Medical research slideshare_june_24_2015

MedicalResearch.com
Exclusive Interviews with Medical Research and
Health Care Researchers from Major and Specialty Medical
Research Journals and Meetings
Editor: Marie Benz, MD
info@medicalresearch.com
June 24 2015
For Informational Purposes Only: Not for Specific Medical Advice.

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States With Stroke Legislation Have More Certified Stroke Centers
MedicalResearch.com Interview with:
Dr. Ken Uchino, MD
Cleveland Clinic Main Campus
Cleveland, OH 44195
• Medical Research: What is the background for this study? What are the main findings?
Dr. Uchino: Stroke center designation started in 2003 and more hospitals have been certified
as primary stroke centers over time. We asked the question how many are certified now?
What are the characteristics of the hospitals that are certified?
• In 2013, nearly a third (23%) of acute short-term adult general hospitals with emergency
departments were certified as stroke centers. 74% of the stroke centers were certified by the
Joint Commission, a non-profit organization that certifies health care facilities and programs.
20% were certified by state health departments. States varied in percentages of hospitals
that were certified, ranging from 4% in Wyoming to 100% in Delaware.
• Not unexpectedly larger hospitals and hospitals in urban locations were more likely to be
certified as stroke centers.
• But a hospital being located in a state with so-called “stroke legislation” more than tripled the
chance of being a certified stroke centers, even accounting for other factors. These states
passed legislation to promote stroke centers and mandated stroke patients to be
preferentially transported to qualified hospitals.
Read the rest of the interviews on MedicalResearch.com
Content NOT an endorsement of efficacy and NOT intended as specific medical advice.

Dr. Ken Uchino, MD
Cleveland, OH 44195
• Medical Research: What should clinicians and patients take away from your report?
• Dr. Uchino: More hospitals are being designated as stroke centers. Certification can be
accomplished in smaller hospitals with appropriate support such as telemedicine and care
protocols. Know whether your local hospital is stroke-certified.
• Changes in policy at state level (stroke legislation) impacts availability of good stroke care.
Remind your legislator the importance of stroke and stroke care.

Dr. Ken Uchino, MD
Cleveland, OH 44195
• Medical Research: What recommendations do you have for future research as a result of
this study?
• Dr. Uchino: Designation of stroke centers and quality improvement programs appear to have
improved stroke care and patient outcomes. Further research needs to show what we can do
next to improve systematic care, whether higher level of comprehensive stroke center
designation improves outcomes, and whether these changes have had impact at population
level.
• Citation:
• Uchino K, et al “Stroke legislation impacts distribution of certified stroke centers in the
United States”
Stroke 2015; DOI: 10.1161/STROKEAHA.114.008007.

Neutrophil-to-Lymphocyte Ratio May Identify Melanoma Patients Likely To Benefit From Ipilimumab
Chiara Martinoli, PhD
Medical Oncology of Melanoma
European Institute of Oncology
Milan, Italy
• MedicalResearch: What is the background for this study? What are the main findings?
• Dr. Martinoli: The recent advent of new immunomodulatory drugs and targeted therapies is
changing the therapeutic algorithm for metastatic melanoma patients. Immunomodulation
with the anti-CTLA-4 antibody ipilimumab improves survival but is not devoid of potential
risks. There is an urgent need for biomarkers to identify patients best suited to receive this
therapy, in order to maximize treatment benefit and spare toxicities.
• In this study, by analyzing pre-therapy hematological parameters of a large group of
metastatic melanoma patients treated with ipilimumab, we showed that neutrophil-to-
lymphocyte ratio is strongly and independently associated to patient outcome. Patients with
a low baseline neutrophil-to-lymphocyte ratio had a double-reduced risk of disease
progression and a two-to-four-fold reduced risk of death, regardless of age, sex and LDH.

Milan, Italy
• MedicalResearch: What should clinicians and patients take away from your report?
• Dr. Martinoli: We suggest that the pre-therapy neutrophil-to-lymphocyte ratio might help
the identification of patients that are more likely to benefit from ipilimumab.
• The identification of patients who are more likely or unlikely to benefit from a therapy in
advance of its initiation would allow to optimize disease-management strategies, by giving
patients the treatment they are best suited to receive, sparing them from un-necessary drug-
related toxicities, and improving their quality of life.
• Moreover, the neutrophil-to-lymphocyte ratio would represent a convenient objective
marker, as it is derived from routine diagnostic procedures, it is does not require additional
expenditure, it is easily and promptly computable.

Milan, Italy
• MedicalResearch: What recommendations do you have for future research as a result of
this study?
• Dr. Martinoli: We would strongly encourage prospective studies with adequately powered
sample size and clinical trials to validate these findings for patients receiving ipilimumab or
other immunotherapies.
• CITATION:
• Br J Cancer. 2015 Jun 9;112(12):1904-10. doi: 10.1038/bjc.2015.180. Epub 2015 May 26.
• Baseline neutrophil-to-lymphocyte ratio is associated with outcome of ipilimumab-treated
metastatic melanoma patients.
• Ferrucci PF1, Gandini S2, Battaglia A1, Alfieri S1, Di Giacomo AM3, Giannarelli D4, Cappellini
GC5, De Galitiis F5, Marchetti P6, Amato G3, Lazzeri A3, Pala L1, Cocorocchio E1, Martinoli C1.

What Is Best Way To Structure Interdisciplinary Hospital Team Work?
Samuel Pannick, MA, MBBS, MRCP
Imperial Patient Safety Translational Research Center, National Institute for Health Research and Imperial College London, London, England
West Middlesex University Hospital National Health Service Trust, Middlesex, England
Response: Improving the quality of general medical ward care is a recognized healthcare
priority internationally. Ward teams have been encouraged to structure their work more
formally, with regular interdisciplinary team meetings and closer daily collaboration with
their colleagues. Some early studies suggested that these changes might benefit patients,
and help ward teams work more efficiently. However, team interventions on medical wards
have been reported with numerous different outcome measures, and prior to this study, it
was unclear what their objective benefits were.
• We showed that there is little agreement on the objective outcomes that best reflect the
quality of interdisciplinary team care on general medical wards. Changes to interdisciplinary
care aren’t reflected in the outcome measures that researchers choose most often, like early
readmission rates or length of stay. Complications of care – although harder to record – might
have more promise as a measure of the quality of inpatient team care in these specific
medical areas.

• Response: Interdisciplinary work in general medicine remains one of the most important –
and enjoyable – components of patient care. However, it’s vital that we don’t try to assess
team performance against inappropriate quality metrics. More nuanced measures require
more resources for data collection, but will ultimately give a truer picture of the quality of
the care.

this study?
• Response: Future research should establish a core set of outcomes that better reflect the
quality of general medical ward care. With these measures in place, new studies can then
focus on how interdisciplinary team care interventions are implemented – an important
factor in their success. Ultimately, we need to understand the preconditions for good
interdisciplinary care, and the way it interacts with other elements of good practice.
• Citation:
• Pannick S, Davis R, Ashrafian H, et al. Effects of Interdisciplinary Team Care Interventions on
General Medical Wards: A Systematic Review. JAMA Intern Med. Published online June 15,
2015. doi:10.1001/jamainternmed.2015.2421.

