• Copyright ᮊ by Walter de Gruyter • Berlin • New York. DOI 10.1515/JPM.2005.087
A clinical evaluation of controlled-release dinoprostone for cervical ripening – a review of current evidence in hospital and outpatient settings Werner Rath*
many clinical circumstances, such as pregnancy-inducedhypertension, prelabor rupture of the membranes, sus-
Department Obstetrics and Gynecology, University of
pected fetal jeopardy or death, or maternal morbidity
(e.g. diabetes), lead to the use of labor induction w1x, itsroutine use in, and recommendation for, post-term preg-
Abstract
nancy is becoming more frequent (for example, NICE
Labor induction is used in approximately 20% of preg-
recommendations in the UK w30x). In many countries,
nancies in Europe and North America. Prostaglandins
induction is routine for pregnancies over 41 weeks, which
and prostaglandin analogs are favored when women
account for over 20% of all pregnancies w35x. Recom-
undergoing labor induction have an unripe cervix. Con-
mendations to induce labor in post-term pregnancy fol-
trolled-release dinoprostone, delivered over 24 h from a
low the finding that the prevalence of stillbirths increases
vaginal insert, results in cervical ripening within 12 h in
from 0.35 per 1000 ongoing pregnancies at 37 weeks to
most women. It is marginally more effective than imme-
2.12 per 1000 at 43 weeks w17x. Furthermore, routine
diate release formulations and has similar efficacy to
induction of labor in pregnancies of more than 41 weeks
misoprostol, a prostaglandin E analog used off-label for
reduces perinatal mortality (OR 0.20 w95% CI 0.06–0.70x)
this indication. The controlled-release preparation offers
many advantages compared with an immediate-release
In attempt to optimize labor induction, there has been
formulation: a single application is sufficient; it is less
an increase in the number of agents available for cervical
invasive; it is easily administered and removed, allowing
ripening/labor induction. In this article, we review the lit-
greater dose control. The most significant adverse effect,
erature on one such agent, a sustained and controlled-
uterine hyperstimulation, with and without an effect on
release dinoprostone vaginal insert (prostaglandin E ;
fetal heart rate, occurs in 5–15% of patients, which is
Propessᮋ or Cervidilᮋ). We review the efficacy and safety
comparable with other formulations or misoprostol. The
of the agent as well as recent data on its use in an out-
insert can be removed easily on the first sign of uterine
patient setting. With outpatient management in obstetrics
hyperstimulation, or as soon as labor starts. The efficacy
being continuously expanding, we address the current
and safety of controlled-release dinoprostone are com-
evidence on this important issue, and its potential impli-
parable whether it is used in the outpatient or the inpa-
cations in terms of cost and patient convenience.
tient setting. For low-risk women, outpatient use may bea highly attractive option, potentially reducing hospital
Aims of labor induction
costs, and improving patient convenience. The ease ofuse of controlled-release dinoprostone and women’s sat-
Induction of labor is indicated when a continuation of the
isfaction emphasize its benefits over many other agents
pregnancy would mean that the risks to the mother or
fetus outweigh the benefits from further observation. The
Keywords: Controlled-release; dinoprostone; outpatient;
aims of induction are straightforward—vaginal delivery or
active labor within 12 h. Undesirable outcomes havebeen clearly defined by the Cochrane CollaborationPregnancy and Childbirth Group and include: vaginal
Introduction
delivery not achieved within 24 h; uterine hyperstimula-tion with fetal heart rate wFHRx changes; requirement for
The frequency of labor induction has increased in Europe
cesarean section; serious neonatal morbidity or perinatal
and North America over the past 10 years w25x. Although
death; and serious maternal morbidity or death w18, 22x. In the guideline published by the Royal College of Obste-
tricians and Gynaecologists, the term hyperstimulation
with and without FHR changes included uterine tachy-
systole ()5 contractions in 10 min for G20 min) and
uterine hypersystole/hypertonus (a contraction lasting
G2 min). However, due to varied reporting of this out-
492 Rath, Clinical efficacy of controlled-release dinoprostone
The Bishop score for assessment of cervical ripeness w5x.
