Disruption of Conscious Access in Psychosis Is Associated with Altered Structural Brain Connectivity

According to global neuronal workspace (GNW) theory, conscious access relies on long-distance cerebral connectivity to allow a global neuronal ignition coding for conscious content. In patients with schizophrenia and bipolar disorder, both alterations in cerebral connectivity and an increased threshold for conscious perception have been reported. The implications of abnormal structural connectivity for disrupted conscious access and the relationship between these two deficits and psychopathology remain unclear. The aim of this study was to determine the extent to which structural connectivity is correlated with consciousness threshold, particularly in psychosis. We used a visual masking paradigm to measure consciousness threshold, and diffusion MRI tractography to assess structural connectivity in 97 humans of either sex with varying degrees of psychosis: healthy control subjects (n = 46), schizophrenia patients (n = 25), and bipolar disorder patients with (n = 17) and without (n = 9) a history of psychosis. Patients with psychosis (schizophrenia and bipolar disorder with psychotic features) had an elevated masking threshold compared with control subjects and bipolar disorder patients without psychotic features. Masking threshold correlated negatively with the mean general fractional anisotropy of white matter tracts exclusively within the GNW network (inferior frontal-occipital fasciculus, cingulum, and corpus callosum). Mediation analysis demonstrated that alterations in long-distance connectivity were associated with an increased masking threshold, which in turn was linked to psychotic symptoms. Our findings support the hypothesis that long-distance structural connectivity within the GNW plays a crucial role in conscious access, and that conscious access may mediate the association between impaired structural connectivity and psychosis.     

Corpus callosum area in patients with bipolar disorder with and without psychotic features: an international multicentre study

Background

Previous studies have reported MRI abnormalities of the corpus callosum (CC) in patients with bipolar disorder (BD), although only a few studies have directly compared callosal areas in psychotic versus nonpsychotic patients with this disorder. We sought to compare regional callosal areas in a large international multicentre sample of patients with BD and healthy controls.

Methods

We analyzed anatomic T₁ MRI data of patients with BD-I and healthy controls recruited from 4 sites (France, Germany, Ireland and the United States). We obtained the mid-sagittal areas of 7 CC subregions using an automatic CC delineation. Differences in regional callosal areas between patients and controls were compared using linear mixed models (adjusting for age, sex, handedness, brain volume, history of alcohol abuse/dependence, lithium or antipsychotic medication status, symptomatic status and site) and multiple comparisons correction. We also compared regional areas of the CC between patients with BD with and without a history of psychotic features.

Results

We included 172 patients and 146 controls in our study. Patients with BD had smaller adjusted mid-sagittal CC areas than controls along the posterior body, the isthmus and the splenium of the CC. Patients with a positive history of psychotic features had greater adjusted area of the rostral CC region than those without a history of psychotic features.

Limitations

We found small to medium effect sizes, and there was no calibration technique among the sites.

Conclusion

Our results suggest that BD with psychosis is associated with a different pattern of interhemispheric connectivity than BD without psychosis and could be considered a relevant neuroimaging subtype of BD.     

The influence of waiting times on cost-effectiveness: a case study of colorectal cancer mass screening

When a cost-effectiveness analysis is implemented, the health-care system is usually assumed to adjust smoothly to the proposed new strategy. However, technological innovations in health care may often induce friction in the organization of care supply, implying the congestion of services and subsequent waiting times. Our objective here is to measure how these short run rigidities can challenge cost-effectiveness recommendations favorable to an innovative mass screening test for colorectal cancer. Using Markov modeling, we compare the standard Guaiac fecal occult blood test (gFOBT) with an innovative screening test for colorectal cancer, namely the immunological fecal occult blood test (iFOBT). Waiting time can occur between a positive screening test and the subsequent confirmation colonoscopy. Five scenarios are considered for iFOBT: no further waiting time compared with gFOBT, twice as much waiting time for a period of 5 or 10 years, and twice as much waiting time for a period of 5 or 10 years combined with a 25 % decrease in participation to confirmation colonoscopies. According to our modeling, compared with gFOBT, iFOBT would approximately double colonoscopy demand. Probabilistic sensitivity analysis enables concluding that the waiting time significantly increases the uncertainty surrounding recommendations favorable to iFOBT if it induces a decrease in the adherence rate for confirmation colonoscopy.     

Efficacy of a Web-Based Computer-Tailored Smoking Prevention Intervention for Dutch Adolescents: Randomized Controlled Trial

Background

Preventing smoking initiation among adolescents is crucial to reducing tobacco-caused death and disease. This study focuses on the effectiveness of a Web-based computer-tailored smoking prevention intervention aimed at adolescents.

Objective

The intent of the study was to describe the intervention characteristics and to show the effectiveness and results of a randomized controlled trial. We hypothesized that the intervention would prevent smoking initiation among Dutch secondary school students aged 10-20 years and would have the largest smoking prevention effect among the age cohort of 14-16 years, as smoking uptake in that period is highest.