Genetic and Environmental Factors Linked To Delay of Aging-Related Diseases
MedicalResearch.com Interview with: Arlene Ash Ph.D., Professor David Hoaglin Ph.D., Professor and
Aimee R. Kroll-Desrosiers, MS
Department of Quantitative Health Sciences
University of Massachusetts Medical School
Worcester, MA
Response: The Long Life Family Study (LLFS) is an international collaborative investigation of
the genetics and familial components of exceptional survival, longevity, and healthy aging. It
has enrolled members of long-lived sibships, their offspring, and spouses of either
group. Medicare claims data is a unique, nationally representative source of data on all
treated diseases for most Americans over the age of 65.
• Our main question was: Does membership in a long-lived family protect against disease?
• For each American LLFS participant who was at least age 65 in 2008 and alive in 2009, we
selected four persons from the general Medicare population who matched the participant on
age, sex, and ZIP code of residence. We then used 2008–2010 Beneficiary Annual Summary
Files from the Centers for Medicare & Medicaid Services (CMS) to compare the prevalence of
17 conditions among 781 LLFS participants in Medicare with those of 3,227 non-LLFS
matches.* Analyses accounted for nesting within LLFS families and adjusted for age, sex, race,
and year.

Worcester, MA
• Among LLFS participants identified as members of a long-lived sibship, 7 of the 17 conditions
were significantly less common than for similarly aged controls (Alzheimer’s, hip fracture,
diabetes, depression, prostate cancer, heart failure and chronic kidney disease); in contrast, 4
(arthritis, cataract, osteoporosis and glaucoma) were significantly more common. Spouses,
offspring and offspring spouses of these long-lived siblings share in significantly lower risk for
Alzheimer’s, diabetes and heart failure.
• Several additional analyses found suggestive (although not statistically significant) evidence
of lower disease prevalence in both genetically and maritally-related LLFS cohort

Worcester, MA
• Response: Both genetic and environmental factors appear to be involved in familial clustering
of delayed onset of age-related disease.

Worcester, MA
this study?
• Response: Because most of the offspring generation is still under age 75, it will be fascinating
to see whether the early evidence for a health advantage in both genetic and marital
relatives of long-lived siblings strengthens as the cohort ages.
• It will also be useful to understand why diagnoses of arthritis, cataract, osteoporosis and
glaucoma are more common among the LLFS siblings than in the general population. If this
cannot be explained by differences in health-seeking behaviors, it is truly puzzling.
• * A small number of LLFS members and matches had been eliminated for data
incompleteness, modestly perturbing the 4:1 study design.
• Citation:
• Arlene S. Ash, Aimee R. Kroll-Desrosiers, David C. Hoaglin, Kaare Christensen, Hua Fang, and
Thomas T. Perls
• Are Members of Long-Lived Families Healthier Than Their Equally Long-Lived Peers? Evidence
From the Long Life Family Study J Gerontol A Biol Sci Med Sci first published online March 5,
2015 doi:10.1093/gerona/glv015

Chocolate Linked To Lowered Heart Disease and Stroke Risk
Professor Phyo Kyaw Myint MBBS MD FRCP(Edin) FRCP(Lond)
Clinical Chair in Medicine of Old Age
Epidemiology Group, Division of Applied Health Sciences
University of Aberdeen
Scotland
Response: The research was carried out by academics from the Universities of Aberdeen,
Manchester, Cambridge and East Anglia, as well as the Lancashire Teaching Hospital, the
Medical Research Council Epidemiology Unit, Cambridge and the Academic Medical Centre,
Amsterdam. It has been published online in the journal Heart. The team base their findings
on almost 21,000 adults taking part in the EPIC-Norfolk study, which is tracking the impact of
diet on the long term health of 25,000 men and women in Norfolk, England, using food
frequency and lifestyle questionnaires. The researchers also carried out a systematic review
of the available international published evidence on the links between chocolate and
cardiovascular disease, involving almost 158,000 people—including the EPIC study
participants.
• The EPIC-Norfolk participants (9214 men and 11 737 women) were monitored for an average
of almost 12 years, during which time 3013 (14%) people experienced either an episode of
fatal or non-fatal coronary heart disease or stroke. Around one in five (20%) participants said
they did not eat any chocolate, but among the others, daily consumption averaged 7 g, with
some eating up to 100 g.

Scotland
• Higher levels of consumption were associated with younger age and lower weight (BMI),
waist: hip ratio, systolic blood pressure, inflammatory proteins, diabetes and more regular
physical activity —all of which add up to a favourable cardiovascular disease risk profile.
Eating more chocolate was also associated with higher energy intake and a diet containing
more fat and carbs and less protein and alcohol.
• The calculations showed that compared with those who ate no chocolate higher intake was
linked to an 11% lower risk of cardiovascular disease and a 25% lower risk of associated
death. It was also associated with a 9% lower risk of hospital admission or death as a result of
coronary heart disease, after taking account of dietary factors. And among the 16,000 people
whose inflammatory protein (CRP) level had been measured, those eating the most
chocolate seemed to have an 18% lower risk than those who ate the least. The highest
chocolate intake was similarly associated with a 23% lower risk of stroke, even after taking
account of other potential risk factors.
• Of nine relevant studies included in the systematic review, five studies each assessed
coronary heart disease and stroke outcome, and they found a significantly lower risk of both
conditions associated with regular chocolate consumption. And it was linked to a 25% lower
risk of any episode of cardiovascular disease and a 45% lower risk of associated death.
• The study concluded that cumulative evidence suggests higher chocolate intake is associated
with a lower risk of future cardiovascular events.

Scotland
• Response: This is an observational study so no definitive conclusions about cause and effect
can be drawn. And the researchers point out that food frequency questionnaires do involve a
certain amount of recall bias and underestimation of items eaten. Reverse causation—
whereby those with a higher cardiovascular disease risk profile eat less chocolate and foods
containing it than those who are healthier—may also help to explain the results.
• The study notes that as milk chocolate, which is considered to be less ‘healthy’ than dark
chocolate, was more frequently eaten by the EPIC-Norfolk participants, the beneficial health
effects may also extend to this type of chocolate. This may indicate that not only flavonoids,
but also other compounds, possibly related to milk constituents, such as calcium and fatty
acids, may provide an explanation for the observed association.
• There doesn’t seem to be any evidence of moderate consumption of chocolate increases the
risk of cardiovascular disease, conclude the researchers.
• The EPIC-Norfolk population is middle and older age group and most studies examined the
relationship in middle or older age. Therefore the study results may not be applicable to
children and younger adults.

Scotland
this study?
• Response: Future research is still needed to explore the association between chocolate and
CVD. Studies are needed to better understand the biological mechanism by which chocolate
and flavonoids reduce the risk of CVD. It is also possible that some individuals will not
benefit from increased chocolate consumption such as those who are overweight or diabetic.
More research is needed to identify individuals who would benefit the most.
• Citation:
• Habitual chocolate consumption and risk of cardiovascular disease among healthy men and
women
• Chun Shing Kwok, S Matthijs Boekholdt, Marleen A H Lentjes, Yoon K Loke, Robert N Luben,
Jessica K Yeong, Nicholas J Wareham, Phyo K Myint, Kay-Tee Khaw
• Heart heartjnl-2014-307050Published Online First: 15 June 2015 doi:10.1136/heartjnl-2014-
307050

New Drug Idarucizumab First To Reverse Anticoagulant Dabigatran
Dr. Stephan Glund Ph.D.
Boehringer Ingelheim Pharma GmbH & Co. KG
Transl. Medicine & Clin. Pharmacology
Dr. Glund: There are currently no specific reversal agents available for any of the non-Vitamin
K antagonist oral anticoagulants (NOACs). We are working on the development of
idarucizumab, a specific reversal agent to dabigatran, the first approved NOAC. The study
now published in The Lancet investigated, for the first time in healthy volunteers, the reversal
of the anticoagulant effect of dabigatran by idarucizumab.
• Our study in healthy male volunteers showed that idarucizumab led to immediate, complete
and sustained reversal of the anticoagulant effect of dabigatran. Participants first received
dabigatran and then idarucizumab. The specific reversal agent was given two hours after the
last dose of dabigatran, when dabigatran concentrations were at peak levels. After a five-
minute infusion of idarucizumab, anticoagulation was immediately reversed back to baseline
levels. The reversal effect was sustained for more than 24 hours for all doses of 2g and above.
Idarucizumab was well tolerated by the study participants.
• In addition, our study also showed that administration of idarucizumab reversed dabigatran-
induced inhibition of wound-site fibrin formation, which plays a key role in the blood clotting
mechanism. This suggests that idarucizumab might also reverse impaired haemostasis due to
dabigatran anticoagulation at a wound site.

