From Pain to Sleep: Listening to Patient-reported Outcomes

8/14/2019 From Pain to Sleep: Listening to Patient-reported Outcomes

http://slidepdf.com/reader/full/from-pain-to-sleep-listening-to-patient-reported-outcomes 1/33

From Pain to Sleep: Listening to

Patient‐Reported

Outcomes

Pediatric Trends 2009

Pamela S. Hinds, PhD, RN, FAAN

Director, Nursing Research

Children’s National Medical Center

Washington, D.C.

Objectives:

• describe the role of nurses in generating clinical

research questions as influenced by patient‐reports.

• analyze the evolution of a research program

centered around nurses’ responses to patient‐

reported outcomes



Amazing Collaborators

• Marilyn Hockenberry, PhD, RN, PNP,FAAN

• Heather Jones, MN

• Sue Zupanec, MN

• Ching‐Hon Pui, M.D.

• Mary Relling, PharmD

• Deo Kumar

Srivastava,

PhD

• Susan Clifton, RN

Amazing Collaborators

• Nancy K. West, BSN, CRA

• Michele Pritchard, PhD, PNP

• Kelly Vallance, M.D.

• Jami Gattuso, MSN

• Jia Yang,

PhD

• Brett Loechelt, MD

• Jane Sande, MD



Patient‐Reported Outcomes

• What are they?

‘a measurement of any aspect of patient’s health

status that comes directly from the patient (i.e.,

without the interpretation of the patient’s

responses by physician or others)’

– FDA, 2006

PROs: why

such

interest?

• Provide clinically valuable information about

the patient’s experience with treatment or

disease‐related care

• Symptoms

• Toxicities

• Burden

• Benefits



PROs: Why such Interest?

• FDA Preference

– Guidance for Industry: Patient‐Reported Outcome

Measures, 2006

• NIH Involvement

– Instrumentation Funding Opportunities

• AHRQ Report

– Lorenz, Lynn,

Hughes

et

al.,

2006

PROs in

Pediatrics

• Not always possible

– Disease or treatment factors

– Developmental status

– Family culture

• Reasonable reliance upon proxy reports

– Early

involvement

of

proxies

–not

just

at

end

of

life



PROs at End of Life

0

1

2

3

4

5

6

7

8

In eligible Patien t Pare nt Staff R ecord Oth er

PROs Require

• Respect for the child’s voice

• Standardized ways to invite the child’s voice

• Action on behalf of the child’s report



From Pain to Sleep:

• Initial study in the pediatric intensive care unit

to study instruments by patient‐reported pain

• Compared scores and acceptability of

instruments to children ages 4 and older

• Faces Scale, Hester Poker Chips, VAS

• Cultural aspects for parents

• Child report:

‘you

think

pain

is

the

worst… it’s

not.’

Fatigue



Distinguishing Fatigue in its Age‐

Related forms

• One of 10 monitored symptoms: Fatigue was rated

as most prevalent and distressing

• Two‐site Fatigue Scholars’ Program (Oncology

Nursing Society)

– Conceptual Definitions

– Instruments

What is

fatigue?

• Cancer‐related fatigue (focus groups,

individual interviews, concept analysis)‐ – In 7 to 12 year olds: a profound sense of being weak or

tired, or of having difficulty with movement such as

arms or legs too heavy to life and eyes to heavy to open.

» Hinds, Hockenberry ‐Eaton, Gilger et al., 1999

– In 13 to 18 year olds: a changing state of

exhaustion that is a physical condition, at other

times a mental

state,

and

at

other

times

a

combination of physical, emotional and mental

tiredness» Hinds, Hockenberry ‐Eaton, Gilger et al.,1999



Method Differences with

Adolescents

• Individual Interviews: Code for Sadness

• Focus groups: Code for Anger

– implications for measurement and clinical

assessment identified

– Education sheets created

CONTRIBUTING FACTORS

Environmental Personal/Behavioral Cultural/Family/Other Treatment-Related

• Lacking a schedule• Interruptions in ahospital environment


FATIGUE

ALLEVIATING FACTORS

• Protected rest time

• Controlled or reducedinterruptions• Being quiet

++ + +

_ _ _ _



Measuring Fatigue and the

Derivation of Screening Items

• Instruments:

– Fatigue Scale – Child (10‐item; 7 day and 24‐hour versions; cut

score)

– Fatigue Scale – Adolescent (14‐item; 7 day and 24‐hour

versions)

– Fatigue Scale – Parent (17‐item; 7 day and 24‐hour versions)

