Association of haemolysis markers, blood viscosity and microcirculation function with organ damage in sickle cell disease in sub-Saharan Africa (the BIOCADRE study).

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.

Cell-derived microparticles and sickle cell disease chronic vasculopathy in sub-Saharan Africa: A multinational study.

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.

Type 2 Diabetes Mellitus Is Independently Associated With Decreased Neural Baroreflex Sensitivity: The Paris Prospective Study III.

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 BRS (nBRS) and mechanical component of the BRS is altered in those with high metabolic risk (HMR, impaired fasting glucose and 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 [time elapsed between two successive R waves] intervals) and mechanical BRS were measured by high-precision carotid echotracking. The associations between overt T2D or HMR as compared with subjects with normal glucose metabolism and nBRS or mechanical BRS 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 normal glucose metabolism (59±6 years, 57% male). Compared with normal glucose metabolism, nBRS was significantly lower in HMR subjects (ß=-0.07 [95% CI, -0.12 to -0.01]; P=0.029) and in subjects with T2D (ß=-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 mechanical BRS 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 normal glucose metabolism subjects.

Automated RBC Exchange has a greater effect on whole blood viscosity than manual whole blood exchange in adult patients with sickle cell disease.

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 manual versus automated 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.

Prevalence and correlates of growth failure in young African patients with sickle cell disease.

Growth failure (GF) in children with sickle cell disease (SCD) tends to decline in high-income countries, but data are lacking in sub-Saharan Africa. We performed a cross-sectional study nested in the CADRE (Cœur, Artères et DREpanocytose) cohort in Mali, Senegal, Cameroon, Gabon and the Ivory Coast. SCD patients and healthy controls aged 5-21 years old were recruited (n = 2583). Frequency of GF, defined as a height, weight or body mass index below the 5th percentile on World health Organization growth charts, was calculated. We assessed associations between GF and SCD phenotypic group, clinical and biological characteristics and history of SCD-related complications. GF was diagnosed in 51% of HbSS, 58% of HbSß0 , 44% of HbSC, 38% of HbSß+ patients and 32% of controls. GF in patients was positively associated with parents' lower education level, male sex, age 12-14 years, lower blood pressure, HbSS or HbSß0 phenotypes, icterus, lower haemoglobin level, higher leucocyte count and microalbuminuria. No association was found between GF and clinical SCD-related complications. In sub-Saharan Africa, GF is still frequent in children with SCD, especially in males and during adolescence. GF is associated with haemolysis and microalbuminuria, but not with the history of SCD-related clinical complications.

A useful scoring system for the prediction and management of delayed graft function following kidney transplantation from cadaveric donors.

Delayed graft function (DGF) is a common complication in kidney transplantation and is known to be correlated with short- and long-term graft outcomes. Here we explored the possibility of developing a simple tool that could predict with good confidence the occurrence of DGF and could be helpful in current clinical practice. We built a score, tentatively called DGFS, from a French multicenter and prospective cohort of 1844 adult recipients of deceased donor kidneys collected since 2007, and computerized in the Données Informatisées et VAlidées en Transplantation databank. Only five explicative variables (cold ischemia time, donor age, donor serum creatinine, recipient body mass index, and induction therapy) contributed significantly to the DGF prediction. These were associated with a good predictive capacity (area under the ROC curve at 0.73). The DGFS calculation is facilitated by an application available on smartphones, tablets, or computers at www.divat.fr/en/online-calculators/dgfs. The DGFS should allow the simple classification of patients according to their DGF risk at the time of transplantation, and thus allow tailored-specific management or therapeutic strategies.

Pediatric Outpatient Prescriptions in Countries With Advanced Economies in the 21st Century: A Systematic Review.

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.

Estimating the risk of child mortality attributable to sickle cell anaemia in sub-Saharan Africa: a retrospective, multicentre, case-control study.

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, Côte 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 ß-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. FUNDING: Fondation Pierre Fabre. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Paediatric outpatient prescriptions in France between 2010 and 2019: A nationwide population-based study: Paediatric outpatient prescriptions in France, 2010 to 2019.

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.

Mandatory Infant Vaccinations in France During the COVID-19 Pandemic in 2020.

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.

Temporal trends of cardiovascular health factors among 366 270 French adults.

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.

Chewing capacity and ideal cardiovascular health in adulthood: A cross-sectional analysis of a population-based cohort study.

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.

Comparison between Adult Patients with Sickle Cell Disease of Sub-Saharan African Origin Born in Metropolitan France and in Sub-Saharan Africa.

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/Sß0 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.

Epidemiological transition in morbidity: 10-year data from emergency consultations in Dakar, Senegal.

