Fluconazole Linked to Increased Risk for Rare Birth Defect

An examination of nearly 1 million birth records revealed a 3-fold increased risk for tetralogy of Fallot among infants whose mothers took fluconazole in the first trimester, according to a study published in the August 29 issue of the New England Journal of Medicine.
The study showed no association between the antifungal and 14 other birth defects previously linked to it. However, Ditte Mølgaard-Nielsen, MSc, from the Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark, and colleagues showed that common therapeutic doses of fluconazole in the first trimester resulted in an adjusted odds ratio of 3.16 (95% confidence interval [CI], 1.49 - 6.71) for tetralogy of Fallot. The absolute risk for tetralogy of Fallot remains small, with an estimated 6.5 excess cases per 10,000 infants exposed to the antifungal (95% CI, 1.5 - 17), the authors report.

transcervical hysteroscopic approach for tubal occlusion with ESSURE and ADRINA devices

Over the past 10 years the transcervical hysteroscopic approach to tubal occlusion has proven to be an excellent option for women seeking permanent contraception. This technique takes advantage of recent innovations, such as miniaturization of endoscopes, continuous flow systems, and advanced cardiovascular technology, to facilitate access and improve the ability to accurately catheterize the fallopian tubes with  the Essure device (Conceptus, Inc) and the Adiana device (Hologic, Inc). (In May 2012, Hologic, Inc withdrew the Adiana Device from the market.) The Essure device has been approved by the US Food and Drug Administration (FDA) since November 2002;

Wiping Mouth and Nose at Birth as Effective as Oronasopharyngeal Suctioning

By Brian Hoyle
BOSTON -- May 3, 2012 -- Comparison of the traditional neonatal
oronasopharyngeal suctioning (ONPS) versus wiping of the mouth and nose has
demonstrated the equivalent outcome in terms of respiratory rate in the first
day after birth, according to a study presented here at the 2012 Pediatric
Academic Societies (PAS).
“Suctioning of neonates is a common procedure throughout the world. It can
reduce airway resistance, stimulate breathing, and prevent aspiration.
Nevertheless, adverse effects of suctioning include apnoea and bradycardia,”
explained John Kelleher, MD, Department of Pediatrics, University of Alabama,
Birmingham, Alabama, on April 29. “Wiping of the mouth and nose as an
alternative to suctioning has been recommended by the [AAP] beginning in 2005.
However, large randomised trials comparing wiping and suctioning have not been
done,” he continued.
The driving hypothesis of this trial was that wiping is equivalent to ONPS in
terms of mean respiratory rate, as judged by a difference of <4 br="" breaths="" min=""> during the first 24 hours after birth. A mean difference of ≥4 breaths/min
would indicate nonequivalence of the approaches.
All newborns aged ≥35 weeks who were delivered at the participating hospital
from October 2010 to November 2011 were eligible for inclusion. Infants were
excluded if they had known congenital anomalies or were not vigourous with
meconium-stained amniotic fluid.
After consent for participation, 503 women were randomised before delivery to
treatment by wiping (intervention group, n = 256) or ONPS (control group, n =
247). The primary outcome was mean respiratory rate recorded manually over 60
seconds at 1, 8, 16, and 24 hours during the first 24 hours after birth. It was
impossible to completely blind those doing the measurements to the study arms.
Secondary outcomes were Apgar scores, delivery room resuscitation, number of
newborns with a respiratory rate >60 breaths/min anytime during the first 24
hours post partum, and admission to the neonatal intensive care unit. Analysis
was by intention to treat.
The mean respiratory rate of the neonates receiving the wipe treatment was
equivalent to the ONPS group of neonates (51 vs 50 breaths/min, respectively;
difference of means = 1 breath/min, 95% confidence interval, -2.2 to 0.2;
P <.001). There was no significant difference between the groups
regarding any of the aforementioned secondary outcomes.
“Our results shown that wiping is equivalent to traditional bulb-and-syringe
suctioning with respect to the mean respiration rate over the first 24 hours
after birth. Wiping avoids the potential adverse effects of suctioning,” said
Dr. Kelleher, adding, “There is no difference regarding prespecified secondary
clinical outcomes,”
“I am perplexed by the use of respiratory rate as the primary outcome,”
commented attendee Lucky Jain, MD, Emory University School of Medicine,
Atlanta, Georgia. “Why not the difference in heart rate or the frequency of
cardiac episodes or something else that is related to the effects of suctioning
or wiping?”
Dr. Kelleher explained that other primary outcomes would have necessitated a
much larger and more expensive study and that the choice reflected these
considerations.
The use of ONPS as the control, rather than no treatment, was also questioned,
in light of the recognition of the adverse effects of ONPS.
“The lung fluid or the fluid that we see in the nares or the oropharynx is not
important in terms of suctioning. I hope that future trials would be wiping
versus no wiping instead of wiping versus suctioning,” said Dr. Jain.
While acknowledging the latter criticism, Dr. Kelleher argued that the study
reflects the reality, at least in the United States, of the delivery room.
“I agree that previous publications have shown that suctioning can have
deleterious consequences,” said Dr. Kelleher. “Nevertheless, it’s been my
experience that in the United States, suctioning is still firmly ingrained in
neonatal care. That is why we chose to use it in comparison with wiping,” he
explained.
The Pediatric Academic Societies (PAS) is cosponsored by the American Pediatric
Society (APS), the Society for Pediatric Research (SPR), the Academic Pediatric
Association (APA), and the American Academy of Pediatrics (AAP).

