Objectives
To aid the development of treatment for cognitive impairment in bipolar disorder, the International Society for Bipolar Disorders (ISBD) convened a task force to create a consensus‐based ...guidance paper for the methodology and design of cognition trials in bipolar disorder.
Methods
The task force was launched in September 2016, consisting of 18 international experts from nine countries. A series of methodological issues were identified based on literature review and expert opinion. The issues were discussed and expanded upon in an initial face‐to‐face meeting, telephone conference call and email exchanges. Based upon these exchanges, recommendations were achieved.
Results
Key methodological challenges are: lack of consensus on how to screen for entry into cognitive treatment trials, define cognitive impairment, track efficacy, assess functional implications, and manage mood symptoms and concomitant medication. Task force recommendations are to: (i) enrich trials with objectively measured cognitively impaired patients; (ii) generally select a broad cognitive composite score as the primary outcome and a functional measure as a key secondary outcome; and (iii) include remitted or partly remitted patients. It is strongly encouraged that trials exclude patients with current substance or alcohol use disorders, neurological disease or unstable medical illness, and keep non‐study medications stable. Additional methodological considerations include neuroimaging assessments, targeting of treatments to illness stage and using a multimodal approach.
Conclusions
This ISBD task force guidance paper provides the first consensus‐based recommendations for cognition trials in bipolar disorder. Adherence to these recommendations will likely improve the sensitivity in detecting treatment efficacy in future trials and increase comparability between studies.
Objectives
Cognition is a new treatment target to aid functional recovery and enhance quality of life for patients with bipolar disorder. The International Society for Bipolar Disorders (ISBD) ...Targeting Cognition Task Force aimed to develop consensus‐based clinical recommendations on whether, when and how to assess and address cognitive impairment.
Methods
The task force, consisting of 19 international experts from nine countries, discussed the challenges and recommendations in a face‐to‐face meeting, telephone conference call and email exchanges. Consensus‐based recommendations were achieved through these exchanges with no need for formal consensus methods.
Results
The identified questions were: (I) Should cognitive screening assessments be routinely conducted in clinical settings? (II) What are the most feasible screening tools? (III) What are the implications if cognitive impairment is detected? (IV) What are the treatment perspectives? Key recommendations are that clinicians: (I) formally screen cognition in partially or fully remitted patients whenever possible, (II) use brief, easy‐to‐administer tools such as the Screen for Cognitive Impairment in Psychiatry and Cognitive Complaints in Bipolar Disorder Rating Assessment, and (III) evaluate the impact of medication and comorbidity, refer patients for comprehensive neuropsychological evaluation when clinically indicated, and encourage patients to build cognitive reserve. Regarding question (IV), there is limited evidence for current evidence‐based treatments but intense research efforts are underway to identify new pharmacological and/or psychological cognition treatments.
Conclusions
This task force paper provides the first consensus‐based recommendations for clinicians on whether, when, and how to assess and address cognition, which may aid patients’ functional recovery and improve their quality of life.
Proposes a new term for psychological treatments for cognitive problems in mood disorders - CET-MD. Suggests in clinical practice the question for each individual patient should be 'how can cognitive ...function be enhanced?' to address all patients with mood disorders. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.
To evaluate the efficacy and safety of retigabine 600, 900, and 1,200 mg/day administered three times daily as adjunctive therapy in patients with partial-onset seizures.
A multicenter, randomized, ...double-blind, placebo-controlled trial was performed. After an 8-week baseline phase, patients were randomized to a 16-week double-blind treatment period (8-week forced titration and 8-week maintenance) followed by either tapering or entry into an open-label extension study. Primary efficacy was the percentage change from baseline in monthly seizure frequency and compared across treatment arms. Secondary efficacy comparisons included the proportion of patients experiencing >/=50% reduction in seizure frequency (responder rate), emergence of new seizure types, and physician assessment of global clinical improvement. Safety/tolerability assessments included adverse events (AEs), physical and neurologic examinations, and clinical laboratory evaluations. Efficacy analyses were performed on the intent-to-treat population.
