What should midlife women know about preventive cardiology?

We are all aware that sex and gender differences are important in the diagnosis and management of cardiovascular diseases. A woman’s risk of a cardiac event and stroke sharply increases after the onset of menopause. Here is an informative video regarding preventing and managing the increased risk of a cardiac event after menopause.

Dr. Beth Abramson is a preventive cardiologist and helps women manage the risk of heart disease.  In this video by North American Menopause Society (NAMS), she answers many vital questions about menopausal hormone therapy, midlife weight gain, smoking, alcohol, and aspirin therapy.  

KEYTRUDA gains FDA approval for treatment of recurrent or metastatic cervical cancer

The U.S. Food and Drug Administration (FDA) has approved Merck’s pembrolizumab (KEYTRUDA®), for the treatment of patients with recurrent or metastatic cervical cancer whose disease had worsened on or after chemotherapy and whose tumors express programmed cell death ligand 1 (PD-L1), as determined by an FDA approved test.

The US FDA has approved the Dako PD-L1 IHC 22C3 pharmDx assay for expanded use as a companion diagnostic test for Keytruda for cervical cancer.

The approval comes in way ahead of the previously decided date of June 28. Furthermore, the drug is approved under the FDA’s accelerated approval regulations based on tumor response rate and durability of response.

Continued approval in future will be based upon verification and description of clinical benefit in the ongoing trials ahead.

The accelerated approval was based on results of ongoing KEYNOTE-158, a multi-center, non-randomized, open-label, multi-cohort trial (NCT02628067). The trial enrolled patients with multiple types of advanced solid tumor, who have not responded to usual chemotherapy or are intolerant to it.

Patients with autoimmune diseases or requiring immunosuppression were excluded from the trial.

The patients received KEYTRUDA intravenously at a dose of 200 mg every three weeks until unacceptable toxicity or documented disease progression or for 24 months in patients without disease progression.

Among the 98 patients with advanced cervical cancer, 77 (79%) had tumors that expressed PD-L1 with a Combined Positive Score (CPS) ≥1 and have received at least one line of chemotherapy in the metastatic setting.

The objective response rate in these 77 patients was 14.3 percent, with a complete response in 2 patients (2.6%) and partial response in 9 patients (11.7%).

Ninety-one percent of patients experienced duration of response exceeding 6 months or longer. Eight patients discontinued the drug because of serious side effects like anemia, fistula, hemorrhage, and infection.

The other common side effects of KEYTRUDA are fatigue, musculoskeletal pain, diarrhea, pain and abdominal pain and decreased appetite (21%).

 No responses were observed in patients whose tumors did not have the PD-L1 expression (CPS<1).

KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells. This increases the ability of the body's immune system to help detect and fight tumor cells.

Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories said, “KEYTRUDA is now the first anti-PD-1 therapy approved for the treatment of advanced cervical cancer, providing an important new second-line option for certain patients with this disease. This approval also marks the first indication for KEYTRUDA in gynecologic cancer and reflects our ongoing commitment to bring forward innovative treatment options across a broad range of cancers, including cancers that disproportionately affect women,” in a news release.

KEYTRUDA has already been approved by FDA for treatment of melanoma, head and neck cancer, lung cancer, urothelial cancer, and gastric cancer.

Merck News Release 

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Use of antimycotics in early pregnancy is not linked to spontaneous abortion

Exposure to antifungals Clotrimazole and miconazole during pregnancy for Vulvovaginal candidiasis (VVC) is not associated with increased risk of spontaneous abortion says the results of a cohort study published in June issue of American Journal of Obstetrics and Gynecology.

VVC is more frequent in pregnancy possibly because of higher estrogen levels and higher glycogen content in vaginal secretions; thereby, creating a favorable environment for the yeast to thrive and grow. It is estimated that about 10% of pregnant women in the USA will have a yeast infection at any given time.

Topical clotrimazole and miconazole are the treatment of choice for VVC in pregnancy. They are easily available over the counter and are known to be safe in pregnancy. A recent study has suggested an increased risk of miscarriage by using these azoles.

The researchers from Beer-Sheva, Israel conducted this historical study to investigate the risk of spontaneous abortion after treatment with vaginal antimycotics.

Data was gathered on all clinically apparent pregnancies over a period of 6 years (2003-2009) at the Soroka Medical Center, Clalit Health Services, Beer-Sheva, Israel. Databases with information on medicines dispensed to these patients and information on births and spontaneous abortions were linked together.

