Context Laryngopharyngeal reflux (LPR) is a major cause of laryngeal inflammation
and presents with a constellation of symptoms different from classic gastroesophageal
reflux disease.
Objective To provide a practical approach to evaluating and managing cases of
LPR.
Evidence Acquisition The PubMed database and the Ovid Database of Systematic Reviews were
systematically searched for laryngopharyngeal reflux, laryngopharyngeal reflux fundoplication, laryngopharyngeal reflux PPI treatment, and gastroesophageal
reflux AND laryngitis. Pertinent subject matter
journals and reference lists of key research articles were also hand-searched
for articles relevant to the analysis.
Evidence Synthesis Reflux of gastric contents is a major cause of laryngeal pathology.
The pathophysiology and symptom complex of LPR differs from gastroesophageal
reflux disease. Laryngeal pathology results from small amounts of refluxate—typically
occurring while upright during the daytime—causing damage to laryngeal
tissues and producing localized symptoms. Unlike classic gastroesophageal
reflux, LPR is not usually associated with esophagitis, heartburn, or complaints
of regurgitation. There is no pathognomonic symptom or finding, but characteristic
symptoms and laryngoscopic findings provide the basis for validated assessment
instruments (the Reflux Symptom Index and Reflux Finding Score) useful in
initial diagnosis. There are 3 approaches to confirming the diagnosis of LPR:
(1) response of symptoms to behavioral and empirical medical treatment, (2)
endoscopic observation of mucosal injury, and (3) demonstration of reflux
events by impedance and pH-monitoring studies and barium swallow esophagram.
While pH monitoring remains the standard for confirming the diagnosis of gastroesophageal
reflux, the addition of multichannel intraluminal impedance technology improves
diagnostic accuracy for describing LPR events. Ambulatory multichannel intraluminal
impedance assessment allows for identification of gaseous as well as liquid
refluxate and detection of nonacid reflux events that are likely significant
in confirming LPR. Although some patients respond to conservative behavioral
and medical management, as is the case with gastroesophageal reflux, most
require more aggressive and prolonged treatment to achieve regression of symptoms
and laryngeal tissue changes. Surgical intervention such as laparoscopic fundoplication
is useful in selected recalcitrant cases with laxity of the gastroesophageal
sphincter.
Conclusions Laryngopharyngeal reflux should be suspected when the history and laryngoscopy
findings are suggestive of the diagnosis. Failure to respond to a 3-month
trial of behavioral change and gastric acid suppression by adequate doses
of proton pump inhibitor medication dictates need for confirmatory studies.
Multichannel intraluminal impedance and pH-monitoring studies are most useful
in confirming LPR and assessing the magnitude of the problem.
Laryngopharyngeal reflux (LPR) is the result of retrograde flow of gastric
contents to the laryngopharynx, where it comes in contact with tissues of
the upper aerodigestive tract. It has been reported in up to 10% of patients
presenting to an otolaryngologist’s office,1 and
more than 50% of patients with hoarseness have been found to have reflux-related
disease.2 There is a danger in failing to recognize
LPR, while overdiagnosis of LPR can lead to unnecessary costs and missed diagnoses.
When a medical practitioner fails to recognize LPR, patients have prolonged
symptoms and delayed healing.3 Inflamed laryngeal
tissues are more easily damaged from intubation, have a greater risk of progressing
to formation of contact ulcers and granulomas, and often evolve to symptomatic
subglottic stenosis4 and lower airway disease.
In a recent report, LPR symptoms were found to be more prevalent in patients
with esophageal adenocarcinoma than were typical gastroesophageal reflux symptoms,
and they often represented the only sign of disease.5Quiz Ref IDHeightened awareness of LPR can lead to overdiagnosis of the condition
because the typical LPR symptoms (excessive throat clearing, cough, hoarseness,
and globus pharyngeus [a sensation of a lump in the throat]) are nonspecific6 and can also be caused by infections, vocal abuse,
allergy, smoking, inhaled environmental irritants, and alcohol abuse.7
The PubMed database was systematically searched using the natural language
phrases laryngopharyngeal reflux, laryngopharyngeal reflux fundoplication, and laryngopharyngeal
reflux PPI treatment. These phrases were used individually, with no
language or date restrictions. PubMed was then searched using the Medical
Subject Heading terms gastroesophageal reflux and laryngitis. These terms were combined using the AND operator
and were limited by language to English, by date range to 2001-2005, and by
publication type to randomized controlled trial OR clinical trial. The Ovid
version of the Cochrane Database of Systematic Reviews was also searched using
the key-word combination of laryngitis.mp and reflux.mp.
