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Additional file 1.

Tables for bivariate associations between demographic variables, burnout, and resilience

Survey information sheet and questions, excluding copyrighted instruments

Supplemental material, sj-pdf-2-pmj-10.1177_02692163221081331 for Symptom burden and lived experiences of patients, caregivers and healthcare professionals on the management of malignant bowel obstruction: A qualitative systematic review by Elin Baddeley, Mala Mann, Alison Bravington, Miriam J Johnson, David Currow, Fliss E M Murtagh, Elaine G Boland, George Obita, Alfred Oliver, Kathy Seddon, Annmarie Nelson, Jason W Boland and Simon I R Noble in Palliative Medicine

Supplemental material, sj-pdf-4-pmj-10.1177_02692163221122352 for The range and suitability of outcome measures used in the assessment of palliative treatment for inoperable malignant bowel obstruction: A systematic review by Alison Bravington, George Obita, Elin Baddeley, Miriam J Johnson, Fliss EM Murtagh, David C Currow, Elaine G Boland, Annmarie Nelson, Kathy Seddon, Alfred Oliver, Simon IR Noble and Jason W Boland in Palliative Medicine

Supplemental material, sj-pdf-3-pmj-10.1177_02692163221122352 for The range and suitability of outcome measures used in the assessment of palliative treatment for inoperable malignant bowel obstruction: A systematic review by Alison Bravington, George Obita, Elin Baddeley, Miriam J Johnson, Fliss EM Murtagh, David C Currow, Elaine G Boland, Annmarie Nelson, Kathy Seddon, Alfred Oliver, Simon IR Noble and Jason W Boland in Palliative Medicine

Supplemental material, sj-pdf-2-pmj-10.1177_02692163221122352 for The range and suitability of outcome measures used in the assessment of palliative treatment for inoperable malignant bowel obstruction: A systematic review by Alison Bravington, George Obita, Elin Baddeley, Miriam J Johnson, Fliss EM Murtagh, David C Currow, Elaine G Boland, Annmarie Nelson, Kathy Seddon, Alfred Oliver, Simon IR Noble and Jason W Boland in Palliative Medicine

Supplemental material, sj-pdf-1-pmj-10.1177_02692163221122352 for The range and suitability of outcome measures used in the assessment of palliative treatment for inoperable malignant bowel obstruction: A systematic review by Alison Bravington, George Obita, Elin Baddeley, Miriam J Johnson, Fliss EM Murtagh, David C Currow, Elaine G Boland, Annmarie Nelson, Kathy Seddon, Alfred Oliver, Simon IR Noble and Jason W Boland in Palliative Medicine

Supplemental material, sj-pdf-1-pmj-10.1177_02692163221081331 for Symptom burden and lived experiences of patients, caregivers and healthcare professionals on the management of malignant bowel obstruction: A qualitative systematic review by Elin Baddeley, Mala Mann, Alison Bravington, Miriam J Johnson, David Currow, Fliss E M Murtagh, Elaine G Boland, George Obita, Alfred Oliver, Kathy Seddon, Annmarie Nelson, Jason W Boland and Simon I R Noble in Palliative Medicine

Supplemental material, sj-pdf-1-pmj-10.1177_02692163221122352 for The range and suitability of outcome measures used in the assessment of palliative treatment for inoperable malignant bowel obstruction: A systematic review by Alison Bravington, George Obita, Elin Baddeley, Miriam J Johnson, Fliss EM Murtagh, David C Currow, Elaine G Boland, Annmarie Nelson, Kathy Seddon, Alfred Oliver, Simon IR Noble and Jason W Boland in Palliative Medicine

Supplemental material, sj-pdf-4-pmj-10.1177_02692163221122352 for The range and suitability of outcome measures used in the assessment of palliative treatment for inoperable malignant bowel obstruction: A systematic review by Alison Bravington, George Obita, Elin Baddeley, Miriam J Johnson, Fliss EM Murtagh, David C Currow, Elaine G Boland, Annmarie Nelson, Kathy Seddon, Alfred Oliver, Simon IR Noble and Jason W Boland in Palliative Medicine

