Brilliant Baby Brainiacs (BBB) - Pediatric BrainTumors: Assessing Healthcare Provider Knowledge

Item Type text; Electronic Dissertation

Authors Tong, Amanda Kai-Lai

Publisher The University of Arizona.

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BRILLIANT BABY BRAINIACS (BBB) – PEDIATRIC BRAIN TUMORS:

ASSESSING HEALTHCARE PROVIDER KNOWLEDGE

by

Amanda Kai-Lai Tong

________________________"Copyright © Amanda Kai-Lai Tong 2015

A DNP Project Submitted to the Faculty of the

COLLEGE OF NURSING

In Partial Fulfillment of the Requirements For the Degree of

DOCTOR OF NURSING PRACTICE

In the Graduate College

THE UNIVERSITY OF ARIZONA

2 0 1 5

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THE UNIVERSITY OF ARIZONA GRADUATE COLLEGE

As members of the DNP Project Committee, we certify that we have read the DNP

Project prepared by Amanda Kai-Lai Tong entitled Brilliant Baby Brainiacs (BBB) –

Pediatric Brain Tumors: Assessing Healthcare Provider Knowledge and recommend that

it be accepted as fulfilling the DNP Project requirement for the Degree of Doctor of

Nursing Practice.

_____________________________________________Date: October 14, 2015 Gloanna Peek, PhD, RN, CPNP _____________________________________________Date: October 14, 2015 Ida (Ki) Moore, DNSc, RN, FAAN _____________________________________________Date: October 14, 2015 Cindy Rishel, PhD, RN, OCN Final approval and acceptance of this DNP Project is contingent upon the candidate’s submission of the final copies of the DNP Project to the Graduate College. I hereby certify that I have read this DNP Project prepared under my direction and recommend that it be accepted as fulfilling the DNP Project requirement. _____________________________________________Date: October 14, 2015 DNP Project Director: Gloanna Peek, PhD, RN, CPNP

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STATEMENT BY THE AUTHOR

This DNP Project has been submitted in partial fulfillment of requirements for an advanced degree at The University of Arizona and is deposited in the University Library to be made available to borrowers under rules of the Library.

Brief quotations from this DNP Project are allowable without special permission, provided that accurate acknowledgment of source is made. Requests for permission for extended quotation from or reproduction of this manuscript in whole or in part may be granted by the copyright holder.

SIGNED: Amanda Kai-Lai Tong

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ACKNOWLEDGEMENTS

First and foremost, I would like to thank my advisor and committee chair Dr. Gloanna Peek for her support and guidance throughout my graduate degree career. I would also like to thank my committee members Dr. Ki Moore and Dr. Cindy Rishel. All three of these professors at the College of Nursing provided expert suggestions on my DNP Project that benefitted all the children I care for as a registered nurse and future pediatric nurse practitioner. I would also like to express my appreciation and gratitude to all of my co-workers at Phoenix Children’s Hospital that continuously supported me throughout my nursing career and my academic career. They were supportive with their words of wisdom, friendship, laughter, and their love of caring for children and their families. I am honored to have taken care of a lot of children and families throughout my nursing career. A few of the patients and families that I cared for inspired this DNP Project. I will never forget the valuable life lessons they all taught me as I cared for them. I would also like to mention that my strong faith and trust in God allowed me to complete this rigorous program and project. Finally, I would like to thank my family and friends, especially my mother, father, and brother. Their love, support, encouragement, and guidance allowed me to complete this DNP Project and my doctoral degree.

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DEDICATION

To all children and families that have ever had to experience the diagnosis of a

brain tumor and to all the nurses that have cared for these children and families. Most

importantly, to the 8-year old girl and 5-month old baby boy and their lovely families that

inspired me to research about pediatric brain tumors.

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TABLE OF CONTENTS

LIST OF FIGURES .............................................................................................................9

LIST OF TABLES .............................................................................................................10

ABSTRACT .......................................................................................................................11

CHAPTER I. BACKGROUND AND SIGNIFICANCE ..............................................12

Introduction ......................................................................................................................12 Clinical Problem ...............................................................................................................13

Overview ...............................................................................................................13 Common Signs and Symptoms of Pediatric Brain Tumors .............................13 Brain Tumor Histology and Brain Tumor Location ........................................14 Pre-Diagnostic Symptom Interval (PSI) ............................................................15 Parental Perceptions ............................................................................................16 Summary ...............................................................................................................16

Clinical Guideline to Assist Healthcare Providers ........................................................17 Head Smart Campaign from the United Kingdom ...........................................17 Knowledge Gap ....................................................................................................18

Significance to Advanced Practice Nursing ...................................................................19 Purpose and Aims of DNP Project .................................................................................20

CHAPTER II. REVIEW OF LITERATURE ...............................................................21

Pediatric Brain Tumor Clinical Presentation ...............................................................21 Common Signs and Symptoms ...........................................................................21 Common Misdiagnoses ........................................................................................25 Tumor Histology and Tumor Location Association with Diagnostic Delay and Signs and Symptoms ....................................................................................25

Diagnostic Delays and Pre-Diagnostic Symptom Interval (PSI) .................................29 Pre-Diagnostic Symptom Interval (PSI) ............................................................29 Parental Delay ......................................................................................................30 Doctor’s Delay ......................................................................................................31 Summary of Diagnostic Delays and Pre-Diagnostic Symptom Interval (PSI)31 Primary Care Providers Versus Specialist Doctors ..........................................34 Number of Consultations or Visits to Healthcare Providers Prior to Diagnosis ...............................................................................................................35 Diagnostic Delay of Pediatric Brain Tumors in Comparison to Other Childhood Cancers ..............................................................................................36

Cost-effectiveness of Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) to Diagnose Pediatric Brain Tumors ...................................................37 Does Prolonged Pre-Diagnostic Symptom Interval (PSI) Decrease Survival? ...........39 Parental Perception and Experiences ............................................................................41

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TABLE OF CONTENTS - Continued

Healthcare Provider Guideline to Assist in Diagnosis of Pediatric Brain Tumors ....42 Synthesis of Literature ....................................................................................................45

CHAPTER III. METHODOLOGY ...............................................................................48

Study Aims ........................................................................................................................48 Model to Implement Guideline: ACE Star Model of Knowledge Transformation ...48

Star Point 1: Discovery Research ......................................................................50 Star Point 2: Evidence Summary ......................................................................50 Star Point 3: Translation to Guidelines ............................................................50 Star Point 4: Practice Integration .....................................................................50 Star Point 5: Process, Outcome Evaluation .....................................................51

Applicability of ACE Star Model of Knowledge Transformation to the Brain Pathways Guideline .........................................................................................................51

Star Points 1-3: The Brain Pathways Guideline .................................................51 Star Point 4 and 5 .................................................................................................52

Methods .............................................................................................................................52 Summary of Expert Evaluations of Pre-Test and Post-Test ........................................55 Sample ...............................................................................................................................57 Protection of Human Subjects and Ethical Considerations .........................................58 Data Collection .................................................................................................................59 Data Analysis ....................................................................................................................59

CHAPTER IV. RESULTS ..............................................................................................60

Description of Sample ......................................................................................................60 Scores on Pre-Test and Post-Test ...................................................................................61 Comparison of Primary Care PNPs to Acute Care PNPs ............................................61 Post-Test Only Questions ................................................................................................62 Wilcoxon Signed Rank Test and Null Hypothesis ........................................................63

CHAPTER V. DISCUSSION AND IMPLICATIONS .................................................64

DNP Project Goals ...........................................................................................................64 Short-Term Goal: Increase Knowledge of Common Signs and Symptoms of Pediatric Brain Tumors .......................................................................................64 Long-Term Goal: Decrease Pre-Diagnostic Symptom Interval (PSI) ............65

Integration of Implementation Model ............................................................................66 Evaluation Questionnaire by Participants ........................................................66

Strengths and Limitations ...............................................................................................67 Relevance to Advanced Practice Nursing ......................................................................69 Future Research and Improvements ..............................................................................70 Conclusion ........................................................................................................................72

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TABLE OF CONTENTS - Continued

APPENDIX A ....................................................................................................................73

APPENDIX B ....................................................................................................................75

APPENDIX C ....................................................................................................................77

APPENDIX D ....................................................................................................................81

APPENDIX E ....................................................................................................................85

APPENDIX F ....................................................................................................................88

APPENDIX G ....................................................................................................................91

APPENDIX H ....................................................................................................................94

APPENDIX I .....................................................................................................................98

APPENDIX J ...................................................................................................................100

REFERENCES ................................................................................................................102

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LIST OF FIGURES

FIGURE 1. The Brain Pathways Guideline: A Guideline To Assist Healthcare

Professionals In The Assessment Of Children Who May Have A Brain Tumour (The

Brain Pathways Guideline) ................................................................................................74

