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Background & Aims: Risk factors for cardiovascular disease, such as obesity and hypertension, have been associated with non-alcoholic fatty liver disease. Psychological distress (symptoms of anxiety and depression) is a risk factor for cardiovascular disease, so it might also be associated, directly or indirectly, with elevated rates of liver disease. We investigated the relation of psychological distress (measured by the 12-item General Health Questionnaire; GHQ) with liver disease mortality. Methods: We performed a meta-analysis of data from individual participants in 16 prospective studies of the general population of the UK, initiated from 1994 through 2008. We categorized GHQ score into four groups: zero (no distress), 1-3, 4-6, and 7-12. Results: We used data from 166,631 individuals (55% women; age, 46.6±18.4 years; range, 16−102 years). During a mean follow-up period of 9.5 years, 17,368 participants died (457 with liver disease). We found a significant increase in risk for liver disease mortality as GHQ score increased across categories (ptrend<0.001). The age- and sex-adjusted hazard ratio for the highest GHQ category (7-12) compared to those scoring zero was 3.48 (95% confidence interval, 2.68−4.52). After adjustment for health behaviors, socioeconomic status, body mass index, and diabetes, the hazard ratio was partially attenuated to 2.59 (95% confidence interval, 1.82–3.68). Conclusions: Our novel finding that psychological distress was associated with liver disease mortality requires testing in other studies. Though results are unlikely to be causal, we provide further evidence for the deleterious effects of psychological problems on physical health.

AIMS/HYPOTHESIS: The aim of this work was to assess the role of well-established cardiovascular risk factors in the late-life cognitive decline of patients with type 2 diabetes. METHODS: Data from 831 participants (aged 60-75 years) attending the 4 year follow-up of the Edinburgh Type 2 Diabetes Study (ET2DS) were used. Smoking history (pack-years), BP, HbA1c, plasma glucose and cholesterol were determined at baseline clinics (single time measurements) and/or from serial data recorded on a clinical management database from diagnosis until recruitment ('historical' data). Principal component analysis derived a factor, g, of general ability from seven cognitive tests. Linear regression models of follow-up g were adjusted for baseline g to represent 4 year cognitive change. 'Accelerated late-life cognitive decline' was defined as scoring in the lowest tertile of '4 year cognitive change' regression scores. Analyses controlled for age and sex. RESULTS: A baseline history of moderate/heavy smoking (>/= 10 pack-years) and a 1% increased historical HbA1c (equivalent to an increase by 11 mmol/mol) predicted a 64% (OR 1.64; 95% CI 1.14, 2.34; p = 0.007) and 21% (OR 1.21; 95% CI 1.00, 1.45; p = 0.046) increased risk of accelerated cognitive decline, respectively. When treated as continuous measures, higher pack-years, historical HbA1c and historical BP emerged as significant independent predictors of 4 year decline in g (standardised beta range -0.07 to -0.14; all p

BACKGROUND & AIMS: It is difficult to determine the different stages of non-alcoholic fatty liver disease without the use of invasive liver biopsy. In this study we investigated five non-invasive biomarkers used previously to detect hepatic fibrosis and determined the level of agreement between them in order to inform future research. METHODS: In the Edinburgh Type 2 Diabetes Study, a population-based cohort aged 60-74 years with type 2 diabetes, 831 participants underwent ultrasound assessment for fatty liver and had serum aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT), aspartate to platelet ratio index (APRI), European Liver Fibrosis panel (ELF), Fibrosis-4 Score (FIB4) and liver stiffness measurement (LSM) measured. RESULTS: Literature based cut-offs yielded marked differences in the proportions of the cohort with probable liver fibrosis in the full cohort. Agreement between the top 5% of the distribution for each biomarker pair was poor. APRI and FIB4 had the best positive agreement at 76.4%, but agreement for all of the other serum biomarker pairs was between 18% and 34%. Agreement with LSM was poor (9-16%). CONCLUSIONS: We found poor correlation between the five biomarkers of liver fibrosis studied. Using the top 5% of each biomarker resulted in good agreement on the absence of advanced liver disease but poor agreement on the presence of advanced disease. Further work is required to validate these markers against liver biopsy and to determine their predictive value for clinical liver-related endpoints, in a range of different low and high risk population groups.

Background Developmental dysplasia of the hip (DDH) remains common. If detected early, DDH can usually be corrected with conservative management. Late presentations often require surgery, and have worse outcomes. Objective We estimated the risk of undergoing surgery for DDH by age 3 years before and after the introduction of enhanced DDH detection services. Design Retrospective cohort study Setting Scotland, 1997/98 – 2010/11 Patients All children Methods Using routinely collected national hospital discharge records we examined rates of first surgery for DDH by age 3 by March 2014. Using a difference in difference analysis we compared rates in two areas of Scotland before (to April 2002) and after (from April 2005) implementation of enhanced DDH detection services to those seen in the rest of Scotland. Results For children born in the study period, the risk of first surgery for DDH by age 3 was 1.18 (95%CI 1.11-1.26) per 1,000 live births (918/777,375). Prior to April 2002, the risk of surgery was 1.13 (95%CI 0.88-1.42) and 1.31 (95%CI 1.16-1.46) per 1,000 live births in the intervention and non-intervention areas respectively. In the intervention areas, from April 2005, this risk halved (RR 0.47; 95%CI 0.32-0.68). The risk remained unchanged in other areas (RR 1.01; 0.86-1.18). The ratio for the difference in change of risk was 0.46 (95%CI 0.31-0.70). Conclusions The implementation of enhanced DDH detection services can produce substantial reductions the number of children having surgical correction for DDH.

