Paradigm shifts in multiple sclerosis management: Implications for daily clinical practice.

Multiple sclerosis (MS) is the most common chronic inflammatory neurological disease. The emergence of disease-modifying therapies (DMTs) has greatly improved disease activity control and progression of disability in MS patients. DMTs differ in their mode of action, route of administration, efficacy, and safety profiles, offering multiple options for clinicians. Personalized medicine aims at tailoring the therapeutic strategy to patients' characteristics and disease activity but also patients' needs and preferences. New therapeutic options have already changed treatment paradigms for patients with active relapsing MS (RMS). The traditional approach consists in initiating treatment with moderate-efficacy DMTs and subsequently, escalating to higher-efficacy DMTs when there is evidence of clinical and/or radiological breakthrough activity. Recent real-world studies suggest that initiation of high-efficacy DMTs from disease onset can improve long-term outcomes for RMS patients. In this article, we review different treatment strategies and discuss challenges associated with personalized therapy.

Secondary progressive multiple sclerosis: A national consensus paper on diagnostic criteria.

BACKGROUND: In clinical practice, the diagnosis of secondary progressive multiple sclerosis (SPMS) is often delayed, retrospective and non-reproducible, as there are no consensus criteria that define the advent of SPMS. Early identification of SPMS is essential to improve patient care. METHODS: Eight regional board meetings in France involving 56 multiple sclerosis (MS) experts (neurologists) were convened to discuss diagnostic criteria for SPMS. Subsequently, a national board meeting of 13 neurologists (with an expert representing each geographical region) was held to review points of convergence or divergence between regions and to develop a national consensus document. RESULTS: Based on the discussions from the regional boards, the MS experts at the national board retained the worsening of the EDSS score, with compatible clinical features, as the only consensus criterion for the diagnosis of SPMS in clinical practice. The patient should have experienced during at least the previous 6 months and in the absence of any relapse, a worsening in the EDSS score of +1.0 point (if the previous EDSS was≤5.0) or of +0.5 point (if the previous EDSS was≥5.5), with a pyramidal or cerebellar functional system score≥2 and without setting a minimum EDSS score; or, in case of a stable EDSS score≥4.0, a worsening of a functional score. This worsening should be confirmed within 3 to 6 months. According to the MS experts, the patient's age, duration of illness and a minimal threshold EDSS score are only risk factors for transition to SPMS. Patient reports during consultation and cognitive impairment are important warning signs, which should trigger an objective assessment with specific tests or closer monitoring. Clinical relapse and/or MRI activities are non-discriminatory for making the diagnosis of SPMS. CONCLUSIONS: The experts defined precise diagnostic criteria adapted to clinical practice for earlier identification of SPMS, paving the way for better management of this stage of the disease.

Optimizing 3D FLAIR to detect MS lesions: pushing past factory settings for precise results.

BACKGROUND: To assess the diagnostic value of three 3D FLAIR sequences with differing repetition-times (TR) at 3-Tesla when detecting multiple sclerosis (MS) lesions. METHODS: In this prospective study, approved by the institutional review board, 27 patients with confirmed MS were prospectively included. One radiologist performed manual segmentations of all high-signal intensity lesions using three 3D FLAIR data sets with different TR of 4800 ms ("FLAIR4800"), 8000 ms ("FLAIR8000") and 10,000 ms ("FLAIR10,000") and two radiologists double-checked it. The main judgment criterion was the overall number of lesions; secondary objectives were the assessment of lesion location, as well as measuring contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR). A non-parametric Wilcoxon's test was used to compare the differing FLAIR. RESULTS: The FLAIR8000 and FLAIR10,000 detected significantly more overall lesions per patient as compared with the FLAIR4800 [116.1 (± 61.7) (p = 0.02) and 115.8 (± 56.3) (p = 0.03) versus 99.2 (± 66.9), respectively]. The FLAIR8000 and FLAIR10,000 detected four and eight times more cortical or juxta-cortical lesions per patient as compared with FLAIR4800 [1.6 (± 2.2) (p = 0.001) and 4.1 (± 5.9) (p = 6 × 10-5) versus 0.4 (± 1.1), respectively]. CNR was significantly correlated to the TR value. It was significantly higher with FLAIR10,000 than it was with FLAIR8000 and FLAIR4800 [16.3 (± 3.5) versus 15 (± 2.4) (p = 0.01) and 12 (± 2.2) (p = 2 × 10-6), respectively] CONCLUSION: An optimized 3D FLAIR with a long TR significantly improved both overall lesion detection and CNR in MS patients as compared to a 3D FLAIR with factory settings.