FIGURE 2. Decision Tree for Children With Headache ...................................................39

FIGURE 3. ACE Star Model of Knowledge Transformation ............................................49

FIGURE 4. Head Smart Symptom Card ............................................................................76

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LIST OF TABLES

TABLE 1. Summary of Pre-Diagnostic Symptom Interval (PSI), Parental Delay, and

Doctor’s Delay From Multiple Research Studies ..................................................................33

TABLE 2. Overall Survival Probabilities (OS) and Progression Free Survival

Probabilities (PFS) in Pediatric Brain Tumor Patients ..........................................................41

TABLE 3. Expert Evaluation by Pediatric Intensive Care Unit Attending with Expertise

in Neuro-Critical Care ............................................................................................................55

TABLE 4. Expert Evaluation by Pediatric Neurosurgeon .....................................................56

TABLE 5. Expert Evaluation by Pediatric Nurse Practitioner in Neurosurgery Specialty ...57

TABLE 6. Descriptive Information of Sample ......................................................................60

TABLE 7. Pre-Test and Post-Test Average Scores ...............................................................61

TABLE 8. Comparison of Primary Care PNPs and Acute Care PNPs ..................................62

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ABSTRACT

Background: Brain tumors are the most common solid tumors found in children. Current

research is determining whether diagnosing brain tumors earlier will help improve

prognosis and reduce long-term deficits; however, childhood brain tumors are often

diagnosed late with a median time of 1-4 months from onset of symptoms. Prolonged

symptom intervals before diagnosis have been associated with life-threatening risks,

neuro-cognitive disabilities, and detrimental professional relationships between

healthcare providers and families. Pediatric brain tumor clinical presentations are often

non-specific and resemble less serious illnesses; therefore, healthcare providers are

failing to include this in their differential diagnoses list.

Purpose: To assess healthcare provider knowledge of signs and symptoms of pediatric

brain tumors using The Brain Pathways Guideline.

Methods: A one group pre-test and post-test e-mailed separately to nurse practitioners

that have active membership in National Association of Pediatric Nurse Practitioners

(NAPNAP) Arizona Chapter.

Results: The Wilcoxon Signed Rank Test revealed that the matched test scores were not

statistically significant (p=0.157) after viewing The Brain Pathways Guideline

educational materials.

Conclusion: The results of this study did not show a statistically significant difference in

the test scores and therefore it cannot be concluded that presenting an evidence-based

guideline to assist healthcare providers to assess and diagnose patients with brain tumors

will be helpful to improve pre-diagnostic symptom intervals.

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CHAPTER I: BACKGROUND AND SIGNIFICANCE

Introduction

Brain tumors are the most common solid tumors found in children (Dobrovoljac,

Hengartner, Boltshauser, & Grotzer, 2002; Klitbo, Nielson, Illum, Wehner, & Carlsen,

2011; Wilne et al., 2012; Wilne et al., 2007; Wilne et al., 2010). About 25% of all

cancers are brain tumors in children ages 1-19 years old and 60% of survivors are left

with devastating disabilities (Dobrovoljac et al., 2002; Klitbo et al., 2011; Wilne et al.,

2012; Wilne et al., 2007; Wilne et al., 2010). Current research is determining whether

diagnosing brain tumors earlier will help improve the prognosis and reduce long-term

deficits; however, childhood brain tumors are most often diagnosed late with a median

time of one to four months from the onset of symptoms (Dobrovoljac et al., 2002;

Dörner, Fritsch, Stark, & Mehdorn, 2007; Edgeworth, Bullock, Bailey, Gallagher, &

Crouchman, 1996; Flores, Williams, Bell, O’Brien, & Ragab, 1986; Klitbo et al., 2011;

Pollock, Brischer, & Vietti, 1991; Reulecke, Erker, Fieldler, Niederstadt, & Kurelmann,

2008; Thulesius, Pola, & Håkansson, 2000; Wilne et al., 2012; Wilne et al., 2007; Wilne

et al., 2010). Prolonged symptom intervals before childhood brain tumor diagnosis in

pediatric patients have been associated with increased life-threatening risks, neurological

disability complications, and worsening cognitive abilities in survivors (Wilne et al.,

2012). Detrimental consequences of late diagnosis occur in the professional relationship

domain between healthcare providers and families due to the family’s perception that the

medical responses are incompetent and delayed (Dixon-Woods, Findlay, Young, Cox, &

Heney, 2001; Wilne et al., 2012).

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Clinical Problem

Overview

The delay in diagnosis of childhood brain tumors dates back to the pre-computed

tomography (CT) and pre-magnetic resonance imaging (MRI) technologies (Edgeworth

et al., 1996). Despite the availability and advances in neuroimaging technologies over

past decades, timely diagnosis of children suspected of having a brain tumor still remains

problematic (Dobrovoljac et al., 2002; Edgeworth et al., 1996). The initial signs and

symptoms of brain tumors are non-specific and often are similar to other common and

less serious illnesses such as gastroenteritis, migraines, or behavioral problems (Wilne et

al., 2007; Wilne et al., 2006). The main clinical problem is that healthcare providers have

difficulty identifying the signs and symptoms associated with pediatric brain tumors due

to the non-specific presentations and failure to consider it as one of the differential

diagnoses (Wilne et al., 2007; Wilne et al., 2010). Consequences of a delayed diagnosis

are that children continue to be symptomatic for a few months and sometimes these

symptoms progress to life-threatening emergencies (Wilne et al., 2012).

Common Signs and Symptoms of Pediatric Brain Tumors

The presentation of pediatric brain tumors is often non-specific with symptoms

mimicking less serious illnesses (Wilne et al., 2010). Wilne et al. (2010) completed a

systematic review and meta-analysis of common signs and symptoms of pediatric brain

tumors. Of the 74 studies that met inclusion criteria, 61 of those studies described signs

and symptoms at diagnosis of 4,171 children with intracranial tumors. The most

common signs and symptoms by listing in order of decreasing frequency are: headache

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(32%), nausea and vomiting (32%), abnormal gait or coordination (27%), papilloedema

(13%), seizures (13%), unspecified signs and symptoms of increased intracranial pressure

(10%), squint (7%), changes in behavior of school performance (7%), macrocephaly

(7%), unspecified cranial nerve palsies (7%), lethargy (6%), abnormal eye movements

(6%), hemiplegia (6%), weight loss (5%), focal motor weaknesses (5%), unspecified

visual or eye abnormalities (5%), and altered level of consciousness (5%). The most

frequent signs and symptoms that healthcare providers may encounter will be headache,

nausea and vomiting, or abnormal gait or coordination. These symptoms alone may

mislead healthcare providers to consider less serious diagnoses on their differential

diagnoses list. Reulecke et al. (2008) found that healthcare providers are aware that a

delay in the diagnosis of a brain tumor may lead to further progression of the tumor thus

worsening the outcome and posing additional risk of brain damage due to prolonged

increased intracranial pressure (ICP).

Brain Tumor Histology and Brain Tumor Location

Other factors that affect the presentation of a child suspected of having a brain

tumor are tumor histology, tumor location, and especially the age of the child (Pollack,

1999). Childhood brain tumors are classified as supratentorial or infratentorial.

Supratentorial tumors develop above the tentorium cerebelli and infratentorial tumors

develop below the tentorium cerebelli (Pollack, 1999). About 60% of children develop

brain tumors in the infratentorial region and supratentorial tumors are predominant in

infants (Pollack, 1999). Supratentorial tumor presentations reflect the compression and

infiltration of adjacent structures; therefore, the patient may have signs and symptoms of

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increased ICP (Pollack, 1999). Infratentorial tumors have a variety of presentations

depending on the tumor type, but these tumors commonly occlude the fourth ventricle

leading to obstructive hydrocephalus and increased ICP signs and symptoms (Pollack,

1999). Depending on the histology of the tumor, signs and symptoms may vary. Signs

and symptoms of benign tumors progress insidiously; conversely, signs and symptoms

for aggressive tumors manifest more rapidly (Pollack, 1999; Reulecke et al., 2008). For

these reasons, healthcare providers need to be cognizant of the common signs and

symptoms that might lead them to a differential diagnosis of a pediatric brain tumor.

