lower in patients with retinopathy ( P  = 0·022). Reticulocyte-derived MPs were significantly negatively and positively associated with a history of priapism ( P  = 0·020) and leg ulcers ( P  = 0·041) respectively. We describe for the first time the comparative patterns of plasma MPs in healthy subjects and patients with SCD living in sub-Saharan Africa and exhibiting various complications. Because our present results show no clear pattern of correlation between erythroid MPs and the classical hyper-haemolytic complications, we hypothesise a weak relevance of the hyper-haemolysis versus hyper-viscous paradigm in Africa.

Background: Paediatric outpatient prescription (POP) monitoring is pivotal to identify inadequate prescriptions and optimize drug use. We aimed at describing recent trends in POPs in France. Methods: All reimbursed dispensations of outpatient prescribed drugs (excluding vaccines) were prospectively collected for the paediatric population (<18 years old) in the French national health database in 2010–2011 and 2018–2019 (mean 117,356,938/year). POP prevalence (proportion of children receiving ≥1 drug prescriptions/year) was calculated by age groups and compared by prevalence rate ratios (PRRs). Given the large sample size, 95% confidence intervals of POP prevalences and PRRs did not differ from estimates. Findings: Among the 14,510,023 children resident in France in 2018–2019, mean POP prevalence was 857‰ children. Most prescribed therapeutic classes were analgesics (643‰), antibiotics (405‰), nasal corticosteroids (328‰), nonsteroidal anti-inflammatory drugs (NSAIDs) (244‰), antihistamines (246‰) and systemic corticosteroids (210‰). POPs decreased with age from 976‰ for infants to 782‰ for adolescents. Children <6 years old were notably more exposed to inhaled corticosteroids (PRR=3.06), non-penicillin beta-lactam antibacterial agents (PRR=3.05) and systemic corticosteroids (PRR=2.11) than older ones. The POP prevalence was slightly higher (PRR=1.04) during 2018–2019 than 2010–2011, with marked increases for anti-emetics (PRR=1.84), vitamin D (PRR=1.49), proton pump inhibitors (PRR=1.42), systemic contraceptives (PRR=1.24) and nasal corticosteroids (PRR=1.21) and decreases for propulsive/prokinetic agents (PRR=0.09), NSAIDs (PRR=0.73) and systemic antibiotics (PRR=0.88). Interpretation: POP remained highly prevalent in France throughout the 2010s, especially for children <6 years old, with only a few improvements for selected therapeutic classes. These findings should prompt clinical guidance campaigns and/or regulatory policies. Funding: Internal funding

Objectives: To describe changes in the dispensation of 11 mandatory vaccines to infants in France during the COVID-19 pandemic in 2020, considering the priming doses and boosters separately. Methods: With data from the French national health database, all dispensations of priming doses and boosters of 11 mandatory vaccines [penta/hexavalent, measles mumps rubella (MMR), meningococcal conjugate type-C (Men-C-C), 13-valent pneumococcal conjugate (PCV13)] for infants ≤24 months old were aggregated by 4-week periods in 2020. Expected counts in 2020 were estimated according to counts in 2019 weighted by a ratio considering the level of vaccine dispensation before the pandemic onset in 2020. Relative differences (RDs) and their 95% confidence intervals (CIs) were computed to compare the observed and expected counts during the first and second lockdown and the period in between. Results: During the first 4 weeks of the first lockdown, as compared with the expected numbers, the observed priming dose counts substantially decreased [RD: from −5.7% (95% CI −6.1; −5.2) for penta/hexavalent to −25.2% (95% CI −25.6; −24.8) for MMR], as did the booster counts [RD: from −15.3% (95% CI −15.9; −14.7) for penta/hexavalent to −20.7% (95% CI −21.3; −20.2) for Men-C-C]. Counts for priming doses and boosters remained slightly below the expected numbers after the lockdown. During 2020, MMR priming doses and the Men-C-C booster had the greatest shortfalls ( N = 84,893 and 72,500, respectively). Conclusions: This study provides evidence of a lack of vaccination catch-up after the first lockdown and a persistent shortfall in infant vaccination after the first 10 months of the COVID-19 pandemic in France, especially for the MMR priming doses and Men-C-C booster.

