MedicalResearch.com: Medical Research Exclusive Interviews October 18 2014

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
October 18 2014
For Informational Purposes Only: Not for Specific Medical Advice.

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Calorie Posting Reduced Adolescent Sugary Drink Purchases
MedicalResearch.comInterview with: Sara N. Bleich, Ph.D.
Associate Professor Department of Health Policy and Management
Johns Hopkins Bloomberg School of Public Health
Baltimore, MD 21205
• Medical Research: What are the main findings of the study?
• Dr. Bleich: Providing easily understandable calorie information — particularly in the form of miles of walking — makes
adolescents more likely to buy a beverage with fewer calories, a healthier beverage or a smaller size beverage. Adolescents
were also more likely to not buy any drink at all after seeing the signs with calorie information.
Medical Research: What was most surprising about the results?
• Dr. Bleich: The healthier choices – buying fewer calories, fewer sugary beverages and fewer large volume sugary beverages
(> 16 ounces) – persisted for 6 weeks after the signs came down. This suggests that adolescent were educated by the signs
and continued to modify their behavior after they were removed.
• Medical Research: What should clinicians and patients take away from your report?
• Dr. Bleich: When clinicians talk to patients about calories, they should make every effort to communicate that information in
a easily understandable format to make it most meaningful. The final rule from the FDA on the implementation of
mandatory calorie posting, which requires chain restaurants with more than 20 locations nationwide to post calories on
their menu boards alongside price, is imminent. Patients should demand that large chain restaurants post the required
calorie information in an easily understandable format so they can make better choices.
• Medical Research: What recommendations do you have for future research as a result of this study?
• Dr. Bleich: Future research needs to examine whether the most persuasive way of presenting easily understandable calorie
information differs among different populations.
• Citation:
• Sara N. Bleich, Colleen L. Barry, Tiffany L. Gary-Webb, and Bradley J. Herring. (2014). Reducing Sugar-Sweetened Beverage
Consumption by Providing Caloric Information: How Black Adolescents Alter Their Purchases and Whether the Effects
Persist. American Journal of Public Health. e-View Ahead of Print.
• doi: 10.2105/AJPH.2014.302150
•

Patient Hospital Gowns: More Can and Want To Wear Pants
MedicalResearch.comInterview with:
Todd C. Lee, MD, MPH Division of General Internal Medicine and Infectious Diseases
Department of Medicine, McGill University Health Centre
McGill Centre for Quality Improvement, Montreal, Quebec, Canada
• Dr. Lee: We found that in our cross-sectional study of six inpatient units in five hospitals that,
in general, only 11% of patients were wearing lower body garments despite the fact that
probably 55% of them could have been doing so. The remainder were wearing open backed
gowns. When specifically asked, the majority of these patients would like to have been
afforded the opportunity to wear more dignified attire and the patients were surprised that
they were allowed to do so.
•
Medical Research What was most surprising about the result?
• Dr. Lee: What was surprising was the fact that most patients were unaware that they could
change into more dignified attire in the hospital and that they need not always remain in the
open-backed gowns, particularly as their health status improved.

Sexting Teens More Likely Sexually Active
MedicalResearch.com Interview with:
Jeff R. Temple, PhD Associate Professor and Psychologist
Director, Behavioral Health and Research Department of Ob/Gyn UTMB Health Galveston, TX 77555-0587
• Dr. Temple: Through previous research, we know that teen sexting is related to actual sexual
behaviors, but we did not have any information on the temporal link between these two
behaviors.
• In short, we found that teens who sexted had 32% higher odds of being sexually active over
the next year relative to youth who did not sext – this was even after controlling for history
of prior sexual behavior, ethnicity, gender, and age. We also found that active sexting
(actually sending a naked picture to another teen) mediated the relationship between
passive sexting (asking for or being asked for a sext) and sexual behaviors. In other words,
while sending a sext was predictive of subsequent sexual behavior, asking for/being asked for
a sext was only associated with sexual behavior through its relationship with active sexting.
• Medical Research: What was most surprising about the results?
• Dr. Temple: It is certainly not a surprise that online behaviors mimic offline behaviors.
However, our finding that sexting precedes actual sexual behavior was not previously known
and holds potentially important implications for the promotion of healthy sexuality and the
prevention of early sexual debut.

Sexting Teens More Likely Sexually Active
Jeff R. Temple, PhD Associate Professor and Psychologist
Director, Behavioral Health and Research Department of Ob/Gyn UTMB Health Galveston, TX 77555-0587
• Dr. Temple: The question of what comes first is not merely academic. If sexting precedes sexual
behavior, as we found, then safe sex interventions could be designed to specifically targetsexting
youth, and prevention programs could aim to reduce sexting as a means of reducing early sexual
debut and promoting healthy sexual interactions.
• Even if we find that no direct relationship exists, research consistently demonstrates that sexting is
an indicator of actual sexual behavior. Thus, parents and health care professionals should use this
as an opportunity to talk to youth about sex and safe sex. And if a kid is “caught” sexting, we should
use this as an opportunity to educate him or her on digital citizenship and healthy sexuality, as
opposed to punishment.
• Medical Research: What recommendations do you have for future research as a result of this
study?
• Dr. Temple: In my opinion, the importance of studying teen sexting lies almost entirely on its
relationship to actual sexual behavior. Early sexual behavior is associated with a host of negative
consequences, including sexually transmitted infections, teen dating violence, unhealthy future
relationships, and unintended pregnancies. Anything we can do to learn about and prevent
premature sexual behaviors and promote healthy adolescent relationships is a step in the right
direction.
• Citation:
• Jeff R. Temple and HyeJeong Choi. Longitudinal Association Between Teen Sexting and Sexual
Behavior. Pediatrics, October 6, 2014 DOI: 10.1542/peds.2014-1974

TIAs, Strokes Decline Over Last Decade
Vijaya Sundararajan, MD, MPH, FACP Associate Professor
Head, Health Outcomes Group, Head, Biostatistics Hub Research Advisor, Centre for Palliative Care
Department of Medicine Eastern Hill Academic Centre Melbourne Medical School
Faculty of Medicine, Dentistry and Health Sciences University of Melbourne
• Medical Research: What are the main findings of this study?
• Dr. Sundararajan: The main findings of the study are that over the last 10 years, there has been a
measurable decline in people having a stroke 3 months after a new mini stroke (TIA); a mini stroke
is also known as a ‘warning sign for stroke’. There has also been an overall decline in of the
proportion of people having these mini strokes in the Australian State of Victoria (population
5.6million). These trends probably reflect improved primary and secondary prevention efforts for
the last decade. These improvements are likely to include increased use of preventive medications
and surgery for carotid artery narrowing in people identified as being at high risk of having a stroke,
as well as improved behaviors (e.g. reducing smoking, improving diets, uptake of physical activity,
among others).
• The most important aspect of our results is many fewer strokes occur when people with a TIA are
managed in a hospital with a stroke unit (up to 6%). Even when the patient’s TIA is managed in
an Emergency Department and the patient released without admission, if the hospital has a stroke
unit, these patients appear to have better outcomes. This likely reflects the cohesion and
organization of the stroke unit in implementing the necessary tests and treatments promptly, and
setting up the infrastructure to follow patients up.
• Medical Research: What should patients and clinicians take away from this report?
• Dr. Sundararajan: Clinicians and patients should take away from the report that the impact of
modifying risk factors such as elevated blood pressure, heart rhythm abnormalities, cholesterol,
blood sugar and smoking is of great importance, and probably has had an impact at a population
level in reducing the risk of stroke, a disease with a large mortality and morbidity burden. The
decline in TIA rates may also reflect improving primary care, with GPs paying much more attention
to these factors than in previous years, although more can possibly be done in this regard.

TIAs, Strokes Decline Over Last Decade
Vijaya Sundararajan, MD, MPH, FACP Associate Professor
Head, Health Outcomes Group, Head, Biostatistics Hub Research Advisor, Centre for Palliative Care
Department of Medicine Eastern Hill Academic Centre Melbourne Medical School
Faculty of Medicine, Dentistry and Health Sciences University of Melbourne
• Medical Research: What further research do you recommend as a result of this study?
• Dr. Sundararajan: The next step is to assess whether we can further differentiate outcomes
after TIA based on levels of treatment with particular medications and the type of care they
receive. For example, do patients who consistently take/refill their anti-hypertensive
medications do better than those who do not? Do patients who see a stroke neurologist as
an outpatient after their TIA have lower stroke rates?
• Citation:
• Trends Over Time in the Risk of Stroke After an Incident Transient Ischemic Attack
• Vijaya Sundararajan, Amanda G. Thrift, Thanh G. Phan, Philip M. Choi, Ben Clissold, and
Velandai K. Srikanth
• Stroke. 2014;STROKEAHA.114.006575published online before print September 25 2014,
doi:10.1161/STROKEAHA.114.006575

Neurotic Symptoms In Midlife May Presage Alzheimer’s Dementia
Lena Johansson, PhD, MSc, RN
Institute of Neuroscience and Physiology
Department of Psychiatry and Neurochemistry Sahlgrenska Academy at Gothenburg University
Dr. Johansson:We found that a higher degree of neuroticism in midlife was associated with
increased risk of Alzheimer’s disease over 38 years. On the 24 point scale, the risk increased with
4% per each step. Women who score high on the neuroticism scale were more likely to experience
feelings such as anxiety, nervousness, worry, and irritability, and they were more moodiness and
stress-prone.
• The association between neuroticism and Alzheimer’s disease diminished after adjusting for
longstanding perceived distress symptoms, which suggest that the associations was at least partly
depended on long-standing distress symptoms.
• When the two personality dimensions were combined, women with high neuroticism/low
extraversion had a double risk of Alzheimer’s disease compared to those with low neuroticism/high
extraversion.
Dr. Johansson: This study have a unique design, due to the long follow-up. No other study have
shown that midlife personality, increased the risk of Alzheimer’s disease over a period of nearly 4
decades. So, from that view are the finding exceptional.
• However, our hypothesis was that a stress-prone personality (neuroticism) might affect the risk of
Alzheimer’s disease. However, over this 4 decades much happened in these women’s life, so to
recognize a significant association between personality and dementia, over such a long period, was
in some way surprising.