Pre-Diagnostic Symptom Interval (PSI)

The period that precedes uncertainty of a brain tumor diagnosis has been termed

pre-diagnostic symptom interval (PSI), which is defined as the time from initial onset of

signs and symptoms to official diagnosis of a brain tumor by neuroimaging or biopsy

(Dobrovoljac et al., 2002; Dörner et al., 2007; Edgeworth et al., 1996; Flores et al., 1986;

Klitbo et al., 2011; Pollock et al., 1991; Wilne et al., 2012; Wilne et al., 2010). The PSI

can be divided into two stages of delay. One stage is parental delay, which is defined as

the interval from the onset of the first sign and symptom to first visit with a healthcare

provider (Dobrovoljac et al., 2002). The second stage is doctor’s delay, which is defined

as the interval from the first consultation to the diagnosis by neuroimaging technology

(CT or MRI) (Dobrovoljac et al., 2002). The delay in diagnosing pediatric brain tumors

ensues in both stages and regardless of when the delay is occurring, childhood brain

tumors are still diagnosed late (Dobrovoljac et al., 2002).

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Parental Perceptions

Parents have expressed the interval from noticing symptoms to finally receiving

an official diagnosis for their child as the most distressing experience (Dixon-Woods et

al., 2001). Many parents experience disputes with their healthcare providers initially.

Dixon-Woods et al. (2001) define disputes as “disagreements between parents and

doctors about the seriousness of [their child’s] symptoms and the need for further

investigations” (p. 670). These parents may have to argue with their providers to demand

more tests to be done because of their rejection of the provider’s common sense

diagnosis. The experience of finally arriving at the diagnosis of a brain tumor after many

disputes with healthcare providers offers relief because at least there is an identifiable

cause for the unusual signs and symptoms. For the parents that do not experience many

disputes with healthcare providers, they are shocked and stunned by the child’s tumor

diagnosis whether it is benign or malignant (Dixon-Woods et al., 2001). Parents are

advocates for their children and healthcare providers are also advocates for their patients.

Lengthy disputes with healthcare providers leave parents with the perception that

healthcare providers are incompetent due to their inadequate and inappropriate responses

to their child’s signs and symptoms (Dixon-Woods et al., 2001).

Summary

Advances in technologies and the education of healthcare providers have not

resulted in earlier diagnosis of pediatric brain tumors as evidenced by a continued lengthy

PSI. The non-specific presentation of children suspected of having a brain tumor to

healthcare providers continues to pose a problem because it puts children at risk for

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further neurological damage and deficits. Negative parental perception of healthcare

providers and the healthcare system may be propagated when parents need to advocate

for their child through disputes. The aforementioned issues with delayed diagnosis

serves as this DNP Project’s significance to implement a guideline to assist healthcare

providers and decrease the PSI as the main outcome measure in primary care settings

(doctor’s offices, urgent care centers, clinics, and emergency departments). The main

clinical problem this DNP Project addresses is that healthcare providers are not

recognizing the signs and symptoms associated with pediatric brain tumors and are not

considering this as a diagnosis on the differential diagnosis list. The purpose of this DNP

Project is to expose healthcare providers to an evidence-based clinical practice guideline

to assess knowledge of pediatric brain tumors to achieve a long-term goal of decreasing

the PSI.

Clinical Guideline to Assist Healthcare Providers

Head Smart Campaign from the United Kingdom

In the United Kingdom, collaboration between healthcare professionals and

families were formed due to their common concern about the prolonged time it was

taking for children with brain tumors to be diagnosed. The response to this concern was

the launch of a national campaign called the Head Smart Campaign (Head Smart, 2011)

after The Children’s Brain Tumour Research Centre at Nottingham University (Walker et

al., 2008) developed a specific evidence-based guideline to aid practitioners in

identifying and assessing children suspected of having a brain tumor. The Head Smart

Campaign has specific aims to enhance the awareness of signs and symptoms of pediatric

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brain tumors and reduce the delay of diagnosis. The goal of this campaign is to reduce

the pre-diagnostic symptom interval to six weeks, when research has shown that

diagnosis of brain tumors have been taking longer than three months (Head Smart, 2011).

The campaign aims to decrease the PSI at all stages, which include: delay in seeing a

healthcare provider, delay in healthcare providers’ recognition of the signs and

symptoms, and delay in referral to appropriate secondary care such as neuroimaging

appointments (CT or MRI), neurosurgery specialty providers, or neuro-oncology

specialty providers (Head Smart, 2011). Currently, the United States does not have the

same national initiative, goal, and campaign compared to the United Kingdom, though

the delay in diagnosis of pediatric brain tumors exists worldwide in developed countries.

Knowledge Gap

Pediatric brain tumors are the most common tumors discovered in children;

however, during a healthcare providers’ career, he/she may only see one case

(Dobrovoljac et al., 2002; Wilne et al., 2012). Without a current implemented guideline

to assist healthcare providers in assessing children that may have a brain tumor, diagnosis

may continue to be delayed. Walker et al. (2008) and Wilne et al. (2010) conducted

multiple research studies to identify the most common signs and symptoms of pediatric

brain tumors and a multi-disciplinary and Delphi process to develop a guideline called

The Brain Pathways Guideline: A Guideline To Assist Healthcare Professionals In The

Assessment Of Children Who May Have A Brain Tumour (The Brain Pathways

Guideline), which will aid healthcare providers in diagnosing pediatric brain tumors (See

Appendix A Figure 1). This guideline assists healthcare providers to consider a brain

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tumor diagnosis when a child presents with headache, nausea and/or vomiting, visual

signs and symptoms, motor signs and symptoms, growth and development abnormalities,

behavioral changes, diabetes insipidus, seizures, or altered consciousness. It also

recommends Central Nervous System (CNS) imaging depending on the clinical

presentation and a focused history and physical examination of the neurological system

(past medical history, predisposing factors, history of present illness, visual system,

motor system, height and weight, head circumference for less than 2 years old,

psychomotor development for less than 5 years old, and pubertal status) (Walker et al.,

2008; Wilne et al., 2010). To date, there is no evidence that this guideline has been

implemented into healthcare settings and therefore there are no available results of its

effectiveness to decrease the PSI (Walker et al., 2008; Wilne et al., 2010). The gap in

knowledge among healthcare providers regarding the diagnosis of brain tumors in

children continues to be a concern due to the lack of consideration of a brain tumor as

one of the differential diagnosis at the initial patient visit. This further delays referral for

neuroimaging for diagnosis and prolongs the PSI that may progress to worsening of

symptoms and distressing experiences for patients and families.

Significance to Advanced Practice Nursing

The Advanced Practice Nurse (APN) especially pediatric specialty nurse

practitioner is responsible for providing care throughout a child’s life. APNs are

responsible for recognizing the signs and symptoms of common and uncommon

childhood diagnoses. Being cognizant of brain tumor signs and symptoms with the

assistance of a clinical guideline may help reduce the PSI and allow children with

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possible brain tumors to receive appropriate care earlier. Providing the APN with a

guideline for assessing pediatric patients for a brain tumor can dramatically affect the

patient and family’s perception of nurse practitioners and the healthcare system.

Implementing the existing clinical guideline available from the Head Smart Campaign

will generate data needed to evaluate whether or not this guideline will decrease the pre-

diagnostic symptom interval in diagnosing children with a suspected brain tumor.

Purpose and Aims of DNP Project

This DNP Project describes an implementation project to assess healthcare

provider knowledge of pediatric brain tumor patients with a long-term goal and aims of

reducing the pre-diagnostic symptom interval by using The Brain Pathways Guideline: A

Guideline To Assist Healthcare Professionals In The Assessment Of Children Who May

Have A Brain Tumour (The Brain Pathways Guideline) developed by The Children’s

Brain Tumour Research Centre at Nottingham University to assist healthcare providers in

assessing and diagnosing children who may have a brain tumor (Walker et al., 2008;

Wilne et al., 2010). A specific Population, Intervention, Comparison, Outcome (PICO)

question has been developed to guide literature search and study design: In children

suspected of having a brain tumor (P), does implementing a diagnostic guideline to assist

healthcare providers (I), compared to not using a guideline (C), increase knowledge about

pediatric brain tumor clinical presentation (short-term) and decrease the pre-diagnostic

symptom interval (long-term) (O)? This DNP Project describes an implementation

project of online educational materials targeting pediatric nurse practitioners with a pre-

test and post-test to assess the short-term goal of knowledge gain.

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CHAPTER II: REVIEW OF LITERATURE

Pediatric Brain Tumor Clinical Presentation

Common Signs and Symptoms

Numerous retrospective studies have sought to identify the most common signs

and symptoms children with brain tumors have presented with to healthcare providers

(Dörner et al., 2007; Hyashi et al., 2010; Klitbo et al., 2011; Mehta, Chapman, McNeely,

Walling, & Howes, 2002; Reulecke et al., 2008; Wilne et al., 2012; Wilne et al., 2007;

Wilne et al., 2006). Researchers have categorized the most common signs and symptoms

in correlation with tumor histology, tumor location, increased ICP, number of symptoms

initially to number of symptoms at the time of diagnosis, and progression of signs and

symptoms. The consensus among these retrospective studies is that the most common

signs and symptoms are non-specific such as headache, nausea and vomiting, and

abnormal gait or coordination (Dörner et al., 2007; Hyashi et al., 2010; Klitbo et al.,

2011; Mehta et al., 2002; Reulecke et al., 2008; Wilne et al., 2012; Wilne et al., 2007;

Wilne et al., 2006).

