MedicalResearch.com: Medical Research Exclusive Interviews April 1 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
April 1 2015
For Informational Purposes Only: Not for Specific Medical Advice.

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Electric Lights Disrupts Human Circadian Rhythm
MedicalResearch.com Interview with:
Richard G. Stevens, Ph.D.,
Professor, Cancer Epidemiologist
UConn Health
• Medical Research: What is the background for this study? What are the main findings?
Dr. Stevens: Since first introducing the concept of a possible connection between exposure to
light at night and breast cancer in the mid-80s, we’ve seen growing evidence of how artificial
light can suppress the circadian hormone melatonin and bring about physiological changes.
• The extent of this “circadian disruption” varies by the type of light and the time of day.
Humans evolved with a body clock that followed the solar clock. Nature intended us to be
awake in daylight and at rest in the dark of night. Therefore, the intense, short-wavelength
light of the sun in the morning triggers us to become awake and alert, just as the absence of
sunlight in the evening allows our body to produce melatonin. Even with the use of fire to
provide light in the evening, the circadian impact was relatively minimal because of firelight’s
place on the red end of the visible spectrum.
• Humans survived under this simple formula for many thousands of years. Then electric light
started to take an increasingly strong foothold in everyday life. Today we are typically
surrounded at all hours of the day and night by artificial light – in many cases it’s not bright
enough during the day to match the sun, and it’s too bright at night to be conducive to the
natural sleep/wake cycle. Think computer screens, tablets, smart phones, e-readers, etc.
These devices emit enough short-wavelength, or blue, light to disrupt our body clocks in the
evening. So do fluorescent and LED lights.
Read the rest of the interviews on MedicalResearch.com
Content NOT an endorsement of efficacy and NOT intended as specific medical advice.

UConn Health
• Our paper – I worked with Dr. Yong Zhu from Yale on this – represents a new analysis and
synthesis of what we know up to now on the effect of lighting on our health. We don’t know
for certain, but there’s growing evidence that the long-term implications of this may have ties
to breast cancer, obesity, diabetes, and depression, and possibly other cancers.
• Exposure to electric light started about 130 years ago, which is a tiny period of time in
evolutionary terms. In other words, not long enough to undo human evolution.

UConn Health
• Medical Research: What should clinicians and patients take away from your report?
• Dr. Stevens: An understanding of the importance of maintaining the sleep/wake cycles, and
the effect even typical lighting in the modern world can have on it, could go a long way in
staving off the potentially harmful long-term impact. Our smart phones and LED bulbs can’t
disrupt our body clocks if we don’t let them. We can opt for reading a book under an
incandescent light before bed, rather than on an e-reader with a blue backlight. And because
we’re gaining more of an understanding about this, we’re starting to see our technology
come equipped with the option of adjusting the type and intensity of light it emits.

UConn Health
• Medical Research: What recommendations do you have for future research as a result of
this study?
• Dr. Stevens: Although studying people assigned to “dark” and “light” groups may tell us a
great deal, we can’t ethically do that. What we can do is continue to study people who
already have lifestyles that would be of interest to the science. We can survey third-shift
workers and compare their health experience to day workers, for example. Or we can follow
children who grow up in a rural area who don’t use smart phones and compare them to city
dwellers who do. We certainly can do studies with animal models. But perhaps most
important would be an understanding of the possibility of long-term health effects associated
with artificial light. If we’re aware of it, perhaps we can take steps today to reduce our
chances of illness tomorrow.
• Citation:
• G. Stevens, Y. Zhu. Electric light, particularly at night, disrupts human circadian rhythmicity: is
that a problem? Philosophical Transactions of the Royal Society B: Biological Sciences, 2015;
370 (1667): 20140120 DOI: 10.1098/rstb.2014.0120

Prostate Cancer: Does Timing of Radiation Therapy Affect Outcome?
Timothy N. Showalter, MD, MPH
Associate Professor & Residency Program Director Department of Radiation Oncology
University of Virginia School of Medicine
Medical Research: What is the background for this study? What are the main findings?
Dr. Showalter: Early radiation therapy has been shown to be an effective curative treatment for
prostate cancer patietns with a rising PSA blood test after radical prostatectomy and for men with
locally advanced prostate cancer who are at high risk of recurrence after prostatectomy. Despite
evidence that radiation therapy is more effective when delivered early (or when the PSA is low),
radiation therapy delivery is often delayed to allow more time for patients to recover urinary and
sexual function. In order to provide evidence regarding whether delaying radiation therapy does
reduce the risks of side effects of treatment, my colleagues and I evaluated outcomes of for a
large cohort of patients who received treatment in the Emilia Romagna Region of Italy. We
identified a total 0f 9,786 prostate cancer patients who received prostatectomy, including 22% of
whom received post-prostatectomy radiation therapy. We found that earlier delivery of radiation
therapy was not associated with increased risk of any adverse events, including gastrointestinal,
urinary or sexual complications.

• Dr. Showalter: This study provides new evidence that radiation therapy timing after
prostatectomy is not a primary determinant of the risk of complications. Therefore, for
patients with an indication for postoperative radiation therapy, treatment need not be
delayed as long as possible in order to maximize urinary and sexual function. This is
potentially reassuring information for patients with high-risk, locally advanced prostate
cancer, for whom earlier radiation therapy has been shown to be more effective at achieving
a prostate cancer cure than delayed radiation therapy.

this study?
• Dr. Showalter: Although this study provides direct evidence regarding the lack of effect of
radiation timing on treatment-related complications, there are a number of other factors to
consider in the decision-making process for prostate cancer patients faced with post-
prostatectomy treatment decisions. Future research should focus on how to use new
genomic tests, which provide a molecular fingerprint of a patient’s tumor, to help guide
treatment decisions based upon the chance of an individual patient’s tumor progressing. This
would be another important piece of evidence for patients contemplating post-
prostatectomy radiation therapy.
• Citation:
• Assessing Adverse Events of Postprostatectomy Radiation Therapy for Prostate Cancer:
Evaluation of Outcomes in the Regione Emilia-Romagna, Italy
Showalter TN1, Hegarty SE2, Rabinowitz C3, Maio V4, Hyslop T5, Dicker AP6, Louis DZ3.
Int J Radiat Oncol Biol Phys. 2015 Mar 15;91(4):752-9. doi: 10.1016/j.ijrobp.2014.11.038.

Tau Protein A Key Driver Of Cognitive Decline in Alzheimer’s disease
Melissa Murray, Ph.D
Assistant Professor of Neuroscience
Mayo Clinic
Dr. Murray: Our study investigates two of the hallmark brain pathologies that underlie Alzheimer’s
disease, abnormally accumulated tau and amyloid proteins. While both are integral to diagnosing
Alzheimer’s disease postmortem, their exclusive relationship with cognitive decline has been
debated. Using a large series from our brain bank we found that while an increase in abnormal
accumulation of both proteins shares a close relationship with a decline in cognition, tau is the key
driver of decline. This was important for us to understand as the second part of our study
investigated amyloid brain scanning. We found that amyloid brain scanning closely represents
amyloid deposits and not tau in postmortem brain tissue. One particular aspect we focused on is
the cutoff for what would be a amyloid-positive brain scan that indicates Alzheimer’s disease. Our
study supports that currently available cutoffs correspond to a level of amyloid accumulation that
occurs before Alzheimer’s disease has too far advanced.
• Dr. Murray: Given the relationship exists between cognitive decline and amyloid if tau is not
considered, amyloid brain scanning can still be used to monitor Alzheimer’s disease in lieu of a
marker for tau accumulation. This will be important as lifestyle risk factors are explored as
Alzheimer’s disease modifiers and as tau therapeutics or combination therapeutics become more
available. More importantly perhaps, evaluation of amyloid brain scanning cutoffs should be
considered for clinical trials evaluating inclusion and exclusion of research participants. This study
would not be possible without the patient’s and families who so selflessly donated their brain
tissue.

