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Background: Interferon (IFN)-induced depression occurs in approximately 30% of chronic hepatitis C (CHC) patients undergoing pegylated (PEG)-IFN-based antiviral therapy. While IFN-free therapy has been developed, it is not accessible to all CHC patients due to the high costs of treatment. This study evaluated the Assessment of Demand for Additional Psychological Treatment (ADAPT) questionnaire as a screening tool for patients at risk of IFN-induced depression, in order to identify patients who may uniquely benefit from IFN-free regimens., Methods: In this prospective study, consecutive patients being treated for CHC with PEG-IFN-based antiviral therapy were examined for the occurrence of depression during a 12-week treatment period. Using univariate and multivariate regression models, the value of the ADAPT questionnaire, in comparison to the Hospital Anxiety and Depression Scale (HADS), and the patients' psychiatric history was analysed., Results: A total of 103 patients (59% male; median age 42) were included, of whom 25% (26/103) developed IFN-induced depression during the study period. HADS-Depression (D) subscale (OR=1.187, P=0.003; area under the curve [AUC]=0.690) and ADAPT-Psychotherapy (PT) subscale (OR=1.020, P=0.006; AUC=0.695) showed the highest accuracy for identification of patients at risk for depression. A HADS-D score of ≥7 and an ADAPT-PT score of ≥37.8 showed a similar sensitivity (61.5% versus 57.7%), whereas ADAPT-PT showed a more favourable specificity (68.9% versus 77.4%)., Conclusions: The ADAPT-PT subscale effectively identifies patients at risk for IFN-induced depression and should therefore be taken into account when allocating patients to IFN-free antiviral treatment regimens.

Objectives: We investigated the effect on compression rate and depth of a conventional metronome and a voice metronome in simulated telephone-assisted, protocol-driven bystander Cardiopulmonary resucitation (CPR) compared to standard instruction., Material and Methods: Thirty-six lay volunteers performed 10 minutes of compression-only CPR in a prospective, investigator-blinded, 3-arm study on a manikin. Participants were randomized either to standard instruction ("push down firmly, 5 cm"), a regular metronome pacing 110 beats per minute (bpm), or a voice metronome continuously prompting "deep-deepdeep- deeper" at 110 bpm. The primary outcome was deviation from the ideal chest compression target range (50 mm compression depth x 100 compressions per minute x 10 minutes = 50 m). Secondary outcomes were CPR quality measures (compression and leaning depth, rate, no-flow times) and participants' related physiological response (heart rate, blood pressure and nine hole peg test and borg scales score). We used a linear regression model to calculate effects., Results: The mean (SD) deviation from the ideal target range (50 m) was -11 (9) m in the standard group, -20 (11) m in the conventional metronome group (adjusted difference [95%, CI], 9.0 [1.2-17.5 m], P=.03), and -18 (9) m in the voice metronome group (adjusted difference, 7.2 [-0.9-15.3] m, P=.08). Secondary outcomes (CPR quality measures and physiological response of participants to CPR performance) showed no significant differences., Conclusion: Compared to standard instruction, the conventional metronome showed a significant negative effect on the chest compression target range. The voice metronome showed a non-significant negative effect and therefore cannot be recommended for regular use in telephone-assisted CPR.

Objectives: Saturation transfer (ST) phosphorus MR spectroscopy ((31)P MRS) enables in vivo insight into energy metabolism and thus could identify liver conditions currently diagnosed only by biopsy. This study assesses the reproducibility of the localized (31)P MRS ST in liver at 7 T and tests its potential for noninvasive differentiation of non-alcoholic fatty liver (NAFL) and steatohepatitis (NASH)., Methods: After the ethics committee approval, reproducibility of the localized (31)P MRS ST at 7 T and the biological variation of acquired hepato-metabolic parameters were assessed in healthy volunteers. Subsequently, 16 suspected NAFL/NASH patients underwent MRS measurements and diagnostic liver biopsy. The Pi-to-ATP exchange parameters were compared between the groups by a Mann-Whitney U test and related to the liver fat content estimated by a single-voxel proton ((1)H) MRS, measured at 3 T., Results: The mean exchange rate constant (k) in healthy volunteers was 0.31 ± 0.03 s(-1) with a coefficient of variation of 9.0 %. Significantly lower exchange rates (p < 0.01) were found in NASH patients (k = 0.17 ± 0.04 s(-1)) when compared to healthy volunteers, and NAFL patients (k = 0.30 ± 0.05 s(-1)). Significant correlation was found between the k value and the liver fat content (r = 0.824, p < 0.01)., Conclusions: Our data suggest that the (31)P MRS ST technique provides a tool for gaining insight into hepatic ATP metabolism and could contribute to the differentiation of NAFL and NASH., Key Points: • 1D localized (31) P MRS saturation transfer in the liver is reproducible at 7 T • NASH patients have decreased hepatic Pi-to-ATP exchange rate • In this study, hepatic metabolic activity correlates with liver fat content.