Statistical analysis was done by time-varying Cox regression models adjusted for maternal demographics like age, ethnicity, tobacco use, and the year of admission; the presence of chronic diseases like diabetes mellitus, hypothyroidism, obesity, hypercoagulable or inflammatory conditions; and reproductive and contraceptive history.

A total of 65,457 pregnancies were included in the analysis of which 58,949 (90.1%) ended with birth and 6508 (9.9%) with a spontaneous abortion.

Out of which 3246 (5%) pregnancies received vaginal antifungal drugs until the 20^th week of gestation: (2712 (4.2%) were exposed to clotrimazole and 633 (1%) to miconazole.

Exposure to vaginal antifungals as a group was not linked to spontaneous abortion (adjusted hazard ratio, 1.11; 95% confidence interval, 0.96–1.29). Individually clotrimazole and miconazole were also not associated with spontaneous abortion.  

There was no dose-response relationship observed between the antifungals and spontaneous miscarriages.

The authors concluded that vaginal use of antimycotics is not linked to spontaneous abortion.

Abstract

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Say goodbye to mosquito bites by a simple wearable blocker on the wrist

Finally, say goodbye to the red itchy bumps and many scary diseases caused by mosquito’s bites by just a high-tech wearable instead of dousing yourself in chemicals. Guarden has just launched an Indiegogo campaign for its latest device named Bandito, that is worn on wrist or attached to your backpack or clothing to ward off the mosquitos.

Guarden is a pest control company based at Chicago, Illinois that specializes in manufacturing eco-friendly products for pest and environmental protection. Bandito combines two different technologies to produce powerful defense against the bites of mosquitos. The device produces sonic waves at a frequency that repels the mosquitos and other bugs but is imperceptible to human and pet ears.

In addition, the device produces scents that are revolting to bugs but is refreshing to human nose. The scent strips consist of Citronella, Peppermint, and Lemongrass.

An individual Bandito device is built to last a single season even when used consistently. It comes with a battery that can go on for about 500 hours, while each strip lasts for 14 days when used daily for 5.5 hours. The device is at the prototype stage at present and c is expected to ship the orders by August 2018. 

Each Bandito device ships with one refill and one battery. The refills can be ordered separately. Currently, the solo pack is priced at $34 and expected to be delivered by August 2018. The device can also be ordered in various combination like friend’s pack (2 devices), family pack (4 devices), party pack (10 devices), and camping pack (25 devices).

The product is cost efficient, non-sticky, harmless towards the skin, non-toxic, and usable for years to come.

The bite of a mosquito can be more serious than just be annoying and itchy. They are known to cause many viral and parasitic diseases which can cause significant morbidity and sometimes be fatal.

CDC reports that mosquitos are responsible for about 1 million deaths a year just because of transmission of the malarial parasite. Other common viral diseases caused by the mosquitos are dengue, Zika, and chikungunya, Lymphatic filariasis (elephantiasis), yellow fever, West Nile fever, Japanese encephalitis, and St. Louis encephalitis.

Recent years have seen a rise in mosquito born illnesses and scientists are predicting an explosion of these diseases in near future because of global warming and climate change worldwide.

Joseph Conlon, American Mosquito Control Association (AMCA) Technical Advisor said in a recent press release, “We already have the mosquitoes. We are continually importing the diseases they carry. We must be prepared to prevent their spread throughout our public health landscape – and this requires safe, effective, sustained mosquito control and awareness in the community.”

The AMCA is celebrating National Mosquito Control Awareness Week (June 24—June 30, 2018) to create awareness among the public about how to keep the mosquitos away and the various diseases caused by mosquito bite.

Indiegogo campaign page

Product page

An official promo about Bandito from Guarden

Order 

Google celebrates the 109th birth anniversary of Dr. Virginia Apgar

Did you look at today's Google Doodle as you went to search something on the internet?  Google celebrates the 109^th birth anniversary of Dr. Virginia Apgar by creating a special doodle in her honor today.

Virginia Apgar was an American Anesthesiologist, widely known for her groundbreaking invention of Apgar neonatal scoring system that has saved countless newborn lives around the world.

Dr. Apgar was born on 7 June 1909 in New Jersey, United States and completed her medical school at Columbia University College of Physicians and Surgeons. She did her surgical residency in 1937 and then invested a year to train in the field of anesthesia.

She had to face several obstacles in finding work, until 1940, when anesthesia was recognized as a separate specialty. Later she also received training in obstetric anesthesia which aspired her to create the Apgar score.

While working in New York, she was deeply troubled by the ways babies were handled after birth. There was no fixed standard of neonatal care and babies who were blue at birth were recorded as stillborn and no attempts were made to resuscitate them.