Mehta et al. (2002) conducted a retrospective and prospective study in Eastern

Canada of 104 pediatric brain tumor symptoms by analyzing information from medical

charts and interviews from families. Sixty-six percent of children experienced nausea

and vomiting with nine patients that were less than 4-years old, 63% of children

complained of headaches, and 50% of children had some change in their behavior noticed

by the parents.

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Wilne et al. (2006) completed a review of 200 case note reviews of patients that

presented with a CNS tumor in the United Kingdom. The most common first symptom

among these patients was headache (41%) with most of these headaches either occurring

early in the morning or nocturnally and the second most common symptom was vomiting

(12%). Special consideration that these researchers discovered was that 21% of the

patients that were 3-years old or younger were less likely to present with headaches or

seizures, but more commonly to present with behavioral problems compared to older

children.

Dörner et al. (2007) retrospectively analyzed 50 pediatric patients with posterior

fossa tumors in Germany over a 4-year period and found that the most common

symptoms healthcare providers documented during chart review were headache, nausea

and vomiting, ataxia, cranial nerve deficits, and hydrocephalus.

Reuleck et al. (2008) retrospectively analyzed records of 245 pediatric brain

tumor patients over a 24-year period in Germany. Comparable to previous mentioned

studies, the most common signs and symptoms included headaches and vomiting

initially.

Hyashi et al. (2010) analyzed medical records of 60 pediatric brain tumor patients

in Japan retrospectively for initial signs and symptoms and the progression and number

of the signs and symptoms. The most common initial signs and symptoms among these

children included vomiting (45%), headache (26.7%), unsteadiness (25%), and paresis

(18.3%). Of the 60 patients, 38 patients had two or more symptoms before diagnosis,

only 16 patients had one symptom before diagnosis, four patients were diagnosed at

23

routine medical check-ups, and two patients were diagnosed during the perinatal period.

A majority of the patients either had headache or vomiting as the first symptom followed

by other common symptoms or more specific neurological symptoms such as cranial

nerve palsies or increased ICP clinical manifestations. Wilne et al. (2012) also found that

between the time of symptom onset and diagnosis, there was an increase in the number of

signs and symptoms (initial onset: ranged from 1-8 symptoms; time at diagnosis: ranged

from 1-17 symptoms). Overall, the initial non-specific signs and symptoms of children

with brain tumors continues to progress to more concerning signs and symptoms such as

paresis, palsies, or increased ICP manifestations.

Klitbo et al. (2011) conducted a retrospective study of 46 children with brain

tumors in Southern Denmark by analyzing medical charts and interviewing parents and

general practitioners. Similar to previous studies, Klitbo et al. (2011) found that the most

common clinical symptom at diagnosis was vomiting (50%), headache (50%), and ataxia

(35%).

Wilne et al. (2012) examined hospital medical records of 139 children diagnosed

with brain tumor in the United Kingdom. The researchers found that the most common

signs and symptoms of children with brain tumors (most common listed first) were

headache, nausea and/or vomiting, motor system abnormalities, cranial nerve palsies,

visual system abnormalities, seizures, endocrine or growth abnormalities, behavior

change, abdominal or back pain, alteration in or loss of consciousness, and spinal

deformity. Over half (56.8%) of these children only had a single symptom at onset,

24

which highlights the non-specificity of these signs and symptoms in relation to a brain

tumor diagnosis.

Wilne et al. (2007) conducted the first known systematic review and meta-

analysis of childhood presentation of CNS tumors to elicit the most common signs and

symptoms of children with brain tumors. The study narrowed the 5,620 potentially

relevant articles down to 74 studies that met the inclusion criteria over a 14-year period

(1991-2005). Sixty-one studies (N = 3,702 children) described signs and symptoms of

intracranial tumors at diagnosis with headaches (33%), nausea and vomiting (32%), and

abnormal gait or coordination (27%) as the most common signs and symptoms. Thirteen

studies (N = 332 children) described signs and symptoms of children with intracranial

tumors under 4-years old with macrocephaly (41%), nausea and vomiting (30%),

irritability (24%), lethargy (21%), abnormal gait and coordination difficulties (19%), and

clinically apparent hydrocephalus with bulging fontanel or splayed sutures (13%) as the

most common signs and symptoms. Eight studies (N = 307 children) described signs and

symptoms of children with neurofibromatosis and intracranial tumors with reduced visual

acuity (41%), exophthalmia (16%), optic atrophy (15%), and squint (13%) as the most

common signs and symptoms. It is important to note that the study had some limitations

including publication bias since unpublished papers were not searched, recall bias due to

data accuracy depended on patient and family history during healthcare visits, and

majority of studies were completed at one center and only four studies included samples

from national trials. Overall, the study provided an estimate of the frequency and types

of the signs and symptoms seen in children with brain tumors.

25

The importance of knowing the most common signs and symptoms that children

may present with to healthcare providers has been recognized by ongoing research.

Without this knowledge of the clinical presentation of childhood brain tumors, healthcare

providers may lack pertinent knowledge and childhood brain tumors will continue to be

misdiagnosed or have prolonged symptom intervals.

Common Misdiagnoses

There was only one study that mentioned common misdiagnoses since

misdiagnoses was not the primary or secondary research question for most studies

included in this review of literature (Dörner et al., 2007). Dörner et al. (2007) noted that

some of the patients were misdiagnosed with common differential diagnoses such as

gastrointestinal infection, appendicitis, psychological behavior problems, cervical spine

strains, or ophthalmologic entities. Though other studies did not mention the common

differential diagnoses that healthcare providers considered, some studies did include the

types of specialists seen before a diagnosis of brain tumor was reached, which will be

mentioned below in this review (Dörner et al., 2007; Edgeworth et al., 1996; Mehta et al.,

2002; Thulesius et al., 2000; Wile et al., 2012).

Tumor Histology and Tumor Location Association with Diagnostic Delay and Signs

and Symptoms

Generally, the type and location of tumor correlates with how early or late a brain

tumor is diagnosed and with the child’s clinical manifestations (Pollack, 1999).

Supratentorial tumors and infratentorial tumors will present differently in children with

brain tumors. Similarly, benign tumors and malignant aggressive tumors will also

26

present differently in children (Pollack, 1999). The diagnosis of a child with a brain

tumor is complicated due to the child’s age and developmental level, especially a younger

child because he/she is unable to express their symptoms verbally; the variety of clinical

presentations depending on histology and location of the tumor, which may potentially

represent other diagnoses; and parental and healthcare provider knowledge of the child’s

medical history, history of present illness, and common signs and symptoms of pediatric

brain tumors (Kukal et al., 2009; Pollack, 1999; Wilne et al., 2010). A specific guideline,

such as the The Brain Pathways Guideline: A Guideline To Assist Healthcare

Professionals In The Assessment Of Children Who May Have A Brain Tumour (The

Brain Pathways Guideline) should provide the healthcare provider with specific steps and

guidance to facilitate the diagnosis of a child with a brain tumor (Walker et al., 2008;

Wilne et al., 2010).

Hyashi et al. (2010) examined medical records of children with brain tumors

retrospectively. The researchers found that vomiting and headache were associated with

every tumor location and that increased ICP clinical manifestations were seen in posterior

fossa tumors (88.2%), supratentorial tumors (69.2%), central tumors (58.8%), uncertain

tumors (50%), and brainstem tumors (18.2%). The aforementioned signs and symptoms

progression are associated with brain tumor location; however, the researchers did not

specify which type of tumor has a more rapid progression of headache and vomiting. The

authors did not examine the tumor histology in correlation to diagnostic delay or signs

and symptoms.

27

Kukal, Dobrovoljac, Boltshauser, Ammann & Grotzer (2009) examined medical

charts retrospectively of pediatric brain tumor patients in Switzerland. Tumor histology

correlated with the PSI meaning that aggressive and fast-growing tumors had shorter PSI

than slow-growing tumors (Kruskal-Wallis statistic=36.09, p

28

and signs and symptoms. High-grade tumors were significantly associated with a shorter

symptom interval. A shorter than median symptom interval was associated with the

initial presentation of nausea and/or vomiting (odds ration [OR]=1.8, p=0.003), abnormal

gait (OR=2.3, p=0.001), coordination difficulties (OR=2.7, p=0.006); focal motor

weakness (OR=2.8, p=0.002), and facial weakness (OR=3.1, p=0.03). A longer than

median symptom interval was associated with initial presentation of head tilt (OR=0.4,

p=0.006) and cranial nerve palsies (OR=0.6, p=0.025).