Chronic inflammatory bile duct diseases such as primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) result in progressive fibrosis of the biliary tract and ultimately cirrhosis of the liver. Since the etiology and pathogenesis of these fibrosing cholangiopathies are still poorly understood, therapeutic options are rather limited at present. Ursodeoxycholic acid (UDCA) is the paradigm therapeutic bile acid and established standard treatment for PBC, but its role for medical therapy of PSC is still under debate. Promising novel bile acid-based therapeutic options include 24-norursodeoxycholic acid, a side chain-shortened C23 homologue of UDCA, and bile acid receptor/farnesoid X receptor agonists (e.g., obeticholic acid) which currently undergo clinical development for fibrosing cholangiopathies such as PBC and PSC. Other nuclear receptors such as vitamin D receptor and fatty acid-activated peroxisome proliferator-activated receptors are also of considerable interest. This review article is a summary of an overview talk given at Falk Symposium 191 on Advances in Pathogenesis and Treatment of Liver Diseases held in London, October 3-4, 2013, and summarizes the recent progress with novel therapeutic bile acids and bile acid derivatives as novel therapies for fibrosing cholangiopathies such as PBC and PSC.

Purpose: Erythropoiesis stimulating agents (ESAs) are used to treat anemia in critically ill patients. This indication is off-label, because it is not licensed by regulatory authorities. Recently ESAs were suspected to harm critically ill patients. Our objective was to assess the safety of ESAs in off-label indications in critically ill patients., Methods: Eleven databases were searched up to April 2012. We considered randomized controlled trials (RCTs) and controlled observational studies in any language that compared off-label ESAs treatment with other effective interventions, placebo or no treatment in critically ill patients. Two authors independently screened and evaluated retrieved records, extracted data and assessed risk of bias and quality of reporting., Results: We used frequentist and Bayesian models to combine studies, and performed sensitivity and subgroup analyses. From 12,888 citations, we included 48 studies (34 RCTs; 14 observational), involving 944,856 participants. Harm reporting was of medium to low quality. There was no statistically significant increased risk of adverse events in general, serious adverse events, the most frequently reported adverse events, and death in critically ill patients treated with ESAs. These results were robust against risk of bias and analysis methods. There is evidence that ESAs increase the risk of clinically relevant thrombotic vascular events, and there is some less certain evidence that ESAs might increase the risk for venous thromboembolism., Conclusions: In critically ill patients, administration of ESAs is associated with a significant increase in clinically relevant thrombotic vascular events but not with other frequently reported adverse events and death.

Objectives: To examine the association of genetic variants in the syntaxin 1A gene (STX1A) with common forms of migraine, and perform a combined analysis of the data from the current study and previously published reports., Methods: We investigated the parent-to-offspring transmission of rs6951030, rs4363087 and rs2293489 in 191 family trios, each with a proband with childhood-onset migraine, and performed a case-control analysis between the probands and 223 unrelated controls. In addition, we performed a combined data analysis with an overall sample of 567 migraine patients and 720 unrelated controls and performed a migraine-specific gene-network analysis., Results: The transmission disequilibrium test revealed significant transmission distortion of rs4363087 in migraine overall (OR = 1.56, p = 0.006; p = 0.01 after correction for multiple testing) and migraine without aura (OR = 1.58, p = 0.01; corrected p = 0.04). Two-marker haplotype analysis revealed transmission distortion of A-G (rs6951030-rs4363087; OR = 1.47, p = 0.01) and A-C (rs4363087-rs2293489; OR = 0.66, p = 0.01). Combined analysis showed significant association of rs941298 with migraine overall (OR = 1.28, p = 0.004) and migraine without aura (OR = 1.3, p = 0.008). Network analysis identified 24 genes relating STX1A to other migraine candidate genes, including KCNK18 (TRESK channel) involved in the cytoplasmatic calcium signalling together with syntaxin 1A., Conclusion: Our results provide support for the hypothesis that STX1A represents a susceptibility gene for migraine.

