Fatigue

21 Fatigue

Christina Ullrich, Shana Jacobs, and Pamela S. Hinds

An 11-year-old boy with osteosarcoma defined fatigue as “being tired, not being able to do much, feeling sleepy, and feeling mentally tired but you can’t go to sleep.”

A 10-year-old girl with Burkitt lymphoma defined fatigue as “feeling so tired that you can’t even keep your head up.”

A 14-year-old girl with rhabdomyosarcoma said fatigue is when “you sleep a lot but still feel tired, heavy eyelids.”

When asked to describe how her body feels, a 12-year-old girl with acute lymphocytic leukemia said, “my body feels tired and sometimes sad and sometimes in a bad mood like I don’t want to get up sometimes.”

Vignette

Dave is a 19-year-old man with a rare immunodeficiency that was diagnosed when he was 2 years old. As an adolescent, he developed chronic hepatitis as well as pulmonary complications, for which he received a liver transplant. At the age of 18, he underwent a bone marrow transplant with the goal of curing his immunodeficiency. He has been working to recover from his bone marrow transplant and is currently working part-time. He hopes to attend college in the near future.

David began to experience bothersome fatigue prior to his liver transplant. He continues to contend with it, even as he approaches the 2-year mark after his bone marrow transplant. He described his fatigue as follows:

Fatigue is very hard to describe and it’s not easy, it’s not necessarily a feeling that you can control nor can you expect. It’s kind of like having your engine running on low fuel, you feel sluggish tired and irritated.

There’s really nothing but time that can help fatigue. It’s not something that just goes away when you want it to. But trying to actually move around and get some fresh air or going for a walk in the sun or just doing an activity that you might enjoy can help.

Advice I would give to someone with serious illness and fatigue. . . . It’ll pass, you won’t realize it but you’re gonna get better with time and you’ll eventually forget about it and start moving on with your life. It’ll take a while but you’ll realize that there are so many things we take for granted. Once you start doing those things again you’ll appreciate not being too tired to do ‘em.

Introduction

Children with life-threatening illness commonly experience fatigue, a unique experience that is complex in its origins and multidimensional in its presentation. The National Comprehensive Cancer Network defines cancer-related fatigue as “a distressing, persistent, subjective sense of physical, emotional and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning.”¹ Distinct from the “everyday fatigue” experienced by health individuals, fatigue experienced by children with serious illness is generally more severe; it is also persistent and can be unrelated to an energy imbalance (i.e., lack of rest). Other distinguishing features are its interference with function and distressing nature. For children with life-threatening illness, fatigue results in physical, social, and psychological consequences. It can exacerbate other symptoms, impair well-being and quality of life, and impede participation in meaningful activities, detracting from a child’s hope, sense of self, and connection to others. Child fatigue may also be detrimental to the well-being of parents. In the adult realm, patient fatigue is also associated with fewer caregiver work and social activities and greater caregiver strain.²

For these reasons, palliative care and other clinicians should routinely monitor for the presence of fatigue and intervene when needed. By monitoring routinely, clinicians legitimate the existence of what can be a baffling symptom to the affected child and the ill child’s parents. While there is a belief that little can be done for this distressing symptom, evidence supporting interventions to mitigate fatigue is emerging. Often, just preparing patients and families for the experience of fatigue and validating the experience can provide benefit.

During the final stages of life, a child’s body slows, and the child may withdraw from family and friends. These changes may provide a form of protection, a shield from suffering when the child’s death is imminent. As such, educating family and caregivers to anticipate such changes is important, and interventions at this time to increase the child’s energy and awareness may be detrimental to the child’s state. Though these changes at this point in care may be referred to as fatigue, they can differ from fatigue occurring upstream in the illness trajectory. The types of fatigue and their chief characteristics, causative factors, probable mechanisms of action, measures of fatigue in ill children, analytic strategies for fatigue scores, and interprofessional interventions to prevent or diminish fatigue are the subjects of this chapter.

