Adipose-derived mesenchymal stem cells (AdMSC) for the treatment of secondary-progressive multiple sclerosis: A triple blinded, placebo controlled, randomized phase I/II safety and feasibility study.

BACKGROUND: Currently available treatments for secondary progressive multiple sclerosis(SPMS) have limited efficacy and/or safety concerns. Adipose-mesenchymal derived stem cells(AdMSCs) represent a promising option and can be readily obtained using minimally invasive procedures. PATIENTS AND METHODS: In this triple-blind, placebo-controlled study, cell samples were obtained from consenting patients by lipectomy and subsequently expanded. Patients were randomized to a single infusion of placebo, low-dose(1x106cells/kg) or high-dose(4x106cells/kg) autologous AdMSC product and followed for 12 months. Safety was monitored recording adverse events, laboratory parameters, vital signs and spirometry. Expanded disability status score (EDSS), magnetic-resonance-imaging, and other measures of possible treatment effects were also recorded. RESULTS: Thirty-four patients underwent lipectomy for AdMSCs collection, were randomized and thirty were infused (11 placebo, 10 low-dose and 9 high-dose); 4 randomized patients were not infused because of karyotype abnormalities in the cell product. Only one serious adverse event was observed in the treatment arms (urinary infection, considered not related to study treatment). No other safety parameters showed changes. Measures of treatment effect showed an inconclusive trend of efficacy. CONCLUSION: Infusion of autologous AdMSCs is safe and feasible in patients with SPMS. Larger studies and probably treatment at earlier phases would be needed to investigate the potential therapeutic benefit of this technique.

Equity, barriers and cancer disparities: study of the Spanish Society of Medical Oncology on the access to oncologic drugs in the Spanish Regions.

PURPOSE: The Spanish Society of Medical Oncology (SEOM) has conducted a study on the access to oncologic drugs across the 17 Spanish Regions with the aim of identifying potential heterogeneities and making proposals for eliminating the barriers identified at the different levels. METHODS: An Expert Panel made up of medical oncologists designed a survey on certain indications approved for 11 drugs in the approach of breast cancer, melanoma, lung cancer, prostate cancer and support treatment. This survey was sent to 144 National Health System (NHS) hospitals. RESULTS: 77 hospitals answered the survey. The information modules analysed were: scope of the Commission that establishes binding decisions related to drug access; conditions, stages and periods of drug application, approval and administration processes; barriers to accessing drugs. CONCLUSIONS: The study shows variability in drug access. The SEOM makes proposals addressed to reducing the differences identified and homogenizing drug access conditions.

School teachers' vocal use, risk factors, and voice disorder prevalence: guidelines to detect teachers with current voice problems.

UNLABELLED: Teachers' voice problems are widely recognized as a consequence of their work. The measurement of vocal demands and risk factors is essential for adjusting occupational safety and health services to this population's needs. OBJECTIVES: To correlate vocal behavior and symptomatology with risk factors and voice disorders, and to further analyze gender influence on these variables. SUBJECTS AND METHODS: 282 kindergarten and elementary education teachers were surveyed in a cross-sectional study using a self-administered questionnaire. For the purpose of this study, voice disorder prevalence was estimated based on the presence of a vocal effort plus 2 frequent symptoms. RESULTS: 81.5% of teachers reported some degree of vocal effort; more than 60% of subjects evidenced frequent throat paresthesias or vocal fatigue at the end of a working day, and about 55% reported hoarseness. Voice disorder prevalence was 59%. Multivariate logistic regression analysis revealed that female gender, time required to alleviate vocal symptoms, perceived general state of health, prolonged use of the voice, and pupils' indiscipline significantly increased the odds of having vocal problems. CONCLUSIONS: Voice disorders affected most teachers and had a multifactorial nature. Vocal health care is particularly necessary for those subjects reporting vocal effort and more than 2 frequent symptoms.

Additive effects of LPL, APOA5 and APOE variant combinations on triglyceride levels and hypertriglyceridemia: results of the ICARIA genetic sub-study.

BACKGROUND: Hypertriglyceridemia (HTG) is a well-established independent risk factor for cardiovascular disease and the influence of several genetic variants in genes related with triglyceride (TG) metabolism has been described, including LPL, APOA5 and APOE. The combined analysis of these polymorphisms could produce clinically meaningful complementary information. METHODS: A subgroup of the ICARIA study comprising 1825 Spanish subjects (80% men, mean age 36 years) was genotyped for the LPL-HindIII (rs320), S447X (rs328), D9N (rs1801177) and N291S (rs268) polymorphisms, the APOA5-S19W (rs3135506) and -1131T/C (rs662799) variants, and the APOE polymorphism (rs429358; rs7412) using PCR and restriction analysis and TaqMan assays. We used regression analyses to examine their combined effects on TG levels (with the log-transformed variable) and the association of variant combinations with TG levels and hypertriglyceridemia (TG > or = 1.69 mmol/L), including the covariates: gender, age, waist circumference, blood glucose, blood pressure, smoking and alcohol consumption. RESULTS: We found a significant lowering effect of the LPL-HindIII and S447X polymorphisms (p < 0.0001). In addition, the D9N, N291S, S19W and -1131T/C variants and the APOE-epsilon4 allele were significantly associated with an independent additive TG-raising effect (p < 0.05, p < 0.01, p < 0.001, p < 0.0001 and p < 0.001, respectively). Grouping individuals according to the presence of TG-lowering or TG-raising polymorphisms showed significant differences in TG levels (p < 0.0001), with the lowest levels exhibited by carriers of two lowering variants (10.2% reduction in TG geometric mean with respect to individuals who were homozygous for the frequent alleles of all the variants), and the highest levels in carriers of raising combinations (25.1% mean TG increase). Thus, carrying two lowering variants was protective against HTG (OR = 0.62; 95% CI, 0.39-0.98; p = 0.042) and having one single raising polymorphism (OR = 1.20; 95% CI, 1.39-2.87; p < 0.001) or more (2 or 3 raising variants; OR = 2.90; 95% CI, 1.56-5.41; p < 0.001) were associated with HTG. CONCLUSION: Our results showed a significant independent additive effect on TG levels of the LPL polymorphisms HindIII, S447X, D9N and N291S; the S19W and -1131T/C variants of APOA5, and the epsilon4 allele of APOE in our study population. Moreover, some of the variant combinations studied were significantly associated with the absence or the presence of hypertriglyceridemia.