Non-absorbable disaccharides versus placebo/no intervention and lactulose versus lactitol for the prevention and treatment of hepatic encephalopathy in people with cirrhosis

Background Non-absorbable disaccharides (lactulose and lactitol) are recommended as first-line treatment for hepatic encephalopathy. The previous (second) version of this review included 10 randomised clinical trials (RCTs) evaluating non-absorbable disaccharides versus placebo/no intervention and eight RCTs evaluating lactulose versus lactitol for people with cirrhosis and hepatic encephalopathy. The review found no evidence to either support or refute the use of the non-absorbable disaccharides and no differences between lactulose versus lactitol. Objectives To assess the beneficial and harmful effects of i) non-absorbable disaccharides versus placebo/no intervention and ii) lactulose versus lactitol in people with cirrhosis and hepatic encephalopathy. Search methods We carried out electronic searches of the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 10), MEDLINE, EMBASE, and Science Citation Index Expanded to 19 October 2015; manual searches of meetings and conference proceedings; checks of bibliographies; and correspondence with investigators and pharmaceutical companies. Selection criteria We included RCTs, irrespective of publication status, language, or blinding. Data collection and analysis Two review authors, working independently, retrieved data from published reports and correspondence with investigators. The primary outcomes were mortality, hepatic encephalopathy, and serious adverse events. We presented the results of meta-analyses as risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI). We assessed the quality of the evidence using 'Grading of Recommendations Assessment Development and Evaluation' (GRADE) and bias control using the Cochrane Hepato-Biliary Group domains. Our analyses included regression analyses of publication bias and other small study effects, Trial Sequential Analyses to detect type 1 and type 2 errors, and subgroup and sensitivity analyses. Main results We included 38 RCTs with a total of 1828 participants. Eight RCTs had a low risk of bias in the assessment of mortality. All trials had a high risk of bias in the assessment of the remaining outcomes. Random-effects meta-analysis showed a beneficial effect of non-absorbable disaccharides versus placebo/no intervention on mortality when including all RCTs with extractable data (RR 0.59, 95% CI 0.40 to 0.87; 1487 participants; 24 RCTs; I2 = 0%; moderate quality evidence) and in the eight RCTs with a low risk of bias (RR 0.63, 95% CI 0.41 to 0.97; 705 participants). The Trial Sequential Analysis with the relative risk reduction (RRR) reduced to 30% confirmed the findings when including all RCTs, but not when including only RCTs with a low risk of bias or when we reduced the RRR to 22%. Compared with placebo/no intervention, the non-absorbable disaccharides were associated with beneficial effects on hepatic encephalopathy (RR 0.58, 95% CI 0.50 to 0.69; 1415 participants; 22 RCTs; I2 = 32%; moderate quality evidence). Additional analyses showed that non-absorbable disaccharides can help to reduce serious adverse events associated with the underlying liver disease including liver failure, hepatorenal syndrome, and variceal bleeding (RR 0.47, 95% CI 0.36 to 0.60; 1487 participants; 24 RCTs; I2 = 0%; moderate quality evidence). We confirmed the results in Trial Sequential Analysis. Tests for subgroup differences showed no statistical differences between RCTs evaluating prevention, overt, or minimal hepatic encephalopathy. The evaluation of secondary outcomes showed a potential beneficial effect of the non-absorbable disaccharides on quality of life, but we were not able to include the data in an overall meta-analysis (very low quality evidence). Non-absorbable disaccharides were associated with non-serious (mainly gastrointestinal) adverse events (very low quality evidence). None of the RCTs comparing lactulose versus lactitol evaluated quality of life. The review found no differences between lactulose and lactitol for the remaining outcomes (very low quality evidence). Authors' conclusions This review includes a large number of RCTs evaluating the prevention or treatment of hepatic encephalopathy. The analyses found evidence that non-absorbable disaccharides may be associated with a beneficial effect on clinically relevant outcomes compared with placebo/no intervention. EnglishCroatianGerman Plain language summary Are non-absorbable disaccharides associated with beneficial or harmful effects in people with cirrhosis and hepatic encephalopathy? Background Cirrhosis is a chronic disorder of the liver. People with cirrhosis may develop hepatic encephalopathy, a condition that results in poor brain functioning. Hepatic encephalopathy may be clinically obvious (overt) with changes including poor concentration, tremor, and alterations in consciousness. Others have no obvious clinical changes (minimal) but, when tested, some aspects of brain function such as attention and the ability to perform complex tasks are impaired. The reason why people develop hepatic encephalopathy is complex. The accumulation of ammonia plays a key role. The non-absorbable disaccharides, lactulose and lactitol, are indigestible sugars that reduce the levels of ammonia in the blood. Review question We investigated the use of non-absorbable disaccharides for the prevention and treatment of hepatic encephalopathy in people with cirrhosis by reviewing randomised clinical trials (RCTs). Search date The search date was October 2015. Study funding sources Seven RCTs received financial support and 11 RCTs received lactitol or inactive placebo free of charge from a pharmaceutical company. Study characteristics We included 29 RCTs comparing non-absorbable disaccharides with inactive placebo or no intervention and nine RCTs comparing lactulose with lactitol. Seven of the included RCTs evaluated the prevention of hepatic encephalopathy and 31 evaluated the treatment of hepatic encephalopathy. Sixteen of the treatment RCTs included people with overt hepatic encephalopathy while 15 included people with minimal hepatic encephalopathy. The duration of treatment varied depending on the type of hepatic encephalopathy from five days to one year. Key results People who received non-absorbable disaccharides were less likely to die than people given a placebo or no treatment. They were also less likely to develop serious complications of their liver disease such as liver failure, bleeding, and infections. The non-absorbable disaccharides were also effective in preventing the development of hepatic encephalopathy and increased the number of participants who recovered from hepatic encephalopathy. There was some evidence from a small number of trials that lactulose has a beneficial effect on the quality of life, but we were unable to include the data in an overall analysis. The non-absorbable disaccharides were associated with adverse events including diarrhoea, nausea, bloating, and flatulence. None of the RCTs comparing lactulose versus lactitol reported quality of life. The analyses showed no differences between the two interventions for the remaining outcomes. Quality of the evidence In the comparison of non-absorbable disaccharides versus placebo/no intervention, we found moderate quality evidence of benefit for the outcomes of death, hepatic encephalopathy, and serious complications. The evidence for the remaining outcomes was of very low quality

