Please contact me if you have any questions. It needs to be done by Sunday morning so I can proofread and make it my own. Do not worry about doing the introduction. The original theory that I am assigned to is the Theory of Unpleasant Symptoms. Please follow the detailed rubric and let me know if you have any questions.
1
N 5327: Exploration of Science and Theories for Nursing
Grading Rubric for Description & Evaluation of Theory Paper
Criteria
Levels of Achievement
Excellent/ Outstanding
90-100%
Above Average
80-89%
Average/
Acceptable
70-79%
Below Average/ Not Acceptable
60-69%
Failing
8 types of errors
(5 or less pts)
N5327 Exploration of Science and Theories for Nursing
Theory Description and Evaluation Paper Criteria
Identify a theory that uses a concept of interest that might be applied in research and nursing practice (clinical, education, or administration). The purpose of this paper is for you to describe and evaluate the theory using the following criteria. This is a professional paper in which headings, full sentences, paragraphs, correct grammar and punctuation, and correct citation of sources are required.
Introduction. Identify your concept of interest and briefly discuss why you chose that concept (explain whether it was observed in clinical practice, identified from relevant literature, or some other reason.) Identify the theory (that utilizes your concept of interest) which will be described and evaluated in this paper. Give the reader a sense of what to expect in this paper. The introduction should be one very short paragraph, and there should not be a heading for the introduction.
Theory Description. Provide a brief description of the theory using an original source or as close to the original source as possible. Include a brief discussion of the origins of the theory and the scope/level (grand, middle range, practice/situation specific) of the theory. Identify the major concepts of the theory and discuss how they are related (propositions). Pick two of the concepts, including your concept of interest, and state the theoretical definitions of these concepts. (30 points)
Application of Theory to Research. Find two published, original sources in which researchers used the theory as a framework to support their research. Briefly discuss how those researchers utilized the theory to support their research. Include in the discussion of each study the purpose of the study, how the researchers used the theory in their study, how the concept of interest was used in their study, and how the researchers operationally defined the concept of interest. (20 points)
Application of Theory to Practice. Briefly discuss how the theory might be used to support nursing practice (clinical, education, or administration). Include in the discussion the purpose of the practice application and how the concept of interest might be operationally defined in practice. Provide an example of how you might use the theoretical and operational definitions of your concept of interest in your future practice or research. Include a potential practice question based on the propositions of your theory. (20 points)
Theory Evaluation. Briefly discuss whether/how the theory appears to be accurate/valid (based on empirical testing of the theory as discussed above). Discuss generalizability of the theory. Summarize the strengths and weaknesses of the theory. Briefly discuss whether/how the theory is congruent with current nursing standards and current nursing interventions or therapeutics. Explain whether/how the theory is relevant socially and cross-culturally. Describe briefly how the theory might contribute to the discipline of nursing. (20 points)
Conclusion . Include a conclusion only if specified by your course section faculty.
Style & Format. The paper will include a title page (using specified format), 7-8 pages of text, and a reference list. It will be double-spaced, written in 12-point Times New Roman font, and have 1-inch margins. Professional and orderly presentation of ideas (precision, clarity, format, headings, grammar, spelling, & punctuation) with appropriate citation of sources in text and reference list is required. Up to 0.5 points will be deducted for each type of grammar, spelling, punctuation, or format error. (10 points)
Fall 2017 – Final version; Minor revision Spring 2018REVIEW PAPER
Integrative review: postcraniotomy pain in the brain tumour patient
Rebecca Elizabeth Guilkey, Diane Von Ah, Janet S. Carpenter, Cynthia Stone & Claire B. Draucker
Accepted for publication 17 November 2015
Correspondence to R.E. Guilkey:
e-mail: refoust@iupui.edu
Rebecca Elizabeth Guilkey PhD(c) RN
CCRN
PhD Candidate
Indiana University School of Nursing,
Indianapolis, Indiana, USA
Diane Von Ah PhD FAAN RN
Assistant Professor
Indiana University School of Nursing,
Indianapolis, Indiana, USA
Janet S. Carpenter PhD FAAN RN
Distinguished Professor and Associate Dean
for Research and Scholarship
Indiana University School of Nursing,
Indianapolis, Indiana, USA
Cynthia Stone DrPH RN
Associate Professor and Director of Health
Policy Management Doctoral Program
Indiana University Fairbanks School of
Public Health, Indianapolis, Indiana, USA
Claire B. Draucker PhD FAAN RN
Angela Barron McBride Endowed Professor
in Mental Health Nursing
Indiana University School of Nursing,
Indianapolis, Indiana, USA
GUILKEY R . E . , VON AH D . , CARPENTER J . S . , STONE C . & DRAUCKER C .B .
( 2 0 1 6 ) Integrative review: postcraniotomy pain in the brain tumour patient. Jour-
nal of Advanced Nursing 72(6), 1221–1235. doi: 10.1111/jan.12890
Abstract Aim. To conduct an integrative review to examine evidence of pain and
associated symptoms in adult (≥21 years of age), postcraniotomy, brain tumour
patients hospitalized on intensive care units.
Background. Healthcare providers believe craniotomies are less painful than
other surgical procedures. Understanding how postcraniotomy pain unfolds over
time will help inform patient care and aid in future research and policy
development.
Design. Systematic literature search to identify relevant literature. Information
abstracted using the Theory of Unpleasant Symptoms’ concepts of influencing
factors, symptom clusters and patient performance. Inclusion criteria were
indexed, peer-reviewed, full-length, English-language articles. Keywords were
‘traumatic brain injury’, ‘pain, post-operative’, ‘brain injuries’, ‘postoperative
pain’, ‘craniotomy’, ‘decompressive craniectomy’ and ‘trephining’.
Data sources. Medline, OVID, PubMed and CINAHL databases from
2000–2014.
Review method. Cooper’s five-stage integrative review method was used to assess
and synthesize literature.
Results. The search yielded 115 manuscripts, with 26 meeting inclusion criteria.
Most studies were randomized, controlled trials conducted outside of the United
States. All tested pharmacological pain interventions. Postcraniotomy brain
tumour pain was well-documented and associated with nausea, vomiting and
changes in blood pressure, and it impacted the patient’s length of hospital stay,
but there was no consensus for how best to treat such pain.
Conclusion. The Theory of Unpleasant Symptoms provided structure to the
search. Postcraniotomy pain is experienced by patients, but associated symptoms
and impact on patient performance remain poorly understood. Further research is
needed to improve understanding and management of postcraniotomy pain in this
population.
Keywords: brain tumour, craniotomy, integrative review, literature review,
nurses, nursing, pain, theory of unpleasant symptoms
© 2016 John Wiley & Sons Ltd 1221
info:doi/10.1111/jan.12890
Introduction
Background
Brain tumour is the seventeenth-most diagnosed cancer
worldwide, with 256,000 new cases of brain tumour diag-
nosed in 2012. Men suffer from brain cancer slightly more
frequently than women (Bondy et al. 2008, World Cancer
Research Fund International 2013, Central Brain Tumor
Registry of the United States 2014, Ferlay et al. 2015) and
incidence rates are higher in developed countries than in
lesser developed countries (Bondy et al. 2008, World Can-
cer Research Fund International 2013, Central Brain Tumor
Registry of the United States 2014). Scientific advances have
resulted in improvements in the diagnosis and treatment of
brain tumours (Bondy et al. 2008). In fact, 1- and 5-year
survival rates have increased from 7�3% in 1970 to over 18% in 2011 (Informational Services Division of the
National Health Services 2010, Cancer Research UK 2014,
Ferlay et al. 2015, Queen’s University Belfast 2015).
Approximately 90% of patients with brain tumours
undergo craniotomies for excision and removal of the
tumour to increase survival (National Cancer Institute
2014). Surgical procedures are generally understood to be
painful (McCaffery & Pasero 1999) but less is understood
about postcraniotomy pain. Healthcare providers commonly
believe that craniotomies are less painful than other types of
surgery due to lack of innervation in the brain (Hassouneh
et al. 2010, American Brain Tumor Association 2012) and
are thus less apt to treat pain. In addition, postcraniotomy
pain is often untreated or undertreated due to concerns that
it may mask neurological changes in these patients (Talke &
Gelb 2005, Durieux & Himmelseher 2007, Lai et al. 2012).
Pain is often associated with other symptoms including anxi-
ety and depression (McCaffery & Pasero 1999, Rocha-Filho
2015) and nausea and/or vomiting (Dolin & Cashman
2005). Understanding postcraniotomy pain in brain tumour
patients is important because postoperative pain is a com-
mon cause of delayed mobilization (Saha et al. 2013),
lengthened hospital stay (Chung et al. 1997, Casler et al.
2005, Saha et al. 2013), disability and decreased quality of
life (Andrasik et al. 2011, O’Connor & Dworkin 2011). In
addition, research has shown that under-treated, generalized
postoperative pain is a predictor of the development of per-
sistent pain (Macrae 2001, Dobrogowski et al. 2008, Watt-
Watson & McGillion 2011, Wu & Raja 2011, Lamacraft
2012). To date, postcraniotomy pain and the symptoms
associated with it is poorly understood. Researchers have
called for additional studies to understand influencing fac-
tors and associated symptoms of postcraniotomy pain and to
determine how to best treat it to prevent negative health out-
comes (Talke & Gelb 2005, Roberts 2005, Watson 2011,
De Oliveira Ribeiro et al. 2013, Rocha-Filho 2015).
