MedicalResearch.com: Medical Research Exclusive Interviews July 2 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
July 2 2015
For Informational Purposes Only: Not for Specific Medical Advice.

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Brain Scans May Predict Which OCD Patients Will Improve With Cogntive-Behavioral Therapy
MedicalResearch.com Interview with:
Jamie D. Feusner, M.D.
Associate Professor of Psychiatry and Biobehavioral Sciences
Director, Adult OCD Program
Director, Eating Disorder and Body Dysmorphic Disorder Research Program
• Medical Research: What is the background for this study? What are the main findings?
Dr. Feusner: Cogntive-behavioral therapy (CBT), is an effective treatment for most people
OCD,with response rates between 50-70%. However, a portion of the people who respond
will experience a return of their symptoms after the therapy, with 20% meeting criteria for
relapse. In this study we set out to determine if brain connectivity patterns prior to
treatment, derived from fMRI brain scans, can help predict worsening of symptoms after a
course of intensive CBT.
• We found that a pattern of “small-worldness,” which is a measure of efficiency of brain
network organization, was significantly associated with worsening of OCD symptoms after 4
weeks of intensive cogntive-behavioral therapy. Those with higher network efficiency,
interestingly, were the ones more likely to experience worsening. Yet almost all of the
participants improved in their OCD symptoms with the treatment. So (although it remains to
be further studied) one possible interpretation is that brain network reorganization may need
to occur contemporaneously with symptom improvement during CBT in order to maintain
the gains beyond the therapy period. Those who are already at the “ceiling” of network
efficiency may not have room for this network reorganization.
• Another interesting finding was that the severity of symptoms prior to treatment, and even
after treatment, did not predict who would experience worsening of symptoms in the follow-
up period.
Read the rest of the interviews on MedicalResearch.com
Content NOT an endorsement of efficacy and NOT intended as specific medical advice.

• Medical Research: What should clinicians and patients take away from your report?
• Dr. Feusner: In addition to the finding that CBT is an effective treatment for obessive
compulive disorder that results in reorganization of brain networks, this is a promising early
indication that in the future we may be able to use brain scans to help predict who may do
better or worse in the long run after CBT. This could potentially help improve personalization
of treatment, so that we can identify which treatments (e.g. shorter or longer courses of
CBT, medications, medications plus CBT, brain stimulation) could be the most likely to help an
OCD sufferer, in the long run. This could reduce time, cost, and suffering otherwise
associated with “trial and error” approaches to treatment for OCD.

• Medical Research: What recommendations do you have for future research as a result of
this study?
• Dr. Feusner: This is a small, preliminary study. Thus, we need to replicate the results in a
larger sample of people with OCD, and with a more controlled follow-up so we can make sure
that other factors are not contributing to changes in symptoms after CBT. In addition, we plan
to test whether combinations of other brain factors such as neurochemistry and other
connectivity patterns may be able to provide even better predictors, which could eventually
be tested to determine their predictive value on the level of an individual person.
• Citation:
• Brain connectivity and prediction of relapse after cognitive-behavioral therapy in obsessive–
compulsive disorder
• Jamie D. Feusner,1,* Teena Moody,1 Tsz Man Lai,1 Courtney Sheen,1 Sahib Khalsa,2,3 Jesse
Brown,4 Jennifer Levitt,1 Jeffry Alger,5 and Joseph O’Neill1
• Front. Psychiatry, 20 May 2015
http://dx.doi.org/10.3389/fpsyt.2015.00074

Tumor DNA In Saliva and Plasma May Be Biomarker For Head and Neck Cancer
Nishant Agrawal M.D.
Associate Professor of Otolaryngology
Johns Hopkins University School of Medicine
Medical Research: What is the background for this study? What are the main findings?
Dr. Agrawal: The idea of the study really arose from the specificity of genetic changes that
characterize and are the hallmark of cancer cells. Only cancer cells contain these mutations so
their detection in bodily fluids was a reasonable expectation. The current study builds on
previous work from our group that tumor DNA can be detected in the bodily fluids of patients
with many different types of solid malignancies. The main findings of the study are that tumor
DNA in saliva and plasma provides a non-invasive biomarker for head and neck cancer. The take
home message is that tumor DNA has potential to be used as a biomarker for screening, early
detection, monitoring during treatment, and surveillance after cancer treatment is completed.

Tumor DNA In Saliva and Plasma May Be Biomarker For Head and Neck Cancer
Nishant Agrawal M.D.
Associate Professor of Otolaryngology
Johns Hopkins University School of Medicine
• Dr. Agrawal: The clinical implications for patients and their oncologists is that in the near
future there will be a non-invasive test that can be used to dynamically monitor cancer
burden.
this study?
• Dr. Agrawal: We still need to improve our test performance, optimizing our gene panel, and
validate our findings in a larger study.
• Citation:
• Nishant Agrawal et al. Detection of somatic mutations and HPV in the saliva and plasma of
patients with head and neck squamous cell carcinomas. Science Translational Medicine, June
2015 DOI: 10.1126/scitranslmed.aaa8507

High-Performance Work Practices Can Reduce Central Line Infections
Ann Scheck McAlearney, Sc.D., M.S.
Professor, Family Medicine
Vice Chair for Research, Department of Family Medicine
College of Medicine Ohio State University
Columbus, Ohio
• MedicalResearch: What is the background for this study? What are the main findings?
• Dr. McAlearney: In this study, we sought to explore the potential role high-performance work
practices (HPWPs) may play in explaining differences in the success of central line-associated
blood stream infection (CLABSI) reduction efforts involving otherwise similar organizations
and approaches. We analyzed data from 194 key informant interviews across eight hospitals
participating in the federally funded ‘‘On the CUSP: Stop BSI’’ initiative. We found evidence
that at sites more successful at reducing central line-associated blood stream infection,
HPWPs facilitated the adoption and consistent application of practices known to prevent
CLABSIs; these HPWPs were virtually absent at lower performing sites.
• In this paper we present examples of management practices and illustrative quotes
categorized into four HPWP subsystems:
(a) staff engagement,
(b) staff acquisition/development,
c) frontline empowerment, and
(d) leadership alignment/development.

Columbus, Ohio
•
• MedicalResearch: What should clinicians and patients take away from your report?
• Dr. McAlearney: We present the high-performance work practices model as an organizing
framework that can be applied to facilitate quality and patient safety improvement efforts in
health care. Managers and senior leaders can use these four HPWP subsystems to select,
prioritize, and communicate about management practices critical to the success of their
CLABSI prevention efforts.

