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Evaluation of a laryngopharyngeal reflux

management protocol,,

Nikita Gupta, MD a , Ross W. Green, MD a , Uchechukwu C. Megwalu, MD, MPH a, b,

a
Department of Otolaryngology-Head and Neck Surgery, Icahn School of Medicine at Mount Sinai, New York, NY
b
Department of Otolaryngology, Queens Hospital Center, Jamaica, NY

ARTI CLE I NFO A BS TRACT

Article history: Purpose: To evaluate the effectiveness of a protocol for management of patients with
Received 10 December 2015 laryngopharyngeal reflux (LPR) in a multi-provider clinic.
Materials and Methods: This is a retrospective cohort study of 188 patients treated for LPR. A
standardized clinical protocol for diagnosis and management was instituted in 2012. Two
cohorts were established: those managed according to the protocol, and those who were
not. For patients managed with the LPR protocol, diagnosis was made using clinical
judgment, guided by the Reflux Symptom Index (RSI) and Reflux Finding Score (RFS).
Patients were treated with proton pump inhibitors (PPI) with the goal of weaning therapy
after symptom resolution. Response to therapy was rated using a global rating scale with
three response levels: no response, partial response, and complete response. The primary
outcome measure was complete response to therapy and the secondary outcome measures
were any response (complete or partial) and successful wean off PPI therapy.
Results: The patients treated with the LPR protocol had higher rates of complete response
(p < 0.001). There was no statistically significant difference in rates of any response
(complete or partial) between the two groups (p = 0.08). Patients treated using the LPR
protocol were more likely to be successfully weaned off PPI therapy (p = 0.006).
Conclusions: The use of an LPR protocol improved treatment effectiveness in our clinic,
highlighting the role of clinical protocols in reducing variability in care, thereby improving
patient outcomes.
2016 Elsevier Inc. All rights reserved.

1. Introduction hoarseness, throat clearing, cough, dysphagia, globus sensa-

tion, and postnasal drip. LPR has been implicated as a cause
Laryngopharyngeal reflux (LPR) is defined as the retrograde or contributing factor to diseases such as subglottic stenosis,
movement of gastric contents into the larynx, pharynx, and laryngeal granuloma, asthma, and sinusitis [15]. LPR symp-
upper aerodigestive tract. Common symptoms include tomatology differs from that of gastroesophageal reflux

Oral Presentation at the American Academy of Otolaryngology Head and Neck Surgery Foundation Annual Meeting, Dallas, Texas,
September 2015.

Financial support: None.

Conflict of interest/Financial disclosures: None.
Corresponding author at: Icahn School of Medicine at Mount Sinai, Queens Hospital Center, 82-68 164th Street, Jamaica, NY 11432. Tel.:
+ 1 718 883 4272; fax: +1 718 883 6100.
E-mail addresses: megwaluu@yahoo.com, uchechukwu.megwalu@mountsinai.org (U.C. Megwalu).

http://dx.doi.org/10.1016/j.amjoto.2016.01.008
0196-0709/ 2016 Elsevier Inc. All rights reserved.

