Symptoms predicting remission after divalproex augmentation with olanzapine in partially nonresponsive patients experiencing mixed bipolar I episode: a post-hoc analysis of a randomized controlled study

<p>Abstract</p> <p>Background</p> <p>Rating scale items in a 6-week clinical trial of olanzapine versus placebo augmentation in patients with mixed bipolar disorder partially nonresponsive to ≥14 days of divalproex monotherapy were analyzed to characterize symptom patterns that could predict remission. At baseline, the two treatment groups were similar.</p> <p>Findings</p> <p>Factor analysis with Varimax rotation was performed <it>post hoc </it>on baseline items of the 21-Item Hamilton Depression Rating Scale (HDRS-21) and Young Mania Rating Scale (YMRS). Backwards-elimination logistic regression ascertained factors predictive of protocol-defined endpoint remission (HDRS-21 score ≤ 8 and YMRS score ≤ 12) with subsequent determination of optimally predictive factor score cutoffs.</p> <p>Factors for Psychomotor activity (YMRS items for elevated mood, increased motor activity, and increased speech and HDRS-21 agitation item) and Guilt/Suicidality (HDRS-21 items for guilt and suicidality) significantly predicted endpoint remission in the divalproex+olanzapine group. No factor predicted remission in the divalproex+placebo group. Patients in the divalproex+olanzapine group with high pre-augmentation psychomotor activity (scores ≥10) were more likely to remit compared to those with lower psychomotor activity (odds ratio [OR] = 3.09, 95% confidence interval [CI] = 1.22-7.79), and patients with marginally high Guilt/Suicidality (scores ≥2) were less likely to remit than those with lower scores (OR = 0.37, 95% CI = 0.13-1.03). Remission rates for divalproex+placebo vs. divalproex+olanzapine patients with high psychomotor activity scores were 22% vs. 45% (p = 0.08) and 33% vs. 48% (p = 0.29) for patients with low Guilt/Suicidality scores.</p> <p>Conclusions</p> <p>Patients who were partially nonresponsive to divalproex treatment with remaining high vs. low psychomotor activity levels or minimal vs. greater guilt/suicidality symptoms were more likely to remit with olanzapine augmentation.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov; <url>http://clinicaltrials.gov/ct2/show/NCT00402324?term=NCT00402324&rank=1</url>, Identifier: NCT00402324</p

Learning to mark: a qualitative study of the experiences and concerns of medical markers

BACKGROUND: Although there is published research on the methods markers use in marking various types of assessment, there is relatively little information on the processes markers use in approaching a marking exercise. This qualitative paper describes the preparation and experiences of general practice (GP) teachers who undertake marking a written assessment in an undergraduate medical course. METHODS: Semi-structured interviews were conducted with seven of the 16 GP tutors on an undergraduate course. The purposive sample comprised two new markers, two who had marked for a couple of years and three experienced markers. Each respondent was interviewed twice, once following a formative assessment of a written case study, and again after a summative assessment. All interviews were audio-taped and analysed for emerging themes. A respondent validation exercise was conducted with all 16 GP tutors. RESULTS: Markers had internal concerns about their ability to mark fairly and made considerable efforts to calibrate their marking. They needed guidance and coaching when marking for the first time and adopted a variety of marking styles, reaching a decision through a number of routes. Dealing with pass/fail borderline scripts and the consequences of the mark on the student were particular concerns. Even experienced markers felt the need to calibrate their marks both internally and externally CONCLUSION: Previous experience of marking appears to improve markers' confidence and is a factor in determining the role which markers adopt. Confidence can be improved by giving clear instructions, along with examples of marking. The authors propose that one method of providing this support and coaching could be by a process of peer review of a selection of papers prior to the main marking. New markers in particular would benefit from further guidance, however they are influenced by others early on in their marking career and course organisers should be mindful of this when arranging double marking

Consistent phenological shifts in the making of a biodiversity hotspot: the Cape flora

