Friday, June 30, 2017

In case you missed it: Here are the top 5 posts this month.

Vaccinations before, during and after pregnancy.
Women who are planning to become pregnant should make sure that they are up to date on their immunizations. This will protect them and the unborn child from many diseases.

The measles, mumps, rubella, and chickenpox (varicella) vaccines are particularly important for women of childbearing age, as these cannot be given when pregnant. If a woman is infected with any of this in pregnancy, particularly first trimester, it results in adverse pregnancy outcome.

New slender hand-held pocket colposcope will make cervical cancer screening comfortable and accessible for more women.
Uncomfortable speculums and high cost colposcopes can soon be replaced by a simple hand-held device for cervical cancer screening say researchers at Duke University.

The “pocket colposcope” is a slender wand that can connect to many devices, including laptops or cell phones. It can be used by woman for self-screening in low resource settings, including some areas in US.

FDA warning against domperidone use by lactating mothers to increase milk production.
The dopamine receptor antagonist domperidone, which may increase milk production in lactating women, is associated with serious cardiac risks, and should not be used for lactation enhancement, according to a commentary published in the June issue of Obstetrics and Gynecology.

What is best for Cesarean Antisepsis? Chlorhexidine-Alcohol versus Povidone-Iodine.
Chlorhexidine-Alcohol is not superior to Povidone-Iodine in reducing the rate of surgical site infection in Cesarean section reports the results of Chlorhexidine-Alcohol Versus Povidone-Iodine for Cesarean Antisepsis (CAPICA) Trial published ahead of print in American Journal of Obstetrics and Gynecology.

Wound infection after a cesarean section (CS) is a major cause of maternal morbidity, lengthy hospital stays and increased medical cost. The rate of surgical site infection after cesarean section range from 3% to 15%.

Making the eggs young again: A new successful solution to age related infertility for $100,000
In 1859, Charles Darwin published his ground-breaking theory ‘On the Origin of Species by Means of Natural Selection which says that “It is not the strongest of the species that survive, nor the most intelligent, but those who learned to collaborate and improvise most effectively have prevailed.” It immediately took the scientific world by storm.

And now a new startup called Darwin Life is pushing the boundaries in the field of assisted reproductive technology by offering controversial fertility treatment to older women to help them get pregnant. 

Thursday, June 29, 2017

Neither 17α-hydroxyprogesterone caproate nor vaginal progesterone is useful for maintenance tocolysis in women with short cervix.

Intravaginal or Intramuscular progesterone used as maintenance therapy did not prolong pregnancy in women with arrested preterm labor and short cervix, reports a study published in July issue of Journal Obstetrics and Gynecology. 
This was a randomized, multi-center trial, conducted at five University hospitals  at University of Modena and Reggio Emilia, Italy across a period of 5 years. The researchers recruited 257 women between 22 0/7 and 31 6/7 weeks of gestation, who had a previous episode of preterm labor that responded well to tocolytics.

Other demographics were similar between the study participants.

All these women had short cervical length of 25 mm or less. The women were randomized to three groups to receive 200 mg of vaginal progesterone or 341 mg per week of intramuscular 17α-hydroxyprogesterone caproate or to an observation group.

The researchers were looking at number of preterm births averted due to use of vaginal or intramuscular progesterone.

Interim analysis was triggered after a specific percentage of preterm labor were observed, and the trial was stopped for futility. A P value of <.025 was defined as statistically significant.

After statistical analysis, it was found that progesterone was not efficient in prolonging pregnancy. 23% of women in 17α-hydroxyprogesterone caproate group had preterm births as compared to 22% in the control group (P=.949).

39% of women who was treated with vaginal progesterone underwent preterm labor as compared to 22% in the control group (P=.027).

The authors concluded that progesterone administered by either route did not prevent preterm labor in women with arrested incidence of preterm labor and short cervix.

Wednesday, June 28, 2017

RealMom, a simulator mimicking real world Vaginal Birthing Techniques launched

courtesy:Operative Experience

Operative Experience, a company pioneering in high-fidelity human patient simulators announced the launch of RealMom, a groundbreaking full body simulator that will revolutionize the way physicians learn the skill of vaginal births.

The RealMom mannequin features very soft, natural looking anatomical parts with an active birth canal and human like cervix that undergo effacement and dilatation. The model baby is full term infant and the model mother has a uterus, placenta, and umbilical cord, amniotic fluid reservoir as well as a fundus that can be massaged.

