Long-term use of mepolizumab in a case of chronic eosinophilic pneumonia: extending interval dosing.

INTRODUCTION: Mepolizumab, a humanized anti IL-5 monoclonal antibody, has been used off-label for chronic eosinophilic pneumonia (CEP), inducing disease remission and saving systemic corticosteroids. CASE STUDY: We present a case of CEP, requiring long-term corticosteroids therapy due to relapse upon withdrawal. Mepolizumab was started and maintained for 2 years and 6 months. RESULTS: Corticosteroids could be withdrawn and mepolizumab dose interval was spared up to 10 wk with no disease relapse. CONCLUSION: Mepolizumab is shown to be useful for chronic eosinophilic pneumonia, allowing corticosteroid withdrawal. Dose interval may be individualized under close monitoring, for a more efficient treatment, reducing medical costs while improving patients' quality of life.

Functional analysis of new variants at the low-density lipoprotein receptor associated with familial hypercholesterolemia.

Familial hypercholesterolemia is an autosomal dominant disease of lipid metabolism caused by defects in the genes LDLR, APOB, and PCSK9. The prevalence of heterozygous familial hypercholesterolemia (HeFH) is estimated between 1/200 and 1/250. Early detection of patients with FH allows initiation of treatment, thus reducing the risk of coronary heart disease. In this study, we performed in vitro characterization of new LDLR variants found in our patients. Genetic analysis was performed by Next Generation Sequencing using a customized panel of 198 genes in DNA samples of 516 subjects with a clinical diagnosis of probable or definitive FH. All new LDLR variants found in our patients were functionally validated in CHO-ldlA7 cells. The LDLR activity was measured by flow cytometry and LDLR expression was detected by immunofluorescence. Seven new variants at LDLR were tested: c.518 G>C;p.(Cys173Ser), c.[684 G>T;694 G>T];p.[Glu228Asp;Ala232Ser], c.926C>A;p.(Pro309His), c.1261A>G;p.(Ser421Gly), c.1594T>A;p.(Tyr532Asn), and c.2138delC;p.(Thr713Lysfs*17). We classified all variants as pathogenic except p.(Ser421Gly) and p.(Ala232Ser). The functional in vitro characterization of rare variants at the LDLR is a useful tool to classify the new variants. This approach allows us to confirm the genetic diagnosis of FH, avoiding the classification as "uncertain significant variants", and therefore, carry out cascade family screening.

Investigating the relationship between multiple sclerosis disability and driving performance: A comparative study of the multiple sclerosis functional composite and expanded disability status scale.

INTRODUCTION: Multiple Sclerosis (MS) can affect the ability to perform complex tasks such as driving. The Expanded Disability Status Scale (EDSS) overlooks cognitive deficits crucial for driving. We investigated the relationship between the Multiple Sclerosis Functional Composite (MSFC), which includes cognitive assessment, and EDSS in relation to driving performance. METHODS:  This exploratory study involved 30 MS patients (mean EDSS 2.4 ± 2.0) and 15 healthy controls. We correlated the results of the EDSS, MSFC, and driving performance tests, namely the Two-Hand Coordination Test (2HAND) and the Speed Anticipation Reaction Test (SART). RESULTS: Patients did not differ from the healthy controls regarding age, sex, and driving experience. However, they exhibited lower mean Z-scores in MSFC, particularly in motor domains, but not in cognitive function. The mean Z-score for the 25-foot Walk test was -0.42 in patients compared to -0.04 in controls. For the 9-hole Peg Test, it was 0.17 in patients versus 1.47 in controls. Patients had a mean total error time of 19.7 seconds for both hands in the 2HAND test, compared to 7.7 seconds in controls. In MS patients, the MSFC and EDSS significantly correlated with SART and 2HAND components. While upper limb function (9-HPT) did not correlate with 2HAND, cognitive function (PASAT) did correlate with the number of 2HAND errors, indicating that cognitive dysfunction impacts driving performance more than physical dysfunction. CONCLUSION: The MSFC may provide valuable insights into the driving abilities of MS patients, potentially offering advantages over the EDSS in predicting driving performance. Further research with larger, more diverse populations across various driving environments is necessary to validate these findings.

