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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 as: age, sex, prior history of GERD, and prior PPI use. In our
symptoms of heartburn and regurgitation [6]. The most facility, we are required to provide telephone interpretation to
frequently reported symptoms of LPR are nonspecific and patients who prefer a different language other than English.
may be due to other factors such as allergy, smoking, We are also required to document this in the patients
environmental irritants, infection, or vocal abuse, possibly medical record. Data on limited English proficiency was
leading to overdiagnosis [7]. This dilemma has thus prompted obtained using documentation of use of telephone inter-
validated measures such as the reflux symptom index (RSI) [8] preters in the chart.
and the reflux finding score (RFS) [9] for improved diagnostic Response to therapy was rated using a global rating scale
reliability. Ford proposed an approach to assessment and with three response levels: no response, partial response, and
management of LPR including diagnosis with RSI and RFS, complete response. The response to therapy was coded as a
then empiric treatment, and further diagnostic studies for complete response if symptoms were noted as resolved or
poorly or nonresponsive patients [10]. However, in general significantly improved (or similar comments) in the pa-
otolaryngology practice, the diagnosis relies on empiric tients chart. It was coded as partial response if symptoms
evaluation of symptomatology and physical examination. were noted as partially improved or slightly improved (or
LPR is often treated with empiric proton pump inhibitor similar comments) in the patients chart. Time to wean off PPI
(PPI) therapy [11]. PPIs have become one of the most was calculated based on the visit during which the patient
commonly prescribed medications in the past two decades was told to discontinue PPI therapy, as long as there was no
[12]. However, recent studies have shown detrimental side subsequent return of LPR or GERD symptoms. For patients
effects of PPI therapy such as fractures due to altered calcium who discontinued therapy on their own, this was based on
absorption and increased community-acquired pneumonia the visit during which the patient reported discontinuing PPI
[1315]. In addition, PPIs have been shown to be less effective therapy, as long as there was no return of symptoms.
than expected in the treatment of LPR, possibly due to other The Otolaryngology Clinic at Queens Hospital Center is
components in gastric aspirate, such as pepsin, which have staffed by physician assistants and rotating residents, under
been implicated in the pathogenesis of LPR [15]. the supervision of an attending otolaryngologist. In August
The Otolaryngology Clinic at our institution is staffed by 2012, a standardized clinical protocol was introduced for the
physician assistants and rotating residents, under the super- diagnosis and management of LPR in the otolaryngology
vision of an attending otolaryngologist. The senior author clinic in order to reduce management variability and improve
(UCM) noted significant variability among providers in the outcomes. This protocol included a modified version of the
frequency of diagnosis of LPR in patients with throat algorithm introduced by Ford [10], and utilized the RSI and
complaints, and the management of patients diagnosed RFS for the diagnosis of LPR. The algorithm is shown in Fig. 1.
with LPR. This prompted the creation of a standardized LPR The RSI is a nine-item symptom questionnaire for the
management protocol in our clinic in 2012. The purpose of diagnosis of LPR, with scores for each item ranging from 0 to
this study is to evaluate the impact of this protocol on 5. A score greater than 13 is considered positive for LPR [8].
treatment outcomes. Our hypothesis was that use of the The RFS is a variably-weighted eight-item clinical severity
protocol would improve selection of patients with LPR, who scale for judging laryngoscopic findings in patients with LPR.
would be more likely to improve with PPI therapy, and would A score greater than 7 is considered abnormal [9]. The RSI and
facilitate earlier weaning of patients off PPI therapy. RFS were administered by the primary provider (attending
physician, resident, or physician assistant) caring for the
patient. The clinical protocol allowed healthcare providers to
2. Materials and methods diagnose LPR using clinical judgment, but guided by the RSI
and RFS. The provider was allowed to offer PPI therapy if they
This was a retrospective cohort study. Data were extracted felt, in their judgment, that the patients symptoms were a
from patients charts. The study cohort included patients due to LPR, even in the absence of positive RSI or RFS.
from the Queens Hospital Center Otolaryngology Clinic, who However, the provider was required to justify the diagnosis
were treated for LPR between April 1, 2011 and April 30, 2014. and document the level of certainty of diagnosis using
It is customary in our clinic to treat LPR with twice daily PPI predetermined diagnostic terms. Patients with positive RSI
therapy. Patients were included if they were started on twice and RFS were diagnosed with LPR. Patients who were positive
daily PPI therapy, and had a diagnosis of laryngopharyngeal on only one of the two scales, but who had symptoms or
reflux, probable laryngopharyngeal reflux, possible findings that were strongly suggestive of LPR were diagnosed
laryngopharyngeal reflux, or esophageal reflux with docu- as probable LPR. Patients who had negative RSI and RFS, but
mentation of upper aerodigestive tract symptoms in the who had symptoms or findings that were strongly suggestive
chart. Patients were excluded if they were younger than of LPR were diagnosed as possible LPR. PPI therapy was
18 years old, or if they had other obvious laryngopharyngeal initiated only if the symptoms had been present for at least
pathology that could confound the diagnosis and treatment 4 weeks. Patients were treated with either esomeprazole or
outcomes of LPR (e.g. vocal polyps, vocal nodules, laryngeal or omeprazole at a starting dose of 20 mg twice daily. Patients
pharyngeal masses, etc). Data collection was performed by all were followed every three months, and the PPI was titrated as
3 authors. Each chart was reviewed by at least 2 people. soon as complete resolution of LPR symptoms (complete
Charts were reviewed by N.G. and U.C.M. if there were response) was achieved. The titration involved reduction of
inconsistencies, and agreement was reached by consensus. PPI dose every 3 months with eventual cessation, if the
Data were collected on demographic and clinical factors such patient remained asymptomatic.

