Properties of galaxies reproduced by a hydrodynamic simulation.

Previous simulations of the growth of cosmic structures have broadly reproduced the 'cosmic web' of galaxies that we see in the Universe, but failed to create a mixed population of elliptical and spiral galaxies, because of numerical inaccuracies and incomplete physical models. Moreover, they were unable to track the small-scale evolution of gas and stars to the present epoch within a representative portion of the Universe. Here we report a simulation that starts 12 million years after the Big Bang, and traces 13 billion years of cosmic evolution with 12 billion resolution elements in a cube of 106.5 megaparsecs a side. It yields a reasonable population of ellipticals and spirals, reproduces the observed distribution of galaxies in clusters and characteristics of hydrogen on large scales, and at the same time matches the 'metal' and hydrogen content of galaxies on small scales.

Supplemental peri-operative intravenous crystalloids for postoperative nausea and vomiting: an abridged Cochrane systematic review.

We conducted a Cochrane systematic review on the effectiveness of supplemental intravenous crystalloid administration in preventing postoperative nausea and vomiting. We included randomised controlled trials of patients undergoing surgery under general anaesthesia and given supplemental peri-operative intravenous crystalloid. Our primary outcomes were the risk of postoperative nausea and the risk of postoperative vomiting. We assessed the risk of bias for each included study and applied the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework for the certainty of evidence. We included 41 studies. We found that the intervention probably reduces the overall risk of postoperative nausea, the risk ratio (95%CI) being 0.62 (0.51-0.75) (I2  = 57%, p < 0.00001, 18 studies; 1766 participants; moderate-certainty evidence). It also probably reduces the risk of postoperative nausea within 6 h of surgery, with a risk ratio (95%CI) of 0.67 (0.58 to 0.78) (I2  = 9%, p < 0.00001, 20 studies; 2310 participants; moderate-certainty evidence) and by around 24 h, the risk ratio (95%CI) being 0.47 (0.32-0.69) (I2  = 38%, p = 0.0001, 17 studies; 1682 participants; moderate-certainty evidence). Supplemental intravenous crystalloid probably also reduces the overall risk of postoperative vomiting, with a risk ratio (95%CI) of 0.50 (0.40-0.63) (I2  = 31%, p < 0.00001, 20 studies; 1970 participants; moderate-certainty evidence). The beneficial effect on vomiting was seen both within 6 h and by around 24 h postoperatively.

Chlorophyll-a, dissolved organic carbon, turbidity and other variables of ecological importance in river basins in southern Ontario and British Columbia, Canada.

Optical sensing of chlorophyll-a (chl-a), turbidity, and fluorescent dissolved organic matter (fDOM) is often used to characterize the quality of water. There are many site-specific factors and environmental conditions that can affect optically sensed readings; notwithstanding the comparative implication of different procedures used to measure these properties in the laboratory. In this study, we measured these water quality properties using standard laboratory methods, and in the field using optical sensors (sonde-based) at water quality monitoring sites located in four watersheds in Canada. The overall objective of this work was to explore the relationships among sonde-based and standard laboratory measurements of the aforementioned water properties, and evaluate associations among these eco-hydrological properties and land use, environmental, and ancillary water quality variables such as dissolved organic carbon (DOC) and total suspended solids (TSS). Differences among sonde versus laboratory relationships for chl-a suggest such relationships are impacted by laboratory methods and/or site specific conditions. Data mining analysis indicated that interactive site-specific factors predominately impacting chl-a values across sites were specific conductivity and turbidity (variables with positive global associations with chl-a). The overall linear regression predicting DOC from fDOM was relatively strong (R2 = 0.77). However, slope differences in the watershed-specific models suggest laboratory DOC versus fDOM relationships could be impacted by unknown localized water quality properties affecting fDOM readings, and/or the different standard laboratory methods used to estimate DOC. Artificial neural network analyses (ANN) indicated that higher relative chl-a concentrations were associated with low to no tree cover around sample sites and higher daily rainfall in the watersheds examined. Response surfaces derived from ANN indicated that chl-a concentrations were higher where combined agricultural and urban land uses were relatively higher.