Objective: We aimed to understand the usage and acceptability of a faecal collection device (FCD) amongst participants of the NHS Bowel Cancer Screening Programme in order to influence future uptake. Setting: Men and women completing faecal occult blood test (FOBt) retests as part of the routine Bowel Cancer Screening Programme in Eastern England. Methods: A FCD and questionnaire was sent to all potential retest participants during a 1 month period collecting information on prior stool collection methods and ease of use and usefulness of the enclosed FCD. Results: Of 1087 invitations to participate, 679 (62.5%) participants returned their questionnaire. Of these 429 (63.2%) trialled the FCD at least once. 163 (38.4%) found the device made collecting their sample easier than previously, with 189 (44.6%) finding it made collection more difficult and 72 (17.0%) feeling it made no difference. Similar numbers reported finding that the FCD made collecting the sample more pleasant (130, 31.5%), less pleasant (103, 25.0%) and no different (179, 43.4%) compared to previous collection without a FCD. Conclusion: Although a small proportion of participants found the FCD helpful a considerable majority did not or did not use it at all. Offering FCDs is unlikely to produce a substantial increase in bowel cancer screening uptake.

OBJECTIVE: To describe associations between alcoholic fatty liver disease (ALD) or non-alcoholic fatty liver disease (NAFLD) hospital admission and cardiovascular disease (CVD), cancer, and mortality in people with T2DM. RESEARCH DESIGN AND METHODS: We performed a retrospective cohort study using linked population-based routine data from the diabetes register, hospital, cancer and death records for people aged 40-89 years, diagnosed with T2DM in Scotland 2004-2013 who had one or more hospital admission records. Liver disease and outcomes were identified using International Classification of Diseases codes. We estimated hazard ratios from Cox proportional hazards models, adjusted for key risk factors (aHRs). RESULTS: There were 134,368 people with T2DM (1707 with ALD and 1452 with NAFLD) with mean follow-up of 4.3 years for CVD and 4.7 years for mortality. Among people with ALD, NAFLD or without liver disease hospital records respectively there were: 378, 320 and 21,873 CVD events, 268, 176 and 15,101 cancers and 724, 221 and 16,203 deaths. For ALD and NAFLD respectively, aHRs (95% CIs) compared to the group with no record of liver disease were: 1.59 (1.43, 1.76) and 1.70 (1.52, 1.90), for CVD; 40.3 (28.8, 56.5) and 19.12(11.71 31.2), for hepatocellular cancer (HCC); 1.28 (1.12, 1.47) and 1.10 (0.94, 1.29) for non-HCC cancer; 4.86 (4.50, 5.24) and 1.60 (1.40, 1.83) for all-cause mortality. CONCLUSIONS: Hospital records of ALD or NAFLD are associated, to varying degrees, with increased risk of CVD, cancer and mortality in people with T2DM.

Background Concerns have been raised about the safety of surgery for stress urinary incontinence and pelvic organ prolapse using transvaginal mesh. We assessed adverse outcomes after first, single mesh procedures and comparable non-mesh procedures. Methods We did a cohort study of women in Scotland aged 20 years or older undergoing a first, single incontinence procedure or prolapse procedure during 1997–98 to 2015–16 identified from a national hospital admission database. Primary outcomes were immediate postoperative complications and subsequent (within 5 years) readmissions for later postoperative complications, further incontinence surgery, or further prolapse surgery. Poisson regression models were used to compare outcomes after procedures carried out with and without mesh. Findings Between April 1, 1997, and March 31, 2016, 16 660 women underwent a first, single incontinence procedure, 13 133 (79%) of which used mesh. Compared with non-mesh open surgery (colposuspension), mesh procedures had a lower risk of immediate complications (adjusted relative risk [aRR] 0·44 [95% CI 0·36–0·55]) and subsequent prolapse surgery (adjusted incidence rate ratio [aIRR] 0·30 [0·24–0·39]), and a similar risk of further incontinence surgery (0·90 [0·73–1·11]) and later complications (1·12 [0·98–1·27]); all ratios are for retropubic mesh. During the same time period, 18 986 women underwent a first, single prolapse procedure, 1279 (7%) of which used mesh. Compared with non-mesh repair, mesh repair of anterior compartment prolapse was associated with a similar risk of immediate complications (aRR 0·93 [95% CI 0·49–1·79]); an increased risk of further incontinence (aIRR 3·20 [2·06–4·96]) and prolapse surgery (1·69 [1·29–2·20]); and a substantially increased risk of later complications (3·15 [2·46–4·04]). Compared with non-mesh repair, mesh repair of posterior compartment prolapse was associated with a similarly increased risk of repeat prolapse surgery and later complications. No diff

Currently the only accepted method (gold standard) for the diagnosis of the fibrotic stages of chronic liver disease (CLD) is liver biopsy, to allow histological assessment. Liver biopsy is an invasive investigation associated with a range adverse events (e.g. pain, haemorrhage) limiting its serial usage in clinical practice. Additionally, its use is further reduced by sampling error and because histology is in effect a surrogate for clinical outcomes. Over recent years, alternative non-invasive biomarkers for the diagnosis of liver fibrosis have been developed. Initially developed in chronic viral hepatitis these have since seen their use expanded to include all aetiologies of CLD. Such markers can be divided into indirect ‘simple’ markers (e.g. transaminases, gamma-glutamyl transferase, platelet count), direct ‘complex’ markers (e.g. procollagen peptides I/III, Type IV collagen), cytokines (e.g. interleukin-10, transforming growth factor alpha) and imaging. Here, we discuss the clinical utility, limitations and development of non-invasive biomarkers in their use as diagnostic and prognostic tests.

