Supportive and Palliative Care

Breathlessness and the brain: the role of expectation Purpose of review Breathlessness debilitates countless people with a wide range of common diseases. For some people, the experience of breathlessness is poorly explained by the findings of medical tests. This disparity complicates diagnostic and treatment options and means that disease-modifying treatments do not always have the expected effect upon symptoms. These observations suggest that brain processing of respiratory perceptions may be somewhat independent of disease processes. This may help to explain the dissonance observed in some patients between physical disease markers and the lived experience of breathlessness. Recent findings A body of breathlessness research using functional neuroimaging has identified a relatively consistent set of brain areas that are associated with breathlessness. These areas include the insula, cingulate and sensory cortices, the amygdala and the periaqueductal gray matter. We interpret these findings in the context of new theories of perception that emphasize the importance of distributed brain networks. Within this framework, these perceptual networks function by checking an internal model (a set of expectations) against peripheral sensory inputs, instead of the brain acting as a passive signal transducer. Furthermore, other factors beyond the physiology of breathlessness can influence the system. Summary A person's expectations and mood are major contributors to the function of the brain networks that generate perceptions of breathlessness. Breathlessness, therefore, arises from inferences made by the brain's integration of both expectations and sensory inputs. By better understanding individual differences across these contributing perceptual factors, we will be better poised to develop targeted and individualized treatments for breathlessness that could complement disease-modifying therapies. Correspondence to Kyle T.S. Pattinson, BM, DPhil, FRCA, Associate Professor, Nuffield Department of Clinical Neurosciences, University of Oxford, Level 6, West Wing, John Radcliffe Hospital, Oxford OX3 9DU, UK. E-mail: kyle.pattinson@nda.ox.ac.uk This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Standardized measurement of breathlessness during exercise Purpose of review Exertional breathlessness is common and pervasive across various chronic disease populations. To accurately assess response to intervention and optimize clinical (symptom) management, detailed assessment of exertional breathlessness is imperative. This review provides an update on current approaches to assess exertional breathlessness and presents the need for individualized assessment of breathlessness standardized for the level of exertion. Recent findings Breathlessness assessment tools commonly invite people to recall their breathlessness while at rest with reference to activities of daily living. To directly quantify breathlessness, however, requires assessment of the dimensions of breathlessness (e.g., sensory intensity, quality, and unpleasantness) in response to a standardized exercise stimulus. Different exercise stimuli (e.g., self-paced, incremental, and constant work rate exercise tests) have been used to elicit a breathlessness response. Self-paced (e.g., 6-min walk test) and incremental exercise tests assess exercise tolerance or endurance, and are not recommended for assessment of exertional breathlessness. Constant work rate tests, however, including recently validated 3-min constant-rate stair stepping and walking tests, standardize the exercise stimulus to enable the breathlessness response to be directly quantified and monitored over time. Summary To adequately guide symptom management and assess intervention efficacy, clinicians and researchers should assess breathlessness with multidimensional assessment tools in response to a standardized and individualized exercise stimulus. Correspondence to Dennis Jensen, Currie Memorial Gymnasium, 475 Pine Avenue West, Montreal, Quebec, H2W 1S4, Canada. Tel: +1 514 398 4184; e-mail: dennis.jensen@mcgill.ca Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Why treatment efficacy on breathlessness in laboratory but not daily life trials? The importance of standardized exertion Purpose of review Treatments for chronic breathlessness, including opioids and oxygen, have shown efficacy in the controlled laboratory setting, whereas effects have been inconsistent or absent in trials in daily life. This review discusses the lack of standardized exertion as a potential cause of false negative findings for breathlessness in daily life. Recent findings The level of breathlessness can be modified by patients by changing their level of physical activity. Effects of opioids and oxygen have been shown at standardized level of exertion (iso-time) but not at the end of symptom-limited (peak) exertion. Trials in daily life reporting no effects on breathlessness did not standardize the exertion or employed insensitive methods, such as the 6-min walk test that should not be used for measuring breathlessness. Novel tests – the 3-min walk and stepping tests have been validated in chronic obstructive pulmonary disease and are responsive for measuring change in breathlessness. Summary Breathlessness should be measured at standardized exertion, otherwise treatment effects may be biased or overlooked. Tests for valid measurement of breathlessness in clinical practice and daily life are available and emerging. Correspondence to Magnus Ekström, MD, PhD, Associate Professor, Department of Clinical Sciences Lund, Respiratory Medicine and Allergology, Faculty of Medicine, Lund