Jane O’Reilly, Global VP of Sales for OE said in a press release, “RealMom is simply the most exciting development in labor and delivery training to date. RealMom looks real and feels real and provides learners with the most realistic and lifelike simulated birthing experience out there. It’s really one of a kind.”

The physician can get ‘real life’ training in conducting vaginal births as well as more complicated procedures, such as breech, shoulder dystocia, nuchal cord, cord prolapse, and assisted delivery with forceps and vacuum devices.

RealMom can be hooked to any computer browser, iOS or Android tablet device and can be operated wirelessly. Various parameters such as cervical dilatation and effacement, fetal heart rate (FHR), contractions, tones, maternal blood pressure and Oxygen concentration can easily be programmed to train physicians to deal with challenging and life-threatening obstetrics scenarios.  

The simulator can even mimic the most dreaded obstetric complication of post-partum hemorrhage, with the ability to control the amount of blood lost and manage it effectively with a Bakri or Ebb balloon.

It is reasonably priced as compared to other simulators with no complicated programming and no simulator downtime.

Other simulators available with Operative Experience are Fetal Extraction Simulator, Postpartum Hemorrhage Control Trainer, Emergency Hysterectomy Trainer, Emergency C-Section Delivery Simulator and C-Section Skills Trainer.

Instructor Control Software

Tuesday, June 27, 2017

Another novel drug for female hypoactive sexual desire shows promising results in phase III trials.

Women who are distressed because of hypoactive sexual desire could soon find relief because of a new drug, Bremelanotide (BMT).

Female Sexual Dysfunctions (FSD) encompasses multifactorial entities affecting about 10% of the population. Few treatment options exist to treat this condition.

auto-injector for Bremelanotide, Palatine Technologies

Bremelanotide, is a novel cyclic 7-amino acid melanocortin-receptor agonist with a high affinity for the type-4 receptor. It increases levels of dopamine and norepinephrine in medial preoptic area, thereby,  modulating the  brain pathways involved in sexual response.

The results of two phase III trials were presented as a poster at the American Society of Clinical Psychopharmacology (ASCP) annual meeting, Florida May 29 – June 2, 2017.

The RECONNECT study comprises 2 Phase 3, multicenter trials involving 1,247 premenopausal women with low sexual desire. The women were in stable, monogamous relationship.

In this intent to treat study, the women underwent a month screening period and a month of treatment with a placebo so that the investigators could have an idea about various baseline scores.

Women were randomized to nearly 6 months of treatment with either self-administered BMT (1.75 mg) or placebo subcutaneously using an auto-injector, as-desired, prior to sexual activity. This was followed by an open label 52 weeks extension.

The control and cases were assessed on various indices like the desire domain of the Female Sexual Function Index (FSFI-D) and the Female Sexual Distress Scale-Desire/Arousal/Orgasm (FSDS-DAO) score for feeling bothered by low sexual desire; FSDS total and bother scores; Women’s Index of Treatment Satisfaction (WITS-9) score; self-assessment of benefit, and satisfying sexual event (SSE) items of the Female Sexual Encounter Profile-Revised (FSEP-R).

Besides significantly improving the scores of all the indices, the women on BMT showed a significant improvement in number of satisfying sexual events, arousal, lubrication and orgasm. The women also reported feeling less distressed and more satisfied with their sexual relations.

Most common side effects encountered were nausea, vomiting, flushing, or headaches resulting in 18% of women to discontinue the drug as compared to 2% in placebo group.

The average age of the study participants was 39 years, more than 80% were white with a mean BMI of 28.7 kg/m2 and most of them were suffering from hypoactive sexual desire disorder (HSDD) with decreased arousal.

In 2015, FDA approved the little pink pill or flibanserin (Addyi) a serotonin 1A receptor agonist and a serotonin 2A receptor antagonist, as the first treatment for hypoactive sexual desire disorder in premenopausal women.

The authors concluded, “Treatment with BMT is associated with clinically meaningful and statistically significant improvement in desire and a decrease in distress; both hallmark characteristics of HSDD. BMT is an efficacious treatment for key aspects of sexual function — desire, arousal, lubrication, and orgasm, in premenopausal women.”

All the poster abstracts at the conference can be accessed here.

Monday, June 26, 2017

ACIP broadens its policy for Influenza vaccination in pregnant women and children
The CDC’s Advisory Committee on Immunization Practices (ACIP) passed new draft recommendations for influenza vaccine in children and pregnant women.

The basic recommendations for Influenza vaccination for 2017-2018 flu season would remain the same.