Neurotic Symptoms In Midlife May Presage Alzheimer’s Dementia
Lena Johansson, PhD, MSc, RN
Institute of Neuroscience and Physiology
Department of Psychiatry and Neurochemistry Sahlgrenska Academy at Gothenburg University
• Dr. Johansson: Results have clinical implications, while a group of women at risk for Alzheimer’s disease
dementia is identified.
• It is important that clinicians pay attention to longstanding and/or severe symptoms of distress; such as
sleeping problems, severe worries, psychosomatic symptoms etc, and consider to treat this symptoms.
• Stress have been associated with a large number of bad outcomes, and here also with Alzheimer’s disease.
• There are several possible explanations for the relationship between neuroticism and Alzheimer’s disease.
Personality may influence the individual’s risk of dementia through its effect on behavior and lifestyle; e.g.,
individuals with low neuroticism more often have a lifestyle with healthier metabolic, cardiovascular, and
inflammatory risk profiles.
• Take this symptoms seriously and do what you can to try to lowering the stress level in life. Maybe through
life-style changes, physical activities, cognitive therapy or autogenic exercise.
• Dr. Johansson: Future studies should examine the etiologic pathways for this associations and test
whether this group responds well to interventions. It remains to be seen whether neuroticism could be
modified, e.g., by medical treatment or through lifestyle changes.
• Citation:
• Midlife personality and risk of Alzheimer disease and distress: A 38-year follow-up
• Lena Johansson, PhD, Xinxin Guo, MD, PhD, Paul R. Duberstein, PhD, Tore Hällström, MD, PhD, Margda
Waern, MD, PhD, Svante Östling, MD, PhD and Ingmar Skoog, MD, PhD
• Published online before print October 1, 2014, doi: 10.1212/WNL.0000000000000907 Neurology
10.1212/WNL.0000000000000907

Metformin May Alter Thyroid Hormone in Diabetics
MedicalResearch.com Interview with: Jean-Pascal Fournier, MD, PhD
Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital,
Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada
• Response: Patients with type II diabetes and treated hypothyroidism showed a 55% increased risk for low
levels of thyroid stimulating hormone (TSH) (below 0.4 mIU/L) when initiating metformin, compared with
those initiating sulfonylurea (hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.09–2.20). In contrast,
this effect of metformin was not observed in euthyroid patients, with an adjusted HR for low TSH of
0.97(95% CI 0.69–1.36).
• Response: The study results confirmed the timing of this phenomenon suggested in previous small
studies, with the highest risk being observed between 90 to 180 days after initiation (HR: 2.33; 95% CI:
1.01-5.36)
• Response: Clinicians should be aware that low TSH could be observed in patients with treated
hypothyroidism initiating metformin, especially between 90 to 180 days of use.
• However, and given the uncertainty of the clinical consequences of this phenomenon, patients should not
be unnecessarily worried, and should not stop their medications without the advice of a clinician.
• Response: Further research is needed to confirm these results, and assess the effect on other thyroid
hormones (triioiothyronine and thyroxine). Furthermore, the clinical implications of this phenomenon
should be investigated, especially regarding the potential cardiovascular consequences.
• Citation:
• Jean-Pascal Fournier, Hui Yin, Oriana Hoi Yun Yu, and Laurent Azoulay
• Metformin and low levels of thyroid-stimulating hormone in patients with type 2 diabetes mellitus CMAJ
cmaj.140688; published ahead of print September 22, 2014, doi:10.1503/cmaj.140688

Evaluating Beta-Blockers In Patients With/Without Prior Myocardial Infarction
MedicalReseach.com Interview with:
Sripal Bangalore, MD, MHA, FACC, FAHA, FSCAI,
Director of Research, Cardiac Catheterization Laboratory, Director, Cardiovascular Outcomes Group,
The Leon H. Charney Division of Cardiology, Associate Professor of Medicine,
New York University School of Medicine New York, NY 10016.
• Dr. Bangalore: Using data from the Clopidogrel for High Atherothrombotic Risk and Ischemic
Stabilization, Management, and Avoidance (CHARISMA) trial, we found that β-blocker use in
patients with prior myocardial infarction but no heart failure was associated with a lower
composite cardiovascular outcome, driven mainly by lower risk of recurrent myocardial
infarction with no difference in mortality. However, in patients without prior myocardial
infarction there was no benefit of β-blocker use with a suggestion of increase in stroke risk.
• Dr. Bangalore: The lack of mortality benefit in patients with prior myocardial infarction was
surprising. In addition, although the finding of increase in stroke risk in those without a
prior myocardial infarction is surprising, this has been consistently shown in our prior analysis
from the REACH registry, in the POISE trial and multiple randomized trials of beta blockers for
hypertension

Evaluating Beta-Blockers In Patients With/Without Prior Myocardial Infarction
MedicalReseach.com Interview with:
Sripal Bangalore, MD, MHA, FACC, FAHA, FSCAI,
Director of Research, Cardiac Catheterization Laboratory, Director, Cardiovascular Outcomes Group,
The Leon H. Charney Division of Cardiology, Associate Professor of Medicine,
New York University School of Medicine New York, NY 10016.
• Dr. Bangalore: Clinicians should really think whether beta blockers are indicated for a patient
subgroup before prescribing these medications. In patients with an myocardial infarction, the
current data suggests short term use of beta blockers and longer term only in patients with
left ventricular systolic dysfunction. In addition, for patients without an myocardial infarction,
the bar is higher and one really needs to consider the risks and benefits before prescribing
this group of agents.
• Medical Research: What recommendations do you have for future research as a result of
this study?
• Dr. Bangalore: We need randomized trials to assess the outcomes with beta blockers in
contemporary practice and to understand how long a duration beta blockers need to be
continued post myocardial infarction.
• Citation:
• Beta-Blockers and Cardiovascular Events in Patients With and Without Myocardial Infarction:
Post Hoc Analysis From the CHARISMA Trial
• Sripal Bangalore, Deepak L. Bhatt, Ph. Gabriel Steg, Michael A. Weber, William E. Boden,
Christian W. Hamm, Gilles Montalescot, Amy Hsu, Keith A.A. Fox, and A. Michael Lincoff
• Circ Cardiovasc Qual Outcomes. 2014;CIRCOUTCOMES.114.001073published online before
print September 30 2014, doi:10.1161/CIRCOUTCOMES.114.001073

Animal Studies Suggest Testosterone May Increase Prostate Cancer Risk
Maarten C. Bosland, DVSc, PhD Professor of Pathology
Department of Pathology, College of Medicine
University of Illinois at Chicago Chicago, IL 60612
• Dr. Bosland: The two main findings are :
• (1) that long-term, low-dose testosterone treatment induces prostate cancer in rats (none
occurred in control rats) and increases the number of rats with malignant tumors at any site
in the body compared to control rats, and
• (2) that in rats treated long-term with testosterone after a single prostate-targeted chemical
carcinogen treatment a high incidence of prostate cancer is induced, even at a very low
testosterone dose.
• Dr. Bosland: Most surprising was the high incidence of prostate cancer in rats that were
treated long-term with a after a single prostate-targeted chemical carcinogen treatment; this
very low dose of testosterone did not significantly raise blood levels of this hormone
compared with control rats.

Animal Studies Suggest Testosterone May Increase Prostate Cancer Risk
Maarten C. Bosland, DVSc, PhD Professor of Pathology
Department of Pathology, College of Medicine
University of Illinois at Chicago Chicago, IL 60612
• Dr. Bosland: These results suggest that testosterone may also increase the risk of prostate
cancer in humans. However, there are not yet adequate epidemiology studies of men on
testosterone therapy to determine whether this is the case. Therefore, it appears prudent to
limit testosterone therapy to those men who suffer from symptomatic clinical hypogonadism,
to consider the low testosterone blood levels that occur in aging men a normal phenomenon
and not a disease that requires treatment, and to avoid testosterone use by men for
nonmedical purposes.
this study?
• Dr. Bosland: Retrospective and prospective epidemiology studies of men on testosterone
therapy are urgently needed, because the currently available studies are of too short a
duration and include too few subjects.
• Citation:
• Testosterone Treatment is a Potent Tumor Promoter for the Rat Prostate
• Endocrinology. 2014 Sep 23:en20141688. [Epub ahead of print]
Bosland MC.

