Objective: To determine the levels of circulating cell-free DNA (cfDNA), a marker of endothelial damage, in patients with sleep apnea-hypopnea syndrome (AHS) with or without hypertension, and the influence of continuous positive airway pressure (CPAP) therapy on its levels. Design and method: We included 30 consecutive patients recently diagnosed of AHS (apnea-hypopnea index (AHI) higher than 15) with no previous treatment with CPAP. We evaluated these patients before and after 3 months of treatment with CPAP. Ambulatory blood pressure monitoring was performed in each patient. There were no changes on drug treatment during the study. The levels of circulating cfDNA were quantified by real time PCR. Results: Mean age was 51.7 ± 11.5 years, and mean AHI: 56.3 ± 25.5. Hypertension was present in 56.7% of patients. Mean 24-hour systolic blood pressure (BP) was 25.3 ± 12.3 and diastolic 76.0 ± 10.5 mmHg diastolic; no dipper pattern 79.3%; the mean heart rate during day was 79.5 ± 10.5 bpm and during the night 70.1 ± 9.9 bpm. After CPAP: systolic BP 121.2 ± 12.6 and diastolic BP72.6 ± 10.9 mmHg, p < 0.01; no dipper pattern 44.8%, p = 0.02; heart rate day 76.8 ± 10.7 (p = 0.04) and night 65.1 ± 9,52 bpm (p < 0.01). Mean circulating cfDNA was 187,93 ± 115,81ng/mL and after 3 months with CPAP therapy it decreased to 121,28 ± 78,98 ng/mL, p < 0.01, but this improvement was due to hypertensive patients, with no changes in normotensives. Conclusions: The circulating cfDNA is considered as a biomarker of cell damage. We have observed that hypertensive patients with AHS under treatment with CPAP have significant lower levels of circulating cfDNA, suggesting that this disorder seems to improve with CPAP in hypertensive patients.

We analyze a large population of patients to determine whether gamma glutamyl transferase (GGT) levels are increased in sleep apnea-hypopnea syndrome (OSA) and whether these levels are related to clinical characteristics or polygraphic indexes.

Objective: This study try to assess the endothelial function in vivo using flow mediated dilatation (FMD) and several biomarkers of endothelium formation/restoration and damage in patients with obstructive sleep apnoea (OSA) syndrome at baseline and after three months with CPAP therapy. Design and method: Observational study, before and after CPAP therapy. We studied 30 patients with apnoea/hypopnoea index > 15/h that were compared with themselves after three months of CPAP therapy. Flow mediated dilatation (FMD) was assessed non-invasively by in vivo using the Laser-Doppler flowmetry. Circulating cell free DNA (cf-DNA) and microparticles (MPs) were measured as markers of endothelial damage and the vascular endothelial growth factor (VEGF) was determined as a marker of endothelial restoration process. Results: After three month with CPAP, FMD significantly increased (1072.26 ± 483.21 vs. 1604.38 ± 915.69 PU, p < 0.005), and cf-DNA and MPs significantly decreased (respectively: 187.93 ± 115.81 vs. 121.28 ± 78.98 pg/ml, p < 0.01 and 69.60 ± 62.60 vs. 39.82 ± 22.14 U/&mgr;L, p < 0.05). Finally, VEGF increased (585.02 ± 246.06 vs. 641.11 ± 212.69 pg/ml, p < 0.05). These changes were higher in patients with more severe disease. There was a relationship between markers of damage (r = -0.53, p < 0.005) but not among markers of damage and restoration, thus suggesting that both types of markers should be measured together. Conclusions: CPAP therapy improves FMD. This improvement may be related to an increase of endothelial restoration process and a decrease of endothelial damage.

