Impact of Caregiving Burden on Caregiver Health Caregiver burden is a multidimensional response that results from taking care of an ill individual. More specifically, caregiver burden refers to the st

The couple’s primary residence was in New Jersey, 143 miles from the trans- plant center. They were therefore re- quired to establish a temporary resi- dence near the transplant center.

Because both the patient and care-giver were unemployed due to disabil- ity, their income was restricted. Social support was limited to a 20-year-old daughter in college and the caregiver’s sister, employed full time in New Jer- sey. In addition, the caregiver’s el- derly mother, aunt, and father also de- pended on her for assistance. The caregiver’s father resided in a nursing home after becoming disabled follow- ing brain surgery. COURSE OF TREATMENT The HSCT initial hospitalization and immediate recovery period was diffi- cult and prolonged, lasting approxi-mately 2 months. The patient experi- enced a pericardial effusion, renal failure, pneumonia, and acute graft vs host disease. After the initial hospital discharge, the patient was readmitted twice: once for coughing, diarrhea, and CME available online at www.jamaarchivescme.com and questions on p 415. Author Affiliations:US Public Health Service, Clini- cal Nurse Scientist, Nursing Research & Translational Science, Nursing & Patient Care Services, Health Clini- cal Center (Dr Bevans); and Neuroendocrine Immu- nology and Behavior Section, National Institute of Men- tal Health (Dr Sternberg), National Institutes of Health, Bethesda, Maryland.

Corresponding Author:Margaret Bevans, RN, PhD, National Institutes of Health, Clinical Center, 10 Cen- ter Dr, Room 2B13, MSC 1151, Bethesda, MD 20892 ([email protected]).

Grand Rounds Section Editor:Mary McGrae McDermott, MD, Contributing Editor,JAMA. Unlike professional caregivers such as physicians and nurses, informal care- givers, typically family members or friends, provide care to individuals with a variety of conditions including advanced age, dementia, and cancer. This ex- perience is commonly perceived as a chronic stressor, and caregivers often ex- perience negative psychological, behavioral, and physiological effects on their daily lives and health. In this report, we describe the experience of a 53-year- old woman who is the sole caregiver for her husband, who has acute myelog- enous leukemia and was undergoing allogeneic hematopoietic stem cell trans- plantation. During his intense and unpredictable course, the caregiver’s burden is complex and complicated by multiple competing priorities. Because care- givers are often faced with multiple concurrent stressful events and ex- tended, unrelenting stress, they may experience negative health effects, me- diated in part by immune and autonomic dysregulation. Physicians and their interdisciplinary teams are presented daily with individuals providing such care and have opportunity to intervene. This report describes a case that exempli- fies caregiving burden and discusses the importance of identifying caregivers at risk of negative health outcomes and intervening to attenuate the stress associated with the caregiving experience.

JAMA. 2012;307(4):398-403www.jama.com 398JAMA, January 25, 2012—Vol 307, No. 4 ©2012 American Medical Association. All rights reserved.Downloaded From: https://jamanetwork.com/ by a Walden University User on 06/28/2020 hematuria with clots; and a second time for acute heart failure and sepsis.

CAREGIVING CHALLENGES This caregiver had multiple caregiv- ing responsibilities, maintained 2 residences, subsisted on limited finances, and managed multiple health conditions of her own. Lack- ing the physical presence of a sup- port system, she shouldered the entire burden of her husband’s brief but intense outpatient care including cleaning, driving, preparing meals, and coordinating medication, oxy- gen, and other treatment-related activities. She struggled to maintain hope for the transplant’s success while living with the constant uncer- tainty of her husband’s survival, a concern that was exacerbated by the sudden death of a close cousin.

Although she complained little, when asked, she reported severe emotional distress, significant fatigue, sleep impairment, and diffi- culty maintaining her focus and energy throughout the transplant tra- jectory.