AIMS:We aimed to investigate time trends in cardiovascular health (CVH) metrics in the population at large, as well as in important subgroups. METHODS AND RESULTS:In this study, we used a community-based sample of 366 270 adults from France who had a standardized examination to assess cardiovascular risk factors between 1992 and 2011 (20 years). Cardiovascular health metrics categorized into ideal, intermediate, and poor categories were computed using smoking, physical activity, body mass index, total cholesterol, blood glucose, and blood pressure. Matching on age, sex, and depression across 5-year periods (1992-96, 1997-2001, 2002-06, and 2007-11) was performed in order to correct for the sociodemographic differences between the examinations at different periods of times. Mean age across all four time periods was 44.7 (SD 13) years and 38% (138 228) were women. Overall, few participants (≤3.5%) met all six ideal CVH metrics at any time point. The prevalence of meeting ≥5 ideal CVH metrics increased from 6.7% in 1992-96 to 15.0% in 2007-11 (P < 0.001). A significant improvement in CVH (meeting ≥5 ideal CVH metrics) from 1992 to 2011 was observed among younger (from 7.5% to 16.6%) and older individuals (from 1.3% to 4.2%), men (from 4.4% to 11.8%) and women (from 10.4% to 20.1%), those with low (from 9.1% to 10.4%) and high education status (from 15% to 18.1%) and those with (from 5.1% to 12.7%) and without depressive symptoms (from 6.8% to 15.1%). However, the rate of improvement was steepest in the most affluent group in comparison with those with lower socio-economic status. CONCLUSION:Overall CVH improved from 1992 until 2006 and slightly decreased between 2006 and 2011 in French adults. From 1992 until 2006, the improvement in CVH was less pronounced among those with low socio-economic status as compared to those with a higher socio-economic status.

Background Blood transfusion is the cornerstone treatment to reduce the clinical severity of sickle cell disease (SCD), but we need to maintain the haematocrit (Hct) within an acceptable range to avoid a deleterious increase in blood viscosity. The aim of this study was to compare the effects of manualversusautomated red blood cell (RBC) Exchange on haematological parameters and blood viscosity. Study design and methods This prospective, single-centre, open nonrandomized observational study included forty-three sickle cell patients: 12 had automated RBC Exchange and 31 manual RBC Exchange. Samples were collected in EDTA tubes just before and within one hour after the end of the RBC Exchange to measure the haematological parameters and blood viscosity. Results Both automated and manual RBC Exchange decreased haemoglobin S levels and leucocyte and platelet counts, but the decrease was greater for automated RBC Exchange. Manual RBC Exchange caused a significant rise in haematocrit and haemoglobin levels and did not change blood viscosity. In contrast, automated RBC Exchange decreased blood viscosity without any significant change in haematocrit and only a very slight increase in haemoglobin levels. The change in blood viscosity correlated with the modifications of haematocrit and haemoglobin levels, irrespective of the RBC Exchange procedure. When adjusted for the volume of RBC Exchange, the magnitude of change in each biological parameter was not different between the two procedures. Conclusion Our study demonstrates that the automated RBC Exchange provided greater haematological and haemorheological benefits than manual RBC Exchange, mainly because of the higher volume exchanged, suggesting that automated RBC Exchange should be favoured over manual RBC Exchange when possible and indicated.