Objective: To assess the effect of continuous positive airway pressure (CPAP) therapy on glucose metabolism and insulin resistance in patients with sleep apnea-hypopnea syndrome (AHS). Design and method: We prospectively included 30 consecutive patients recently diagnosed of AHS with an apnea-hypopnea index of 15 or higher and without prior treatment with CPAP. Patients were evaluated before and after 3-month CPAP therapy. There was no change on drug treatment during the study. Fasting blood glucose (FBG), insulin and HbA1c were measured. Beta-cell function, insulin sensitivity (IS) and insulin resistance index (IR) were estimated using the Homeostasis Model Assessment (HOMA) equations. Results: Mean (SD) age was 51.7 ± 11.5 years, and mean AHI: 56.3 ± 25.5. 63.3% were males. 23.3% had type 2 diabetes mellitus and 56.7% hypertension. Body mass index, FBG and HbA1c at baseline were 35.8 ± 6.5 kg/m2, 108.8 ± 26.5 mg/dL and 6.1 ± 0.7%, respectively, and they remained unchanged at the end of follow-up (p = 0,939, p = 0.300 and p = 0.307, respectively). At baseline, AHI correlated with IS (r = -0.45, p = 0.017) and IR (r = 0.43, p = 0.022). 3-month treatment with CPAP significantly decreased insulin levels (microU/ml, baseline: 23.5 ± 23.9; postCPAP therapy: 16.9 ± 11.6; p = 0.008) and IR (baseline: 2.5 ± 1.4; post-CPAP therapy: 2.2 ± 1,56; p = 0.024). Changes in IS (baseline 54,2 ± 30,0; postCPAP therapy: 60,0 ± 26,5; p = 0.055) and beta-cell function (%, baseline 137,8 ± 70,1; postCPAP therapy: 121,7 ± 48,9; p = 0.060) tended to be significant. Conclusions: Our results suggest that more severe AHS is related to an impaired IS and higher IR, and that treatment with CPAP may improve the insulin resistance syndrome.

Objective: To assess the effect of continuous positive airway pressure (CPAP) therapy on glucose metabolism and insulin resistance in patients with sleep apnea-hypopnea syndrome (AHS). Design and method: We prospectively included 30 consecutive patients recently diagnosed of AHS with an apnea-hypopnea index of 15 or higher and without prior treatment with CPAP. Patients were evaluated before and after 3-month CPAP therapy. There was no change on drug treatment during the study. Fasting blood glucose (FBG), insulin and HbA1c were measured. Beta-cell function, insulin sensitivity (IS) and insulin resistance index (IR) were estimated using the Homeostasis Model Assessment (HOMA) equations. Results: Mean (SD) age was 51.7 ± 11.5 years, and mean AHI: 56.3 ± 25.5. 63.3% were males. 23.3% had type 2 diabetes mellitus and 56.7% hypertension. Body mass index, FBG and HbA1c at baseline were 35.8 ± 6.5 kg/m2, 108.8 ± 26.5 mg/dL and 6.1 ± 0.7%, respectively, and they remained unchanged at the end of follow-up (p = 0,939, p = 0.300 and p = 0.307, respectively). At baseline, AHI correlated with IS (r = -0.45, p = 0.017) and IR (r = 0.43, p = 0.022). 3-month treatment with CPAP significantly decreased insulin levels (microU/ml, baseline: 23.5 ± 23.9; postCPAP therapy: 16.9 ± 11.6; p = 0.008) and IR (baseline: 2.5 ± 1.4; post-CPAP therapy: 2.2 ± 1,56; p = 0.024). Changes in IS (baseline 54,2 ± 30,0; postCPAP therapy: 60,0 ± 26,5; p = 0.055) and beta-cell function (%, baseline 137,8 ± 70,1; postCPAP therapy: 121,7 ± 48,9; p = 0.060) tended to be significant. Conclusions: Our results suggest that more severe AHS is related to an impaired IS and higher IR, and that treatment with CPAP may improve the insulin resistance syndrome.

Objective: This study try to assess the endothelial function in vivo using flow mediated dilatation (FMD) and several biomarkers of endothelium formation/restoration and damage in patients with obstructive sleep apnoea (OSA) syndrome at baseline and after three months with CPAP therapy. Design and method: Observational study, before and after CPAP therapy. We studied 30 patients with apnoea/hypopnoea index > 15/h that were compared with themselves after three months of CPAP therapy. Flow mediated dilatation (FMD) was assessed non-invasively by in vivo using the Laser-Doppler flowmetry. Circulating cell free DNA (cf-DNA) and microparticles (MPs) were measured as markers of endothelial damage and the vascular endothelial growth factor (VEGF) was determined as a marker of endothelial restoration process. Results: After three month with CPAP, FMD significantly increased (1072.26 ± 483.21 vs. 1604.38 ± 915.69 PU, p < 0.005), and cf-DNA and MPs significantly decreased (respectively: 187.93 ± 115.81 vs. 121.28 ± 78.98 pg/ml, p < 0.01 and 69.60 ± 62.60 vs. 39.82 ± 22.14 U/μL, p < 0.05). Finally, VEGF increased (585.02 ± 246.06 vs. 641.11 ± 212.69 pg/ml, p < 0.05). These changes were higher in patients with more severe disease. There was a relationship between markers of damage (r = -0.53, p < 0.005) but not among markers of damage and restoration, thus suggesting that both types of markers should be measured together. Conclusions: CPAP therapy improves FMD. This improvement may be related to an increase of endothelial restoration process and a decrease of endothelial damage.