Tau Protein A Key Driver Of Cognitive Decline in Alzheimer’s disease
Melissa Murray, Ph.D
Assistant Professor of Neuroscience
Mayo Clinic
this study?
• Dr. Murray: The next exciting chapter in the field of Alzheimer’s disease is the possibility of
tau brain scanning. More work needs to be done make this possibility a reality. The
combination of tau and amyloid brain scanning would enable clinicians to improve diagnostic
accuracy and enhance efforts toward early detection. The shift toward Tau therapeutics will
be a necessary step toward managing and hopefully one day preventing the effects of
Alzheimer’s disease on cognitive decline.
• Citation:
• Clinicopathologic and 11C-Pittsburgh compound B implications of Thal amyloid phase across
the Alzheimer’s disease spectrum
• Co-authors of the study are, from Mayo Clinic in Jacksonville: Neill Graff-Radford, M.D.,
Amanda Liesinger, Ashley Cannon, Ph.D., Bhupendra Rawal, M.S., Owen Ross, Ph.D., and
Dennis Dickson, M.D.; from Mayo Clinic in Rochester: Val Lowe, M.D., Scott Przybelski, Joseph
Parisi, M.D., Ronald Petersen, M.D., Ph.D., Kejal Kantarci, M.D., David Knopman, M.D., and
Clifford Jack, Jr., M.D.; and Ranjan Duara, M.D., from Mount Sinai Medical Center.
• Clinicopathologic and 11C-Pittsburgh compound B implications of Thal amyloid phase across
the Alzheimer’s disease spectrum

Physician-Pharmacist Collaboration in Primary Care Offices Improved Blood Pressure Control
Barry L. Carter, PharmD
Professor of Pharmacy Professor of Family Medicine
U Iowa Carver College of Medicine
Response: Numerous studies and meta-analyses have found physician-pharmacist collaborative models
can improve blood pressure (BP) control. In these models, pharmacists are located within primary care
offices to assist with patient management. The physician delegates responsibility to pharmacists to
perform a medication history, identify problems and barriers to achieving disease control, perform
counseling on lifestyle modification and adjust medications following hypertension
guidelines. However, it was not known if this model would be implemented in a large number of
diverse primary care offices, if the effect could be sustained after discontinuation and if the intervention
was as effective in under-represented minorities as in Whites. In this study, 32 clinics from throughout
the U.S. were randomized to a 9 month intervention that was discontinued, a 24-month pharmacist
intervention our usual care. All subjects received structured research measured blood pressure at
baseline, 6, 9, 12, 18 and 24 months. We enrolled 625 subjects and 53% were from minority groups,
53% had < 12 years of education, 50% had diabetes or chronic kidney disease and 25% had Medicaid or
self-pay for their care payments. All of these variables typically make it much more difficult to achieve
BP control. BP control was 43% in the intervention groups and 34% in the control group at 9-months
(adjusted OR 1.57 [95% CI 0.99-2.50], p = 0.059). However, when using the higher BP goals in the 2014
guidelines, blood pressure control was achieved in 61% of intervention subjects and 45% of control
subjects at 9 months [(adjusted OR, 2.03 [95% CI 1.29-3.22], p=0.003). Of importance was the finding
that the degree of systolic BP reduction (6 mm Hg) with the intervention compared to usual care was
not only statistically significant but also the same in minority subjects (2/3 Black and 1/3 Hispanic)
compared to all subjects. Interestingly, BP control seemed to be maintained in the subjects from
minority groups at 18 and 24 months in both the group with the short (9-month) or sustained (24
month) intervention. In contrast, blood pressure control deteriorated slightly in non-minority subjects in
all three groups.

• Response: Many primary care offices now employ clinical pharmacists to assist with patient
management. This study demonstrates that the physician-pharmacist collaborative model
can be implemented in very diverse primary care offices, even when they did not provide
these types of services in the past. The study also demonstrates very good BP improvements
in Blacks and Hispanics. Clinicians and health systems continue to implement patient-
centered strategies and strive for high rates for risk factor control, immunizations and other
preventative services. This study provides one model that can be used to improve
outcomes and increase the numbers of patients who can achieve these important
benchmarks.

this study?
• Response: While many studies have utilized this model, we still need research to determine
the optimal use of various team members to maximize performance and efficiency. We are
currently conducting cost-effectiveness analyses for this study to assist health systems and
providers with implementation of this model. We also need additional research to continue
to evaluate patient-specific interventions especially for under-represented minorities.
• Citation:
Cluster-Randomized Trial of a Physician/Pharmacist Collaborative Model to Improve Blood
Pressure Control
• Barry L. Carter, Christopher S. Coffey, Gail Ardery, Liz Uribe, Dixie Ecklund, Paul James, Brent
Egan, Mark Vander Weg, Elizabeth Chrischilles,and Thomas Vaughn
• Circ Cardiovasc Qual Outcomes. 2015;CIRCOUTCOMES.114.001283published online before
print March 24 2015, doi:10.1161/CIRCOUTCOMES.114.001283

Mental Health Issues Increase Hospital Readmissions
Brian K. Ahmedani, PhD, LMSW
Research Scientist Henry Ford Health System
Center for Health Policy & Health Services Research Detroit, MI 48202
Dr. Ahmedani: The Centers for Medicare and Medicaid Services (CMS) have begun penalizing
hospitals for excessive all-cause hospital readmissions within 30 days after discharge for
pneumonia, heart failure, and myocardial infarction. We wanted to determine the influence
of comorbid mental health and substance use conditions on the rate of 30-day hospital
readmissions for individuals with these conditions. Overall, individuals with a comorbid
mental health condition were readmitted to the hospital within 30-days approximately 5%
more often than those without one (21.7% versus 16.5%). Comorbid depression and anxiety
were associated with a 30-day readmission rate of more than 23% each, overall.
• Dr. Ahmedani: The main message is that health systems and clinicians should assess and
treat mental health as part of their initiatives to reduce hospital readmissions. Patients
should be screened for these conditions and offered during-hospitalization and post-
discharge mental health care, if needed.

Mental Health Issues Increase Hospital Readmissions
Brian K. Ahmedani, PhD, LMSW
Research Scientist Henry Ford Health System
Center for Health Policy & Health Services Research Detroit, MI 48202
this study?
• Dr. Ahmedani: Current initiatives within health systems have been able to reduce hospital
readmissions overall, but have not typically included mental health components. Future
research needs to test comprehensive readmissions reduction models, which include mental
health screening, assessment, and treatment.
• Citation:
• Psychiatric Comorbidity and 30-Day Readmissions After Hospitalization for Heart Failure,
AMI, and Pneumonia
• Brian K. Ahmedani, Ph.D., L.M.S.W.; Leif I. Solberg, M.D.; Laurel A. Copeland, Ph.D.; Ying Fang-
Hollingsworth, M.P.H., M.S.; Christine Stewart, Ph.D.; Jianhui Hu, Ph.D.; David R. Nerenz,
Ph.D.; L. Keoki Williams, M.D., M.P.H.; Andrea E. Cassidy-Bushrow, Ph.D.; Jeanette
Waxmonsky, Ph.D.; Christine Y. Lu, Ph.D.; Beth E. Waitzfelder, Ph.D.; Ashli A. Owen-Smith,
Ph.D.; Karen J. Coleman, Ph.D.; Frances L. Lynch, Ph.D.; Ameena T. Ahmed, M.D., M.P.H.; Arne
Beck, Ph.D.; Rebecca C. Rossom, M.D., M.S.C.R.; Gregory E. Simon, M.D., M.P.H.
• http://dx.doi.org/10.1176/appi.ps.201300518

Air Pollution Linked To Increased Risk Of Stroke
Dr Anoop Shah
Cardiology Research fellow Centre of Cardiovascular sciences
University Of Edinburgh Edinburgh
Response: Stroke accounts for five million deaths each year and is a major cause of disability. The
incidence of stroke is increasing, particularly in low and middle income countries, where two thirds
of all strokes occur. The global burden of stroke related disability is therefore high and continues to
rise. This has been primarily attributed to an aging population in high income countries and the
accumulation of risk factors for stroke, such as smoking, hypertension, and obesity, in low and
middle income countries. The impact of environmental factors on morbidity and mortality from
stroke, however, might be important and is less certain.
• From 103 studies and across 6.2 million fatal and non-fatal strokes, our findings suggest a strong
association between short term exposure to both gaseous (except ozone) and particulate air
pollution, and admissions to hospital for stroke or mortality from stroke. These associations were
strongest in low and middle income countries, suggesting the need for policy changes to reduce
personal exposure to air pollutants especially in highly polluted regions.
Medical Research: What should clinicians and patients take away from your report?
• Response: Clinicians should realize that in addition to more traditional risk factors for stroke such as
high blood pressure, environmental risk factors also play a significant role. However unlike
traditional risk factors such diabetes or hypertension where only a fraction of the pollution are
exposed, air pollution affects the whole population.

