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8:00AM 11/13/2014 – 10th Annual Personalized Medicine Conference at the Harvard Medical School, Boston

REAL TIME Coverage of this Conference by Dr. Aviva Lev-Ari, PhD, RN – Director and Founder of LEADERS in PHARMACEUTICAL BUSINESS INTELLIGENCE, Boston http://pharmaceuticalintelligence.com

8:00 A.M. Welcome from Gary Gottlieb, M.D.

Opening Remarks:

Partners HealthCare is the largest healthcare organization in Massachusetts and whose founding members are Brigham and Women’s Hospital and Massachusetts General Hospital. Dr. Gottlieb has long been a supporter of personalized medicine and he will provide his vision on the role of genetics and genomics in healthcare across the many hospitals that are part of Partners HealthCare.

Opening Remarks and Introduction

Scott Weiss, M.D., M.S. @PartnersNews
Scientific Director, Partners HealthCare Personalized Medicine;
Associate Director, Channing Laboratory/
Professor of Medicine, Harvard Medical School 
@harvardmed

Welcome

Engine of innovations

  • lower cost – Accountable care
  • robust IT infrastructure on the Unified Medical Records
  • Lab Molecular Medicine and Biobanks
  • 1. Lab Molecular medicine
  • 2. Biobank
  • 3. Translations Genomics: RNA Sequencing
  • 4. Medical Records integration of coded diagnosis linked to Genomics

BIOBANKS – Samples and contact patients, return actionable procedures

LIFE STYLE SURVEY – supplements the medical record

GENOTYPING and SEQUENCING – less $50 per sequence available to researcher / investigators

RECRUITMENT – subject to biobank, own Consents – e-mail patient – consent online consenting — collects 16,000 patients per month – very successful Online Consent

LAB Molecular Medicine – CLIA — genomics test and clinical care – EGFR identified as a bio-marker to cancer in 3 month a test was available. Best curated medical exon databases Emory Genetics Lab (EMVClass) and CHOP (BioCreative and MitoMAP and MitoMASTER). Labs are renowned in pharmacogenomics and interpretability.

IT – GeneInsight – IT goal Clinicians empowered by a workflow geneticist assign cases, data entered into knowledge base, case history, GENEINSIGHT Lab — geneticists enter info in a codified way will trigger a report for the Geneticist – adding specific knowledge standardized report enters Medical Record. Available in many Clinics of Partners members.

Example: Management of Patient genetic profiles – Relationships built between the lab and the Clinician

Variety of Tools are in development

GenInsight Team –>> Pathology –>> Sunquest Relationship

The Future

Genetic testing –>> other info (Pathology, Exams, Life Style Survey, Meds, Imaging) — Integrated Medical Record

Clinic of the Future-– >> Diagnostics – Genomics data and Variants integrated at the Clinician desk

Gary Gottlieb, M.D. @PartnersNews
President and CEO, Partners HealthCare

Translational Science
Partners 6,000 MDs, MGH – 200 years as Teaching Hospital of HMS, BWH – magnets in HealthCare

2001  – Center for Genomics was started at Partners, 2008 Genomics and Other Omis, Population Health, PM – Innovations at Partners.

Please Click on Link  Video on 20 years of PartnersHealthcare

Video of Dr. Gottlieb at ECRI conference 2012

Why is personalized medicine  important to Partners?

From Healthcare system to the Specific Human Conditions

  • Lab translate results to therapy
  • Biobank +50,000 specimens links to Medical Records of patients – relevant to Clinician, Genomics to Clinical Applications

Questions from the Podium

  • test results are not yet available online for patients
  • clinicians and liability – delays from Lab to decide a variant needs to be reclassified – alert is triggered. Lab needs time to accumulated knowledge before reporting a change in state.
  • Training Clinicians in above type of IT infrastructure: Labs around the Nations deal with VARIANT RECLASSIFICATION- physician education is a must, Clinicians have access to REFERENCE links.
  • All clinicians accessing this IT infrastructure — are trained. Most are not yet trained
  • Coordination within Countries and Across Nations — Platforms are Group specific – PARTNERS vs the US IT Infrastructure — Genomics access to EMR — from 20% to 70% Nationwide during the Years of the Obama Adm.
  • Shakeout in SW linking Genetic Labs to reach Gold Standard

Click to see Advanced Medical Education Partners Offers

 

– See more at: http://personalizedmedicine.partners.org/Education/Personalized-Medicine-Conference/Program.aspx#sthash.qGbGZXXf.dpuf

@HarvardPMConf

#PMConf

@SachsAssociates

@PartnersNews

@MassGeneral

@HarvardHealth

@harvardmed

@BrighamWomens

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Multivitamins – Don’t help Extend Life or ward off Heart Disease and Improve state of Memory Loss

Reporter: Aviva Lev-Ari, PhD, RN

 

Experts: Don’t Waste Your Money on Multivitamins – Three studies find the supplements don’t help extend life or ward off heart disease and memory loss

http://www.nlm.nih.gov/medlineplus/news/fullstory_143473.html

Monday, December 16, 2013

HealthDay news image 

MONDAY, Dec. 16, 2013 (HealthDay News) — With three new studies finding that a daily multivitamin won’t help boost the average American’s health, the experts behind the research are urging people to abandon use of the supplements.

The studies found that popping a daily multivitamin didn’t ward off heart problems or memory loss, and wasn’t tied to a longer life span.

The studies, published in the Dec. 17 issue of the journal Annals of Internal Medicine, found that multivitamin and mineral supplements did not work any better than placebo pills.

Dietary supplements are a multibillion-dollar industry in the United States, and multivitamins account for nearly half of all vitamin sales, according to the U.S. Office of Dietary Supplements.

But a growing body of evidence suggests that multivitamins offer little or nothing in the way of health benefits, and some studies suggest that high doses of certain vitamins might cause harm.

As a result, the authors behind the new research said it’s time for most people to stop taking them.

“We believe that it’s clear that vitamins are not working,” said Dr. Eliseo Guallar, a professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health.