[Presentation title: A Randomized Controlled Equivalency
Trial of Oronasopharyngeal Suctioning Versus Wiping the Mouth. Abstract 2170.5]

Oronasopharyngeal suction versus wiping of the mouth and nose at birth:

Oronasopharyngeal suction versus wiping of the mouth and nose at birth: a randomised equivalency trial.

Kelleher J, Bhat R, Salas AA, Addis D, Mills EC, Mallick H, Tripathi A, Pruitt EP, Roane C, McNair T, Owen J, Ambalavanan N, Carlo WA.

Source

Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA.

BACKGROUND:

Wiping of the mouth and nose at birth is an alternative method to oronasopharyngeal suction in delivery-room management of neonates, but whether these methods have equivalent effectiveness is unclear.

METHODS:

For this randomised equivalency trial, neonates delivered at 35 weeks' gestation or later at the University of Alabama at Birmingham Hospital, Birmingham, AL, USA, between October, 2010, and November, 2011, were eligible. Before birth, neonates were randomly assigned gentle wiping of the face, mouth (implemented by the paediatric or obstetric resident), and nose with a towel (wipe group) or suction with a bulb syringe of the mouth and nostrils (suction group). The primary outcome was the respiratory rate in the first 24 h after birth. We hypothesised that respiratory rates would differ by fewer than 4 breaths per min between groups. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01197807.

FINDINGS:

506 neonates born at a median of 39 weeks' gestation (IQR 38-40) were randomised. Three parents withdrew consent and 15 non-vigorous neonates with meconium-stained amniotic fluid were excluded. Among the 488 treated neonates, the mean respiratory rates in the first 24 h were 51 (SD 8) breaths per min in the wipe group and 50 (6) breaths per min in the suction group (difference of means 1 breath per min, 95% CI -2 to 0, p<0 p="">

INTERPRETATION:

Wiping the nose and mouth has equivalent efficacy to routine use of oronasopharyngeal suction in neonates born at or beyond 35 weeks' gestation.
Lancet. 2013 Jul 27;382(9889):326-30. doi: 10.1016/S0140-6736(13)60775-8. Epub 2013 Jun 3.

