Health state utilities of a population of Nigerian hypertensive patients

<p>Abstract</p> <p>Background</p> <p>Establishment of the health impact of hypertension on quality of life of Nigerians is a step towards controlling the disease. The study aimed to provide a Nigerian specific reference list of utility scores of hypertensive patients with various interacting conditions.</p> <p>Findings</p> <p>An interviewer-based, cross-sectional study was conducted using hypertensive patients in two purposively selected tertiary hospitals located in South-Eastern Nigeria. Health Utility Index Mark 3 (HUI3) was used.</p> <p>A total of 384 participants with either hypertension alone or with hypertension-associated complications were interviewed in the two tertiary hospitals.</p> <p>The overall mean utility score was 0.35 +/- 0.42. Patients with hypertension alone had the highest overall mean utility score (0.57 +/- 0.29) while hypertensive patients with stroke had the lowest overall mean score (0.04 +/- 0.36). Being a male, increase in age and mean arterial blood pressure, emergency visit and loss of work due to illness were associated with significant decrease in overall utility scores.</p> <p>Conclusions</p> <p>This study presented a reference for health state utilities of a population of Nigerian hypertensive patients.</p

Effects of asenapine on depressive symptoms in patients with bipolar I disorder experiencing acute manic or mixed episodes: a post hoc analysis of two 3-week clinical trials

<p>Abstract</p> <p>Background</p> <p>Asenapine demonstrated superiority over placebo for mania in bipolar I disorder patients experiencing acute current manic or mixed episodes in 2 randomized, placebo-and olanzapine-controlled trials. We report the results of exploratory pooled post hoc analyses from these trials evaluating asenapine's effects on depressive symptoms in patients from these trials with significant baseline depressive symptoms.</p> <p>Methods</p> <p>In the original trials (A7501004 [NCT00159744], A7501005 [NCT00159796]), 977 patients were randomized to flexible-dose sublingual asenapine (10 mg twice daily on day 1; 5 or 10 mg twice daily thereafter), placebo, or oral olanzapine 5-20 mg once daily for 3 weeks. Three populations were defined using baseline depressive symptoms: (1) Montgomery-Asberg Depression Rating Scale (MADRS) total score ≥20 (n = 132); (2) Clinical Global Impression for Bipolar Disorder-Depression (CGI-BP-D) scale severity score ≥4 (n = 170); (3) diagnosis of mixed episodes (n = 302) by investigative site screening. For each population, asenapine and olanzapine were independently compared with placebo using least squares mean change from baseline on depressive symptom measures.</p> <p>Results</p> <p>Decreases in MADRS total score were statistically greater with asenapine versus placebo at days 7 and 21 in all populations; differences between olanzapine and placebo were not significant. Decreases in CGI-BP-D score were significantly greater with asenapine versus placebo at day 7 in all categories and day 21 in population 1; CGI-BP-D score reductions were significantly greater with olanzapine versus placebo at day 21 in population 1 and day 7 in populations 2 and 3.</p> <p>Conclusions</p> <p>These post hoc analyses show that asenapine reduced depressive symptoms in bipolar I disorder patients experiencing acute manic or mixed episodes with clinically relevant depressive symptoms at baseline; olanzapine results appeared to be less consistent. Controlled studies of asenapine in patients with acute bipolar depression are necessary to confirm the generalizability of these findings.</p

Plasma Brain-Derived Neurotrophic Factor Levels Predict the Clinical Outcome of Depression Treatment in a Naturalistic Study

Remission is the primary goal of treatment for major depressive disorder (MDD). However, some patients do not respond to treatment. The main purpose of this study was to determine whether brain-derived neurotrophic factor (BDNF) levels are correlated with treatment outcomes. In a naturalistic study, we assessed whether plasma BDNF levels were correlated with clinical outcomes by measuring plasma BDNF in patients with depressive syndrome (MADRS score ≥18), and subsequently comparing levels between the subgroup of patients who underwent remission (MADRS score ≤8) and the subgroup who were refractory to treatment (non-responders). Patients with depressive syndrome who underwent remission had significantly higher plasma BDNF levels (p<0.001), regardless of age or sex. We also found a significant negative correlation between MADRS scores and plasma BDNF levels within this group (ρ = –0.287, p = 0.003). In contrast, non-responders had significantly lower plasma BDNF levels (p = 0.029). Interestingly, plasma BDNF levels in the non-responder group were significantly higher than those in the remission group in the initial stage of depressive syndrome (p = 0.002). Our results show that plasma BDNF levels are associated with clinical outcomes during the treatment of depression. We suggest that plasma BDNF could potentially serve as a prognostic biomarker for depression, predicting clinical outcome

Feedforward Inhibition and Synaptic Scaling – Two Sides of the Same Coin?

Feedforward inhibition and synaptic scaling are important adaptive processes that control the total input a neuron can receive from its afferents. While often studied in isolation, the two have been reported to co-occur in various brain regions. The functional implications of their interactions remain unclear, however. Based on a probabilistic modeling approach, we show here that fast feedforward inhibition and synaptic scaling interact synergistically during unsupervised learning. In technical terms, we model the input to a neural circuit using a normalized mixture model with Poisson noise. We demonstrate analytically and numerically that, in the presence of lateral inhibition introducing competition between different neurons, Hebbian plasticity and synaptic scaling approximate the optimal maximum likelihood solutions for this model. Our results suggest that, beyond its conventional use as a mechanism to remove undesired pattern variations, input normalization can make typical neural interaction and learning rules optimal on the stimulus subspace defined through feedforward inhibition. Furthermore, learning within this subspace is more efficient in practice, as it helps avoid locally optimal solutions. Our results suggest a close connection between feedforward inhibition and synaptic scaling which may have important functional implications for general cortical processing

MEKK1-MKK4-JNK-AP1 Pathway Negatively Regulates Rgs4 Expression in Colonic Smooth Muscle Cells

Background: Regulator of G-protein Signaling 4 (RGS4) plays an important role in regulating smooth muscle contraction, cardiac development, neural plasticity and psychiatric disorder. However, the underlying regulatory mechanisms remain elusive. Our recent studies have shown that upregulation of Rgs4 by interleukin (IL)-1b is mediated by the activation of NFkB signaling and modulated by extracellular signal-regulated kinases, p38 mitogen-activated protein kinase, and phosphoinositide-3 kinase. Here we investigate the effect of the c-Jun N-terminal kinase (JNK) pathway on Rgs4 expression in rabbit colonic smooth muscle cells. Methodology/Principal Findings: Cultured cells at first passage were treated with or without IL-1b (10 ng/ml) in the presence or absence of the selective JNK inhibitor (SP600125) or JNK small hairpin RNA (shRNA). The expression levels of Rgs4 mRNA and protein were determined by real-time RT-PCR and Western blot respectively. SP600125 or JNK shRNA increased Rgs4 expression in the absence or presence of IL-1b stimulation. Overexpression of MEKK1, the key upstream kinase of JNK, inhibited Rgs4 expression, which was reversed by co-expression of JNK shRNA or dominant-negative mutants for MKK4 or JNK. Both constitutive and inducible upregulation of Rgs4 expression by SP600125 was significantly inhibited by pretreatment with the transcription inhibitor, actinomycin D. Dual reporter assay showed that pretreatment with SP600125 sensitized the promoter activity of Rgs4 in response to IL-1b. Mutation of the AP1-binding site within Rgs