* Station of fetus relative to the ischial spine
come, possible subjective bias in interpretation exists
venous infusion of oxytocin, which rapidly stimulates
w30x. Where possible, we used these outcomes in
uterine contractions but has no direct effect on the con-
dition of the cervix w20x. Prostaglandins (dinoprostoneand dinoprost wprostaglandin F x), however, are used for
Methods of labor induction
cervical ripening w21, 42x. Dinoprostone is favored overdinoprost for several reasons, including relative potency
A pre-requisite for successful labor induction is cervical
ripening (or cervical maturation). Many clinicians regardlabor induction and cervical ripening as essentially the
Dinoprostone formulations
same process. If labor is induced when the cervix isunripe and unable to yield in response to contractions,
The risk of systemic side effects with prostaglandins has
high rates of failure are observed w9x.
led to the development of various formulations for local
Because of the importance of cervical ripening, meth-
application. These include, intra-vaginal tablets or sup-
ods of evaluating the status of the cervix have been
positories, intra-cervical or intra-vaginal gels in a single-
developed. The most widely used is the Bishop score w5x
use syringe, and sustained release intra-vaginal inserts.
or the modified Bishop score w8x. The Bishop score rates
Tablets or suppositories are the simplest formulation to
the dilatation, consistency, and length of the cervix, and
administer, but outcome can be unpredictable w27x. In
the position of the fetus. A combined score gives a
addition, a second dose of the tablets is often adminis-
measure of cervical ripeness on a scale from 0 to 13
tered 6–8 h after the first (if the single dose is considered
(Table 1). The state of the cervix is not favorable enough
ineffective), but since the onset of labor may be 8–12 h
to commence labor induction when the Bishop score is
after induction, this double dosing increases the risk of
below a certain level. No consensus exists on the precise
uterine hyperstimulation. Gel formulations of dinopros-
score that indicates the need for cervical ripening, but
tone provide more predictable results, but administration
generally a Bishop score -6 are considered too low to
(particularly of intra-cervical gels) requires an experi-
enced clinician and can be uncomfortable for the woman.
Approximately, 50% of women undergoing induction of
Spillage from the cervical canal can reduce efficacy or, if
labor have an unfavorable cervix and, therefore, require
the dose passes into the extra-amniotic space, cause
cervical ripening w2x. The optimal method of labor induc-
uterine hyperstimulation w27x. Both intra-vaginal and
tion should ideally also ripen the cervix. Dilatation and
intra-cervical gels may also cause uterine hyperstimula-
labor can be induced by mechanical means, such as
tion by delivering dinoprostone too quickly (i.e. dose-
membrane sweeping, artificial rupture (amniotomy), dig-
dumping). In the event of such an adverse reaction, gel
ital stretching of the cervix, or insertion of catheters, but
formulations are quite impossible to remove.