Appalled by the lack of care, she designed a scoring system in 1952 which evaluates the newborns' health on five factors: heart rate, respiration, skin color, muscle tone, and reflexes. It soon became evident that even babies with a low Apgar rating at birth could be revived to a good score at 5 minutes by giving Oxygen and maintain the warmth.

Soon, the Apgar score was adopted by the hospitals in the US and is credited with lowering the Infant Mortality Rate.

Rachel Swaby, the author of "Headstrong: 52 Women who Changed Science-and the World," included Virginia Apgar in her list and told CNN in 2015, "It [the Apgar Score] was a huge public health breakthrough. Virginia Apgar had such amazing energy and such an energetic mind."

Today, Apgar score is recognized as standardized assessment for infants after delivery worldwide. The score is reported at 1 minute and 5 minutes after birth for all infants, and at 5-minute intervals thereafter until 20 minutes for infants with a score less than 7.

It reports the condition of the newborn at birth and its response to the neonatal resuscitation attempts; however, it has been inappropriately used to predict an individual adverse neurologic outcome.

It does provide a guidance whether continues resuscitative efforts are indicated or not in a newborn with an Apgar score that remains 0 beyond 10 minutes of age because very few infants with a score of 0 at the end of 10 minutes have survived with a normal neurological performance.

Apgar score has its limitations because it is a snapshot of the physiological condition of the newborn at one point in time and also includes subjective components. It can be affected by gestational age, maternal sedation or anesthesia, congenital malformations and interobserver variability.

When properly applied gives us a standardized assessment of newborn at birth and its response to resuscitation efforts. It does diagnose asphyxia nor it predicts individual neonatal mortality, neurological outcome.  

Virginia Apgar went to medical schools in early 1900 when medical schools seldom accepted female students. Undaunted, Virginia continued her journey in the field of Medicine and became the first full-time woman professor at Columbia in 1949.

She was awarded three privileged doctorates and earned a degree in public health from John’s Hopkins. She has several publications and articles to her name, including a book “Is My Baby All Right”?

She dies in 1974 due to cirrhosis of the liver and was posthumously inducted into the National Women's Hall of Fame in 1955.

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FDA approves Imvexxy to treat moderate to severe dyspareunia due to menopause

The United States Food and Drug Administration (FDA) has approved TX-004HR: IMVEXXY (estradiol vaginal inserts) for the treatment of moderate-to-severe dyspareunia due to vulvar and vaginal atrophy (VVA) of menopause.

Imvexxy is the only product in its therapeutic class to offer a 4 mcg and 10 mcg dose, the 4 mcg representing the lowest approved dose of vaginal estradiol currently available in the market. The product will be available to the consumers in July.

Imvexxy should be administered intravaginally as follows: one vaginal insert daily for 2 weeks, followed by one insert twice weekly.

Brian Bernick, MD, Chief Clinical Officer of TherapeuticsMD, said in a press release, “Imvexxy is a bio-identical vaginal estrogen product that offers a fraction of the estrogen contained in the average doses of many existing products currently on the market.”

“Imvexxy is the only product specifically designed to be applicator-free. It dissolves completely without mess or additional cleanup and can be used any time of day. It allows women the freedom to immediately return to their normal daily activities. Studies showed that, in patients who used Imvexxy, systemic absorption of estradiol remained within postmenopausal range," he further added.

The product was approved following the results of Phase 3, randomized, double-blind, placebo-controlled study (REJOICE, NCT02253173), published in April 2017 issue of Journal Menopause. The study results showed that Imvexxy was safe and well tolerated in all three doses (4, 10, and 25 μg).

In 2 weeks there was considerable improvement in dyspareunia, even with the lowest dose of 4 μg and vaginal dryness as early as 6 weeks as compared to women who received placebo.

A substudy of the REJOICE trial evaluated the pharmacokinetics of the 4-μg and 10-μg inserts and placebo.

There was negligible or very low systemic absorption as evident by the serum levels with no accumulation of the drug as seen by the low endogenous values observed at day 84.

Other products like vaginal estradiol tablet, vaginal creams, and vaginal estrogen ring used for the treatment of VVA limit systemic estrogen absorption but does not completely eliminate it.

The Pharmacokinetics profile for Imvexxy (ie, negligible to very low systemic absorption) could allow clinicians to follow the recommendation of The North American Menopause Society (NAMS) to use low-dose vaginal estrogens without a concomitant progestin.