BACKGROUND Family caregivers are essential part- ners in the delivery of complex health care services and this case exemplifies the burden and stress associated with providing care during cancer treat- ment. Unlike professional caregivers such as physicians and nurses, infor- mal caregivers, typically family mem- bers or friends, provide care to indi- viduals with a variety of conditions, most commonly advanced age, demen- tia, and cancer. 1As mounting evi- dence suggests that caregiving is del- eterious to one’s health, increased attention is being paid to the day-to- day well-being of caregivers. 2Com- pared with noncaregivers, caregivers often experience psychological, behav- ioral, and physiological effects that are associated with impaired immune sys- tem function, coronary heart disease, and early death. 3-5 The level of burden on caregivers of cancer patients is greater than the bur-den experienced by those caring for older persons and similar to that expe- rienced by caregivers of patients with dementia. 6To receive a diagnosis of cancer is recognized as a significant stressor to the patient and family. How- ever, the resultant treatment creates ad- ditional fears and challenges and fre- quently requires the direct support of a caregiver including assisting with ac- tivities of daily living, administering medications, providing transporta- tion, preparing meals, managing fi- nances, advocating for health care, and providing emotional support. 7Care- giving is labor intensive, with approxi- mately one-quarter of those caring for cancer patients spending in excess of 40 hours a week providing these ser- vices to family or friends. 1The level of care required by the care recipient is a major factor that influences the care- giver’s life and health effects. Care- givers of cancer patients providing higher levels of support are more likely to report negative outcomes, less likely to be effective partners in the patient’s care, and are more likely to postpone their own health care needs.

Although cancer patients in general report high-symptom severity result- ing in a greater need for support from the health care team, 8one of the most complex cancer treatments, alloge- neic HSCT, is particularly burden- some. Even an uncomplicated or re- duced-intensity allogeneic HSCT may require a 2- to 4- week hospitaliza- tion, followed by 3 to 4 months of in- tense outpatient management. Alloge- neic HSCT recipients are often debilitated and frequently experience complications and other treatment- related toxic effects that result in mul- tiple hospital readmissions. 9For this reason, the caregiver in the case pre- sented herein and her husband were re- quired to establish a residence near the transplant center. Without a care- giver, transplant options may be lim- ited and survival shortened.

10,11 Al- though this potentially curative treatment provides hope, it also car- ries a 30% mortality rate within the first year. 12As a result, caregivers experi-ence substantial stress as the burden of caring (often exclusively) for their sick loved ones, being separated from their own support systems, and balancing other life responsibilities threatens to overwhelm them. 7 PRESENTING SIGNS AND SYMPTOMS OF STRESS As evident in the case study, the most obvious signs and symptoms of care- giving stress are often psychological problems, most commonly anxiety, de- pression, worry, and loneliness. 13These psychological reactions are related to the caregiver’s appraisal of the experi- ence, with those reporting more ben- efit and deriving more meaning from the experience saying that they feel less stress and report a better quality of life. 14 The level of distress reported by many of those caring for someone with can- cer can be equal to or greater than that of the cancer patient, 15 with adult daughters seeming to have the great- est difficulties. 14In addition, those re- porting higher levels of emotional dis- tress also report more problems with fatigue, sleep impairment, and un- healthy behaviors.

16 Caregivers of patients with cancer re- port having to modify their lifestyles to accommodate the care recipient’s needs including restricting leisure activity and contact with friends and family. 13Thus, at a time when caregivers are most in need of the restorative benefits of re- laxation, they have the least amount of time and resources available. Further complicating matters, caregivers of can- cer patients prioritize the needs of the patient over their own, 17leaving little time for maintaining good nutrition, ex- ercising, and undertaking health evalu- ations. As a result, caregivers have nu- merous health-related problems, such as sleep disturbances and fatigue, which worsen as the patient’s physical func- tion and symptom burden increase. 18 The symptom burden in HSCT recipi- ents can be significant for weeks to months following the treatment 19and may contribute to the symptoms re- ported by HSCT caregivers during the survivorship phase. 20 HEALTH EFFECTS OF CAREGIVERS OF ADULT CANCER PATIENTS ©2012 American Medical Association. All rights reserved. JAMA, January 25, 2012—Vol 307, No. 4 399Downloaded From: https://jamanetwork.com/ by a Walden University User on 06/28/2020 PATHOGENESIS OF HEALTH EFFECTS IN CAREGIVERS One’s perception of an event plays a large role in the body’s response, and the experience of caring for an individual undergoing HSCT trans- plantation is inherently stressful. All stressors activate the hypothalamic- pituitary-adrenal axis and the adren- ergic sympathetic nervous system.