BACKGROUND: It is thought that low-income countries are undergoing an epidemiological transition from infectious to non-communicable diseases; however, this phenomenon is yet to be examined with long-term data on morbidity. METHODS: We performed a prospective evaluation of all emergency medical consultations at a major emergency service provider in Dakar, Senegal from 2005 to 2014. Using standardised definitions, the primary diagnosis for each consultation was classified using the International Classification of Diseases-10 and then broadly categorised as 'infectious', 'non-communicable' and 'other' diseases. Morbidity rates for each year in the 10-year observation period were plotted to depict the epidemiological transition over time. To quantify the yearly rate ratios of non-communicable over infectious diagnosis, we used a generalised Poisson mixed model. RESULTS: Complete data were obtained from 49 702 visits by African patients. The mean age was 36.5±23.2 and 34.8±24.3 years for women and men, respectively. Overall, infections accounted for 46.3% and 42.9% and non-communicable conditions 32.2% and 40.1% of consultations in women and men, respectively. Consultation for non-communicable compared with infectious conditions increased by 7% every year (95% CI: 5% to 9%; p<0.0001) over the 10 years. Consultations for non-communicable condition were more likely in women compared with men (RR=1.29, 95% CI: 1.18, 1.40) and at older ages (RR=1.27; 95% CI 1.25, 1.29 for 10-year increase in age). CONCLUSION: Using high-quality disease morbidity data over a decade, we provide novel data showing the epidemiological transition of diseases as manifested in emergency service consultations in a large Sub-Saharan African city. These results can help reorientation of healthcare policy in Sub-Saharan Africa.

Carotid Artery Stiffness and Incident Depressive Symptoms: The Paris Prospective Study III.

BACKGROUND: Arterial stiffness may contribute to late-life depression via cerebral microvascular damage, but evidence is scarce. No longitudinal study has evaluated the association between arterial stiffness and risk of depressive symptoms. Therefore, we investigated the association between carotid artery stiffness and incident depressive symptoms in a large community-based cohort study. METHODS: This longitudinal study included 7013 participants (mean age 59.7 ± 6.3 years; 35.8% women) free of depressive symptoms at baseline. Carotid artery stiffness (high-resolution echo tracking) was determined at baseline. Presence of depressive symptoms was determined at baseline and at 4 and 6 years of follow-up, and was defined as a score ≥7 on the validated Questionnaire of Depression, Second Version, Abridged and/or new use of antidepressant medication. Logistic regression and generalized estimating equations were used. RESULTS: In total, 6.9% (n = 484) of the participants had incident depressive symptoms. Individuals in the lowest tertile of carotid distensibility coefficient (indicating greater carotid artery stiffness) compared with those in the highest tertile had a higher risk of incident depressive symptoms (odds ratio: 1.43; 95% confidence interval: 1.10-1.87), after adjustment for age, sex, living alone, education, lifestyle, cardiovascular risk factors, and baseline Questionnaire of Depression, Second Version, Abridged scores. Results were qualitatively similar when we used carotid Young's elastic modulus as a measure of carotid stiffness instead of carotid distensibility coefficient, and when we used generalized estimating equations instead of logistic regression. CONCLUSIONS: Greater carotid stiffness is associated with a higher incidence of depressive symptoms. This supports the hypothesis that carotid stiffness may contribute to the development of late-life depression.

Association Between Occupational, Sport, and Leisure Related Physical Activity and Baroreflex Sensitivity: The Paris Prospective Study III.

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 ß=-0.02; [95% CI, -0.04 to -0.003]; P=0.022) whereas sport PA was associated with better nBRS (ß=0.04; [95% CI, 0.02-0.07]; P=0.003) and mBRS (ß=-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 (ß=-0.08; [95% CI, -0.15 to 0.02]; P=0.012 and ß=-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.

Influence of centre expertise on the diagnosis and management of hypertrophic cardiomyopathy: A study from the French register of hypertrophic cardiomyopathy (REMY).

BACKGROUND: Our knowledge of hypertrophic cardiomyopathy (HCM) mainly originates from quarternary centres. The objective is to assess the current management of HCM patients in a large multicentre French register according to the level of expertise. METHODS AND RESULTS: A total of 1431 HCM patients were recruited across 26 (11 expert and 15 non-expert) centres in REMY, a prospective hospital-based register of adult HCM patients. A sarcomeric origin was suspected in 1284 (89.7%) patients [261 (20.3%) with a reported gene mutation, 242 (18.8%) genotype-negative], while 107 (7.5%) had a diagnosis of non-sarcomeric HCM. Patients managed in non-expert centres were older (P < 0.01) and presented more often with NYHA III/IV class dyspnoea (P < 0.01), congestive heart failure (P < 0.01), low LEVF (P < 0.01), less often with a syncope history (P < 0.01) and lower LV obstruction (P < 0.01) than patients in expert centres. Genotype positive sarcomeric aetiologies were less frequent in non-expert centres (P < 0.01). The use of diagnostic and prognostic tests as cardiac MRI (P < 0.001), genetic (P < 0.001) and alpha-galactosidase A enzyme level testing (P < 0.001), Holter ECG (P < 0.001), and exercise test (P < 0.001), was lower in non-expert centres. Septal ablation procedures using alcohol (P < 0.001) or myectomy (P < 0.001) were more frequent in expert centres. CONCLUSION: In real life practice, only a minority of HCM patients are identified as sarcomere positive as per genetic testing. The management of HCM patients varies according to the centre's level of expertise, with less access to diagnostic and prognostic tests in non-expert centres. Non-sarcomeric HCM may therefore be overlooked despite specific treatment in some aetiologies.