A randomized phase 2 study of MK-2206 versus everolimus in refractory renal cell carcinoma.

Background: Activation of the phosphoinisitide-3 kinase (PI3K) pathway through mutation and constitutive upregulation has been described in renal cell carcinoma (RCC), making it an attractive target for therapeutic intervention. We performed a randomized phase II study in vascular endothelial growth factor (VEGF) therapy refractory patients to determine whether MK-2206, an allosteric inhibitor of AKT, was more efficacious than the mammalian target of rapamycin inhibitor everolimus. Patients and methods: A total of 43 patients were randomized in a 2:1 distribution, with 29 patients assigned to the MK-2206 arm and 14 to the everolimus arm. Progression-free survival (PFS) was the primary endpoint. Results: The trial was closed at the first futility analysis with an observed PFS of 3.68 months in the MK-2206 arm and 5.98 months in the everolimus arm. Dichotomous response rate profiles were seen in the MK-2206 arm with one complete response and three partial responses in the MK-2206 arm versus none in the everolimus arm. On the other hand, progressive disease was best response in 44.8% of MK2206 versus 14.3% of everolimus-treated patients. MK-2206 induced significantly more rash and pruritis than everolimus, and dose reduction occurred in 37.9% of MK-2206 versus 21.4% of everolimus-treated patients. Genomic analysis revealed that 57.1% of the patients in the PD group had either deleterious TP53 mutations or ATM mutations or deletions. In contrast, none of the patients in the non-PD group had TP53 or ATM defects. No predictive marker for response was observed in this small dataset. Conclusions: Dichotomous outcomes are observed when VEGF therapy refractory patients are treated with MK-2206, and MK-2206 does not demonstrate superiority to everolimus. Additionally, mutations in DNA repair genes are associated with early disease progression, indicating that dysregulation of DNA repair is associated with a more aggressive tumor phenotype in RCC.

The reliability of the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) among dermatologists, rheumatologists and neurologists.

BACKGROUND: Previous studies have shown that skin disease in dermatomyositis (DM) is best assessed using the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI). Although the CDASI has been validated for use by dermatologists, it has not been validated for use by other physicians such as rheumatologists and neurologists, who also manage patients with DM and assess skin activity in clinical trials. OBJECTIVES: To assess the reliability of the CDASI among dermatologists, rheumatologists and neurologists. METHODS: Fifteen patients with cutaneous DM were assessed using the CDASI and the Physician Global Assessment (PGA) by five dermatologists, five rheumatologists and five neurologists. RESULTS: The mean CDASI activity scores for dermatologists, rheumatologists and neurologists were 21·0, 21·8 and 20·8, respectively. These mean scores were not different among the specialists. The CDASI damage score means for dermatologists, rheumatologists and neurologists were 5·3, 7·0 and 4·8, respectively. The mean scores between dermatologists and rheumatologists were significantly different, but the means between dermatologists and neurologists were not. The intraclass correlation coefficients (ICCs) for interrater reliability for CDASI activity and damage were good to excellent for dermatologists and rheumatologists, and moderate to excellent for neurologists. The ICCs for intrarater reliability for CDASI activity and damage were excellent for dermatologists and rheumatologists and moderate to excellent for neurologists. The PGA displayed lower interrater and intrarater reliability relative to the CDASI. CONCLUSIONS: Our results confirm the reliability of the CDASI when used by dermatologists and rheumatologists. The data for its use by neurologists were not as robust.

Phylogeny and expression analysis of C-reactive protein (CRP) and serum amyloid-P (SAP) like genes reveal two distinct groups in fish.

