How does discharge against medical advice affect risk of mortality and unplanned readmission? A retrospective cohort study set in a large UK medical admissions unit.

OBJECTIVES: To assess the frequency of discharge against medical advice (DAMA) in a large UK teaching hospital, explore factors which increase the risk of DAMA and identify how DAMA impacts patient risk of mortality and readmission. DESIGN: Retrospective cohort study. SETTING: Large acute teaching hospital in the UK. PATIENTS: 36 683 patients discharged from the acute medical unit of a large UK teaching hospital between 1 January 2012 and 31 December 2016. MEASUREMENTS: Patients were censored on 1 January 2021. Mortality and 30-day unplanned readmission rates were assessed. Deprivation, age and sex were taken as covariates. RESULTS: 3% of patients discharged against medical advice. These patients were younger (median age (years) (IQR)): planned discharge (PD) 59 (40-77); DAMA 39 (28-51), predominantly of male sex (PD 48%; DAMA 66%) and were of greater social deprivation (in three most deprived quintiles PD 69%; DAMA 84%). DAMA was associated with increased risk of death in patients under the age of 33.3 years (adjusted HR 2.6 (1.2-5.8)) and increased incidence of 30-day readmission (standardised incidence ratio 1.9 (1.5-2.2)). LIMITATIONS: Readmission to acute hospitals outside of the local health board may have been missed. We were unable to include information regarding comorbidity or severity of presentation. CONCLUSIONS: These data highlight the vulnerability of younger patients who DAMA, even in a free-at-the-point-of-delivery healthcare setting.

Addition of hyaluronic acid to the FIB-4 liver fibrosis score improves prediction of incident cirrhosis and hepatocellular carcinoma in type 2 diabetes: The Edinburgh Type 2 Diabetes Study.

BACKGROUND: Type 2 diabetes (T2D) is associated with increased risk of progression to cirrhosis and hepatocellular carcinoma (HCC) in people with chronic liver diseases, particularly non-alcoholic fatty liver disease (NAFLD). However, the absolute risk of progression is low. So, it is crucial to accurately identify patients who would benefit most from hepatology referral and intensified management. Current risk-stratification tools are suboptimal and perform worse in people with diabetes. AIMS: To determine whether the addition of complementary biomarker(s) to current NAFLD risk-stratification tools in people with T2D could improve the identification of people who are at increased risk of developing incident cirrhosis or HCC. METHODS: The Edinburgh Type 2 diabetes Study (ET2DS) is a cohort study of men and women with T2D (n = 1066, age 60-75 at baseline). Cases of cirrhosis and HCC were identified over 11 years of follow-up. Biomarkers were measured at baseline and year 1 and association with incident disease was assessed using logistic regression. RESULTS: Of existing risk-stratification scores tested, the Fibrosis-4 (FIB-4) index and the AST:platelet ratio index (APRI) performed best in this cohort. Addition of hyaluronic acid (cut-point ≥ 50  µ  g/L) to FIB-4 (cut-point ≥ 1.3) maintained a false negative rate of ≤25% and reduced the number of people incorrectly identified as "high risk" for incident disease by ∼50%. CONCLUSIONS: The addition of hyaluronic acid to FIB-4 reduced the proportion of people inappropriately identified as "high risk" for development of cirrhosis/HCC in a community population of otherwise asymptomatic people with T2D. These findings require a validation in independent cohorts.

Retinal venular tortuosity and fractal dimension predict incident retinopathy in adults with type 2 diabetes: the Edinburgh Type 2 Diabetes Study.