Columbus, Ohio
• MedicalResearch: What recommendations do you have for future research as a result of
this study?
• Dr. McAlearney: Future research in larger and more diverse samples will allow for
quantitative analyses of associations between high-performance work practices and central
line-associated blood stream infections and other healthcare-associated infection (HAI)
outcomes. There is also an important future opportunity to reexamine these hospitals’
management practices and central line-associated blood stream infection prevention efforts
to improve our understanding about what may promote sustainability and success with
respect to improved HAI outcomes over time.
• Citation:
• Internet Citation: High-Performance Work Practices in CLABSI Prevention Interventions: Final
Report: Executive Summary. May 2015. Agency for Healthcare Research and Quality,
Rockville, MD. http://www.ahrq.gov/professionals/quality-patient-safety/cusp/clabsi-
hpwpreport/index.html

Acidification May Be Counterproductive For Some Patients With Urinary Tract Infections
Jeffrey P. Henderson, M.D., Ph.D.
Assistant Professor of Medicine and Molecular Microbiology
Center for Women’s Infectious Diseases Research
Division of Infectious Diseases
• Medical Research: What is the background for this study?
Response: Increasing antibiotic resistance, together with an appreciation that many patients
are particularly susceptible to recurrent Urinary Tract Infections UTIs following antibiotic
therapy, motivated interest in the events that occur during early stages of UTI pathogenesis.
• Abundant evidence suggests that uropathogenic E.coli must obtain iron from human hosts in
order to cause a clinical infection. Early in infection, human cells secrete a protein called
siderocalin that is known to limit bacterial growth by sequestering iron. This protein is
detectable in the urine of Urinary Tract Infections patients.

• Medical Research: What are the main findings?
• Response: We obtained urine from a diverse panel of healthy volunteers, inoculated them
individually with a uropathogenic E.coli strain, and monitored growth in the presence and
absence of a fixed amount of siderocalin. Siderocalin exhibited a remarkably wide range of
activity between individuals.
• We traced this variation back to differences in urinary pH and to phenolic urinary
metabolites. We could significantly facilitate siderocalin’s antibacterial activity in urine by
alkalinizing it above 6.5 and adding phenolic metabolites. The metabolites that potentiate
siderocalin’s antibacterial effect have been linked to dietary sources such as coffee, tea, and
berries. Some of these compounds may further derive from the actions of gut microbes on
dietary phenols. The functional basis for these compounds’ properties seems to arise from
siderocalin’s ability to use them as molecular grips that chelate iron ions in a form that is
difficult for bacteria to access.
• From the pathogen perspective, we found that enterobactin, a molecule secreted by E.coli,
acts as a microbial countermeasure to urinary siderocalin. Adding a drug-like inhibitor to
urine that blocks enterobactin biosynthesis greatly increased siderocalin’s antibacterial effect.

• Response: The results suggest that unappreciated deficiencies in specific dietary phenolic
metabolites may contribute to UTI risk and that urinary acidification may be
counterproductive in some E.coli urinary tract infections patients.
• The work also suggests that non-classical antibiotic strategies based upon cooperation with
antibacterial innate immune proteins may be possible for preventing, and possibly treating,
urinary tract infections.

this study?
• Response: It will be necessary to more carefully identify the urinary metabolites that
facilitate siderocalin’s antibacterial activities. It will also be necessary to understand how
these metabolites are generated and how they might be delivered to patients. This may take
the form of dietary supplements, probiotics, and/or modification of the gut microbiome.
Identifying siderophore biosynthesis inhibitors would be an additional, complementary line
of investigation. Once candidate approaches are identified, clinical trials aimed at secondary
prevention would be a feasible place to start.
• Citation:
• Robin R. Shields-Cutler, Jan R. Crowley, Chia S. Hung, Ann E. Stapleton, Courtney C. Aldrich,
Jonas Marschall, and Jeffrey P. Henderson
• Human Urinary Composition Controls Antibacterial Activity of Siderocalin J. Biol. Chem. 2015
290: 15949-15960. First Published on April 10, 2015, doi:10.1074/jbc.M115.645812

Flu Vaccine Less Effective This Year Because Flu Virus Acquired A Mutation
Scott E. Hensley, Ph.D.
Assistant Professor
Wistar Institute
Philadelphia, PA 1910
• Response: Previous studies documented that the the 2014-2015 H3N2 flu vaccine strain was
antigenically distinct compared to most recent H3N2 flu strains. Recent H3N2 strains possess
several mutation and it was previously unknown which of these mutations contributed to the
2014-2015 vaccine mismatch. We used a reverse-genetic engineering approach to identify
specific viral mutations that contributed to the 2014-2015 vaccine mismatch.

Assistant Professor
Wistar Institute
•
• Response: Annual flu vaccines are necessary because flu viruses are constantly
changing. There was a vaccine-mismatch this past year because flu viruses acquired a
mutation that changed how the virus is recognized by the immune system. Most years,
vaccine strains are well matched to most circulating strains, and seasonal flu vaccines are
usually more effective. The best way to prevent flu infection is by getting a flu vaccine.

Assistant Professor
Wistar Institute
this study?
• Response: We are now trying to determine what type of immune responses are elicited by
the new 2015-2016 H3N2 flu vaccine strain. We hope to use this information to predict how
flu viruses might mutate in the future.
• Citation:
• Scott E. Hensley et al. Identification of Hemagglutinin Residues Responsible for H3N2
Antigenic Drift during the 2014–2015 Influenza Season. Cell Reports, June 2015 DOI:
10.1016/j.celrep.2015.06.005

More Sunshine Linked to Better IVF Outcomes
Frank Vandekerckhove, MD, PhD
Clinical Head, Centre for Reproductive Medicine
University Hospital Ghent
Belgium
• Dr. Vandekerckhove: Several retrospective studies have evaluated seasonal variations in the
outcome of IVF treatment. Some also included weather conditions, mostly temperature and
hours of daylight. The results were conflicting. We focused on individual variables provided as
monthly results by our national meteorological institute. We shifted the results in IVF
outcome to the weather results of one month earlier, as we supposed that the selection of
good quality oocytes may start in the weeks before.
• Between January 2007 and December 2013, the IVF outcome of all Belgian patients treated
in our university center was compared to the quarter of the year and monthly mean values of
temperature, rain fall, rainy days and sunshine hours during the month when gonadotropins
were started or the month before.

Belgium
• 11494 patients started an IVF cycle and were included. Firstly bivariate correlation was
performed by linear modelling between monthly weather conditions and IVF results.
Secondly the same IVF outcome variables were plotted against the weather results stratified
per quartile for each individual meteorological variable.
• There was no relationship between IVF outcome and the quarter of the year.
• When looking for a linear correlation between IVF results and the mean monthly values for
the weather, the results were inconsistent.
• However, when the same analysis was repeated with the weather results of 1 month earlier,
there was a clear trend towards better IVF outcome with higher temperature, less rain and
more sunshine hours. The live birth rate per cycle was significantly different (p 0.019)
between different groups (Q=quartile) of mean number of sunshine hours (Q1=60.75,
Q2=136.00, Q3=174.50).

Belgium
• Dr. Vandekerckhove: Because of the retrospective design of the study, further adjusting for
possible confounding factors such as age of the woman, type of infertility and indication for
IVF is mandatory.
• The weather conditions seem to have their strongest impact on live birth rates.

Belgium
this study?
• Dr. Vandekerckhove: The impact of sunlight on the early selection of good quality oocytes is
an important finding for future research. Maybe we should focus further on environmental
factors during the early phases of oocyte recruitment during the period just before ovarian
stimulation for IVF. A strong impact of light, as illustrated by the importance of sunny
weather, brings melatonin again in the picture for further research and treatment options.
• Citation:
• Abstract presented at the annual meeting of the European Society for Reproductive Health
(ESHRE) in Lisbon June 2015, discussing the Effects of Sun Exposure on Fertility.

