Jean Pierre Daures

Prognostic factors of 10-year radiographic outcome in early rheumatoid arthritis: a prospective study

IntroductionThe objectives of this study were to determine the predictive factors of long-term radiographic outcome of rheumatoid arthritis (RA) and to describe the relationship between joint damage and disability over the course of the disease.MethodsA cohort of 191 patients with early RA referred from primary care physicians were prospectively followed for 10 years. To determine the predictive factors of radiographic outcome, univariate analysis of the relationship between baseline values and outcome measures was undertaken using a chi-squared or Fishers exact test. Stepwise multiple logistic regression was also performed to select independent prognostic factors.ResultsFrom data available for 112 patients, univariate analysis revealed a total Sharp score at 10 years that was significantly correlated with erythrocyte sedimentation rate (ESR), presence and level of IgA rheumatoid factor, presence of an anti-citrullinated protein antibody (ACPA), serum level of matrix metalloproteinase-3 and radiographic score at baseline. Logistic regression identified the baseline erosion score to be the most important baseline parameter as an independent prognostic factor of total radiographic score at 10 years (odds ratio = 5.64; 95% confidence interval = 1.78 to 17.86). After excluding radiographic scores from the entry parameters, the presence of ACPA and ESR were also predictive of the final total Sharp score. The Health Assessment Questionnaire (HAQ) score was strongly correlated with disease activity parameters, such as disease activity score and pain, at baseline and at three, five and 10 years. No correlation was found between total radiographic Sharp score and HAQ score throughout the study.ConclusionsIn this prospective study, baseline radiographic score, ESR and ACPA were the best predictive factors of 10-year radiographic outcome in early RA. HAQ disability was associated with disease activity throughout the 10-year follow-up but not with joint damage. This discrepancy with previous reports may be due in part to the early start of therapy with disease-modifying anti-rheumatic drugs.

Prenatal environmental risk factors for genital malformations in a population of 1442 French male newborns: a nested case–control study

BACKGROUND Over the past decades, an increasing trend in male external genital malformations such as cryptorchidism and hypospadias has led to the suspicion that environmental chemicals are detrimental to male fetal sexual development. Several environmental pollutants, including organochlorine pesticides, polychlorinated biphenyls, bisphenol A, phthalates, dioxins and furans have estrogenic and anti-androgenic activity and are thus considered as endocrine-disrupting chemicals (EDCs). Since male sex differentiation is critically dependent on the normal production and action of androgens during fetal life, EDCs may be able to alter normal male sex differentiation. OBJECTIVE The objective of this study was to determine the incidence of external genital malformations in a population of full-term newborn males in southern France. We also performed a case-control study to identify the risk factors for male external genital malformations, with a focus on parental occupational exposure to EDCs. METHODS Over a 16-month period, 1615 full-term newborn males with a birth weight above 2500 g were registered on a level-1 maternity ward, and the same pediatrician systematically examined 1442 of them (89%) for cryptorchidism, hypospadias and micropenis. For every male newborn with genital malformation, we enrolled nearly two males matched for age, parity and term. All parents of the case and control newborns were interviewed about pregnancy aspects, personal characteristics, lifestyle and their occupational exposure to EDCs using a detailed questionnaire. RESULTS We report 39 cases of genital malformation (2.70%), with 18 cases of cryptorchidism (1.25%), 14 of hypospadias (0.97%), 5 of micropenis (0.35%) and 2 of 46,XY disorders of sexual differentiation (DSD; 0.14%). We observed a significant relationship between newborn cryptorchidism, hypospadias or micropenis and parental occupational exposure to pesticides [odds ratio (OR) = 4.41; 95% confidence interval (95% CI), 1.21-16.00]. Familial clustering for male external genital malformations (OR = 7.25; 95% CI, 0.70-74.30) and medications taken by mothers during pregnancy (OR = 5.87; 95% CI, 0.93-37.00) were associated with the risk of cryptorchidism, hypospadias and micropenis, although the association was not statistically significant. CONCLUSIONS Although the causes of male genital malformation are multifactorial, our data support the hypothesis that prenatal contamination by pesticides may be a potential risk factor for newborn male external genital malformation and it should thus be routinely investigated in all undervirilized newborn males.

Treatment of hypertension with renin-angiotensin system inhibitors and renal dysfunction: a systematic review and meta-analysis.

