Download Chimes study cmv faye kentucky

CHIMES STUDY: CONGENITAL
CYTOMEGALOVIRUS INFECTION AND
HEARING MULTICENTER SCREENING STUDY
Karen Fowler, DrPH
University of Alabama
in Birmingham
Faye P. McCollister, EdD
University of Alabama, Emeritus
Diane Sabo, PhD
University of Pittsburgh
Confusion Regarding Congenital
CMV Infection & Hearing Loss
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Studies/Reports of etiology of pediatric hearing loss
seldom include routine screening for congenital
CMV infection
Most congenital CMV infection is asymptomatic
(90%)
No profile for audiometric configuration is available
Hearing may be normal; loss may be unilateral or
bilateral; present at birth or delayed in onset; may
be fluctuating and/or may be progressive
Review of Congenital CMV Infection
•Common virus although not easily spread person to
person
•Diagnosis needs to be made in the first 3 weeks of life
•Clinical observation of infection in the newborn
period identifies < 5% of all infants with congenital
CMV infection
•Delayed onset sequelae may occur over a long period
with sensorineural hearing loss being the most
common
Review of Congenital CMV and Hearing
Loss Research
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1960s - CID/symptomatic CMV infection and hearing loss first
reported. Medearis, l964; McCracken, et al. 1969
1970s - inapparent / asymptomatic CMV infection and HL was
first reported. Reynolds, et al. 1974; Dahle, et al. 1974;
Hanshaw, et al. 1976; Stagno, et al. 1977
1970s & 1980s, progression and delayed onset HL first
described. Dahle, et al, 1979; Williamson et al. 1982
3.9% at birth will have hearing loss; 8.3% at 6 yrs
Symptomatic infection – 16.5% HL at birth; 36.4% at 6 yrs
Asymptomatic infection – 2.9% HL at birth; 11.3% at 6 yrs
NIH/NIDCD Contract
The Natural History of CMV-Related Hearing
Loss and the Feasibility of CMV Screening
as Adjunct to Hearing in the Newborn
CHIMES Study
NIDCD CMV Grant, UAB
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Multi-site investigation, 7 sites
100,000 newborns to be screened for congenital
CMV infection
Link newborn hearing results
Evaluate methods for CMV screening
 Saliva vs. dried blood spots (DBS)
Audiological follow up of CMV positive infants
for 4 years
Project Design
Screen at least 100,000 newborns for CMV
infection who currently undergo newborn hearing
screening
Audiological follow-up of all CMV positive infants
Compare the accuracy of two diagnostic methods
for CMV screening (traditional rapid saliva cell
culture vs. real time PCR on DBS)
Objectives
Define the long-term audiologic/otologic outcome
in children with congenital CMV infection
Determine the clinical validity and utility of CMV
screening:
in the detection of hearing impairment in the
newborn
in the prediction of hearing impairment with
onset during infancy or in the early years of life
Project Staff
 The
project is directed by Drs. Suresh
Bopanna & Karen Fowler
 Each site will have a person designated as a
co-principal investigator
 Site audiologists direct audiological
assessments
 Project consultants: Faye McCollister, Judy
Gravel, Karl White
Site Audiologists
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Julie Woodruff
Belinda Blackstone
William Mustain
Marci Schwab
Edie Cox
David Brown
Dan Choo
John Greinwald
Diane Sabo
Angela Shoup
Kris Owen
Birmingham, AL
Birmingham, AL
Jackson, MS
New Brunswick, NJ
Charlotte, NC
Cincinnati, OH
Cincinnati, OH
Cincinnati, OH
Pittsburgh, PA
Dallas, TX
Dallas, TX
Participating Hospitals
Birmingham, AL
University Hospital & Cooper Green Hospital
Jackson, MS
University of Mississippi Medical Center
New Brunswick, NJ
Saint Peters University Hospital
Charlotte, NC
Carolinas Medical Center
Cincinnati, OH
Good Samaritan Hospital
Pittsburgh, PA
Magee Women’s Hospital
Dallas, TX
Parkland Memorial Hospital
Selected Hospital Populations
38% Caucasian, Non Hispanic
34% Caucasian, Hispanic
24% African American
4% Asian
Challenges to the CHIMES Study (1)
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Establishing consistency in protocols across 7
sites, getting everyone on the same page
Challenges inherent in longitudinal investigation: 6
year period of study, equipment changes, staff
changes, protocol changes
Age of subjects, birth through age 4 years, more
difficult to evaluate audiologically
Multiple disabilities, including developmental,
vision, and motor for children with symptomatic
infection
Challenges to the CHIMES Study (2)
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Variability of hearing loss: progression, delay in
onset, and fluctuation
Subject ethnic background with language
differences, cultural differences, social differences
Otitis media resulting in conductive overlay for sn
hearing loss, delay in getting assessment data
Subject compliance with study protocol
Subject retention