Micronutrients in Pregnancy after Bariatric Surgery: A Narrative Review.

Bariatric surgery is increasingly used in women of childbearing age due to the rising prevalence of obesity and the effectiveness and availability of this treatment. Pregnancy in women with previous bariatric surgery deserves special attention. Weight loss induced by surgery reduces the risks that obesity poses to pregnancy. But on the other hand, decreased intake and malabsorption may increase the risk of malnutrition and micronutrient deficiency and negatively affect maternal and foetal health. The aim of this narrative review is to provide an updated analysis of the impact of different bariatric surgery techniques on mineral and micronutrient nutritional status during pregnancy and the possible effect on maternal-foetal health.

Site of mitochondrial reactive oxygen species production in skeletal muscle of chronic obstructive pulmonary disease and its relationship with exercise oxidative stress.

Exercise triggers skeletal muscle oxidative stress in patients with chronic obstructive pulmonary disease (COPD). The objective of this research was to study the specific sites of reactive oxygen species (ROS) production in mitochondria isolated from skeletal muscle of patients with COPD and its relationship with local oxidative stress induced by exercise. Vastus lateralis biopsies were obtained in 16 patients with COPD (66 ± 10 yr; FEV(1), 54 ± 12% ref) and in 14 control subjects with normal lung function who required surgery because of lung cancer (65 ± 7 yr; FEV(1), 91 ± 14% ref) at rest and after exercise. In these biopsies we isolated mitochondria and mitochondrial membrane fragments and determined in vitro mitochondrial oxygen consumption (Mit$$\stackrel{.}{\hbox{ V }}$$o(2)) and ROS production before and after inhibition of complex I (rotenone), complex II (stigmatellin), and complex III (antimycin-A). We related the in vitro ROS production during state 3 respiration), which mostly corresponds to the mitochondria respiratory state during exercise, with skeletal muscle oxidative stress after exercise, as measured by thiobarbituric acid reactive substances.State 3 Mit$$\stackrel{.}{\hbox{ V }}$$o(2) was similar in patients with COPD and control subjects (191 ± 27 versus 229 ± 46 nmol/min/mg; P = 0.058), whereas H(2)O(2) production was higher in the former (147 ± 39 versus 51 ± 8 pmol/mg/h; P < 0.001). The addition of complexI, II, and III inhibitors identify complex III as the main site of H(2)O(2) release by mitochondria in patients with COPD and in control subjects. The mitochondrial production of H(2)O(2) in state 3 respiration was related (r = 0.69; P < 0.001) to postexercise muscle thiobarbituric acid reactive substance levels. Our results show that complex III is the main site of the enhanced mitochondrial H(2)O(2) production that occurs in skeletal muscle of patients with COPD, and the latter appears to contribute to muscle oxidative damage.

The effects of adiponectin and leptin on human endothelial cell proliferation: a live-cell study.

The effect of adiponectin and leptin on the proliferation of the human microvascular endothelial cell line (HMEC-1) was studied in the absence or presence of fetal bovine serum (FBS). The participation of extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase/Akt (PI-3K/Akt) pathways in this effect were evaluated. We studied the effect of both adipokines on the motility, mitosis, proliferation and cell death processes of HMEC-1 cells using live-cell imaging techniques. Adiponectin but not leptin further increased the proliferative effect induced by FBS on HMEC-1. This effect seems to be the consequence of an increase in the mitotic index in adiponectin-treated cells when compared to untreated ones. The presence of either the mitogen-activated protein kinase (MAPK) inhibitor (PD98059), or PI-3K inhibitor (LY294002), reduced the effect of adiponectin in a dose-dependent manner. Neither adipokine was able to affect HMEC-1 proliferation in FBS-free conditions. Duration of mitosis, cell motility and the cell death process were similar in all conditions. These data suggest that adiponectin and leptin exert different effects on endothelial cell function. Adiponectin was able to potentiate proliferation of HMEC-1. This effect involves the activation of both PI3-K/Akt and ERK/MAPK pathways. However, it seems to exert minimal effects on HMEC-1 function in the case of leptin.