A major update was allowing of any licensed, recommended and age-appropriate trivalent or quadrivalent inactivated influenza vaccine (IIV) or recombinant influenza vaccine (RIV) for pregnant women as against the previous recommendation which only specified inactivated vaccine (IIV).
Some of the committee members were uncertain about safety of recombinant influenza vaccine (RIV), Flublok.

Lisa Grohskopf, MD, MPH, medical officer of the influenza division of the CDC, did acknowledge that there were more data on the safety of inactivated influenza vaccines, she asserted to the committee that “the general overall safety profile of Flublok in comparison to inactivated vaccines is reassuring.”

In addition, the committee advised against use of quadrivalent live attenuated influenza vaccine (LAIV4), which is given by nasal spray, in the coming season because of its declining efficacy. The vaccine failed to show any statistically significant benefits in pediatric age group during last three seasons.

Also, Afluria, an inactivated influenza vaccine in both trivalent and quadrivalent formulas can now be safely administered to children aged 5 years and above instead of 9 years and above. This is because similar rates for febrile seizures and reactions were observed in both the age range.

The director of the CDC and the U.S. Department of Health and Human Services will look into the approved recommendations.  Once reviewed and approved, the final recommendations will be published in the CDC’s Morbidity and Mortality Weekly Report.

ACOG updates its mammography screening guidelines; stressing emphasis on shared decision making.

courtesy: CBS news

ACOG today released a committee opinion updating its guidelines on Breast Cancer Risk Assessment and Screening in Average-Risk Women. This replaces the Practice Bulletin Number 122, August 2011.

This recent update lays emphasis on joint decision making, involving the patient and her physician.
Women who are average risk for breast cancer should be offered her first screening mammogram at age 40. No additional benefits are gained by starting screening before age 40. If women have not begun screening in 40s, they should begin screening mammography by no later than age 50 years.

The physician should have detail conversation with the patients about potential benefits and harm. For women who begin screening in early 40s, the benefits derived are smaller as compared to women who are older. But, the women can make an informed decision and opt for regular screening or wait till they reach 50s.

Average risk women should undergo screening mammography every 1 or 2 years, based on shared decision. “Biennial screening mammography, particularly after age 55 years, is a reasonable option to reduce the frequency of harms, as long as patient counseling includes a discussion that with decreased screening comes some reduction in benefits,” says the bulletin. 

The screening should continue till 75 years of age. Screening past 75 years depends on individual patient characteristics like her general health and expected life span.

The U.S.Preventive Services Task Force recommends that women should start regular mammograms at 50, and that women in their 40s should make an individual decision about whether or not to screen. The American Cancer Society says screening should be offered starting at age 40, and outright recommends starting at 45. And the National Comprehensive Cancer Network, an alliance of major cancer centers, recommends starting at 40.                                    

Recommendations from various organizations compared. Adapted from ACOG Bulletin.

Click to Enlarge 

The different recommendations stem from a desire of all these groups to balance the benefits and harms of mammography and the way these societies interpret the data.

Christopher Zahn, vice president of practice activities at ACOG says,” "All three [schedules] are reasonable approaches to take, a patient's preferences and values need to be an important part."
Harms of screening mammography are anxiety and distress, false positive results, unnecessary biopsy and surgeries and radiation exposure.

Based on limited or inconsistent scientific evidence, Breast Self-Examinations (BSE) are not recommended because there is a risk of harm from false-positive test results and a lack of evidence of benefit. Screening clinical breast examination may be offered to these average risk women after a detailed discussion about uncertainty of additional benefits and the possibility of adverse consequences of clinical breast examination. The frequency of screening clinical breast examination is every 1–3 years for women aged 25–39 years and annually for women aged 40 years and older are reasonable.

Screening clinical breast examination is an important part of evaluation of high risk women and women with symptoms.

It should be noted that all these recommendations apply to average risk women. Women who are high risk should follow different set of guidelines as advised by their physicians. The high-risk factors for developing breast cancer according to the bulletin are female sex and advancing age, family history, BRCA mutation, dense breast, nulliparity, older age at first birth, older age at menopause, younger age at menarche and receiving therapeutic ionizing radiations.

The full text of  committee opinion can be accessed here.

Saturday, June 24, 2017

Dark color hair dyes and relaxer linked to breast cancer.

New research suggests that women of color who use the dark brown or black hair dyes are at increased risk of cancer while use of straighteners and conditioners increase the odds in white women.

The study was published online 09 June 2017 in journal Carcinogenesis.

The safety of hair colors has been debated for years, but no studies have demonstrated conclusively, that using hair dye leads to increased risks of cancer or other diseases.