BACKGROUND To determine whether inhibitors of the renin-angiotensin system (RAS) reduce the incidence of renal dysfunction when compared to other antihypertensive treatments in patients with essential hypertension and no pre-existent renal disease. METHODS The search strategy used the Cochrane Library, Medline, previous meta-analyses, and journal reviews. The selection criteria included randomized, controlled trials of antihypertensive drugs that compared a RAS inhibitor with another treatment in essential hypertension. Studies that specifically enrolled only patients with diabetes or renal disease were not included. The quality assessment and data extraction of studies were performed by two independent reviewers. Effects on dichotomous renal outcome (serum creatinine (SCreat) higher than a prespecified value, doubling of SCreat or end-stage renal disease) and secondary continuous marker of renal outcome (change in SCreat) were calculated using Petos method. RESULTS 33,240 patients met the inclusion criteria for studies with a dichotomous outcome and 10,634 patients for studies with a continuous outcome. The mean follow-up was 42 ± 13 months. Patients randomized to RAS inhibitors did not show a significant reduction in the risk of developing renal dysfunction as compared to other antihypertensive strategies (odds ratio = 1.05; 95% confidence interval (CI) 0.89-1.25; P = 0.54). There was no significant difference in change of SCreat between groups (mean difference = 0.0005 mg/dl; 95% CI -0.0068 to 0.0077 mg/dl; P = 0.91). CONCLUSION In patients with essential hypertension and no pre-existent renal disease, prevention of renal dysfunction is not significantly different with RAS inhibitors when compared to other antihypertensive agents.

Effectiveness and Safety of an Intracameral Injection of Cefuroxime for the Prevention of Endophthalmitis After Cataract Surgery With or Without Perioperative Capsular Rupture.

IMPORTANCE Postoperative endophthalmitis (POE) often results in severe visual impairment. In clinical studies, an intracameral cefuroxime injection at the end of surgery was found to be effective at reducing the incidence of POE. Two important issues are the retinal safety of cefuroxime and its use for patients with perioperative capsular rupture where the risk of POE is dramatically increased. OBJECTIVE To assess the effectiveness and retinal safety of an intracameral injection of cefuroxime sodium for the prevention of POE and its possible use in cases of a perioperative capsular rupture of the lens. DESIGN, SETTING, AND PARTICIPANTS Population-based cohort study of patients 40 years of age or older who underwent cataract surgery at 1 of 1546 French health care facilities, public or private, and whose medical records were obtained from the national administrative database. Data analyses were performed between March and November 2015. MAIN OUTCOMES AND MEASURES The effectiveness and safety of the prophylactic injection of cefuroxime as measured by the incidence of POE and cystoid macular edema. RESULTS From January 2010 to October 2014, a total of 3 351 401 eyes of 2 434 008 patients 40 years of age or older (58.9% were women, and the mean [SD] age was 73.9 [9.5] years) underwent cataract surgery; 1941 patients (0.08%) developed POE during the 6 weeks after cataract surgery. The incidence of POE after cataract surgery decreased over the course of the study (0.11%, 0.09%, 0.08%, 0.06%, and 0.05% in 2010, 2011, 2012, 2013, and 2014, respectively [P = .001 for trend]) as the use of cefuroxime prophylactic injections increased (11.1%, 14.4%, 32.8%, 64.8%, and 79.1% in 2010, 2011, 2012, 2013, and 2014, respectively [P = .001 for trend]). After multivariate adjustment, the risk of POE was reduced with the use of cefuroxime (odds ratio, 0.61 [95% CI, 0.56-0.68]). The retinal safety of an injection of cefuroxime, which was assessed by multiadjusted odds of retinal cystoid macular edema, was not increased for patients receiving cefuroxime injections (odds ratio, 0.86 [95% CI, 0.71-1.05]). For patients with a perioperative capsular rupture of the lens (the major risk factor for POE), the incidence of POE was lower for those who received an injection of cefuroxime than for those who did not (0.37% vs 0.51%, respectively [P = .001]), whereas an increased risk of cystoid macular edema was not identified for those who received or did not receive an injection of cefuroxime (5.6% vs 7.3%, respectively [P = .12]). CONCLUSIONS AND RELEVANCE These data suggest that, in routine practice, the intracameral injection of cefuroxime at the conclusion of cataract surgery is associated with a lower risk of POE and is safe for patients with or without a perioperative capsular rupture. While these data might be used to support the consideration of its routine use to prevent POE, in the absence of a randomized clinical trial, they cannot prove a direct cause-and-effect relationship between the injection of cefuroxime and POE.

