Tuesday, November 29, 2016

New hope for infertility patients with premature ovarian insufficiency: IVA treatment using fresh ovarian tissue grafting.

courtesy: www.ivf-worldwide.com 

Premature ovarian insufficiency (POI) affects 1 in 100 women below the age of 40 years.  It causes amenorrhea, elevated FSH and hypoestrogenism. Diagnosed with POI is a life changing situation for many women, especially those who have still not completed their family. [1] POI is due to early exhaustion of ovarian follicles due to genetic, autoimmune, iatrogenic or other causes.[2]

Autologous ovarian transplantation is used in patients with malignancy to preserve fertility while radiotherapy and chemotherapy treatments. But, traditional transplantation is not useful in patients with POI because the endocrine and reproductive functions of the ovaries have already ceased. Until now, women with POI does conceive by In-Vitro fertilization by donor’s egg or go for surrogacy or adoption. By undergoing IVA, she has a chance to have her own biological child.

IVA or In Vitro Activation, is a new procedure to obtain mature eggs for women with POI, it involves a twostep procedure consisting of in vitro activation of follicles followed by fragmentation into smaller ovarian cubes and incubation with drugs before grafting.  The second step consists of oocyte retrieval followed by IVF and embryo transfer before pregnancy.

Phosphatase and tensin homolog (PTEN) enzyme inhibitors and phosphatidylinositol-3 kinase activators were used to activate the AKT pathway in dormant follicles leading to follicular growth. Ovarian fragmentation also interferes with the Hippo signaling leading to ovarian follicular development.[3]

A study results published in The Journal of clinical endocrinology and metabolism have translated this lab based IVA results into actual clinical practice resulting in birth of two healthy babies without cryopreservation of the ovarian tissue.

In this groundbreaking prospective observational cohort study, 14 patients with POI underwent IVA. The women were average 4 years past LMP, around 29 years of age and mean FSH level of 94.5 mIU/mL.

All the patients have received prior gonadotrophins treatment with no results before entering the study. The larger of the two ovaries was removed by laparoscopy, cut into strips and the strips were further cubed. The ovarian cubes were incubated to activate the AKT pathway. The cubes were cultured for two days and after 2 days of In Vitro activation they were transplanted back beneath the serosa of both fallopian tubes. A part of the ovarian tissue was cryopreserved for use at later date and 10-20% of the tissue was examined microscopically for residual follicles.

The patients underwent routine follicle stimulating protocols. Six (43%) of the fourteen patients showed follicular development. Four patients had successful oocyte retrieval, resulting in four embryos. Two women successfully delivered healthy infants following embryo transfer while 3 embryos were cryopreserved for future use.

An earlier study by Suzuki N et al published in Journal of Human Reproduction also reported two successful live birth following ovarian tissue vitrification in patients with primary ovarian insufficiency.[4]

"Although I believed, based on our previous research, that this IVA approach would work, I monitored the pregnancy closely and, when the baby was in a breech presentation, I performed the caesarean section myself," said Dr. Kazuhiro Kawamura, an associate professor of obstetrics and gynecology who led the team at St. Marianna.

"I could not sleep the night before the operation, but when I saw the healthy baby, my anxiety turned to delight. The couple and I hugged each other in tears. I hope that IVA will be able to help patients with primary ovarian insufficiency throughout the world."

Future randomized studies are needed before IVA can become a part of routine clinical practice for infertility patients. The researchers are considering several aspects like new drugs to target the Hippo and PTEN pathways to stimulate the ovaries without surgery.

It is too early to say that it can be used for wider application, but a new option has certainly been added to the ART armamentarium.