A 3T Phase-Sensitive Inversion Recovery MRI Sequence Improves Detection of Cervical Spinal Cord Lesions and Shows Active Lesions in Patients with Multiple Sclerosis.

BACKGROUND AND PURPOSE: Magnetic Resonance Imaging is the modality of choice to detect spinal cord lesions in patients with Multiple Sclerosis (MS). However, this imaging is challenging. New sequences such as phase-sensitive inversion recovery have been developed to improve detection. Our aim was to compare a 3D phase-sensitive inversion recovery and a conventional imaging dataset including postcontrast T2WI and T1WI to detect MS spinal cord lesions. MATERIALS AND METHODS: This retrospective single-center study included 100 consecutive patients with MS (mean age, 41 years) from January 2015 to June 2016. One senior neuroradiologist and 1 junior radiologist blinded to clinical data checked for new spinal cord lesions, individually analyzing conventional and 3D phase-sensitive inversion recovery datasets separately, placing a 3-week delay between the 2 readings. A consensus reading was done with a third senior neuroradiologist. A Wilcoxon test was used to compare the 2 imaging datasets. Intra- and interobserver agreement was assessed by the κ coefficient. RESULTS: 3D phase-sensitive inversion recovery detected significantly more lesions than conventional imaging (480 versus 168, P < .001). Eleven patients had no detected lesions on T2WI, whereas 3D phase-sensitive inversion recovery detected at least 1 lesion. All postcontrast T1WI enhancing lesions were also visible on 3D phase-sensitive inversion recovery. The signal-to-noise ratio was significantly higher using 3D phase-sensitive inversion recovery (0.63 versus 0.46, P = .03). Mean reading confidence was significantly higher using 3D phase-sensitive inversion recovery. Inter- and intraobserver agreement was good for both datasets. CONCLUSIONS: Our study showed that 3D phase-sensitive inversion recovery significantly improved detection of cervical spinal cord lesions, including both enhancing and nonenhancing lesions in patients with MS.

Acute idiopathic optic neuritis: not always benign.

BACKGROUND AND PURPOSE: Few recent data are available concerning idiopathic optic neuritis (ON). We aimed to describe a large cohort of patients with idiopathic ON. We compared this cohort with patients with ON related to myelin oligodendrocyte glycoprotein (MOG) or ON related to aquaporin-4 (AQP4) antibodies. METHODS: This was a monocentric retrospective observational study. Inclusion criteria for idiopathic ON were as follows: age ≥ 16 years, follow-up of at least 2 years, negative for antibodies against MOG and AQP4 immunoglobulin G, and no magnetic resonance imaging (MRI) lesions suggestive of demyelination (two brain MRI scans, one at baseline and one during follow-up, and one spinal cord MRI scan). RESULTS: Among 23 patients with idiopathic ON (female, 82.6%; median age, 36 years; median follow-up time, 41.4 months), 56.5% had recurrent ON (median time to a second ON episode, 6 months). The final visual acuity in this group (median, 0; mean, 0.43; range, 0-3) was similar to that in the AQP4 group (n = 18; P-value after Bonferroni correction = 0.936) but worse than that in the MOG group (n = 25; P-value after Bonferroni correction = 0.019). At the last evaluation, visual acuity levels were ≤0.5 and <0.2, respectively, in 36.8% and 21% of the idiopathic ON group, 58.3% and 26.7% of the AQP4 group, and 0% and 0% of the MOG group. CONCLUSION: The recovery of visual acuity among patients with idiopathic ON was poor, similar to that observed in the AQP4 group.