Identification of a Plasma Microrna Signature as Biomarker of Subaneurysmal Aortic Dilation in Patients with High Cardiovascular Risk.

Patients with subaneurysmal aortic dilation (SAD; 25-29 mm diameter) are likely to progress to true abdominal aortic aneurysm (AAA). Despite these patients having a higher risk of all-cause mortality than subjects with aortic size <24 mm, early diagnostic biomarkers are lacking. MicroRNAs (miRs) are well-recognized potential biomarkers due to their differential expression in different tissues and their stability in blood. We have investigated whether a plasma miRs profile could identify the presence of SAD in high cardiovascular risk patients. Using qRT-PCR arrays in plasma samples, we determined miRs differentially expressed between SAD patients and patients with normal aortic diameter. We then selected 12 miRs to be investigated as biomarkers by construction of ROC curves. A total of 82 significantly differentially expressed miRs were found by qPCR array, and 12 were validated by qRT-PCR. ROC curve analyses showed that seven selected miRs (miR-28-3p, miR-29a-3p, miR-93-3p, miR-150-5p, miR-338-3p, miR-339-3p, and miR-378a-3p) could be valuable biomarkers for distinguishing SAD patients. MiR-339-3p showed the best sensitivity and specificity, even after combination with other miRs. Decreased miR-339-3p expression was associated with increased aortic abdominal diameter. MiR-339-3p, alone or in combination with other miRs, could be used for SAD screening in high cardiovascular risk patients, helping to the early diagnosis of asymptomatic AAA.

Effect of Pectin on the Expression of Proteins Associated with Mitochondrial Biogenesis and Cell Senescence in HT29-Human Colorectal Adenocarcinoma Cells.

Mitochondria dynamic is regulated by different proteins, maintaining a balance between fission and fusion. An imbalance towards mitochondrial fission has been associated with tumor cell proliferation. The aim of this study was to analyze whether pectin modifies the viability of human colon cancer cells and the expression of proteins involved in mitochondrial fusion and fission. The human colon carcinoma cell line HT29 cells was growth in 10% fetal bovine serum in the absence and presence of pectin. Pectin reduced HT29 cell viability in a concentration-dependent manner, reaching a plateau at 150~300 µmol/L pectin. The presence of 200 µmol/L pectin reduced the expression of dynamin-related protein-1 and increased expression of the mitochondrial fusion-associated proteins mitofusin-1 and 2. Expression of cyclin B1, a protein involved in G2/M transition, was found decreased in pectin-incubated HT29 cells. Moreover, expression of p53 protein, the amount of p53 in the nucleous and ß-galactosidase activity, which are all biomarkers for cellular senescence, were significantly higher in pectin-incubated HT29 cells than in HT29 cells incubated without pectin. Expression of the protein B-cell lymphoma 2 (Bcl-2) homologous antagonist/killer was increased in response to incubation with pectin. However, incubation with pectin did not affect expression of Bcl-2-associated X protein or Bcl-2, or the caspase-3 activity. Overall, we concluded that pectin reduces the viability of human HT29 colon cancer cells, which is accompanied with a shift in the expression of proteins associated with mitochondrial dynamics towards mitochondrial fusion. Moreover, incubation with pectin favors cellular senescence over apoptosis in HT29 cells.

[European Guidelines on Cardiovascular Disease Prevention in Clinical Practice: CEIPC 2008 Spanish adaptation]. / Guía europea de prevención cardiovascular en la práctica clínica: Adaptación española del CEIPC 2008.