Objective: Impaired baroreflex function is an early indicator of cardiovascular autonomic imbalance. Patients with type 2 diabetes mellitus (T2D) have decreased baroreflex sensitivity (BRS), however, whether the neural and/or mechanical component of the BRS (nBRS and mBRS, respectively) is altered in those with high metabolic risk (HMR, impaired fasting glucose and/or metabolic syndrome) or with overt T2D, is unknown. We examined this in a community-based observational study, the Paris Prospective Study III (PPS3). Approach and Results: In 7626 adults aged 50 to 75 years, resting nBRS (estimated by low-frequency gain, from carotid distension rate and RR intervals [time intervals between successive R waves]) and mBRS were measured by high-precision carotid echotracking. The associations between overt T2D or HMR as compared with subjects with normal glucose metabolism (NGM) and nBRS or mBRS were quantified using multivariable linear regression analysis. There were 319 subjects with T2D (61±6 years, 77% male), 1450 subjects with HMR (60±6 years, 72% male), and 5857 subjects with NGM (59±6 years, 57% male). Compared with NGM subjects, nBRS was significantly lower in HMR subjects (β=−0.07 [95% CI, −0.12 to −0.01]; P =0.029) and in subjects with T2D (β=−0.18 [95% CI, −0.29 to −0.07]; P =0.002) after adjustment for confounding and mediating factors. Subgroup analysis suggests significant and independent alteration in mBRS only among HMR patients who had both impaired fasting glucose and metabolic syndrome. Conclusions: In this community-based study of individuals aged 50 to 75, a graded decrease in nBRS was observed in HMR subjects and patients with overt T2D as compared with NGM subjects.

Background: The impact of changes in cardiovascular health (CVH) on cardiovascular disease (CVD) and total and all-cause mortality has yet to be described. Methods: CVH was computed according to smoking, body mass index, total cholesterol, blood glucose and blood pressure, physical activity and diet. Change in CVH was defined as a point-to-point difference in each metric or the score. We used time-dependent Cox Proportional Hazard models to calculate hazard ratios for all-cause mortality and CVD events among 10,656 adult participants from the ARIC study, aged 44 to 66 years at baseline (1987-1989) and followed up until 2014. Hazard ratios for all-cause mortality and CVD event according to CVH change at the component metrics and an aggregate score level were calculated with Cox Proportional Hazard models with consistently low CVH considered as the reference group. Results: Overall, 17% of the sample improved their overall CVH, while the percentage which maintained a low CVH or decreased CVH was 29% and 21%, respectively. Higher levels of overall CVH over time were associated with a graded decrease in risk in CVD events and all-cause mortality. The hazard ratios for all-cause mortality among participant that decreased their overall CVH from favorable to low or moderate, that increased their CVH from low to moderate or favorable, and had consistently favorable CVH, as compared with the constantly low CVH group, were: 0.47 (95% confidence interval [CI], 0.39 to 0.57), 0.80 (95 CI%, 0.72 to 0.89), and 0.37 (95% CI, 0.30 to 0.46). The risk reductions were of a same magnitude for CVD events. In the adjusted Cox time dependent model, compared with low overall CVH, having moderate or favorable CVH was associated with a decreased risk in mortality: 24% (HR=0.76, 95% CI, 0.72 to 0.80) and 44% (HR=0.56, 95% CI, 0.51 to 0.62), respectively and a decreased risk in CVD 37% (HR=0.63, 95% CI, 0.59 to 0.66) and 56% (HR=0.44, 95% CI, 0.39 to 0.49), respectively. Conclusion: Earlier life stage favorable CVH was associated with lower CVD events and total and cause-specific mortality regardless of CVH change patterns over time. Furthermore, improving CVH is associated with lower CVD event risk and lower total and all-cause mortality. However, we observed an alarming low percentage of overall CVH improvement and a high percentage of maintaining low overall CVH. Understanding the mechanisms underlying CVH change patterns may help to tackle the low prevalence of moderate or optimal CVH.