Improved Detection of New MS Lesions during Follow-Up Using an Automated MR Coregistration-Fusion Method.

BACKGROUND AND PURPOSE: MR imaging is the key examination in the follow-up of patients with MS, by identification of new high-signal T2 brain lesions. However, identifying new lesions when scrolling through 2 follow-up MR images can be difficult and time-consuming. Our aim was to compare an automated coregistration-fusion reading approach with the standard approach by identifying new high-signal T2 brain lesions in patients with multiple sclerosis during follow-up MR imaging. MATERIALS AND METHODS: This prospective monocenter study included 94 patients (mean age, 38.9 years) treated for MS with dimethyl fumarate from January 2014 to August 2016. One senior neuroradiologist and 1 junior radiologist checked for new high-signal T2 brain lesions, independently analyzing blinded image datasets with automated coregistration-fusion or the standard scroll-through approach with a 3-week delay between the 2 readings. A consensus reading with a second senior neuroradiologist served as a criterion standard for analyses. A Poisson regression and logistic and γ regressions were used to compare the 2 methods. Intra- and interobserver agreement was assessed by the κ coefficient. RESULTS: There were significantly more new high-signal T2 lesions per patient detected with the coregistration-fusion method (7 versus 4, P < .001). The coregistration-fusion method detected significantly more patients with at least 1 new high-signal T2 lesion (59% versus 46%, P = .02) and was associated with significantly faster overall reading time (86 seconds faster, P < .001) and higher reader confidence (91% versus 40%, P < 1 × 10-4). Inter- and intraobserver agreement was excellent for counting new high-signal T2 lesions. CONCLUSIONS: Our study showed that an automated coregistration-fusion method was more sensitive for detecting new high-signal T2 lesions in patients with MS and reducing reading time. This method could help to improve follow-up care.

Etiologies of acute demyelinating optic neuritis: an observational study of 110 patients.

BACKGROUND AND PURPOSE: New criteria for the diagnosis of multiple sclerosis (MS) and discovery of myelin oligodendrocyte glycoprotein (MOG) or aquaporin-4 (AQP4) antibodies (Abs) have changed the management of optic neuritis (ON). Our aim was to specify, in view of these recent advances, the etiologies of acute demyelinating ON for consecutive patients. METHODS: Retrospective database analysis was undertaken of consecutive adult patients with acute ON admitted from 1 December 2014 to 31 January 2016. Diagnosis of MS was made according to the 2010 McDonald criteria. Patients with Abs to AQP4 or MOG were classified as ON-AQP4 and ON-MOG, respectively. Patients who did not fulfill the diagnostic criteria and were negative for AQP4 and MOG Ab tests were classified as having idiopathic ON. RESULTS: Of 110 patients assessed, 78 had ON related to MS (70.9%). All patients without MS were tested for AQP4 and MOG Abs: 11 had MOG Ab (10%), 5 had AQP4 Ab (4.5%) and 16 were considered as having idiopathic ON (14.5%). Presence of intrathecal IgG oligoclonal bands was strongly associated with MS (mean, 88.4% vs. 34.4% in patients without MS; after Bonferroni correction, P < 0.0001). CONCLUSIONS: Optic neuritis related to MOG Ab was the second cause identified of demyelinating ON in our center. Idiopathic ON was as frequent as both ON-AQP4 and ON-MOG combined.

A two-phase sampling survey for nonresponse and its paradata to correct nonresponse bias in a health surveillance survey.