most mechanical methods can traumatize the cervix and
A sustained and controlled release of dinoprostone is
are associated with discomfort and bleeding in a sub-
needed to overcome the potential problems with gel and
stantial number of women w49x. In addition, women
tablet formulations. A retrievable vaginal insert is availa-
undergoing labor induction tend to favor less invasive
ble that releases a continuous and predictable dose of
pharmacological methods to mechanical methods, such
dinoprostone at a rate of approximately 0.3 mg/h for 24 h
as artificial rupture of membranes w41x. Pharmacological
w28x. The controlled-release formulation of dinoprostone,
compounds for inducing labor are therefore preferred—
minimizes the risk of uterine hyperstimulation, is easy to
the most widely used agents are oxytocin, prostaglan-
apply, and can be removed quickly when labor starts, or
in the event of an adverse reaction. Furthermore, the pro-
The ideal agent must effectively induce labor and con-
gressive cervical ripening induced by the controlled
vert an unfavorable cervix to one receptive to delivery,
release of dinoprostone may be more acceptable to
but also needs to be safe, easy to administer, and
patients than the rapid onset of contractions observed
acceptable to the patient. The most frequently used
with some agents w44x. The controlled release of dino-
pharmacological method for inducing labor is an intra-
prostone from the vaginal insert continues for up to 24 h
Rath, Clinical efficacy of controlled-release dinoprostone
w28x allowing longer induction, if required, with only one
18.32 w95% CI 9.49–35.38x; P-0.0001), and overall
treatment success (OR 4.93 w95% CI 3.36–7.24x;P-0.0001) compared to placebo w11x. Controlled-releasedinoprostone was also associated with a significantly
Efficacy of controlled-release dinoprostone
lower rate of oxytocin use (OR 0.14 w95% CI 0.06–0.32x;P-0.0001) and a non-significantly lower rate of cesarean
Placebo-controlled trials
delivery. While parity did not affect most of the outcomemeasures, multiparous women had 50% shorter labors
Three randomized, double-blind, clinical trials have
assessed the efficacy of controlled-release dinoprostone
The efficacy of controlled-release dinoprostone was
vs. placebo in 485 women at term (referred to as studies
reviewed by Kelly et al. w23x. The primary aim of the
1, 2 and 3, respectively) w34, 47, 48x. A subsequent meta-
review was to determine the effects of vaginal prosta-
analysis including these trials and other studies compar-
glandin E for cervical ripening or induction of labor in
ing dinoprostone with different cervical ripening agents
comparison with placebo, no treatment, or other vaginal
were performed by Crane and Bennett w11x.
prostaglandins (except misoprostol). This was reflected
The three placebo-controlled trials were similar with
by an increase in successful vaginal delivery rates within
respect to design. Inclusion criteria were singleton preg-
24 h, no increase in operative delivery rates, and signif-
nancy G37 weeks’ duration, cephalic presentation, Bish-
icant improvement in cervical condition within 24 to 48 h.
op score F4 at admission, medical or obstetric reasonfor induction, and F3 previous viable deliveries. Exclu-
Comparative trials
sion criteria included previous uterine scar, vaginal bleed-ing, ruptured membranes, FHR abnormalities, and
A number of trials have examined the efficacy of con-
medical conditions precluding dinoprostone administra-
trolled-release dinoprostone compared with vaginal or
tion. The primary outcome measure for these trials was
intra-cervical gel formulations of dinoprostone, and the
cervical ripening with treatment success defined as vag-
prostaglandin E analog, misoprostol. However, most of
inal delivery within 12 h, or a Bishop score G6, or an
the comparative trials involve small numbers of patients,
increase from baseline in Bishop score G3 at 12 h. A
reducing the statistic power. The latter agent is widely
number of secondary outcomes were also measured
used off-label in both the USA and Europe for cervical
including time to vaginal delivery, time to onset of labor,
ripening. Misoprostol oral tablets are indicated for the
need for oxytocin (reflecting induction failure) and cesa-
prevention and treatment of NSAID gastric and duodenal
ulcers and were not approved for induction of labor.
The baseline characteristics were similar in each trial
Three prospective trials and one retrospective study
and did not differ between placebo and active-treatment
have assessed the comparative efficacy of controlled-
groups, with the exception that in study 3, the mean age
release dinoprostone and vaginal or intra-cervical gel
of women in the multiparous group receiving placebo
dinoprostone w10, 31, 33x. The aggregated data from the
was significantly higher than for those receiving active
two prospective trials were also analyzed in the Crane
treatment (28.2"5.1 vs. 25.6"5.3 years; Ps0.03) w48x.
