Transthyretin amyloid polyneuropathy in France: A cross-sectional study with 413 patients and real-world tafamidis meglumine use (2009-2019).

OBJECTIVE: We aimed to describe characteristics of patients with ATTR variant polyneuropathy (ATTRv-PN) and ATTRv-mixed and assess the real-world use and safety profile of tafamidis meglumine 20mg. METHODS: Thirty-eight French hospitals were invited. Patient files were reviewed to identify clinical manifestations, diagnostic methods, and treatment compliance. RESULTS: Four hundred and thirteen patients (296 ATTRv-PN, 117 ATTRv-mixed) were analyzed. Patients were predominantly male (68.0%) with a mean age of 57.2±17.2 years. Interval between first symptom(s) and diagnosis was 3.4±4.3 years. First symptoms included sensory complaints (85.9%), dysautonomia (38.5%), motor deficits (26.4%), carpal tunnel syndrome (31.5%), shortness of breath (13.3%), and unexplained weight loss (16.0%). Mini-invasive accessory salivary gland or punch skin and nerve biopsies were most common, with a performance of 78.8-100%. TTR genetic sequencing, performed in all patients, revealed 31 TTR variants. Tafamidis meglumine was initiated in 156/214 (72.9%) ATTRv-PN patients at an early disease stage. Median treatment duration was 6.00 years in ATTRv-PN and 3.42 years in ATTRv-mixed patients. Tafamidis was well tolerated, with 20 adverse events likely related to study drug among the 336 patients. CONCLUSION: In France, ATTRv patients are usually identified early thanks to the national network and the help of diagnosis combining genetic testing and mini-invasive biopsies.

Persistence of treatment with biologics for patients with psoriasis: a real-world analysis of 16 545 biologic-naïve patients from the French National Health Insurance database (SNIIRAM).

BACKGROUND: Long-term clinical effectiveness of biologics in psoriasis is needed. OBJECTIVES: We aimed to assess the long-term persistence of biologics used to treat psoriasis in a real-life setting. METHODS: All adults with psoriasis having been registered in the French National Health Insurance database (SNIIRAM) between 2008 and 2016 were eligible for inclusion. Psoriasis was defined as the fulfilment of at least two prescriptions for topical formulations of a vitamin D derivative within a 2-year period. The study population comprised biologic-naïve patients, i.e. those with a first prescription of etanercept, infliximab, adalimumab or ustekinumab. Persistence of treatment with a biologic was defined as the time interval between initiation and discontinuation. RESULTS: In this nationwide population-based cohort, 16 545 out of 874 549 patients with psoriasis were biologic-naïve (mean age 48·6 years; males 57·3%, mean follow-up 3·6 years). The mean ± SD length of follow-up for biologic-naïve patients was 3·6 ± 2·4 years. There were 9988 treatment discontinuations. Kaplan-Meier survival analyses revealed a persistence rate of 61·9% for the first, 33·3% for the third and 22·6% for the fifth year. Ustekinumab had a higher persistence rate than the other biologics. This finding should be interpreted with caution, in view of differences in administration between the biologics. About 85% of patients, having discontinued their first biologic, resumed systemic treatment of some type in the following year (biologics in 85% of cases). CONCLUSIONS: Our data suggest that biologics are less effective than physicians have been led to believe in a real-life, nonselected population. Further, long-term disease control requires several courses of different biologics.

Genetic polymorphisms of Th2 interleukins, history of asthma or eczema and childhood acute lymphoid leukaemia: Findings from the ESCALE study (SFCE).