Challenges to the CHIMES Study (3)
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Specified protocol modified to accommodate
clinical needs with rapidly progressive hearing
loss
Accuracy/consistency in data collection, recording,
transfer, and storage
Interpretation of data and clinical judgment
Ensuring client confidentiality
Addressing the Challenges
to the CHIMES Study
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Standardized collection of data: developed data forms using
barcoded labels with unique study identifier for all data sent
from 7 sites (scanned and processed)
Developed detailed Manual of Procedures (MOP) for study
policies and procedures
Developed audiology protocols establishing optimal and
minimal goals for audiology data at visits
Site Visits and Review of protocols
Detailed retention plan with computerized database at each
site and data forms (Visit Forms & Missed Visit Forms) to
collect information on amount of contact each site had with a
study participant during the intervals between visits
Addressing the Challenges to the CHIMES
Study
Subject Variables
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Additional Disabilities (symptomatic infection)
 Vision
 Can not see visual reinforcers
 Can not process visual instructions
 Need glasses for assessment, if prescribed
 Seizure disorder
 Flicker stimulation with lighted reinforcer
 Absence, petit mal, and grand mal seizures
Cultural Diversity
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Racial, cultural, socioeconomic differences exist
among individuals from same country
Interpreters may have difficulty explaining medical /
technical information
 May be difficult for family to understand
 will not qualify for public assistance medical and
technical services (hearing aids)
 finding financial assistance challenging, at best
Cultural Diversity
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Project informational materials will be provided
in English and Spanish for parents and at
understandable reading levels.
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Communication options chosen by families for
their child will be respected and supported.
CHIMES STUDY
Audiological Assessment
Protocol
Diane Sabo, PhD
University of Pittsburgh
Components of Study Audiological
Assessment
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ABR tone bursts, bone conduction,
Otoacoustic emissions, (DPs)
Immittance with high frequency probe for subjects
less than 7 months of age, only when conductive
involvement needs greater definition
Behavioral assessment
 VRA
 Play
Screening Data Obtained
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Physiologic data
 ABR
 Automated-ABR
 OAEs
 Automated OAEs
 Combinations of the tests
Objective Hearing Diagnostic Methods
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Auditory Brainstem Response (ABR)
 Tone Bursts –air and bone conduction
Auditory Steady State Response (ASSR) not required,
optional
Acoustic Immittance
Evoked Otoacoustic Emissions (EOAEs)
 Distortion Product OAEs (DPOAEs)
Entry or Baseline Data
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Physiologic tests
 ABR
 Tone bursts at .5, 1, 2 and 4k Hz
 Bone conduction if air conduction abnormal
(>25)
 DPOAEs
 2-8k Hz
 60/45
 Signal and noise levels recorded
Physiologic Assessment with
ABR and EOAEs
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Advantages
“Objective”
• Reliable
• Correlate well with hearing
• Age not a factor (but sometimes
an issue)
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Physiologic Assessment
with ABR and EOAEs
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Limitations
 Not completely “objective”
 Not tests of hearing
 Not always good at predicting threshold
 Not independent of infant’s behavior,
state, or other factors
Click Spectrum
Frequency
Frequency
Comparison of Frequency Range for ABR
Clicks and Tone Bursts
What We Know About ABR Clicks
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Click commonly used, but……can give misleading
information
Click has energy at all frequencies transduced by
earphone
 Within limits, regions of normal hearing will generate
ABR, even with regions of hearing loss
 ABR tests avoid problems associated with reverse
middle ear transmission, but potential still exists for
missing hearing loss with click-evoked ABR
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Progressive HL Secondary to SX CMV
in Six Month Period
ABR Assessment at Enrollment Visit
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Enrollment visit at 3-6 weeks of age
 Objective is to obtain valid/accurate estimates of ear
specific, frequency specific hearing thresholds for
each ear and to characterize the type of any permanent
loss present as baseline information
 Case history/parent observation report
 Otoscopic inspection
 DPOAE