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246 AM ER IC AN JOURNAL OF OT OLA RYNGOLOGYH E A D A N D NE CK M E D ICI N E AN D S U RGE RY 3 7 (2 0 1 6) 2 45 2 5 0
disease (GERD), as it often does not include the classic
symptoms of heartburn and regurgitation [6]. The most
frequently reported symptoms of LPR are nonspecific and
may be due to other factors such as allergy, smoking,
environmental irritants, infection, or vocal abuse, possibly
leading to overdiagnosis [7]. This dilemma has thus prompted
validated measures such as the reflux symptom index (RSI) [8]
and the reflux finding score (RFS) [9] for improved diagnostic
reliability. Ford proposed an approach to assessment and
management of LPR including diagnosis with RSI and RFS,
then empiric treatment, and further diagnostic studies for
poorly or nonresponsive patients [10]. However, in general
otolaryngology practice, the diagnosis relies on empiric
evaluation of symptomatology and physical examination.
LPR is often treated with empiric proton pump inhibitor
(PPI) therapy [11]. PPIs have become one of the most
commonly prescribed medications in the past two decades
[12]. However, recent studies have shown detrimental side
effects of PPI therapy such as fractures due to altered calcium
absorption and increased community-acquired pneumonia
[1315]. In addition, PPIs have been shown to be less effective
than expected in the treatment of LPR, possibly due to other
components in gastric aspirate, such as pepsin, which have
been implicated in the pathogenesis of LPR [15].
The Otolaryngology Clinic at our institution is staffed by
physician assistants and rotating residents, under the super-
vision of an attending otolaryngologist. The senior author
(UCM) noted significant variability among providers in the
frequency of diagnosis of LPR in patients with throat
complaints, and the management of patients diagnosed
with LPR. This prompted the creation of a standardized LPR
management protocol in our clinic in 2012. The purpose of
this study is to evaluate the impact of this protocol on
treatment outcomes. Our hypothesis was that use of the
protocol would improve selection of patients with LPR, who
would be more likely to improve with PPI therapy, and would
facilitate earlier weaning of patients off PPI therapy.
2. Materials and methods
This was a retrospective cohort study. Data were extracted
from patients charts. The study cohort included patients
from the Queens Hospital Center Otolaryngology Clinic, who
were treated for LPR between April 1, 2011 and April 30, 2014.
It is customary in our clinic to treat LPR with twice daily PPI
therapy. Patients were included if they were started on twice
daily PPI therapy, and had a diagnosis of laryngopharyngeal
reflux, probable laryngopharyngeal reflux, possible
laryngopharyngeal reflux, or esophageal reflux with docu-
mentation of upper aerodigestive tract symptoms in the
chart. Patients were excluded if they were younger than
18 years old, or if they had other obvious laryngopharyngeal
pathology that could confound the diagnosis and treatment
outcomes of LPR (e.g. vocal polyps, vocal nodules, laryngeal or
pharyngeal masses, etc). Data collection was performed by all
3 authors. Each chart was reviewed by at least 2 people.
Charts were reviewed by N.G. and U.C.M. if there were
inconsistencies, and agreement was reached by consensus.
Data were collected on demographic and clinical factors such
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as: age, sex, prior history of GERD, and prior PPI use. In our
facility, we are required to provide telephone interpretation to
patients who prefer a different language other than English.
We are also required to document this in the patients
medical record. Data on limited English proficiency was
obtained using documentation of use of telephone inter-
preters in the chart.
Response to therapy was rated using a global rating scale
with three response levels: no response, partial response, and
complete response. The response to therapy was coded as a
complete response if symptoms were noted as resolved or
significantly improved (or similar comments) in the pa-
tients chart. It was coded as partial response if symptoms
were noted as partially improved or slightly improved (or
similar comments) in the patients chart. Time to wean off PPI
was calculated based on the visit during which the patient
was told to discontinue PPI therapy, as long as there was no
subsequent return of LPR or GERD symptoms. For patients
who discontinued therapy on their own, this was based on
the visit during which the patient reported discontinuing PPI
therapy, as long as there was no return of symptoms.
The Otolaryngology Clinic at Queens Hospital Center is
staffed by physician assistants and rotating residents, under
the supervision of an attending otolaryngologist. In August
2012, a standardized clinical protocol was introduced for the
diagnosis and management of LPR in the otolaryngology
clinic in order to reduce management variability and improve
outcomes. This protocol included a modified version of the
algorithm introduced by Ford [10], and utilized the RSI and
RFS for the diagnosis of LPR. The algorithm is shown in Fig. 1.
The RSI is a nine-item symptom questionnaire for the
diagnosis of LPR, with scores for each item ranging from 0 to
5. A score greater than 13 is considered positive for LPR [8].
The RFS is a variably-weighted eight-item clinical severity
scale for judging laryngoscopic findings in patients with LPR.
A score greater than 7 is considered abnormal [9]. The RSI and
RFS were administered by the primary provider (attending
physician, resident, or physician assistant) caring for the
patient. The clinical protocol allowed healthcare providers to
diagnose LPR using clinical judgment, but guided by the RSI
and RFS. The provider was allowed to offer PPI therapy if they
felt, in their judgment, that the patients symptoms were a
due to LPR, even in the absence of positive RSI or RFS.
However, the provider was required to justify the diagnosis
and document the level of certainty of diagnosis using
predetermined diagnostic terms. Patients with positive RSI
and RFS were diagnosed with LPR. Patients who were positive
on only one of the two scales, but who had symptoms or
findings that were strongly suggestive of LPR were diagnosed
as probable LPR. Patients who had negative RSI and RFS, but
who had symptoms or findings that were strongly suggestive
of LPR were diagnosed as possible LPR. PPI therapy was
initiated only if the symptoms had been present for at least
4 weeks. Patients were treated with either esomeprazole or
omeprazole at a starting dose of 20 mg twice daily. Patients
were followed every three months, and the PPI was titrated as
soon as complete resolution of LPR symptoms (complete
response) was achieved. The titration involved reduction of
PPI dose every 3 months with eventual cessation, if the
patient remained asymptomatic.
 AM ER IC AN JOURNAL OF OT OLARYNGOLOGYH E A D A N D NE CK M E D IC IN E A ND S U RGE RY 3 7 (2 0 1 6) 2 452 5 0 247

Fig. 1 Laryngopharyngeal reflux management protocol.

