Thesis

Herma H. Lennaerts-Kats Palliative care for people with Parkinson’s disease and their family caregivers

Herma H. Lennaerts Palliative care for people with Parkinson’s disease and their family caregivers

Design/lay-out Promotie In Zicht | www.promotie-inzicht.nl Print Ipskamp Printing © Herma H. Lennaerts, 2022 All rights are reserved. No part of this book may be reproduced, distributed, stored in a retrieval system, or transmitted in any form or by any means, without prior written permission of the author.

Proefschrift ter verkrijging van de graad van doctor aan de Radboud Universiteit Nijmegen op gezag van de rector magnificus prof. dr. J.H.J.M. van Krieken, volgens besluit van het college voor promoties in het openbaar te verdedigen op woensdag 6 juli 2022 om 10.30 uur precies door Herma Hendrika Kats geboren op 15 november 1983 te Westerbork Palliative care for people with Parkinson’s disease and their family caregivers

Promotoren Prof. dr. B.R. Bloem Prof. dr. K.C.P. Vissers Copromotoren Dr. C.M. Groot Dr. M.J. Meinders Manuscriptcommissie Prof. dr. H. Vermeulen Prof. dr. Y. Schoon Prof. dr. T. van Laar (Rijksuniversiteit Groningen)

Contents General introduction 7 Chapter 1 Palliative care for patients with Parkinson’s disease: study protocol for a mixed methods study 23 Chapter 2 Why palliative care applies to Parkinson’s disease 37 Chapter 3 Dementia and Parkinson’s disease: Similar and divergent challenges in providing palliative care 49 Chapter 4 Palliative care for persons with Parkinson’s disease: a qualitative study on the experiences of healthcare professionals 79 Chapter 5 RADPAC-PD: a tool to support healthcare professionals in timely identifying palliative care needs of people with Parkinson’s disease 99 Chapter 6 “How long can I carry on?” – The need for palliative care in Parkinson’s disease: a qualitative study from the perspective of bereaved family caregivers 133 Chapter 7 “No one can tell me how Parkinson’s disease will unfold”: a mixed methods case study on palliative care for people with Parkinson’s disease and their family caregivers 153 Discussion 179 Appendices Summary Nederlandse samenvatting Data management Dankwoord List of publications Curriculum vitae RIHS portfolio Proefschriftenlijst 203 207 211 213 217 219 221 223

General introduction

General introduction | 9 General introduction This thesis aims to contribute to the understanding of palliative care for people with Parkinson’s disease (PD) and their families. Understanding the needs and experiences of people with PD, their families, bereaved family caregivers and healthcare professionals can help in optimizing palliative care, support decision-making, facilitate advance care planning and develop specific supportive treatments. This general introduction explains the context and the outline of this thesis. Parkinson’s disease The first detailed description of PD was made by the British surgeon James Parkinson in his “Essay on the Shaking Palsy” in 1817. Nowadays, PD is the second most common neurodegenerative disease worldwide. The incidence of PD increases with age and rises around an age of 65.(1) As the number and proportion of individuals over 65 is growing due to the aging population, the incidence of PD is expected to double in 20 years from now.(2) The diagnosis of PD is made on the clinical presence of bradykinesia, muscular rigidity, resting tremor or postural instability. PD is traditionally featured by motor symptoms, but nowadays PD is recognized as a multisystem disorder consisting of both motor and non-motor symptoms.(3-5) Non-motor symptoms vary from sleep disorders, pain, autonomic disturbance till neuropsychiatric disorders as depression, anxiety and hallucinations.(6, 7) These non-motor symptoms are frequently present before diagnosis and significantly affect a persons’ with PD quality of life.(8, 9) The management of PD is disease-oriented mainly focusing on neurological symptom control. The success of dopaminergic replacement therapy and allied health care has enabled the majority of patients to live independently with a relatively low symptom burden for the first 5 years after diagnosis.(10) Thereafter, the disease trajectory of PD is variable and hard to predict. Survival studies suggest that PD patients have a shorter life expectancy than those without the disease.(11-14) People live on average of 15 years after diagnosis, but individual survival can be up to 20 years depending, for example, on the age of onset.(15-17) After a disease duration of 10 years ormore, most patients have developed bilateral symptoms. Falls and fall-related fractures or other injuries are common. Furthermore, patients often experience a wide range of symptoms like immobility, pain, fatigue, sleeping problems, cognitive deficits and dementia.(5, 18, 19) Dysarthria has a great impact on a patient’s condition, and hinders communication, whereas dysphagia is a frequent cause of choking and aspiration pneumonia, sometimes necessitating tube

10 | General introduction feeding. An increasing number of patients become at least partially wheelchair-bound and a nursing home admission is inevitable in 20-40% of PD patients.(20-24) Most frequent cause of death in PD is pneumonia, followed by cardiovascular events, stroke and cancer.(15-17) Although, there is an increasing body of evidence on which symptoms occur in advanced PD, little is known about patients and (bereaved) family caregivers experiences. Most studies focuses on patients with PD needs in early stages and paid less attention to patients with advanced PD.(25, 26) Palliative care: from deathbed to proactive palliative care A short history From ancient times, people in communities were responsible for the care of sick and dying people. Death was embedded in the social environment and a common present day event. In the Middle Ages, death rates were high due to childbirth, pandemics with cholera, pox or influenza and accidents. Life expectancy at birth was 33 years (by the Middle Ages) and raised up to 55 years in the early 1900s.(30) Death attitudes changed gradually due to culture, socioeconomics environment and for example religion. Most religions does reveal that death is a spiritual passage to another life (heaven or hell). People were taught that a good life would help them in order to receive a place in heaven. For Buddhists and Hindus death is undergoing another rebirth. Death is part of the living, but how people cope with dying is susceptible by many factors. For centuries doctors primarily played a role in predicting a person’s death so that he or she could organize the final hours. Gradually this role changed with the upcoming of improved medical care. From the midst of the 19th century, opium, chloroform and morphine were found and helped to relieve pain.(31) As a consequence doctors became to play an important role in the care for people who were dying. In 1900 most people still died at home surrounded by family, a doctor and often a religious person. However, by 1950 approximately half of all deaths occurred in hospitals, nursing homes or other institutions. The medicalization of death appeared unmarked, but was a consequence of improvements in medical care, better hygiene and disappearance of large pandemics. As the place of death has shifted from the home to the hospital, society was less involved in thinking about ‘a good death’. The concept of ‘the good death’ is subjective and different for each person in time and culture. Furthermore, health care gradually puts its focus on ‘staying in live’ and the care for people who were dying became out of vogue. Usual practice was, for example, that cancer diagnosis and prognosis was rarely discussed. In this light, palliative care as a newmedicine began to developing. Pioneers in this field were Cicely

