Cirrhosis is under-recognised in patients subsequently diagnosed with hepatocellular cancer.

BACKGROUND: Most clinical practice guidelines recommend screening for HCC in patients with cirrhosis. However, patients with compensated cirrhosis are often asymptomatic and may remain unrecognised for years. AIMS: To determine the extent to which cirrhosis is unrecognised in a US Veteran population with HCC, and to evaluate the association between lack of cirrhosis recognition and stage of HCC at diagnosis. METHODS: We reviewed the electronic medical records of a random sample of HCC cases diagnosed in the national Veterans Affairs system between 2005 and 2011. We conducted multivariable analyses adjusting for patients' demographics, comorbidity, aetiology of underlying disease and healthcare utilisation including HCC surveillance. RESULTS: Of 1201 patients with HCC and cirrhosis, 24.6% had unrecognised cirrhosis prior to HCC diagnosis. Older patients [>65 years, odds ratio (OR) 2.32], African Americans (OR 1.93), patients with alcoholic or NAFLD liver disease (OR 1.69 and 4.77 respectively), HIV (OR 3.02), and fewer comorbidities (Deyo 0 vs. 3, OR 2.42) had significantly higher odds of having unrecognised cirrhosis than comparison groups. Furthermore, patients with unrecognised cirrhosis were 6.5 times more likely to have advanced stage HCC at diagnosis. The effect of cirrhosis recognition on HCC stage remained significant after adjusting for pre-specified covariates (OR 3.37). CONCLUSIONS: In one quarter of patients, cirrhosis was unrecognised prior to HCC diagnosis, and this group was significantly more likely to have advanced stage HCC. These findings emphasise the importance of timely evaluation for cirrhosis in at-risk populations as a critical step to improving outcomes for patients with HCC.

Circular closure is associated with the lowest rate of surgical site infection following stoma reversal: a systematic review and multiple treatment meta-analysis.

AIM: Stoma reversal is frequently complicated by surgical site infection (SSI). To reduce SSI, several techniques for skin closure have been studied, with no agreement on which is best. The aim of this study was to identify the skin closure technique associated with the lowest rate of SSI following stoma reversal. METHOD: We systematically searched MEDLINE (PubMed and OvidSP), Scopus and clinical registries from 1 January 1980 to 24 March 2012, and included original reports on adult patients following stoma reversal. A network of treatments was created to map the comparisons between skin closure techniques, including primary closure, primary closure with a drain, secondary closure, delayed primary closure, loose primary closure and circular closure. Pairwise meta-analyses were performed for all available direct comparisons of closure types and heterogeneity was assessed. A multiple-treatments meta-analysis was conducted to estimate relative treatment effects between competing closure types (reported as an odds ratio with 95% credible interval, and a probability that each treatment is best). Several sensitivity analyses were performed. RESULTS: Fifteen studies were identified with a total of 2921 cases of stoma reversal. Overall, study quality was poor with observed low (one study), moderate (seven studies) and high (seven studies) risk of bias. Circular closure was associated with the lowest SSI risk (OR 0.12; 95% CI 0.02-0.40) and was the best of six skin closure techniques (probability of being best = 68.9%). Circular closure remained the best after sensitivity analyses. CONCLUSION: This study showed that circular closure is the best skin closure technique after stoma reversal in terms of SSI rate, but the quality of supporting evidence is limited, precluding definite conclusions.

Genetic consequences of interglacial isolation in a steppe bird.