Defining Fatigue in Ill Children and Adolescents

Fatigue is characterized as a distressing, pervasive symptom with physical, mental, social, and emotional components characterized by a lack of energy that is both perceived internally by the ill child and observed by others around the child.³ Children are able to use expressive descriptors of physical fatigue such as “not being able to run or play with friends” or looking in a mirror and seeing themselves as a “dull face.” They also describe aspects of emotional fatigue in terms of withdrawing from others, being irritable and feeling “mad” or “sad.” Researchers exploring fatigue in seriously ill children confirm that perceptions of fatigue differ by developmental age 6–8 years. Younger children tend to emphasize the physical sensation of fatigue (“I am too tired to lift my head up from this table”) somewhat more than emotional and cognitive aspects. Relatedly, they can describe how fatigue has altered their usual activities from playing and running to watching television or reading. Adolescents tend to report the impact of fatigue on their thinking, their physical sensations and limitations, and their social interactions and feelings. They also highlight mental tiredness that alternates and at times merges with the physical sensation of fatigue.³^,⁴^,⁵ Adolescents report being aware of friends and relatives being in their hospital room to visit with them but being “too tired to open my eyes” or “too tired to talk or answer questions.” Their reports of fatigue may also include their interpretation of this symptom being linked to a more serious illness or other contributory condition. In a qualitative study of children receiving treatment for cancer, researchers generated a detailed description of fatigue that reflected loss of or diminished energy and a typology of three types of fatigue: typical tiredness, treatment fatigue, and shutdown fatigue.⁶ Although the majority of descriptors are from studies involving children in treatment for cancer, including those with advanced cancers,⁷ the descriptors are similar from other groups of ill children as well.⁸ However, not yet documented is whether or to what extent these descriptions offered by seriously ill children differ from descriptions by children with non–life-threatening illnesses or how the descriptions vary or not in seriously ill children over the course of their illness.

Fatigue in Various Conditions and Populations

Fatigue is prevalent among children with a range of chronic or serious conditions. For example, children with rheumatologic conditions such as juvenile rheumatoid (idiopathic) arthritis commonly report fatigue.⁹^,¹⁰ Fatigue is also encountered in children with multiple sclerosis,¹¹ with a prevalence as high as 79%, and it has a well-established association with impaired quality of life.¹² Almost two-thirds (59%) of children with mild to moderate physical disabilities (Gillette Functional Assessment Questionnaire levels 7–10) experience fatigue greater than that experienced by healthy children.¹³ Children with epilepsy also experience more fatigue than do their healthy counterparts, with higher seizure frequency being associated with greater fatigue.¹⁴ Sleep impairment and depression also aggravate fatigue in this population.¹⁵ Among patients aged 8–47 with cystic fibrosis at end of life, the majority (96%) experienced fatigue that their caregivers described as distressing, second only in prevalence to dyspnea. Similarly, 77% of parents of children older than 2 years who died of advanced heart disease reported that their child suffered from a high degree of fatigue, and fatigue was the most commonly reported symptom in the child’s last month of life.¹⁶

In pediatric cancer, cancer-related fatigue is known to be common and highly burdensome. In one study of 58 children with cancer, the most commonly reported symptom was fatigue (52%).¹⁷ In one large, cross-sectional study of 502 children, 414 (82.5%) reported some degree of bothersome fatigue,¹⁸ while in a longitudinal study of 104 children with advanced cancer followed over 9 months, 87% reported fatigue at least once. Of these children, 97% reported highly distressing fatigue.¹⁹^,²⁰

Like fatigue occurring earlier in the illness trajectory, fatigue occurring in advanced illness is also common and may be bothersome. Within the oncology population, a study of symptoms and suffering during the last month of life found that 96% of 141 parents surveyed reported that their child had experienced fatigue.²¹ Such fatigue is also associated with impaired child well-being. In a Swedish nationwide survey of 449 parents of children with cancer, 86% reported physical fatigue as the most frequently reported symptom that had moderate or high impact on their child’s well-being during the last month of life.²² Indeed, at least in some instances, parents of children with advanced cancer view it as a source of significant suffering for their children at end of life and find it highly concerning.²³^,²⁴^,²⁵^,²⁶^,²⁷

In looking even further along the illness trajectory, interviews with 30 parents whose children had received pediatric home hospice services for any diagnosis, fatigue was one of the most frequently identified symptoms during the last week of their child’s life.²⁸ In an integrative overview of selected physical and psychosocial symptoms experienced by children approaching end of life, fatigue was described as an independent symptom, rather than a symptom taken as a “given” of the effects of illness or activity. Additionally, fatigue was described as an intrinsic part of a child dying and that its presence may actually bring relief to the dying child.⁸ For children in the last moments of life, it may be helpful to describe this type of fatigue as an expected part of the process at the close of their child’s life. In some instances, framing it as protective for the child may also be helpful.