 Medical referral if testing deferred because of
otologic problems
Physiologic Assessment with
ABR and EOAEs
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Advantages
“Objective”
• Reliable
• Correlate well with hearing
• Age not a factor (but sometimes
an issue)
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Optimal Goal for ABR Assessment at
Enrollment Visit (3-6 Weeks)
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ABR minimum response levels at .5, 1.0, 2.0, and 4.0
kHz for each ear
DPOAE information at five frequency bands centered
at 2,3,4,6, and 8
Bone conduction, tympanometry, and ipsilateral
reflexes may be required if loss suspected
Record on ABR data form CF107
Record on OAE data form
Record on immittance data form CF110
Minimal Goal for ABR Assessment at
Enrollment Visit at 3-6 Weeks of Age
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Due to the importance of obtaining baseline information that
is a clear and accurate reflection of infant’s hearing level a
minimum goal was set:
 Obtain MRL at 0.5, 2.0, and 4.0 kHz for each ear
 Bone conduction, tympanometry, and ipsilateral acoustic
reflexes may be necessary if loss is suspected
 If additional assessment apt necessary, use sequence
system of 1,2, and 3 on forms for enrollment visit
 Prolonged delays between assessments avoided if
possible
ABR Protocol
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Order for tone bursts: 2000, 4000, 500 and 1000
Use 2-0-2 for 500 Hz
Use 4-0-4 for
Rate 27-29
Filter setting of 30-3000
Two replications
<1000 sweeps for 2.0 and 4.0
No less than 2000 sweeps for 0.5 and 1.0 kHz
ABR Parameters
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15-20 msec window
At least two replications at no response level and
next level up, using a 10dB step above the last
response level; threshold determination is
midpoint between these two levels
Electrode configuration of high forehead to
earlobe, with low forehead as ground; assuming a
two channel recording
Insert earphones
Entry Data
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Acoustic Immittance Data
 Tympanometry
 High frequency tymps (1k) < 7 months
 Acoustic reflex thresholds
 IPSI reflexes @ 1k only, if necessary
Use Insert Earphones
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Separation of stimulus artifact from the onset of
the response makes wave I more visible
Prevent ear canal collapse
Increase interaural attenuation
Provide greater comfort for long periods of time
Can attenuate surrounding environmental noise
more efficiently
 Absolute latencies delayed by 0.9ms
 Affect amplitude of wave I, lower
CHIMES STUDY
Faye P. McCollister, EdD
University of Alabama, Emeritus
Behavioral Audiological
Assessment Protocols
Request Parental Help in Preparing for
Behavioral Diagnostic Assessment
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Try to have child rested and feed, comfortable and
attentive for test
Schedule appointment away from nap time
 Bring diapers for diaper change
 Bring bottle for comforting
 Bring pacifier, if used
 Bring familiar car seat for test
Manage Baby/Mom/Diagnostic
Environment
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Quietest environment possible, no talking, no noisy toys
Reduce undesirable visual, auditory, tactile distractions
calm, alert child preferred, but not after heavy feeding,
will fall asleep
Do not separate child from parent and create crying,
agitated child
Wait for child to calm prior to initiating test
Child/Parent Handling Issues
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Child State
 Activity level
 Comfort level
Infection control
 Clinic protocol
 Gloves, disposables, cross contamination
Parent inclusion
 Pre-test information sharing
 Time during testing
 Time spent informing about procedure
 Informing about the results
Visual Reinforcement Audiometry
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Developmentally appropriate technique that gives valid
estimate of hearing
Gives ear specific, frequency specific information
Reliable method for early years
Practical for repeat use
Schedule for Behavioral Audiological
Assessment
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Visual Reinforcement Audiometry
scheduled at 7,12, 18, and 24 month
follow-up visits
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Play Audiometry scheduled
at 24, 30, 36, 42, and 42 month follow-up
visit
VRA Assessment Information
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Beginning stimulus type
 warble tone, speech
Beginning transducer
 earphone, speaker
 # beginning conditioning trials
 # reconditioning trials
 # stimulus trials
 # control trials, if greater than 0, # correct
VRA Assessment Information
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Test time
Number of breaks taken
DPs completed, 2,3,4,6,and 8
Acoustic Immittance Measures Done?
