MedicalResearch.com: Medical Research Exclusive Interviews December 4 2014

MedicalResearch.com
Exclusive Interviews with Medical Research and
Health Care Researchers from Major and Specialty Medical
Research Journals and Meetings
Editor: Marie Benz, MD
info@medicalresearch.com
December 4 2014
For Informational Purposes Only: Not for Specific Medical Advice.

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MedicalResearch.com

Minimally Invasive Surgery May Not Be Best For Disc Removal
MedicalResearch.comInterview with:
Nathan Evaniew MD
Division of Orthopaedics
McMaster University
• Medical Research: What is the background for this study?
Dr. Evaniew: Symptomatic cervical and lumbar spinal disc diseases affect at least 5% of the population and they cause a
great deal of pain, disability, social burden, and economic impact. For carefully selected patients that fail to improve with
nonsurgical management, conventional open discectomy surgery often provides good or excellent results.
• Minimally invasive techniques for discectomy surgery were introduced as alternatives that are potentially less destructive,
but they require specialized equipment and expertise, and they may involve increased risks for technical complications.
• Medical Research: What are the main findings?
• Dr. Evaniew: In this study, we found that the current evidence from research does not support the routine use of minimally
invasive surgery for cervical or lumbar discectomy. We also found an overall lack of high-quality evidence, which suggests
that further research is warranted.
• Medical Research: What should clinicians and patients take away from your report?
• Dr. Evaniew: The current evidence suggests a risk–benefit ratio that does not support the routine use of minimally invasive
surgery for cervical and lumbar discectomy. Appropriate patient selection and technically adequate nerve-root
decompression may be the most important determinants of long-term outcomes, and surgeons embarking on
minimally invasive surgical techniques should consider obtaining specialized training.
• Medical Research: What recommendations do you have for future research as a result of this study?
• Dr. Evaniew: Given the lack of high-quality evidence, well-designed randomized trials are needed, as are large observational
studies and economic evaluations. Future studies should also further examine and clearly report the influence of surgeon
expertise on patient-important outcomes.
• Citation:
• Nathan Evaniew, Moin Khan, Brian Drew, Desmond Kwok, Mohit Bhandari, and Michelle Ghert. Minimally invasive versus
open surgery for cervical and lumbar discectomy: a systematic review and meta-analysis. CMAJ Open, November 2014
DOI: 10.9778/cmajo.20140048
Read the rest of the interview on MedicalResearch.com
Content Not Intended as Specific Medical Advice

Yogurt May Lower Risk of Diabetes
Medicalresearch.comwith:
Frank B. Hu, MD, PhD Professor of Nutrition and Epidemiology
Harvard School of Public Health
Professor of Medicine Harvard Medical School Boston, MA 02115
• Dr. Hu: Type 2 diabetes (T2D) affects approximately 26 million people in the United States and 366 million
people worldwide, and thus primary prevention of T2D has become a public health imperative. The
relation between consumption of different types of dairy and risk of type 2 diabetes remains uncertain.
• Dr. Hu: We found that higher yogurt intake is associated with lower risk of developing type 2 diabetes, but
the consumption of other types of dairy was not associated with diabetes risk.
• Dr. Hu: Our study provides convincing evidence that higher consumption of yogurt is beneficial for
reducing risk of diabetes, but randomized clinical trials are needed to confirm this benefit for diabetes
prevention. Our study also indicates that other types of dairy such as milk and cheese are not related to
diabetes risk.
• Dr. Hu: We also hope to conduct randomized clinical trials to look at the effects of yogurt on adiposity and
biomarkers of insulin resistance.
• Citation:
Dairy consumption and risk of type 2 diabetes: 3 cohorts of US adults and an updated meta-analysis
Mu Chen1, Qi Sun, Edward Giovannucci, Dariush Mozaffarian, JoAnn E Manson, Walter C Willett and Frank
B Hu
• BMC Medicine 2014, 12:215 doi:10.1186/s12916-014-0215-1

Dramatic Increase in Subthreshold Psychiatric Diagnoses In Young People
Medicalresearch.comwith: Daniel Safer MD
Department of Psychiatry
Johns Hopkins University School of Medicine
Baltimore, Maryland
• Medical Research: What is the nature of this study?
• Dr. Safer: A large national sample of annual physician office-based visits by youth (aged 2-19)
covering 12 years (1999-2010), focusing on trends in psychiatric DSM-IV diagnoses, with
psychiatric diagnostic data analyzed proportionally comparing diagnoses that were
subthreshold (not otherwise specified) with those that met full diagnostic criteria.
• Dr. Safer: Subthreshold diagnoses for mood disorders, anxiety disorders, bipolar disorders
and depressive disorders in youth visits increased more proportionally over the 12 year study
period compared to diagnostic visits meeting full criteria.
• Consequences:
• 1) Over 50% of mood, anxiety, bipolar and depressive disorders in youth diagnosed during
community physician outpatient visits are now subthreshhold.
• 2) Subthreshold diagnoses are less reliable than full criteria diagnoses and this constitutes a
problem for detailed research.
• 3) Psychiatric medication treatment for subthreshold diagnoses are off-label; that is, unlike
many full criteria diagnoses they have not received an FDA indication for medication
treatment.
• 4) Subthreshold psychiatric diagnoses are expanding proportionally more than full criteria
diagnoses and this frustrates the hope in DSM-5 that dimensional full criteria psychiatric
diagnoses with become the dominant diagnostic method.

Dramatic Increase in Subthreshold Psychiatric Diagnoses In Young People
Medicalresearch.comwith: Daniel Safer MD
Department of Psychiatry
Johns Hopkins University School of Medicine
Baltimore, Maryland
• Medical Research: What future research do you recommend as a result of this report?
• Dr. Safer: Future research should ascertain if this diagnostic trend also exists for adults and to
what degree the trend alters the community psychotropic medication patterns.
• Citation:
• Safer DJ, Rajakannan T, Burcu M, Zito JM. Trends in Subthreshold Psychiatric Diagnoses for
Youth in Community Treatment. JAMA Psychiatry. Published online November 26, 2014.
doi:10.1001/jamapsychiatry.2014.1746.
•

Out-of-Hospital Cardiac Arrest: Continuous vs Interrupted Chest Compressions?
Siobhan Brown, Ph.D.
Biostatistician, ROC Clinical Trials Center
University of Washington
• Medical Research: What is the background for this study? What are the main findings?
• Dr. Brown: There are several observational studies suggesting that patients with out-of-hospital cardiac arrest may be more likely to survive to
hospital discharge when emergency medical service provides do not pause for ventilations while performing CPR (i.e., give continuous compressions);
however, the American Heart Association recommends that rescuers pause after each 30 compression to give two ventilations (interrupted
compressions). We designed and are conducting a randomized clinical trial comparing the two approaches to see which results in better survival.
• The trial is still ongoing, so watch for results in late 2015!
• Dr. Brown: We hope that the physicians, medics, and other care providers will be aware of the uncertainty about the best approach to performing
ventilations during CPR, and that the results of a large study addressing that question will be available soon.
• Dr. Brown: Because the trial is still ongoing, we can’t make any recommendations at this time.
• Citation:
• A Randomized Trial of Continuous Versus Interrupted Chest Compressions in Out-of-Hospital Cardiac Arrest: Rationale for and Design of the
Resuscitation Outcomes Consortium CCC Trial
Brown, Siobhan P. et al.
American Heart Journal
Published Online: November 20, 2014
DOI: http://dx.doi.org/10.1016/j.ahj.2014.11.011
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• By By: Marie Benz MD FAAD
• Physician in practice over 30 years. Editor of MedicalResearch.com. All interviews conducted exclusively for MedicalResearch.com by Marie Benz,
MD.
• Google+ Authorship for Editor Marie Benz MD
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Diabetes Risk Increased in Poor Neighborhoods
MedicalResearch.com Interview with:
Longjian Liu, MD, PhD, MSc(LSHTM), FAHA
Interim Chair, Department of Environmental and Occupational Health Associate Professor, Department of Epidemiology and Biostatistics,
Senior Investigator, Center for Health Equality Drexel University School of Public Health, and
Adjunct Associate Professor of Medicine, Drexel U. College of Medicine
• Dr. Liu: The prevalence of diabetes is increasing rapidly in the United States and worldwide.
In 2010, 25.8 million Americans, or 8.3% of the population had diabetes in the United States.
In 2012, these figures were 29.1 million, or 9.3% in the nation. Philadelphia, the largest city in
PA, ranks as the 5th largest city in the nation. However, the city also had the highest
prevalence of diabetes according to the national surveys in 2009. We face a great challenge
to stop the epidemic of diabetes locally and nationally. It is well-known personal risk factors
at individual level, including lifestyles, play a role in the prevention and control of diabetes.
However very limited studies addressed the importance that physical and socioeconomic
environmental factors at community level may also play a pivotal role in the prevention and
control of the disease. This study aimed to quantitatively examine (1) the trend of diabetes
from 2002 to 2010 in the city of Philadelphia, and (2) the impact of physical and
socioeconomic environmental factors at community level (assessed using zip-codes based
neighborhoods) on the risk of the prevalence of diabetes.
• The main findings support our hypotheses that
• (1) the prevalence of diabetes significantly increased from 2002 to 2012.
• (2) residents who lived in neighborhoods with physical and socioeconomic disadvantage had
an increased risk of the prevalence of diabetes.