University, Lund, Karlskrona SE-371 85, Sweden. Tel: +46(0)455731000; e-mail: pmekstrom@gmail.com Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Recent research on the social network concept and cancer Purpose of review This review covers articles in 2018 and early 2019 that employed the concept of networks and social interactions in research on how patients with cancer cope, receive and respond to medical treatment and allied support. The use of social aspects, and more formally the method of social network analysis for research on cancer is quite new. Although we paid special attention to articles that used formal social network analysis, we noted that those articles cover just over a quarter of the material we reviewed. Most articles that incorporated social aspects of cancer did not intend to formalize them by measuring specific relationships but treated the network concept as a way to characterize social support, social influence, or social responsibilities. Recent findings We identified 74 recent articles that mentioned the network concept for research about cancer, excluding gene interaction networks. Of those 74 articles, 21 measured specific relationships between individuals or organizations and/or attributes of those individuals or organizations connected to participants or to others. Primary foci of the network analysis and nonnetwork analysis studies were breast cancer and social support for patients, and they usually at least considered sex and age of the cancer patients/survivors. Social media received some attention, and there were some studies considering quality of life and mental health. Among network analysis studies, size of network and number of people providing emotional/informational/instrumental support occurred in more than a couple studies but not the majority. There was little similarity among studies – whether using network analysis or not – suggesting that theory building and methodological development are in early stages. Summary Implications of the review include opportunities for more systematic research using the network concept to understand people's experience of cancer as well as research on cancer. Researchers can make considerable contributions at this stage in the field's development, and practitioners can help develop interventions that make fuller use of the insights of social network analysis. Correspondence to Eric C. Jones, UTHSCH, 1851 Wiggins Way, HSN 487, El Paso, TX 79968, USA. Tel: +1 915 747 8503; fax: +1 915 747 8512; e-mail: Eric.C.Jones@uth.tmc.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Multimorbidity in older adults living with and beyond cancer Purpose of review The current review draws attention to the need for longer term management of multiple conditions in older adults with cancer. Recent findings Older people living with and beyond cancer are more likely than younger people to have higher prevalence of multimorbidity leading to an overall increase in illness and treatment burdens, limiting health-related quality of life (QoL), and capacity to self-manage. Older age presents a higher risk of cancer treatment side-effects and development or progression of other conditions, leading to worsening health, long-lasting functional problems, and social isolation. Although many prioritize functional independence and continuance of valued activities over survival, older people living with multimorbidity are more likely to experience poor physical functioning during and beyond cancer treatment. Summary Cancer treatment decisions and survivorship plans should be developed in the context of other conditions and in line with the individual's priorities for continued QoL. More research is needed to guide service development and clinical practice in this important area. Correspondence to Dr Teresa Corbett, School of Health Sciences, University of Southampton, Building 67 Room 3031, Highfield, Southampton SO17 1BJ, UK. Tel: +44 2380598292; e-mail: t.k.corbett@soton.ac.uk Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Caring for the informal cancer caregiver Purpose of review Informal cancer caregivers play a vital role in the physical, functional, and emotional well being of cancer patients. However, the majority of informal caregivers are not prepared for their caregiving role. We reviewed and synthesized the recent literature (last 18 months) and focused on research in the following understudied areas: technology-driven interventions for informal caregivers; informal caregivers of older adults with cancer; interrelationship between informal caregiver and dyadic outcomes; and research priorities and guidelines to improve informal caregiver support. Recent findings Studies focused on technology-driven informal caregiver interventions, with evidence of good feasibility and acceptability with benefits for burden and quality of life (QOL). Studies also focused on QOL for caregivers of older adults with cancer. Finally, research priorities and clinical guidelines were established through Delphi survey studies. Summary Despite the substantial evidence on informal cancer caregiving, more research is needed to further characterize caregivers at high risk for burden, explicate interrelationships between caregiver/patient outcomes, and test innovative and scalable interventions. Studies are also needed to understand the specific needs of informal caregivers in cancer surgery, an understudied treatment population. Correspondence to Virginia Sun, PhD, RN, Associate Professor, Division of Nursing Research and Education, Department of Population Sciences, City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA. Tel: +1 626/218 3122; e-mail: vsun@coh.org Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Complexity when living with cancer No abstract available