Lowering Hospital Readmissions Through Peer-to-Peer Coaching
Elizabeth Blanchard Hills, BSN MSJ
President, Informed Health Solutions
• Medical Research: What is your role?
• Response: My name is Elizabeth Blanchard Hills, BSN, MSJ. My company, Informed Health Solutions, currently has the privilege of “transitioning” Dr.
Smith’s work into clinical practice. We have been conducting an on-going pilot project with the University of Kansas Hospital since November 2013,
and our results are corroborating the results of Dr. Smith’s randomized clinical trial. We have renamed SMAC-HF; it is now called CareConnext.
Medical Research: What are the main findings of the study?
• Response: That we could, in fact, significantly lower hospital readmissions among heart failure patients.
• Response: We have found several surprises:
• The importance of managing emotions when managing a chronic disease such as heart failure.
• Dr. Smith’s randomized clinical trial showed depression puts heart failure patients at risk for readmission; this mirrors what we are now finding in the
literature.
• Helping patients feel emotionally and spiritually better is now a signature piece of CareConnext. We screen for depression using the PHQ9, and watch
our patients rebuild hope by regaining a sense of control. We do so by talking frankly and directly about sensitive issues that are often time-consuming
to address: end-of-life planning, the loss of independence, or asking family members to participate in a change of diet.
• The value of peer-to-peer coaching.
• As nursing professionals, we are hard-wired to teach. Because of the time constraints we face, we too often resort to “lecturing” our patients, leaving
us little time to validate our patients’ understanding, or their ability to take positive action. For example, it is easy to “tell” someone to limit their
sodium intake to 2G a day. But does the patient even understand how to read a food label? If not, would he or she feel comfortable revealing that?
• CareConnext provides a safe environment for patients to recognize and overcome knowledge gaps because they rely on one another for real-life
strategies and emotional support.
• Our providers are mostly on “standby,” available to address specific questions or misconceptions that specifically require the expertise of an
advanced practice nurse or licensed clinical social worker.
• Our data holds across varying patient populations.
• Patients who struggle with literacy or language benefit from our intervention as do patients who are affluent, well-educated and compliant.
• Our providers enjoy the CareConnext model, too.
• Our advance practice nurses are quite talented, and therefore much in demand at the University of Kansas Hospital. They are often recruited for
interesting projects always in play at a large academic medical center. They were key members of Dr. Smith’s initial SMAC-HF team, and continue to
advance our efforts and advocate for CareConnext. They tell us CareConnext is professionally rewarding, and a welcome change from the standard,
one-on-one office visit.

Lowering Hospital Readmissions Through Peer-to-Peer Coaching
Elizabeth Blanchard Hills, BSN MSJ
President, Informed Health Solutions
• Response: This particular patient population requires special expertise to motivate, but will remain
engaged if they find something of value.
• Initially, only two out of ten patients referred would agree to attend CareConnext. As a small
business, this number was unsustainable, so we quickly implemented a data-driven, automated
outreach effort. Today, almost six out of every ten patients we contact agrees to attend
CareConnext.
• Given the initial recruiting challenges, our “drop rate” came as complete surprise:
• Almost 90% of the patients who attend their first CareConnext session (we meet weekly for one
month) attend all four sessions.
• This suggests being “noncompliant” is a convenient label we often misuse with our patients. Heart
Failure patients have logical reasons for being skeptical of what they perceive as “yet another
doctor’s appointment,” such as a lack of energy.
• We have been quite strategic in attempting to meet our patients’ emotional needs. The “clinical
stuff” (monitoring fluid volume, especially overload) we offer as part of CareConnext are the
‘greens fees’ we pay so we can address and change patient behavior. By making patients feel
emotionally and spiritually empowered, we help them change the feelings they have and the
choices they make.
• Medical Research: Where does one go for more information?
• Response: Our website is located here: www.informedhealthsolutions.com
• Citation:
• To Improve Heart Failure (HF) Self-Management through Patients Group Clinic Appointments
• Smith, Carol E. Journal of Cardiac Failure , Volume 20 , Issue 8 , S47

Understanding BRCA2 Molecule May Lead To Cancer Prevention Strategies
Professor Xiaodong Zhang
Professor of Macromolecular Structure and Function Department of Medicine
Imperial College, London, UK
• Prof. Zhang: Since its discovery 20 years ago, the BRCA2 gene and its protein product, BRCA2,
have been under intensive investigations. The importance of the BRCA2 protein lies in the
central roles it plays in the most faithful DNA damage repair pathway. Mutations in BRCA2
thus can cause defects in this repair pathway, making the repair inefficient or forcing cells to
use alternative repair methods that are prone to mistakes, all of which contribute to
mutations in the genomic DNA, thus increase the risk of cancer development. Our study aims
to understand how BRCA2 works through studying its 3-dimensional structures and its
interactions with other key partners in the repair pathway.
• Our study provides first 3-dimensional views of BRCA2 and BRCA2-RAD51 and reveals that
BRCA2 molecules exist as pairs and a BRCA2 pair recruit two sets of RAD51 molecules
arranged in opposite orientations. Our study also shows a single stranded DNA binds across
the BRCA2 dimer and that BRCA2 increases the frequency of RAD51 filament formation
events, presumably to increase the efficiency of establishing a longer filament required for
searching for matching strands of DNA in intact sister chromatin. Our results thus not only
define the precise roles of BRCA2 in helping RAD51 filament formation, but how it helps
RAD51 loading onto single stranded DNA.
•
• Prof. Zhang: BRCA2, one of the largest proteins in the cell, still works in pairs

Understanding BRCA2 Molecule May Lead To Cancer Prevention Strategies
Professor Xiaodong Zhang
Professor of Macromolecular Structure and Function Department of Medicine
Imperial College, London, UK
• Prof. Zhang: Through a molecular understanding of its structures and mechanisms, such as
how intact BRCA2 protein works in the DNA repair, what is the nature of the cancer
predisposition mutations, we could start to develop strategies to correct the defects in
BRCA2 to ensure repair could be carried out, thus to prevent cancer development.
Alternatively, we could develop ways to hamper repairs in cancer cells, thus to promote cell
death.
this study?
• Prof. Zhang: Our current research focuses on revealing greater details of the BRCA2
molecule, its interactions with other proteins in the repair pathway as well as its regulation.
With increasing knowledge of this protein, how it interacts with and recruits RAD51 precisely
and how it is regulated, we will be a step closer to develop therapeutics to protect healthy
cells and/or to combat cancer cells.
• Citation:
• Structure and Mechanism of Action of the BRCA2 Breast Cancer Tumor Suppressor
Taha Shahid, Joanna Soroka, Eric H Kong, Laurent Malivert, Michael J McIlwraith, Tillmann
Pape, Stephen C West , Xiaodong Zhang
• Nature Structural & Molecular Biology(2014) doi:10.1038/nsmb.28

Team Management of Stroke Improved Patient Satisfaction, Decreased Hospital Days
John Falconer MD FRCPC
Neurologist, Kelowna General Hospital; Clinical Associate Professor of Neurology,
University of British Columbia
• Medical Research: What are the main findings of this study?
• Dr. Falconer: This study set out to investigate the possible benefits of having a
physician with a proprietorial interest (Pro-MD) in a stroke unit, tightly
combined with a multidisciplinary inter-professional team, and including
the family and the patient in as essential members for the management of a
stroke patient. This also involved the introduction of a geographic
located Acute Stroke Unit. We compared Acute Bed Days used by patients
from the five months before to five months after this system was put in
place. Our main end point was number of days in acute hospital care before
and after, but we also informally tracked patient and caregiver
satisfaction and staff morale.
• The Proprietary Physician, or Pro-M Drefers to a physician who has a “proprietorial” interest in a hospital unit or ward. In
other words, I was working at this unit in a
wholistic sense, trying not only to manage patients as best they can, but
also interested in the patient flow and family-patient communications.
• We found that patient bed days were reduced by approximately 25% overall,
while at the same time, patient and family satisfaction was improved, and
staff morale increased.
• Initially, we had supposed that patients and their family would be more
satisfied, but we were surprised at the reduction in Acute Bed Days that
resulted.
Medical Research: What should patients and clinicians take away from this study?
• Dr. Falconer: Clinicians should take away from this the multiple areas of benefit from
using this approach, which could be useful in many other areas of an acute
care hospital. Expanding research of this Proprietary Physician, or Pro-MD system is encouraged, to see if this can be
replicated in other hospitals and other specialties.
• Citation:
• Canadian Stroke Congress abstract:
Heart and Stroke Foundation of Canada. “Innovative stroke patient management system cuts hospital bed usage by more than 25
percent.”