– Fatigue

Scale

– Staff

(9‐

item;

7

day

and

24‐

hour

versions)

– Symptom Distress Scale – Patient (10‐item; ‘this day’)

InstrumentationInstrument Internal

Consistency

Construct Validity‐

Factor Analysis

Construct

Validity ‐

Correlations

FS‐Child 0.84 Lack of energy

Can’t function

Altered mood

0.35/FS‐Parent

0.16/FS‐Staff

0.45/

Depression

FS‐Adolescent 0.95 Lack of energy

Can’t function

Altered mood

Can’t engage

0.76/FS‐Parent

0.27/FS‐Staff

0.87/

Depression

FS‐Parent 0.88 Lack of energy

Can’t function

Altered Sleep

Altered Mood

0.43/Staff



Instrumentation

• Child and Adolescent versions distinguished between

those experiencing anemia and those who were not.

• Gender differences: females reporting more

symptoms of fatigue and higher intensity

• Age: adolescents

reported

more

symptoms

of

fatigue

and higher intensity than did children

Clinical Screen

Item:

• ‘Tired’ Item from the SDS:

Please put a circle around the number that most closely

measures how tired you are feeling today.

Could not feel I am not

more

tired

5 4

3

2

1 tired

at

all

(score of 3 or higher invites a full fatigue assessment)



Clinical Screen Item

• NCCN Guidelines

Research Instruments to Measure Cancer‐related Fatigue

in Children and Adolescents

• Child Fatigue Scale (7‐to 12‐year olds) – Hockenberry et al., 2003

• Adolescent Fatigue Scale (13‐to18‐ year olds) – Hinds et al., 2007

• The Revised Memorial Symptom Assessment Scale (7‐to 12‐year olds) – Collins et al., 2002

• The Pediatric FACT Scale

– Lai et

al.,

2007

• The Symptom Distress Scale (8‐ to 18‐ year olds) – Hinds, et al., 2000; Hinds et al., 2002

• PedsQL Fatigue Scale (8 to 12; 13 to 18 year olds) – Varni et al., 2004



Incidence of Fatigue in Children and Adolescents

with Cancer “nearly universal”

• Distressing levels reported at:

– time of diagnosis (fatigue at diagnosis is predictive of fatigue during

treatment)

– Collins et al., 2002; Hinds et al., 1999

– During treatment (significantly increased during reinduction for ALL and

during hospitalizations)

– Hockenberry et al., 2003; Hinds et al., 1990; Hinds et al, 2007

– Up to 23 years following treatment (most distressing)

– Crom et

al.,

200x;

Meeske

et

al.,

2005

– During the last 30 days of life – Wolfe et al., 2000

CONTRIBUTING FACTORS


• Lacking a schedule• Interruptions in a

hospital environment


FATIGUE

ALLEVIATING FACTORS

• Protected rest time

• Controlled or reducedinterruptions

• Being quiet

++ + +

_ _ _ _



Actigraph• Sleep Parameters

– Sleep duration

– Sleep efficiency

– Nocturnal

awakenings

– Actual sleep minutes

– Total daily sleep

minutes

– Total daily nap

minutes

– Total nocturnal sleep

minutes

– Sleep latency

– Wake after sleep

onset

https://reader010.{domain}/reader010/html5/0627/5b3378f5a84ba/5b3378fc51b3e.jpg



Benefits of Actigraphy

• Small and innocuous

• Able to attach to wrist or ankle for prolonged periods of

time- able to assess motion and thus sleep patterns

overtime

• Provides continuous activity data with little interference

or limitations imposed on the subject

• Can be used in the home environment

• Does not require ongoing monitoring by professionals• Cost effective

American Academy of Sleep Medicine

Recommendations

• Actigraphy has proven useful for

delineating sleep patterns and

documenting treatment response in

normal children, as well as in special

populations

Morgenthaler et al(2007)



The first

Intervention

• Enhanced Activity in Hospitalized Children

with Cancer

• 2‐site, randomized pilot study

• 27 patients with a solid tumor or AML

diagnosis admitted for chemotherapy

• Peddling twice daily for 20 minutes

• Intervention successfully delivered 85.4% of

scheduled times



The first Intervention

• Trend towards the activity arm having better quality

sleep (more efficient) (F=4.17, p=0.053)

• Children experiencing 19 or more nocturnal

awakenings were significantly more fatigued the

next day

• Children with higher nocturnal awakenings had

longer

sleep

duration

(F=6.35,

p=0.0007)