Introduction A high level of case ascertainment by cancer registries is essential to allow estimation of accurate incidence rates and survival. Nearly 20 years ago, researchers assessed the completeness and accuracy of registration of primary intracranial tumours (Scottish Cancer Registry [SCR]) compared to a database assembled in the context of a detailed incidence study carried out in the Lothian region of Scotland covering the period of diagnosis, 1989–1990.1 and 2 Disappointingly, SCR identified only 54% of cases, although the registry at that time did not attempt to collect information on ‘benign’ intracranial neoplasms which were included in the detailed incidence study. Even so, only 84% of neuro-epithelial tumours were identified by SCR, probably related in part to the fact that the cancer registry was not receiving neuropathology data from the regional neuro-oncology centre. An English study reported similar findings with only 52% of cases appearing in the regional cancer registry.3 Over time, access to diagnostic techniques has improved alongside improvements and changes in classification and clinical coding. Furthermore, SCR now receives neuropathology data from all neuro-oncology centres in Scotland, and has sought to collect information on benign tumours of the brain and spinal cord since the year of diagnosis, 2000. In light of these developments, we aimed to determine the completeness of ascertainment of primary intracranial tumours by SCR through independent/clinical case ascertainment in NHS Lothian for the period of diagnosis, 2011–2012. Methods Scottish Cancer Registry SCR operates by bringing together predominantly electronic information from hospital patient administration systems including patient discharges from hospital (Scottish Morbidity Record 01), radiotherapy, oncology, and pathology records; death records from National Records Scotland; and private hospital records.4 All primary malignant and benign brain tumours are recorded on the SCR

Background: Type 2 diabetes is an independent risk factor for chronic liver disease, however disease burden estimates and knowledge of prognostic indicators are lacking in community populations. Aims: To describe the prevalence and incidence of clinically significant chronic liver disease amongst community-based older people with Type 2 diabetes and to determine risk factors which might assist in discriminating patients with unknown prevalent or incident disease. Design: Prospective cohort study. Methods: Nine hundred and thirty-nine participants in the Edinburgh Type 2 Diabetes Study underwent investigation including liver ultrasound and non-invasive measures of non-alcoholic steatohepatitis (NASH), hepatic fibrosis and systemic inflammation. Over 6-years, cases of cirrhosis and hepatocellular carcinoma were collated from multiple sources. Results: Eight patients had known prevalent disease with 13 further unknown cases identified (prevalence 2.2%) and 15 incident cases (IR 2.9/1000 person-years). Higher levels of systemic inflammation, NASH and hepatic fibrosis markers were associated with both unknown prevalent and incident clinically significant chronic liver disease (all P < 0.001). Conclusions: Our study investigations increased the known prevalence of clinically significant chronic liver disease by over 150%, confirming the suspicion of a large burden of undiagnosed disease. The disease incidence rate was lower than anticipated but still much higher than the general population rate. The ability to identify patients both with and at risk of developing clinically significant chronic liver disease allows for early intervention and clinical monitoring strategies. Ongoing work, with longer follow-up, including analysis of rates of liver function decline, will be used to define optimal risk prediction tools.

Background & Aims: Risk factors for cardiovascular disease, such as obesity and hypertension, have been associated with non-alcoholic fatty liver disease. Psychological distress (symptoms of anxiety and depression) is a risk factor for cardiovascular disease, so it might also be associated, directly or indirectly, with elevated rates of liver disease. We investigated the relation of psychological distress (measured by the 12-item General Health Questionnaire; GHQ) with liver disease mortality. Methods: We performed a meta-analysis of data from individual participants in 16 prospective studies of the general population of the UK, initiated from 1994 through 2008. We categorized GHQ score into four groups: zero (no distress), 1-3, 4-6, and 7-12. Results: We used data from 166,631 individuals (55% women; age, 46.6±18.4 years; range, 16−102 years). During a mean follow-up period of 9.5 years, 17,368 participants died (457 with liver disease). We found a significant increase in risk for liver disease mortality as GHQ score increased across categories (ptrend<0.001). The age- and sex-adjusted hazard ratio for the highest GHQ category (7-12) compared to those scoring zero was 3.48 (95% confidence interval, 2.68−4.52). After adjustment for health behaviors, socioeconomic status, body mass index, and diabetes, the hazard ratio was partially attenuated to 2.59 (95% confidence interval, 1.82–3.68). Conclusions: Our novel finding that psychological distress was associated with liver disease mortality requires testing in other studies. Though results are unlikely to be causal, we provide further evidence for the deleterious effects of psychological problems on physical health.

BACKGROUND & AIMS: It is difficult to determine the different stages of non-alcoholic fatty liver disease without the use of invasive liver biopsy. In this study we investigated five non-invasive biomarkers used previously to detect hepatic fibrosis and determined the level of agreement between them in order to inform future research. METHODS: In the Edinburgh Type 2 Diabetes Study, a population-based cohort aged 60-74 years with type 2 diabetes, 831 participants underwent ultrasound assessment for fatty liver and had serum aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT), aspartate to platelet ratio index (APRI), European Liver Fibrosis panel (ELF), Fibrosis-4 Score (FIB4) and liver stiffness measurement (LSM) measured. RESULTS: Literature based cut-offs yielded marked differences in the proportions of the cohort with probable liver fibrosis in the full cohort. Agreement between the top 5% of the distribution for each biomarker pair was poor. APRI and FIB4 had the best positive agreement at 76.4%, but agreement for all of the other serum biomarker pairs was between 18% and 34%. Agreement with LSM was poor (9-16%). CONCLUSIONS: We found poor correlation between the five biomarkers of liver fibrosis studied. Using the top 5% of each biomarker resulted in good agreement on the absence of advanced liver disease but poor agreement on the presence of advanced disease. Further work is required to validate these markers against liver biopsy and to determine their predictive value for clinical liver-related endpoints, in a range of different low and high risk population groups.

