Cost-utility analysis of operative versus non-operative treatment for colorectal liver metastases

Abstract Background Surgical resection of colorectal liver metastases (CRLMs) is the standard of care when possible, although this strategy has not been compared with non-operative interventions in controlled trials. Although survival outcomes are clear, the cost-effectiveness of surgery is not. This study aimed to estimate the cost-effectiveness of resection for CRLMs compared with non-operative treatment (palliative care including chemotherapy). Methods Operative and non-operative cohorts were identified from a prospectively maintained database. Patients in the operative cohort had a minimum of 10 years of follow-up. A model-based cost–utility analysis was conducted to quantify the mean cost and quality-adjusted life-years (QALYs) over a lifetime time horizon. The analysis was conducted from a healthcare provider perspective (UK National Health Service) in a secondary care (hospital) setting. Results Median survival was 41 and 21 months in the operative and non-operative cohorts respectively (P &amp;lt; 0·001). The operative strategy dominated non-operative treatments, being less costly (€22 200 versus €32 800) and more effective (4·017 versus 1·111 QALYs gained). The results of extensive sensitivity analysis showed that the operative strategy dominated non-operative treatment in every scenario. Conclusion Operative treatment of CRLMs yields greater survival than non-operative treatment, and is both more effective and less costly. </jats:sec

The distribution of pond snail communities across a landscape: separating out the influence of spatial position from local habitat quality for ponds in south-east Northumberland, UK

Ponds support a rich biodiversity because the heterogeneity of individual ponds creates, at the landscape scale, a diversity of habitats for wildlife. The distribution of pond animals and plants will be influenced by both the local conditions within a pond and the spatial distribution of ponds across the landscape. Separating out the local from the spatial is difficult because the two are often linked. Pond snails are likely to be affected by both local conditions, e.g. water hardness, and spatial patterns, e.g. distance between ponds, but studies of snail communities struggle distinguishing between the two. In this study, communities of snails were recorded from 52 ponds in a biogeographically coherent landscape in north-east England. The distribution of snail communities was compared to local environments characterised by the macrophyte communities within each pond and to the spatial pattern of ponds throughout the landscape. Mantel tests were used to partial out the local versus the landscape respective influences. Snail communities became more similar in ponds that were closer together and in ponds with similar macrophyte communities as both the local and the landscape scale were important for this group of animals. Data were collected from several types of ponds, including those created on nature reserves specifically for wildlife, old field ponds (at least 150 years old) primarily created for watering livestock and subsidence ponds outside protected areas or amongst coastal dunes. No one pond type supported all the species. Larger, deeper ponds on nature reserves had the highest numbers of species within individual ponds but shallow, temporary sites on farm land supported a distinct temporary water fauna. The conservation of pond snails in this region requires a diversity of pond types rather than one idealised type and ponds scattered throughout the area at a variety of sites, not just concentrated on nature reserves

Financial control, blame avoidance and Radio Caroline: Talkin’ ‘bout my generation

This research examines the use of financial mechanisms that simultaneously impose controls and facilitate blame avoidance by public office-holders. A qualitative historical examination is used to examine legislation designed to prevent Radio Caroline, a pirate radio station, from broadcasting into Britain in the 1960s. Radio Caroline made a mockery of the British Government’s power to manage radio through a monopolist, the British Broadcasting Corporation. In addition, Radio Caroline played the type of rock music the British Government sought to suppress as representing the undesirable side of youth culture. This research examines the suppression of Radio Caroline through the Marine & Broadcasting (Offences) Act (UK) 1967 and the legislative scapegoating of Radio Caroline by targeting its revenue-earning potential. Inter-generational conflict underpinned the legislative scapegoating of Radio Caroline. This research demonstrates how financial controls can mask scapegoating and blame avoidance strategies by governments

Risk factors for hospital morbidity and mortality after the Norwood procedure: A report from the Pediatric Heart Network Single Ventricle Reconstruction trial

ObjectivesWe sought to identify risk factors for mortality and morbidity during the Norwood hospitalization in newborn infants with hypoplastic left heart syndrome and other single right ventricle anomalies enrolled in the Single Ventricle Reconstruction trial.MethodsPotential predictors for outcome included patient- and procedure-related variables and center volume and surgeon volume. Outcome variables occurring during the Norwood procedure and before hospital discharge or stage II procedure included mortality, end-organ complications, length of ventilation, and hospital length of stay. Univariate and multivariable Cox regression analyses were performed with bootstrapping to estimate reliability for mortality.ResultsAnalysis included 549 subjects prospectively enrolled from 15 centers; 30-day and hospital mortality were 11.5% (63/549) and 16.0% (88/549), respectively. Independent risk factors for both 30-day and hospital mortality included lower birth weight, genetic abnormality, extracorporeal membrane oxygenation (ECMO) and open sternum on the day of the Norwood procedure. In addition, longer duration of deep hypothermic circulatory arrest was a risk factor for 30-day mortality. Shunt type at the end of the Norwood procedure was not a significant risk factor for 30-day or hospital mortality. Independent risk factors for postoperative renal failure (n = 46), sepsis (n = 93), increased length of ventilation, and hospital length of stay among survivors included genetic abnormality, lower center/surgeon volume, open sternum, and post-Norwood operations.ConclusionsInnate patient factors, ECMO, open sternum, and lower center/surgeon volume are important risk factors for postoperative mortality and/or morbidity during the Norwood hospitalization