Lymph Node Cancer Metastases Do Not Require Growth of New Blood Vessels
Timothy P. Padera, PhD
Edwin L. Steele Laboratories
Department of Radiation Oncology
• Dr. Padera: Systemic therapy benefits cancer patients with lymph node metastases; however
all phase III clinical trials to date of antiangiogenic therapy have failed in the adjuvant setting.
We have previously reported the lack of efficacy of antiangiogenic therapies in pre-clinical
models of spontaneous lymphatic metastasis, however there were no mechanistic data to
explain these observations. Here, we developed a novel chronic lymph node window model
to facilitate new discoveries in the mechanisms of growth and spread of lymph node
metastases. Our new data provide pre-clinical evidence along with supporting clinical
evidence that angiogenesis does not occur in the growth of metastatic lesions in the lymph
node. These results reveal a mechanism of treatment resistance to antiangiogenic therapy in
adjuvant setting, particularly those involving lymph node metastases.

• Dr. Padera: In the adjuvant setting, anti-angiogenic therapy has failed to show a benefit for
cancer patients in all Phase III trials. Our new data provide one potential mechanism for the
lack of efficacy of anti-angiogenic therapy in the adjuvant setting. The primary implication of
our findings is that, since lymph node metastases do not require the growth of new blood
vessels, antiangiogenic therapy will not inhibit lymphatic metastases. Other therapies are
needed for the treatment of patients at risk for lymph node metastasis.

this study?
• Dr. Padera: We need to continue to learn about the biology of small metastases in lymph
nodes in order to design effective adjuvant therapy for patients at risk of developing lymph
node metastases.
• Citation:
• Investigation of the Lack of Angiogenesis in the Formation of Lymph Node Metastases
• Han-Sin Jeong, Dennis Jones, Shan Liao, Daniel A. Wattson, Cheryl H. Cui, Dan G. Duda,
Christopher G. Willett, Rakesh K. Jain, and Timothy P. Padera
JNCI J Natl Cancer Inst (2015) 107 (9): djv155 doi:10.1093/jnci/djv155

Active Surveillance Utilization For Prostate Cancer Remains Low
MedicalResearch.com Interview with: Hui Zhu, MD, ScD
Section Chief, Urology Section
Louis Stokes Cleveland Veterans Affairs Medical Center
and Staff, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation
Cleveland, Ohio
• MedicalResearch: Tell me a little bit about the impetus for this study. What gap in
knowledge were you trying to fill?
• Dr. Zhu: Prostate cancer is a very challenging disease to understand and manage. For the
minority of men, prostate cancer is a lethal disease, and in fact, it is the second leading cause
of cancer death in American men, behind only lung cancer. However, for the majority of men,
prostate cancer poses little risk of death. In fact, about 1 man in 7 will be diagnosed with
prostate cancer during his lifetime, but only 1 man in 38 will die from prostate cancer.
• In an effort to avoid suffering and death from prostate cancer for those men with the lethal
form, the early detection of prostate cancer (before the disease has reached a stage when it
is no longer curable) through widespread prostate cancer screening was instituted in the late
1980s and early 1990s. As a result, prostate cancer diagnosis increased substantially, and
most prostate cancers were detected at an early, treatable stage. Screening successfully
reduced the risk of death from prostate cancer by 20%.

Cleveland, Ohio
• Unfortunately, our best available screening tests, i.e. prostate-specific antigen (PSA) testing
and the digital rectal exam, do not differentiate well between lethal and nonlethal prostate
cancer. Consequently, screening is associated with a high risk of overdiagnosis of nonlethal
prostate cancer. As a result, about 800 men must be screened and about 30 men must be
diagnosed and treated to avoid one death from the prostate cancer, according to recent
results from the largest prostate cancer screening trial.
• Since the natural history of newly diagnosed screen-detected prostate cancer is difficult to
predict (i.e. lethal or nonlethal), most prostate cancers have been treated aggressively,
leading to overtreatment of many nonlethal cancers. Aside from receiving unnecessary
treatment, these men are exposed to the potential side effects and complications of
treatment, including erectile dysfunction and urinary incontinence.

Cleveland, Ohio
• In response to the harms associated with screening and treatment, the US Preventative
Services Task Force issued a statement in 2011 (formalized in 2012) recommending against
prostate cancer screening in all men. Unfortunately, while minimizing the risks of
overdiagnosis and overtreatment for men with nonlethal prostate cancer, this solution
eliminates any of the potential benefits of screening for those men with the lethal form of
the disease.
• As urologists, our solution is different. Rather than throw the baby out with the bathwater,
we prefer to preserve PSA screening and its benefits by addressing and hopefully minimizing
its associated risks. To achieve this, our goal is to better distinguish between those men who
have lethal vs. nonlethal prostate cancer, limiting treatment only to those men who have the
lethal form of the disease at an early stage when it is still curable. The dilemma is that our
currently available diagnostic tests are unable to accurately differentiate lethal from
nonlethal prostate cancer with 100% certainty at the time of initial diagnosis.

Cleveland, Ohio
• The solution, or at least part of the solution, is active surveillance. In men who appear to
have nonlethal (“low risk”) cancer at the time of diagnosis, it now appears to be safe to
observe these cancers, at least initially. This is the concept behind active surveillance. Active
surveillance entails carefully monitoring men with low-risk prostate cancer using serial testing
and reserving the option of treatment for those men with prostate cancers that exhibit lethal
characteristics. In this way, active surveillance preserves the benefits of screening while
minimizing the harms of overdiagnosis and overtreatment.
• Active surveillance was first introduced in the early 2000s, but its efficacy and safety have
only been elucidated recently over the last 5 years. Given that active surveillance may be one
solution to the screening dilemma, we wanted to evaluate contemporary active surveillance
utilization, which is the impetus for our study. Based on the most recent data available to us,
we chose the years 2010-2011, which coincide to the time immediately before and during
the release of the US Preventative Services Task Force statement against PSA screening.

Cleveland, Ohio
• MedicalResearch: We’re talking about men with low-risk prostate cancer, correct? Can you
elaborate about what that means for these men?
• Dr. Zhu: Low-risk prostate cancer is a term we use as urologists to describe prostate cancer
that has a low-risk of clinical progression, that is, prostate cancer that is unlikely to invade
outside the prostate, metastasize to other organs, or become lethal. These prostate cancers
are usually small in size and of low grade (e.g., Gleason grade 3). The PSA values of those
patients are also relatively low, e.g., less than 10 ng/dL. Unfortunately, our diagnostic means
of characterizing localized prostate cancers through the digital rectal exam, PSA, and biopsy
results has limited accuracy. For example, about 30% of men who are initially characterized
as having low-risk disease may actually have more aggressive occult disease that is not
initially detected, according to recent studies.