BACKGROUND: The decline in participation rates in surveys, including epidemiological surveillance surveys, has become a real concern since it may increase nonresponse bias. The aim of this study is to estimate the contribution of a complementary survey among a subsample of nonrespondents, and the additional contribution of paradata in correcting for nonresponse bias in an occupational health surveillance survey. METHODS: In 2010, 10,000 workers were randomly selected and sent a postal questionnaire. Sociodemographic data were available for the whole sample. After data collection of the questionnaires, a complementary survey among a random subsample of 500 nonrespondents was performed using a questionnaire administered by an interviewer. Paradata were collected for the complete subsample of the complementary survey. Nonresponse bias in the initial sample and in the combined samples were assessed using variables from administrative databases available for the whole sample, not subject to differential measurement errors. Corrected prevalences by reweighting technique were estimated by first using the initial survey alone and then the initial and complementary surveys combined, under several assumptions regarding the missing data process. Results were compared by computing relative errors. RESULTS: The response rates of the initial and complementary surveys were 23.6% and 62.6%, respectively. For the initial and the combined surveys, the relative errors decreased after correction for nonresponse on sociodemographic variables. For the combined surveys without paradata, relative errors decreased compared with the initial survey. The contribution of the paradata was weak. CONCLUSION: When a complex descriptive survey has a low response rate, a short complementary survey among nonrespondents with a protocol which aims to maximize the response rates, is useful. The contribution of sociodemographic variables in correcting for nonresponse bias is important whereas the additional contribution of paradata in correcting for nonresponse bias is questionable.

Impact of diabetes mellitus onset on sickness absence from work--a 15-year follow-up of the GAZEL Occupational Cohort Study.

AIMS: Previous studies do not provide an accurate estimate of the burden of diabetes on sickness absence. The aim of this study was to measure the impact of diabetes onset on absenteeism starting from the earliest occurrence of the disease. METHODS: The authors used data from a subsample of the French GAZEL cohort of 506 employees with incident diabetes and 2530 matched diabetes-free participants. Medically certified sickness absence data were obtained from company records (1989-2007). Number of sickness absence days and incidence rates of overall and cause-specific absence spells were compared according to diabetes status across three 5-year periods ranging from 10 years before to 5 years after onset of cases' diabetes. RESULTS: The mean number of sickness absence days was persistently higher in participants with diabetes compared with those without diabetes. This difference increased from 16.4 days (95% confidence interval 7.2-25.5) during the 5-year period preceding diabetes onset to 28.5 days (95% CI 16.1-40.9) during the following 5-year period (P = 0.04). This was due to a steeper relative increase in the incidence of long (but not short) absence spells in participants with diabetes versus those without diabetes [incidence rate ratios 1.33 (95% CI 1.08-1.64) and 1.75 (95% CI 1.43-2.14), respectively; P = 0.02]. Diabetes onset was associated with increased rates of circulatory and metabolic absence spells. CONCLUSIONS: Onset of diabetes is associated with a substantial increase in sickness absence. This suggests that in addition to its burden on work cessation, diabetes weighs heavily on working ability among people who manage to remain employed.

[Intracranial hypertension and lupus]. / Hypertension intracrânienne et lupus.

INTRODUCTION: Idiopathic intracranial hypertension (IH) occurs most commonly in women and overweight subjects. It must be reported associated to general diseases, like systemic lupus erythematosus (SLE). METHODS: We report an observation of a patient with lupus complicated by glomerulonephritis and IH. OBSERVATION: A 29 years old woman, without overweight, was followed for a SLE with skin and arthritic involvement . Four years after onset, a renal complication appeared with severe nephrotic syndrome. Six weeks after, bilateral papillar oedema was discovered, revealing an IH, as the patient was treated by oral steroids at 1mg/kg/d and bimonthly intravenous cyclophosphamide. The patient was completely asymptomatic. Brain MRI with veino-RMN was normal, without cerebral venous thrombosis. Lumbar punction showed an elevated opening pressure of 30,5 cmH(2)0 but with normal cerebrospinal fluid (CSF) contents. Evacuation of 30 mL of CSF and immunosuppressive treatment allowed symptoms regression. DISCUSSION/CONCLUSION: Twenty-seven cases of IH associated to SLE with nephritis have been reported in literature. Young women are more frequently involved with in half of cases a diffuse proliferative glomerulonephritis. Predisposing factors, like anaemia, must be associated. IH allows SLE diagnose in more than the third of the cases. Then, SLE has to be searched as an etiology of IH, in particular in non-obese patients and when nephritis is associated.

Prevalence of educational inequalities in obesity between 1970 and 2003 in France.