Positive Impact of Genetic Test on the Management and Outcome of Patients With Paraganglioma and/or Pheochromocytoma.

CONTEXT: Pheochromocytomas and paragangliomas (PPGLs) are characterized by a strong genetic component, with up to 40% of patients carrying a germline mutation in a PPGL susceptibility gene. International guidelines recommend that genetic screening be proposed to all patients with PPGL. OBJECTIVE: Our objective was to evaluate how a positive genetic test impacts the management and outcome of patients with SDHx or VHL-related PPGL. DESIGN: We performed a multicentric retrospective study involving 221 propositi carrying an SDHB, SDHD, SDHC, or VHL germline mutation. Patients were divided into two groups: genetic patients, who were informed of their genetic status within the year following the first PPGL diagnosis, and historic patients, who only benefited from the genetic test several years after initial PPGL diagnosis. RESULTS: Genetic patients had better follow-up than historic patients, with a greater number of examinations and a reduced number of patients lost to follow-up (9.6% vs 72%, respectively). During follow-up, smaller (18.7 vs 27.6 mm; P = 0.0128) new PPGLs and metastases as well as lower metastatic spread were observed in genetic patients. Of note, these differences were reversed in the historic cohort after genetic testing. Genetic patients who developed metachronous metastases had a better 5-year survival rate than historic patients (P = 0.0127). CONCLUSION: Altogether, our data suggest that early knowledge of genetic status had a positive impact on the management and clinical outcome of patients with a germline SDHx or VHL mutation.

High bone mineral density in sickle cell disease: Prevalence and characteristics.

BACKGROUND: Osteosclerosis (OSC) is a rarely studied complication of sickle cell disease (SCD). The objective of our study was to determine the prevalence and characteristics of high bone mineral density (BMD) and its radiological features in adult SCD patients. METHODS: This prospective observational study was conducted from May 2007 to May 2016 in consecutive patients with steady-state SCD at two university hospitals. The BMD of the lumbar spine (L1-L4) and right femoral neck was determined by dual energy X-ray absorptiometry. Clinical, laboratory and radiographic data were recorded. High BMD was defined as a BMD Z-score of at least +2.5 standard deviations at the lumbar spine or hip. The characteristics of the patients with high BMD were compared to those of individuals with low or middle BMD, using multivariate ordinal logistic regression. RESULTS: 135 patients (86 women and 49 men) with a median age of 27 (IQR 23-33) years were included. High BMD was diagnosed in 20 (15%) patients with a median age of 33.5 (IQR 28-45) years. The SCD genotypes of these patients were SS in 11, SC in 5, S/beta+ in 3, and S/beta0 in 1. High BMD patients more frequently harbored the S/beta SCD genotype (21% vs 5% in non-high BMD patients; p=0.047) and were older (p=0.0007). Compared to patients with low or middle BMD, after adjustment for age and SCD genotype, high BMD patients had a higher prevalence of avascular necrosis history (p=0.009), higher BMI (p=0.007), and lower serum resorption marker CTX (p=0.04), bilirubin (p=0.02) and parathyroid hormone levels (p=0.02). There were no differences between groups regarding fracture history, H-shaped vertebrae or other biological variables. CONCLUSION: High-BMD values is a common manifestation in SCD patients, especially in those with the S/beta-thalassemia genotypes. The prevalence of high-BMD in SCD is associated with older age, suggesting that it will be more common in the future because the life span of patients with SCD is increasing thanks to significant progress in SCD treatment.

Subclinical Cardiac Dysfunction Is Associated With Extracardiac Organ Damages.

Background: Several studies conducted in America or Europe have described major cardiac remodeling and diastolic dysfunction in patients with sickle cell disease (SCD). We aimed at assessing cardiac involvement in SCD in sub-Saharan Africa where SCD is the most prevalent. Methods: In Cameroon, Mali and Senegal, SCD patients and healthy controls of the CADRE study underwent transthoracic echocardiography if aged ≥10 years. The comparison of clinical and echocardiographic features between patients and controls, and the associations between echocardiographic features and the vascular complications of SCD were assessed. Results: 612 SCD patients (483 SS or Sß0, 99 SC, and 19 Sß+) and 149 controls were included. The prevalence of dyspnea and congestive heart failure was low and did not differ significantly between patients and controls. While left ventricular ejection fraction did not differ between controls and patients, left and right cardiac chambers were homogeneously more dilated and hypertrophic in patients compared to controls and systemic vascular resistances were lower (p < 0.001 for all comparisons). Three hundred and forty nine SCD patients had extra-cardiac organ damages (stroke, leg ulcer, priapism, microalbuminuria or osteonecrosis). Increased left ventricular mass index, cardiac dilatation, cardiac output, and decreased systemic vascular resistances were associated with a history of at least one SCD-related organ damage after adjustment for confounders. Conclusions: Cardiac dilatation, cardiac output, left ventricular hypertrophy, and systemic vascular resistance are associated with extracardiac SCD complications in patients from sub-Saharan Africa despite a low prevalence of clinical heart failure. The prognostic value of cardiac subclinical involvement in SCD patients deserves further studies.