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Gastroesophageal reflux in obstructive sleep apnea

Gastro-esophageal reflux in obstructive sleep apnea
*Amr Badr-El Din, **Gad El-Hak N, ***Younis A, ****Mostafa M, *Mohmad Abdel-Hady
Abstract
Introduction: Obstructive sleep apnea syndrome (OSAS)

index in OSAS patients with GERD were significant
and gastro-esophageal reflux disease (GERD) are common
higher than OSAS patients without GERD (p=0.023 and
chronic diseases and share several similar risk factors.
0.001 respectively) while the sleep efficiency was
Gastro esophageal reflux is very common with 7% of
significantly lower in OSAS patients with GERD than
adults experiencing symptoms daily and 20% experiencing
OSAS patients without GERD (p<0.001). The severity of
symptoms at least weekly. Currently, sleep related GERD
arousal index and severity of hypoxemia (% TST SoaO2 <
is underappreciated from a clinical standpoint., There is
90%) showed significantly positive correlation with
considerable evidence to indicate that GERD can affect
severity of GERD (De Mesteer Score) p<0.001 for each.
normal sleep physiology, and cause sleep disturbances and
while severity of OSAS (AHI) showed no significant
poor quality of sleep.
correlation with severity of GERD (De Mesteer Score) (p =
The aim of this work: was to assess the frequency of
GERD in patient with OSAS and to assess the relationship
Conclusion: We can conclude from this study that GERD
of severity of GERD to the severity of OSAS.
occur more common in OSAS patients as compared to
controls (40% versus 10%). There were significantly

Patients and methods: This study included 30 OSAS
positive correlation between arousal index and hypoxemic
patients and 20 controls. The patients and controls were
index with severity of GERD (DeMeesre score) while no
subjected to the following. thorough history taking, with
correlation exist between severity of OSAS (AHI) and
stress on symptoms of GERD, symptoms of OSAS, clinical
severity of GERD (DeMeesre score). It is recommended for
examination, chest x-ray and full-night polysomnography
sleep specialist to inquire about GERD symptoms in
and 24 hour pH monitoring.
patients with OSAS. Also gastroenterologists must inquire
about OSAS symptoms in patients with GERD especially

Results: The heartburn and regurgitation in patients with
those not responding to proton pump inhibitor.
OSAS were significantly higher than controls (p= 0.005
and 0.035 respectively) while the difference in dysphagia
Key words: Obstructive sleep apnea (OSA), Gastro-
was statistically non significant (p= 0.145). The frequency
esophageal reflux disease (GERD)
of GERD in patients with OSAS was significantly higher
*Chest Medicine Banha University, **Gastroenterology
than controls (40% versus 10%, p= 0.021). The OSAS
surgery Mansoura University ***Chest Medicine,
symptoms (snoring, excessive daytime sleepiness,
Mansoura University, ****Internal Medicine Mansoura
nocturnal chocking) in OSAS patients with GERD were
University.
significantly higher than OSAS patients without GERD
(p=0.025,0.003,0.025 respectively). The AHI and arousal
Introduction:

pressure gradually decreases relative to
respiratory efforts during OSAS events (7,8).

Although we spend approximately one
Based on this finding, the pressure gradient
third of our lives sleeping, rarely do we consider
between negative esophageal pressure and
that sleep may contribute to medical condition
positive gastric pressure during OSAS has been
(1).The association between sleep apnea and
assumed to induce GER events.
gastro-esophageal reflux had been noted more
than 20 years ago by Samelson (2) It seemed

Aim of the work:
natural that both diseases might be related,
since the majority of patients with these

The aim of this work was to assess the
disorders shares a common predisposing factors
frequency of gastro-esophageal reflux in patient
(obesity). Further more, some of the clinical
with obstructive sleep apnea and to assess the
manifestations such as nocturnal choking and
relationship of severity of gastro-esophageal
gasping are present in both conditions (3). The
reflux to the severity of obstructive sleep apnea.
relationship between GERD and sleep disorders
such as obstructive sleep apnea Syndrome