This paper examines trends in obesity rates and education-related absolute and relative inequalities in obesity over the last 40 years in France. Data are drawn from the French Decennial Health Surveys of 1970, 1980, 1991 and 2003. The difference in obesity rates between the least- and most-educated, the Slope Index of Inequality, is used to estimate absolute inequalities in obesity. The ratio of the corresponding rates, the Relative Index of Inequality, reveals the relative inequalities in obesity. Obesity rates were similar in men and women, but educational inequalities were greater in women. Obesity rates were similar over the first three surveys but increased for all in the 2003 survey. This increase was accompanied by increases in absolute inequalities in men (P = 0.04) from a Slope Index of Inequality of 4.80% (95% confidence interval [CI] = 2.27, 7.32) to 8.64% (95% CI = 5.97, 11.32) and women (P = 0.004) from 8.90% (95% CI = 6.18, 11.63) to 14.57% (95% CI = 11.83, 17.32). Relative inequalities in obesity remained stable over the 40 years. Recent increase in obesity rates in France is accompanied by increases in absolute education-related inequalities, while relative inequalities have remained stable; this suggests that obesity rates have increased at a much faster rate in the low-education groups.

Socioeconomic position and cognitive decline using data from two waves: what is the role of the wave 1 cognitive measure?

BACKGROUND: Analysis of change in health status using data from two waves can be examined either adjusted or unadjusted for baseline health status. The effect of socioeconomic position (SEP) on cognitive change was assessed using both these strategies and the implications of the analyses are discussed. METHODS: Data from 1261 men and 483 women of the Whitehall II cohort study, aged 50-55 years at wave 1, were used. Cognition was assessed at both waves using a test of verbal memory, and two tests of verbal fluency. Analysis of variance (ANOVA) was used to estimate the effect of SEP on change score and analysis of covariance (ANCOVA) was used to estimate this effect adjusted for the baseline cognitive score. The ANCOVA estimates were corrected for bias due to measurement error (estimated based on 3-month test-retest). Finally, ANCOVA estimates were examined for increasing levels of measurement error. RESULTS: The results of the ANOVA suggest no effect of SEP on cognitive decline. In contrast, the ANCOVA suggests significantly greater cognitive decline in the lower SEP groups. However, the ANCOVA estimates for the effect of wave 1 cognition show evidence for regression to the mean due to the presence of measurement error. The corrected ANCOVA estimates show no association between SEP and cognitive decline. CONCLUSIONS: Results from analysis of change using two waves of observational data, when adjusted for baseline, should be interpreted with caution.

Pain relief by rTMS: differential effect of current flow but no specific action on pain subtypes.

OBJECTIVES: To assess, against placebo, the pain-relieving effects of high-rate repetitive transcranial magnetic stimulation (rTMS) on neuropathic pain. METHODS: Double-blind, randomized, cross-over study of high-rate rTMS against placebo in 28 patients. The effect of a change in coil orientation (posteroanterior vs lateromedial) on different subtypes of neuropathic pain was further tested in a subset of 16 patients. Pain relief was evaluated daily during 1 week. RESULTS: High-frequency, posteroanterior rTMS decreased pain scores significantly more than placebo. Posteroanterior rTMS also outmatched placebo in a score combining subjective (pain relief, quality of life) and objective (rescue drug intake) criteria of treatment benefit. Changing the orientation of the coil from posteroanterior to lateromedial did not yield any significant pain relief. The analgesic effects of posteroanterior rTMS lasted for approximately 1 week. The pain-relieving effects were observed exclusively on global scores reflecting the most distressing type of pain in each patient. Conversely, rTMS did not modify specifically any of the pain subscores that were separately tested (ongoing, paroxysmal, stimulus-evoked, or disesthesic pain). CONCLUSIONS: Posteroanterior repetitive transcranial magnetic stimulation (rTMS) was more effective than both placebo and lateromedial rTMS. When obtained, pain relief was not specific of any particular submodality, but rather reduced the global pain sensation whatever its type. This is in accord with recent models of motor cortex neurostimulation, postulating that its analgesic effects may derive in part from modulation of the affective appraisal of pain, rather than a decrease of its sensory components.