• Dr. Liu: Early diagnosis of diabetes is the key to control the disease. However, more than one
third of patients with diabetes are undiagnosed. If a physician understands that
environmental factors, not only personal factors, play a role in the risk of diabetes, they may
identify patients with high risk of diabetes at early stage when they provide healthcare
service for population who live in certain disadvantaged areas.
• Patients: Findings of the study support previous studies that risk factors at individual level,
including overweight, obesity and physical inactivity, remain the key risk factors of the
development of diabetes. Patients should adhere to healthy lifestyles in order to prevent and
control of the disease. Meanwhile, residents and local health policymakers should be aware
of the importance of improving physical and socioeconomic environment status at
community level that may offers an additional positive impact on the control of diabetes.

• Medical Research: What recommendations do you have for future research as a result of
this study?
• Dr. Liu: On the basis of the findings from the study we are setting up a project, entitled,
Health Outcomes, Prevention and Evaluation (HOPE) Study with focusing on studies of
diabetes and cardiovascular disparity in the city of Philadelphia.
• Citation:
• Longjian Liu, Ana E. Núñez. Multilevel and Urban Health Modeling of Risk Factors for
Diabetes Mellitus: A New Insight into Public Health and Preventive Medicine. Advances in
Preventive Medicine, 2014; 2014: 1 DOI: 10.1155/2014/246049

Healthy Skin Guards Against Infection By Constant Immune Surveillance
Univ.-Prof. Dr. med. Tilo Biedermann Klinikdirektor
Klinik und Poliklinik für Dermatologie und Allergologie
der Technischen UniversitätMünchen
Biedersteinerstr. München
Prof. Biedermann: The skin is constantly exposed to microbes and skin developed during
evolution under the constant influence of microbes. Tightly regulated communication
between microbes and the skin can be expected and levels of regulation still needed to be
explored. We found that Gram-positive bacteria when sensed by one certain innate immune
receptor (hetero dimer TLR 2-6 suppresses immunity both in animal models and in humans.
Following the sensing of lipoproteins by toll like receptor 2-6) skin produces high levels of
InterleukinL6 that induce the accumulation of so called myeloid-derived suppressor cells.
These cells can be found in the blood but also migrate to the skin suppressing T-cell-immunity
allowing infections to spread on the skin.
Prof. Biedermann: Our investigations highlight the importance of even limited skin infections
and how important it is to treat both inflammation and infection of the skin. These
investigations also highlight that it is not any microbe that regulates this type of immune
response but that it needs certain microbes with certain types of ligands that stimulate
immunity. Stabilizing healthy skin including the microflora probably best prevents this type of
vicious circle of inflammation.

Healthy Skin Guards Against Infection By Constant Immune Surveillance
Univ.-Prof. Dr. med. Tilo Biedermann Klinikdirektor
Klinik und Poliklinik für Dermatologie und Allergologie
der Technischen UniversitätMünchen
Biedersteinerstr. München
• Medical Research: What recommendations do you have for future research as a result of the
study?
Prof. Biedermann: It is very important to understand when induction of myeloid-derived
suppressor cells (MDSC) is “good” and when it is “bad” for the host. E.g. by terminating cutaneous
inflammation, by regulating excessive immune responses or by supplying important precursor cells
for new cutaneous resident immune cells, MSDC exert beneficial functions for the host. On the
other hand MDSC suppress immune responses against tumors, against infections, against parasites.
These functions are harmful for the host. Questions arise such as “When are these cells bad?”
“How can they be regulated, inhibited or avoided?” Aside from understanding the mechanisms of
suppressions by myeloid derived suppressor cells, induction and accumulation, and the migration
to different tissue sites that we have started to analyze in our publication should be studied in more
detail. Targeting the regulation of specific cellular subsets will be a basis for powerful new
strategies for immune therapy.
• Citation:
Cutaneous Innate Immune Sensing of Toll-like Receptor 2-6 Ligands Suppresses T Cell Immunity by
Inducing Myeloid-Derived Suppressor Cell
• Yuliya Skabytska,FlorianWölbing,Claudia Günther,Martin Köberle,Susanne Kaesler,Ko-Ming
Chen,Emmanuella Guenova,Doruk Demircioglu,Wolfgang E. Kempf,Thomas Volz,Hans-Georg
Rammensee,Martin Schaller,Martin Röcken,Friedrich Götz,Tilo Biedermann
• DOI: http://dx.doi.org/10.1016/j.immuni.2014.10.00
• CellPress Immunity Volume 41, Issue 5, p762–775, 20 November 2014

Congenital Heart Disease Linked To Long Term Inpatient Costs
Dr. Roberta Williams MD
Professor and Chair, Department of Pediatrics, Keck School of Medicine
VP for Pediatrics and Academic Affairs,
Childrens Hospital Los Angeles
• MedicalResearch.com: What is the background for this study?
• Dr. Williams: Although a large number of children with chronic disease are surviving into
adulthood, the extent and type of health resource needs remains a mystery. Patients with
congenital heart disease (CHD) require lifelong care, so it is important to understand present
resource utilization both as a foundation for planning services and as a reference point to assess
the changes that occur with presumed improved access to care due to health care reform.
• MedicalResearch.com: What are the main findings?
• Dr. Williams: Our study indicates that much of inpatient care utilization is determined by the
natural history of congenital heart disease as patients enter young adulthood, with a smaller
proportion of hospitalizations for surgery and more for congenital heart disease sequalae such as
congestive heart failure (CHF), and arrhythmia. The influence of poor access to care was not the
focus of this study, but it will be instructive to see how resource utilization changes over time. One
hypothesis is that more proactive outpatient care may reduce hospitalization for CHF and
arrhythmia but on the other hand, improved survival of increasingly complex patients may drive up
inpatient expenditures.
• Citation:
• Inpatient admissions and costs of congenital heart disease from adolescence to young adulthood
• Lu, Yang et al.
• American Heart Journal , Volume 168 , Issue 6 , 948 – 955
Published Online: September 13, 2014
• DOI: http://dx.doi.org/10.1016/j.ahj.2014.08.006

Testosterone Therapy May Not Increase Risk of Prostate CancerMedicalResearch.com Interview with:
Prof. h.c.* Dr. Farid Saad (on behalf of Dr. Haider and co-authors)
Global Medical Affairs Andrology
c/o Bayer Pharma AG, D-13342 Berlin
*Gulf Medical University, Ajman, UAE
• Response: In early 1940s Dr. Charles Huggins demonstrated that in few men with metastatic
prostate cancer, castration reduced tumor growth and androgen administration promoted
tumor growth. This observation became the corner stone of androgen deprivation therapy
(ADT) in men with prostate cancer for the past 7 decades without any clinical evidence to the
contrary.
• Indeed, normal prostate growth depends on androgens and therefore testosterone and its
metabolite DHT are responsible for the biochemical signaling in the prostate cells through
interaction with the androgen receptor. Since tumor cells have been transformed from
normal epithelial cells, it is no surprise that they retained the expression of the androgen
receptor and continue to depend on their growth on the androgen signal. For the past 7
decades, physicians thought that testosterone is a carcinogen for the prostate, despite lack of
any biochemical or clinical data. This long period of training physicians on this unproven
concept, has precipitated in the minds of many clinicians that testosterone (T) causes
prostate cancer. Based on a plethora of clinical data, there is no evidence to support such
myth. In fact, many recent studies have debunked this hypothesis based on longitudinal and
prospective studies.
• A newly advanced hypothesis was formulated suggesting that “T therapy does not pose a
greater risk for development of PCa.” However this hypothesis is met with considerable
skepticism. Interestingly, however, no new compelling evidence is available to discredit or
dismiss this newly advanced hypothesis.