Subjects and methods:
(OSAS) has been the topic of many studies.
Fifty patients were referred to Mansoura
Investigators have reported that the prevalence
University Hospital in the period from
of GERD or reflux esophagitis is high in OSAS
December 2008 to May 2010 for the
patients as revealed by symptomatology (4),
investigation of suspected obstructive sleep
esophageal pH monitoring and endoscopic
apnea on the basis of snoring, excessive daytime
findings (5), it has been thought that nocturnal
sleepiness without regard to presence or
gastro-esophageal reflux (GER) is induced by
absence of reflux symptoms.
OSAS as continuous positive airway pressure
Exclusion criteria:
reduced nocturnal GER events in OSAS
1- Respiratory disorders others than OSAS.
patients (6). Esophageal end-inspiratory
2- Known esophageal disease as cancer,
controls (p= 0.426, 0.0950 and 0.470
achalasia and stricture, and history of
respectively) (Table 1).
gastrointestinal surgery.
The heartburn and regurgitation in
The eligible patients for the study were
patients with OSAS were significantly higher
subjected to:
than controls (p = 0.005 and 0.035 respectively)
1- Thorough history taking with stress on
while the difference in dysphagia was
symptoms of obstructive sleep apnea (loud
statistically non significant (p = 0.145) (Table 2).
habitual snoring, excessive daytime
sleepiness if Epworth sleepiness scale > 9,

The Demeester score was significantly
morning headach, nocturnal choking,
higher in patients with OSAS versus controls
witnessed apnea) and symptoms of gastro-
(p=0.009), also all components of Demeester
esophageal reflux (heartburn, regurgitation,
score (% time pH < 4 in supine position, % time
dysphagia).
pH < 4 in upright position, total % time pH < 4,
2- Clinical examination with stress on
number of episodes pH < 4, number of episodes
examination of the upper airway to exclude
> 5 min, longest episode) were significantly
anatomic causes of obstructive sleep apnea
higher in patients with OSAS versus controls (p
like enlarged tonsils or tongue and also to
= 0.003, 0.009, 0.009, 0.019, 0.009, 0.007
assess possible other risk factors for
respectively) (Table 3).
obstructive sleep apnea like hypothyroidism
The frequency of GERD in patients with
or risk factor for gastro-esophageal reflux
OSAS was significantly higher than controls
like obesity.
(40% versus 10%, p= 0.021) (Table 4).
3- All cases were subjected to over night
polysomnography and according to the
The difference in heartburn and
results, patients were classified into a)
regurgitation in OSAS patients with GERD
patients with obstructive sleep apnea
were significantly higher than OSAS patients
syndrome (apnea hypopnea index > 5/hour
without GERD (p< 0.001 and 0.001
together with at least 2 symptoms of OSAS)
respectively), but the difference in dysphagia
and b) patients without obstructive sleep
was statistically non significant (p= 0.320)
apnea syndrome (apnea hypopnea index <
(Table 5).
5/hour). This group was used as control
The OSAS symptoms (snoring, excessive
daytime sleepiness, nocturnal chocking) in
4- Both groups were subjected to 24 hour PH
OSAS patients with GERD were significantly
monitoring and gastro-esophageal reflux
higher than OSAS patients without GERD (p=
was considered present if DeMeester score
0.025, 0.003, 0.025 respectively), while the
was >14.72 (9).
differences in morning headache and witnessed
apnea in OSAS patients with GERD versus

Statistics: Data were analyzed using SPSS
OSAS patients without GERD were statistically
(Statistical Package for Social Sciences) version
non significant (p = 0.051 and 0.361) (Table 6).
10. Qualitative data were presented as number
and percent. Comparison between groups was

The AHI and arousal index in OSAS
done by Chi-square test. Normally distributed
patients with GERD were significant higher
data was presented as mean ± SD. Student t-test
than OSAS patients without GERD (p=0.023
was used to compare between two groups.
and 0.001 respectively) while the sleep efficiency
Pearson’s correlation coefficient was used to
was significantly lower in OSAS patients with
test correlation between variables. P < 0.05 was
GERD than OSAS patients without GERD (p <
considered to be statistically significant.
0.001). Also the hypoxemic parameters
(Desaturation index, average SaO2 < 90%, %

Results:
total sleep time SaO2 < 90%) and % time in
snoring in OSAS patients with GERD were

This prospective study comprised 30
significant higher than OSAS patients without
patients with OSAS and 20 controls (without
GERD (p < 0.001, for all) (Table 7).
OSAS). The mean age, mean BMI and
percentage of males were statistically non