BACKGROUND: Previous studies on the putative role of allergy in the aetiology of childhood leukaemia have reported contradictory results. The present study aimed to analyse the relation between a medical history of asthma or eczema and childhood acute lymphoid leukaemia (ALL) in light of potential candidate gene-environment interactions. METHODS: Analyses were based on a subset of 434 cases of ALL and 442 controls successfully genotyped and of European ancestry children enrolled in a French population-based case-control study conducted in 2003-2004. Information about medical history was obtained during a standardized interview with the mothers. Candidate polymorphisms in genes of the Th2 cytokines IL4, IL10, IL13 and IL4-receptor, were genotyped or imputed. RESULTS: None of the variant alleles were directly associated with childhood acute lymphoid leukaemia. A medical history of asthma or eczema was reported more often in the control group (OR = 0.7 [0.5-1.0]). This association was mostly seen in the group of children not carrying the IL13-rs20541 variant allele (Interaction Odds Ratio IOR 1.9, p-interaction = 0.07) and in those carrying the IL10 triple variant haplotype (IOR 0.5, p-interaction = 0.04). No interaction was observed with the candidate polymorphisms in IL4 and IL4R. CONCLUSION: This study provides a new insight into the relationship between allergic symptoms and childhood acute lymphoid leukaemia, by suggesting this inverse association could be limited to children carrying certain genetic polymorphisms. If confirmed, these results could help better understand the biological mechanisms involved in the development of childhood acute lymphoid leukaemia.

Value of a national administrative database to guide public decisions: From the système national d'information interrégimes de l'Assurance Maladie (SNIIRAM) to the système national des données de santé (SNDS) in France.

In 1999, French legislators asked health insurance funds to develop a système national d'information interrégimes de l'Assurance Maladie (SNIIRAM) [national health insurance information system] in order to more precisely determine and evaluate health care utilization and health care expenditure of beneficiaries. These data, based on almost 66 million inhabitants in 2015, have already been the subject of numerous international publications on various topics: prevalence and incidence of diseases, patient care pathways, health status and health care utilization of specific populations, real-life use of drugs, assessment of adverse effects of drugs or other health care procedures, monitoring of national health insurance expenditure, etc. SNIIRAM comprises individual information on the sociodemographic and medical characteristics of beneficiaries and all hospital care and office medicine reimbursements, coded according to various systems. Access to data is controlled by permissions dependent on the type of data requested or used, their temporality and the researcher's status. In general, data can be analyzed by accredited agencies over a period covering the last three years plus the current year, and specific requests can be submitted to extract data over longer periods. A 1/97th random sample of SNIIRAM, the échantillon généraliste des bénéficiaires (EGB), representative of the national population of health insurance beneficiaries, was composed in 2005 to allow 20-year follow-up with facilitated access for medical research. The EGB is an open cohort, which includes new beneficiaries and newborn infants. SNIIRAM has continued to grow and extend to become, in 2016, the cornerstone of the future système national des données de santé (SNDS) [national health data system], which will gradually integrate new information (causes of death, social and medical data and complementary health insurance). In parallel, the modalities of data access and protection systems have also evolved. This article describes the SNIIRAM data warehouse and its transformation into SNDS, the data collected, the tools developed in order to facilitate data analysis, the limitations encountered, and changing access permissions.

[The use of administrative health databases in infectious disease epidemiology and public health]. / Apport des bases médico-administratives en épidémiologie et santé publique des maladies infectieuses.

BACKGROUND: The public health burden resulting from infectious diseases requires efforts in surveillance and evaluation of health care. The use of administrative health databases (AHD) and in particular the French national health insurance database (SNIIRAM) is an opportunity to improve knowledge in this field. The SNIIRAM data network (REDSIAM) workshop dedicated to infectious diseases conducted a narrative literature review of studies using French AHD. From the results, benefits and limits of these new tools in the field of infectious diseases are presented. METHODS: Publications identified by the members of the workgroup were collected using an analytical framework that documented the pathology of interest, the aim of the study, the goal of the developed algorithm, the kind of data, the study period, and the presence of an evaluation or a discussion of the performance of the performed algorithm. RESULTS: Fifty-five articles were identified. A majority focused on the field of vaccination coverage and joint infections. Excluding vaccine coverage field, the aim of 28 studies was epidemiological surveillance. Twenty-six studies used hospital databases exclusively, 18 used ambulatory databases exclusively and 4 used both. Validation or discussion of the performed algorithm was present in 18 studies. CONCLUSIONS: The literature review confirmed the interest of the French AHD in the infectious diseases field. The AHD are additional tools of the existing surveillance systems and their use will probably be more frequent in the coming years given their advantage and reliability. However, incoming users need to be assisted. Thus, the workgroup will contribute to a reasonable use of AHD and support future developments.

