History of pre-eclampsia does not appear to be a risk factor for vascular phenotype in women with systemic sclerosis.

BACKGROUND: Vascular phenotype is associated with a poor prognosis in systemic sclerosis (SSc). The identification of its risk factors could facilitate its early detection. OBJECTIVES: To explore risk factors for a vascular phenotype of SSc, among them a history of pre-eclampsia. METHODS: This observational multicentre case-control study enrolled adult women fulfilling European Alliance of Associations for Rheumatology 2013 diagnosis criteria for SSc and having a pregnancy history≥6 months before SSc diagnosis in 14 French hospital-based recruiting centres from July 2020 to July 2022. Cases had specific vascular complications of SSc defined as history of digital ischaemic ulcers, pulmonary arterial hypertension, specific cardiac involvement or renal crisis. Women with SSc were included during their annual follow-up visit and filled in a self-administered questionnaire about pregnancy. A case report form was completed by their physician, reporting data on medical history, physical examination, clinical investigations and current medication. The main outcome was the presence/absence of a personal history of pre-eclampsia before SSc diagnosis, according to the validated pre-eclampsia questionnaire. RESULTS: 378 women were included: 129 cases with a vascular phenotype and 249 matched controls. A history of pre-eclampsia was reported in 5 (3.9%) cases and 12 (4.8%) controls and was not associated with a vascular phenotype (OR=0.96, 95% CI 0.28 to 3.34, p=0.9). Besides, Rodnan skin score and disease duration≥5 years were risk factors for vascular phenotype. CONCLUSIONS: In women with SSc and a pregnancy history≥6 months before SSc, a history of pre-eclampsia is not associated with a vascular phenotype.

Women with severe postpartum hemorrhage have a decreased endogenous thrombin potential before delivery.

BACKGROUND: Severe postpartum hemorrhage (PPH), defined as a blood loss ≥1000 mL, is associated with maternal morbidity and mortality. OBJECTIVES: We aimed at characterizing coagulation properties of predelivery plasmas from pregnant women with thrombin generation assay and hemostatic biomarkers (plasminogen activator inhibitor-1, tissue factor [TF], and thrombomodulin). METHODS: A nested case-control study was conducted within the "Study of Biological Determinants of Bleeding Postpartum," a French prospective cohort study, in order to compare women with severe PPH (cases) and controls matched for age, body mass index, term, and mode of delivery. Plasma was collected at entry in the delivery room, and blood loss was measured objectively. The predelivery endogenous thrombin generation potential (ETP) was measured in plasma using calibrated automated thrombinography and low TF concentration. Hemostatic biomarkers were measured using ELISA kits. RESULTS: A total of 142 women (71 cases and 71 controls) were investigated. There was no difference in the median lag phase, thrombin peak, and time to peak between cases and controls. However, median predelivery ETP was lower in cases than in controls (2170 vs 2408 nM.min, P < .0001), independently of mode of delivery and PPH etiology. Median plasminogen activator inhibitor-1 and TF levels were higher in cases compared with controls (107.4 vs 68.1 ng/mL, P = .0003; 34.4 vs 27.4 pg/mL, P = .007), whereas thrombomodulin levels did not differ between the 2 groups. CONCLUSION: Among thrombin generation assay parameters, predelivery ETP levels may have a predictive value for severe PPH.

Family history of postpartum hemorrhage is a risk factor for postpartum hemorrhage after vaginal delivery: results from the French prospective multicenter Haemorrhages and Thromboembolic Venous Disease of the Postpartum cohort study.

BACKGROUND: Postpartum hemorrhage is a major component of perinatal morbidity and mortality that affects young women worldwide and is still often unpredictable. Reducing the incidence of postpartum hemorrhage is a major health issue and identifying women at risk for postpartum hemorrhage is a key element in preventing this complication. OBJECTIVE: This study aimed to estimate postpartum hemorrhage prevalence after vaginal delivery and to identify postpartum hemorrhage risk factors. STUDY DESIGN: Unselected pregnant women ≥16 years of age admitted to 1 of 6 maternity wards in Brittany (France) for vaginal birth after 15 weeks of gestation were recruited in this prospective, multicenter cohort study between June 1, 2015, and January 31, 2019. Postpartum hemorrhage was defined as blood loss ≥500 mL in the 24 hours following delivery. Independent risk factors for postpartum hemorrhage were determined using logistic regression. Missing data were imputed using the Multivariate Imputation by Chained Equations method. RESULTS: Among 16,382 included women, the postpartum hemorrhage prevalence was 5.37%. A first-degree family history of postpartum hemorrhage (adjusted odds ratio, 1.63; 95% confidence interval, 1.24-2.14) and a personal transfusion history (adjusted odds ratio, 1.90; 95% confidence interval, 1.23-2.92) were significantly associated with postpartum hemorrhage. The use of oxytocin during labor was also a risk factor for postpartum hemorrhage (adjusted odds ratio, 1.24; 95% confidence interval, 1.06-1.44). Inversely, smoking during pregnancy and intrauterine growth restriction were associated with a reduced risk for postpartum hemorrhage (adjusted odds ratio, 0.76; 95% confidence interval, 0.63-0.91, and 0.34; 95% confidence interval, 0.13-0.87, respectively). CONCLUSION: In addition to classical risk factors, this study identified a family history of postpartum hemorrhage and personal transfusion history as new characteristics associated with postpartum hemorrhage after vaginal delivery. The association of postpartum hemorrhage with a family history of postpartum hemorrhage suggests a hereditary hemorrhagic phenotype and calls for genetic studies. Identifying women at risk for postpartum hemorrhage is a key element of being prepared for this complication.