The severity of arousal index and severity of
significant between patients with OSAS versus
hypoxemia (% total sleep time SaO2 < 90%)
showed significantly positive correlation with

severity of GERD (De Mesteer Score) p < 0.001
no significant correlation with severity of
for each. while severity of OSAS (AHI) showed
GERD (De Mesteer Score) (p = 0.076) (Table 8).
Table (1): Demographic data of patients with OSAS versus Controls
Patients with OSA
Controls (n = 20)
Statistics
56.2 ± 3.48
55.5 ± 2.14
31.10 ± 1.13
30.49 ± 1.39
χ2 = 0.521

Table (2): GERD symptoms in patients with OSAS versus Controls.

GERD symptoms
Patients with
Controls (n = 20)
OSAS (n = 30)
Statistics
χ2 = 7.792
Heart burn
χ2 = 4.435
Regurgitation
χ2 = 2.128
Dysphagia

Table (3): Variables of 24 hours pH monitoring in patients with OSAS versus controls

Variables of 24 hours pH
Patients with
Controls (n = 20)
Statistics
monitoring
OSAS (n = 30)
% time pH < 4 in supine
2 (0.8 – 18)
1 (0.2 – 10)
position
% time pH < 4 in upright
2.5 (0 – 7)
0.55 (0 – 4)
position
Total % time pH < 4
2 (0.7 – 10.9)
1 (0.2 – 6.2)
Number of episodes (pH < 4)
41 (10 – 172)
29 (7 – 172)
Number of episodes > 5 min
1 (0 – 8)
0 (0 – 1)
Longest episode
6 (1 – 32)
2.5 (1 – 7)
Demeester score
10.55 (3.7 – 68)
6 (1 – 29)
Table (4): Frequency of GERD in patients with OSAS versus Controls.
Patients with
Controls (n = 20)
OSAS (n = 30)
Statistics
GERD (De Me Master score >
χ2 = 5.357
Without GERD (De Master
score < 14.72)

Table (5): GERD symptoms in OSAS patients with GERD versus OSAS patients without
GERD.

GERD symptoms
OSAS Patients
OSAS Patients
with GERD
without GERD
Statistics
χ2 = 13.333
Heart burn
P < 0.001
χ2 = 19.286
Regurgitation
P < 0.001
χ2 = 0.988
Dysphagia
Table (6): OSA symptoms in OSAS patients with GERD versus OSAS patients without
GERD.

OSA symptoms
OSAS Patients
OSAS Patients
with GERD
without GERD
Statistics
χ2 = 5.00
χ2 = 8.571
Excessive daytime sleepiness
χ2 = 3.810
Morning headache
χ2 = 5.00
Nocturnal chocking
χ2 = 0.833
Witnessed apnea
Table (7): Variables of polysomnography in OSAS patients with GERD versus OSAS patients
without GERD.

OSAS Patients
OSAS Patients
Variables of polysomnography
with GERD
without GERD
Statistics
Sleep efficiency
89.92 ± 1.51
95.39 ± 1.91
P < 0.001
37.58 ± 4.06
33.50 ± 5.23
Arousal index
24.25 ± 3.77
14.89 ± 3.72
P < 0.001
t = 15.481
Desaturation index
19.08 ± 1.31
10.78 ± 1.52
P < 0.001
Average SaO2 < 90%
25.25 ± 3.57
14.56 ± 3.87
P < 0.001
t = 11.561
% total sleep time SaO2 < 90%
3.54 ± 0.49
1.20 ± 0.62
P < 0.001
% time in snoring
18.50 ± 0.90
7.50 ± 5.31
P < 0.001
Table (8): Correlation of severity of OSAS, severity of arousal index and severity of percentage
total sleep time SaO2 < 90% to severity of GERD.