In conclusion, tumor histology and location plays a role in how early or late

childhood brain tumors are diagnosed and also contributes to the clinical presentation of

the child (Hyashi et al., 2010; Kukal et al., 2009; Reulecke et al., 2008; Wilne et al.,

2012). High-grade tumors are diagnosed sooner than low-grade tumors and aggressive

and malignant tumors are diagnosed earlier than benign tumors due to the tumor

histology and clinical presentation of the child (Kukal et al., 2009; Pollack, 1999; Wilne

et al., 2012). The knowledge and understanding of these important concepts will be of

utmost importance in assisting healthcare providers to recognize the signs and symptoms

of a child suspected of a brain tumor earlier. The use of The Brain Pathways Guideline:

A Guideline To Assist Healthcare Professionals In The Assessment Of Children Who May

Have A Brain Tumour (The Brain Pathways Guideline) can support the healthcare

provider with an easy to access and use tool to assist in the differential diagnosis of

pediatric brain tumors (Walker et al., 2008; Wilne et al., 2010).

29

Diagnostic Delays and Pre-Diagnostic Symptom Interval (PSI)

In an attempt to concentrate efforts in detecting pediatric brain tumors earlier,

researchers have conducted studies to identify where the delays are occurring (i.e. parent

versus doctor), how long the delays are, and compare or correlate the PSI with patient

characteristics (Dobrovoljac et al., 2002; Edgeworth et al., 1996; Flores et al., 1986;

Hyashi et al., 2010; Klitbo et al., 2011; Kukal et al., 2009; Mehta et al., 2002; Pollock et

al., 1991; Thulesius et al., 2000; Wilne et al., 2012; Wilne et al., 2006). Each of these

will be addressed in the following sections.

Pre-Diagnostic Symptom Interval (PSI)

Pre-diagnostic symptom interval refers to the time from initial onset of signs and

symptoms to official diagnosis of a brain tumor by neuroimaging or biopsy (Dobrovoljac

et al., 2002; Edgeworth et al., 1996; Flores et al., 1986; Hyashi et al., 2010; Klitbo et al.,

2011; Kukal et al., 2009; Mehta et al., 2002; Pollock et al., 1991; Thulesius et al., 2000;

Wilne et al., 2012; Wilne et al., 2006). The PSI has been one of the main outcome

measures for majority of studies in this literature review

Dobrovoljac et al. (2002) found that the median PSI of all patients was 60 days

and only 32% of the patients were diagnosed within 30 days after initial presentation of

signs and symptoms. Age was significantly correlated with the PSI (Pearson’s

correlation r=0.32, p

30

technologies. Edgeworth et al. (1996) found a mean PSI of 20 weeks (SD=29.1,

range=

31

(1996) reported mean parental delay of 3 weeks (SD=13.4, range=0-104 weeks). Klitbo

et al. (2011) described a median parental delay of 7 days (range=0-365 days). Kukal et

al. (2009) reported a median parental delay of 14 days (range=0-1,835 days) with

significantly shorter parental delays in younger children (Jonckheere-Terpstra [JT]

statistic=2.23, p=0.025).

Doctor’s Delay

Doctor’s delay refers to the interval from the first consultation to the diagnosis by

neuroimaging technology (CT or MRI). Dobrovoljac et al. (2002) found that the median

doctor’s delay was 30 days and doctor’s delay did not significantly correlate with the

child’s age. Edgeworth et al. (1996) reported mean doctor’s delay of 16 weeks

(SD=24.4, range=0-103 weeks). Klitbo et al. (2011) found a median doctor’s delay of 15

days (range=0-730 days). Kukal et al. (2009) reported a median doctor’s delay of 14

days (range=0-3,480 days) that was not significantly associated with the age of the child

at diagnosis (Jonckheere-Terpstra [JT] statistic=1.5, p=0.13).

Summary of Diagnostic Delays and Pre-Diagnostic Symptom Interval (PSI)

Although availability of neuroimaging technology has increased, the PSI remains

relatively similar to older studies and continues to be unacceptably long. Although the

literature suggests a decreased PSI may lead to detection of smaller brain tumors that are

easier to resect thus resulting in better patient outcome, more research is needed on this

particular matter (Dobrovoljac et al., 2002; Klitbo et al., 2011; Mehta et al., 2002;

Reulecke et al., 2008). From the research studies that did report parental delay and

doctor’s delay, there is an assumption that diagnostic delay can occur at every stage

32

(Dobrovoljac et al., 2002; Edgeworth et al., 1996; Klitbo et al., 2011; Kukal et al., 2009).

Hence, adequate education is not only important for healthcare providers, but also parents

or other family members involved in the child’s care. In other subspecialties, screening

tests are done to allow for earlier detection of illnesses (Mehta et al., 2002), such as

phenylketonuria (PKU), cystic fibrosis (CF), congenital heart defects, and many more

(Centers for Disease Control and Prevention, 2014); the pertinent question for children

suspected of brain tumors is: does this population possibly require screening tests or

tools. From the data presented about the PSI, it appears that screening tests, tools, or

guidelines should be implemented.

33

TABLE 1. Summary of Pre-Diagnostic Symptom Interval (PSI), Parental Delay, and

Doctor’s Delay From Multiple Research Studies

Research Study (Author, Year)

PSI Parental Delay Doctor’s Delay

Dobrovoljac et al. (2002)

Median = 60 days Median = 14 days Median = 30 days

Edgeworth et al. (1996)

Mean = 20 weeks (140 days)

Range =

34

Note: Presence of dashes (–) means that these values were not reported in the study. Text

in parentheses means that the values were converted to days for comparison between all

studies (1 month = 30 days; 1 week = 7 days).

Primary Care Providers Versus Specialist Doctors

Diagnostic delay and lengthy PSI has been established as problematic in pediatric

brain tumor patients from conducting retrospective studies (Dörner et al., 2007;

Edgeworth et al., 1996; Mehta et al., 2002; Wilne et al., 2012). Questions about whether

the diagnostic delay is occurring with primary care providers or specialty doctors and the

frequency of consultation before diagnosis have been mentioned. Some studies have

taken this into consideration when conducting the retrospective studies of children with

brain tumors; however, the studies included in this review of literature do not

differentiate the timing of diagnosis among the different physicians and whether seeing a

primary care provider versus a specialist resulted in earlier or later diagnosis (Dörner et

al., 2007; Edgeworth et al., 1996; Mehta et al., 2002; Wilne et al., 2012). The studies

included address the fact that children with brain tumors see primary care providers and

specialists as well as request consultations more frequently than children without brain

tumors (Dörner et al., 2007; Edgeworth et al., 1996; Mehta et al., 2002; Wilne et al.,

2012). In one study, patients were seen by two other physicians of different specialties

on average before admission into the hospital department (Dörner et al., 2007). These

specialties included pediatrics (hospital), pediatrics (praxis), ears, nose, throat (ENT),

general practitioner, ophthalmologist, neurologist, and orthopedics (Dörner et al., 2007).

In another study, researchers calculated the percentages of different consultations with

35

healthcare providers. Prior to diagnosis, general practitioners were consulted the most

(45.5%), followed by pediatrician (13%), opticians (9%), neurologists (2%), and

psychologists (1%) (Edgeworth et al., 1996). Prior to diagnosis, 63% of all visits were

with primary care providers and 37% were with specialists that included pediatricians,

gastroenterologists, orthopedic surgeons, neurologists, ophthalmologists, and

neurosurgeons (Mehta et al., 2002). Of the 182 children in the study conducted by Wilne

et al. (2012), 81 patients visited the general practitioner, followed by 79 with hospital

pediatrician, 24 with ophthalmologists, 15 with opticians, and 29 with emergency

department doctors. The range of primary care providers and specialists consulted by

pediatric patients with brain tumors highlights the need for all practitioners to have

knowledge of brain tumor presentations because these children did not only present to

primary care providers, but also many different specialist doctors. All of the studies

included in this review of literature did not differentiate between whether the general

practitioners or primary care providers were Doctor of Medicine (MD), Doctor of

Osteopathic Medicine (DO), or Nurse Practitioners (NP).