In a strongly worded editorial on the three studies, Guallar and his co-authors urged people to stop spending money on multivitamins.

Even a representatives of the vitamin industry asked people to temper their hopes about dietary supplements.

“We all need to manage our expectations about why we’re taking multivitamins,” Duffy MacKay, vice president of scientific and regulatory affairs for the Council for Responsible Nutrition, a trade group that represents supplement manufacturers, said in a prepared statement.

“Research shows that the two main reasons people take multivitamins are for overall health and wellness and to fill in nutrient gaps,” MacKay said. “Science still demonstrates that multivitamins work for those purposes, and that alone provides reason for people to take a multivitamin.”

However, Guallar said, it’s not clear that taking supplements to fill gaps in a less-than-perfect diet really translates into any kind of health boost.

“It would be great if all dietary problems could be solved with a pill,” he said. “Unfortunately, that’s not the case.”

For the first study, researchers randomly assigned almost 6,000 male doctors over the age of 65 to take either a daily Centrum Silver multivitamin or a look-alike placebo pill. Every few years, the researchers gave the men a battery of tests over the telephone to check their memories.

The men in the study were in pretty good health to begin with, and 84 percent said they faithfully took their pills each day.

After 12 years, there was no difference in memory problems between the two groups.

“No matter which way we broke it down, there was a null effect,” said study author Jacqueline O’Brien, a research associate at Brigham and Women’s Hospital in Boston. “Supplements are often marketed to have benefits for brain health and things like that, and this is a pretty clear takeaway message.”

The same study, however, had previously found that multivitamins might modestly reduce the risk of cancer and cataracts. Cancer risk was reduced by 8 percent, while the risk of cataracts dropped by 9 percent, compared to a placebo.

In the second study, researchers randomly assigned 1,700 heart attack survivors enrolled in a trial of therapy known as intravenous chelation to a daily regimen of high doses of vitamins and minerals or placebo pills.

Participants were asked to take six large pills a day, and researchers think many developed pill fatigue. Nearly half the participants in each part of the study stopped taking their medication before the end of the study. The average time people stuck with it was about two and a half years.

After an average of 55 months, there was no significant difference between the two groups in a composite measure that counted the number of deaths, second heart attacks, strokes, episodes of serious chest pain and procedures to open blocked arteries.

The third study, a research review, assessed the evidence from 27 studies on vitamin and mineral supplements that included more than 450,000 people. That study, conducted for the U.S. Preventive Services Task Force, found no evidence that supplements offer a benefit for heart disease or that they delay death from any cause. They found only a minimal benefit for cancer risk.

The results of the studies are so clear and consistent, the editorial writers said, that it’s time to stop wasting research money looking for evidence of a benefit.

“The probability of a meaningful effect is so small that it’s not worth doing study after study and spending research dollars on these questions,” Guallar said.

SOURCES: Eliseo Guallar, M.D., professor of epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore; Jacqueline O’Brien, Sc.D., research associate, Brigham and Women’s Hospital, Boston; Dec. 16, 2013, news release, Council for Responsible Nutrition, Washington, D.C.; Dec. 17, 2013, Annals of Internal Medicine

HealthDay
Copyright (c) 2013 HealthDay. All rights reserved.
SOURCES
http://www.nlm.nih.gov/medlineplus/news/fullstory_143473.html

http://consumer.healthday.com/cognitive-health-information-26/brain-health-news-80/experts-don-t-waste-your-money-on-multivitamins-683104.html

 

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A quartet of Boston-area research centers including Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Boston Children’s Hospital, and the Broad Institute have teamed to create a new Clinical Cancer Genomics Center that will be headquartered at Dana-Farber.

Reporter: Aviva Lev-Ari, PhD, RN

See also

Personalized Cardiovascular Genetic Medicine at Partners HealthCare and Harvard Medical School

November 12, 2013

NEW YORK (GenomeWeb News) – A quartet of Boston-area research centers including Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Boston Children’s Hospital, and the Broad Institute have teamed to create a new clinical cancer genomics center that will be headquartered at Dana-Farber.

Dana-Farber said today that the new Joint Center for Cancer Precision Medicine will harness a wide range of scientific resources and clinical capabilities from the partners to treat cancer patients and feed treatment data into research programs. The multiple capabilities these partners will share and use in the new center include DNA sequencing and other tumor molecular profiling tools, pathology, radiology, surgery, computational interpretation, and tumor modeling systems, they said.

“The center is creating a new capability to use these huge resources in sequencing and pathology and making sure the data gets to caregivers to help customize cancer treatment,” Dana-Farber President Edward Benz said in a statement.

A core part of the center will be a program to obtain and characterize biopsies from patients during treatment by looking at the tumors’ DNA, RNA, and proteins.

The center also will create a computational biology working group that will spread across Dana-Farber, Broad, and Brigham and Women’s Hospital and will include biologists, bioinformaticians, and software designers to develop algorithms aimed at interpreting genome sequencing data.

The partners also plan to support a translational innovation lab that will pursue studies on actionable cancer mutations and drug resistance, as well as preclinical studies of targeted drug combinations. In addition, they will work with members of the Profile cancer genetics research study, a project already launched by Dana-Farber and Brigham and Women’s that is focused on analyzing tumor DNA and creating a database of relevant mutations.

The CanSeq study, a whole-exome sequencing effort involving Dana-Farber, Brigham and Women’s and Broad investigators, will become “an integral part of the new center,” as researchers plan to study the value of whole-exome sequencing in cancer treatment, Dana-Farber said. Currently, the CanSeq partners are sequencing the whole exomes of 50 lung and colon cancer patients as part of a pilot phase.

“This center will allow us to be optimally positioned to answer the big questions in cancer genetics, especially as they affect clinical decision-making,” said Levi Garraway, an associate professor at Dana-Farber and the new center’s director, as well as head of the CanSeq study.

“We seek to understand which genetic and other molecular alterations predict how tumors will respond to targeted drugs, why some patients become resistant to drugs, and what that means about the treatments that should be tried next,” he added.