Background: Current time trends of objectively measured cardiovascular health and their relation with population attributable risk for mortality over time -in Western Europe are unknown.We aimed to investigate time trends in cardiovascular health metrics and estimate the population attributable risks of these metrics in relation to all-cause mortality in the population at large, as well as in important subgroups. Methods: In this study, we used a community-based sample of 366,270 adults from France who had a standardized examination to assess cardiovascular risk factors between 1992 and 2011 and with outcome surveillance spanning until 2016 (25 years), Temporal trends of cardiovascular health metrics were computed using metrics defined by the American Heart Association:smoking, body mass index, total cholesterol, blood glucose and blood pressure and physical activity. Population attributable fraction for all-cause mortality over 25 years were measure. Results: Mean age was 44.7 (SD 13) years and 38% (138,228) were women. Overall, few participants (≤3.5%) met all 6 ideal cardiovascular health metrics at any timepoint. The prevalence of meeting ≥5 ideal cardiovascular health metrics increased from 6.2% in 1992-1996 to 16.6% in 2007-2011 (P<.001). An improvement in cardiovascular health was observed in all subgroups, i.e. younger (from 7.1% to 18.5%) and older individuals (from 1.2% to 4.2%), men (from 3.9% to 12.2%) and women (from 10.1% to 22.5%), those with low (from 8.6% to 11.6%) and high education status (from 14.0% to 19.5%) and those with (from 4.7% to 14.8%)and without depressive symptoms (from 6.5% to 16.8%). However, the rate of improvement was steepest in the most affluent group in comparison with those with lower socio-economic status. Furthermore, the improvement in overall cardiovascular health plateaued between 2002-2006 and 2007-2011, and the population attributable risks for all-cause mortality remained high over time. Conclusions and relevance: Overall cardiovascular health improved from 1992 until 2011 in French adults from the community who benefited from a free standardized health examination. However, the improvement in cardiovascular health was less strong in those with low socio-economic status as compared to those with a higher socio-economic status. Furthermore, the fraction of all-cause mortality attributable to cardiovascular health remained high throughout the study period.

Physical activity (PA) is a preventative behavior for noncommunicable disease. However, little consideration is given as to whether different domains of PA have differing associations with health outcomes. We sought to determine the association between occupational, sport, leisure, and total PA with baroreflex sensitivity (BRS), distinguishing between neural (nBRS) and mechanical (mBRS) BRS. In a cross-sectional analysis of 8649 adults aged 50 to 75 years, resting nBRS (estimated by low-frequency gain, from carotid distension rate and heart rate) and mBRS (carotid stiffness) were measured by high-precision carotid echo-tracking. PA was self-reported using the validated Baecke questionnaire. The associations between PA and nBRS and mBRS were quantified using multivariate linear regression analysis, separately in the working and nonworking population. In working adults (n=5039), occupational PA was associated with worse nBRS (unstandardized β=-0.02; [95% CI, -0.04 to -0.003]; P=0.022) whereas sport PA was associated with better nBRS (β=0.04; [95% CI, 0.02-0.07]; P=0.003) and mBRS (β=-0.05; [95% CI, -0.09 to -0.00001]; P=0.049). Neither leisure PA nor total PA was associated with nBRS or mBRS. In nonworking adults (n=3610), sport PA and total PA were associated with better mBRS (β=-0.08; [95% CI, -0.15 to 0.02]; P=0.012 and β=-0.05; [95% CI, -0.10 to 0.009]; P=0.018) but not nBRS. These findings suggest differential associations between domains of PA and BRS and may provide insights into the mechanisms underlying the association between occupational PA and cardiovascular disease.

Sickle cell disease (SCD) prevalence has increased rapidly in Europe as a result of an increase in the life expectancy of these patients and the arrival of SCD migrants from Africa. The aim of our study was to compare the phenotypes of adult patients born in Sub-Saharan Africa (SSA) who migrated to France with those of patients with the same origin who were born in France. This single-center observational study compared the demographic, clinical and biological characteristics of SCD adult patients of SSA origin who were born in France or SSA. Data were collected from computerized medical charts. Groups were compared using multivariate logistic regression with adjustment for age, gender and type of SCD. Of the 323 SCD patients followed in our center, 235 were enrolled, including 111 patients born in France and 124 patients born in SSA. SCD genotypes were balanced between groups. Patients born in Africa were older (median age 32.1 (24.4–39) vs. 25.6 (22.1–30.5) years, p < 0.001) and more often women (n = 75 (60.5%) vs. 48 (43.2%), p = 0.008). The median age at arrival in France was 18 years (13–23). The median height was lower among patients born in SSA (169 (163–175) vs. 174.5 cm (168–179), p < 0.001). Over their lifetimes, patients born in France had more acute chest syndromes (median number 2 (1–4) vs. 1 (0–3), p = 0.002), with the first episode occurring earlier (19 (11.6–22.3) vs. 24 (18.4–29.5) years, p < 0.007), and were admitted to intensive care units more often (53.3% vs. 34.9%, p = 0.006). This difference was more pronounced in the SS/Sβ0 population. Conversely, patients born in SSA had more skin ulcers (19.4% vs. 6.3%, p = 0.03). No significant differences were found in social and occupational insertion or other complications between the two groups. Patients born in SSA had a less severe disease phenotype regardless of their age than those born in France. This difference could be related to a survival bias occurring in Africa during childhood and migration to Europe that selected the least severe phenotypes.