Among children who survive cancer, the experience of fatigue is somewhat variable. Among adolescents and young adults who have recently completed cancer treatment (median 18 months), fatigue was the most prevalent symptom, experienced by 85%, and was ranked as more severe than any other symptom. Interestingly, those greater than 1 year out from treatment reported worse fatigue than those closer to treatment.²⁹^,³⁰ Other studies also support the finding of unmitigated fatigue even more than three decades after treatment. In contrast, a study of 286 childhood cancer survivors, aged 12–49 years, did not report higher rates of fatigue (14%) compared with healthy populations. However, the few who did report bothersome fatigue were more likely to have multiple chronic conditions, report depressive symptoms, and have lower quality of life scores. Fatigue as a late effect may be related to the original cancer diagnosis, as well as to other late effects. Long-term childhood acute lymphoblastic leukemia survivors with fatigue concurrently experienced poor neurocognitive function, such as executive function, task efficiency, and emotional regulation.³¹^,³²

Child Impact

A key characteristic of fatigue in pediatric life-threatening illness is its profound impact on the child’s experience. For instance, a qualitative study exploring factors that influenced quality of life in 49 children and adolescents with epilepsy found excessive fatigue as a barrier to academic and social pursuits. Participants described how intermittent or continuous fatigue made it difficult to think clearly and fully participate in classroom learning.³³ For children with cerebral palsy, fatigue is negatively associated with duration of physical activity and motivations to participate in social activities.³⁴ Children with leukemia describe fatigue, both disease- and treatment-related, as having the greatest impact on their quality of life by altering participation in school, sports, and family activities.³⁵

Multiple studies have documented cancer-related fatigue to be a debilitating symptom with physical, cognitive, social, and emotional components that are detrimental to health-related quality of life (HRQL).³⁶^,³⁷^,³⁸^,³⁹^,⁴⁰ For example, interviews with 6- to 19-year-olds unveiled multiple terms that children use to refer to their fatigue. The negative effects of the fatigue on daily functioning and mood and their need for rest were also revealed. Perceived alleviators varied by the ill child’s age and included distractions, rest, nutrition, and exercise. Through impairment of a child’s function and ability to participate in meaningful activities, fatigue may lead to loss of control in a situation that likely already feels out of control and a sense of loneliness and isolation. It is no wonder that, for many, fatigue is one of the most distressing symptoms that children may experience.⁴¹^,⁴²^,⁴³

Beyond the child’s day-to-day experience, fatigue may also be relevant in terms of its relationship with indicators of worsening health or health complications and worse prognosis (i.e., survival). Adults with cancer who experience fatigue are most likely to require unplanned clinic visits and emergency room visits.⁴⁴^,⁴⁵ Several studies of adults with both early-stage and advanced cancer have demonstrated that fatigue independently predicts worse prognosis.⁴⁶^,⁴⁷^,⁴⁸^,⁴⁹ While it seems logical that similar relationships between fatigue and prognosis and healthcare utilization would exist in pediatrics, they have yet to be examined.

Fatigue in Caregivers

Note should also be taken of the significant fatigue that parents (and other caregivers) are likely to experience throughout a child’s illness. Caregiving for the ill child (e.g., obtaining and coordinating services, medical and therapy appointments, providing hands-on care, being “on-call” 24/7), parenting siblings, household and/or employment responsibilities, and emotional factors (e.g., depression, anxiety, coping with the experience) may all contribute to parent fatigue. Experiencing such fatigue of their own may influence how a parent perceives fatigue in their ill child. The inpatient setting can also contribute to parent fatigue through sleep disturbance.

Parents/caregivers of children undergoing hematopoietic stem cell transplant, who often actively care for and remain with their child throughout the hospitalization, experience profound sleep disruption. In one sample of parents/caregivers, 71% demonstrated significant sleep disturbance, and the same proportion rated sleep quality as poor. Parents/caregivers attributed their sleep disturbance to cardiac monitor alarms (76%), infusion pump alarms (82%), staff assessments (82%), and door openings (71%).⁵⁰

Parents of children with progressive neurodegenerative conditions also report fatigue to be a common problem for themselves. It can impact them in multiple ways, including their relationships, ability to work outside the home, injuries, and exacerbation of their own medical conditions.⁵¹ Interventions such as those supporting coping skills may be helpful to caregivers and can improve caregiver distress and burden and reduce fatigue.⁵²

Clinician Recognition and Treatment of Fatigue

As depicted in Table 21.1, multiple challenges exist in clinician recognition and response to fatigue, as well as in patient–clinician and family–clinician communication about the ill child’s fatigue. The greatest challenge may be to effectively inquire about a child’s fatigue, as several studies demonstrate underrecognition of fatigue by clinicians.⁵³^,⁵⁴ Complicating the challenges of assessment is the changeability of fatigue in terms of its presence, intensity, and interference in a child’s life. Because of these challenges, clinicians should routinely inquire about fatigue. By doing so, clinicians convey their recognition that it is reasonable and acceptable for a child or parent to raise concerns about fatigue, if it occurs. If fatigue is not a problem for the child, education and anticipatory guidance that fatigue is common, is manifest in many ways, and need not be simply endured will open the door to future conversations, if the need arises.