All retrieval sets generated by the PubMed and Ovid searches were reviewed
for relevant citations addressing core issues of diagnosis, assessment, and
management. The reference lists of all relevant citations were reviewed for
further material describing validation of diagnostic instruments and basic
science addressing pathogenesis and evolving technology. References in the
Cochrane Database of Systematic Reviews protocol for reviewing acid reflux
treatment of hoarseness were particularly useful.
Laryngopharyngeal reflux differs from gastroesophageal reflux disease
(GERD) in that it is often not associated with heartburn and regurgitation
symptoms.8 The larynx is vulnerable to gastric
reflux, so patients often present with laryngopharyngeal symptoms in the absence
of heartburn and regurgitation.8Quiz Ref IDThere are 4 physiological barriers protecting the upper aerodigestive tract
from reflux injury: the lower esophageal sphincter, esophageal motor function
with acid clearance, esophageal mucosal tissue resistance, and the upper esophageal
sphincter.1 The delicate ciliated respiratory
epithelium of the posterior larynx that normally functions to clear mucus
from the tracheobronchial tree is altered when these barriers fail, and the
resultant ciliary dysfunction causes mucus stasis.9 The
subsequent accumulation of mucus produces postnasal drip sensation and provokes
throat clearing. Direct refluxate irritation can cause coughing and choking
(laryngospasm) because sensitivity in laryngeal sensory endings is up-regulated
by local inflammation.9 This combination of
factors can lead to vocal fold edema, contact ulcers, and granulomas that
cause other LPR-associated symptoms: hoarseness, globus pharyngeus, and sore
throat.1
Recent investigations suggest that vulnerable laryngeal tissues are
protected from reflux damage by the pH-regulating effect of carbonic anhydrase
in the mucosa of the posterior larynx.10 Carbonic
anhydrase catalyzes hydration of carbon dioxide to produce bicarbonate; this
protects tissues from acid refluxate. In the esophagus, there is active production
of bicarbonate in the extracellular space that functions to neutralize refluxed
gastric acid. There is no active pumping of bicarbonate in laryngeal epithelium
and carbonic anhydrase isoenzyme III, expressed at high levels in normal laryngeal
epithelium,wass absent in 64% (47/75) of biopsy specimens from laryngeal tissues
of LPR patients.11
History. It is important for physicians to
appreciate the potential significance of hoarseness and the relative nonspecificity
of laryngitis. Laryngitis is a nonspecific designation of laryngeal inflammation.12 Often, it is mild and resolves spontaneously. When
persistent, laryngitis must be further defined based on probable etiologic
factors: viral or bacterial infection, allergy, vocal trauma, postnasal discharge,
or LPR (Table). Persistent or progressive
hoarseness lasting beyond 2 to 3 weeks requires examination of the laryngopharynx
to rule out cancer and other serious conditions. This is generally considered
good practice; however, laryngeal examination is particularly important in
suspected LPR because of the apparent known association of LPR and upper aerodigestive
tract cancer.5,13
Laryngopharyngeal reflux should be suspected when clinical history and
initial findings are suggestive. Failure to appreciate LPR as different from
GERD has been a major source of skepticism about the diagnosis in the past.