In response to climate changes that have occurred during Pleistocene glacial cycles, taxa associated to steppe vegetation might have followed a pattern of historical evolution in which isolation and fragmentation of populations occurred during the short interglacials and expansion events occurred during the long glacial periods, in contrast to the pattern described for temperate species. Here, we use molecular genetic data to evaluate this idea in a steppe bird with Palaearctic distribution, the little bustard (Tetrax tetrax). Overall, extremely low genetic diversity and differentiation was observed among eight little bustard populations distributed in Spain and France. Mismatch distribution analyses showed that most little bustard populations expanded during cooling periods previous to, and just after, the last interglacial period (127,000-111,000 years before present), when steppe habitats were widespread across Europe. Coalescent-based methods suggested that glacial expansions have resulted in substantial admixture in Western Europe due to the existence of different interglacial refugia. Our results are consistent with a model of evolution and genetic consequences of Pleistocene cycles with low between-population genetic differentiation as a result of short-term isolation periods during interglacials and long-term exchange during glacial periods.

Permanent Genetic Resources added to Molecular Ecology Resources database 1 January 2009-30 April 2009.

This article documents the addition of 283 microsatellite marker loci to the Molecular Ecology Resources Database. Loci were developed for the following species: Agalinis acuta; Ambrosia artemisiifolia; Berula erecta; Casuarius casuarius; Cercospora zeae-maydis; Chorthippus parallelus; Conyza canadensis; Cotesia sesamiae; Epinephelus acanthistius; Ficedula hypoleuca; Grindelia hirsutula; Guadua angustifolia; Leucadendron rubrum; Maritrema novaezealandensis; Meretrix meretrix; Nilaparvata lugens; Oxyeleotris marmoratus; Phoxinus neogaeus; Pristomyrmex punctatus; Pseudobagrus brevicorpus; Seiridium cardinale; Stenopsyche marmorata; Tetranychus evansi and Xerus inauris. These loci were cross-tested on the following species: Agalinis decemloba; Agalinis tenella; Agalinis obtusifolia; Agalinis setacea; Agalinis skinneriana; Cercospora zeina; Cercospora kikuchii; Cercospora sorghi; Mycosphaerella graminicola; Setosphaeria turcica; Magnaporthe oryzae; Cotesia flavipes; Cotesia marginiventris; Grindelia Xpaludosa; Grindelia chiloensis; Grindelia fastigiata; Grindelia lanceolata; Grindelia squarrosa; Leucadendron coniferum; Leucadendron salicifolium; Leucadendron tinctum; Leucadendron meridianum; Laodelphax striatellus; Sogatella furcifera; Phoxinus eos; Phoxinus rigidus; Phoxinus brevispinosus; Phoxinus bicolor; Tetranychus urticae; Tetranychus turkestani; Tetranychus ludeni; Tetranychus neocaledonicus; Tetranychus amicus; Amphitetranychus viennensis; Eotetranychus rubiphilus; Eotetranychus tiliarium; Oligonychus perseae; Panonychus citri; Bryobia rubrioculus; Schizonobia bundi; Petrobia harti; Xerus princeps; Spermophilus tridecemlineatus and Sciurus carolinensis.

Permanent Genetic Resources added to Molecular Ecology Resources Database 1 May 2009-31 July 2009.

This article documents the addition of 512 microsatellite marker loci and nine pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Alcippe morrisonia morrisonia, Bashania fangiana, Bashania fargesii, Chaetodon vagabundus, Colletes floralis, Coluber constrictor flaviventris, Coptotermes gestroi, Crotophaga major, Cyprinella lutrensis, Danaus plexippus, Fagus grandifolia, Falco tinnunculus, Fletcherimyia fletcheri, Hydrilla verticillata, Laterallus jamaicensis coturniculus, Leavenworthia alabamica, Marmosops incanus, Miichthys miiuy, Nasua nasua, Noturus exilis, Odontesthes bonariensis, Quadrula fragosa, Pinctada maxima, Pseudaletia separata, Pseudoperonospora cubensis, Podocarpus elatus, Portunus trituberculatus, Rhagoletis cerasi, Rhinella schneideri, Sarracenia alata, Skeletonema marinoi, Sminthurus viridis, Syngnathus abaster, Uroteuthis (Photololigo) chinensis, Verticillium dahliae, Wasmannia auropunctata, and Zygochlamys patagonica. These loci were cross-tested on the following species: Chaetodon baronessa, Falco columbarius, Falco eleonorae, Falco naumanni, Falco peregrinus, Falco subbuteo, Didelphis aurita, Gracilinanus microtarsus, Marmosops paulensis, Monodelphis Americana, Odontesthes hatcheri, Podocarpus grayi, Podocarpus lawrencei, Podocarpus smithii, Portunus pelagicus, Syngnathus acus, Syngnathus typhle,Uroteuthis (Photololigo) edulis, Uroteuthis (Photololigo) duvauceli and Verticillium albo-atrum. This article also documents the addition of nine sequencing primer pairs and sixteen allele specific primers or probes for Oncorhynchus mykiss and Oncorhynchus tshawytscha; these primers and assays were cross-tested in both species.