 

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Myocardial Strain and Segmental Synchrony: Age and Gender in Speckle-tracking-based Echocardiographic Study

Reporter: Aviva Lev-Ari, PhD, RN

  • Original Article

Age- and Sex-based Reference Limits and Clinical Correlates of Myocardial Strain and Synchrony: The Framingham Heart Study

  1. Susan Cheng1*,
  2. Martin G. Larson2,
  3. Elizabeth L. McCabe3,
  4. Ewa Osypiuk4,
  5. Birgitta T. Lehman4,
  6. Plamen Stanchev4,
  7. Jayashri Aragam5,
  8. Emelia J. Benjamin6,
  9. Scott D. Solomon7 and
  10. Ramachandran S. Vasan8

+Author Affiliations


  1. 1Framingham Heart Study, Framingham, MA; Brigham and Women’s Hospital, Boston, MA

  2. 2Framingham Heart Study, Framingham, MA; Boston University, Boston, MA

  3. 3Boston University, Boston, MA

  4. 4Framingham Heart Study, Framingham, MA

  5. 5Veterans Administration Hospital, West Roxbury, MA

  6. 6Framingham Heart Study, Framingham, MA; Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA; Boston University School of Public Health, Boston, MA

  7. 7Brigham and Women’s Hospital, Boston, MA

  8. 8Framingham Heart Study, Framingham, MA; Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA
  1. * Brigham and Women’s Hospital, 75 Francis Street, PBB-119 Boston, MA 02115scheng3@partners.org

Abstract

Background—There is rapidly growing interest in applying measures of myocardial strain and segmental synchrony in clinical investigations and in practice, but data are limited regarding their reference ranges in healthy individuals.

Methods and Results—We performed speckle-tracking-based echocardiographic measures of left ventricular (LV) myocardial strain and segmental synchrony in healthy Framingham Heart Study participants (n=738, mean age 63 years, 64% women) who were free of cardiovascular disease. Reference values (2.5th, 50th, 97.5th quantiles) were estimated using quantile regression. Age- and sex-based upper (97.5th quantile) limits were as follows:

  • 15.5% to -16.9% (women) and -14.5 to -15.4% (men) for longitudinal strain;
  • -21.9% to -24.3% (women) and -18.9% to -25.0% (men) for circumferential strain;
  • 114-158 msec (women) and 133-206 msec (men) for longitudinal segmental synchrony (SD of regional time-to-peak strains); and,
  • 204-224 msec (women) and 201-288 msec (men) for transverse segmental synchrony.

In multivariable analyses, women compared to men had

  • ~1.7% greater longitudinal strain,
  • ~2.2% greater transverse strain, and
  • ~3.2% greater circumferential strain (P<0.0001 for all).

Older age and higher diastolic blood pressure, even within the normal range, was associated with worse transverse segmental synchrony (P<0.001). Overall, clinical covariates contributed ≤12% of the variation in myocardial strain or synchrony in this healthy sample.

Conclusions—We estimated age- and sex-specific reference limits for echocardiographic measures of LV strain and synchrony in a healthy community-based sample, wherein clinical covariates contributed only a modest proportion of the variation. These data may facilitate interpretation of LV strain-based measures obtained in future clinical research and practice.

Key Words:

  • Received November 19, 2012.
  • Accepted July 18, 2013.

SOURCE

CIRCIMAGING.112.000627Published online before print August 5, 2013,doi: 10.1161/​CIRCIMAGING.112.000627

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Reporter: Aviva Lev-Ari, PhD, RN

 

  • Original Article

Comparison of Echocardiographic and Cardiac Magnetic Resonance Imaging in Hypertrophic Cardiomyopathy Sarcomere Mutation Carriers without Left Ventricular Hypertrophy

  1. Anne Marie Valente1,
  2. Neal K. Lakdawala2,
  3. Andrew J. Powell3,
  4. Sarah P. Evans3,
  5. Allison L. Cirino4,
  6. E. J. Orav4,
  7. Calum A. MacRae4,
  8. Steven D. Colan3 and
  9. Carolyn Y. Ho4*

+Author Affiliations


  1. 1Brigham and Women’s Hospital & Boston Children’s Hospital, Boston, MA

  2. 2Brigham and Women’s Hospital & VA Boston Healthcare System, Boston, MA

  3. 3Boston Children’s Hospital, Boston, MA

  4. 4Brigham and Women’s Hospital, Boston, MA
  1. * Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115 cho@partners.org

Abstract

Background—Left ventricular hypertrophy (LVH) typically manifests during or after adolescence in sarcomere mutation carriers at risk for developing hypertrophic cardiomyopathy (HCM). Guidelines recommend serial imaging of mutation carriers without LVH (G+/LVH-) to monitor for phenotypic evolution, but the optimal strategy is undefined. Compared with echocardiography (echo), cardiac magnetic resonance imaging (CMR) offers improved endocardial visualization and potential to assess scar. However the incremental advantage offered by CMR for early diagnosis of HCM is unclear. Therefore, we systematically compared echo and CMR in G+/LVH- subjects.

Methods and Results—Forty sarcomere mutation carriers with normal echo wall thickness (< 12 mm or z-score < 2.5 in children) underwent concurrent CMR. Mean age was 21.7 ± 11.1 years, 55% were female). If LV wall thickness appeared non-uniform, the size and location of relatively thickened segments were noted. Late gadolinium enhancement (LGE) was assessed with CMR. Diagnostic agreement between echo and CMR was good (90%), although CMR measurements of LV wall thickness were ~19% lower than echo. Four subjects had mild hypertrophy (12.6-14 mm, ≤2 segments) appreciated by CMR but not echo. No subjects had LGE. During median 35-month follow up, 2 subjects developed overt HCM, including 1 with mild LVH by CMR at baseline.

Conclusions—Echo is unlikely to miss substantial LVH; however CMR identified mild hypertrophy in ~10% of mutation carriers with normal echo wall thickness. CMR may be a useful adjunct in HCM family screening, particularly in higher risk situations, or if echocardiographic images are suboptimal or suggest borderline LVH.