General introduction | 11 Saunders (nurse and doctor, 1918 – 2005), Elisabeth Kübler-Ross (psychiatrist, 1926– 2004) and Balfour Mount (doctor, 1939 - ). In the late 1960s Saunders propagated for a holistic care model for terminal patients, where families were welcome and patients died peacefully. She was founder of St Christopher’s Hospice in London in 1967 and encouraged a radical new approach to end of life care combining attention to physical, social, emotional and spiritual problems.(32, 33) Balfour Mount introduced the term “palliative care” in 1973 after he visited St Christopher’s Hospice. Afterwards, a new framework for understanding death, the process of dying, and how to act when death approaches became the field of palliative care. Palliative care was primarily developed for patients with cancer and was only required in the last fewdays andweeks of life. Gradually, a palliative care approachwas described that could be offered alongside curative treatment, with a gradual increase in palliative care as the disease progresses and active treatment is withdrawn. Later on, palliative care was also discussed for other group of patients such as heart failure, COPD and dementia. The translation of palliative care into other fields took years but there is a growing awareness of palliative care for patients with non-malignant diseases. Definitions on palliative care The first definition on palliative care was launched by the World Health Organization (WHO) in 1990. This definition was developed by a group of members who had their roots in cancer care, which was number one cause of death at that time. Gradually, the need for a broader definition on palliative care increased. In 2002, the WHO developed the current definition that “palliative care is an approach that improves the quality of life of patients and their families facing the problems associated with life threatening illness, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial and spiritual.”(34) An important and novel aspect of this definition is that it is an approach to care rather than a medical specialty. Furthermore, this definition encompasses any life limiting illness rather than just one condition such as cancer. Although this definition was an important step forward numerous other terms have been used to describe palliative care, including “care of the dying,” “end of-life care,” “continuing care,” “supportive care,” “holistic care,” “comprehensive care,” and “comfort care”.(35) The unclarity of definitions and terms might be one of the reasons why the term palliative care is not well understood by society and healthcare professionals. Definitions on end of life care, palliative care and terminal care show similarities but also differences in ‘what palliative care is’, ‘when to start’, ‘for whom’ and ‘by whom’. A systematic literature review on the transition of curative care to palliative care describes three main approaches to improve palliative care in practice: a sharp transition point, a phased transition and a simultaneous care approach.(36)

12 | General introduction A sharp transition point: identification The identification, or in other words sharp transition point, of palliative care is challenging. Therefore, a framework of typical illness trajectories was developed by Murray in 2005. Aim was to define trajectories that may help clinicians to meet their patient’s palliative care needs better, and help patients and carers to cope with their situation.(37) Three distinct illness trajectories have been described for people with chronic illnesses (figure 1): Figure 1 Typical illness trajectories for people with progressive chronic illness(75)

General introduction | 13 1) a trajectory with steady progression and usually a clear terminal phase, mostly cancer; 2) a trajectory (for example, respiratory and heart failure) with gradual decline, punctuated by episodes of acute deterioration and some recovery, with more sudden, seemingly unexpected death; 3) a trajectory with prolonged gradual decline (typical of frail elderly people, people with dementia or PD). Although this framework helped in thinking about palliative care, it also encounters its limitations as the time between diagnosis of a life-threatening disease and death can vary from weeks till decades. Besides, patients often deny having a life-limiting disease, and are learning how to live with it without facing advanced stages of the disease. Starting palliative care after diagnosis seems inappropriate and in some cases even stigmatize patients. However, the importance of identification of palliative care needs lies in the fact that it enables patients and healthcare professionals to shift from a disease-oriented treatment into palliative care. Effects of palliative care There is international evidence, particularly in cancer, on the benefits of palliative care in improving quality of life, increasing satisfaction with care and, for some patients, a prolongation of life.(43-45) Furthermore, palliative care may also improve home death rates. There is evidence that suggests that outcomes are better if palliative care is incorporated earlier in the disease trajectory.(43, 46-48) A study in patients with stage IV lung cancer showed that early palliative care improved patient functioning and quality of life with potentially reducing the cost of care.(43) This finding is also reflected in a systematic review on the effect of palliative care and advance care planning on Intensive care Unit (ICU) utilization. This study showed a pattern in a decreased ICU admissions and reduced ICU length of stay.(49) Health care policy regarding palliative care in the Netherlands Different models of palliative care have been developed in several countries. In the Netherlands, palliative care is an integral part of regular healthcare. Dutch government policy is based on the idea that palliative care is generalist care and should therefore be provided by any healthcare professionals whenever necessary. As such, palliative care is not a distinct medical specialty as it is in many other countries. Core elements of palliative care, such as basic symptom management and aligning treatment with patient’s goals, should be integrated in care as it is delivered by any healthcare professional.(50) In case of complex problems, such as managing refractory symptoms or negotiating a difficult family meeting, specialist palliative care should be available. Palliative care teams (PCTs) can be consulted by professionals involved in palliative care and can provide such specialist palliative care, either in or outside the hospital.