Cleveland, Ohio
• MedicalResearch: To make sure I understand the statistics: 11-40 percent of the men were
eligible to undergo active surveillance. But of ALL the men, only 6-12 percent actually underwent
active surveillance.
• The rest got one or more kinds of medical, surgical and radiation treatment? Is that correct?
• Dr. Zhu: Yes, approximately 11-40% of men were eligible for active surveillance, depending on the
criteria used to define “low-risk” disease. Since we cannot be 100% sure that a low-risk prostate
cancer is nonlethal at first glance, we use different criteria (based on Gleason grade, PSA level,
clinical stage, and cancer volume) to further stratify low-risk patients. As the inclusion criteria
become more stringent, our certainty that the cancer is truly nonlethal increases, but the number
of men who meet the criteria decreases. By the least stringent (most inclusive) criteria (e.g., Klotz
criteria), 40% of men in the study were eligible for active surveillance. By the most stringent (least
inclusive) criteria (e.g., modified Epstein criteria), only 11% of men in the study were eligible. Of
men eligible for active surveillance by Klotz criteria, only 6.5% received active surveillance. Of men
eligible for active surveillance by modified Epstein criteria, only 12.1% received active surveillance.
Therefore, as our certainty in the nonlethal nature of the prostate cancer increased, so did our use
of active surveillance. Having said that, the actual utilization was very low. By comparison, in
Europe, where active surveillance is more widely accepted (i.e. professionally and culturally
accepted), active surveillance rates range from 16-59%. In all fairness, however, it is only recently
that long-term data revealing the safety and efficacy of active surveillance has been released. For
example, it is now clear that using Klotz criteria to determine a man’s suitability for active
surveillance is safe. Based on recently published long-term followup data, 55% of men on active
surveillance using Klotz criteria remain untreated on active surveillance at 15 years, while only 2.8%
of men develop metastatic disease and only 1.5% of men die from prostate cancer.

Cleveland, Ohio
• MedicalResearch: What’s the take-home message of your report? What should the public
take from it?
• Dr. Zhu: The diagnosis and management of prostate cancer is dynamic. The use of active
surveillance, although low in this study, is an ongoing process that is gaining acceptance
among urologists and patients. Urologists and researchers are currently working on ways to
better differentiate lethal from nonlethal prostate cancer through the use of systematic
needle biopsies, serial PSA levels, tissue biomarkers including genetic markers, and modern
MRI imaging techniques. These new strategies have shown promise in helping urologists
better identify which patients may benefit from upfront treatment and which may be better
served with active surveillance.

Cleveland, Ohio
• MedicalResearch: Do these findings mean that many men are getting treatments that they
don’t need and could be harmful? What are your thoughts about that?
• Dr. Zhu: Yes, many men are overtreated for prostate cancer, and aside from the risks of
unnecessary treatment itself, these men are exposed to the complications associated with
treatment, including erectile dysfunction and urinary incontinence. However, at the time of
treatment, it is not always clear which men “need” treatment, i.e. which men have lethal vs.
nonlethal prostate cancer. This is where active surveillance helps. The initial period of
observation and careful monitoring can help tease out which cancers are more likely to
become lethal and should be treated from those cancers that are nonlethal and better left
untreated.

Cleveland, Ohio
• MedicalResearch: What can we learn from your report about the places that use active
surveillance more and less?
• Dr. Zhu: During the study period, active surveillance use seemed to be used more heavily at
centers of excellence and regionally within the Northeast. These practices likely reflect both
provider factors as well as patient preferences. As active surveillance has gained more
national exposure and acceptance, its current use may be more widespread.

Cleveland, Ohio
• MedicalResearch: What is the message here for patients and their loved ones/caretakers?
What should they take from this? What about physicians?
• Dr. Zhu: Prostate cancer is a challenging disease. Early prostate cancer detection through
screening has potential risks and benefits. By limiting treatment only to lethal forms of the
disease, active surveillance has the potential to mitigate some of these risks while
maintaining the possibility of cure for those men with lethal disease. Age-appropriate men
should discuss the risks and benefits of screening with their physicians, and men with newly
diagnosed localized prostate cancer should ask their physicians whether active surveillance is
a good option for them.

Cleveland, Ohio
• MedicalResearch: What else should readers know?
• Dr. Zhu: Prostate cancer, even the lethal form, is highly treatable when it is detected at an
early stage through the use of screening. Men aged 55 to 69 years who are considering being
screened for prostate cancer should have a discussion with their physicians which involves
weighing the benefits of preventing death from prostate cancer against the known potential
harms associated with screening and treatment.
• Citation:
• Maurice MJ, Abouassaly R, Kim SP, Zhu H. Contemporary Nationwide Patterns of Active
Surveillance Use for Prostate Cancer. JAMA Intern Med. Published online June 29, 2015.
doi:10.1001/jamainternmed.2015.2835.

Women With PTSD At Higher Risk For Heart Disease
Jennifer A. Sumner, Ph.D.
Columbia University Mailman School of Public Health
New York, NY 10032
Dr. Sumner: Cardiovascular disease, which includes conditions like heart attack and stroke, is the
leading cause of death worldwide. Stress has long been thought to increase risk of cardiovascular
disease, and posttraumatic stress disorder (PTSD) is the quintessential stress-related mental
disorder. Some individuals who are exposed to traumatic events, such as unwanted sexual
contact, the sudden unexpected death of a loved one, and physical assault, develop PTSD, which
is characterized by symptoms of re-experiencing the trauma (e.g., nightmares), avoidance of
trauma reminders (e.g., avoiding thinking about the trauma), changes in how one thinks and feels
(e.g., feeling emotionally numb), and increased physiological arousal and reactivity (e.g., being
easily startled). PTSD is twice as common in women as in men; approximately 1 in 10 women will
develop PTSD in their lifetime. Research has begun to suggest that rates of cardiovascular disease
are higher in people with PTSD. However, almost all research has been done in men.

New York, NY 10032
My colleagues and I wanted to see whether PTSD was associated with the development of
cardiovascular disease in a large sample of women from the general public. We looked at
associations between PTSD symptoms and new onsets of heart attack and stroke among nearly
50,000 women in the Nurses’ Health Study II over 20 years, beginning in 1989. Women with the
highest number of PTSD symptoms (those reporting 4+ symptoms on a 7-item screening
questionnaire) had 60% higher rates of developing cardiovascular disease (both heart attack and
stroke) compared to women who were not exposed to traumatic events. Unhealthy behaviors,
including lack of exercise and obesity, and medical risk factors, including hypertension and
hormone replacement use, accounted for almost 50% of the association between elevated PTSD
symptoms and cardiovascular disease. We also found that trauma exposure alone (reporting no
PTSD symptoms on the screening questionnaire) was associated with elevated cardiovascular
disease risk compared to no trauma exposure.

New York, NY 10032
Our study is the first to look at trauma exposure and PTSD symptoms and new cases of
cardiovascular disease in a general population sample of women. These results add to a growing
body of evidence suggesting that trauma and PTSD have profound effects on physical health as
well as mental health.

New York, NY 10032
• Dr. Sumner: PTSD is not exclusively a psychological problem but also increases risk of chronic
disease. Treatment providers, including primary care physicians, serving individuals at risk for
PTSD should screen for cardiovascular risk and monitor health indicators in those with PTSD.
Treatment for PTSD also needs to consider the long-term health consequences of the
disorder. Ultimately, integration of mental and physical health care is key. Women with PTSD
should be aware that they may be at elevated risk of developing a heart attack or stroke and
that engaging in unhealthy behaviors, like smoking cigarettes and eating an unhealthy diet,
may increase this risk.