Background The best documented survival responses of organisms to past climate change on short (glacial-interglacial) timescales are distributional shifts. Despite ample evidence on such timescales for local adaptations of populations at specific sites, the long-term impacts of such changes on evolutionary significant units in response to past climatic change have been little documented. Here we use phylogenies to reconstruct changes in distribution and flowering ecology of the Cape flora - South Africa's biodiversity hotspot - through a period of past (Neogene and Quaternary) changes in the seasonality of rainfall over a timescale of several million years. Results Forty-three distributional and phenological shifts consistent with past climatic change occur across the flora, and a comparable number of clades underwent adaptive changes in their flowering phenology (9 clades; half of the clades investigated) as underwent distributional shifts (12 clades; two thirds of the clades investigated). Of extant Cape angiosperm species, 14-41% have been contributed by lineages that show distributional shifts consistent with past climate change, yet a similar proportion (14-55%) arose from lineages that shifted flowering phenology. Conclusions Adaptive changes in ecology at the scale we uncover in the Cape and consistent with past climatic change have not been documented for other floras. Shifts in climate tolerance appear to have been more important in this flora than is currently appreciated, and lineages that underwent such shifts went on to contribute a high proportion of the flora's extant species diversity. That shifts in phenology, on an evolutionary timescale and on such a scale, have not yet been detected for other floras is likely a result of the method used; shifts in flowering phenology cannot be detected in the fossil record

Tailored vs. Standardized Internet-Based Cognitive Behavior Therapy for Depression and Comorbid Symptoms: A Randomized Controlled Trial

Background and Aims:Major depression can be treated by means of cognitive behavior therapy, delivered via the Internet as guided self-help. Individually tailored guided self-help treatments have shown promising results in the treatment of anxiety disorders. This randomized controlled trial tested the efficacy of an Internet-based individually tailored guided selfhelp treatment which specifically targeted depression with comorbid symptoms. The treatment was compared both to standardized (non-tailored) Internet-based treatment and to an active control group in the form of a monitored online discussion group. Both guided self-help treatments were based on cognitive behavior therapy and lasted for 10 weeks. The discussion group consisted of weekly discussion themes related to depression and the treatment of depression. Methods:A total of 121 participants with diagnosed major depressive disorder and with a range of comorbid symptoms were randomized to three groups. The tailored treatment consisted of a prescribed set of modules targeting depression as well as comorbid problems. The standardized treatment was a previously tested guided self-help program for depression. Results:From pre-treatment to post-treatment, both treatment groups improved on measures of depression, anxiety and quality of life. The results were maintained at a 6-month follow-up. Subgroup analyses showed that the tailored treatment was more effective than the standardized treatment among participants with higher levels of depression at baseline and more comorbidity, both in terms of reduction of depressive symptoms and on recovery rates. In the subgroup with lower baseline scores of depression, few differences were seen between treatments and the discussion group. Conclusions:This study shows that tailored Internet-based treatment for depression is effective and that addressing comorbidity by tailoring may be one way of making guided self-help treatments more effective than standardized approaches in the treatment of more severe depression

Does delayed measurement affect patient reports of provider performance? Implications for performance measurement of medical assistance with tobacco cessation: A Dental PBRN study

<p>Abstract</p> <p>Background:</p> <p>We compared two methods of measuring provider performance of tobacco control activities: immediate "exit cards" versus delayed telephone follow-up surveys. Current standards, e.g. HEDIS, use delayed patient measures that may over or under-estimate overall performance.</p> <p>Methods:</p> <p>Patients completed exit cards in 60 dental practices immediately after a visit to measure whether the provider "asked" about tobacco use, and "advised" the patient to quit. One to six months later patients were asked the same questions by telephone survey. Using the exit cards as the standard, we quantified performance and calculated sensitivity (agreement of those responding yes on telephone surveys compared with exit cards) and specificity (agreement of those responding no) of the delayed measurement.</p> <p>Results:</p> <p>Among 150 patients, 21% reporting being asked about tobacco use on the exit cards and 30% reporting being asked in the delayed surveys. The sensitivity and specificity were 50% and 75%, respectively. Similarly, among 182 tobacco users, 38% reported being advised to quit on the exit cards and this increased to 51% on the delayed surveys. The sensitivity and specificity were 75% and 64%, respectively. Increasing the delay from the visit to the telephone survey resulted in increasing disagreement.</p> <p>Conclusion:</p> <p>Patient reports differed considerably in immediate versus delayed measures. These results have important implications because they suggest that our delayed measures may over-estimate performance. The immediate exit cards should be included in the armamentarium of tools for measuring providers' performance of tobacco control, and perhaps other service delivery.</p