[1] http://www.uptodate.com/contents/early-menopause-primary-ovarian-insufficiency-beyond-the-basics
[2] http://humrep.oxfordjournals.org/content/early/2015/01/06/humrep.deu353.full.pdf
[3] Kawamura K, Cheng Y, Suzukia N, et al. Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment. PNAS. 2013. 
[4] Suzuki N, Yoshioka N, Takae S, Sugishita Y, Tamura M, Hashimoto S, Morimoto Y, Kawamura K.
Hum Reprod. 2015 Mar;30(3):608-15

Sunday, November 27, 2016

What is the optimum Interpregnancy Interval following miscarriage? A systematic review and meta-analysis

The time elapsed since last pregnancy may be one of the many factors that affects the fate of the current pregnancy. The optimum interpregnancy interval (IPI) following a delivery or miscarriage to avoid adverse pregnancy outcome has always been debated. Both longer and shorter IPI have been associated with adverse pregnancy outcome. IPI interval can be modified by women to improve the pregnancy outcome. But, to determine the role played by IPI as a single modifiable factor in pregnancy outcome is a difficult task because of multiple confounding factors.

Usually a shorter interpregnancy interval following a term delivery is believed to be associated with an adverse outcome. Meta-analysis of Studies conducted in Latin America have shown that IPI of 24 months is optimal and shorter (< 18 months) and longer (> 5 years) is associated with poor pregnancy outcome. [1] [2] But, studies documenting the optimal IPI after a miscarriage are few and inconsistent. Spontaneous miscarriage is a common event affecting 1 in 20 pregnancies. [3]  

The WHO has recommended avoiding pregnancy for 6 months after a miscarriage for a good pregnancy outcome in next pregnancy. WHO recommendations also state that IPI of less than 6 months is associated with elevated risks of premature rupturing of membranes, anemia and bleeding, pre-term and very pre-term births, and low birth weight, compared with longer intervals.[4]

A systemic review and meta-analysis published online on November 17,2016 in Journal Human Reproduction Update aims to determine whether a shorter (< 6 months) IPI is associated with poor reproductive outcome in next pregnancy.

Two investigators independently worked on the project and selected 16 studies from PubMed, Embase and Medline with no language or time restrictions. Studies comprising women with at least one miscarriage comparing pregnancy outcome in subsequent pregnancy with IPI less than 6 months and more than 6 months formed the part of the analysis.

The meta-analysis analyzed the risk of recurrent miscarriage, premature labor, stillbirth, pre-eclampsia and low birthweight babies in the subsequent pregnancy following a shorter or longer IPI. 
A total of 977 972 women from 10 studies met the inclusion criteria. IPI of less than 6 months is associated with 18% less risk of subsequent miscarriage, 11% less risk of preterm birth when compared to IPI of more than 6 months. The risks of still births, low birthweight and preeclampsia were independent of IPI.

Thissystemic review and meta-analysis clearly documented that IPI of less than 6 months following a miscarriage is not associated with adverse pregnancy outcome of in the form of recurrent miscarriage and preterm delivery in subsequent pregnancy. Outcomes such as still births, preeclampsia and low birth weight babies in next pregnancies are independent of time elapsed since  last mishap.

[1] Conde-Agudelo A, Rosas-Bermúdez A, Kafury-Goeta AC. Effects of birth spacing on maternal health: a systematic review. Am J Obstet Gynecol. 2007;196(4):297–308.
[2] Conde-Agudelo A, Rosas-Bermúdez A, Kafury-Goeta AC. Birth spacing and risk of adverse perinatal outcomes: A meta-analysis. JAMA. 2006;295(15):1809–23.
[3] http://whe.sagepub.com/content/7/2/139.full
[4] http://www.who.int/maternal_child_adolescent/documents/birth_spacing.pdf

Wednesday, November 23, 2016

WHO declares the end of Zika public health emergency, but the threat of disease still exists!

current Zika transmission worldwide

The World Health Organization (WHO) declared on Friday that the Zika virus and related neurological complications no longer constitute an international public health emergency but said that it would continue to work on the outbreak through a "robust long term program".[i]

The fifth meeting of the Emergency Committee (EC) was held via teleconference under the International Health Regulations (IHR 2005) regarding microcephaly, other neurological disorders and Zika virus. The director general preceded over the meeting and briefed the EC members based on the reports from previous 4 meetings.

The WHO EC has declared Zika virus infection as The Public Health Emergency of International Concern (PHEIC) in February,2016. This led to an urgent, massive and coordinated response worldwide and led us to understand many aspects of Zika virus infection.