and Bennett meta-analysis w11x. In one trial, 73 women
In all three trials, the most frequent indication for labor
who had an indication for induction of labor for a variety
of reasons were randomized to receive either intra-cer-
Dinoprostone was significantly better than placebo for
vical gel (ns36) or a controlled-release (ns37) dinopros-
all primary outcomes (Table 2), and in general, the results
tone insert w10x. Although changes in Bishop scores were
were unchanged when nulliparous women were analyzed
similar in the two groups, the mean times to cervical rip-
separately. However in study 3, the response to con-
ening, active labor, and delivery were significantly shorter
trolled-release dinoprostone in nulliparous women was
with the use of controlled-release dinoprostone (Figure
primarily a cervical change (Bishop score was improved
1). Hospital stay was also shorter with the controlled-
but there were no vaginal deliveries in either placebo
release formulations than with the gel; 3.7 vs. 4.4 days,
recipients or dinoprostone recipients), whereas in multi-
respectively (Ps0.03). If active labor had not already
parous women the response was mainly higher rates of
begun, oxytocin infusion was initiated 6 h after the final
delivery within 12 h w48x. Furthermore, in both nulliparous
dose of gel or 30 min after removal of the insert. Oxytocin
and multiparous women, the time to onset of labor and
was administered in 97% of patients receiving dinopros-
to vaginal delivery was significantly shorter in those
tone gel and in only 76% of patients receiving the con-
women receiving controlled-release dinoprostone w34,
trolled-release dinoprostone insert (Ps0.014) w10x. In a
previous study, this figure was even less for the dino-
The meta-analysis of these three trials confirmed that
prostone insert group whereby 54% of patients required
controlled-release dinoprostone was associated with a
labor to be initiated or augmented with oxytocin w47x. At
significantly higher rate of cervical ripening (OR 3.99
least 50% of women required three doses of the gel to
w95% CI 2.71–5.86x; P-0.0001), onset of labor (OR
494 Rath, Clinical efficacy of controlled-release dinoprostone
Primary efficacy outcomes from the three placebo-controlled trials of controlled-release dinoprostone w34, 47, 48x.
aTreatment success is defined as a change in Bishop score of G3, or a Bishop score of G6 at 12 h or delivery within 12 h of insertplacement. *In nulliparous and multiparous women separately. In all other cases, figures are combined.
In a more recent comparison by Ottinger et al. w31x, 90
prostone gel (ns50) (29.8"22.0 h vs. 62.0"78.8 h,
women with an indication for labor induction were ran-
respectively wPs0.039x) w43x. Additionally, controlled-
domized to receive either intra-cervical gel (ns45) or
release dinoprostone was associated with a higher rate
controlled-release dinoprostone (ns45), and the advan-
of cervical ripening and a higher rate of deliveries within
tages of controlled-release formulations were noted. The
24 h than dinoprostone gel (80% vs. 56% and 62% vs.
investigators found that controlled-release dinoprostone
was associated with a greater mean change in Bishop
In a more recent study, controlled-release dinopros-
score (1.8"1.9 vs. 3.2"3.1, Ps0.01) than the gel. In this
tone had generally equivalent efficacy to an intra-cervical
study, there was no significant difference between treat-
gel formulation of dinoprostone w13x. In this trial of 115
ments in the percentage of deliveries within 24 h, and
women, the majority needing labor induction for post-
there was a non-significant decrease in the application-
term pregnancies, there was a slightly higher occurrence
to-delivery interval (28.3 and 24.0 h for gel and con-
of vaginal delivery in the group receiving controlled-
trolled-release formulations, respectively wPs0.19x) w31x.
release dinoprostone than in those receiving the gel, but
A prospective multicenter German study found similar
this difference did not reach statistical significance.
results. In this study, 158 pregnant women with a Bishop
Other studies have shown advantages of a controlled-
Score F4 were randomized to receive either controlled-
release formulation over vaginal gels in terms of initiating
release dinoprostone (ns83) or intra-cervical application
sustained high-amplitude contractions w29x or initiating
of 0.5 mg prostaglandin E gel (ns75) w33x. The study
labor w39x. However, a meta-analysis of nine published
found that there was no significant difference in the per-
studies concluded that there were no clinically significant
centage of vaginal deliveries within 24 h between the
differences between controlled-release dinoprostone and
women given controlled-release dinoprostone and those
alternatives, such as gels, used for cervical ripening
in the intra-cervical gel group, and no significant differ-
(however, no sub-analysis was done on trials with intra-
ence in the mean induction to delivery interval (28 h for
cervical or vaginal gels specifically) w19x.
the gel and 21.5 h for the controlled-release formulation).