Dietary Interventions Depend On Community Nutrition Environment
MedicalResearch.comInterview with: Dr. Wenjun Li PhD
Associate Professor of Medicine (Biostatistics)
University of Massachusetts Medical School of Medicine
University of Massachusetts Medical School
• Dr. Li: The study discovered that the effectiveness of dietary interventions is significantly influenced by
the presence of a supportive community nutrition environment.
•
• Dr. Li: The strength of the influence of community environment on the likelihood of positive dietary
behavioral changes is surprisingly strong, even among the participants who were highly motivated to
improve their diet. Such influence appeared to be consistent among participants, men or women, having
a college degree or not, and relatively wealthier or not.
• Dr. Li: Environmental influences on the effectiveness should be carefully considered when delivering
behavioral interventions. Approaches to overcoming such barriers may need to be included as a critical
component of the interventions.
• Dr. Li: Because changing the environment alone cannot produce results and efforts to try to change a
person will be very limited without improving the environment, both aspects should be pursued at the
same time with coordinated efforts. Future research should explore such integrated approaches.
• Citation:
• Access to Healthy Food Stores Modifies Effect of a Dietary Intervention
• Nicole M. Wedick, Yunsheng Ma, Barbara C. Olendzki, Elizabeth Procter-Gray, Jie Cheng, Kevin J. Kane, Ira
S. Ockene, Sherry L. Pagoto, Thomas G. Land, Wenjun Li
• Publication stage: In Press Corrected Proof
American Journal of Preventive Medicine Published online: October 6, 2014
• Views vs UniqueViews2014-09-122014-09-172014-09-222014-09-272014-10-02

Specialized MRI May Predict Early Cognitive Decline
Sven Haller, M.D.
University of Geneva in Geneva, Switzerland
• Dr. Haller: The main finding is that some elderly individuals with intact cognitive function at baseline
already have visible alterations of the brain perfusion measured in Arterial Spin Labeling (ASL) MRI, which
is similar to patients with mild cognitive impairment (MCI). This elderly individual may initially maintain
intact cognitive functions due to the activation of their cognitive reserve, yet eventually the cognitive
reserve is exhausted and those individuals develop subtle cognitive decline at follow-up 18 months later.
• Consequently, Arterial Spin Labeling MRI may predict the very earliest form of cognitive decline.
•
• Dr. Haller: Previous investigations of Arterial Spin Labeling MRI in patients with mild cognitive impairment
and AD showed similar results, yet at later stages of the neurodegenerative process. It was interesting to
see that ASL may already detect incipient cognitive decline at a much earlier phase.
• Dr. Haller: Arterial Spin Labeling MRI has the potential to predict subsequent cognitive decline at the
earliest stage. It does not require contrast agent or irradiation and simply prolongs the routinely
performed structural MRI for a few minutes
• Dr. Haller: These promising results should be confirmed in larger and multi-center studies. Notably, it is
important to standardize Arterial Spin Labeling MRI acquisitions across different institutions
• Citation:
• Aikaterini Xekardaki, Cristelle Rodriguez, Marie-Louise Montandon, Simona Toma, Eline Tombeur, François
R. Herrmann, Dina Zekry, Karl-Olof Lovblad, Frederik Barkhof, Panteleimon Giannakopoulos, Sven Haller.
Arterial Spin Labeling May Contribute to the Prediction of Cognitive Deterioration in Healthy Elderly
Individuals. Radiology, 2014; 140680 DOI: 10.1148/radiol.14140680.

US Dietary Quality Better But Leaves Room For Improvement
Daniel (Dong) Wang MD, MSc
Department of Nutrition, Harvard School of Public Health
Boston, MA 02115
• Dr. Wang:
• The overall dietary quality in US adults improved modestly from 1999 to 2010, but the quality
of US diet remains far from optimal and huge room exists for further improvements.
• The improvement in dietary quality was greater among adults with higher socioeconomic
status and healthier body weight, thus disparities that existed in 1999 increased over the
next decade.
• More than half of the improvement in diet quality was due to a large reduction in
consumption of trans fat.
• Dr. Wang:
• The gap in dietary quality between low and high socioeconomic status widened over time.
• The gradually increasing sodium intake over the 12 years was surprising given constant
efforts to reduce salt intake by the federal dietary guidelines, the American Heart
Association, as well as other public health organizations.
• The quality of the US diet steadily improved over the 12 years. This was somewhat surprising
because this period included a severe economic recession.

US Dietary Quality Better But Leaves Room For Improvement
Daniel (Dong) Wang MD, MSc
Department of Nutrition, Harvard School of Public Health
Boston, MA 02115
• Dr. Wang:
• Considering the elevated disease risk associated with poor dietary quality, dietary assessment and
counseling in clinical settings deserves greater attention. Our previous study based on data from the
Nurses’ Health Study has found that a 7.2 point increase in AHEI-2010 was associated with a 15% lower
risk of major chronic disease in women; this 7.2-point improvement could be readily translated into
clinicians’ advice, e.g., increasing whole fruits consumption by three servings per day or cutting back
consumption of sugar sweetened beverages from one or more per day to two 8-oz glasses per week,
which could result in substantial reduction in disease burden.
• Dr. Wang:
• In addition to creating scientific evidence to inform dietary recommendations and consumer’s practice,
future studies and public health programs that focus on changing the food environment through collective
actions, such as structural interventions and regulations, are imperative for sustainable dietary quality
improvement; population with low socioeconomic status are likely to benefit most from the collective
actions.
• The widened gap in dietary quality between low and high socioeconomic status over time suggests the
need for additional actions to improve dietary quality for those with low socioeconomic status.
• Citation:
• Trends in Dietary Quality Among Adults in the United States, 1999 Through 2010
• Wang DD, Leung CW, Li Y, et al. Trends in Dietary Quality Among Adults in the United States, 1999 Through
2010. JAMA Intern Med. 2014;174(10):1587-1595. doi:10.1001/jamainternmed.2014.3422.

Prior Bird Flu Vaccination Offers Some Protection Against Newer Strains
Robert B Belshe, MD
Division of Infectious Diseases, Allergy & Immunology
Saint Louis University School of Medicine
• Response: A vaccine that protects against an old strain of avian flu primes the immune
system to mount a rapid response when a vaccine designed to protect against a related but
different and new strain of avian flu is given a year later, according to Saint Louis University
research findings reported in JAMA.
• In addition, when combined with an adjuvant, which is a chemical that stimulates the
immune system to produce more antibodies, a lower dose of the new avian flu vaccine
worked better in triggering an immune response than a stronger dose without adjuvant. That
means the amount of vaccine against a new strain of bird flu can be stretched to protect
more people if an adjuvant is added.
• Both findings represent important strategies researchers can continue to study to fight new
strains of bird flu that people previously have not been exposed to, and consequently can
rapidly turn into a pandemic outbreak and public health emergency, said Robert Belshe,
M.D., professor of infectious diseases, allergy and immunology at Saint Louis University and
the lead author of the article, which appeared in the Oct. 8, 2014 issue of JAMA.
• Response: “People who had been primed a year ago when they received the Vietnam bird flu
vaccine had developed an immunologic memory,” Belshe said. “Our findings suggest if a
threat of bird flu spreading from person to person was very real, it makes sense to prime with
a bird flu vaccine that is related to but does not directly match the circulating strain.”

Prior Bird Flu Vaccination Offers Some Protection Against Newer Strains
Robert B Belshe, MD
Division of Infectious Diseases, Allergy & Immunology
Saint Louis University School of Medicine
• Response: “This is important because of the need to respond quickly to potential pandemics. We continue to see avian flu as
the possible cause of a pandemic virus in the future,” Belshe said. “Planning for influenza pandemics is of vital importance,
with vaccine being a cornerstone of control efforts.”
• As bird flu evolves, it could change enough to cross between species and easily spread to people whose have no pre-existing
immunity to fight the new flu strain, possibly leading to a global pandemic that could kill millions.
• Response: Belshe said that those at high risk of contracting bird flu, such as certain laboratory scientists, field
epidemiologists and health care workers in areas with emerging avian influenza, might consider receiving a pre-pandemic
vaccine. If bird flu begins to spread rapidly, those workers could then receive a vaccination that matches the pandemic
strain, theoretically triggering a quicker immune response.
• “Whether priming itself has value in protecting against death is not known, but it is possible that primed individuals would
have better outcomes in the face of avian flu infections,” Belshe said.
• He was clear that while the study provides data to help guide pre-pandemic bird flu vaccine strategies, it is not an efficacy
study.
• “We do not know what amount of antibodies would be associated with protection from infection, disease or death. Each of
these end points might have different correlates of protection,” Belshe said.
• “The continued drift of H5 avian flu viruses means that the strain of H5 used for the boosting vaccine will need to be
updated to keep pace with newer H5 bird flu viruses that emerge. Furthermore, the emergence of H7 avian influenza viruses
as human pathogens will require a different priming vaccine than the H5 Vietnam vaccine used in the present study.”
• Belshe also noted that because the research was limited to healthy young adults, other groups need to be studied, including
older adults, adults with underlying chronic conditions, pregnant women and children, since their dose and safety profiles
might differ.
• Citation:
• Belshe RB, Frey SE, Graham IL, et al. Immunogenicity of Avian Influenza A/Anhui/01/2005(H5N1) Vaccine With MF59
Adjuvant: A Randomized Clinical Trial. JAMA. 2014;312(14):1420-1428. doi:10.1001/jama.2014.12609.
•