Of the 399 randomized patients, 279 (69.9%) completed the double-blind treatment period. The median percent change in monthly total partial seizure frequency from baseline was -23% for 600 mg/day, -29% for 900 mg/day, and -35% for 1,200 mg/day vs -13% for placebo (p < 0.001 for overall difference across all treatment arms). Responder rates for retigabine were 23% for 600 mg/day, 32% for 900 mg/day (p = 0.021), and 33% for 1,200 mg/day (p = 0.016), vs 16% for placebo. The most common treatment-emergent AEs were somnolence, dizziness, confusion, speech disorder, vertigo, tremor, amnesia, abnormal thinking, abnormal gait, paresthesia, and diplopia.
Adjunctive therapy with retigabine is well tolerated and reduces the frequency of partial-onset seizures in a dose-dependent manner.
Although neurocognitive impairment has been widely reported in major depressive disorder (MDD), confounding factors, such as the effects of psychotropic medication, have rarely been controlled for.
...To examine neurocognitive function in medication-free patients with MDD and healthy controls.
Forty-four patients meeting DSM-IV criteria for MDD, all psychotropic-medication-free for at least 6 weeks, and 44 demographically matched, healthy comparison subjects completed a comprehensive neurocognitive battery.
Patients with depression were impaired significantly in a range of cognitive domains, including attention and executive function and visuospatial learning and memory, compared with controls. Motor and psychomotor functions were intact. Severity of depression correlated with learning and memory performance, but not executive function.
Pronounced neurocognitive impairment was found in this sample of young adult out-patients with MDD. This is not attributable to the confounding effects of psychotropic medication and could therefore provide an objective marker of brain dysfunction in depression.
GPS-based transit signal priority (TSP) is a new type of transit preferential tool being considered in many North American cities. With GPS detection and advanced communications, GPS-based TSP ...provides flexible and conditional signal priority to transit vehicles. This is a relatively new system with limited field implementations and evaluations. The research in this study used microscopic simulation, to create a set of TSP scenarios for a 3-mi bus corridor and evaluated the influences of GPS-based TSP on transit and traffic operations. The simulation network was the 3300 South corridor, including side streets, in Salt Lake County, Utah. A proposal was evaluated to upgrade the Utah Transit Authority Bus Route 33 operating along the corridor into a bus rapid transit (BRT) line running in mixed traffic. Eight simulation scenarios were created to cover (a) current field conditions, (b) regular bus with traditional TSP implementation, (c) regular bus with GPS-based TSP, (d) BRT implementation with no TSP, (e) BRT with traditional TSP implementation, (f) BRT with GPS-based TSP, (g) BRT with conditional TSP, and (h) BRT with multiconditional TSP implementation. The evaluation included transit and nontransit operations, and the impacts on side-street traffic. The results show that GPS-based TSP performed as effectively as did traditional TSP. Conditional and multi-conditional TSP strategies showed benefits in providing the transit system considerable delay reduction (13% and 3%, respectively) and travel time savings (7% and 3%, respectively) while having the smallest impacts on side-street traffic (3% and 1% increase in delay, respectively) compared with other TSP strategies.