Key Words:

Received July 10, 2012.

Revision received April 25, 2013.
Accepted May 3, 2013.

 

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Reporter: Aviva Lev-Ari, PhD, RN

 

 

Nature. 2012 Dec 5. doi: 10.1038/nature11682. [Epub ahead of print]

Mammalian heart renewal by pre-existing cardiomyocytes.

Senyo SESteinhauser MLPizzimenti CLYang VKCai LWang MWu TDGuerquin-Kern JLLechene CPLee RT.

Source

Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Cambridge, Massachusetts 02139, USA.

Abstract

Although recent studies have revealed that heart cells are generated in adult mammals, the frequency of generation and the source of new heart cells are not yet known. Some studies suggest a high rate of stem cell activity with differentiation of progenitors to cardiomyocytes. Other studies suggest that new cardiomyocytes are born at a very low rate, and that they may be derived from the division of pre-existing cardiomyocytes. Here we show, by combining two different pulse-chase approaches-genetic fate-mapping with stable isotope labelling, and multi-isotope imaging mass spectrometry-that the genesis of cardiomyocytes occurs at a low rate by the division of pre-existing cardiomyocytes during normal ageing, a process that increases adjacent to areas of myocardial injury. We found that cell cycle activity during normal ageing and after injury led to polyploidy and multinucleation, but also to new diploid, mononucleate cardiomyocytes. These data reveal pre-existing cardiomyocytes as the dominant source of cardiomyocyte replacement in normal mammalian myocardial homeostasis as well as after myocardial injury.

PMID: 23222518

 

http://www.ncbi.nlm.nih.gov/pubmed/23222518
December 17, 2012

Source of New Heart Cell Growth Discovered

A study in mice suggests that new heart cells arise from pre-existing heart cells and that the renewal process slows with age. The findings may lead to improved regenerative therapy for people with heart damage.

Image of mouse heart cells with brightly colored nuclei.

Dividing heart cells in newborn mice incorporate a tracer that can be seen in the cells’ nuclei. The color scale at the bottom shows the intensity of the tracer signal, with higher intensity toward the right side. Image by Senyo et al., courtesy of Nature.

The heart’s muscle cells, called cardiomyocytes, don’t readily replenish themselves. So an injured heart isn’t easy to mend. After a heart attack, a significant number of cardiomyocytes die. This jeopardizes heart function and can lead to chronic heart failure and possibly death. To help heal damaged hearts, scientists have been searching for a group of cells in the heart that can replenish damaged tissue.

Recent research has shown that the human heart generates new cardiomyocytes throughout its lifespan, but how frequently the cells are generated and where they come from is still debated. Studying heart tissue and cell turnover rate is technically very challenging. Some research has hinted that new cells can arise from progenitor cells at a fairly high rate. Other work has suggested that pre-existing cardiomyocytes divide at a fairly low rate to give rise to new cells.

A team led by Dr. Richard T. Lee of Brigham and Women’s Hospital and Harvard Medical School applied novel technology to investigate heart cell regeneration in mice. They used a technique called multi-isotope imaging mass spectrometry (MIMS). MIMS can detect nonradioactive stable isotope tracers. In contrast to most other tracers, these don’t alter biochemical reactions and aren’t harmful to the organism.

The scientists incorporated a rare stable isotope of nitrogen, nitrogen-15 (15N), into thymidine—one of the building blocks of DNA. When cells divide, the [15N] thymidine is taken up and added to new DNA. It can then be seen in the cells’ nuclei using MIMS. The work was supported in part by several NIH institutes, including the National Institute on Aging (NIA) and National Heart, Lung and Blood Institute (NHLBI). The study appeared online on December 5, 2012, in Nature.

To study cell turnover at different ages, the scientists gave 3 groups of mice [15N] thymidine for 8 weeks starting at day 4 (newborn), 10 weeks (young adult) or 22 months (old adult). To distinguish which types of cells created new cardiomyocytes, they performed similar experiments in mice genetically engineered with fluorescent tags to mark cardiomyocytes.

The scientists found that new heart cells were generated from pre-existing cardiomyocytes rather than progenitor cells. They estimated a yearly renewal rate of less than 1% during normal, healthy conditions. The rate of cell regeneration, they found, declined with age.

The team next used MIMS to study cell turnover following a heart attack. In the 8 weeks after the damage, roughly 3% of heart cells regenerated in the area next to the injured site. However, the researchers also noted that many cells had taken up 15N but not completed cell division.

“Our data show that adult cardiomyocytes are primarily responsible for the generation of new cardiomyocytes and that as we age, we lose some capacity to form new heart cells,” Lee says. “This means that we are losing our potential to rebuild the heart in the latter half of life, just when most heart disease hits us. If we can unravel why this occurs, we may be able to unleash some heart regeneration potential.”

—by Miranda Hanson, Ph.D.

RELATED LINKS:

Reference: Nature. 2012 Dec 5. doi: 10.1038/nature11682. [Epub ahead of print]. PMID: 23222518.

 

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Reporter: Aviva Lev-Ari, PhD, RN

 

 

Study Counters WHI on Heart Risk of Hormones in Menopause

By Crystal Phend, Senior Staff Writer, MedPage Today

Published: October 03, 2012

 

 

 

 

Hormone therapy may actually help the heart in some respects for newly menopausal women, a randomized trial showed, although the impact on hard outcomes like stroke and breast cancer still remains to be seen.

Oral estrogen plus progesterone improved lipid levels, while a transdermal patch improved insulin sensitivity in the KEEPS trial, according to researchers led by S. Mitchell Harman, MD, PhD, of the nonprofit Kronos Longevity Research Institute, which sponsored the trial.

Neither combination hormone treatment altered atherosclerosis progression or raised blood pressure, according to a Kronos press release summarizing a report to be presented Wednesday at the North American Menopause Society meeting in Orlando.

“The results provide reassurance for women who are recently menopausal and taking hormone therapy for short-term treatment of menopausal symptoms,” the group concluded in the release.