Two patient cohorts were established: those who were
treated according to the LPR clinical protocol, and those who
were not. The protocol group included patients who were
treated after the establishment of the LPR protocol in our
clinic, while the non-protocol patients included patients who
were treated prior to that. There were no set diagnostic criteria for
the non-protocol patients; diagnosis was made based on clinical
symptoms and judgment of findings on fiberoptic laryngoscopy,
without the aid of symptom and finding scores. No set follow up
regimen was used for the non-protocol patients. All patients
received twice daily PPI therapy.
IBM SPSS version 20 was used for statistical analysis.
Survival analysis was performed using KaplanMeier analy-
sis. The primary outcome measure was complete response of
LPR symptoms. The secondary outcome measures were any
response to therapy (defined as either complete or partial
improvement in LPR symptoms), and successful wean off PPI
therapy. The primary independent variable was use of the LPR
clinical protocol. Cox proportional hazards regression model
was used for multivariable survival analysis. Age, gender,
limited English proficiency, history of GERD, and prior PPI use
were entered a priori into the model. This study was approved
by the Icahn School of Medicine at Mount Sinai Institutional
Review Board.
3. Results
3.1. Univariable analysis
Chart review identified a total of 188 patients meeting the
inclusion criteria. The patient characteristics are displayed in
Table 1. All patients had at least 1 follow up visit after
diagnosis. The timing of the first follow up visit was not
significantly different between the two groups (p = 0.89). The
mean number of months from diagnosis to first follow up visit
was 2.84 (95% CI 2.623.06, range 16, median 3) for the
protocol patients, and 2.82 (95% CI 2.55 to 3.09, range 1 to 11,
median 3) for the non-protocol patients. Sixty-seven percent
of the non-protocol patients had at least 6 months of follow
up, compared with 49% of the protocol patients (p = 0.02). The
results of the univariable analysis are shown in Table 2.
Patients who were treated using the LPR clinical protocol had
higher rates of complete response than patients who were

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Table 1 Patient characteristics. 3.2. Multivariable analysis

Variable Protocol Non-protocol p Value
patients patients The results of the multivariable analysis are shown in
Tables 3, 4, and 5. Patients who were treated using the LPR
N 73 115
clinical protocol had higher rates complete response (HR 2.36,
Mean Age (SD) 56.2 (13.4) 58.8 (12.1) 0.17
Male 18 (24.7%) 30 (26.1%) 0.83 p < 0.001) after adjusting for age, sex, low English proficiency,
Low English proficiency 4 (5.5%) 5 (4.3) 0.74 prior history of GERD, and prior PPI use. There was no
History of GERD 20 (27.4%) 42 (36.5%) 0.20 statistically significant difference in rates of any response
Prior PPI use 17 (23.3%) 30 (26.1%) 0.67 (either complete or partial) between the two cohorts (HR 1.36,
LPR: laryngopharyngeal reflux; GERD: gastroesophageal reflux
p = 0.08) after adjusting for age, sex, low English proficiency,
disease; PPI: proton pump inhibitor. prior history of GERD, and prior PPI use. Patients who were
treated using the LPR clinical protocol were more likely to be
successfully weaned off PPI therapy (HR 2.63, p = 0.006) after
adjusting for age, sex, low English proficiency, prior history of
treated without (p < 0.001). There was no statistically signif- GERD, and prior PPI use. Age, sex, low English proficiency, prior
icant difference in rates of any response (either complete or history of GERD, and prior PPI use had no impact on response to
partial) between the two groups (p = 0.09). Patients who were treatment, or successful wean off PPI in our cohorts.
treated using the LPR clinical protocol were more likely to be
successfully weaned off PPI therapy (p < 0.001). The 12-month 3.3. Adverse events
wean rate was 52% for patients treated with the LPR clinical
protocol vs. 23% for patients treated without. The mean time There were 7 reported adverse events: 3 in the protocol group
to wean was 15.5 months (95% CI 12.318.6) for patients and 4 in the non-protocol group. Four of these were consistent
treated with the LPR clinical protocol vs. 31.3 months (95% CI with known adverse effects of PPI therapy: the first patient
27.035.5) for patients treated without. The median time to had a mild allergic reaction, the second patient had abdom-
wean was 11 months (95% CI 6.515.5) for patients treated inal bloating, the third patient had headaches, and the fourth
with the LPR clinical protocol vs. 43 months (95% CI 43.043.0) patient was instructed to discontinue PPI therapy by her
for patients treated without. primary care physician due to osteoporosis. Other adverse