Hepatitis C Linked To Higher Risk of Coronary Artery Disease
Naga Pothineni, MD
Division of Cardiology
University of Arkansas for Medical Science
• MedicalResearch: What are the main findings of the study?
• Dr. Pothineni: Hepatitis C is a blood borne infection that is very common worldwide. Most pateints who contract hepatitis C
develop a chronic form on infection that progresses to liver damage and eventually hepatocellular cancer. Coronary heart
disease is a worldwide problem as well. There has been interest in chronic infections being a mechanism of progression of
atherosclerosis and coronary heart disease. We wanted to study the association of coronary heart disease events in patients
with hepatitis C. We conducted a retrospective study of around 24,000 patients of which around 10,000 were hepatitis C
positive. Our study showed that patients who have hepatitis C have a higher incidence of coronary heart disease events
(myocardial infarction) when compared to patients who are negative for hepatitis C. In our analysis, we found that hepatitis
C positivity is an independent risk factor for coronary events after adjusting for traditional cardiovascular risk factors like age,
hypertension, smoking and diabetes.
• Another interesting finding in our study was that patients with hepatitis C have lower levels of cholesterol compared to
patients without hepatitis C. Low cholesterol levels in these patients do not seem to be protective against future coronary
heart disease events.
•
MedicalResearch: What was most surprising about the results?
• Dr. Pothineni: A novel and surprising result in our study was that patients with persistent (active) hepatitis C infection
have higher incidence of coronary heart disease events compared to patients who have remote or treated infection.
• Some patients who have hepatitis C spontaneously clear their infection by the natural immune responses. Those that fail to
do so appear to be at a higher cardiovascular risk
• MedicalResearch: What should clinicians and patients take away from your report?
• Dr. Pothineni: Clinicians should be aware of hepatitis C being a potential cardiac risk factor. Active infection can be detected
by checking for hepatitis C RNA levels. It might be reasonable to aggressively control traditional cardiovascular risk factors in
patients with active infection to decrease the incidence of coronary heart disease events in this population
• MedicalResearch: What recommendations do you have for future research as a result of this study?
• Dr. Pothineni: Treatment for hepatitis C has advanced tremendously and it is now possible to achieve cure. Future research
can show us if treatment of hepatitis C with the currently available therapies can help decrease cardiovascular risk in these
patients.
• Citation:
• Impact of Hepatitis C Seropositivity on the Risk of Coronary Heart Disease Events Pothineni, Naga Venkata et al. American
Journal of Cardiology

Rivaroxaban For Venous Thromboembolism Prevention In Cancer Patients
Prof Martin H Prins MD
Maastricht University Medical Centre, Maastricht, Netherlands
• Dr. Prins: Patients with active cancer, i.e. a cancer that was diagnosed or treated within 6
months before the episode, that was recurrent or metastatic, or that was diagnosed during
treatment, who had a symptomatic episode of venous thromboembolism, were included in
this pooled subgroup analysis of the Einstein DVT and PE studies. The incidence of recurrent
venous thromboembolism was similar between groups. It occurred in 16 (5%) of 354 patients
allocated to rivaroxaban and 20 (7%) of 301 patients allocated to enoxaparin and vitamin K
antagonist (hazard ratio [HR] 0•67, 95% CI 0•35 to 1•30). Clinically relevant bleeding was
also similar and occurred in 48 (14%) of 353 patients receiving rivaroxaban and in 49 (16%) of
298 patients receiving standard therapy (HR 0•80, 95% CI 0•54 to1•20). However, major
bleeding was less frequent among rivaroxaban recipients and occurred in eight (2%) of 353
patients receiving rivaroxaban and in 15 (5%) of 298 patients receiving standard therapy (HR
0•42, 95% CI 0•18 to 0•99). Mortality was also similar.
• Dr. Prins: That the results for major bleeding were most favourable for major bleeding in
those patients where you would expect a benefit of dose adjustment based on a coagulation
parameter (INR) in the enoxaparin/vitamin K antagonist group, compared to a fixed, non-adjusted
dose of rivaroxaban, namely in those who had a decreased renal function or were
elderly. These conditions are frequent among cancer patients.

Rivaroxaban For Venous Thromboembolism Prevention In Cancer Patients
Prof Martin H Prins MD
Maastricht University Medical Centre, Maastricht, Netherlands
• Dr. Prins: In patients with active cancer and venous thromboembolism, rivaroxaban can be
considered as an alternative in those cases in which the attending physician would have given
therapy including a vitamin K antagonist rather than long-term lowmolecular-weight heparin.
this study?
• Dr. Prins: Based on these results in patients with cancer, a head-to-head comparison of
rivaroxaban with long-term low-molecular-weight heparin is warranted.
Citation:
• Prof Martin H Prins MD,Anthonie W A Lensing MD,Tim A Brighton MBBS,Roger M Lyons
MD,Jeffrey Rehm MD,Mila Trajanovic MD,Bruce L Davidson MD,Jan Beyer-Westendorf
MD,Ákos F Pap MSc,Scott D Berkowitz MD,Alexander T Cohen MD,Prof Michael J Kovacs
MD,Prof Philip S Wells MD,Prof Paolo Prandoni MD
The Lancet Haematology – 1 October 2014 ( Vol. 1, Issue 1, Pages e37-e46 )
DOI: 10.1016/S2352-3026(14)70018-3

Robotic Ovarian Surgery May Increase Both Costs and Complications
Posted on October 8, 2014 Interview with:
Jason D. Wright, M.D.
Sol Goldman Associate Professor of Obstetrics and Gynecology Chief, Division of Gynecologic Oncology
Columbia University College of Physicians and Surgeons New York, New York 10032
• Dr. Wright: The use of robotic assisted ovarian surgery (oophorectomy and cystectomy) has increased
rapidly and compared to laparoscopic alternatives, robotically assisted surgery is associated with a small
increase in complication rates and substantially greater costs.
• Dr. Wright:We noted a rapid increase in the use of robotic-assisted adnexal surgery despite minimal data.
• Dr. Wright: Our findings suggest that robotic ovarian surgery is associated with a small increase in
intraoperative complications and significant costs. It is unclear if there are specific groups of women who
may benefit from these techniques.
• Dr. Wright: Based on these findings, further studies to examine the effectiveness of robotic-assisted
ovarian cancer surgery are needed prior to wide spread use of the procedures.
•
• Citation:
• Comparative Effectiveness of Robotic-Assisted Compared to Laparoscopic Adnexal Surgery for Benign
Gynecologic Disease
• Alessandra Kostolias, MD (CUMC), Cande V. Ananth, PhD, MPH (CUMC), William M. Burke, MD (CUMC),
Ana I. Tergas, MD (CUMC), Eri Prendergast, MS (CUMC), Scott D. Ramsey, MD, PhD (Fred Hutchinson
Cancer Research Center), and Alfred I. Neugut, MD, PhD (CUMC).
• Obstetrics & Gynecology:: October 6, 2014
doi: 10.1097/AOG.0000000000000483

ID Week 2014: Universal MRSA Screening May Be Too Expensive To Implement
Medical Research’s Interview with:
James A. McKinnell, MD
Los Angeles Biomedical Research Institute
• Dr. McKinnell: Numerous experts and policy makers have called for hospitals to screen patients for methicillin-resistant
Staphylococcus aureus (MRSA) infections and isolate anyone testing positive to prevent the spread of these so-called
“Superbugs” in healthcare settings. Several states have enacted laws requiring patients be screened for MRSA upon
admission.
• We conducted two studies, both of which were presented as abstracts at IDWeek, the annual scientific meeting for
infectious disease specialists, which found universal MRSA screening and isolation of high-risk patients will help prevent
MRSA infections but may be too economically burdensome for an individual hospital to adopt.
• Researchers at Los Angeles Biomedical Research Institute, the University of California, Irvine and John Hopkins University
examined the cost of a hospital infection prevention strategy that tested all patients for MRSA and then took precautions to
avoid contact with potential carriers. We found that using the traditional method of testing for MRSA in the nose, or nares
surveillance, and then isolating MRSA carriers prevented nearly three MRSA infections. But it cost the hospital $103,000 per
10,000 hospital admissions. More extensive screening, through the use of other testing methods, which included PCR-based
screening, prevented more infections, but increased the cost.
• In the second study, we also evaluated the cost of a hospital infection prevention strategy that targeted high-risk patients.
Again, we found the costs of the program exceeded the potential savings to the hospital that would be generated by
preventing MRSA infections.
• We found nares screening and isolation of high-risk patients prevented fewer than one infection (0.6) per 1,000 high-risk
admissions to the hospital and created a financial loss of $36,899 for the hospitals. Using more extensive MRSA screening –
which included nares, pharynx and inguinal folds screening – prevented slightly more infections (0.8 infections per 1,000
high-risk admissions), according to the study. But our abstract reported an even larger financial loss of $51,478 with the
more extensive screening.
• Dr. McKinnell: Although more extensive MRSA testing and isolation could prevent hospital-acquired MRSA infections, we
found the cost of such a program far exceeds any savings to the hospital. Our results are surprising because we know that
preventing MRSA infections is better for the healthcare system as a whole, but the rewards of this effort do not seem to
come back to the hospital in a meaningful way. In today’s constrained healthcare environment, hospitals must either be
given better financial incentives or better and more cost-effective infection prevention strategies to provide the greatest
benefit to the people they serve.