Number of Consultations or Visits to Healthcare Providers Prior to Diagnosis

Some researchers have noted that children diagnosed with brain tumors have

more visits to doctor’s offices than children without brain tumors (Ansel et al., 2010;

Edgeworth et al., 1996; Mehta et al., 2002; Wilne et al., 2012). Edgeworth et al. (1996)

reported a mean number of 4.6 visits with healthcare providers before diagnosis was

confirmed (45.5% with general practitioner and 9% with an accident and emergency

department). In one study, the number of visits to healthcare providers ranged from 0 to

36

more than 10 where 41% of patients received diagnosis within 3 visits (Mehta et al.,

2002). Wilne et al. (2012) analyzed the number of visits a step further and reported that

patients with longer than average symptom interval were significantly associated with

increased number of healthcare visits. In a retrospective study conducted in the United

Kingdom by Ansel et al. (2010), the number of general practitioner visits was compared

between case and control children. Each case (child diagnosed with brain tumor) was

matched with two controls by gender, month and year of birth, and region of residence.

Case children saw a general practitioner more than controls (31.5 times compared to 25.6

times; 1.22 times more often, 95% CI=1.09-1.36) (Ansel et al., 2010). If a healthcare

provider consistently sees the same child for similar signs and symptoms as previous

visits, then the assumption should be that more examination or diagnostic tests are needed

to evaluate the child appropriately (Ansel et al., 2010; Edgeworth et al., 1996; Mehta et

al., 2002; Wilne et al., 2012).

Diagnostic Delay of Pediatric Brain Tumors in Comparison to Other Childhood

Cancers

Two studies included in this review of literature investigated the PSI of children

with brain tumors compared to other childhood cancers such as leukemia, Hodgkin and

non-Hodgkin lymphoma, and bone tumor groups (Pollock et al., 1991; Thulesius et al.,

2000). According to Pollock et al. (1991), the median PSI for brain tumors was 31 days

compared neuroblastoma of 21 days, non-Hodgkin lymphoma of 26 days, Hodgkin

lymphoma of 49 days, osteosarcoma of 56 days, and Ewing sarcoma of 72 days. Overall,

the longest PSI was seen in Hodgkin lymphoma and bone tumor groups with Ewing

37

sarcoma at the top of the list. In another study conducted by Thulesius et al. (2000), a

comparison of diagnostic delay between children diagnosed with leukemia and brain

tumors was conducted. The median PSI for children diagnosed with leukemia was 3

weeks (range 0-15 weeks) and 9 weeks (range 1-199 weeks) for children with brain

tumors. The parental delay (χ2=9.59, p=0.002) and doctor’s delay (χ2=5.50, p=0.019)

was significantly shorter for leukemia patients compared to brain tumor patients. The

overall PSI was significantly less for leukemia patients compared to brain tumor patients

(χ2=9.52 p=0.002). The two studies present conflicting views about the diagnostic delay

of brain tumors in comparison to other childhood cancers. A conclusion that most

childhood cancers are diagnosed late can be made, but the two studies are not strong

enough to indicate that brain tumors are diagnosed significantly later than other

childhood cancers.

Cost-Effectiveness of Computed Tomography (CT) and Magnetic Resonance

Imaging (MRI) to Diagnose Pediatric Brain Tumors

Children suspected of having a brain tumor are typically referred to places to

obtain imaging of the brain. Because signs and symptoms of pediatric brain tumors are

non-specific, healthcare providers may feel hesitant between ordering neuroimaging

studies with risks of sedation, use of contrast, and false-positive rates and detection of

brain tumor (Medina, Kuntz, & Pomeroy, 2001). Medina et al. (2001) conducted a cost-

effectiveness analysis and quality adjusted life years (QALY) study of three diagnostic

strategies for children with headaches (MRI, CT followed by MRI with positive results

[CT-MRI], and no neuroimaging with close monitoring and follow-up). The sample of

38

children with headaches were divided into three groups: low-risk (non-migraine

headaches for >6 months and normal neurologic exam), intermediate-risk (migraine

headache and normal neurologic exam), and high-risk (headaches for $1 million (US dollars) per QALY

saved compared with no imaging. For the high-risk group with a baseline prevalence of

4%, MRI was the most effective diagnostic strategy because it was less costly than CT-

MRI strategy due to the CT false-positive rate leading to unnecessary workup with MRI.

MRI compared with CT-MRI and no imaging maximized QALY gained meaning that it

was less expensive per QALY when the probability of having a brain tumor increased.

Overall, the MRI strategy in high-risk children with headache maximizes QALY

expectancy at a reasonable cost-effectiveness ratio. MRIs tend to be more expensive than

CTs, but as the cost difference lessened, MRIs became more cost-effective than CTs

because MRIs are more effective at diagnosing brain tumors. The researchers further

suggest a decision tree for use in children with headaches (See Figure 2). This decision

39

tree may be applied to children with other signs and symptoms in addition to headache or

without headache that indicate a space-occupying lesion such as a brain tumor.

FIGURE 2. Decision Tree for Children With Headache (from Medina et al., 2001)

Does Prolonged Pre-Diagnostic Symptom Interval (PSI) Decrease Survival?

Healthcare providers and researchers have the assumption that diagnosing

pediatric brain tumors earlier will increase survival and decrease neurological deficits

(Dobrovoljac et al., 2002; Dörner, et al., 2007; Edgeworth et al., 1996; Flores et al., 1986;

Klitbo et al., 2011; Pollock et al., 1991; Reulecke et al., 2008; Thulesius et al., 2000;

Wilne et al., 2012; Wilne et al., 2007; Wilne et al., 2010). Parents also often question

whether an earlier diagnosis could have been accomplished and whether the diagnostic

delay affects the child’s prognosis adversely (Dixon-Woods et al., 2001; Kukal et al.,

2009). Unfortunately, there is only one current study that has considered whether or not

dictors of a surgical brain tumor such as an abnormalneurologic examination.7,15 Changes in our approachto health care emphasize the need to consider long-term outcomes and costs in evaluating medical diag-nostic strategies. Accordingly, we performed a deci-sion analytic Markov model and CEA of 3 riskgroups incorporating the quality-of-life adjustmentsand costs associated with early versus late braintumor diagnosis and treatment.

The low-risk group with baseline pretest probabil-ity of 0.01% (1/10 000) consisted of patients with thesole finding of chronic headaches of !6 months’duration.25,26 The most effective strategy was no im-aging with close clinical follow-up. Furthermore, thisstrategy was cost-saving when compared with theCT-MRI and MRI strategies because of its greatereffectiveness at a lower cost. Therefore, the risks offalse-positive neuroimaging results, contrast use,and sedation outweigh the benefit of early diagnosisof a rare brain tumor in this risk group (Table 4).

The intermediate-risk group with baseline pretestprobability of 0.4% (4/1000) consisted of childrenwith migraine headaches and a normal neurologicexamination.14,25 CT-MRI was a slightly more effec-tive diagnostic strategy than MRI alone. However,the cost-effectiveness ratio of the CT-MRI strategywas !$1 million per QALY saved.

The high-risk group with baseline prevalence (pri-or probability) of 4% consisted of children with head-ache of "6 months’ duration and at least 1 otherclinical predictor suggestive of a surgical brain tu-mor such as an abnormal neurologic examination.15MRI maximized QALY gained compared with CT-MRI or no imaging in this risk group. An increase inthe number of predictors has been highly correlatedwith an increased risk of brain tumor.15 Assessment

of this variable revealed a decrease in the cost-effec-tiveness ratio from $113 800 to $67 000 per QALYsaved when the prior probability was increased from4% to 8% (Table 4).

The cost-effectiveness ratios allow comparisonswith alternative health care programs and may assistin resource allocation decisions.23 The high-riskgroup cost-effectiveness ratios compared favorablywith other well-accepted diagnostic procedures. Forexample, annual mammography for women 55 to 64years old costs $110 000 per LY saved (updated to1993 US dollars),38 annual cervical cancer screeningfor women beginning age 20 costs $220 000 per LYsaved (updated to 1993 US dollars),38,39 and colonos-copy for colorectal cancer screening for people olderthan 40 years costs $90 000 per LY saved (updated to1993 US dollars).38,40

In the high-risk group we found our analysis to besensitive to the percentage of favorable prognosistumors that progressed to unfavorable prognosis be-cause of delayed diagnosis and treatment, and in-creased risk of death from brain herniation. That is,the incremental cost-effectiveness ratio for MRI waslower for patients who had a greater probability ofprogression because of delayed tumor diagnosis andtreatment, and greater risk of dying from brain her-niation (Table 5).

We also found in our high-risk group that thediagnostic performance of the neuroimaging testsaffected our base case-results. MRI became a domi-nated strategy if its specificity was "97%. CT was nolonger dominated if its specificity was greater than97%. A decrease in the MRI test sensitivity revealedan increase in the cost-effectiveness ratio of the MRIstrategy (Table 5). Therefore, the exact diagnosticperformance (sensitivity and specificity) of MRI and

Fig 2. Suggested decision tree for usein children with headache. For patientsin the high- and intermediate-riskgroup, neuroimaging is suggested. Forpatients in the low-risk group or thosewith negative findings from imagingstudies, clinical follow-up with peri-odic reassessment is recommended.