Table 2 Response to treatment (univariable analysis).

Complete response Any response (complete or partial)

Variable 3-month 6-month p Value 3-month 6-month p Value

Protocol patients 28% 54% <0.001 66% 86% 0.09

Non-protocol patients 13% 26% 50% 72%

Table 3 Factors predictive of complete response.

Variable Coefficient (SE) Wald 2 Hazard ratio 95% CI p Value

LPR protocol 0.86 (0.23) 14.18 2.36 1.513.68 <0.001

Age 0.01 (0.01) 0.65 1.01 0.991.02 0.42
Male 0.06 (0.12) 0.26 1.06 0.841.35 0.61
Low English proficiency 0.20 (0.30) 0.43 1.22 0.682.20 0.51
History of GERD 0.11 (0.15) 0.53 1.12 0.831.50 0.47
Prior PPI Use 0.07 (0.17) 0.18 1.08 0.771.50 0.67

LPR: laryngopharyngeal reflux; GERD: gastroesophageal reflux disease; PPI: proton pump inhibitor

Table 4 Factors predictive of any response (either partial or complete).

Variable Coefficient (SE) Wald 2 Hazard ratio 95% CI p Value

LPR protocol 0.30 (0.18) 3.02 1.36 0.961.91 0.08

Age 0.01 (0.01) 0.53 1.01 0.991.02 0.47
Male -0.02 (0.10) 0.06 0.98 0.811.18 0.81
Low English proficiency 0.36 (0.23) 2.77 1.47 0.932.31 0.10
History of GERD -0.10 (0.12) 0.68 0.90 0.711.15 0.41
Prior PPI use 0.17 (0.14) 1.41 1.18 0.901.56 0.24

LPR: laryngopharyngeal reflux; GERD: gastroesophageal reflux disease; PPI: proton pump inhibitor.