Definitions and theory
The International Society for the Study of Pain describes
pain as a subjective sensory and emotional experience
(McCaffery & Pasero 1999, Watt-Watson & McGillion
2011, Gelinas et al. 2013). Pain is a complex symptom com-
prised of at least four dimensions (intensity, affect, quality
and location) (Puntillo et al. 2002, Jensen & Karoly 2011).
Physical, psychological, social and cultural factors influence
the experience of pain (Melzack 1999, Saha et al. 2013).
The Theory of Unpleasant Symptoms (TOUS), which
suggests that symptoms such as pain are multidimensional
and interactive, is commonly used to support pain research,
because it is relevant to practice and can be used as a
Why is this research or review needed?
� Brain tumour patients have long been believed to experi- ence little pain postcraniotomy due to lack of innervation
in the brain.
� Understanding symptoms correlated with postcraniotomy pain in brain tumour patients will help healthcare provi-
ders provide better treatment.
� Addressing untreated and undertreated postcraniotomy pain will improve patient-centred outcomes and quality of
life.
What are the key findings?
� Postcraniotomy patients experience significant levels of pain, but current treatment of postcraniotomy pain lacks
evidence-based guidelines.
� Postcraniotomy pain in brain tumour patients may be asso- ciated with nausea, vomiting and changes in blood pres-
sure and may play a role in health care use such as longer
hospital stays.
How should the findings be used to influence policy/ practice/research/education?
� Understanding the manner in which postcraniotomy pain unfolds should inform healthcare providers’ recognition of
the symptom.
� Recognition of the intensity of postcraniotomy pain and its impact should lead to timely treatment of the symptom
and improve patient outcomes.
1222 © 2016 John Wiley & Sons Ltd
R.E. Guilkey et al.
framework for making decisions related to patient care
(Myers 2009, Lenz et al. 2013). The TOUS includes three
main concepts: (1) physiological, measureable symptoms
experienced by the patient; (2) influencing factors which
alter the patient’s experience of the symptom and (3)
patient performance (Lenz et al. 1997, 2013). Influencing
factors are physiological, psychological and situational in
nature and can catalyse each other affecting patient perfor-
mance (Lenz et al. 1997, 2013). Performance is the impact
of the symptom on patient outcomes including functional
performance (the ability to physically function) and cogni-
tive performance (the ability to think) (Lenz et al. 1997,
2013). Researchers using the TOUS have termed groups of
associated symptoms as ‘clusters’ (Lenz et al. 1997). This
review will also use the term cluster to identify these groups
of co-related symptoms.
The review
Aim
The aim of this study was to conduct an integrative review
using the TOUS as a guiding framework to synthesize and
examine what is known about the phenomenon of pain in
adult (≥21 years of age), postcraniotomy, brain tumour
patients. Specifically, this review sought to answer the
following research questions: (1) What is the evidence for
postcraniotomy, postbrain tumour pain in adult (≥21 years
of age) patients hospitalized on intensive care units?; and
(2) What is the evidence for a postcraniotomy symptom
cluster associated with pain in adult (≥21 years of age)
patients hospitalized on intensive care units?
Design
Cooper’s (2010) integrative review method guided the
review. This method of integrative review was chosen
because it provides a systematic framework to synthesize the
current literature about postcraniotomy pain in the brain
tumour patient (Whittemore & Knafl 2005, Cooper 2010).
Cooper’s method includes five stages: advance formulation of
the problem, data collection, data extraction, evaluation,
analysis and interpretation (Cooper 2010). The formulation
of the problem, the first stage of the method, was informed
by a preliminary literature search and the researchers’ clinical
experience that suggested a greater understanding of acute
postcraniotomy pain was warranted. The authors felt an inte-
grative review was necessary to synthesize the current litera-
ture and further the state of the science (Whittemore & Knafl
2005, Cooper 2010).
Search methods
Data collection, the second stage, consisted of a literature
search. Studies were identified for inclusion by purposive
searching of electronic databases including Medline, OVID,
PubMed and CINAHL. In addition, hand-searching of ref-
erences and an examination of citations from identified
published reviews were conducted. Two experienced
reference librarians provided consultation on the search
process. Search terms for all databases and searches
included traumatic brain injury; pain, postoperative; brain
injuries; postoperative pain; craniotomy; decompressive
craniectomy; and trephining. Inclusion criteria were as fol-
lows: (1) data-based quantitative and qualitative articles
focused on postcraniotomy pain in adult brain tumour
patients aged 21 or older; (2) published between 1 January
2000–12 December 2014; (3) English-language; (4) neuro-
surgical inpatients and (5) intensive care unit settings.
Abstracts, editorials, dissertations, theses, reviews and
articles concerning intraoperative pain control, end-of-life
care, or institutional practices were excluded.
Search outcome
The search strategy generated 115 studies. The studies
which were recorded in a Preferred Reporting Items for Sys-
tematic Review and Meta-Analyses (PRISMA) diagram
(Figure 1). A total of 109 potentially relevant studies
remained after the initial screening of titles for duplicates,
publication in English and publication dates. The remaining
abstracts were reviewed for type of study, population, study
setting and discussion of pain. After application of the
inclusion and exclusion criteria, we eliminated 83 addi-
tional articles from review, including five qualitative studies
that either did not meet inclusion criteria because they did
not focus on pain or the participants were not inpatients.
This resulted in a sample of 26 quantitative articles to be
reviewed in full-text format (Table 1). Data from eligible
studies were abstracted into tables listing general informa-
tion, level of evidence and concepts defined in the TOUS.
Quality appraisal
In the third stage, two authors completed a quality apprai-
sal on the 26 articles. Using a 3-point scale (yes, no,
unclear) described by Gazarian, they rated the studies on
nine criteria including aims, design, methods, sample,
ethical considerations, results, limitations, implications and
sponsorship (2013). The studies were also appraised for
bias using the Cochrane Risk of Bias tool. Twenty-one of
© 2016 John Wiley & Sons Ltd 1223
JAN: REVIEW PAPER Integrative review – postcraniotomy pain
the studies used a randomized design. Of the five studies
that did not use randomization, two were retrospective
(Thibault et al. 2007, Ducic et al. 2012) and three were
prospective trials (Irefin et al. 2003, Grossman et al. 2007,
Nair & Rajshekhar 2011). The team determined that these
five studies nonetheless met inclusion criteria and thus all
26 studies are included in the review.
Data abstraction
The fourth stage includes data analysis and interpretation
(Cooper 2010). In this stage, all of the included studies
were read in full and relevant data were extracted and tab-
ulated. Table 1 displays the authors’ names; dates and
countries of publication; purpose and design; sample, set-
ting and intervention; medication tested; and pain preva-
lence, incidence and intensity. (Table 1).
Data synthesis
In the fifth and final stage, the tabulated data were synthe-
sized to address the research questions (Cooper 2010). The
authors grouped the data into categories suggested by the
TOUS including incidence of pain, influencing factors, cluster
and patient performance (Table 2). Two of the authors (RG
&DVA) reviewed each study and verified the accuracy of data
as presented and over several meetings compiled the results.
Results
Description of the studies
Of the 26 studies included, all were pharmacological pain
management trials (pain medications) and most were ran-
domized, controlled trials (RCTs) (n = 21). The studies
included 1892 total patients and were originally designed to
test local wound infiltration or medications to control pain
(intravenous, intramuscular, oral medications, nerve blocks,
general anaesthesia) (Table 1). The medications that were
tested varied but mostly included bupivacaine, ropivacaine,
tramadol, parecoxib, paracetamol and morphine.
The mean ages of the participants in the studies ranged
from 45-55 and approximately equal numbers of men and
women were represented. The comprehensive search identi-
fied five qualitative studies; however, these did not meet
inclusion criteria (focus not on pain or participants not
inpatients) and were excluded from final analysis. The
majority of trials took place outside of the United States at
non-profit, urban, academic medical institutions. Only one
study reported racial characteristics of the sample that con-
sisted mostly of Caucasians (52 vs. 12 non-Caucasian)
(Morad et al. 2009). Reports included both supratentorial
surgeries and infratentorial surgeries with mean lengths of
surgery ranging between 200 and 300 minutes.
115 total papers screened from
electronic search of 4 databases (OVID
Medline, Nursing @ OVID, PubMed, and
CINAHL) 6 articles excluded for not meeting inclusion criteria (duplicates, not published
in English, published prior to 2000)
83 articles excluded for not meeting inclusion
criteria: 27 not solely brain tumor population
16 not pain focused 11 traumatic brain injury 8 pediatric/adolescent 6 technique/procedure
focused 5 not postoperative
5 review 4 healthcare staff focus
1 letter to editor
109 potentially relevant citations
identified
26 articles to be reviewed in full-text
format
Figure 1 PRISMA diagram of systematic search.
1224 © 2016 John Wiley & Sons Ltd
R.E. Guilkey et al.
Table 1 Summarization of studies.
