Management of diabetic macular oedema in France from 2012 to 2018: The nationwide LANDSCAPE study.

OBJECTIVE: To describe the management of diabetic macular oedema (DME) patients from the entire French population between 2012 and 2018. METHODS: In this retrospective longitudinal study, we identified adults treated for DME from the French population using the exhaustive French National Health Information database (SNDS), and an algorithm based on diagnosis and procedure codes, and reimbursed treatments. RESULTS: Between 2012 and 2018, we identified 53 584 treated DME patients, who were followed for up to 7 years from DME treatment initiation. Optical coherence tomography (OCT) became the predominant imaging tool to diagnose DME. Only 14% of patients consulted a diabetologist or endocrinologist in the 3 months prior to initiating DME treatment, whereas 84% consulted a general practitioner. The percentage of patients consulting an ophthalmologist declined over time, from 97% of patients in Year 1 (median of 9 consultations), to 46% in Year 7 (median of 7 consultations). The median DME treatment duration with an anti-VEGF and/or dexamethasone implant treatment was 9 months; 54% of patients had a treatment duration less than 1 year. First-line treatment was more common with ranibizumab (55% of patients) than with aflibercept (30%), or dexamethasone implant (15%). About 25% of patients who initiated anti-VEGF treatment switched treatment at least once, while 30% of patients who initiated dexamethasone implant switched to anti-VEGF treatment at least once. CONCLUSIONS: French DME patients seem well-monitored by their ophthalmologist, but median DME treatment duration was just 9 months. These results emphasise the challenge to manage and treat patients with DME over the long term.

Management of Neovascular Age-Related Macular Degeneration Treatment in France from 2008-2018: The Nationwide LANDSCAPE Study.

INTRODUCTION: The aim of this study was to describe the management of neovascular age-related macular degeneration (nAMD) in French patients between 2008 and 2018. METHODS: This was a retrospective longitudinal cohort study using exhaustive nationwide health records from the French National Health Information database. Enrollment criteria were adults aged ≥ 50 years, nAMD diagnosis, or reimbursement for nAMD treatments (anti-vascular epithelial growth factor [VEGF] injection or dynamic phototherapy with verteporfin). Exclusion criteria were high myopia, diagnosis of other retinal diseases, and treatments for other macular diseases (dexamethasone implant, laser). Main outcome measures were consumption of medical care and nAMD treatments per calendar year and number of years of follow-up. RESULTS: Between 2008 and 2018, we identified 342,961 patients who have been treated for nAMD. Median duration of ophthalmological follow-up exceeded 7 years (90 months). The median annual number of ophthalmology consultations decreased from nine visits in year 1 after treatment initiation to four visits from year 7 onwards. The median duration of nAMD treatment was 10.1 months for all patients, with 48.5% of patients undergoing treatment for < 1 year. Only 24.4% of patients had maintained treatment at year 11. Patients remaining under treatment had a median of four anti-VEGF treatments per year throughout the 10-year study period. Ranibizumab was the more common first-line treatment (67.5% of patients) compared to aflibercept (32.4%). About 20% of patients who initiated treatment switched treatment at least once. CONCLUSIONS: LANDSCAPE provides exhaustive nationwide data on the real-world management of nAMD in France over a 10-year period. Further investigation into short treatment duration is required, especially in terms of understanding its relation to visual outcomes.

Detection and Management of Intraocular Inflammation after Brolucizumab Treatment for Neovascular Age-Related Macular Degeneration.