The need for reassurance stems from results released a decade ago from the Women’s Health Initiative (WHI), which showed an elevated risk of cardiovascular disease, stroke, and thromboembolic events as well as breast cancer with estrogen plus progestin.

Subsequent studies largely affirmed those risks and pointed to others, including ovarian cancer, lung cancer mortality, and probable dementia.

Menopause organizations largely recommended “the lowest dose for the shortest time” but have started backing away from that stance, instead endorsing a more flexible approach based on type and timing of hormone therapy.

Contradiction or Clarification?

The new study didn’t show significant differences in adverse events between women taking oral or transdermal estrogen with progesterone and those on placebo, including:

  • Breast cancer
  • Endometrial cancer
  • Myocardial infarction
  • Transient ischemic attack
  • Stroke
  • Venous thromboembolic disease

“However, the absolute numbers of such events were extremely small in all three treatment groups, making definitive conclusions impossible,” the researchers acknowledged.

Nor is the KEEPS study ever likely to definitively determine safety, because it was too small to assess clinical events, session moderator and presenter JoAnn E. Manson, MD, DrPH, commented in an email to ABC News and MedPage Today.

But that wasn’t the point of the trial, said Manson, who serves as chief of preventive medicine at Brigham and Women’s Hospital in Boston and is outgoing president of the menopause society.

“The KEEPS trial does not challenge the conclusions of WHI about the risks of clinical events with hormone therapy,” she wrote. “KEEPS and WHI were addressing entirely different questions.”

The earlier study tested hormone therapy as it was in clinical use at the time, for cardiovascular prevention based on epidemiologic suggestion of benefit.

The evidence has clearly come down against hormone therapy for that use, Manson noted.

The question that KEEPS is now answering is how perimenopausal women should approach management of menopausal symptoms — if relatively short periods of hormone therapy are safe, noted Sharonne N. Hayes MD, of the Women’s Heart Clinic at the Mayo Clinic in Rochester, Minn.

So it may be enough that these risks weren’t substantially elevated in the trial, several experts contacted by ABC and MedPage Today agreed.

“The safety of HRT in this newly menopausal population is very reassuring and will likely increase usage as well as demand for HRT in women suffering with vasomotor symptoms,” commented neurologist Cynthia L. Harden, MD, of the North Shore-Long Island Jewish Health System in Great Neck, N.Y., who said the KEEPS data adds nuance rather than contradiction.

The results don’t change the post-WHI clinical approach of yearly reassessment targeting discontinuation after a few years of hormone therapy, added Wendy Vitek, MD, an ob/gyn at the University of Rochester Medical Center in Rochester, N.Y.

Different Populations, Different Drugs

There were some differences between the Women’s Health Initiative and the KEEPS trial that may lead to real differences in outcome, though, researchers suggested.

The KEEPS trial included 727 healthy women ages 42 to 58 who were all within 3 years of the onset of menopause at baseline.

The mean age was 52, whereas the vast majority of women in the nine hormone therapy trials done to date, including the WHI, were in their 60s.

KEEPS randomized its newly-menopausal population to double-blind treatment with cyclical micronized progesterone (Prometrium) plus one of the following:

  •  

    Oral conjugated equine estrogen (Premarin) given at 0.45 mg/day, which was lower than the 0.625 mg/d used in the WHI

  •  

    Transdermal estradiol (Climara) at 50 µg/day, an option not available in the WHI

  • Placebo

 

Even the two different estrogen administration routes showed some differential effects on cardiovascular risk factors, the investigators pointed out.

HDL cholesterol and triglycerides rose while LDL fell with the oral estrogen.

The patch didn’t affect any lipid levels, but it did lower insulin resistance, which the oral form did not.

Neither drug boosted systolic or diastolic blood pressure, unlike the blood pressure increases seen with oral estrogen in the WHI.

Atherosclerosis neither accelerated nor reversed with 48 months of either treatment as monitored by carotid ultrasound, although there was a nonsignificant trend for less coronary artery calcium accumulation compared with placebo, noted Harman, who also practices at the Phoenix VA Medical System.

But that’s not necessarily reassuring with regard to cardiovascular outcomes for this younger group of women, Jacques Rossouw, MBChB, MD, chief of the WHI Branch of the National Heart, Lung and Blood Institute, noted in an email to ABC and MedPage Today.

“Changes in arteries in younger women have little relation to risk of stroke,” he explained. “Estrogen/progestin have [effects] on clotting mechanisms, on inflammation mechanisms. Those are things that trigger acute heart attack or stroke [in younger women]. Perfectly healthy young women can have strokes but have completely normal arteries. ”

Really, “the lack of effect on atherosclerosis reinforces the results of the WHI that hormone therapy is not good preventive therapy for heart disease,” added Lewis H. Kuller, MD, DrPH, of the University of Pittsburgh.

 

As expected, hormone therapy cut down on hot flashes and night sweats while raising bone density and mood, co-investigator Sanjay Asthana, MD, of the University of Wisconsin in Madison, said in the Kronos press release.

Sexual function also improved compared with placebo, in accord with the reduction in vaginal dryness although not the lack of improvement in sex drive seen in prior studies.

“KEEPS also highlights the need for individualized decision making about hormone therapy, given that oral conjugated equine estrogen and transdermal estradiol may have different profiles of effects, and different women have different symptom profiles and priorities for treatment,” the researchers noted in the press release.

KEEPS Sponsor Biased?

Kronos has long had an openly declared interest in countering the 2002 WHI findings of increased health risks from postmenopausal hormone therapy. In 2007, it issued a series of press releases attacking the WHI conclusions and touting KEEPS — one of which included a synopsis describing the nascent trial as “one of the studies to refute the WHI.”

The money behind Kronos comes from the Aurora Foundation. The latter was established by John Sperling, the billionaire founder of the University of Phoenix and other for-profit education ventures.

About 90% of Kronos’ $5.3 million in funding in 2010, the last year for which public records are available, came from Aurora. The $4.8 million given to Kronos that year was more than half of Aurora’s total giving.