Polymorphic microsatellite markers for the lizard Psammodromus algirus (Squamata: Lacertidae).

Eight microsatellite loci are described for the lizard Psammodromus algirus, a species widely used as a model in behavioural and ecological studies. All loci were highly polymorphic (six alleles or more per locus) in a sample of 24 individuals from a single site near Navacerrada (central Spain). Observed heterozygosity ranged from 0.29 to 0.96. These markers will be used to study mating strategies and determinants of reproductive success in this species.

The validity of viral hepatitis and chronic liver disease diagnoses in Veterans Affairs administrative databases.

BACKGROUND: The validity of International Classification of Diseases-9 codes for liver disease has not been determined. AIM: To examine the accuracy of International Classification of Diseases-9 codes for cirrhosis with hepatitis C virus or alcoholic liver disease and HIV or hepatitis B virus coinfection with hepatitis C virus in Veterans Affairs data. METHODS: We conducted a retrospective study comparing the Veterans Affairs administrative data with abstracted data from the Michael E. DeBakey VA Medical Center's medical records. We calculated the positive predictive value, negative predictive value, per cent agreement and kappa. RESULTS: For cirrhosis codes, the positive predictive value (probability that cirrhosis is present among those with a code) and negative predictive value (probability that cirrhosis is absent among those without a code) were 90% and 87% with 88% agreement and kappa = 0.70. For hepatitis C virus codes, the positive predictive value and negative predictive value were 93% and 92%, yielding 92% agreement and kappa = 0.78. For alcoholic liver disease codes, the positive predictive value and negative predictive value were 71% and 98%, with 89% agreement and kappa = 0.74. All parameters for HIV coinfection with hepatitis C virus were >89%; however, the codes for hepatitis B virus coinfection had a positive predictive value of 43-67%. CONCLUSION: These diagnostic codes (except hepatitis B virus) in Veterans Affairs administrative data are highly predictive of the presence of these conditions in medical records and can be reliably used for research.

Applying new inter-individual approaches to assess fine-scale population genetic diversity in a neotropical frog, Eleutherodactylus ockendeni.

We assess patterns of genetic diversity of a neotropical leaflitter frog, Eleutherodactylus ockendeni, in the upper Amazon of Ecuador without a priori delineation of biological populations and with sufficiently intensive sampling to assess inter-individual patterns. We mapped the location of each collected frog across a 5.4 x 1 km landscape at the Jatun Sacha Biological Station, genotyped 185 individuals using five species-specific DNA microsatellite loci, and sequenced a fragment of mitochondrial cytochrome b for a subset of 51 individuals. The microsatellites were characterized by high allelic diversity and homozygote excess across all loci, suggesting that when pooled the sample is not a panmictic population. We conclude that the lack of panmixia is not attributable to the influence of null alleles or biased sampling of consanguineous family groups. Multiple methods of population cluster analysis, using both Bayesian and maximum likelihood approaches, failed to identify discrete genetic clusters across the sampled area. Using multivariate spatial autocorrelation, kinship coefficients and relatedness coefficients, we identify a continuous isolation by distance population structure, with a first patch size of ca. 260 m and apparently large population sizes. Analysis of mtDNA corroborates the observation of high genetic diversity at fine scales: there are multiple haplotypes, they are non-randomly distributed and a binary haplotype correlogram shows significant spatial genetic autocorrelation. We demonstrate the utility of inter-individual genetic methods and caution against making a priori assumptions about population genetic structure based simply on arbitrary or convenient patterns of sampling.