Supplemental material, sj-pdf-2-pmj-10.1177_02692163221122352 for The range and suitability of outcome measures used in the assessment of palliative treatment for inoperable malignant bowel obstruction: A systematic review by Alison Bravington, George Obita, Elin Baddeley, Miriam J Johnson, Fliss EM Murtagh, David C Currow, Elaine G Boland, Annmarie Nelson, Kathy Seddon, Alfred Oliver, Simon IR Noble and Jason W Boland in Palliative Medicine

Supplemental material, sj-pdf-1-pmj-10.1177_02692163221081331 for Symptom burden and lived experiences of patients, caregivers and healthcare professionals on the management of malignant bowel obstruction: A qualitative systematic review by Elin Baddeley, Mala Mann, Alison Bravington, Miriam J Johnson, David Currow, Fliss E M Murtagh, Elaine G Boland, George Obita, Alfred Oliver, Kathy Seddon, Annmarie Nelson, Jason W Boland and Simon I R Noble in Palliative Medicine

Supplemental material, sj-pdf-3-pmj-10.1177_02692163221081331 for Symptom burden and lived experiences of patients, caregivers and healthcare professionals on the management of malignant bowel obstruction: A qualitative systematic review by Elin Baddeley, Mala Mann, Alison Bravington, Miriam J Johnson, David Currow, Fliss E M Murtagh, Elaine G Boland, George Obita, Alfred Oliver, Kathy Seddon, Annmarie Nelson, Jason W Boland and Simon I R Noble in Palliative Medicine

Supplemental material, sj-pdf-3-pmj-10.1177_02692163221122352 for The range and suitability of outcome measures used in the assessment of palliative treatment for inoperable malignant bowel obstruction: A systematic review by Alison Bravington, George Obita, Elin Baddeley, Miriam J Johnson, Fliss EM Murtagh, David C Currow, Elaine G Boland, Annmarie Nelson, Kathy Seddon, Alfred Oliver, Simon IR Noble and Jason W Boland in Palliative Medicine

Supplemental material, sj-pdf-3-pmj-10.1177_02692163221081331 for Symptom burden and lived experiences of patients, caregivers and healthcare professionals on the management of malignant bowel obstruction: A qualitative systematic review by Elin Baddeley, Mala Mann, Alison Bravington, Miriam J Johnson, David Currow, Fliss E M Murtagh, Elaine G Boland, George Obita, Alfred Oliver, Kathy Seddon, Annmarie Nelson, Jason W Boland and Simon I R Noble in Palliative Medicine

Supplemental material, sj-pdf-2-pmj-10.1177_02692163221081331 for Symptom burden and lived experiences of patients, caregivers and healthcare professionals on the management of malignant bowel obstruction: A qualitative systematic review by Elin Baddeley, Mala Mann, Alison Bravington, Miriam J Johnson, David Currow, Fliss E M Murtagh, Elaine G Boland, George Obita, Alfred Oliver, Kathy Seddon, Annmarie Nelson, Jason W Boland and Simon I R Noble in Palliative Medicine

BACKGROUND: Delirium is a distressing neuropsychiatric disorder affecting patients in palliative care. Although many delirium screening tools exist, their utility, and validation within palliative care settings has not undergone systematic review. AIM: To systematically review studies that validate delirium screening tools conducted in palliative care settings. DESIGN: Systematic review with narrative synthesis (PROSPERO ID: CRD42019125481). A risk of bias assessment via Quality Assessment Tool for Diagnostic Accuracy Studies-2 was performed. DATA SOURCES: Five electronic databases were systematically searched (January 1, 1982-May 3, 2020). Quantitative studies validating a screening tool in adult palliative care patient populations were included. Studies involving alcohol withdrawal, critical or perioperative care were excluded. RESULTS: Dual-reviewer screening of 3749 unique titles and abstracts identified 95 studies for full-text review and of these, 17 studies of 14 screening tools were included (n = 3496 patients). Data analyses revealed substantial heterogeneity in patient demographics and variability in screening and diagnostic practices that limited generalizability between study populations and care settings. A risk of bias assessment revealed methodological and reporting deficits, with only 3/17 studies at low risk of bias. CONCLUSIONS: The processes of selecting a delirium screening tool and determining optimal screening practices in palliative care are complex. One tool is unlikely to fit the needs of the entire palliative care population across all palliative care settings. Further research should be directed at evaluating and/or adapting screening tools and practices to fit the needs of specific palliative care settings and populations.