14 | General introduction Palliative care for people with PD Palliative care is widely advocated for persons with PD and their caregivers.(51-53) For PD the effects of palliative care could be considerable as PD is a highly prevalent disease and despite improvements in management, many will live and die with PD. Furthermore, there is substantial evidence that describes the burden of disease and poor quality of life of patients and their families living with advanced PD.(54-58) However, current existing palliative care is not implemented to the care for PD. Needs of patients with PD in advanced stages Comparisons between end stage cancer patients and patients with PD, reveal that the level of disability and quality of life do not differ between those two groups.(59, 60) Furthermore, patients with PD experience major changes in physical- and cognitive functioning, social interaction and self-awareness.(61) The severity of symptoms results in limitations in activities of daily living and care dependency. PD patients at advanced stages often are unable to live alone due to their gradual increasing disabilities.(52) Patients worry about being a burden to family and friends.(61, 62) Advance care planning often remains undiscussed although patients may have opinions on, for example, preferred place of death. According to patients there is a need for better information and education about the advanced stage of PD.(61, 63) Needs of family caregivers of patients in advanced PD Family caregivers of patients with advanced PD reported in numerous qualitative studies considerable changes in their life due to the care for their loved ones.(52, 56, 58, 64, 65) Patients with advanced PD are cared for by family members, usually older spouses.(58) Especially, spouses felt that their primary role in the relationship changed, due to cognitive deficits and speech problems of the patients. Family caregivers experiences difficulties in caring for their loved ones, when striving to care for them as long as possible. Results from a study of pre-death grief in family caregivers of advanced PD patients showed that pre-death grief was a significant finding in family caregivers and was associated with the presence of patient’s cognitive decline.(66) Studies also reported that family caregivers had fewer social contacts and opportunities to socialize, had a reduced financial income and tended to experience poorer health; this is particularly related to features of advanced stage PD.(58, 67) Identification of palliative care needs in PD Difficulties in the identification of palliative care needs are similar for PD as for other chronic diseases.(51, 69) General screenings tools are available, but no studies have used these in PD. However, a few specific disease symptoms have been recognized as indicators for starting the palliative phase, which includes: the first episode of

General introduction | 15 aspiration and the occurrence of clinical features such as visual hallucinations, regular falls, dementia and admission to residential care. Patients who experiencing such symptoms might be in need of palliative care.(69, 70) Palliative care services in PD At least three challenges exist when aiming for palliative care for all patients with PD. Overall, patients with PD do often not receive palliative care and have limited access to palliative care services.(64, 65) A few studies describe patients with PD who receive palliative care. Findings showed a poor coordination between services.(63) There was a lack of clarity regarding different specialty clinicians’ roles and the need for improved communication between all professionals. Secondly, healthcare professionals lack the necessary competences and skills for palliative care in PD and feel inexperienced.(2729) In addition, the management of physical and psychosocial symptoms is complex for patients with advanced PD and little evidence is available on effective (medical) interventions. Studies highlighting the importance of advanced care planning as part of palliative care for PD.(71) Advance care planning (ACP) is a complex form of shared decision making which becomes increasingly important as PD progresses, particularly when patients are faced with cognitive impairment and communication problems which may cause difficulty in discussions about a person’s goals or preferences.(72) However, health care professionals struggle with implementing ACP. Barriers such as time pressure, lack of competence, restricted financial resources and an increasing demand to be efficient have a negative effect on the provision of ACP and palliative care.(27, 29) Thirdly, specific palliative care services, such as palliative care teams and hospices, have been recommended to meet the complex needs of patients with PD throughout the disease trajectory.(51, 69) However, how and when patients should be referred remains unclear as well as how they should be treated.(73, 74) A close working relationship between PD specialists and palliative care specialists, from the time of diagnosis onwards might help to improve palliative care for patients with PD.(69) Objectives of this thesis The overarching goal of this thesis is to achieve a better understanding of the needs and experiences of people with PD, their families, bereaved family caregivers and healthcare professionals, in order to optimize palliative care for PD. To this end we formulate the following objectives: (1) To understand how palliative care for PD patients should be approached. (2) To investigate the experiences with care of people with advanced stage of PD, their families, bereaved family caregivers and healthcare professionals.

16 | General introduction (3) To define a set of indicators in PD that may assist in the timely identification of palliative care needs in people with advanced PD. Outline of this thesis To address the objectives of this thesis we evaluate the experiences of people with PD, their (bereaved) family caregivers and health care professionals. Chapter 1 describes the study protocol for this thesis and outlines our qualitative approach for individual interviews with health care professionals, individual interviews with bereaved family caregivers and a case study. Chapters 2 and 3 includes a non-systematic review on palliative care for people with PD and their family caregivers. Chapter 2 focuses on literature from palliative care for PD, whereas in Chapter 3 we specifically look at similarities and divergency between the field of palliative care for people with dementia and PD. Chapter 4 concerns a study in were we retrospectively explored the experiences of health care professionals by conducting individual interviews (n=10) and three focus group interviews (n=29). Data was analyzed according a thematic analysis. Subsequent, Chapter 5 describes the development of the RADPAC-PD for timely identification of palliative care needs. For this study, we did a Delphi study to achieve consensus on statements of palliative care in PD among health care professionals (n=56). We explored the experiences of bereaved family caregivers, which is presented into Chapter 6. We chose in this part for an Interpretative Phenomenological analysis (IPA). This method is in particular useful in areas that are highly emotional. Following a picture of palliative care in PD, we present a longitudinal case study on ten persons with advanced PD and their family caregivers in Chapter 7. For this case study, we held semi-structured interviews and questionnaires at three consecutive contact moments during a 12 month period. Finally, we present and discuss the main findings of the separate studies and put forward suggestions for future implementation and research.