• Response: The main finding of our studies are the incidence of prostate cancer from three
large independent observational cohorts, in which more than 1,000 hypogonadal men were
treated with T therapy for up to 17 years, no significant increase in the incidence of prostate
cancer (<2%) was found.
• In fact, the incidence of prostate cancer in the testosterone treated men was far less than
that detected in general screening trials. In a large screening trial in the U.S., in which 38,345
men age 55 to 74 years in the control arm were followed for 7 years, 7.35% were diagnosed
with prostate cancer. Similarly, data from an European study in which 72,891 patients, age 50
to 74 years and followed up for 11 years showed that 9.6% of men were diagnosed with
prostate cancer,
• Our findings suggest that the incidence of prostate cancer in patients on T therapy was not
greater than in the general population. To date, there is no convincing evidence that T
therapy is a risk factor for PCa. Thus, fear that T therapy causes PCa may not be justified in
light of the aforementioned arguments.

• Response: Although definitive safety data regarding testosterone therapy must await large,
long-term, controlled trials, our data suggest that testosterone therapy does not increase the
risk of prostate cancer. Clinicians and patients need to appreciate that in the absence of
prostate cancer and in patients with history of prostate cancer which were treated and are
free of the disease, testosterone therapy of hypogonadism is warranted, with appropriate
and close monitoring. The risk of prostate cancer in hypogonadal men receiving testosterone
therapy seems lower than in the general population. Careful evaluations and monitoring is
necessary.

this study?
• Response: We believe that clinical trials which are well designed and controlled, with a large
number of patients and for a reasonable long period of time is important to finally solidify
the evidence that testosterone does not represent a risk of prostate cancer. Unfortunately,
these studies are costly and no government agency or industry is willing to invest the
enormous amount of resources needed to answer this very critical question. Nevertheless, as
we move along, all types of studies, irrespective of its nature will produce evidence which
will either support or dismiss the notion that use of testosterone is safe in hypogonadal men.
• Citation:
• Incidence of Prostate Cancer in Hypogonadal Men Receiving Testosterone Therapy:
Observations from 5-Year Median Followup of 3 Registries
Haider A, Zitzmann M, Doros G, Isbarn H, Hammerer P, Yassin A
J Urol. 2014 Jun 26. pii: S0022-5347(14)03885-3. doi: 10.1016/j.juro.2014.06.071.
[Epub ahead of print]

High Quality Diet Reduces Systemic Inflammation
Joana Alves Dias, MPH
Department of Clinical Sciences in Malmö,
Lund University Malmö, Sweden
• Response: The evidence that chronic inflammation may be in the genesis of diseases such as
cardiovascular disease, type-II diabetes, and certain types of cancer is increasing. It is
suggested that lifestyle factors such as diet, physical activity, smoking, and alcohol
consumption could influence the inflammatory state. Instead of focusing on single nutrient
effects, we used a hypothesis-driven approach to food pattern studies, and constructed a diet
quality index based on the Swedish Nutrition Recommendations and Swedish Dietary
guidelines (DQI-SNR). The DQI-SNR consisted of 6 components. Individuals were assigned 0
when not adhering to a recommendation and 1 when adhering, resulting in total scores
ranging from 0 to 6. We classified individuals in low (0 or 1 points), medium (2 or 3) and high
(4-6 points) diet quality. We explored the association between the index scores and low-grade
inflammation.
• Our study indicates that adherence to a high quality diet is associated with lower systemic
inflammation, as measured by several soluble and cellular biomarkers of inflammation, in
middle-aged individuals. In other words, adherence to the general nutrition
recommendations could help prevent the development of diseases associated with chronic
inflammation. The anti-inflammatory effects of Mediterranean-like diets have been studied
extensively, but this study focused on the Swedish dietary habits and recommendations for
the Swedish population, and reached similar conclusions.

• Response: The value of the general nutrition recommendations and the dietary guidelines in
a healthy population goes beyond the sole prevention of CDV. Also, adherence to the
recommendations is expected to improve the general health and wellbeing in many ways, not
only to prevent chronic inflammation. It would be important to convey the message that
Nordic foods and the Swedish Nutrition Recommendations, which are tailored to this specific
population, appear to achieve similar health benefits as those found with Mediterranean
diets.

this study?
• Response: We have reported previously that the DQI-SNR is associated with lower risk of
overall and CVD-specific mortality, as well as with lower risk of CVD incidence in the same
population. This suggests, together with the results of the current study, that a lower degree
of systemic inflammation preceded by adherence to the dietary recommendations may
protect against chronic diseases development and early mortality. More studies are needed
to investigate this hypothesis and to replicate results in other populations.
Citation:
A high quality diet is associated with reduced systemic inflammation in middle-aged
individuals
Dias, Joana Alves et al.
• Atherosclerosis Accepted: November 6, 2014; Published Online: November 13, 2014
• DOI: http://dx.doi.org/10.1016/j.atherosclerosis.2014.11.006

Breast Cancer: Gene Mediating Tamoxifen Resistance Identified
Ben Ho Park, M.D., Ph.D.
Associate Professor of Oncology, Breast Cancer Program
Associate Director, Hematology/Oncology Fellowship Training Program
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, MD 21287
• Dr. Park: To discover genetic mediators of tamoxifen resistance in breast cancers, we used
genetic screening of breast cancer cell line models and patient data to identify a new gene
that can mediate drug resistance. We found that amplification and overexpression of this
gene in estrogen receptor positive breast cancers results in tamoxifen resistance and is
associated with worse outcomes in patients whose tumors demonstrate
amplification/overexpression of this gene.
• Dr. Park: This is still too early for use in clinical practice. It is mostly a laboratory based finding
to identify the function of MACROD2 after we demonstrated that it is
overexpressed/amplified in actual human breast cancers, and though future possibilities are
compelling to think about, we need to proceed with additional high level evidence before we
can use this information for clinical practice.

Breast Cancer: Gene Mediating Tamoxifen Resistance Identified
Ben Ho Park, M.D., Ph.D.
Associate Professor of Oncology, Breast Cancer Program
Associate Director, Hematology/Oncology Fellowship Training Program
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, MD 21287
this study?
• Dr. Park: We need to expand the study in a prospective fashion to confirm these results in
patients. We also need to see whether existing and future drugs can overcome tamoxifen
resistance mediated by MACROD2 in both the lab and clinical settings.
• Citation:
• Morassa Mohseni, Justin Cidado, Sarah Croessmann, Karen Cravero, Ashley Cimino-Mathews,
Hong Yuen Wong, Rob Scharpf, Daniel J. Zabransky, Abde M. Abukhdeir, Joseph P. Garay,
Grace M. Wang, Julia A. Beaver, Rory L. Cochran, Brian G. Blair, D. Marc Rosen, Bracha
Erlanger, Pedram Argani, Paula J. Hurley, Josh Lauring, Ben Ho Park.
MACROD2overexpression mediates estrogen independent growth and tamoxifen
resistance in breast cancers. Proceedings of the National Academy of Sciences, 2014;
201408650 DOI: 10.1073/pnas.1408650111

Genetics Plays Large Role in Allergic Esophagitis
Dr. Hakon HakonarsonMD PhD
The Center for Applied Genomics, The Children’s Hospital of Philadelphia
Department of Pediatrics, The Perelman School of Medicine,
University of Pennsylvania Philadelphia, Philadelphia, Pennsylvania
• Dr. Hakonarson: We have built the world’s largest pediatric biobank at the Center for Applied
Genomics at CHOP. Eosinophilic esophagitis (EoE) is among the projects we have sampled in
collaboration with the EoE Center in collaboration with Dr. Spergel. We have nearly 1,000
samples now of this relatively rare disorder, which is now well powered for GWAS. We
previously reported association of the TSLP locus with Eosinophilic esophagitis. Here we
report genome-wide significant associations at four additional loci; c11orf30 and STAT6,
which have been previously associated with both atopic and autoimmune diseases, and two
EoE-specific loci, ANKRD27 that regulates the trafficking of melanogenic enzymes to
epidermal melanocytes and CAPN14, that encodes a calpain whose expression is highly
enriched in the esophagus in EoE. This discovery not only improves our understanding of the
pathobiology of EoE, but also represents novel targets for the development of new therapies
to treat the disease.
• Dr. Hakonarson: That EoE is a complex genetic disorder that is highly heritable and as we
learn more about the genetic underpinnings of EoE we will be able to develop more
innovative and effective therapies to treat EoE.