Air Pollution Linked To Increased Risk Of Stroke
Dr Anoop Shah
Cardiology Research fellow Centre of Cardiovascular sciences
University Of Edinburgh Edinburgh
this study?
• Response: There are two areas of research that now need to take place. One to study
effective measures that may reduce exposure to air pollution and how this may improve
health in the future and two to understand the underlying mechanisms by which air pollution
triggers stroke.
• Citation:
• Short term exposure to air pollution and stroke: a systematic review and meta analysis
• Anoop S V Shah, clinical lecturer in cardiology,
• Kuan Ken Lee, core medical trainee,
• David A McAllister, senior lecturer in epidemiology,
• Amanda Hunter, specialist trainee in cardiology,
• Harish Nair, senior research fellow in epidemiology,
• William Whiteley, MRC clinician scientist and consultant neurologist,
• Jeremy P Langrish, clinical lecturer in cardiology,
• David E Newby, professor of cardiology,
• Nicholas L Mills, reader in cardiology and consultant cardiologist.
• BMJ 2015; 350 doi: http://dx.doi.org/10.1136/bmj.h1295 (Published 24 March 2015

Prenatal Exposure To Air Pollutants May Produce Structural Brain Abnormalities
Dr. Bradley S. Peterson, M.D
Director of the Institute for the Developing Mind
The Saban Research Institute of Children’s Hospital Los Angeles Children’s Hospital Los Angeles
Medical Research: What is the background for this study?
Dr. Peterson: Neurotoxic PAH (polycyclic aromatic hydrocarbons) are ubiquitous in the
environment, in the home and in the workplace. Emissions from motor vehicles, oil and coal
burning for home heating or power generation, wildfires and agricultural burning, hazardous
waste sites, tobacco smoke and charred foods are all sources of exposure. PAH readily crosses the
placenta and affects an unborn child’s brain; earlier animal studies showed that prenatal
exposure impaired the development of behavior, learning and memory. Our group previously
reported that exposure to airborne PAH during gestation was associated with multiple
neurodevelopmental disturbances, including development delay by age 3, reduced verbal IQ at
age 5, and symptoms of anxiety and depression at age 7.

Medical Research: What are the main findings?
Dr. Peterson: Together with Virginia Rauh, ScD and Frederica Perera, DrPH, PhD of Columbia
University’s Mailman School of Public Health, we conducted a brain imaging study to test the
effects on brain structure of PAH exposure during the final trimester of pregnancy. We used
magnetic resonance imaging (MRI) to measure the brains of 40 children from a cohort of more
than 600 mother-baby pairs from minority communities in New York City. These 40 children were
carefully selected to have no other exposures that would affect brain development. Our findings
showed that prenatal PAH exposure led to reductions in nearly the entire white matter surface of
the brain’s left hemisphere – losses that were associated with slower processing of information
during intelligence testing and more severe behavioral problems, including ADHD and
aggression. Postnatal PAH exposure – measured at age 5 – was found to contribute to additional
disturbances in development of white matter in the dorsal prefrontal region of the brain, a
portion of the brain that supports concentration, reasoning, judgment, and problem-solving
ability.

• Dr. Peterson: Exposure to PAH from smoke and exhaust during pregnancy and infancy seems
to produce a distinct pattern of abnormalities in brain structure that subsequently lead to
ADHD-like symptoms and poorer cognitive functioning. Clinicians should educate prospective
parents, especially early in pregnancy, about these risks and urge them to avoid, to the extent
possible and for the health of their baby, exposure to smoke, exhaust, and other sources of
PAH.

this study?
• Response: Additional research should focus on identifying the nature of this PAH-related
abnormality in white matter. This will include new brain imaging studies in humans and more
basic science research using animal models. Those research efforts will help us to identify
ways of countering the adverse effects of PAH exposure on the developing brain. In addition,
other research should assess how changing policies affect the level of environmental PAH
exposure and the prevalence of these PAH-related brain abnormalities, focusing on their
associated societal impact, including the economic consequences of reducing these adverse
long-term outcomes.
• Citation:
• Peterson BS, Rauh VA, Bansal R, et al. Effects of Prenatal Exposure to Air Pollutants (Polycyclic
Aromatic Hydrocarbons) on the Development of Brain White Matter, Cognition, and Behavior
in Later Childhood. JAMA Psychiatry. Published online March 25, 2015.
doi:10.1001/jamapsychiatry.2015.57.

Imiquimod Cream May Be Effective In Primary And Adjuvant Treatment Of Lentigo Maligna
Susan Swetter, MD
Professor of Dermatology and Director, Pigmented Lesion and Melanoma Program
Stanford University Medical Center and Cancer Institute.
Medical Research: What is the background for this study?
Dr. Swetter: This retrospective cohort study sought to explore the role of the topical
immunomodular – imiquimod 5% cream – as both primary and adjuvant therapy (following
optimal surgery) for patients with the lentigo maligna subtype of melanoma in situ. Assessment
of alternative treatments to surgery for this melanoma in situ subtype are warranted given the
increasing incidence of lentigo maligna in older, fair-complexioned individuals in the United
States. Surgical management of lentigo maligna is complicated by its location on cosmetically
sensitive areas such as the face, histologic differentiation between lentigo maligna and actinic
melanocytic hyperplasia in chronically sun-damaged skin, and potential surgical complications in
the elderly who may have medical co-morbid conditions.

Susan Swetter, MD
Dr. Swetter: We conducted a retrospective review of 63 cases of lentigo maligna in 61 patients
(mean age 71.1 years) who used topical 5% imiquimod cream instead of surgery (22 of 63 cases,
34.9%) or as an adjuvant therapy following attempted complete excision (63 cases, 65.1%), in
which no clinical residual tumor was present but the histologic margins were transected or
deemed narrowly excised. Our study showed overall clinical clearance of 86.2% in the 58 patients
analyzed for local recurrence at a mean of 42.1 months of follow-up (standard deviation 27.4
months), with primarily treated cases demonstrating 72.7% clearance at a mean of 39.7 months
(standard deviation 23.9 months), and adjuvant cases showing 94.4% clearance at a mean of 39.7
months (standard deviation 23.9 months). We found a statistically significant association
between imiquimod-induced inflammation and clinical or histologic clearance in primary but not
adjuvant cases, although this latter finding may be explained by a lack of residual atypical
melanocytes or true LM in the adjuvant setting, in which wide local excision had already been
performed.

Susan Swetter, MD
• Dr. Swetter: While our study is not a prospective clinical trial assessing the use of imiquimod
cream in the treatment of lentigo maligna, it adds to the body of published data
demonstrating efficacy of this topical agent in both the primary and adjuvant settings.
Current National Comprehensive Cancer Network and American Academy of Dermatology
Guidelines recommend surgical excision of lentigo maligna when possible, but also recognize
the role of alternative therapies in cases where surgery has been optimized or is not possible.
The use of topical imiquimod for melanoma in situ, lentigo maligna type, remains “off-label”
(non-FDA-approved), and a thorough discussion with the patient/family must occur regarding
potential risks, benefits, and limitations of topical therapy in place of, or as an adjunct to
surgery. Imiquimod field therapy requires close clinical surveillance and patient compliance
with treatment and follow-up.

Susan Swetter, MD
this study?
• Dr. Swetter: A multi-center, randomized controlled prospective trial should be conducted to
determine the long term efficacy of topical imiquimod compared with or as an adjunct to
surgical resection of lentigo maligna. Given the high and increasing rates of the lentigo
subtype in older individuals, further study of this topical field treatment is warranted.
• Citation:
• Imiquimod 5% cream as primary or adjuvant therapy for melanoma in situ, lentigo maligna
type
• Susan M. Swetter, MD, Frank W. Chen, MD David D. Kim, BA, Barbara M. Egbert, MD
• DOI: http://dx.doi.org/10.1016/j.jaad.2015.02.008

Anxiety Symptoms Raised by Air Pollution
Melinda C Power, ScD
Post-Doctoral Research Fellow
Epidemiology Department, Johns Hopkins Bloomberg School of Public Health
Neurology Department, Johns Hopkins School of Medicine
Dr. Power: Air pollution may be related to mental health, particularly anxiety, through effects
on oxidative stress and systemic inflammation or through promotion or aggravation of
chronic diseases. However, there has been very little research on the relation between air
pollution exposures and anxiety in people. Our study found that those with higher
exposures to fine particulate matter, a type of air pollution, were more likely to experience
elevated anxiety symptom levels. Our study also suggests that recent exposures to find
particulate matter air pollution are potentially more relevant to anxiety symptom levels than
long-term past exposures.
• Dr. Power: Everyday exposures to toxicants and pollutants may play a role in mental
health. Further research is needed to confirm our findings and to further explore this
possibility.