ARTICLES 261 at Univ Of Arizona on August 20, 2013pediatrics.aappublications.orgDownloaded from

40

diagnostic delay results in decreased survival in this patient population (Kukal et al.,

2009). The researchers calculated 5-year and 10-year overall survival rates (OS) and 5-

year and 10-year progression free survival rates (PFS) for their sample size of 315

patients. The OS was defined as the survival probability with death as the only event and

the PFS was defined as “the probability of being alive and free of progression/relapse;

death and progression/relapse were considered as events” (p. 304). The 5-year OS was

73% (95% confidence interval [CI]=68%-79%) and 10-year OS was 71% (95% CI=66%-

77%). The 5-year PFS was 53% (95% CI=47%-59%) and 10-year PFS was 48% (95%

CI=42%-55%). The patients were categorized into groups according to PSI measured in

days (PSI >180 days group, PSI 60-179 days group, PSI 20-59 days group, and PSI 180 days had a higher survival probability, followed by

PSI

41

TABLE 2. Overall Survival Probabilities (OS) and Progression Free Survival

Probabilities (PFS) in Pediatric Brain Tumor Patients (Kukal et al., 2009)

PSI Groups 10-Year OS 10-year PFS All Tumors (n=315) χ2=16.4, p

42

care. Some parents experienced lengthy disputes with their primary healthcare providers

and secondary healthcare providers such as specialty doctors. Parents in the lengthy

dispute category described healthcare providers as incompetent due to their failure to

recognize the seriousness of the signs and symptoms. They also perceived the healthcare

system or medical response as inadequate because of the delay in appropriate

investigation of their child’s signs and symptoms. After finally obtaining a diagnosis, the

parents felt relieved because at least there was an identifiable cause for the unusual signs

and symptoms and it validated their initial concerns. Trustworthiness of this study may

be questioned due to a small sample size (20 families), inclusion of only one pediatric

oncology unit, and inadequate description of analysis procedures because it is unknown

whether researchers performed investigator triangulation or member checking.

The study conducted by Dixon-Woods et al. (2001) offers valuable insights into

where diagnostic delays may occur in the healthcare system. Parental concerns of their

child are valuable information for healthcare providers and shows that parents play an

important role in improving the PSI. Attention has been given to the roles of healthcare

providers in attempt to improve the PSI, but consideration should also be given to the

roles of parents, children, teachers, school nurses, and other people involved in the

child’s care. Attentiveness to the different roles each group plays may help decrease the

PSI, however, future research studies will need to examine these aspects.

Healthcare Provider Guideline to Assist in Diagnosis of Pediatric Brain Tumors

From the aforementioned research studies and issues addressed, there is an

identified need for a guideline to help healthcare providers assess and diagnose children

43

who may have a brain tumor. Appendix A Figure 1 illustrates The Brain Pathways

Guideline, an evidence-based guideline developed by The Children’s Brain Tumour

Research Centre at Nottingham University to assist practitioners in identifying, assessing,

and investigating children suspected of having a brain tumor (Walker et al., 2008; Wilne

et al., 2010). The guideline is developed from evidence in systematic reviews, meta-

analysis, and cohort studies. In order to translate the research evidence into a clinical

guideline, a multidisciplinary workshop and Delphi process that included healthcare

providers and parents with children diagnosed with brain tumors was assembled to

address key issues of signs and symptoms, specificity, assessment, referrals, and imaging.

The guideline addresses when healthcare providers should consider a brain tumor in a

child (i.e. when the child presents with headache, nausea and/or vomiting). It also

addresses each common sign and symptom separately that are grouped into categories

(headaches, nausea and vomiting, visual symptoms and signs, motor symptoms and signs,

growth and development, and behavior) and recommends referral and imaging pathways

depending on the healthcare provider’s assessment (i.e. imaging required if patient has

persistent vomiting upon awakening) (Walker et al., 2008; Wilne et al., 2010).

The aims of this guideline are for healthcare providers to be aware of pediatric

brain tumor signs and symptoms and offer an understandable guideline to assess and

investigate children suspected of having a brain tumor. Currently, there is no evidence on

whether or not the guideline is effective in decreasing the pre-diagnostic symptom

interval, but the researchers are planning and developing a dissemination program to

implement the guideline. The researchers plan to review the evidence, literature, audit,

44

and feedback from users 5 years after publications to evaluate and update the guideline

(Walker et al., 2008; Wilne et al., 2010). The aims of this DNP Project to assess

healthcare provider knowledge of pediatric brain tumors will help add evidence to the

researchers evaluation of the guideline.

The aim of any guideline is to assist healthcare providers and patients to make

appropriate health care decisions for a specific clinical situation. Guidelines may be

beneficial in the healthcare setting, but are only as good as the evidence that supports the

development of the guideline. Rigorous methodologies and strategies are needed when

developing a guideline that can be implemented successfully in the practice setting.

Guidelines may vary in its quality hence the requirement for an instrument to assess the

quality. The Appraisal of Guidelines for Research and Evaluation (AGREE) Instrument

has been developed to “assess the quality of guidelines; provide a methodological

strategy for the development of guidelines; and inform what information and how

information ought to be reported in guidelines” (Brouwers et al., 2010, p. 1). The

AGREE II Instrument is composed of six domains with 23 items and each item receives a

score from 1 (strongly disagree) to 7 (strongly agree). The six domains include: scope

and purpose (three items), stakeholder involvement (three items), rigor and development

(eight items), clarity of presentation (three items), applicability (four items), and editorial

independence (two items) (Brouwers et al., 2010). The AGREE II Instrument is used by

the primary investigator (AT) to evaluate the quality of the guideline developed by The

Children’s Brain Tumour Research Centre at Nottingham University. The scoring of the

guideline based on the AGREE II Instrument domains are as follows: domain 1 = 21/21

45

(domain score 100%); domain 2 = 17/21 (domain score 82.35%); domain 3 = 43/56

(domain score 72.92%); domain 4 = 19/21 (domain score 88.89%); domain 5 = 25/28

(domain score 87.5%); and domain 6 = 14/14 (domain score 100%). Overall, the quality

of the guideline is rated at a 6 out of 7 though it has a few weaknesses such as the lack of

expert review prior to its publication and minimal evidence from systematic reviews and

meta-analyses.

Synthesis of Literature

Literature shows that children are diagnosed late because healthcare providers

consistently do not recognize the clinical presentation of pediatric brain tumors (Dörner

et al., 2007; Hyashi et al., 2010; Klitbo et al., 2011; Mehta et al., 2002; Reulecke et al.,

2008; Wilne et al., 2012; Wilne et al., 2007; Wilne et al., 2006). There is agreement that

the initial signs and symptoms of children with brain tumors are non-specific and may

resemble other less serious illnesses leading to an exclusion of a brain tumor diagnosis on

the differential diagnosis list (Dörner et al., 2007; Hyashi et al., 2010; Klitbo et al., 2011;

Mehta et al., 2002; Reulecke et al., 2008; Wilne et al., 2012; Wilne et al., 2007; Wilne et

al., 2006). Numerous studies have sought to identify the common signs and symptoms

related to pediatric brain tumors in hopes of increasing awareness among healthcare

providers (Dörner et al., 2007; Hyashi et al., 2010; Klitbo et al., 2011; Mehta et al., 2002;

Reulecke et al., 2008; Wilne et al., 2012; Wilne et al., 2007; Wilne et al., 2006).

Consensus is that the signs and symptoms of brain tumors in children are related to tumor

location, tumor histology, and age of child, but the initial sign and symptom is not

46

specific to a brain tumor diagnosis and fails to alert the healthcare provider (Hyashi et al.,

2010; Kukal et al., 2009; Pollack, 1999; Reulecke et al., 2008; Wilne et al., 2012).

The pre-diagnostic symptom interval (PSI) has not improved dramatically with

the increase availability of neuroimaging technologies (Dobrovoljac et al., 2002;

Edgeworth et al., 1996; Medina et al., 2001). There continues to be concerning

diagnostic delay of childhood brain tumors leading to life-threatening emergencies and

devastating neurological deficits among survivors (Dobrovoljac et al., 2002; Edgeworth

et al., 1996; Flores et al., 1986; Hyashi et al., 2010; Klitbo et al., 2011; Kukal et al., 2009;

Mehta et al., 2002; Pollock et al., 1991; Thulseius et al., 2000; Wilne et al., 2012; Wilne

et al., 2006). Literature demonstrates that diagnostic delay is occurring at multiple levels

of care involving parents, primary care providers, and specialists (Dörner et al., 2007;

Mehta et al., 2002; Wilne et al., 2012). Children with brain tumors often see a doctor

more than children without brain tumors and still healthcare providers are missing these

subtle signs (Ansel et al., 2010; Edgeworth et al., 1996; Mehta et al., 2002; Wilne et al.,

2012). These factors impact the relationship between healthcare providers dramatically

because parents of children with brain tumors question whether or not an earlier

diagnosis was possible and if an earlier diagnosis would lead to better prognosis and less

complications or deficits (Dixon-Woods et al., 2001).