The Impact of NOD2 Genetic Variants on the Gut Mycobiota in Crohn's Disease Patients in Remission and in Individuals Without Gastrointestinal Inflammation

Background and aims: Historical and emerging data implicate fungi in Crohn's disease [CD] pathogenesis. However, a causal link between mycobiota, dysregulated immunity, and any impact of NOD2 variants remains elusive. This study aims to evaluate associations between NOD2 variants and faecal mycobiota in CD patients and non-CD subjects. Methods: Faecal samples were obtained from 34 CD patients [18 NOD2 mutant, 16 NOD2 wild-type] identified from the UK IBD Genetics Consortium. To avoid confounding influence of mucosal inflammation, CD patients were in clinical remission and had a faecal calprotectin <250 μg/g; 47 non-CD subjects were included as comparator groups, including 22 matched household [four NOD2 mutant] and 25 non-household subjects with known NOD2 genotype [14 NOD2 mutant] identified by the NIHR BioResource Cambridge. Faecal mycobiota composition was determined using internal transcribed spacer 1 [ITS1] sequencing and was compared with 16S rRNA gene sequences and volatile organic compounds. Results: CD was associated with higher numbers of fungal observed taxonomic units [OTUs] [p = 0.033]. Principal coordinates analysis using Jaccard index [p = 0.018] and weighted Bray-Curtis dissimilarities [p = 0.01] showed Candida spp. clustered closer to CD patients whereas Cryptococcus spp. clustered closer to non-CD. In CD, we found higher relative abundance of Ascomycota [p = 0.001] and lower relative abundance Basidiomycota [p = 0.019] phyla. An inverse relationship was found between bacterial and fungal Shannon diversity in NOD2 wild-type which was independent of CD [r = -0.349; p = 0.029]. Conclusions: This study confirms compositional changes in the gut mycobiota in CD and provides evidence that fungi may play a role in CD pathogenesis. No NOD2 genotype-specific differences were observed in the faecal mycobiota.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.This work was supported by CORE, the Digestive Diseases Foundation [now Guts UK], and the Wellcome Trust [grant number 097943 to NAK and 093885 to CAL] for stool collection, bacterial sequencing, and VOC profiling. Further financial support for fungal sequencing was provided from Northumbria University and NU-OMICS.published version, accepted version (12 month embargo), submitted versio

OPCML Is a Broad Tumor Suppressor for Multiple Carcinomas and Lymphomas with Frequently Epigenetic Inactivation

Background: Identification of tumor suppressor genes (TSGs) silenced by CpG methylation uncovers the molecular mechanism of tumorigenesis and potential tumor biomarkers. Loss of heterozygosity at 11q25 is common multiple tumors including nasopharyngeal carcinoma (NPC). OPCML, located at 11q25, is one of the downregulated genes we identified through digital expression subtraction. Methodology/Principal Findings: Semi-quantitative RT-PCR showed frequent OPCML silencing in NPC and other common tumors, with no homozygous deletion detected by multiplex differential DNA-PCR. Instead, promoter methylation of OPCML was frequently detected in multiple carcinoma cell lines (nasopharyngeal, esophageal, lung, gastric, colon, liver, breast, cervix, prostate), lymphoma cell lines (non-Hodgkin and Hodgkin lymphoma, nasal NK/T-cell lymphoma) and primary tumors, but not in any non-tumor cell line and seldom weakly methylated in normal epithelial tissues. Pharmacological and genetic demethylation restored OPCML expression, indicating a direct epigenetic silencing. We further found that OPCML is stress-responsive, but this response is epigenetically impaired when its promoter becomes methylated. Ecotopic expression of OPCML led to significant inhibition of both anchorage-dependent and -indendent growth of carcinoma cells with endogenous silencing. Conlusions/Significance: Thus, through functional epigenetics, we identified OPCML as a broad tumor suppressor, which is frequently inactivated by methylation in multiple malignancies. © 2008 Cui et al.published_or_final_versio

Economic Impacts of Non-Native Forest Insects in the Continental United States

Reliable estimates of the impacts and costs of biological invasions are critical to developing credible management, trade and regulatory policies. Worldwide, forests and urban trees provide important ecosystem services as well as economic and social benefits, but are threatened by non-native insects. More than 450 non-native forest insects are established in the United States but estimates of broad-scale economic impacts associated with these species are largely unavailable. We developed a novel modeling approach that maximizes the use of available data, accounts for multiple sources of uncertainty, and provides cost estimates for three major feeding guilds of non-native forest insects. For each guild, we calculated the economic damages for five cost categories and we estimated the probability of future introductions of damaging pests. We found that costs are largely borne by homeowners and municipal governments. Wood- and phloem-boring insects are anticipated to cause the largest economic impacts by annually inducing nearly $1.7 billion in local government expenditures and approximately$830 million in lost residential property values. Given observations of new species, there is a 32% chance that another highly destructive borer species will invade the U.S. in the next 10 years. Our damage estimates provide a crucial but previously missing component of cost-benefit analyses to evaluate policies and management options intended to reduce species introductions. The modeling approach we developed is highly flexible and could be similarly employed to estimate damages in other countries or natural resource sectors