The EC now feels that the emergency is now over and the programme should now transition into a more sustainable, resource orientated long term programme addressing many aspects of the disease and the future management.

"We are not downgrading the importance of Zika, by placing this as a longer program of work, we are sending the message that Zika is here to stay," Dr. Peter Salama, Executive Director of WHO's Health Emergencies Program, told a news briefing.

"It remains crucially important that pregnant women avoid traveling to areas with local transmission of Zika, because of the devastating complications that can occur in fetuses that become infected during pregnancy," the U.S. Centers for Disease Control (CDC) said in a statement.

Some public health experts have second thoughts on removing the emergency label as the disease still continues to cause infection in USA and elsewhere.

"Although Zika's spread has waned, it still holds the potential for an explosive epidemic. If it were to reemerge in the Americas or jump to another part of the world, it would significantly threaten a new generation of children born with disabilities such as microcephaly." said Lawrence Gostin, a global health law expert from Georgetown University. He further added that “I think WHO's decision is unwise."

Much work still needs to be done, including development of a vaccine.
As per WHO about 70 countries worldwide have reported evidence of Zika virus infection/transmission since 2007.  

There are 2,300 confirmed cases worldwide of babies born with microcephaly, most in Brazil, but the figure is most likely a "significant under-estimate.” Says Dr. Peter Salama.

[i] http://www.who.int/mediacentre/news/statements/2016/zika-fifth-ec/en/

Monday, November 21, 2016

Eye-opening lessons learned by a physician when he ended up as a patient!

This article is based on an emotional lecture delivered by Dr. Philip Katz at the American college of Gastroenterology 2016 annual conference at Las Vegas, Nevada.[1] All of us as physicians have very little experience of what it feels like to be on the ‘other side of the bed’. Dr. Katz    6′ 3″, 195-pound, 60-year-old gastroenterologist is a Clinical Professor of Medicine at Sidney Kimmel Medical College at Thomas Jefferson University, and Chairman of the Division of Gastroenterology at Einstein Medical Center in Philadelphia, PA. Till now he has not spent a single day in hospital as a patient.

"My view from the other side of the bed has given me insight into a part of medicine that I'd never experienced," Dr Katz said during the David Graham Lecture he delivered here at the American College of Gastroenterology (ACG) 2016 Annual Scientific Meeting.

He was very healthy, did not have any chronic disease, did not take any regular medicines except statin to manage hypercholesterolemia. On evening of October 4, 2013, he had a sudden cardiac arrest, with barely detectable pulse landing him in ER and subsequently into Cath lab necessitating multistent angioplasty. He went into coma and also has developed flash pulmonary edema and required a balloon pump and extracorporeal membrane oxygenation.

He woke up from his coma ten says after his admission feeling lost, confused, disoriented, perplexed and bewildered questioning himself that was it really happening to him.

Eventually while still in hospital he developed ischemic stricture, had two sigmoidoscopies and needed surgery. During those two months in hospital, he lost 50 pounds, could not eat or walk.
None of his hospital colleagues agreed to do a primary repair for his stricture, so Dr Katz he decided to take a second opinion from a specialist. The surgeon also advised him against primary repair.
He ended up into temporary ileostomy that got obstructed, requiring constant care. At 3 months’ ileostomy was removed only to end in an intra-abdominal hernia with suspected incarcerated bowel needing an emergency repair.  The follow-up needed constant care from his colleagues, nurses and other healthcare professional.

He took a trip to Ireland only to suffer a G.I bleed landing him in hospital from the airport. All in all, it took him 8 months to heal.

Do you believe in miracles? I said, ‘I kind of have to.’ ... But I actually believe I’m alive because of everything good about our profession, I believe I’m the beneficiary of everybody doing their best — not just the best they could. To me, that’s our obligation every day. To be our best no matter how freaking hard our job is. Can it make you a better doctor? Probably. I believe I am. But I wouldn't recommend this as a way to become a better doctor, not in the least.”