Some observational and epidemiological studies have found increased incidence of bladder cancer in hairdressers and barbers.

It is estimated that nearly 66%- 70% of women in US use some kind of hair color.

Nearly 5000 different chemical compounds are used to make the dyes. Permanent hair dyes occupy 80% of market and are made with aromatic amines, which are known to be carcinogenic in animals.

The study by Rutgers University looked into data from 4,285 African-American and Caucasian women with ages between 20-75 years. Nearly 2,280 were breast cancer survivors.

Besides, looking into the patient’s demographics, lifestyle and hormone use, they also looked into family and personal history. But the study specifically looked into history of use of hair products like hair dyes, chemical relaxers and cholesterol or placenta-containing conditioners and incidence of breast cancer. 

Cholesterol is marketed as a moisture restorer, and placenta is sold as a hair repairer.

The women who were breast cancer survivors were labelled as cases (2,280) whereas, the rest 2,005 women constituted the control group.

The study found out that African American women(AAs) who used dark color hair dye where at 51 % greater risk of developing breast cancer. When use of dark shades and greater frequency of dying the hair was combined, the risk of getting ER+ cancer increased by 72%.

White women who used relaxer were at 74% increased risk of breast cancer while combined use of relaxer and hair dye increased the risk 2.5 times. Dark dyes were associated with ER+ disease and relaxer was liked to ER- disease.

"One hypothesis is that the chemical composition of hair products marketed for and used among whites may differ from the products marketed for use by African-Americans," Lead author Llanos said. "More research is needed to determine specifically which compounds and chemicals are dangerous and even which specific consumer products and brands contain those chemicals."

Among the control arm of the study, greater percentage of white women (58%) used hair dye as compared to AAs (30%), while AAs women used more relaxer and deep conditioner.

Adana Llanos cautioned, "Our findings do not suggest that simply using hair dyes, relaxers or both will cause a woman to get breast cancer. The reality is that we regularly encounter a variety of harmful exposures, which we have no control over."

However, she added, "we should limit or reduce the possibility of harmful exposures when we are able to do so."

The authors concluded in a press release, “Our findings highlight the need for further examinations of the link between the use of hair products as important exposures that may contribute to the development of breast cancer, as well as ways to reduce the associated risks.”  

Friday, June 23, 2017

Novartis Breast Cancer drug Kisqali wins market approval in European Union as first-line treatment for HR+/HER2-

European Medicines Agency (EMA) panel approves Kisqali (CDK4/6 inhibitor ribociclib) in combination with hormone therapy as a first-line treatment for hormone receptor positive, human epidermal growth factor receptor-2 negative locally advanced or metastatic breast cancer.
FDA has already cleared Kisqali in March 2017.

This approval challenges the market share of rival, Pfizer's Ibrance which is in market since 2015.

Kisqali is sold in US packaged with aromatase inhibitor letrozole but, the Committee for Medicinal Products for Human Use (CHMP) recommends combining Kisqali with any aromatase inhibitor like letrozole, anastrozole or exemestane, giving the physician the discretion to select the therapy they believe is most appropriate for each individual patient.

This approval is based on results of a pivotal Phase III  MONALEESA-2 trial that showed Kisqali plus letrozole reduced risk of disease progression or death by 44% over letrozole alone among postmenopausal women with HR+/HER2- advanced breast cancer.

After nearly one year of additional follow-up, Kisqali plus letrozole demonstrated median progression-free survival (PFS) of 25.3 months compared to 16.0 months for placebo in combination with letrozole.

Bruno Strigini, CEO, Novartis Oncology said, "This positive CHMP opinion brings us one step closer to improving the lives of women diagnosed with advanced or metastatic breast cancer throughout Europe. There is currently no cure for advanced breast cancer, and approximately 30 percent of those affected by early-stage breast cancer will go on to develop advanced disease.”

FDA Clearance of Interson SiMPLi™ Series linear and convex USB array probes will revolutionize the future of Ultrasound.

FDA today announced that it has cleared Interson SiMPLi™ Series linear and convex USB array probes to be used for medical application. 

Both linear and convex array probes are used for point of care USB Ultrasound and can directly be plugged into Windows OS tablets, laptops, and desktops to display real-time ultrasound images at resolution and detail that were, until now, only available on high-end ultrasound systems.

These probes are lightweight, easy to handle and can be easily brought to bedside or can be transported to any location outside the office for point of care imaging.

Roman Solek, President & CEO said, “These new array probes continue on our company vision to bring affordable, high-quality ultrasound imaging to every medical professional. SiMPLi Series is the most portable, real-time ultrasound solution available. We are proud to keep pushing the market forward on performance and practicality while also driving the cost lower.”