Background: Migraine and bipolar disorder are characterized by a high level of co-morbidity, and a common familial-genetic basis has recently been hypothesized for the 2 disorders. Genome-wide association studies have reported strong evidence of association between the polymorphisms rs10994336[T] in the ANK3 gene and rs1006737[A] in the CACNA1C gene and risk of bipolar disorder., Objective: The aim of this study was to evaluate the hypothesis of a genetic linkage between migraine and bipolar disorder by investigating the familial transmission of the 2 bipolar disorder risk polymorphisms, in a sample of family trios with probands with childhood migraine, and unrelated controls., Methods: Our sample comprised 192 family trios, each with a proband with childhood migraine (137 migraine without aura, 44 migraine with aura) and 228 unrelated controls. The markers rs10994336 and rs1006737 were genotyped using a TaqMan single nucleotide polymorphism Genotyping Assay. The transmission disequilibrium test analysis for the family trios and the case-control analysis were performed using the program UNPHASED., Results: The allelic and genotypic transmission disequilibrium test analysis did not show any evidence of transmission distortion of the 2 markers in both migraine overall (rs10994336: OR = 1.61, P = .11; rs1006737: OR = 1.12, P = .49) and in the migraine without aura and migraine with aura subgroups. Likewise, the case-control analysis of alleles and genotypes frequencies did not show any evidence of association., Conclusion: In the present study, we did not find evidence for association between the bipolar disorder risk polymorphisms rs10994336 in the ANK3 gene and rs1006737 in the CACNA1C gene in migraine. However, as these are variants that have a small effect on the risk of bipolar disorder (OR < 1.5), we cannot exclude a similar small effect on migraine susceptibility with the present sample size., (© 2011 American Headache Society.)

Aim: To assess long-term efficacy of initially successful endo-sponge assisted therapy., Methods: Between 2006 and 2009, consecutive patients who had undergone primary successful endo-sponge treatment of anastomotic leakage following rectal cancer surgery were enrolled in the study. Patients were recruited from 6 surgical departments in Vienna. Clinical and oncologic outcomes were assessed through routine endoscopic and radiologic follow-up examination., Results: Twenty patients (7 female, 13 male) were included. The indications for endo-sponge treatment were anastomotic leakage (n = 17) and insufficiency of a rectal stump after Hartmann's procedure (n = 3). All patients were primarily operated for rectal cancer. The overall mortality rate was 25%. The median follow-up duration was 17 mo (range 1.5-29.8 mo). Five patients (25%) developed a recurrent abscess. Median time between last day of endo-sponge therapy and occurrence of recurrent abscess was 255 d (range 21-733 d). One of these patients was treated by computed tomography-guided drainage and in 3 patients Hartmann's procedure had to be performed. Two patients (10%) developed a local tumor recurrence and subsequently died., Conclusion: Despite successful primary outcome, patients who receive endo-sponge therapy should be closely monitored in the first 2 years, since recurrence might occur.

Objective: As dopamine plays an important role in the pathophysiology of migraine and antimigraine drugs have an effect on the dopamine system, the objective of this study was to examine the dopamine D4 receptor gene for involvement in the cause of migraine., Methods: We tested a VNTR-polymorphism in the dopamine D4 receptor gene, the exon 3 VNTR, in a sample of 190 family trios each with a proband with childhood migraine by using transmission disequilibrium test tests., Results: We found a trend for transmission distortion of this marker in migraine, with the common seven-repeat allele of the VNTR transmitted 58 times and not transmitted 82 times (global likelihood ratio score (LRS) = 12.27, degress of freedom (DF) = 6, p = 0.06; for the 7-repeat allele: chi(2) = 5.1, p = 0.02). This effect came only from migraine without aura (145 trios), with the common 7-repeat allele transmitted 45 times and not transmitted 69 times (global LRS = 15.18; DF = 6, p = 0.019; for the 7-repeat allele: chi(2) = 6.4, p = 0.01; odds ratio, 0.47), whereas in migraine with aura (45 trios) there was no transmission distortion of the 7-repeat allele., Interpretation: We conclude that seven-repeat allele of the dopamine D4 receptor VNTR is a protective factor for migraine without aura. Because migraine is a common disorder, this protective effect may have contributed to the positive selection acting on the dopamine D4 receptor exon 3 VNTR seven-repeat allele in recent human history. We speculate that dopamine function in the lateral parabrachial nucleus is involved in migraine without aura.

Attention-Deficit/Hyperactivity Disorder (ADHD) is one of the most commonly diagnosed disorders in child and adolescent psychiatry. Patients with ADHD show increased risk for comorbid psychiatric disorders such as mood disorders, anxiety disorders, tic disorders and disruptive behavior disorders. Using criteria and methods of evidence-based medicine, in this paper possible algorithms for ADHD and comorbid disorders are presented. In conclusion, these algorithms aim to support health care professionals and can serve as guideline in decision making in pharmacotherapy. Stimulants are first-line medication treatment of ADHD without comorbid disorder. In co-existing aggression, major depressive disorder and tic disorder treatment with stimulants should be initialized at first. Only in case of unchanged persistence of comorbid symptoms specific pharmacological therapy should be combined. In comorbid anxiety disorders atomoxetine can be used as first-line treatment.