AIMS/HYPOTHESIS: Our aim was to determine whether a range of prespecified retinal vessel traits were associated with incident diabetic retinopathy in adults with type 2 diabetes. METHODS: In the prospective observational cohort Edinburgh Type 2 Diabetes Study of 1066 adults with type 2 diabetes, aged 60-75 years at recruitment, 718 were free from diabetic retinopathy at baseline. Baseline retinal traits including vessel widths, tortuosity (curvature) and fractal dimensions (network complexity), were quantified using fundus camera images and semiautomated software, and analysed using logistic regression for their association with incident diabetic retinopathy over 10 years. RESULTS: The incidence of diabetic retinopathy was 11.4% (n = 82) over 10 years. After adjustment for a range of vascular and diabetes-related risk factors, both increased venular tortuosity (OR 1.51; 95% CI 1.15, 1.98; p = 0.003) and decreased fractal dimension (OR 0.75; 95% CI 0.58, 0.96; p = 0.025) were associated with incident retinopathy. There was no evidence of an association with arterial tortuosity, and associations between measurements of vessel widths and retinopathy lost statistical significance after adjustment for diabetes-related factors and vascular disease. Adding venular tortuosity to a model including established risk factors for diabetic retinopathy (HbA1c, BP and kidney function) improved the discriminative ability (C statistic increased from 0.624 to 0.640, p = 0.013), but no such benefit was found with fractal dimension. CONCLUSIONS/INTERPRETATION: Increased retinal venular tortuosity and decreased fractal dimension are associated with incident diabetic retinopathy, independent of classical risk factors. There is some evidence that venular tortuosity may be a useful biomarker to improve the predictive ability of models based on established retinopathy risk factors, and its inclusion in further risk prediction modelling is warranted.

Depression as a risk factor for dementia in older people with type 2 diabetes and the mediating effect of inflammation.

AIMS/HYPOTHESIS: We aimed to determine the association of depression with dementia risk in people with type 2 diabetes, and to explore the possible mediating role of inflammation in this relationship. METHODS: The Edinburgh Type 2 Diabetes Study is a prospective cohort of 1066 men and women with type 2 diabetes aged 60-75 years. Cox proportional hazards regression analysis was used to investigate the association between depression, assessed at baseline, and subsequent risk of dementia over 10 years. Depression was defined using the Hospital Anxiety and Depression Scale, while incident dementia was defined using medical records, prescription data and death certificates. The potential mediating effect of systemic inflammation was assessed by adjusting models for a generalised inflammation factor, derived from four inflammatory markers measured at baseline (C-reactive protein, IL-6, TNF-α and fibrinogen), and carrying out an exploratory mediation analysis. RESULTS: Dementia developed in 105 participants over a median follow-up of 10.6 years. After adjusting for age and sex, depression was associated with over a 2.5-fold increase in risk of dementia (HR 2.59 [95% CI 1.62, 4.15]). Additional adjustment for the generalised inflammation factor and other covariates did not attenuate the size of association between depression and incident dementia and mediation analysis showed that it was not a mediator. Adjusted logistic regression models showed cross-sectional associations of C-reactive protein and IL-6 with depression. CONCLUSIONS/INTERPRETATION: Depression is an important risk factor for dementia in people with type 2 diabetes. Some inflammatory markers were associated with depression, but systemic inflammation does not appear to mediate the relationship between depression and dementia. Graphical abstract.

Non-invasive risk scores do not reliably identify future cirrhosis or hepatocellular carcinoma in Type 2 diabetes: The Edinburgh type 2 diabetes study.

BACKGROUND: The incidence of cirrhosis and hepatocellular carcinoma (HCC) is increased in Type 2 diabetes, primarily secondary to non-alcoholic fatty liver disease (NAFLD). European guidelines recommend screening for NAFLD in Type 2 diabetes. American guidelines, while not advocating a screening protocol, suggest using non-invasive markers of fibrosis for risk-stratification and guiding onward referral. AIMS: To test the ability of individual fibrosis scores and the European screening algorithm to predict 11-year incident cirrhosis/HCC in an asymptomatic community cohort of older people with Type 2 diabetes. METHODS: The Edinburgh Type 2 Diabetes Study investigated men and women with Type 2 diabetes (n = 1066, aged 60-75 at baseline). Liver markers were measured at baseline and year 1; steatosis and fibrosis markers were calculated according to independently published calculations. During 11 years of follow-up, cases of cirrhosis and HCC were identified. RESULTS: Forty-three out of 1059 participants with no baseline cirrhosis/HCC developed incident disease. All scores were significantly associated with incident liver disease by odds ratio (P < .05). The ability of the risk-stratification tools to accurately identify those who developed incident cirrhosis/HCC was poor with low-positive predictive values (5-46%) and high false-negative and -positive rates (up to 60% and 77%) respectively. When fibrosis risk scores were used in conjunction with the European algorithm, they performed modestly better than when applied in isolation. CONCLUSIONS: In a cohort with a moderately low incidence of cirrhosis/HCC, existing risk scores did not reliably identify participants at high risk. Better prediction models for cirrhosis/HCC in people with Type 2 diabetes are required.