New York, NY 10032
this study?
• Dr. Sumner: Our results suggest that women with PTSD are at increased risk of developing
cardiovascular disease. Future research efforts should be focused on understanding
why women with PTSD are at higher risk and how to prevent this increased risk. It is also of
interest to study whether treatment for PTSD helps to reduce cardiovascular risk.
• Citation:
• Trauma Exposure and Posttraumatic Stress Disorder Symptoms Predict Onset of
Cardiovascular Events in Women
Jennifer A. Sumner, Laura D. Kubzansky, Mitchell S.V. Elkind, Andrea L. Roberts, Jessica
Agnew-Blais, Qixuan Chen, Magdalena Cerdá, Kathryn M. Rexrode, Janet W. Rich-Edwards,
Donna Spiegelman, Shakira F. Suglia, Eric B. Rimm, and Karestan C. KoenenCirculation.
2015;CIRCULATIONAHA.114.014492published online before print June 29 2015,
doi:10.1161/CIRCULATIONAHA.114.014492

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.

Sugar and Fat Absorption Increased In Obesity
Dr. Karine Clément M.D., Ph.D.
Assistant Professor, Nutrition Department
Hotel-Dieu hospital Paris
Dr. Clément: Obesity, associated with insulin resistance, is a chronic inflammatory
disease revealed by a moderate but long-term increase in the levels of inflammatory
molecules in the blood.
• Our groups and others have shown that several organs such as adipose tissues, liver,
pancreas and muscles are also sites of inflammation with accumulation of immune cells such
as macrophages and lymphocytes. This low-grade inflammatory state perturbs the tissue
biology and contributes to the development and/or maintenance of insulin resistance and
diabetes. In addition our teams and others showed that the intestinal functions are altered in
obesity such as sugar and lipid absorption of and enteroendocrine nutrient signaling to the
whole body.

Our teams showed modifications of immunity in the obese intestine, and particularly in
the jejunum part where most of sugar and lipid absorption takes place. Obesity increases the
absorptive surface of the intestine and the colonization of the epithelium by CD8αβ T
lymphocytes not affecting tissue integrity, thus differing from IBD inflammation. The cytokines
secreted by the CD8 T cells of obese, but not lean subjects, are able to inhibit insulin action in
enterocytes. In these patients, the increase of intestinal CD8 T cell density correlates with sugar
absorption capacity and with the level of obesity and associated complications such as liver
disease (NASH – Non-Alcoholic SteatoHepatitis) and dyslipidemia.

• Dr. Clément: There has been tremendous progress in understanding the complex
pathophysiology of obesity and, particularly through the identification of the pathological
alteration of organs starting with the alteration of the adipose tissues during
obesity development.
• Obesity is not only simply driven by excessive eating and insufficient physical activity, it is
evidently a complex disease relying on pathological crosstalk between many organs (brain,
adipose tissue, muscle, liver pancreas) with functional alteration.
• Thanks to the extensive clinical phenotyping of obese subjects in our study, it is possible to
include the small intestine as a contributor in this complex crosstalk. In particular, sugar and
fat absorption is increased in an insulin resistant body and therefore in obesity.
Furthermore, the intestinal mucosa is a physical and immune barrier sensing bacterial and
food antigens. Here we show that changes in intestinal immunity and inflammation might
contribute to metabolic perturbation in obese subjects.

this study?
• Dr. Clément: Next aims are to understand how deeply these perturbations of the intestine
impact on the human body; in particular, how the gut microbiota, the intestinal immune
system and beyond the gut, body metabolism are interrelated. Gut microbiota is indeed
perturbed in obesity and diabetes. Non-invasive intervention targeting intestinal
inflammation in relation to nutrient and local microbiota could help gain metabolic health
• Citation:
• Milena Monteiro-Sepulveda, Sothea Touch, Carla Mendes-Sá, Sébastien André, Christine
Poitou, Omran Allatif, Aurélie Cotillard, Hélène Fohrer-Ting, Edwige-Ludiwyne Hubert,
Romain Remark, Laurent Genser, Joan Tordjman, Kevin Garbin, Céline Osinski, Catherine
Sautès-Fridman, Armelle Leturque, Karine Clément, Edith Brot-Laroche. Jejunal T Cell
Inflammation in Human Obesity Correlates with Decreased Enterocyte Insulin Signaling. Cell
Metabolism, 2015; DOI: 10.1016/j.cmet.2015.05.020

Surgery for GERD May Improve Reflux But Risks Complications
John Maret-Ouda MD, PhD candidate
Upper Gastrointestinal Surgery Department of Molecular medicine and Surgery
Karolinska Institutet
Stockholm, Sweden
• Dr. Maret-Ouda : This review is part of the BMJ series “Uncertainties pages”, where clinically
relevant, but debated, medical questions are highlighted and discussed. The present study is
assessing treatment of severe gastro-oesophageal reflux disease, where the current
treatment options are medical (proton-pump inhibitors) or surgical (laparoscopic antireflux
surgery). The clinical decision-making is often left to the clinician and local guidelines. We
evaluated the existing literature to compare the two treatment options regarding reflux
control, complications, future risk of oesophageal adenocarcinoma, health related quality of
life, and cost effectiveness.

Stockholm, Sweden
The main findings were that surgery might provide slightly better reflux control and health
related quality of life, but is associated with higher risks of complications compared to
medication. A possible preventive effect regarding oesophageal adenocarcinoma remains
uncertain. Regarding cost effectiveness, medication seems more cost effective in the short term,
but surgery might be more cost effective in the longer term. Since medication provides good
treatment of severe gastro-oesophageal reflux disease, but with lower risks of complications, this
remains the first line treatment option.

Stockholm, Sweden
• Dr. Maret-Ouda : Both antireflux surgery and medical treatment with proton-pump inhibitors
provide good and sufficient long-term results for severe gastro-oesophageal reflux disease.
However, there is a slightly higher risk of complications associated with antireflux surgery.
Therefore, these patients should primarily be offered proton-pump inhibitors. If insufficient
results are achieved after eight weeks of adequately dosed medical treatment, antireflux
surgery should be considered a good treatment option. In young, physically fit patients with
severe gastro-oesophageal reflux disease, where treatment is probable to be ongoing for a
very long time, surgery is a possible first line treatment, which also seems to be more cost
effective in a long term perspective.

Stockholm, Sweden
this study?
• Dr. Maret-Ouda :
• First, due to the advances in surgical and postsurgical care, the absolute risk of death or other
severe complications associated with antireflux surgery needs to be further evaluated.
• Second, the long-term results of both treatments should be assessed, especially regarding
long-term complications, such as oesophageal adenocarcinoma as well as cost-effectiveness
in relation to reflux control.
• Third, there are several endoscopic techniques currently being developed and studied, which
need to be assessed and further evaluated, since these might potentially pose good
treatment options for gastro-oesophageal reflux disease.
• Citation:
• Maret-Ouda John, Brusselaers Nele, Lagergren Jesper. What is the most effective treatment
for severe gastro-oesophageal reflux disease? 2015; 350 :h3169

Both Young and Old Lose Muscle Strength After Short Term Inactivity
Andreas Vigelsø PhD, research assistant
University of Copenhagen Faculty of Health Sciences Center for Healthy Aging
Dept. of Biomedical Sciences
Copenhagen Denmark
Medical Research: What is the background for this study?
Response: According to the UN, the number of individuals more than 60 years old is expected to
more than double, from 841 million worldwide today to more than 2 billion in 2050.
Furthermore, the aging process is associated with a reduction in muscle mass, strength and
fitness level. Collectively, this may contribute to frailty and may limit independent living. In
addition, disease or injuries that can cause short-term immobilization are a further threat to
independent living for older individuals. Despite its clinical importance for an increasing
population of older individuals, few studies have examined older individuals after immobilization.
Thus, our aim was to determine the effect of aerobic retraining as rehabilitation after short-term
leg immobilization on leg strength, leg work capacity, and leg muscle mass in young and older
men.

