Lipoprotein lipase activity and mass, apolipoprotein C-II mass and polymorphisms of apolipoproteins E and A5 in subjects with prior acute hypertriglyceridaemic pancreatitis

BACKGROUND Severe hypertriglyceridaemia due to chylomicronemia may trigger an acute pancreatitis. However, the basic underlying mechanism is usually not well understood. We decided to analyze some proteins involved in the catabolism of triglyceride-rich lipoproteins in patients with severe hypertriglyceridaemia. METHODS Twenty-four survivors of acute hypertriglyceridaemic pancreatitis (cases) and 31 patients with severe hypertriglyceridaemia (controls) were included. Clinical and anthropometrical data, chylomicronaemia, lipoprotein profile, postheparin lipoprotein lipase mass and activity, hepatic lipase activity, apolipoprotein C II and CIII mass, apo E and A5 polymorphisms were assessed. RESULTS Only five cases were found to have LPL mass and activity deficiency, all of them thin and having the first episode in childhood. No cases had apolipoprotein CII deficiency. No significant differences were found between the non-deficient LPL cases and the controls in terms of obesity, diabetes, alcohol consumption, drug therapy, gender distribution, evidence of fasting chylomicronaemia, lipid levels, LPL activity and mass, hepatic lipase activity, CII and CIII mass or apo E polymorphisms. However, the SNP S19W of apo A5 tended to be more prevalent in cases than controls (40% vs. 23%, NS). CONCLUSION Primary defects in LPL and C-II are rare in survivors of acute hypertriglyceridaemic pancreatitis; lipase activity measurements should be restricted to those having their first episode during childhood.

Peripheral arterial disease in HIV patients older than 50 years of age

Our objective was to analyze the prevalence of peripheral arterial disease (PAD) in HIV patients at risk and to compare them with the general population. All HIV patients older than 50 years who attended our unit from October 2005-July 2006 and all persons attending for an annual medical checkup at an employees' insurance association during the same period were invited to participate in the study. Of the latter (n = 407), a person of the same sex and age (+/-5 years) was included for each HIV patient. PAD was assessed by the ankle-brachial index (ABI) in all subjects, and all completed the Edinburgh questionnaire. Ninety-nine HIV patients and 99 persons from the general population of the same age and sex were included in the study. The HIV patients had a greater prevalence of dyslipidemia, diabetes, and PAD, which was symptomatic in five of them and in one subject from the general population. Patients with HIV infection older than 50 had a high prevalence of PAD, and as it was asymptomatic in half the cases, an ABI may be performed in this population to actively look for PAD. Control of cardiovascular risk factors and the use of such drugs as platelet antiaggregation agents should therefore be optimized in this population.

Inverse relation between levels of anti-oxidized-LDL antibodies and eicosapentanoic acid (EPA).

Oxidative modification of LDL is thought to play an important role in the development of atherosclerosis. Susceptibility of LDL to peroxidation may partly depend on the compositional characteristics of the antioxidant and fatty acid content. The aim of this study was to examine the association between levels of antibodies to oxidized LDL and the various serum fatty acids in women. A total of 465 women aged 18-65 years were selected randomly from the adult population census of Pizarra, a town in southern Spain. Measurement of anti-oxidized-LDL was done by ELISA and the fatty acid composition of serum phospholipids was determined by GC. The levels of anti-oxidized-LDL antibodies were significantly related with age (r - 0.341, P < 0.001), BMI (r - 0.239, P < 0.001), waist:hip ratio (r - 0.285, P < 0.001), glucose (r - 0.208, P < 0.001), cholesterol (r - 0.243, P < 0.001), LDL-cholesterol (r - 0.185, P = 0.002), EPA (r - 0.159, P = 0.003), DHA (r - 0.121, P = 0.026), and the sum of the serum phospholipid n-3 PUFA (r - 0.141, P = 0.009). Multiple regression analysis showed that the variables that explained the behaviour of the levels of anti-oxidized-LDL antibodies were age (P < 0.001) and the serum phospholipid EPA (P < 0.001). This study showed that the fatty acid composition of serum phospholipids, and especially the percentage of EPA, was inversely related with the levels of anti-oxidized-LDL antibodies.

Tumor necrosis-like weak inducer of apoptosis as a proinflammatory cytokine in human adipocyte cells: up-regulation in severe obesity is mediated by inflammation but not hypoxia.