We present the Spanish adaptation from the CEIPC of the European Guidelines on Cardiovascular Disease Prevention in Clinical Practice 2008. This guide recommends the SCORE model for risk evaluation. The aim is to prevent premature mortality and morbidity due to CVD by means of dealing with its related risk factors in clinical practice. The guide focuses on primary prevention and emphasizes the role of the nurses and primary care medical doctors in promoting a healthy life style, based on increasing physical activity, change dietary habits, and non smoking. The therapeutic goal is to achieve a Blood Pressure <140/90 mmHg, but among patients with diabetes, chronic kidney disease, or definite CVD, the objective is <130/80 mmHg. Serum cholesterol should be <200 mg/dl and cLDL <130 mg/dl, although among patients with CVD or diabetes, the objective is <100 mg/dl (80 mg/dl if feasible in very high-risk patients). Patients with type 2 diabetes and those with metabolic syndrome must lose weight and increase their physical activity, and drugs must be administered whenever applicable, with the objective guided by BMI -body mass index- and waist circumference. In diabetic type 2 patients, the objective is glycated haemoglobin <7%. Allowing people to know the guides and developing implementation programs, identifying barriers and seeking solutions for them, are priorities for the CEIPC in order to put the recommendations into practice.

Disappearance of recurrent pancreatitis after splenectomy in familial chylomicronemia syndrome.

BACKGROUND AND AIMS: Recurrent pancreatitis is a severe complication of familial chylomicronemia syndrome (FCS) mainly secondary to lipoprotein lipase deficiency. The mechanism and interindividual variability of pancreatitis in FCS are not fully understood, but abnormalities in the drainage system of pancreatic veins could be involved. METHODS AND RESULTS: Two cases of typical FCS are described with a past history of recurrent pancreatitis that dramatically improved after splenectomy performed in both cases for reasons non-related to FCS. CONCLUSIONS: These are the first reports of the disappearance of pancreatitis after splenectomy in FCS and they should be considered of anecdotal nature at this time. The disappearance of pancreatitis following splenectomy could be in part due to subsequent improvements in pancreatic drainage. Extrahepatic portal hypertension induced by hypertriglyceridemic splenomegaly leading to pancreatic congestion could also be a contributing factor.

Usefulness of compounds with monacolin K in a case of statins intolerance.

Many patients with familial hypercholesterolaemia (FH) or in secondary prevention situations and with statin intolerance do not achieve LDL-C targets, and require treatment with PCSK9 inhibitors (iPCSK9) and ezetimibe. The case is presented on a patient with FH and total intolerance to statins. Treatment with iPCSK9 and ezetimibe failed to achieve her LDL-C target. A compound with red yeast rice derivatives containing 3mg of monacolin K was added, with good therapeutic compliance, and a very good control of LDL-C. The addition of red yeast rice derivatives containing low doses of monacolin K, together with IPCSK9 in patients with total intolerance to statins, may open a new path to obtain LDL-C targets in patients with high/very high cardiovascular risk.

Ethanol beverages containing polyphenols decrease nuclear factor kappa-B activation in mononuclear cells and circulating MCP-1 concentrations in healthy volunteers during a fat-enriched diet.

AIMS: Different epidemiological studies have demonstrated that some ethanol containing beverages intake could be associated with a reduction of cardiovascular mortality, effect attributed in part to its antioxidant properties. Nuclear factor-kappa B (NF-kappaB) is a redox sensitive transcription factor implicated in the pathogenesis of atherosclerosis. We have examined the effect of four different ethanol containing beverages on the activation of NF-kappaB in peripheral blood mononuclear cells (PBMC) and circulating concentrations of monocyte chemoattractant protein-1 (MCP-1) in healthy volunteers receiving a fat-enriched diet. METHODS AND RESULTS: Sixteen volunteers received 16 g/m(2) of ethanol in form of red wine, spirits (vodka, rum, and brandy) or no ethanol intake along with a fat-enriched diet during 5 days and all of them took all alcohols at different periods. NF-kappaB activation (electrophoretic mobility shift assay) and circulating MCP-1 levels (ELISA) were examined in blood samples taken before and after 5 days of ethanol intake. Subjects receiving a fat-enriched diet had increased NF-kappaB activation in PBMC at day 5. Furthermore, MCP-1 levels were increased in plasma at day 5. Red wine intake and some ethanol beverages containing polyphenols (brandy and rum) prevented NF-kappaB activation and decreased MCP-1 release. CONCLUSION: Consumption of moderate amounts of alcoholic drinks containing polyphenols decreases NF-kappaB activation in PBMCs and MCP-1 plasma levels during a fat-enriched diet. Our results provide additional evidence of the anti-inflammatory effects of some ethanol containing beverages, further supporting the idea that its moderate consumption may help to reduce overall cardiovascular mortality.