Ketamine and lidocaine infusions decrease opioid consumption during vaso-occlusive crisis in adolescents with sickle cell disease Purpose of review Recurrent exposure to opioids can lead to development of opioid tolerance and opioid-induced hyperalgesia through activation of N-methyl-D-aspartate receptors. N-methyl-D-aspartate receptor antagonists ketamine and lidocaine can modulate development of opioid tolerance and OIH. This study evaluated the utility of ketamine and/or lidocaine in decreasing opioid consumption during acute pain episodes in adolescents with sickle cell disease. There has been an increased effort to promote opioid-sparing pain relieving methods given the ongoing opioid epidemic. Recent findings There have been six studies published over the past decade that highlight the ability of ketamine to reduce opioid consumption in the management of sickle cell disease-related pain, primarily in adult patients. There has been one study (2015) that demonstrated a similar benefit with lidocaine, however this was also in adult patients. Summary We retrospectively evaluated treatment with ketamine and/or lidocaine infusions in adolescents hospitalized for vaso-occlusive crisis (VOC). Patients served as self-controls using a comparison with a previous control admission for VOC. The use of ketamine and/or lidocaine as adjuncts to opioids resulted in lower daily opioid consumption in three of four patients. Our study suggests that ketamine and/or lidocaine infusions may be useful adjuncts in reducing opioid exposure during VOC pain. Correspondence to Doralina L. Anghelescu, MD, Department of Pediatric Medicine, Division of Anesthesiology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Mail Stop 130, Memphis, TN 38105, USA. Tel: +1 901 595 4032; fax: +1 901 595 4061; e-mail: doralina.anghelescu@stjude.org Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Interdisciplinary management of chronic breathlessness Purpose of review Breathlessness is a common yet complex symptom of advanced disease. Effective management will most likely draw upon the skills of multiple disciplines and professions. This review considers recent advances in the management of chronic breathlessness with regards to interdisciplinary working. Recent findings There are growing data on interventions for chronic breathlessness that incorporate psychosocial mechanisms of action, for example, active mind–body treatments; and holistic breathlessness services that exemplify interprofessional working with professionals sharing skills and practice for user benefit. Patients value the personalized, empathetic and understanding tenor of care provided by breathlessness services, above the profession that delivers any intervention. Workforce training, decision support tools and self-management interventions may provide methods to scale-up these services and improve reach, though testing around the clinical effects of these approaches is required. Summary Chronic breathlessness provides an ideal context within which to realize the benefits of interdisciplinary working. Holistic breathlessness services can commit to a comprehensive approach to initial assessment, as they can subsequently deliver a wide range of interventions suited to needs as they are identified. Correspondence to Dr Matthew Maddocks, Cicely Saunders Institute of Palliative Care, Policy and Rehabilitation, King's College London, Bessemer road, London SE5 9PJ, UK. Tel: +44 202 7848 5252; e-mail: matthew.maddocks@kcl.ac.uk Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Multidimensional measurement of breathlessness: recent advances Purpose of review Breathlessness is a multidimensional sensation for which a range of instruments exists for children, youth and adults, capable or unable to self-report distress with breathing. This review presents developments and applications of multidimensional assessments of breathlessness. Recent findings Excluding unidimensional measures and instruments assessing the impact of breathlessness, at least eight psychometrically robust instruments exist, which comprehensively assess one or more specific domains of the sensation of breathlessness (intensity, sensory quality, affective distress). These instruments have evolved from modest beginnings (describing breathlessness in various patient cohorts) to a growing use as primary or secondary outcomes in observational, clinical, and experimental trials exploring breathlessness mechanisms and intervention effects. For adults and children unable to consciously communicate breathing discomfort, instruments include combinations of physiological and behavioural markers of distress. Nonverbal (graphic scales) have potential use beyond paediatric applications. Summary Traditionally, breathlessness has been considered as a ‘black box’ with unidimensional measures reflecting box size (intensity, unpleasantness). Multidimensional instruments reveal the composition of the black box of breathlessness allowing detailed descriptions of an individual's breathlessness experience, quantification of sensory qualities, affective distress, and emotional responses with the potential to capture change over time and treatment effects in each dimension. Correspondence to Dr Marie T. Williams, Alliance for Research in Exercise, Nutrition and Activity (ARENA), School of Health Sciences, University of South Australia, North Terrace, Adelaide, SA 5000, South Australia, Australia. Tel: +61 8 8302 1153; fax: +61 8 830 22853; e-mail: Marie.williams@unisa.edu.au Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.