CONTEXT Adipose tissue hypoxia and endoplasmic reticulum (ER) stress may link the presence of chronic inflammation and macrophage infiltration in severely obese subjects. We previously reported the up-regulation of TNF-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible 14 (Fn14) axis in adipose tissue of severely obese type 2 diabetic subjects. OBJECTIVES The objective of the study was to examine TWEAK and Fn14 adipose tissue expression in obesity, severe obesity, and type 2 diabetes in relation to hypoxia and ER stress. DESIGN In the obesity study, 19 lean, 28 overweight, and 15 obese nondiabetic subjects were studied. In the severe obesity study, 23 severely obese and 35 control subjects were studied. In the type 2 diabetes study, 11 type 2 diabetic and 36 control subjects were studied. The expression levels of the following genes were analyzed in paired samples of sc and visceral adipose tissue: Fn14, TWEAK, VISFATIN, HYOU1, FIAF, HIF-1a, VEGF, GLUT-1, GRP78, and XBP-1. The effect of hypoxia, inflammation, and ER stress on the expression of TWEAK and Fn14 was examined in human adipocyte and macrophage cell lines. RESULTS Up-regulation of TWEAK/Fn14 and hypoxia and ER stress surrogate gene expression was observed in sc and visceral adipose tissue only in our severely obese cohort. Hypoxia modulates TWEAK or Fn14 expression in neither adipocytes nor macrophages. On the contrary, inflammation up-regulated TWEAK in macrophages and Fn14 expression in adipocytes. Moreover, TWEAK had a proinflammatory effect in adipocytes mediated by the nuclear factor-kappaB and ERK but not JNK signaling pathways. CONCLUSIONS Our data suggest that TWEAK acts as a pro-inflammatory cytokine in the adipose tissue and that inflammation, but not hypoxia, may be behind its up-regulation in severe obesity.

Mes de la diabetes

Buenas prácticas en gestión clínica

Responsiveness of the Multiple Sclerosis International Quality of Life questionnaire to disability change: a longitudinal study.

BACKGROUND Responsiveness, defined as the ability to detect a meaningful change, is a core psychometric property of an instrument measuring quality of life (QoL) rarely reported in multiple sclerosis (MS) studies. OBJECTIVE To assess the responsiveness of the Multiple Sclerosis International Quality of Life (MusiQoL) questionnaire to change in disability over 24 months, defined by change in the Expanded Disability Status Scale (EDSS) score. METHODS Patients with MS were enrolled into a multicenter, longitudinal observational study. QoL was assessed using both the MusiQoL and the 36-Item Short-Form (SF-36) instruments at baseline and every 6 months thereafter up to month 24; neurological assessments, including EDSS score, were performed at each evaluation. RESULTS The 24-month EDSS was available for 524 patients. In the 107 worsened patients, two specific dimensions of MusiQoL, the sentimental and sexual life and the relationships with health care system dimensions, and 'physical' scores of SF-36 showed responsiveness. CONCLUSIONS Whereas specific dimensions of MusiQoL identified EDSS changes, the MusiQoL index did not detect disability changes in worsened MS patients in a 24-month observational study. Future responsiveness validation studies should include longer follow-up and more representative samples.

Characteristics and effectiveness of diabetes self-management educational programs targeted to racial/ethnic minority groups: a systematic review, meta-analysis and meta-regression.

BACKGROUND It is not clear to what extent educational programs aimed at promoting diabetes self-management in ethnic minority groups are effective. The aim of this work was to systematically review the effectiveness of educational programs to promote the self-management of racial/ethnic minority groups with type 2 diabetes, and to identify programs' characteristics associated with greater success. METHODS We undertook a systematic literature review. Specific searches were designed and implemented for Medline, EMBASE, CINAHL, ISI Web of Knowledge, Scirus, Current Contents and nine additional sources (from inception to October 2012). We included experimental and quasi-experimental studies assessing the impact of educational programs targeted to racial/ethnic minority groups with type 2 diabetes. We only included interventions conducted in countries members of the OECD. Two reviewers independently screened citations. Structured forms were used to extract information on intervention characteristics, effectiveness, and cost-effectiveness. When possible, we conducted random-effects meta-analyses using standardized mean differences to obtain aggregate estimates of effect size with 95% confidence intervals. Two reviewers independently extracted all the information and critically appraised the studies. RESULTS We identified thirty-seven studies reporting on thirty-nine educational programs. Most of them were conducted in the US, with African American or Latino participants. Most programs obtained some benefits over standard care in improving diabetes knowledge, self-management behaviors and clinical outcomes. A meta-analysis of 20 randomized controlled trials (3,094 patients) indicated that the programs produced a reduction in glycated hemoglobin of -0.31% (95% CI -0.48% to -0.14%). Diabetes knowledge and self-management measures were too heterogeneous to pool. Meta-regressions showed larger reduction in glycated hemoglobin in individual and face to face delivered interventions, as well as in those involving peer educators, including cognitive reframing techniques, and a lower number of teaching methods. The long-term effects remain unknown and cost-effectiveness was rarely estimated. CONCLUSIONS Diabetes self-management educational programs targeted to racial/ethnic minority groups can produce a positive effect on diabetes knowledge and on self-management behavior, ultimately improving glycemic control. Future programs should take into account the key characteristics identified in this review.