Methods

The intervention consisted of a questionnaire and fully automated computer-tailored feedback on intention to start smoking and motivational determinants. A total of 89 secondary schools were recruited via postal mail and randomized into either the computer-tailored intervention condition or the control condition. Participants had to complete a Web-based questionnaire at baseline and at 6-month follow-up. Data on smoking initiation were collected from 897 students from these schools. To identify intervention effects, multilevel logistic regression analyses were conducted using multiple imputation.

Results

Smoking initiation among students aged 10-20 years was borderline significantly lower in the experimental condition as compared to the control condition 6 months after baseline (OR 0.25, 95% CI 0.05-1.21, P=.09). Additional analyses of the data for the 14-16 year age group showed a significant effect, with 11.5% (24/209) of the students in the control condition reporting initiation compared to 5.7% (10/176) in the experimental condition (OR 0.22, 95% CI 0.05-1.02, P=.05). No moderation effects were found regarding gender and educational level.

Conclusions

The findings of this study suggest that computer-tailored smoking prevention programs are a promising way of preventing smoking initiation among adolescents for at least 6 months, in particular among the age cohort of 14-16 years. Further research is needed to focus on long-term effects.

Trial Registration

International Standard Randomized Controlled Trial Number (ISRCTN): 77864351; http://www.controlled-trials.com/ISRCTN77864351 (Archived by WebCite at http://www.webcitation.org/6BSLKSTm5).     

Evaluation of group and self-directed formats of the Arthritis Foundation's Walk With Ease Program

Objective

To evaluate the effects of a revised 6‐week walking program for adults with arthritis, Walk With Ease (WWE), delivered in 2 formats, instructor‐led group or self‐directed.

Methods

In an observational pre‐post study design, 462 individuals with self‐reported arthritis selected either a group format (n = 192) or a self‐directed (n = 270) format. Performance and self‐reported outcomes were assessed at baseline and at 6 weeks. Self‐reported outcomes were assessed at 1 year. Adjusted mean outcome values for group and self‐directed participants were determined using regression models, adjusting for covariates.

Results

At 6 weeks, significant adjusted mean improvements (P < 0.05) were seen for nearly all self‐report and performance measures in both formats. Modest to moderate effect sizes (ES) were seen for disability (ES 0.16–0.23), pain, fatigue, and stiffness (ES 0.21–0.40), and helplessness (ES 0.24–0.28). The Arthritis Self‐Efficacy (ASE) pain and symptom scales had modest improvements (ES 0.09–0.21). The performance measures of strength (ES 0.29–0.35), balance (ES 0.12–0.36), and walking pace (ES 0.12–0.32) all showed modest to moderate improvements. No adverse events were reported for either format. At 1 year, both formats showed modest improvement in ASE pain, but there were 5 outcomes where self‐directed participants showed significant improvement, while the group participants did not.

Conclusion

The revised WWE program decreases disability and improves arthritis symptoms, self‐efficacy, and perceived control, balance, strength, and walking pace in individuals with arthritis, regardless of whether they are taking a group class or doing the program as self‐directed walkers. At 1 year, some benefits are maintained, particularly among the self‐directed. This is a safe, easy, and inexpensive program to promote community‐based physical activity.     

Effect of bipolar electrode orientation on local electrogram properties

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ABT-737 increases tyrosine kinase inhibitor-induced apoptosis in chronic myeloid leukemia cells through XIAP downregulation and sensitizes CD34(+) CD38(-) population to imatinib

Chronic myeloid leukemia (CML) tumorigenicity is driven by the oncogenic BCR-ABL tyrosine kinase. Specific tyrosine kinase inhibitors (TKI) have been designed and are now used for the treatment of CML. These TKI induce apoptosis in leukemic cells in a BIM-dependent mechanism. We hypothesized that an increase in BIM activity could sensitize CML cells to TKI. We blocked the anti-apoptotic proteins of the Bcl-2 family by using ABT-737, a Bcl-2 and Bcl-XL inhibitor. ABT-737 modified Bcl-2 protein interactions toward a pro-apoptotic phenotype. Its combination with TKI resulted in a strong synergism in CML cell lines. The association also induced a large decrease in X-linked inhibitor of apoptosis (XIAP), followed by caspase-3 activation. This XIAP decrease was due to post-translational events. The mitochondrial serine protease HtrA2/Omi was identified as being responsible for this off-target effect. Then, ABT-737 and TKI cooperate at several levels to induce apoptosis of CML cells lines, and the benefit of this association was also observed in CML hematopoietic progenitors. Interestingly, a lethal effect was also observed in the more immature CD34(+)CD38(-) TKI-insensitive population. Combination therapy might by an interesting strategy for the treatment of CML patients.