Background: Performance status, a predictor of cancer survival, and ability to maintain independent living deteriorate in advanced disease. Understanding predictors of performance status trajectory could help identify those at risk of functional deterioration, target support for independent living and reduce service costs. The relationship between symptoms, analgesics and performance status is poorly delineated. Aim: The aim of this study is to determine whether demographics, analgesics, disease characteristics, quality-of-life domains and C-reactive protein predict the trajectory of Karnofsky Performance Status (KPS) in patients with advanced cancer. Design: The study design is the secondary data analysis of the international prospective, longitudinal European Palliative Care Cancer Symptom study (ClinicalTrials.gov: NCT01362816). A multivariable regression model was built for KPS area under the curve per day (AUC). Setting and participants: This included adults with advanced, incurable cancer receiving palliative care, without severe cognitive impairment and who were not imminently dying (n = 1739). Results: The mean daily KPS AUC (n = 1052) was 41.1 (standard deviation = 14.1). Opioids (p < 0.001), co-analgesics (p = 0.023), poorer physical functioning (p < 0.001) and appetite loss (p = 0.009) at baseline were explanatory factors for lower KPS AUC. A subgroup analysis of participants with C-reactive protein data (n = 240) showed that only C-reactive protein (p = 0.040) and physical function (p < 0.001) were associated with lower KPS AUC. Conclusion: This study is novel in determining explanatory factors for subsequent functional trajectories in an international dataset and identifying systemic inflammation as a candidate therapeutic target to improve functional performance. The effect of interventions targeting physical function, appetite and inflammation, such as those used for cachexia management, on maintaining functional status in patients with advanced cancer needs to be investigated.

Supplemental material, sj-pdf-3-pmj-10.1177_02692163211065278 for Risk factors for delirium in adult patients receiving specialist palliative care: A systematic review and meta-analysis by Imogen Featherstone, Trevor Sheldon, Miriam Johnson, Rebecca Woodhouse, Jason W Boland, Annmarie Hosie, Peter Lawlor, Gregor Russell, Shirley Bush and Najma Siddiqi in Palliative Medicine

Supplemental material, sj-docx-2-pmj-10.1177_0269216321994730 for Delirium screening tools validated in the context of palliative care: A systematic review by Christine L Watt, Mary Scott, Colleen Webber, Lindsey Sikora, Shirley H Bush, Monisha Kabir, Jason W Boland, Rebecca Woodhouse, Megan B Sands and Peter G Lawlor in Palliative Medicine

Supplemental material, sj-pdf-4-pmj-10.1177_02692163211065278 for Risk factors for delirium in adult patients receiving specialist palliative care: A systematic review and meta-analysis by Imogen Featherstone, Trevor Sheldon, Miriam Johnson, Rebecca Woodhouse, Jason W Boland, Annmarie Hosie, Peter Lawlor, Gregor Russell, Shirley Bush and Najma Siddiqi in Palliative Medicine

Supplemental material, sj-docx-1-pmj-10.1177_0269216321994730 for Delirium screening tools validated in the context of palliative care: A systematic review by Christine L Watt, Mary Scott, Colleen Webber, Lindsey Sikora, Shirley H Bush, Monisha Kabir, Jason W Boland, Rebecca Woodhouse, Megan B Sands and Peter G Lawlor in Palliative Medicine

Supplemental material, sj-docx-1-pmj-10.1177_0269216321994730 for Delirium screening tools validated in the context of palliative care: A systematic review by Christine L Watt, Mary Scott, Colleen Webber, Lindsey Sikora, Shirley H Bush, Monisha Kabir, Jason W Boland, Rebecca Woodhouse, Megan B Sands and Peter G Lawlor in Palliative Medicine

Supplemental material, sj-pdf-2-pmj-10.1177_02692163211065278 for Risk factors for delirium in adult patients receiving specialist palliative care: A systematic review and meta-analysis by Imogen Featherstone, Trevor Sheldon, Miriam Johnson, Rebecca Woodhouse, Jason W Boland, Annmarie Hosie, Peter Lawlor, Gregor Russell, Shirley Bush and Najma Siddiqi in Palliative Medicine