AIMS/HYPOTHESIS: The aim of this work was to assess the role of well-established cardiovascular risk factors in the late-life cognitive decline of patients with type 2 diabetes. METHODS: Data from 831 participants (aged 60-75 years) attending the 4 year follow-up of the Edinburgh Type 2 Diabetes Study (ET2DS) were used. Smoking history (pack-years), BP, HbA1c, plasma glucose and cholesterol were determined at baseline clinics (single time measurements) and/or from serial data recorded on a clinical management database from diagnosis until recruitment ('historical' data). Principal component analysis derived a factor, g, of general ability from seven cognitive tests. Linear regression models of follow-up g were adjusted for baseline g to represent 4 year cognitive change. 'Accelerated late-life cognitive decline' was defined as scoring in the lowest tertile of '4 year cognitive change' regression scores. Analyses controlled for age and sex. RESULTS: A baseline history of moderate/heavy smoking (>/= 10 pack-years) and a 1% increased historical HbA1c (equivalent to an increase by 11 mmol/mol) predicted a 64% (OR 1.64; 95% CI 1.14, 2.34; p = 0.007) and 21% (OR 1.21; 95% CI 1.00, 1.45; p = 0.046) increased risk of accelerated cognitive decline, respectively. When treated as continuous measures, higher pack-years, historical HbA1c and historical BP emerged as significant independent predictors of 4 year decline in g (standardised beta range -0.07 to -0.14; all p

Background & Aims: Risk factors for cardiovascular disease, such as obesity and hypertension, have been associated with non-alcoholic fatty liver disease. Psychological distress (symptoms of anxiety and depression) is a risk factor for cardiovascular disease, so it might also be associated, directly or indirectly, with elevated rates of liver disease. We investigated the relation of psychological distress (measured by the 12-item General Health Questionnaire; GHQ) with liver disease mortality. Methods: We performed a meta-analysis of data from individual participants in 16 prospective studies of the general population of the UK, initiated from 1994 through 2008. We categorized GHQ score into four groups: zero (no distress), 1-3, 4-6, and 7-12. Results: We used data from 166,631 individuals (55% women; age, 46.6±18.4 years; range, 16−102 years). During a mean follow-up period of 9.5 years, 17,368 participants died (457 with liver disease). We found a significant increase in risk for liver disease mortality as GHQ score increased across categories (ptrend<0.001). The age- and sex-adjusted hazard ratio for the highest GHQ category (7-12) compared to those scoring zero was 3.48 (95% confidence interval, 2.68−4.52). After adjustment for health behaviors, socioeconomic status, body mass index, and diabetes, the hazard ratio was partially attenuated to 2.59 (95% confidence interval, 1.82–3.68). Conclusions: Our novel finding that psychological distress was associated with liver disease mortality requires testing in other studies. Though results are unlikely to be causal, we provide further evidence for the deleterious effects of psychological problems on physical health.

Objective: We aimed to understand the usage and acceptability of a faecal collection device (FCD) amongst participants of the NHS Bowel Cancer Screening Programme in order to influence future uptake. Setting: Men and women completing faecal occult blood test (FOBt) retests as part of the routine Bowel Cancer Screening Programme in Eastern England. Methods: A FCD and questionnaire was sent to all potential retest participants during a 1 month period collecting information on prior stool collection methods and ease of use and usefulness of the enclosed FCD. Results: Of 1087 invitations to participate, 679 (62.5%) participants returned their questionnaire. Of these 429 (63.2%) trialled the FCD at least once. 163 (38.4%) found the device made collecting their sample easier than previously, with 189 (44.6%) finding it made collection more difficult and 72 (17.0%) feeling it made no difference. Similar numbers reported finding that the FCD made collecting the sample more pleasant (130, 31.5%), less pleasant (103, 25.0%) and no different (179, 43.4%) compared to previous collection without a FCD. Conclusion: Although a small proportion of participants found the FCD helpful a considerable majority did not or did not use it at all. Offering FCDs is unlikely to produce a substantial increase in bowel cancer screening uptake.

OBJECTIVE: To describe associations between alcoholic fatty liver disease (ALD) or non-alcoholic fatty liver disease (NAFLD) hospital admission and cardiovascular disease (CVD), cancer, and mortality in people with T2DM. RESEARCH DESIGN AND METHODS: We performed a retrospective cohort study using linked population-based routine data from the diabetes register, hospital, cancer and death records for people aged 40-89 years, diagnosed with T2DM in Scotland 2004-2013 who had one or more hospital admission records. Liver disease and outcomes were identified using International Classification of Diseases codes. We estimated hazard ratios from Cox proportional hazards models, adjusted for key risk factors (aHRs). RESULTS: There were 134,368 people with T2DM (1707 with ALD and 1452 with NAFLD) with mean follow-up of 4.3 years for CVD and 4.7 years for mortality. Among people with ALD, NAFLD or without liver disease hospital records respectively there were: 378, 320 and 21,873 CVD events, 268, 176 and 15,101 cancers and 724, 221 and 16,203 deaths. For ALD and NAFLD respectively, aHRs (95% CIs) compared to the group with no record of liver disease were: 1.59 (1.43, 1.76) and 1.70 (1.52, 1.90), for CVD; 40.3 (28.8, 56.5) and 19.12(11.71 31.2), for hepatocellular cancer (HCC); 1.28 (1.12, 1.47) and 1.10 (0.94, 1.29) for non-HCC cancer; 4.86 (4.50, 5.24) and 1.60 (1.40, 1.83) for all-cause mortality. CONCLUSIONS: Hospital records of ALD or NAFLD are associated, to varying degrees, with increased risk of CVD, cancer and mortality in people with T2DM.