Anxiety Symptoms Raised by Air Pollution
Melinda C Power, ScD
Post-Doctoral Research Fellow
Epidemiology Department, Johns Hopkins Bloomberg School of Public Health
Neurology Department, Johns Hopkins School of Medicine
this study?
• Dr. Power: We hope that our findings will be replicated in other settings. If our results are
confirmed, we would recommend additional research on whether reductions in exposure to
ambient fine particulate matter air pollution would have a meaningful impact on the
population-level burden of anxiety.
• Citation:
• The relation between past exposure to fine particulate air pollution and prevalent anxiety:
observational cohort study
• BMJ 2015; 350 doi: http://dx.doi.org/10.1136/bmj.h1111 (Published 24 March 2015)

Women, Young Drivers More Likely to Talk or Text While Driving
Michelle Wilkinson, MPH
Doctoral Candidate Epidemiology
UT Houston School of Public Health
Houston, TX 77030
Response: Cell phone use (CPU) while driving impairs visual awareness and reaction time,
increasing frequency of near-collisions, collisions, and accidents with injuries. National
prevalence estimates of driver cell phone use range from 5-10%. Medical and academic
centers have large concentrations of young, ill, or elderly pedestrians and drivers, who are
often unfamiliar with the congested environment. Drivers distracted by Cell phone use are a
safety threat to pedestrians and drivers in these demanding environments. This study aimed
to describe the prevalence and correlates of cell phone use among Texas drivers in major
medical and academic centers, 2011-2013. This study found the overall prevalence of cell
phone use while driving was 18%. The prevalence of Cell phone useand talking declined,
while texting increased during the study period. Cell phone users were more likely to be
female, <25 years old, and driving without a passenger.
• Response: Cell phone use remains prevalent among drivers in Texas academic and medical
campuses. This study found a higher prevalence of CPU than previous studies. Females and
younger drivers appear to be more likely to engage in Cell phone use , thus public safety
campaigns should target these groups.

Women, Young Drivers More Likely to Talk or Text While Driving
Michelle Wilkinson, MPH
Doctoral Candidate Epidemiology
UT Houston School of Public Health
Houston, TX 77030
this study?
• Response: Future legislation should incorporate public health campaigns targeting high risk
groups to stop CPU while driving and reduce traffic related injuries.
• Citation:
• Prevalence and correlates of cell phone use among Texas drivers
• Michelle L. Wilkinson, Austin L. Brown, Iman Moussa R. Sue Day
Preventive Medicine Reports Volume 2, 2015, Pages 149–151

Vascular Calcification Can Predict Mortality in Predialysis Chronic Kidney Disease
Dr. José L. Górriz
Department of Medicine and Nephrology
Valencia Hospital Universitario Valencia. Spain
• MedicalResearch: What is the background for this study? What are the main findings?
• Dr. Górriz: The background of the study is that several studies have reported on the high prevalence
of vascular calcification in chronic kidney disease (CKD) patients not on dialysis. Vascular
calcification (VC) has been associated with high cardiovascular mortality in patients on dialysis, but
there are no studies in patients in stages before dialysis which analyse the prognostic significance of
the presence of Vascular calcification assessed by simple X-ray.
• Vascular calcification can occur in both the intima and media of the vessel wall. Intimal calcification
is an indicator of atherosclerosis and is associated with ischemic heart disease and medial
calcification is associated with arterial stiffness, systolic hypertension, and left ventricular
hypertrophy.
• Although Vascular calcification can be assessed by various methods, such as ultrasonography,
tomography, and arteriography, simple radiology has the advantages of being simple, inexpensive,
and commonly applicable in daily clinical practice.
• OSERCE 2 is an observational, multicentre and 3-year prospective study performed in 39
Nephrology centres in Spain, which analyzes the presence of Vascular calcification in CKD patients
stages 3 and 4 (eGFR between 15-59 ml/min/1,73 m2) and its effect on morbimortality (death,
hospitalization and renal progression).
• The main findings of the study were that Vascular calcification is highly prevalent in patients with
chronic kidney disease, and Vascular calcification assessment using AS independently predicts
death and time to hospitalization.
• Therefore, it could be a useful index to identify patients with chronic kidney disease at high risk of
death and morbidity as previously reported in patients on dialysis.

• MedicalResearch: What should clinicians and patients take away from your report?
• Dr. Górriz: Using X-ray assessment, they are two indexes which analyse Vascular calcification,
Kauppila score (aortic calcification of lumbar aorta) and Adragao score (detects VC in iliac,
femoral, radial, and digital arteries). Our study demonstrates the Kauppila is mainly related to
atherosclerotic traditional risk factors and age and don’t predict mortality after adjusting by
age. But Adragao score predicts mortality and risk of hospitalization in chronic kidney disease
patients. When we analysed only Vascular calcification in hands (Adragado score-hands) we
can predict mortality, since Vascular calcification in hand only affects to muscular arteries and
it is related to alterations in mineral metabolism due to CKD. A simple X-ray of the hands can
predict mortality in chronic kidney disease patients.
• The main message of the study is that Vascular calcification is common in predialysis CKD, can
predict mortality and hospitalization. The study supports the importance of differentiating
intimal and medial calcification because participants with medial calcification had a higher
risk of all-cause and cardiovascular mortality, but patients with intimal calcification did not
(based on plain radiography).
• This information may be used to update the guidelines and management of CKD-MBD and
improve its diagnosis, treatment, and prognosis through a multidisciplinary approach.
• The nephrology community needs to focus on studies of Vascular calcification as a way of
improving outcomes for our patients.

• MedicalResearch: What recommendations do you have for future research as a result of
this study?
• Dr. Górriz: Concerning the assessment of Vascular calcification, it would be of interest to
validate our results with other more complex imaging techniques such as vascular
ultrasonography, carotid ultrasonography or computed tomography in other territories (i.e.
coronary arteries)
• On the other hand, once we have assessed the importance of Vascular calcification and
chronic kidney disease we need clinical trials to assess if interventions to slow the
progression of Vascular calcification in this population may be feasible, especially
interventions in chronic kidney disease-mineral bone disorders markers (calcium,
phosphorus, parathyroid hormone, vitamin D and other) that were not fully evaluated in the
study.
• Citation:
• Vascular Calcification in Patients with Nondialysis CKD over 3 Years.
• José L. Górriz, Pablo Molina, M. Jesús Cerverón, Rocío Vila, Jordi Bover, Javier Nieto,
Guillermina Barril, Alberto Martínez-Castelao, Elvira Fernández, Verónica Escudero, Celestino
Piñera, Teresa Adragao, Juan F. Navarro-Gonzalez, Luis M. Molinero, Cristina Castro-Alonso,
Luis M. Pallardó, and Sophie A. Jama
• CJASN CJN.07450714; published ahead of print March 13, 2015, doi:10.2215/CJN.07450714

Low Dose Vitamin C May Improve Iron Deficiency in Dialysis Patients
Dr. Tanjim Sultana MD
Department of Nephrology
Lenox Hill Hospital New York
Response: Almost all dialysis patients are anemic. One quarter of patients requiring High dose
Epogen have functional iron deficiency, which means they have adequate iron store but unable to
utilize it. Vitamin C has been shown to mobilize iron from their storage and making it available to
use in red blood cell production. Prior studies showed intravenous high dose vitamin C could
increase hemoglobin levels and decrease epogen requirement. In our study we used daily low dose
oral vitamin C in functional iron deficient patients to achieve the same goals. Patients taking daily
low dose vitamin C for 3 months had significant decrease in their epogen dose compared to the
control group.
• Response: Low Dose vitamin C was shown to be effective in our small group of functional iron
deficient dialysis patients.
• Medical Research: What recommendations do you have for future research as a result of this
study?
• Response: Further research should include more patients and have longer duration of vitamin C
supplementation. Since vitamin C can convert to oxalate which is poorly dialyzed in ESRD patients,
oxalate levels needs to be measured before wide spread long term use of vitamin C can be
implemented
• Citation:
• Abstract presented at the 2015 National Kidney Foundation meeting
• ORAL VITAMIN C SUPPLEMENTATION FOR FUNCTIONAL IRON
DEFICIENCY IN DIALYSIS PATIENTS

High Fluid Intake Reduces Risk Of New Kidney Stones
Wisit Cheungpasitporn, MD, Nephrology Fellow
Program director: Suzanne Norby, MD Project mentors: Stephen B. Erickson, MD and John C. Lieske, MD
Departments of Nephrology and Hypertension Mayo Clinic, Rochester, MN
• MedicalResearch: What is the background for this study?
• Dr.Cheungpasitporn: Kidney stones are very common urologic problems. In addition, once
someone has a kidney stone, the likelihood of having another episode increases to 50%
within 5 years. Increased fluid intake has been suggested as a simple strategy for kidney
stone prevention. However the data on conclusions regarding the benefit, adherence and
safety of high fluid intake for the primary or secondary prevention of stones were limited.
Thus, we conducted this meta-analysis to evaluate the treatment effect of high fluid intake on
the incidence of kidney stones, and to assess the compliance and safety of high fluid intake to
prevent kidney stones. Our data presented at the National Kidney Foundation’s 2015 Spring
Clinical Meetings may help improve clinicians’ ability to manage kidney stones.
• MedicalResearch: What are the main findings?
• Dr.Cheungpasitporn: Our meta-analysis included 9 studies with 273,954 patients. According
to the findings of our study, individuals with daily high fluid intake (to achieve a urine volume
of at least 2.0‒2.5 L per day) had lower risk of new kidney stones by approximately 50%. High
fluid intake provided the same benefit in men and women. In addition, high fluid intake
reduced the risk of recurrent kidney stones by 40%. Overall, high fluid intake is safe with low
adverse events.