No Increased Risk for Primary Osteoarthritis in Liver Cirrhosis:A Danish Nationwide Cohort Study

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L-ornithine L-aspartate for people with cirrhosis and hepatic encephalopathy

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the beneficial and harmful effects of L-ornithine L-aspartate versus placebo, no intervention, or other active interventions for people with cirrhosis and hepatic encephalopathy

The role of aerodynamic drag in propagation of interplanetary coronal mass ejections

Context. The propagation of interplanetary coronal mass ejections (ICMEs) and the forecast of their arrival on Earth is one of the central issues of space weather studies. Aims. We investigate to which degree various ICME parameters (mass, size, take-off speed) and the ambient solar-wind parameters (density and velocity) affect the ICME Sun-Earth transit time. Methods. We study solutions of a drag-based equation of motion by systematically varying the input parameters. The analysis is focused on ICME transit times and 1 AU velocities. Results. The model results reveal that wide ICMEs of low masses adjust to the solar-wind speed already close to the sun, so the transit time is determined primarily by the solar-wind speed. The shortest transit times and accordingly the highest 1 AU velocities are related to narrow and massive ICMEs (i.e. high-density eruptions) propagating in high-speed solar wind streams. We apply the model to the Sun-Earth event associated with the CME of 25 July 2004 and compare the results with the outcome of the numerical MHD modeling

How to assess intra- and inter-observer agreement with quantitative PET using variance component analysis:a proposal for standardisation

