Risk of 12-month mortality among hospital inpatients using the surprise question and SPICT criteria: a prospective study.

OBJECTIVES: People with serious life-limiting disease benefit from advance care planning, but require active identification. This study applied the Gold Standards Framework Proactive Identification Guidance (GSF-PIG) to a general hospital population to describe high-risk patients and explore prognostic performance for 12-month mortality. METHODS: Prospective cohort study conducted in a metropolitan teaching hospital in Australia. Hospital inpatients on a single day aged 18 years and older were eligible, excluding maternity and neonatal, mental health and day treatment patients. Data sources included medical record and structured questions for medical and nursing staff. High-risk was predefined as positive response to the surprise question (SQ) plus two or more SPICT indicators of general deterioration. Descriptive variables included demographics, frailty and functional measures, treating team, advance care planning documentation and hospital utilisation. Primary outcome for prognostic performance was 12-month mortality. RESULTS: We identified 540 eligible inpatients on the study day and 513 had complete data (mean age 60, 54% male, 30% living alone, 19% elective admissions). Of these, 191 (37%) were high-risk; they were older, frailer, more dependent and had been in hospital longer than low-risk participants. Within 12 months, 92 participants (18%) died (72/191(38%) high-risk versus 20/322(6%) low-risk, P<0.001), providing sensitivity 78%, specificity 72%, positive predictive value 38% and negative predictive value 94%. SQ alone provided higher sensitivity, adding advanced disease indicators improved specificity. CONCLUSIONS: The GSF-PIG approach identified a large minority of hospital inpatients who might benefit from advance care planning. Future studies are needed to investigate the feasibility, cost and impact of screening in hospitals.

Localization of a brain sulfotransferase, SULT4A1, in the human and rat brain: an immunohistochemical study.

Cytosolic sulfotransferases are believed to play a role in the neuromodulation of certain neurotransmitters and drugs. To date, four cytosolic sulfotransferases have been shown to be expressed in human brain. Recently, a novel human brain sulfotransferase has been identified and characterized, although its role and localization in the brain are unknown. Here we present the first immunohistochemical (IHC) localization of SULT4A1 in human brain using an affinity-purified polyclonal antibody raised against recombinant human SULT4A1. These results are supported and supplemented by the IHC localization of SULT4A1 in rat brain. In both human and rat brains, strong reactivity was found in several brain regions, including cerebral cortex, cerebellum, pituitary, and brainstem. Specific signal was entirely absent on sections for which preimmune serum from the corresponding animal, processed in the same way as the postimmune serum, was used in the primary screen. The findings from this study may assist in determining the physiological role of this SULT isoform.

Structure of a human carcinogen-converting enzyme, SULT1A1. Structural and kinetic implications of substrate inhibition.

Sulfonation catalyzed by sulfotransferase enzymes plays an important role in chemical defense mechanisms against various xenobiotics but also bioactivates carcinogens. A major human sulfotransferase, SULT1A1, metabolizes and/or bioactivates many endogenous compounds and is implicated in a range of cancers because of its ability to modify diverse promutagen and procarcinogen xenobiotics. The crystal structure of human SULT1A1 reported here is the first sulfotransferase structure complexed with a xenobiotic substrate. An unexpected finding is that the enzyme accommodates not one but two molecules of the xenobiotic model substrate p-nitrophenol in the active site. This result is supported by kinetic data for SULT1A1 that show substrate inhibition for this small xenobiotic. The extended active site of SULT1A1 is consistent with binding of diiodothyronine but cannot easily accommodate beta-estradiol, although both are known substrates. This observation, together with evidence for a disorder-order transition in SULT1A1, suggests that the active site is flexible and can adapt its architecture to accept diverse hydrophobic substrates with varying sizes, shapes and flexibility. Thus the crystal structure of SULT1A1 provides the molecular basis for substrate inhibition and reveals the first clues as to how the enzyme sulfonates a wide variety of lipophilic compounds.