High Fluid Intake Reduces Risk Of New Kidney Stones
Wisit Cheungpasitporn, MD, Nephrology Fellow
Program director: Suzanne Norby, MD Project mentors: Stephen B. Erickson, MD and John C. Lieske, MD
Departments of Nephrology and Hypertension Mayo Clinic, Rochester, MN
• MedicalResearch: What should clinicians and patients take away from your report?
• Dr.Cheungpasitporn: Our study confirmed the effectiveness of water therapy. Protective
effect of high fluid intake against stone formation by increasing the urine flow rate and urine
volume is likely the key. Our study clearly demonstrates a reduction in the risk of new and
recurrent kidney stones among individuals with high fluid intake. The magnitude of risk
reduction is high.
• MedicalResearch: What recommendations do you have for future research as a result of
this study?
• Dr.Cheungpasitporn: Kidney stones have recently been linked to many comorbid conditions
including hypertension, diabetes, kidney disease and heart diseases. It would be nice if we
can further identify the effects of high fluid intake on the reduction of those kidney stone
related comorbidities.
• Citation:
• Abstract presented at the National Kidney Foundation Spring 2015 Abstract
• TREATMENT EFFECT AND SAFETY OF HIGH FLUID INTAKE FOR THE PREVENTION OF INCIDENT
AND RECURRENT KIDNEY STONES

Senna May Relieve Itching In Some Dialysis Patients
Mohammad Kazem Fallahzadeh Abarghouei, M.D.
Baylor University Medical Center, Dallas, TX
• Medical Research: What is the background for this study?
Response: Uremic pruritus (itch) is a common problem in hemodialysis patients. No effective
treatment exists for uremic pruritus due to its complex pathogenesis. Systemic inflammation
and elevated serum levels of interleukin-2 (IL-2) are implicated in the pathogenesis of uremic
pruritus. Senna is an herbal drug commonly used for treatment of constipation. Senna also
has anti-inflammatory properties. We performed this randomized double-blind placebo-
controlled trial to evaluate the effect of senna on reduction of uremic pruritus and serum
levels of IL-2 in hemodialysis patients.
• Medical Research: What are the main findings?
Response: Sixty hemodialysis patients with moderate to severe pruritus (visual analogue
scale ≥4) of at least 6 week duration were enrolled in this study. Enrolled patients were
randomized into 2 equal groups to receive either senna or placebo tablets for 8 weeks.
Severity of pruritus and serum levels of IL-2 were measured before and at the end of
treatment phase. At the end of treatment phase, pruritus decreased in both groups;
however, the mean reduction in the severity of pruritus was significantly higher in senna than
placebo group (p<0.05). Mean serum levels of IL-2 decreased in the senna group but
increased in the placebo group; the mean reduction in IL-2 serum levels in the senna group
was significantly different from the mean increase in the placebo group (p<0.05).

Senna May Relieve Itching In Some Dialysis Patients
Mohammad Kazem Fallahzadeh Abarghouei, M.D.
Baylor University Medical Center, Dallas, TX
• Response: Senna can potentially be an effective medication for treatment of itch (uremic
pruritus) in hemodialysis patients.
this study?
• Response: Further studies with larger sample sizes and longer duration of follow-up are
needed to better evaluate the effect of senna on reduction of uremic pruritus in hemodialysis
patients.
• Citation: Abstract Presented at the 2015 National Kidney Foundation Meeting
• EFFECT OF SENNA ON REDUCTION OF UREMIC PRURITUS IN HEMODIALYSIS PATIENTS: A
RANDOMIZED DOUBLE-BLIND PLACEBO-CONTROLLED TIRAL
• Authors:
• Mohammad Kazem Fallahzadeh1, Pouya Faridi2, Arian Kamali Sarvestani2, Mohammad Mahdi
Sagheb2, Joan Blondin3, Abdolali Mohagheghzadeh2, Jamshid Roozbeh2
• Baylor University Medical Center, Dallas, TX
• Shiraz University of Medical Sciences, Shiraz, Iran.
• LSUHSC-S, Shreveport, LA

Study Finds Medicaid Improves Depression But Not Physical Health
Peter Muennig, MD, MPH
Columbia University
Mailman School of Public Health NYC 10032
• Dr. Muennig: The Oregon Health Insurance Experiment (OHIE) is one of just two experimental
investigations of the health benefits of medical insurance. The first was the Rand Health Insurance
Experiment, which was conducted over 3 decades ago. The OHIE randomly assigned participants to
receive Medicaid or their usual care. It found that Medicaid protected families from financial ruin
caused by medical illness, that it reduced depression, and that it increased preventive screening
tests. However, it produced no medical benefits with respect to high blood pressure, diabetes, or
high cholesterol. Medicaid opponents suggested that this meant that we should get rid of Medicaid
because Medicaid does not improve physical health. But Medicaid proponents suggested that too
few participants enrolled to detect a benefit, and, regardless of the study’s flaws, reduced
depression, financial protections, and improved screening were reason enough to continue.
• We found that the Medicaid opponents were right. Medicaid actually didn’t produce any
meaningful benefits with respect to blood pressure, diabetes, or cholesterol. But we also found that
the Medicaid proponents were right. It’s impacts on depression alone rendered it cost-effective
even if one does not account for the benefits of financial protections or medical screening.
• Dr. Muennig: All of the benefits of screening for blood pressure, diabetes, and high cholesterol
have been very thoroughly documented in carefully managed experiments. But in the real world,
many people might not actually take their medicines or listen to the advice of their doctor.

Study Finds Medicaid Improves Depression But Not Physical Health
Peter Muennig, MD, MPH
Columbia University
Mailman School of Public Health NYC 10032
this study?
• Dr. Muennig: We need to understand how to make preventive screening work better for low-
income populations. We also need to know whether other kinds of screening (such as breast
cancer screening) actually save lives. In this study, that question might have been answered if
we had enough participants.
• The most important take home message, though, is that we need more research on social
policies. We are spending over a trillion dollars on social programs that have not been
adequately studied. It is astounding that this study—which cost less than a tenth of a percent
of the annual Medicaid budget—took so long to actually be conducted. Education, housing,
and other social policies have potential, but we really don’t know whether they work. Only a
very limited number of programs (such as welfare reform) have been tested rigorously in this
way.
• Citation:
• Considering Whether Medicaid Is Worth the Cost: Revisiting the Oregon Health Study
Peter A. Muennig, Ryan Quan, Codruta Chiuzan, and Sherry Glied. (2015). Considering
Whether Medicaid Is Worth the Cost: Revisiting the Oregon Health Study. American Journal
of Public Health. e-View Ahead of Print.
doi: 10.2105/AJPH.2014.302485

Pediatric Meningococcal Vaccine Immunity May Wane By Adolescence
Dr Fiona McQuaid
Clinical Research Fellow
University of Oxford, United Kingdom
• Response: Meningococcal B disease is a common cause of sepsis and meningitis
with significant mortality and morbidity. A multicomponent vaccine
against serogroup B meningococcus has been licensed for use in the
Europe, Australia, Canada and recently the USA (though only in the
10-25 years age group) but questions remain about how long the
bactericidal antibodies induced by infant vaccination persist and the
likely breath of strain coverage. This was a follow on study looking
at a group of children aged 5 years who had been vaccinated as infants
and a different group who were vaccinated for the first time at 5
years of age.
• Medical Research: What are the main findings?
• Response: The percentage of children with protective antibody levels who had
been immunized as infants fell in the 20 months since their last
immunization but this varied by the strain of meingococcus B tested
and by the different infant/toddler vaccination schedules.
• The children who were vaccinated for the first time at 5 years of age
showed a good antibody response, but most reported pain and redness
around the site of vaccination and 4-10% had a fever.

