Home parenteral nutrition with an omega-3-fatty-acid-enriched MCT/LCT lipid emulsion in patients with chronic intestinal failure (the HOME study):study protocol for a randomized, controlled, multicenter, international clinical trial

BACKGROUND: Home parenteral nutrition (HPN) is a life-preserving therapy for patients with chronic intestinal failure (CIF) indicated for patients who cannot achieve their nutritional requirements by enteral intake. Intravenously administered lipid emulsions (ILEs) are an essential component of HPN, providing energy and essential fatty acids, but can become a risk factor for intestinal-failure-associated liver disease (IFALD). In HPN patients, major effort is taken in the prevention of IFALD. Novel ILEs containing a proportion of omega-3 polyunsaturated fatty acids (n-3 PUFA) could be of benefit, but the data on the use of n-3 PUFA in HPN patients are still limited. METHODS/DESIGN: The HOME study is a prospective, randomized, controlled, double-blind, multicenter, international clinical trial conducted in European hospitals that treat HPN patients. A total of 160 patients (80 per group) will be randomly assigned to receive the n-3 PUFA-enriched medium/long-chain triglyceride (MCT/LCT) ILE (Lipidem/Lipoplus® 200 mg/ml, B. Braun Melsungen AG) or the MCT/LCT ILE (Lipofundin® MCT/LCT/Medialipide® 20%, B. Braun Melsungen AG) for a projected period of 8 weeks. The primary endpoint is the combined change of liver function parameters (total bilirubin, aspartate transaminase and alanine transaminase) from baseline to final visit. Secondary objectives are the further evaluation of the safety and tolerability as well as the efficacy of the ILEs. DISCUSSION: Currently, there are only very few randomized controlled trials (RCTs) investigating the use of ILEs in HPN, and there are very few data at all on the use of n-3 PUFAs. The working hypothesis is that n-3 PUFA-enriched ILE is safe and well-tolerated especially with regard to liver function in patients requiring HPN. The expected outcome is to provide reliable data to support this thesis thanks to a considerable number of CIF patients, consequently to broaden the present evidence on the use of ILEs in HPN. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03282955. Registered on 14 September 2017

The combined effects of obesity, abdominal obesity and major depression/anxiety on health-related quality of life: The lifelines cohort study

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The Eurolight project: the impact of primary headache disorders in Europe. Description of methods

The Eurolight project is the first at European Union level to assess the impact of headache disorders, and also the first of its scale performed by collaboration between professional and lay organizations and individuals. Here are reported the methods developed for it. The project took the form of surveys, by structured questionnaire, conducted in ten countries of Europe which together represented 60% of the adult population of the European Union. In Lithuania, the survey was population-based. Elsewhere, truly population-based studies were impractical for reasons of cost, and various compromises were developed. Closest to being population-based were the surveys in Germany, Luxembourg, the Netherlands, Italy and Spain. In Austria, France and UK, samples were taken from health-care settings. In addition in the Netherlands, Spain and Ireland, samples were drawn from members of national headache patient organizations and their relatives. Independent double data-entry was performed prior to analysis. Returned questionnaires from 9,269 respondents showed a moderate female bias (58%); of respondents from patients’ organizations (n = 992), 61% were female. Mean age of all respondents was 44 years; samples from patients’ organizations were slightly older (mean 47 years). The different sampling methods worked with differing degrees of effectiveness, as evidenced by the responder-rates, which varied from 10.8 to 90.7%. In the more population-based surveys, responder-rates varied from 11.3 to 58.8%. We conclude that the methodology, although with differences born of necessity in the ten countries, was sound overall, and will provide robust data on the public ill-health that results from headache in Europe

Gene expression changes induced by the tumorigenic pyrrolizidine alkaloid riddelliine in liver of Big Blue rats