Koufman1 was the first to clearly distinguish
LPR from GERD, noting that in a combined reported series of 899 patients,
throat clearing was a complaint of 87% of LPR patients vs 3% of those with
GERD, while only 20% of LPR patients complained of heartburn vs 83% in the
GERD group. An international survey of American Bronchoesophagological Association
members revealed that the most common LPR symptoms were throat clearing (98%),
persistent cough (97%), globus pharyngeus (95%), and hoarseness (95%).14 Based on a careful study of pH probe–confirmed
LPR cases, Belafsky et al15 developed a useful
self-administered tool, the Reflux Symptom Index, that can help clinicians
assess the relative degree of LPR symptoms during initial evaluation and after
treatment. Patients are asked to use a 0- to 5-point scale to grade the following
symptoms: (1) hoarseness or voice problem, (2) throat clearing, (3) excess
throat mucus or postnasal drip, (4) difficulty swallowing, (5) coughing after
eating or lying down, (6) breathing difficulties or choking spells, (7) troublesome
or annoying cough, (8) sensation of something sticking or a lump in the throat,
and (9) heartburn, chest pain, indigestion, or stomach acid coming up. The
Reflux Symptom Index score in untreated LPR patients was significantly higher
than in controls (21.2 vs 11.6; P<.001). Since
the 95% upper confidence limit for controls was 13.6, a Reflux Symptom Index
score greater than 13 is considered abnormal. When hoarseness is a prominent
symptom, acoustic voice analysis measuring frequency, intensity, perturbation,
and signal-to-noise ratio provides an objective way to document symptom severity
and progress of the disease.2
Laryngoscopy. Nonspecific signs of laryngeal
irritation and inflammation are usually seen, but several findings are highly
suggestive of LPR. Although not pathognomonic, thickening, redness, and edema
concentrated in the posterior larynx—“posterior laryngitis”—is
a common finding.7 Based on a color analysis,
Hanson and Jiang9 quantified the degree of
erythema as a measure of posterior laryngitis. Other laryngoscopic findings
have a strong association with LPR. Contact granuloma was found to be associated
with pH monitoring–confirmed cases of LPR in 65% to 74% of patients.16,17Quiz Ref IDFrequently, the
medial edge of the vocal fold appears to have a linear indentation due to
diffuse infraglottic edema (Figure 1).
Although this gives the illusion of a pathological condition of the vocal
fold called sulcus vocalis, in which there is a medial edge concavity of the
vocal fold (sulcus) due to fibrosis and tissue loss, it lacks the fibrotic
changes of pathological sulcus vocalis.18 This
finding is termed pseudosulcus and has been reported in as much as 90% of
LPR cases.19 In a comparison of 30
LPR patients and 30 controls, those with pseudosulcus were 2.5 times more
likely to have pH testing–confirmed LPR (P<.001).20 Although the sensitivity and specificity of finding
pseudosulcus in LPR patients were only 70% and 77%, respectively, pseudosulcus
remains highly suggestive of LPR.
Since there is no pathognomonic LPR finding, Belafsky et al21 developed an 8-item clinical severity scale for judging
laryngoscopic findings, the Reflux Finding Score, which appears to be useful
for assessment and follow-up of LPR patients. They rated 8 LPR-associated
findings on a variably weighted scale from 0 to 4: subglottic edema, ventricular
obliteration, erythema/hyperemia, vocal fold edema, diffuse laryngeal edema,
posterior commissure hypertrophy, granuloma, and thick endolaryngeal edema.
The results could range from 0 (normal) to 26 (worst possible score). Based
on their analysis, one can be 95% certain that a patient with a Reflux Finding
Score of 7 or more will have LPR.
Confirming Reflux. There are 3 approaches to
confirming the diagnosis: response of symptoms to behavioral and empirical
medical treatment, endoscopic observation of mucosal injury, and demonstration
of reflux events by multichannel impedance and pH-monitoring studies. Additional
studies, including radiography, esophageal manometry, spectrophotometric measurement
of bile reflux, and mucosal biopsy, can provide information useful in targeting
therapy.
Because many patients respond well to behavioral modification and initial
medical management, an acid suppression trial is a frequently used approach
to initial diagnosis.22 The mainstay of empirical
treatment is proton pump inhibitor (PPI) medication for at least 3 months.
Endoscopic examination should include flexible or rigid laryngoscopy
in all suspected cases. Transnasal esophagoscopy and esophagogastroduodenoscopy
(EGD) are useful in detecting characteristic associated mucosal injury, esophagitis,
and Barrett esophagus. Overall, EGD and 24-hour pH-monitoring studies have
proven less useful in detecting LPR than in identifying GERD. While EGD reveals
esophageal lesions in 50% of typical GERD patients, it is abnormal in less
than 20% of LPR laryngitis patients.23
Demonstration of reflux events is best achieved with ambulatory multichannel
intraluminal impedance (MCII) and pH-monitoring studies.24 This
approach is based on changes in resistance to alternating current between
a series of metal electrodes produced by intraluminal gas, liquid, or bolus.