The acute phase response (APR) is an early innate immune function that is initiated by inflammatory signals, leading to the release of acute phase proteins to the bloodstream to re-establish homeostasis following microbial infection. In this study we analysed the Atlantic salmon (Salmo salar) whole-genome database and identified five C-reactive protein (CRP)/serum amyloid P component (SAP) like molecules namely CRP/SAP-1a, CRP/SAP-1b, CRP/SAP-1c, CRP/SAP-2 and CRP/SAP-3. These CRP/SAP genes formed two distinct sub-families, a universal group (group I) present in all vertebrates and a fish/amphibian specific group (group II). Salmon CRP/SAP-1a, CRP/SAP-1b and CRP/SAP-1c and CRP/SAP-2 belong to the group I family whilst salmon CRP/SAP-3 is a member of group II. Gene expression analysis showed that the salmon CRP/SAP-1a as well as serum amyloid A-5 (SAA-5), one of the major acute phase proteins, were significantly up-regulated by recombinant cytokines (rIL-1ß and rIFNγ) in primary head kidney cells whilst the other four CRP/SAPs remained refractory. Furthermore, SAA-5 was produced as the main acute phase protein (APP) in Atlantic salmon challenged with Aeromonas salmonicida (aroA(-) strain) whilst salmon CRP/SAPs remained unaltered. Overall, these data illustrate the potential different functions of expanded salmon CRP/SAPs to their mammalian homologues.

First- and second-trimester tests to predict stillbirth in unselected pregnant women: a systematic review and meta-analysis.

BACKGROUND: Several biophysical and biochemical tests have been proposed to predict stillbirth but their predictive ability remains unclear. OBJECTIVE: To assess the accuracy of tests performed during the first and/or second trimester of pregnancy to predict stillbirth in unselected women with singleton, structurally and chromosomally normal fetuses through use of formal methods for systematic reviews and meta-analytic techniques. SEARCH STRATEGY: Electronic databases, bibliographies and conference proceedings. SELECTION CRITERIA: Observational studies that evaluated the predictive accuracy for stillbirth of tests performed during the first two trimesters of pregnancy. DATA COLLECTION AND ANALYSIS: Two reviewers selected studies, assessed risk of bias and extracted data. Summary receiver operating characteristic curves, pooled sensitivities, specificities and likelihood ratios (LRs) were generated. Data were synthesised separately for stillbirth as a sole category and for specific stillbirth categories. MAIN RESULTS: Seventy-one studies, evaluating 16 single and five combined tests, met the inclusion criteria. A uterine artery pulsatility index >90th centile during the second trimester and low levels of pregnancy-associated plasma protein A (PAPP-A) during the first trimester had a moderate to high predictive accuracy for stillbirth related to placental abruption, small-for-gestational-age or pre-eclampsia (positive and negative LRs from 6.3 to 14.1, and from 0.1 to 0.4, respectively). All biophysical and biochemical tests assessed had a low predictive accuracy for stillbirth as a sole category. CONCLUSIONS: Currently, there is no clinically useful first-trimester or second-trimester test to predict stillbirth as a sole category. Uterine artery pulsatility index and maternal serum PAPP-A levels appeared to be good predictors of stillbirth related to placental dysfunction disorders.

Movement patterns and genetic diversity of wild and reintroduced common dormice, Muscardinus avellanarius.

Movement is an important life history trait that can have an impact on local adaptation, and other evolutionary phenomena. We used a combination of nestbox survey data and genetic techniques (genotyping at 10 microsatellite loci) to quantify patterns of movement in common dormice Muscardinus avellanarius at two distinct sites in the UK: 1) Bontuchel (a natural population) and 2) Wych (captive-bred individuals that were reintroduced to this site), over three consecutive years (2006-2008). Both methods revealed a consistent pattern of sex-biased movement (movements by adult males and females) in both populations that allowed isolation-by-distance genetic structure to develop within 1 km. The similarity of data from captive-bred and natural individuals indicated that ex situ programing has not significantly altered the natural movement behavior of common dormice; consequently, the two populations could be managed with the same conservation strategies. We also found that the reintroduced dormice in Wych maintained relatively high levels of genetic diversity. This first report of movement patterns in reintroduced and natural populations of M. avellanarius combining genetic and field-survey data highlights the role of genetic studies in the investigation of ecological behaviour and for conservation management.