Cost-effectiveness analysis of apixaban compared to low-molecularweight heparins and vitamin k antagonists for treatment and secondary prevention of venous thromboembolism.

OBJECTIVE: Cost-effectiveness analysis of a 6-month treatment of apixaban (10 mg/12h, first 7 days; 5 mg/12h afterwards) for the treatment of the first event of venous thromboembolism (VTE) and prevention of recurrences, versus low-molecular-weight heparins/vitamin K antagonists treatment (LMWH/VKA). MATERIAL AND METHODS: A lifetime Markov model with 13 health states was used for describing the course of the disease. Efficacy and safety data were obtained from AMPLIFY and AMPLIFY-EXT clinical trials; health outcomes were measured as life years gained (LYG) and quality-adjusted life years (QALY). The chosen perspective of this analysis has been the Spanish National Health System (NHS). Drugs, management of VTE and complications costs were obtained from several Spanish data sources (€, 2014). A 3% discount rate was applied to health outcomes and costs. Univariate and probabilistic sensitivity analyses (SA) were performed in order to assess the robustness of the results. RESULTS: Apixaban was the most effective therapy with 7.182 LYG and 5.865 QALY, versus 7.160 LYG and 5.838 QALYs with LMWH/VKA. Furthermore, apixaban had a lower total cost (€13,374.70 vs €13,738.30). Probabilistic SA confirmed dominance of apixaban (led to better health outcomes with less associated costs) in 89% of the simulations. CONCLUSIONS: Apixaban 5 mg/12h versus LMWH/VKA was an efficient therapeutic strategy for the treatment and prevention of recurrences of VTE from the NHS perspective.

Objetivo: Analizar la relación coste-efectividad de 6 meses de tratamiento con apixaban (10 mg/12 h, 7 primeros días; 5 mg/12 h después) para el primer evento de tromboembolismo venoso (TEV) y prevención de recurrencias, frente a heparinas de bajo peso molecular/antagonistas de vitamina K (HBPM/ AVK). Material y métodos: Se ha empleado un modelo de Markov con 13 estados de salud que describen la evolución de la enfermedad a lo largo de la vida de los pacientes. Los datos de eficacia y seguridad se han obtenido de los ensayos clínicos AMPLIFY y AMPLIFY- EXT, calculándose los años de vida ganados (AVG) y los años de vida ajustados por calidad (AVAC) de las opciones terapéuticas evaluadas. En este análisis se adoptó la perspectiva del Sistema Nacional de Salud (SNS). El coste de la medicación, de las complicaciones y del manejo del TEV se obtuvo de distintas fuentes españolas (€, 2014). Se aplicó una tasa de descuento anual del 3% a costes y beneficios en salud. Se realizaron análisis de sensibilidad univariante y probabilístico (ASP) para evaluar la robustez de los resultados. Resultados: Apixaban generó mejores resultados en salud con 7,182 AVG y 5,865 AVAC, frente a 7,160 AVG y 5,838 AVAC para HBPM/AVK, y con menor coste total (13.374,70 € versus 13.738,30 €). El ASP confirmó la dominancia de apixaban (produce mejores resultados con menores costes asociados) en el 89% de las simulaciones. Conclusiones: Apixaban 5 mg/12 h versus HBPM/AVK fue una estrategia eficiente para el SNS en el tratamiento y prevención de recurrencias de TEV.