Author, year, Country Design, sample size, medication Existence of pain and pain intensity, rating scale used
Bala et al. (2006)
India
Prospective, double-blind RCT; N = 40
Medication: Scalp nerve block (bupivacaine)
60% experienced moderate-severe pain in first
12 hours post-op (control)
25% experienced moderate-severe pain in first
12 hours post-op (intervention)
Rating Scale: NRS; scores 0-22�5 out of 100 Batoz et al. (2009)
France
Prospective, single-blinded study; N = 52
Medication: Incisional infiltration (ropivacaine);
nalbuphine postsurgery
VAS scores higher in control group
Persistent pain significantly lower in intervention
group at 2 months (56% in control group vs. 8%
in intervention group)
Rating Scale: VAS; scores 0-35 out of 50
Biswas and
Bithal (2003)
India
Prospective, double-blind RCT; N = 50
Medication: Incisional infiltration (bupivacaine)
vs. fentanyl
Additional medication needed in 60% of
bupivacaine group and 57% of fentanyl group
Rating Scale: VAS; scores 0-4 out of 10
Ducic et al. (2012)
United States
Retrospective interview of patients; N = 7
Medication: None tested
86% experienced pain greater than 80% on
migraine index
Rating Scale: VAS; scores 2-10 out of 10
Ferber et al. (2000)
Poland
Multi-stage prospective study; N = 35
Medication: Intravenous tramadol
Pain relief in 50% of patients receiving one dose;
in 88% of patients receiving 2 or 3 doses
Rating Scale: VRS; scores 0-4 out of 5
Girard et al. (2010)
Canada
Prospective, double-blind RCT; N = 30
Medication: Cervical plexus nerve block
(lidocaine and bupivacaine) vs. intravenous
morphine bolus
Similar pain scores between nerve block and
morphine groups
Rating Scale: NRS; scores 2-7 out of 10
Grossman et al. (2007)
Israel
Open, prospective, double-blind non-randomized,
placebo- controlled study; N = 40
Medication: Incisional infiltration (lidocaine and
bupivacaine); metamizol intra-operatively
13 patients needed additional pain medication
Rating Scale: NRS; scores 0-4 out of 10
Irefin et al. (2003)
United States
Prospective study; N = 128
Medication: None tested
No significant difference in pain scores between
groups
Rating Scale: VAS; scores 0-5 out of 10
Jellish et al. (2006)
United States
Prospective, double-blind RCT; N = 120
Medication: PCA (morphine or morphine plus
ondansetron)
Up to 76% experienced post-op pain
Administered analgesia was inadequate
Rating Scale: VAS; scores 4�5-6�1 out of 10 Jones et al. (2009)
Australia
Prospective, double-blind RCT; N = 50
Medication: Intravenous parecoxib; morphine
postoperatively
89% of patients required additional pain
medication (morphine)
Pain scores significantly lower in parecoxib group
only at 6 hours
Rating Scale: VAS; scores 0-35 out of 100
Law-Koune et al. (2005)
France
Prospective, double-blind RCT; N = 80
Medication: Incisional infiltration (bupivacaine
plus epinephrine) vs. ropivacaine
Placebo group received more morphine than
bupivacaine or ropivacaine groups (22�2 mg; 12�7 mg; 10�5 mg respectively) Rating Scale: VAS; scores 0-7 out of 10
Magni et al. (2005)
Italy
Prospective, randomized, open-label clinical trial;
N = 120
Medication: General anaesthesia
(sevoflurane-fentanyl vs. propofol-remifentanil)
10% of ropivacaine group and 6% of sevoflurane
group experienced pain at 45 minutes
Rating Scale: VAS; scores unclear out of 100
Magni et al. (2009)
Italy
Prospective, double-blind RCT; N = 120
Medication: General anaesthesia
(sevoflurane vs. desflurane)
22% of sevoflurane group and 17% of desflurane
group required additional medication for pain
Rating Scale: VAS; scores unclear out of 100
Morad et al. (2009)
United States
Prospective RCT (unblinded); N = 64
Medication: as needed intravenous
fentanyl vs. PCA (fentanyl)
Patients in PCA group had significantly lower pain
scores than PRN group (2�53 vs. 3�62, respectively)
PCA group received significantly more fentanyl
Rating Scale: NRS; scores 2-4�7 out of 10
© 2016 John Wiley & Sons Ltd 1225
JAN: REVIEW PAPER Integrative review – postcraniotomy pain
Table 1 (Continued).
Author, year, Country Design, sample size, medication Existence of pain and pain intensity, rating scale used
Nair and Rajshekhar
(2011)
India
Prospective longitudinal study; N = 43
Medication: Oral paracetamol
5% had moderate pain in first post-op hour
Significant pain reported by 63% of patients
during first 48 hours; severe pain in 12% within
first 12 hours; incidence decreased over first
48 hours
Rating Scale: VAS; not stated out of 10
Nguyen et al. (2001)
Canada
RCT; N = 30
Medication: Scalp nerve block (ropivacaine)
70% of patients in saline group experienced
moderate pain in first 48 hours post-op
Rating Scale: VAS; scores 1�6-4�4 out of 10 Rahimi et al. (2006)
United States
Prospective, single-blinded RCT; N = 27
Medication: Oral narcotics vs. oral COX-2
inhibitors
Pain scores significantly higher in narcotics-alone
group than COX-2 group (P = 0�003) Rating Scale: VAS; scores 2-5�3 out of 10
Rahimi et al. (2010)
United States
Prospective, blinded RCT; N = 50
Medication: Oral narcotics vs. tramadol
Tramadol group had significantly lower pain scores
than narcotics-alone group (P < 0�005) Pain scores between groups significantly different
(P = 0�001435) Rating Scale: VAS; scores 1-8 (narcotics-along
group), 0-7 (tramadol group) out of 10
Saringcarinkul and
Boonsri (2008)
Thailand
Prospective, double-blind RCT; N = 50
Medication: Incisional infiltration (bupivacaine)
33% of bupivacaine group pain free at 30 minutes;
decreased to 4% at 8 hours
16% of control group pain free at 30 minutes;
decreased to 4% at 1 hour
Rating Scale: VNS; scores 2�5-3�5 out of 10 Simon et al. (2012)
Hungary
Prospective RCT; N = 90
Medication: Pre-operative oral diclofenac
Significant difference in incidence of pre-operative
headache between intervention and control
groups (P = 0�0045) 77�7% experienced pain (first post-op day); 69�4% experienced pain (fifth post-op day) Rating Scale: VAS; scores 0-9 out of 10
Sudheer et al. (2007)
Wales
Prospective RCT; N = 60
Medication: PCA (morphine vs. tramadol) vs.
intramuscular codeine
4 patients did not require additional medication in
first postoperative hour; 5 had severe pain
necessitating withdrawal from study
Less pain in morphine and codeine groups;
significant residual pain noted in tramadol group
Rating Scale: VRS; scores 0-10 out of 10
Thibault et al. (2007)
Canada
Retrospective chart review; N = 299
Medication: None tested
24% experienced mild pain, 51�5% moderate pain and 24�5% severe pain Overall prevalence of pain = 76%
Rating Scale: VRS; scores unclear out of 10
Ture et al. (2009)
Turkey
Prospective RCT; N = 80; 75 completed study
Medication: Oral gabapentin vs. oral phenytoin
Pain scores significantly higher in phenytoin group
at 15, 30 and 60 minutes (P < 0�001) Total morphine consumption significantly higher
in phenytoin group (P = 0�01) Rating Scale: VAS; scores 0-4 out of 10
Verchere et al. (2002)
France
Prospective, blind, RCT; N = 64
Medication: Paracetamol vs. paracetamol plus
tramadol vs. paracetamol plus nalbuphine
Paracetamol-only group stopped quickly due to
inadequate analgesia in 75% of patients
Rating Scale: VAS; scores 5-30 out of 100
Williams et al. (2011)
Australia
Prospective, double-blind RCT; N = 100
Medication: Intravenous parecoxib
70% of control group and 61% of parcoxib group
needed additional pain medication
Rating Scale: VAS; scores 2-5 out of 10
1226 © 2016 John Wiley & Sons Ltd
R.E. Guilkey et al.
Main results
As previously discussed, we used the TOUS as the guiding
framework for describing the experiences and cluster associ-
ated with postcraniotomy pain in brain tumour patients,
which resulted in five categories: (1) evidence of pain; (2)
manner of pain assessment; (3) influencing factors; (4) symp-
tom cluster and (5) patient performance (Tables 1 and 2).
Evidence of pain
Fifteen studies reported specific percentages of participants
experiencing moderate-severe pain. These percentages were
as high as 60-96% within the first 2 days after surgery,
despite the use of analgesics. Participants in eight studies
required additional pain medications and in one study,
inadequate analgesia in 75% of participants necessitated
the removal of one study arm (Verchere et al. 2002). In
this arm, six of eight patients experienced inadequate
analgesia and multiple infusions of additional pain
medication were required to reduce pain intensity scores
to below 30 (out of 100) (Verchere et al. 2002). An
additional study reported the withdrawal of five partici-
pants for severe pain in the first postoperative hour
(Sudheer et al. 2007).
Manner of pain assessment
Measures that were used to assess pain varied but most
used one-dimensional assessments of intensity including
visual analogue scales (VAS), numerical rating scales
(NRS), visual rating scales (VRS) or visual numeric
scales (VNS). Study authors did not measure other
dimensions of pain such as timing, distress, affect and
quality. Twenty-one studies (81%) identified inadequate
pain relief.
Influencing factors
Table 2 displays the evidence of postcraniotomy pain,
factors that may influence its development, an associ-
ated symptom cluster and possible impact on patient
performance. Many authors did not report all elements of
the TOUS. Eleven of the 26 studies (42%) discussed some
physiological, psychological or situational factors influenc-
ing postcraniotomy pain.