These probes can be used for wide varieties of medical sub specialties like women’s health, rehab facilities, primary care, hospice care and telemedicine.

These probes also allow remote ultrasound viewing. Healthcare personal at the remote location connects their USB ultrasound probe and streams their local view to the central hospital. The experts at the central facility can provide a real-time diagnosis.

If real time remote viewing is not possible, the local exam may be saved and forwarded to an expert for analysis. Saving a simple jpeg often is not enough for the expert to provide a diagnosis. Save all of the exam’s frames by selecting Cine Save and then send the frames to the expert. The expert can load the Cine file into their SeeMore application and adjust gains, intensity, and contrast to optimize the view. They can add annotations and make measurements. The expert can then save and archive the best frame of the exam.

The probes were also displayed at the American Telemedicine trade show in Orlando Florida.

"Our SiMPLi probes appear as a connected webcam to the system. Telemedicine can now realize all of the benefits of ultrasound diagnostics without having to connect to a floor standing or cart mounted ultrasound.” says Bill Wiedemann, Director Systems Integration.

Ultrasound is the next revolution in Healthcare. 

Image courtesy:

Thursday, June 22, 2017

Breast and Ovarian Cancer risk with BRCA mutation precisely quantified for first time.

Women with BRCA1 and BRCA2 mutations have an average risk of 72% and 69% respectively of developing breast cancer by the age of 80. The corresponding life time risks for ovarian cancer is 44% for BRCA1 and 17% for BRCA2 says the results of first ever prospective study published June 20, 2017 in JAMA.

BRCA1 was first discovered 23 years ago in 1994 by Mary-Claire King, professor of genome sciences and of medicine at University of Washington, BRCA2 followed later.

Today it is an established fact that women who test positive for BRCA mutation are not only at increased risk for breast cancer but also at increased risk for ovarian cancer, but all the studies so far have been retrospective in nature.

According to NIH, together, BRCA1 and BRCA2 mutations account for about 20 to 25 percent of hereditary breast cancers and about 5 to 10 percent of all breast cancers. Similarly, mutations in BRCA1 and BRCA2 account for around 15 percent of ovarian cancers.

This current prospective study was made possible by collaboration between researchers at Australia, Europe and USA. The team recruited 10,000 women with BRCA1(6036) and BRCA2 (3820) mutations from 1997 to 2011 from various registries across U.K, Netherlands and France.

Some very important findings of the study are:

Women with BRCA1 and BRCA2 mutations have an average risk of 72% and 69% respectively of developing breast cancer by the age of 80. The corresponding life time risks for ovarian cancer is 44% for BRCA1 and 17% for BRCA2 

Of nearly 10,000 women, 5046 were unaffected and 4810 were diagnosed with breast or ovarian cancer or both at baseline.

At follow up, 11% of women developed breast cancer, 2% developed ovarian cancer and 11% were affected with contralateral breast cancer.

The median age of women at diagnosis of the breast and ovarian cancer was 38 years and 47 years for contralateral breast cancer.

Another important finding in the study was, breast cancer risk for women with faults in BRCA1 increases till age 40, and for BRCA2 it increases till age 50 years of age and then remains constant high level for the rest of their lives.

The risk of getting a diagnosis of second breast cancer for contralateral breast up to 20 years of first cancer was 40% for BRCA1 carriers and 26% for BRCA2 carriers.

The incidence of ovarian cancer increased with age up to 61 to 70 years for both mutations but was about 3 times higher for BRCA1 carriers.

The risk of breast cancer nearly doubles for both BRCA1 and BRCA2 carriers, with an increase in number of first and second-degree relatives having breast cancer.

The lead author, Antonis Antoniou, PhD, from the Centre for Cancer Genetic Epidemiology, University of Cambridge, United Kingdom explained "This is important information to inform the clinical management also of women with mutations over the age of 60 years old."

The study also revealed that the risk for breast cancer is stratified according to location of the mutation in certain regions, but location did not appear to affect the risk for ovarian cancer.

Dr Antoniou said, "The results from this study show clearly, and again for the first time in a prospective study, that the cancer risks for women with BRCA1 and BRCA2 mutations depend on the position of the specific fault within the gene."

"Moreover, the study provides for the first-time cancer risk estimates for mutations at different locations," he added. "Therefore, mutation location can now be confidently incorporated in the risk assessment of women with BRCA1 and BRCA2 mutations."
This study has important implications for physicians in clinical practice as they can improve the advice and counselling, precisely pointing at the risk faced by the women. It also emphasizes the importance of family history and following the risk reducing life style changes.