Background Concerns have been raised about the safety of surgery for stress urinary incontinence and pelvic organ prolapse using transvaginal mesh. We assessed adverse outcomes after first, single mesh procedures and comparable non-mesh procedures. Methods We did a cohort study of women in Scotland aged 20 years or older undergoing a first, single incontinence procedure or prolapse procedure during 1997–98 to 2015–16 identified from a national hospital admission database. Primary outcomes were immediate postoperative complications and subsequent (within 5 years) readmissions for later postoperative complications, further incontinence surgery, or further prolapse surgery. Poisson regression models were used to compare outcomes after procedures carried out with and without mesh. Findings Between April 1, 1997, and March 31, 2016, 16 660 women underwent a first, single incontinence procedure, 13 133 (79%) of which used mesh. Compared with non-mesh open surgery (colposuspension), mesh procedures had a lower risk of immediate complications (adjusted relative risk [aRR] 0·44 [95% CI 0·36–0·55]) and subsequent prolapse surgery (adjusted incidence rate ratio [aIRR] 0·30 [0·24–0·39]), and a similar risk of further incontinence surgery (0·90 [0·73–1·11]) and later complications (1·12 [0·98–1·27]); all ratios are for retropubic mesh. During the same time period, 18 986 women underwent a first, single prolapse procedure, 1279 (7%) of which used mesh. Compared with non-mesh repair, mesh repair of anterior compartment prolapse was associated with a similar risk of immediate complications (aRR 0·93 [95% CI 0·49–1·79]); an increased risk of further incontinence (aIRR 3·20 [2·06–4·96]) and prolapse surgery (1·69 [1·29–2·20]); and a substantially increased risk of later complications (3·15 [2·46–4·04]). Compared with non-mesh repair, mesh repair of posterior compartment prolapse was associated with a similarly increased risk of repeat prolapse surgery and later complications. No diff

Currently the only accepted method (gold standard) for the diagnosis of the fibrotic stages of chronic liver disease (CLD) is liver biopsy, to allow histological assessment. Liver biopsy is an invasive investigation associated with a range adverse events (e.g. pain, haemorrhage) limiting its serial usage in clinical practice. Additionally, its use is further reduced by sampling error and because histology is in effect a surrogate for clinical outcomes. Over recent years, alternative non-invasive biomarkers for the diagnosis of liver fibrosis have been developed. Initially developed in chronic viral hepatitis these have since seen their use expanded to include all aetiologies of CLD. Such markers can be divided into indirect ‘simple’ markers (e.g. transaminases, gamma-glutamyl transferase, platelet count), direct ‘complex’ markers (e.g. procollagen peptides I/III, Type IV collagen), cytokines (e.g. interleukin-10, transforming growth factor alpha) and imaging. Here, we discuss the clinical utility, limitations and development of non-invasive biomarkers in their use as diagnostic and prognostic tests.

Background & Aims: Risk factors for cardiovascular disease, such as obesity and hypertension, have been associated with non-alcoholic fatty liver disease. Psychological distress (symptoms of anxiety and depression) is a risk factor for cardiovascular disease, so it might also be associated, directly or indirectly, with elevated rates of liver disease. We investigated the relation of psychological distress (measured by the 12-item General Health Questionnaire; GHQ) with liver disease mortality. Methods: We performed a meta-analysis of data from individual participants in 16 prospective studies of the general population of the UK, initiated from 1994 through 2008. We categorized GHQ score into four groups: zero (no distress), 1-3, 4-6, and 7-12. Results: We used data from 166,631 individuals (55% women; age, 46.6±18.4 years; range, 16−102 years). During a mean follow-up period of 9.5 years, 17,368 participants died (457 with liver disease). We found a significant increase in risk for liver disease mortality as GHQ score increased across categories (ptrend<0.001). The age- and sex-adjusted hazard ratio for the highest GHQ category (7-12) compared to those scoring zero was 3.48 (95% confidence interval, 2.68−4.52). After adjustment for health behaviors, socioeconomic status, body mass index, and diabetes, the hazard ratio was partially attenuated to 2.59 (95% confidence interval, 1.82–3.68). Conclusions: Our novel finding that psychological distress was associated with liver disease mortality requires testing in other studies. Though results are unlikely to be causal, we provide further evidence for the deleterious effects of psychological problems on physical health.

AIMS/HYPOTHESIS: The aim of this work was to assess the role of well-established cardiovascular risk factors in the late-life cognitive decline of patients with type 2 diabetes. METHODS: Data from 831 participants (aged 60-75 years) attending the 4 year follow-up of the Edinburgh Type 2 Diabetes Study (ET2DS) were used. Smoking history (pack-years), BP, HbA1c, plasma glucose and cholesterol were determined at baseline clinics (single time measurements) and/or from serial data recorded on a clinical management database from diagnosis until recruitment ('historical' data). Principal component analysis derived a factor, g, of general ability from seven cognitive tests. Linear regression models of follow-up g were adjusted for baseline g to represent 4 year cognitive change. 'Accelerated late-life cognitive decline' was defined as scoring in the lowest tertile of '4 year cognitive change' regression scores. Analyses controlled for age and sex. RESULTS: A baseline history of moderate/heavy smoking (>/= 10 pack-years) and a 1% increased historical HbA1c (equivalent to an increase by 11 mmol/mol) predicted a 64% (OR 1.64; 95% CI 1.14, 2.34; p = 0.007) and 21% (OR 1.21; 95% CI 1.00, 1.45; p = 0.046) increased risk of accelerated cognitive decline, respectively. When treated as continuous measures, higher pack-years, historical HbA1c and historical BP emerged as significant independent predictors of 4 year decline in g (standardised beta range -0.07 to -0.14; all p