Several studies examined physiological influencing factors
such as included gender and age but findings were inconsis-
tent. One study found that women tended to experience
higher pain levels than men (Morad et al. 2009) while
another study found that men were more likely to ask for
pain medication than women (Jellish et al. 2006). The
impact of age in the development of postcraniotomy pain
also was not clear. One study found that older age was
associated with less pain (Thibault et al. 2007) while
another found increased pain levels in older patients (van
der Zwan et al. 2005).
Psychological influencing factors are the patient’s emo-
tional reactions to the disease and can include mood and
perceived level of self-sufficiency (Lenz et al. 1997, 2013).
No studies examined psychological factors that may influ-
ence the experience of postcraniotomy pain.
Situational factors are found in the social and physical
environment and can include surgical positioning, site of
surgery and use of anaesthetics. Three studies reported less
pain among patients with frontal craniotomies (Thibault
et al. 2007, Morad et al. 2009, Ducic et al. 2012) and one
study found that perioperative nerve blockade decreased the
incidence of postoperative pain (Morad et al. 2009). Gen-
eral anaesthetics used included sevoflurane and desflurane.
The use of sevoflurane resulted in less pain in one study
(Magni et al. 2005), while in another, patients receiving
sevoflurane required additional medication to control their
pain (Magni et al. 2009).
Clusters
Clusters in the TOUS are groups of co-related symptoms
that interact, affecting the patient’s symptom experience
(Lenz et al. 1997, 2013). Although the researchers did not
explicitly explore ‘symptom clusters’, 21 (81%) studies
discussed symptoms related to pain. Symptoms reported
Table 1 (Continued).
Author, year, Country Design, sample size, medication Existence of pain and pain intensity, rating scale used
van der Zwan et al. (2005)
The Netherlands
Prospective, double-blind RCT; N = 50
Medication: Remifentanil vs. fentanyl
No significant difference in pain intensity between
groups
13 of remifentanil group (45%) required
additional pain medication
Rating Scale: VAS; scores 1-4 out of 10
RCT, randomized controlled trial; 4NRS, numerical rating scale; VAS, visual analogue scale; VRS, visual rating scale; VNS, visual numeric scale.
© 2016 John Wiley & Sons Ltd 1227
JAN: REVIEW PAPER Integrative review – postcraniotomy pain
Table 2 Summarization of studies using theory of unpleasant symptoms concepts.
Author, Year Influencing factors Symptom cluster Patient performance
Bala et al. (2006) • Length of surgery – – Batoz et al. (2009) – • Vomiting
• Agitation • Shivering • Hypertension
–
Biswas and Bithal (2003) – • Change in diastolic blood pressure
–
Ducic et al. (2012) • Surgical site ● Altered intracranial pressure
● Altered quality of life ● Development of persistent pain
Ferber et al. (2000) – – • Change in systolic and/or diastolic blood pressure
• Changes in heart rate • Changes in partial pressure of
oxygen
• Altered intracranial pressure Girard et al. (2010) – • Nausea
• Vomiting • Change in systolic
blood pressure
–
Grossman et al. (2007) – • Nausea • Vomiting • Elevated blood
pressure
–
Irefin et al. (2003) • Gender • Surgical site
● Nausea ● Vomiting
–
Jellish et al. (2006) • Surgical approach • Gender
● Nausea ● Vomiting ● Headache
● Length of hospital stay ● Patient satisfaction ● Increased cost of medication used ● Delayed discharge from hospital
Jones et al. (2009) – • Nausea • Vomiting
● Sedation
Law-Koune et al. (2005) – • Nausea • Vomiting • Itching • Change in blood
pressure
• Bladder dysfunction
● Sedation
Magni et al. (2005) – • Nausea • Vomiting • Shivering • Change in blood
pressure
• Change in heart rate
• Change in Glasgow Coma Scale
Magni et al. (2009) – • Change in heart rate • Change in partial
pressure of oxygen
● Need for reintubation ● Changes in Glasgow Coma Scale
Morad et al. (2009) • Gender • Age • Surgical site • Surgical approach • Perioperative
neural blockade
● Nausea ● Vomiting ● Change in blood pressure ● Change in heart rate ● Change in mean arterial
pressure
● Neurological deterioration
1228 © 2016 John Wiley & Sons Ltd
R.E. Guilkey et al.
include headache nausea and vomiting, shivering, fatigue,
dizziness, respiratory depression, constipation, neurologic
changes, increased risk of intracranial bleeding and
agitation. The top three most common symptoms
described were nausea (15 studies; 58%), vomiting (16
studies; 62%) and changes in blood pressure including,
but not limited to, the development of hypertension (9
studies, 35%).
Table 2 (Continued).
Author, Year Influencing factors Symptom cluster Patient performance
Nair and
Rajshekhar (2011)
– • Agitation • Sympathetic Nervous
System (SNS)
stimulation
• Altered blood pressure • Brain swelling
● Development of postoperative complications
● Increased length of hospital stay ● Increased mortality rate
Nguyen et al. (2001) • Incisional site – – Rahimi et al. (2006) • Surgical site • Nausea
• Vomiting • Respiratory depression • Constipation • Neurological changes • Constipation
● Altered mental status ● Increased cost of medication used
Rahimi et al. (2010) – – • Increased cost of medication used • Increased length of hospital stay
Saringcarinkul and Boonsri (2008) – • Nausea • Vomiting
● Sedation ● Change in Glasgow Coma Scale
Simon et al. (2012) • Headache (presence prior to surgery
increased postsurgical
pain)
– • Increased length of hospital stay
Sudheer et al. (2007) • Surgical site (frontal associated with
less pain)
● Nausea ● Vomiting ● Change in partial
pressure of oxygen
–
Thibault et al. (2007) • Surgical site (frontal associated with less pain)
• Age (increased age associated with lower
pain scores)
• Muscle reflection
● Nausea ● Vomiting
–
Ture et al. (2009) – • Fatigue • Dizziness
–
Verchere et al. (2002) – • Nausea • Vomiting • Shivering • Risk of intracranial
bleeding
• Agitation • Hypertension
–
Williams et al. (2011) – • Nausea • Vomiting
● Sedation ● Change in Glasgow Coma Scale
van der Zwan et al. (2005) • Age (increasing age experienced more pain)
• Surgical site
● Nausea ● Vomiting ● Change in partial pressure
of oxygen
–
Total Studies Discussing Concept 11 21 14
NRS, numerical rating scale; VAS, visual analogue scale; VRS, visual rating scale; VNS, visual numeric scale.
© 2016 John Wiley & Sons Ltd 1229
JAN: REVIEW PAPER Integrative review – postcraniotomy pain
Patient performance
Patient performance is frequently assessed in terms of
tangible functional outcomes, such as length of stay, readi-
ness to be discharged and perceived quality of life.
Although performance related to postcraniotomy pain was
not explicitly examined, almost half of the studies described
potential results of postcraniotomy pain (Table 2). How-
ever, it was unclear if the impact on patient performance
was a direct result of pain, the use of pain medication, or
other factors. Other functional performance outcomes
reported included increased cost of medication and
increased hospital length-of-stay. In two different studies,
poorly managed postcraniotomy pain resulted in delayed
discharge and altered quality of life (Jellish et al. 2006,
Ducic et al. 2012). Four studies described changes in cogni-
tive performance using the proxy measure of level of con-
scious assessed by the Glasgow Coma Scale (GCS) (Magni
et al. 2005, Saringcarinkul & Boonsri 2008, Magni et al.
2009, Williams et al. 2011). Two studies found changes in
level of consciousness due to type and amount of analgesic
used (Saringcarinkul & Boonsri 2008, Williams et al. 2011)
and one identified these changes as being the result of
uncontrolled pain (Magni et al. 2005).
Discussion
To our knowledge, this is the first integrative review of
data-based studies examining: (1) evidence for postcran-
iotomy, postbrain tumour pain; and (2) the evidence for a
postcraniotomy pain symptom cluster in brain tumour
patients. Brain tumours affect many worldwide and pain
has been identified as a public health priority. Accordingly,
most research on postcraniotomy pain has been conducted
in other countries. Research to date has focused solely on
pharmacological intervention and fails to explore the multi-
dimensional nature of pain through comprehensive assess-
ment (Leslie & Troedel 2002, Nemergut et al. 2007,
Hansen et al. 2011, Guilfoyle et al. 2013). Although phar-
macological interventions exist, no one therapeutic medica-
tion has been identified as most efficacious (National
Pharmaceutical Council 2003, Paolino et al. 2006, Institute
of Medicine Committee on Advancing Pain Research, C.
and Education 2011, Saha et al. 2013). Our review found
that despite the use of 18 different analgesics, moderate to
severe pain still occurred among postcraniotomy brain
tumour patients and that many patients expressed inade-
quate pain management resulting in the need for more anal-
gesics. This review provides strong evidence for the
existence of postcraniotomy pain and the need for more
research to develop evidence-based practice guidelines in
this population.
While researchers have begun to study patients’ subjective
experiences after craniotomy, such as their fears, expecta-
tions and satisfaction (Khu et al. 2010, Milian et al. 2014),
these investigations have not yet addressed pain. Patients’
experiences of pain will necessarily be affected by amount
of pain control and healthcare provider interaction, but the
extent to which these influence postcraniotomy, postbrain
tumour patient experience has not yet been made clear.
Due to the complicated nature of postcraniotomy pain, fur-
ther research is warranted to provide evidence-based care.