PURPOSE: To present interim descriptive insights from the OCTOPUS and SWIFT studies on incidence, clinical features, management, and outcomes of intraocular inflammation (IOI), vasculitis, and occlusive vasculitis with brolucizumab treatment (Beovu, Novartis) in patients with neovascular age-related macular degeneration (nAMD) who were anti-VEGF naive or pretreated with anti-VEGFs (ranibizumab or aflibercept). DESIGN: OCTOPUS (NCT04239027) and SWIFT (NCT04264819) studies are prospective phase IIIb single-arm, open-label, multicenter studies assessing brolucizumab. SUBJECTS: Anti-VEGF naive (OCTOPUS) and pretreated (SWIFT) patients with nAMD. METHODS: Interim prespecified analysis on the efficacy end point provided an opportunity to analyze IOI-related safety. Reports of IOI-related adverse events (AEs) were reviewed, and AE images and clinical features and outcomes of each case were analyzed by a review committee. RESULTS: Of 505 brolucizumab-treated eyes/patients with median brolucizumab treatment of 8.8 months, 53 eyes demonstrated at least 1 IOI-related AE. The incidence of overall IOI-related AEs was 10.5%; among these events, the incidence was 7.1% for IOI only without retinal involvement and 3.4% for IOI with retinal involvement (2.0% with vasculitis, 1.4% with vascular occlusion with or without vasculitis). Incidence was similar in naive and pretreated patients. Before the onset of the first IOI-related AE, eyes received a median of 2 brolucizumab injections; 81.1% of IOI-related AEs occurred during the loading phase (median, 25.0 days from the last brolucizumab injection). At AE onset, most frequently reported symptoms were floaters (52.8%) and blurred or decreased vision (37.8%). Of the 86.8% of AEs that were treated, most were treated with topical corticosteroids (75.5%), 28.3% by systemic corticosteroids, and 26.8% by intraocular corticosteroids. No severe vision loss was reported for the 7 nontreated AEs. Overall, the median best-corrected visual acuity (BCVA) change at IOI-related AEs resolution from baseline was 1 letter (range, -74 to +32 letters), and 2 patients with occlusive vasculitis had BCVA loss ≥ 15 letters due to IOI-related AEs. All eyes permanently discontinued brolucizumab after the first IOI-related AE. CONCLUSIONS: This analysis highlights the need for monitoring and education of patients to report any signs of IOI-related events immediately when being treated with brolucizumab. IOI should be treated promptly and intensely with corticosteroids. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Epidemiology of Treated Diabetes Ocular Complications in France 2008-2018-The LANDSCAPE French Nationwide Study.

AIM: LANDSCAPE aimed to estimate the annual incidence and prevalence of treated diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) between 2008 and 2018. METHODS: This French nationwide observational study used data from the French National Health Insurance Databases covering 99% of the French population. Data about healthcare consumption were used to identify adults treated with anti-VEGFs or dexamethasone implants (for DME) and with pan-retinal photocoagulation (for PDR). All French patients newly treated between 2008 and 2018 were included. Incidence and prevalence of treated DME and PDR were estimated for the age-matched general population and the population with diabetes in France. Sociodemographic characteristics and medical history were described in both populations. RESULTS: We identified 53,584 treated DME patients and 127,273 treated PDR patients between 2008 and 2018, and 11,901 DME and 11,996 PDR new incident patients in 2018. The treated DME incidence in 2018 was 2.5 per 10,000 in the general population and 37.3 per 10,000 in the population with diabetes. Prevalence in 2018 was 9.5 and 143.7 per 10,000 in the respective populations. Treated PDR incidence in 2018 was 2.3 per 10,000 in the general population and 31.2 per 10,000 in the population with diabetes. Prevalence in 2018 was 19.9 and 270.3 per 10,000 in the respective populations. Incidence and prevalence were not age-dependent. Incidence of treated PDR incidence was relatively stable from 2008-2018. Incidence of treated DME incidence rose from 2012-2018, probably due to widening access to newly available treatments, such as anti-VEGFs. CONCLUSIONS: We provide exhaustive nationwide data on the incidence and prevalence of treated diabetic ocular complications in France over a 10-year period.

Incidence and Prevalence of Neovascular Age-Related Macular Degeneration in France between 2008 and 2018: The LANDSCAPE Study.

Purpose: This study aimed to estimate the incidence and prevalence of neovascular age-related macular degeneration (nAMD) in the French population between 2008 and 2018. Design: This was a retrospective, longitudinal population study using health care consumption data from the Système National des Données de Santé (SNDS; the French National Health Information Database), which covers approximately 99% of the French population. Participants: We identified individuals treated for nAMD from the French population 50 years of age and older. Identification criteria were nAMD diagnosis or reimbursement of nAMD treatments (anti-vascular endothelial growth factor intravitreal injection or dynamic phototherapy with verteporfin). Exclusion criteria were high myopia, diagnosis of other retinal diseases, and other treatments for macular diseases (dexamethasone implant, laser therapy, etc.). Methods: We calculated incidence and prevalence based on the age-matched general population in France. Adjustment for age and sex was also performed for incidence. Main Outcome Measures: Incidence and prevalence of nAMD in the French population between 2008 and 2018. Results: Between 2008 and 2018, we identified 342 961 patients with nAMD (67.5% women). Mean ± standard deviation age at nAMD diagnosis or first treatment increased from 78.8 ± 8.1 years in 2008 to 81.2 ± 7.9 years in 2018. In 2018, annual incidence was 0.149% and prevalence was 1.062% for the French population 50 years of age or older. Incidence was stable over the 10-year period. Annual incidence increased with age (0.223%, 0.380%, and 0.603% in those 60 years of age or older, 70 years of age or older, and 80 years of age or older, respectively), with similar trends for prevalence. No major differences were observed among the 14 regions of France for incidence or prevalence. Neovascular age-related macular degeneration incidence in 2018 was not impacted by the availability of primary or ophthalmology care in patients' localities. Conclusions: The LANDSCAPE study provides exhaustive nationwide data on incidence and prevalence of nAMD in France over a 10-year period.