General introduction | 17 References 1. Van Den Eeden SK, Tanner CM, Bernstein AL, Fross RD, Leimpeter A, Bloch DA, et al. Incidence of Parkinson’s disease: variation by age, gender, and race/ethnicity. American journal of epidemiology. 2003;157(11):1015-22. 2. Dorsey ER, Bloem BR. The Parkinson pandemic—a call to action. JAMA neurology. 2018;75(1):9-10. 3. Goldman JG, Postuma R. Premotor and non-motor features of Parkinson’s disease. Current opinion in neurology. 2014;27(4):434. 4. Antonini A, Barone P, Marconi R, Morgante L, Zappulla S, Pontieri FE, et al. The progression of non-motor symptoms in Parkinson’s disease and their contribution to motor disability and quality of life. Journal of neurology. 2012;259(12):2621-31. 5. Higginson IJ, Gao W, Saleem TZ, Chaudhuri KR, Burman R, McCrone P, et al. Symptoms and quality of life in late stage Parkinson syndromes: a longitudinal community study of predictive factors. PloS one. 2012;7(11):e46327. 6. Chaudhuri KR, Healy DG, Schapira AH, National Institute for Clinical E. Non-motor symptoms of Parkinson’s disease: diagnosis and management. Lancet Neurol. 2006;5(3):235-45. 7. Martinez-Martin P, Schapira AH, Stocchi F, Sethi K, Odin P, MacPhee G, et al. Prevalence of nonmotor symptoms in Parkinson’s disease in an international setting; study using nonmotor symptoms questionnaire in 545 patients. Mov Disord. 2007;22(11):1623-9. 8. Martinez-Martin P, Rodriguez-Blazquez C, Kurtis MM, Chaudhuri KR, Group NV. The impact of nonmotor symptoms on health-related quality of life of patients with Parkinson’s disease. Mov Disord. 2011;26(3):399-406. 9. Kalia LV, Lang AE. Parkinson disease in 2015: evolving basic, pathological and clinical concepts in PD. Nature reviews Neurology. 2016;12(2):65. 10. Macleod AD, Taylor KS, Counsell CE. Mortality in Parkinson’s disease: a systematic review and metaanalysis. Mov Disord. 2014;29(13):1615-22. 11. Morgante L, Salemi G, Meneghini F, Di Rosa AE, Epifanio A, Grigoletto F, et al. Parkinson disease survival: a population-based study. Archives of neurology. 2000;57(4):507-12. 12. Diamond SG, Markham CH, Hoehn MM, McDowell FH, Muenter MD. An examination of male-female differences in progression and mortality of Parkinson’s disease. Neurology. 1990;40(5):763-. 13. Morens DM, Davis JW, Grandinetti A, Ross GW, Popper JS, White LR. Epidemiologic observations on Parkinson’s disease. Incidence andmortality in a prospective study of middle-agedmen. 1996;46(4):1044-50. 14. Dommershuijsen LJ, Heshmatollah A, Darweesh SK, Koudstaal PJ, Ikram MA, Ikram MK. Life expectancy of parkinsonism patients in the general population. Parkinsonism & Related Disorders. 2020;77:94-9. 15. Coelho M, Marti MJ, Tolosa E, Ferreira JJ, Valldeoriola F, Rosa M, et al. Late-stage Parkinson’s disease: the Barcelona and Lisbon cohort. Journal of neurology. 2010;257(9):1524-32. 16. Coelho M, Marti MJ, Sampaio C, Ferreira JJ, Valldeoriola F, Rosa MM, et al. Dementia and severity of parkinsonism determines the handicap of patients in late-stage Parkinson’s disease: the BarcelonaLisbon cohort. Eur J Neurol. 2015;22(2):305-12. 17. Sveinbjornsdottir S. The clinical symptoms of Parkinson’s disease. Journal of neurochemistry. 2016;139 Suppl 1:318-24. 18. Lee MA, Prentice WM, Hildreth AJ, Walker RW. Measuring symptom load in Idiopathic Parkinson’s disease. Parkinsonism Relat Disord. 2007;13(5):284-9. 19. Buter TC, van den Hout A, Matthews FE, Larsen JP, Brayne C, Aarsland D. Dementia and survival in Parkinson disease: a 12-year population study. Neurology. 2008;70(13):1017-22. 20. Hely MA, Morris JGL, Traficante R, al. e. The Sydney multicentre study of Parkinson’s Disease: progression and mortality al 10 years. Journal of neurology, neurosurgery, and psychiatry. 1999;67:300-7. 21. Aarsland D, Larsen JP, Tandberg E, Laake K. Predictors of nursing home placement in Parkinson’s disease: a population-based, prospective study. Journal of the American Geriatrics Society. 2000;48(8):938-42. 22. Lapane KL, Fernandez HH, Friedman JH. Prevalence, clinical characteristics, and pharmacologic treatment of Parkinson’s disease in residents in long-term care facilities. SAGE Study Group. Pharmacotherapy. 1999;19(11):1321-7.