This 11-piece advised he offered to his peers from the point of view of physician turned patient.[2]

1.“The lesson there is trust your colleagues. Trust the people who take care of you to have good back-up,” Katz said. “It’s nice to be taken care of by someone you know and trust. ... It may be difficult for them. My bias is it’s better for you as the patient.”

2. “Avoid assumptions about patient knowledge and health behaviors. It is difficult, and challenging, but imperative to treat us as we would treat any other patient; To assume they know nothing is maybe the best idea,” Katz said. “Ignore the physician-patient’s background. ... Acknowledge the background and negotiate care, but then treat them like any other patient.”

3. Remember the niceties: “Utilize the nurses, the technicians, the med-techs ... even the housekeeper can help by being nice and being comfortable and talking to your patient when they’re in the room. It all matters.”

4. “There’s a new normal. ... It’s crucial to remember there’s an aftermath even if small in the big picture. It’s the patient who gets to live with what’s left,” Katz said. “I am normal with minor exceptions but it still feels lousy to have those exceptions. I can’t help it and it helps me take care of my patients to remember that.”

5. “Our systems are not patient-friendly and they never will be. We will not fix all the crap going on in medicine today even though we have to try.”

6. “Explain. Do not make excuses. Don’t apologize ... but be comforting and explain why that needs to be done. It helps,” he said.

7. “Please revisit your outcomes as a physician. We’re expected to be perfect. Obviously, we can’t always be, but we can always be our best if we try. The end result is important but we really need to learn how we got there because the next one might not turn out as well.”

8. “Understand and, in the best way you can, communicate honestly with your patients. Validate their feelings; validate their illness.”

9. “We’ve earned what we earn. We should not in any way suggest that we are not worth what we get. We are worth more. Nevertheless, the expectations of us are high and they’re going to get higher.”

10. “Respect Murphy’s law because it is real. Respect the procedure that you’re doing every single time you do it because you will never, never predict when you will have an adverse event. I expected none of it.”

11. “Compromise as little as possible in your life and work choices. Do as much as you want to do as often as you can. ... If the glass is not at least half full, get another freaking drink. If you have a real bucket list, do it when you can," said Dr Katz. "You can always make another one. There's no rule about only having one he said. Live life to the fullest. Have no regrets. Work your butts off and enjoy your profession.” 

[1] http://acgmeetings.gi.org/
[2] http://www.healio.com/gastroenterology/practice-management/news/online/%7Bd729c7be-c6fa-4b23-b996-7cfdf3711aa1%7D/11-pieces-of-advice-from-the-physician-patient

Saturday, November 19, 2016

Cleveland Clinic's Top 10 Medical Innovations for 2016

Cleveland Clinic Innovations hosts the Medical Innovation Summit every Fall to bring together all stakeholders in healthcare industry to advance the conversation of medical innovation. They not only discuss the medical breakthroughs in the current year and but also sketch the blueprint for forthcoming innovations in the coming year.
The stakeholders in the summit includes investors, entrepreneurs, researchers, scientists and government personnel and policy makers that will influence the development and marketing of the new discoveries.
This year the summit was held from October 24-26,2016 at Cleveland, Ohio.
The top ten medical innovations for the year 2016 are:

1)      Vaccines to Prevent Public Health Epidemics.

The top spot in the top ten medical innovation list goes to researchers, scientists and public health personnel who are working tirelessly to develop safe, efficient and effective vaccines to prevent disease epidemics. These efforts were geared up by the 2014 Ebola epidemic in Africa and of bacterial meningococcal (Meningococcal B) outbreaks in the United States. The most promising Ebola vaccines was fast-tracked in less just a year. The researchers incorporated a small fragment of surface protein into a harmless cattle vaccine, which retains its capacity to generate a full blown immune response, but loses its ability to cause disease.  Phase-3 clinical trials in population with full exposure to Ebola virus has shown 100% efficacy in just 10 days.
Similarly, the Meningococcal B vaccine is freely available to all in the year 2016.[1]

2)      Genomic Directed Clinical Trials

Identification of essential tumor growth drivers has initiated a new era of targeted genomic cancer therapy. It gives cancer patients a higher chance of survival, longevity and best chance of cure when they need it most. Patients are waiting too long to enter clinical trials which may decrease their chances of cure or survival. RCT which has long been the gold standard of clinical trials are not keeping in pace with rapid expanding world of gene based and genomic therapy. Genomic based clinical trials can help identify the molecular profile of patient cancer cells and help getting them faster into clinical trials. Those patients with rare type of cancers can also hope for a cure due to genomic trials.