Rare genetic variants with large effect on triglycerides in subjects with a clinical diagnosis of familial vs nonfamilial hypertriglyceridemia.

BACKGROUND: Most primary severe hypertriglyceridemias (HTGs) are diagnosed in adults, but their molecular foundations have not been completely elucidated. OBJECTIVE: We aimed to identify rare dysfunctional mutations in genes encoding regulators of lipoprotein lipase (LPL) function in patients with familial and non-familial primary HTG. METHODS: We sequenced promoters, exons, and exon-intron boundaries of LPL, APOA5, LMF1, and GPIHBP1 in 118 patients with severe primary HTG (triglycerides >500 mg/dL) and 53 normolipidemic controls. Variant functionality was analyzed using predictive software and functional assays for mutations in regulatory regions. RESULTS: We identified 29 rare variants, 10 of which had not been previously described: c.(-16A>G), c.(1018+2G>A), and p.(His80Arg) in LPL; p.(Arg143Alafs*57) in APOA5; p.(Val140Ile), p.(Leu235Ile), p.(Lys520*), and p.(Leu552Arg) in LMF1; and c.(-83G>A) and c.(-192A>G) in GPIHBP1. The c.(1018+2G>A) variant led to deletion of exon 6 in LPL cDNA, whereas the c.(-16A>G) analysis showed differences in the affinity for nuclear proteins. Overall, 20 (17.0%) of the patients carried at least one allele with a rare pathogenic variant in LPL, APOA5, LMF1, or GPIHBP1. The presence of a rare pathogenic variant was not associated with lipid values, family history of HTG, clinical diagnosis, or previous pancreatitis. CONCLUSIONS: Less than one in five subjects with triglycerides >500 mg/dL and no major secondary cause for HTG may carry a rare pathogenic mutation in LPL, APOA5, LMF1, or GPIHBP1. The presence of a rare pathogenic variant is not associated with a differential phenotype.

[PREVENCAT study: control of cardiovascular risk in primary care]. / Estudio PREVENCAT: control del riesgo cardiovascular en atención primaria.

BACKGROUND AND OBJECTIVE: Most studies of cardiovascular risk factors (CVRF) conducted in our environment concentrate in a single CVRF. The PREVENCAT study was designed to estimate the control of CVRF in the population attended in primary care presenting arterial hypertension (HT), type 2 diabetes mellitus (DM2) and/or hypercholesterolemia (HC) as well as to assess the prevalence of Metabolic Syndrome in these patients. PATIENTS AND METHOD: Multicenter, cross-sectional study, in patients with HT, DM2 and/or HC, consecutively recruited by primary care physicians in Spain. The blood pressure, cholesterol, basal glycaemia, obesity, smoking and physical activity were assessed. The degree of control of these CVRF and the prevalence of MS were estimated. RESULTS: 2,649 patients were recruited, aged 64 (11.3) years, with a 51.6% of women. The most frequent diagnosis was HT (78.9%), followed by HC (58.4%) and DM2 (37.4%). In the whole sample, the percentages of patients who had a control or had initially normal values of blood pressure, cholesterol and basal glycemia were 40.0% (confidence interval [CI], 95% 38.2-41.9), 42.6% (95% CI, 40.5-44.7) and 62.7% (95% CI, 60.8-64.5), respectively. 15.6% of cases (95% CI, 14.3-17.0) had body mass index < or = 25 kg/m2; 87.5% were non-current smokers (95% CI, 86.2-88.8); and 46.2% practiced regular physical activity (95% CI, 44.3-48.1). 40% of patients had < or = 2 CVRF in good control. The prevalence of metabolic syndrome was 50.6% (95% CI, 48.7-52.5). CONCLUSIONS: The control of the CVRF considered in primary care attended population is insufficient. Hardly one of each 2 patients with HT, DM2 and HC is under control. The overweight and sedentarism control is still poorer.