Severity of GERD (De Mesteer Score)
Severity of OSAS (AHI)
Severity of arousal index
< 0.001
Severity of % total sleep time SaO2 < 90%
< 0.001
standpoint (13). Reflux events during sleep
Discussion:
differ from those during the day as the
result of physiological changes that occur

Gastro-esophageal reflux disease and
with the onset of sleep. These physiological
obstructive sleep apnea syndrome are often
changes include marked decline in the
co-morbid disorders (10,11). OSAS is a
frequency of swallowing events resulting in
condition marked by pharyngeal reduced primary peristalsis and
narrowing, resulting in upper airway
consequently in reduced delivery of saliva to
obstruction during sleep which in turn,
the distal portion of the esophagus, loss of
produces repeated episodes of decreased
gravitational drainage, slower gastric
oxygen saturation and brief arousals from
emptying and diminished conscious
sleep. It is well recognized clinically that
perception of GERD events. These sleep
patients with OSAS often complain of
related changes may lead to delayed
heartburn, and they clearly share a major
esophageal acid clearance and as a result,
overlapping risk factor, which is obesity.
increased acid-mucosal contact time. Thus,
Gastro esophageal reflux is very common
there is considerable evidence to indicate
with 7% of adults experiencing symptoms
that GERD can affect normal sleep
daily and 20% experiencing symptoms at
physiology, and cause sleep disturbances
least weekly (12). Currently, sleep related
and poor quality of sleep. Conversely, it is
GERD is underappreciated from a clinical
also possible that disturbed sleep enhances
perception of intra-esophageal reflux
nocturnal reflux events in comparison to
events, perhaps through centrally-mediated
controls (110/night versus 23/night). Also
mechanisms. However, evidence supporting
OSAS patients spent more time of the night
such a hypothesis is lacking (9).
with an abnormally acidic esophageal PH
and had longer episodes of GERD. Valipour

This prospective study comprised 30
et al. (11) reported that subjects with OSA
patients with OSAS and 20 controls
had a significantly higher esophageal
(without OSAS). The two groups were age,
clearance time and more frequent
BMI and sex matched (p= 0.426, 0.095 and
esophageal PH drops compared with those
0.470 respectively) table (1). So the two
without OSA.
groups were comparable. The heartburn
and regurgitation were significantly higher