3)       Gene Editing Using CRISPR

CRISPR or clustered, regularly interspaced, short palindromic repeat (CRISPR) is a versatile tool for genome engineering used to generating RNA-guided nucleases, such as Cas9, with customizable specificities. It has many innovative application from treating diseases to editing the genes of human embryos to eliminate many genetic diseases. [2]

4)       Water Purification Systems for Prevention of Infectious Diseases.

Developing countries all over the world are struggling to provide clean drinking water to its majority of population. Sewage often pile up and eventually end up contaminating the drinking water. This contributes to more than 10% of disease in the world
An estimated 700million people in the world are drinking contaminated water
According to the world health organization - more than a million children under the age of five (in developing countries) die each year as a result to contaminated water and poor sanitation [3] LifeStraw has developed a system which transforms sewage into safe drinking water, not for a small group of people but larger communities for extended period of time. The machine collects the waste from the sewage then boils it and collects the condensed water vapor and process it into clean and safe drinking water. One processor is said to generate enough water for 100,000 people.[4]

5)      Cell-Free Fetal DNA Testing

In USA, cell-free DNA analysis became clinically available in 2011 and the American College of Obstetricians and Gynecologists and the Society for Maternal–Fetal Medicine recommended it as a screening option for women at increased risk of fetal aneuploidy. Its use has since been expanded as a screening tool in general obstetric population.Fetal circulating cell free DNA is derived mostly from placenta and is present in maternal blood for testing as early as 10 weeks of gestation. Different laboratories have validated different techniques and mainly rely on next-generation sequencing technologies and advanced bioinformatic analyses.Cell free DNA is commonly used to screen for only the common trisomies and, if requested, sex chromosome composition. The sensitivity and specificity as well as the negative predictive value of the method is >99% for trisomy 21 (Down syndrome), with slightly lower performance for trisomy 13 and 18.

6)      Cancer Screening via Protein Biomarker Analysis

Scientist and researchers have long focused on detection of change in concentration of single protein in biological fluids such as blood or urine to screen for cancer. But, the tests have been of limited use due to low sensitivity and specificity. Currently Studying cancer proteomics holds promise in near future to detect tell-tale proteins that provides insight into biological process of alteration in protein due to cancer. This is very true for detection of prostate cancer and colorectal cancers.

The Lerner Research Institute (LRI) of the Cleveland Clinic maintains the Proteomics Core, a protein-sequencing facility that uses tandem mass spectrometry methods to sequence and identify proteins. [5]
In an Australian study published in PLOS one Fung KYC et al identified three biomarkers that discriminated between the controls and the colorectal cancer patients with 73 percent sensitivity at 95 percent specificity.[6] Similarly tests for prostate cancer showed 100 percent sensitivity with no false negatives and approximately 80 percent specificity.  

7)       Naturally Controlled Artificial Limbs

Numerous innovations in prosthetics over the last decade have improved quality of life for numerous amputees and paraplegics in United States. Researchers have discovered that neural signals for limb movements can be de-coded by computers. This advance was made possible by technologies developed under Defense Advanced Research Projects Agency. Now people living with missing or paralyzed limbs will be able to get a feel of the objects they are touching via prosthesis but also will be able to send signals to the robotic prosthesis device form brain.

“We’ve completed the circuit,” said DARPA program manager Justin Sanchez. “Prosthetic limbs that can be controlled by thoughts are showing great promise, but without feedback from signals traveling back to the brain it can be difficult to achieve the level of control needed to perform precise movements. By wiring a sense of touch from a mechanical hand directly into the brain, this work shows the potential for seamless bio-technological restoration of near-natural function.”[7]

8)      First-ever Treatment For HSDD

The little pink pill or Flibanserin (Addyi, Sprout Pharmaceuticals) also dubbed  as the "Female Viagra" was approved by the US Food and Drug Administration (FDA) for the treatment of  hypoactive sexual desire disorder (HSDD) in premenopausal women,  in August 2015, despite  being unsure  about suboptimal risk-benefit trade-offs.