18 | General introduction 23. Tison F, Dartigues JF, Dubes L, Zuber M, Alperovitch A, Henry P. Prevalence of Parkinson’s disease in the elderly: a population study in Gironde, France. Acta neurologica Scandinavica. 1994;90(2):111-5. 24. Mitchell SL, Kiely DK, Kiel DP, Lipsitz LA. The epidemiology, clinical characteristics, and natural history of older nursing home residents with a diagnosis of Parkinson’s disease. Journal of the American Geriatrics Society. 1996;44(4):394-9. 25. Ghoche R. The conceptual framework of palliative care applied to advanced Parkinson’s disease. Parkinsonism Relat Disord. 2012;18 Suppl 3:S2-5. 26. Razali R, Ahmad F, Rahman FN, Midin M, Sidi H. Burden of care among caregivers of patients with Parkinson disease: a cross-sectional study. Clinical neurology and neurosurgery. 2011;113(8):639-43. 27. Waldron M, Kernohan WG, Hasson F, Foster S, Cochrane B. What do social workers think about the palliative care needs of people with Parkinson’s disease? BJSW. 2013;43:81-98. 28. Waldron M, Kernohan WG, Hasson F, Foster S, Cochrane B, Payne C. Allied health professional’s views on palliative care for people with advanced Parkinson’s disease. Int J Ther Rehabil. 2011;18:48-57. 29. Fox S, Cashell A, Kernohan WG, Lynch M, McGlade C, O’Brien T, et al. Interviews with Irish healthcare workers fromdifferent disciplines about palliative care for people with Parkinson’s disease: a definite role but uncertainty around terminology and timing. BMC Palliat Care. 2016;15(1):1-9. 30. Jonker MA. Estimation of life expectancy in the Middle Ages. Journal of the Royal Statistical Society: Series A (Statistics in Society). 2003;166(1):105-17. 31. Robinson DH, Toledo AH. Historical development of modern anesthesia. Journal of Investigative Surgery. 2012;25(3):141-9. 32. Saunders C. The evolution of palliative care. Pharos Alpha Omega Alpha Honor Med Soc. 2003;66(3):4-7. 33. Saunders DCM, Clark D. Cicely Saunders: selected writings 1958-2004: Oxford University Press; 2006. 34. World Health Organization (WHO). WHO definition of palliative care [Internet]. 2010 [Available from: http://www.who.int/cancer/palliative/definition/en/. 35. Hui D, De La Cruz M, Mori M, Parsons HA, Kwon JH, Torres-Vigil I, et al. Concepts and definitions for “supportive care,”“best supportive care,”“palliative care,” and “hospice care” in the published literature, dictionaries, and textbooks. Supportive Care in Cancer. 2013;21(3):659-85. 36. Gardiner C, Ingleton C, Gott M, Ryan T. Exploring the transition from curative care to palliative care: a systematic review of the literature. BMJ Support Palliat Care. 2011;1(1):56-63. 37. Murray SA, Kendall M, Boyd K, Sheikh A. Illness trajectories and palliative care. Bmj. 2005;330(7498):1007-11. 38. Highet G, Crawford D, Murray SA, Boyd K. Development and evaluation of the Supportive and Palliative Care Indicators Tool (SPICT): a mixed-methods study. BMJ Support Palliat Care. 2014;4(3):285-90. 39. Thoonsen B, Engels Y, van Rijswijk E, Verhagen S, van Weel C, Groot M, et al. Early identification of palliative care patients in general practice: development of RADboud indicators for PAlliative Care Needs (RADPAC). Br J Gen Pract. 2012;62(602):e625-31. 40. Thomas K, Armstrong Wilson J, GSF Team - National Gold Standards Framework Centre in End of Life Care. The Gold Standards Framework Proactive Identification Guidance (PIG). United Kingdom2016. 41. Murray S, Boyd K. Using the ‘surprise question’ can identify people with advanced heart failure and COPD who would benefit from a palliative care approach. Palliat Med. 2011;25:382. 42. Downar J, Goldman R, Pinto R, Englesakis M, Adhikari NK. The “surprise question” for predicting death in seriously ill patients: a systematic review and meta-analysis. CMAJ. 2017;189(13):E484-E93. 43. Temel JS, Greer JA, Admane S, Gallagher ER, Jackson VA, Lynch TJ, et al. Longitudinal perceptions of prognosis and goals of therapy in patients with metastatic non–small-cell lung cancer: Results of a randomized study of early palliative care. J Clin Oncol. 2011;29(17):2319-26. 44. Zimmermann C, Swami N, Krzyzanowska M, Hannon B, Leighl N, Oza A, et al. Early palliative care for patients with advanced cancer: a cluster-randomised controlled trial. The Lancet. 2014;383(9930):1721-30. 45. Ferrell BR, Temel JS, Temin S, Alesi ER, Balboni TA, Basch EM, et al. Integration of palliative care into standard oncology care: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2017;35(1):96-112. 46. Kelley AS, Meier DE. Palliative care—a shifting paradigm. Mass Medical Soc; 2010. 47. Higginson IJ, Evans CJ. What is the evidence that palliative care teams improve outcomes for cancer patients and their families? The Cancer Journal. 2010;16(5):423-35.