BACKGROUND & AIMS: It is difficult to determine the different stages of non-alcoholic fatty liver disease without the use of invasive liver biopsy. In this study we investigated five non-invasive biomarkers used previously to detect hepatic fibrosis and determined the level of agreement between them in order to inform future research. METHODS: In the Edinburgh Type 2 Diabetes Study, a population-based cohort aged 60-74 years with type 2 diabetes, 831 participants underwent ultrasound assessment for fatty liver and had serum aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT), aspartate to platelet ratio index (APRI), European Liver Fibrosis panel (ELF), Fibrosis-4 Score (FIB4) and liver stiffness measurement (LSM) measured. RESULTS: Literature based cut-offs yielded marked differences in the proportions of the cohort with probable liver fibrosis in the full cohort. Agreement between the top 5% of the distribution for each biomarker pair was poor. APRI and FIB4 had the best positive agreement at 76.4%, but agreement for all of the other serum biomarker pairs was between 18% and 34%. Agreement with LSM was poor (9-16%). CONCLUSIONS: We found poor correlation between the five biomarkers of liver fibrosis studied. Using the top 5% of each biomarker resulted in good agreement on the absence of advanced liver disease but poor agreement on the presence of advanced disease. Further work is required to validate these markers against liver biopsy and to determine their predictive value for clinical liver-related endpoints, in a range of different low and high risk population groups.

Background & Aims: Risk factors for cardiovascular disease, such as obesity and hypertension, have been associated with non-alcoholic fatty liver disease. Psychological distress (symptoms of anxiety and depression) is a risk factor for cardiovascular disease, so it might also be associated, directly or indirectly, with elevated rates of liver disease. We investigated the relation of psychological distress (measured by the 12-item General Health Questionnaire; GHQ) with liver disease mortality. Methods: We performed a meta-analysis of data from individual participants in 16 prospective studies of the general population of the UK, initiated from 1994 through 2008. We categorized GHQ score into four groups: zero (no distress), 1-3, 4-6, and 7-12. Results: We used data from 166,631 individuals (55% women; age, 46.6±18.4 years; range, 16−102 years). During a mean follow-up period of 9.5 years, 17,368 participants died (457 with liver disease). We found a significant increase in risk for liver disease mortality as GHQ score increased across categories (ptrend<0.001). The age- and sex-adjusted hazard ratio for the highest GHQ category (7-12) compared to those scoring zero was 3.48 (95% confidence interval, 2.68−4.52). After adjustment for health behaviors, socioeconomic status, body mass index, and diabetes, the hazard ratio was partially attenuated to 2.59 (95% confidence interval, 1.82–3.68). Conclusions: Our novel finding that psychological distress was associated with liver disease mortality requires testing in other studies. Though results are unlikely to be causal, we provide further evidence for the deleterious effects of psychological problems on physical health.

AIMS/HYPOTHESIS: The aim of this work was to assess the role of well-established cardiovascular risk factors in the late-life cognitive decline of patients with type 2 diabetes. METHODS: Data from 831 participants (aged 60-75 years) attending the 4 year follow-up of the Edinburgh Type 2 Diabetes Study (ET2DS) were used. Smoking history (pack-years), BP, HbA1c, plasma glucose and cholesterol were determined at baseline clinics (single time measurements) and/or from serial data recorded on a clinical management database from diagnosis until recruitment ('historical' data). Principal component analysis derived a factor, g, of general ability from seven cognitive tests. Linear regression models of follow-up g were adjusted for baseline g to represent 4 year cognitive change. 'Accelerated late-life cognitive decline' was defined as scoring in the lowest tertile of '4 year cognitive change' regression scores. Analyses controlled for age and sex. RESULTS: A baseline history of moderate/heavy smoking (>/= 10 pack-years) and a 1% increased historical HbA1c (equivalent to an increase by 11 mmol/mol) predicted a 64% (OR 1.64; 95% CI 1.14, 2.34; p = 0.007) and 21% (OR 1.21; 95% CI 1.00, 1.45; p = 0.046) increased risk of accelerated cognitive decline, respectively. When treated as continuous measures, higher pack-years, historical HbA1c and historical BP emerged as significant independent predictors of 4 year decline in g (standardised beta range -0.07 to -0.14; all p

Objective: We aimed to understand the usage and acceptability of a faecal collection device (FCD) amongst participants of the NHS Bowel Cancer Screening Programme in order to influence future uptake. Setting: Men and women completing faecal occult blood test (FOBt) retests as part of the routine Bowel Cancer Screening Programme in Eastern England. Methods: A FCD and questionnaire was sent to all potential retest participants during a 1 month period collecting information on prior stool collection methods and ease of use and usefulness of the enclosed FCD. Results: Of 1087 invitations to participate, 679 (62.5%) participants returned their questionnaire. Of these 429 (63.2%) trialled the FCD at least once. 163 (38.4%) found the device made collecting their sample easier than previously, with 189 (44.6%) finding it made collection more difficult and 72 (17.0%) feeling it made no difference. Similar numbers reported finding that the FCD made collecting the sample more pleasant (130, 31.5%), less pleasant (103, 25.0%) and no different (179, 43.4%) compared to previous collection without a FCD. Conclusion: Although a small proportion of participants found the FCD helpful a considerable majority did not or did not use it at all. Offering FCDs is unlikely to produce a substantial increase in bowel cancer screening uptake.