ETOILE: Real-World Evidence of 24 Months of Ranibizumab 0.5 mg in Patients with Visual Impairment Due to Diabetic Macular Edema.

PURPOSE: To evaluate the real-world effectiveness of intravitreal ranibizumab 0.5 mg (Lucentis) in improving visual acuity (VA) in adults with decreased VA due to diabetic macular edema (DME). PATIENTS AND METHODS: Real-world prospective observational 24-month study. Ranibizumab-naïve patients (n=116) were enrolled, treated and followed up according to investigators' usual procedures. Outcomes included change from baseline to month 24 in best-corrected VA (BCVA; primary outcome), central retinal thickness (CRT), treatment exposure and safety. RESULTS: Overall, 62.9% of patients completed the study per protocol, 68.6% completed the induction phase (first three injections one month apart). On average, patients had 12.5 ophthalmologist visits and 5.74 injections in year 1, decreasing to 4.6 visits and 1.94 injections in year 2. Mean baseline BCVA was 58.4 letters, mean gain at M24 was +6.08 letters (95% CI: 2.95, 9.21). Gains were higher for patients who completed induction, and for patients who did not switch treatment. Mean CRT improved by 149.17 µm at M24. There were no new safety signals. BCVA variation of ≥6 letters by M3 was predictive of BCVA gains at M24 (p=0.007), as was hypertension medication at baseline (p=0.022). CONCLUSION: Real-world ranibizumab treatment improved VA in DME patients, despite fewer injections than recommended.

Real-World Outcomes with Ranibizumab 0.5 mg in Patients with Visual Impairment due to Diabetic Macular Edema: 12-Month Results from the 36-Month BOREAL-DME Study.

PURPOSE: To report the real-world effectiveness and safety of ranibizumab 0.5 mg in patients with visual impairment due to diabetic macular edema (DME). METHODS: This is a French, 36-month, multicenter, observational cohort study. Between December 2013 and April 2015, ophthalmologists enrolled diabetic patients aged ≥18 years with DME-related visual impairment and for whom ranibizumab 0.5 mg was initiated. Here, we present the 12-month results from this cohort. The primary endpoint was the mean change in best-corrected visual acuity (BCVA); sample size calculations were based on RESTORE trial data (BCVA mean change = 6.8 letters, preci sion = 0.7 letters). Secondary endpoints included the change in central subfield thickness (CSFT), number of visits, number of injections received, and frequency of ocular and nonocular adverse events and serious adverse events. RESULTS: Between December 2013 and April 2015, a total of 290 patients with DME were enrolled by 84 ophthalmologists; 12-month data are available for 242 patients (due to low recruitment rates, precision was recalculated for 242 evaluable patients: the precision was then of 1.0 letters). Mean age (± standard deviation) was 66.1 ± 11.0 years and 56.6% were male. The mean baseline BCVA and CSFT were 59.2 letters (95% confidence interval [CI] 57.3, 61.0) and 457 µm (95% CI: 438, 476), respectively. At month 12, the mean gain in BCVA from baseline was 7.4 letters (95% CI: 5.4, 9.4), with 36.8% of patients with BCVA > 70 letters versus 13.2% at baseline. Mean change in CSFT was -125 µm (95% CI: -146, -103). The mean number of ranibizumab injections was 5.1 ± 2.3 over an average of 10.4 ± 3.0 visits. No new safety findings were identified. CONCLUSIONS: The BOREAL study confirms the effectiveness and safety of ranibizumab for the treatment of DME-related visual impairment in routine clinical practice with fewer injections than reported in clinical trials.