General introduction | 19 48. Higginson IJ, Finlay IG, Goodwin DM, Hood K, Edwards AG, Cook A, et al. Is there evidence that palliative care teams alter end-of-life experiences of patients and their caregivers? Journal of pain and symptom management. 2003;25(2):150-68. 49. Khandelwal N, Kross EK, Engelberg RA, Coe NB, Long AC, Curtis JR. Estimating the effect of palliative care interventions and advance care planning on ICU utilization: a systematic review. Critical care medicine. 2015;43(5):1102. 50. IKNL/Palliactief. Kwaliteitskader palliatieve zorg Nederland. 2017. 51. Kluger BM, Fox S, Timmons S, Katz M, Galifianakis NB, Subramanian I, et al. Palliative care and Parkinson’s disease: Meeting summary and recommendations for clinical research. Parkinsonism Relat Disord. 2017;37:19-26. 52. Miyasaki JM, Kluger B. Palliative care for Parkinson’s disease: has the time come? Curr Neurol Neurosci Rep. 2015;15(5):26. 53. Boersma I, Miyasaki J, Kutner J, Kluger B. Palliative care and neurology: time for a paradigm shift. Neurology. 2014;83. 54. Schrag A, Jahanshahi M, Quinn N. How does Parkinson’s disease affect quality of life? A comparison with quality of life in the general population. Mov Disord. 2000;15(6):1112-8. 55. Schrag A, Jahanshahi M, Quinn N. What contributes to quality of life in patients with Parkinson’s disease? Journal of neurology, neurosurgery, and psychiatry. 2000;69(3):308-12. 56. Goy ER, Carter JH, Ganzini L. Needs and experiences of caregivers for family members dying with Parkinson disease. J Palliat Care. 2008;24(2):69-75. 57. Martinez-Martin P, Rodriguez-Blazquez C, Forjaz MJ. Quality of life and burden in caregivers for patients with Parkinson’s disease: concepts, assessment and related factors. Rev Pharmacoecon Outcomes Res. 2012;12(2):221-30. 58. McLaughlin D, Hasson F, Kernohan WG, Waldron M, McLaughlin M, Cochrane B, et al. Living and coping with Parkinson’s disease: perceptions of informal carers. Palliat Med. 2011;25(2):177-82. 59. Goy ER, Carter JH, Ganzini L. Parkinson disease at the end of life: caregiver perspectives. Neurology. 2007;69(6):611-2. 60. Miyasaki JM, Long J, Mancini D, Moro E, Fox SH, Lang AE, et al. Palliative care for advanced Parkinson disease: an interdisciplinary clinic and new scale, the ESAS-PD. Parkinsonism Relat Disord. 2012;18 (suppl 3):S6-9. 61. Boersma I, Jones J, Carter J, Bekelman D, Miyasaki J, Kutner J, et al. Parkinson disease patients’ perspectives on palliative care needs: What are they telling us? Neurol Clin Pract. 2016;6(3):209-19. 62. Fox S, Cashell A, KernohanWG, LynchM, McGlade C, O’Brien T, et al. Palliative care for Parkinson’s disease: Patient and carer’s perspectives explored through qualitative interview. Palliat Med. 2017;31(7):634-41. 63. Giles S, Miyasaki J. Palliative stage Parkinson’s disease: patient and family experiences of health-care services. Palliat Med. 2009;23:120-5. 64. Hasson F, Kernohan WG, McLaughlin M, Waldron M, McLaughlin D, Chambers H, et al. An exploration into the palliative and end-of-life experiences of carers of people with Parkinson’s disease. Palliat Med. 2010;24(7):731-6. 65. Giles S, Miyasaki J. Palliative stage Parkinson’s disease: patient and family experiences of health-care services. Palliat Med. 2009;23(2):120-5. 66. Carter JH, Lyons KS, Lindauer A, Malcom J. Pre-death grief in Parkinson’s caregivers: a pilot survey-based study. Parkinsonism Relat Disord. 2012;18 Suppl 3:S15-8. 67. Schrag A, Hovris A, Morley DQuinn N, Jahanshahi M. Caregiver-burden in parkinson’s disease is closely associated with psychiatric symptoms, falls, and disability. Parkinsonism Relat Disord 2006;12(1):35-41. 68. Hall K, Sumrall M, Thelen G, Kluger BM. Palliative care for Parkinson’s disease: suggestions from a council of patient and carepartners. NPJ Parkinsons Dis. 2017;3:16. 69. Richfield EW, Jones EJ, Alty JE. Palliative care for Parkinson’s disease: a summary of the evidence and future directions. Palliat Med. 2013;27(9):805-10. 70. Pennington S, Snell K, LeeM, Walker R. The cause of death in idiopathic Parkinson’s disease. Parkinsonism Relat Disord. 2010;16(7):434-7. 71. Lum HD, Jordan SR, Brungardt A, Ayele R, Katz M, Miyasaki JM, et al. Framing advance care planning in Parkinson disease: Patient and care partner perspectives. Neurology. 2019;92(22):e2571-e9.

20 | General introduction 72. Abu Snineh M, Camicioli R, Miyasaki JM. Decisional capacity for advanced care directives in Parkinson’s disease with cognitive concerns. Parkinsonism Relat Disord. 2017;39:77-9. 73. Sleeman KE, Ho YK, Verne J, Glickman M, Silber E, Gao W, et al. Place of death, and its relation with underlying cause of death, in Parkinson’s disease, motor neurone disease, and multiple sclerosis: a population-based study. Palliat Med. 2013;27(9):840-6. 74. Sethi S, Hohler AD. The Application of palliative care principles in advanced Parkinson’s disease. Advances in Parkinson’s Disease. 2016;5(4):73-86. 75. Lorenz KA, Lynn J, Dy SM, Shugarman LR, Wilkinson A, Mularski RA, Morton SC, Hughes RG, Hilton LK, Maglione M, Rhodes SL, Rolon C, Sun VC, Shekelle PG. Evidence for improving palliative care at the end of life: a systematic review. Ann Intern Med. 2008 Jan 15;148(2):147-59. doi: 10.7326/0003-4819-1482-200801150-00010. Erratum in: Ann Intern Med. 2009 Nov 3;151(9):674. PMID: 18195339.