There were significantly higher
in patients with OSAS as compared to
frequency of GERD in patients with OSAS
controls (p= 0.005 and 0.035 respectively)
versus controls (40% versus 10% p = 0.021)
while dysphagia showed no significant
table (4). These were in accordance to
difference (p = 0.145) table (2). This confirm
Penzel et al (15) who found reflux in
the common existence of classic symptoms
53.3%(8 out of 15) of patients with OSAS
of GERD (heartburn and regurgitation) in
Berg et al (3) reported reflux in 6 out of 14
patients with OSAS in comparison to those
(42.9%)of patients with OSAS. Wise et al
without OSAS. This was in accordance to
(16) reported that 64.3% of patients with
Teramoto et (4), Valipour et al (11), Green
OSA had GERD. Several other studies
et al (10) and Guda et al (14), who reported
showed higher incidence of GERD in OSAS
a significant increase in reflux symptoms in
(10,11,17,18). Since episodes of esophageal
patients with demonstrated OSAS. The high
acidification vary with age (4), posture and
frequency of GERD in OSAS can be
sleep stages (19), this may account for the
explained by large negative intrapleural
differences in reflux episodes observed by
pressure swings that occur during sleep
different investigators.
apnea. Also sleep disordered Breathing
Heartburn and regurgitation in OSAS
events that increase tension in the phreno-
patients with GERD were significantly
esophageal ligament which connect the
higher than OSAS patients without GERD
diaphragm to the lower esophageal
(p < 0.001 for both) while the dysphagia
sphincter, could lead partly to the loss of
showed no significant difference p = 0.320
cardia muscle tone. Dickman (9) reported
table (5). This illustrate that the heartburn
that in case of persistent reflux despite
and regurgitation were reliable symptoms
proton pump inhibitor treatment do they
for diagnosis of GERD in OSAS patients
think about OSAS as one of reasons that
while dysphagia was of less importance.
could cause such problem.
This was in accordance to Matinez et al (20)
The DeMeester score was significantly
who reported that dysphagia had no
higher in patients with OSAS versus
association with abnormal 24 hour PH
controls (p = 0.009), also all components of
studies while heartburn and regurgitation
DeMeester score (% time pH < 4 in supine
were positively associated with abnormal 24
position, % time pH < 4 in upright position,
hour PH monitoring. Multiple investigators
total % time pH < 4, number of episodes pH
noted the validity of establishing GERD on
< 4, number of episodes > 5 min, longest
the basis of symptoms (21,22). Kim et al.
episode) were significantly higher in
(23) reported that clinician typically
patients with OSAS versus controls (p =
diagnose and treat patients with GERD on
0.003, 0.009, 0.009, 0.019, 0.009, 0.007
just clinical ground, so in certain clinical
respectively) table (3). This was in
situation, it can obviate the need for 24 hour
accordance to Ing et al (6) who reported
PH monitoring.
that OSAS patients had significantly higher
The OSAS symptoms (snoring,
improved upper airway anatomic findings
excessive daytime sleepiness, nocturnal
as well as improved subjective sleep quality
chocking) in OSAS patients with GERD
associated with an objective reduction in
were significantly higher than OSAS
acid contact via powerful acid suppression
patients without GERD (p = 0.025, 0.003,
treatment. These document the possible
0.025 respectively) table (6), The % time in
positive feedback effect of GERD on the
snoring in OSAS patients with GERD were
pathophysiology of OSAS. So sleep
significant higher than OSAS patients
professionals need to inquire about GER
without GERD table (8). this was in
symptoms in patients who present with
accordance to Valipour et al (11) who
awakenings and excessive daytime
reported that GER may precipitate
sleepiness. This is supported by Friedman et
symptoms suggestive of OSAS including
al (25) who reported that the combination
awakening and nocturnal choking and
of OSAS with clinical evidence of GERD
reduced sleep efficiency. Lipan et al (24)
should be a basis for either PH monitoring
reported that GERD may increase the
studies or ongoing treatment with proton
symptoms of OSAS in several ways.
pump inhibitor.
Arousals caused by reflux may increase
The AHI in OSAS patients with
daytime somnolence. Friedman et al (25)
GERD was significant higher than OSAS
reported that repeated reflux causes tissue
patients without GERD (37.58 ± 4.06 versus
swelling and this contribute to further
33.50 ± 5.23. P = 0.023) table (7). This was
airway obstruction with subsequent snoring
in accordance to Kuribayashi et al (29) who
and nocturnal choking. So GERD and
reported that AHI was significantly higher
OSAS adversely affect the symptoms and
in OSAS patients with GERD than OSAS
severity of the co-morbid condition. Dekel
patients without GERD (42.0 ±9.8 versus
et al (26) reported that GER may result in
35.7 ± 6.5 p < 0.05). This signify that the
anamnestic short awakenings that lead to
positive feedback of GER on the
sleep fragmentation and feeling un-
pathogenesis of OSAS may occur by causing
refreshed the next morning, dozing off and
edema of the upper airway by the acidic
daytime sleepiness. Shaker et al (13)
reflux with subsequent more AHI. Also the
reported that in a survey of 1000 subjects
arousal index was significantly higher and
with GERD, 75% of the participants
sleep efficiency was significantly lower in
reported that GERD symptoms affect their
OSAS patients with GERD versus OSAS
sleep, 63% believed that heartburn
patients without GERD (P < 0.001 for both)
negatively affect their ability to sleep well.
table (7). This was in accordance to
The prevalence of sleep disturbances among
Kuribayashi et al (29) who reported that
respondents increase with increase in
arousal index was significantly higher in
frequency of nocturnal heartburn episodes.
OSAS patients with GERD than OSAS
Additionally 42% could not sleep through
patients without GERD (p < 0.05). This
the night and 39% took naps whenever
suggest that arousal index and subsequent
possible. The frequency and severity of
decrease in sleep efficiency may be
GERD symptoms were correlated with
implicated in the pathogenesis of GERD
patients quality of sleep. Demeter et al (5)
This was in accordance to Kerr et al (30)
reported close connection between severity
who reported that arousals may trigger
of GERD and score of Epworth sleepiness
GERD by causing transient alteration in the
scale as an indicator of daytime somnolence.
pressure gradient across the lower
Steward et al (27) reported that proton
esophageal sphincter. Dickman et al (9)
pump inhibitor will markedly improve
reported that quality of sleep in persons
symptoms of sleepiness and reflux
with GERD may be affected by acid reflux
symptoms in patients with documented
related short arousals, for which the
OSAS. Orr et al (28) reported that
persons is commonly anamnestic, but these
arousals lead to sleep fragmentation. Orr et
occur in patients with OSA, it is probably
al (31) reported that the pathophysiologic
caused by a combination of increased
mechanisms proposed to link GERD and
transdiaphragmatic pressure gradient and
OSAS are not mutually exclusive and it
coexisting pathology of lower esophageal
seems possible that the two conditions may
sphincter causing incomplete closure. The
in fact interact creating a kind of self
lack of consistent relationship between
perpetuating positive feedback loop.
episodes of esophageal acidification and
apneic events suggest that GER is not