A recent study by Perry and Leaphart w32x reported
There was no significant difference in perinatal outcome.
that intra-cervical placement of the sustained-release
The investigators concluded that controlled-release dino-
dinoprostone insert decreased time to delivery without
prostone is appropriate for use across the whole range
increasing the cesarean delivery rate, infectious morbi-
of Bishop Scores, from the unripe to the ripe cervix. This
dity, or other complications of labor. However, when
is of benefit to the obstetrician as only one formulation
induction of labor is undertaken with prostaglandins,
for induction is required, independent of cervical status.
intravaginal prostaglandin E should be used in prefer-
The study also monitored FHR in both sample groups
ence to intracervical preparations, because despite being
w33x. Fetal heart rate was monitored for 20–30 min in the
effective, administration of the vaginal insert is less inva-
controlled-release dinoprostone group in accordance
sive w30x. In addition, it should be noted that the vaginal
with product guidelines, and for 2 h in the intra-cervical
insert is not licensed for intra-cervical administration and
gel group. No significant difference in fetal outcome as
the safety and efficacy of administration by this route has
measured by pH or Apgar score was detected.
In a retrospective analysis of 100 records, the time for
A recent randomized trial by Garry et al. w15x suggest-
application to delivery in women who received con-
ed that induction of labor with misoprostol, results in a
trolled-release dinoprostone (ns50) was significantly
higher rate of vaginal delivery and a shorter induction
shorter than in those who received intra-cervical dino-
time than induction with controlled-release dinoprostone.
Rath, Clinical efficacy of controlled-release dinoprostone
changes was 2.6% in the dinoprostone group and 0%and 7.5% in the misoprostol 35 mg and 50 mg groups,respectively (Ps0.328). Tachysystole more frequentlyoccurred after dinoprostone (15.4%) compared withmisoprostol (2.6 and 5.6% for the 35 mg and 50 mg dos-es, respectively). In general, there are safety aspects ofmisoprostol that have not been fully evaluated and it isnot currently licensed for obstetric use. Twenty-four hour use
Most clinical trials have compared controlled-release
Comparison of controlled-release dinoprostone with
dinoprostone for 12 h with placebo or other agents, but
dinoprostone gel for induction of labor and cervical ripening
the use of controlled-release dinoprostone for longer
periods can maintain prostaglandin E levels for up to
24 h if required w16x. Furthermore, Lyrenas et al. w28x
The mean time to vaginal delivery was 13.2 h and 16.8 h
revealed that the prostaglandin E release rate was linear
in the misoprostol (50 mg every 3 h) and controlled-
over 24 h in patients with intact membranes. The two
release dinoprostone groups (P-0.02), respectively, and
comparative trials by Wing et al. and Khoury et al. w24,
44% of women receiving misoprostol had delivered at
46x allowed the vaginal insert to be left in place for up to
-12 h compared with 12% in the dinoprostone group
24 h and 22.5 h, respectively. The efficacy of controlled-
(P-0.0001) w15x. However, two earlier comparisons of
release dinoprostone and misoprostol were similar and
controlled-release dinoprostone and misoprostol showed
there was no evidence of adverse effects associated with
no significant differences in any of these parameters (Fig-
the 24-h use of controlled-release dinoprostone. These
ure 2) w24, 46x. This could potentially be explained by
trials show the potential for the prolonged use of con-
slightly lower dosages of misoprostol used in these stud-
trolled-release dinoprostone when 12-h exposure has not
ies—25 mg every 4 h w46x and 35 mg or 50 mg every
resulted in adequate cervical ripening or the onset of
4.5 h w24x—compared with the 50 mg every 3 h used by