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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 0 247

Fig. 1 Laryngopharyngeal reflux management protocol.

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

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248 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

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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Table 5 Factors predictive successful wean off PPI therapy.


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

LPR protocol 0.97 (0.35) 7.68 2.63 1.335.22 0.006


Age 0.01 (0.01) 0.28 1.01 0.981.03 0.60
Male -0.02 (0.18) 0.02 0.98 0.681.40 0.89
Low English proficiency -0.43 (0.29) 2.26 0.65 0.371.14 0.13
History of GERD 0.21 (0.28) 0.60 1.24 0.722.13 0.44
Prior PPI use -.07 (0.30) 0.06 0.93 0.521.66 0.81

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

events which could not be linked directly to PPI use include: between groups. In addition, patients treated with the LPR
one patient with transient elevation of liver enzymes of protocol may have been more likely to be escalated to a higher
unknown etiology, one case of infectious gastroenteritis, and PPI dosage if they had a partial response, leading to higher
one case of xerostomia. 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
4. Discussion carries the risk of adverse events, including complications
associated with reduced calcium absorption such as hip
This study was designed to evaluate the impact of a standard fractures. Long-term PPI therapy has also been shown to
management protocol on treatment outcomes in patients increase the risk of community acquired pneumonia and
with LPR in a multi-provider clinic. Patients who were treated Clostridium difficile diarrhea [1315]. Few adverse events were
with the LPR clinical protocol had significantly higher rates of noted in our study. However, this is prone to ascertainment
complete response than patients who were treated without. error due to the retrospective nature of our study.
However, there was no statistically significant difference in The use of clinical protocols and care pathways in health
rates of any response (either complete or partial) between the care is gaining in popularity. Clinical protocols help standard-
two groups. Patients treated with the protocol were more ize the delivery of care, thereby reducing variability and
likely to be successfully weaned off of PPI therapy. These improving quality of care [18]. Care pathways have also been
results remained consistent after adjusting for potential shown to reduce cost and improve documentation [18,19].
confounders. Having a standardized management protocol was especially
Our protocol incorporates the use of the RSI and RFS for useful in our clinic due to the presence of providers with
diagnosis, as well as standard treatment regimens. The LPR varying levels of training and experience. The use of
protocol was designed to improve the diagnosis of LPR, and management protocols is particularly important in LPR due
prevent unnecessary treatment of patients, who did not have to the high degree of uncertainty in diagnosis. LPR is most
LPR. We attribute some of the success of the protocol to often diagnosed based on symptoms and exam findings.
improved selection of patients, who are more likely to benefit Unfortunately, most of the symptoms associated with LPR are
from PPI therapy. Habermann et al evaluated the effective- non-specific, potentially leading to overdiagnosis [7]. Even
ness of PPI therapy in patients with abnormal RSI and RFS. 24-hour pH probe testing, which is the gold standard test, has
They found that therapy was highly successful in their cohort. low sensitivity [20]. One potential disadvantage of clinical
Treatment success was measured by significant improve- protocols is that they may impede the use of clinical
ment in RSI and RFS scores, physician and patient assess- judgment if used improperly. Our protocol addresses this
ments of treatment effect, and quality of life measures. Their issue, by allowing the healthcare provider to diagnose LPR
study defined RSI > 9 as abnormal, which is lower than the using clinical judgment, but guided by the RSI and RFS. In
published threshold for this measure (RSI >13) [16]. Watson et addition, the treatment plan is not prescriptive, but allows for
al. investigated the agreement between diagnosis of LPR using deviation to meet the needs of individual patients.
RSI, RFS, or clinical judgment without the use of symptom or The main strength of our study lies in the systematic
finding scores [17]. They found that diagnosis of LPR by RFS collection and analysis of data. We used Kaplan-Meier and
did not agree with diagnosis by either RSI or clinical Cox regression survival analysis to compare outcomes,
judgment. However, diagnosis by clinical judgment agreed instead of logistic regression. Using chi square and standard
with diagnosis by RSI. The authors suggested that RSI and RFS logistic regression to estimate the probability of an event at a
are not reliable when used in isolation, but may be more specific time produces a biased estimate because patients
useful when used in combination. who are lost to follow-up prior to the time of interest are not
Our results show higher rates of complete response in the included in the calculation. Survival analysis was designed to
protocol patients. However, there was no statistically signif- address this variability in length of follow-up between
icant difference in rates of any response (i.e. composite of subjects. It accounts for censored observations, thereby
partial and complete response) between groups. One possible reducing bias due to loss to follow up [21,22]. In addition, the
explanation for this is that our study was not adequately power of the analysis is increased since all patients are
powered to detect the small difference in overall response included in the analysis regardless of length of follow up. Our