Genetics Plays Large Role in Allergic Esophagitis
Dr. Hakon HakonarsonMD PhD
The Center for Applied Genomics, The Children’s Hospital of Philadelphia
Department of Pediatrics, The Perelman School of Medicine,
University of Pennsylvania Philadelphia, Philadelphia, Pennsylvania
this study?
• Dr. Hakonarson: The results from this study inform us that genetics plays a key role in the
pathogenesis of Eosinophilic esophagitis. By future sequencing of EoE samples, we will be
able to explain the major genetic factors and gene networks that cause EoE and develop
more effective therapies and preventive measures to treat this devastating disease.
• Citation:
• GWAS identifies four novel eosinophilic esophagitis loci
Patrick M. A. Sleiman,Mei-LunWang, Antonella Cianferoni,Seema Aceves,Nirmala Gonsalves,
Kari Nadeau, Albert J. Bredenoord, Glenn T. Furuta, Jonathan M. Spergel,Hakon Hakonarson
Nature Communications 5, Article number: 5593 doi:10.1038/ncomms659

Luminosity Study Finds Cognitive Performance Affected By Sleep, Time of Day
Daniel Sternberg PhD.
Data Scientist at Lumosity
Dr. Sternberg: We were interested in examining how lifestyle factors such as sleep, mood and time
of day impact cognitive game play performance. We analyzed game play performance data on
Lumosity tasks from more than 60,000 participants and found that performance on the tasks
designed to challenge memory, speed, and flexibility peaked in the morning, while performance on
tasks designed to challenge aspects of crystallized knowledge such as arithmetic and verbal fluency
peaked in the afternoon. Overall, game performance for most tasks was highest after seven hours
of sleep and with positive moods, though performance on tasks that challenged crystallized
knowledge sometimes peaked with less sleep.
•
Medical Research: What should clinicians and patients take away from your report?
Dr. Sternberg: The changes within an individual’s daily life can impact cognitive performance. Once
an individual’s differences and peak performance are better understood, there may be a way to
optimize the scheduling of different tasks throughout the day.
• Medical Research: What recommendations do you have for future research as a result of this
study?
Dr. Sternberg: Future studies can combine these findings with the growing health and lifestyle data
from smartphones and wearable devices to help individuals and researchers better understand the
relationships between our daily lives and cognitive performance.
• Citation:
Abstract Presented at 2014 Society for Neuroscience conference
Lifestyle effects on Cognitive Training

42 Million US Adults Still Smoke
Darryl Konter
Health Communications Specialist, Office on Smoking and Health at Centers for Disease Control and Prevention
• Response: Tobacco use is the leading cause of preventable disease and death in the United
States, resulting in more than 480,000 premature deaths and $289 billion in direct health
care expenditures and productivity losses each year. Despite progress over the past several
decades, millions of adults still smoke cigarettes, the most commonly used tobacco product
in the United States. Cigarette smoking among U.S. adults declined from 20.9% in 2005 to
17.8% in 2013. Among cigarette smokers who smoke daily, the average number of cigarettes
smoked per day declined from 16.7 in 2005 to 14.2 in 2013, and the proportions of daily
smokers who smoked 20–29 or ≥30 cigarettes per day also declined. However, an estimated
42.1 million adults still smoked cigarettes in 2013. Moreover, cigarette smoking remains
particularly high among certain groups, including adults who are male, younger, multiracial or
American Indian/Alaska Native, have less education, live below the federal poverty level, live
in the South or Midwest, have a disability/limitation, or who are lesbian, gay, or bisexual.

Darryl Konter
• Response: For Clinicians: To reduce the burden of tobacco use, healthcare providers could
play a vital role in educating their patients about the health risks of tobacco use, and
providing effective cessation interventions. The U. S. Public Health Service Clinical Practice
Guideline recommends that clinicians and health care delivery systems consistently identify
and document tobacco use status and treat every tobacco user seen in a health care setting.
• For Patients: Tobacco use continues to be the leading cause of preventable disease and death
in the United States. Patients should be aware of the available clinical preventive services,
including, tobacco cessation counseling/medication and its insurance coverage. Additionally,
adults should quit smoking if they currently use tobacco, and if they can’t stop yet, never use
tobacco or allow tobacco to be used around children. Finally, additional information and
support for quitting is available by telephone (800-QUIT-NOW [800-784-8669]). CDC’s Tips
from Former Smokers campaign features real persons living with the consequences of
smoking-related diseases and offers additional quit resources at http://www.cdc.gov/tips.

Darryl Konter
this study?
• Response: Although the decline in overall cigarette smoking prevalence during 2005–2013 is
encouraging, approximately 42.1 million adults still smoke cigarettes; this underscores the
need for continued implementation of evidence-based interventions including increasing the
price of tobacco products, implementing and enforcing comprehensive smoke-free laws,
warning about the dangers of tobacco use with high-impact antismoking media campaigns,
and increasing access to help with quitting. Disparities exist in smoking prevalence. Future
research is needed to assess the implementation of proven strategies to prevent and reduce
tobacco use among these groups, as well as documenting and expanding questions on
surveillance tools to better capture data on subpopulations with the greatest burden of
tobacco use.
• Citation:
• MMWRWeekly
• November 28, 2014 / 63(47);1108-1112
Current Cigarette Smoking Among Adults — United States, 2005–2013
•

Rhinoplasty: Complications Associated With Using Rib Cartilage
Hong Ryul Jin, MD Professor and Chair
Department of Otorhinolaryngology-HNS Seoul National University
BoramaeMedical Center, Seoul, Korea
• Response: Although autologous rib cartilage is a useful graft material for rhinoplasty,
surgeons sometimes encounter unpleasant complication such as warping or donor-site
morbidity. These complications are not infrequent, but there has been no systematic review
with regarding this matter. For evidence-based practice, we aimed to assess the long-term
safety of using rib cartilage by means of meta-analysis.
• By reviewing the 10 selected, eligible articles after extensive screening, we found that rates
of warping, resorption, infection, and displacement were 3.1, 0.2, 0.6, and 0.4%, respectively.
Hypertrophic scar at chest was found in 5.5%, with highest report of 23.8%. Warping and
hypertrophic chest scarring showed relatively higher rates, warranting a surgeon’s attention
• Response: From the result, autologous rib cartilage is considered as one of the safest graft
materials that is resistant to infection and absorption. We hope surgeons who are using rib
cartilage for rhinoplasty aware of the occurrence of warping and chest scar and do their best
avoid them. However, even with this warning to surgeons, the reported incidence is within an
acceptable range for the patients.

Rhinoplasty: Complications Associated With Using Rib Cartilage
Hong Ryul Jin, MD Professor and Chair
Department of Otorhinolaryngology-HNS Seoul National University
BoramaeMedical Center, Seoul, Korea
• Medical Research: What recommendations do you have for futue research as a result of
this study?
• Response: Because a limited number of studies and patients were eligible, and consistent
definitions of complications were lacking in this meta-analysis, future studies with a larger
series of patients and objective outcome measurements are needed to obtain more reliable
results. In addition, research for biomechanical properties and their changes after
implantation of rib cartilage will elucidate the aforementioned concerns in rhinoplasty.
• Citation:
• Complications Associated With Autologous Rib Cartilage Use in Rhinoplasty: A Meta-analysis
• Wee J, Park M, Oh S, Jin H. Complications Associated With Autologous Rib Cartilage Use in
Rhinoplasty: A Meta-analysis. JAMA Facial Plast Surg. Published online November 27, 2014.
doi:10.1001/jamafacial.2014.914.
•

Discovery Pinpoints How Some Aggressive Cancers Turn Off Tumor Suppressor Genes
MedicalResearch.comInterview with: Charles Brenner, PhD
Roy J. Carver Chair & Head of Biochemistry
Departments of Biochemistry & InternalMedicine Carver College of Medicine
University of Iowa Iowa City, IA 52242
• Dr. Brenner: KRAS mutations are extremely common in human malignancies. The KRAS gene is an
oncogene that drives cell growth pathways and that leads to silencing and inactivation of tumor
suppressor genes. It was known that KRAS mutant cancer cells silence tumor suppressor genes but the
precise mechanism for gene silencing was not known. In this study, we discovered that KRAS mutations
turn off the TET1 gene. TET1 functions as an “eraser” of gene silencing marks. When KRAS mutations
occur, the TET1 eraser isn’t expressed any longer, and a series of tumor suppressor genes become
silenced. This is an essential part of the aggressiveness of KRAS-dependent cancers and is controlled by
the ERK pathway that is turned on by KRAS. In short, KRAS turns on ERK, which turns off TET1. When TET1
is off, a set of tumor suppressor genes are also turned off, which drives cancer formation.
• Dr. Brenner: If genes such as EGFR, KRAS or BRAF are activated in cancer, ERK pathway inhibition might
restore TET1 gene expression and consequent tumor suppressor gene function.
• Dr. Brenner:We plan to test whether human tumors with mutations in the KRAS pathway respond to ERK
pathway inhibitors by increasing TET1 expression and reducing their aggressiveness.
• Citation:
• Suppression of TET1-Dependent DNA Demethylation Is Essential for KRAS-Mediated Transformation
• Bo-Kuan Wu, Charles Brenner
• DOI: http://dx.doi.org/10.1016/j.celrep.2014.10.063
CellReports Published Online: November 26, 2014