GI Epidemiology: databases for epidemiological studies.

BACKGROUND: Large databases are being increasingly used for examining the epidemiology and outcomes of digestive and liver disorders. The complexity and rigor of the methods used to conduct these studies are often underestimated. AIMS: For the most commonly used databases, we provide a brief description of the contents, highlight strengths and weakness, and provide links for more detailed information. We also present a systematic approach to utilizing large databases for addressing research questions, highlighting commonly encountered study design issues, as well as strategies for resolving these issues. CONCLUSIONS: 1. Research using large databases requires the same essential skills needed to conduct research studies using other data sources. These include a rigorous study design, expertise in analytic methods, and relevant research questions. 2. The completeness and accuracy of information contained in the database must be assessed. Methods for improving the quality and completeness of this information should be considered. 3. Despite similarities among large databases, gaining insight and experience into the structure and content of each database is essential. Key points *Large databases can be a powerful source of information to examine the clinical epidemiology and outcomes of digestive and liver disorders. * Research using large databases requires the same essential skills needed to conduct research studies using other data sources. These include a rigorous study design, expertise in analytic methods, and relevant research questions. * The completeness and accuracy of information contained in the database must be assessed. Methods for improving the quality and completeness of this information should be considered. * Despite similarities among large databases, gaining insight and experience into the structure and content of each database is essential. * Examples of commonly used large databases are presented with a synopsis of information contained in the database, as well as strengths and limitations of using the database for research.

The epidemiology of pancreatic cancer in the United States: changes below the surface.

BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer death in the United States. AIM: To examine temporal changes in the incidence and survival of patients with pancreatic adenocarcinoma. METHODS: Using data from nine registries of the Surveillance, Epidemiology and End Results programme, age-adjusted incidence rates per 100 000 and survival rates were calculated for pancreatic cancer between 1977 and 2001. RESULTS: We identified 58 655 cases of pancreatic cancer. The age-adjusted incidence rate remained stable during the study period (11.3 in 1977-1981 and 10.9 in 1997-2001). Overall, men were 30% more affected than women (age-adjusted incidence rate of 13.0 in men and 9.8 in women). The age-adjusted incidence rates were almost 50% higher among Blacks (16.4) than Whites (10.8) and people of other races (9.8). Over time the proportions of patients with localized disease decreased from 12.3% to 7.4% and those with regional disease increased from 18.6% to 25.8%, while metastatic disease remained stable (52.5% vs. 49.8%). The 1-year relative survival increased from 15.2% in 1977-1981 to 21.6% in 1997-2001. CONCLUSIONS: The incidence of pancreatic cancer is stable. A shift from localized to regional disease was observed over time. The overall survival remains poor despite important improvements among patients with early stage disease.

Diabetes increases the risk of hepatocellular carcinoma in the United States: a population based case control study.