• Dr. Glund: The data now published in The Lancet show in an impressive manner how
effective idarucizumab was for reversing dabigatran in healthy volunteers. This supports the
specific reversal agent as a highly targeted treatment option if reversal of the anticoagulant
effect is needed, e.g. for urgent interventions.
• But as the current study was conducted in healthy young volunteers, further efficacy and
safety testing is of course required and actually ongoing.

this study?
• Dr. Glund: The clinical study programme for idarucizumab is ongoing. In 2014, Boehringer
Ingelheim has initiated RE-VERSE AD™, a global Phase III patient study to investigate
idarucizumab in emergency settings. Up to 300 patients taking dabigatran, aged 18 years or
over are expected to be enrolled from more than 400 centres in 38 countries worldwide. This
is the first study in patients investigating a specific reversal agent under development for a
non-Vitamin K antagonist oral anticoagulant.
• Citation:
• Safety, tolerability, and efficacy of idarucizumab for the reversal of the anticoagulant effect of
dabigatran in healthy male volunteers: a randomised, placebo-controlled, double-blind phase
1 trial
• Glund, Stephan et al.
• The Lancet Published Online: 15 June 2015
• DOI: http://dx.doi.org/10.1016/S0140-6736(15)60732-2

Average New Yorker Spends More Than Seven Hours Per Day Sitting
Stella Yi, PhD, MPH
New York University Langone School of Medicine,
Department of Population Health
New York, NY 10016
• Dr. Yi: Sedentary behaviors, such as sitting time, are an emerging risk factor in the field of
physical activity epidemiology. Recent studies have demonstrated the negative health
consequences associated with extended sitting time, including metabolic disturbances and
decreased life expectancy independent of the effects of regular exercise.
• We also assessed mean values of self-reported sitting time to characterize these behaviors in
a diverse, urban sample of adults. The average New York City resident sits more than seven
hours a day—greatly exceeding the three hours or more per day that is associated with
decreased life expectancy.

Stella Yi, PhD, MPH
New York, NY 10016
• Among the findings:
• At the lower economic end, individuals spent 6.3 hours per day sitting, while those with
higher incomes spent 8.2 hours per day sitting
• College graduates spent 8.2 hours per day sitting, compared with 5.5 hours per day for those
with less than a high school education
• Whites spent on average 7.8 hours per day sitting, African Americans spent 7.4 hours sitting,
Hispanics spent 5.4 hours sitting, and Asian Americans spent 7.9 hours per day sitting
• Sitting time was highest in Manhattan, compared to other boroughs.
• In the current analysis, we also assessed the validity of a two-question survey method of
sitting time during waking hours using accelerometers to measure sedentary time in a
subsample of our study participants. The correlation between sitting time reported in the
survey and accelerometer-measured sedentary time was modest (r=0.32, p<0.01) with wide
limits of agreement. We interpreted this to mean that while self-reported sitting might be
useful at the population-level to provide rankings and subgroups, it may be limited in
assessing an individual’s actual behavior.

Stella Yi, PhD, MPH
New York, NY 10016
• Dr. Yi: Sitting is distinct from a lack of recreational or non-recreational physical activity and
may potentially impact health outcomes via alternative biological mechanisms. Research in
this area has given rise to the ‘inactivity physiology paradigm,’ or that “sitting too much is not
the same as lack of exercise, and as such, has its own unique metabolic consequences” such
as decreased lipoprotein lipase activity in skeletal muscles in the legs (Hamilton et al., 2008).
Individuals who exercise regularly but are still sedentary for several hours a day may have a
risk of adverse health outcomes that is higher than would be expected given their overall
physical activity levels.
• Despite this, there are no formal recommendations on how much sitting time is detrimental
to health outcomes. Clinicians and patients should use an individual and tailored approach to
decreasing sitting time based on age, mobility and cardiometabolic health. It has been
suggested that taking breaks and standing up to walk around in between sitting times may be
beneficial.

Stella Yi, PhD, MPH
New York, NY 10016
• MedicalResearch: What recommendations do you have for future research as a result of this
study?
• Dr. Yi: Interventions that introduce breaks in sitting time with short walks are feasible, particularly
in areas with high walkability scores. This highlights the potential for intervention through locating
worksites in walkable neighborhoods around the U.S., and to consider walkability in the design of
new business districts. In addition to promoting walking breaks among workers in walkable
neighborhoods, other potential interventions include putting sit-stand desks in offices, holding
walking meetings, promoting stair use, and encouraging movement during television time,
approaches which have not yet been fully characterized in the literature.
• Further, specific public health activities to reduce sitting time should consider cultural and
socioeconomic differences, sex, and age, as well as the time of day the sitting is occurring. For
example, whites and Asian Americans have the highest sitting times, but Asian Americans tend to
hold occupations at both ends of the socioeconomic spectrum. Asian Americans hold desk jobs
where sitting may be addressed by broad workplace wellness programs, but interventions should
also be targeted toward jobs in commercial settings like nail salons or taxi driving, which offer little
opportunity for reducing sitting time.
• Citation:
• Yi SS, Bartley KF, Firestone MJ, Lee KK, Eisenhower DL. Self-Reported Sitting Time in New York City
Adults, The Physical Activity and Transit Survey, 2010–2011. Prev Chronic Dis 2015;12:140488. DOI:
http://dx.doi.org/10.5888/pcd12.140488.

Hospital Autopsy Rate Drops To Near Zero
Mr. Angus Turnbull
Imperial College School of Medicine,
London UK
Mr. Turnbull: Autopsy has been used to advance medical knowledge and understanding of
pathological processes for millennia but increasing evidence indicates its decline in the UK
and elsewhere. This study not only confirms that but suggests autopsy for learning purposes
has almost disappeared.
• In the United Kingdom autopsy is divided into medico-legal autopsy (that required by law
under the jurisdiction of HM Coroner) and consented autopsy (performed with the consent
of the bereaved or their family). Over the past half-century, small single site studies
have noted a marked decline in consented autopsy rates, however there has been no study
for over 20 years to determine the extent of the decline nationwide.
• This study examined all acute NHS Trusts within England, NHS Boards in Scotland and Wales
and Social Care Trusts in Northern Ireland. We found that the average autopsy rate (the
percentage of adult inpatient deaths which under go consented autopsy) in the United
Kingdom in 2013 was only 0.7%. The study showed that in nearly a quarter (23%) of all NHS
Trusts in the United Kingdom, consented autopsy is now extinct.
• These findings may have implications for training, for research and for learning from
mortality – a key aspect of patient safety.

