Article

Faster absorption of ethanol and higher peak concentration in women after gastric bypass surgery: Ethanol kinetics after gastric bypass

Department of Surgery, University Hospital, Orebro, Sweden.
British Journal of Clinical Pharmacology (Impact Factor: 3.88). 01/2003; 54(6):587-91. DOI: 10.1046/j.1365-2125.2002.01698.x
Source: PubMed
ABSTRACT
To investigate the absorption, distribution and elimination of ethanol in women with abnormal gut as a result of gastric bypass surgery. Patients who undergo gastric bypass for morbid obesity complain of increased sensitivity to the effects of alcohol after the operation.
Twelve healthy women operated for morbid obesity at least 3 years earlier were recruited. Twelve other women closely matched in terms of age and body mass index (BMI) served as the control group. After an overnight fast each subject drank 95% v/v ethanol (0.30 g kg-1 body weight) as a bolus dose. The ethanol was diluted with orange juice to 20% v/v and finished in 5 min. Specimens of venous blood were taken from an indwelling catheter before drinking started and every 10 min for up to 3.5 h post-dosing. The blood alcohol concentration (BAC) was determined by headspace gas chromatography.
The maximum blood-ethanol concentration (Cmax) was 0.741 +/- 0.211 g l-1 (+/- s.d.) in the operated group compared with 0.577 +/- 0.112 g l-1 in the controls (mean difference 0.164 g l-1, 95% confidence interval (CI) 0.021, 0.307). The median time to peak (tmax) was 10 min in the bypass patients compared with 30 min in controls (median difference -15 min (95% CI -10, -20 min). At 10 and 20 min post-dosing the BAC was higher in the bypass patients (P < 0.05) but not at 30 min and all later times (P > 0.05). Other pharmacokinetic parameters of ethanol were not significantly different between the two groups of women (P > 0.05).
The higher sensitivity to ethanol after gastric bypass surgery probably reflects the more rapid absorption of ethanol leading to higher Cmax and earlier tmax. The marked reduction in body weight after the operation might also be a factor to consider if the same absolute quantity of ethanol is consumed.

Full-text

Available from: Alan Wayne Jones
© 2002 Blackwell Science Ltd
Br J Clin Pharmacol
,
54
, 587–591
587
Blackwell Science, Ltd
Oxford, UK
BCPBritish Journal of Clinical Pharmacology
0306-5251Blackwell Publishing 2002
54Original Article
Ethanol kinetics after gastric bypassH. Klockhoff
et al.
Correspondence:
Dr A.W. Jones, Department of Forensic Toxicology, University
Hospital, 581 85 Linköping, Sweden. Tel:
+
46 13 252114; Fax:
+
46 13 104875;
E-mail: wayne.jones@rmv.se
Accepted 22 July 2002.
Faster absorption of ethanol and higher peak concentration in women
after gastric bypass surgery
H. Klockhoff,
1
I. Näslund
1
& A. W. Jones
1,2
1
Department of Surgery, University Hospital, Örebro, and
2
Department of Forensic Toxicology, University Hospital, Linköping, Sweden
Aims
To investigate the absorption, distribution and elimination of ethanol in
women with abnormal gut as a result of gastric bypass surgery. Patients who undergo
gastric bypass for morbid obesity complain of increased sensitivity to the effects of
alcohol after the operation.
Methods
Tw elve healthy women operated for morbid obesity at least 3 years earlier
were recruited. Twelve other women closely matched in terms of age and body mass
index (BMI) served as the control group. After an overnight fast each subject drank
95% v/v ethanol (0.30 g kg
-
1
body weight) as a bolus dose. The ethanol was diluted
with orange juice to 20% v/v and finished in 5 min. Specimens of venous blood
were taken from an indwelling catheter before drinking started and every 10 min
for up to 3.5 h post-dosing. The blood alcohol concentration (BAC) was determined
by headspace gas chromatography.
Results
The maximum blood-ethanol concentration (
C
max
) was 0.741
±
0.211 g
l
-
1
(
±
s.d.) in the operated group compared with 0.577
±
0.112 g l
-
1
in the controls
(mean difference 0.164 g l
-
1
, 95% confidence interval (CI) 0.021, 0.307). The
median time to peak (
t
max
) was 10 min in the bypass patients compared with 30 min
in controls (median difference
-
15 min (95% CI
-
10,
-
20 min). At 10 and 20 min
post-dosing the BAC was higher in the bypass patients (
P
<
0.05) but not at 30 min
and all later times (
P
>
0.05). Other pharmacokinetic parameters of ethanol were
not significantly different between the two groups of women (
P
>
0.05).