Supplemental material, sj-pdf-5-pmj-10.1177_02692163211065278 for Risk factors for delirium in adult patients receiving specialist palliative care: A systematic review and meta-analysis by Imogen Featherstone, Trevor Sheldon, Miriam Johnson, Rebecca Woodhouse, Jason W Boland, Annmarie Hosie, Peter Lawlor, Gregor Russell, Shirley Bush and Najma Siddiqi in Palliative Medicine

Supplemental material, sj-pdf-1-pmj-10.1177_02692163211065278 for Risk factors for delirium in adult patients receiving specialist palliative care: A systematic review and meta-analysis by Imogen Featherstone, Trevor Sheldon, Miriam Johnson, Rebecca Woodhouse, Jason W Boland, Annmarie Hosie, Peter Lawlor, Gregor Russell, Shirley Bush and Najma Siddiqi in Palliative Medicine

Supplemental material, sj-pdf-6-pmj-10.1177_02692163211065278 for Risk factors for delirium in adult patients receiving specialist palliative care: A systematic review and meta-analysis by Imogen Featherstone, Trevor Sheldon, Miriam Johnson, Rebecca Woodhouse, Jason W Boland, Annmarie Hosie, Peter Lawlor, Gregor Russell, Shirley Bush and Najma Siddiqi in Palliative Medicine

Supplemental material, sj-pdf-5-pmj-10.1177_02692163211065278 for Risk factors for delirium in adult patients receiving specialist palliative care: A systematic review and meta-analysis by Imogen Featherstone, Trevor Sheldon, Miriam Johnson, Rebecca Woodhouse, Jason W Boland, Annmarie Hosie, Peter Lawlor, Gregor Russell, Shirley Bush and Najma Siddiqi in Palliative Medicine

Supplemental material, sj-pdf-7-pmj-10.1177_02692163211065278 for Risk factors for delirium in adult patients receiving specialist palliative care: A systematic review and meta-analysis by Imogen Featherstone, Trevor Sheldon, Miriam Johnson, Rebecca Woodhouse, Jason W Boland, Annmarie Hosie, Peter Lawlor, Gregor Russell, Shirley Bush and Najma Siddiqi in Palliative Medicine

Supplemental material, sj-pdf-4-pmj-10.1177_02692163211065278 for Risk factors for delirium in adult patients receiving specialist palliative care: A systematic review and meta-analysis by Imogen Featherstone, Trevor Sheldon, Miriam Johnson, Rebecca Woodhouse, Jason W Boland, Annmarie Hosie, Peter Lawlor, Gregor Russell, Shirley Bush and Najma Siddiqi in Palliative Medicine

Supplemental material, sj-pdf-8-pmj-10.1177_02692163211065278 for Risk factors for delirium in adult patients receiving specialist palliative care: A systematic review and meta-analysis by Imogen Featherstone, Trevor Sheldon, Miriam Johnson, Rebecca Woodhouse, Jason W Boland, Annmarie Hosie, Peter Lawlor, Gregor Russell, Shirley Bush and Najma Siddiqi in Palliative Medicine

Supplemental material, sj-pdf-8-pmj-10.1177_02692163211065278 for Risk factors for delirium in adult patients receiving specialist palliative care: A systematic review and meta-analysis by Imogen Featherstone, Trevor Sheldon, Miriam Johnson, Rebecca Woodhouse, Jason W Boland, Annmarie Hosie, Peter Lawlor, Gregor Russell, Shirley Bush and Najma Siddiqi in Palliative Medicine

Supplemental material, sj-docx-2-pmj-10.1177_0269216321994730 for Delirium screening tools validated in the context of palliative care: A systematic review by Christine L Watt, Mary Scott, Colleen Webber, Lindsey Sikora, Shirley H Bush, Monisha Kabir, Jason W Boland, Rebecca Woodhouse, Megan B Sands and Peter G Lawlor in Palliative Medicine

Supplemental material, sj-pdf-7-pmj-10.1177_02692163211065278 for Risk factors for delirium in adult patients receiving specialist palliative care: A systematic review and meta-analysis by Imogen Featherstone, Trevor Sheldon, Miriam Johnson, Rebecca Woodhouse, Jason W Boland, Annmarie Hosie, Peter Lawlor, Gregor Russell, Shirley Bush and Najma Siddiqi in Palliative Medicine

