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.

Paradoxical refractory hypotension following adrenaline administration in a patient taking clozapine.

Clozapine is a potent antipsychotic commonly used for refractory schizophrenia. Adverse effects are well recognised including constipation, intestinal obstruction, agranulocytosis and cardiomyopathy. We present a case of paradoxical refractory hypotension following epinephrine administration in a patient taking clozapine. A psychiatric inpatient who had been taking clozapine for many years developed paralytic ileus and obstruction requiring surgical intervention. Following initiation of epinephrine administration intraoperatively he developed refractory hypotension which improved only when epinephrine was weaned off. This effect is likely due to uninterrupted ß2-agonist activity in the presence of clozapine-induced α-blockade. Clinicians need to have greater awareness of this serious interaction and avoid the use of epinephrine in patients taking clozapine.

Targeting mTOR in Pancreatic Ductal Adenocarcinoma.

Treatment options for advanced pancreatic ductal adenocarcinoma (PDAC) are limited; however, new therapies targeting specific tumor-related molecular characteristics may help certain patient cohorts. Emerging preclinical data have shown that inhibition of mammalian target of rapamycin (mTOR) in specific KRAS-dependent PDAC subtypes leads to inhibition of tumorigenesis in vitro and in vivo. Early phase II studies of mono-mTOR inhibition have not shown promise. However, studies have shown that combined inhibition of multiple steps along the mTOR signaling pathway may lead to sustained responses by targeting mechanisms of tumor resistance. Coordinated inhibition of mTOR along with specific KRAS-dependent mutations in molecularly defined PDAC subpopulations may offer a viable alternative for treatment in the future.