labor. Controlled-release dinoprostone is now approved
Garry et al. w15x. However, the higher dosages used in
the latter study may be associated with unacceptablelevels of adverse effects. In the study by Garry andcoworkers, uterine hyperstimulation occurred in 4% of
Safety of controlled-release dinoprostone
women receiving misoprostol compared with 1% in thedinoprostone group (Ps0.37 w15x). In contrast, Wing
Placebo-controlled trials
et al. w46x observed uterine hyperstimulation with abnor-mal FHR patterns in 4.1% of the patients receiving the
The most significant adverse effect of any method of
dinoprostone vaginal insert compared with 1.0% in the
labor induction is uterine hyperstimulation. Compared
misoprostol group (Ps0.21). In the study by Khoury et
with placebo, controlled-release dinoprostone increased
al. w24x, the rate of uterine hyperstimulation with FHR
the rate of hyperstimulation in all three clinical trials w34,47, 48x. The incidence of uterine hyperstimulation rangedfrom 5 to 16% in patients treated with controlled-releasedinoprostone w34, 48x, but in the trial with the highestincidence w34x the insert was left in situ after the onsetof labor (in error—the dinoprostone insert should beremoved at the onset of labor) and this would explainthese higher rates (75% of cases occurred after the onsetof labor with dinoprostone insert still in place). In all threetrials, uterine hyperstimulation resolved within 15 minafter removal of the insert. Fetal distress or FHR abnor-malities were observed in 3–10% of dinoprostone-recip-ients, but these also resolved immediately after removalof the dinoprostone insert w34, 47, 48x. Importantly, theproportion of women requiring cesarean section due tonon-reassuring FHR tracing was similar in the dinopros-
Time interval between induction and vaginal delivery
with controlled-release dinoprostone (DP), misoprostol 25 mg
tone-treated group to the placebo-treated group w34, 47,
every 4 h (M25), misoprostol 35 mg every 4.5 h (M35), or miso-
48x. Other than the adverse effects discussed above,
prostol 50 mg every 4.5 h (M50) w24, 47x.
controlled-release dinoprostone was relatively well toler-
496 Rath, Clinical efficacy of controlled-release dinoprostone
Comparison of odds ratios (OR) for uterine hypertonus with fetal heart rate change between controlled-release dinoprostone
(treatment) and other vaginal or cervical prostaglandin formulations (control) w19x.
ated and there were no laboratory abnormalities that
Comparative trials
were drug-related in the three placebo-controlled trials
A number of trials compared the safety of controlled-release dinoprostone with other prostaglandin E formu-lations. None of the trials comparing intra-cervical gels
Experience in clinical practice
with controlled-release dinoprostone showed significant-ly different rates of uterine hyperstimulation or cesarean
Post-marketing assessments of controlled-release dino-
section w10, 13, 31x. Similarly, controlled-release dino-
prostone confirmed the safety profile and incidence of
prostone has a similar safety profile to vaginal gel for-
uterine hyperstimulation in clinical practice. An exami-
mulations w29, 39x. The same is generally true in
nation of 173 cases over a 16-month period found a fre-
comparisons of controlled-release dinoprostone with
quency of uterine hyperstimulation of 5.2% (8.4% of
misoprostol w24, 46x, but higher doses of misoprostol
primiparous women and 1.3% of multiparous women)
(50 mg every 3 h) may result in more cesarean sections
w6x. As in the clinical studies, women experiencing
because of non-reassuring FHR tracing w15x.
hyperstimulation delivered healthy infants without the
Because most comparative trials involved small num-
additional risk of requiring a cesarean section, and the
bers of patients, the data on safety from these trials were
nursing staff quickly learned to remove the vaginal insert
amalgamated in a meta-analysis by Hughes et al. w19x.