Flibanserin, a 5-HT1A agonist, a 5-HT2A antagonist, and a very weak partial agonist on dopamine D4 receptors, increases levels of dopamine and norepinephrine and decreases serotonin in animal brain areas. Therefore, since dopamine and norepinephrine are thought to promote and serotonin is thought to inhibit sexual desire and arousal, it was suggested that flibanserin enhances sexual desire in HSDD.

9)      Frictionless Remote Monitoring

Monitoring the blood glucose by pricking the finger will soon be a thing of past.
Wearable  biosensors now measure glucose levels using tissue fluids like tears and sweat and not blood. The WBS transmits data over WiFi to the mobile receiver. The patient hence will be able to continuously monitor his or her glucose level and share the results with healthcare providers. Other frictionless remote monitoring devices in development include a bandage that reads sweat molecules to diagnose pregnancy, hypertension or hydration.[8]

10)  Neurovascular Stent Retriever

Neurovascular stent retrievers are a crucial type of medical equipment used in the treatment of strokes. They are used to clear up intracranial arteries and restore normal blood flow following a stroke. Their rapid action in clearing arteries and retrieving clots in large arteries has been noted by health-care authorities after preliminary trials showed promising results. In June, the American Heart Association and American Stroke Association updated its guidelines and added the use of stent retrievers in conjunction with tPA for first-line treatment in some patients with acute ischemic stroke. The stent retrievers are the Solitaire (Medtronic) or Trevo ProVue (Stryker).

[1] http://innovations.clevelandclinic.org/Summit/Top-10-Medical-Innovations/Top-10-for-2016/1-Vaccines-to-Prevent-Public-Health-Epidemics.aspx
[2] http://www.nature.com/news/crispr-gene-editing-is-just-the-beginning-1.19510
[3] https://prezi.com/crxawgoncdfn/water-purification-systems-for-prevention-of-infectious-dise/
[4] http://www.ippinka.com/blog/lifestraw-water-purification-project-for-millions/
[5] http://journals.lww.com/oncology-times/blog/onlinefirst/Pages/post.aspx?PostID=1352
[6] Fung KYC, Tabor B, Buckley MJ, Priebe IK, Purins L, Pompeia C, et al. (2015) Blood-Based Protein Biomarker Panel for the Detection of Colorectal Cancer. PLoS ONE 10(3): e0120425. doi:10.1371/journal.pone.0120425
[7] http://www.darpa.mil/news-events/2015-09-11
[8] https://www.mepits.com/tutorial/180/Biomedical/Wearable-Biosensors

Thursday, November 17, 2016

FDA approves Prasterone (DHEA) for postmenopausal women experiencing dyspareunia.

Image courtesy: Prasterone.org

Clinical Pearls: 

·         Intrarosa Approval History

1.      FDA approved: Yes (First approved November 17th, 2016)
2.      Brand name: Intrarosa
3.      Generic name: prasterone
4.      Company: Endoceutics Inc.
5.      Treatment for: Dyspareunia

·         Local application of DHEA rapidly and effectively corrects the signs of vulvo-vaginal atrophy, relieving mild to moderate dyspareunia.
·         It has also shown marked improvement in all aspects of sexual function in post-menopausal women namely desire, arousal, orgasm, and pleasure.
·         It is devoid of any systemic increase in hormone level, thus avoiding potential systemic risks.
·         Prasterone (Intrarosa, Endoceutics Inc) is marketed as 0.50% (6.5 mg) Vaginal Ovules. 