Dr Antonis Antoniou says, "We have been able to provide the most precise estimates of age-specific risks to date. These should provide more confidence in the counseling and clinical management of women with faults in the BRCA1 and BRCA2 genes."

The strengths of the study are its prospective nature, prolong follow-up and large data base because of sharing of data across multiple centers.

Wednesday, June 21, 2017

Oophorectomy during premenopausal hysterectomy: Evaluating the prevalence

Nearly 1 in 3 women undergo oophorectomy during premenopausal hysterectomy in absence of appropriate indication, reports a study published ahead of print May 8, 2017 in North American Menopausal Society (NAMS) journal Menopause.  

Bilateral Oophorectomy before the age of menopause is associated with increased the risk of parkinsonism, cognitive impairment or dementia, and anxiety or depression. These women, particularly those who were below 45 years at the time of oophorectomy face 67% increase risk of all-cause mortality.

Analysis of data from Nurses’ Health Study also revealed that in 24 years follow up, women who were below 45 years at the time of surgery had 17% increased chances of non-fatal CHD.

In-fact, evidence suggests that at no age, oophorectomy shows any survival benefit.

The current study was a cross sectional analysis of data-base from California Office of Statewide Health Planning Development during a span of 6 years. (2008-2011).

Appropriate indications for oophorectomy with hysterectomy in the study were ovarian cyst, breast cancer susceptibility gene carrier status, and other diagnoses.

A total of 57,776 benign premenopausal hysterectomies with oophorectomies were performed during the 6-year study period.

Out of these 57,776, 21,783 were found to be ‘inappropriate’ as no indication was found among the records.

Through the 6 years of study, the researchers observed a decreasing trend to perform oophorectomy with hysterectomy, but the percentage remain unchanged.

Women with Hispanic and African American ethnicity were more likely to undergo oophorectomy as compared to white women. (P < 0.001).

The authors concluded that, “the rate of inappropriate oophorectomy in California has not changed since the 2008 American College of Obstetricians and Gynecologists guidelines, and over one-third undergo oophorectomy without an appropriate indication documented”.

What does this mean for daily clinical practice?

Prophylactic Hysterectomy should only be done in cases were preponderance of evidence suggests that it will be beneficial to patient.

All patients should be counselled in detail before the surgery regarding the pros and cons of retaining the ovaries at the time of hysterectomy.

ACOG also recommends in favor of retaining normal ovaries in premenopausal women who are not at increased genetic risk of ovarian cancer.

In women with endometriosis, pelvic inflammatory disease, and chronic pelvic pain a decision should be taken after balancing the risk of reoperation vs the benefits of ovarian retention.

ACOG further recommends considering prophylactic salpingectomy in those women who are at population risk for ovarian cancer, and who opt for retention of ovaries.

Tuesday, June 20, 2017

Even low levels of prenatal alcohol exposure will be reflected on the baby’s face

A small amount of drinking by an expectant mother will show itself by changes in child's craniofacial shape at 12 months reports a study published online in JAMA.

Guidelines from physicians and experts around the world advise against drinking in pregnancy.

The ACOG writes that “there is no safe level of alcohol use during pregnancy,” as also UK’s Department of health which previously advised pregnant women to limit themselves to 1 to 2units once or twice per week. Now the updated guidelines in January 2016, advises even against a small amount of drinking.

The concurrent occurrence of 3 classic facial features( small palpebral fissure, a smooth philtrum, and a thin upper lip is hallmark of fetal alcohol syndrome (FAS). If only 2 features are concurrently present, the condition is labelled as partial FAS.

Some fetuses also present with heavy prenatal alcohol exposure (PAE), but no evidence of FAS or partial FAS.

The study by Evelyne Muggli and her colleagues, shed some light on relationship between low alcohol exposure and changes in child craniofacial shape.

The facial measurements were performed at 12 months of age with the help of 3-D images.

A total of 415 white children were included in the study over a period of 3 years. The mothers were recruited early in first trimester and the amount of alcohol consumed was well documented throughout the pregnancy, including records of drinking even before the pregnancy was documented.

Other confounders which can affect the development of face were taken into consideration.

The authors found consistent association between craniofacial shape and PAE, regardless of whether the exposure occurred early in pregnancy or throughout the pregnancy.  