A full understanding of the postcraniotomy pain experi-
ence from the patients’ perspectives would improve assess-
ment of pain, planning of interventions and evaluation of
care (Melzack 1999, Andrasik et al. 2011, Watt-Watson &
McGillion 2011). This review serves as a call to action to
describe the context and unfolding of postcraniotomy brain
tumour pain from the patient’s perspective and provides
evidence to challenge the commonly held belief that
postcraniotomy pain is not an important problem (Has-
souneh et al. 2010, American Brain Tumor Association
2012).
The intensity of postcraniotomy, postbrain tumour pain
is well-documented. Measures such as VASs are capable of
reflecting this intensity and change in pain over time (Jensen
& Karoly 2011). However, pain intensity is not necessarily
correlated with level of patient distress and resulting patient
performance (Melzack 1999, Jensen & Karoly 2011, Turk
& Melzack 2011, Turk & Robinson 2011, Watt-Watson &
McGillion 2011). Consequences such as the development of
dysfunction and disability reflect broader dimensions of
pain that cannot be assessed by mere measures of intensity
and distress (Turk & Melzack 2011, Watt-Watson &
McGillion 2011). Current research fails to explore the pain
experience beyond intensity and does not address the clus-
ter of associated symptoms that may magnify pain and/or
moderate treatment effects.
The limited and conflicting nature of the evidence con-
cerning physiological factors that influence the development
of postcraniotomy pain in the brain tumour patient suggests
that additional, more comprehensive description is needed.
Increased awareness of the experiences of postcraniotomy
pain across age groups is needed (Andrasik et al. 2011).
Investigations of the experience of postcraniotomy, post-
brain tumour pain by gender could lead to the development
of targeted approaches for men and women. Similarly,
while incidence of brain tumour is higher in Caucasians
than in those of other racial backgrounds (National Cancer
Institute 2014), few authors report racial characteristics of
1230 © 2016 John Wiley & Sons Ltd
R.E. Guilkey et al.
the study sample, preventing clear understanding of the
manner in which postcraniotomy pain unfolds among
different groups.
Psychological factors influencing the development of
postcraniotomy, postbrain tumour pain are also thought to
be important (McCaffery & Pasero 1999, Melzack 1999
Andrasik et al. 2011, Turk & Robinson 2011, Lenz et al.
2013). None of the studies in the review, however,
addressed these factors and thus it is not yet clear what role
emotions, mood and perceived level of self-sufficiency play
in the unfolding and experience of postcraniotomy pain.
Situational factors that affect the unfolding and experi-
ence of postcraniotomy pain also need further clarification.
Longer surgical time influences length of intensive care unit
stays in cardiac patients (Chu et al. 2008) and length of
surgery influences the severity of postoperative pain in
ambulatory care surgical patients (Chung et al. 1997). In
postcraniotomy patients, longer surgeries may increase post-
surgical pain due to greater time spent in surgical positions,
increased duration of muscle retraction, larger incisions and
the potential for more involved surgical procedures (Casler
et al. 2005, Ducic et al. 2012). Researchers should there-
fore investigate the impact of length of surgery on the
development of postcraniotomy pain.
More detailed comparisons could also be made if surgical
diagnoses were consistently reported. For example, it is
known that postoperative headache in occipital surgeries
stems from resulting occipital neuralgia (Ducic et al. 2012).
Examining the effect of surgical location on development of
postcraniotomy headache could lead to better targeted
interventions.
The existence of a symptom cluster would call for com-
prehensive postcraniotomy pain assessment (Melzack 1999
Andrasik et al. 2011, Saha et al. 2013). Little is known,
however, about the cluster associated with postcraniotomy,
postbrain tumour pain. In the current science, effects of
pharmaceutical interventions, postcraniotomy pain, other
symptoms such as pain and anxiety and patient perfor-
mance are often confounded. Research that explicates the
nature of symptom clusters in this population is needed.
Literature shows that postoperative pain may affect
performance by increasing length of stay, cost of hospital-
ization and delaying discharge (Watt-Watson & McGillion
2011, Saha et al. 2013). Some research links postcran-
iotomy pain to increased length of stay and delayed readi-
ness to be discharged in the traumatic head injury
population (Honeybul 2010, Honeybul & Ho 2010).
However, only a few studies have examined the impact of
postcraniotomy pain on brain tumour patients’ functional
and cognitive performance.
In the broader pain literature, untreated acute pain has
been correlated with the development of long-term pain
due to nervous system plasticity (Melzack 1999, Turk &
Robinson 2011, Watt-Watson & McGillion 2011, Ducic
et al. 2012). In addition, researchers of general postsurgical
pain have shown that inadequate postoperative analgesia
has led to the development of persistent pain (Horn &
Munafo 1997, McCaffery & Pasero 1999, Watt-Watson &
McGillion 2011). Batoz et al. (2009) have shown that
improved pain management in postcraniotomy patients
during the acute postoperative period decreases the devel-
opment of persistent pain at 2 months, but the relationship
between postoperative pain management and persistent
pain has not been well-studied in postcraniotomy brain
tumour patients. Therefore, describing the connection
between postcraniotomy pain and patient performance
could lead to the development of interventions to prevent
or minimize both postcraniotomy pain and its resulting
effects.
Over 40 years of research have repeatedly illustrated that
pain is under-assessed, under-recognized and undertreated.
The treatment of postcraniotomy pain is further compli-
cated by a lack of understanding of the manner in which it
unfolds over the course of the postoperative period and a
reluctance to treat it aggressively for fear of masking neuro-
logical changes. The result is an unclear risk-benefit ratio
associated with the treatment of postcraniotomy pain in
brain tumour patients. Additional research would illuminate
the relationship between postcraniotomy pain, influencing
factors, associated clusters and patient performance, leading
to the development of timely interventions to control pain
without increasing risk to patients.
Limitations
This review was limited to examining studies that discussed
particular influencing factors, associated clusters and the
effect of postcraniotomy, postbrain tumour pain on patient
performance. It is possible that studies looking at postcran-
iotomy pain in a different context were missed. In addition,
this review does not represent ongoing or unpublished
studies, nor does it include published work that has not
undergone the peer review process.
Conclusion
Evidence suggests that postcraniotomy, postbrain tumour
patients experience significant postsurgical pain but no
guidelines have been established to treat this pain. Postcran-
iotomy pain may influence length of hospital stay, cost of
© 2016 John Wiley & Sons Ltd 1231
JAN: REVIEW PAPER Integrative review – postcraniotomy pain
medications, quality of life and development of persistent
pain. However, little research has been conducted on the
complex nature and experience of postcraniotomy, post-
brain tumour pain. Mitigating or preventing postcran-
iotomy pain in the brain tumour population will likely
result in improved patient outcomes. Patient-centred out-
comes research should focus on attempting to understand
postcraniotomy pain, which will pave the way for the
development of timely interventions and standardization of
treatment for postcraniotomy pain to improve functional
outcomes and quality of life.
Acknowledgement
The authors thank and acknowledge the T32 programme
leadership of Dr. Susan Rawl.
Funding
The work reported in this publication was supported by the
National Institute of Nursing Research of the National
Institutes of Health under Award Number T32NR007066.
The content is solely the responsibility of the authors and
does not necessarily represent the official views of the
National Institutes of Health. This work was also sup-
ported by a Jonas Leadership Scholarship from the Jonas
Center for Nursing Excellence, and the Irene and Nathaniel
Aycock Scholarship and the Cheryl A. Bean Scholarship
from the Indiana University School of Nursing.
Conflict of interest
The authors had no conflicts of interest.
Author contributions
All authors have agreed on the final version and meet at
least one of the following criteria [recommended by the
ICMJE (http://www.icmje.org/recommendations/)]:
� substantial contributions to conception and design, acquisition of data or analysis and interpretation of
data;
� drafting the article or revising it critically for impor- tant intellectual content.
Supporting Information
Additional Supporting Information may be found in the
online version of this article at the publisher’s web-site.
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Original Article
Symptom Cluster as a Predictor of Physical Activity in Multiple Sclerosis: Preliminary Evidence Robert W. Motl, PhD, and Edward McAuley, PhD Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA
Abstract Thepresent studyexamined thesymptomcluster of fatigue, pain, anddepression, and itsdirect and indirect prediction of physical activitybehavior in a sampleof individualswith multiple sclerosis(MS) usingaprospectiveresearchdesign andtheTheoryof Unpleasant Symptoms. The sampleincluded 292 individualswith a definitediagnosisof MS. Theparticipantscompleted self-report measuresof fatigue, depression, pain, self-efficacy, and functional limitationsat baselineand six monthslater, worean accelerometer for seven daysand completed a self-report measureof physical activitybehavior. Thedata analysisindicated that: 1) fatigue, depression, and pain represented a symptom cluster; 2) thesymptom cluster had a strong and negative predictiverelationship with physical activitybehavior; and 3) functional limitations, but not self-efficacy, accounted for thepredictiverelationshipbetween thesymptomcluster and physical activitybehavior. Such findingsprovidepreliminarysupport totheimportanceof considering symptomclustersasameaningful correlateof physical activitybehavior in personswithMS. J Pain Symptom Manage 2009;38:270e 280. Ó 2009 U.S. Cancer Pain Relief Committee. Published byElsevier Inc. All rightsreserved.