Supplemental material, sj-pdf-3-pmj-10.1177_02692163211065278 for Risk factors for delirium in adult patients receiving specialist palliative care: A systematic review and meta-analysis by Imogen Featherstone, Trevor Sheldon, Miriam Johnson, Rebecca Woodhouse, Jason W Boland, Annmarie Hosie, Peter Lawlor, Gregor Russell, Shirley Bush and Najma Siddiqi in Palliative Medicine

Supplemental material, sj-pdf-1-pmj-10.1177_02692163211065278 for Risk factors for delirium in adult patients receiving specialist palliative care: A systematic review and meta-analysis by Imogen Featherstone, Trevor Sheldon, Miriam Johnson, Rebecca Woodhouse, Jason W Boland, Annmarie Hosie, Peter Lawlor, Gregor Russell, Shirley Bush and Najma Siddiqi in Palliative Medicine

Supplemental material, sj-pdf-2-pmj-10.1177_02692163211065278 for Risk factors for delirium in adult patients receiving specialist palliative care: A systematic review and meta-analysis by Imogen Featherstone, Trevor Sheldon, Miriam Johnson, Rebecca Woodhouse, Jason W Boland, Annmarie Hosie, Peter Lawlor, Gregor Russell, Shirley Bush and Najma Siddiqi in Palliative Medicine

Supplemental material, sj-pdf-6-pmj-10.1177_02692163211065278 for Risk factors for delirium in adult patients receiving specialist palliative care: A systematic review and meta-analysis by Imogen Featherstone, Trevor Sheldon, Miriam Johnson, Rebecca Woodhouse, Jason W Boland, Annmarie Hosie, Peter Lawlor, Gregor Russell, Shirley Bush and Najma Siddiqi in Palliative Medicine

Objectives: There is increased interest in cannabinoids for cancer pain management and legislative changes are in progress in many countries. This study aims to determine the beneficial and adverse effects of cannabis/cannabinoids compared with placebo/other active agents for the treatment of cancer-related pain in adults. Methods: Systematic review and meta-analysis to identify randomised controlled trials of cannabinoids compared with placebo/other active agents for the treatment of cancer-related pain in adults to determine the effect on pain intensity (primary outcome) and adverse effects, including dropouts. Searches included Embase, MEDLINE, PsycINFO, Web of Science, ClinicalTrials.gov, Cochrane and grey literature. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Results: We identified 2805 unique records, of which six randomised controlled trials were included in this systematic review (n=1460 participants). Five studies were included in the meta-analysis (1442 participants). All had a low risk of bias. There was no difference between cannabinoids and placebo for the difference in the change in average Numeric Rating Scale pain scores (mean difference -0.21 (-0.48 to 0.07, p=0.14)); this remained when only phase III studies were meta-analysed: mean difference -0.02 (-0.21 to 0.16, p=0.80). Cannabinoids had a higher risk of adverse events when compared with placebo, especially somnolence (OR 2.69 (1.54 to 4.71), p

Supplemental material, Chapman_Supplementary_File_2_R1 for Practice review: Evidence-based and effective management of pain in patients with advanced cancer by Emma J Chapman, Zoe Edwards, Jason W Boland, Matthew Maddocks, Lucy Fettes, Catherine Malia, Matthew R Mulvey and Michael I Bennett in Palliative Medicine

Supplemental material, sj-pdf-1-pmj-10.1177_0269216320972049 for Implementing person-centred outcome measures in palliative care: An exploratory qualitative study using Normalisation Process Theory to understand processes and context by Andy Bradshaw, Martina Santarelli, Malene Mulderrig, Assem Khamis, Kathryn Sartain, Jason W. Boland, Michael I. Bennett, Miriam Johnson, Mark Pearson and Fliss E. M. Murtagh in Palliative Medicine

Supplemental material, Chapman_Supplementary_File_1_R1 for Practice review: Evidence-based and effective management of pain in patients with advanced cancer by Emma J Chapman, Zoe Edwards, Jason W Boland, Matthew Maddocks, Lucy Fettes, Catherine Malia, Matthew R Mulvey and Michael I Bennett in Palliative Medicine