<p>Abstract</p> <p>Background</p> <p>Pyrrolizidine alkaloids (PAs) are probably the most common plant constituents that poison livestock, wildlife, and humans worldwide. Riddelliine is isolated from plants grown in the western United States and is a prototype of genotoxic PAs. Riddelliine was used to investigate the genotoxic effects of PAs via analysis of gene expression in the target tissue of rats in this study. Previously we observed that the mutant frequency in the liver of rats gavaged with riddelliine was 3-fold higher than that in the control group. Molecular analysis of the mutants indicated that there was a statistically significant difference between the mutational spectra from riddelliine-treated and control rats.</p> <p>Results</p> <p>Riddelliine-induced gene expression profiles in livers of Big Blue transgenic rats were determined. The female rats were gavaged with riddelliine at a dose of 1 mg/kg body weight 5 days a week for 12 weeks. Rat whole genome microarray was used to perform genome-wide gene expression studies. When a cutoff value of a two-fold change and a <it>P</it>-value less than 0.01 were used as gene selection criteria, 919 genes were identified as differentially expressed in riddelliine-treated rats compared to the control animals. By analysis with the Ingenuity Pathway Analysis Network, we found that these significantly changed genes were mainly involved in cancer, cell death, tissue development, cellular movement, tissue morphology, cell-to-cell signaling and interaction, and cellular growth and proliferation. We further analyzed the genes involved in metabolism, injury of endothelial cells, liver abnormalities, and cancer development in detail.</p> <p>Conclusion</p> <p>The alterations in gene expression were directly related to the pathological outcomes reported previously. These results provided further insight into the mechanisms involved in toxicity and carcinogenesis after exposure to riddelliine, and permitted us to investigate the interaction of gene products inside the signaling networks.</p

Exposure-in-vivo containing interventions to improve work functioning of workers with anxiety disorder: a systematic review

<p>Abstract</p> <p>Background</p> <p>Anxiety disorders are associated with functional disability, sickness absence, and decreased productivity. Effective treatments of anxiety disorders can result in remission of symptoms. However the effects on work related outcomes are largely unknown. Exposure in vivo is potentially well fit to improve work-related outcomes. This study systematically reviews the effectiveness of exposure-in-vivo containing interventions in reducing work-related adverse outcomes in workers with anxiety disorders.</p> <p>Methods</p> <p>A systematic study search was conducted in Medline, Cinahl, Embase and Psycinfo. Two reviewers independently extracted data and from each study assessed the quality of evidence by using the GRADE approach. We performed a meta-analysis if data showed sufficient clinical homogeneity.</p> <p>Results</p> <p>Seven studies containing 11 exposure-in-vivo interventions were included. Four studies were focused on Obsessive Compulsive Disorder (OCD), two on Post Traumatic Stress Disorder (PTSD), and one on a mixed group of OCD and severe phobias. The studies were grouped according to type of anxiety disorder and subsequently according to type of comparisons. For OCD, exposure-in-vivo containing interventions can yield better work-related outcomes compared to medication (SSRIs) and relaxation but not better compared to response prevention. The results on anxiety outcomes were similar. The net contribution of exposure in vivo in two OCD intervention programs is also presented as a meta-analysis and shows significant positive results on work role limitations. The calculated pooled effect size with 95% confidence interval was 0.72 (0.28, 1.15). For PTSD, exposure-in-vivo containing interventions can yield better work-related and anxiety-related outcomes compared to a waiting-list but not better compared to imaginal exposure.</p> <p>Conclusions</p> <p>Exposure in vivo as part of an anxiety treatment can reduce work-related adverse outcomes in workers with OCD and PTSD better than various other anxiety treatments or a waiting-list. We recommend that it should be studied how the results of these studies can be transferred to the practice of occupational health professionals and how clinicians can make better use of them to improve work-related outcomes. In future research, priority should be given to high-quality randomised controlled trials (RCTs) in which exposure-in-vivo containing interventions are applied to a variety of anxiety disorders and compared with other clinical anxiety treatments such as SSRIs. Work-related outcomes, in particular work functioning and sickness absence, need to be assessed with reliable and valid measures.</p

Peripheral blood and neuropsychological markers for the onset of action of antidepressant drugs in patients with Major Depressive Disorder

<p>Abstract</p> <p>Background</p> <p>In Major Depressive Disorder (MDD), treatment outcomes with currently available strategies are often disappointing. Therefore, it is sensible to develop new strategies to increase remission rates in acutely depressed patients. Many studies reported that true drug response can be observed within 14 days (early improvement) of antidepressant treatment. The identical time course of symptom amelioration after early improvement in patients treated with antidepressants of all classes or with placebo strongly suggests a common biological mechanism, which is not specific for a particular antidepressant medication. However, the biology underlying early improvement and final treatment response is not understood and there is no established biological marker as yet, which can predict treatment response for the individual patient before initiation or during the course of antidepressant treatment. Peripheral blood markers and executive functions are particularly promising candidates as markers for the onset of action and thus the prediction of final treatment outcome in MDD.</p> <p>Methods/Design</p> <p>The present paper presents the rationales, objectives and methods of a multi-centre study applying close-meshed repetitive measurements of peripheral blood and neuropsychological parameters in patients with MDD and healthy controls during a study period of eight weeks for the identification of biomarkers for the onset of antidepressants' action in patients with MDD. Peripheral blood parameters and depression severity are assessed in weekly intervals from baseline to week 8, executive performance in bi-weekly intervals. Patients are participating in a randomized controlled multi-level clinical trial, healthy controls are matched according to mean age, sex and general intelligence.</p> <p>Discussion</p> <p>This investigation will help to identify a biomarker or a set of biomarkers with decision-making quality in the treatment of MDD in order to increase the currently disappointing remission rates of antidepressant treatment.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00974155">NCT00974155</a></p