HER2 overexpression a major risk factor for recurrence in pT1a-bN0M0 breast cancer: results from a French regional cohort.

The management of pT1a‐bN0M0 breast cancer remains an area of controversy. Data from 714 patients classified as having pT1a‐bN0M0 breast cancer and treated, from 1999 to 2004 in the Languedoc‐Roussillon France, were analyzed. The human epidermal growth factor receptor 2 (HER2) status analyses were centralized. The objective of this study was to describe the prognosis of pT1a‐bN0M0 breast cancer according to HER2 distribution and hormonal status. The median follow‐up was 6.4 years. Ten‐year overall survival was 94%. HER2 overexpression was observed in 6.1% of the patients. The 10‐year prognosis of patients with HER2‐positive tumors was worse than that of those with HER2‐negative (disease‐free survival 73% vs. 89%, P < 0.0001). Tumor size (T1a/T1b) was not a relevant prognostic factor. The co‐expression of HER2 with hormonal receptors (HR) was associated with high recurrence at 10 years. In both univariate and multivariate analyses, the most relevant prognostic factor for this population was HER2 amplification. In multivariate analysis, patients with HER2‐positive tumors had higher risk of mortality (HR, 3.89; 95% CI, 1.58–9.56). In pT1a‐bN0M0 breast cancers, HER2 amplification or overexpression is a risk factor for recurrence. In HER2‐positive breast cancers, HR expression is associated with a poor prognosis despite the hormone therapy. For this population, a personalized management may be required.

Is Screening for Hepatitis B and Hepatitis C Useful in Patients with Recent-Onset Polyarthritis? The ESPOIR Cohort Study

Objective. To evaluate the seroprevalence of hepatitis B (HBV) and C (HCV) in patients living in France with recent-onset polyarthritis suggesting rheumatoid arthritis. Methods. The 813 patients in the ESPOIR cohort were screened for anti-HCV antibodies and HBs antigen. Results. Seroprevalence was 0.86% for HCV (n = 7) and 0.12% for HBV (n = 1). HCV-related arthritis was diagnosed in 4 (0.5%) patients; no patient had HBV-related arthritis. HCV-seropositive patients had significantly higher transaminase levels (ALAT, 41.5 IU vs 23.2 IU, p = 0.02; and ASAT, 39.2 IU vs 21.8 IU, p = 0.001) but only 2 patients had ASAT or ALAT levels > 40 IU. No significant differences were found for anti-CCP antibodies, C-reactive protein, erythrocyte sedimentation rate, or other test. HCV seroprevalence was significantly higher in the subgroup with history of blood transfusion than in other patients (3.7% vs 0.42%, p = 0.02). Two of the 7 HCV positive patients and the single patient with confirmed hepatitis B infection were born in areas with higher prevalence of viral hepatitis (Togo, Senegal, Vietnam). Positive hepatitis status was known before study inclusion in 4 of the 7 HCV-positive patients and in the HBV-positive patient. Conclusion. The prevalence of HBV and HCV in a population of patients with recent-onset polyarthritis suggestive of RA was not greater than expected based on data from the general population in the same geographic area. Routine HBV and HCV serological testing did not contribute substantially to the diagnosis of recent-onset polyarthritis. Although advisable before initiating immunosuppressive or hepatotoxic drugs, serological testing for HCV and HBV is unnecessary in routine diagnostic evaluation of recent-onset polyarthritis.

Is routine viral screening useful in patients with recent‐onset polyarthritis of a duration of at least 6 weeks? Results from a nationwide longitudinal prospective cohort study

To study the contribution of routine viral screening tests in patients with early rheumatoid arthritis (RA) or a potential for progressing to RA.