Insulin sensitivity not modulated 24 to 78 h after acute resistance exercise in type 2 diabetes patients.

Resistance exercise is recommended as part of the exercise guidelines to prevent and manage type 2 diabetes (T2D), however, the frequency of exercise required to improve glycaemic control and insulin sensitivity is not clear. We recruited and tested 10 individuals with T2D by collecting a fasting blood sample immediately prior to, a whole-body moderate-high intensity resistance exercise session, and 24, 48 and 72 h afterwards. No changes to estimates of insulin sensitivity (HOMA2), glucose or insulin were observed using a repeated measures analysis of variance (p > 0.05). Further, there were no changes observed to markers of inflammation at 24 h following the resistance exercise session (p > 0.05). These findings suggest that insulin sensitivity is not acutely modified, positively or negatively, at 24, 48 or 72 h after a bout of resistance exercise. Nor are markers of inflammation altered during this time frame in a way that could cause transient insulin resistance.

Isolation of RAG-1 and IgM transcripts from the striped trumpeter (Latris lineata), and their expression as markers for development of the adaptive immune response.

A partial sequence of the recombination activating gene-1 (RAG-1) and several full length sequences of the immunoglobulin M (IgM) heavy chain mRNA were obtained from the striped trumpeter (Latris lineata). The RAG-1 fragment consisted of 205 aa and fell within the core region of the open reading frame. The complete IgM heavy chain sequences translated into peptides ranging between 581 and 591 aa. Both genes showed good homology to other vertebrate sequences. The expression of the two genes was assessed throughout the early developmental stages of striped trumpeter larvae (5-100 dph) and used as markers to follow the ontogeny of the adaptive immune response. Using RT-PCR, RAG-1 mRNA expression was detectable at 5 dph and remained so until 80 dph, before becoming undetectable at 100 dph. IgM expression was also detectable at 5 dph, and remained so throughout. These patterns of expression may suggest that the striped trumpeter possess mature B cells with surface IgM at 100 dph. However, complete immunological competence is likely not reached until some time later. The early detection of IgM mRNA at 5 dph led to the investigation of its presence in oocytes. Both RAG-1 and IgM mRNA transcripts were detected in unfertilized oocytes, suggesting that they are maternally transferred. The biological significance of such a phenomenon remains to be investigated.

Insulin sensitivity in response to a single resistance exercise session in apparently healthy individuals.

BACKGROUND: Regular resistance exercise completed for a number of weeks has been shown to increase insulin sensitivity and reduce the risk of diabetes-related complications. However, the acute responses to resistance exercise have not been adequately investigated in relation to training frequency. AIM: To investigate the changes to insulin sensitivity in apparently healthy individuals following a single session of unaccustomed resistance exercise. SUBJECTS AND METHODS: Ten sedentary, apparently healthy individuals performed a baseline oral glucose tolerance test and maximal strength testing. Participants then performed a single session of moderate-high intensity resistance exercise which was followed by 4 consecutive days of oral glucose tolerance testing, for which participants replicated their initial diet. Mean estimated insulin sensitivity change scores from baseline values and their 95% confidence intervals were compared to the previously determined values for a clinically meaningful change. RESULTS: Two participants were identified as having hyperinsulinemia and their data were therefore removed from the main analysis. There was a clinically meaningful increase in insulin response (mean >7237 pmol·l⁻¹·120 min⁻¹) on all days following the exercise session and a clinically meaningful increase in glucose response (mean >81 mmol·l⁻¹·120 min⁻¹) on only the 3rd day following exercise. These changes suggest a potentially adverse short-term effect. Additionally, the 2 individuals with hyperinsulinemia displayed more extreme results. CONCLUSION: These results suggest that insulin sensitivity may be impaired following a single session of unaccustomed resistance exercise for approximately 4 days in healthy untrained, older individuals. Further research is required for individuals with hyperinsulinemia.