L'insuffisance rénale chronique est devenue l'une des principales causes de mortalité de l'adulte drépanocytaire. Pour autant l'histoire naturelle de la néphropathie drépanocytaire est encore mal connue. L'identification des patients à risque de progression vers la maladie rénale chronique est importante pour permettre la mise en place d'interventions précoces. L'objectif de cette étude est la recherche de facteurs de risque de dégradation de la fonction rénale chez les patients drépanocytaires africains. Cœur, Artères et DREpanocytose (CADRE) est une étude prospective observationnelle multicentrique menée dans 5 pays d'Afrique (Cameroun, Sénégal, Côte d'Ivoire, Mali et République Démocratique du Congo). La phase d'inclusion a eu lieu de 2011 à 2013, la phase de suivi est en cours depuis 2016. Tous les patients drépanocytaires âgés de plus de 5 ans pouvaient être inclus. L'exploration des paramètres mesurés : cliniques, biologiques et échocardiographiques était réalisée en situation clinique stable. Le débit de filtration glomérulaire (DFG) a été calculé avec la formule CK-EPI. Deux groupes phénotypiques ont été réalisés pour les analyses : les sujets SS ou Sβ0 (SS/Sβ0) et les sujets SC ou Sβ+ (SC/Sβ+). Le critère de jugement principal était la pente de dégradation du DFG (DFG final-DFG initial/durée de suivi). Les analyses multivariées ont été réalisées avec ajustement sur l'âge, le sexe, le pays à l'aide de régression linéaire et ont été stratifiées selon le phénotype. Au total, 1404 patients avaient été revus au moment de notre analyse intermédiaire, 154 ont été exclus en l'absence de créatininémie mesurée à l'inclusion, 76 patients sont décédés ayant d'avoir pu être réévalués et les 165 patients du Sénégal ont été exclus en raison d'un excès de données biologiques manquantes. Au total, 1009 patients ont été inclus, 424 provenant de Côte d'Ivoire, 585 provenant du Mali. Quatre cent quarante patients avaient un phénotype SC/Sβ+ et 569 patients avaient un phénotype SS/Sbeta0. Leur durée de suivi moyenne était de 4,7 années. L'âge médian des patients était de 21 ans et 26 ans respectivement dans les groupes SS/Sβ0 et SC/Sβ+. Le ratio femme/homme était de 1,3. La dégradation médiane du DFG était de 1,04 mL/min/an pour les SS/Sβ0 et de 1,19 mL/min/an pour les SC/Sβ+. Seulement 82 patients avaient un DFG inférieur à 90 mL/min et 16 patients avaient un DFG inférieur à 60 mL/min. En analyse univariée, l'âge, l'IMC, la pression artérielle systolique, la présence d'ictère, un taux bas d'hémoglobine, un taux élevé de polynucléaires neutrophiles, une hyperfiltration initiale étaient associés à une dégradation significativement plus importante du DFG alors qu'un antécédent d'ostéonécrose et une fréquence plus élevée de crises vaso-occlusives étaient significativement associés à une diminution moins importante du DFG. En analyse multivariée, la pente de dégradation du DGF était associée au sexe masculin (bêta = −1,5576, p = 0,01), aux paramètres d'hémolyse initiaux (ictère [bêta = −2,06, p = 0,001] et hémoglobinémie [bêta = 0,75, p = 0,001]) chez les patients SS/Sβ0, mais pas chez les patients SC/Sβ+. Pour tous les phénotypes, un taux de polynucléaires élevé était associé à une dégradation plus importante du DFG (B = −1,07, p < 0,001 et B = −1,06, p = 0,02). À notre connaissance, cette étude est la première étude prospective de patients drépanocytaires en Afrique étudiant l'évolution de la fonction rénale chez l'enfant et l'adulte et incluant tous les phénotypes drépanocytaires. Du fait de leur jeune âge, peu de patients de notre cohorte ont un DFG inférieur à 60 mL/min. En l'absence de critère de substitution validé pour étudier la néphropathie drépanocytaire, nous avons choisi d'étudier la pente de dégradation du DFG. Une association avec les paramètres d'hémolyse (ictère et hémoglobine) est retrouvée uniquement chez les patients SS/Sβ0. De façon inattendue la présence initiale de micro-albuminurie n'est pas prédictive de dégradation du DFG. Mais on observe également, que les patients ayant un DFG initial très élevé, ont une dégradation plus rapide de leur DFG. L'hyperfiltration glomérulaire initiale correspond donc probablement à un facteur de confusion. Il est impossible de différentier les patients dont le DFG revient simplement à la normale de ceux qui vont évoluer vers une insuffisance rénale chronique. L'analyse des données complètes de la cohorte CADRE nous permettra d'affiner nos résultats, mais pour éviter de potentielles erreurs induites par l'analyse de critère intermédiaires non validés, un suivi prolongé sera nécessaire afin d'étudier un nombre suffisant de patients atteignant le stade d'insuffisance rénale.