Dexamethasone (DEX), Sleep and

Fatigue

• Examining treatment influences on fatigue

and sleep in children with ALL

• Study purpose:

– To assess the relationship between systemic

exposure to DEX and sleep quality and fatigue in

patients with ALL during continuation



DEX, Sleep and Fatigue

• Two hypotheses:

– 1. DEX contributes to changes in sleep efficiency,

actual sleep minutes, sleep duration, nocturnal

awakenings, total daily sleep minutes, and daily

nap minutes and to increased fatigue

– 2. patient age, sex and ALL risk category influence

the extent

of

change

in

sleep

and

fatigue

observed during DEX treatment

Study Design

Days: 1 2 3 4 5 6 7 8 9 10

No DEX DEX

Actigraph worn

•Sleep Diary•Fatigue Scale(parent and patient)

•Sleep Diary•Fatigue Scale(parent and patient)

Blood SamplesPre-DEX, 1,2,4,8 h

10 Continuous



Actigraph Readings

1200 06001800 0000 1200

Time (hours)

1

2

3

4

5

6

7

8

910

C o n s e c u t i v e

D a y s

DEX

Study

Findings

• DEX does alter sleep parameters – Increases sleep duration, total daily sleep minutes,

total nap minutes

– Diary reports: restless sleep, increased nap times, increased tiredness and loss of energy

• DEX Increases Fatigue

– PATIENT REPORT—Day

5 on

dex:

significant

increases

in fatigue in 7‐12 year olds and 13‐18 year olds

– PARENT REPORT—significant increases in fatigue

during the on dex period



• Age: teens were in bed less time on DEX and had

slept fewer minutes

• Risk group: significantly associated with sleep

efficiency, actual sleep minutes and nocturnal awakenings, but not with fatigue (patient or parent report) – St Jude Standard risk received highest dose DEX (significantly lower

sleep efficiency)

• Gender : males

had

more

nocturnal

awakenings

(and

lower sleep efficiency); females napped more

Fatigue

in

Children

with

Cancer(2 separate studies and populations)

• Hospitalized Fatigue score 23 (9-43)

• Home, pre dex Fatigue score 7.5-11.9

• Home, on dex Fatigue score 13-21

• Highest fatigue score possible is 70

• On dexamethasone, fatigue scores are similar to thescores of hospitalized patients



Fatigue in Adolescents with Cancer(2 separate studies and populations)

• Hospitalized Fatigue score 32

• Home, pre dex Fatigue score 23-29

• Home, on dex Fatigue score 32-33

• On dexamethasone, fatigue is the same as whenhospitalized

• Adolescents report higher fatigue scores than do children

Daily Parent

Report

Diary

• 15 item parent report scale

• Reports parents perceptions of child’s sleep and nap

patterns during the previous 24 hours

• Additional items relate to naps, tiredness,

consumption of selected food items and perceived

energy levels

• Items strongly correlated with actigraph findings(r=0.89;p=0.001) (Sadeh, 1994)

• Completed 4 times during 10 day study period





Consistency of wake time by

gender, weekday vs weekend,

and DEX

vs.

No

Dex

•Girls did not have significant differences in wake time consistency

weekday versus weekend

•Boys had more consistent wake time on weekdays compared to

weekends

•Boys had more consistent wake times compared to girls

•Dexamethasone (week 2) did not significantly alter wake time

consistency

Association of fatigue with consistent

wake time

• Multiple regression analysis: younger boys

with more consistent wake times had

lower fatigue scores

• May suggest that consistent morning wake times

for the

younger

child

on

ALL

maintenance

therapy

can help to minimize fatigue



Potential Biological Mechanisms of

Sleep Disturbance and of Fatigue

• What are the potential biological mechanisms? – Steroids?

– PK, PGN

– Albumin?

– Cytokines?

– Neuroanatomy or Neurophysiology?

– Neurochemicals?



• Steroids contribute to altered sleep

disturbances and fatigue

– How?

• Pharmacokinetics

– Exposure to dexamethasone (AUC) increases with age and is higher

in standard care ALL risk compared to low risk groups

– Wake after

sleep

onset

increases

as

AUC

increases

– A decrease in time to attain threshold of 100 nM is significantly

associated with increased sleep efficiency

– No PK association with fatigue

– No association with clearance and sleep or fatigue





• Steroids contribute to altered sleep

disturbances and fatigue

– How?