Unanswered clinical questions in the management of cardiometabolic risk in the elderly: a statement of the Spanish society of internal medicine.

BACKGROUND Despite the progressive increase in life expectancy and the relationship between aging with multi-morbidities and the increased use of healthcare resources, current clinical practice guidelines (CPG) on cardiometabolic risk cannot be adequately applied to elderly subjects with multiple chronic conditions. Its management frequently becomes complicated by both, an excessive use of medications that may lead to overtreatment, drug interactions and increased toxicity, and errors in dosage and non-compliance. Concerned by this gap, the Spanish Society of Internal Medicine created a group of independent experts on cardiometabolic risk who discussed what they considered to be unanswered questions in the management of elderly patients. DISCUSSION Current guidelines do not specifically address the problem of elderly with multiple chronic conditions. For this reason, the combined use of the limited available evidence, clinical experience and common sense, could all help us to address this unmet need. In very old people, life expectancy and functionality are the most important factors for guiding potential treatments. Their higher propensity to develop serious adverse events and their shorter lifespan could prevent them from obtaining the potential benefits of the interventions administered. SUMMARY In this document, experts on cardiometabolic risk factors have established a number of consensual recommendations that have taken into account international guidelines and clinical experience, and have also considered the more effective use of healthcare resources. This document is intended to provide general recommendations for clinicians and to promote the effective use of procedures and medications.

Impaired adipose tissue expandability and lipogenic capacities as ones of the main causes of metabolic disorders.

Obesity is considered a major health problem. However, mechanisms involved and its comorbidities are not elucidated. Recent theories concerning the causes of obesity have focused on a limit to the functional capacity of adipose tissue, comparing it with other vital organs. This assumption has been the central point of interest in our laboratory. We proposed that the failure of adipose tissue is initiated by the difficulty of this tissue to increase its cellularity due to excess in fat contribution, owing to genetic or environmental factors. Nevertheless, why the adipose tissue reduces its capacity to make new adipocytes via mesenchymal cells of the stroma has not yet been elucidated. Thus, we suggest that this tissue ceases fulfilling its main function, the storage of excess fat, thereby affecting some of the key factors involved in lipogenesis, some of which are reviewed in this paper (PPARγ, ROR1, FASN, SCD1, Rab18, BrCa1, ZAG, and FABP4). On the other hand, mechanisms involved in adipose tissue expandability are also impaired, predominating hypertrophy via an increase in apoptosis and a decrease in adipogenesis and angiogenesis. However, adipose tissue failure is only part of this great orchestra, only a chapter of this nightmare.

Added Value of Deep Sequencing Relative to Population Sequencing in Heavily Pre-Treated HIV-1-Infected Subjects.

OBJECTIVE: To explore the potential of deep HIV-1 sequencing for adding clinically relevant information relative to viral population sequencing in heavily pre-treated HIV-1-infected subjects. METHODS: In a proof-of-concept study, deep sequencing was compared to population sequencing in HIV-1-infected individuals with previous triple-class virological failure who also developed virologic failure to deep salvage therapy including, at least, darunavir, tipranavir, etravirine or raltegravir. Viral susceptibility was inferred before salvage therapy initiation and at virological failure using deep and population sequencing genotypes interpreted with the HIVdb, Rega and ANRS algorithms. The threshold level for mutant detection with deep sequencing was 1%. RESULTS: 7 subjects with previous exposure to a median of 15 antiretrovirals during a median of 13 years were included. Deep salvage therapy included darunavir, tipranavir, etravirine or raltegravir in 4, 2, 2 and 5 subjects, respectively. Self-reported treatment adherence was adequate in 4 and partial in 2; one individual underwent treatment interruption during follow-up. Deep sequencing detected all mutations found by population sequencing and identified additional resistance mutations in all but one individual, predominantly after virological failure to deep salvage therapy. Additional genotypic information led to consistent decreases in predicted susceptibility to etravirine, efavirenz, nucleoside reverse transcriptase inhibitors and indinavir in 2, 1, 2 and 1 subject, respectively. Deep sequencing data did not consistently modify the susceptibility predictions achieved with population sequencing for darunavir, tipranavir or raltegravir. CONCLUSIONS: In this subset of heavily pre-treated individuals, deep sequencing improved the assessment of genotypic resistance to etravirine, but did not consistently provide additional information on darunavir, tipranavir or raltegravir susceptibility. These data may inform the design of future studies addressing the clinical value of minority drug-resistant variants in treatment-experienced subjects.