Ranibizumab for choroidal neovascularization secondary to pseudoxanthoma elasticum: 4-year results from the PIXEL study in France.

PURPOSE: To evaluate the long-term effectiveness and safety of ranibizumab 0.5 mg in patients with choroidal neovascularization (CNV) secondary to pseudoxanthoma elasticum (PXE) in a real-world setting. METHODS: A descriptive, observational, multicenter study in a retrospective and prospective cohort was conducted in France that included patients who had received at least one injection of ranibizumab 0.5 mg during the period October 2011 to October 2014, for CNV secondary to PXE. Eligible patients were identified by review of medical records or during routine consultations. The main objectives were to describe patient characteristics, assess changes in best-corrected visual acuity [VA, Early Treatment Diabetic Retinopathy Study (ETDRS) letters] over time, the number and reasons for ranibizumab treatment and overall safety. RESULTS: Of the 72 enrolled patients (98 eyes) from 23 centers, 39 (54.2%) were male and mean [±standard deviation (SD)] age was 59.6 (±8.3) years. The mean VA was 64.6 letters at the first ranibizumab injection, which was maintained at the 1-year follow-up (64.7 letters). Thereafter, the mean VA was stable until the 4-year follow-up. At 4 years, the proportion of eyes with VA gain of ≥15 letters was 3/19 (15.8%) and stable VA (change between -15 and +15 letters) was 10/19 (52.6%). Mean (±SD) annual number of ranibizumab injections was 4.1 (±4.0), lower in the second versus first year. The most common reason for ranibizumab treatment was progression of neovascular activity (42.9%). No deaths or new safety findings were reported. CONCLUSIONS: In patients with CNV secondary to PXE, ranibizumab 0.5 mg resulted in stable VA over 4 years with a limited number of injections. Safety findings were consistent with the established safety profile of ranibizumab.

Patient characteristics and treatment of neovascular age-related macular degeneration in France: the LUEUR1 observational study.

BACKGROUND: Age-related macular degeneration is the primary cause of blindness in developed countries. Current treatments of this degenerative disease mainly include laser, photodynamic therapy with verteporfin and administration of anti-vascular endothelial growth factors. The LUEUR (LUcentis® En Utilisation Réelle) study is composed of a cross-sectional part (LUEUR1), which examined the current management of wet AMD in France, and a follow-up part (LUEUR2), which will assess the development of patients treated for wet AMD over 4 years. Here we describe the results of LUEUR1. METHODS: Patients with wet AMD were enrolled during a routine medical examination in LUEUR1, a cross-sectional, observational, prospective, multicentre study. Investigators recorded patient demographics, visual acuity, characteristics of wet AMD lesions, date of AMD diagnosis, comorbidities, previous treatments, treatments prescribed at inclusion, and low vision rehabilitation. RESULTS: A total of 72 investigators recruited 1,019 patients with wet AMD, corresponding to 1,405 eyes affected by the disease. The mean age of patients was 78.7 ± 7.3 years. Most were female (62.3%) and non-smokers (66.9%). The mean visual acuity was 49.12 ± 24.18 Early Treatment Diabetic Retinopathy Study letters. Most eyes showed occult (52.8%) and subfoveal (84.6%) choroidal neovascularisation. Bilateral wet AMD affected 37.9% of patients. The median time since diagnosis was 12 months. Ranibizumab-based therapy (67.3%) and photodynamic therapy (29.8%) were the most frequent previous treatments. Prior to inclusion, 5.6% of patients had low vision rehabilitation. When a treatment was prescribed on the day of inclusion, it was most often ranibizumab (89.0% of all treatments at inclusion). CONCLUSIONS: The results of this study illustrate the impact of anti-vascular endothelial growth factor therapies on the treatment of wet AMD in a real-life context. Specifically, ranibizumab-based therapy appears to have largely replaced laser photocoagulation and verteporfin-based photodynamic therapy.

Insights into severe asthma control as assessed by guidelines, pulmonologist, patient, and partner.