Pediatric Meningococcal Vaccine Immunity May Wane By Adolescence
Dr Fiona McQuaid
Clinical Research Fellow
University of Oxford, United Kingdom
• Response: These data will be useful for those planning the introduction of this
vaccine into routine vaccine schedules. It seems unlikely that
immunity to meningococcal B disease will persist into adolescence,
when the second peak of disease occurs, therefore an a teenager
booster dose may be required. Five year old children immunised for the
first time with the vaccine showed a good response one month after
their second vaccine which is important if it were to be used in an
outbreak setting and the reactogenicity data will be helpful for
providers when explaining to parents what to expect after vaccination.
• Of note, the vaccine is currently not licensed for use under the age
of 10 in the USA and these data may not necessarily apply to older age
groups. Clinicians should continue to follow their locally recommended
vaccination schedules.
• Medical Research: What recommendations do you have for future research as a result of this study?
• Response: A larger study has been completed and the results of this will give
further details about persistence after infant vaccination. Further
follow up would be required to assess the persistence of vaccine
inured antibodies into adolescence and the potential role for a
teenage booster. It will be important to continue monitor for any
evidence of waning vaccine effectiveness. If vaccine is introduced
routinely into the UK, as recommended by the UK Joint Committee on
Vaccination and Immunization, this will provide a great deal of
important information on how the vaccine works in a real-world setting
• Citation:
• McQuaid, M. D. Snape, T. M. John, S. Kelly, H. Robinson, L.-M. Yu, D. Toneatto, D. D’Agostino, P. M. Dull, A. J. Pollard.
Persistence of specific bactericidal antibodies at 5 years of age after vaccination against serogroup B meningococcus in
infancy and at 40 months. Canadian Medical Association Journal, 2015; DOI: 10.1503/cmaj.141200

Mobile Health Technologies Will Change Chronic Disease Management
Ryan Jeffrey Shaw, PhD, MS, RN
Assistant Professor School of Nursing Center for Health Informatics
Center for Precision Medicine Duke University
Dr. Shaw: Primary care delivery revolves around a series of episodes, rather than functioning
as a continuum. When patients come to a clinic data on their health is collected as a single
data point. This model neglects potentially meaningful data from patients’ daily lives and
results in less informed treatment and scheduling of follow-up visits. Lack of meaningful data
further blinds clinicians to patients’ health outside of the clinic and can contribute to
unnecessary emergency department visits and hospitalizations.
• Personalized care through mobile health technologies inspires the transition from isolated
snapshots based on serial visits to real time and trended data. By using technologies from cell
phones to wearable sensors, providers have the ability to monitor patients and families
outside of the traditional office visit.

• Dr. Shaw: As mobile technologies and access to the Internet become universal, healthcare
systems and private practices will leverage capabilities that allow the transfer of data on a
daily and hourly basis. This has the potential to catapult the personalized or precision
medicine movement forward. By gathering real-time data from patients in their homes and
work sites, additional insight can be gained into what day-to-day health actually looks like.
Although “snapshot” clinic visits will still be important, the ability to see a real-time trend of
patients’ blood glucose or blood pressure level will change chronic disease management.
• There are still challenges regarding data validity, collection, privacy, presentation, and
overflow that will need to be addressed though. However, technology, innovation, and the
need to rethink chronic disease management and decrease healthcare costs will drive
solutions to these problems

this study?
• Dr. Shaw: With the recent announcement of Meaningful Use Stage 3, CMS reimbursement
will in part soon be tied to leveraging these new mobile technologies and their data. Thus,
future research will need to focus on how to integrate models of care delivery capable of
deciphering meaningful information from patients’ mobile health devices, to enable
physician to deliver true personalized medicine- the right treatment for the right patient at
the right time.
• Citation:
• Mobile Health Technology for Personalized Primary Care Medicine
• Ryan J. Shaw, PhD, RN, Jonathan Bonnet, MD, Farhad Modari, DO, Aaron George, DO,
Mohammad Shaheshebi, MD, MBA
• Received: December 19, 2014; Received in revised form: January 8, 2015; Accepted: January
8, 2015; Published Online: January 19, 2015

Chronic Rhinosinusitis Varies By Bacterial Microbiome
Vijay R. Ramakrishnan, MD
Assistant Professor University of Colorado
Department of Otolaryngology Aurora, CO 80045
Dr. Ramakrishnan: Chronic rhinosinusitis (CRS) is an extremely common problem, associated
with major quality of life alterations and financial burden. Bacteria are thought to play a role
in the initiation or sustenance of the disease, at least in a subset of CRS patients. Chronic
rhinosinusitis is probably a group of heterogeneous diseases with different pathways that
result in the same endpoint. Here, we study the bacterial microbiome of a large group of CRS
and healthy sinuses, and discover that a few clinical subtypes display unique bacterial
microbiome profiles and that the microbiome may predict outcomes from severe Chronic
rhinosinusitis patients electing to undergo surgery.
• Dr. Ramakrishnan: We should really start thinking about subtypes of Chronic rhinosinusitis in
the clinical setting, rather than lumping everyone into the same treatment algorithm. It is
likely that Chronic rhinosinusitis patients with asthma, for instance, have a unique
pathophysiology. As such, therapies can be selectively administered, and a better
understanding of the disease course and prognosis can be offered to the patient.

Chronic Rhinosinusitis Varies By Bacterial Microbiome
Vijay R. Ramakrishnan, MD
Assistant Professor University of Colorado
Department of Otolaryngology Aurora, CO 80045
this study?
• Dr. Ramakrishnan: We need to continue research efforts in this field to determine if these
bacteria are actively promoting health or disease, and knowing what these bacteria are doing
may allow us to intervene in a completely novel way.
• Citation:
• Sinus microbiota varies among chronic rhinosinusitis phenotypes and predicts surgical
outcome
• Vijay R. Ramakrishnan, MD, Leah J. Hauser, MD, Leah M. Feazel, MS, Diana Ir, BS, Charles E.
Robertson, PhD, Daniel N. Frank, PhD
• The Journal of Allergy and Clinical Immunology Published Online: March 26, 2015
• DOI: http://dx.doi.org/10.1016/j.jaci.2015.02.008

Psoriasis: Effective Two Year Response to IL-17A Antagonist Cosentyx
Andrew Blauvelt, M.D., M.B.A.
President and Investigator
Research Excellence & Personalized Patient Care Portland, OR 97223
Dr. Blauvelt: A2303E1 is a multicenter, double-blind, randomized withdrawal extension to the
FIXTURE and ERASURE pivotal phase III studies. The purpose of this extension study was to
collect additional long term efficacy, safety, and tolerability data on secukinumab (i.e.,
Cosentyx) in patients who demonstrated a PASI 75 response to Cosentyx at Week 52 of these
core studies in moderate-to-severe plaque psoriasis.
• In the extension phase, 995 patients who achieved Psoriasis Area Severity Index (PASI) 75
responses after 52 weeks of therapy received either Cosentyx 300 mg, Cosentyx 150 mg, or
placebo for an additional year (Week 104). After two full years of therapy in patients treated
with Cosentyx 300 mg, almost 9 out of 10 (88.2%) patients maintained their PASI 75
response, 7 out of 10 (70.6%) had clear or almost clear skin (PASI 90), and 4 out of 10 (43.9)
had clear skin (PASI 100) at Week 104. For patients treated with Cosentyx 150 mg, 75.5%
maintained their PASI 75 response, 44.6% had clear or almost clear skin (PASI 90), and 23.5%
had clear skin (PASI 100) at Week 104. In addition, 94.8% of patients who initially received
placebo (at the start of the extension), and were switched to receive Cosentyx 300 mg after
relapse, were able to achieve PASI 75 and 70.3% achieved PASI 90 within 12 weeks of re-
starting Cosentyx.