Rheumatoid Arthritis of the Hand: Monitoring with a Simplified MR Imaging Scoring Method—Preliminary Assessment

PURPOSE To assess a simplified scoring method (Simplified Rheumatoid Arthritis Magnetic Resonance Imaging Score [SAMIS]) developed to shorten interpretation time, while retaining both correlation with Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) and same or better intra- and interreader reliability. MATERIALS AND METHODS Ethics board approval and written patient consent were obtained. The study was HIPAA compliant. Thirty-eight patients with rheumatoid arthritis and 20 patients with no or early unclassified arthritis underwent magnetic resonance imaging of both wrists and hands. RAMRIS was used to evaluate erosions (scale, 0-10), edema (scale, 0-3), and synovitis (scale, 0-3). SAMIS assessed only one hand and was based on the radiographic Simple Erosion Narrowing Score, thus reducing the number of study areas from 116 to 36. Erosions were scored with a scale from 1 to 10. Edema and synovitis were, respectively, scored with scales from 0 to 1 and 0 to 2. SAMIS correlation with RAMRIS was tested by using the Spearman test. Last, the intra- and interobserver reproducibility of both scores were calculated. RESULTS SAMIS was closely correlated with RAMRIS for the entire series (r = 0.91, 0.79, and 0.94, respectively, for erosion, edema, and synovitis), as well as in patients with rheumatoid arthritis (r = 0.93, 0.81, and 0.92) and those with no or unclassified arthritis (r = 0.83, 0.73, and 0.94). The time needed to assess examination results with RAMRIS ranged from 5 to 20 minutes (13 minutes +/- 3.90 [standard deviation]), whereas it ranged from 2 to 7 minutes (5 minutes +/- 1.45) with SAMIS. For each of the three features (erosion, edema, and synovitis), intraobserver agreement (RAMRIS: kappa = 0.67, 0.94, 0.81, respectively; SAMIS: kappa = 0.66, 1.0, 0.91) and interobserver agreement (RAMRIS: kappa = 0.61, 0.58, 0.74, respectively; SAMIS: kappa = 0.59, 0.81, 0.81) were good to excellent. CONCLUSION This simplified reproducible scoring scheme could be used to monitor joint damage in rheumatoid arthritis. (c) RSNA, 2010.