It could also be used for the treatment of vaginal symptoms in survivors of estrogen-dependent breast cancer as recommended by the American Congress of Obstetricians and Gynecologists (ACOG).

The most commonly reported side effect by the users of vaginal inserts was a headache but it was not statistically significant when compared to placebo users.

VVA affects an estimated 32 million postmenopausal women in the United States. Approximately 7% (2.3 million) of these women receive prescription treatment. In addition, nearly 1 out of 2 women will experience pain during intercourse due to VVA at some point during their lives.

Dr. Sheryl Kingsberg, President, North American Menopause Society, said in a statement issued by TherapeuticsMD, “Studies have shown that many women are not seeking treatment for VVA, and 81% are unaware that VVA is a treatable medical condition and part of a constellation of symptoms associated with loss of estrogens."

 "I am delighted that our patients will now have a convenient treatment option with IMVEXXY and hope that the excitement generated by this new option will encourage women to talk to their healthcare provider and get relief from their pain and discomfort due to VVA,” she further added.

The product comes with a boxed warning about the increased risk of endometrial cancer, stroke, deep vein thrombosis (DVT), and dementia when used as estrogen-alone therapy without progesterone therapy.

Imvexxy is contraindicated in women with any of the following conditions: undiagnosed abnormal genital bleeding; known, suspected, or history of breast cancer; known or suspected estrogen-dependent neoplasia; active DVT, PE, or history of these conditions; active arterial thromboembolic disease or a history of these conditions; known anaphylactic reaction or angioedema to Imvexxy; known liver impairment or disease; known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders.

REJOICE Trial

TherapeuticsMD Press Release

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ACOG guidance on prevention of surgical-site infection in gynecologic surgery

Surgical site infection(SSI) after gynecological surgery is a significant cause of postoperative morbidity leading to repeated hospital visits.  These infections also incur heavy social and economic burden on patients and the healthcare system.

Two previous research papers have estimated that each SSI during a hysterectomy is going to add $5000 inpatient cost.

CDC defines SSI as an infection occurring at or near the surgical incision within 30 days of surgery and 12 months if a surgical implant was used.

A number of factors, both modifiable and not modifiable, contribute to the ultimate development of an SSI.

Steiner. Surgical-site infection in gynecologic surgery. Am J Obstet Gynecol 2017.

The recent ACOG practice bulletin is published in the June issue of Journal of Obstetrics and Gynecology and replaces Practice Bulletin Number 104, May 2009, and Committee Opinion Number 571, September 2013.

The practice bulletin includes guidelines about pre-operative and intraoperative prophylaxis, procedure-based antibiotic regimen, guidelines for patients with a history of Methicillin-resistant Staphylococcus aureus (MRSA) colonization, and penicillin allergy.

Preoperative prophylaxis:

Treat any remote infections before any elective gynecological procedure.

It is preferable not to shave the incision site unless it interferes with the procedure. When necessary, do not use a razor, clippers are preferred.

Screen women for diabetes before the procedure and if found hyperglycemic, aim at blood  glucose <200 mg/dL with or without diabetes.

Patients should have a full body shower or bath with Chlorhexidine instead of soap.

Pre-op abdominal skin preparation is preferably done with alcohol-based preparations, and chlorhexidine-alcohol was significantly more effective than a povidone-iodine scrub in preventing superficial and deep incisional infection.

Vaginal cleaning before surgery is done by 4% chlorhexidine gluconate or povidone-iodine, only povidone–iodine is FDA approved for vaginal preparation. Chlorhexidine gluconate with high alcohol concentration (70% isopropyl alcohol) is contraindicated for vaginal prep due to the risk of irritation.

Screen for bacterial vaginosis pre-operatively, if found positive initiate treatment with metronidazole or another CDC recommended regimen.

All members of the surgical team should maintain aseptic techniques and traffic in the OR should be limited

Intraoperative Prophylaxis:

Use excellent surgical techniques gentle tissue handling, good hemostasis, avoid hypothermia and short operative time < 100 minutes.

Use appropriate antimicrobial prophylaxis one hour before the surgery, in obese patients, the dose should be calculated accordingly.

In cases of long surgical procedures (> 4 hours) or blood loss > 1500 ml, repeat Cefazolin

Procedure based antibiotic regimens:

In all types of hysterectomy (abdominal, vaginal, laparoscopic, and robotic), Laparotomy, Vaginal sling, and Colporrhaphy: 2 g IV cefazolin (≤120 kg) and 3 g IV cefazolin (>120 kg)

In Uterine evacuation (suction D&C/D&E): 200 mg doxycycline orally or IV, Metronidazole is an effective second line of therapy.