• Dr. Blauvelt: The two-year extension data shows that 7 out of 10 psoriasis patients who were
PASI 75 responders at 52 weeks, achieved clear to almost clear skin (PASI 90) after two years
of Cosentyx 300 mg treatment. After two full years of therapy with Cosentyx 300 mg, almost
9 out of 10 psoriasis patients sustained their PASI 75 response.
• Psoriasis is a chronic condition causing itching, scaling, and pain; patients need therapies that
provide relief and clear skin over a long period of time. The two-year data is significant
because it represents results from the longest continuous phase III study to date evaluating
an IL-17A antagonist in the treatment of psoriasis. The study not only strengthens our
understanding of the efficacy and safety of Cosentyx, but it shows that Cosentyx responses
are durable over time for individuals suffering from moderate-to-severe plaque psoriasis.

this study?
• Dr. Blauvelt: The data on IL-17A inhibitors presented at the AAD annual meeting continue to
demonstrate the benefits of blocking this new target in psoriasis. As with any new therapy,
additional long-term safety studies are needed, as we still don’t know whether long-term use
of Cosentyx, as well as other biologics, will have a positive benefit on cardiovascular function
over time. I believe this will likely be the case, however, given that long-term biologic
therapy for patients with rheumatoid arthritis has been associated with decreased risk of
cardiovascular disease in these patients. The dermatology community looks forward to
additional safety and efficacy findings with long-term therapy.
• Citation:
• 2015 American Academy of Dermatology Meeting abstract:
Secukinumab treatment maintains efficacy in moderate to severe plaque psoriasis through
second year of treatment: A randomized extension of the ERASURE

Living Past 100 May Be In Your Genes
Thomas Perls, MD, MPH Professor
Boston University School of Medicine
Dr. Perls: For years now, Gerontology scholars continue to state that 25% of what they interchangeably call aging, longevity,
life expectancy and life span is genetic and 75% is due to the environment and health-related behaviors. This assertion is
based on Scandinavian twins reared apart, but the oldest participants in those studies lived to their 70s and 80s. Part of the
problem here is the lack of consistency in what people mean by the terms Aging, Life Span and Longevity.
• In fact, the Seventh Day Adventists, who generally have a high prevalence of healthy behaviors (vegetarian, daily exercise,
eat in moderation, abstain from tobacco and alcohol, and activities that help manage stress well) have an average live
expectancy of approximately 88 years. Yet, 7th Day Adventists are ethnically and racially heterogeneous and thus it appears
that those healthy behaviors explain the vast majority of the variation in how old these people live to be. This finding is
consistent with the optimistic view of the twin studies, that much of living to one’s 80’s is in our hands. Living to only our
50s-70’s is also in our hands (e.g. 75% behaviors) if we choose to smoke, eat red meat frequently, be obese, not exercise, be
exposed to gun violence, have unsafe sex, do IV drugs, etc. So it is safe to say, in my opinion, that 75% of the variation in how
old we live to be, is on average due to our behavior and exposure choices. The empowering and important point is that if we
all lived like the Seventh Day Adventists, average life expectancy would increase almost 8 years and health costs would
markedly decline because we would be getting to these older ages because we are healthier not because we are pouring
more resources into more effectively treating diseases.
• The New England Centenarian Study, which I direct, and a number of other studies of nonagenarians (people in their 90s)
have demonstrated via direct genetic studies as well as studies of family trees where at least some family members get to
these very old ages, that with older and older ages of survival beyond age ~95 years, variations in genetic profiles explain a
greater and greater proportion of the variation in how old people live to be at these ages. So much so that I believe the
findings to date are consistent with the roles of genes and environment being reversed for survival to age 106+ years, that is,
75% genetics and 25% environment/behaviors. This supposition is based upon several observations:
• (1) as people reach the age of 105+ years, they become more and more alike in terms of what age-related diseases they get
and when they get them. Consistent with Jim Fries; “Compression of Morbidity” hypothesis, people who survive to ages
110+ (called supercentenarians) and who therefore approximate the limit of human lifespan are on average disease and
disability-free up until the last 5 or so years of their lives. This increasing homogeneity, especially compared to the increasing
heterogeneity in the rates of aging and incidences of age-related diseases at younger percentiles or ages of survival, suggests
underlying genetic similarities (similar genetic profiles) amongst groups of these supercentenarians;

• (2) the New England Centenarian Study previously discovered genetic signatures (made up of
longevity-associated variations of about 130 genes) that were associated with surviving to
age 106+ years with 80% accuracy, but with only 60% accuracy for accurately picking out
people living to ~100 years. This increasing accuracy with older and older ages also suggests a
stronger and stronger genetic influence upon survival to these rarest percentiles of survival.
• With the above background, we set out in this study and subsequent paper, to
• (1) assess sibling relative risk using the largest-ever collection of validated pedigrees of
centenarians,
• (2) to assess the risk of a sibling achieving the same age as their very old sibling (e.g. ages 95,
100, or 105+ years) relative to average people born around the same time, and
• (3) to look at how when a person was born (eg before or after 1890) made a difference in
these relative risks.

Dr. Perls: In this study, we analyzed survival data of the families of 1,500 participants in the New
England Centenarian Study, the largest study of centenarians and their family members in the
world, based at Boston Medical Center. Among those families, we looked at more than 1,900
sibling relationships that contained at least one person reaching the age of 90. We found that for
people who live to 90 years old, the chance of their siblings also reaching age 90 is relatively small
– about 1.7 times greater than for the average person born around the same time. But for people
who survive to age 95, the chance of a sibling living to the same age is 3.5 times greater – and for
those who live to 100, the chance of a sibling reaching the same age grows to about nine times
greater. At 105 years old, the chance that a sibling will attain the same age is 35 times greater
than for people born around the same time. However, this does not mean there are many 105
year old siblings running around. Because getting to such an age is so incredibly rare, just 10
sibships out of a 100 that contain a 105 year old will have another sibling living to that age. We
also noted that the relative risks are higher for people born before 1890 versus those born after
and this makes sense given that there were major changes in the public health around this time
with cleaner water supplies, better socioeconomic conditions and so on and therefore the
mortality rate, particularly among infants was dramatically declining.

• Dr. Perls: These much higher relative chances of survival likely reflect different and more
potent genetic contributions to the rarity of survival being studied, and strongly suggest that
survival to age 90 and survival to age 105 are dramatically different phenotypes or traits, with
very different underlying and respectively stronger genetic influences.
this study?
• Dr. Perls: Because genes play a much stronger differentiating role in living to 105-plus years,
studies of such individuals are much more powerful in discovering longevity-related genes
than studies of people in their 90s. Therefore my co-authors and I call for investigators who
are studying the determinants of living to the oldest ages to be precise in describing the
rarity or percentile of survival that study participants achieve.
• Citation:
• Paola Sebastiani, Lisa Nussbaum, Stacy L. Andersen, Mara J. Black, and Thomas T. Perls.
Increasing Sibling Relative Risk of Survival to Older and Older Ages and the Importance of
Precise Definitions of “Aging,” “Life Span,” and “Longevity”. J Gerontol A Biol Sci Med Sci,
2015 DOI: 10.1093/gerona/glv020

Genetic Fingerprint May Lead To Blood Test For Colon Cancer
Professor Massimiliano Mazzone and Professor Hans Prenen
Lab of Molecular Oncology and Angiogenesis VIB Vesalius Research Center
University of Leuven Leuven Belgium
Response: Monocytes are circulating cells with patrolling behaviour. In case of harmful situations,
they go to the site of injury rapidly to ensure immune and wound-healing functions. Once in the
inflammation site, they differentiate into macrophages which are versatile cells adopting different
phenotypes according to the stimuli they are subjected to. We hypothesized that cancer cells
might release signals and soluble factors that educate and change monocytes already when in
circulation. In this work, we proved our hypothesis and found that soluble molecules released by
colorectal cancer cells imprint a specific signature in the circulating monocytes. Now, by collecting
these monocytic cells from the blood, we are able to determine if colorectal cancer cells are
present in the body, either at the primary site (in the colon) or in distant organs (where cancer
cells give rise to metastases). (M. Mazzone).

• Response: Since most patients can be cured from colorectal cancer when the disease is
detected early, there is an urgent need for a specific and sensitive screenings tool. Moreover
even in relapsing disease, the outcome depends on early detection of metastases. This is the
first study that defined a genetic fingerprint, called the monomark, which is induced
specifically in circulating monocytes of colorectal patients at early disease onset. We also
showed that the genetic fingerprint found during disease rapidly reverted to normal (as
found in healthy people) after resection of the primary tumor. This feature makes our
signature also a potential good tool to study disease relapse. These findings will hopefully
lead to an easy to use blood test that uses monocytes for early detection of colon cancer.
Obviously, this test has the potential to reach a better compliance (since based on few
millilitres of peripheral blood) thus allowing to screen more people at reasonable costs (the
method is relatively cheap) and to select a more narrow population of at-risk population that
will receive confirmation of the diagnosis by colonoscopy (thus reducing the needs for this
costly and invasive, yet precise, detection method). (M. Mazzone, H. Prenen).