Purpose: Individuals with polycystic ovary syndrome (PCOS) are at increased risk of depression and anxiety symptoms and impairment in aspects of cognitive function. However, there is little evidence ...regarding effects of standard treatment for PCOS on these features of the syndrome. The aim of this study was to examine the effect of 12 weeks of naturalistic treatment of PCOS, with usual medications, on depression symptoms, anxiety symptoms and cognitive function. Patients and Methods: Thirty-three participants with PCOS received 12 weeks of individualised treatment based on clinical presentation. Changes in depression and anxiety symptoms were assessed with the self-report Hospital Anxiety and Depression Scale at baseline and 12 weeks, and cognitive function was assessed at the same time-points with a battery of tests spanning cognitive domains of verbal learning and memory, visuospatial learning and memory, psychomotor speed, attention and executive function. Outcomes were compared with a control group of 40 healthy participants. Results: Participants with PCOS (mean age = 29.2 years; mean Body Mass Index = 27.4) were treated with a variety of medications, predominantly spironolactone (n = 22) and oral contraceptives (n = 16). Depression and anxiety symptoms improved significantly over the course of treatment, with moderate effect sizes (Cohen's d 0.43-0.55, p < 0.05). Effect sizes of the difference in change from that of the control group were moderate but did not reach statistical significance. Women undergoing PCOS treatment demonstrated significant improvements in aspects of cognitive function, but improvement did not differ significantly from controls and effect size changes were similar, suggesting practise effects in both groups. Conclusion: Our study provides preliminary evidence that treatment of PCOS may be associated with improvement in psychiatric aspects of the syndrome, particularly depressive symptoms. Keywords: androgen, depression, cognitive function, testosterone, spironolactone
IntroductionBarrett’s oesophagus (BO) defined by metaplastic columnar epithelium in the distal oesophagus is a pre-malignant lesion for oesophageal adenocarcinoma (OAC). HMGB1 impacts genomic ...stability, influences epithelial cell behaviour and immune response. We previously reported loss of nuclear and emergence of cytoplasmic epithelial HMGB1 in BO and dysplasia. Our aim was to define expression of HMGB1 in upper GI malignancy, assess expression of HMGB1 downstream effector proteins p53 and RUNX3 and characterise lymphocytic infiltrate in oesophageal neoplastic progression.MethodTissue was sourced from the Grampian Biorepository (n=241 total). Intensity of epithelial nuclear and cytoplasmic expression of target proteins were assessed immunohistochemically in a tissue microarray representing 150 upper gastrointestinal cancers (58 OAC, 9 oesophageal squamous cancer, 83 gastric adenocarcinoma), 15 normal oesophageal mucosa, 24 normal gastric mucosa and 14 BO mucosa adjacent to OAC. Expression of p53, RUNX3 and lymphocytic inflammatory cell infiltrate was also assessed in 78 and 13 biopsies from 19 and 10 patients with non-dysplastic or dysplastic BO. Data was analysed by relative frequencies of staining correlated to clinico-pathological data, Fisher’s exact test and Mann-Whitney U test.ResultsThere was loss of nuclear HMGB1 across all cancer phenotypes. Epithelial cytoplasmic HMGB1 expression was associated with OAC compared to normal epithelium (p<0.001), albeit with weaker intensity to non-dysplastic (p=0.001) or dysplastic BO (p=0.002). In gastric adenocarcinoma, a strong cytoplasmic HMGB1 (p=0.010) and strong nuclear p53 (p=0.033) was associated with improved survival. Dysplastic BO expressed strong nuclear p53 as expected (p<0.001 compared to normal mucosa) and this was lost on malignant transformation (p<0.001). Epithelial nuclear RUNX3 was associated with dysplastic BO (p=0.004). A robust RUNX3 positive lymphocytic stromal inflammatory infiltrate was seen in BO. Immunophenotyping revealed that dysplastic BO is associated with increased Foxp3+ regulatory T cells (p<0.002) and non-dysplastic BO with reduced CD20+ B cell (p<0.001), CD4+ (p<0.001) and CD8+ (p<0.001) T cell subset infiltration.ConclusionThis study offers new insight into the pathogenesis of oesophageal neoplastic progression. The biological significance of dynamic localisation and intensity of HMGB1 and RUNX3, and changes in adjacent stromal inflammatory cell infiltrate warrant further investigation to determine a protective or pathogenic role in oesophageal neoplasia.Disclosure of InterestNone Declared
Although it is generally expected that wider lines will have a positive effect on vehicle safety, there have not been any convincing evidence based on the crash data analysis, partly because of the ...lack of relevant data. In this paper, the safety effect of wider edge lines was examined by analyzing crash frequency data for road segments with and without wider edge lines. The data from three states, Kansas, Michigan, and Illinois, have been analyzed. Because of different nature of data from each state, a different statistical analysis approach was employed for each state: an empirical Bayes, before-after analysis of Kansas data, an interrupted time series design and generalized linear segmented regression analysis of Michigan data, and a cross sectional analysis of Illinois data. Although it is well-known that causation is hard to establish based on observational studies, the results from three extensive statistical analyses all point to the same findings. The consistent findings lend support to the positive safety effects of wider edge lines installed on rural, two-lane highways.
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