BACKGROUND: Quantitative measurement procedures need to be accurate and precise to justify their clinical use. Precision reflects deviation of groups of measurement from another, often expressed as proportions of agreement, standard errors of measurement, coefficients of variation, or the Bland-Altman plot. We suggest variance component analysis (VCA) to estimate the influence of errors due to single elements of a PET scan (scanner, time point, observer, etc.) to express the composite uncertainty of repeated measurements and obtain relevant repeatability coefficients (RCs) which have a unique relation to Bland-Altman plots. Here, we present this approach for assessment of intra- and inter-observer variation with PET/CT exemplified with data from two clinical studies. METHODS: In study 1, 30 patients were scanned pre-operatively for the assessment of ovarian cancer, and their scans were assessed twice by the same observer to study intra-observer agreement. In study 2, 14 patients with glioma were scanned up to five times. Resulting 49 scans were assessed by three observers to examine inter-observer agreement. Outcome variables were SUVmax in study 1 and cerebral total hemispheric glycolysis (THG) in study 2. RESULTS: In study 1, we found a RC of 2.46 equalling half the width of the Bland-Altman limits of agreement. In study 2, the RC for identical conditions (same scanner, patient, time point, and observer) was 2392; allowing for different scanners increased the RC to 2543. Inter-observer differences were negligible compared to differences owing to other factors; between observer 1 and 2: −10 (95 % CI: −352 to 332) and between observer 1 vs 3: 28 (95 % CI: −313 to 370). CONCLUSIONS: VCA is an appealing approach for weighing different sources of variation against each other, summarised as RCs. The involved linear mixed effects models require carefully considered sample sizes to account for the challenge of sufficiently accurately estimating variance components. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12880-016-0159-3) contains supplementary material, which is available to authorized users

Which Tumor Suppressor Gene Plays an Important Role in Oncogenesis of Oral Cancer?

口腔領域癌の遺伝子学的解析はあまり行われていないため, 本稿では当科における癌抑制遺伝子異常の検索結果を用いて, 口腔癌においてどの遺伝子が重要な役割を果たしているのかを検討した。試料は, 口腔扁平上皮癌組織と, 同一症例の正常組織を用いた。RB遺伝子とWT遺伝子についてはサザンブロッティング法により, また, APC, P53, VHL, p15, p16, p18遺伝子についてはPCR-SSCP法および塩基配列決定法を用いて検索した。さらに, APC遺伝子についてはエクソン11のポリモルフィズムを利用したPCR-LOH分析をあわせて行った。以下に示す結果を得た。(1)APC遺伝子の点突然変異は8.3%, APC-LOHは informative 症例中の72.7%に認められた。(2)p16遺伝子とp18遺伝子の点突然変異はそれぞれ4.0%, 3.8%に認められた。p15遺伝子異常は認められなかった。(3)p53心遺伝子異常は7.7%に認められた。(4)WT遺伝子の部分欠失を6.5%に認めた。(5)RB遺伝子とVHL遺伝子の異常は認められなかった。以上の結果から, 種々の癌抑制遺伝子のうち, 特にAPC遺伝子が口腔扁平上皮癌発生に重要な役割を果たしていることが示唆された。Since there are few molecular biological studies on oral cancer, we evaluated genes which would play an important role in the oncogenesis of oral cancer based on our previous studies. To elucidate whether or not abnormalities of RB and WT genes could contribute to the development of oral squamous-cell carcinoma (SCC), genomic DNAs obtained from tumors and corresponding normal tissues were examined with Southern blotting. On the other hand, PCR-SSCP (polymerase chain reaction single-strand conformation polymorphism) and sequence analyses were performed to detect possible mutations of APC, VHL, p15, p16, p18 and p53. We also examined the tissue samples to detect loss of heterozygosity (LOH) at exon 11 of APC gene by PCR-LOH assay. We obtained the following results: (1) Point mutations of APC gene in tumor tissues were identified in 8.3(nil)atients with oral SCC, and PCR-LOH assay revealed LOH at exon 11 of APC gene in 72.71024720030f informative cases. (2) Point mutations of p16 and p18 genes were detected in 4.0-0x1.db55b085084p-148nd 3.80f oral SCC patients, respectively. However, no mutation of p15 gene was found. (3) Abnormalities of p53 gene were detected in 7.726725462457f all cases. (4) Southern blotting revealed partial deletions and rearrangements of WT gene in 6.50f the cases. (5) No abnormality of VHL and RB genes was detected in any of the cases. These results suggest that APC gene is most significantly associated with the development of human oral SCC among the known tumor suppressor genes

