Do screening tools assess palliative care needs and 12-month mortality in patients admitted to hepatology in-patient wards?

BACKGROUND: Many liver patients have unmet palliative care needs, but liver clinicians are unclear whom to refer to specialist palliative care (SPC). The Supportive and Palliative Care Indicator Tool (SPICT) and the Bristol Prognostic Screening Tool (BPST) could help identify suitable patients, but neither has been tested for this role. This study evaluated their role as screening tools for palliative care needs and for predicting 12-month mortality. METHODS: A case note review of hepatology in-patients, who were not peritransplant and post-transplant status, was conducted in one tertiary unit. Main outcomes were clinical judgement of need for SPC referral, BPST scores, SPICT attribution of caseness and 12-month survival status. Discriminatory ability of tools was assessed using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the receiver operating characteristic (AUROC) curve. RESULTS: 117 medical notes were reviewed for survival analysis, 47 of which were additionally assessed for suitability for SPC referral, using clinical judgement. SPICT (sensitivity=93%; PPV=93%; AUROC=0.933) and BPST (sensitivity=59%, PPV=79%, AUROC=0.693) demonstrated excellent and good performance, respectively, in predicting patients’ need for SPC referral. SPICT and BPST only had moderate ability at predicting death at 12 months (PPV: 54% and 56%, respectively). CONCLUSION: SPICT and BPST show potential as screening tools for identifying patients for referral to SPC. Further work is needed to determine how to implement these tools in a clinical setting