INTRODUCTION: The most recent guidelines on asthma management advocate a treatment strategy based on control of the disease rather than severity, a switch based on reported evidence. AIMS: This observational, questionnaire-based study set out to investigate how control of the disease is assessed by the physician as well as the patient and his/her live-in partner and to compare these assessments with an assessment made according to the guidelines. METHODS: In 169 patients with severe, persistent asthma on at least a high-dose inhaled corticosteroid plus an inhaled long-acting ß2-agonist, control of the disease was assessed by the pulmonologist, the patient, and the patient's live-in partner. These assessments were compared with an assessment based on the guidelines. Results. Both patients and partners tended to judge disease control as better than their pulmonologists who, in turn, estimated control as acceptable in 58% of their patients in whom the guidelines would advocate more aggressive treatment. The most common guidelines criteria defining inadequate control in the "uncontrolled" 87.4% of this population were "limitation of physical activity" (72.3%) and "FEV1" ≤ 85% of personal best" (63.3%). CONCLUSIONS: To assess control in severe asthma, the patient's opinion is of limited value, as is that of their partners. Although a guidelines-based strategy has been shown to be effective in clinical trials conducted on large-scale populations in which mild or moderate disease is predominant, more aggressive treatment to achieve definitive control may not be appropriate in the 10% of asthma sufferers with severe disease; in everyday practice, lung specialists appear to implement such a strategy.

Capillary isotachophoresis study of lipoprotein network sensitive to apolipoprotein E phenotype. 2. ApoE and apoC-III relations in triglyceride clearance.

The plasma (P), VLDL (V) triglyceride and apoB (B) clearance rates were measured both as 'mass' clearance (k (1)) and 'within the particle' clearance in three patient groups (E33, E23 and E34 phenotypes) at heparin-induced lipolysis in vivo. The lipid (C)- and apoE (E)-specific lipoprotein profiles both before and after heparin were followed by capillary isotachophoresis. The displacement of apoE by exogenous apoC-III at plasma titration in vitro was measured as well. The phenotype-sensitive lipoprotein networks were constructed based on an established set of metabolic rules. The k (1)(V) values did not differ between the three groups, but the lower k (1)(P) values showed significant differences. The k (1)(P) values for E33 and E23 groups were twofold higher compared to E34. A twofold increase in the rate constant for VLDL triglyceride clearance within the particle in E34 group compared to E23 reflected the inhibition of lipolysis by apoE2. For E33 group, (i) the k (1)(V) value was negatively correlated to the size of non-displaceable apoE pool in 2E lipoprotein and to the maximal apoE sorbtion capacity for 2E and 3E lipoproteins; (ii) the k (1)(P) value was not associated to the apoE binding parameters; (iii) the k (1)(V) value was positively correlated to the 4C level and the magnitude of apoC-III removal from VLDL particle; (iv) the k (1)(P) value was positively correlated to the content of apoE, while negatively with apoC-III, in VLDL remnants. For E34 group, the k (1)(V) value was positively correlated to 11C and 1-7C pool levels. Lipolysis- and receptor-mediated TG runways seem to be mostly balanced in E33 group, and VLDL TG clearance may be controlled by HDL through apoE dissociation from VLDLs and apolipoprotein accumulation within 'fast' HDLs at lipolysis.

Capillary isotachophoresis study of lipoprotein network sensitive to apolipoprotein E phenotype. 1. ApoE distribution between lipoproteins.

Sixteen patients differing widely in plasma triglyceride content were divided into three groups by their apolipoprotein E (apoE) phenotype-E33 homozygotes, E23, and E34 heterozygotes. The plasma lipid and apoE distribution between individual lipoproteins was followed by capillary isotachophoresis (CITP) of plasma samples pre-stained with lipid fluorescent probe NBD-C6-ceramide and by fluorescein-labeled apoE, respectively. Among 12 peaks visualized by ceramide staining, an individual peak with very low density lipoproteins (VLDL) was identified. The VLDL cholesterol and apoE content determined by CITP directly in whole plasma were significantly related to their content as determined by conventional analysis with isolated VLDL. The ceramide distribution among lipoprotein pools was insensitive to apoE phenotype (49-53 : 7-11 : 39-43% for HDL, VLDL, and IDL/LDL, respectively) while the preferential binding of apoE to VLDL was observed in E34 patients compared to E33 (62 : 19 : 20 vs. 70 : 9 : 22%). In a study of apoE/F displacement from lipoproteins at plasma titration by apoC-III in vitro, apoE was found to bind more tightly to VLDL from E34 compared to E33 patients as evidenced by both the increased non-displaceable apoE pool, the increased VLDL sorbtion capacity for apoE, and the decreased displacement parameter in a "container" model of lipoprotein binding. Two different types of apoE package in a whole lipoprotein profile were observed. ApoE structure in a particular lipoprotein may underlie the phenotype-sensitive apoE distribution and apoC-III interference in hypertriglyceridemia.