• Medical Research: What recommendations do you have for future research as a result of this
study?
• Response: A first research goal would be to use the monocyte profile to follow-up disease
recurrence. Given the strong plasticity of these cells and their ability to promptly revert this
signature, we hypothesize that the genetic profile will be reactivated upon disease relapse,
meaning that the relapsing patients will be positive at the Monomark test, thus allowing an easier
followup than routine CT scans.
• Secondly, the monomark test should be compared with the available stool and blood based
screening tools to compare sensitivity and specificity. Finally, the monomark should be evaluated in
metastatic colorectal cancer patients, responding to a chemotherapeutic therapy. We hypothesize
that tumor cells responding to chemotherapy, will not produce the factors that change the
circulating monocytes, and therefore the Monomark (as we called this colorectal cancer specific
monocyte-signature) could be used for response prediction. (M. Mazzone, H. Prenen)
• Citation:
• Tumour-Educated Circulating Monocytes are Powerfule Candidate Biomarkers for Diagnosis and
Disease Follow-up of Colorectal Cancer
• Alexander Hamm, Hans Prenen, Wouter Van Delm, Mario Di Matteo, Mathias Wenes, Estelle
Delamarre, Thomas Schmidt, Jürgen Weitz, Roberta Sarmiento, Angelo Dezi, Giampietro Gasparini,
Françoise Rothé, Robin Schmitz, André D’Hoore, Hannes Iserentant, Alain Hendlisz, Massimiliano
Mazzone
• Gut gutjnl-2014-308988Published Online First: 26 March 2015 doi:10.1136/gutjnl-2014-308988

Heart Attack Carries Worse Prognosis In Dialysis Patients
Tanush Gupta, MD
Department of Medicine, Division of Cardiology
New York Medical College, NY
Dr. Gupta: There are approximately 600,000 prevalent cases of end stage renal disease
(ESRD) in the United States. Cardiovascular disease is the leading cause of death in ESRD
patients. Moreover, approximately 20% of these deaths due to cardiovascular disease are
attributable to acute myocardial infarction (AMI). Multiple studies have shown that ESRD
patients have poor short- and long-term survival after AMI relative to the general population.
We analyzed the publicly available Nationwide Inpatient Sample (NIS) databases from 2003
to 2011 to examine the temporal trends in ST-elevation myocardial infarction (STEMI), use of
mechanical revascularization for STEMI, and in-hospital outcomes in adult ESRD patients in
the United States.
• We found that from 2003 to 2011, whereas the number of acute myocardial infarction
hospitalizations in ESRD patients increased from 13,322 to 20,552, there was a decline in the
number of STEMI hospitalizations from 3,169 to 2,558. The use of percutaneous coronary
intervention (PCI) for STEMI increased from 18.6% to 37.8%, whereas there was no significant
change in the use of coronary artery bypass grafting. During the study period, in-hospital
mortality in ESRD patients with STEMI increased from 22.3% to 25.3%. We also observed an
increase in average hospital charges and a decrease in mean length of stay during the study
period.

Heart Attack Carries Worse Prognosis In Dialysis Patients
Tanush Gupta, MD
Department of Medicine, Division of Cardiology
New York Medical College, NY
• Dr. Gupta:: ESRD patients comprise a very sick sub-group of the overall STEMI population and
are often managed sub-optimally with lower use of revascularization and proven medical
therapies. In this analysis, although we observed favorable trends in the use of PCI and length
of stay, there was a temporal increase in in-hospital mortality. The increasing trend in in-
hospital mortality in ESRD patients with STEMI is worrisome and is in stark contrast to the
trends in outcomes of STEMI in the general population, where in-hospital mortality has
decreased dramatically in the modern era of reperfusion therapy.
this study?
• Dr. Gupta: Reversal of the above mentioned adverse trends in in-hospital mortality in ESRD
patients with STEMI should be the focus of future investigations.
• Citation:
• Gupta T, Harikrishnan P, Kolte D, Khera S, Subramanian KS, Mujib M, Masud A, Palaniswamy
C, Sule S, Jain D, Ahmed A, Lanier GM, Cooper HA, Frishman WH, Bhatt DL, Fonarow GC,
Panza JA, Aronow WS. Trends in Management and Outcomes of ST-Elevation Myocardial
Infarction in Patients With End Stage Renal Disease in the United States. Am J Cardiol
2015;115:1033-1041.

Diagnosing TB in Children: Evaluating Xpert Assay
Dr Anne K Detjen, MD
Child Lung Health Consultant
International Union Against Tuberculosis and Lung Disease
• Dr. Detjen: The bacteriological diagnosis of tuberculosis (TB) in children is challenging due to
the difficulty in obtaining specimens such as sputum and the lack of an accurate and
accessible diagnostic test. In most cases, diagnosis is made on clinical grounds based on a
contact history and a combination of signs and symptoms. We included 15 studies in a
systematic review and meta-analysis of Xpert for the diagnosis of pulmonary TB in children.
• The accuracy of Xpert for diagnosing TB in children is suboptimal, and the majority of
children will still have to be diagnosed clinically. However, in settings where it replaces smear
microscopy Xpert will increase the likelihood of bacteriological confirmation of TB as well as
MDR TB among children. Xpert does not increase the number of confirmed TB cases among
culture-negative children. We also found that smear status highly impacted Xpert results, i.e.
a higher yield among smear positive compared to smear negative children. Smear positivity
increases with bacillary load and might be a proxy for disease severity. Unfortunately, we
were not able to assess the performance among children with different stages of disease
severity since this was not classified in any of the studies included.

• Dr. Detjen: Access to Xpert will increase the likelihood of confirming TB in children in settings
where it replaces smear microscopy. At the same time, it will increase diagnosis of MDR TB
among children. If available, Xpert should be used as part of the diagnostic workup among
children with presumed TB. However, Xpert cannot be used as a rule-out test. The sensitivity
of Xpert is suboptimal and a negative test does not exclude TB. In order to improve diagnostic
yield it is important to collect quality specimens from children, either expectorated sputum
(in older children), induced sputum or gastric fluids. Training of health care workers in
specimen collection is crucial to optimize the use of Xpert. Results have to be interpreted in
the context of other signs and symptoms including contact history and severity of disease.

this study?
• Dr. Detjen: Future research should address the performance of Xpert in children managed at
different levels of the health care system (in- versus outpatients, higher-level versus
secondary and primary level of care) as well as its performance in children with different
stages of disease severity. These data are urgently needed to inform the scale-up of Xpert
into routine programmes. Routine data should be collected and analyzed, including the
impact of Xpert on empiric treatment and treatment outcomes among children.
• Citation:
• Xpert MTB/RIF assay for the diagnosis of pulmonary tuberculosis in children: a systematic
review and meta-analysis
• Detjen, Anne K et al.
• The Lancet Respiratory Medicine Published Online: 23 March 2015
DOI: http://dx.doi.org/10.1016/S2213-2600(15)00095-8

Cardiorespiratory Fitness May Decrease Cancer Risk and Improve Survival
MedicalResearch.com Interview with: Susan G. Lakoski, M.D.
Assistant Professor of Medicine, Hematology/Oncology DivisionDepartment of Medicine Director, Cardiovascular Prevention Program for
Cancer PatientsVermont Cancer Center, Division of Hematology/OncologyUniversity of Vermont, BurlingtonCo-Investigators from Cooper
Center Longitudinal Study Cooper Institute in Dallas, Texas
•
Dr. Lakoski:
• High cardiorespiratory fitness (CRF) is associated with 55% reduction in lung cancer and 44%
reduction in colorectal cancer in white men. These results were similar even among non-
smokers.
• High cardiorespiratory fitness is associated with a one-third risk reduction in all cancer-
related deaths among men who developed lung, colorectal, or prostate cancer at age 65
years or older compared with low cardiorespiratory fitness.
• High cardiorespiratory fitness is associated with a two-thirds reduction in cardiovascular
death compared with low cardiorespiratory fitness among men who developed cancer at age
65 years or older.
• There is an strong inverse relationship association between fitness and subsequent diagnosis
of incident lung and colorectal cancer, but not prostate cancer, in white men.

MedicalResearch.com: Medical Research Exclusive Interviews April 1 2015

MedicalResearch.com: Medical Research Exclusive Interviews April 1 2015

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MedicalResearch.com: Medical Research Exclusive Interviews April 1 2015