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

High-throughput spheroid screens using volume, resazurin reduction and acid phosphatase activity

Mainstream adoption of physiologically-relevant three-dimensional models has been slow in the last 50 years due to long, manual protocols with poor reproducibility, high price and closed commercial platforms. This chapter describes high-throughput, low-cost, open methods for spheroid viability assessment which use readily-available reagents and open-source software to analyse spheroid volume, metabolism and enzymatic activity. We provide two ImageJ macros for automated spheroid size determination - for both single images and for images in stacks. We also share an Excel template spreadsheet allowing users to rapidly process spheroid size data, analyse plate uniformity (such as edge effects and systematic seeding errors), detect outliers and calculate dose-response. The methods would be useful to researchers in preclinical and translational research planning to move away from simplistic monolayer studies and explore 3D spheroid screens for drug safety and efficacy without substantial investment in money or time

Visual, Motor and Attentional Influences on Proprioceptive Contributions to Perception of Hand Path Rectilinearity during Reaching

We examined how proprioceptive contributions to perception of hand path straightness are influenced by visual, motor and attentional sources of performance variability during horizontal planar reaching. Subjects held the handle of a robot that constrained goal-directed movements of the hand to the paths of controlled curvature. Subjects attempted to detect the presence of hand path curvature during both active (subject driven) and passive (robot driven) movements that either required active muscle force production or not. Subjects were less able to discriminate curved from straight paths when actively reaching for a target versus when the robot moved their hand through the same curved paths. This effect was especially evident during robot-driven movements requiring concurrent activation of lengthening but not shortening muscles. Subjects were less likely to report curvature and were more variable in reporting when movements appeared straight in a novel “visual channel” condition previously shown to block adaptive updating of motor commands in response to deviations from a straight-line hand path. Similarly, compromised performance was obtained when subjects simultaneously performed a distracting secondary task (key pressing with the contralateral hand). The effects compounded when these last two treatments were combined. It is concluded that environmental, intrinsic and attentional factors all impact the ability to detect deviations from a rectilinear hand path during goal-directed movement by decreasing proprioceptive contributions to limb state estimation. In contrast, response variability increased only in experimental conditions thought to impose additional attentional demands on the observer. Implications of these results for perception and other sensorimotor behaviors are discussed

Consumer perceptions of safety in hospitals

BACKGROUND: Studies investigating adverse events have traditionally been principally undertaken from a medical perspective. The impact that experience of an adverse event has on consumer confidence in health care is largely unknown. The objectives of the study were to seek public opinion on 1) the rate and severity of adverse events experienced in hospitals; and 2) the perception of safety in hospitals, so that predictors of lack of safety could be identified. METHODS: A multistage, clustered survey of persons residing in South Australia (2001), using household interviews (weighted n = 2,884). RESULTS: A total of 67% of respondents aged over forty years reported having at least one member of their household hospitalised in the past five years; with the average being two hospital admissions in five years. Respondents stated that 7.0% (95%CI: 6.2% to 7.9%) of those hospital admissions were associated with an adverse event; 59.7% of respondents (95% CI: 51.4% to 67.5%) rated the adverse event as really serious and 48.5% (95% CI: 40.4% to 56.8%) stated prolonged hospitalisation was required as a consequence of the adverse event. Perception of safety in hospitals was largely affected by the experience of an adverse event; really serious events were the most significant predictor of lack of safety in those aged 40 years and over (RR 2.38; p<0.001). CONCLUSION: The experience of adverse events negatively impacted on public confidence in hospitals. The consumer-reported adverse event rate in hospitals (7.0%) is similar to that identified using medical record review. Based on estimates from other studies, self-reported claims of adverse events in hospital by consumers appear credible, and should be considered when developing appropriate treatment regimes

Outcome after extended follow-up in a prospective study of operable breast cancer: key factors and a prognostic index

In 1990, 215 patients with operable breast cancer were entered into a prospective study of the prognostic significance of five biochemical markers and 15 other factors (pathological/chronological/patient). After a median follow-up of 6.6 years, there were 77 recurrences and 77 deaths (59 breast cancer-related). By univariate analysis, patient outcome related significantly to 13 factors. By multivariate analysis, the most important of nine independent factors were: number of nodes involved, steroid receptors (for oestrogen or progestogen), age, clinical or pathological tumour size and grade. Receptors and grade exerted their influence only in the first 3 years. Progestogen receptors (immunohistochemical) and oestrogen receptors (biochemical) were of similar prognostic significance. The two receptors were correlated (r=+0.50, P=0.001) and displaced each other from the analytical model but some evidence for the additivity of their prognostic values was seen when their levels were discordant