Fenoldopam Does Not Prevent Acute Kidney Injury After Cardiac Surgery
Giovanni Landoni, M.D.
Head of Research,Department of Anesthesiology and Intensive Care
Associate Professor at Università Vita-Salute San Raffaele, Milan
• Dr. Landoni: The prevention and treatment of acute kidney injury after cardiac surgery is a
major therapeutic goal, but no effective agents have yet been identified. Meta-analyses
suggested that fenoldopam might be effective.
• Dr. Landoni: We found that in cardiac surgery patients with early acute kidney injury (defined
as a ≥50% increase of serum creatinine from baseline or oliguria for ≥6 hours), fenoldopam
had no impact on the need for renal replacement therapy or 30-day mortality, while
increasing the rate of hypotension.
• Dr. Landoni: Fenoldopam is available in Europe and the USA. It was approved by FDA in 1997
and indicated for the in-hospital, short-term management of severe hypertension.
Fenoldopam has not gained FDA approval for renal indications although it has been widely
used off label in the USA for kidney protection in various settings. Our trial demonstrates that
fenoldopam is not effective for the prevention and treatment of AKI in cardiac surgery and,
by analogy, suggests that effectiveness might also be absent in other patients with early AKI.

Fenoldopam Does Not Prevent Acute Kidney Injury After Cardiac Surgery
Giovanni Landoni, M.D.
Head of Research,Department of Anesthesiology and Intensive Care
Associate Professor at Università Vita-Salute San Raffaele, Milan
this study?
• Dr. Landoni: The study provides evidence against fenoldopam use as an off-label kidney
protection strategy in cardiac surgery, but other settings and other populations of patients
with early AKI should be investigated to strengthen this statement. Furthermore, there is a
need for a paradigm change in kidney protection after surgery and this study contributes to
highlight the need for new strategies and molecules in this field.
• Citation:
• Effect of Fenoldopam on Use of Renal Replacement Therapy Among Patients With Acute
Kidney Injury After Cardiac Surgery: A Randomized Clinical Trial
Bove T1, Zangrillo A2, Guarracino F3, Alvaro G4, Persi B5, Maglioni E6, Galdieri N7, Comis M8,
Caramelli F9, Pasero DC10, Pala G11, Renzini M12, Conte M13, Paternoster G14, Martinez B15,
Pinelli F16, Frontini M17, Zucchetti MC18, Pappalardo F1, Amantea B4, Camata A5, Pisano A7,
Verdecchia C8, Dal Checco E9, Cariello C3, Faita L4, Baldassarri R3, Scandroglio AM1, Saleh O1,
Lembo R1, Calabrò MG1, Bellomo R19, Landoni G2.
JAMA. 2014 Sep 29. doi: 10.1001/jama.2014.13573. [Epub ahead of print]

Test Helps Determine Which Patients May Not Benefit From Elevated HDL
Thomas Weichhart, PhD
Associate Professor, Medical University of Vienna
Institute of Medical Genetics Vienna Austria
• Dr. Weichhart: Impairment of high-density lipoprotein (HDL) function has been associated
with cardiovascular events in patients with kidney failure on hemodialysis. The protein
composition of HDLs is altered in these patients presumably compromising the
cardioprotective effects of HDLs. In an earlier study we found that two proteins in particular,
namely Serum Amyloid A (SAA) and Surfactant Protein B (SP-B), are significantly raised in the
HDL of dialysis patients, and these also contribute towards HDL losing its protective effect. In
the current study we have now developed an novel test that can quickly and directly measure
the SAA and SP-B bound to HDL.
• Dr. Weichhart: We have measured the concentrations of HDL-associated SAA and SP-B in
1152 patients with type 2 diabetes mellitus on hemodialysis. High levels of SAA in the HDL
were associated with an increased occurrence of heart attacks, while high levels of SP-B in
the HDL acted as a marker for a generally increased risk of mortality. Importantly, these
effects were independent of the HDL-cholesterol levels

Test Helps Determine Which Patients May Not Benefit From Elevated HDL
Thomas Weichhart, PhD
Associate Professor, Medical University of Vienna
Institute of Medical Genetics Vienna Austria
• Dr. Weichhart: High HDL levels are generally regarded as the best type to have and are believed to
protect against cardiovascular diseases such as heart attacks and strokes. Clinical practice currently
only measures the amount of cholesterol in the HDL (known as the HDL-C) and the protective effect
against future cardiovascular disease is derived from this. Our research together with other studies
shows, however, that in many chronic diseases such as coronary heart disease, diabetes mellitus or
in patients receiving dialysis, the quantity of HDL-C in the blood cannot be used as a prognostic
marker. As a result, new methods are needed in order to better estimate the risk of cardiovascular
disease. The new test may in future allow a much more precise risk prediction for cardiovascular
diseases in order to decisively improve the overall prognosis.
study?
• Dr. Weichhart: The laboratory test needs to be evaluated in other patient collectives in order to
confirm the results.
• Citation:
• Quantification of HDL Proteins, Cardiac Events, and Mortality in Patients with Type 2 Diabetes on
Hemodialysis
• Chantal Kopecky, Bernd Genser, Christiane Drechsler, Vera Krane, Christopher C. Kaltenecker,
Markus Hengstschläger, Winfried März, Christoph Wanner, Marcus D. Säemann, and Thomas
Weichhart
CJASN CJN.06560714; published ahead of print November 25, 2014, doi:10.2215/CJN.06560714

Standardized Approach Markedly Reduces Cardiac Monitor Alarms
Christopher E. Dandoy, MD, MSc
Divisions of Bone Marrow Transplantation and Immunodeficiency, and
James M. Anderson Center for Health Systems Excellence
Cincinnati Children’s Hospital Medical Center
• Medical Research: What is the background for this study? Why did you decide to do this study?
• Dr. Dandoy: During our three month investigation period we had roughly a million alarms go off in
our intensive care unit. Our unit nurses reported spending 30-40 minutes per day responding to the
various alarms.
• We first looked to see if there were established guidelines in the literature for cardiac monitors and
found there were none. The alarms were a source of frustration and anxiety not just for the unit
staff but also for patients and family members.
• Medical Research: What are the elements of your alarm reduction program?
• Dr. Dandoy: The first element was simply to have a plan or a process for initial ordering of monitor
parameters based on age-appropriate standards. In our case, we established a standard order set in
Epic, our electronic records program.
• The second element was to change the patient monitor leads daily. We know that lead conductivity
and sensitization fades our after 24 hours, leading to inaccurate monitoring. The challenge was to
find a way of changing the leads daily with a minimum of patient discomfort. We discovered that by
soaking the leads first, pain could be eliminated. To reduce staff time, the nurses perform the
monitor lead changes when they bath the patient.
• The third element consisted of evaluating the cardiac monitor parameter settings. For example:
• We increased the SpO2 alarm delay from 5 to 10 seconds because the majority of the SpO2 alarms
self-correct within the delay period set.
We also found that a high respiratory rate alarm, without other vital sign abnormalities, is nearly
always a false alarm.
The fourth element consisted of determining a reliable method for appropriate discontinuation of
the monitoring devices. We now routinely assess whether the monitors are necessary or can be
discontinued.

