Interventions to facilitate return to work in adults with adjustment disorders

BACKGROUND: Adjustment disorders are a frequent cause of sick leave and various interventions have been developed to expedite the return to work (RTW) of individuals on sick leave due to adjustment disorders. OBJECTIVES: To assess the effects of interventions facilitating RTW for workers with acute or chronic adjustment disorders. SEARCH METHODS: We searched the Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) to October 2011; the Cochrane Central Register of Controlled Trials (CENTRAL) to Issue 4, 2011; MEDLINE, EMBASE, PsycINFO and ISI Web of Science, all years to February 2011; the WHO trials portal (ICTRP) and ClinicalTrials.gov in March 2011. We also screened reference lists of included studies and relevant reviews. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) evaluating the effectiveness of interventions to facilitate RTW of workers with adjustment disorders compared to no or other treatment. Eligible interventions were pharmacological interventions, psychological interventions (such as cognitive behavioural therapy (CBT) and problem solving therapy), relaxation techniques, exercise programmes, employee assistance programmes or combinations of these interventions. The primary outcomes were time to partial and time to full RTW, and secondary outcomes were severity of symptoms of adjustment disorder, work functioning, generic functional status (i.e. the overall functional capabilities of an individual, such as physical functioning, social function, general mental health) and quality of life. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies, assessed risk of bias and extracted data. We pooled studies that we deemed sufficiently clinically homogeneous in different comparison groups, and assessed the overall quality of the evidence using the GRADE approach. MAIN RESULTS: We included nine studies reporting on 10 psychological interventions and one combined intervention. The studies included 1546 participants. No RCTs were found of pharmacological interventions, exercise programmes or employee assistance programmes. We assessed seven studies as having low risk of bias and the studies that were pooled together were comparable. For those who received no treatment, compared with CBT, the assumed time to partial and full RTW was 88 and 252 days respectively. Based on two studies with a total of 159 participants, moderate-quality evidence showed that CBT had similar results for time (measured in days) until partial RTW compared to no treatment at one-year follow-up (mean difference (MD) -8.78, 95% confidence interval (CI) -23.26 to 5.71). We found low-quality evidence of similar results for CBT and no treatment on the reduction of days until full RTW at one-year follow-up (MD -35.73, 95% CI -113.15 to 41.69) (one study with 105 participants included in the analysis). Based on moderate-quality evidence, problem solving therapy (PST) significantly reduced time until partial RTW at one-year follow-up compared to non-guideline based care (MD -17.00, 95% CI -26.48 to -7.52) (one study with 192 participants clustered among 33 treatment providers included in the analysis), but we found moderate-quality evidence of no significant effect on reducing days until full RTW at one-year follow-up (MD -17.73, 95% CI -37.35 to 1.90) (two studies with 342 participants included in the analysis). AUTHORS' CONCLUSIONS: We found moderate-quality evidence that CBT did not significantly reduce time until partial RTW and low-quality evidence that it did not significantly reduce time to full RTW compared with no treatment. Moderate-quality evidence showed that PST significantly enhanced partial RTW at one-year follow-up compared to non-guideline based care but did not significantly enhance time to full RTW at one-year follow-up. An important limitation was the small number of studies included in the meta-analyses and the small number of participants, which lowered the power of the analyses

Легочная гипертензия при диастолической дисфункции левого желудочка у больных с ишемической кардиомиопатией

На основании данных эхокардиографического исследования выявлена взаимосвязь между степенью легочной гипертензии и тяжестью диастолической дисфункции левого желудочка у больных с ишемической кардиомиопатией. Показано, что рестриктиное наполнение левого желудочка наблюдается в основном при выраженной легочной гипертензии.The findings of echocardiography were used to reveal interrelation between the degree of pulmonary hypertension and severity of diastolic dysfunction of the left ventricle in patients with ischemic cardiomyopathy. Restrictive filling of the left ventricle is shown to be observed in marked pulmonary hypertension

Rare functional missense variants in CACNA1H: what can we learn from Writer's cramp?

