Long-term follow-up of hemodynamic responders to pharmacological therapy after variceal bleeding

Although it is assumed that hemodynamic responders to pharmacological therapy after a variceal hemorrhage are adequately protected from rebleeding, there is no evidence that either this response or its protective effect extend beyond the usual 2-year follow-up featured in available studies. We aimed to assess the maintenance of hemodynamic response and its impact on outcomes in a large cohort of hemodynamic responders during a long follow-up. One hundred three patients with cirrhosis admitted with acute variceal bleeding between 2001 and 2010 were prospectively evaluated. The hepatic venous pressure gradient (HVPG) was determined 5 days after the bleeding and repeated 5-7 days after maximal tolerated doses of nadolol and nitrates. Hemodynamic responders (HVPG ≤ 12 mm Hg or ≥ 20% decrease from baseline) were maintained on drugs and followed up with annual HVPG measurements. Forty-eight patients (47%) were hemodynamic responders. The median follow-up was 48 months (range, 2-108 months). Long-term HVPG evaluations could not be performed in eight patients (four deaths, two rebleedings, two follow-ups <1 year). Among the remaining 40 patients, hemodynamic response was maintained in 26 (65%) and lost in 14 (35%). There were no baseline differences between the two subgroups. However, 100% of alcoholic patients who remained abstinent maintained long-term response, compared with 36% of nonabstinent alcoholics and 50% of patients with viral cirrhosis. Patients with loss of hemodynamic response rebled more during follow-up and showed a higher incidence of death or liver transplantation. Conclusions: After variceal bleeding, long-term maintenance of hemodynamic response to drug therapy is mainly restricted to patients with alcoholic cirrhosis who remain abstinent. The loss of this long-term response carries worse clinical outcomes.     

Quality of Life in 833 outpatients with major depression treated with open-label venlafaxine extended release: An observational 24-week study

BACKGROUND Quality of Life (QoL) assessments are common in medicine and, recently, in psychiatry, mostly in patients with chronic mental illness. We evaluated QoL in depressed outpatients treated with venlafaxine-XR over a period of 24 weeks. METHOD We evaluated 833 patients with DSM-IV major depression using the Hamilton Depression Rating Scale (HAM-D), the Hamilton Anxiety Rating Scale (HAM-A), the Montgomery-Åsberg Depression Rating Scale (MÅDRS), and the QoL in Depression Scale (QLDS). The patients received venlafaxine-XR and we evaluated them after 4, 8, and 24 weeks of treatment. RESULTS HAM-D scores decreased from a baseline of 24.6 &#45 6.3 to 6.0 &#45 5.5 (mean &#45 SD; P <0.0001) after 24 weeks. HAM-A scores decreased from a baseline of 32.3 &#45 7.9 to 6.8 &#45 6.8 ( P <0.0001) after 24 weeks. QLDS scores decreased from a baseline of 25.8 &#45 5.8 to 6.6 &#45 7.5 ( P <0.0001) after 24 weeks, indicating improvement in QoL. The response after 4 weeks was also significant and continued improving during the study. Venlafaxine-XR was shown to be safe and well tolerated. DISCUSSION Open-label venlafaxine-XR was safe, effective, well tolerated, and improved not only depression and anxiety symptoms, but also QoL, in outpatients with major depression. This study has the limitations of any non-randomized, non-blinded multiple-site clinical trial.     

Suggestive evidence for association between L‐type voltage‐gated calcium channel (CACNA1C) gene haplotypes and bipolar disorder in Latinos: a family‐based association study

Objectives: Through recent genome‐wide association studies (GWASs), several groups have reported significant association between variants in the calcium channel, voltage‐dependent, L‐type, alpha 1C subunit (CACNA1C) and bipolar disorder (BP) in European and European‐American cohorts. We performed a family‐based association study to determine whether CACNA1C is associated with BP in the Latino population. Methods: This study included 913 individuals from 215 Latino pedigrees recruited from the USA, Mexico, Guatemala, and Costa Rica. The Illumina GoldenGate Genotyping Assay was used to genotype 58 single‐nucleotide polymorphisms (SNPs) that spanned a 602.9‐kb region encompassing the CACNA1C gene including two SNPs (rs7297582 and rs1006737) previously shown to associate with BP. Individual SNP and haplotype association analyses were performed using Family‐Based Association Test (version 2.0.3) and Haploview (version 4.2) software. Results: An eight‐locus haplotype block that included these two markers showed significant association with BP (global marker permuted p = 0.0018) in the Latino population. For individual SNPs, this sample had insufficient power (10%) to detect associations with SNPs with minor effect (odds ratio = 1.15). Conclusions: Although we were not able to replicate findings of association between individual CACNA1C SNPs rs7297582 and rs1006737 and BP, we were able to replicate the GWAS signal reported for CACNA1C through a haplotype analysis that encompassed these previously reported significant SNPs. These results provide additional evidence that CACNA1C is associated with BP and provides the first evidence that variations in this gene might play a role in the pathogenesis of this disorder in the Latino population.     