Key Words Symptom cluster, fatigue, depression, pain, physical activity behavior, multiplesclerosis
Introduction There is accumulating evidence that physi-
cal activity behavior is associated with desirable consequences in persons with multiple sclero- sis (MS). Two recent meta-analyses have dem- onstrated that physical activity behavior is
associated with improvements in walking mo- bility1 and quality of life 2 in persons with MS. Nevertheless, there is considerable evi- dence that individuals with MS are largely sed- entary, as demonstrated by a literature review3 and a meta-analysis.4 One objective of current research has been the identification of vari- ables that correlate with physical activity behav- ior among those with MS. This is based on the assumption that such variables might serve as targets of a well-designed intervention for in- creasing physical activity behavior in this population. Symptoms are perceived indicators of change
in normal functioning, sensation, or appear- ance,5 and have been identified as a correlate of
Funded by the National Institute of Neurological Diseases and Stroke (NS054050) . Address correspondence to: Robert W. Motl, PhD, De- partment of Kinesiology and Community Health , University of Illinois at Urbana-Champaign, 350 Freer Hall, 906 S. Goodwin Avenue, Urbana, IL 61801, USA. E-mail: robmotl@uiuc.edu Accepted for publication: August 17, 2008.
Ó 2009 U.S. Cancer Pain Relief Committee Published by Elsevier Inc. All rights reserved.
0885-3924/ 09/ $e see front matter doi:10.1016/ j.jpainsymman.2008.08.004
270 Journal of Pain and Symptom Management Vol. 38 No. 2 August 2009
physical activitybehavior among personswith MS in cross-sectional analyses. For example, one study reported that the number of symptoms ex- perienced during the past 30 days was negatively associated with physical activity behavior,6 whereas a second study reported that worsening of overall symptomsacross a three-to five-year pe- riod was independentlyand negativelyassociated with self-reported levels of physical activitybehav- ior.7 Another studyreported that higher levels of overall symptoms were directly and indirectly as- sociated with lower levels of physical activity behavior, and the indirect pathwayinvolved diffi- culty walking (i.e., functional limitations8) . One final studyreported that the frequencyof overall symptomsand motor symptomswere directlyand indirectly associated with physical activity behav- ior bywayof self-efficacy.9 These previous studies have generally focused
on either a single dimension of overall symptoms or a single specific symptom as cross-sectional or temporally proximal correlates of physical activ- ity behavior in MS. There are definitional, con- ceptual, and theoretical bases for considering a symptom cluster rather than an overall or spe- cific symptom as a prospective or temporally dis- tal correlate ofphysical activitybehavior in MS.By definition, a symptom cluster represents ‘‘three or more concurrent symptoms (e.g., pain, fa- tigue, sleep in sufficiency) that are related to each other.’’ 10, p. 465 This definition underscores the two primary features of a symptom cluster, namelythe existence of three or more symptoms and an interrelationship, either through a com- mon etiology or statistically as a cluster or latent variable.11 Conceptually, the studyof a symptom cluster recognizes that: 1) multiple symptoms of- ten occur concurrently and 2) co-occurring symptoms likely provide a better prediction of consequences (e.g., behavior, function, or quality of life) than a single symptom. The concept of a symptom cluster and its
possible influence on performance outcomes, including physical activitybehavior, is the central theme of the Theory of Unpleasant Symptoms.5 This theory suggests that symptoms can occur as separate entities or concurrently as a symptom cluster, and the symptoms have antecedents (e.g., physiological, environmental, and per- sonal factors) and temporally proximal and dis- tal consequences (e.g., functional limitations and physical inactivity) . Significantly, one central tenet of the Theoryof Unpleasant Symptoms5 is
that concurrent symptoms likelyhave a stronger effect on consequences compared with a single symptom. This stronger effect is based on the fact that co-occurring symptoms likely catalyze each other (e.g., pain is considerably worse when one is fatigued) , thereby resulting in a dis- proportionately more severe and disruptive symptom experience.5 We further note that the inclusion of both temporally proximal (e.g., cross-sectional) and distal (e.g., prospective) per- formance consequences in this theory provides a basis for considering a symptom cluster as po- tentially having a prospective association with physical activity behavior. One commonlyreported cluster of symptoms
includes fatigue, depression, and pain . This symptom cluster has been identified in persons undergoing treatment for cancer,12 and the same symptom cluster might exist in persons with MS and influence physical activity behav- ior. The symptoms of fatigue, depression, and pain often co-occur in persons with MS,13e 17 and are likelyto have synergistic effects.14 These symptoms are interrelated through common neuropathic consequences, including co-occur- ring and diffuse axonal damage ( i.e., lesions) across different regions of the central nervous system.18 To our knowledge, researchers have neither established the existence of this symp- tom cluster in persons with MS nor examined the prospective or temporally distal relation- ship between the symptom cluster and physical activity behavior in th is population. The present study examined the symptom
cluster of fatigue, pain , and depression, and its direct and indirect association with physical ac- tivitybehavior in a sample of individualswith MS using a prospective research design and the TheoryofUnpleasant Symptoms.We first exam- ined the existence of fatigue, pain , and depres- sion as a prespecified symptom cluster in persons with MS, and secondly, examined the possibility that th is symptom cluster would pre- dict levels of physical activitybehavior after a six- month period. This second purpose examined the possibility of a temporally distal association between the symptom cluster and physical activity in persons with MS. We subsequentlyex- amined the possibility that the symptom cluster predicted physical activity behavior directly or indirectly through a pathway that included self-efficacy and functional limitations, in part, consistent with our previous research.6e 9
Vol. 38 No. 2 August 2009 271Symptom Cluster
Methods Participants This study included a convenience sample of
persons with MS. The sample was recruited through: 1) research announcements mailed to previous study participants; 2) advertisements placed in MSConnection; and 3) e-bursts distrib- uted to registered members of three state chap- ters of the National MS Society. There were 511 individuals who expressed interest in the study, and 387 underwent screening for possible inclu- sion. The screening criteria were: 1) a definite di- agnosis of MS; 2) relapse free in the last 30 days; and 3) ambulatory with minimal assistance. Of those who underwent screening, 27 individuals did not satisfyour inclusion criteria, and 16 indi- viduals declined participation. We sent an in- formed consent document and verification letter to the remaining 344 individuals, and the forms were returned by 300 of the individ- uals (87% response rate) . Of those who re- turned the forms, eigh t did not continue with participation, resulting in the final sample of 292 individuals with MS (3% attrition) . The cat- egorical descriptive characteristics of the sam- ple are provided in Table 1. The mean age of the sample was 48.0 years (standard deviation
[SD] ¼ 10.3) , and the mean duration since diag- nosis of MS was 10.3 years (SD ¼ 7.9) .
Instruments
Physical Activity. We measured physical activity behavior using an ActiGraph accelerometer (model 7164 version; Health One Technology, Fort Walton Beach, FL) and the Godin Lei- sure-Time Exercise Questionnaire (GLTEQ).19 Both the accelerometer and the GLTEQ have evidence of validity in individuals with MS,20,21 and the combined use of self-report and objective measures has been recognized as ideal by experts,22 and allowed for modeling physical activity behavior as a latent variable. The ActiGraph accelerometer has a vertical axis piezoelectric bender element that gener- ates an electrical signal that is proportional to the force acting on it. The positive and negative acceleration signals are digitized by an analog-to-digital converter, numerically in- tegrated over an epoch interval, and the inte- grated value of movement counts is stored in random access memory and the integrator is reset. The accelerometer is programmed for start time and epoch interval, and the move- ment counts are retrieved for analysis by means of a personal computer in terface and software provided with the ActiGraph. The downloaded data from the accelerometers are then entered into Microsoft Excel for pro- cessing. Regarding processing, participants re- corded the time that the accelerometer was worn on a log, and this was verified by inspec- tion of the minute-by-minute accelerometer data. We further examined the accelerometer data for long periods of continuous zeros as a check of compliance with wearing the device, and we used a criterion of 60 minutes of con- tinuous zeros for noncompliance. We based the judgment of a valid day of measurement on 10 hours of wear time during the waking hours, defined as the moment of getting out of bed in the morning through the moment of getting to bed in the evening. We consid- ered the data to be spurious when counts ex- ceeded 20,000 per minute, and we required the participants to have three valid days of data for a reliable estimate of weekly physical activity behavior. There were four participants with three valid days, seven with four valid days, 13 with five valid days, 12 with six valid
Table1 Categorical Demographic Characteristics of the Sample of 292 Individuals with MS
Variable n %
Type of MS Relapsing-remitting 239 82 Secondary progressive 34 12 Primary progressive 12 4 Benign 7 2
Sex Female 245 84 Male 47 16
Race Caucasian 272 93 African American 20 7
Marital status Married 199 69 Single 45 15 Divorced/ separated 39 13 Widow/ widower 9 3
Employment status Employed 154 53 Unemployed 138 47
Education High school 41 14 Some college 83 28 College graduate 168 58
272 Vol. 38 No. 2 August 2009Motl and McAuley
days, and 229 with seven valid days of acceler- ometer data; 27 participants had missing accel- erometer data based on either unit malfunction or not wearing the unit. The movement counts for each day were summed and then averaged across the period of valid days of data. This resulted in accelerometer data expressed in total movement counts per day ( i.e., usual physical activity behavior) . The intraclass correlation for those with seven days of accelerometer data was 0.92. The GLTEQ is a self-administered two-part
measure of usual physical activity behavior; we only included the first part in th is study, consistent with previous research .20,21 The first part has three items that measure the fre- quency of strenuous (e.g., jogging) , moderate (e.g., fast walking) , and mild (e.g., easy walk- ing) exercise for periods of more than 15 min- utes during one’s free time in a typical week. The weekly frequencies of strenuous, moder- ate, and mild activities are multiplied by 9, 5, and 3 metabolic equivalents, respectively, and summed to form a measure of total leisure ac- tivity. This study used the previous week as a time frame for the GLTEQ, and participants completed the GLTEQ after wearing an accel- erometer for the seven-day period.