BACKGROUND: Diabetes has been associated with an increased risk of hepatocellular carcinoma (HCC) in studies of referred patients. This is the first population based case control study in the USA to examine this association while adjusting for other major risk factors related to HCC. METHODS: We used the Surveillance Epidemiology and End-Results Program (SEER)-Medicare linked database to identify patients aged 65 years and older diagnosed with HCC and randomly selected non-cancer controls between 1994 and 1999. Only cases and controls with continuous Medicare enrollment for three years prior to the index date were examined. Inpatient and outpatient claims files were searched for diagnostic codes indicative of diabetes, hepatitis C virus (HCV), hepatitis B virus (HBV), alcoholic liver disease, and haemochromatosis. HCC patients without these conditions were categorised as idiopathic. Unadjusted and adjusted odds ratios were calculated in logistic regression analyses. RESULTS: We identified 2061 HCC patients and 6183 non-cancer controls. Compared with non-cancer controls, patients with HCC were male (66% v 36%) and non-White (34% v 18%). The proportion of HCC patients with diabetes (43%) was significantly greater than non-cancer controls (19%). In multiple logistic regression analyses that adjusted for demographics features and other HCC risk factors (HCV, HBV, alcoholic liver disease, and haemochromatosis), diabetes was associated with a threefold increase in the risk of HCC. In a subset of patients without these major risk factors, the adjusted odds ratio for diabetes declined but remained significant (adjusted odds ratio 2.87 (95% confidence interval 2.49-3.30)). A significant positive interaction between HCV and diabetes was detected (p<0.0001). Similar findings persisted in analyses restricted to diabetes recorded between two and three years prior to HCC diagnosis. CONCLUSIONS: Diabetes is associated with a 2-3-fold increase in the risk of HCC, regardless of the presence of other major HCC risk factors. Findings from this population based study suggest that diabetes is an independent risk factor for HCC.

Increased use of low anterior resection for veterans with rectal cancer.

BACKGROUND: Two surgical procedures with curative intent are available to patients with rectal cancer: lower anterior resection and abdominoperineal resection; however, lower anterior resection may improve quality of life and functional status. AIM: To examine temporal changes in after lower anterior resection and abdominoperineal resection between 1989 and 2000. Potential factors associated with the use of lower anterior resection were evaluated. METHODS: Using national administrative data, we identified patients who received lower anterior resection or abdominoperineal resection. Logistic regression models examined the association between use of lower anterior resection and time period of surgical resection. RESULTS: A total of 5201 rectal cancer patients underwent resection. The use of lower anterior resection increased from 40.0% (1989-91) to 50.1% (1998-2000) paralleled by a corresponding decline in abdominoperineal resection (60.1 to 49.9%; P < 0.001). Patients who received surgery during 1992-94, 1995-97 and 1998-2000 were 6, 7 and 28% more likely to receive lower anterior resection, when compared with 1989-1991 after adjusting for demographic characteristics, co-morbidity and hospital surgical volume. Older age, lower co-morbidity score and lower hospital surgical volume were predictive of lower anterior resection. CONCLUSIONS: An increase in the use of lower anterior resection for rectal cancer was observed over time. This observed increase in use is not confined to high-volume hospitals.

Outcomes in elderly patients following surgery for colorectal cancer in the veterans affairs health care system.

AIM: To compare 30-day and 5-year mortality in elderly vs. younger patients following surgical resection for colorectal cancer. METHODS: A cohort study of patients admitted to VA hospitals with a new diagnosis of colorectal cancer who underwent surgical resection between October 1990 and September 2000. Cumulative survival rates (30-day and 5-year) were calculated from Kaplan-Meier estimates and adjusted risks of death were estimated using Cox proportional hazards models. RESULTS: We identified 34,888 individuals with a new diagnosis of colorectal cancer between October 1990 and September 2000, of whom 22 633 (65%) underwent surgical resection. The 30-day mortality following resection for rectal and colon cancer, respectively, for patients <65 years was 2.1 and 2.8% compared with 4.9 and 5.6% for those > or =65 years. The 5-year cumulative survival for rectal and colon cancer for patients <65 years was 54.0 and 57.6% compared with 44.5 and 46.6% for those > or =65 years. In patients > or =65 years with rectal or colon cancer, after adjustment, 30-day mortality was 2 times greater and 5-year mortality was 1 times greater than in younger patients. CONCLUSIONS: Older age is an independent predictor of increased short-term and long-term mortality following surgery in patients with rectal and colon cancer.