Incidence and Characteristics of Cystoid Macular Edema after Cataract Surgery

Despite surgical improvements, pseudophakic cystoid macular edema (CME) is the most common cause of decreased vision after cataract surgery and could lead to permanently impaired central vision owing to altered outer photoreceptor features. In this study, we aimed to determine the ageand sex-specific incidence of CME after primary uncomplicated phacoemulsification in communitybased outpatient clinics in the Languedoc-Roussillon region of France. The secondary objective was to assess the characteristics of CME, including time of onset and duration. Data for all patients>40 years old who underwent cataract surgery between January and December 2010 were collected from the administrative database Extraction Recherches Analyses pour un Suivi Médico-Economique (ERASME) previously used to assess the incidence of pseudophakic retinal detachment. We selected only cases of uncomplicated phacoemulsification with intraocular lens implantation in a capsular bag (ERASME code BFGA004). We tracked CME by acetazolamide prescription with the pharmaceutical code 3400930305270. Acetazolamide is the first-line therapy mandated by the French Society of Ophthalmology for symptomatic CME along with topical nonsteroidal anti-inflammatory drugs and corticosteroids. Data on diabetic status were collected by pharmaceutical codes for insulin and/or oral diabetes medications. To not include patients receiving acetazolamide for a medical indication other than CME, we did not include patients who previously received acetazolamide and respected a 2-week wash-out period after cataract surgery. The time between cataract surgery and CME with treatment was calculated. The duration of treatment was calculated. All analyses involved use of SAS 9.4 (SAS Inc, Cary, NC). Over 1 year, 19 980 eyes in 13 556 patients (60% women; mean age, 71.2 9.4 years) underwent uncomplicated phacoemulsification. The incidence of YAG laser capsulotomy was 10.6%, with a median delay of 12.0 months (interquartile range, 6.8-15.7) after cataract surgery. A total of 128 patients received acetazolamide for CME after cataract surgery, for a 2-year incidence of 0.95% (Table 1). In all, 90.82% received complementary local treatment with nonsteroidal anti-inflammatory drugs and/or steroids along with acetazolamide. The median CME occurrence was 2.7 months (interquartile range, 1.1e9.4). The mean standard deviation consumption of acetazolamidewas670 77.5mg/d. In13patients (9.4%),CMEpersisted for 6 to 12 months and in 11 patients (8.6%) for >12 months (Fig 1, available at www.aaojournal.org). The median duration of CME was 2.8 months (range, 1.9e4.9). The overall incidence of CME was higher for younger than older adults (2.38%, 1.30%, 0.90%, 0.68%, and 0.48% for patients 40e54, 55e64, 65e74, 75e84, and 85 years old, respectively; Ptrend 1⁄4 0.0009) and higher for men than women (1.25% vs 0.74%; P 1⁄4 0.002). The frequency of diabetes did not differ between patients with and without CME (1.05% vs 0.90%; P 1⁄4 0.48). Cystoid macular edema is divided into angiographic, optical coherence tomography, and clinical types. Angiographic CME refers to the macular edema seen on fluorescein angiography or optical coherence tomography without visual loss. Clinical CME refers to macular edema associated with decreased visual acuity. In a recent study, the incidence of CME at 12 weeks postoperatively was 3.2% on angiography and 5.5% on optical coherence tomography. The incidence of clinical CME after modern cataract surgery associated with visual loss up to 20/40 or worse ranges from 0.1% to 2.35%. We assessed CME with data from a medicoadministrative database tracked by acetazolamide prescription, mandatory first-line treatment for clinical pseudophakic CME according to the French Society of Ophthalmology, and found an incidence of CME of 0.95%. Most episodes of clinical CME resolve spontaneously over several months. However, CME that lasts more than 6 months is considered chronic. In a prospective study by Henderson et al, for 39 cases of CME among 1659 phakoemulsification cases, the proportion of chronic CME over 6 months was 12.8%. In the present study, the proportion of CME from 6 to 12 months was 9.4% and for >12 months 8.6%. In a recent study including all potential CME risk factors in a multivariate model, a history of retinal vein occlusion, epiretinal membrane, and preoperative prostaglandin use was associated with an increased risk of pseudophakic CME. The pathophysiology of increased incidence of CME after cataract surgery we found in relatively young patients remains speculative. One explanation may be the status of the vitreous at the time of cataract extraction. Cataract extraction increases the risk of posterior vitreous detachment, and pseudophakic eyes have an altered vitreous humor structure not seen in phakic eyes. Consequently, cataract extraction in relatively young patients without previous posterior vitreous detachment may alter the microenvironment of the vitreous and retina, thereby increasing the risk of CME. In the present analysis, CME incidence was higher in men. An increased risk of retinal detachment after cataract surgery was previously observed in men. One hypothesis to explain higher retinal complications in men could be a higher rate of history of eye trauma in men compared with women. Diabetes mellitus represents a state in which the integrity of the blooderetinal barrier is compromised. Intraocular surgery, even uneventful, is a proinflammatory event that may increase the risk of postoperative CME in diabetic patients. In this study, CME incidence was not higher in diabetic than nondiabetic patients. In the Henderson et al study, among 1659 cataract surgeries, patients with diabetes mellitus did not have an increased risk of CME compared with nondiabetic patients. The strengths of the study are the population size, the representativeness, the importance of the findings, and the potential impact on public health. Given the reliance on ERASME codes for selecting patients and ascertaining outcomes, there was potential for misclassificationor underdetection-related biases. This study is limited to clinical CME requiring treatment with acetazolamide, which may have underestimated the incidence of CME. Although there are few studies of acetazolamide efficiency in CME, the treatment is used widely by ophthalmologists in France and is mandatory as first-line therapy according to the French Society of Ophthalmology.

Investigating the completeness of a histopathological cancer registry: Estimation by capture–recapture analysis in a French geographical unit Alpes-Maritimes, 2008

INTRODUCTION Cancer population studies require reliable and complete baseline data, which should theoretically be available by collecting histopathology records. The completeness of such a collection was evaluated using capture-recapture analysis based on three data sources concerning breast and colorectal cancers over an identical period and within the same geographical area. METHOD The total number of breast and colon cancer cases was estimated using capture-recapture analysis based on the number of cases which were common or not between sources recording screened, diagnosed and treated cancers in the French Alpes Maritimes district. RESULT The estimated total number of new cases of breast cancer diagnosed among Alpes Maritimes residents women aged 50-75 was 791 (95% CI: 784-797) in 2008. Of these 791 cases, 729 were identified through histopathology records, thus amounting to 92.2% completeness (95% CI: 91.5-93.0%). The total estimated number of new cases of colorectal cancer diagnosed among Alpes Maritimes residents aged 50-75 was 527 (95% CI: 517-536). Of these 527 cases, 481 were identified through histopathology records, thus amounting to 91.3% completeness (95% CI: 89.7-93.0%). CONCLUSION The estimated completeness of cancer records collected from histopathology laboratories was higher than 90% for new cases of breast and colorectal cancer within the age range concerned by the screening programme. A verified and validated histopathology data collection may be useful for cancer population studies.