Introduction: Risk assessment of sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM) remains subject of debate. Hypothesis: Use of implantable cardioverter defibrillator (...

SummaryAlthough most individuals with sickle cell disease (SCD) live in sub‐Saharan Africa, the natural history of the disease on this continent remains largely unknown. Intravascular haemolysis results in activation of circulating blood cells and release of microparticles (MPs) that exert pro‐inflammatory effects and contribute to vascular damage. We designed a case‐control study nested in the CADRE cohort (Coeur‐Artère‐DRÉpanocytose, clinical trials.gov identifier NCTO3114137) and based on extreme phenotypes, to analyse blood cell‐derived MPs in 232 adult SS patients at steady state in Bamako and Dakar. Thirty‐six healthy adult controls matched by age and sex were recruited in Bamako. The MPs concentrations were higher in SS patients compared to AA controls with a predominance of erythrocyte‐ and reticulocyte‐derived MPs. These erythroid‐derived MPs were significantly lower in patients with retinopathy (P = 0·022). Reticulocyte‐derived MPs were significantly negatively and positively associated with a history of priapism (P = 0·020) and leg ulcers (P = 0·041) respectively. We describe for the first time the comparative patterns of plasma MPs in healthy subjects andpatients with SCD living in sub‐Saharan Africa and exhibiting various complications. Because our present results show no clear pattern of correlation between erythroid MPs and the classical hyper‐haemolytic complications, we hypothesise a weak relevance of the hyper‐haemolysis versus hyper‐viscous paradigm in Africa.