OBJECTIVE: To describe associations between alcoholic fatty liver disease (ALD) or non-alcoholic fatty liver disease (NAFLD) hospital admission and cardiovascular disease (CVD), cancer, and mortality in people with T2DM. RESEARCH DESIGN AND METHODS: We performed a retrospective cohort study using linked population-based routine data from the diabetes register, hospital, cancer and death records for people aged 40-89 years, diagnosed with T2DM in Scotland 2004-2013 who had one or more hospital admission records. Liver disease and outcomes were identified using International Classification of Diseases codes. We estimated hazard ratios from Cox proportional hazards models, adjusted for key risk factors (aHRs). RESULTS: There were 134,368 people with T2DM (1707 with ALD and 1452 with NAFLD) with mean follow-up of 4.3 years for CVD and 4.7 years for mortality. Among people with ALD, NAFLD or without liver disease hospital records respectively there were: 378, 320 and 21,873 CVD events, 268, 176 and 15,101 cancers and 724, 221 and 16,203 deaths. For ALD and NAFLD respectively, aHRs (95% CIs) compared to the group with no record of liver disease were: 1.59 (1.43, 1.76) and 1.70 (1.52, 1.90), for CVD; 40.3 (28.8, 56.5) and 19.12(11.71 31.2), for hepatocellular cancer (HCC); 1.28 (1.12, 1.47) and 1.10 (0.94, 1.29) for non-HCC cancer; 4.86 (4.50, 5.24) and 1.60 (1.40, 1.83) for all-cause mortality. CONCLUSIONS: Hospital records of ALD or NAFLD are associated, to varying degrees, with increased risk of CVD, cancer and mortality in people with T2DM.

Background Concerns have been raised about the safety of surgery for stress urinary incontinence and pelvic organ prolapse using transvaginal mesh. We assessed adverse outcomes after first, single mesh procedures and comparable non-mesh procedures. Methods We did a cohort study of women in Scotland aged 20 years or older undergoing a first, single incontinence procedure or prolapse procedure during 1997–98 to 2015–16 identified from a national hospital admission database. Primary outcomes were immediate postoperative complications and subsequent (within 5 years) readmissions for later postoperative complications, further incontinence surgery, or further prolapse surgery. Poisson regression models were used to compare outcomes after procedures carried out with and without mesh. Findings Between April 1, 1997, and March 31, 2016, 16 660 women underwent a first, single incontinence procedure, 13 133 (79%) of which used mesh. Compared with non-mesh open surgery (colposuspension), mesh procedures had a lower risk of immediate complications (adjusted relative risk [aRR] 0·44 [95% CI 0·36–0·55]) and subsequent prolapse surgery (adjusted incidence rate ratio [aIRR] 0·30 [0·24–0·39]), and a similar risk of further incontinence surgery (0·90 [0·73–1·11]) and later complications (1·12 [0·98–1·27]); all ratios are for retropubic mesh. During the same time period, 18 986 women underwent a first, single prolapse procedure, 1279 (7%) of which used mesh. Compared with non-mesh repair, mesh repair of anterior compartment prolapse was associated with a similar risk of immediate complications (aRR 0·93 [95% CI 0·49–1·79]); an increased risk of further incontinence (aIRR 3·20 [2·06–4·96]) and prolapse surgery (1·69 [1·29–2·20]); and a substantially increased risk of later complications (3·15 [2·46–4·04]). Compared with non-mesh repair, mesh repair of posterior compartment prolapse was associated with a similarly increased risk of repeat prolapse surgery and later complications. No diff

Currently the only accepted method (gold standard) for the diagnosis of the fibrotic stages of chronic liver disease (CLD) is liver biopsy, to allow histological assessment. Liver biopsy is an invasive investigation associated with a range adverse events (e.g. pain, haemorrhage) limiting its serial usage in clinical practice. Additionally, its use is further reduced by sampling error and because histology is in effect a surrogate for clinical outcomes. Over recent years, alternative non-invasive biomarkers for the diagnosis of liver fibrosis have been developed. Initially developed in chronic viral hepatitis these have since seen their use expanded to include all aetiologies of CLD. Such markers can be divided into indirect ‘simple’ markers (e.g. transaminases, gamma-glutamyl transferase, platelet count), direct ‘complex’ markers (e.g. procollagen peptides I/III, Type IV collagen), cytokines (e.g. interleukin-10, transforming growth factor alpha) and imaging. Here, we discuss the clinical utility, limitations and development of non-invasive biomarkers in their use as diagnostic and prognostic tests.

Background: Type 2 diabetes is an independent risk factor for chronic liver disease, however disease burden estimates and knowledge of prognostic indicators are lacking in community populations. Aims: To describe the prevalence and incidence of clinically significant chronic liver disease amongst community-based older people with Type 2 diabetes and to determine risk factors which might assist in discriminating patients with unknown prevalent or incident disease. Design: Prospective cohort study. Methods: Nine hundred and thirty-nine participants in the Edinburgh Type 2 Diabetes Study underwent investigation including liver ultrasound and non-invasive measures of non-alcoholic steatohepatitis (NASH), hepatic fibrosis and systemic inflammation. Over 6-years, cases of cirrhosis and hepatocellular carcinoma were collated from multiple sources. Results: Eight patients had known prevalent disease with 13 further unknown cases identified (prevalence 2.2%) and 15 incident cases (IR 2.9/1000 person-years). Higher levels of systemic inflammation, NASH and hepatic fibrosis markers were associated with both unknown prevalent and incident clinically significant chronic liver disease (all P < 0.001). Conclusions: Our study investigations increased the known prevalence of clinically significant chronic liver disease by over 150%, confirming the suspicion of a large burden of undiagnosed disease. The disease incidence rate was lower than anticipated but still much higher than the general population rate. The ability to identify patients both with and at risk of developing clinically significant chronic liver disease allows for early intervention and clinical monitoring strategies. Ongoing work, with longer follow-up, including analysis of rates of liver function decline, will be used to define optimal risk prediction tools.