Mr. Angus Turnbull
London UK
• Mr. Turnbull: Consented autopsy has the potential to bring multiple benefits to the medical
community by aiding in clinical audit, quality assurance, public health, misdiagnosis (a key
contributor to avoidable harm), epidemiology and the teaching of trainee pathologists and
medical students. For many of today’s consultants and professors, autopsy may have been a
frequent and important educational experience yet now the majority of medical students
graduate having never seen an autopsy performed.
• Families may request an autopsy or be approached for consent following the loss of a
relative. Unfortunately this practice is dwindling despite research showing that autopsy can
help relieve feelings of guilt and aid closure. It may also reveal underlying inheritable
medical conditions which would have important implications for the health of their children.
• Clinicians and patients should understand that autopsy, which once was of vital importance,
has been reduced to a rarity in modern medicine – for the better or the worse. Unless the
medical and lay community act now then consented autopsy shall soon be extinct along with
all the benefits it can bring. This may be a societal decision but if clinicians recognise an
importance in autopsy, they should act soon to prevent its demise.

Mr. Angus Turnbull
London UK
this study?
• Mr. Turnbull: Further research should be focused on quantifying the benefits of autopsy and
examining the reasons for the decline in numbers. It should look at the impact that low
autopsy figures have on patient safety, clinical audit and research, public health, and
teaching. Ultimately, while this research and the debate on consent autopsy occurs, unless
action is swiftly taken it shall be too late to revive this tried and tested method. It should
examine whether alternative methods of understanding the cause of death are valid and
whether limited, focused autopsy has a role.
• Citation:
• Hospital autopsy: Endangered or extinct?
Angus Turnbull, Michael Osborn, Nick Nicholas
• J Clin Pathol jclinpath-2014-202700Published Online First: 15 June 2015
doi:10.1136/jclinpath-2014-202700

Breast Cancer Conserving Surgery Still Faces Socioeconomic Challenges
Isabelle Bedrosian, M.D., F.A.C.S.
Associate Professor, Department of Surgical Oncology, Division of Surgery,
Medical Director, Nellie B. Connelly Breast Center
The University of Texas MD Anderson Cancer Center, Houston, TX
• Dr. Bedrosian: There have been a number of reports on the rates of Breast Conserving
Therapy (BCT) and mastectomy among women with early stage breast cancer. These reports
have been discordant, with some suggesting that index mastectomy rates have increased and
others suggestion Breast Conserving Therapy rates have actually increased. We hypothesized
that these differences in reporting may be due to data source (ie tertiary referral centers vs
population based studies) and turned to the NCDB, which captures 70% of cancer cases in
the US and as such provides us with the most comprehensive overview on patient treatment
patterns.

• Dr. Bedrosian: The most important message is that the majority of women with early stage
breast cancer are opting for Breast Conserving Therapy, and this proportion has increased
over time. This increase over time has come in part due to improvements in age based use,
geographic disparity and practice based disparities. These are all very important gains.

this study?
• Dr. Bedrosian: Our results also indicate that further improvements in rates of Breast
Conserving Therapy will likely only be made when we address some of the socio-economic
factors that currently appear to be driving the disparities in the surgical treatment of breast
cancer. Therefore, there is a need to better define the factors behind these socio-economic
disparities. These socio-economic factors are likely surrogates for the broad range of
considerations such as child care, transportation challenges, time of work, cultural beliefs,
etc. Better clarity on these fronts is needed in order to implement strategies to overcome
these socio-economic gaps in use of Breast Conserving Therapy for treatment of early stage
breast cancer.
• Citation:
• Lautner M, Lin H, Shen Y, et al. Disparities in the Use of Breast-Conserving Therapy Among
Patients With Early-Stage Breast Cancer . JAMA Surg. Published online June 17, 2015.
doi:10.1001/jamasurg.2015.1102.

Vascular ALK1 May Be Biomarker Indicating Breast Cancer Metastases
Kristian Pietras, Ph.D.
Göran & Birgitta Grosskopf Professor of Molecular Medicine
Strategic Director of Cancer Research Lund University Dept of Laboratory Medicine Lund
Div of Translational Cancer Research Lund, Sweden
Dr. Pietras: Breast cancer is the largest malignant disease among women with 1.7 million
new cases worldwide each year (25% of all new cancer cases for women). The prognosis for
breast cancer patients is relatively good when the disease is detected at early stages (close to
90% of patients are still alive 5 years after diagnosis). Nevertheless, metastatic disease is the
cause of 90% of all cancer-related deaths. Thus, learning more about the metastatic process
and finding new cures for widespread disease is justifiably at the center of clinical attention.
• The current study is part of our ongoing efforts to map support functions performed by the
various cell types comprising the tumor stroma with the premise that decisive treatment
benefit can only be achieved by targeting multiple, but distinct, cell types and pathways that
collectively sustain the growth of tumors. The development of a rich vascular supply is
recognized as a key hallmark of a growing tumor necessary for the development into a
clinically relevant disease.

• Our focus is the role of the tumor vasculature in preventing or promoting metastatic dissemination
from the primary tumor. For a metastasis to form, a cancer cell must,
• 1) detach from its neighboring cells in the mother tumor,
2) traverse the vascular wall to escape into the blood stream,
3) exit the vasculature to enter the metastatic site, and
4) colonize the metastatic site.
• Recent evidence points to that the transmigration into and out of the vasculature is a regulated
process of previously unrecognized importance for the metastatic process. Importantly, the fact
that the process of escape into/from the vasculature is regulated also implies that it is possible to
use drugs to block this process.
• In the present study, we have combined functional studies in advanced models of cancer and
computational biology approaches to investigate the specific contribution to the metastatic process
of a molecular signaling pathway emanating from the ALK1 protein expressed by endothelial cells in
the vasculature. Using information from 2 different patient cohorts including a total of nearly 2000
breast tumors, we found that patients specifically having high levels of ALK1 in the vasculature of
their tumor were much more likely to develop metastatic/recurrent disease. Accordingly,
therapeutic administration of a drug (dalantercept) blocking the action of ALK1 prevented
metastatic dissemination in multiple mouse models of breast cancer to a large degree. In addition,
combination therapy of dalantercept and a commonly used chemotherapeutic drug (docetaxel) was
exceedingly effective in preventing spread of the primary tumor to the lungs.
• Our results suggest that the molecular features of the tumor vasculature are important to consider
as potential determinants of breast cancer dissemination and that metastatic spread can be
delayed by targeting the tumor vasculature.

• Dr. Pietras: Our results suggest that the presence of high levels of ALK1 in the breast tumor
vasculature is a prognostic biomarker for metastatic disease. Moreover, our work encourages
clinical testing of drugs blocking ALK1 in breast cancer with prevention of metastatic
dissemination as the primary outcome.
• Furthermore, our study reiterates the active participation of the tumor vasculature in the
process of metastatic dissemination, and highlights that specific molecular features of
endothelial cells (in this case, high expression of ALK1) can serve as both prognostic
biomarkers and drug targets in breast cancer.

this study?
• Dr. Pietras: We are currently more in detail describing the molecular features of a tumor
vasculature conducive to metastatic dissemination, as well as those that are protective of
metastatic dissemination. Our hope is that this will reveal an even more precise and global
prognostic biomarker of recurrent disease, as well as identify additional and complementary
drug targets. In addition, we are currently performing therapeutic studies with dalantercept
in models of breast cancer in order to pinpoint the precise therapeutic regimen and disease
stage at which the treatment is the most effective.
• Citation:
• Endothelial ALK1 Is a Therapeutic Target to Block Metastatic Dissemination of Breast Cancer
• Sara I. Cunha, Matteo Bocci, John Lövrot, Nikolas Eleftheriou, Pernilla Roswall, Eugenia
Cordero, Linda Lindström, Michael Bartoschek, B. Kristian Haller, R. Scott Pearsall, Aaron W.
Mulivor, Ravindra Kumar, Christer Larsson, Jonas Bergh, and Kristian Pietras
• Cancer Res June 15, 2015 75:2445-2456; doi:10.1158/0008-5472.CAN-14-3706