The faces of affected children had difference in midface, nose, lips, and eyes regions. They also had mid-facial hypoplasia, with shorter and upturned nose. Further analysis showed that different regions of face were affected according to level of drinking in first trimester: in low exposure (forehead), moderate to high exposure (eyes, midface, chin, and parietal region), and binge-level exposure (chin) were affected.

According to a survey, 40% of OB-GYN advice the patients that some amount of alcohol in pregnancy is fine. According to CDC’s Morbidity and Mortality Weekly Report (MMWR), One in 10 pregnant women in the United States reports drinking alcohol and 3.1 percent of pregnant women report binge drinking – defined as 4 or more alcoholic beverages on one occasion.

The study strength’s lies in well documentation of exposure and outcome. The clinical implications of changes in craniofacial features is not yet known but, the study provides evidence in favor of total abstinence of alcohol during pregnancy.

Monday, June 19, 2017

What is best for Cesarean Antisepsis? Chlorhexidine-Alcohol versus Povidone-Iodine.

Chlorhexidine-Alcohol is not superior to Povidone-Iodine in reducing the rate of surgical site infection in Cesarean section reports the results of Chlorhexidine-Alcohol Versus Povidone-Iodine for Cesarean Antisepsis (CAPICA) Trial published ahead of print in American Journal of Obstetrics and Gynecology.

Wound infection after a cesarean section (CS) is a major cause of maternal morbidity, lengthy hospital stays and increased medical cost. The rate of surgical site infection after cesarean section range from 3% to 15%.

Researchers and investigators are always looking at ways to minimize the surgical site infection in cesarean section. Numerous interventions have been proposed from changing gloves at timeof abdominal closure to preoperative antibiotic prophylaxis.

But, no previous randomized control trial has compared chlorhexidine-alcohol to povidone-iodine aqueous scrub and paint in reduction of cesarean-related surgical site infections (SSIs).

The CAPICA Trial is the first single center pragmatic randomized trial conducted at urban tertiary care center over a period of 3+ years. The trial compared efficacy of 26ml chlorhexidine-alcohol applied as single step versus 236mL povidone-iodine aqueous scrub as preoperative skin preparation in cesarean section in reducing the SSIs.

The trial recruited 932 study participants, who were 18 years or older, with no chorioamnionitis, non-allergic to povidone iodine or alcohol and who were ready to be compliant with the follow up protocols.

Women who had elective cesarean section as well as those who had emergency cesarean sections were included in the study. 

Statistical analysis was performed to look at categorical and continuous outcomes in comparing incidence of superficial or deep SSIs or endometritis as defined by CDC, including allergic skin reactions, hematomas, wound separation, dehiscence.

461 women were assigned to chlorhexidine-alcohol, and 471 assigned to povidone-iodine group. About 97% to 99% women came for follow up at 30 days. SSIs occurred in 7% of women in the povidone-iodine group vs 6.3% chlorhexidine-alcohol group(p=0.38).

Individually the difference in sub-component of infections are: superficial surgical site infection (4.6% v 5.5%, p=0.55), deep surgical site infection (0.0% v 0.4%; p=0.50), and endometritis (1.7% v 1.1%; p=0.42) in chlorhexidine-alcohol versus povidone-iodine arms respectively.

The authors concluded that use of chlorhexidine-alcohol does not results in less frequent infections as compared to using povidone-iodine.

Sunday, June 18, 2017

FDA warning against domperidone use by lactating mothers to increase milk production.

The dopamine receptor antagonist domperidone, which may increase milk production in lactating women, is associated with serious cardiac risks, and should not be used for lactation enhancement, according to a commentary published in the June issue of Obstetrics and Gynecology.

Catherine A. Sewell, MD, MPH, from the U.S. Food and Drug Administration in Silver Spring, Maryland, and colleagues published this commentary to discuss the safety issues associated with use of domperidone and to raise the awareness among healthcare providers in US against the use of domperidone as galactagogue.

Although domperidone is approved in several countries outside the U.S. to treat certain gastric disorders, it is not approved in any country, including the U.S., for enhancing breast milk production in lactating women and is also not approved in the U.S. for any indication.

According to a release by FDA “The serious risks associated with domperidone include cardiac arrhythmias, cardiac arrest, and sudden death. These risks are related to the blood level of domperidone, and higher levels in the blood are associated with higher risks of these events.”

The U.S. Food and Drug Administration (FDA) issued an import alert in 2004, updated in 2016, explaining that the importation of domperidone is illegal with limited exceptions, including when imported pursuant to an investigational new drug application.

A public safety warning has already been issued for domperidone, as the drug is sometimes illegally obtained from other countries and used to enhance milk production.