Background: Type 2 diabetes is an independent risk factor for chronic liver disease, however disease burden estimates and knowledge of prognostic indicators are lacking in community populations. Aims: To describe the prevalence and incidence of clinically significant chronic liver disease amongst community-based older people with Type 2 diabetes and to determine risk factors which might assist in discriminating patients with unknown prevalent or incident disease. Design: Prospective cohort study. Methods: Nine hundred and thirty-nine participants in the Edinburgh Type 2 Diabetes Study underwent investigation including liver ultrasound and non-invasive measures of non-alcoholic steatohepatitis (NASH), hepatic fibrosis and systemic inflammation. Over 6-years, cases of cirrhosis and hepatocellular carcinoma were collated from multiple sources. Results: Eight patients had known prevalent disease with 13 further unknown cases identified (prevalence 2.2%) and 15 incident cases (IR 2.9/1000 person-years). Higher levels of systemic inflammation, NASH and hepatic fibrosis markers were associated with both unknown prevalent and incident clinically significant chronic liver disease (all P < 0.001). Conclusions: Our study investigations increased the known prevalence of clinically significant chronic liver disease by over 150%, confirming the suspicion of a large burden of undiagnosed disease. The disease incidence rate was lower than anticipated but still much higher than the general population rate. The ability to identify patients both with and at risk of developing clinically significant chronic liver disease allows for early intervention and clinical monitoring strategies. Ongoing work, with longer follow-up, including analysis of rates of liver function decline, will be used to define optimal risk prediction tools.

Background & Aims: Risk factors for cardiovascular disease, such as obesity and hypertension, have been associated with non-alcoholic fatty liver disease. Psychological distress (symptoms of anxiety and depression) is a risk factor for cardiovascular disease, so it might also be associated, directly or indirectly, with elevated rates of liver disease. We investigated the relation of psychological distress (measured by the 12-item General Health Questionnaire; GHQ) with liver disease mortality. Methods: We performed a meta-analysis of data from individual participants in 16 prospective studies of the general population of the UK, initiated from 1994 through 2008. We categorized GHQ score into four groups: zero (no distress), 1-3, 4-6, and 7-12. Results: We used data from 166,631 individuals (55% women; age, 46.6±18.4 years; range, 16−102 years). During a mean follow-up period of 9.5 years, 17,368 participants died (457 with liver disease). We found a significant increase in risk for liver disease mortality as GHQ score increased across categories (ptrend<0.001). The age- and sex-adjusted hazard ratio for the highest GHQ category (7-12) compared to those scoring zero was 3.48 (95% confidence interval, 2.68−4.52). After adjustment for health behaviors, socioeconomic status, body mass index, and diabetes, the hazard ratio was partially attenuated to 2.59 (95% confidence interval, 1.82–3.68). Conclusions: Our novel finding that psychological distress was associated with liver disease mortality requires testing in other studies. Though results are unlikely to be causal, we provide further evidence for the deleterious effects of psychological problems on physical health.

AIMS/HYPOTHESIS: The aim of this work was to assess the role of well-established cardiovascular risk factors in the late-life cognitive decline of patients with type 2 diabetes. METHODS: Data from 831 participants (aged 60-75 years) attending the 4 year follow-up of the Edinburgh Type 2 Diabetes Study (ET2DS) were used. Smoking history (pack-years), BP, HbA1c, plasma glucose and cholesterol were determined at baseline clinics (single time measurements) and/or from serial data recorded on a clinical management database from diagnosis until recruitment ('historical' data). Principal component analysis derived a factor, g, of general ability from seven cognitive tests. Linear regression models of follow-up g were adjusted for baseline g to represent 4 year cognitive change. 'Accelerated late-life cognitive decline' was defined as scoring in the lowest tertile of '4 year cognitive change' regression scores. Analyses controlled for age and sex. RESULTS: A baseline history of moderate/heavy smoking (>/= 10 pack-years) and a 1% increased historical HbA1c (equivalent to an increase by 11 mmol/mol) predicted a 64% (OR 1.64; 95% CI 1.14, 2.34; p = 0.007) and 21% (OR 1.21; 95% CI 1.00, 1.45; p = 0.046) increased risk of accelerated cognitive decline, respectively. When treated as continuous measures, higher pack-years, historical HbA1c and historical BP emerged as significant independent predictors of 4 year decline in g (standardised beta range -0.07 to -0.14; all p

Background: Type 2 diabetes is an independent risk factor for chronic liver disease, however disease burden estimates and knowledge of prognostic indicators are lacking in community populations. Aims: To describe the prevalence and incidence of clinically significant chronic liver disease amongst community-based older people with Type 2 diabetes and to determine risk factors which might assist in discriminating patients with unknown prevalent or incident disease. Design: Prospective cohort study. Methods: Nine hundred and thirty-nine participants in the Edinburgh Type 2 Diabetes Study underwent investigation including liver ultrasound and non-invasive measures of non-alcoholic steatohepatitis (NASH), hepatic fibrosis and systemic inflammation. Over 6-years, cases of cirrhosis and hepatocellular carcinoma were collated from multiple sources. Results: Eight patients had known prevalent disease with 13 further unknown cases identified (prevalence 2.2%) and 15 incident cases (IR 2.9/1000 person-years). Higher levels of systemic inflammation, NASH and hepatic fibrosis markers were associated with both unknown prevalent and incident clinically significant chronic liver disease (all P < 0.001). Conclusions: Our study investigations increased the known prevalence of clinically significant chronic liver disease by over 150%, confirming the suspicion of a large burden of undiagnosed disease. The disease incidence rate was lower than anticipated but still much higher than the general population rate. The ability to identify patients both with and at risk of developing clinically significant chronic liver disease allows for early intervention and clinical monitoring strategies. Ongoing work, with longer follow-up, including analysis of rates of liver function decline, will be used to define optimal risk prediction tools.