Gender and the professional career of primary care physicians in Andalusia (Spain).

Background: Although the proportion of women in medicine is growing, female physicians continue to be disadvantaged in professional activities. The purpose of the study was to determine and compare the professional activities of female and male primary care physicians in Andalusia and to assess the effect of the health center on the performance of these activities. Methods: Descriptive, cross-sectional, and multicenter study. Setting: Spain. Participants: Population: urban health centers and their physicians. Sample: 88 health centers and 500 physicians. Independent variable: gender. Measurements: Control variables: age, postgraduate family medicine specialty (FMS), patient quota, patients/day, hours/day housework from Monday to Friday, idem weekend, people at home with special care, and family situation. Dependent variables: 24 professional activities in management, teaching, research, and the scientific community. Self-administered questionnaire. Descriptive, bivariate, and multilevel logistic regression analyses. Results: Response: 73.6%. Female physicians: 50.8%. Age: female physicians, 49.1 ± 4.3 yrs; male physicians, 51.3 ± 4.9 yrs (p < 0.001). Female physicians with FMS: 44.2%, male physicians with FMS: 33.3% (p < 0.001). Female physicians dedicated more hours to housework and more frequently lived alone versus male physicians. There were no differences in healthcare variables. Thirteen of the studied activities were less frequently performed by female physicians, indicating their lesser visibility in the production and diffusion of scientific knowledge. Performance of the majority of professional activities was independent of the health center in which the physician worked. Conclusions: There are gender inequities in the development of professional activities in urban health centers in Andalusia, even after controlling for family responsibilities, work load, and the effect of the health center, which was important in only a few of the activities under study.

Optimization of treatment with interferon beta in multiple sclerosis. Usefulness of automatic system application criteria

Background. A software based tool has been developed (Optem) to allow automatize the recommendations of the Canadian Multiple Sclerosis Working Group for optimizing MS treatment in order to avoid subjective interpretation. METHODS: Treatment Optimization Recommendations (TORs) were applied to our database of patients treated with IFN beta1a IM. Patient data were assessed during year 1 for disease activity, and patients were assigned to 2 groups according to TOR: "change treatment" (CH) and "no change treatment" (NCH). These assessments were then compared to observed clinical outcomes for disease activity over the following years. RESULTS: We have data on 55 patients. The "change treatment" status was assigned to 22 patients, and "no change treatment" to 33 patients. The estimated sensitivity and specificity according to last visit status were 73.9% and 84.4%. During the following years, the Relapse Rate was always higher in the "change treatment" group than in the "no change treatment" group (5 y; CH: 0.7, NCH: 0.07; p < 0.001, 12 m - last visit; CH: 0.536, NCH: 0.34). We obtained the same results with the EDSS (4 y; CH: 3.53, NCH: 2.55, annual progression rate in 12 m - last visit; CH: 0.29, NCH: 0.13). CONCLUSION: Applying TOR at the first year of therapy allowed accurate prediction of continued disease activity in relapses and disability progression.