General introduction | 21

Palliative care for patients with Parkinson’s disease: study protocol for a mixed methods study Authors: Herma Lennaerts, Marieke Groot, Maxime Steppe, Jenny T. van der Steen, Marieke van den Brand, Dorian van Amelsvoort, Kris Vissers, Marten Munneke, Bastiaan R. Bloem Chapter 1

24 | Chapter 1 Abstract Background Parkinson’s disease (PD) is a chronic, progressive neurological disorder with many intractable consequences for patients and their family caregivers. Little is known about the possibilities that palliative care could offer to patients and their proxies. Guidelines strongly recommend palliative care to improve the quality of life and – if needed – the quality of dying. However, providing palliative care to persons with PD involves specific challenges. For example, a timely initiation of palliative interventions is difficult because due to the gradually progressive nature of PD, there is often no clear marker for the transition from curative towards palliative care. Furthermore, there is little evidence to indicate which palliative care interventions are effective. Here, we describe the contours of a study that aims to examine the experiences of patients, (bereaved) family caregivers and professionals, with the aim of improving our knowledge about palliative care needs in PD. Methods We will perform a mixed methods study to evaluate the experiences of patients, (bereaved) family caregivers and palliative care professionals. In this study, we focus on Quality of Life, Quality of Care, perceived symptoms, caregiver burden and collaboration between professionals. In phase 1, we will retrospectively explore the views of bereaved family caregivers and professionals by conducting individual interviews and focus group interviews. In phase 2, 5-15 patients with PD and their family caregiver will be followed prospectively for 8-12 months. Data collection will involve semi-structured interviews and questionnaires at three consecutive contact moments. Qualitative data will be audio recorded, transcribed and analyzed using CAQDAS. If patients pass away during the study period, a bereavement interview will be done with the closest family caregiver. Discussion This study will offer a broad perspective on palliative care, and the results can be used to inform a palliative care protocol for patients with PD. By describing the experiences of patients, (bereaved) family caregivers and professionals with palliative care, this investigation will also establish an important ground for future intervention research. Key words Parkinson’s disease; palliative care; patient experiences; mixed methods; study design

Studyprotocol | 25 1 Background Parkinson’s disease (PD) is a common neurodegenerative disorder, affecting approximately 1% of the population over the age of 65 in Western countries.1 PD is an incurable disease, and treatment exists of symptomatic strategies (such as suppressing symptoms, or offering support). As PD progresses, patients can experience a wide range of symptoms like immobility, pain, fatigue, sleeping problems, cognitive deficits and dementia.2-4 A nursing home admission is inevitable in 20-40% of PD patients.5-9 Disease management in advanced stages of PD becomes increasingly difficult, whereas the emphasis on quality of life becomes more important. Patients with PD experience considerable discomfort at the end of life; in fact, their symptom burden is comparable to that of advanced cancer patients.2, 10 Palliative care is “an approach that improves the quality-of-life of patients and their families facing problems associated with life-threatening illness, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial and spiritual”.11 However, there is barely any knowledge about the effective and useful components for palliative care in PD.12 Hasson et al reviewed the current evidence and reported several challenges that may occur in clinical practice.14 Problematic is the (timely) identification of PD patients and their palliative care needs. The absence of a concrete starting point for focusing on palliative care needs makes it difficult to identify palliative care needs during the disease course. A few specific disease symptoms have been recognized as indicators for palliative care needs. This includes the first episode of aspiration and the occurrence of key clinical features such as visual hallucinations, regular falls, dementia and admission to residential care; patients experiencing such symptoms might need special attention and start of the palliative care phase can be considered.12, 13 However, the appearance of these specific symptoms do not always lead to recognition of palliative care needs or referral to palliative care services. PD patients and family caregivers described a lack of knowledge about palliative care services.14 And if they had received care from a palliative care service, then coordination of care was reported to be poor.14-16 Studies conclude that family caregivers often feel alone in the care for the patient with advanced PD.14 Only few PD patients and family caregivers receive palliative care in contrast to patients with malignant diseases.17 Most studies evaluated patients with PD needs in early stages and paid less attention to patients with advanced PD.18, 19 However, a few studies found unmet needs in advanced PD.20 Patients with advanced PD are cared for by family members, usually older spouses.21 Schrag et al. reported that for patients at advanced stages, caregiver burden rises with increasing disability, and also with the appearance of symptoms such

26 | Chapter 1 as hallucinations, depression and falls.22 Family caregivers of patients with advanced PD reported considerable changes in their life.14, 15, 20, 21, 23 More specifically, spouses felt that their primary role in the relationship changed, due to cognitive deficits and speech problems of the patients. Family caregivers struggled with caring for their loved ones as long as possible and specifically with the point of admission to a nursing home. Studies also reported that family caregivers had fewer social contacts and opportunities to socialize, had a reduced financial income and tended to experience poorer health; this is particularly related to features of late stage PD.21, 22 Likewise Carter et al. explored pre-death grief in family caregivers of advanced PD patients and the results suggests that pre-death grief was a significant finding in family caregivers and was more associated with the presence of patient’s cognitive decline.24 Four studies reported professionals’ experiences with (the concept of) palliative care and PD.25-28 Waldron et al. showed that professionals often misconceive the putative value of rehabilitation in the palliative care phase. Moreover, professionals felt unsure about the care they delivered in this phase. Several studies reported that professionals experienced a lack of education and competence in this field. Furthermore, the collaboration between palliative care services and more general professionals was missed. Perceived barriers in the collaboration were inadequate referral and lack of communication. In order to address the existing knowledge gap, we will now launch the ParkinsonSupport study, with the aim of identifying the experiences with end of life issues among both people with PD, their family caregivers and the professionals involved. Part of this project is a qualitative after-death study with professionals and widowed family caregivers, as well as a prospective multiple case study with patients and their family caregivers. These issues will be explored by asking patients, (bereaved) family caregivers and professionals about their experiences and ideas about optimizing palliative care. Important aspects of this exploration also include identifying terminal care strategies that have already been used in practice by professionals, and the identification of ‘red flags’ in order to get more insight information to start palliative care interventions timely. Additional questions emerging from our main research question include: (1) What opinions do patients, (bereaved) family caregivers and professionals have about the quality of care provided? (2) What are specific disease symptoms that may assist in the timely identification of palliative care needs in patients with advanced PD? (3) How do disease care needs progress over 8 - 12 months in PD patients and family caregivers? (4) What are the major decisions and symptoms in dying with Parkinson disease? The objective of this paper is to provide a detailed description of the study design and research protocol.