Sperling, who is the foundation’s sole trustee, has a long history of involvement in sometimes controversial biological research involving life extension. He funded a successful, multimillion-dollar effort to clone his girlfriend’s dog in 2007, and later a similar cloning project for house cats.

Previously, he had bankrolled a medical clinic in a Phoenix suburb called the Kronos Group — not related to the Kronos Longevity Research Institute — that offered anti-aging remedies to older patients. It has since morphed into Kronos Optimal Health, which markets relatively conventional health and wellness programs to employers and individuals.

2004 article in Wired magazine reported that Sperling had also invested in a group of biotechnology companies seeking to develop anti-aging technologies based on cloning and stem cells.

The study was sponsored by the Kronos Longevity Research Institute with funding from the National Institutes of Health for the ancillary cognitive and affective portion.

The presentation was supported by grant funding from Noven Pharmaceuticals.

This article was developed in collaboration with ABC News. 

 

Primary source: North American Menopause Society
Source reference:
Manson JE, et al “New findings from the Kronos early estrogen prevention study (keeps) Randomized trial” NAMS2012.


Crystal Phend

Staff Writer

Crystal Phend joined MedPage Today in 2006 after roaming conference halls for publications including The Medical PostOncology TimesDoctor’s Guide, and the journal IDrugs. When not covering medical meetings, she writes from Silicon Valley, just south of the San Francisco fog.

SOURCE:

http://www.medpagetoday.com/MeetingCoverage/NAMS/35106?utm_source=breaking-news&utm_medium=email&utm_campaign=breaking-news

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Reporter: Aviva Lev-Ari, PhD, RN

NATIONAL CENTERS FOR BIOMEDICAL COMPUTING

An overarching approach to several disciplines:

  • Other Genomics related subdisciplines:
  • The Biomedical Computing Space

An illustration of the systems approach to biology

http://en.wikipedia.org/wiki/Systems_biology

 

The National Centers for Biomedical Computing (NCBCs) are part of the U.S. NIH plan to develop and implement the core of a universal computing infrastructure that is urgently needed to speed progress in biomedical research. Their mission is to create innovative software programs and other tools that will enable the biomedical community to integrate, analyze, model, simulate, and share data on human health and disease.

Biomedical Information Science and Technology Initiative (BISTI): Recognizing the potential benefits to human health that can be realized from applying and advancing the field of biomedical computing, the Biomedical Information Science and Technology Initiative (BISTI) was launched at the NIH in April 2000. This initiative is aimed at making optimal use of computer science and technology to address problems in biology and medicine. The full text of the original BISTI Report (June 1999) is available.

Current Centers

SimBioS
National Center for Simulation of Biological Structures (SimBioS) at Stanford University
MAGNet
National Center for the Multiscale Analysis of Genomic and Cellular Networks (MAGNet) at Columbia University
NA-MIC Logo
National Alliance for Medical Image Computing (NA-MIC) at Brigham and Women’s Hospital, Boston, MA
I2B2
Integrating Biology and the Bedside (I2B2) at Brigham and Women’s Hospital, Boston, MA
NCBO
National Center for Biomedical Ontology (NCBO) at Stanford University
IDASH
Integrate Data for Analysis, Anonymization, and Sharing (IDASH) at the University of California, San Diego

Biositemap is a way for a biomedical research institution of organisation to show how biological information is distributed throughout their Information Technology systems and networks. This information may be shared with other organisations and researchers.

The Biositemap enables web browserscrawlers and robots to easily access and process the information to use in other systems, media and computational formats. Biositemaps protocols provide clues for the Biositemap web harvesters, allowing them to find resources and content across the whole interlink of the Biositemap system. This means that human or machine users can access any relevant information on any topic across all organisations throughout the Biositemap system and bring it to their own systems for assimilation or analysis.

http://en.wikipedia.org/wiki/Biositemaps

http://www.ncbcs.org/

For

Genome and Genetics: Resources @Stanford, @MIT, @NIH’s NCBCS

go to

https://pharmaceuticalintelligence.com/2012/09/18/genome-and-genetics-resources/

 

Biomedical Computation Review (BCR) is a quarterly, open-access magazine funded by the National Institutes of Health and published by Simbios, one of the National Centers for Biomedical Computing located at Stanford University. First published in 2005, BCR covers such topics as molecular dynamicsgenomicsproteomicsphysics-based simulationsystems biology, and other research involvingcomputational biology. BCR’s articles are targeted to those with a general science or biology background, in order to build a community among biomedical computational researchers who come from a variety of disciplines.

http://en.wikipedia.org/wiki/Biomedical_Computation_Review

 

REFERENCES on BIOINFORMATICS

  1. ^ Biositemaps online editor
  2. a b Dinov ID, Rubin D, Lorensen W, et al. (2008). “iTools: A Framework for Classification, Categorization and Integration of Computational Biology Resources”PLoS ONE 3 (5): e2265. doi:10.1371/journal.pone.0002265PMC 2386255PMID 18509477.
  3. ^ M.L. Nelson, J.A. Smith, del Campo, H. Van de Sompel, X. Liu (2006). “Efficient, Automated Web Resource Harvesting”WIDM’06.
  4. ^ Brandman O, Cho J, Garcia-Molina HShivakumar N (2000). “Crawler-friendly Web Servers”ACM SIGMETRICS Performance Evaluation Review 28 (2). doi:10.1145/362883.362894.
  5. ^ Cannata N, Merelli E, Altman RB (December 2005). “Time to organize the bioinformatics resourceome”PLoS Comput. Biol. 1 (7): e76.doi:10.1371/journal.pcbi.0010076PMC 1323464PMID 16738704.
  6. ^ Chen YB, Chattopadhyay A, Bergen P, Gadd C, Tannery N (January 2007). “The Online Bioinformatics Resources Collection at the University of Pittsburgh Health Sciences Library System—a one-stop gateway to online bioinformatics databases and software tools”.Nucleic Acids Res. 35 (Database issue): D780–5. doi:10.1093/nar/gkl781PMC 1669712PMID 17108360.
 REFERENCES on GENOMICS