• Pharmacogenomics: SNP genotype and sleep and

fatigue

– AHSG/C>G exon 7 (sleep efficiency)

– CYP11B2/K1733R (sleep duration)

– IL6/IL6_C‐634‐G (sleep duration)



• Albumin and dexamethasone – Low albumin likely leads to higher and longer exposure to dexamethasone

– Relationship between albumin and fatigue established in adults (direct

relationship not mediated by a steroid)

• Wang et al., 2002, JCO

– albumin and

dexamethasone

associated

during

reinduction

• Yang, et al., 2008, JCO

– No relationship between albumin and dexamethasone PK during

continuation



Can we improve sleep and fatigue in

children with cancer?

• Increase daytime physical activity

• Modify the hospital sleep environment

• Use relaxation interventions

• Administer pharmacologic interventions

• Consider complimentary therapies

• Implement Educational interventions:

‐ preparing families for likely and fatigue changes

‐ share with families sleep hygiene principles and hours

of sleep needed for their child

Sleep Hygiene

Principles

• consistent bed times and wake times

• making sure that your child receives enough sleep every

day to feel alert and well rested

• naps based on developmental age and stage

• limiting caffeine before bedtime

• child's bedroom at a comfortable temperature

• Child not

going

to

bed

hungry

• child's bed and bedroom are inviting and comfortable

• a regular bedtime ritual to help child prepare for nighttime

sleep





What will happen to me in this study?

You will have to wear the Actigraph all the time you are in the hospital.The Actigraph looks like a watch. It is a little computer.It will tell us how well you sleep.

You will answer questions one time a day.We will ask you about your sleep and how you feel.



You will choose special things to do before you go to bed.These are things to help you sleep. We will visit you and help you.

You will choose some soothing sounds to listen to at night.



You will choose your “lights out” and “lights on” time

You will let us draw a little bit of extra blood for special tests.This would be with morning labs.



What will we do?

The staff will try hard to go in and out of your room less at night.They will come in if you want them to.

We will put up an extra window cover to keep light out of your roomwhen you are sleeping.



From Pain to Sleep: PROs

• Asking and then Listening to our patients

• Having a standardized way of asking

• Acting on patients’ reports



Reference List

Carskadon MA. Patterns of sleep and sleepiness in adolescents. Pediatrician. 1990;17:5‐12.

Cleeland CS, Bennett GJ, Dantzer R et al. Are the symptoms of cancer and cancer treatment due to a shared biologic mechanism? A cytokine‐

immunologic model of cancer symptoms. Cancer 2003;97:2919‐2925.

Hinds PS, Hockenberry‐Eaton M, Gilger E et al. Comparing patient, parent, and staff descriptions of fatigue in pediatric oncology patients. Cancer Nurs. 1999;22:277‐288.

Hinds PS, Schum L, Srivastava DK. Is clinical relevance sometimes lost in summative scores? West J.Nurs.Res. 2002;24:345‐353.

Hinds P, Scholes S, Gattuso J, Riggins M, Heffner B. Adaptation to illness in adolescents with cancer. J.Pediatr.Oncol.Nurs. 1990;7:64‐65.

Hinds PS, Hockenberry MJ, Gattuso JS et al. Dexamethasone alters sleep and fatigue in pediatric patients with acute lymphoblastic leukemia. Cancer 2007;110:2321‐2330.

Hart CN, Palermo TM, Rosen CL. Health‐related quality of life among children presenting to a pediatric sleep disorders clinic. Behav.Sleep

Med. 2005;3:4‐17. K

Kurzrock R. Cytokine deregulation in hematological malignancies: clinical and biological implications. Clin.Cancer Res. 1997;3:2581‐2584.

Kurzrock R. The role of cytokines in cancer‐related fatigue. Cancer 2001;92:1684‐1688.

Lee BN, Dantzer R, Langley KE et al. A cytokine‐based neuroimmunologic mechanism of cancer‐related symptoms. Neuroimmunomodulation.

2004;11:279‐292.

Meeske KA, Siegel SE, Globe DR, Mack WJ, Bernstein L. Prevalence and correlates of fatigue in long‐term survivors of childhood leukemia. J.Clin.Oncol. 2005;23:5501‐5510.

Mindell, J. A. and Owens, J. A. Lee BN, Dantzer R, Langley KE et al. A cytokine‐based neuroimmunologic mechanism of cancer‐related

symptoms. Neuroimmunomodulation. 2004;11:279‐292.