When combined with pH transducers, it makes it possible to give a more complete
description of reflux events.25 Not only can
acid and nonacid reflux events be detected but, also, liquid (decreased impedance)
as well as gaseous (increased impedance) events can be identified. Although
controversy exists, an LPR event is evident when pH in the proximal sensor
abruptly drops to less than 4 during or immediately after distal acid exposure
(exposure near the lower esophageal sphincter) and LPR is confirmed when total
acid exposure time (percentage of time during 24-hour monitoring when the
sensor detects pH levels <4) is more than 1%.24 Reflux
is often associated with esophageal dysmotility, including nonprogressive
(tertiary) contractions, increased amplitude and duration of contractions,
and increased tone.1 Multichannel intraluminal
impedance software technology combined with manometry allows for graphic displays
of simulated esophageal motility, sphincter competence, and bolus transport,
so the use of barium swallow studies is more limited in LPR assessment.
Patient Education and Behavioral Change.Quiz Ref IDPatients with LPR should be educated as to the nature of the problem
and counseled on helpful behavioral and dietary changes.26 Important
behavioral changes include weight loss, smoking cessation, and alcohol avoidance.
Ideal dietary changes would restrict chocolate, fats, citrus fruits, carbonated
beverages, spicy tomato-based products, red wines, caffeine, and late-night
meals. Such behavioral changes appear to be an independently significant variable
in determining response to medical therapy.27 Education
should include the optimal schedule for taking PPI medications (omeprazole,
esomeprazole, rabeprazole, lansoprazole, and pantoprazole), which work best
when taken 30 to 60 minutes before meals.
Medical Management. There are 4 categories
of drugs used in treating LPR: PPIs, H2-receptor antagonists, prokinetic
agents, and mucosal cytoprotectants. Proton pump inhibitors are considered
the mainstay of medical treatment,28 although
there is some controversy regarding their efficacy. A 3-month empirical trial
is a cost-effective approach to initial assessment and management.29,30 Responders can be weaned, while nonresponders
should undergo studies to confirm LPR.
Other drugs have been used to treat LPR. Ranitidine has proven a more
potent inhibitor of gastric secretion than cimetidine and is the H2-receptor
antagonist of choice,31 although it has been
found to be of limited value in treating LPR.32 Prokinetic
agents that accelerate esophageal clearance and increase lower esophageal
sphincter pressure have fallen out of favor because of reported adverse effects
of ventricular arrhythmias and diarrhea.33 Cisapride
has been discontinued because of such serious adverse effects. Tegaserod is
a prokinetic agent that was recently demonstrated to decrease reflux and lower
esophageal sphincter relaxation events34 and
that we have found useful in treating some LPR cases with associated esophageal
dyskinesia. Sucralfate is a polysulfated salt of sucrose that may be helpful
as an adjunct in protecting injured mucosa from harmful effects of pepsin
and acid.35,36 Antacids (sodium
bicarbonate–, aluminum-, and magnesium-containing over-the-counter antacids)
may relieve GERD symptoms but do not play a role in LPR management.26
Surgery. When medical management fails, patients
with demonstrable high-volume liquid reflux and lower sphincter incompetence
are often candidates for surgical intervention. Fundoplication, either complete
(Nissen or Rossetti) or partial (Toupet or Bore), is the most common procedure
performed, and the laparoscopic approach is preferred.2 The
goal of surgery is to restore competence of the lower esophageal sphincter,
and the outcome measures for LPR include demonstration of reduced pharyngeal
reflux episodes. Excellent results have been reported in 85% to 95% of reflux
cases37 but results with LPR are not as impressive.22 Focusing on a carefully screened group of patients
with demonstrable extraesophageal reflux (LPR), Oelschlager et al38 reported a significant decrease in pharyngeal reflux
(7.9 to 1.6 episodes per 24 hours; P<.05) and
esophageal acid exposure (7.5% to 2.1%; P<.05)
following basic laparoscopic Nissen fundoplication surgery. Fundoplication
appears superior to medical management in preventing Barrett metaplasia.39 Although there is interest in recent nonfundoplication
endoscopic techniques (Bard EndoCinch System for endoluminal plication, C.