Table 21.1 Considerations and challenges in initial response to the ill child’s fatigue

Challenges in clinician detection and response to fatigue	Strategies to address challenges	Challenges in patient–clinician communication about fatigue	Strategies to address challenges
Prevalence (and impact) under-appreciated. For example, fatigue may be overshadowed by more visible symptoms	Clinician education	Not wanting to “bother” the clinician	Anticipatory guidance and education (see text) Routine inquiry about child’s fatigue, including the question: “How tired have you been in the past 7 days?” (see text)
Multidimensional presentation of fatigue	More investigation into the presentation and patient descriptions of fatigue Further incorporation of fatigue assessments into practice Clinician education regarding assessment queries to ask of the ill child	Fear of appearing to be a “complainer”	Anticipatory guidance and education (see text) Routine inquiry about child’s fatigue (see text)
Belief that fatigue is “to be expected”	Clinician education	Belief that fatigue is “to be expected”	Anticipatory guidance and education (see text) Routine inquiry about child’s fatigue (see text)
Belief that fatigue is unavoidable/effective interventions do not exist	Clinician education Further research into current and novel interventions	Belief that fatigue is unavoidable/effective interventions do not exist	Anticipatory guidance and education (see text) Routine inquiry about child’s fatigue (see text)
Focus on disease-directed treatment	Clinician education	Worry that fatigue indicates disease progression or will result in de-intensification of treatment	Anticipatory guidance and education (see text)
Systems issues (e.g., time, documentation practices)	Systems changes that allow routine assessment and that facilitate documentation and clinician attention to fatigue Adoption of single item fatigue measure¹¹⁹	Need for standardized clinical query regarding fatigue to facilitate communication and accurate assessment	Development and adoption of measures, such as the PROMNIS single-item fatigue measure¹¹⁹
Lack of established risk factors for fatigue (particularly ones that are modifiable)	Research elucidating (modifiable) risk factors for fatigue
Need for pediatric-specific guidelines and evidence-based interventions	Further research in both existing and novel interventions

These challenges to recognizing and labeling fatigue in ill children account in part for the undertreatment of fatigue which has been documented.²¹^,²⁵ In one study of children with advanced cancer and fatigue, only 13% received fatigue-directed treatment.²¹ Undertreatment of recognized fatigue may stem from a variety of factors, including a need for more education regarding fatigue interventions and their effectiveness.⁵⁵^,⁵⁶ When guidance or treatment is provided, clinicians usually recommend rest, which is not an intervention well-supported by evidence.⁵⁷^,⁵⁸ Among the children with advanced cancer and fatigue described earlier, treatment was successful in only 25%, suggesting that education and evidence from rigorous studies to guide clinicians and provide them with effective interventions for fatigue are likely both essential.

Fatigue Assessment and Measurement

Fatigue assessment clinically receives guidance from the Guidelines from the National Comprehensive Cancer Network (NCCN) that recommend routine screening for fatigue as the sixth vital sign.¹ According to the NCCN guidelines, children older than 12 years of age should be screened using a simple numeric rating scale such as 0, “no fatigue,” to 10, “worst fatigue you can imagine.” For children 7–12 years of age, a 5-point scale is recommended with the word anchors being “not tired” to “worst.” For children aged 5 and 6 years, the words “tired” or “not tired” are recommended for use to assess the presence of fatigue. If the screening confirms the presence of fatigue, the clinical assessment moves to a deeper level with an assessment of eight treatable contributing factors to fatigue: anemia, pain, sleep disturbance or poor sleep hygiene, nutritional deficits, changes in functional status, emotional distress, medications or side effects and drug interactions, and presence of comorbidities. The healthcare team should assess for the onset and type of fatigue, aggravating or alleviating factors, and degree of interference with the child’s functioning.¹ This assessment should be done at standardized points in care and at times of change in the ill child’s condition.