Differing Neisseria gonorrhoeae bacterial loads in the pharynx and rectum in men who have sex with men: implications for gonococcal detection, transmission, and control.

The bacterial loads for gonococcal infections of the pharynx and rectum were determined among men with male sexual partners. The median bacterial load for rectal infections (18,960 copies/swab) was significantly higher than the load for pharyngeal infections (2,100 copies/swab; P = 0.001). Bacterial loads among men with symptomatic proctitis were strikingly high (median, 278,000 copies/swab).

The influence of hepatitis C and alcohol on liver-related morbidity and mortality in Glasgow's injecting drug user population.

Infection with the hepatitis C virus (HCV) is associated with the development of severe liver disease, but cofactors--namely alcohol abuse--in Scotland's HCV-positive population complicate estimation of the unique contribution of HCV. We compared the risk of hospital admission/death for a liver-related cause in a large cohort of Glasgow's injecting drug users (IDUs) testing HCV-positive with IDUs testing HCV negative. Data for 6566 current/former IDUs who had been tested for anti-HCV and/or HCV RNA by polymerase chain reaction in Greater Glasgow health board between 1993 and 2007 were linked to the national hospitalization database and deaths registry to identify all admissions and deaths from a liver-related condition. Relative risks were estimated using Cox proportional hazards regression for recurrent events. Time at risk was censored at 2 years following an HCV test to address bias owing to unobserved seroconversion. The risk of hospitalization/death from a liver-related or an alcoholic liver-related condition following HCV testing was greater for those IDUs with no prior alcohol-related hospitalization who tested positive [adjusted hazard ratio (HR) = 3.2, 95% CI: 1.5-6.7; 4.9, 95% CI: 1.8-13.1, respectively], compared with those who tested anti-HCV negative, but not for those IDUs with a prior alcohol admission (HR = 0.8, 95% CI: 0.4-1.5; 0.8, 95% CI: 0.4-1.6). There was little evidence for an increased risk of hospitalization/death for an exclusively nonalcoholic liver condition for those testing positive (HR = 1.5, 95% CI: 0.8-2.7), after adjustment for previous alcohol-related admission. Within Glasgow's IDU population, HCV positivity is associated with an increased risk of a liver-related outcome, but this is not observed for those IDUs whose problem alcohol use already increases their risk.

Uptake of hepatitis C antibody testing in patients with end-stage liver disease in Glasgow, 1993-2007.

Individuals infected with hepatitis C virus (HCV) need to be diagnosed well before developing end-stage liver disease to benefit from treatment. We aimed to ascertain what proportion of cases had been tested for HCV to inform on the effectiveness of current guidelines. Record linkage between national databases of HCV tests, hospital discharges and deaths identified 10,645 persons who were hospitalized or had died with mention of end-stage liver disease in Glasgow, Scotland, between 1993 and 2007. We estimated HCV test uptake and prevalence of HCV infection within the study population. The associations between both HCV test uptake and HCV-antibody status and sex, age group and deprivation quintile were estimated using logistic regression. We found that 43% of those hospitalized (n = 9153) and 23% of those who otherwise died (n = 1492) with first-time mention of end-stage liver disease had been tested for HCV during this period. Test uptake in those hospitalized increased from 13 (95% CI: 12-14%) in 1993-1997 to 58% (56-59%) in 2003-2007. The adjusted odds of being tested for HCV were significantly higher for men (OR=1.3, 95% CI: 1.2-1.5), for ages 25-54 (25-34 years: 2.7, 95% CI: 2.1-3.4; 35-44 years: 2.3, 95% CI: 2.0-2.6; 45-54 years: 1.5, 95% CI: 1.4-1.7) compared with 55+ years, and for those residing in the two most deprived quintiles (1.1, 95% CI: 1.0-1.2). Twenty-eight per cent of the HCV testees aged 25-44 years were HCV infected. These results highlight the continuing need for raising awareness among medical professionals for comprehensive HCV testing in patients with liver disease.