Childhood Adversity Doubles Heart Disease Risk in Adulthood
Jaana Halonen Ph.D
Finnish Institute of Occupational Health
Kuopio, Finland
• Dr. Halonen: Research on predictors of cardiovascular disease has increasingly focused on
exposures to risk factors other than the conventional behavioral and biological ones, such as
smoking, hypertension, dyslipidaemia, or diabetes. One of the potential predictors beyond
the conventional risks is exposure to childhood psychosocial adversities. Previous studies
have found that people who had experienced financial difficulties, serious conflicts and long-
term disease in the family in childhood have a higher level of cardiovascular risk factors and
increased cardiovascular morbidity in adulthood, but the underlying mechanisms linking
childhood exposure to adult disease remain unclear. It is possible that childhood adversity
sets an individual on a risk pathway leading to adverse future exposures. An important source
of adversity experienced in adulthood is residence in a socioeconomically disadvantaged
neighborhood. However, no previous study had examined the combined effect of childhood
psychosocial adversity and adult neighborhood disadvantage on cardiovascular disease risk.
• We found that exposure to childhood psychosocial adversity and adult neighborhood
disadvantage in combination was associated with a doubling of the risk of incident
cardiovascular disease in adulthood when compared to the absence of such exposures. This
association was not explained by conventional cardiovascular risk factors. Neither childhood
psychosocial adversity nor adult neighborhood disadvantage alone were significantly
associated with incident CVD, although they were associated with CVD risk factors.

Jaana Halonen Ph.D
Kuopio, Finland
• Dr. Halonen: Clinical implications of the present findings should be drawn cautiously. Because
factors included in a conventional cardiovascular risk assessment did not explain the
association between childhood psychosocial adversity, adult neighborhood disadvantage, and
incident cardiovascular heart disease, tackling smoking, hypertension, dyslipidaemia and
other conventional risk factors only might not remove the excess CVD risk among individuals
exposed to childhood adversity and adult disadvantage. Thus, the reduction of childhood
adversity and adult disadvantage remains an important goal for health policies.

Jaana Halonen Ph.D
Kuopio, Finland
• MedicalResearch:What recommendations do you have for future research as a result of
this study?
• More research is needed to increase understanding about the nature of these associations in
the aetiology of cardiovascular diseases. We need to assess whether the association is
replicable in other populations and whether it is causal or only indicative of other risk factors.
We also need evidence of the potential benefits of interventions targeting childhood
adversity and adult disadvantage in the prevention of cardiovascular diseases, and how these
factors can realistically be modified in clinical settings in a cost-effective manner.
• Circulation. 2015 Jun 11. pii: CIRCULATIONAHA.115.015392. [Epub ahead of print]
• Childhood Psychosocial Adversity and Adult Neighborhood Disadvantage as Predictors of
Cardiovascular Disease: A Cohort Study.
• Halonen JI1, Stenholm S2, Pentti J3, Kawachi I4, Subramanian SV4, Kivimäki M5, Vahtera J6.

Adolescent Hyperinsulinemic Androgen Excess: Insulin Sensitization May Slow Biologic Aging
Francis de Zegher, MD, PhD
Department of Development and Regeneration, University of Leuven Leuven, Belgium &
Lourdes Ibáñez, MD, PhD
Hospital Sant Joan de Déu, University of Barcelona
Barcelona, Spain
• Medical Research: What is the background for this study?
Response: Hyperinsulinemic androgen excess is the most frequent hormonal disorder of
adolescent girls. It seems to be mainly driven by an excessive and/or inappropriate storage of
fat due to a chronically positive energy balance.
• The traditional approach (not approved by FDA or EMA) is to silence the ovaries by giving an
oral contraceptive.
• An alternative approach is to change the storage of fat by giving an insulin-sensitizing
combination of generics in low dose.

Barcelona, Spain
• Medical Research: What are the main findings?
• Response: It has previously been shown that the insulin-sensitizing approach has more
normalizing effects than the oral-contraceptive approach.
• Here, we add that prolonged insulin sensitization is also accompanied by a lengthening of
telomeres and thus conceivably by a slower biologic aging of the girls.

Barcelona, Spain
• Medical Research: What should clinicians and patients take away from your report? What
recommendations do you have for future research as a result of this study?
• Response: More head-to-head comparisons are needed before an insulin-sensitizing
intervention can be approved (as an adjunct to lifestyle intervention) to treat adolescent girls
with hyperinsulinemic androgen excess.
• Citation:
• de Zegher F, Díaz M, Ibáñez L. Association Between Long Telomere Length and Insulin
Sensitization in Adolescent Girls With Hyperinsulinemic Androgen Excess. JAMA Pediatr.
Published online June 15, 2015. doi:10.1001/jamapediatrics.2015.0439.

Erythomycin Allows Gastric Emptying To Prevent Aspiration In ER Patients
Christoph Czarnetzki MD, MBA
Division of Anesthesiology
Geneva University Hospitals
Geneva, Switzerland
Medical Research: What is the background for this study? What are the main findings?
Dr. Czarnetzki: In the US, about 40 million patients undergo a general anesthetic each year, and
approximately 12,000 broncho-aspirate. Broncho-aspiration of gastric juice may lead to acute
respiratory distress syndrome, carrying a 40% mortality rate. The risk is increased 10-fold in
patients undergoing emergency surgery. Trauma patients may have ingested food before their
accident, or have swallowed blood from oral or nasal injuries. Also, gastric emptying is delayed
due to head injury, stress, pain, and opioid medication. Non-trauma patients may have delayed
gastric emptying due to paralytic ileus and critical illness, leading to significant residual stomach
content even after long fasting periods. Erythromycin, a macrolide antibiotic, and motilin
receptor agonist induces antral contractions, and increases the lower esophageal sphincter tone,
which is an important barrier against gastro-esophageal reflux. Although gastric emptying
properties of erythromycin are well known, its efficacy in patients undergoing emergency surgery
has never been investigated before to our knowledge.

Geneva, Switzerland
In our study we included 132 patients undergoing general anesthesia for emergency procedures
and we could show that erythromycin increased the proportion of clear stomach and decreased
acidity of residual gastric liquid. Dependent of the definition of empty stomach (less than 40 ml
and absence of solid food or completely empty stomach) the absolute risk reduction ranged from
17% to 24%, equivalent to a number needed to treat of four to six patients to produce one
completely cleared stomach. Erythromycin was particularly efficacious in non-trauma patients.
Adverse effects were minor.

Geneva, Switzerland
• Dr. Czarnetzki: In emergency patients we have now a medication at hand with wich we can
promote gastric emptying. 3 mg/kg of Erythromycin should be given intravenously at least 15
minutes prior to intubation. In patients which ingested solid food Erythomycin should be
given earlier, maybe at arrival in the emergency room, as emptying of solid food takes more
time than liquids.

Geneva, Switzerland
this study?
• Dr. Czarnetzki: Future research could investigate to what extent Erythromycine reduces
bronchoaspiration and its consequences. On the other hand thousands of patients have to be
included in a multicenter study to have sufficient power to investigate this outcome. In view
of the strong results of our study it should be questioned if such a study is still necessary.
• Citation:
• Czarnetzki C, Elia N, Frossard J, et al. Erythromycin for Gastric Emptying in Patients
Undergoing General Anesthesia for Emergency Surgery: A Randomized Clinical Trial. JAMA
Surg. Published online June 17, 2015. doi:10.1001/jamasurg.2015.0306.