  1. ^ National Human Genome Research Institute (2010-11-08).“FAQ About Genetic and Genomic Science”Genome.gov. Retrieved 2011-12-03.
  2. ^ EPA Interim Genomics Policy
  3. ^ [1]
  4. ^ Min Jou W, Haegeman G, Ysebaert M, Fiers W (1972). “Nucleotide sequence of the gene coding for the bacteriophage MS2 coat protein”. Nature 237 (5350): 82–88. Bibcode1972Natur.237…82Jdoi:10.1038/237082a0.PMID 4555447.
  5. ^ Fiers W, Contreras R, Duerinck F, Haegeman G, Iserentant D, Merregaert J, Min Jou W, Molemans F, Raeymaekers A, Van den Berghe A, Volckaert G, Ysebaert M (1976). “Complete nucleotide sequence of bacteriophage MS2 RNA: primary and secondary structure of the replicase gene”. Nature 260 (5551): 500–507.Bibcode 1976Natur.260..500Fdoi:10.1038/260500a0.PMID 1264203.
  6. ^ Sanger F, Air GM, Barrell BG, Brown NL, Coulson AR, Fiddes CA, Hutchison CA, Slocombe PM, Smith M (1977). “Nucleotide sequence of bacteriophage phi X174 DNA”. Nature 265 (5596): 687–695. Bibcode 1977Natur.265..687S.doi:10.1038/265687a0PMID 870828.
  7. ^ Fleischmann RD, Adams MD, White O, Clayton RA, Kirkness EF, Kerlavage AR, Bult CJ, Tomb JF, Dougherty BA, Merrick JM, et al. (1995). “Whole-genome random sequencing and assembly of Haemophilus influenzae Rd”. Science 269 (5223): 496–512.Bibcode 1995Sci…269..496Fdoi:10.1126/science.7542800.PMID 7542800.
  8. ^ “Complete genomes: Viruses”NCBI. 2011-11-17. Retrieved 2011-11-18.
  9. ^ “Genome Project Statistics”Entrez Genome Project. 2011-10-07. Retrieved 2011-11-18.
  10. ^ Hugenholtz, Philip (2002). “Exploring prokaryotic diversity in the genomic era”. Genome Biology 3 (2): reviews0003.1-reviews0003.8. ISSN 1465-6906.
  11. ^ BBC article Human gene number slashed from Wednesday, 20 October 2004
  12. ^ CBSE News, Thursday, 16 October 2003
  13. ^ National Human Genome Research Institute (2004-07-14).“Dog Genome Assembled: Canine Genome Now Available to Research Community Worldwide”Genome.gov. Retrieved 2012-01-20.
  14. ^ McGrath S and van Sinderen D, ed. (2007). Bacteriophage: Genetics and Molecular Biology (1st ed.). Caister Academic Press. ISBN 978-1-904455-14-1.
  15. ^ Herrero A and Flores E, ed. (2008). The Cyanobacteria: Molecular Biology, Genomics and Evolution (1st ed.). Caister Academic Press. ISBN 978-1-904455-15-8.
  16. ^ McElheny, Victor (2010). Drawing the map of life : inside the Human Genome Project. New York NY: Basic Books. ISBN 978-0-465-04333-0.
  17. ^ Hugenholz, P; Goebel BM, Pace NR (1 September 1998).“Impact of Culture-Independent Studies on the Emerging Phylogenetic View of Bacterial Diversity”J. Bacteriol 180 (18): 4765–74. PMC 107498PMID 9733676.
  18. ^ Eisen, JA (2007). “Environmental Shotgun Sequencing: Its Potential and Challenges for Studying the Hidden World of Microbes”PLoS Biology 5 (3): e82.doi:10.1371/journal.pbio.0050082PMC 1821061.PMID 17355177.
  19. ^ Marco, D, ed. (2010). Metagenomics: Theory, Methods and Applications. Caister Academic Press. ISBN 978-1-904455-54-7.
  20. ^ Marco, D, ed. (2011). Metagenomics: Current Innovations and Future TrendsCaister Academic PressISBN 978-1-904455-87-5.
  21. ^ Wang L (2010). “Pharmacogenomics: a systems approach”.Wiley Interdiscip Rev Syst Biol Med 2 (1): 3–22.doi:10.1002/wsbm.42PMID 20836007.
  22. ^ Becquemont L (June 2009). “Pharmacogenomics of adverse drug reactions: practical applications and perspectives”.Pharmacogenomics 10 (6): 961–9. doi:10.2217/pgs.09.37.PMID 19530963.
  23. ^ “Guidance for Industry Pharmacogenomic Data Submissions” (PDF). U.S. Food and Drug Administration. March 2005. Retrieved 2008-08-27.
  24. ^ Squassina A, Manchia M, Manolopoulos VG, Artac M, Lappa-Manakou C, Karkabouna S, Mitropoulos K, Del Zompo M, Patrinos GP (August 2010). “Realities and expectations of pharmacogenomics and personalized medicine: impact of translating genetic knowledge into clinical practice”.Pharmacogenomics 11 (8): 1149–67. doi:10.2217/pgs.10.97.PMID 20712531.

http://en.wikipedia.org/wiki/Genomics

 

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Reporter: Aviva Lev-Ari, PhD, RN

A pivotal study of a third drug will end later this year, and results from a small, early test of it will be reported next week at an Alzheimer’s conference in Vancouver, British Columbia.

These three treatments are practically the “last men standing” in late-stage trials, after more than a decade of failed efforts to develop a drug to halt the mind-robbing disease. Current medicines such as Aricept and Namenda just temporarily ease symptoms. There is no known cure.

Experts say that if these fail, drug companies may pull out of the field in frustration, leaving little hope for the millions of people with the disease. An estimated 35 million people worldwide have dementia, which includes Alzheimer’s. In the U.S., experts say about 5 million have Alzheimer’s.

http://www.timesleader.com/stories/Last-drugs-standing,176933#ixzz20uq13yCg

http://www.timesleader.com/stories/Last-drugs-standing,176933

The three drugs and their developers are:

• Bapineuzumab (bap-ih-NOOZ-uh-mab), by Pfizer Inc. and Johnson & Johnson’s Janssen Alzheimer Immunotherapy unit.