ID Week 2014: Universal MRSA Screening May Be Too Expensive To Implement
Medical Research’s Interview with:
James A. McKinnell, MD
Los Angeles Biomedical Research Institute
• Dr. McKinnell: Screening for MRSA is becoming an accepted weapon against the spread of
these antibiotic-resistant infections, but little thought has been given to how a hospital would
actually implement such a program. Our studies found that universal MRSA screening and
isolation would prevent hospital-acquired MRSA infections, but that such a program would be
very expensive for an individual hospital to launch. Our results may provide some explanation
why this approach has not been adopted by all hospitals.
• Medical Research: What recommendations do you have for future policies and research as
a result of this study?
• Dr. McKinnell: We recommend consideration of specific financial incentives to hospitals to
support infection prevention and further examination of the costs and benefits of other
strategies, including the improvement of environmental cleaning and the use of the
antimicrobial disinfectant, chlorhexidine, to eliminate MRSA bacteria. We are currently
completing a study of the benefits of chlorhexidine bathing in preventing healthcare-related
MRSA infections and hope to have the findings soon.
• Citation:
• Abstracts presented at 2014 Infectious Disease Week Meetings
• APA citation: Universal screening for MRSA may be too costly (2014, October 8)

Lower Transfusion Threshold Safe For Most Sepsis Patients
MedicalResearch.comInterview with: Anders Perner,MD, PhD
Overlæge / Senior staff specialist
Professor / Professor in Intensive Care Dept of Intensive Care
Rigshospitalet Copenhagen Denmark
• Dr. Perner: In the large international randomised trial, we showed similar outcomes in patients with septic shock with
anemia transfused at a lower vs. a higher hemoglobin threshold. The lower threshold group received 50 % fewer
transfusions and one-third of these patients were never transfused in ICU.
• Dr. Perner: The results were remarkably clear.
• Dr. Perner: Clinicians treating patients with septic shock can safely wait and transfuse at a hemoglobin level at 7 g/dl
• Dr. Perner: For the vast majority of patients 7 g/dl should be the transfusion threshold, but we need more data in those with
acute coronary syndrome or severe bleeding
Citation:
•
• Lars B. Holst, M.D., Nicolai Haase, M.D., Ph.D., Jørn Wetterslev, M.D., Ph.D., Jan Wernerman, M.D., Ph.D., Anne B.
Guttormsen, M.D., Ph.D., Sari Karlsson, M.D., Ph.D., Pär I. Johansson, M.D., Ph.D., Anders Åneman, M.D., Ph.D., Marianne L.
Vang, M.D., Robert Winding, M.D., Lars Nebrich, M.D., Helle L. Nibro, M.D., Ph.D., Bodil S. Rasmussen, M.D., Ph.D., Johnny
R.M. Lauridsen, M.D., Jane S. Nielsen, M.D., Anders Oldner, M.D., Ph.D., Ville Pettilä, M.D., Ph.D., Maria B. Cronhjort, M.D.,
Lasse H. Andersen, M.D., Ulf G. Pedersen, M.D., Nanna Reiter, M.D., Jørgen Wiis, M.D., Jonathan O. White, M.D., Lene
Russell, M.D., Klaus J. Thornberg, M.D., Peter B. Hjortrup, M.D., Rasmus G. Müller, M.D., Morten H. Møller, M.D., Ph.D.,
Morten Steensen, M.D., Inga Tjäder, M.D., Ph.D., Kristina Kilsand, R.N., Suzanne Odeberg-Wernerman, M.D., Ph.D., Brit
Sjøbø, R.N., Helle Bundgaard, M.D., Ph.D., Maria A. Thyø, M.D., David Lodahl, M.D., Rikke Mærkedahl, M.D., Carsten Albeck,
M.D., Dorte Illum, M.D., Mary Kruse, M.D., Per Winkel, M.D., D.M.Sci., and Anders Perner, M.D., Ph.D. for the TRISS Trial
Group and the Scandinavian Critical Care Trials Group
• N Engl J Med 2014; 371:1381-1391
October 9, 2014DOI: 10.1056/NEJMoa1406617

Community Acquired Pneumonia May Require Two Antibiotics
Dr. Nicolas Garin MD
Division of General Internal Medicine, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland
Division of Internal Medicine, Hôpital Riviera-Chablais, Monthey, Switzerland
• Dr. Garin: Empiric treatment with a betalactam drug (monotherapy) was not equivalent to the
combination of a betalactam and a macrolide in patients hospitalized for moderate severity
pneumonia (proportion of patients not having reached clinical stability at day 7 was 41.2 % in the
monotherapy vs. 33.6 % in the combination therapy arm, between arm difference 7.6 %). This
occurred despite systematic search for Legionella infection in the monotherapy arm. There was no
difference in early or late mortality, but patients in the monotherapy arm were more frequently
readmitted. Patients with higher severity of disease (in PSI category IV, or with a CURB-65 score
higher than 1) seemed to benefit from combination therapy (HR 0.81 for the primary outcome of
clinical instability at day 7), although it was statistically not significant. There was no difference in
the primary outcome for patients in PSI category I to III.
•
• Dr. Garin: Previous meta-analysis of randomized-controlled trials did not find any difference
between empiric treatment with or without systematic coverage of so-called “atypical pathogens ”
(i.e Legionella sp., Mycoplasma pneumoniae and Chlamydia pneumoniae). We were surprised to
find less patients reaching clinical stability at day 7 in the monotherapy arm. This difference was
particularly striking for patients with higher severity of disease, and persisted after excluding
patients with proven infection by an atypical pathogen. Our results can be explained either by the
lack of coverage of atypical pathogens not detected by current testing, or by a non-antibiotic, anti-inflammatory
effect of the macrolide.

Community Acquired Pneumonia May Require Two Antibiotics
Dr. Nicolas Garin MD
Division of General Internal Medicine, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland
Division of Internal Medicine, Hôpital Riviera-Chablais, Monthey, Switzerland
• Dr. Garin: Pending more investigations, patients hospitalized for community-acquired
pneumonia and in PSI category IV or more, or with a CURB-65 score of 2 or more, should be
treated with a betalactam and a macrolide.
this study?
• Dr. Garin: Our results should be replicated in other geographical contexts. Larger studies
should test if the combination therapy has an impact on “hard” endpoints (early and late
mortality). We should explore the cause of the apparent superiority of the combination
therapy : coverage of undetected atypical pathogens, or modulation of the host
inflammatory response?
• Citation:
• Garin N, Genné D, Carballo S, et al. β-Lactam Monotherapy vs β-Lactam–Macrolide
Combination Treatment in Moderately Severe Community-Acquired Pneumonia: A
Randomized Noninferiority Trial. JAMA Intern Med. Published online October 06, 2014.
doi:10.1001/jamainternmed.2014.4887.

Cardiometabolic Risks Begin Early in Schizophrenic Spectrum Disorders
MedicalResearch.comInterview with: Christoph U. Correll, MD
Professor of Psychiatry and Molecular Medicine Hofstra North Shore LIJ School of Medicine
Medical Director, Recognition and Prevention (RAP) Program The Zucker Hillside Hospital Investigator Feinstein Institute for Medical Research
North Shore Long Island Jewish Health System
• Dr. Correll: The main findings of the study of 398 patients with first-episode schizophrenia-spectrum
disorders who were on average in their mid twenties are that:
• 1) despite their young age, an average of only 47 days lifetime antipsychotic exposure and
overweight/obesity figures that were comparable to similarly aged US population members, there
was a clear pattern of increased smoking and several metabolic risk parameters compared to
similarly aged persons in the general US population;
• 2) dyslipidemia, a constellation of at least one relevant abnormal blood fat value, was as frequent
as in a 15-20 years older general US population;
• 3) body composition related risk markers were significantly associated with longer total psychiatric
illness duration, whereas metabolic risk markers were significantly associated with the overall very
short mean lifetime antipsychotic treatment duration; and
• 4) relevant for treatment choice and recommendations for patients, significantly higher continuous
metabolic risk factor values were associated with olanzapine treatment and, less so, with
quetiapine treatment.
Medical Research: What was most surprising about the results?Dr. Correll: Two findings were
most surprising to us.
• First, the cardiometabolic burden was this strong this early in the disease course.
• Second, certain antipsychotics already differentiated as having worse effects than the others after
only 47 days of lifetime antipsychotic exposure.

Cardiometabolic Risks Begin Early in Schizophrenic Spectrum Disorders
MedicalResearch.comInterview with: Christoph U. Correll, MD
Professor of Psychiatry and Molecular Medicine Hofstra North Shore LIJ School of Medicine
Medical Director, Recognition and Prevention (RAP) Program The Zucker Hillside Hospital Investigator Feinstein Institute for Medical Research
North Shore Long Island Jewish Health System
• Dr. Correll: Clinicians should routinely and proactively assess all patients on antipsychotics for
cardiometabolic risk prior to and throughout treatment, promote healthy lifestyle behaviors,
choose low-risk antipsychotics early on and whenever possible, and manage cardiometabolic
adverse effects that emerge in the care of patients with first-episode psychosis and other
severe mentally disorders.
this study?
• Dr. Correll: Future research is sorely needed to assess the trajectory of cardiometabolic risk
over time, identify underlying mechanisms and mediating variables, detect safer treatments,
and test interventions to reduce or reverse cardiometabolic burden.
• Citation:
• Correll CU, Robinson DG, Schooler NR, et al. Cardiometabolic Risk in Patients With First-
Episode Schizophrenia Spectrum Disorders: Baseline Results From the RAISE-ETP Study. JAMA
Psychiatry. Published online October 08, 2014. doi:10.1001/jamapsychiatry.2014.1314.