Background: Obstructive sleep apnea (OSA) is related to obesity and metabolic disorders. The main clinical symptoms are excessive daytime sleepiness (EDS) and snoring. However, not all patients with OSA manifest EDS. Hypocretin-1, neuropeptide Y, leptin, ghretin and adiponectin are implicated in both metabolic and sleep regulation, two conditions affected by OSA. We hypothesized that levels of these peptides may be related to EDS in OSA patients.Methods: We included 132 patients with EDS, as defined by an Epworth Sleepiness Scale (ESS) score >= 13 (mean +/- SD, 15.7 +/- 2.3) and 132 patients without EDS as defined by an ESS score <= 9 (6.5 +/- 1.9). All patients had an apnea-hypopnea index (AHI) >= 20 h(-1). Both groups were matched for gender (males; 83.3% vs. 85.6%), age (50.15 +/- 11.2 yrs vs. 50.7 +/- 9.9 yrs), body mass index (BMI) (31.8 +/- 5.6 kg m(-2) vs. 32.1 +/- 4.8 kg m(-2)), and apnea-hypopnea index (AHI) (45.5 +/- 19.1 h(-1) vs. 43 +/- 19.2 h(-1)).Results: USA patients with EDS showed significantly higher plasma hypocretin-1 levels (p < 0.001) and lower plasma ghrelin levels (p < 0.001) than USA patients without EDS. There were no statistically significant differences in neuropeptide Y (p = 0.08), leptin (p = 0.07) and adiponectin (p = 0.72) between the two groups. In the multiple linear regression model ESS score was associated with plasma levels of hypocretin-1, ghrelin and total sleep time.Conclusion: Our study shows that EDS in patients with OSA is associated with increased circulating hypocretin-1 and decreased circulating ghrelin levels, two peptides involved in the regulation of body weight, energy balance, sympathetic tone and sleep-wake cycle. This relationship is independent of AHI and obesity (two key phenotypic features of OSA). (C) 2011 Elsevier Ltd. All rights reserved.

It has been suggested that sleep-related breathing disorders (SRBD) involve a continuum that develops over the course of life. If modifiable factors could be identified, the progression of SRBD could perhaps be addressed early in life. Although some studies have looked at the evolution of SRBD in pre-pubertal children, very few studies obtained data in adolescents. Anthropometric, clinical and polygraphic variables were collected during a 4-yr follow-up study among 148 normal adolescents after initial cross-sectional analysis. From a total of 267 adolescents studied at baseline (mean+/-sd age 14.3+/-2.1 yrs), 148 (55.4%) were followed up for 4 yrs. During follow-up, there were no significant changes in snoring and polygraphic parameters. However, a tendency toward weight gain with centrally distributed fat was observed. Habitual snorers had a significantly higher body mass index and more centrally distributed fat than nonsnorers. Males had a higher snoring prevalence and a higher number of respiratory events than females. Snoring at baseline, male sex and poor academic performance were significant predictors of snoring at follow-up. Snoring tends to persist during adolescence and male sex acts as a risk factor. A relationship between snoring and academic performance was observed. These findings may have implications for long-term management of sleep-related breathing disorders.