Spatial Proximity and Similarity of the Epigenetic State of Genome Domains

Recent studies demonstrate that the organization of the chromatin within the nuclear space might play a crucial role in the regulation of gene expression. The ongoing progress in determination of the 3D structure of the nuclear chromatin allows one to study correlations between spatial proximity of genome domains and their epigenetic state. We combined the data on three-dimensional architecture of the whole human genome with results of high-throughput studies of the chromatin functional state and observed that fragments of different chromosomes that are spatially close tend to have similar patterns of histone modifications, methylation state, DNAse sensitivity, expression level, and chromatin states in general. Moreover, clustering of genome regions by spatial proximity produced compact clusters characterized by the high level of histone modifications and DNAse sensitivity and low methylation level, and loose clusters with the opposite characteristics. We also associated the spatial proximity data with previously detected chimeric transcripts and the results of RNA-seq experiments and observed that the frequency of formation of chimeric transcripts from fragments of two different chromosomes is higher among spatially proximal genome domains. A fair fraction of these chimeric transcripts seems to arise post-transcriptionally via trans-splicing

Sunlight exposure or vitamin D supplementation for vitamin D-deficient non-western immigrants: a randomized clinical trial

Summary: Vitamin D deficiency is very common in non-western immigrants. In this randomized clinical trial, vitamin D 800 IU/day or 100,000 IU/3 months were compared with advised sunlight exposure. Vitamin D supplementation was more effective than advised sunlight exposure in improving vitamin D status and lowering parathyroid hormone levels. Introduction: Vitamin D deficiency (25-hydroxyvitamin D [25(OH)D]<25 nmol/l) is common among non-western immigrants. It can be treated with vitamin D supplementation or sunlight exposure. Methods: To determine whether the effect of vitamin

New Insights into the Skull of Istiodactylus latidens (Ornithocheiroidea, Pterodactyloidea)

The skull of the Cretaceous pterosaur Istiodactylus latidens, a historically important species best known for its broad muzzle of interlocking, lancet-shaped teeth, is almost completely known from the broken remains of several individuals, but the length of its jaws remains elusive. Estimates of I. latidens jaw length have been exclusively based on the incomplete skull of NHMUK R3877 and, perhaps erroneously, reconstructed by assuming continuation of its broken skull pieces as preserved in situ. Here, an overlooked jaw fragment of NHMUK R3877 is redescribed and used to revise the skull reconstruction of I. latidens. The new reconstruction suggests a much shorter skull than previously supposed, along with a relatively tall orbital region and proportionally slender maxilla, a feature documented in the early 20th century but ignored by all skull reconstructions of this species. These features indicate that the skull of I. latidens is particularly distinctive amongst istiodactylids and suggests greater disparity between I. latidens and I. sinensis than previously appreciated. A cladistic analysis of istiodactylid pterosaurs incorporating new predicted I. latidens skull metrics suggests Istiodactylidae is constrained to five species (Liaoxipterus brachyognathus, Lonchengpterus zhoai, Nurhachius ignaciobritoi, Istiodactylus latidens and Istiodactylus sinensis) defined by their distinctive dentition, but excludes the putative istiodactylids Haopterus gracilis and Hongshanopterus lacustris. Istiodactylus latidens, I. sinensis and Li. brachyognathus form an unresolved clade of derived istiodactylids, and the similarity of comparable remains of I. sinensis and Li. brachyognathus suggest further work into their taxonomy and classification is required. The new skull model of I. latidens agrees with the scavenging habits proposed for these pterosaurs, with much of their cranial anatomy converging on that of habitually scavenging birds