Developing New Biomarkers To Detect Early Organ Transplant Failure
Stan Rose, PhD
President & CEO of Transplant Genomics
Dr. Rose is also a kidney transplant recipient
• MedicalResearch: What is the background for these studies?
• Dr. Rose: The studies by the founding scientists of Transplant Genomics (TGI) presented at the
World Transplant Congress (WTC) 2014 represent years of work by our scientific founders and their
collaborators at leading institutions in their search for minimally invasive diagnostic and monitoring
tools enabling earlier and more accurate detection and characterization of graft injury in organ
transplant recipients.
• In kidney transplant recipients, for example, current methods consist of tracking creatinine levels
and periodic direct assessment of grafts through biopsies. But by the time creatinine levels are
elevated, more than 50% of kidney function may be lost. Biopsies, considered the gold standard for
assessing graft status, are invasive, risky, unsuited for serial monitoring, and yield inconclusive
results as often as 30% of the time.
• Transplant Genomics is addressing the need for better monitoring by developing a peripheral blood
test for genomic biomarkers of transplant graft status to detect early signs of graft injury,
differentiate between actionable causes and enable optimization of immunosuppressive therapy.
• MedicalResearch: Can you explain what peripheral blood gene expression profiling is?
• Dr. Rose: Recent studies have identified a number of genes that are differentially expressed in both
the blood of kidney transplant recipients and kidney biopsies themselves, as conditions which lead
to dysfunction begin and progress. Gene expression profiling, in this case using microarrays, allows
the simultaneous analysis of expression levels of a large number of genes, and correlation of such
multi-gene expression level “signatures” with specific phenotypes of interest. It can be done using
peripheral blood samples, which are easy to collect and noninvasive compared to collecting tissue
biopsies.

Stan Rose, PhD
• MedicalResearch: What are the main findings of these reports?
• Dr. Rose: The studies presented at the World Transplant Congress represent the foundation
for the company’s development of genomic tests for transplant graft status:
• Classification of Graft Status
• The study Molecular Phenotyping of Kidney Biopsies by Global Gene Expression Tightly
Correlates with Histology Phenotypes and Long-term Outcomes1 compared gene expression
profiling data from biopsy tissue against biopsy results in 292 patients. The authors showed
that gene expression profiling has a predictive accuracy of 90–94% for acute rejection, acute
dysfunction no rejection, chronic allograft nephropathy and transplant excellence samples,
when compared to histology-documented phenotypes.
• Discovery of Peripheral Blood and Biopsy-Based Molecular Classifiers in Brazilian Kidney
Transplant Patients2 validated biopsy molecular phenotypes created with a US population in
an independent cohort of significantly different racial/ethnic backgrounds. Predictive
accuracies ranged from 87% to 94%.

Stan Rose, PhD
• Subclinical Acute Kidney Rejection
• A major challenge in kidney transplant management is detecting subclinical acute rejection
(SCAR), defined as histologic rejection even though the patient’s serum creatinine readings
are normal. In Molecular Signature in the Peripheral Blood for Sub-clinical Acute Kidney
Rejection,3 the researchers showed that peripheral blood gene expression profiling can
correctly classify kidney transplant patients with subclinical acute rejection, acute rejection
and transplant excellence. The discovery of this signature represents a true breakthrough in
efforts to develop predictive tests that can be used for routine serial monitoring of kidney
transplant recipients.
• Gene Expression Profiling in Liver Transplants
• Blood and Biopsy mRNA Expression Signatures Can Distinguish Major Causes of Graft Injury in
Liver Transplant Recipients4 demonstrated that genomic signatures of specific types of liver
graft injuries can be identified from both blood and biopsy tissue. The signatures are able to
distinguish acute rejection in liver transplant recipients from other major causes of graft
injury, such as hepatitis C virus recurrence and alternative causes with high predictive
accuracy. This discovery paves the way for a noninvasive differential diagnostic test that can
be used to monitor liver graft status and guide treatment decisions when problems are
detected.

Stan Rose, PhD
• MedicalResearch: What should clinicians and patients take away from this investigation?
• Dr. Rose: A genomics approach to organ transplant testing can yield more accurate and more complete diagnostic
information, providing new, noninvasive tools for transplant monitoring with the ability to detect organ injury earlier, even in
advance of dysfunction. Transplant Genomics’s first test will be a blood test used to routinely monitor kidney transplant
recipients, indicating when treatment or biopsy is required.
• MedicalResearch: What is happening next as a result of these studies?
• Dr. Rose: A large ongoing, multi-center study, funded by the National Institutes of Health through the Clinical Trials in Organ
Transplant (CTOT) consortium and other groups, is underway involving prospective serial sample collection from 300 kidney
transplant recipients and 300 liver transplant recipients. The results of this work will provide further independent validation
of our signatures and support our efforts to move these peripheral blood tests from bench to bedside.
• We are also working with several major transplant centers on clinical trials aimed at establishing clinical utility and cost
effectiveness under various scenarios, the results of which will support efforts to drive test adoption by clinicians and
reimbursement by payers. Commercial testing services will be offered through an independent CLIA laboratory we are
establishing with plans to be operational early in 2015.
• References:
• Kurian SM, Modena B, Friedewald J, et al. Molecular phenotyping of kidney biopsies by global gene expression tightly
correlates with histology phenotypes and long-term outcomes. Poster presentation A495 at World Transplant Congress, July
27, 2014.
• Ventura C, Kurian SM, Gelbart T, David-Neto E, Salomon DR. Discovery of peripheral blood and biopsy-based molecular
classifiers in Brazilian kidney transplant patients. Poster presentation A523 at World Transplant Congress, July 27, 2014.
• Friedewald J, Kurian S, Levitsky J, et al. Molecular signature in the peripheral blood for sub-clinical acute kidney rejection.
Presentation at World Transplant Congress, July 30, 2014.
• Levitsky J, Salomon D, Kurian S, et al. Blood and biopsy mRNA expression signatures can distinguish major causes of graft
injury in liver transplant recipients. Presentation at World Transplant Congress, July 31, 2014.

Ebola: Genetic Data Helps Predict Epidemic’s Spread
Tanja Stadler, ETH Zürich
Department of Biosystems Science & Engineering (D-BSSE)
Basel, Switzerland
• Response: We quantified the speed of spread of the ebola epidemic using the genetic information
of ebola.
• Response: Genetic data confirms previous epidemiological parameters, such as the number of
infections until the end of June in Sierra Leone. Thus we claim that our additional estimates are also
reliable. In particular, for Sierra Leone, the reproductive number – i.e. the number of people a
single infected individual infects on average – is estimated to be about 2. It was constant during the
first 2 month of the epidemic, ie until June, meaning public health interventions were ineffective
during that time period.
• Response: Having recent genetic data of ebola will allow us to evaluate recent public heath
interventions, such as assessing if the 3-day shut down in Sierra Leone did reduce the number of
new transmissions. Such an evaluation will allow us to identify the best strategies for the future.
We hope that sampling blood from infected people will be done again to perform these analyses,
despite the catastrophic situation in the affected countries.
• Citation:
• Stadler T, Kühnert D, Rasmussen DA, du Plessis L. Insights into the Early Epidemic Spread of Ebola in
Sierra Leone Provided by Viral Sequence Data. PLOS Currents Outbreaks. 2014 Oct 6. Edition 1.

Cardiac Stress Tests Increase Over Two Decades
Joseph A. Ladapo, MD, PhD
New York University School of Medicine
Department of Population Health New York, NY 10016
• Dr. Ladapo: We showed that the use of cardiac stress testing has risen briskly over the past two decades, with the use of
imaging growing particularly rapidly. We also showed that national growth in cardiac stress test use can largely be explained
by population and provider characteristics, but the use of imaging cannot. Importantly, nearly one third of cardiac stress
tests with imaging tests were probably inappropriate, because they were performed in patients who rarely benefit from
imaging. These tests–about 1 million each year–are associated with about half a billion dollars in healthcare costs annually
and lead to about 500 people developing cancer in their lifetime because of radiation they received during that cardiac
stress test.
• Dr. Ladapo: The sheer number of imaging cardiac stress tests being performed. We focused on patients without a known
history of coronary heart disease, and this is not a population that routinely needs or benefits from imaging. But the fact is
that most tests in this population are being performed with imaging.
• Dr. Ladapo: Inappropriate cardiac stress tests are increasing healthcare costs and contributing, though only marginally, to
the incidence of cancer. Clinically, we need effective decision support tools to help physicians more appropriately identify
patients who would benefit from imaging cardiac stress tests.
• Dr. Ladapo: We need to better understand what ecological, behavioral, and economic factors drive physician decision
making and increase the use of more intensive technologies with marginal incremental value.
• Citation:
• Physician Decision Making and Trends in the Use of Cardiac Stress Testing in the United States: An Analysis of Repeated
Cross-sectional Data
• Joseph A. Ladapo, MD, PhD; Saul Blecker, MD, MHS; and Pamela S. Douglas, MD
Ann Intern Med. 2014;161(7):482-490. doi:10.7326/M14-0296

Hospital Acquired C. diff Infections Increase Both Length of Stay and Mortality
Esther van Kleef
London School of Hygiene and Tropical Medicine, London, UK
• Response: Existing evidence reveals a wide variation in estimated excess length of hospital stay
(LoS) associated with healthcare-acquired C. difficile infection (HA-CDI), ranging from 2.8 to 16.1
days. Few studies considered the time-dependent nature of healthcare-acquired C. difficile (i.e.
patients that spent a longer time in hospital have an increased risk of infection), and none have
considered the impact of severity of healthcare-acquired C. difficile on expected delayed discharge.
Using a method that adjusted for this so-called time-dependent bias, we found that compared to
non-infected patients, the excess length of stay of severe patients (defined by increased white
blood cell count, serum creatinine, or temperature, or presence of colitis) was on average, twice
(11.6 days; 95% CI: 3.6-19.6) that of non-severe cases (5.3 days; 95% CI: 1.1-9.5). However, severely
infected patients did not have a higher daily risk of in-hospital death than non-severe patients.
Overall, we estimated that healthcare-acquired C. difficile prolonged hospital stay with an average
of ~7 days (95% CI: 3.5-10.9) and increased in-hospital daily death rate with 75% (Hazard Ratio (HR):
1.75; 95% CI: 1. 16 – 2.62).
•
• Response: Two earlier studies that accounted for time-dependent bias showed contradicting
results (i.e. a Canadian study found an excess length of stay of 6 days, whereas an Australian study
concluded that HA-CDI did not prolong length of stay). We hypothesised that such difference in
findings might relate to heterogeneity in prevalence of severity of the infection among the different
hospital settings, as well as to differences in case-mix. However, our results revealed that both
patients with severe and non-severe infection had an excess hospital stay. Moreover, when we
adjusted our results for age and co-morbidity, both younger and older healthcare-acquired C.
difficile patients had an increased average length of stay . The same was true for patients with
different co-morbidity scores.

