No abstract

Context-Many clinical disciplines report high rates of burnout, which lead to low quality of care. Palliative care clinicians routinely manage patients with significant suffering, aiming to improve quality of life. As a major role of palliative care clinicians involves educating patients and caregivers regarding identifying priorities and balancing stress, we wondered how clinician selfmanagement of burnout matches against the emotionally exhaustive nature of the work. Objectives-We sought to understand the prevalence and predictors of burnout using a discipline-wide survey. Methods-We asked American Academy of Hospice and Palliative Medicine clinician members to complete an electronic survey querying demographic factors, job responsibilities, and the Maslach Burnout Inventory. We performed univariate and multivariate regression analyses to identify predictors of high rates of burnout. Results-We received 1357 responses (response rate 30%). Overall, we observed a burnout rate of 62%, with higher rates reported by nonphysician clinicians. Most burnout stemmed from emotional exhaustion, with depersonalization comprising a minor portion. Factors associated with higher rates of burnout include working in smaller organizations, working longer hours, being younger than 50 years, and working weekends. We did not observe different rates between palliative care clinicians and hospice clinicians. Higher rated self-management activities to mitigate burnout include participating in interpersonal relationships and taking vacations.

BACKGROUNDThe specialty of palliative care has experienced remarkable acceptance over the last decade, with teams present in 85% of medium/large hospitals in the US. 1 For many serious illnesses like cancer, advanced heart disease, stroke, and chronic obstructive pulmonary disease, routine integration of palliative care is considered standard of care.

Specialized palliative care teams improve outcomes for the steadily growing population of people living with serious illness. However, few studies have examined whether the specialty palliative care workforce can meet the growing demand for its services. We used 2018 clinician survey data to model risk factors associated with palliative care clinicians leaving the field early, and we then projected physician numbers from 2019 to 2059 under four scenarios. Our modeling revealed an impending "workforce valley," with declining physician numbers that will not recover to the current level until 2045, absent policy change. However, sustained growth in the number of fellowship positions over ten years could reverse the worsening workforce shortage. There is an immediate need for policies that support high-value, team-based palliative care through expansion in all segments of the specialty palliative care workforce, combined with payment reform to encourage the deployment of sustainable teams.

Background/Aims: Clusterin (CLU), also known as Apolipoprotein J (ApoJ) is a highly glycosylated extracellular chaperone. In humans it is expressed from a broad spectrum of tissues and related to a plethora of physiological and pathophysiological processes, such as Alzheimer's disease, atherosclerosis and cancer. In its dominant form it is expressed as a secretory protein (secreted CLU, sCLU). During its maturation, the sCLU-precursor is N-glycosylated and cleaved into an α- and a β-chain, which are connected by five symmetrical disulfide bonds. Recently, it has been demonstrated that besides the predominant sCLU, rare intracellular CLU forms are expressed in stressed cells. Since these forms do not enter or complete the secretory pathway, they are not proteolytically modified and show either no or only core glycosylation. Due to their sparsity, these intracellular forms are functionally poorly characterized. To evaluate the function(s) of these stress-related intracellular forms, we investigate for the first time the impact of proteolytic cleavage, differential glycosylation and the influence of the redox environment on the chaperone activity of CLU. Methods: Non-cleavable sCLU was generated by expression from a mutant construct of sCLU, in which the furin-like proprotein convertase (PC) recognition site was modified. After purification of recombinant uncleaved sCLU from the medium of over-expressing cells, we performed chaperone activity assays to compare the activities of wild-type (cleaved) and uncleaved mutant sCLU. Additionally, this approach enabled us to investigate the role of carbohydrates, the proteolytic maturation and reducing conditions on CLU chaperone activity. Further, we characterized the differentially treated CLU forms by using MALDI-TOF, CD-spectroscopy and Western blotting in addition to the functional assay. Results: We show that the PC-cleavage is dispensable for sCLU chaperone activity. Moreover, our data demonstrate that while fully deglycosylated sCLU lacks chaperone activity, partially deglycosylated sCLU is still capable of solubilizing target proteins. Most importantly, we here demonstrate for the first time that uncleaved sCLU is highly sensitive towards reducing conditions. Conclusions: Our study provides evidence that unglycosylated intracellular CLU forms cannot exhibit a chaperone activity compared to sCLU. Additionally, we support recent postulates that glycosylated intracellular CLU forms may act as a redox sensor under oxidative stress conditions. Furthermore, we conclude that the proteolytic cleavage of sCLU is important to maintain full chaperone activity, i.e. in the presence of necrosis.

Patients with COPD, ESRD, and HF were less functional and more likely to be hospitalized at time of referral to palliative care than cancer patients. These findings may be reflective of the slower and more varied trajectory of non-cancer serious illness. One aim of palliative care for those with non-cancer severe illness should be directed toward improving and assisting with functionality and decreasing frequency of hospital admissions. These interventions could take place in the palliative care office, but could also be integrated into hospital discharge plans.

Patients with chronic lung disease have symptom burdens similar to those of patients with lung cancer at the time of first palliative care encounter. Given the population burden of chronic lung disease and limitations in the palliative care workforce, attention should be focused on ensuring that pulmonologists are prepared to assess and manage the common palliative care needs of patients with chronic lung disease.

A biocatalytic cascade for the analysis of the simultaneous increase in the concentration of two biomarkers characteristic of liver injury (alanine transaminase, ALT, and lactate dehydrogenase, LDH) was tested on real samples acquired from an animal model (domestic pigs, Sus scrofa domesticus) suffering from traumatic liver injury. A two-step reaction biocatalyzed in the presence of both enzyme-biomarkers resulted in the oxidation of NADH followed by optical absorbance measurements. A simple qualitative, YES/NO, test allowed for distinction between animals with and without the presence of liver injury with the probability of 92%. These data represent the first demonstration of applying binary logic systems for the analysis of real biomedical samples.