The hypoxemic parameters caused by OSA but may be facilitated by it
(Desaturation index, average SaO2 < 90%,
provided that there is already abnormal
% total sleep time SaO2 < 90%) in OSAS
pathology in the lower esophageal
patients with GERD was significant higher
sphincter. It is possible that minor
than OSAS patients without GERD (p <
esophageal acidification in patients with
0.001, for all) table (7). Also, the severity of
sleep apnea will eventually result in lower
hypoxemia (% TST SaO2 < 90%) showed
esophageal sphincter incompetence leading
significantly positive correlation with
to established GER. Ozturk et al (34)
severity of GERD (De Mesteer Score) p <
reported that the classification of OSA is
0.001 table (8). These suggest the possible
traditionally based on AHI and severity of
role of hypoxemia in the pathogenesis of
OSA which is defined as higher score of
GERD. This was in accordance to Termato
AHI, does not reflect the magnitude of
et al (4) who reported increased GER
respiratory effort during obstruction. Also
episodes during hypoxia due to an impaired
the upper airway resistance syndrome
swallowing function.
which is associated with respiratory effort is
The severity of OSAS (AHI) showed
not included in the AHI, therefore it is not
no significant correlation with severity of
easy to conclude that the occurrence of
GERD (De Mesteer Score) p = 0.076 table
GER is related to the number of AHI rather
(8). This was in accordance to Graf et al
than the respiratory effort during each
(32) and Kuribayashi et al (29) who
breathing cessation period. Beside the
reported that the severity of sleep GER is
respiratory effort, repetitive stimulation of
not correlated to the severity of OSA. Morse
lower esophageal sphincter via phreno-
et al (33) reported that patients subjectively
esophageal ligament may also be linked
report that the quality of sleep is affected by
with a threshold value of respiratory effort.
the severity of GERD, however, objective
The severity of arousal index showed
correlation between OSA and GERD which
significantly positive correlation with
may suggest that both are common entities
severity of GERD (De Mesteer Score) p <
sharing similar risk factors but may not to
0.001 table (8). This illustrate the possible
be causally linked. Penzel et al (15) did not
pathophysiologic role of arousals in the
find a causal relationship between OSA and
development of GERD. This was in
GERD as sequence of time between the
accordance to Orr et al (35) who reported
respiratory and reflux events did not prove
that during sleep, GER occurs most
a causal relationship. Berg et al (3) reported
commonly during the brief stages of
that they found approximately six times as
arousals. Heinemann et al (19) reported
many respiratory events as PH events with
that no direct association between
no consistent relationship between AHI and
obstructive respiratory events and the
reflux events. This suggest that the control
occurrence of GER events. Penzel et al (15)
of the lower esophageal sphincter tone is
reported that 68 of 69 reflux events were
active rather than passive. Lower
associated with an arousal but only 37 were
esophageal sphincter is able to constrict and
associated with an apnea and so no causal
resist mechanical reflux promoting events.
association between the reflux events and
When acidification of the lower esophagus
the apnea could be noted. Kuribayashi et al
(29) reported that arousals precede
with GERD especially those not responding
transient lower esophageal sphincter
to proton pump inhibitor.
relaxation, so arousals may be related to the
occurrence of transient lower esophageal

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Source: http://muh.mans.edu.eg/depts/sdbu/Research/Papers/Gastroesophageal.pdf

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Andrea’s Help Sheet on Preparing Solutions There are several types of stock solutions made in the research lab: Percent (%) solutions, Molar (M) solutions, X solutions, and mg/ml solutions. First are instructions on how to make % solutions. First, know the definition of a % solution: 1% = 1g/100ml That’s the basic formula, and it is logical because “per cent” means “per hundred

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