Copenhagen Denmark
Medical Research: What are the main findings?
Response: Interestingly, our study reveals that inactivity affects the muscular strength in young
and older men equally. Having had one leg immobilized for two weeks, young people lose up to a
third of their muscular strength, while older people lose approx. one fourth. A young man who is
immobilized for two weeks loses muscular strength in his leg equivalent to ageing by 40 or 50
years. Moreover, short-term leg immobilization had marked effects on leg strength, and work
capacity and 6 weeks’ retraining was sufficient to increase, but not completely rehabilitate,
muscle strength, and to rehabilitate aerobic work capacity and leg muscle mass.

Copenhagen Denmark
• Response: Therefore, aerobic training alone should not be used as rehabilitation training
after short-term immobilization. But, aerobic retraining may be considered as a partial
alternative in combination with strength training without impeding the rehabilitation
process. Moreover, aerobic retraining could be considered due to the beneficial effect of
counteracting the increased risk of lifestyle-related diseases in the older population and may
be advantageous for therapists, as not all individuals will enjoy or adhere to a single protocol.
• For the patient our results pinpoints the importance for rehabilitation training after even
short-term inactivity to maintain independent living throughout life.

Copenhagen Denmark
this study?
• Response: This study included subjects who were average for their age group. However, the
clinical relevance may be more pronounced in the proportion of the older population that is
less physically active. Hence, our approach is applicable to a large proportion of the
population, but possibly not to the weakest. Therefore, future research should search to
optimize rehabilitation training that rehabilitates and improves strength, muscle mass and
fitness level in the weaker part of the older population.
• Citation:
• Six weeks’ aerobic retraining after two weeks’ immobilization restores leg lean mass and
aerobic capacity but does not fully rehabilitate leg strenght in young and older men.
• Vigelsø A1, Gram M, Wiuff C, Andersen JL, Helge JW, Dela F.
J Rehabil Med. 2015 Apr 21. doi: 10.2340/16501977-1961. [Epub ahead of print]

High Fiber Diet During Pregnancy May Reduce Risk of Childhood Asthma
Dr. Alison Thorburn Ph.D.
School of Medical and Applied Sciences, Central Queensland University
Rockhampton, Queensland 4702, Australia
Medical Research: What is the background for this study?
Dr. Thorburn: Asthma is a highly prevalent disease in the Western World. The prevailing
explanation for this has been the hygiene hypothesis, which proposes that a decline in family size
and improved hygiene has decreased exposure to infectious agents and therefore resulted in
dysregulated immune responses that lead to asthma. However, recently there has been more
attention on the role of diet and the gut microbiota in explaining the prevalence of inflammatory
diseases in Western World. Indeed, many studies implicate obesity, as well as a high fat, low fruit
and vegetable diet with higher prevalence of asthma. On the other hand, a Mediterranean diet,
which is high in fruit and vegetables, is associated with lower prevelance of asthma. Interestingly,
the consumption of dietary fiber is reduced in severe asthmatics. These and other data suggest
that the diet (particularly dietary fibre) and the gut microbiota may play an important role in the
development of asthma.

• Dr. Thorburn: The main findings of this study are that:
• – In mice: A high-fiber diet promotes a gut microbiota that produces high levels of anti-
inflammatory short-chain fatty acids (SCFAs), particularly acetate. Acetate (alkaline form of
vinegar) suppressed the development of allergic airways disease (AAD, a model for human
asthma) in adult mice and the offspring of pregnant mice.
• – In humans: High dietary fiber intake during late pregnancy is associated with higher
acetate levels in the serum and a decrease in the percentage of infants showing predictors
for asthma development in later life.
• – The mechanism underlying these findings involves increasing T regulatory cell number
and function through epigenetic mechanisms, which enhance immune regulation to prevent
inflammation.

• Dr. Thorburn: The take home message is “eat more fibre” to protect yourself and your
offspring against the development of asthma. Fibre is important for the production of the
anti-inflammatory molecule acetate, which helps regulate the immune response.
this study?
• Dr. Thorburn: Future research is required to determine if the effect of fiber also offers
protection against other Western World associated diseases such as allergies and
cardiovascular disease. Further studies should also investigate whether the consumption of
vinegar has similar effects.
• Citation:
• Evidence that asthma is a developmental origin disease influenced by maternal diet and
bacterial metabolites
• Alison N. Thorburn, Craig I. McKenzie,
• Sj Shen, Dragana Stanley,Laurence Macia, Linda J. Mason, Laura K. Roberts, Connie H. Y.
Wong, Raymond Shim, Remy Robert, Nina Chevalier, Jian K. Tan, Eliana Mariño, Rob J. Moore,
Lee Wong, Malcolm J. McConville, Dedreia L. Tull, Lisa G. Wood, Vanessa E. Murphy, Joerg
Mattes et al.
• Nature Communications 6, Article number: 7320
doi:10.1038/ncomms8320 Published 23 June 2015

2013 ACC/AHA Cholesterol Guidelines Increase Number Of Adults Eligible For Statin Therapy
Duk-Woo Park, MD, PhD.
Professor, Division of Cardiology
Asan Medical Center, University of Ulsan College of Medicine
Seoul, Korea
Response: The applicability and potential clinical effects of the 2013 ACC/AHA cholesterol
guidelines on major cardiovascular outcomes in the “real-world” population remains
uncertain and also should also be evaluated in multiple groups of various ethnic backgrounds.
We determined the proportions of adult persons eligible for statin therapy by changes of
2013 ACC/AHA cholesterol guidelines using a nationally representative sample from an Asian
country (South Korea) and also we evaluated the potential clinical effects of this cholesterol
guideline on future cardiovascular outcomes using an external validation cohort from the
Korean National Health Examination.
• Similar to findings from the United States and the European cohort, our study showed that
the 2013 ACC/AHA guidelines would substantially increase the number of adults who would
be potentially eligible for statin therapy in Korean population. In addition, the 2013 ACC/AHA
guidelines would have identified more cases with higher events of cardiovascular disease
(CVD) for statin treatment than the ATP-III guidelines.