Conclusions
The higher sensitivity to ethanol after gastric bypass surgery probably
reflects the more rapid absorption of ethanol leading to higher
C
max
and earlier
t
max
.
The marked reduction in body weight after the operation might also be a factor to
consider if the same absolute quantity of ethanol is consumed.
Keywords:
absorption, ethanol, gastric bypass, gut, obesity, pharmacokinetics, women
Introduction
Gastric bypass surgery is the most efficient means of
treating morbid obesity in individuals with a body mass
index (BMI) over 40 kg m
-
2
[1–5]. This operation has
become the most commonly performed procedure in
bariatric surgery [3, 4]. A small pouch is formed by the
upper part of the stomach and kept separate from the
main part of the stomach. The pouch empties into the
jejunum in a Roux-en-Y fashion [6, 7] and the resulting
surgical anatomy resembles that of extended gastric resec-
tion for peptic ulcers and gastrectomy procedures for
neoplastic diseases.
Many of those who undergo gastric bypass surgery
complain of an increased sensitivity or reduced tolerance
to the effects of alcohol compared with their experience
before the operation. This might be explained in two
ways. First, the dramatic reduction in body weight (20–
40% within 1–2 years) means that for the same number
of drinks consumed the person receives a higher ethanol
dose expressed per kilogram of body weight. Second, the
rapid absorption of ethanol after the surgery would pro-
duce a higher
C
max
and earlier
t
max
and more pro-
nounced feelings of inebriation during and shortly after
drinking [8, 9]. A more rapid absorption of ethanol and
higher
C
max
after obesity surgery could have ramifica-
tions when skilled tasks are performed, such as driving a
motor vehicle [10]. The risk of causing a crash increases
as blood alcohol concentration (BAC) increases and pun-
ishable alcohol concentration limits exist in most coun-
tries [11].
Page 1
H. Klockhoff
et al
.
588
© 2002 Blackwell Science Ltd
Br J Clin Pharmacol
,
54
, 587–591
The aim of this study was to investigate the absorption,
distribution and elimination kinetics of ethanol in healthy
women after gastric bypass surgery for morbid obesity.
Another group of women, who had not been operated
on, served as controls and received the same dose of
ethanol under otherwise identical conditions.
Methods
Subjects
Tw elve women who had undergone gastric bypass sur-
gery with mean age 40 years and mean body weight
75 kg volunteered for this study and 12 other healthy
non-operated women mean age 40 years, mean body
weight 78 kg served as controls. Their demographic
details are presented and compared in Table 1. All
women in the treatment group had reached a stable body
weight 3 years or more after surgery. Both groups were
confirmed to be in good health by questioning and
laboratory blood screening tests. They were all non-
smokers and considered themselves social drinkers and
none took any medication at the time of the study. The
study protocol was approved by the ethics review board
at the University Hospital in Örebro, Sweden.
After an overnight fast the subjects received a standard
dose of ethanol equivalent to 0.30 g kg
-
1
body weight.
Pure ethanol (95% v/v) was mixed with orange juice to
give a concentration of about 20% v/v, and was drunk
in 5 min. This amount of ethanol corresponds to 220 ml
table wine (12 vol%) for a person with body weight of
70 kg. Both groups received the drink in a supine posi-
tion. Intake of food or other drink was not allowed
during the experiment, which lasted for about 4 h.
Blood sampling and analysis of ethanol
Venous blood was obtained through an indwelling
catheter before ethanol ingestion and every 10 min for
3.5 h after the start of drinking. Specimens were drawn
into 5 ml Vacutainer tubes containing sodium fluoride
(20 mg) and heparin (120 units). Aliquots of blood
(100
m
l) were removed from each tube and immediately
diluted 1 in 10 with an aqueous solution of n-propanol
(0.08 g l
-
1
) as internal standard. The diluted blood spec-
imens were transferred into 22 ml glass vials, which were
made airtight with crimped-on aluminium caps in prep-
aration for analysis by headspace gas chromatography as
described in detail elsewhere [12]. The analytical preci-
sion of this method of analysis, expressed as coefficient
of variation, was
<
1% at a mean BAC of 0.80 g l
-
1
.