Sildenafil citrate in the treatment of pain in primary dysmenorrhea: RCT

Human Reproduction, 08/16/2013  Clinical Article

Dmitrovic R et al. – A number of medications have been investigated to improve the treatment options for PD, but most have proven unsuccessful or to have an unfavorable risk/benefit ratio. Since PD is a condition that most women suffer from and seek treatment for at some point in their lives, this study offers hope that vaginal sildenafil citrate is a safe and effective option for patients who do not desire or are unresponsive to treatments now available on the market.
Methods

• A double–blind, randomized, controlled trial comparing vaginal preparation of sildenafil citrate (100 mg single dose) to a placebo in 62 PD patients at the time of painful menstruation was conducted.
• The primary outcome was total pain relief over 4 consecutive hours (TOPAR4) comparing sildenafil citrate to placebo, where higher TOPAR4 scores represent better pain relief.
• Secondary outcomes were pain relief as measured by the visual analog scale (VAS) and uterine artery pulsatility index (PI).
• Subjects were recruited from December 2007 to January 2011.
• The trial was stopped due to closeout of the funding for the study.
• Participants were women in good health, were aged 18–35 years and suffered from moderate to severe PD.
• They were randomized to either vaginal placebo or 100 mg vaginal sildenafil citrate in a 1:1 ratio using random permuted blocks having a block size of 4.
• At baseline and 1, 2, 3, and 4 h post–treatment, patients were asked to provide assessment of their degree of pain using two scales: (i) pain on the 5–level ordinal scale used for TOPAR4 calculation and (ii) pain level on the VAS.
• The study ended 4 h after treatment initiation.

Results

• Twenty–five subjects completed the study.
• Using the TOPAR4 score, the sildenafil citrate group had significantly better pain relief compared with the placebo group [mean (SD): 11.9 (3.2) versus 6.4 (2.1), respectively; difference in means = 5.3; 95% CI: (2.9,7.6); P < 0.001)].
• On the VAS, sildenafil citrate provided better pain relief than placebo at each time point.
• At the 2–h time point, the PI was significantly lower in the sildenafil citrate group compared with the placebo group [mean (SD): 1.6 (0.6) versus 2.3 (0.5), respectively; difference in means = –0.7; 95% CI: (–1.2, –0.1); P = 0.01)].

Mifepristone to treat uterine myoma:

Mifepristone versus placebo to treat uterine myoma: a double-blind, randomized clinical trial                                                                           Esteve Carbonell JL et al. – This study aimed to evaluate the efficacy, safety, and quality of life of 5 mg mifepristone per day compared with a placebo in treating uterine fibroids. The 5 mg dosage of mifepristone presented significantly superior efficacy compared to the placebo.

Methods

• A randomized, double–blind clinical study.
• Eusebio Hernández Gynecology and Obstetrics Teaching Hospital, Havana, Cuba.
• One hundred twenty–four subjects with symptomatic uterine fibroids.
• One daily capsule of 5 mg mifepristone or a mifepristone placebo over 3 months.
• Changes in fibroid and uterine volumes, changes in symptom prevalence and intensity, and changes in quality of life.

Results

• Three months into treatment, fibroid volume was reduced by 28.5% in the mifepristone group with an increase of 1.8% in the placebo group (P = 0.031).
• There were significant differences between the groups with respect to pelvic pain prevalence (P = 0.006), pelvic pressure (P = 0.027), rectal pain (P = 0.013), hypermenorrhea (P < 0.001), and metrorrhagia (P = 0.002) at the end of treatment.
• Amenorrhea was 93.1% and 4.3% in the mifepristone and placebo groups, respectively (P < 0.001).
• Treatment side effects were significantly greater in the mifepristone group.
• Estradiol levels did not differ significantly between the placebo and mifepristone groups at the end of treatment.
• Improvement in quality of life was significantly greater in the categories of "symptoms" (P = 0.004) and "activity" (P = 0.045) in the mifepristone group.