Suicidality in primary care patients who present with sadness and anhedonia: a prospective European study

Background: Sadness and anhedonia (loss of interest in activities) are central symptoms of major depression. However, not all people with these symptoms meet diagnostic criteria for major depression. We aimed to assess the importance of suicidality in the outcomes for primary care patients who present with sadness and anhedonia. Method: Cohort study of 2,599 unselected primary care attenders in six European countries followed up at 6 and 12 months. Results: 1) In patients with sadness and/or anhedonia who were not depressed at entry to the study, suicide plans (OR = 3.05; 95 % CI = 1.50–6.24; p = 0.0022) and suicide attempts (OR = 9.08; 95 % CI = 2.57–32.03; p = 0.0006) were significant predictors of developing new onset depression at 6 or 12 months. 2) In patients with sadness and/or anhedonia who met CIDI criteria for major depression at entry, suicidal ideation (OR = 2.93; 95 % CI = 1.70–5.07; p = 0.0001), suicide plans (OR = 3.70; 95 % CI = 2.08–6.57; p < 0.0001), and suicide attempts (OR = 3.33; 95 % CI = 1.47–7.54; p = 0.0040) were significant predictors of persistent depression at 6 or 12 months. Conclusions: Three questions on suicidality could help primary care professionals to assess such patients more closely without necessarily establishing whether they meet criteria for major depression.This research was funded by a grant from The European Commission, referencePREDICT-QL4-CT2002-00683. We are also grateful for part support in Europe from: the Estonian Scientific Foundation (grant number 5696); the Slovenian Ministry for Research (grant No.4369-1027); the Spanish Ministry of Health (grant FIS references: PI041980, PI041771, PI042450) and the Spanish Network of Primary Care Research, redIAPP (ISCIII-RETICS RD06/0018) and SAMSERAP group; and the UK NHS Research and Development office for providing service support costs in the UK. We are also grateful for the support from the University of Malaga (Spain) and to Carlos García from Loyola Andalucía University (Spain)

Referred pain from myofascial trigger points in head and neck–shoulder muscles reproduces head pain features in children with chronic tension type headache

Our aim was to describe the referred pain pattern and areas from trigger points (TrPs) in head, neck, and shoulder muscles in children with chronic tension type headache (CTTH). Fifty children (14 boys, 36 girls, mean age: 8 ± 2) with CTTH and 50 age- and sex- matched children participated. Bilateral temporalis, masseter, superior oblique, upper trapezius, sternocleidomastoid, suboccipital, and levator scapula muscles were examined for TrPs by an assessor blinded to the children’s condition. TrPs were identified with palpation and considered active when local and referred pains reproduce headache pain attacks. The referred pain areas were drawn on anatomical maps, digitalized, and also measured. The total number of TrPs was significantly greater in children with CTTH as compared to healthy children (P < 0.001). Active TrPs were only present in children with CTTH (P < 0.001). Within children with CTTH, a significant positive association between the number of active TrPs and headache duration (rs = 0.315; P = 0.026) was observed: the greater the number of active TrPs, the longer the duration of headache attack. Significant differences in referred pain areas between groups (P < 0.001) and muscles (P < 0.001) were found: the referred pain areas were larger in CTTH children (P < 0.001), and the referred pain area elicited by suboccipital TrPs was larger than the referred pain from the remaining TrPs (P < 0.001). Significant positive correlations between some headache clinical parameters and the size of the referred pain area were found. Our results showed that the local and referred pains elicited from active TrPs in head, neck and shoulder shared similar pain pattern as spontaneous CTTH in children, supporting a relevant role of active TrPs in CTTH in children