After exposure to stressful stimuli, the hypothalamus releases corticotropin- releasing hormone, which stimulates the pituitary gland to release adreno- corticotropic hormone, which in turn triggers the release of glucocorticoids (cortisol) from the adrenal cortex. At the same time, the sympathetic ner- vous system is activated with release of epinephrine (adrenalin) from the adrenal medulla and norepinephrine from sympathetic nerves. In combina- tion, the molecules released during the stress response have profound effects on the function of most cells and organs throughout the body including the brain, heart, respiratory system, muscles, skin, liver, gastroin- testinal tract, and, importantly, the immune system. 21 Activation of the acute stress re- sponse is life-saving and prepares the organism to avoid impending danger with enhanced vigilance, focused at- tention, and increased energy. In con- trast, chronic stress has negative con- sequences on health. In chronic stress,the healthy diurnal rhythm of the hy- pothalamic-pituitary-adrenal axis, with a late evening nadir and a morning peak, is flattened showing instead low morning and elevated afternoon or eve- ning cortisol levels. 22This represents a state of physiological burnout that of- ten accompanies psychological burn- out. In the early stages of burnout, hy- pothalamic-pituitary-adrenal axis activity is increased. Months later, hy- pothalamic-pituitary-adrenal axis ac- tivity decreases. One explanation for this progression may be related to changes in caregivers’ psychological coping and expectations, with active coping occurring early and loss of ex- pectations of being able to cope suc- cessfully occurring later in the pro- cess. More recent studies indicate that dysregulation of the circadian rhythm during chronic stress also has an en- docrine basis. Thus, even mild eleva- tions in evening cortisol, as occurs in chronic stress, can disrupt theCLOCK (circadian locomotor output cycles ka- put) gene mechanism of circadian regu- lation of the hypothalamic-pituitary- adrenal axis, resulting in functional hypercortisolism. 23Family caregivers of cancer patients also show autonomic imbalance with a shift toward the sym- pathetic and away from the parasym- pathetic tone. 24,25 Although a single stressful event or multiple events with time to recover be- tween events may not affect health,multiple stressors without adequate re- covery time or chronic stressful events as presented in the case study may in- crease the risk of illness. The term coined to define the load or total bur- den of multiple stressors similar to those to which caregivers are exposed daily is calledallostatic load. 26A large allo- static load is a potential mechanism that links caregiving to adverse health out- comes. 27Chronic stress, including that experienced by caregivers of Alzhei- mer patients, has been shown to in- crease risk of infection 28,29 ; decrease the take rate of vaccine immunization; slow wound healing 29; speed cancer growth via -adrenergic mechanisms that stimulate angiogenesis 30; and speed chromosomal aging as indicated by telo- mere shortening. 31Stress does not cause these conditions but can foster them through the effects of stress hormones and neurotransmitters on disease pro- cesses and immune responses. On the other hand, a blunted hypothalamic- pituitary-adrenal axis response and functional glucocorticoid resistance have been associated with proinflam- matory states and predispose to auto- immune/inflammatory diseases, 21car- diovascular disease, 32 diabetes, and metabolic syndrome, which are char- acterized by central or abdominal obe- sity, high blood pressure, elevated cho- lesterol and insulin resistance, 33and depression. 34 EVALUATING AND MANAGING STRESS IN CAREGIVERS OF CANCER PATIENTS Although stressful events are inevi- table, it is possible to identify a care- giver who is at increased risk of nega- tive outcomes, assess the degree to which the caregiver’s life and health may be negatively affected, and recom- mend interventions that could attenu- ate the negative repercussions of the caregiving experience. Recognizing the psychological, behavioral, and physiological effects of caring for a loved one with cancer provides an excellent opportunity for primary pre- vention. A common barrier in primary prevention typically is access to pri- Table 1.Brief Depression and Distress Screening Tools for Caregivers Questionnaire Source Description Distress Thermometer National Comprehensive Cancer NetworkA single-item measure of global distress with 36 common problems that can contribute to distress (yes/no) Caregiver Self-Assessment QuestionnaireAmerican Medical AssociationAn18-item questionnaire to measure emotional and physical distress PROMIS Depression Anxiety Sleep disturbance FatiguePatient Reported Outcomes Measurement Information System—NIHIndividual 4-item measure to independently assess depression, anxiety, sleep disturbance, or fatigue PROMIS-Global Patient Reported Outcomes Measurement Information System—NIHA10-item questionnaire that measures emotional and physical distress HEALTH EFFECTS OF CAREGIVERS OF ADULT CANCER PATIENTS 400JAMA, January 25, 2012—Vol 307, No. 4 ©2012 American Medical Association. All rights reserved.Downloaded From: https://jamanetwork.com/ by a Walden University User on 06/28/2020 mary care physicians. In this popula- tion, caregivers cross the thresholds of offices and health care agencies on a regular basis. Should a caregiver of a patient with cancer visit his/her own primary care physician, it rightly can be assumed he/she has experienced adverse health affects. 15 However, when accompanying a cancer patient for a medical visit, the caregiver may hide or minimize these adverse effects in an effort to shield the patient and to avoid shifting attention to herself or himself. Therefore, it is imperative that the patient’s history and physical be expanded to include assessment of the caregiver. Fortunately, in the case presented herein, the interdisciplinary team, including an oncology social worker, assessed both the patient’s and the caregiver’s needs. The caregiver assessment included the knowledge level of the caregiver related to role expectations, the patient care needs or degree of burden, and the presence of competing responsibilities. The oncol- ogy social worker served as coordina- tor for the provision of appropriate psychological and social services in the agency and community.