Children's very low food security is associated with increased dietary intakes in energy, fat, and added sugar among Mexican-origin children (6-11 y) in Texas border Colonias

<p>Abstract</p> <p>Background</p> <p>Food insecurity among Mexican-origin and Hispanic households is a critical nutritional health issue of national importance. At the same time, nutrition-related health conditions, such as obesity and type 2 diabetes, are increasing in Mexican-origin youth. Risk factors for obesity and type 2 diabetes are more common in Mexican-origin children and include increased intakes of energy-dense and nutrient-poor foods. This study assessed the relationship between children's experience of food insecurity and nutrient intake from food and beverages among Mexican-origin children (age 6-11 y) who resided in Texas border <it>colonias</it>.</p> <p>Methods</p> <p>Baseline data from 50 Mexican-origin children were collected in the home by trained <it>promotora</it>-researchers. All survey (demographics and nine-item child food security measure) and 24-hour dietary recall data were collected in Spanish. Dietary data were collected in person on three occasions using a multiple-pass approach; nutrient intakes were calculated with NDS-R software. Separate multiple regression models were individually fitted for total energy, protein, dietary fiber, calcium, vitamin D, potassium, sodium, Vitamin C, and percentage of calories from fat and added sugars.</p> <p>Results</p> <p>Thirty-two children (64%) reported low or very low food security. Few children met the recommendations for calcium, dietary fiber, and sodium; and none for potassium or vitamin D. Weekend intake was lower than weekday for calcium, vitamin D, potassium, and vitamin C; and higher for percent of calories from fat. Three-day average dietary intakes of total calories, protein, and percent of calories from added sugars increased with declining food security status. Very low food security was associated with greater intakes of total energy, calcium, and percentage of calories from fat and added sugar.</p> <p>Conclusions</p> <p>This paper not only emphasizes the alarming rates of food insecurity for this Hispanic subgroup, but describes the associations for food insecurity and diet among this sample of Mexican-origin children. Child-reported food insecurity situations could serve as a screen for nutrition problems in children. Further, the National School Lunch and School Breakfast Programs, which play a major beneficial role in children's weekday intakes, may not be enough to keep pace with the nutritional needs of low and very low food secure Mexican-origin children.</p

Dyadic adjustment, family coping, body image, quality of life and psychological morbidity in patients with psoriasis and their partners

Background Psoriasis is an incurable and chronic disease that includes unpredictable periods of remission and relapse requiring long-term therapy. Purpose This paper focuses on the relationship among family coping, psychological morbidity, body image, dyadic adjustment and quality of life in psoriatic patients and their partners. Method One hundred and one patients with psoriasis and 78 partners comprised the sample. They were regular users of the Dermatology Service of a Central Northern hospital in Portugal and a private dermatology clinic. Patients with psoriasis were assessed on anxiety, depression, body image, quality of life, dyadic adjustment and family coping. Partners were assessed on the same measures except body image and quality of life. Results A positive relationship among dyadic adjustment, psychological morbidity and family coping in patients and their partners was found. Also, patients with lower levels of quality of life had partners with higher levels of depressive and anxious symptoms. Better dyadic adjustment predicted family coping in the psoriatic patient. High levels of dyadic adjustment in patients and low partners’ trait anxiety predicted better dyadic adjustment in partners. Conclusion The results highlight the importance of incorporating family variables in psychological interventions in psoriasis’ care, particularly family coping and dyadic adjustment as well as the need for psychological intervention to focus both on patients and partners

Precise measurement of the W-boson mass with the CDF II detector

We have measured the W-boson mass MW using data corresponding to 2.2/fb of integrated luminosity collected in proton-antiproton collisions at 1.96 TeV with the CDF II detector at the Fermilab Tevatron collider. Samples consisting of 470126 W->enu candidates and 624708 W->munu candidates yield the measurement MW = 80387 +- 12 (stat) +- 15 (syst) = 80387 +- 19 MeV. This is the most precise measurement of the W-boson mass to date and significantly exceeds the precision of all previous measurements combined

IL-12p35 induces expansion of IL-10 and IL-35-expressing regulatory B cells and ameliorates autoimmune disease

We thank Dr. Haohua Qian and Yichao Li (Visual function core, NEI, NIH) for technical assistance with OCT; Phyllis Silver (NEI, NIH) for EAU scoring of the eyes; Rashid Mahdi. M.J.M. for technical assistance with western blot analyses and Rafael Villasmil (NEI FLOW Cytometry Core facility) for assistance with FACS analysis.Peer reviewedPublisher PD