The US Food and Drug Administration gave approval for use of prasterone (Intrarosa, Endoceutics Inc) to treat postmenopausal women complaining of moderate to severe pain during sexual intercourse (dyspareunia).[1]

Declining estrogen levels lead to Vulvovaginal atrophy (VVA) which has significant effect on women’s sexual health and quality of life (QOL). It is estimated that it affects 20% to 45% of midlife and older women, but only minority seek help for the symptoms. Nearly 93% of the women do not receive any treatment for the fear of estrogen related side effects. [2]

"Pain during sexual intercourse is one of the most frequent symptoms of VVA reported by postmenopausal women," said Audrey Gassman, M.D., deputy director of the Division of Bone, Reproductive, and Urologic Products (DBRUP) in the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research (CDER). "Intrarosa provides an additional treatment option for women seeking relief of dyspareunia caused by VVA."

Prasterone marketed as Intrarosa is manufactured by Quebec-based Endoceutics Inc. EndoCeutics is a private bio-pharma company operating in the field of women’s health and hormone-sensitive cancer prevention and treatment.[3]

 After the cessation of estrogen and progesterone by the postmenopausal ovaries, DHEA is the only exclusive source of these hormones made inside the vaginal cell layers physiologically by a process called as intracrinology. Intrarosa which comes as 0.50% DHEA (6.5 mg) daily vaginal insert does not have any systemic increase in circulating estrogens or androgens.

Per FDA, the efficacy of Intrarosa was demonstrated in a 12 week, prospective, randomized, double-blind, and placebo-controlled phase III clinical trial. The intent-to-treat population included 157 and 325 women in the placebo and DHEA-treated groups, respectively. Improvement was seen for all the four primary objectives namely percentage of parabasal cells, percentage or superficial cells, vaginal pH, and percentage of parabasal cells, percentage or superficial cells, vaginal pH, and moderate to severe pain at sexual activity (dyspareunia).[4] At clinical examination epithelial integrity, epithelial surface thickness, color and vaginal secretion showed marked improvement (86% to 121%) as compared to placebo effect (P < 0.0001).

No increase in systemic steroids levels was observed. The only side effects reported by 6% of women was an increase in vaginal secretions due to melting of the vehicle.

[1] http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm529641.htm
[2] http://www.endoceutics.com/therapeutic-areas/vulvovaginal-atrophy-vva/
[3] http://www.pr.com/press-release/652714
[4] http://journals.lww.com/menopausejournal/Citation/2016/03000/Efficacy_of_intravaginal_dehydroepiandrosterone.6.aspx

Sunday, November 13, 2016

Sugar is as big a threat as tobacco: We need to treat it that way.

Courtesy: Fateclick 

This article is based on a speech by Dr. Aseem Malhotra, MBChB, MRCP at the UK parliamentary “Sugar Summit.” [1]The sugar summit was convened by a distressed mother Rend Platings, after learning that today’s generation of parents will be the first to bury their children because of increasing obesity. She launched ‘Sugarwise’ an organization for increasing attention, education, awareness and giving people options on sugar in their food and drink.[2]

Keith Vaz chaired the event which included number of representatives from high-profile UK retailers as Tesco, Caffè Nero, and the Jamie Oliver Group, as well as such influential stakeholders as the UK Department of Health, Public Health England, the British Soft Drinks Association, and the Food and Drink Federation. [3]

About 2 years back the WHO and Scientific Advisory Committee on Nutrition (SACN) made a recommendation to halve the amount of sugar in our diet. But, we are still far behind in meeting that mark.  Sugar continues to play a major role as an important cause of obesity for two-thirds of the U.K. population.

The U.K government has recently made an announcement of an introduction of a 20% tax on sugar-sweetened beverages in 2017,[4] similarly WHO also announced to tax sugary drink by 20% to check the global epidemics of obesity and type 2 diabetes. [5]

Scientists, researchers and public health personal has long raised voices against the hidden sugar found in daily food items and paralleled the addiction to tobacco. Legislative measures against tobacco use and smoking is the single most driving factor behind the drop in cardiovascular mortality since 3 decades.