Brief screening questionnaires can be helpful in a busy clinical environment (T ABLE 1). Caregivers can complete the questionnaire independently and the re- sponses are easy to interpret by a nurse, social worker, or physician who then can provide guidance regarding pos- sible referrals for specialized care. The Distress Thermometer 35 is a self- report measure of distress including a single-item distress rating scale from 0 to 10 and has been validated for HSCT caregivers. 36In addition, the Ameri- can Medical Association (AMA) devel- oped the Caregiver Self-Assessment Questionnaire 37 to assess caregiver stress and health, which was validated as a self-report screening measure for depression in caregivers of patients with dementia. 38The AMA Healthier Life Steps Program’s Personal Health Hab- its Questionnaire 39assesses key life- style behaviors including smoking, use of alcohol, nutrition practices, and ex- ercise. Web-based collection systemssuch as the Patient Reported Out- comes Measurement Information Sys- tem (PROMIS) are now available to both researchers and clinicians, allow- ing collection of a large variety of out- come data including symptoms com- monly prevalent in caregivers of cancer patients such as depression, anxiety, fa- tigue, and sleep disturbance. 40 Two unique functions of the PROMIS pro- gram are the ability to collect patient outcomes longitudinally, making it pos- sible to follow changes in function over time and the ability to compare pa- tients’ outcomes against national norms.

Many well-validated psychological questionnaires are sensitive but are also subjective, indicating the need for de- velopment of more objective, quanti- tative measures of allostatic load. In a research setting, a comprehensive as- sessment of allostatic load or cumula- tive stress includes psychological mea-sures of stress such as distress, anxiety, and depression; hormonal measures of the hypothalamic-pituitary-adrenal axis response (cortisol); physiological mea- sures of the sympathetic and parasym- pathetic nervous system (blood pres- sure, heart rate, heart rate variability, 41,42 and salivary amylase 43); and measures of end-organ effects such as immune system function and chromosomal damage. 26,31 Some newer noninvasive methods include cortisol levels in hair 44 and stress and immune biomarkers in eluates from sweat patches. 45-47 Al- though many of these approaches show promise, they are not yet applicable in the clinical setting. More research is needed to develop and validate sensi- tive, noninvasive, quantitative mea- sures of allostatic load and models that predict health outcomes.