2013 ACC/AHA Cholesterol Guidelines Increase Number Of Adults Eligible For Statin Therapy
Duk-Woo Park, MD, PhD.
Professor, Division of Cardiology
Asan Medical Center, University of Ulsan College of Medicine
Seoul, Korea
this study?
• Response: In our study, given lower basal event rates in the Korean population compared
with the US population, the pooled cohort equations tended to overestimate atherosclerotic
cardiovascular disease (ASCVD) risk when applied to adults in Korea, particularly among
adults at the highest levels of predicted risk. Therefore, further researches regarding
implementing a country- or ethnic-specific risk equation and setting appropriate population-
wide thresholds are required to facilitate better clinical decision-making in the Asian
population.
• Citation:
• Applicability and Potential Clinical Effects of 2013 Cholesterol Guidelines on Major
Cardiovascular Events
• Min Jung Ko, Ph.D., Yun Jung Kim, M.P.H., Chan Mi Park, Ph.D.,Sun-Mi Lee, Ph.D.,Woo Je Lee,
M.D., Ph.D. Michael J. Pencina, Ph.D. Ann Marie Navar-Boggan, M.D., Ph.D. Duk-Woo Park,
MD, Ph.D.
• DOI: http://dx.doi.org/10.1016/j.ahj.2015.06.012

Some Breast Cancer Patients Have Excellent Results With Partial Breast Radiation
Dr. Mitchell Kamrava MD
University of California Los Angeles
Los Angeles, CA
Dr. Kamrava: Breast conservation (lumpectomy followed by radiation) is known, based on
multiple randomized trials with over 20 years of follow-up, to provided equivalent outcomes
as mastectomy. The radiation component of breast conservation has standardly been
delivered to the whole breast. Studies show that the majority of breast recurrences occur
near the lumpectomy cavity causing some to ask whether it is necessary to treat the whole
breast in order to reduce the risk of a recurrence.
• Partial breast radiation delivers treatment just to the lumpectomy cavity with a small margin
of 1-2 cm. It’s delivered in a shorter time of 1 week compared with about 6 weeks for
standard whole breast radiation and 3-4 weeks for hypofractionated whole breast radiation.

Los Angeles, CA
• The original method developed to deliver partial breast radiation is interstitial tube and
button brachytherapy. This uses multiple small little tubes that are placed through the
lumpectomy cavity to encompass the area at risk. One end of these tubes can be connected
to a high dose rate brachytherapy machine that allows a motorized cable with a very small
radiation source welded to the end of it to be temporarily pushed in and out of each of the
tubes so that the patient can be treated from “inside out”. This helps concentrate the
radiation to the area of the lumpectomy cavity while limiting exposure to normal
tissues. This treatment is most commonly delivered as an out-patient two times per day for a
total of 10 treatments.
• The main finding from our paper is that in reviewing the outcomes on over 1,000 women
treated with this technique with an average follow-up of 6.9 years that the 10 year actuarial
local recurrence rate was 7.6% and in women with more than 5 years of follow-up physician
reported cosmetic outcomes were excellent/good in 84% of cases.

Los Angeles, CA
• Dr. Kamrava: There are groups of women who are appropriate candidates for partial breast
radiation. For these women a 1 week course of radiation to just a portion of the breast
around the lumpectomy cavity demonstrates similar local control outcomes and
excellent/good cosmetic outcomes compared with the results we would expect using a more
standard whole breast approach.

Los Angeles, CA
this study?
• Dr. Kamrava: We eagerly await the results of randomized clinical trials comparing whole
breast versus partial breast radiation. We need level 1 evidence prior to being able to
routinely offer partial breast radiation. It is anticipated that results from the European
randomized trial will be presented before the end of this year. Until this data is available
multiple national organizations have published guidelines identifying patients who are
candidates for partial breast radiation outside of a clinical trial. We believe that our data
further confirms that it is appropriate to be treating certain groups of women with partial
breast radiation outside of a clinical trial.
• Citation:
• Ann Surg Oncol. 2015 Apr 28. [Epub ahead of print]
• Outcomes of Breast Cancer Patients Treated with Accelerated Partial Breast Irradiation Via
Multicatheter Interstitial Brachytherapy: The Pooled Registry of Multicatheter Interstitial Sites
(PROMIS) Experience.
• Kamrava M1, Kuske RR, Anderson B, Chen P, Hayes J, Quiet C, Wang PC, Veruttipong D, Snyder
M, Jeffrey Demanes D.

Health Care Organizations Require Different Tactics To Implement Change
Ingrid M. Nembhard PhD MS
Yale University
New Haven, CT
Dr. Nembhard: Many health care organizations (hospital, medical groups, etc.) have sought to
address well-documented quality problems by implementing evidence-based innovations, that is,
practices, policies, or technologies that have been proven to work in other organizations. The
benefits of these innovations are often not realized because adopting organizations experience
implementation failure—lack of skillful and consistent use of innovations by intended users (e.g.,
clinicians). Past research estimates that implementation failure occurs at rates greater than 50%
in health care. The past work also shows organizational factors expected to be facilitators of
implementation are not always helpful.

Yale University
New Haven, CT
In this work, we examined a possible explanation for the mixed results: different innovation
types have distinct enabling factors. Based on observation and statistical analyses, we
differentiated role-changing innovations, altering what workers do, from time-changing
innovations, altering when tasks are performed or for how long. We then examined our
hypothesis that the degree to which access to groups that can alter organizational learning—staff,
management, and external network— facilitates implementation depends on innovation type.
Our longitudinal study of 517 hospitals’ implementation of evidence-based practices for treating
heart attack confirmed our thesis for factors granting access to each group: improvement team’s
representativeness (of affected staff), senior management engagement, and network
membership. Although team representativeness and network membership were positively
associated with implementing role-changing practices, senior management engagement was not.
In contrast, senior management engagement was positively associated with implementing time-
changing practices, whereas team representativeness was not, and network membership was not
unless there was limited management engagement.

Yale University
New Haven, CT
• Dr. Nembhard: For clinicians, patients, and others leading implementation efforts, our results
indicate the importance of considering the nature of the innovation to be implemented, and
specifically the change that it brings for workers, when selecting organizational factors to
leverage in service of implementation. Some factors will be more effective than others
because of the type of innovation. Our findings provide insights that can help health care
organizations to implement innovations successfully, resulting in better quality of care for
patients.

Yale University
New Haven, CT
this study?
• Dr. Nembhard: Given our findings, implementation research should consider innovations’
change for workers as it moves forward. It should also examine the interaction of
organizational factors, as we found that the effectiveness of senior management engagement
and network membership for the implementation of time-changing practices was influenced
by the presence of the other. Providing additional insight about strategies for implementing
different types of innovations is the next stage of implementation and improvement
research.
• Citation:
• Implementing Role-Changing Versus Time-Changing Innovations in Health Care
• Differences in Helpfulness of Staff Improvement Teams, Management, and Network for
Learning
• Nembhard IM1, Morrow CT2, Bradley EH2.
Med Care Res Rev. 2015 Jun 26. pii: 1077558715592315.

Shorter UVB Wavelength Light Most Damaging To Mitochondrial DNA
Jennifer Latimer PhD
Department of Dermatology at Newcastle University
Newcastle, UK
• MedicalResearch: What is the background for this study?
• Dr. Latimer: There is extensive knowledge of the wavelength effects of UV on the skin to the
nuclear DNA level. However the effects on mitochondrial DNA were unknown. The
mitochondria have important links with aging and skin cancer and therefore knowing the
individual UV wavelength effects is important.
• MedicalResearch: What are the main findings?
• Dr. Latimer: The main findings of this study were that the shorter and more energetic UVB
wavelengths of UV were the most damaging to mitochondrial DNA. Furthermore we found
that the skin fibroblast cells – those predominant in the deeper dermis layers of the skin
were more sensitive to UV than keratinocytes, the main cells within the upper epidermis
layer of the skin.