Writer's cramp (WC) is a task-specific focal dystonia that occurs selectively in the hand and arm during writing. Previous studies have shown a role for genetics in the pathology of task-specific focal dystonia. However, to date, no causal gene has been reported for task-specific focal dystonia, including WC. In this study, we investigated the genetic background of a large Dutch family with autosomal dominantinherited WC that was negative for mutations in known dystonia genes. Whole exome sequencing identified 4 rare variants of unknown significance that segregated in the family. One candidate gene was selected for follow-up, Calcium Voltage-Gated Channel Subunit Alpha1 H, CACNA1H, due to its links with the known dystonia gene Potassium Channel Tetramerization Domain Containing 17, KCTD17, and with paroxysmal movement disorders. Targeted resequencing of CACNA1H in 82 WC cases identified another rare, putative damaging variant in a familial WC case that did not segregate. Using structural modelling and functional studies in vitro, we show that both the segregating p.Arg481Cys variant and the non-segregating p.Glu1881Lys variant very likely cause structural changes to the Cav3.2 protein and lead to similar gains of function, as seen in an accelerated recovery from inactivation. Both mutant channels are thus available for re-activation earlier, which may lead to an increase in intracellular calcium and increased neuronal excitability. Overall, we conclude that rare functional variants in CACNA1H need to be interpreted very carefully, and additional studies are needed to prove that the p.Arg481Cys variant is the cause of WC in the large Dutch family.Genetics of disease, diagnosis and treatmen

Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling

Objective: Our previous coeliac disease genome-wide association study (GWAS) implicated risk variants in the human leucocyte antigen (HLA) region and eight novel risk regions. To identify more coeliac disease loci, we selected 458 single nucleotide polymorphisms (SNPs) that showed more modest association in the GWAS for genotyping and analysis in four independent cohorts. Design: 458 SNPs were assayed in 1682 cases and 3258 controls from three populations (UK, Irish and Dutch). We combined the results with the original GWAS cohort (767 UK cases and 1422 controls); six SNPs showed association with p Results: We identified two novel coeliac disease risk regions: 6q23.3 (OLIG3-TNFAIP3) and 2p16.1 (REL), both of which reached genome-wide significance in the combined analysis of all 2987 cases and 5273 controls (rs2327832 p= 1.3x10(-08), and rs842647 p= 5.26x10(-07)). We investigated the expression of these genes in the RNA isolated from biopsies and from whole blood RNA. We did not observe any changes in gene expression, nor in the correlation of genotype with gene expression. Conclusions: Both TNFAIP3 (A20, at the protein level) and REL are key mediators in the nuclear factor kappa B (NF-kappa B) inflammatory signalling pathway. For the first time, a role for primary heritable variation in this important biological pathway predisposing to coeliac disease has been identified. Currently, the HLA risk factors and the 10 established non-HLA risk factors explain similar to 40% of the heritability of coeliac disease

The design, construction, and commissioning of the KATRIN experiment

The KArlsruhe TRItium Neutrino (KATRIN) experiment, which aims to make a direct and model-independent determination of the absolute neutrino mass scale, is a complex experiment with many components. More than 15 years ago, we published a technical design report (TDR) [1] to describe the hardware design and requirements to achieve our sensitivity goal of 0.2 eV at 90% C.L. on the neutrino mass. Since then there has been considerable progress, culminating in the publication of first neutrino mass results with the entire beamline operating [2]. In this paper, we document the current state of all completed beamline components (as of the first neutrino mass measurement campaign), demonstrate our ability to reliably and stably control them over long times, and present details on their respective commissioning campaigns

Brain specific proteins in serum: do they reliably reflect brain damage?

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SCA19 and SCA22: evidence for one locus with a worldwide distribution.

Contains fulltext : 59319.pdf (publisher's version ) (Open Access

Genetics of the dominant ataxias.

The relevant clinical, genetic, and cell biologic aspects of the dominantly inherited spinocerebellar ataxias (SCAs) are reviewed in this article. SCAs are diseases of the entire nervous system; in addition to cerebellar ataxia, the central (but not obligate) disease feature, many noncerebellar complications can be present as well. There are over 35 genetic subtypes: although those caused by expanded CAG repeats are still the more common ones, the majority of the recent SCAs have been caused by more conventional mutations. Genotype-phenotype correlations do exist and are most clear for the repeat expansion, where repeat length partially explains age at onset, disease severity and progression, and the core clinical phenotype. Some common themes within the disease mechanisms seem to emerge, including misfolding and aggregation, impairment of the protein quality control system, abnormal protein interactions, disruption of gene transcription, RNA toxicity, and changes in glutamate and calcium signaling. Yet despite this exciting progress in the molecular genetic background and suggested corresponding pathways, there is still no drug available that is specifically designed for or targeted at the mechanisms at play