Standardized Approach Markedly Reduces Cardiac Monitor Alarms
Christopher E. Dandoy, MD, MSc
Divisions of Bone Marrow Transplantation and Immunodeficiency, and
James M. Anderson Center for Health Systems Excellence
Cincinnati Children’s Hospital Medical Center
• Medical Research: What are the barriers to implementing this program in a wider fashion? How
expensive is it to implement and maintain?
• Dr. Dandoy: The main barrier to implementation was the daily lead change, which we overcame by
incorporating into the daily bathing time, decreasing both patient discomfort and staff time. The
cost of the daily lead change was minimal at just about $1 dollar per lead.
• There was general acceptance of the program by the unit’s staff. The median time that individual
nurses spent addressing monitor alarms decreased from 20 to 25 minutes per shift to 10 minutes
per shift, including the time it took each nurse to complete the monitor log.
• As a measure of success, the program has been self-sustaining in the unit since the study ended
and has spread to other units in the hospital.
• Medical Research: What further research do you plan in this area?
• Dr. Dandoy:We plan to address the effects of monitor alarms on sleep and whether a reduction in
alarms can have a positive impact on patient sleep and satisfaction.
• Citation:
• A Team-Based Approach to Reducing Cardiac Monitor Alarms
• Christopher E. Dandoy, Stella M. Davies, Laura Flesch, Melissa Hayward, Connie Koons, Kristen
Coleman, Jodi Jacobs, Lori Ann McKenna, Alero Olomajeye, Chad Olson, Jessica Powers, Kimberly
Shoemaker, Sonata Jodele, Evaline Alessandrini, and Brian Weiss
• Pediatrics peds.2014-1162; published ahead of print November 10, 2014, doi:10.1542/peds.2014-
1162

Dedicated Neuro Emergency Department Improves Stroke Outcomes
Karen Greenberg, DO, FACOEP
Capital Health Center for Neurologic Emergencies
750 Brunswick Ave, NJ 08638
• Dr. Greenberg: Capital Health Regional Medical Center in Trenton, NJ opened the first dedicated
Neurologic Emergency Department in the country in January of 2011. Dr. Veznedaroglu, our chief
neurosurgeon, recognized the importance and emergent nature of patients with neurologic
complaints. He recruited dedicated Emergency Medicine Physicians, one of which is myself, who
would be assigned to see patients with neurologic complaints during peak hours of 7a-6p daily
seven days a week. Having a section of the ED dedicated to identifying, triaging, and treating
patients with neurologic emergencies has led to more advanced and efficient care. Due to the
initial success of the neuro ED, 5 dedicated physicians became educated and comfortable in
administering IV-tPA to acute ischemic stroke patients. This decision was made to eliminate delays
associated with teleneurology or neurology consultation prior to administering thrombolytics in
order to improve door-to-needle times and outcomes in acute stroke patients. As far as we know,
we are still the only dedicated Neuro ED in the country.
• Dr. Greenberg: From 2012-2014, 67 acute stroke patients received IV tpa in either our Neuro ED
which is run from 7a-6p, or the main ED from 6p-7a. 35 patients were evaluated in the Neuro ED
and 32 in the main ED. Average door-to-needle times (DTN) were significantly faster in the
neurologic ED at 35 minutes, compared to main ED DTN times of 83 minutes. Discharge NIHSS
score was significantly lower and more patients were discharged to home in the Neurologic ED
group compared to the main ED group. There were no cases of symptomatic intracranial
hemorrhage in either group.

• Dr. Greenberg: Many emergency medicine physicians and patients recognize airway and
circulation problems as true emergencies, but there is still a lack of urgency when it comes to
recognizing and treating acute stroke symptoms. For every minute that treatment is delayed
in a typical large vessel stroke, nearly 2 million neurons die. Therefore, rapid treatment is a
critical factor in the outcomes of patients with acute stroke who are treated with IV-tPA.
Physicians and patients alike need to respond quickly: Patients by getting themselves to
an emergency department as quickly as possible, and ED physicians by having an extreme
sense of urgency to consider treatment with IV-tPA and then administer rapidly.
• The current guidelines of the American Heart Association/American Stroke Association
(AHA/ASA) recommend the delivery of thrombolytic therapy within 60 minutes of hospital
arrival,. However, less than 30% of patients treated with IV tPA have a DTN of the
recommended less than 60 minutes here in the United States. With the unique, independent
ability of the Neuro ED physicians to adminster IV-tPA without specialty consultation, DTN
averaged 35 minutes, well below the recommended delivery time of 60 minutes.
• It is well known that ultra-early thrombolysis has been shown to cut long term disability in
mild to moderate stroke. Our study is again unique in that we demonstrate a short term
benefit as well:

• -If treated in the Neuro ED, average discharge NIHSS score was 2, compared to discharge
NIHSS of 6 for the Main ED.
• -In addition, more patients were able to be discharged to home, rather than subacute
rehabilitation or extended care facility, when treated by the Neuro ED compared to the Main
ED.
this study?
• Dr. Greenberg: Our recent publication is a retrospective study. We hope to next continue
our study in a prospective manner that can continue to show improved short term outcomes,
but also evaluate patients’ long term outcome at 90 days along the lines of the NINDs trial.
• Citation:
• Improved Door-to-Needle Times and Neurological Outcomes when IV-tPA is Administered by
Emergency Physicians with Advanced Neuroscience Training
• Karen Greenberg, Christina R. Maxwell, Keisha D. Moore, Michael D’Ambrosio, Kenneth
Liebman, Erol Veznedaroglu, Geri Sanfillippo MSN, Cynthia Diaz, Mandy J. Binning
DOI: http://dx.doi.org/10.1016/j.ajem.2014.11.025
Publication stage: In Press Accepted Manuscript Published online: November 28, 2014
•

3D Printing Will Guide and Improve Face Transplantation
MedicalResearch.comInterview with Frank J. Rybicki, MD PhD
Director, Applied Imaging Science Laboratory
Director, Cardiac CT and Vascular CT / MRI Brigham and Women’s Hospital
Associate Professor, Harvard Medical School Boston, MA
• Dr. Rybicki: Face transplantation restores form and function to patients with catastrophic facial
injuries. To date, surgical planning a vascular anastamoses have been well described. While all 7
patients at BWH have had 3d printed models from their CT scans, to date the findings and impact of
3D printing has not been described. Also, the role of printing the soft tissues of the face has not
been described.
•
Medical Research: What should clinicians and patients take away from your report?
• Dr. Rybicki: There are many emerging aspects of medicine for which 3D printing will have a positive
impact. Full face transplantation is an excellent and dramatic example of how one of the most
complex procedures to date can be improved with the new technology.
study?
• Dr. Rybicki: 3D printing in medicine, and in particular radiology, will continue to grow. Surgical
planning will expand to include 3D printing.
• Citation:
• RSNA 2014 100th Scientific Assembly and Annual Meeting Abstract
• Researchers Use 3-D Printing to Guide Human Face Transplants
• Co-authors on the study are Maximilian Kueckelhaus, M.D., Kanako K. Kumamaru, M.D., Ph.D.,
Nicole Wake, M.S., Dimitris Mitsouras, Ph.D., Elizabeth George, M.D., Gerald T. Grant, D.M.D., M.S.,
Peter C. Liacouras, Ph.D., and Edward J. Caterson, M.D., Ph.D.

Rash and Blisters May Accompany Ebola Infection
Victoria Vaughan
Medical College of Georgia, Augusta, Georgia
• Response: The Global Mortality of Skin Disease study compares age adjusted mortality of disease with skin manifestations
between developing and developed countries for the years 1990 and 2010. The main findings were that mortality from
infectious conditions was greater in the developing world while melanoma contributed to mortality in the developed world.
Ebola Virus Disease has cutaneous manifestations and affects the developing world preferentially. As of November 27, 2014,
the mortality in West Africa totals 5444 according to the CDC. However, the United States has had only two deaths from
Ebola Virus Disease.
• Response: A nonpruritic morbilliform eruption may occur between days 2 to 7 of the symptom onset of Ebola Virus Disease.
The patient’s body becomes enveloped in erythematous papules and petechiae which progress to hemorrhagic bullae and
ecchymoses.1
• Response: The authors recommend greater documentation of the clinical sequelae of Ebola Virus Disease to enable teaching
and promote swift recognition of the illness both during this outbreak and in the event of a future outbreak. The Global
Burden of Disease database studies focus on diseases with higher mortality rates in order to distribute resources to the
greatest area of need. However, Ebola Virus Disease highlights the importance of disease surveillance even while the disease
burden is low in order to prevent outbreaks and save resources at a later time.
• Nkoghe D, Leroy EM, Toung-MveM, Gonzalez JP. Cutaneous manifestations of filovirus infections. Int J Dermatol. 2012;51:
1037-1043.
• Citation:
• Effect of recent Ebola outbreaks on estimating the global burden of diseases with skin manifestations
• Authors: Victoria Vaughan BA1, Chante Karimkhani BA2, Lindsay Boyers BA3, Robert Dellavalle MD, PhD, MSPH4
• 1 Medical College of Georgia, Augusta, Geogia 2 Columbia University College of Physicians and Surgeons, New York, USA 3
Georgetown University School of Medicine, Washington D.C., USA 4 Department of Dermatology, Denver Veterans
Administration Hospital, Colorado, USA
• JAAD November 19, 2014 DOI: http://dx.doi.org/10.1016/j.jaad.2014.10.037