Protective Effects of Cilastatin against Vancomycin-Induced Nephrotoxicity.

Vancomycin is a very effective antibiotic for treatment of severe infections. However, its use in clinical practice is limited by nephrotoxicity. Cilastatin is a dehydropeptidase I inhibitor that acts on the brush border membrane of the proximal tubule to prevent accumulation of imipenem and toxicity. The aim of this study was to investigate the potential protective effect of cilastatin on vancomycin-induced apoptosis and toxicity in cultured renal proximal tubular epithelial cells (RPTECs). Porcine RPTECs were cultured in the presence of vancomycin with and without cilastatin. Vancomycin induced dose-dependent apoptosis in cultured RPTECs, with DNA fragmentation, cell detachment, and a significant decrease in mitochondrial activity. Cilastatin prevented apoptotic events and diminished the antiproliferative effect and severe morphological changes induced by vancomycin. Cilastatin also improved the long-term recovery and survival of RPTECs exposed to vancomycin and partially attenuated vancomycin uptake by RPTECs. On the other hand, cilastatin had no effects on vancomycin-induced necrosis or the bactericidal effect of the antibiotic. This study indicates that cilastatin protects against vancomycin-induced proximal tubule apoptosis and increases cell viability, without compromising the antimicrobial effect of vancomycin. The beneficial effect could be attributed, at least in part, to decreased accumulation of vancomycin in RPTECs.

Usefulness of midregional proadrenomedullin to predict poor outcome in patients with community acquired pneumonia.

BACKGROUND: midregional proadrenomedullin (MR-proADM) is a prognostic biomarker in patients with community-acquired pneumonia (CAP). We sought to confirm whether MR-proADM added to Pneumonia Severity Index (PSI) improves the potential prognostic value of PSI alone, and tested to what extent this combination could be useful in predicting poor outcome of patients with CAP in an Emergency Department (ED). METHODS: Consecutive patients diagnosed with CAP were enrolled in this prospective, single-centre, observational study. We analyzed the ability of MR-proADM added to PSI to predict poor outcome using receiver operating characteristic (ROC) curves, logistic regression and risk reclassification and comparing it with the ability of PSI alone. The primary outcome was "poor outcome", defined as the incidence of an adverse event (ICU admission, hospital readmission, or mortality at 30 days after CAP diagnosis). RESULTS: 226 patients were included; 33 patients (14.6%) reached primary outcome. To predict primary outcome the highest area under curve (AUC) was found for PSI (0.74 [0.64-0.85]), which was not significantly higher than for MR-proADM (AUC 0.72 [0.63-0.81, p > 0.05]). The combination of PSI and MR-proADM failed to improve the predictive potential of PSI alone (AUC 0.75 [0.65-0.85, p=0.56]). Ten patients were appropriately reclassified when the combined PSI and MR-proADM model was used as compared with the model of PSI alone. Net reclassification improvement (NRI) index was statistically significant (7.69%, p = 0.03) with an improvement percentage of 3.03% (p = 0.32) for adverse event, and 4.66% (P = 0.02) for no adverse event. CONCLUSION: MR-proADM in combination with PSI may be helpful in individual risk stratification for short-term poor outcome of CAP patients, allowing a better reclassification of patients compared with PSI alone.

A six-month, multicenter, open-label, noncomparative, prospective, observational study of the efficacy and tolerability of atorvastatin in the primary care setting(estudio del control de las hiperlipidemiasen atención primaria): the cheap study.