Excess morbidity in the hepatitis C-diagnosed population in Scotland, 1991-2006.

We estimated the excess risk of in-patient hospitalization in a large cohort of persons diagnosed with hepatitis C virus (HCV) infection, controlling for social deprivation. A total of 20 749 individuals diagnosed with HCV in Scotland by 31 December 2006 were linked to the Scottish hospital discharge database, and indirectly standardized hospitalization rates, adjusting for sex, age, year and deprivation were calculated. We observed significant excess morbidity considering episodes for: any diagnosis [standardized morbidity ratio (SMR) 3·4, 95% CI 3·3-3·5]; liver-related diagnoses (SMR 41·3, 95% CI 39·6-43·0); and only non-liver-related diagnoses (SMR 2·14, 95% CI 2·08-2·19). Cox regression analyses of the 2000-2006 data indicated increased relative risks of hospitalization for males [hazard ratio (HR) 1·1, 95% CI 1·0-1·2], older age (per 10 years) (HR 1·55, 95% CI 1·5-1·6), and those testing HIV-positive (HR 1·6, 95% CI 1·3-1·8). This study has revealed substantial excess all-cause and liver-related morbidity in the Scottish HCV-diagnosed population, even after allowing for deprivation.

Increasing drug-related mortality rates over the last decade in Scotland are not just due to an ageing cohort: A retrospective longitudinal cohort study.

BACKGROUND: In Europe, North America, and Australia, mortality due to drug-related (DR) causes amongst people who inject drugs (PWID) is a major issue. Our objective was to characterise temporal trends in DR mortality rates in a large cohort of PWID in Scotland over the past decade, all of whom had been diagnosed with hepatitis C virus (HCV) infection, and to investigate factors associated with DR mortality. METHODS: Retrospective longitudinal cohort study linking Scotland's national HCV Diagnosis Database and deaths registry. The study cohort consisted of all individuals with likely injection drug use-related route of HCV acquisition, who had been diagnosed with HCV between 1991 and 2018, and were alive and aged under 65 years on 1 January 2009. We used Lexis expansion to adjust for ageing cohort effects and calculated the mortality rate from an underlying/contributing DR cause over the period 2009-2018. We fitted Poisson regression models to estimate the temporal trend adjusting for attained age, sex, referral setting, region, and viraemic status at baseline. RESULTS: Amongst the study population (n = 35,065; 236,914 person-years), a total of 1900 DR deaths occurred; the DR mortality rate increased from 5.6/1000 [101 deaths] in 2009 to 12.4/1000 [342] person-years in 2018. Increasing trends were observed for all age-groups except 55-64 years. The overall DR mortality rate was highest for referrals for HCV testing from prison (11.0/1000) and hospital settings (10.0/1000). Mortality increased with calendar time period, with significantly raised adjusted rate ratios (RRs) from 2015 (RR=1.40, 95% CI:1.16-1.69) to 2018 (RR=2.23, 95% CI:1.88-2.64), compared with 2011-2012, for older age (35-44: RR=1.37, 95% CI:1.20-1.56; 45-54: RR=1.32, CI:1.14-1.53) compared with <35 years, for persons diagnosed with HCV since 2009 (RR=1.34, 95% CI:1.21-1.49), and for prison and hospital referrals (RRs of 1.30, 1.37) compared with GP referrals. CONCLUSION: Increasing DR mortality rates in Scotland over the past decade are not just due to an ageing cohort. Harm reduction services will likely need to expand and adapt to reverse the recent upward trends in DR mortality in PWID.

Ezetimibe added to atorvastatin compared with doubling the atorvastatin dose in patients at high risk for coronary heart disease with diabetes mellitus, metabolic syndrome or neither.