Gender and viability selection on morphology in fledgling pied flycatchers.

Until recently, analyses of gender-dependent differences in viability selection and the ontogeny of sexual size dimorphism have been plagued by difficulties in determining the sex of nestling birds on the basis of morphology. Recently, this problem was overcome using molecular sex identification to report for the first time body-size-mediated antagonistic selection on the viability of male and female collared flycatchers. We used molecular sex identification to analyse natural selection on fledgling viability, sexual size dimorphism and effects of parasites in relation to gender in a Mediterranean population of the related pied flycatcher Ficedula hypoleuca. There was directional positive selection on fledgling weight but no selection on tarsus length. Fledgling weight was the most important determinant of fledgling survival, with heavier fledglings having increased viability. Although selective trends were of the same sign for both sexes, only among female fledglings were selection differentials and gradients statistically significant. Therefore, similar trends in selection were revealed in analyses of a data set where sex was ignored and in separate analyses using same-sex sibship trait means. Mite nest ectoparasites negatively affected fledgling weight, and the effects were stronger in female than male fledglings. There was no effect of parasitism on the tarsus length in males, as previously reported in retrospective analyses performed without knowledge of sex until recruitment. Overall, selection on fledgling viability on the basis of morphological traits and hatching date was not confounded by an individual's gender.

Comparison of RAMP and SSR markers for the study of wild barley genetic diversity.

Two molecular marker technologies, random amplified microsatellite polymorphism (RAMP) and simple sequence repeats (SSR), were used to determine genetic diversity of 27 accessions of the wild barley Hordeum vulgare ssp. spontaneum. 19 primer combinations were used to generate RAMP fragments and 16 SSR loci were analysed. A high level of polymorphism was found with both kind of markers as revealed by the mean polymorphism information content (PIC) values obtained: 0.838 and 0.855 for RAMP and SSR, respectively. Genetic dissimilarities between genotypes were estimated from RAMP and SSR data. A lack of correlation was found between both sets of data. This was reflected in the two dendrograms obtained which presented accessions clustered differently. The results suggest that both sets of markers reveal genetic variation induced by different mechanisms. The dendrogram produced from the RAMP dissimilarity estimates showed most of the groups related to the geographic origin of the accessions.

Simple sequence repeat primers used in polymerase chain reaction amplifications to study genetic diversity in barley.

In combination with oligonucleotides of arbitrary sequence, 5' anchored oligonucleotides based on simple sequence repeats were used in polymerase chain reaction amplifications to produce barley DNA fingerprints. The aim of this work was (i) to develop a simple nonradioactive experimental procedure to reveal polymorphism in regions containing SSRs, (ii) to determine the genetic nature of polymorphisms, and (iii) to investigate the efficacy of polymorphisms contained in such fingerprints in disclosing genetic relationships between 14 European barley cultivars with known pedigrees. Different 10-mer oligonucleotides containing a dinucleotide motif were used as single primers and also in pairs with 10-mer oligonucleotides of arbitrary sequence. Further, the arbitrary oligonucleotides were used as single primers to produce RAPDs. Thirteen combinations of primers containing either GT(CA)4 or GC(CA)4 were selected on the basis of number and intensity of scorable bands in silver-stained 7% polyacrylamide gels. Of the fragments scored, 58.4% were polymorphic. Inheritance of these random amplified microsatellite polymorphic fragments (RAMP) was studied in doubled-haploid lines from the F1 of 'Steptoe' x 'Morex'. Fifty percent of the primers generated codominant markers. Genetic similarities between cultivars were estimated from RAMP and RAPD data. Principal coordinate analysis performed on RAMP data revealed a clear separation of winter six-rowed, winter two-rowed, and spring two-rowed barley. The dendograms generated faithfully reflected the genealogies of the barley cultivars. RAPD failed to show clearly the germplasm sources of the experimental cultivars.