Pharmacokinetics of ethanol
Concentration-time profiles of ethanol were constructed
from 21 venous blood samples and these curves
were evaluated as described by Mathews
et al.
(13).
Pharmacokinetic parameters of ethanol were calculated
assuming a one-compartment model with zero-order
elimination after reaching the post-absorptive phase [14,
15]. The peak blood-alcohol concentration (
C
max
) and
Table 1
Comparison of subject demographics and pharmacokinetic parameters of ethanol in gastric bypass patients (operated group) and
a control group of women. Values are mean
±
s.d. except for time to peak (
t
max
) where medians and range are given. For definition of
the parameters see Methods section.
Parameter
Operated group
(
n
=
12)
Control group
(
n
=
12)
Mean difference
(95% confidence interval)
Age (years) 39.6
±
7.6 40.3
±
9.0
-
0.7 (
-
6.35, 7.75)
Body weight (kg) 74.9
±
8.48 78.1
±
10.0
-
3.2 (
-
4.65, 11.05)
Height (m) 1.67
±
0.065 1.66
±
0.032 0.01 (
-
0.033, 0.053)
BMI (kg m
-
2
) 26.9
±
4.0 28.2
±
3.76
-
1.3 (
-
1.98, 4.58)
BAC (g l
-
1
)
10 min 0.713
±
0.252 0.171
±
0.138 0.542 (0.371, 0.715)
1
20 min 0.611
±
0.120 0.471
±
0.180 0.140 (0.010, 0.270)
1
30 min 0.508
±
0.075 0.529
±
0.150
-
0.022 (
-
0.124, 0.081)
C
max
(g l
-
1
) 0.741
±
0.211 0.577
±
0.112 0.164 (0.021, 0.307)
1
t
max
(min) 10 (10–20) 30 (20–50)
-
15 (
-
10, –20)
1
C
o
(g l
-
1
) 0.497
±
0.073 0.516
±
0.073 -0.019 (-0.043, 0.081)
Estimated time to zero BAC (min
o
) 211 ± 33.7 227 ± 9.8 -16 (5, -37)
Rate of BAC decline (g l
-1
h
-1
) 0.144 ± 0.029 0.139 ± 0.029 0.005 (-0.019, 0.030)
Area under the curve (g l
-1
min) 56.1 ± 12.8 54.6 ± 10.2 1.5 (-8.3, 11.3)
V
d
(l kg
-1
) 0.616 ± 0.100 0.592 ± 0.087 0.024 (-0.055, 0.103)
Rate of elimination from body (g kg
-1
h
-1
) 0.087 ± 0.0136 0.081 ± 0.0127 0.006 (-0.004, 0.018)
1
Statistically significant mean difference.
Page 2
Ethanol kinetics after gastric bypass
© 2002 Blackwell Science Ltd Br J Clin Pharmacol, 54, 587–591 589
the time of its occurrence t
max
were noted. The rate
constant for blood-alcohol concentration decline (k
o
)
was obtained by linear regression analysis using selected
concentration-time points. Each profile was inspected
and only those data points on the post-absorptive
declining phase were used in the calculations. The
apparent volume of distribution of ethanol (V
d
) was
found by dividing the dose of ethanol given (0.30 g
kg
-1
) by the y-intercept of the regression line
(C
extrapolated
). The areas under the concentration-time pro-
files (AUC) were calculated by the linear trapezoidal
method. The rate of elimination of ethanol from the
whole body was calculated by dividing the dose given
by the estimated time to reach zero BAC (min), which
was also obtained by extrapolation (16).
Results
The individual BAC curves for the gastric bypass patients
are shown in Figure 1a and the corresponding curves for
the controls are shown in Figure 1b. Figure 1c compares
the average BAC profiles for the two groups of women.
A more rapid absorption of alcohol with higher C
max
and earlier t
max
can be seen for most of the bypass
group.