Shorter UVB Wavelength Light Most Damaging To Mitochondrial DNA
Jennifer Latimer PhD
Department of Dermatology at Newcastle University
Newcastle, UK
• Dr. Latimer: This study stresses the damaging effects of UV and therefore emphasizes the
importance of protecting your skin from it.
this study?
• Dr. Latimer: Future research as a result of this study could involve investigating newer
technologies and campaigns in an aim to improve attitudes, enthusiasm and ability to protect
skin from the damaging effects of UV.
• Citation:
• Determination of the Action Spectrum of UVR-Induced Mitochondrial DNA Damage in
Human Skin Cells
Latimer JA1, Lloyd JJ2, Diffey BL3, Matts PJ4, Birch-Machin MA3.
• J Invest Dermatol. 2015 Jun 1. doi: 10.1038/jid.2015.194. [Epub ahead of print]

Occupational Exposure To Low Dose Radiation Linked To Leukemia
Dr Klervi Leuraud, Epidemiologist
Institute for Radiological Protection and Nuclear Safety
Cedex, France
• Dr. Leuraud: INWORKS was performed to quantify the risk of cancer mortality associated to
protracted low doses of ionizing radiation typical of occupational or environmental
exposures, as well as of diagnostic medical exposures. While such risks are well known for
acute exposures as those experienced by the Japanese survivors of the A-bombs, there is still
a lack of information for exposures experienced by the workers and the public. Our study
confirms the existence of an association between leukemia mortality and chronic exposure to
low doses received by nuclear workers.

Cedex, France
• Dr. Leuraud: Transposition of our results to other exposure situations should be done
cautiously. Nevertheless, our results reinforce the importance of adopting radiological
protection equipment by the medical staff, and the need for justification for exposures to
patients.

Cedex, France
• What recommendations do you have for future research as a result of this study?
• Dr. Leuraud: We conducted this study among nuclear workers as these historical cohorts
provide detailed information on individual exposure to ionizing radiation. Similar studies
should be conducted among medical workers to take account of the specificity of their
exposures to provide new insight on the radiation-related risk they are possibly exposed to.
• CITATION:
• Ionising radiation and risk of death from leukaemia and lymphoma in radiation-monitored
workers (INWORKS): an international cohort study
• Leuraud, Klervi et al. The Lancet Haematology
• DOI: http://dx.doi.org/10.1016/S2352-3026(15)00094-0

New Therapeutic Target May Make Chemotherapy More Effective Against Pancreatic Cancer
Dr. Janaiah Kota
Assistant Professor, Department of Medical and Molecular Genetics
Indiana University School of Medicine
Indianapolis, IN,
• Medical Research: What is the background for this study?
• Dr. Kota: Pancreatic cancer tumors are surrounded by a thick fibrotic shell known as “stroma”
which protects the cancer cells from anticancer drugs such as chemotherapy. However,
complete depletion of tumor stroma leads to more aggressive disease and decreases
survival. The stromal abundance needs to be appropriately moderated (i.e. not too much nor
too little) in pancreatic tumors. None of the current anti-stromal therapies have been
effective enough to resolve this problem. Unless we understand the molecular signatures
associated with tumor stroma, it will be challenging to develop an effective therapeutic
strategy.
• There is a desperate need to develop new therapies for pancreatic cancer as only 7 percent
of people with the disease survive more than 5 years after diagnosis. According to the
National Cancer Institute, there will be an estimated 48,960 new cases of pancreatic cancer
and 40,560 deaths from the disease in 2015.

Dr. Janaiah Kota
Indianapolis, IN,
• Dr. Kota: We found that the loss of microRNA-29 (miR-29) is a common phenomenon of
pancreatic cancer stromal cells, and that by restoring it, the viability and growth of the
cancerous cells and stromal accumulation was reduced. The use of miR-29 as a therapeutic
agent may be more effective in targeting reactive stroma, as a single miRNA regulates the
expression of several genes associated with disease mechanisms. We expect that this novel
approach has the potential to overcome the problems associated with current anti-stromal
drugs and could lead to improved therapeutic strategies, enhanced drug delivery to the
tumor bed, and, in the future, improved patient survival.

Dr. Janaiah Kota
Indianapolis, IN,
this study?
• Dr. Kota: To take these basic research findings into the clinic, anti-cancer properties of miR-29
need to be evaluated in preclinical animal models, and the precise molecular mechanisms
associated with the effect of miR-29 overexpression in stromal cells on cancer cells need to
be elucidated.
• Citation:
• Pathophysiological role of microRNA-29 in pancreatic cancer stroma
• Jason J. Kwon,Sarah C. Nabinger,Zachary Vega,Smiti Snigdha Sahu,Ravi K. Alluri, Zahi Abdul-
Sater, Zhangsheng Yu,Jesse Gore,Grzegorz Nalepa,Romil Saxena, Murray Korc & Janaiah Kota
• Scientific Reports 5, Article number:11450
• doi:10.1038/srep11450 June 22 2015

Indoor Tanning Declines But Still Popular
Gery P. Guy Jr., PhD, MPH
Health Economist
Division of Cancer Prevention and Control
Centers for Disease Control and Prevention
Dr. Guy: Indoor tanning exposes users to intense ultraviolet radiation, which damages the
skin and can cause skin cancer, including melanoma (the deadliest type of skin cancer), basal
cell carcinoma, and squamous cell carcinoma. Previous research has demonstrated that
indoor tanning is common among adults in the United States.
• This study examined the changes in prevalence and frequency of indoor tanning among
adults in the United States. Our study found significant reductions in indoor tanning among
all adults, women, and men. From 2010 to 2013, 1.6 million fewer women and 400,000 fewer
men indoor tanned. While these reductions are encouraging, nearly 10 million adults
continue to indoor tan at least once a year. These individuals are trading a tan for an
increased risk of skin cancer. While the tan is temporary, the risk for skin cancer is
permanent.

Health Economist
• Medical Research: What should clinicians and patients take away from
your report?
• Dr. Guy: Clinicians can play a role in encouraging individuals to avoid
indoor tanning and to embrace their natural, untanned skin color. The US
Preventive Services Task Force recommends behavioral counseling about
minimizing UV exposure to reduce skin cancer risk for fair-skinned
individuals aged 10-24 years. Studies show that appearance-focused
messages may work best among this population, such as messages that
indoor tanning can cause premature wrinkles and age spots.
• In addition to avoiding indoor tanning, everyone can:
• Understand that tanned skin is damaged skin
• Protect themselves and their families by:
– Wearing a wide-brimmed hat, sunglasses, and protective clothing outdoors.
– Finding shade, especially during midday hours.
– Using broad-spectrum sunscreen with SPF 15 or higher, even on cloudy days.
– Avoid sunbathing

Health Economist
this study?
• Dr. Guy: Ongoing surveillance efforts are needed to monitor the use of indoor tanning and
changes in this behavior over time. This work will provide insight into the impact of efforts to
reduce indoor tanning and prevent future cases of skin cancer. More research is needed to
develop effective, evidence-based messages that are proven to change tanning attitudes and
behaviors among adults. Additionally, research is needed to identify what strategies are most
effective for creating social and physical environments that facilitate a reduction in indoor
tanning.
• Citation:
• Gery P. Guy, Zahava Berkowitz, Dawn M. Holman, Anne M. Hartman. Recent Changes in the
Prevalence of and Factors Associated With Frequency of Indoor Tanning Among US Adults.
JAMA Dermatology, 2015; DOI: 10.1001/jamadermatol.2015.1568

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