Safety and Effectiveness of two treatment regimes with tranexamic acid to minimize inflammatory response in elective cardiopulmonary bypass patients: a randomized double-blind, dose-dependent, phase IV clinical trial

Background. In cardiopulmonary bypass (CPB) patients, fibrinolysis may enhance postoperative inflammatory response. We aimed to determine whether an additional postoperative dose of antifibrinolytic tranexamic acid (TA) reduced CPB-mediated inflammatory response (IR). Methods. We performed a randomized, double-blind, dose-dependent, parallel-groups study of elective CPB patients receiving TA. Patients were randomly assigned to either the single-dose group (40 mg/Kg TA before CPB and placebo after CPB) or the double-dose group (40 mg/Kg TA before and after CPB). Results. 160 patients were included, 80 in each group. The incident rate of IR was significantly lower in the double-dose-group TA2 (7.5% vs. 18.8% in the single-dose group TA1; P = 0.030). After adjusting for hypertension, total protamine dose and temperature after CPB, TA2 showed a lower risk of IR compared with TA1 [OR: 0.29 (95% CI: 0.10-0.83), (P = 0.013)]. Relative risk for IR was 2.5 for TA1 (95% CI: 1.02 to 6.12). The double-dose group had significantly lower chest tube bleeding at 24 hours [671 (95% CI 549-793 vs. 826 (95% CI 704-949) mL; P = 0.01 corrected-P significant] and lower D-dimer levels at 24 hours [489 (95% CI 437-540) vs. 621(95% CI: 563-679) ng/mL; P = 0.01 corrected-P significant]. TA2 required lower levels of norepinephrine at 24 h [0.06 (95% CI: 0.03-0.09) vs. 0.20(95 CI: 0.05-0.35) after adjusting for dobutamine [F = 6.6; P = 0.014 corrected-P significant]. We found a significant direct relationship between IL-6 and temperature (rho = 0.26; P < 0.01), D-dimer (rho = 0.24; P < 0.01), norepinephrine (rho = 0.33; P < 0.01), troponin I (rho = 0.37; P < 0.01), Creatine-Kinase (rho = 0.37; P < 0.01), Creatine Kinase-MB (rho = 0.33; P < 0.01) and lactic acid (rho = 0.46; P < 0.01) at ICU arrival. Two patients (1.3%) had seizure, 3 patients (1.9%) had stroke, 14 (8.8%) had acute kidney failure, 7 (4.4%) needed dialysis, 3 (1.9%) suffered myocardial infarction and 9 (5.6%) patients died. We found no significant differences between groups regarding these events. Conclusions. Prolonged inhibition of fibrinolysis, using an additional postoperative dose of tranexamic acid reduces inflammatory response and postoperative bleeding (but not transfusion requirements) in CPB patients. A question which remains unanswered is whether the dose used was ideal in terms of safety, but not in terms of effectiveness.

Validation of the spanish version of the multiple sclerosis international quality of life (musiqol) questionnaire

BACKGROUND: The Multiple Sclerosis International Quality Of Life (MusiQoL) questionnaire, a 31-item, multidimensional, self-administrated questionnaire that is available in 14 languages including Spanish, has been validated using a large international sample. We investigated the validity and reliability of the Spanish version of MusiQoL in Spain. METHODS: Consecutive patients with different types and severities of multiple sclerosis (MS) were recruited from 22 centres across Spain. All patients completed the MusiQoL questionnaire, the 36-Item Short Form (SF-36) health survey, and a symptoms checklist at baseline and 21 days later. External validity, internal consistency, reliability and reproducibility were tested. RESULTS: A total of 224 Spanish patients were evaluated. Dimensions of MusiQoL generally demonstrated a high internal consistency (Cronbach's alpha: 0.70-0.92 for all but two MusiQoL domain scores). External validity testing revealed that the MusiQoL index score correlated significantly with all SF-36 dimension scores (Pearson's correlation: 0.46-0.76), reproducibility was satisfactory (intraclass correlation coefficient: 0.60-0.91), acceptability was high, and the time taken to complete the 31-item questionnaire was reasonable (mean [standard deviation]: 9.8 [11.8] minutes). CONCLUSIONS: The Spanish version of the MusiQoL questionnaire appears to be a valid and reliable instrument for measuring quality of life in patients with MS in Spain and constitutes a useful instrument to measure health-related quality of life in the clinical setting.

Current status of pediatric home enteral nutrition in Spain: the importance of the NEPAD register.

Home enteral nutrition (HEN) is a type of enteral nutrition (EN) which is becoming progressively more widespread in pediatrics due to the benefits it affords to patients, their families and to reducing hospital costs. However, the true extent of its use is unknown in Spain as the data-base set up for this purpose is still underused (Registro de Nutrición Enteral Pediátrica Ambulatoria y Domiciliaria -NEPAD-). More thorough registration of patients in the NEPAD online register will provide information about the characteristics of HEN in Spain: prevalence, diagnosis, the population sector being administered HEN, complications and developments. Likewise, forecast and planning of the necessary resources could be made while those in use could be analysed.