Hospital Acquired C. diff Infections Increase Both Length of Stay and Mortality
Esther van Kleef
London School of Hygiene and Tropical Medicine, London, UK
• Response: A majority of the published estimates regarding additional length of stay due to
healthcare-acquired infections (HAI) are an overestimate, as the earlier mentioned time-dependent
bias has not been considered. In addition, the impact of healthcare-acquired C.
difficile can vary between settings. When quantifying the health and economic burden of
hospital-onset of healthcare-acquired C. difficile, this should be accounted for.
this study?
• Response: In order to gain further understanding of the identified variation in the impact
of healthcare-acquired C. difficile we urge for additional analysis, using similar methods, of
large, linked individual patient-level data, which will allow for identification of a wide range of
factors predicting the potential burden of healthcare-acquired C. difficile in addition to
severity of the infection, such as causative PCR ribotype, the patient’s treatment specialty,
previous hospital admissions and history of CDI.
•
• Citation:
• Excess length of stay and mortality due to Clostridium difficile infection: a multi-state
modelling approach
• van Kleef, E. et al. Journal of Hospital Infection

Chronic Contact Dermatitis May Promote Skin Cancer Development
Shawn Demehri, M.D., Ph.D.
Wayne M. Yokoyama, M.D.
Washington University Medical Center St. Louis, MO 63110-1093
• MedicalResearch: What are the main findings of the study?
• Research: This bedside to bench research has clearly demonstrated a cause and effect
relationship between chronic allergic contact dermatitis and skin cancer development. This
research originated from a clinical case of invasive skin cancer that developed in the context
of chronic allergic contact dermatitis to a nickel-containing metal implant. Using animal
models, we have demonstrated that chronic exposure to a contact allergen creates an
inflammation that drive skin cancer development.
MedicalResearch: Were any of the findings unexpected?
• Research: The finding that chronic allergic contact dermatitis drives skin cancer development
is a clear shift in the field. Previously, allergic contact dermatitis was thought to prevent skin
cancer formation because the studies were mainly focused on the acute phase of the
disease. But now we show that in its chronic form, as seen with allergic implants, contact
dermatitis has an opposite pro-tumor effect on skin cancer. In addition, our findings highlight
skin cancer as a previously unrecognized severe adverse event associated with allergic metal
implants.

Chronic Contact Dermatitis May Promote Skin Cancer Development
Shawn Demehri, M.D., Ph.D.
Wayne M. Yokoyama, M.D.
Washington University Medical Center St. Louis, MO 63110-1093
• MedicalResearch: What should clinicians and patients take away from this study?
• Research: To prevent such adverse events, the potential for allergic reactions to metal
implants may be assessed in patients who have had the implants and in patients preparing to
receive them using skin patch testing especially in patients with previous history of metal
allergies.
• MedicalResearch: What recommendations do you have for future research as a result of
your study?
• Research: When we examined the cells and molecules involved in chronic allergic contact
dermatitis in mice, we identified several that are linked to tumor development. Several of
these cells and molecules also were present in biopsy samples from our patient. Currently,
we are working to identify which of these inflammatory cells and molecules are most
supportive of cancer formation in order to block them and prevent skin cancer development
in chronic inflammation.
• Citation:
• Chronic allergic contact dermatitis promotes skin cancer
• Shadmehr Demehri … David M. Sheinbein, Wayne M. Yokoyama
Published October 8, 2014
Citation Information: J Clin Invest. 2014. doi:10.1172/JCI77843.

Bacterial Biofilms Make Joint Infections Resistant to Antibiotics
MedicalResearch.comInterview with:Sana Dastgheyb
National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, MDDepartment of Orthopedic Surgery,
Thomas Jefferson University, Philadelphia, PA and
Dr. Noreen HickokDepartment of Orthopedic SurgeryThomas Jefferson University, Philadelphia, PA
• Response: Physicians have long been resigned to the fact that staphylococcal joint infections
are among the most challenging to treat. Our study points towards a definitive mechanism
whereby bacteria become insensitive to antibiotics in the human joint environment. We
added MRSA to synovial fluid and observed dense, biofilm-like aggregates, as well as a
relative insensitivity to antibiotics as compared to ideal medium. Our findings suggest that
serum/extracellular matrix proteins within synovial fluid contribute greatly to staphylococcal
antibiotic insensitivity in synovial fluid. Furthermore, pre-treatment of synovial fluid with the
enzyme plasmin, which degrades extracellular matrix proteins, significantly inhibits aggregate
formation, and restores normal antibiotic sensitivity to MRSA.
•
• Response: We found that bacteria formed large aggregates in every sample of synovial fluid
that we tested. These aggregates were so large that we could see them with the naked eye.
Millions of bacteria in a single aggregate mean that not only are the innermost bacteria
protected from antibiotics, but there is no way for immune cells to effectively engulf and kill
the bacteria.

Bacterial Biofilms Make Joint Infections Resistant to Antibiotics
MedicalResearch.comInterview with:Sana Dastgheyb
National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, MDDepartment of Orthopedic Surgery,
Thomas Jefferson University, Philadelphia, PA and
Dr. Noreen HickokDepartment of Orthopedic SurgeryThomas Jefferson University, Philadelphia, PA
• Response: The insidious nature of joint infections is made clear in this study. A joint infection
may be biding its time, evading both antibiotics as well as the immune system. Even after
antibiotic intervention, live bacteria may be buried in dense, matrix-coated aggregates in an
ostensibly culture-negative joint.
this study?
• Response: Now that we know what is happening to bacteria in the joint and why they
become so difficult-to-treat, the next step is to figure out a way to allow antibiotics to
penetrate the large aggregates- or better yet, to block aggregate formation in the first place.
•
• Citation:
Biofilms cause recalcitrance of staphylococcal joint infection to antibiotic treatment
• Sana Dastgheyb, Javad Parvizi, Irving M. Shapiro, Noreen J. Hickok, and Michael Otto
• Biofilms cause recalcitrance of staphylococcal joint infection to antibiotic treatment J Infect
Dis. first published online September 11, 2014 doi:10.1093/infdis/jiu514
• Views vs UniqueViews2014-09-152014-09-202014-09-252014-09-302014-10-05

Hepatitis C May Be Spread Through Semen, Especially in HIV+ Men
Dr Daniel Bradshaw
Chelsea and Westminster Hospital, London
• Dr. Bradshaw: Over 40% of men with hepatitis C (HCV) infection have HCV RNA in their semen, although the level of RNA
was much lower than blood (usually 4 log less than blood).
Neither HIV nor acute hepatitis C led to increased shedding of HCV RNA in semen. Interestingly, however, in acute HCV, HIV-positive
men with higher blood levels of HCV RNA were more likely to shed RNA in their semen.
• Dr. Bradshaw: In men who attended a follow up visit and gave a second semen sample, nearly three quarters had hepatitis C
RNA detected in their semen at least once in the study ie a very high level of shedding of HCV in semen compared to other
studies.
• Dr. Bradshaw: Hepatitis C can be detected in the semen of many HCV-infected men. As HIV itself wasn’t associated with
increased detection of hepatitis C in semen, the high level of sexual transmission of HCV seen in HIV-positive but not HIV-negative
communities may be driven by other factors such as high risk sexual and drug-taking behaviours in HIV-positive
MSM. Nevertheless, HIV-positive MSM should be counselled that semen may contain potentially infectious hepatitis C .
• Dr. Bradshaw:
Firstly, work looking at the infectivity of seminal HCV RNA would be important.
Secondly, we were not able to recruit many HIV-negative men with acute hepatitis C . Further work with this group would
help shed light on any differences with HIV-positive men with acute HCV.
• Citation:
• A Comparison of Seminal HCV RNA Levels During Recent and Chronic HCV Infection in HIV-Infected and HIV-Uninfected
Individuals
• Daniel Bradshaw, Francois Lamoury, Beth Catlett, Tanya L. Applegate, John Mcallister, Gregory J. Dore, Gail V. Matthews, and
Mark Danta
• J Infect Dis. first published online October 6, 2014 doi:10.1093/infdis/jiu550

MedicalResearch.com: Medical Research Exclusive Interviews October 18 2014

MedicalResearch.com: Medical Research Exclusive Interviews October 18 2014

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MedicalResearch.com: Medical Research Exclusive Interviews October 18 2014