Quantitative measurement of fatigue by the ill child, caregiver (parent or other proxy), and clinician occurs in two forms: disease-specific or general measures. Caregiver and clinician reports have a longer history of use than do child reports. Because ill children, their caregivers, and their clinicians define fatigue differently and identify different causative factors,⁵⁹^,⁶⁰ soliciting reports from all three may be essential to the clinical management of fatigue. Another principle in fatigue measurement is timing. Because fatigue has features such as persistence and intensity, it is important to solicit the reports of the ill child, caregiver, and clinician over time. This would include scheduled, standardized times as well as at unexpected changes in the ill child’s health status.

Examples and descriptions of disease-specific and general pediatric fatigue and multisymptom measures that include items about fatigue follow. Completed reviews of pediatric measures being used to index fatigue indicate that all three types of fatigue measures have been assessed for key characteristics including their psychometric properties. Fatigue measures declared ready for incorporation into clinical research by one or both of the fatigue instrument reviews include the Fatigue Scale-Child, Fatigue Scale-Adolescent (FS-A), the PedsQL Multidimensional Fatigue Scale, and the PROMIS Pediatric Fatigue measure.⁵^,⁶¹^,⁶²^,⁶³^,⁶⁴^,⁶⁵^,⁶⁶ Original studies have reported on these established measures and support their psychometric properties, including responsiveness to change over time.

The Childhood Fatigue Scale (CFS) is a 10-item (4-point Likert scale) questionnaire that asks children (7–12 years) about their tiredness during the previous week. The three subscales are lack of energy, inability to function, and altered mood. The Parent Fatigue Scale (PFS) is a 17-item inventory of parents’ perception of their child’s fatigue in the previous week. In addition to the three subscales on the children’s version, it also includes a scale of altered sleep. The FS-A is a 13-item questionnaire that asks adolescents (13–18 years) to evaluate their fatigue experience during the previous week. The child and parent scales are available in English and Spanish; the adolescent form in English only. The CFS, PFS, and FS-A are validated research instruments, easy to administer, and require limited time to complete in the clinical setting.

The PedsQL Multidimensional Fatigue Scale is an 18-item research instrument (ages 2–18) with three subscales of six items each: general fatigue, sleep-rest fatigue, and cognitive fatigue. The scale is self-administered for 8- to 18–year-olds, interview-administered in 5- to 7-year-olds, and done by parent proxy for the youngest children. The 5-point Likert response option format solicits ratings to the prompt: “How much of a problem has this been for you in the past month?: The measure has strong reliability and construct validity coefficients in its testing in children with cancer, sickle cell disease, and other health conditions. It is available in 22 languages.⁶²^,⁶⁷^,⁶⁸ The Pediatric Functional Assessment of Chronic Illness Therapy-Fatigue (Peds FACIT-F) is an 11-item scale for children with cancer that measures fatigue in the past 7 days.⁶⁹ The Peds FACIT-F has very acceptable internal consistency coefficients and concurrent validity. It is available in English and Spanish.⁶⁹

The PROMIS Pediatric Measures, including the PROMIS Pediatric Fatigue measures were developed using item response theory (IRT) and created to document child and adolescent reports of their symptom, function, and quality-of-life experience with illness and treatment. The measures were developed first from qualitative methods with children 8 years and older for item development, identification of extant questionnaire items for an item pool, item review, and revision by experts.⁷⁰^,⁷¹ Very acceptable item and scale reliability, as well as diverse forms of validity have been reported for the measures and specifically for the PROMIS Pediatric Fatigue measure, including responsiveness to change over time. Items are scored from 0 (“never”) to 4 (“almost always”) for symptom (fatigue) interference. Items are considered equivalent psychometrically and therefore can be selected from the item bank to be used for the same measurement purpose. Generally, 6–8 items are recommended to achieve acceptable to strong internal consistency coefficients. The time period is “in the past 7 days.”