Fatigue. Fatigue was measured with the Fa- tigue Severity Scale (FSS23) . The FSS has nine items that are rated on a 7-point scale of 1 (strongly disagree) and 7 (strongly agree) . The item scores are averaged, and the overall scores range between 1 and 7,with higher scores forming an overall measure of fatigue’s impact on activities. This scale has good evidence of in- ternal consistency, test-retest reliability, and score validity.23 Coefficient alpha for the FSS was 0.93 in the present study.
Depression. Depression was measured using the Hospital Anxiety and Depression Scale (HADS24) . The HADS contains 14 items; seven items measure anxiety symptoms and seven items measure depression symptoms. The items are rated on a 4-point scale of 0 (most of the time) and 3 (not at all) , and items are reverse-scored and then summed. HADS de- pression and anxiety scores range between 0 and 21, and higher scores indicate more fre- quent depression and anxiety symptoms. This scale has good evidence of score reliability
and validity.24 Coefficient alpha for the depres- sion component of the HADS was 0.82 in the present study. We only included the measure of depression because of our a priori focus on its role in the symptom cluster.
Pain. Pain was measured with the short-form McGill Pain Questionnaire (SF-MPQ25) . The SF-MPQ contains a 15-item adjective checklist that assesses sensory (e.g., ‘‘stabbing,’’ ‘‘sharp’’) and affective (e.g., ‘‘sickening,’’ ‘‘tiring-exhaust- ing’’) dimensions of typical whole bodypain in- tensity. The items are rated using a 4-point in tensity scale of 0 (none) and 3 (severe) , and the item scores are summed. Scores on the SF- MPQ range between 0 and 45, and higher scores indicate more intense overall pain . The scores from the items are summed to form a pain-rat- ing index. The SF-MPQ is internally consistent, reliable across time, and has evidence of score validity.25 Coefficien t alpha for the SF-MPQ was 0.88 in the present study.
Self-Efficacy. Self-efficacy was assessed by the Exercise Self-Efficacy Scale (EXSE) .26 The EXSE scale has six items that assess an individ- ual’s beliefs in his or her ability to engage in 20þ minutes of moderate physical activity be- havior three times per week, in one-month in- crements, across the next six months. The first item on the EXSE was: ‘‘I am able to participate in physical activity behavior three times per week at a moderate intensity, for 20þ minutes without quitting for the NEXT MONTH.’’ The next five items on the EXSE progressively in- creased the length of the physical activitybehav- ior period in one-month increments from two through six months. The items on the EXSE scale are rated based on a 100-point percentage scale comprised of 10-point increments, rang- ing from 0% (not at all confiden t) to 100% (highly confident) . An overall exercise self-effi- cacy score is computed by averaging the item scores from the EXSE scale with higher scores represen ting greater efficacy for engaging in physical activity behavior; scores range from 0 to 100. This scale is in ternally consistent and has evidence of score validity.26 Coefficient al- pha for EXSE was 0.99 in the present study.
Functional Limitation. Functional limitation was measured using the function component of the abbreviated version of the Late-Life
Vol. 38 No. 2 August 2009 273Symptom Cluster
Function and Disability Instrument (LL- FDI) .27 The function component of the abbre- viated LL-FDI contains a 15-item self-report measure of functional limitations ( limitations in a person’s ability to perform discrete actions or activities) that correspond to advanced lower extremity function, basic lower extremity function, and upper extremity function. The 15 items were rated using a 5-point scale of 1 (none) and 5 (cannot do) , and were reverse- scored and then summed to form a composite measure of functional limitation; higher scores represent better functioning. Researchers have provided evidence for the reliability and valid- ity of LL-FDI scores in individuals with MS.28
Procedure All participants provided written informed
consent, and the procedures were approved by a University Institutional Review Board. The baseline and follow-up materials for the study were delivered and returned through the U.S. postal service, and all participants received $40 on returning the study materials. The participants completed self-report mea- sures of fatigue, depression, pain , self-efficacy, and functional limitations at baseline and six months later, wore an accelerometer for seven days and completed the self-report measure of physical activity behavior after the week of ac- celerometer data collection. The six-month follow-up of physical activity behavior allowed for an examination of the prospective or distal relationship between the symptom cluster and physical activity behavior.
Data Analysis The data were primarily analyzed using
covariance modeling with Full Information Maximum Likelihood (FIML) estimation in Mplus 3.0 (Muthen & Muthen , Los Angeles, CA).29 The FIML estimator was selected be- cause there were missing accelerometer (9% missing data) and GLTEQ (5% missing data) data, and the rate of missing data was different per measure. The FIML estimator is a theoreti- callybased method for the treatment of missing data in covariance modeling.30 This approach is standard in covariance modeling programs, and does not require any manipulation of the data (e.g., mean centering) ; it estimates the model and its parameters using all available data from the participants, and has resulted in
unbiased estimates of parameters and model fit with up to 25% of simulated missing data.30 We initially tested a measurement model, whereby FSS, HADS, and MPQ scores served as indicators of the symptom cluster latent vari- able. We then performed a cluster analysis in SPSS, version 15.0 for Windows (SPSS, Chicago, IL) as a method of clustering persons with MS into groupsbased on experienceswith the three symptoms. After establishing the symptom clus- ter as a latent variable, we conducted an analysis, whereby the symptom cluster latent variable predicted physical activity behavior as a latent variable with accelerometer counts and GLTEQ scores as indicators. The final analysis involved testing EXSE and LL-FDI scores as mediators of the relationship between the symptom clus- ter and physical activity behavior latent vari- ables. We based a good-model data fit on a nonsignificant Chi-square value and combina- tory rules of standardized root mean squared residual (SRMR) # 0.08 and comparative fit index (CFI) $ 0.95.31
Results DescriptiveStatistics The descriptive statistics and correlations
among the variables are provided in Tables 2 and 3, respectively. We did not transform the physical activity behavior data as the estimates of skewness and kurtosis for the accelerometer were 1.3 and 2.6, respectively, and for the GLTEQ were 1.6 and 3.1, respectively, indicating a reason- able approximation of a normal distribution. The correlations among FSS, HADS, and MPQ scores, in particular, were moderate in magni- tude,32 supporting the notion of a symptom clus- ter.10,33 There was a moderate correlation between GLTEQ scores and accelerometer counts, consistent with previous research20,21
Table2 Descriptive Statistics for the Measures
in the Sample of 292 Individuals with MS
Measure Mean Score
Standard Deviation
Range of Scores
FSS 5.0 1.4 1e 7 HADS 6.0 4.2 0e 18 MPQ 10.7 7.8 0e 33 EXSE 72.1 32.9 0e 100 FDI 55.0 11.8 28e 75 GLTEQ 26.1 23.9 0e 133 Accelerometer 207,475 105,419 26,541e 694,878
274 Vol. 38 No. 2 August 2009Motl and McAuley
and our expectations. We expected a moderate rather than strong association given that accel- erometer counts provided an overall measure of usual physical activity behavior, whereas the GLTEQ provided a measure of leisure-time physical activity behavior. There were no significant differences be-
tween men and women on FSS, HADS, MPQ, EXSE, LL-FDI, GLTEQ, or accelerometer scores. There were significant differences on FSS, HADS, MPQ, EXSE, LL-FDI, and acceler- ometer scores as a function of employment status. Those who were unemployed reported higher levels of fatigue, depression, pain , and functional limitations, and had less self-efficacy and physical activitybehavior on the accelerom- eter. Age was not significantly correlated with FSS, HADS,MPQ, or EXSE scores, but it was cor- related with LL-FDI, GLTEQ, and accelerome- ter scores. Those who were older reported more functional limitations and had less physi- cal activitybehavior on both the GLTEQ and ac- celerometer measures. Therefore, we controlled for employment status and age in the analyses examining symptom cluster as a predictor of physical activity behavior.
Model 1: Symptom Cluster Latent Variable The single-factor measurement model in
Fig. 1 provided an excellent fit for the data (c 2 ¼ 0, df ¼ 0, P ¼ 0.73, SRMR ¼ 0.00, CFI ¼ 1.00) . The factor loadings for the indicators of the symptom cluster laten t variable were all statistically significant and sufficiently large in magnitude.33 The additional cluster analysis identified three groups or clusters of individ- uals with relatively low (n ¼ 58; 20%), moder- ate (n ¼ 140; 48%), and high (n ¼ 94; 32%) scores across the measures of FSS, HADS, and MPQ. This is displayed in Fig. 2.