Alina Buture,1 Jason W Boland,2 Fayyaz Ahmed,1,3 Lisa Dikomitis4,51Hull York Medical School, University of Hull, Hull, UK; 2Wolfson Palliative Care Research Centre, Hull York Medical School, University of Hull, Hull, UK; 3Department of Neurology, Hull Royal Infirmary, Hull, UK; 4School of Medicine, Keele University, Newcastle-under-Lyme, UK; 5School of Primary, Community and Social Care, Keele University, Newcastle-under-Lyme, UKCorrespondence: Alina ButureHull York Medical School, University of Hull, Cottingham Road, Hull HU6 7RX, UKTel +44 745 987 2950Email hyab20@hyms.ac.ukIntroduction and objective: The diagnosis of primary headaches is based on the International Classification of Headache Disorders (ICHD-3). Cluster headache (CH), a debilitating primary headache, is often misdiagnosed as migraine. In the absence of biological markers, a new visual screening tool with images depicting pain could aid the correct diagnosis of CH. The objective of the study is to test the tool on healthy participants and participants with CH and migraine.Methods: In phase 1, 6 images portraying people with pain were tested on 150 healthy participants. The healthy participants were asked to rate the images as mild, moderate, severe or excruciating pain. In phase 2, the images were further tested on 116 participants with headache (16 participants with CH, 100 participants with migraine). The participants were recruited prospectively from a tertiary headache center between February and May 2017. The participants were asked to choose which image best illustrated their headache attacks.Results: Phase 1 results showed that the images represent a range of headache pain severities from mild to excruciating as rated by healthy participants. They rated two images as excruciating, one image as severe, one image as moderate/severe, one image as moderate and one image as mild. Phase 2 results showed that two-thirds of participants with CH (69%) and half of the participants with migraine (52%) chose an image described as excruciating by the healthy participants.Conclusion: We developed a screening tool with six drawings depicting headache pain severities from mild to excruciating as rated by the healthy participants. Although the images did not differentiate between CH and migraine, the study indicated the potential of using visual aids to assess headache severity.Keywords: drawings, migraine, screening tool, diagnosis, visual, pictures, excruciating

Alina Buture,1,2 Jason W Boland,2 Lisa Dikomitis,3 Fayyaz Ahmed1,2 1Department of Neurology, Hull Royal Infirmary, Hull, UK; 2Hull York Medical School, University of Hull, Hull, UK; 3School of Medicine and Institute of Primary Care and Health Sciences, Keele University, Newcastle, UK Objective: Cluster headache (CH) is the most severe primary headache condition. Its pathophysiology is multifaceted and incompletely understood. This review brings together the latest neuroimaging and neuropeptide evidence on the pathophysiology of CH.Methods: A review of the literature was conducted by searching PubMed and Web of Science. The search was conducted using the following keywords: imaging studies, voxel-based morphometry, diffusion-tensor imaging, diffusion magnetic resonance imaging, tractography, connectivity, cerebral networks, neuromodulation, central modulation, deep brain stimulation, orexin-A, orexin-B, tract-based spatial statistics, single-photon emission computer tomography studies, positron-emission tomography, functional magnetic resonance imaging, magnetic resonance spectroscopy, trigeminovascular system, neuropeptides, calcitonin gene-related peptide, neurokinin A, substance P, nitric oxide synthase, pituitary adenylate cyclase-activating peptide, vasoactive intestinal peptide, neuropeptide Y, acetylcholine, noradrenaline, and ATP. “Cluster headache” was combined with each keyword for more relevant results. All irrelevant and duplicated records were excluded. Search dates were from October 1976 to May 2018.Results: Neuroimaging studies support the role of the hypothalamus in CH, as well as other brain areas involved in the pain matrix. Activation of the trigeminovascular system and the release of neuropeptides play an important role in CH pathophysiology. Among neuropeptides, calcitonin gene-related peptide, vasoactive intestinal peptide, and pituitary adenylate cyclase-activating peptide have been reported to be reliable biomarkers for CH attacks, though not specific for CH. Several other neuropeptides are involved in trigeminovascular activation, but the current evidence does not qualify them as reliable biomarkers in CH.Conclusion: CH has a complex pathophysiology and the pain mechanism is not completely understood. Recent neuroimaging studies have provided insight into the functional and structural network bases of CH pathophysiology. Although there has been important progress in neuropeptide studies, a specific biomarker for CH is yet to be found. Keywords: voxel-based morphometry, single-photon emission computer tomography, positron-emission tomography, functional magnetic resonance imaging, calcitonin gene-related peptide, pituitary adenylate cyclase-activating peptide&nbsp