Beth Levine in memoriam

Beth Levine was born on 7 April 1960 in Newark, New Jersey. She went to college at Brown University where she received an A.B. Magna Cum Laude, and she attended medical school at Cornell University Medical College, receiving her MD in 1986. She completed her internship and residency in Internal Medicine at Mount Sinai Hospital in New York, and her fellowship in Infectious Diseases at The Johns Hopkins Hospital. Most recently, Beth was a Professor of Internal Medicine and Microbiology, Director of the Center for Autophagy Research, and holder of the Charles Sprague Distinguished Chair in Biomedical Science at the University of Texas Southwestern Medical Center in Dallas. Beth died on 15 June 2020 from cancer. Beth is survived by her husband, Milton Packer, and their two children, Rachel (26 years old) and Ben (25 years old). Dr. Levine was as an international leader in the field of autophagy research. Her laboratory identified the mammalian autophagy gene BECN1/beclin 1; identified conserved mechanisms underlying the regulation of autophagy (e.g. BCL2-BECN1 complex formation, insulin-like signaling, EGFR, ERBB2/HER2 and AKT1-mediated BECN1 phosphosphorylation); and provided the first evidence that autophagy genes are important in antiviral host defense, tumor suppression, lifespan extension, apoptotic corpse clearance, metazoan development, Na,K-ATPase-regulated cell death, and the beneficial metabolic effects of exercise. She developed a potent autophagy-inducing cell permeable peptide, Tat-beclin 1, which has potential therapeutic applications in a range of diseases. She was a founding Associate Editor of the journal Autophagy and an editorial board member of Cell and Cell Host & Microbe. She has received numerous awards/honors in recognition of her scientific achievement, including: The American Cancer Society Junior Faculty Research Award (1994); election into the American Society of Clinical Investigation (2000); the Ellison Medical Foundation Senior Scholars Award in Global Infectious Diseases (2004); elected member, American Association of Physicians (2005); appointment as a Howard Hughes Medical Institute Investigator (2008); Edith and Peter O’Donnell Award in Medicine (2008); elected fellow, American Association for the Advancement of Science (2012); election into the National Academy of Sciences (2013); election into the Academy of Medicine, Engineering and Science of Texas (2013); the ASCI Stanley J. Korsmeyer Award (2014); Phyllis T. Bodel Women in Medicine Award, Yale University School of Medicine (2018); recipient, Barcroft Medal, Queen’s University Belfast (2018).Fil: An, Zhenyi. No especifíca;Fil: Ballabi, Andrea. No especifíca;Fil: Bennett, Lynda. No especifíca;Fil: Boya, Patricia. No especifíca;Fil: Cecconi, Francesco. No especifíca;Fil: Chiang, Wei Chung. No especifíca;Fil: Codogno, Patrice. No especifíca;Fil: Colombo, Maria Isabel. No especifíca;Fil: Cuervo, Ana Maria. No especifíca;Fil: Debnath, Jayanta. No especifíca;Fil: Deretic, Vojo. No especifíca;Fil: Dikic, Ivan. No especifíca;Fil: Dionne, Keith. No especifíca;Fil: Dong, Xiaonan. No especifíca;Fil: Elazar, Zvulun. No especifíca;Fil: Galluzzi, Lorenzo. No especifíca;Fil: Gentile, Frank. No especifíca;Fil: Griffin, Diane E.. No especifíca;Fil: Hansen, Malene. No especifíca;Fil: Hardwick, J. Marie. No especifíca;Fil: He, Congcong. No especifíca;Fil: Huang, Shu Yi. No especifíca;Fil: Hurley, James. No especifíca;Fil: Jackson, William T.. No especifíca;Fil: Jozefiak, Cindy. No especifíca;Fil: Kitsis, Richard N.. No especifíca;Fil: Klionsky, Daniel J.. No especifíca;Fil: Kroemer, Guido. No especifíca;Fil: Meijer, Alfred J.. No especifíca;Fil: Meléndez, Alicia. No especifíca;Fil: Melino, Gerry. No especifíca;Fil: Mizushima, Noboru. No especifíca;Fil: Murphy, Leon O.. No especifíca;Fil: Nixon, Ralph. No especifíca;Fil: Orvedahl, Anthony. No especifíca;Fil: Pattingre, Sophie. No especifíca;Fil: Piacentini, Mauro. No especifíca;Fil: Reggiori, Fulvio. No especifíca;Fil: Ross, Theodora. No especifíca;Fil: Rubinsztein, David C.. No especifíca;Fil: Ryan, Kevin. No especifíca;Fil: Sadoshima, Junichi. No especifíca;Fil: Schreiber, Stuart L.. No especifíca;Fil: Scott, Frederick. No especifíca;Fil: Sebti, Salwa. No especifíca;Fil: Shiloh, Michael. No especifíca;Fil: Shoji, Sanae. No especifíca;Fil: Simonsen, Anne. No especifíca;Fil: Smith, Haley. No especifíca;Fil: Sumpter, Kathryn M.. No especifíca;Fil: Thompson, Craig B.. No especifíca;Fil: Thorburn, Andrew. No especifíca;Fil: Thumm, Michael. No especifíca;Fil: Tooze, Sharon. No especifíca;Fil: Vaccaro, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Virgin, Herbert W.. No especifíca;Fil: Wang, Fei. No especifíca;Fil: White, Eileen. No especifíca;Fil: Xavier, Ramnik J.. No especifíca;Fil: Yoshimori, Tamotsu. No especifíca;Fil: Yuan, Junying. No especifíca;Fil: Yue, Zhenyu. No especifíca;Fil: Zhong, Qing. No especifíca

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Improving Communication in Outpatient Consultations in People With Cirrhosis: The Development of a Question Prompt List (QPL)

Background and Aims: Liver health professionals have difficulty discussing liver cirrhosis and its prognosis with patients and families. Question Prompt Lists (QPLs), which are evidence-based lists of “recommended questions,” may improve communication but need to be designed specifically for the target population. This study aimed to develop and pilot a QPL for patients with cirrhosis. Methods: A mixed-methods design in 3 phases. In phase 1 (item generation), potential questions for inclusion in the QPL were identified from 3 sources—a scoping literature review; an online survey; and interviews with patients, family members, and health professionals. In phase 2 (QPL construction), a multidisciplinary expert panel finalized the selection of questions and the format of the QPL. In phase 3 (pilot study), the QPL was assessed for acceptability and feasibility in a hepatology outpatient clinic population. Results: From 258 topics initially identified, 30 questions were included in the first draft of the QPL. After review by a multidisciplinary expert panel including patients, the QPL was reduced to 22 questions. In the pilot study, 133/215 eligible patients consented to participate, although only 67/133 used the QPL in their clinic appointment. Among those who used the QPL, all questions were asked at least once. The most commonly asked question related to life expectancy. Most participants expressed support for the content of the QPL. Conclusions: A QPL, suitable for use in patients with liver cirrhosis attending hepatology outpatient clinics, has been developed and piloted. The QPL seems to be feasible to use and acceptable to patients and clinicians. Further work is needed to evaluate its effectiveness and to determine optimum delivery in clinical practice