Model 2: Direct Association Between Symptom Cluster and Physical Activity The second model that we tested had a di-
rect path between symptom cluster and physi- cal activity behavior latent variables, and it represen ted a good fit for the data (c 2 ¼ 4.98, df ¼ 4, P ¼ 0.29, SRMR ¼ 0.03, CFI ¼ 1.00) . The path coefficient in Fig. 3 between the symptom cluster and physical activity be- havior was statistically significant (g ¼ 0.49) , and indicated that those who reported
the symptom cluster of worse fatigue, depres- sion, and pain were less physically active. This relationsh ip was unaffected in an additional analysis that accounted for employment status and age. Figure 4 provides the mean acceler- ometer and GLTEQ scores across the three groups of individuals with low, moderate, and
Table3 Correlations Among Variables for the Sample of 292 Individuals with MS
Latent/ Manifest Variable 1 2 3 4 5 6 7
1. FSS d 2. HADS 0.50 d 3. MPQ 0.42 0.35 d 4. EXSE 0.43 0.30 0.24 d 5. FDI 0.55 0.42 0.44 0.53 d 6. GLTEQ 0.23 0.16 0.07 0.30 0.29 d 7. Accelerometer 0.35 0.18 0.19 0.25 0.47 0.43 d All correlations are statistically significant (P < 0.05) with the exception of the correlation between MPQ and GLTEQ.
Symptom Cluster
FSS HADS MPQ
.77 .65 .54
Fig. 1. Single-factor model tested using confirma- tory factor analysis for establishing the symptom cluster of fatigue, depression, and pain in the sam- ple of 292 individuals with multiple sclerosis. All coefficients are standardized estimates.
Vol. 38 No. 2 August 2009 275Symptom Cluster
high symptom experiences based on the symp- tom cluster of fatigue, depression, and pain .
Model 3: Indirect Association Between Symptom Cluster and Physical Activity The th ird model that we tested had an indi-
rect path between symptom cluster and physi- cal activity behavior latent variables by way of self-efficacy and functional limitations as man- ifest variables. The model represented a good fit for the data (c 2 ¼ 21.79, df ¼ 11, P ¼ 0.03, SRMR ¼ 0.04, CFI ¼ 0.98) . The
statistically significan t path coefficients are provided in Fig. 5, which indicate that those who reported the symptom cluster of worse fa- tigue, depression, and pain had lower function (g ¼ 0.71) and self-efficacy (g ¼ 0.51) , and those who reported lower function (b ¼ 0.55) , but not self-efficacy (b ¼ 0.07) , had less physi- cal activity behavior. Therefore, the relation- ship between the symptom cluster and physical activity behavior was significantly and indirectly accounted for by functional limita- tions (gb ¼ 0.39) , but not self-efficacy (gb ¼ 0.04) . These relationsh ips were unaffected in an additional analysis that accounted for employment status and age.
Discussion Using a prospective research design and the
Theory of Unpleasant Symptoms, the current study examined the symptom cluster of fa- tigue, depression, and pain as a predictor of physical activity behavior among persons with MS. Our results indicated that: 1) fatigue, de- pression , and pain represented a symptom cluster based on bivariate correlations, covari- ance modeling, and cluster analysis; 2) th is symptom cluster had a moderate and negative predictive relationsh ip with physical activity be- havior; and 3) functional limitation, but not self-efficacy, accounted for the predictive rela- tionship between the symptom cluster and physical activity behavior. Such findings
0
4
8
12
16
20
FSS HADS MPQ Measure
M ea
n ±
St an
da rd
E rr
or
Low (n=58) Moderate (n=140) High (n=94)
Fig. 2. Mean scores and standard errors for the measures of fatigue, depression, and pain based on the low, moderate, and high symptom clusters identified in the cluster analysis with the sample of 292 individuals with multiple sclerosis.
Symptom Cluster
FSS HADS MPQ
Physical Activity
GLTEQ ACCEL
D1
−.49
.54 .80.84 .60 .51
Fig. 3. Model tested using covariance modeling for understanding the association between symptom cluster and physical activity behavior in a sample of 292 individuals with multiple sclerosis. All coefficients are standardized estimates. Accel ¼ accelerometer counts.
276 Vol. 38 No. 2 August 2009Motl and McAuley
provide preliminary support for the impor- tance of considering a symptom cluster as a meaningful correlate of physical activity be- havior in persons with MS. There is a growing body of research that has
identified symptoms as a cross-sectional or tem- porally proximal correlate of physical activity behavior in MS.6e 9 All these studies were af- fected by a set of limitations that included the general focus on the overall frequency or
intensity of symptoms, lack of a guiding symp- tom-based theoretical framework, and a cross- sectional research design. The present study extended previous research by focusing on a symptom cluster of fatigue, depression, and pain as a temporally distal predictor of physical activity behavior after a six-month period using a prospective design and based on the Theoryof Unpleasant Symptoms.5 Our findings are con- sistent with the Theory of Unpleasant Symp- toms, that is, 1) the symptom cluster of fatigue, depression, and pain was moderately and negatively associated with physical activity behavior; and 2) the relationship between the symptom cluster and physical activity behavior was indirect through functional limitations. The present study further extended previous research6e 9 by considering both self-efficacy and functional limitations as possible interven- ing variables between the symptom cluster and physical activity behavior in MS. To that end, our results provided evidence that functional limitations, rather than self-efficacy, repre- sented the stronger intermediate variable in the temporally distal association between the symptom cluster and physical activity behavior. The results of previous research and the cur-
rent studymight have implications for the pro- motion and maintenance of a physically active lifestyle in persons with MS. Indeed, individuals
0
10
20
30
40
50
Low (n=58) Moderate (n=140) High (n=94)
Accelerometer GLTEQ
Fig. 4. Mean scores and standard errors for the ac- celerometer counts and GLTEQ scores across the three groups of individuals with low, moderate, and high symptom experiences identified in the cluster analysis. Accelerometer data are expressed in units of original values 10 4 so that the units are easily graphed and compared in magnitude with GLTEQ scores.
Symptom Cluster
FSS HADS MPQ
Physical Activity
GLTEQ ACCEL
D3
.53 .81.79 .62 .56
EXSE
D1
FDI
D2
−.51
−.71 .55
.07
Fig. 5. Model tested using covariance modeling for understanding the associations among symptom cluster, self- efficacy, functional limitation, and physical activity behavior in a sample of 292 individuals with multiple sclerosis. All coefficients are standardized estimates. Solid lines represent statistically significant paths, and dashed lines represent nonsignificant paths. Accel ¼ accelerometer counts.
Vol. 38 No. 2 August 2009 277Symptom Cluster
with MS are often physically inactive and seden- tary,3,4 and emerging evidence indicates that symptoms might be a determinan t of inactivity among persons with MS. The management of symptoms, therefore, represents a possible strat- egy for the promotion and maintenance of physical activity behavior among those with MS. This might be accomplished, in particular, through a program that includes provisions for the management of fatigue, depression, and pain as a cluster of symptoms. To that end, there is a growing bodyof evidence regard- ing programs for managing symptoms, such as fatigue, depression, and pain in MS.34e 36We be- lieve that one direction for future research in- volves incorporating elements of these programs into a multidimensional in tervention for promoting physical activity behavior in per- sons with MS. An additional important finding of this
study is the confirmation of a symptom cluster of fatigue, depression, and pain in persons with MS. The symptom cluster has been identi- fied in persons undergoing treatment for can- cer,12 and was established in the current study based on three sets of analyses, including 1) the bivariate correlations among the three vari- ables; 2) the fit of a single latent variable for the three variables; and 3) the cluster analysis that yielded three distinct groups of individ- uals with relatively low, moderate, and high scores across the cluster of three variables. This is consistent with the recommendations in the literature for statistically identifying a symptom cluster,10,33,37 particularly the re- cent call for using two conceptual approaches for identifying symptom clusters ( i.e., bivariate correlations and factor analysis) and sub- groups of individuals based on experiences with a symptom cluster ( i.e., cluster analysis38) . We further note that the symptoms of fatigue, depression, and pain are linked through a com- mon etiology based on neuropathic conse- quences, including co-occurring and diffuse axonal damage ( i.e., lesions) across different regions of the central nervous system.18 There- fore, we provide preliminary evidence for the existence of a symptom cluster of fatigue, de- pression, and pain in individuals with MS, and this is consistent with the literature on persons with cancer.12 There are several limitations of the current
study. One limitation is that we focused on
a six-month follow-up for measuring symptoms, and the magnitude of the relationship between the symptom cluster and physical activitymight differ with shorter or longer follow-up periods. The second limitation is that we did not control for baseline activityin the analysis nor did we ex- amine the relationship between changes in the symptom cluster and physical activity behavior across time. The focus on only three symptoms of fatigue, depression, and pain is a third limita- tion, and future researchers might consider ad- ditional symptoms within this cluster and other clusters of symptoms in MS. The symptom di- mensions that were measured varied across the FSS, HADS, and SF-MPQ. For example, the FSSmeasured the impact of fatigue on activ- ities, whereas the HADS measured the fre- quency of depressive symptoms. This is a the fourth limitation of the present study, and fu- ture researchers should be cautious in using measures that share common symptom dimen- sions. The final limitation is that the relation- ship between the symptom cluster and physical activity behavior was only studied in a sample of persons with MS, and future re- searchers might consider extending our find- ings into those with other disease conditions, including cancer. In conclusion, the results of the present
study provide a preliminary basis for consider- ing the role of the symptom cluster of fatigue, depression, and pain within the growing body of knowledge that symptoms play a role in mul- tiple behavioral outcomes, including physical activity behavior, in persons with MS. The role of symptoms in physical activity behavior of individuals with MS, in particular, is an area substantial with research potential for promoting and main taining physical activity behavior. The promotion and maintenance of an activity lifestyle is an important compo- nent for enhancing the lives of persons with MS.1,2
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