Important considerations of the review of relevant literature are that most studies

were conducted outside of the United States, mainly the United Kingdom. The majority

of studies used a retrospective design which itself has limitations due to recall bias when

parents are giving the child’s medical history or inaccurate documentation by healthcare

47

providers regarding dates of signs and symptoms and official diagnosis. Also,

generalizability of the studies included in this literature review is difficult due to sample

characteristics (children) and setting characteristics (mainly United Kingdom). Even

with these internal and external validity concerns, the literature review is representative

of the diagnostic delay concern in the population of children with brain tumors.

In conclusion, the literature review conducted identifies the need for a guideline

to support healthcare providers in recognizing the signs and symptoms of childhood brain

tumors and investigating further with appropriate referrals and neuroimaging in a timely

manner. A guideline has been developed by The Children’s Brain Tumour Research

Centre at Nottingham University (Walker et al., 2008; Wilne et al., 2010) called The

Brain Pathways Guideline and is identified as appropriate for this DNP Project’s aims to

assess healthcare provider knowledge of pediatric brain tumors with a long-term goal of

evaluating whether a guideline assisting healthcare providers will decrease the pediatric

brain tumor pre-diagnostic symptom interval.

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CHAPTER III: METHODOLOGY

Study Aims

This DNP Project aimed to assess healthcare provider knowledge of pediatric

brain tumor patients using The Brain Pathways Guideline: A Guideline To Assist

Healthcare Professionals In The Assessment Of Children Who May Have A Brain

Tumour (The Brain Pathways Guideline). While the long-term goal is to evaluate the

effectiveness of the guideline in decreasing the pre-diagnostic symptom interval among

children who may have a brain tumor, this DNP Project was the first step to achieving the

long-term goal by assessing healthcare provider knowledge of pediatric brain tumors.

Model to Implement Guideline: ACE Star Model of Knowledge Transformation

Healthcare continues to demand quality improvements that include evidence-

based practices to achieve effective and safe patient outcomes (Stevens, 2012b).

According to the Institute of Medicine (2001), there continues to be a gap in translational

research where the results of studies are not being clinically practiced in a timely manner.

Many studies present an estimate of 17 years for results from research studies to be

transitioned into clinical practice (Morris, Wooding, & Grant, 2011). In addition,

researchers have noticed that 30-40% of patients receive care that is not consistent with

the most recent scientific evidence (Eccles, Foy, Sales, Wensing, & Mittman 2012). The

need to implement evidence-based results into practice continues to be a general

consensus among healthcare providers and researchers (Stevens, 2012b). Evidence has

shown that using a conceptual model is one of the most effective ways in achieving

implementation of evidence-based practice (EBP) into clinical settings. However, there

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is uncertainty as to which model is the most effective (Stevens, 2012b). Each model has

its own strengths and weaknesses and the appropriateness of the model depends on the

innovation being considered (Bucknall & Rycroft-Malone, 2010).

This DNP Project used the Academic Center for Evidence-based Practice (ACE)

Star Model of Knowledge Transformation to guide the implementation of The Brain

Pathways Guideline by first assessing healthcare provider knowledge of pediatric brain

tumor patients. The ACE Star Model of Knowledge Transformation “emphasizes crucial

steps to convert one form of knowledge to the next and incorporates best research

evidence with clinical expertise and patient preferences” (Stevens, 2012b, p. 19). The

model uses a five-star point figure to illustrate the steps of knowledge transformation:

Point 1: Discovery Research; Point 2: Evidence Summary; Point 3: Translation to

Guidelines; Point 4: Practice Integration; Point 5: Process, Outcome Evaluation (See

Figure 3) (Stevens, 2012a; Stevens, 2012b).

FIGURE 3. ACE Star Model of Knowledge Transformation (from Stevens, 2012a)

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Star Point 1: Discovery Research

Discovery research involves generating new knowledge from traditional scientific

methodologies and inquiry. In this stage, knowledge is found by using quantitative and

qualitative methods. This point sets the stage for research studies that answers a variety

of research questions (Stevens, 2012a; Stevens, 2012b).

Star Point 2: Evidence Summary

Evidence summary involves synthesizing primary research studies from Star

Point 1 to meaningful statements or summaries such as systematic reviews. Summaries

may also generate new knowledge by combining results from multiple studies to identify

any gaps in knowledge, detect bias results, and recognize chance effects (Stevens,

2012a).

Star Point 3: Translation to Guidelines

Translation to guidelines aims at forming useful summaries, Clinical Practice

Guidelines (CPGs), for healthcare providers and patients to use in the appropriate

situations. CPGs are considered tools that guide organizations, healthcare providers, and

patients to make informed decisions that are contextualized to a specific patient

population and clinical setting (Stevens, 2012a).

Star Point 4: Practice Integration

Practice integration implicates that individual and organizational practices will be

changed through formal and informal techniques. In order for CPGs to accomplish its

purpose, CPGs must be implemented into practice to benefit patients. This stage requires

implementation of innovations that are discovered and developed from Star Points 1 to 3

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and may perhaps be viewed as the most familiar and important stage (Stevens, 2012a).

Within this stage, the complexity of behavior change is also considered because many

factors can influence the uptake of evidence-based practices and clinical practice

guidelines. Hence, prior to implementation, assessment of knowledge, barriers, supports,

and stakeholders are necessary to facilitate successful implementation of any CPG or

EBP (Graham & Tetroe, 2007).

Star Point 5: Process, Outcome Evaluation

Evaluation is the final stage in the model and may contribute to the cultivating

knowledge base. Evaluation occurs at multiple endpoints that may focus on

organizations, healthcare providers, and/or patients. The purpose of evaluation is to ask,

“what works and what does not work?” so that adjustments can be made to facilitate

successful implementation and sustain the innovation to benefit patients (Stevens, 2012a).

Applicability of ACE Star Model of Knowledge Transformation to The Brain

Pathways Guideline

Star Points 1-3: The Brain Pathways Guideline

The Children’s Brain Tumour Research Centre at Nottingham University

conducted primary studies, systematic reviews, and multidisciplinary workshops and

Delphi process that accomplished the first three points of the ACE model with the end

product called The Brain Pathways Guideline (Walker et al., 2008; Wilne et al., 2010).

Therefore, this DNP Project did not address the first three star points of the ACE model.

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Star Point 4 and 5

This DNP Project’s long-term goal is to implement The Brain Pathways

Guideline to evaluate its effectiveness in decreasing the pre-diagnostic symptom interval

among the pediatric brain tumor population. Prior to the achievement of this goal was to

assess healthcare provider knowledge of pediatric brain tumor patients, which was of

utmost importance as this may help guide future research studies pertaining to this topic

so that successful implementation of the guideline can be achieved to benefit patients. In

addition, the process of dissemination of The Brain Pathways Guideline was evaluated.

Methods

A one group pre-test and post-test quantitative approach was used to assess

healthcare provider knowledge of pediatric brain tumor patients. Pre-tests and post-tests

are commonly chosen for behavioral research because it allows researchers to measure

change that resulted from the intervention (Dimitrov & Rumrill, Jr., 2003; Polit & Beck,

2012). For this DNP Project, the intervention was The Brain Pathways Guideline

portrayed in a figure/chart (See Appendix A), a symptom card (See Appendix B), and a

quick reference guide that is a shortened version of the original guideline.

The pre-test and post-test (See Appendix C and D) was developed by the primary

investigator and reviewed by three experts in the area of pediatric brain tumor diagnosis

and pediatric neurology/neurosurgery (Table 3, 4, and 5). The pre-test and post-test

questions were identical; however, the post-test had additional questions to evaluate the

process. The pre-test and post-test had five questions that specifically pertained to The

Brain Pathways Guideline with three distractor questions. Types of questions consisted

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of demographics; the healthcare provider’s identification of correct signs, symptoms, and

diagnosis; knowledge and skills for additional focused assessment of child; and

healthcare provider’s plan for either follow-up or referral. The pre-test, post-test, and The

Brain Pathways Guideline were conducted via electronic mail (e-mail). Part one of the

implementation included an e-mail that was sent to the participants with only the pre-test.

Part two of the imple