Table 1 compares demographic details of the subjects
and pharmacokinetic parameters of ethanol between the
groups. The mean BAC was higher at 10 and 20 min
post-dosing in the bypass group (P < 0.05) but not at
30 min and all later times (P > 0.05). The mean C
max
was
higher and t
max
occurred earlier in the bypass patients
(P < 0.05). Other parameters of ethanol kinetics were not
significantly different in the bypass and control groups.
The rate constant for blood-concentration decline (k
o
)
was 0.144 ± 0.029 g l
-1
h
-1
vs 0.139 ± 0.029 g l
-1
h
-1
and
the apparent distribution volume (V
d
) was
0.616 ± 0.100 l kg
-1
vs 0.592 ± 0.087 l kg
-1
, in the bypass
and control groups, respectively.
Discussion
The absorption, distribution, and elimination kinetics of
ethanol in humans have been studied extensively but to
our knowledge controlled studies in subjects with abnor-
mal gut after gastric bypass surgery have not been
reported [16–18]. The present study was prompted by
complaints from patients undergoing surgery for morbid
obesity, who claimed they had become more sensitive to
the effects of drinking alcohol. Because of the dramatic
decrease in body weight 3 years after the operation, it
was not practical to use subjects as their own controls.
Instead we used a parallel group design with another
group of women matched in terms of age and body mass
index and who had not had this surgery.
Figure 1 Concentration–time profiles of ethanol in women after
gastric bypass surgery (a) and a control group (b). The bottom
panel (c) shows mean curves (± s.d.) for the two groups of women
(n = 12) after they drank ethanol (0.30 g kg
-1
body weight) on an
empty stomach ( operated, control).
0
a
1.2
1.0
0.8
0.6
0.4
0.2
0
60 120 180
240
0
b
1.2
1.0
0.8
0.6
0.4
0.2
0
60 120 180 240
Blood alcohol (g l
–1
)
0
c
1.2
1.0
0.8
0.6
0.4
0.2
0
60 120
Time from start of drinking (min)
180 240
Page 3
H. Klockhoff et al.
590 © 2002 Blackwell Science Ltd Br J Clin Pharmacol, 54, 587–591
The main finding from this study was a higher C
max
and earlier t
max
in the bypass group of women. However,
the BAC remained higher than controls only for 30 min
post-dosing and thereafter concentrations in the control
group were slightly higher than the bypass group. The
small volume of the stomach after the operation, when
the stomach pouch is only about 25 ml, and also the
absence of normal stomach emptying probably accounts
for the faster transfer of fluids into the jejunum and
consequently an increased rate of alcohol absorption [8,
9]. Other pharmacokinetic parameters, such as the rate
of blood-alcohol concentration decline, apparent volume
of distribution and AUC were not significantly different
between the two groups of women.
The higher C
max
and earlier t
max
probably explains the
enhanced feelings of inebriation after gastric bypass sur-
gery [19]. Gastric emptying rate is a major determinant
of alcohol absorption owing to the larger surface area
available in the jejunum [16–18]. As a consequence of
bypass surgery there is a higher C
max
and earlier t
max
[15].
In some of the bypass subjects, the BAC-time profiles
during the first 60 min post-drinking resembled those
seen when ethanol was given intravenously [20]. After
reaching C
max
the BAC drops precipitously, a phenome-
non called a diffusion plunge, when alcohol distributes
from the central (blood) compartment into the peripheral
tissues, where most of the body water is present [9]. Even
in some of the control group who have intact stomachs,
absorption of ethanol occurred rapidly after drinking on
an empty stomach after an overnight fast, which also
facilitates rapid gastric emptying [8, 9, 15, 19].
The higher C
max
in bypass patients after drinking small
amounts of alcohol could have negative consequences
when skilled tasks are performed, such as driving a motor
vehicle. The effects of alcohol on performance and
behaviour are more pronounced when the BAC is rising
and near C
max
[21]. Not infrequently BAC is back-cal-
culated from the concentration at the time of blood
sampling to an earlier time, such as that of a traffic
accident [22, 23]. In retrograde calculations of this kind,
factors influencing the rate and extent of absorption of
alcohol are important to consider including an abnormal
gut after gastric bypass or other surgery.
We evaluated concentration-time profiles of ethanol
using a one-compartment model with zero-order elimi-
nation, the so called Widmark method [14, 15]. This
model is intuitive and has proven itself over many years,
especially when alcohol is taken as a bolus dose on an
empty stomach [15–17]. When comparing two groups of
subjects or two treatments, we feel that the Widmark
method is appropriate to compare and contrast the con-
centration-time profiles for individual subjects [14].