Resveratrol May Help Convert Bad Fat to Good
Dr. Min Du Ph.D
Department of Animal Sciences Washington Center for Muscle Biology Washington State University
Pullman, WA
Medical Research: What is the background for this study? What are the main findings?
Response: The beige fat is only recently identified and is highly inducible. we observed that
polyphenolic compounds including resveratrol enhances AMPK activity, and hypothesized that
resveratrol might enhance the formation of beige fat through activation of AMPK. Therefore, we
used resveratrol, a very well characterized polyphenolic compound as a representative of
polyphenolic compounds in fruits, to check its effects on the formation of beige fat. We found
that resveratrol induced the formation of beige adipocytes both in vitro and in vivo. We further
found that the lipid oxidation rate was enhanced due to the formation of beige fat, which is
correlated with the anti-obesity effect of resveratrol.

Dr. Min Du Ph.D
Pullman, WA
• Response: The anti-obesity effects of polyphenolic rich fruits might be stronger than we
thought. In addition to fruits, certain other foods or drinks with high polyphenol contents
such as tea and coffee, or red wine, might also have good anti-obesity effects.

Dr. Min Du Ph.D
Pullman, WA
this study?
• Response: Studies using the whole fruit supplementation might be warranted. We are
planning to conduct a mice study by directly feeding mice with raspberry powder to examine
whether we observe similar or even better preventive effects on obesity.
• Citation:
• Resveratrol induces brown-like adipocyte formation in white fat through activation of AMP-
activated protein kinase (AMPK) α1
• Wang S1, Liang X2, Yang Q2, Fu X2, Rogers CJ2, Zhu M3, Rodgers BD2, Jiang Q4, Dodson MV2, Du
M2.
• Int J Obes (Lond). 2015 Jun;39(6):967-76. doi: 10.1038/ijo.2015.23. Epub 2015 Mar 12.

Wireless Devices Can Still Cause Interference With Some Medical Devices
Mehdi Ardavan
Concordia University/Université Concordia
• Medical Research: What is the background for this study?
• Response: That thousands patients die each year in US hospitals due to medical errors that
could be prevented if medical staff were provided with instant access to patient records.
Wireless technology (such as portable tablets) is one way of providing this instant access. But
using such devices can cause electromagnetic interference (EMI) with electronic medical
devices and can lead to dangerous consequences for patients. Hospitals may have a policy of
minimum separation distance (MSD) which means that the staff members carrying wireless
devices cannot approach sensitive medical devices closer than the specified MSD. The
problem was that the recommend values of the minimum separation distance were not
based on a quantitative and thorough analysis of the problem. We wanted to see what is the
correct value of MSD, and how it’s determined.

Mehdi Ardavan
• Medical Research: What are the main findings?
• Response: We developed new and fast methods for estimating the electromagnetic field
distribution. We also mathematically modeled the roaming nature of the staff members
carrying the wireless transmitters. Then we modeled the minimum separation distance policy
and added an option to account for a possibility of non-compliance with the policy.
• First, we assumed a full compliance with MSD policy and found that the risk of interference
decreased constantly as the minimum separation distance was increased. Quantitative
recommendations are made for the value of the MSD. But once we considered a small non-
compliance probability, an interesting and unexpected phenomenon was observed: the EMI
risk does not decrease beyond a certain value and remains almost constant for all MSDs
bigger than a value we call the optimal MSD. If we increase the minimum separation distance
beyond its optimal value, the risk of EMI does not decrease but more restrictions and thus
more inconvenience is put on the staff members. So larger values of MSD are not necessarily
safer and are not recommended. We also find that the risk and the optimal minimum
separation distance are both sensitive to the rate of compliance with the MSD policy.

Mehdi Ardavan
• Response: Clinicians and patients must recognize that the electromagnetic interference is an
important issue, and compliance with the MSD policy is the key factor in controlling the risk
of EMI. An MSD of about arm’s length seems to be sufficient for most general scenarios. We
recommend that the staff members are educated in this regard and both staff members and
patients are constantly reminded that a near full compliance rate is expected.

Mehdi Ardavan
this study?
• Response: We modeled up to two roaming transmitters. Future research should develop new
algorithms that make it possible to consider more transmitters easily. It would also be
interesting to adapt and reapply our model to an operating room where many staff members
are constantly near the patient’s bedside with their portable electronic devices.
• Citation:
• EMI Risk Assessment in a Hospital Ward With One and Two Roaming Wireless Transmitters
• Ardavan, M. ; Eng. & Comput. Sci. Fac., Concordia Univ., Montreal, QC, Canada ; Trueman,
C.W. ; Schmitt, K.A.
• 10.1109/TEMC.2014.2362717

Concomitant Proton-Pump Inhibitors With Antiplatelet Drugs Requires Caution
José C. Nicolau, MD, PhD, FACC
Professor -University of São Paulo Medical School
Director – Acute Coronary Disease Unit, Heart Institute
• MedicalResearch: What is the background for this study?
• Dr. Nicolau: Previous studies, mainly performed in patients undergoing percutaneous
coronary intervention (PCI), have shown that concomitant use of proton-pump inhibitors
(PPIs) diminishes the antiplatelet effect of the drug clopidogrel. This diminished response to
clopidogrel has in turn been associated with an increased risk of stent thrombosis and
ischemic events. Our paper presented results from a secondary analysis performed in
patients enrolled in the TRILOGY ACS randomized clinical trial. Our study is the first to
examine the influence of interactions between PPIs and clopidogrel or the newer, more
potent antiplatelet drug prasugrel, as well as correlations with platelet reactivity and clinical
outcomes in high-risk patients who were receiving medical management without
revascularization following acute coronary syndrome (ACS).

•
MedicalResearch: What are the main findings?
• Dr. Nicolau: Among patients who were receiving proton-pump inhibitors at baseline (23% of
total), the adjusted hazard ratio (HR) for the composite outcome of cardiovascular
death/myocardial infarction/stroke was 0.73 (95% CI, 0.54-0.98) when comparing prasugrel
with clopidogrel. Among patients who were not taking PPIs, the HR was 1.01(95% CI, 0.85-
1.19). The main factor driving these results was myocardial infarction (HR=0.61 [95% CI, 0.42-
0.88]; P for interaction=0.012). These findings could not be explained by the results obtained
in a subgroup of patients who participated in platelet reactivity testing.
• Dr. Nicolau: We need to be careful with the concomitant utilization of clopidogrel and
proton-pump inhibitors.

this study?
• Dr. Nicolau: Additional studies are needed to delineate optimal antiplatelet strategies in high-
risk Acute Coronary Syndrome patients who are managed medically without revascularization
and who also require long-term proton-pump inhibitors therapy.
• Citation:
• Concomitant proton-pump inhibitor use, platelet activity, and clinical outcomes in patients
with acute coronary syndromes treated with prasugrel vs. clopidogrel and managed without
revascularization: Insights from the TRILOGY ACS Trial
• Nicolau, Jose Carlos et al.
• American Heart Journal
• Received: December 22, 2014; Accepted: May 31, 2015; Published Online: June 10, 2015
Publication stage: In Press Accepted Manuscript

Comorbidities Increase Mortality Risk of Atrial Fibrillation In Blacks and Hispanics
MedicalResearch.com Interview with: Dr. Mary Vaughan Sarrazin Ph.D.
Associate Professor University of Iowa Roy and Lucille Carver College of Medicine, and Iowa City VA Medical Center, Center
for Comprehensive Access & Delivery Research and Evaluation (CADRE) Iowa City, IA
Dr. Rajesh Kabra MD Division of Cardiology, Department of Internal Medicine
University of Tennessee Health Science Center, Memphis, Tennessee
• Response: Atrial fibrillation is associated with high risk of stroke and death. It is not known if
these outcomes are different in whites, blacks and Hispanics.
• In our study of over 500,000 Medicare patients over the age of 65 years with newly
diagnosed atrial fibrillation, we noted that compared to whites, blacks and Hispanics had a
higher risk of stroke (46% and 11% higher respectively) and mortality(66% and 21%
respectively). However after correcting for other co-morbidities and illnesses, the risk of
mortality was the same in all the races; the higher risk of stroke was decreased in blacks and
eliminated in Hispanics. This suggests that in blacks and Hispanics, atrial fibrillation is a
marker for higher mortality and identifies patients at higher risk of death.