Rates of uterine hypertonus with FHR changes were sim-
In a study of women undergoing vaginal birth after
ilar in controlled-release dinoprostone to rates with other
cesarean section (VBAC), six out of 58 women (10.3%)
prostaglandin E products (OR 1.19 wCI 0.58–2.54x) (Fig-
receiving controlled-release dinoprostone experienced
ure 3), but misoprostol induced higher rates of this
uterine rupture compared with only 1.1% of women who
adverse effect compared with controlled-release dino-
did not w40x. However, three of the six women were also
prostone (OR 1.53 wCI 1.05–2.22x). An analysis of cesa-
using oxytocin and were low-weight women (possibly
rean delivery also showed similar rates between different
indicating an increase in overall bioavailability of dino-
formulations and agents w19x. The similar safety of con-
prostone in low-weight women). Although there is a low
trolled-release dinoprostone with other formulations is
risk of uterine rupture in women undergoing VBAC with
now well established with the publication of these trials.
controlled-release dinoprostone, this risk may be similar
Furthermore, there are no safety issues associated with
to dinoprostone gels w40x. The labeling for Propessᮋ
leaving the insert for longer than 12 h and up to 24 h.
takes this risk into account and contraindicates its use inwomen with previous uterine surgery, such as cesarean
Outpatient use of controlled-release dinoprostone
section. However, controlled-release dinoprostone is nolonger contraindicated for use in PROM cases, but
An increasingly important aspect of labor induction (or
should, nonetheless, be used with caution.
any obstetric care) is patient satisfaction. Controlled-
Rath, Clinical efficacy of controlled-release dinoprostone
release dinoprostone has therefore been investigated in
ture seems contradictory. No pharmacological agent has
an outpatient setting to test if the insert had favorable
shown consistent benefit over other agents or formula-
safety and whether it improves patient satisfaction. Such
tions in clinical trials when both safety and efficacy are
outpatient use of agents for labor induction may also
considered. However, unlike other agents such as miso-
reduce hospital stay, thus freeing space, time, and staff
prostol, dinoprostone has been licensed specifically for
for the care of high-risk inductions, and may be more
use in cervical ripening and has therefore been subjected
to rigorous trials. Irrespective of whether or not an agent
The safety of outpatient use of controlled-release dino-
is licensed for use in pregnancy, the cost, ease of use,
prostone has been assessed in four studies. In a retro-
and the patient preference may be the deciding factors
spective study by Sennik, a cohort of 201 women were
when choosing an agent for induction of labor. Patient
monitored for 2 h after the insertion of the insert before
acceptability of controlled-release dinoprostone is excel-
being allowed home if no adverse effects were detected
lent and the potential to use this formulation in an out-
w37x. Of the 192 women discharged, only two (1.0%) had
patient setting may make it more acceptable to women
uterine hyperstimulation and three other women (1.6%)
and therefore superior to other agents. In addition, the
experienced uterine hyperstimulation during the 2-h
administration method of controlled release dinoprostone
monitoring period. All newborn infants were healthy and
minimizes the risk of uterine hyperstimulation in compar-
73.1% of the deliveries were vaginal. In a prospective
ison to intra-vaginal or intra-cervical gels as the insert
study, 150 women were given controlled-release dino-
can quickly be removed when labor starts or at the onset
prostone to induce labor in an inpatient setting and were
of any adverse events. The efficacy and safety of con-
compared with those given controlled-release dinopros-
trolled-release dinoprostone in an outpatient setting
tone, monitored for 1 h, and then allowed home w4x. The
make the product an appropriate choice for cervical
proportion of inpatients that were in labor or delivered
within 24 h (71%) was similar to the proportion in theoutpatient group (77%). The median times to labor anddelivery were also similar in the two treatment groups,but the proportion of women reporting satisfaction in the
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Chapter 4 Mental disorders among the elderly population in Israel Perla Werner In Israel, as in other countries, the proportion of elderly persons in the population is growing. According to estimates of the Central Bureau of Statistics, the proportion of the population aged 65 and over will rise from 10% in 2005 to 12.3% in 2025 (1). This increase will be accompanied by a sharp rise in
Patient Guide to Spirometry Welcome to Me Cure Healthcare Limited. This information booklet aims to answer questions that you may have about your Spirometry exam. Frequently Asked Questions Purpose Spirometry is the most commonly performed pulmonary function test (PFT). The test can be performed at the bedside, in a physician's office, or in a pulmonary laboratory. It is often