Although more sophisticated multicompartment models
involving Michaelis-Menten kinetics have been advo-
cated for ethanol and are useful after intravenous infusion
[20], these methods are less practical when alcohol is
taken by mouth. Indeed, support for the one-
compartment model comes from using ethanol as a tracer
to estimate total body water (TBW) by the dilution
principle [24]. A recent study in women concluded that
the zero-order model was valid from 0.5 h after C
max
until BAC reached 0.2 g l
-1
because at lower concentra-
tions the main alcohol metabolizing enzymes are no
longer saturated [25].
Much attention has focused on the notion of first-pass
metabolism of ethanol occurring in the stomach by class
IV isoforms of alcohol dehydrogenase (ADH) located in
gastric mucus [26–29]. In the present study, one might
expect a greater contribution from gastric ADH in the
control group of subjects with intact gut compared with
the bypass group with a much smaller absorption surface
and presumably less ADH enzyme. Assuming equal rates
of alcohol clearance in the two groups of women, the
lack of any differences in AUC speaks against any differ-
ences in pre-systemic metabolism of ethanol whether
gastric or hepatic.
In conclusion, we suggest that after gastric bypass sur-
gery patients should be warned about drinking alcohol
too quickly because even relatively small amounts of
alcohol, such as two small glasses of wine (0.3 g kg
-1
)
might produce unexpectedly high BAC shortly after the
end of drinking. Also when other surgical procedures are
performed on the gut such as gastric resection and gas-
trectomy, a more rapid absorption of ethanol can be
expected. The present experiment with alcohol as a
model substance might have implications for the absorp-
tion and pharmacological effects of other drugs or when
prescription drugs are taken together with alcohol [30].
The costs of this study were supported in part by the Swedish
National Board of Forensic Medicine (Rättsmedicinalverket).
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insert Table 1 near hereinsert Figure 1 near here wayne.jones@RMV.SE
Page 5
    • "Further, the mechanisms underlying the change of substance absorption may fasten the onset of substance-related pharmacological effects on bariatric surgery patients, and increase substancerelated adverse events. Higher maximum blood ethanol concentration , faster speed of absorption of ethanol, longer time to return to sober were observed among bariatric surgery patients, comparing with controls without history of bariatric surgery (Klockhoff et al., 2002; Maluenda et al., 2010; Woodard et al., 2011). Additionally, postoperative weight loss may be related to opportunities of substance use. "
    [Show abstract] [Hide abstract] ABSTRACT: Background: Prevalence of obesity has increased dramatically. Obese individuals may undergo bariatric surgery to lose excessive body fat and mitigate obesity-related comorbidities. However, bariatric patients are particularly vulnerable to substance use problems. We conducted a review to examine the prevalence change and factors associated with substance use and determine the association between substance use and health status after weight loss among bariatric patients. Methods: We searched peer-reviewed articles published between January 1990 and January 2015 in several databases (PubMed, PsycINFO, Cochrane Library, Google Scholar) using different keywords combinations. Studies that focused on pre-surgery substance use only or without reported effect measurements were excluded. Results: Overall, 40 studies were included in the review. Preoperative history of substance use was a reliable correlate of postoperative substance use. The prevalence of postoperative alcohol use was higher among patients with preoperative history of alcohol use than those without. Postoperative prevalence of alcohol use ranged from 7.6% to 11.8%. No significant prevalence change in cigarette smoking from pre-to postoperative period was observed. Time effect was not observed on smoking or drug use prevalence, while an increase in alcohol consumption was inconsistent across studies. The proportion of new-onset substance users among bariatric patients after surgery ranged from 34.3% to 89.5%. Conclusion: Substance use is associated with poor health among bariatric patients. Preoperative assessment and postoperative follow-up should include interventions to reduce relapse among users and prevent substance use initiation.