The PROMIS Pediatric Fatigue measure has been tested in diverse pediatric groups such as children with advanced disease receiving palliative care and children receiving treatment for cancer, sickle cell disease, and nephrotic syndrome.⁶²^,⁷²^,⁷³^,⁷⁴^,⁷⁵^,⁷⁶^,⁷⁷ Additionally, the PROMIS Pediatric Fatigue measure has been evaluated for clinically important change over time using the scale-judgment method to establish the minimally important difference (MID); the MID is a 3-point difference in scores over time.⁷⁷

More recently validated multisymptom measures that include fatigue items validated in pediatric samples include the Symptom Screening in Pediatrics Tool (SSPedi) (https://www.sungresearch.com/sspedi), the Pediatric PRO-CTCAE measurement system, and the Pediatric Quality of Life and Evaluation of Symptoms Technology (PediQUEST). The SSPedi is a 15-item, 5-point Likert measure for children aged 8–18 years to report their symptoms “since yesterday” during cancer treatment and stem cell transplantation. The tool is viewed as a screening measure and has a matching proxy version. Reliability, different forms of validity, and responsiveness to change have been positively assessed. A mini-SSPedi for children 4–7 years of age has been derived from the older age group version and is in testing now.

The Pediatric PRO CTCAE measurement system, begun from qualitative work with pediatric oncology experts and followed by cognitive interviewing involving children and their caregivers, includes 62 subjective cancer treatment toxicities and 1–3 questions per toxicity in terms of frequency, intensity, and interference. The recall period is “the past 7 days,: and child- or proxy-reported scores can be mapped onto the National Cancer Institute’s Common Toxicity Criteria Adverse Events (CTCAE) grades.⁷⁸ The items have been validated in 7- to 18-year-olds in treatment for cancer (i.e., content validity, construct validity), including for responsiveness to change over time. In addition, the items have been mapped to clinician-reporting of treatment toxicities.⁷⁸ A matching proxy measure is also available and has been validated in 7- to 18-year-olds in treatment for cancer.⁷⁶^,⁷⁹^,⁸⁰^,⁸¹^,⁸²^,⁸³

PediQUEST is a computer-based child or parent report of multiple symptoms including the child’s fatigue as well as the child’s quality of life and includes an adapted version of the MSAS.¹⁹^,²⁰ The age of eligible children is 2–18 years, with parents typically completing the items on behalf of their child younger than 7 years. Response options use a 4- or a 5-point Likert format for the 24 physical or psychological symptoms in three age-specific versions: 2–6 years (proxy), 7–12 years, and 13–18 years. The symptom presence, frequency, severity, and bother in the preceding week are solicited. Psychometric characteristics including responsiveness to change have not yet been reported.

In summary, multiple validated measures exist of fatigue or inclusive of fatigue items in ill children. The measures have been most commonly validated in children with cancer, including advanced stages and at end of life. Several of the preceding measures and fatigue items have the documented ability of capturing responsiveness to change over time, and it is these measures that would be most well-suited for longitudinal and clinical trial studies. This includes children with incurable cancer. The multiplicity of validated fatigue measures, including in pediatrics, is considered to be a research challenge and was addressed by one working group in oncology convened by the National Cancer Institute. After weighing the features of multiple fatigue measures, the working group recommended the use of the PROMIS Fatigue measures in cancer research (adult or pediatric) whenever possible.⁸⁴ Certainly, the selection of a measure is based on multiple factors including preference of the study team, match with study purpose, and target participants but having the same measure used across studies has the advantage of allowing for direct comparison of findings from different patient groups.

Assessment of Fatigue as a Dose-Limiting Toxicity

Clinicians have reported that fatigue can be a dose-limiting toxicity in pediatric oncology for some patients enrolled on a Phase I study.⁸⁵^,⁸⁶ Importantly, children enrolled on Phase I/II trials for incurable cancers have willingly completed self-report fatigue measures (e.g., PROMIS Pediatric Fatigue) at more than one time point, among other symptom and function measures, with a minimal amount of missing data, indicating that the measures are not perceived by these children as burdensome or troublesome.⁸⁷ Being able to collect subjective treatment toxicity information, such as fatigue, from the ill child at this point in their cancer treatment would enhance the completeness and accuracy of the impact of the Phase I agent on the child.

Fatigue Mechanisms

As depicted in Figure 21.1, fatigue in children with serious illness is a complex process. Across illness conditions, research aimed at defining fatigue mechanisms has been limited. It is likely that significant differences between populations of children (e.g., differences in disease pathophysiology, disease-directed treatments, and in child characteristics such as age and gender) result in fatigue stemming from different mechanisms. However, such varying mechanisms have yet to be described and delineated.

Figure 21.1 Diagram representing predisposing host and contextual factors that may exacerbate or mitigate fatigue; physical and psychosocial (illness-related) factors, as well as biochemical and physiologic alterations contributing to fatigue and prolonged fatigue. The potential impact of fatigue and prolonged fatigue are also displayed.

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