LICAVAL: combination therapy in acute and maintenance treatment of bipolar disorder

Background: The challenge of Bipolar Disorder (BD) treatment is due to the complexity of the disease. Current guidelines represent an effort to help clinicians in their everyday practice but still have limitations, specially concerning to long term treatment. LICAVAL (efficacy and tolerability of the combination of LIthium and CArbamazepine compared to lithium and VALproic acid in the treatment of young bipolar patients) study aim to evaluate acute and maintenance phase of BD treatment with two combined drugs. Methods: LICAVAL is a single site, parallel group, randomized, outcome assessor blinded trial. BD I patients according to the DSM-IV-TR, in depressive, manic,/hypomanic or mixed episode, aged 18 to 35 years are eligible. After the diagnostic assessments, the patients are allocated for one of the groups of treatment (lithium + valproic acid or lithium + carbamazepine). Patients will be followed up for 8 weeks in phase I (acute treatment), 6 months in phase II (continuation treatment) and 12 months in phase III (maintenance treatment). Outcome assessors are blind to the treatment. The main outcome is the evaluation of changes in mean scores on CGI-BP-M between baseline and endpoint at the end of each phase of the study. Results: LICAVAL is currently in progress, with patients in phase I, II or III. It will extended until august 2012. Conclusions: Trials comparing specific treatments efficacy in BD (head to head) can show relevant information in clinical practice. Long term treatment is an issue of great important and should be evaluated carefully in more studies as long as BD is a chronic disease.

COMBINATION OFGENERAL AND SPECIFICWARM-UPS IMPROVES LEG-PRESS ONE REPETITION MAXIMUM COMPARED WITH SPECIFIC WARM-UP IN TRAINED INDIVIDUALS

Abad, CCC, Prado, ML, Ugrinowitsch, C, Tricoli, V, and Barroso, R. Combination of general and specific warm-ups improves leg-press one repetition maximum compared with specific warm-up in trained individuals. J Strength Cond Res 25(8): 2242-2245, 2011-Accurate assessment of muscular strength is critical for exercise prescription and functional evaluation. The warm-up protocol may affect the precision of the 1 repetition maximum (1RM) test. Testing guidelines recommend performing both general and specific warm-ups before strength tests. The general warm-up intends to raise muscle temperature, whereas the specific warm-up aims to increase neuromuscular activation. Although there is scientific evidence for performing the specific warm-up, the effects of general warm-up on strength tests are still unclear. The purpose of this study was to investigate whether the combination of a general with a specific warm-up (G + SWU) protocol would improve leg press 1RM values compared with a specific warm-up (SWU) protocol. Thirteen participants were tested for leg-press 1RM under 2 warm-up conditions. In the first condition, participants performed the SWU only, which was composed of 1 set of 8 repetitions at approximately 50% of the estimated 1RM followed by another set of 3 repetitions at 70% of the estimated 1RM. In the second condition (G + SWU), participants performed the 1RM test after a 20-minute general warm-up on a stationary bicycle at 60% of HRmax and the same specific warm-up as in the SWU. Values of 1RM in SWU and in G + SWU were compared by a paired t-test, and significance level was set at p <= 0.05. Strength values were on average 8.4% (p = 0.002) higher in the G + SWU compared with the SWU. These results suggest that the G + SWU induced temperature-dependent neuromuscular adjustments that increased muscle force production capacity. Therefore, these results support the recommendations of the testing guidelines to perform a moderate intensity general warm-up in addition to the specific warm-up before maximum strength assessments.