Disease severity, self-reported experience of workplace discrimination and employment loss during the course of chronic HIV disease: differences according to gender and education.

OBJECTIVES: Evidence for the existence of a harmful effect of chronic disease on employment status has been provided. Although this effect of chronic illness on employment has been reported to be higher among the groups with the lowest position on the labour market, the mechanisms of such inequalities are poorly understood. The present study aimed at investigating social inequalities in the chances of maintaining employment during the course of HIV infection and at examining the correlates of such inequalities. METHODS: The authors used data from a national representative sample of people living with HIV in France (ANRS-EN12-VESPA survey). Retrospective information on social trajectory and disease characteristics from the time of HIV diagnosis was available. The risk of employment loss associated with indicators of disease severity and HIV-related workplace discrimination was computed over time since HIV diagnosis according to sociodemographic and occupational factors, using Cox proportional hazards models. RESULTS: Among the 478 working-age participants diagnosed as being HIV-infected in the era of multitherapies and employed at the time of HIV diagnosis, 149 experienced employment loss. After adjusting for sociodemographic and occupational factors, disease severity and self-reported HIV-related discrimination at work were significantly associated with the risk of employment loss in a socially-differentiated manner: advancement in HIV disease was associated with an increased risk of employment loss among women (HR 4.45, 95% CI 2.10 to 9.43) but not among men; self-reported experience of HIV-related discrimination at work was associated with an increased risk of employment loss among individuals with a primary/secondary educational level (HR 8.85, 95% CI 3.68 to 21.30) but not among those more educated. CONCLUSIONS: Chronic HIV disease affects the chances of maintaining employment in a socially-differentiated manner, resulting in increasing inequalities regarding workforce participation. Disease severity and workplace HIV-related discrimination, particularly affecting the employment status of the most socioeconomically disadvantaged, may play a major role.

Molecular markers of cartilage breakdown and synovitis at baseline as predictors of structural progression of hip osteoarthritis. The ECHODIAH Cohort.

OBJECTIVE: To determine whether systemic markers of bone, cartilage, and synovium can predict structural progression of osteoarthritis (OA). METHODS: Patients with painful hip OA were treated with diacerein or placebo in a multicentre, prospective, double blind, 3 year follow up trial. The following information was collected at entry: demographics, characteristics of hip OA, and 10 markers: N-propeptides of collagen types I and III, cartilage oligomeric matrix protein, YKL-40, hyaluronan (sHA), matrix metalloproteinases-1 and -3, C reactive protein, C-terminal crosslinking telopeptides of collagen types I and II (uCTX-II). Radiographs were obtained at entry and every year. Structural progression was defined as a joint space decrease > or =0.5 mm or requirement for total hip replacement. Grouped survival analysis was performed with time to structural progression as dependent variable, and clinical data, radiographic findings, treatment groups (diacerein versus placebo), and markers as explanatory measures. RESULTS: In the 333 patients in whom all markers were measured, high functional impairment, a joint space width <2 mm, and lateral migration of the femoral head at baseline increased the risk of progression, but diacerein had a protective effect (relative risk = 0.75; 95% confidence interval (CI) 0.54 to 0.96). In addition, patients in whom uCTX-II and sHA were in the upper tertile had a relative risk of progression of 3.73 (95% CI 2.48 to 5.61) compared with patients with markers in the two lower tertiles. CONCLUSION: In this large cohort, combined measurements of uCTX-II and sHA were a new predictor of the structural progression of hip OA.

Using a representative sample of workers for constructing the SUMEX French general population based job-exposure matrix.

