Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Work productivity loss in early arthritis during the first 3 years of disease. A study from the ESPOIR cohort.

International audience: 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 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 and 11% reported permanent disability. Only a few patients (1%) reported early retirement. Mean number of days on sick leave due to EA decreased regularly from 44 to 13, whereas mean number of days on permanent disability tripled from 10 to 33. Mean annual cost was 1,333€ (95% confidence interval 1,075-1,620€). A sick leave longer than 30 days due to EA before inclusion and a decrease in mental and physical scores of the MOS SF-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. © 2014 American College of Rheumatology

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.

International audienceOBJECTIVES: 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

Multivariate analysis of the effects of demographic and clinical variables and treatment strategy on total costs over 4 years.

<p>The reported Rate Ratios describe the variations in costs expressed as a multiplicative factor for patients presenting the associated characteristic compared to those who did not, all other things being equal.</p><p>MCMC = Markov Chain Monte Carlo; CI = Confidence Intervalle; HAQ = Health Assessment Questionnaire; RA = Rheumatoid Arthritis; ICC = Intraclass Correlation Coefficient.</p>1<p>Median and range for all 24 imputed datasets.</p

Baseline patient characteristics.

<p>Values are mean values (SD) or number of patients (%).</p>1<p>Eular Guideline: 1st rheumatologist visit after RA onset <45 days; ESR = Erythrocyte sedimentation rate, CRP = C-Reactive Protein, DAS-28 = Disease Activity Score 28, HAQ = Health Assessment Questionnaire, ACR = American College of Rheumatology, VAS = Visual analogue scale, EULAR = European League Against Rheumatism, DMARD = Disease-modifying antirheumatic drug, ACPA = anti-citrullinated protein antibody.</p

Mean costs per period according to treatment strategy.

<p>(A) Mean total costs according to treatment strategy; (B) Mean other health resource use costs according to treatment strategy.</p

Multivariate analysis of the effects of demographic and clinical variables and treatment strategy on other health resource use costs over 4 years.

<p>The reported Rate Ratios describe the variations in costs expressed as a multiplicative factor for patients presenting the associated characteristic compared to those who did not, all other things being equal.</p><p>MCMC = Markov Chain Monte Carlo; CI = Confidence Intervalle; HAQ = Health Assessment Questionnaire; RA = Rheumatoid Arthritis; ICC = Intraclass Correlation Coefficient.</p>1<p>Median and range for all 24 imputed datasets<b>.</b></p

Disease activity per period among matched groups of FYB and LYB users.

<p>* 37 FYB users and 37 LYB users were matched for clinical and sociodemographic baseline characteristics using a logistic regression propensity score. ** Low disease activity is defined as DAS-28≤3.2.</p

Annual costs over the 4-year follow-up by resource component.

1<p>Physician visit costs used were the following: 28.27€ for rheumatologists, 28.61€ for internists, 22.13€ for general practitioners and 30.56€ for orthopaedist surgeons.</p>2<p>Health professional consultation costs used were the following: 11.30 € for nurses, 16.32 € for physiotherapists, 40.82 € for psychologists and 14.90 € for occupational therapists.</p>3<p>Lab test costs used were the following: 173.80 € for inclusion biologic investigations, 28.86 € for monthly biologic tests and 42.63 € for annual biologic tests.</p>4<p>Imaging and other devices costs included the following: 19.95 to 39.95 € for X-ray depending on the number of X-rays (19.95 € for the 1st X-ray, 39.95 € for the 2nd, 21.28 € for the 3rd, 20.00 € for the 4th), 69.00 € for MRI, 25.27 € for CT-scanner, 96.00 € for gastric endoscopy and 204.18 € for colonoscopy.</p>5<p>Transportation costs were calculated on the basis of a reimbursement fee of 1.17 € per km.</p>6<p>Inpatient costs were based on DRG tariffs.</p><p>DMARD = Disease-modifying antirheumatic drugs.</p

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

International audienceBACKGROUND: 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