Parental smoking, maternal alcohol, coffee and tea consumption during pregnancy, and childhood acute leukemia: the ESTELLE study.

PURPOSE: To investigate the role of parental smoking during pre-conception and pregnancy, maternal beverage consumption (alcohol, coffee and tea) during pregnancy and their possible interactions, in the etiology of childhood acute leukemia (CL). METHODS: The ESTELLE study included 747 cases of CL [636 cases of acute lymphoblastic leukemia (ALL) and 100 cases of acute myeloblastic leukemia (AML)] diagnosed in France in 2010-2011 and 1,421 population controls frequency-matched with the cases on age and gender. Data were obtained from structured telephone questionnaires administered to the mothers. The odds ratios (OR) and their 95 % confidence intervals were estimated using unconditional logistic regression models adjusted for potential confounders. RESULTS: AML, but not ALL, was non-significantly associated with alcohol drinking during pregnancy [OR = 1.3 (0.8-2.0)] with a significant positive dose-response trend (p-trend = 0.02). Pre-conception paternal smoking was significantly associated with ALL [OR = 1.2 (1.1-1.5)] and AML [OR = 1.5 (1.0-2.3)]. CL was not associated with maternal smoking [OR = 1.0 (0.8-1.2)], or maternal coffee [OR = 0.9 (0.8-1.1)] or tea drinking [OR = 0.9 (0.8-1.1)] during pregnancy. However, a high consumption of coffee (>2 cups/day) was significantly associated with ALL [OR = 1.3 (1.0-1.8)]. CONCLUSIONS: The findings constitute additional evidence that maternal alcohol drinking during pregnancy may be involved in AML, and that paternal smoking before pregnancy may be a risk factor for CL. The role of maternal coffee drinking in CL remains unclear and should be investigated further in consortium analyses and in large birth cohort studies with exposure assessment more contemporaneous with the exposure, before the occurrence of the disease.

Childhood acute lymphoblastic leukaemia and indicators of early immune stimulation: the Estelle study (SFCE).

BACKGROUND: Factors related to early stimulation of the immune system (breastfeeding, proxies for exposure to infectious agents, normal delivery, and exposure to animals in early life) have been suggested to decrease the risk of childhood acute lymphoblastic leukaemia (ALL). METHODS: The national registry-based case-control study, ESTELLE, was carried out in France in 2010-2011. Population controls were frequency matched with cases on age and gender. The participation rates were 93% for cases and 86% for controls. Data were obtained from structured telephone questionnaires administered to mothers. Odds ratios (OR) were estimated using unconditional regression models adjusted for age, gender, and potential confounders. RESULTS: In all, 617 ALL and 1225 controls aged ⩾1 year were included. Inverse associations between ALL and early common infections (OR=0.8, 95% confidence interval (CI): 0.6, 1.0), non-first born (⩾3 vs 1; OR=0.7, 95% CI: 0.5, 1.0), attendance of a day-care centre before age 1 year (OR=0.7, 95% CI: 0.5, 1.0), breastfeeding (OR=0.8, 95% CI: 0.7, 1.0), and regular contact with pets (OR=0.8, 95% CI: 0.7, 1.0) in infancy were observed. CONCLUSIONS: The results support the hypothesis that conditions promoting the maturation of the immune system in infancy have a protective role with respect to ALL.

[Study of morbidity in Libreville (Gabon) in 2008]. / Étude de la morbidité exprimée à Libreville (Gabon) en 2008.