 Acoustic reflex threshold
 tympanometry
Follow up/ reschedule, no, yes- mark reason
 Fussy scared, wax occluding canal, time, refused
earphones/inserts, habituated, test reliability poor, failed to
condition, mrl > 20, cnd if sn loss present, other- specify
Medical Follow-up Recommended- yes, no- mark reason
 Conductive component, tymps abnormal, ab gap, draining
ear, hearing aid clearance
Visual Reinforcement Audiometry
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Affix study id label, site initials, al, ms, nj, nc, oh, pa, tx
Record ideal visit month according to protocol
Record sequence number, 1 for first test in ideal month
sequence, sequence number of repeat assessments
required to obtain complete assessment data
Was VRA testing done
Date of assessment
Minimal threshold level for each frequency
 Lowest threshold level
 999 frequency not tested
 555 could not determine
 888 tested, but no response
VRA at Follow Up Visits at
8, 12, 18, and 24 Months of Age
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Optimal goal: obtain pure tone minimum response level of 15
dB HL at 0.5, 1.0, 2.0, and 4.0 kHz
If MRLs elevated above 20 dB HL, tymps and/or bc will be
needed to distinguish between sn, cond. Or mixed loss
Record VRA data on CF108
If immittance is administered, record data on CF110
Minimal goal: Obtain MRLs at 0.5, 2.0, and 4.0 kHz
If MRLs elevated above 20 dB HL, administer tymps and/or bc
If MRLs for Minimal goal can not be obtained, schedule up to 3
additional visits and report any valid data collected using
sequenced numbered data forms: visit 1, 2, or 3, for 8 month
data
Visual Reinforcement Audiometry
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Optional, 8000 hz and speech awareness
threshold, record if obtained
Bc not required, leave field blank
VRA Protocol (Widen)
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Pulsed, FM Tones, 1-2 sec. Duration, LV speech
at 35 dB unconditioned, 2 responses naturally go to test protocol
35 dB no response, go to 55 dB
If no response, go to conditioning at higher level
Training - pair the reinforcer with stimulus at 55 dB, 2 chances
then go to probe with reinforcement presented with correct head
turn response, do second correct probe trial, then TEST
If training does not work at 55 dB, go to 75 dB and repeat
process
Use down 20 dB, up 10 dB in TEST mode in first reversal, then
down 10 up 5 thereafter
Next frequency, begin at level of previous response
MRL – lowest level with 2 responses out of 3
Ensuring Stimulus Control For
Behavioral Responses
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Control trials - observation intervals in which no
stimulus was present, but examiner notes head
turn behavior and no reinforcement provided to
ensure head turn linked to stimulus presentation
(inserted at a rate of 25%) >30%, test validity ???
Probe trials - stimulus presentations at
suprathreshold levels used to confirm
conditioning at beginning and throughout
session
When Child Does Not Condition
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Change ear
Change stimulus type- another frequency or
speech
Mode of presentation change – sound field
Change reinforcer, strength of video reinforcer
not strong enough
Take a 10 minute break
Play Audiometry Data Form
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Complete at 24, 30, 36, 42, and 48 month follow up visits
Complete Header
 Affix study id label, complete site id with state initials
 Was testing done- yes, no give reason,
 Parental refusal, late for apt, missed slot, uncooperative,
would not participate
 Date of audiology evaluation – mm/dd/yy
 Minimal threshold level, enter lowest threshold for each
freq. for each ear.
 Could not test, enter 555
 Was not tested, enter 999
 Was tested, no response , enter 888
Play Audiometry Data Form (2)
Optional – if 12 kHz or speech recognition
threshold (SRT) were obtained, enter
otherwise, leave blank
Primary Language of household
Dps completed
Acoustic immittance measures completed
Follow up/reschedule, specify reason
Medical follow up recommended, specify reason
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Looks Good, But…….
Visual alerting by examiner can give normal
audiogram for child who is deaf
 Results may look confusing,
but be accurate, evaluate carefully
 Hearing is dynamic, does not
necessarily stay the same, be
alert to progression
 Use all sources of information
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Contact the CHIMES Study
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www.uab.edu/chimesstudy
Karen Fowler
[email protected]