Although most individuals with sickle cell disease (SCD) live in sub-Saharan Africa, the history of the disease in this continent remains largely unknown. SCD is characterized by chronic hemolytic anemia, acute-vaso occlusive events and progressive vascular organ damage. The CADRE study is a large cohort of SCD patients in five countries of West and Central Africa aiming at studying SCD-related vascular complications. The inclusion data of this study did not match the hyper-hemolysis paradigm (Dubert et al. Blood 2018), but several methodological limitations were raised, including probable mortality bias and questionable reliability of classical hemolysis markers in Africa. For the 5-year follow-up of the CADRE study, we designed a case-control study nested in the cohort, based on extreme phenotypes, to look for new markers of vasculopathy, including new markers of hemolysis. Patients and Methods SS adult patients of the CADRE cohort were selected in the centres of Dakar (Senegal) and Bamako (Mali), depending on the presence of none or at least one of the following complications at inclusion: tricuspid regurgitant jet velocity (TRJV)>2,5 m/s (which may indicate pulmonary hypertension), albuminuria/creatininuria>100 mg/g, leg ulcer, priapism, aseptic osteonecrosis and retinopathy. We chose the youngest patients with a vascular complication and the oldest without any complication. Overall, 6 groups of 40 SS patients with extreme phenotypes were constituted (20 in each centre). Patients were called for a specific visit and investigated at steady state. Besides clinical examination, usual laboratory blood tests and albuminuria measure, additional plasma and saliva samples were collected. A trained investigator isolated microparticles immediately after blood sampling by successive centrifugations, measured blood and plasma viscosities and assessed microcirculation function using peripheral arterial tonometry. A cardio-echography was performed by a trained cardiologist. Plasma samples were stored at -80 °C and shipped to Paris. High technology tests were performed in Paris, including blood cell derived microparticles, free hemoglobin, inflammatory cytokines, neutrophile extracellular trap (NETs). Using saliva DNA, we also genotyped the known SCD genetic modifiers and new candidate genes implicated in the catabolism of hemoglobin. Potential associations between those markers, usual hematological parameters, and the vascular complications were assessed statistically . Results We recalled 240 selected patients 5 years after their first visit: 38 could not be retrieved, 21 had deceased, 62 had at least one new complication, and only 15 still had no complication. Therefore, we selected 56 more patients to obtain at least 30 patients in each group. 237 SS adults were eventually investigated and the plasma samples of 232 SS patients were analyzable in Paris (106 from Bamako and 126 from Dakar). In these patients, at a mean age of 29 years (+/- 11), high TRJV was present in 58, macroalbuminuria in 33, leg ulcers in 36, priapism in 43, aseptic osteonecrosis in 45 and retinopathy in 31 whereas 28 had no vascular complication. A principal component analysis found no cluster of complications. Among patients with one "hyper-viscous" complication (retinopathy or osteonecrosis) or more, 78% also had at least one "hyper-haemolytic" complication (high TRJV, albuminuria, leg ulcer or priapism) and 49% of patients with a "hyper-haemolytic" complication also had a "hyper-viscous" complication. The microvascular function was not associated with any of the complications, whereas higher blood viscosity was associated with retinopathy. The results of the associations between the vascular complications and specific biological tests are presented in other publications. Conclusion This study illustrates the feasibility of high-technology experiments in SCD patients living in sub-Saharan Africa, but was particularly challenging because of the difficulty to prepare, store and transport frozen plasma samples. Moreover, in agreement with previously published data from the CADRE study, we found that the dichotomization of vascular complications into hyperhemolytic and hyperviscous subgroups is not clinically relevant in Africa. Other simple predictive markers of vascular complication are needed to optimize the follow-up of African patients with SCD. Disclosures No relevant conflicts of interest to declare.

Background and aims: To study the association between chewing capacity-a prerequisite for eating- and the level of cardiovascular health (CVH). Methods: This is a cross-sectional analysis conducted on 5430 study participants from the Paris Prospective Study 3 that were subjected to an oral examination by trained dentists at study recruitment between 2008 and 2012. Chewing capacity was determined by the number of functional tooth units (FTUs), and >= 5FTUs defined adequate chewing capacity. Subjects were categorized into poor, intermediate, or ideal CVH for the 4 behavioural (smoking status, body mass index, physical activity, diet) and the 3 biological (total cholesterol, fasting glycemia, and blood pressure) factors according to the American Heart Association Life's Simple 7. Multinomial logistic regression was used to explore the association between the number of FTUs (exposure) and ideal or intermediate vs. poor CVH (main outcome). Results: 10.31% of the study participants had an ideal CVH and 7% presented an impaired chewing capacity (<5 FTUs). Subjects with at least 5 FTUs (OR = 2.37; 95% CI: 1.37-4.12) were more likely to have an ideal global CVH, after adjustment for age, sex, marital status, education, deprivation, depressive status, and dental plaque. This association existed for the behavioural but not the biological CVH, with the strongest association being observed with the diet metric. Conclusion: This is the first study suggesting that adults with a preserved chewing capacity have an increased likelihood to be at an ideal behavioural CVH. (C) 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.