Only scant evidence exists to support its use as lactation enhancer but considerable information exists on domperidone's cardiac risks including QT prolongation, torsades de pointes, and sudden cardiac death, including among lactating women.

“In light of limited efficacy data that do not offset safety concerns from a public health perspective, we continue to caution against using domperidone for lactation enhancement,” the commentary states.

The FDA warning release can be accessed here.

FDA approves first cancer treatment drug based on tumor biomarker, instead of tumor origin.

courtesy: Merck 
In an important announcement, The U.S. Food and Drug Administration (FDA) granted accelerated approval to Merck’s Keytruda (pembrolizumab) for treatment in patients whose cancers have a specific genetic feature (biomarker).

This is the first time the agency has approved a cancer treatment based on a common biomarker rather than the location in the body where the tumor originated.

Keytruda (pembrolizumab) is indicated for the treatment of adult and pediatric patients who have unresectable or metastatic solid tumors that have been identified as having a biomarker referred to as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR).

Tumors with these biomarkers are most commonly found in colorectal, endometrial and gastrointestinal cancers, but also less commonly appear in cancers arising in the breast, prostate, bladder, thyroid gland and other places.

“This is an important first for the cancer community,” said Richard Pazdur, M.D., acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research and director of the FDA’s Oncology Center of Excellence. “Until now, the FDA has approved cancer treatments based on where in the body the cancer started—for example, lung or breast cancers. We have now approved a drug based on a tumor’s biomarker without regard to the tumor’s original location.”

Keytruda works by blocking the cellular pathway known as PD-1/PD-L1 (proteins found on the body’s immune cells and some cancer cells). Keytruda is currently used in patients with metastatic melanoma, metastatic non-small cell lung cancer, recurrent or metastatic head and neck cancer, refractory classical Hodgkin lymphoma, and urothelial carcinoma.

The FDA approval comes in wake of results of 5 clinical trial involving 149 patients with 15 different cancer types. The common cancers were endometrial, gastrointestinal and colorectal.
Nearly 40% of patients in this trial responded well to the treatment with 78% of those were symptom free for more than 6 months.

Common side effects of Keytruda include fatigue, itchy skin (pruritus), diarrhea, decreased appetite, rash, fever (pyrexia), cough, difficulty breathing (dyspnea), musculoskeletal pain, constipation and nausea.

 Keytruda can cause serious conditions known as immune-mediated side effects, including inflammation of healthy organs such as the lungs (pneumonitis), colon (colitis), liver (hepatitis), endocrine glands (endocrinopathies) and kidneys (nephritis).

The FDA press release can be accessed here

Friday, June 16, 2017

Frequent, loud snoring increases the risk of preterm delivery: News from the sleep conference

Another interesting paper presented at the annual meeting of the Associated Professional Sleep Societies linking obstructive sleep apnea and preterm and early preterm delivery. Women who are frequent, loud snorers during pregnancy and also before they were pregnant have a definite higher risk of preterm delivery as compared to their counterpart who sleep soundly throughout night.

The paper was presented at the 31st Annual Meeting of the Associated Professional Sleep Societies LLC (APSS), Boston. by Galit Levi Dunietz, PhD, MPH, of the University of Michigan.

It is already known that women with Sleep disordered breathing (SDB) do not fare well in pregnancy and many particularly have maternal hypertension and diabetes and possibly fetal growth restriction.

The study looked at 904 non-hypertensive, non-diabetic women, pregnant women in their third trimester, attending a prenatal clinic at a large medical center.

The women were divided into 4 groups based on their snoring pattern: non-snorers, infrequent-quiet, frequent-quiet, or frequent-loud snorers.

Only 6% of women were frequent loud-snorers and about 50% did not snore at all. 

About 25% of women in the pre-pregnancy frequent, loud- snoring category had a preterm delivery.
After adjusting for all pre-pregnancy and pregnancy confounders, those women who were frequent loud-snorers had an 81% increased risk of preterm delivery.  

The mean time to delivery in frequent loud snoring group was 37.1 weeks as compared to 38.6 weeks in controls.

Non-loud, infrequent, or pregnancy-onset snorers did not face the risk for preterm delivery.

Galit Levi Dunietz, PhD, MPH, of the University of Michigan said, “The fact that there is an association between snoring and time to delivery in a cohort which is not hypertensive is alarming, and I think that treatment for snoring earlier on in pregnancy may alleviate some of these outcomes.”

She further added that “The combination of snoring frequency and intensity may be a clinically useful marker to identify otherwise low-risk women who are likely to deliver earlier.”