Studyprotocol | 27 1 Methods/Study design This study includes two parts. We will start with an explorative, qualitative after-death study. In-depth individual and focus group interviews with bereaved family caregivers and professionals involved in the care for people with PD will be held. The second part consists of a qualitative prospective multiple case study design.29 This design facilities the understanding of circumstances and experiences of patients with advanced PD and their family caregivers. Explorative after-death study A topic list will be developed based on a literature study. A pre-test will be held in a test panel to ensure comprehensibility and completeness of the topic guide. Subsequently, 10 professionals coming from different disciplines and 10 bereaved family caregivers will be interviewed. Also, focus group interviews will be held with professionals until saturation is reached. This design allows for obtaining in-depth information about the needs of bereaved family caregivers of patients with advanced PD and professionals. Multiple-case study Patients and their family caregivers will be involved in the multiple-case study. We will follow around 5 to 15 PD patients (and if present one family caregiver per patient) to address how quality of life and quality of care is being perceived and any changes over 8 to 12 months. PD patients will be included based on an affirmative answer from the attending physician on the so-called “surprise question”: ‘Would I be surprised if this patient died in the next 12 months?’.30 Patients will be visited at home at baseline, at 6 months and at 12 months after baseline to assess experiences, symptoms, quality of life and quality of care. Data will be collected by in-depth interviews with the PD patient as well as his/her family caregiver. Alongside the interviews, questionnaires and documents (e.g. medical records) will be used. If patients die during the study period, the closest family caregiver will be invited for a bereavement interview. Selection of participants We will recruit professionals via the Dutch ParkinsonNet, a professional Parkinsonspecific healthcare network with full nationwide coverage, consisting of 69 regional networks with than 3,000 professionals specialized in the treatment of patients with PD, including groups of specifically trained neurologists, PD nurse specialists and nursing home physicians.31, 32 We also include bereaved family caregivers via a partnership with the Dutch Parkinson Patient Association, and via the web-based community for PD patients and families (www.ParkinsonConnect.nl). For the case study, we will identify patients in advanced stages in hospitals, general practices and nursing homes.

28 | Chapter 1 We will ask neurologists, PD nurse specialists and elderly care physicians who are member of ParkinsonNet to screen their population. Signed informed consent forms from the patient and family caregiver will be obtained before study entry. Explorative after death study Bereaved caregivers who have been involved in the care for a patient with advanced PD during the past two years, will be invited for an individual interview. We aim to conduct 10 individual interviews. We aim for a diversity of professional disciplines as the care for PD is multi-professional. Focus groups will be heterogeneous. Participants need to meet the inclusion criteria (see “Inclusion criteria for bereaved family caregivers and professionals”) in order to be eligible for participation. Inclusion criteria bereaved family caregivers 1. 18 years or above; 2. cognitively able to participate in interviews; 3. bereaved family caregiver who has been involved in the care for a patient with advanced PD over the last 2 years. Inclusion criteria professionals 1. Professionals who were involved in the care for a patient with advanced PD over the last 2 years. Multiple case study We aim to achieve a total sample of around 5-15 patients and family caregivers. Patients (and if present one family caregiver per patient) will be recruited by their attending neurologist or general practitioner. A family caregiver, defined as the person who non-professionally takes care and supports the patient for most of the time, will be identified by the patient. Family caregivers need not necessarily be a family member. Participants need to meet the inclusion criteria (see “Inclusion criteria for patients and family caregivers”) in order to be eligible to take part in the study. In order to gain variation in patients’ experiences with care provision, we strive to purposively recruit patients who live at different settings e.g. at home or in a nursing home. Inclusion criteria patients 1. 18 years or above; 2. Diagnosis of “idiopathic PD” according to UK Parkinson’s Disease Society Brain Bank clinical diagnostic criteria; 3. Patients who are suffering from late-stage Parkinsonism classified according to Hoehn and Yahr stage (H&Y) IV or V in the “On”-state; OR who have developed significant disability (Schwab and England stage 50% or less) in the “On”-state;

Studyprotocol | 29 1 4. Cognitively able to complete questionnaires and to participate in interviews; 5. The patient’s attending doctor answers “No” to the surprise question: “Would you be surprised if the patient died within the coming 12 months?” Inclusion criteria family caregivers 1. 18 years or above; 2. Cognitively able to complete questionnaires and to participate in interviews; 3. Identified by the patient as family caregiver. Data collection Explorative after death study We will start with semi-structured interviews with 10 bereaved family caregivers and 10 professionals. We will use the COREQ-checklist for reporting qualitative studies as far as this is applicable to our study. Based on the literature, a semi-structured interview guide will be developed for the individual interviews (see Table 1 for topic areas). Individual interviews will be conducted by trained researchers from the project team. All interviews will be audio recorded and transcribed verbatim. Two researchers undertake the data collection independently and roughly analyze the transcripts. Focus groups will be used to obtain further insight into the experiences of the professionals with (their) palliative care, until saturation is reached. Common and consistent themes Table 1 Interview topic areas for individual interviews Bereaved family caregiver Professionals Demographic data: age, gender, years of caring Demographic data: age, gender, profession, years of experience, highest level of education - History of family member’s illness - Exploration of problems and needs of the patient during advanced PD and end of life phase (palliatieve care domains: physical, psychosocial, mental and spiritual) - Exploration of problems and unmet and met needs of the bereaved family caregiver (palliative care domains: physical, psychosocial and spiritual) - Problems and needs in the dying phase (including end of life decisions) - Exploration of the collaboration between professionals and access to palliative care services - Bereavement support - Defining palliative care - Perceptions of patients’ and carers’ palliative care needs - Barriers and facilitators in providing palliative care - Exploration of ethical issues and end of life decisions - exploration of the collaboration between professionals and palliative care services - Expectations and/or future improvements

RkJQdWJsaXNoZXIy MjY0ODMw