Prognostic scores are often constructed to classify patients in prognostic groups thanks to pre-treatment characteristics easily accessible. Once constructed, scores are applied to new patients. Scores are helpful in identifying patients with advanced stage, selecting the appropriate treatmen to individual patients, and in stratifying patients in prospective trials. Models selection is usually based on adequation to initial sample data. Thus prediction on initial data overestimates prediction on new patients. This difference between predictions, so called model optimism, has to been taken into account when studying predictive ability of models for new patients. The methodology used to build two prognostic scores is presented. Similar constraints were stated at the beginning (£5 variables in the final score, 3-risk-group score). For follicular lymphomas (Solal-Céligny, 2004), 8 variables were significantly associated with overall survival. The best model including 5 variables was selected on predictive ability. Optimism was corrected using bootstrap. The largest likelihood identified the best score. External validation confirmed the score predictive ability. For Hodgkin lymphoma (Maucort-Boulch, 2007), 4 variables were significantly associated with 10-year overall survival. The best 3-group score was selected on predictive ability. Optimism was corrected using bootstrap. A first external validation confirmed the better predictive ability in comparison with known scores. Different measures of prognostic scores predictive ability were proposed (Harrell D, adapted R2, penalized likelihood, Parkes criterion). Those measures could be used for model selection. Their respective properties are still under study. Internal and external validations account for models optimism. Solal-Céligny P, et al. Follicular lymphoma international prognostic index. Blood 2004; 104: 1258-65. Maucort-Boulch D, et al. Predictive and discriminating three-risk-group prognostic scoring system for staging Hodgkin lymphomas. Cancer. 2007; 109: 256-64.

Abstract The Internet is changing the way that people learn about health and illness. At present do not exist data of the use of Internet by patients of lymphoma and her caregivers in Spain. OBJECTIVE: To investigate the distribution and patterns of Internet use by patients with lymphoma and her caregivers. PATIENTS AND METHODS: 585 subjects (258 patients, 264 relatives and 63 health professionals), 228 male and 357 female, they have responded a questionnaire on diverse aspects of the use of Internet. RESULTS: Two hundred fifty (42,7%) subjects use Internet, although only 27% make to obtain data on lymphoma. With respect to the group of patients 31% recognize to use Internet, but only the 23,3% do it by questions related to their disease. The main reasons for Internet use are to obtain information about treatments (74.7%) or second opinion medical (9.3%). The 77,6% have been using Internet for more than 3 years; the 47,2% have university studies and the 58,4% have between 33–50 years. Mainly the information search is made in Spanish language and through the Google finder. They consider that Information on lymphoma is acceptable (44.9%) or of enough quality (43.7%), trustworthy (50.6%) or of enough reliability (33.5%) and useful (45.6%) or quite useful (37.3%). COMMENTARIES: This study contributes data on the use of Internet by patients with lymphoma and her caregivers in Spain. Oncologists should be familiar with this important resource to help patients access appropriate material.

8092 Background: In patients with relapsed or refractory follicular lymphoma (FL) who attain a response with either cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) alone or Rituximab + CHOP, maintenance treatment with Rituximab has shown to significantly improve overall survival (OS) (85% at 3 years vs. 77%, p=0.011) and progression free survival (PFS) (51,5 vs. 14.9 months, p<0.001) as compared to observation alone (OA). We analyzed the cost-effectiveness, from a Spanish perspective, of Rituximab maintenance therapy (375mg/m2 every 3 months until progression or for 2 years) versus OA according to the population and data described for the European Organization for Research Treatment of Cancer (EORTC) 20981 study (van Oers MHJ Blood 2006). Methods: Incremental cost-effectiveness was assessed through a deterministic, three health states model (disease-free, progression and death) transition model. Base case model: PFS and OS were extrapolated from EORTC 20981 data using a Weibull distribution, Rituximab maintenance benefit was assumed to last 5 years, 10 years time horizon, 3.5% discount rate on costs and benefits, and Spanish National Health Service perspective (direct costs only). Resource use was estimated from a Spanish expert panel and EORTC 20981 study. Unit costs were obtained from local databases (May 2006 €). Health states utility values were derived from an ad hoc study. Sensitivity analyses were performed for all mentioned variables. Results: For the base case, more quality-adjusted life years (QALY), life-years (LY) and progression-free survival years per patient on maintenance therapy were obtained versus OA (incremental values of 0.85, 0.94 and 1.46, respectively). Total cost per patient was higher with Rituximab than with OA (+8,026€). Incremental cost per QALY gained was 9,358€, with a cost per LY gained of 8.493€ and a cost per PFS year gained of 5,485€. In the sensitivity analysis, values ranged between 7.263€ and 22.160€ per QALY gained. Conclusions: This study confirms that in patients with relapsed /refractory FL who attain a response with further therapy, maintenance treatment with Rituximab compared to observation alone is cost-effective. No significant financial relationships to disclose.