Vardy J, Chiew KS, Galica J, Pond GR, Tannock IF. Side effects associated with the use of dexamethasone for prophylaxis of delayed emesis after moderately emetogenic chemotherapy. Br.J.Cancer 2006;94:1011‐1015.

Wood LJ, Nail LM, Gilster A, Winters KA, Elsea CR. Cancer chemotherapy ‐related symptoms: evidence to suggest a role for proinflammatorycytokines. Oncol.Nurs.Forum 2006;33:535‐542.

References II

Belluco C, Olivieri F, Bonafe M et al. ‐174 G>C polymorphism of interleukin 6 gene promoter affects interleukin 6 serum level in

patients with colorectal cancer. Clin.Cancer Res. 2003;9:2173‐2176.

Fayad L, Cabanillas F, Talpaz M, McLaughlin P, Kurzrock R. High serum interleukin‐6 levels correlate with a shorter failure‐free

survival in indolent lymphoma. Leuk.Lymphoma 1998;30:563‐571.

Hong S, Mills PJ, Loredo JS, Adler KA, Dimsdale JE. The association between interleukin‐6, sleep, and demographic characteristics.

Brain Behav.Immun. 2005;19:165‐172.

Rich T, Innominato PF, Boerner J et al. Elevated serum cytokines correlated with altered behavior, serum cortisol rhythm, and

dampened 24‐hour rest‐activity patterns in patients with metastatic colorectal cancer. Clin.Cancer Res. 2005;11:1757‐1764.

Schiller JH, Storer BE, Witt PL et al. Biological and clinical effects of intravenous tumor necrosis factor‐alpha administered three

times weekly. Cancer Res. 1991;51:1651‐1658.

Vgontzas AN, Bixler EO, Lin HM et al. IL‐6 and its circadian secretion in humans. Neuroimmunomodulation. 2005;12:131‐140.

Vgontzas AN, Zoumakis E, Bixler EO et al. Adverse effects of modest sleep restriction on sleepiness, performance, and

inflammatory cytokines. J.Clin.Endocrinol.Metab 2004;89:2119‐2126.

Vgontzas AN,

Zoumakis

E,

Lin

HM

et

al.

Marked

decrease

in

sleepiness

in

patients

with

sleep

apnea

by

etanercept,

a tumor

necrosis factor‐alpha antagonist. J.Clin.Endocrinol.Metab 2004;89:4409‐4413.



References

Kurzrock R. The role of cytokines in cancer‐related fatigue. Cancer 2001;92:1684‐1688.

Fayad L, Cabanillas F, Talpaz M, McLaughlin P, Kurzrock R. High serum interleukin‐6 levels correlate with a shorter failure‐free

survival in indolent lymphoma. Leuk.Lymphoma 1998;30:563‐571.

Rich T, Innominato PF, Boerner J et al. Elevated serum cytokines correlated with altered behavior, serum cortisol rhythm, and

dampened 24‐hour rest‐activity patterns in patients with metastatic colorectal cancer. Clin.Cancer Res. 2005;11:1757‐1764.

Belluco C, Olivieri F, Bonafe M et al. ‐174 G>C polymorphism of interleukin 6 gene promoter affects interleukin 6 serum level in

patients with colorectal cancer. Clin.Cancer Res. 2003;9:2173‐2176.

Vgontzas AN, Bixler EO, Lin HM et al. IL‐6 and its circadian secretion in humans. Neuroimmunomodulation. 2005;12:131‐140.

Vgontzas AN, Zoumakis E, Bixler EO et al. Adverse effects of modest sleep restriction on sleepiness, performance, and

inflammatory cytokines. J.Clin.Endocrinol.Metab 2004;89:2119‐2126.

Hong S, Mills PJ, Loredo JS, Adler KA, Dimsdale JE. The association between interleukin‐6, sleep, and demographic characteristics.

Brain Behav.Immun. 2005;19:165‐172.

Vgontzas AN, Zoumakis E, Lin HM et al. Marked decrease in sleepiness in patients with sleep apnea by etanercept, a tumor

necrosis factor‐alpha antagonist. J.Clin.Endocrinol.Metab 2004;89:4409‐4413.

Schiller JH, Storer BE, Witt PL et al. Biological and clinical effects of intravenous tumor necrosis factor‐alpha administered three

times weekly. Cancer Res. 1991;51:1651‐1658.

Date post:	30-May-2018
Category:	Documents
Upload:	childrens-national-medical-center
View:	214 times
Download:	0 times

From Pain to Sleep: Listening to Patient-reported Outcomes

Documents