Young Adults Who Do Not Attend College At Increased Risk of Opioid Abuse
Silvia S. Martins, MD, PHD Associate Professor of Epidemiology
Department of Epidemiology Mailman School Of Public Health
Columbia University New York, NY 10032
• MedicalResearch: What is the background for this study? What are the main findings?
• Dr. Martins: While a large proportion of young adults, ages 18 to 22, are prescribed opiates, non-medical
use of opioids is second only to marijuana as the most prevalent form of illegal drug use among young
adults.
• Until this study, little was known about nonmedical use of prescription drugs among non-college-attending
young adults in the United States. Approximately 70 percent of all U.S. young adults enroll in some form of
college education, but around 30% do not.
• We analyzed public data for 36,781 young adults between the ages of 18 and 22 over a 12-month period
in 2008 through 2010 from the National Survey on Drug Use and Health, an annual cross-sectional survey
of the Substance Abuse and Mental Health Administration. Using the Kessler 6 screening instrument, we
also measured past-year serious psychological distress as self-reported by the respondents.
• Among non-college-attending young adults with at least a high school degree, 13.1 percent reported using
prescription opioids for non-medical reasons. The figure rose slightly to 13.2 percent for those who did not
graduate from high school, and declined to 11.3 percent among college attendees.
• Non-Hispanic Blacks and Asians were less likely to use prescription opioids non-medically in the past-year
compared to non-Hispanic Whites. Those who reported experiencing psychological distress most recently
were more likely than those without distress to be non-medical users of the drugs.
• The relationship between educational attainment and prescription drug use disorder was seen to a greater
extent in women: young women who completed high school but were not enrolled in college were at a
significantly greater risk of opioid disorder than their college-attending counterparts, while the difference
between male college students and males with a high school diploma/GED for past-year opioid disorder
was negligible.

• We also looked at non-medical use of prescription stimulants. The result was the opposite of
what we found with opioids: Those without a high school degree and those who completed
high school or equivalency were less likely to have used nonmedical stimulants compared to
their college-attending peers. Asian users of the stimulants for non-medical purposes were
more likely than whites to develop a stimulant use disorder. Living in a large metropolitan
area was associated with a greater use of stimulants that were not prescribed compared to
those living in less urban areas. Hometown size also had a bearing on whether this led to a
stimulant-use disorder.
• MedicalResearch: What should clinicians and patients take away from your report?
• Dr. Martins: Our findings clearly show there is a need for young adult prevention and
intervention programs to target nonmedical prescription drug use beyond college campuses,
since this study illustrates that young adults who do not attend college are at particularly high
risk for nonmedical prescription opioid use and disorder.There are few NMUPO prevention
programs tailored for young adults with less years of formal education—most prescription
drug use prevention messages are targeted towards college students. As such, prevention
programs are also needed for non-college attending young adults, not only at the media
level, but also in workplaces.

• MedicalResearch: What recommendations do you have for future research as a result of
this study?
• Dr. Martins: Future research should examine in greater detail drug use patterns among
young adults who are nonmedical prescription opioid users and do not attend college as well
as further examine nonmedical prescription drug use patterns among those who attend 2-
year versus 4-year colleges and those who drop-out of college.
• Citation:
• Nonmedical prescription drug use among US young adults by educational attainment
Silvia S. Martins, June H. Kim, Lian-Yu Chen, Deysia Levin, Katherine M. Keyes, Magdalena
Cerdá, Carla L. Storr
Social Psychiatry and Psychiatric Epidemiology, 12/01/2014
•

Sculptra Injections: More Lumps If Patients Massage Skin
Dr. Tanveer Janjua MD
Janjua Facial Surgery,
Bedminster, New Jersey
• Dr. Janjua: This study was conducted to determine if massage plays an important role in the
prevention of lumps and nodules that can occur after injection of PLLA (Poly-L Lactic Acid), i.e.,
Sculptra. The study revealed a higher incidence of lump formation in patients who massaged. This
goes against the commonly held belief that massage is critical in after care of Sculptra injections.
• Dr. Janjua: The clinicians should continue to address all factors that play a role in lump formation
after Sculptra injections, namely the technique and dilution of the product and not just rely on
massage to prevent nodule formation.
• The patients should understand that risk of nodules is inherent to the injection of Sculptra and
massage alone will not prevent lump formation. They need to seek physician injectors with
significant experience with Sculptra to minimize their risk.
study?
• Dr. Janjua: It will be very helpful to have a future prospective study that looks at increased levels of
dilution of up to 20ml per injection and compare it with smaller dilution of 8ml. It will also be
helpful to look into possibly prolonged pre-hydration at the time of manufacturing the product.
• Citation:
• Role of Massage in Preventing Formation of Papules and Nodules After Injecting Poly-L-Lactic Acid
• Janjua TA. Role of Massage in Preventing Formation of Papules and Nodules After Injecting Poly-L-Lactic
Acid. JAMA Facial Plast Surg. 2014;16(6):457. doi:10.1001/jamafacial.2014.1173.

Childhood Falls May Be Decreased By Supervision and Safety Devices
Prof. Denise Kendrick
Professor of Primary Care Research
Division of Primary Care, University Park Nottingham UK
• Prof. Kendrick: More than 1 million US children aged 0-4 years attend emergency
departments because of a fall each year. Approximately half of all ED attendances in this age
group are for falls, and most of these are falls from furniture, most commonly from beds,
chairs , baby walkers, bouncers, changing tables and high chairs. In the US around 18,000 0-4
year olds are admitted to hospital following a fall each year and in 2012 there were 31
deaths in the US in 0-4 year olds from falls. Healthcare costs for falls in the US were
estimated at $439 million for hospitalised children and $643 million for ED attendances in
2005.
• We found that children were more likely to attend hospital because of a fall from furniture in
families that did not use safety gates across doorways or on stairs. For infants (aged 0-12
months) we found they were more likely to attend hospital because of a fall from furniture if
they had been left on a raised surface (e.g. beds, sofas, work tops etc), had diapers changed
on a raised surface or been put in a car seat or bouncing cradle on a raised surface. We also
found that children aged over 3 years who had climbed or played on furniture were more
likely to have a fall requiring a hospital visit than children who had not. Finally we found that
children whose parents had not taught their children rules about climbing on objects in the
kitchen were more likely to have a fall needing a hospital visit than children whose parents
had taught these rules.

Prof. Kendrick: Our findings suggest some falls may be prevented by using safety gates
across door ways and on stairs (note they are only recommended for use up to the age of
two, by when children may be able to climb over them or open them) and by not leaving
children on raised surfaces, not placing car seats or bouncing cradles on raised surfaces and
not changing diapers on raised surfaces (e.g. changing them on the floor instead). Supervising
children who are climbing or paying on furniture may help prevent some falls which occur
this way. Teaching children about not climbing on objects may also help reduce falls.
• Children develop and learn to do new things very quickly. It is important to anticipate what a
child is likely to be able to do in the near future and adapt the home to suit them. Also
children don’t always use furniture in the way it is intended to be used – e.g. drawers can be
pulled open and used to climb on, so parents need to try and keep one step ahead and look
at the home and it’s potential hazards in a way a child might. Also very young infants, who
are not old enough to roll over, can still wriggle enough to fall from things such as beds, so
even though a child is not yet mobile, they are still at risk of falls.

Prevention needs to focus on a range of strategies; no single strategy will prevent all falls in all
circumstances. It’s important not to rely on single strategies because none are completely child-proof.
For example, a safety gate on stairs will only protect from falls if it is always closed after
use and if a child cannot open it or climb over it. Even with a safety gate, children still need to be
taught to climb stairs safely and actively supervised whilst doing so. Some strategies are
impossible to do 100% of the time – parent’s cannot be within arm’s reach of their children all
day, every day; and things happen which distract parents from supervising, so it’s important to
use other strategies as well as supervision e.g. having somewhere you can leave a child (e.g.
playpen or stationary activity centre) whilst you need to do something else. Teaching children
safety rules will only be effective if children understand those rules and follow them. Just because
a child can repeat or remember a safety rule doesn’t mean they will always comply with that rule.
Some families may not be able to make some changes to their home, for example, if they are
renting their homes or cannot afford to buy safety equipment, so it also important that families
are given advice that is tailored to their needs and circumstances and given support to enable the
changes to be made that are needed. Some organisations offer home safety assessments and
provide or fit free or low-cost safety equipment specific to the needs of individual families, so
making these services more widely available and encouraging families to use these services is
important. .

• There is useful advice about preventing falls at home from a range of agencies and charities
such as CDC, Safekids Worldwide, the Child Accident Prevention Trust and the Royal Society
for the Prevention of Accidents.
• 1. CDC: A National Action Plan for Child Injury Prevention:
Reducing Fall-Related Injuries in Children
• 2. Safekids Worldwide
• 3 Child Accident Prevention Trust
• 4. Royal Society for the Prevention of Accidents

this study?
• Prof. Kendrick: Further studies are required exploring the risk or protective role of items of
nursery equipment such as baby walkers, playpens and stationary activity centres. We did not
include sleeping in, climbing or playing on bunk beds as exposures in our study. Bunk beds
are an important, but relatively uncommon cause of childhood falls from
furniture, accounting for approximately 10% of all falls from beds. Further studies are
required to quantify the risk of falls associated with bunk bed use.
• Citation:
• Kendrick D, Maula A, Reading R, et al. Risk and Protective Factors for Falls From Furniture in
Young Children: Multicenter Case-Control Study. JAMA Pediatr. Published online December
01, 2014. doi:10.1001/jamapediatrics.2014.2374.