•
MedicalResearch: What should clinicians and patients take away from your report?
• Response: Blacks and Hispanics with atrial fibrillation are at much higher risk of stroke and
death compared to the whites and need to be aggressively treated not only for atrial
fibrillation but also for other associated co-morbidities.

this study?
• Response: Future studies need to address the factors that increase the risk of death and
stroke in blacks and Hispanics with atrial fibrillation so that preventative measures can be
taken to prevent these devastating outcomes.
• Citation:
• Effect of Race on Outcomes (Stroke and Death) in patients > 65 Years of Age with Atrial
Fibrillation
• Kabra, Rajesh et al.
• American Journal of Cardiology , Volume 116 , Issue 2 , 230 – 235
DOI: http://dx.doi.org/10.1016/j.amjcard.2015.04.012

Bariatric Surgery Reduces Urinary Incontinence As Well As Obesity
Leslee L. Subak, MD
University of California, San Francisco
Professor, Departments of Obstetrics, Gynecology & Reproductive Sciences, Urology and Epidemiology & Biostatistics
Chief of Gynecology, SF Veterans Affairs Medical Center
UCSF Women’s Health Clinical Research Center
• Dr. Subak: Urinary incontinence is very common, affecting an estimated 30 million adults in
the U.S., and may account for as much as $60 billion in annual medical costs. Incontinence
can cause significant distress, limitations in daily functioning, and reduced quality of life.
Obesity is an important risk factor, with each 5-unit increase in body mass index – a ratio of
someone’s weight divided by the square of their height – above normal weight associated
with far higher rates of incontinence. The prevalence of incontinence has been reported to
be as high as 70 percent among severely obese women, and 24 percent among severely
obese men (BMI greater than 40, or more than about 100 pounds greater than ideal body
weight).
• Since obesity is a risk factor for incontinence, several studies have examined whether weight
loss is a treatment for incontinence among obese people with the condition. Clinical trials
have shown the low calorie diets, behavioral weight reduction, and bariatric surgery
are associated with improvement in incontinence in obese women and men through one
year, but evidence on the durability of this effect is lacking.
• We performed this study to examine changes in urinary incontinence and identify factors
associated with improvement among women and men in the first 3 years following bariatric
surgery.

Leslee L. Subak, MD
• This study included 1987women and men in the Longitudinal Assessment of Bariatric
Surgery-2 (LABS-2) study performed at 10 hospitals at 6 clinical centers in the
U.S. who underwent bariatric surgery between 2005 and 2009. The study participants
ranged in age from 18 to 78 years old – the median age was 47. The analysis controlled for
factors such as age, race, smoking status and recent pregnancy. Nearly 79 percent of the
participants in the study were women with 49% reporting at least weekly incontinence,
compared with 2% of men reporting incontinence.
• Following surgery and large weight loss of 29% for women and 26% for men, substantial
improvements in incontinence were observed, with a majority of women and men achieving
remission at 3 years post-surgery. The more weight lost, the higher the chances of
improvement. While the risk of relapse rose with each gain of about 10 pounds, overall there
was substantial improvement for both women and men. People who were older, had severe
walking limitations or were recently pregnant showed less improvement.

Leslee L. Subak, MD
• Dr. Subak: Obesity is a strong risk factor for incontinence, with nearly half of women and
more than a fifth of the men with severe obesity reporting having at least one episode of
incontinence a week.
• Surgical weight loss for severely obese men and women is an effective treatment with
sustained improvement in incontinence through 3 years after surgery.
• Improvement in urinary incontinence may be another important long-term benefit among
the extensive health improvements associated with bariatric surgery.
• Improvement in urinary incontinence may help motivate severely obese men and women
with incontinence to undergo bariatric surgery or other weight loss interventions and
improve long-term weight maintenance.

Leslee L. Subak, MD
this study?
• Dr. Subak: Explore why weight loss is an effective treatment and how to use incontinence
(and other quality of life conditions such as erectile dysfunction) to motivate weight loss and
weight maintenance.
• Citation:
• Subak LL, King WC, Belle SH, et al. Urinary Incontinence Before and After Bariatric Surgery.
JAMA Intern Med. Published online June 22, 2015. doi:10.1001/jamainternmed.2015.2609.

Oncology Evidence Based On Surrogate Survival May Be Poor
Vinay Prasad, MD, MPH
Medical Oncology Service, National Cancer Institute
National Institutes of Health
Bethesda, Maryland
• Dr. Prasad: In medicine, there are two types of endpoints: clinical endpoints and
surrogate endpoints. Clinical endpoints, such as survival or quality of life, measure how a
patient, feels, functions or lives. In contrast, a surrogate endpoint is not a measure of patient
benefit. Instead, it is merely hoped to correlate with one. LDL levels are a surrogate for
cardiovascular risk, for instance.
• Oncologists use and trust surrogate endpoints, such as response rate, progression free
survival and disease free survival. The majority of drug approvals and many guideline
recommendations are based on improvements in surrogates. Surrogates are assumed to
correlate with overall survival, but we wanted to know if this was true, and under what
circumstances.
• We reviewed all well done studies of surrogate-survival association. We found that the
majority–especially in the setting of metastatic disease–found a poor correlation between a
surrogate and survival. In fact, correlations were strong in only a handful of settings, such as
adjuvant colorectal cancer. Moreover, we found that correlations were always based on a
subset of potentially informative literature, even when authors surveyed unpublished
trials. Missing data in these association studies raises the concern that correlations would be
different if all data had been considered.
• Our overall conclusion was that most surrogate-survival correlations in oncology are based on
weak evidence and are poor.

Bethesda, Maryland
•
• Dr. Prasad: Clinicians should be skeptical of new cancer drugs or combinations that merely
improve surrogates. Clinicians should consult our paper to see if the specific surrogate-
survival correlation they are considering is strong or weak.

Bethesda, Maryland
this study?
• Dr. Prasad: Oncologists who have conducted clinical trials, and have access to those primary
data should share those datasets, so that researchers may better study the strength of
correlation between surrogates and survival.
• Citation:
• Prasad V, Kim C, Burotto M, Vandross A. The Strength of Association Between Surrogate End
Points and Survival in Oncology: A Systematic Review of Trial-Level Meta-analyses. JAMA
Intern Med. Published online June 22, 2015. doi:10.1001/jamainternmed.2015.2829.

Early Palliative Care Consultations Are Well Received By Patients But Don’t Decrease Health Services
Gabrielle Rocque MD
Division of Hematology & Oncology
University of Alabama
Birmingham, Alabama
• Dr. Rocque: This study grew out of a retrospective study we conducted in 2010 in which we
evaluated the characteristics of patients admitted to our solid tumor oncology service, what
occurred during their hospitalization, and what their outcomes were after discharge. We
identified that the average life expectancy of the population was less than 4 months and
therefore, inpatient admission was an opportunity for palliative care support. Therefore, we
conducted a sequential, prospective cohort study of patients before and after
implementation of triggered palliative care consults for patients with advanced cancer. We
found that patients’ prognostic awareness meaningfully and significantly improved after the
implementation of consults, but there was little impact on utilization of health services. We
did identify that providing consults to the entire population of patients was logistically
challenging due to short stays, high-acuity symptoms, and individual provider resistance, but
overall the oncology providers found the consults to be beneficial.