Health Benefits:

Dr Assem Malhotra has included the following research data in his editorial. Oxford researchers have estimated that a 15% reduction in sugar consumption through such a tax would prevent 180,000 people in the UK from becoming obese within a year and a larger number from becoming overweight.[6] But the scientific evidence reveals that the positive health benefits for the whole population of such a tax goes beyond a mere reduction in calories:

  • An econometric analysis of 175 countries (considered the highest quality of study with the exception of randomized controlled trials) revealed that for every additional 150 sugar calories available for consumption, there was an 11-fold increase in the prevalence of type 2 diabetes in the population. This is compared with 150 calories from another source such as fat or protein and independent of body mass index (BMI) and physical activity levels.
  • The prevalence of type 2 diabetes in the US population between 1988 and 2012 increased by 25% in both obese and normal-weight populations, which goes to show that type 2 diabetes is not a condition related purely to obesity.
  • A high-quality prospective cohort study revealed a trebling in cardiovascular mortality among US adults who consumed more than 25% of calories from added sugar versus those who consumed less than 10%, with consistent findings across physical activity levels and BMI.
  • The positive health effects of reducing sugar intake appear to be quite rapid. In a study of 43 Latino and African-American children with metabolic syndrome, keeping total calories and calories from carbohydrate identical, a reduction from a mean of 28% of calories from added sugar to 10% significantly reduced triglycerides, LDL cholesterol, blood pressure, and fasting insulin within just 10 days.

Here is a video of Dr. Aseem Malhotra’s lecture at Cape Town Sugar Free Breakfast” Sugar is public enemy number one.”

 How much sugar is safe?

No amount of added sugar is needed by our body, as it does not have any nutritional value. Just a very little amount of free sugar, which includes sugar in fruit juices, honey and syrup has a very deleterious impact on most common global disease of tooth decay. It is the single most important cause of chronic pain and hospital admission in young children.

WHO recently recommended that no more than 3% of our daily calorie intake should come from sugar which amounts to three teaspoons. The average US and UK citizen consumes nearly 4-7 times the recommended amount. This is also because of much of the sugar is consumed unknowingly because it comes from foods that are normally not considered to have much added sugar like Tomato ketchup, salad dressings, and bread. The rest comes from sugary drinks and junk foods like cookies, ice-cream and chocolates.

He also further added that in US, there is no reference range of sugar printed on the food labels. In Europe and UK, food labels carry the range but does not differentiate between children and adults. A can of regular cola contains 9 teaspoons of added sugar which is triple the amount of daily recommendation made in 2009. The public lacks knowledge because of confusing food labels and nearly 80% of processed food contains sugar.[7]

It took nearly 50 years of research and lobbying before a link was established between tobacco and lung cancer. Dr. Cristin Kearns, University of California, San Francisco reveals in her recent paper published in JAMA internal medicine how sugar industry paid scientist and researcher to downplay its role in causation of coronary artery disease. [8]

Sugar Research Foundation paid two scientists, Mark Hegsted and his colleague Dr. Robert McGandy to write a review that countered the link between sucrose and   coronary artery disease. Both of them, overlooked the studies that implicated sugar as a culprit, instead  made only one recommendation of  changing fat and cholesterol intake to prevent coronary heart disease.[9] Similarly, Coca-Cola and candy makers have both tried to influence research practice in favor of their products.  

The message is very clear. There is nothing wrong in an occasional treat, but sugar cannot be a part of “healthy balanced diet”.

Dr. Aseem Malhotra's other articles can be read at his blog: http://doctoraseem.com/

[1] http://www.thesugarreductionsummit.co.uk/

[2] http://sugarwise.org/

[4] https://petition.parliament.uk/petitions/106651
[5] http://www.who.int/mediacentre/news/releases/2016/curtail-sugary-drinks/en/
[6] Briggs ADM, Mytton OT, Kehlbacher A, et al. Overall and income specific effect on prevalence of overweight and obesity of 20% sugar sweetened drink tax in UK: econometric and comparative risk assessment modelling study. BMJ. 2013;347:f6189.
[7] Aseem M. The dietary advice on added sugar needs emergency surgery. BMJ. 2013;346:f3199.
[8] http://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2548255
[9] https://www.statnews.com/2016/09/12/sugar-industry-harvard-research/