R. Bard, Murray Hill, NJ; Stretta System for radiofrequency-induced thermal
injury, Curon Medical, Fremont, Calif; and Enteryx liquid polymer injection,
Boston Medical, Natick, Mass) to improve lower esophageal sphincteric function,
there are no controlled studies and there is no long-term follow-up evidence
to support their use.40
While there is an increased appreciation of LPR as distinct from GERD,
controversy remains regarding how to confirm the diagnosis and what comprises
appropriate medical management. In mild LPR cases, symptoms and physical findings
lack sufficient specificity; similar symptoms can result from smoking, toxic
inhalants, allergies, and postnasal discharge. Assessing treatment regimens
is complicated because clinical trials are vulnerable to placebo effect, uncontrolled
behavioral changes, and the variable natural history of LPR.23,41,42 Apparently,
25% of LPR patients experience spontaneous resolution of symptoms and 50%
have a chronic course of disease, with intermittent exacerbations and remissions.1
Laryngoscopic findings can be misleading, as shown in several studies
in which asymptomatic participants revealed findings similar to those seen
in LPR-proven patients. Lundy et al43 found
posterior erythema in 73% of asymptomatic singing students and Hicks et al41 found tissue changes associated with LPR in a group
of more than 100 asymptomatic volunteers. Lack of a reliable clinical marker
has confounded progress in the diagnosis and treatment of LPR.23 Some
trials based on clinical diagnosis have been misinterpreted because of lax
inclusion criteria. The symptoms and physical findings of mild LPR can be
confused with other laryngeal inflammations and nonpathological variations.
Since patients with advanced LPR and obvious posterior laryngitis probably
differ from patients with milder cases that might have alternative etiologies;
future efficacy studies should be rigorous in their exclusion criteria and/or
stratify patients in the treatment group.44 A
breakthrough in LPR diagnosis may evolve from recent immunohistochemical studies
of laryngeal biopsy specimens showing concentration of pepsin and depletion
of carbonic anhydrase isoenzyme III in documented LPR cases.45
Hydrogen ion concentration monitoring is considered the gold standard
in detecting GERD, but it is less reliable in confirming LPR.46 Variability
in testing methods and lack of agreement on normative values have raised questions
about the sensitivity of pH-monitoring studies for detecting LPR.44,47,48 In some studies,
the proximal probe was placed below the upper esophageal sphincter and in
others in the hypopharynx, where it is considered closer to the site of injury.49 High placement of the proximal probe is subject to
spurious drops in pH related to the wide-open pharynx and intermittent probe
drying. The recently developed Bravo wireless pH-monitoring system (Medtronic
Inc, Shoreview, Minn) allows for precise endoscopic placement of the pH transducer
at the upper esophageal sphincter. A pinch of esophageal mucosa is used to
secure the Bravo capsule, and the patient wears a pager-sized monitor during
48 hours of normal activity. The capsule passes in 3 to 5 days with the superficial
sloughing of mucosa. This has been proven more effective in children and some
adults who fail to tolerate an external catheter.50
Disagreement about normative values adds to the controversy. An abrupt
decrease in pH to less than 4 in the proximal probe following or synchronous
with a drop at the lower esophageal sphincter is considered a default cutoff
value,51 but this is largely based on lower
esophageal standards applied to GERD. In the hypopharynx, a drop to less than
5 is probably a more reliable indicator of proximal reflux because neutralizing
factors such as saliva and airway secretions can raise pH values.52 Failure to demonstrate clinical correlation in pH
studies can result from not recognizing the minimal amount of gastric refluxate
necessary to cause laryngeal inflammation (in patients with LPR) or from not
considering alternative sources of laryngeal inflammation in control groups.48
An important recent meta-analysis of 16 double pH-probe studies showed
consistency and accuracy in distinguishing healthy persons vs those with LPR
where techniques were tightly controlled.51 Upper
probe placement at 2 cm above the upper esophageal sphincter was considered
critical; higher placement reduces contact of the sensor with mucosa, drying,
and false-positive readings, whereas events at or below the sphincter fail
to correlate with LPR symptoms. This study affirmed that while healthy persons
experienced some reflux events, the acid exposure time percentage is very
reliable in differentiating persons with and without LPR. Using a mixed-effects
model, LPR was found to be a statistically significant risk factor for experiencing
objective reflux events (odds ratio, 9.19; 95% confidence interval, 5.4-15.4; P<.001).
Another problem with standard pH probe–monitoring studies is failure
to account for bouts of potentially harmful gaseous and/or nonacid refluxate.
