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.

Long-term outcomes of patients investigated for suspected upper extremities deep venous thrombosis irrespective of imaging results.

BACKGROUND: Outcome data are limited for upper extremity deep venous thrombosis (UEDVT). The outcomes of patients investigated for, but without UEDVT remain uncertain. METHODS: Retrospective analysis of clinical records of adult patients undergoing Doppler ultrasound for potential UEDVT between 1 January 2007 and 31 December 2014 was undertaken. Primary outcome was all-cause mortality. Secondary outcomes were new cancer diagnosis and thromboembolic recurrence. RESULTS: The final cohort (n = 528) comprised 25 primary UEDVT, 100 secondary UEDVT, 40 superficial-venous thrombosis and 363 without thrombus patients. There were 207 deaths. Survival was higher in primary than in secondary UEDVT (log-rank p < 0.0001) or those without thrombus (log-rank p = 0.001). Pre-existing cancer [hazard ratio 3.6 (95% confidence interval 1.5-8.9)] was the biggest independent predictor of mortality and leading cause of death. Developing UEDVT was a poor prognostic marker in cancer patients. CONCLUSION: There was high early mortality regardless of radiological findings, with the exception of primary UEDVT. Prospective studies evaluating aggressive treatment of underlying comorbidities in these patients are needed.

Proteomic profiling of cellular steatosis with concomitant oxidative stress in vitro.

BACKGROUND: Nutrient excess underpins the development of nonalcoholic fatty liver disease (NAFLD). The ensuing metabolic derangement is characterised by increased cellular respiration, oxidative stress and mitochondrial impairment. We have previously recapitulated these events in an in vitro cellular steatosis model. Here, we examined the distinct patterns of protein expression involved using a proteomics approach. METHODS: Human hepatoblastoma C3A cells were treated with a combination of energy substrates; lactate (L), pyruvate (P), octanoate (O) and ammonia (N). Proteins extracts were trypsinized and analyzed on a capillary HPLC OrbitrapXL mass spectrometer. Proteins were quantified using a label-free intensity based approach. Functional enrichment analysis was performed using ToppCluster via Gene Ontology (GO) database. RESULTS: Of the 1327 proteins identified, 104 were differentially expressed between LPON and untreated cells (defined as: ≥2 peptides; fold change ≥1.5; p-value <0.05). Seventy of these were upregulated with LPON. Functional enrichment analysis revealed enhanced protein biosynthesis accompanied by downregulation of histones H2A type 1-A, H1.2, H1.5 and H1.0I in LPON cells. Lipid binding annotations were also enriched as well as proteins involved in cholesterol synthesis, uptake and efflux. Increased expression of aldo-keto reductase family 1, member C1 and C3 suggests enhanced sterol metabolism and increased ROS-mediated lipid peroxidation. CONCLUSIONS: The surge of energy substrates diverts free fatty acid metabolism towards pathways that can mitigate lipotoxicity. The histones depletion may represent an adaptation to increased protein synthesis. However, this can also expose DNA to oxidative stress thus should be explored further in the context of NAFLD progression.

Interrelationships between hepatic fat and insulin resistance in non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is strongly associated with insulin resistance, and its prevalence is rising in parallel with worldwide increases in obesity and type 2 diabetes. However, the nature of this relationship remains debatable. In particular, it is unclear whether insulin resistance causes NAFLD or hepatic steatosis per se reduces insulin sensitivity. This review will examine data from recent studies on the link between insulin resistance and NAFLD, focusing on studies that have attempted to dissociate fatty liver and hepatic insulin resistance.