Residents of Disadvantaged Neighborhoods At Increased Risk of Hospital Readmission
Amy Jo Haavisto Kind, M.D., Ph.D.
Assistant Professor, Division of Geriatrics
University of Wisconsin School of Medicine and Public Health
William S Middleton VA- GRECC Madison, WI 53705
• Dr. Kind: By way of background:
• Socioeconomic disadvantage is a complex theoretical concept which describes the state of
being challenged by low income, limited education and substandard living conditions for both
the person and his or her neighborhood or social network.
• It is plausible that disadvantage would influence rehospitalization because vulnerable
patients depend upon their neighborhood supports for stability, generally, and these needs
are likely to be increased after a hospitalization.
• Yet, it is difficult to assess socioeconomic disadvantage during clinical encounters, yet the ADI
provides an option for beginning such a discussion.
• ADI or Area Deprivation Index is a composite measure of neighborhood disadvantage, similar
to other geographic measures of disadvantage employed in other countries for resource
planning and health policy development.

• Dr. Kind: The results demonstrated:
• Residence within the most disadvantaged 15% of neighborhoods was associated with an
increased risk for 30-day rehospitalization, increasing from 22-27% with worsening ADI.
• When comparing 2 patients who are otherwise the same but differ by reason of
neighborhood deprivation index and arrive at the same hospital, the association of
deprivation and readmission remains.
• Patients in the most disadvantaged neighborhoods were more apt to be black, be on
Medicaid and have greater rates of comorbid conditions. Most patients in the most
disadvantaged 5% of neighborhoods lived in urban core areas, however those in the second-and
third- most disadvantage 5% groups were most likely to live in rural areas or large towns.
• Prevalence of disadvantaged neighborhoods vary by geographic region.
• Nearly 1/3 of eligible patients residing in rural areas lived in neighborhoods that were among
the most disadvantaged.

• Dr. Kind: The main message of this study is:
• Residence within a disadvantaged neighborhood is a rehospitalization predictor of magnitude
similar to chronic pulmonary disease.
• Living in a severely disadvantaged neighborhood predicts rehospitalization as powerfully as
the presence of serious illnesses, like chronic pulmonary disease.
• Patients from disadvantaged neighborhoods are at greater risk for rehospitalization
regardless of their treating hospital.
• Residence within a disadvantaged US neighborhood is a rehospitalization predictor of
magnitude similar to important chronic diseases (that we would not dream of ignoring).
• Measure of neighborhood disadvantage, such as the ADI, are easily created using data
already routinely collected by the US government and freely available to the public. These
may be useful in targeting patient- and community-based initiatives designed to lower
unwanted rehospitalizations.

• MedicalResearch: What recommendations do you have for future research as a result of this
study?
• Dr. Kind: Our findings suggest that neighborhood disadvantage is associated with a threshold effect,
with strong and increasing risk for rehospitalization for residents of the most disadvantaged 15%. It
is clear that social support and a patient’s environment can influence clinical outcomes, including
rehospitalization.
• Unfortunately, however, issues of social disadvantage are often overlooked. The use of a measure
like the ADI could enable early targeting of transitional care services, prompt discussions of social
supports, and activate additional community resources. It could also help
in refining characterizations of hospital service regions, and be used to identify neighborhoods that
could most benefit from additional outreach and services, or innovative programs, funding.
• Future research is needed to explore use of the ADI as an adjuster for the current Medicare
hospital-based readmissions measures/penalties.
• Citation:
• Neighborhood Socioeconomic Disadvantage and 30-Day Rehospitalization
Amy J.H. Kind, MD, PhD; Steve Jencks, MD, MPH; Jane Brock, MD, MSPH; Menggang Yu, PhD;
Christie Bartels, MD; William Ehlenbach, MD, Msc; Caprice Greenberg, MD; and Maureen Smith,
MD, MPH, PhD
Ann Intern Med. 2014;161(11):765-774. doi:10.7326/M13-2946

Cimetidine (Tagamet) May Have Anti-Cancer Properties
Dr. Pan Pantziarka
Anticancer Fund, Brussels Belgium
The George Pantziarka TP53 Trust, London, UK
• MedicalResearch: What is the background for this study?
• Dr. Pantziarka: The background of this study is that it is part of a series of investigations by
the Repurposing Drugs in Oncology (ReDO) project into well-known non-cancer drugs which
have evidence of activity that may be useful in cancer therapies. These drugs include
mebendazole, itraconazole, diclofenac, nitroglycerin and cimetidine.
MedicalResearch: What are the main findings?
• Dr. Pantziarka: The main finding from this paper is that there exists sufficient pre-clinical and
clinical evidence of a positive effect of cimetidine in cancer. In partciular there is evidence of
positive effect on overall survival if used peri-operatively at the time of curative resection of
colorectal cancer. Additionally we outline the multiple mechanisms of action of cimetidine in
cancer, which includes several different effects on the immune system. Finally we propose a
series of drug combinations with cimetidine for different cancer types.

Cimetidine (Tagamet) May Have Anti-Cancer Properties
Dr. Pan Pantziarka
Anticancer Fund, Brussels Belgium
The George Pantziarka TP53 Trust, London, UK
• Dr. Pantziarka: The big take home from this paper is that cimetidine has multiple positive
effects in cancer. The toxicity is very low and the cost is also small. Clinicians have the
evidence summarised for them in our paper so that they can evaluate whether the addition
of cimetidine to a patient’s therapy is warranted.
this study?
• Dr. Pantziarka: We believe that clinical trials of cimetidine as a perioperative addition to
therapy is warranted in a number of cancers, including colorectal, breast, NSCLC,
osteosarcoma, ovarian, pancreatic. Additionally there is some evidence of effect in
melanoma, RCC, gastric cancer and glioblastoma.
• Citation:
• Repurposing drugs in oncology (ReDO)—Cimetidine as an anti-cancer agent
Pan Pantziarka, Gauthier Bouche, Lydie Meheus, Vidula Sukhatme and Vikas P Sukhatme
ecancer 8 485 / DOI: 10.3332/ecancer.2014.485

Public Restrooms May Contain Very Few Dangerous Bacteria
Jack A Gilbert PhD Department of Ecology & Evolution
Graduate Program in Biophysical Sciences
University of Chicago, Chicago, IL 60637
• Dr. Gilbert: We have performed extensive analysis of the microbial distribution between
humans and home surfaces in peoples houses. And are still exploring how bacteria are
distributed around hospitals. Here we wanted to explore how bacteria from humans were
distributed into a space in real time. By taking samples every hour post sterilization and
seeing how the community stabilized, who remained active and whether they were
pathogenic. We found that communities stabilized on a skin-associated microbiome within 5
hours, that staphylococcus remained active and yet none of these were particularly
pathogenic. Yet we were able to identify pathogenic MRSA on surfaces around the bathroom,
but they were extremely rare.
MedicalResearch: What should clinicians and patients take away from your report?
• Dr. Gilbert: Public Bathrooms are actually not as dirty as we all think, they contain very few
pathogens, and we should refrain from sterilizing them, unless there is a major pathogen
outbreak.

Public Restrooms May Contain Very Few Dangerous Bacteria
Jack A Gilbert PhD Department of Ecology & Evolution
Graduate Program in Biophysical Sciences
University of Chicago, Chicago, IL 60637
this study?
• Dr. Gilbert: We now want to explore how communication and gene sharing between bacteria
on a surface support the development or suppression of pathogens. We hypothesize that the
presence of a complex microbiome on the surface can significantly reduce the likelihood of a
pathogen dominating on a surface, and as such we should embrace microbial biodiversity as
a control of disease spread in public spaces.
• Citation:
• Ecological succession and viability of human-associated microbiota on restroom surfaces
• Sean M. Gibbons, Tara Schwartz, Jennifer Fouquier, Michelle Mitchell, Naseer Sangwan, Jack
A. Gilbert, and Scott T. Kelley
• Appl. Environ. Microbiol. AEM.03117-14; published ahead of print 14 November 2014,
doi:10.1128/AEM.03117-14

MedicalResearch.com: Medical Research Exclusive Interviews December 4 2014

MedicalResearch.com: Medical Research Exclusive Interviews December 4 2014

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