This is where impedance testing is superior.24 Gaseous
reflux events associated with small pH drops (>1) have been found with significantly
greater frequency in patients with LPR than in those with GERD or in healthy
controls. The ability to detect gaseous and mixed (gaseous-liquid) events
is particularly important in patients with LPR because gases are more diffusible
and can reach higher laryngeal structures. Furthermore, impedance testing
detects potentially harmful nonacidic reflux. Pellegrini et al53 called
attention to alkaline gastroesophageal reflux long ago, and Galli et al54 demonstrated laryngopharyngeal damage in patients
whose gastrectomy procedures resulted in anatomically predictable bile reflux.
In a recent report, Sasaki et al55 demonstrated
marked inflammatory histological changes in rat laryngeal mucosa exposed to
bile salts in both acid and alkaline media; he suggested that biliary and
acid reflux may exert a synergistic role in damaging esophageal mucosa. This
finding might also explain some of the therapeutic failures of acid suppression
used as the sole treatment for LPR.
Efficacy of PPI Treatment
Quiz Ref IDUnlike with GERD, response to PPI therapy in patients
with LPR has been described as highly variable.22 This
is in part because LPR requires more aggressive and prolonged therapy than
GERD.56 Clinical trials have failed to quell
the controversy because studies have had different inclusion criteria, failed
to stratify populations based on LPR severity, lacked adequate controls, and,
often, used inappropriate dosage or duration of therapy.27,29,42,57,58 Confounding
factors can undermine conclusions; for example, in a class 1 randomized, placebo-controlled
trial designed to demonstrate the efficacy of PPI therapy for LPR, Steward
et al27 found that lifestyle modification for
2 months, with or without PPI therapy, significantly improved chronic laryngitis
symptoms. In a recent open-labeled, prospective cohort study, Park
et al56 shed some light on the controversy.
They concluded that twice-daily dosing of PPI resulted in significantly higher
symptom relief than daily dosing (P = .03)
and noted that nonresponders improved when twice-daily dosage was extended
from 2 to 4 months. Like Fackler et al,32 they
found that the addition of H2-antagonist therapy at bedtime was
of no added benefit. Further clarification is anticipated based on the Cochrane
Database of Systematic Reviews protocol that will focus on clinical trials
with attention to randomization, selection bias, blinding process, and outcome
assessment in reviewing acid reflux treatment of hoarseness.2
Recommendations and conclusions
The algorithm in Figure 2 summarizes
an approach to assessment and management of LPR-induced hoarseness. It begins
with clinical evaluation and progresses to an empirical trial of lifestyle
and dietary changes and initiation of PPI therapy. Although most patients
can experience symptomatic improvement in 3 months, it often takes at least
6 months for the laryngeal symptoms and related physical findings to resolve.9 Unlike GERD, treatment for LPR must be more aggressive
and prolonged in many cases to achieve resolution.8,56 Patients
whose LPR has resolved should have drugs titrated off, while others who show
signs of improvement should be treated with omeprazole, 40 mg (or an equivalent
PPI), twice daily 30 to 60 minutes before meals.
Cases that fail to substantially improve with aggressive medical management
over 3 months require definitive assessment. Ambulatory MCII with pH monitoring
is currently the most effective way to demonstrate LPR. Where such technology
is not available, multichannel pH monitoring remains a well-tested option.
Mucosal injury, hiatal hernia, and other esophageal pathology such as Barrett
esophagus should be documented by esophagoscopy (transnasal esophagoscopy
or EGD). Barium swallow esophagoscopy, manometry, and MCII with manometry
can be helpful in demonstrating pathology, describing dysmotility problems,
and guiding the surgeon in planning fundoplication surgery. Patients whose
LPR fails to resolve after definitive medical or surgical treatment must be
followed indefinitely with careful examination of the upper aerodigestive
tract for signs of complications and malignancy.5
Corresponding Author: Charles N. Ford, MD,
University of Wisconsin Clinical Science Center, 600 Highland Ave, K4/714,
Madison, WI 53792 (ford@surgery.wisc.edu).
Financial Disclosures: None reported.
Acknowledgment: I thank Eric A. Gaumnitz, MD,
Gastroenterology Section, University of Wisconsin, for his careful reading
of an early version of the manuscript and helpful suggestions.
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