We studied population morbidity in three neighborhoods in Libreville (Gabon), selected to represent the city center, the areas bordering the suburbs, and the areas in between. We surveyed 601 households and found that at least one resident was ill in 35% of the households. Malaria remains the leading cause of morbidity in all three districts, followed by fevers and diarrhea. Thus, the causes of morbidity in the general population with Libreville in 2008 matched those of hospital morbidity at the national level, where malaria remains the leading cause of medical visits.

Childhood leukaemia close to high-voltage power lines--the Geocap study, 2002-2007.

BACKGROUND: High-voltage overhead power lines (HVOLs) are a source of extremely low-frequency magnetic fields (ELF-MFs), which are classified as possible risk factors for childhood acute leukaemia (AL). The study was carried out to test the hypothesis of an increased AL incidence in children living close to HVOL of 225-400 kV (VHV-HVOL) and 63-150 kV (HV-HVOL). METHODS: The nationwide Geocap study included all the 2779 cases of childhood AL diagnosed in France over 2002-2007 and 30 000 contemporaneous population controls. The addresses at the time of inclusion were geocoded and precisely located around the whole HVOL network. RESULTS: Increased odds ratios (ORs) were observed for AL occurrence and living within 50 m of a VHV-HVOL (OR=1.7 (0.9-3.6)). In contrast, there was no association with living beyond that distance from a VHV-HVOL or within 50 m of a HV-HVOL. CONCLUSION: The present study, free from any participation bias, supports the previous international findings of an increase in AL incidence close to VHV-HVOL. In order to investigate for a potential role of ELF-MF in the results, ELF-MF at the residences close to HVOL are to be estimated, using models based on the annual current loads and local characteristics of the lines.

Time trends and seasonal variations in the diagnosis of childhood acute lymphoblastic leukaemia in France.

BACKGROUND: Several studies have evidenced an increase in the incidence of childhood leukaemia since the 1970s but the variations since 2000 have received little attention. Seasonal variations in incidence have also been widely investigated, with however inconsistent conclusions. The present study aimed to investigate jointly the temporal trends and the seasonal variations in the month of diagnosis of childhood acute lymphoblastic leukaemia (ALL). METHODS: All the cases of ALL registered in the French National Registry of Childhood Haematological malignancies during 1990-2007 were included in the study. The overall temporal trend and seasonality of ALL were tested with Poisson regression models on 0-14-year-old ALL cases, and specifically on the B-cell precursor ALL (Bcp-ALL) cases. The analyses were also stratified by age groups and gender. RESULTS: Over 1990-2007, a significant time trend in risk of +0.48% (0.02-0.95%) per year for all ALL and +0.85% (0.33-1.37%) for Bcp-ALL was found. The increase was more marked for 7-14-year-old girls with a trend of +2.84% (1.34-4.36%) per year for Bcp-ALL. Seasonal variations were also evidenced for 1-6-year-old boys, with a standardised incidence ratio of 1.11 (1.04-1.18) for Bcp-ALL in April, August and December. CONCLUSION: The study showed an increase in childhood ALL risk over 1990-2007, which tended to be stronger for 7-14-year-old Bcp-ALL, particularly in girls (about one case per year, on average). However, although in accordance with the log-linear assumption, the increase in risk seemed less marked after 2001. The study also suggested seasonal variations in the month of diagnosis for 1-6-year-old boys.

[Availability and access to the public healthcare facilities in sub-Saharan Africa: situation in Libreville, Gabon]. / L'offre et l'accès aux soins publics dans les villes d'Afrique subsaharienne: le cas de Libreville au Gabon.

Availability and access to primary healthcare facilities is a subject of great concern in African countries south of the Sahara. Problems remain not only in the range of services but also in equality of access. By definition the public health sector has a responsibility to provide citizens with equal access to care facilities. The purpose of this study was to analyze availability and access to healthcare facilities in Libreville, the capital of Gabon, using health geography tools. These methods allowed measurement of the accessibility of public primary healthcare facilities in Libreville. Specifically the method consisted of quantitative analysis based on maps illustrating patient attraction and buffer zones. Results showed gaps in health care coverage that could lead to unequal access. The main implication of this finding is that the grid of primary healthcare facilities requires revision. A geographical approach to analyze physical geography and requirements in terms of healthcare and healthcare networks would be helpful to assist planning healthcare infrastructure in Libreville.