Safety and efficacy of daclatasvir-sofosbuvir in HCV genotype 1-mono-infected patients.

BACKGROUND & AIMS: We report the first real-life results of the sofosbuvir+daclatasvir combination in hepatitis C virus (HCV) genotype 1 infected patients. METHODS: The France REcherche Nord&Sud Sida-hiv Hépatites (ANRS) CO22 HEPATHER "Therapeutic options for hepatitis B and C: A French cohort" is a multicentre observational cohort which aims to include 15,000 HCV- and 10,000 HBV-infected patients. We selected all participants (n=768) with a HCV genotype 1 who initiated sofosbuvir (400mg/day) and daclatasvir (60mg/day) before October 1st 2014, with or without ribavirin (1-1.2g/day) for a duration of 12weeks or 24weeks. The main endpoint criterion was sustained virological response at 12weeks (SVR12), defined by the absence of detectable HCV-RNA 12weeks after the last treatment intake. Missing SVR12 measurements were imputed using SVR24 measurements (n=45), otherwise considered as virological failure (n=18). RESULTS: A SVR12 was obtained in 729/768 (95%) patients, ranging from 92% (12-week sofosbuvir+daclatasvir) to 99% (24-week sofosbuvir+daclatasvir+ribavirin). The SVR12 rates did not significantly differ between the 24-week (550/574 (96%)) and the 12-week (179/194 (92%); p=0.0688) durations or between regimens with (165/169 (98%)) or without ribavirin (564/599 (94%); p=0.0850). The SVR12 rate was greater than 97% in non-cirrhotic patients irrespective of the treatment duration or the addition of ribavirin. Among cirrhotic patients, the SVR12 rate was higher with 24 than 12-week regimen (423/444 (95%) vs. 105/119 (88%); p=0.0054). CONCLUSION: The sofosbuvir+daclatasvir combination is associated with a high rate of SVR12 in patients infected by genotype 1, with an optimal duration of 12weeks in non-cirrhotic and 24weeks in cirrhotic patients. The number of patients receiving ribavirin was too low to adequately assess its impact. LAY SUMMARY: The sofosbuvir+daclatasvir combination of antiviral drugs is associated with a high rate (95%) of viral eradication in patients infected by HCV genotype 1. The best duration of a ribavirin-free sofosbuvir+daclatasvir combination seems to be 12weeks in non-cirrhotic patients and 24weeks for those with cirrhosis. Clinical trial number: NCT01953458.

Evolution of direct costs in the first years of rheumatoid arthritis: impact of early versus late biologic initiation--an economic analysis based on the ESPOIR cohort.

OBJECTIVES: To estimate annual direct costs of early RA by resource component in an inception cohort, with reference to four distinct treatment strategies: no disease modifying antirheumatic drugs (DMARDs), synthetic DMARDs only, biologic DMARDs in the first year ('first-year biologic', FYB), and biologic DMARDs from the second year after inclusion ('later-year biologic', LYB); to determine predictors of total and non-DMARD related costs. METHODS: The ESPOIR cohort is a French multicentric, prospective study of 813 patients with early arthritis. Data assessing RA-related resource utilisation and disease characteristics were collected at baseline, biannually during the first two years and annually thereafter. Costs predictors were determined by generalised linear mixed analyses. RESULTS: Over the 4-year follow-up, mean annual direct total costs per treatment strategy group were €3,612 for all patients and €998, €1,922, €14,791, €8,477 respectively for no DMARDs, synthetic DMARDs only, FYB and LYB users. The main predictors of higher costs were biologic use and higher Health Assessment Questionnaire (HAQ) scores at baseline. Being a biologic user led to a higher total cost (FYB Rate Ratio (RR) 7.22, [95% CI 5.59-9.31]; LYB RR 4.39, [95% CI 3.58-5.39]) compared to non-biologic users. Only LYB increased non-DMARD related costs compared to all other patients by 60%. CONCLUSIONS: FYB users incurred the highest levels of total costs, while their non-DMARD related costs remained similar to non-biologic users, possibly reflecting better RA control.

Work productivity loss in early arthritis during the first 3 years of disease: a study from a French National Multicenter Cohort.

OBJECTIVE: To assess work productivity (WP) loss during the first 3 years of disease in a cohort of patients with early arthritis (EA) diagnosed between 2002 and 2005. METHODS: The ESPOIR (Etude et Suivi des Polyarthrites Indifférenciées Récentes) cohort included 813 EA patients; we included those of working age at baseline in the present study. WP loss was assessed by 3 components: sick leave, permanent disability, and early retirement. The proportion of affected patients and the mean number of days off work were assessed for each component. WP costs were estimated and determinants of positive and extreme costs were assessed by logistic regression models. RESULTS: Among the 664 patients included, 81.6% were in the workforce at baseline. During the first 3 years of disease, 45% reported at least 1 sick leave day and 11% reported permanent disability. Only a few patients (1%) reported early retirement. The mean number of days on sick leave due to EA decreased regularly from 44 to 13, whereas the mean number of days on permanent disability tripled from 10 to 33. The mean annual cost was 1,333 (95% confidence interval 1,075-1,620). Sick leave longer than 30 days due to EA before inclusion and a decrease in mental and physical scores of the Medical Outcomes Study Short Form 36 at inclusion were independent determinants of positive and extreme costs in multivariate models. CONCLUSION: WP loss is substantial in EA patients and is due to permanent disability before the third year of disease. Work absence and poor mental and physical health status at baseline are major determinants of WP costs.