Multiple sclerosis (MS) is a multifocal demyelinating disease of the central nervous system, with lesions widespread through the brain and spinal cord. An important manifestation is cognitive impairment, which, though difficult to measure, may have a major social impact. To better understand the relationship between structural tissue damage and cognitive impairment, we examined the extent and spatial distribution of brain lesions, as measured by magnetic resonance imaging (MRI), in relation to abnormal cognitive performance as measured by the Brief Repeatable Battery (BRB) in 82 MS patients. Possible confounders, like fatigue, pain and depression were also assessed. Brain MR image analysis included hyperintense T2 and hypointense T1 lesion load in the whole brain and the four lobes separately, as well as whole brain volume measurements. Cognitive impairment (defined as more than two abnormal tests) was found in 67% of the patients. Moderately strong correlations were found between the subtests of the BRB and the lesion loads in the brain regions hypothesized to be associated with that cognitive test, although these correlations were in general not much stronger than those between the subtests and the overall lesion load (due to strong interrelationships). The Spatial Recall Test correlated best with parietal lesion load; the Symbol Digit Modalities Test, the Paced Auditory Serial Addition Task (PASAT) and the Word List Generation best with frontal, parietal and temporal lesion load; while the Verbal List Generation Test Index correlated only with atrophy. Atrophy and lesion load were the main factors determining the test scores, explaining 10-25% of the variance in the test results, and were more important than fatigue, pain and depression; only depression had a minor, but significant, additional effect on the PASAT. In conclusion, cognitive impairment in MS is moderately dependent on amount (and distribution) of structural brain damage, especially in the more physically impaired patients group.

Background Anxiety and depressive disorders are prevalent in adolescents and young adults. However, most young people with mental health problems do not receive treatment. Computerized cognitive behavior therapy (cCBT) may provide an accessible alternative to face-to-face treatment, but the evidence base in young people is limited. Objective The objective was to perform an up-to-date comprehensive systematic review and meta-analysis of the effectiveness of cCBT in treating anxiety and depression in adolescents and young adults compared with active treatment and passive controls. We aimed to examine posttreatment and follow-up effects and explore the moderators of treatment effects. Methods We conducted systematic searches in the following six electronic databases: PubMed, EMBASE, PsycINFO, CINAHL, Web of Science, and Cochrane Central Register of Controlled Trials. We included randomized controlled trials comparing cCBT with any control group in adolescents or young adults (age 12-25 years) with anxiety or depressive symptoms. The quality of included studies was assessed using the Cochrane risk-of-bias tool for randomized trials, version 2.0. Overall quality of evidence for each outcome was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Posttreatment means and SDs were compared between intervention and control groups, and pooled effect sizes (Hedges g) were calculated. Random-effects meta-analyses were conducted using Comprehensive Meta-Analysis software. Subgroup analyses and meta-regression analyses were conducted to explore whether age, guidance level, and adherence rate were associated with treatment outcome. Results The search identified 7670 papers, of which 24 studies met the inclusion criteria. Most included studies (22/24) had a high risk of bias owing to self-report measures and/or inappropriate handling of missing data. Compared with passive controls, cCBT yielded small to medium posttreatment pooled effect sizes regarding depressive symptoms (g=0.51, 95% CI 0.30-0.72, number needed to treat [NNT]=3.55) and anxiety symptoms (g=0.44, 95% CI 0.23-0.65, NNT=4.10). cCBT yielded effects similar to those of active treatment controls regarding anxiety symptoms (g=0.04, 95% CI −0.23 to 0.31). For depressive symptoms, the nonsignificant pooled effect size favored active treatment controls (g=−0.70, 95% CI −1.51 to 0.11, P=.09), but heterogeneity was very high (I2=90.63%). No moderators of treatment effects were identified. At long-term follow-up, cCBT yielded a small pooled effect size regarding depressive symptoms compared with passive controls (g=0.27, 95% CI 0.09-0.45, NNT=6.58). No other follow-up effects were found; however, power was limited owing to the small number of studies. Conclusions cCBT is beneficial for reducing posttreatment anxiety and depressive symptoms in adolescents and young adults compared with passive controls. Compared with active treatment controls, cCBT yielded similar effects regarding anxiety symptoms. Regarding depressive symptoms, however, the results remain unclear. More high-quality research involving active controls and long-term follow-up assessments is needed in this population. Trial Registration PROSPERO CRD42019119725; https://tinyurl.com/y5acfgd9.

Ancestry-based carrier screening in the Ashkenazi Jewish population entails screening for specific autosomal recessive founder mutations, which are rarer among the general population. As it is now technically feasible to screen for many more diseases, the question arises whether this population prefers a limited ancestry-based offer or a pan-ethnic expanded carrier screening panel that goes beyond the diseases that are frequent in their own population, and is offered regardless of ancestry. An online questionnaire was completed by 145 individuals from the Dutch Jewish community (≥18 years) between April and July 2014. In total, 64.8% were aware of the existence of ancestry-based carrier screening, and respondents were generally positive about screening. About half (53.8%) preferred pan-ethnic expanded carrier screening, whereas 42.8% preferred ancestry-based screening. Reasons for preferring pan-ethnic screening included 'everyone has a right to be tested', 'fear of stigmatization when offering ancestry-based panels', and 'difficulties with identifying risk owing to mixed backgrounds'. 'Preventing high healthcare costs' was the most important reason against pan-ethnic carrier screening among those in favor of an ancestry-based panel. In conclusion, these findings show that people from the Dutch Jewish community have a positive attitude regarding carrier screening in their community for a wide range of diseases. As costs of expanded carrier screening panels are most likely to drop in the near future, it is expected that these panels will receive more support in the future.

Both patients and employers mentioned work-related and patient-related facilitators, work-related and condition-related barriers, and work-related solutions to RTW-problems. Patients mentioned lack of guidance and support as barriers, and stressed the need for understanding and acceptance of the limitations resulting from ABI in any RTW-solution. Implications for rehabilitation •Patients and employers are important stakeholders in the return to work (RTW) process of a patient with acquired brain injury (ABI) •Professionals in rehabilitation practice, occupational and insurance physicians need to help patients and employers to realize RTW •Professionals have to be aware of the perspectives of patients and employers regarding RTW, such as: ^Little understanding of limitations resulting from ABI ^Work-related aspects hindering RTW, such as sensory overload and high work pressure ^Condition-related barriers to RTW such as (invisible) cognitive limitations and fatigue ^Need for professional assistance during the RTW process.