Acute childhood leukaemia and residence next to petrol stations and automotive repair garages: the ESCALE study (SFCE).

BACKGROUND: The association between acute childhood leukaemia and residing next to petrol stations and automotive repair garages was analysed in a national registry-based case-control study carried out in France in 2003-2004. METHODS: Population controls were frequency matched with cases on age and gender. Data were collected by standardised telephone interview with the mothers. The latter were asked to report the proximity of their homes to petrol stations, automotive repair garages and other businesses from the conception of the index child to the diagnosis (for cases) or interview (for controls). Odds ratios were estimated using unconditional regression models adjusted for age, gender, number of children under 15 years of age in the household, degree of urbanisation and type of housing. RESULTS: 765 cases of acute leukaemia and 1681 controls were included. Acute leukaemia was significantly associated with residence next to petrol stations or automotive repair garages (OR 1.6, 95% CI 1.2 to 2.2) and next to a petrol station (OR 1.9, 95% CI 1.2 to 3.0). The OR showed no tendency to increase with duration of exposure. The results were not modified by adjustment for potential confounding factors including urban/rural status and type of housing. CONCLUSIONS: The results support the findings of our previous study and suggest that living next to a petrol station may be associated with acute childhood leukaemia. The results also suggest that the role of low-level exposure to benzene in acute childhood leukaemia deserves further evaluation.

Childhood leukaemia and population movements in France, 1990-2003.

In a national study, we investigated the incidence of childhood leukaemia (CL) over a 14-year period in France in relation to several measures based on the proportion of individuals who changed address between the last two national censuses. A positive association was found with the proportion of migrants who came from a distant place. The further the migrants came, the higher was the incidence of leukaemia, particularly among children aged 0-4 years in 'isolated' communes at the time of diagnosis (RR=1.4, 95% CI: 1.1,1.8 in the highest category of migration distance). Although the role of the population density was less obvious, a more marked association was found above a certain threshold. No association with the proportion of commuters was observed.

Population-mixing at the place of residence at the time of birth and incidence of childhood leukaemia in France.

The association between the risk of childhood leukaemia before age 7 years and population-mixing at the place of residence at birth was investigated by retrospectively considering all the children born in mainland French communes between 1st January 1990 and 31st December 1998. An increased risk of acute lymphoblastic leukaemia was found with higher levels of migration for children residing at birth in isolated communes with a population density > or =50 people per km2 (SIRR = 2.59, 95% CI: 1.48-4.49). No association was observed with lower population densities. For children residing in non-isolated communes at birth, the results were similar but less marked. The risk tended to increase only for population densities > or =5000 people per km2 (SIRR = 1.57, 95% CI: 0.99-2.52). The findings are consistent with epidemic models and support the hypothesis of an infectious aetiology relating to population-mixing. Population density may be seen as an indicator of the opportunity of contacts between inhabitants and should therefore be taken into account when investigating an infectious hypothesis. This is the first systematic study of population-mixing at the place of residence at the time of birth to be conducted on a national scale.

Spatial and space-time clustering of childhood acute leukaemia in France from 1990 to 2000: a nationwide study.

This study aimed to investigate the spatial and space-time distributions of cases of childhood acute leukaemia (CL) during 1990-2000 over the whole French territory. A global spatial heterogeneity and a spatial autocorrelation were first considered using the methods proposed by Potthoff and Whittinghill, Moran and Rogerson methods. The presence of space-time interaction between the places of residence and the dates of diagnosis was investigated with the Knox's test. Finally, the Kulldorff's statistic permitted to scan the whole territory in search for localised clusters. Two time periods were considered (1990-1994, 1995-2000). Overall, a statistically significant spatial heterogeneity of a very small magnitude was observed in the incidence of CL over 1990-1994, but neither over 1995-2000 nor over the whole time period. Moreover, a significant overdispersion of 5.5% was evidenced for 0-4 year children living in isolated areas with more than 50 inhabitants per km(2). Cases older than 10 years living in the same area at diagnosis also tended to cluster within 6 months.