The assessment of stress and how it affects the health of family caregivers Table 2.Caregiver Resources Resource Web Site Address Description American Cancer Societywww.cancer.org/treatment /caregivers/indexCaregiver support Coping information Cancercare www.cancercare.org/tagged /caregivingSupport groups, Education, Workshops Counseling services Financial assistance CarePages.com www.carepages.com Site to create video or Web site blog to connect with others CaringBridge www.CARINGBRIDGE.org Site to connect with friends and family Family Caregiving Alliancewww.caregiver.org Information, education, links to services, research, and advocacy for caregivers Leukemia and Lymphoma Societywww.lls.org/#/diseaseinformation /forcaregiversEducational resources specific for cancer caregivers National Alliance for Caregivingwww.caregiving.org Conduct research and develop national programs to increase the awareness of caregiving in the United States Educational resources, Web casts and conferences on caregiving National Caregiving Foundationwww.caregivingfoundation.org Links to caregiving resources Free caregiver support kit National Family Caregivers Associationwww.nfcacares.org Educational and support Empowering caregivers NIH Medline Plus www.nlm.nih.gov/medlineplus /caregivers.htmlEducational resources Links to research Health information and care tips for the caregiver The National Cancer Institutewww.cancer.gov/cancertopics /coping/familyfriendsSupport for caregivers Resources for children and teens with family members diagnosed with cancer HEALTH EFFECTS OF CAREGIVERS OF ADULT CANCER PATIENTS ©2012 American Medical Association. All rights reserved. JAMA, January 25, 2012—Vol 307, No. 4 401Downloaded From: https://jamanetwork.com/ by a Walden University User on 06/28/2020 should be followed by guidance and in- dividualized interventions to attenu- ate the health consequences. The mere act of assessing and listening to the care- givers’ needs communicates empathy, which may in itself improve out- comes. 48,49 At a minimum, offering the patient and caregiver how-to informa- tion regarding patient care, mainte- nance of family and marital relation- ships, and the importance of self-care may help caregivers be more prepared and less distressed. 50Community or Web-based resources for caregivers are plentiful (http://www.cc.nih.gov/wecare /resources.html) with a select few high- lighted inT ABLE 2. A growing body of evidence supports simple stress man- agement practices such as walking, meditating, and adopting nutritional changes such as the Mediterranean diet that may help reduce fatigue, improve sleep, and reduce the risk of some stress-related illnesses. 51,52 Clinicians should remain alert to stress-related signs such as elevated blood pressure and heart rate, as well as delayed wound healing or increased frequency of in- fections. 3,24,25 Looking toward the future, a num- ber of questions remain. First, while a substantial body of evidence has accu- mulated regarding the health effects of caregiving, most of these studies have involved small sample sizes and single sites, and the translation of interven- tion research into practice has been slow. How preventive services such as screening, education, and referrals are systematically incorporated into our health care system is a policy issue be- yond the scope of this article, but an is- sue clearly worthy of future attention.

Although providing the level of care de- scribed herein requires some thought, planning, and time, it is not without re- ward because improving the experi- ences of caregivers may in itself pro- vide “greater sustenance and meaning” for the physician. 49 CASE STUDY FOLLOW-UP The patient died during his second re- admission, within 6 months of begin- ning the HSCT treatment. His wife then“had to go thr[ough] the phases of plan- ning his funeral, which [she] was not prepared for, feeling like there was nothing left for [her].” She “went through the grieving process like ev- eryone else...just trying to survive.” She had the daunting task of explain- ing to her sick elderly father that her husband had passed away; 4 months later he too passed away, only 2 days before his 90th birthday. Shortly there- after, she experienced another myocar- dial infarction and required the place- ment of a pacemaker.

More recently, financial pressures forced the caregiver to sell her house and downgrade to more affordable housing, and her cardiovascular dis- ease continues to require careful man- agement. On a happier note, her daugh- ter, now 22 years old, is expecting the family’s first grandchild. Financial Disclosures:All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest, and none were reported.

Additional Contributions:The authors would like to acknowledge the family featured in the case study and for providing permission to publish their story. We also thank Leslie Wehrlen, RN, BSN, OCN; Alyson Ross, RN, MS; Stephen Klagholz, BS, Gwenyth Wallen, RN, PhD; and Clare Hastings, RN, PhD, FAAN, at the NIH Clinical Center for their support of this program of research and help with the manuscript, none of whom received compensa- tion beyond their regular salaries.

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