Gabrielle Rocque MD
Birmingham, Alabama
• Dr. Rocque: Palliative Care consultation for hospitalized cancer patients are well-received and
enhance communication including an improved understanding of their cancer and their
prognosis. The oncologists also report an improved understanding of their patients’
perspective. We recommend implementing a standardized approach to palliative care
consultation.

Gabrielle Rocque MD
Birmingham, Alabama
this study?
• Dr. Rocque: While hospitalization is a time of high palliative care needs, life expectancy and
hospital lengths of stay are short so the impact of palliative care consultation is
limited. Given the substantial benefits of early outpatient palliative care, we suggest that
future research focus on strategies for earlier integration of ambulatory palliative care
services after inpatient consultation.
• Citation:
• J Pain Symptom Manage. 2015 Jun 15. pii: S0885-3924(15)00251-1. doi:
10.1016/j.jpainsymman.2015.04.022. [Epub ahead of print]
• A Quantitative Study of Triggered Palliative Care Consultation for Hospitalized Patients with
Advanced Cancer.
• Rocque GB1, Campbell TC2, Johnson SK2, King J3, Zander MR4, Quale RM4, Eickhoff JC5, Cleary
JF3.

Commuter Patterns Can Help Predict Influenza Spread
Brooke Bozick Ph.D. Candidate
Population Biology, Ecology, & Evolution Program
Emory University
• MedicalResearch: What is the background for this study?
• Response: Previous research at the global scale has shown that air travel is important for the
spread of disease. For example, much work has focused on the recent Ebola epidemic in
Africa, identifying where this disease emerged and then using air travel networks to predict
the path of spread from there.
• At a more local scale, other modes of transportation may be more important to structuring
pathogen populations. We were interested in investigating seasonal influenza in the United
States. Previous research has shown that once the winter influenza epidemic starts, it
spreads very rapidly across the continental states, suggesting that the US may act as one
large, well-mixed population. Previous work using genetic data to look for spatial structure at
this scale didn’t identify any patterns. However, these studies used geographic proximity to
define the distance between states; we wanted to see whether similar patterns existed at
this spatial scale if we instead used movement data as a proxy for the distance between
locations. Commuter movements have previously been shown to correlate with influenza
timing and spread based on influenza-like-illness and mortality data.

Emory University
• MedicalResearch: What are the main findings?
• Response: We found that spatial structure is detectable within the US. We used data on the
genetic distance between sequences collected from different states and compared that to
different measures of ‘distance’ between states—geographic proximity, the daily number of
people flying between states and the daily number of commuters traveling between states
using ground transportation—to see whether any correlations were present. Further, we did
this for two different subtypes of seasonal influenza: A/H3N2 and A/H1N1. These subtypes
have different epidemiological properties, so there was reason to believe that the observed
patterns might differ depending on subtype.
• We found that some correlations were present for all the distance metrics studied, but that
they were observed a greater proportion of the time when looking at commuter movements,
and when looking at the A/H1N1 subtype. Since A/H1N1 is generally milder and spreads
more slowly throughout the US compared to A/H3N2, we interpret this to mean that spatial
structure is likely more easily detected in this subtype. If A/H3N2 spreads rapidly from coast
to coast, any signature of spatial structure is likely obscured before we have a chance to
observe it

Emory University
• Response: The detection of network structure implies that patterns of epidemic spread are,
to some extent, predictable. The absence of predictability is problematic for the design of
targeted surveillance and control strategies, since it suggests that the annual seasonal spread
of influenza within countries is highly variable and depends heavily on chance events. In that
case, broad scale surveillance and mitigation strategies must be utilized, and these generally
perform worse than more directed approaches. We showed here that there are underlying
spatial patterns in the genetic data, and that these are dependent on how the ‘distance’
between locations is being measured. This information can then be used to target
surveillance and control to certain geographic locations or host groups.

Emory University
this study?
• Response: Our study demonstrates the importance of incorporating host movement data
when trying to predict how diseases will spread. Humans can move long distances very
rapidly so the idea that geographic proximity is key to determining disease spread doesn’t
always hold.
• Our findings based on genetic data are in agreement with previous research using influenza-
like illness case data; both show that patterns do exist, with strongly connected states having
similarly timed epidemic peaks and similar genetic variants circulating. The patterns we found
are likely influenced by states with many commuters, and the identification of these states, as
well as network pathways that contribute substantially to influenza spread, is an important
next step for epidemiological research.
• Citation:
• The Role of Human Transportation Networks in Mediating the Genetic Structure of Seasonal
Influenza in the United States
• Brooke A. Bozick Leslie A. Real
• PLOS Published: June 18, 2015 DOI: 10.1371/journal.ppat.1004898

Newer Glaucoma Treatments May Be Best For Less Advanced Disease
Pradeep Ramulu MD MHS PhD
Associate Professor of Ophthalmology
Wilmer Eye Institute
Johns Hopkins University
• Dr. Ramulu: Looking at what procedures are used allows us to understand what doctors are
doing, and how the landscape of our field is changing. We noted that overall numbers for
glaucoma procedures were down – a surprise given that our population is aging, there are
more Medicare beneficiaries, and there have not been recent advances in medical therapy
for glaucoma.

• Dr. Ramulu: There is a strong trend towards newer glaucoma procedures, particularly
endocyclophotocoagulation, external mini-shunts, and canaloplasty. At the same time,
traditional procedures such as trabeculectomy and tube shunts are still quite common, and
the growth of these newer procedures should not imply that they treat glaucoma better than
conventional therapies. It is also important for patients to realize that these newer therapies
are often best suited as an initial therapy for less advanced disease.

this study?
• Dr. Ramulu: Our hope is that there is increasing research to help understand the efficacy of
these newer treatments in the treatment of glaucoma, particularly in the form of head-to-
head trials with more conventional therapy.
• Citation:
• Use of Various Glaucoma Surgeries and Procedures in Medicare Beneficiaries from 1994 to
2012
• Arora, Karun S. et al.
• Ophthalmology
DOI: http://dx.doi.org/10.1016/j.ophtha.2015.04.015

New Skin MedicalResearch.com Interview with:
Dr. Alexander Golberg Ph.D.
Center for Engineering in Medicine
Department of Surgery, Massachusetts General Hospital
Harvard Medical School, and Shriners Burns Hospital
Boston, MA, 02114
• Dr. Golberg: Well, the population grows and becomes older. Degenerative skin diseases
affect one third of individuals over the age of sixty. Current therapies use various physical and
chemical methods to rejuvenate skin; but since the therapies affect many tissue components
including cells and extracellular matrix, they may also induce significant side effects, such as
scarring.
• We report on a new, non-invasive, non-thermal technique to rejuvenate skin with pulsed
electric fields. The fields destroy cells while simultaneously completely preserving the
extracellular matrix architecture and releasing multiple growth factors locally that induce
new cells and tissue growth. We have identified the specific pulsed electric field parameters
in rats that lead to prominent proliferation of the epidermis, formation of microvasculature,
and secretion of new collagen at treated areas without scarring. Our results suggest that
pulsed electric fields can improve skin function and thus can potentially serve as a novel non-
invasive skin therapy for multiple degenerative skin diseases.

Medical research slideshare_june_24_2015

Medical research slideshare_june_24_2015

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