BACKGROUND: Job-exposure matrices (JEMs) applicable to the general population are usually constructed by using only the expertise of specialists. AIMS: To construct a population based JEM for chemical agents from data based on a sample of French workers for surveillance purposes. METHODS: The SUMEX job-exposure matrix was constructed from data collected via a cross-sectional survey of a sample of French workers representative of the main economic sectors through the SUMER-94 survey: 1205 occupational physicians questioned 48 156 workers, and inventoried exposure to 102 chemicals. The companies' economic activities and the workers' occupations were coded according to the official French nomenclatures. A segmentation method was used to construct job groups that were homogeneous for exposure prevalence to chemical agents. The matrix was constructed in two stages: consolidation of occupations according to exposure prevalence; and establishment of exposure indices based on individual data from all the subjects in the sample. RESULTS: An agent specific matrix could be constructed for 80 of the chemicals. The quality of the classification obtained for each was variable: globally, the performance of the method was better for less specific and therefore more easy to assess agents, and for exposures specific to certain occupations. CONCLUSIONS: Software has been developed to enable the SUMEX matrix to be used by occupational physicians and other prevention professionals responsible for surveillance of the health of the workforce in France.

Occupational mobility and risk factors in working men: selection, causality or both? Results from the GAZEL study.

OBJECTIVE: To explore the relation between risk factors (RF) and occupational mobility in working men. SETTING: 20 000 volunteers working at the French National Electricity and Gas Company (GAZEL cohort). PARTICIPANTS: Men aged 43 to 53 years in 1992. DESIGN: Three designs were used for analysis. (1) The association between occupational mobility experienced before 1992 and RF reported at that date was analysed among 10 383 men. (2) The predictive role of RF on occupational mobility over 1992-1999 was studied in a subsample of 4715 men. (3) Reciprocally, occupational mobility in 1985-1992 was analysed in relation to RF changes over 1993-1999. MAIN OUTCOME MEASURES: Self reported smoking status, excessive alcohol consumption, arterial hypertension, and overweight. Occupational mobility defined by any upward transition between senior executives and professionals/middle executives/employees, and workers. RESULTS: (1) Cross sectionally, non-mobile men as their entry into the company had a higher risk of being smokers, excessive alcohol drinkers, and overweight in 1992 than mobile men. (2) Longitudinally, smokers and excessive alcohol drinkers in 1992 had a higher risk of non-mobility than, respectively, non-smokers and non-excessive alcohol drinkers. (3) Non-mobile men in 1985-1992 had a higher risk of becoming smokers, excessive alcohol drinkers, and hypertensive in 1993-1999 than upwardly mobile men. CONCLUSION: These results suggest a complex relation between RF and occupational mobility. A high level of RF, particularly health behaviours, might account for a selection process reducing upward occupational mobility. In turn, a lack of upward occupational mobility might be associated with an increased incidence of RF.

Sex differences in hip osteoarthritis: results of a longitudinal study in 508 patients.

OBJECTIVE: To evaluate sex differences in the clinical and structural presentation, and natural history of hip OA. METHODS: A multicentre, prospective, longitudinal, five year follow up study of 508 patients (302 women, 206 men, mean age 63 (7) years) with painful hip OA. Data collected were baseline demographics, symptomatic, therapeutic, and structural variables; symptomatic variables and changes in joint space width (JSW) during the first year's follow up; requirement for total hip arthroplasty (THA) between the end of the first and fifth years. STATISTICAL ANALYSIS: evaluation of sex differences (a) at baseline, in the main characteristics of hip OA using multivariate logistic regression; (b) during the first year of follow up, in the radiological progression of the disease; (c) during the five years of follow up, in the requirement for THA using Kaplan-Meier curves and the log rank test, and of the parameters related to THA, using a multivariate Cox analysis. RESULTS: At entry, women presented more frequently than men with polyarticular OA (mean (SD) articular score 306 (162) v 235 (127)), and superomedial migration of the femoral head (40% v 19%), and had more severe symptomatic disease (patient's overall assessment 46 (23) v 40 (26)). The change in JSW did not differ between women and men after one year, but a greater proportion of women had rapid structural progression (OR=2.34, 95% CI 1.1 to 5.2). THA was performed more often in women. Multivariate analysis suggested that the decision to perform surgery was related more closely to the symptomatic and structural severity of the disease than to the sex of the patient. CONCLUSION: Hip OA in women is more frequently part of a polyarticular OA, and displays greater symptomatic and structural severity.