Evidence of historical isolation and genetic structuring among broadnose sevengill sharks (Notorynchus cepedianus) from the world’s major oceanic regions

Cosmopolitan marine pelagic species display variable patterns of population connectivity among the world’s major oceans. While this information is crucial for informing management, information is lacking for many ecologically important species, including apex predators. In this study we examine patterns of genetic structure in the broadnose sevengill shark, Notorynchus cepedianus across its global distribution. We estimate patterns of connectivity among broadnose sevengill shark populations from three major oceanic regions (South Atlantic, Oceania and Eastern Pacific) by contrasting mitochondrial and nuclear DNA haplotype frequencies. We also produced time calibrated Bayesian Inference phylogenetic reconstructions to analyses global phylogeographic patterns and estimate divergence times among distinctive shark lineages. Our results demonstrate significant genetic differentiation among oceanic regions (ΦST = 0.9789, P \u3c 0.0001) and a lack of genetic structuring within regions (ΦST = − 0.007; P = 0.479). Time calibrated Bayesian Inference phylogenetic reconstructions indicate that the observed patterns of genetic structure among oceanic regions are historical, with regional populations estimated to have diverged from a common ancestor during the early to mid-Pleistocene. Our results indicate significant genetic structuring and a lack of gene flow among broadnose sevengill shark populations from the South Atlantic, Oceania and Eastern Pacific regions. Evidence of deep lineage divergences coinciding with the early to mid-Pleistocene suggests historical glacial cycling has contributed to the vicariant divergence of broadnose sevengill shark populations from different ocean basins. These finding will help inform global management of broadnose sevengill shark populations, and provides new insights into historical and contemporary evolutionary processes shaping populations of this ecologically important apex predator

Evidence of historical isolation and genetic structuring among broadnose sevengill sharks (Notorynchus cepedianus) from the world’s major oceanic regions

Cosmopolitan marine pelagic species display variable patterns of population connectivity among the world’s major oceans. While this information is crucial for informing management, information is lacking for many ecologically important species, including apex predators. In this study we examine patterns of genetic structure in the broadnose sevengill shark, Notorynchus cepedianus across its global distribution. We estimate patterns of connectivity among broadnose sevengill shark populations from three major oceanic regions (South Atlantic, Oceania and Eastern Pacific) by contrasting mitochondrial and nuclear DNA haplotype frequencies. We also produced time calibrated Bayesian Inference phylogenetic reconstructions to analyses global phylogeographic patterns and estimate divergence times among distinctive shark lineages. Our results demonstrate significant genetic differentiation among oceanic regions (ΦST = 0.9789, P < 0.0001) and a lack of genetic structuring within regions (ΦST = − 0.007; P = 0.479). Time calibrated Bayesian Inference phylogenetic reconstructions indicate that the observed patterns of genetic structure among oceanic regions are historical, with regional populations estimated to have diverged from a common ancestor during the early to mid-Pleistocene. Our results indicate significant genetic structuring and a lack of gene flow among broadnose sevengill shark populations from the South Atlantic, Oceania and Eastern Pacific regions. Evidence of deep lineage divergences coinciding with the early to mid-Pleistocene suggests historical glacial cycling has contributed to the vicariant divergence of broadnose sevengill shark populations from different ocean basins. These finding will help inform global management of broadnose sevengill shark populations, and provides new insights into historical and contemporary evolutionary processes shaping populations of this ecologically important apex predator