Accurate Recycling of Parental Histones Reproduces the Histone Modification Landscape during DNA Replication

Chromatin organization is disrupted genome-wide during DNA replication. On newly synthesized DNA, nucleosomes are assembled from new naive histones and old modified histones. It remains unknown whether the landscape of histone post-translational modifications (PTMs) is faithfully copied during DNA replication or the epigenome is perturbed. Here we develop chromatin occupancy after replication (ChOR-seq) to determine histone PTM occupancy immediately after DNA replication and across the cell cycle. We show that H3K4me3, H3K36me3, H3K79me3, and H3K27me3 positional information is reproduced with high accuracy on newly synthesized DNA through histone recycling. Quantitative ChOR-seq reveals that de novo methylation to restore H3K4me3 and H3K27me3 levels occurs across the cell cycle with mark- and locus-specific kinetics. Collectively, this demonstrates that accurate parental histone recycling preserves positional information and allows PTM transmission to daughter cells while modification of new histones gives rise to complex epigenome fluctuations across the cell cycle that could underlie cell-to-cell heterogeneity

Participation in cancer rehabilitation and unmet needs: a population-based cohort study

PURPOSE: To investigate associations between cancer survivors’ sex, age, and diagnosis in relation to their (1) need for rehabilitation, (2) participation in rehabilitation activities, and (3) unmet needs for rehabilitation in a 14-month period following date of diagnosis. METHODS: A population-based cohort study was performed on incident cancer patients diagnosed from 1 October 2007 to 30 September 2008. Fourteen months after diagnosis, participants completed a questionnaire developed to measure the aspects of rehabilitation. Logistic regression analyses were used to explore the association between sex, age, and diagnosis, and the outcome variables for rehabilitation. RESULTS: A total of 3,439 patients participated, yielding an overall response rate of 70%. One third of the cancer patients reported a need for physical rehabilitation and one third for psychological rehabilitation. Half of the patients participated in at least one activity. Unmet needs were most often reported in psychological, sexual, and financial areas. Women expressed more needs, participated more often in rehabilitation activities, and had, to a higher extent, their emotional needs fulfilled. Breast cancer patients participated more often in physical rehabilitation. Elderly who expressed rehabilitation needs more often had them unresolved. CONCLUSIONS: A substantial variation in rehabilitation needs, participation in activities, and unmet needs in relation to sex, age, and cancer type was observed. Cancer care ought to systematically address the wide range of needs in all groups through integration of systematic needs assessment and targeted supply of offers

Organizing in the Public Interest: Participatory Organizing and Art’s Organizational Turn

Art’s engagement with social practices has promoted reflections in art theory about strategies of organizing. Whether in the form of temporary self-organized initiatives, interventions into society or as the possibility of art developing alternative, sustainable organizations, questions of organizing come to the fore. In this article, I suggest that art theory will benefit from engaging with organizational theory, and I point to sociologist John Law’s concept of “modes of ordering” as a useful analytical tool with which to study the organizing practices involved in and affecting contemporary art. In particular, the article targets the field of participatory practices and suggests that they might be interpreted as the effect of cross-institutional modes of ordering. The potential of such an analysis is twofold. First, it offers an alternative analytical entrance point into the field of participatory practices, as opposed to the two dominant positions of a durational-dialogical and a conflictual-interventionist perspective. Second, it underlines how organizational processes cut across disciplinary fields and institutional barriers, generating networks of processual relations that support and strengthen certain practices, while challenging and impeding other practices