AIM: Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) are both associated with increased risk for atherosclerotic coronary heart disease (CHD). Thus, it is useful to know the relative efficacy of lipid-altering drugs in these patient populations. METHODS: A double-blind, parallel group trial of adult patients with hypercholesterolaemia at high-CHD risk receiving atorvastatin 40 mg/day compared atorvastatin 40 mg plus ezetimibe 10 mg (ezetimibe) vs. doubling atorvastatin to 80 mg. This post hoc analysis reports lipid efficacy results in patients grouped by diagnosis of T2DM, MetS without T2DM or neither. Per cent change from baseline at week 6 was assessed for LDL-C, total cholesterol, HDL-C , non-HDL-C , Apo A-I, Apo B and triglycerides. Safety was monitored through clinical and laboratory adverse events (AEs). RESULTS: Compared with doubling atorvastatin, atorvastatin plus ezetimibe resulted in greater reductions in LDL-C, triglycerides, Apo B, non-HDL-C, total cholesterol and lipid ratios in the T2DM, MetS and neither groups. Treatment effects were of similar magnitude across patient groups with both treatments, except triglycerides, which were slightly greater in the T2DM and MetS groups vs. neither group. Changes in HDL-C , Apo A-I and high sensitivity C-reactive protein (hs-CRP) were comparable for both treatments in all three groups. Safety and tolerability profiles were generally similar between treatments and across patient groups, as were the incidence of liver and muscle AEs. CONCLUSIONS: Compared with doubling atorvastatin to 80 mg, addition of ezetimibe to atorvastatin 40 mg produced greater improvements in multiple lipid parameters in high-CHD risk patients with T2DM, MetS or neither, consistent with the significantly greater changes observed in the full study cohort (clinical trial # NCT00276484).

Diagnosis of hepatitis C virus infection in Scotland's injecting drug user population.

We estimated the extent of undiagnosed hepatitis C virus (HCV) infection in injecting drug users (IDUs) in Scotland. We used record-linkage to determine HCV diagnosis status for 41 062 current/former IDUs attending drug treatment and support services between 1 April 1995 and 31 March 2006; the extent of undiagnosed HCV infection was estimated by comparing the number HCV-diagnosed to the number HCV-infected (estimated from an unlinked anonymous testing survey of 2141 current/former IDUs). In all, 9145 IDUs (22%) were diagnosed HCV antibody-positive since first attendance at drug services (diagnosis rate of 33.6/1000 person-years, 95% CI 32.7-34.4). By 31 March 2006, of the 19 632 current/former IDUs who had attended drug services and were determined to be living with HCV, an estimated 58% (95% CI 45-62) had not been HCV-diagnosed. It is essential that the deployment of resources for identifying at-risk IDUs with a view to offering antiviral therapy is guided by evidence.

The growing contribution of hepatitis C virus infection to liver-related mortality in Scotland.

The large number of individuals in Scotland who became infected with the hepatitis C virus (HCV) in the 1970s and 1980s leads us to expect liver-related morbidity and mortality to increase in the coming years. We investigated the contribution of HCV to liver-related mortality in the period January 1991 to June 2006. The study population consisted of 26,861 individuals whose death record mentioned a liver-related cause (underlying or contributing). Record-linkage to the national HCV Diagnosis database supplied HCV-diagnosed status for the study population. The proportion diagnosed with HCV among people dying from a liver-related cause rose from 2.8% (1995-1997) to 4.4% (2004-June 2006); the largest increase occurred in those aged 35-44 years at death (7% to 17%). Among all deaths from a liver-related cause, an HCV-positive diagnosis was more likely in those who died in 2001 or later than those who died in 1995-1997 (2001-2003: odds ratio (OR)=1.4, 95% confidence interval (CI): 1.1-1.7; 2004-June 2006: 1.6, 1.3-2.0), and in those who died at under 55 compared with at least 55 years of age. HCV infection represents a significant, growing, public health burden in Scotland in terms of early deaths from liver disease.