    No preview · Article · Jan 2016 · Journal of Psychiatric Research
  • Source
    • "For example, Wee and colleagues (2014) found that over 70% of RYGB patients reported amelioration in high-risk drinking behaviors 1 year after surgery, compared to only 48% of AGB patients. As discussed earlier, physiologic changes that result from the RYGB procedure may offer a putative explanation for an increased vulnerability for postsurgical AUDs (Hagerdorn et al., 2007; Klockhoff et al., 2002; Woodard et al., 2011). Common theories about the causes of these changes reflect anatomy after the gastric bypass, which allows for rapid absorption of alcohol into the blood stream. "
    [Show abstract] [Hide abstract] ABSTRACT: Emerging research suggests that some bariatric surgery patients are at a heightened risk for developing substance use problems, especially alcohol use problems. An exhaustive literature review was conducted in January 2015 to investigate all articles published that included data on postoperative alcohol use, alcohol use disorders, and illicit drug use among bariatric surgery patients. Twenty-three studies reported on alcohol and/or substance use among bariatric patients. Six studies longitudinally assessed alcohol use behaviors; 3 of these studies found an increase in alcohol use following surgery. Six studies were cross-sectional, and 2 studies assessed medical records. Five studies investigated the prevalence of admissions to substance abuse treatment, and 3 studies combined alcohol and drug use data in a single index. Six studies reported on illicit drug use and reported low-postoperative use. The studies' samples were primarily non-Hispanic white females in their upper 40s, and only 11 of the 23 studies utilized validated assessment instruments. Studies employing longitudinal designs and large sample sizes indicate that bariatric patients who had the gastric bypass procedure are at an elevated risk for alcohol use problems postoperatively. Research also indicates that bariatric surgery patients might be overrepresented in substance abuse treatment facilities. Risk factors for problematic postoperative alcohol use include regular or problematic alcohol use presurgery, male gender, younger age, tobacco use, and symptoms of attention deficient and hyperactivity disorder. As a whole, however, studies indicate bariatric surgery patients demonstrate a low prevalence of problematic alcohol use, and studies about gastric bypass patients are not entirely conclusive. Prospective, longitudinal studies are needed, utilizing standardized and validated alcohol assessment instruments that follow postoperative bariatric patients well beyond 2 years, and account for types of bariatric procedure. Finally, study samples with greater racial/ethnic diversity and wider age ranges are needed. Copyright © 2015 by the Research Society on Alcoholism.
    Full-text · Article · Aug 2015 · Alcoholism Clinical and Experimental Research
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    • "NSAID use is associated with an increased risk of bleeding. If analgesic or anti-inflammatory treatment is needed, the use of acetaminophen is preferred in a dose of 1-2 g/ daily4142434445 . Other factors associated with increased risk of ulcer formation are smoking, alcohol, spicy food, gastrogastric fistulas, ischemia at the site of surgical anastomosis, poor tissue perfusion due to tension , presence of foreign material, such as staples and/or Helicobacter pylori infection. "
    [Show abstract] [Hide abstract] ABSTRACT: Obesity is a major and growing health care concern. Large epidemiologic studies that evaluated the relationship between obesity and mortality, observed that a higher body-mass index (BMI) is associated with increased rate of death from several causes, among them cardiovascular disease; which is particularly true for those with morbid obesity. Being overweight was also associated with decreased survival in several studies. Unfortunately, obese subjects are often exposed to public disapproval because of their fatness which significantly affects their psychosocial behavior. All obese patients (BMI ≥ 30 kg/m(2)) should receive counseling on diet, lifestyle, exercise and goals for weight management. Individuals with BMI ≥ 40 kg/m(2) and those with BMI > 35 kg/m(2) with obesity-related comorbidities; who failed diet, exercise, and drug therapy, should be considered for bariatric surgery. In current review article, we will shed light on important medical principles that each surgeon/gastroenterologist needs to know about bariatric surgical procedure, with special concern to the early post operative period. Additionally, we will explain the common complications that usually follow bariatric surgery and elucidate medical guidelines in their management. For the first 24 h after the bariatric surgery, the postoperative priorities include pain management, leakage, nausea and vomiting, intravenous fluid management, pulmonary hygiene, and ambulation. Patients maintain a low calorie liquid diet for the first few postoperative days that is gradually changed to soft solid food diet within two or three weeks following the bariatric surgery. Later, patients should be monitored for postoperative complications. Hypertension, diabetes, dumping syndrome, gastrointestinal and psychosomatic disorders are among the most important medical conditions discussed in this review.
    Full-text · Article · Nov 2014
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