Using a combination of MLPA kits to detect chromosomal imbalances in patients with multiple congenital anomalies and mental retardation is a valuable choice for developing countries

Conventional karyotyping detects anomalies in 3-15% of patients with multiple congenital anomalies and mental retardation (MCA/MR). Whole-genome array screening (WGAS) has been consistently suggested as the first choice diagnostic test for this group of patients, but it is very costly for large-scale use in developing countries. We evaluated the use of a combination of Multiplex Ligation-dependent Probe Amplification (MLPA) kits to increase the detection rate of chromosomal abnormalities in MCA/MR patients. We screened 261 MCA/MR patients with two subtelomeric and one microdeletion kits. This would theoretically detect up to 70% of all submicroscopic abnormalities. Additionally we scored the de Vries score for 209 patients in an effort to find a suitable cut-off for MLPA screening. Our results reveal that chromosomal abnormalities were present in 87 (33.3%) patients, but only 57 (21.8%) were considered causative. Karyotyping detected 15 abnormalities (6.9%), while MLPA identified 54 (20.7%). Our combined MLPA screening raised the total detection number of pathogenic imbalances more than three times when compared to conventional karyotyping. We also show that using the de Vries score as a cutoff for this screening would only be suitable under financial restrictions. A decision analytic model was constructed with three possible strategies: karyotype, karyotype + MLPA and karyotype + WGAS. Karyotype + MLPA strategy detected anomalies in 19.8% of cases which account for 76.45% of the expected yield for karyotype + WGAS. Incremental Cost Effectiveness Ratio (ICER) of MLPA is three times lower than that of WGAS, which means that, for the same costs, we have three additional diagnoses with MLPA but only one with WGAS. We list all causative alterations found, including rare findings, such as reciprocal duplications of regions deleted in Sotos and Williams-Beuren syndromes. We also describe imbalances that were considered polymorphisms or rare variants, such as the new SNP that confounded the analysis of the 22q13.3 deletion syndrome. (C) 2011 Elsevier Masson SAS. All rights reserved.

Combination of Multiple Molecular Markers Can Improve Prognostication in Patients With Locally Advanced and Lymph Node Positive Bladder Cancer

Purpose: We tested whether the combination of 4 established cell cycle regulators (p53, pRB, p21 and p27) could improve the ability to predict clinical outcomes in a large multi-institutional collaboration of patients with pT3-4N0 or pTany Npositive urothelial carcinoma of the bladder. We also assessed whether the combination of molecular markers is superior to any individual biomarker. Materials and Methods: The study comprised 692 patients with pT3-4N0 or pTany Npositive urothelial carcinoma of the bladder treated with radical cystectomy and bilateral lymphadenectomy (median followup 5.3 years). Scoring was performed using advanced cell imaging and color detection software. The base model incorporated patient age, gender, stage, grade, lymphovascular invasion, number of lymph nodes removed, number of positive lymph nodes, concomitant carcinoma in situ and adjuvant chemotherapy. Results: Individual molecular markers did not improve the predictive accuracy for disease recurrence and cancer specific mortality. Combination of all 4 molecular markers into number of altered molecular markers resulted in significantly 1 higher predictive accuracy than any single biomarker (p < 0.001.). Moreover addition of number of altered molecular markers to the base model significantly improved the predictive accuracy for disease recurrence (3.9%, p < 0.001) and cancer specific mortality (4.3%, p < 0.001). Addition of number of altered molecular markers retained statistical significance for improving the prediction of clinical outcomes in the subgroup of patients with pT3N0 (280), pT4N0 (83) and pTany Npositive (329) disease (p < 0.001). Conclusions: While the status of individual molecular markers does not add sufficient value to outcome prediction in patients with advanced urothelial carcinoma of the bladder, combinations of molecular markers may improve molecular staging, prognostication and possibly prediction of response to therapy.

Combination micrografting and tattooing in the reconstruction of eyebrows of patients with craniofacial clefts

The absence of an eyebrow, either partial or total, has been observed in patients with craniofacial clefts, such as the Tessier 9 to 13 cleft. Several techniques have been used to improve the appearance of the region, such as island scalp flaps and scalp strip grafting, with limited or marginally satisfactory aesthetic results. The authors report 2 patients with craniofacial clefts in whom a novel technique combining 2 separate surgical approaches, micrografting and tattooing, was used. The use of micrografting with single or double hair units, properly angulated, produces natural-looking and satisfactory results with a minimum of morbidity. Excellent volume and appearance of the eyebrow may be achieved in a single session using this technique. Tattooing performed subsequently over the microimplanted hairs provides the illusion of greater density to the eyebrow, resulting in an appearance closer to normal.