Phototherapy and resistance training prevent sarcopenia in ovariectomized rats

The aim of this study was to histologically and biochemically analyze the effects of light-emitting diode therapy (LEDT) associated with resistance training to prevent sarcopenia in ovariectomized rats. Forty female Wistar rats (12 months old, 295–330 g) were bilaterally ovariectomized and divided into four groups (n?=?10 per group): control–sedentary (C), resistance training (T), LEDT–sedentary (L), and LEDT plus resistance training (LT). Trained rats performed a 12-week water-jumping program (3 days per week) carrying a load equivalent to 50–80 % of their body mass strapped to their back. Depending on the group protocol, the LED device (850 nm, 100 mW, 120 J/cm², spot size 0.5 cm²) was used either as the only method or after the resistance training had been performed. The device was used in the single point contact mode (for 10 min). The irradiated region was the center of the greater trochanter of the right femur and the middle third of the rectus femoris muscle was subsequently analyzed histomorphometrically. Significant increases (p?<?0.05) were noted for the muscle volume of the T (68.1?±?19.7 %), the L (74.1?±?5.1 %), and the LT (68.2?±?11.5 %) groups compared to the C group (60.4?±?5.5 %). There were also significant increases in the concentrations of IGF-1, IL-1, and TNF-α in the muscles of the treated groups (p?<?0.05). Animals in the LT group showed a significant increase in IL-6 compared to T, L, and C groups (p?<?0.05). These findings suggest that resistance training and LEDT can prevent sarcopenia in ovariectomized rats.     

Prognostic power of proadrenomedullin in community-acquired pneumonia is independent of aetiology

Biomarkers are useful in community-acquired pneumonia (CAP). Recently, midregional (MR) proadrenomedullin (proADM) has been shown to be of potential prognostic use. We sought to determine whether this prognostic role depends on the cause of CAP. We conducted a prospective cohort study of immunocompetent patients with CAP. Pneumonia Severity Index (PSI) and CURB-65 score (confusion (abbreviated mental test score of ≤ 8), urea ≥ 7 mol · L(-1), respiratory rate ≥ 30 breaths · min(-1), blood pressure <90 mmHg systolic or <60 mmHg diastolic, and age ≥ 65 yrs), blood C-reactive protein, procalcitonin, MR-proADM, and microbiological studies were systematically performed. Patients were grouped as bacterial, viral/atypical and mixed CAP, and were followed up at 30, 90 and 180 days, and 1 yr. We recruited 228 CAP patients. Identification of at least one pathogen was achieved in 155 (68%) patients. MR-proADM levels closely correlated with increasing severity scores, and showed an important predictive power for complications and short- and long-term mortality (1 yr). Its addition to PSI and CURB-65 significantly improved their prognostic accuracy. A MR-proADM cut-off of 0.646 nmol · L(-1) identified 92% of patients scored as PSI classes IV and V as high risk. MR-proADM outcome prediction power was not affected by different aetiologies. MR-proADM has high short- and long-term prognostic accuracy, and increases the accuracy of clinical scores. The prognostic value of MR-proADM is not modified by different possible CAP aetiologies.     

Relation Between Chronic Obstructive Pulmonary Disease and Antibiotics

Chronic obstructive pulmonary disease (COPD) constitutes a major health problem. Recurrent acute exacerbations are characteristic of the course of COPD (AECOPD) associated with significant healthcare costs and contribute to the progress of the disease. Given that almost half of AECOPD is caused by bacteria, administration of antibacterial agents is recommended for patients with severe exacerbations or severe underlying COPD. Optimal antibiotic selection for exacerbations has therefore incorporated quantifying the risk for a poor outcome of the exacerbation and choosing antibiotics differently for low risk and high risk patients. It is unclear whether antibiotics should be provided as prophylactic agents in COPD patients although ongoing trials are reexamining the question of whether the antiinflammatory action of antibiotics such as macrolides can be useful in preventing exacerbations. In addition, nowadays, the occurrence of pneumonia in COPD has received considerable recent attention as it appears to be increased by the use of inhaled corticosteroids.