Accuracy and reproducibility of computer-assisted measurement of polyethylene wear in knee arthroplasty.

When using computer-assisted methods to evaluate polyethylene wear in knee arthroplasty (TKA), variations in the inclination of the X-ray beam and lack of standard calibration may affect accuracy and reproducibility. To address these issues, we evaluated the polyethylene thickness of unimplanted specimens of known dimensions using the Imagika software. Radiographs were taken with small controlled variations in the inclination of the X-ray beam. Reproducibility was studied based on triplicate measurement of 132 fluoroscopic images by three observers. Calibration was tested against a reference based on a spherical metal ball with a known diameter. The mean differences between the measured and true values ranged from 0.6 mm to 0.8 mm. The repeatability coefficient revealed a maximum variation of 0.43 mm for the same observer, and 0.39 mm between observers. There were significant differences between the measurements of polyethylene thickness performed using two different calibration methods. The variance of measurements was lower with digitized images than with fluoroscopic images. Imagika was not efficient to measure wear in TKA.

Factors limiting complete tumor ablation by radiofrequency ablation.

The purpose of this study was to determine radiological or physical factors to predict the risk of residual mass or local recurrence of primary and secondary hepatic tumors treated by radiofrequency ablation (RFA). Eighty-two patients, with 146 lesions (80 hepatocellular carcinomas, 66 metastases), were treated by RFA. Morphological parameters of the lesions included size, location, number, ultrasound echogenicity, computed tomography density, and magnetic resonance signal intensity were obtained before and after treatment. Parameters of the generator were recorded during radiofrequency application. The recurrence-free group was statistically compared to the recurrence and residual mass groups on all these parameters. Twenty residual masses were detected. Twenty-nine lesions recurred after a mean follow-up of 18 months. Size was a predictive parameter. Patients' sex and age and the echogenicity and density of lesions were significantly different for the recurrence and residual mass groups compared to the recurrence-free group (p < 0.05). The presence of an enhanced ring on the magnetic resonance control was more frequent in the recurrence and residual mass groups. In the group of patients with residual lesions, analysis of physical parameters showed a significant increase (p < 0.05) in the time necessary for the temperature to rise. In conclusion, this study confirms risk factors of recurrence such as the size of the tumor and emphasizes other factors such as a posttreatment enhanced ring and an increase in the time necessary for the rise in temperature. These factors should be taken into consideration when performing RFA and during follow-up.

Comparison of a functional restoration program with active individual physical therapy for patients with chronic low back pain: a randomized controlled trial.

OBJECTIVE: To compare the short-term outcomes of active individual therapy (AIT) with those of a functional restoration program (FRP). DESIGN: Prospective randomized controlled study. SETTING: Two rehabilitation centers and private ambulatory physiotherapy facilities. PARTICIPANTS: One hundred thirty-two adults with chronic low back pain. Fifty-one percent of patients on sick leave or out of work (mean duration, 180d in the 2y before treatment). INTERVENTIONS: For 5 weeks, FRP (at 25h/wk) or AIT (at 3h/wk). MAIN OUTCOME MEASURES: Trunk flexibility, back flexor, and extensor endurance (Ito and Sorensen tests), general endurance, pain intensity, Dallas Pain Questionnaire (DPQ) scores, daily activities, anxiety depression, social interest, and work and leisure activities, and self-reported improvement (work ability, resumption of sport and leisure activities). RESULTS: All outcome measures improved after treatment except endurance in AIT. There was no between-group difference for pain intensity or DPQ daily activities or work and leisure activities scores. Better results were observed in FRP for all other outcome measures. There was a significant effect of treatment and the initial value for the gain of the Sorensen score with a treatment or initial value interaction; a significant effect of treatment and initial value on the gains of Ito, endurance, and DPQ social interest and anxiety depression scores, with no treatment or initial value interaction; and a significant effect of initial value but not treatment for the gains of DPQ daily activities and work and leisure activities scores. CONCLUSIONS: Low-cost ambulatory AIT is effective. The main advantage of FRP is improved endurance. We speculate that this may be linked to better self-reported work ability and more frequent resumption of sports and leisure activities.

Biological determinants of serum ICAM-1, E-selectin, P-selectin and L-selectin levels in healthy subjects: the Stanislas study.

