What are the risk factors for avoidable transitions in the last year of life? A qualitative exploration of professionals' perspectives for improving care in Germany.

BACKGROUND: Little is known about the nature of patients' transitions between healthcare settings in the last year of life (LYOL) in Germany. Patients often experience transitions between different healthcare settings, such as hospitals and long-term facilities including nursing homes and hospices. The perspective of healthcare professionals can therefore provide information on transitions in the LYOL that are avoidable from a medical perspective. This study aims to explore factors influencing avoidable transitions across healthcare settings in the LYOL and to disclose how these could be prevented. METHODS: Two focus groups (n = 11) and five individual interviews were conducted with healthcare professionals working in hospitals, hospices and nursing services from Cologne, Germany. They were asked to share their observations about avoidable transitions in the LYOL. The data collection continued until the point of information power was reached and were audio recorded and analysed using qualitative content analysis. RESULTS: Four factors for potentially avoidable transitions between care settings in the LYOL were identified: healthcare system, organization, healthcare professional, patient and relatives. According to the participants, the most relevant aspects that can aid in reducing unnecessary transitions include timely identification and communication of the LYOL; consideration of palliative care options; availability and accessibility of care services; and having a healthcare professional taking main responsibility for care planning. CONCLUSIONS: Preventing avoidable transitions by considering the multicomponent factors related to them not only immediately before death but also in the LYOL could help to provide more value-based care for patients and improving their quality of life.

Role of a multidimensional prognosis in-hospital monitoring for older patients with prolonged stay.

OBJECTIVES: The Multidimensional Prognostic Index (MPI) is a prognostic tool-amongst others-validated for mortality, length of hospital stay (LHS) and rehospitalisation risk assessment. Like the Comprehensive Geriatric Assessment (CGA), the MPI is usually obtained at hospital admission and discharge, not during the hospital stay. The aim of the present study was to address the role of an additional CGA-based MPI measurement during hospitalisation as an indicator of "real-time" in-hospital changes. STUDY DESIGN AND MAIN OUTCOME MEASURES: Two-hundred consecutive multimorbid patients (128 M, 72 F, median age 75 (78-82)) admitted to an internal medicine ward of a German metropolitan university hospital prospectively underwent a CGA and a prognosis calculation using the MPI on admission and discharge. Seven to 10 days later, an intermediate assessment (IA) was performed for patients needing a longer stay. RESULTS: The median LHS was 10 (6-19) days. As expected, patients who received an IA had poorer prognosis as measured by higher MPI values (P = .037) and a worse functional status at admission than patients who had a shorter stay (P = .025). In case of prolonged hospitalisation, significant changes in the MPI were detected between admission and IA, both in terms of improvement and deterioration (P < .001). Different overtime courses were observed during prolonged hospitalisation according to the severity of prognosis (P < .001). CONCLUSION: A CGA-based MPI evaluation during hospitalisation can be used as an objective instrument to detect changes in multidimensional health course. Prompt identification of the latter may enable quick tailored interventions to ensure overall better outcomes at and after discharge.

Hypercholesterolaemia-induced oxidative stress at the blood-brain barrier.

Blood cholesterol levels are not consistently elevated in subjects with age-related cognitive decline, although epidemiological studies suggest that Alzheimer's disease and cardiovascular diseases share common risk factors. These include the presence of an unusual genetic variant, the APOE4 (apolipoprotein E4) allele, which modulates LDL (low-density lipoproteins) metabolism, increases free radical formation and reduces plasma antioxidant concentrations. Together, these risk factors support a mechanism for increased LDL circulation time and free radical modification of LDL. Plasma oxycholesterols, hydroxylated metabolites of cholesterol, are carried by oxidized LDL, and elevated lipids in mid-life are associated with increased long-term risk of dementia. Although brain cholesterol metabolism is segregated from the systemic circulation, during oxidative stress, plasma oxycholesterols could have damaging effects on BBB (blood-brain barrier) function and consequently on neuronal cells. Cholesterol-lowering drugs such as statins may prevent the modifications to LDL in mid-life and might show beneficial effects in later life.

Oxidized LDL lipids increase ß-amyloid production by SH-SY5Y cells through glutathione depletion and lipid raft formation.

Elevated total cholesterol in midlife has been associated with increased risk of dementia in later life. We have previously shown that low-density lipoprotein (LDL) is more oxidized in the plasma of dementia patients, although total cholesterol levels are not different from those of age-matched controls. ß-Amyloid (Aß) peptide, which accumulates in Alzheimer disease (AD), arises from the initial cleavage of amyloid precursor protein by ß-secretase-1 (BACE1). BACE1 activity is regulated by membrane lipids and raft formation. Given the evidence for altered lipid metabolism in AD, we have investigated a mechanism for enhanced Aß production by SH-SY5Y neuronal-like cells exposed to oxidized LDL (oxLDL). The viability of SH-SY5Y cells exposed to 4µg oxLDL and 25µM 27-hydroxycholesterol (27OH-C) was decreased significantly. Lipids, but not proteins, extracted from oxLDL were more cytotoxic than oxLDL. In parallel, the ratio of reduced glutathione (GSH) to oxidized glutathione was decreased at sublethal concentrations of lipids extracted from native and oxLDL. GSH loss was associated with an increase in acid sphingomyelinase (ASMase) activity and lipid raft formation, which could be inhibited by the ASMase inhibitor desipramine. 27OH-C and total lipids from LDL and oxLDL independently increased Aß production by SH-SY5Y cells, and Aß accumulation could be inhibited by desipramine and by N-acetylcysteine. These data suggest a mechanism whereby oxLDL lipids and 27OH-C can drive Aß production by GSH depletion, ASMase-driven membrane remodeling, and BACE1 activation in neuronal cells.