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study is primarily limited by its retrospective nature. In suspected gastroesophago-pharyngeal reflux. Laryngoscope
addition, 24-hour pH probe testing is not available at our 2001;111:173541.
[8] Belafsky PC, Postma GN, Koufman JA. Validity and reliability
facility, which limits our ability to confirm the diagnosis of
of the reflux symptom index (RSI). J Voice 2002;16:2747.
LPR, especially in poor responders. However, this increases
[9] Belafsky PC, Postma GN, Koufman JA. The validity and
the generalizability of our findings as many general otolaryn- reliability of the reflux finding score (RFS). Laryngoscope
gologists do not have access to this technology. 2001;111:13137.
[10] Ford CN. Evaluation and management of laryngopharyngeal
reflux. JAMA 2005;294:153440.
[11] Abou-Ismail A, Vaezi MF. Evaluation of patients with
5. Conclusions suspected laryngopharyngeal reflux: a practical approach.
Curr Gastroenterol Rep 2011;13:2138.
Our study shows that the use of a standardized LPR management [12] Altman KW, Stephens RM, Lyttle CS, et al. Changing impact
protocol improved the rate of complete response to PPI therapy, of gastroesophageal reflux in medical and otolaryngology
and facilitated earlier weaning of patients off PPI therapy in our practice. Laryngoscope 2005;115:114553.
otolaryngology clinic. Further studies are needed to clearly define [13] Yang YX, Lewis JD, Epstein S, et al. Long-term proton pump
inhibitor therapy and risk of hip fracture. JAMA 2006;296:
the diagnostic criteria for LPR and to evaluate the efficacy and
294753.
effectiveness of the various proposed treatment regimens. This
[14] Laheij RJ, Sturkenboom MC, Hassing RJ, et al. Risk of
will facilitate the development of evidence-based guidelines and community- acquired pneumonia and use of gastric acid-
management protocols, and eventually, the development of a suppressive drugs. JAMA 2004;292:195560.
laryngopharyngeal reflux clinical care pathway. [15] Altman KW, Radosevich JA. Unexpected consequences of
proton pump inhibitor use. Otolaryngol Head Neck Surg 2009;
141:5646.
[16] Habermann W, Schmid C, Neumann K, et al. Reflux symptom
REFERENCES index and reflux finding score in otolaryngologic practice. J
Voice 2012;26:e1237.
[17] Watson NA, Kwame I, Oakeshott P, et al. Comparing the
[1] Tauber S, Gross M, Issing WJ. Association of diagnosis of laryngopharyngeal reflux between the reflux
laryngopharyngeal symptoms with gastroesophageal re- flux symptom index, clinical consultation and reflux finding
disease. Laryngoscope 2002;112:87986. score in a group of patients presenting to an ENT clinic with
[2] Blumin JH, Johnston N. Evidence of extraesophageal reflux in an interest in voice disorders: a pilot study in thirty-five
idiopathic subglottic stenosis. Laryngoscope 2011;121: patients. Clin Otolaryngol 2013;38:32933.
126673. [18] Every NR, Hochman J, Becker R, et al. AHA Scientific
[3] Ylitalo R, Ramel S. Extraesophageal reflux in patients with Statement: Critical Pathways, A Review. Circulation 2000;101:
contact granuloma: a prospective controlled study. Ann Otol 4615.
Rhinol Laryngol 2002;111:4416. [19] Altman KW. Improving health outcomes and value with care
[4] Irwin RS, Curley FJ, French CL. Difficult-to-control asthma. pathways: the otolaryngologist's role. Otolaryngol Head Neck
Contributing factors and outcome of a systematic manage- Surg 2014;151:5279.
ment protocol. Chest 1993;103:16629. [20] Vaezi MF, Schroeder PL, Richter JE. Reproducibility of proxi-
[5] Tan BK, Chandra RK, Pollak J, et al. Incidence and associated mal probe pH parameters in 24-hour ambulatory esophageal
premorbid diagnoses of patients with chronic rhinosinusitis. pH monitoring. Am J Gastroenterol 1997;92:8259.
J Allergy Clin Immunol 2013;131:135060. [21] Rich JT, Neely JG, Paniello RC, et al. A practical guide to
[6] Koufman JA. The otolaryngologic manifestations of gastro- understanding Kaplan-Meier curves. Otolaryngol Head Neck
esophageal reflux disease. Laryngoscope 1991;101(Suppl 53): Surg 2010;143:3316.
178. [22] Stangerup SE, Drozdziewicz D, Tos M, et al. Recurrence of
[7] Ylitalo R, Lindestad PA, Ramel S. Symptoms, laryngeal attic cholesteatoma: different methods of estimating recur-
findings, and 24-hour pH monitoring in patients with rence rates. Otolaryngol Head Neck Surg 2000;123:2837.

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