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 AM ER IC AN JOURNAL OF OT OLARYNGOLOGYH E A D A N D NE CK M E D IC IN E A ND S U RGE RY 3 7 (2 0 1 6) 2 452 5 0
Table 5 Factors predictive successful wean off PPI therapy.
Variable Coefficient (SE) Wald 2
LPR protocol 0.97 (0.35) 7.68
Age 0.01 (0.01) 0.28
Male -0.02 (0.18) 0.02
Low English proficiency -0.43 (0.29) 2.26
History of GERD 0.21 (0.28) 0.60
Prior PPI use -.07 (0.30) 0.06
LPR: laryngopharyngeal reflux; GERD: gastroesophageal reflux disease; PPI: proton pump inhibitor.
events which could not be linked directly to PPI use include:
one patient with transient elevation of liver enzymes of
unknown etiology, one case of infectious gastroenteritis, and
one case of xerostomia.
4. Discussion
This study was designed to evaluate the impact of a standard
management protocol on treatment outcomes in patients
with LPR in a multi-provider clinic. Patients who were treated
with the LPR clinical protocol had significantly higher rates of
complete response than patients who were treated without.
However, there was no statistically significant difference in
rates of any response (either complete or partial) between the
two groups. Patients treated with the protocol were more
likely to be successfully weaned off of PPI therapy. These
results remained consistent after adjusting for potential
confounders.
Our protocol incorporates the use of the RSI and RFS for
diagnosis, as well as standard treatment regimens. The LPR
protocol was designed to improve the diagnosis of LPR, and
prevent unnecessary treatment of patients, who did not have
LPR. We attribute some of the success of the protocol to
improved selection of patients, who are more likely to benefit
from PPI therapy. Habermann et al evaluated the effective-
ness of PPI therapy in patients with abnormal RSI and RFS.
They found that therapy was highly successful in their cohort.
Treatment success was measured by significant improve-
ment in RSI and RFS scores, physician and patient assess-
ments of treatment effect, and quality of life measures. Their
study defined RSI > 9 as abnormal, which is lower than the
published threshold for this measure (RSI >13) [16]. Watson et
al. investigated the agreement between diagnosis of LPR using
RSI, RFS, or clinical judgment without the use of symptom or
finding scores [17]. They found that diagnosis of LPR by RFS
did not agree with diagnosis by either RSI or clinical
judgment. However, diagnosis by clinical judgment agreed
with diagnosis by RSI. The authors suggested that RSI and RFS
are not reliable when used in isolation, but may be more
useful when used in combination.
Our results show higher rates of complete response in the
protocol patients. However, there was no statistically signif-
icant difference in rates of any response (i.e. composite of
partial and complete response) between groups. One possible
explanation for this is that our study was not adequately
powered to detect the small difference in overall response
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249
Hazard ratio 95% CI p Value
2.63 1.335.22 0.006
1.01 0.981.03 0.60
0.98 0.681.40 0.89
0.65 0.371.14 0.13
1.24 0.722.13 0.44
0.93 0.521.66 0.81
between groups. In addition, patients treated with the LPR
protocol may have been more likely to be escalated to a higher
PPI dosage if they had a partial response, leading to higher
likelihood of complete response.
Our study shows that patients treated with the LPR
protocol were more likely to be weaned off of PPI therapy.
This is an important finding since long-term PPI therapy
carries the risk of adverse events, including complications
associated with reduced calcium absorption such as hip
fractures. Long-term PPI therapy has also been shown to
increase the risk of community acquired pneumonia and
Clostridium difficile diarrhea [1315]. Few adverse events were
noted in our study. However, this is prone to ascertainment
error due to the retrospective nature of our study.
The use of clinical protocols and care pathways in health
care is gaining in popularity. Clinical protocols help standard-
ize the delivery of care, thereby reducing variability and
improving quality of care [18]. Care pathways have also been
shown to reduce cost and improve documentation [18,19].
Having a standardized management protocol was especially
useful in our clinic due to the presence of providers with
varying levels of training and experience. The use of
management protocols is particularly important in LPR due
to the high degree of uncertainty in diagnosis. LPR is most
often diagnosed based on symptoms and exam findings.
Unfortunately, most of the symptoms associated with LPR are
non-specific, potentially leading to overdiagnosis [7]. Even
24-hour pH probe testing, which is the gold standard test, has
low sensitivity [20]. One potential disadvantage of clinical
protocols is that they may impede the use of clinical
judgment if used improperly. Our protocol addresses this
issue, by allowing the healthcare provider to diagnose LPR
using clinical judgment, but guided by the RSI and RFS. In
addition, the treatment plan is not prescriptive, but allows for
deviation to meet the needs of individual patients.
The main strength of our study lies in the systematic
collection and analysis of data. We used Kaplan-Meier and
Cox regression survival analysis to compare outcomes,
instead of logistic regression. Using chi square and standard
logistic regression to estimate the probability of an event at a
specific time produces a biased estimate because patients
who are lost to follow-up prior to the time of interest are not
included in the calculation. Survival analysis was designed to
address this variability in length of follow-up between
subjects. It accounts for censored observations, thereby
reducing bias due to loss to follow up [21,22]. In addition, the
power of the analysis is increased since all patients are
included in the analysis regardless of length of follow up. Our
250 AM ER IC AN JOURNAL OF OT OLA RYNGOLOGYH E A D A N D NE CK M E D ICI N E AN D S U RGE RY 3 7 (2 0 1 6) 2 45 2 5 0
study is primarily limited by its retrospective nature. In
addition, 24-hour pH probe testing is not available at our
facility, which limits our ability to confirm the diagnosis of
LPR, especially in poor responders. However, this increases
the generalizability of our findings as many general otolaryn-
gologists do not have access to this technology.
5. Conclusions
Our study shows that the use of a standardized LPR management
protocol improved the rate of complete response to PPI therapy,
and facilitated earlier weaning of patients off PPI therapy in our
otolaryngology clinic. Further studies are needed to clearly define
the diagnostic criteria for LPR and to evaluate the efficacy and
effectiveness of the various proposed treatment regimens. This
will facilitate the development of evidence-based guidelines and
management protocols, and eventually, the development of a
laryngopharyngeal reflux clinical care pathway.
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