No antibiotics are recommended: Colposcopy, Cervical tissue excision procedures (LEEP/biopsy/ECC), Endometrial biopsy, Cystoscopy, HSG, Hysteroscopy (operative/diagnostic), endometrial adhesions, IUD insertion, Oocyte retrieval and embryo transfer, D&C for nonpregnancy indications, and laparoscopic procedures.

History of MRSA Colonization or Infection:

It is recommended to follow the hospital protocol for MRSA antibiotic prophylaxis or a single preoperative intravenous dose of vancomycin (15 mg/kg) is included in the preoperative antibiotic prophylaxis regimen

Penicillin allergy:

In case of Immediate hypersensitivity reaction or Stevens-Johnson syndrome use Clindamycin 900 mg or metronidazole 500 mg PLUS Gentamicin 5mg/kg or aztreonam 2 g 

If there is no immediate hypersensitivity reaction (anaphylaxis, urticaria, bronchospasm) cephalosporins can be used. If there is a history of allergy to cephalosporins use Clindamycin 900 mg or metronidazole 500 mg PLUS Gentamicin 5mg/kg or aztreonam 2 g 

ACOG Practice Bulletin 195: Prevention of Infection After Gynecologic Procedures (login required)

JAMA Full Text: Centers for Disease Control and Prevention Guideline for the Prevention of Surgical Site Infection, 2017

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ASCO 2018: Many women with early-stage breast cancer can safely skip chemotherapy

A majority of women with early-stage breast cancer will not require to undergo chemotherapy says the results of very important clinical trial presented Sunday, June 3, 2018, at the American Society of Clinical Oncology (ASCO) annual clinical meeting in Chicago, Illinois and is also being published simultaneously in the New England Journal of Medicine.

This federally funded phase III randomized clinical trial is a game changer for most women diagnosed with early-stage breast cancer who are hormone receptor-positive, HER2-negative, axillary node-negative and who received a mid-range score on the Oncotype DX gene test.

"Half of all breast cancers are hormone receptor-positive, HER2-negative, and axillary node-negative," noted study author Dr. Joseph Sparano, MD, Associate Director for Clinical Research at the Albert Einstein Cancer Center and Montefiore Health System in New York, and Vice-Chair of the ECOG-ACRIN Cancer Research Group.

"Our study shows that chemotherapy may be avoided in about 70 percent of these women when its use is guided by the test, thus limiting chemotherapy to the 30 percent who we can predict will benefit from it," Sparano said in a news release from the American Society of Clinical Oncology (ASCO).

The Oncotype DX test looks at 21 separate genes in breast tumor cells samples and quantifies the individual risk of recurrence and likelihood of benefits from post-surgical chemotherapy. The test results give patients a "score" based on a continuous scale from 0-100.

Onco-surgeons are using this score since long to guide them about decisions on post-surgical chemotherapy. A woman with a low score (1-10) will only receive hormonal therapy while if she scores high (26-100), she receives additional chemotherapy also to prevent recurrence.

It was not clear how to proceed with treatment decisions for women who received the scores in mid-range 11-25. “The trial was designed to address this question, and provides a very definitive answer,” added Sparano.

The Trial Assigning IndividuaLized Options for TReatment (TAILORx) (ClinicalTrials.gov: NCT00310180) recruited 10,273 women 18-75 years of age diagnosed with hormone receptor-positive, HER2-negative, axillary node-negative breast cancer.

Of those, 6,711 had a mid-range Oncotype DX test score of 11-25 and were randomly assigned to receive hormone therapy alone or hormone therapy and chemotherapy.

After a median follow-up of 7.5 years, it was seen that the rates of overall survival, disease-free survival, or cancer spread beyond the breast was comparable for both the groups.

Adding chemotherapy only benefited a small subgroup of women who scored between 16-25 on the Oncotype DX test and were younger than 50 years.

Based on the results, the researchers concluded:

Chemotherapy can be safely omitted in women with this type of breast cancer who have an Oncotype score under 26 and are older than 50 years (85 % of women with breast cancer in this age group).

Chemotherapy can also be omitted in women who are younger than 50 and have an Oncotype score less than 16 (about 40% of women with breast cancer in this age group).

This study received funding primarily from the National Cancer Institute, part of the National Institutes of Health. Additional support was provided by the Breast Cancer Research Foundation, Komen Foundation, and the U.S. Postal Service Breast Cancer Stamp. The ECOG-ACRIN Cancer Research Group designed and conducted the study.

ASCO press release

Full-Text NEJM

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