[Morbi-mortality after Hartmann procedure for peritonitis complicating sigmoid diverticulitis. A retrospective analysis of 85 cases]. / Morbimortalité de l'intervention de Hartmann pour péritonite diverticulaire. Etude rétrospective multicentrique à propos de 85 patients.

INTRODUCTION: Hartmann's procedure (HP) is a simple operation, which can be performed by all the surgeons. However, it remains criticized (high morbimortality, low rate of intestinal continuity restoration). The aim of this study was to analyse natural history of HP and intestinal continuity restoration for sigmoid diverticulitis, and to assess risk factors for mortality, morbidity and absence of intestinal continuity restoration. PATIENTS AND METHODS: In three centers, from 1992 to 2002, 85 patients underwent HP. A retrospective analysis was performed on mortality, early and late morbidity of HP and intestinal continuity restoration. RESULTS: 22% of patients (mean age, 68 years) presented comorbidity, 17% of them, an altered immunity, and 3 or 4 Hinchey score for 64%. ASA score was > or =3 in 49% of the cases. Mean AFC and Mannheim scores were 2 and 21 respectively. Mortality rate was 14% and in-hospital morbidity, 50%. Main complications were: cardiorespiratory (18%), wound abcess (14%) and stomal (6%). No rectal stump fistula was noted. Mean hospital stay was 19+/-13 days. Late morbidity rate was 29%, mainly due to stomal complications (12%) and small bowel obstruction (7%). Intestinal continuity restoration was done in 77% of the cases, followed by only 1 fistula. Mortality rate for intestinal continuity restoration was 0% and morbidity was 13%. Mean hospital stay was 10+/-3 days. Age >75 years, ASA score > or =3 and comorbidity were risk factors for morbidity and mortality and for absence of intestinal continuity restoration. CONCLUSIONS: HP is associated with a high morbidity and mortality rates. Intestinal continuity restoration rate was high in this series. HP is a simple operation in high-risk patients with advanced peritonitis. This study allows to precise natural history of HP. Knowledge of this history is crucial for choosing the best operation (between HP and anastomosis) for patient with peritonitis complications sigmoid diverticuitis.

World Health Organization grade 'a' motility and zona-binding test accurately predict IVF outcome for mild male factor and unexplained infertilities.

BACKGROUND: The aim of this study was to determine the pronostic value of a sperm-zona pellucida (ZP) binding assay, combined with World Health Organization (WHO) grade 'a' sperm motility on the day of the IVF attempt, to predict sperm fertilizing ability in unexplained and moderate male factor infertilities. METHODS: In total, 84 couples (64 unexplained infertility; 20 male factor) underwent both a sperm-ZP binding assay and an IVF attempt, irrespective of the test's result. The test was negative when grade 'a' motility was #5% and/or the ZP binding index was <0.7. Fertilization and pregnancy rates were related to the test's results. RESULTS: Thirty-one patients had a negative test (group N) and 53 a positive test (group P). A difference was observed concerning the fertilization rate [median (range): 0 (0-75%) versus 50 (0-100%); P = 0.0001] and the number of cycles with fertilization rate <20% (65 versus 23%; P = 0.0002) between groups N and P respectively. In the group of unexplained and male factor infertilities, the test showed a sensitivity of 83 and 60%, specificity of 50 and 90%, positive predictive value of 76 and 86%, and negative predictive value of 61 and 69% respectively. CONCLUSION: Sperm-ZP binding test, combined with WHO grade 'a' motility assessment, is relevant to prevent IVF fertilization failures in unexplained infertility and, most particularly, in moderate male factor infertility.