BACKGROUND: A close relationship exists between high levels of total cholesterol (TC) (particularly low-density lipoprotein cholesterol [LDL-C]) and low levels of high-density lipoprotein cholesterol (HDL-C), which is associated with an increased risk for arteriosclerosis and cardiovascular disease (CVD). Evidence shows that atorvastatin produces significantly greater reductions in LDL-C and TC than other hydroxymethylglutaryl-coenzyme A reductase inhibitors. However, the results achieved in clinical studies could be different from those found in general clinical practice, where patient follow-up is less thorough and poorer compliance may reduce the effectiveness of the lipid-lowering therapy. OBJECTIVE: The aim of this study was to assess the effectiveness of atorvastatin in achieving the LDL-C levels recommended by several Spanish scientific societies, as well as its tolerability in standard clinical use. METHODS: This 6-month, open-label, noncomparative, prospective, observational study was conducted in 1351 primary care centers in Spain. All patients were aged 18 to 80 years and had primary hypercholesterolemia (TC >200 mg/dL and triglycerides [TG] 200 mg/dL and fasting TG 200-400 mg/dL). All patients also had LDL-C levels higher than those established by the Spanish Society of Arteriosclerosis (Sociedad Española de Arteriosclerosis [SEA]) according to baseline cardiovascular risk and previous use of lipid-lowering therapy (for patients with low, moderate, or high cardiovascular risk, the recommended LDL-C goals are ≤175 mg/dL, ≤155 mg/dL, and ≤135 mg/dL, respectively; for patients with CVD, the LDL-C goal is ≤100 mg/dL). None of the patients had creatine kinase activity ≥540 U/L or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels ≥60 U/L. Study visits occurred at months 0, 2, and 6 of treatment. Patients received atorvastatin calcium 10 mg/d for 2 months. The dosage was then doubled to 20 mg/d in patients who did not achieve the SEA LDL-C goal and also in those patients whose primary care physicians (PCPs) deemed this higher dosage necessary; this dosage was continued for at least 4 additional months, to complete at least a 6-month course of treatment. The percentage of patients who achieved their goals was used to measure atorvastatin effectiveness. Percentages of change in LDL-C, TC, TG, and HDL-C from baseline to the final study visit also were used as measures of effectiveness. The incidence of adverse events (AEs) per 10,000 patient-months was used for the primary tolerability analysis. A secondary tolerability analysis was performed in all patients treated with atorvastatin who had some recorded follow-up, regardless of whether the patient met inclusion criteria. Information was obtained from data recorded in the case-report forms. RESULTS: A total of 5317 outpatients (2715 women, 2598 men, 4 sex unknown; mean [SD] age, 58.7 [10.5] years) were enrolled. Among patients receiving known dosages of atorvastatin, 1580 of 4033 (39.2%) and 2378 of 3585 (66.3%) patients met the SEA LDL-C goal after 2 and 6 months of therapy, respectively (P

[Spanish adaptation of the European Guidelines on Cardiovascular Disease Prevention]. / Adaptación española de la guía europea de prevención cardiovascular.

We are pleased to present the European Guidelines on Cardiovascular Disease Prevention, translated and adapted by the Interdisciplinary Spanish Committee for Cardiovascular Disease Prevention. This guide is focused on the prevention of cardiovascular disease as a whole, recommending the SCORE model for risk assessment and placing priority on the care of patients and high-risk individuals. The objective is to prevent premature death due to CVD by means of dealing with its related risk factors in clinical practice. Hence, a maintained professional intervention is required in order to obtain an increase of physical activity and of healthy diets in patients high-risk individuals, and smoking cessation in smokers. The decision to start blood pressure treatment will depend upon the BP values, cardiovascular risk and possible damage to target organs. The treatment goal is to achieve BP < 140/90 mmHg, but among patients with diabetes, chronic kidney disease, a past history of ictus, coronary heart disease or heart failure, lower levels must be pursued. Serum cholesterol must be below 200 mg/dl and LDL cholesterol below 130 mg/dl, although among patients with CVD or diabetes, levels respectively below 175 mg/dl and 100 mg/dl must be pursued. Advice of a professional dietitian is always required in order to keep blood sugar levels controlled. Proper insulin therapy is required in Type I diabetes. Patients with Type II diabetes and those with metabolic syndrome must lose weight and increase their physical activity.,dngus beiln aiministered wherever applicable. Lastly, an appendix is included providing diet recommendations adapted to our environment and criteria related to referral or seeing a specialist for hypertensive or dyslipemic patients.