Supplemental material, pmj_supp_mat for Online training improves medical students’ ability to recognise when a person is dying: The ORaClES randomised controlled trial by Nicola White, Linda JM Oostendorp, Christopher Tomlinson, Sarah Yardley, Federico Ricciardi, Hülya Gökalp, Ollie Minton, Jason W Boland, Ben Clark, Priscilla Harries and Patrick Stone in Palliative Medicine

Background: Morphine can cause central nervous system side effects which impair driving skills. The legal blood morphine concentration limit for driving is 20 µg/L in France/Poland/Netherlands and 80 µg/L in England/Wales. There is no guidance as to the morphine dose leading to this concentration. Aim: The in silico (computed) relationship of oral morphine dose and plasma concentration was modelled to provide dose estimates for a morphine plasma concentration above 20 and 80 µg/L in different patient groups. Design: A dose–concentration model for different genders, ages and oral morphine formulations, validated against clinical pharmacokinetic data, was generated using Simcyp®, a population-based pharmacokinetic simulator. Setting/participants: Healthy Northern European population parameters were used with age, gender and renal function being varied in the different simulation groups. In total, 36,000 simulated human subjects (100 per modelled group of different ages and gender) received repeated simulated morphine dosing with modified-release or immediate-release formulations. Results: Older age, women, modified-release formulation and worse renal function were associated with higher plasma concentrations. Across all groups, morphine doses below 20 mg/day were unlikely to result in a morphine plasma concentration above 20 µg/L; this was 80 mg/day with the 80 µg/L limit. Conclusion: This novel study provides predictions of the in silico (computed) dose–concentration relationship for international application. Individualised morphine prescribing decisions by clinicians must be informed by clinical judgement considering the individual patient’s level of impairment and insight irrespective of the blood morphine concentration as people who have impaired driving will be breaking the law. Taking into account expected morphine concentrations enables improved individualised decision making.

Supplemental material, Supplementary_Figure_2 for In silico (computed) modelling of doses and dosing regimens associated with morphine levels above international legal driving limits by Jason W Boland, Miriam Johnson, Diana Ferreira and David J Berry in Palliative Medicine

Source at https://doi.org/10.1186/s12904-018-0362-9. Licensed CC BY-NC-ND 4.0. Background: Radiation therapy (RT) results in pain relief for about 6 of 10 patients with cancer induced bone pain (CIBP) caused by bone metastases. The high number of non-responders, the long median time from RT to pain response and the risk of adverse effects, makes it important to determine predictors of treatment response. Clinical features such as cancer type, performance status and pain intensity, and biomarkers for osteoclast activity are proposed as predictors of response to RT. However, results are inconsistent and there is a need for better predictors of RT response. A similar argument can be stated for the development of cachexia; there are currently no predictors that can identify patients who will develop cachexia later in the cancer disease trajectory. Experimental and preclinical studies show that pain, depression and cachexia are related to inflammation. However, it is not known if inflammatory biomarkers can predict CIBP, depression or development of cachexia. Methods: This multicenter, multinational longitudinal observational study will include 600 adult patients receiving RT for CIBP. Demographic data, clinical variables, osteoclast and inflammatory biomarkers will be assessed before start of RT, and 3, 8, 16, 24 and 52 weeks after last course of RT. The primary aim of the study is to identify potential predictors for pain relief from RT. Secondary aims are to explore potential predictors for development of cachexia, the longitudinal relationship between pain intensity and depression, and if inflammatory biomarkers are associated with changes in pain intensity, cachexia and depression during one-year follow up. Discussion: The immediate clinical implication of the PRAIS study is to identify potential predictive factors for a RT response on CIBP, and thereby reduce non-efficacious RT. Patient benefits are fewer hospital visits, reduced risk of adverse effects and more individualized pain treatment. The long-term clinical implication of the PRAIS study is to improve the knowledge about inflammation in relation to CIBP, cachexia and depression and potentially identify associations and mechanisms that can be targeted for treatment. Trial registration: ClinicalTrials.gov NCT02107664, date of registration April 8, 2014 (retrospectively registered). Trial sponsor: The European Palliative Care Research Centre (PRC), Department of Clinical and Molecular Medicine, NTNU, Faculty of medicine and Health Sciences, Trondheim, N-7491, Norway.