Solanezumab (sol-ah-NAYZ-uh-mab), by Eli Lilly & Co.- Antibody

• Gammagard, by Baxter International Inc. – IV Immune Globulin

http://www.timesleader.com/stories/Last-drugs-standing,176933#ixzz20ulwcTEP

All are given as periodic intravenous infusions; some companies are trying to reformulate them so they could be given as shots. If a major study shows that one of the drugs works, there will be a huge effort to make it more convenient and practical, Thies predicted.

Still, it would probably be very expensive.

The first two on the list are lab-made, single antibodies against amyloid. Gammagard is intravenous immune globulin, or IVIG — multiple, natural antibodies culled from blood. Half a dozen companies already sell IVIG to treat immune system and blood disorders. It takes 130 plasma donations to make enough to treat one patient for a year.

Treating Alzheimer’s with IVIG would cost $2,000 to $5,000 every two weeks, depending on the patient’s weight, said Dr. Norman Relkin, head of a memory disorders program at New York-Presbyterian Hospital/Weill Cornell Medical Center. He consults for some drugmakers and has patents for tests that measure amyloid.

http://www.timesleader.com/stories/Last-drugs-standing,176933#ixzz20uoQU79G

Concern arose when an earlier study found possible bleeding or brain abnormalities in up to 10 percent of patients on the drug. However, most had no symptoms and were able to resume treatment after a brief break, Yuen said. In fact, some researchers think these changes might be a sign the drug is working to clear the amyloid plaque.

The fact that independent monitors have not stopped the new studies has made Dr. Reisa Sperling optimistic the drug will prove to be safe. Director of the Alzheimer’s center at Brigham and Women’s Hospital in Boston, she has consulted for Janssen and Pfizer and enrolled patients in the studies.

Relkin, who is leading the Gammagard study, said that if all three of these drugs fail, “we’re in trouble.” There hasn’t been a new drug even to help symptoms in nine years, he said.

Petersen of the Mayo Clinic agrees.

“If they’re dead-flat negative, the impact on the field and the implication for Big Pharma could be huge,” he said. Companies “may bail” from the field entirely. “They may just say, ‘This nut is too tough to crack.”’

http://www.timesleader.com/stories/Last-drugs-standing,176933#ixzz20upXXNJ6

 

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Reporter: Prabodh Kandala, PhD.

Researchers from Brigham and Women’s Hospital (BWH) have made a groundbreaking discovery that will shape the future of melanoma therapy. The team, led by Thomas S. Kupper, MD, chair of the BWH Department of Dermatology, and Rahul Purwar, PhD, found that high expression of a cell-signaling molecule, known as interleukin-9, in immune cells inhibits melanoma growth.

After observing mice without genes responsible for development of an immune cell called T helper cell 17 (TH17), researchers found that these mice had significant resistance to melanoma tumor growth, suggesting that blockade of the TH17 cell pathway favored tumor inhibition. The researchers also noticed that the mice expressed high amounts of interleukin-9.

“These were unexpected results, which led us to examine a possible contribution of interleukin-9 to cancer growth suppression.” said Purwar.

The researchers next treated melanoma-bearing mice with T helper cell 9 (TH9), an immune cell that produces interleukin-9. They saw that these mice also had a profound resistance to melanoma growth. This is the first reported finding showing an anti-tumor effect of TH9 cells.

Moreover, the researchers were able to detect TH9 cells in both normal human blood and skin, specifically in skin-resident memory T cells and memory T cells in peripheral blood mononuclear cells. In contrast, TH9 cells were either absent or present at very low levels in human melanoma. This new finding paves the way for future studies that will assess the role of interleukin-9 and TH9 cells in human cancer therapy.

“Immunotherapy of cancer is coming of age, and there have been exciting recent results in patients with melanoma treated with drugs that stimulate the immune system,” said Kupper. “We hope that our results will also translate to the treatment of melanoma patients, but much work still needs to be done.”

According to the researchers, other cell-signaling molecules have been used in treating melanoma; however, this study is the first to investigate the role of interleukin-9 in melanoma tumor immunity.

Melanoma is the most dangerous form of skin cancer. The National Cancer Institute estimates that in 2012, there will be more than 76,000 new cases of melanoma in the United States and 9,180 deaths. Melanoma is curable if recognized and treated early.

Abstract:

Interleukin-9 (IL-9) is a T cell cytokine that acts through a γC-family receptor on target cells and is associated with inflammation and allergy. We determined that T cells from mice deficient in the T helper type 17 (TH17) pathway genes encoding retinoid-related orphan receptor γ (ROR-γ) and IL-23 receptor (IL-23R) produced abundant IL-9, and we found substantial growth inhibition of B16F10 melanoma in these mice. IL-9–blocking antibodies reversed this tumor growth inhibition and enhanced tumor growth in wild-type (WT) mice. Il9r−/− mice showed accelerated tumor growth, and administration of recombinant IL-9 (rIL-9) to tumor-bearing WT and Rag1−/− mice inhibited melanoma as well as lung carcinoma growth. Adoptive transfer of tumor-antigen–specific TH9 cells into both WT and Rag1−/− mice suppressed melanoma growth; this effect was abrogated by treatment with neutralizing antibodies to IL-9. Exogenous rIL-9 inhibited tumor growth in Rag1−/− mice but not in mast-cell–deficient mice, suggesting that the targets of IL-9 in this setting include mast cells but not T or B cells. In addition, we found higher numbers of TH9 cells in normal human skin and blood compared to metastatic lesions of subjects with progressive stage IV melanoma. These results suggest a role for IL-9 in tumor immunity and offer insight into potential therapeutic strategies.

Ref:

http://www.sciencedaily.com/releases/2012/07/120708162314.htm.

http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.2856.html

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