BACKGROUND: Circulating levels of adhesion molecules increase in various inflammation-related diseases, such as atherosclerosis. However, data about factors influencing their concentrations in physiological conditions are scarce. METHODS: We have studied the determinants of serum levels of intercellular adhesion molecule-1 (ICAM-1), E-selectin, P-selectin and L-selectin in a sample of healthy individuals: 303 children (4-17 years) and 493 adults (18-55 years). The concentrations of these molecules have been measured by enzyme-linked immunosorbant assay. RESULTS: As far as the children are concerned, a decrease in the levels of ICAM-1, E-selectin, P-selectin and L-selectin has been noticed for both boys and girls aged 4-17 years, without any difference between genders. For the adults, no age-related variation has been found for the ICAM-1, E-selectin and P-selectin levels, while the L-selectin level decreased until 55 years old. In the adult group, no sex-related difference in the concentrations of ICAM-1, E-selectin and L-selectin has been seen. As to the P-selectin level, men had significantly higher levels than women. Multiple regression analysis showed that smoking, homeostasis model assessment (HOMA) index, aspartate aminotransferase (AST), alkaline phosphatase (ALP) and C-reactive protein (CRP) were significant positive determinants of the ICAM-1 concentration, whereas age and apo AI were negative ones. The E-selectin level was positively associated with body mass index (BMI), leukocyte, platelet and erythrocyte counts, glucose, ALP and tumor necrosis factor-alpha (TNF-alpha), and negatively related to the use of oral contraceptive (OC). Positive determinants of the P-selectin concentration were leukocyte, platelet and erythrocyte counts, whereas sex, the use of oral contraceptive, glucose and TNF-alpha were negative determinants of P-selectin. Only two determinants have been noticed for the concentration of serum L-selectin: age, which was negatively correlated, and leukocyte count, which was positively associated. CONCLUSION: Our study contributes to the understanding of the regulation of adhesion molecules in physiological conditions.

IL-6, TNF-alpha and atherosclerosis risk indicators in a healthy family population: the STANISLAS cohort.

There are no satisfactory data on circulating concentrations of inflammatory cytokines and their potential relationship with traditional and nontraditional atherosclerosis risk factors in a large healthy young population. The present study was conducted to examine, in 179 healthy families selected from the STANISLAS cohort, the association between interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), C-reactive protein (CRP), orosomucoid, haptoglobin, cell-adhesion molecules (ICAM-1, E-, L- and P-selectin) and lipid parameter concentrations. Age, BMI, white blood cells and tobacco consumption contributed to the variation of IL-6 concentrations. Age and tobacco contributed also to TNF-alpha variation. Taking into account potential covariates, we showed strong positive correlation between IL-6 and both inflammatory markers TNF-alpha and CRP in parents and in offspring (P<0.001). In parents, IL-6 was associated with ICAM-1 and L-selectin (P<0.01), while IL-6 and TNF-alpha predicted E-selectin in offspring only (0.001

Association between Gly241Arg ICAM-1 gene polymorphism and serum sICAM-1 concentration in the Stanislas cohort.

Intracellular adhesion molecule-1 (ICAM-1), a cellular adhesion molecule that mediates the interaction of activated endothelial cells with leukocytes, is involved in various inflammatory and cardiovascular disorders. The relation between these markers and genetic polymorphism, however, remains to be elucidated. The aim of this study is to estimate the effect of a single-base polymorphism at codon 241 in exon 4 of ICAM-1 gene on serum sICAM-1 concentration in a healthy population, taking into account other biological determinants of sICAM-1 level. Serum sICAM-1 levels and the G/R241 polymorphism of the ICAM-1 gene were measured in a large healthy population consisting of 413 children aged 6-21 years and 363 adults aged 38-55 years extracted from the Stanislas cohort. The R241 allele was significantly associated with lower sICAM-1 levels and explained 3.4 and 1.9% of the sICAM-1 variability in children and adults, respectively. A codominant pattern contributed better to the model after adjustment for covariates as the RR homozygote effect was higher than that of the GR heterozygote. Moreover, significant independent associations were found between sICAM-1 and smoking, insulin resistance index (HOMA IR), interleukin-6 level, and alkaline phosphatase and aspartate aminotransferase activities. In conclusion, this study revealed a significant association between the G/R241 ICAM-1 polymorphism and serum sICAM-1 levels, probably due to the impairment in binding of ICAM-1 to leukocyte integrin Mac-1 protein.