MedicalResearch.com Leading Medical Research Interviews August 24 2015

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

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Hospital Improvements Have Led To Marked Decreased In Inpatient Mortality Over Ten Years
Posted on August 16, 2015
MedicalResearch.com Interview with:
Kevin Heslin, Ph.D., Staff Service Fellow, Center for Delivery, Organization and Markets, Agency for Healthcare Research and
Quality
Medical Research: What is the background for this study?
Dr. Heslin: Previous trends in inpatient mortality suggest that rates have been decreasing for
acute myocardial infarction (AMI), congestive heart failure (CHF), stroke, and pneumonia (Hines
et al., 2010; Stepanova et al., 2013). Continued study of these trends can help researchers and
policymakers assess the impact of health care quality efforts. Further, examining trends across
patient and hospital subgroups may inform strategies for addressing disparities in health care
quality by identifying groups that are leading and lagging in improvement.
Read the rest of the interviews on MedicalResearch.com
Content NOT an endorsement of efficacy and NOT intended as specific medical advice.

Quality
• Medical Research: What is the background for this study
• Dr. Heslin: From 2002 to 2012, inpatient mortality decreased among patients admitted to
U.S. hospitals for pneumonia (45 percent decrease, from 65.0 to 35.8 deaths per 1,000
admissions), AMI (41 percent decrease, from 94.0 to 55.9 deaths per 1,000 admissions), CHF
(29 percent decrease, from 44.4 to 31.4 deaths per 1,000 admissions), and stroke (27 percent
decrease, from 112.6 to 82.6 deaths per 1,000 admissions). The inpatient mortality rate for
all four conditions decreased among both younger and older patients, and among men and
women.

Quality
• Medical Research: What should clinicians and patients take away from your report?
• Dr. Heslin: The reductions in inpatient mortality rates reported by this brief suggest that
hospitals are improving care for these conditions. This explanation is supported by other
work on the quality of inpatient care for AMI, CHF, and pneumonia. Specifically, Nuti and
colleagues (2015) analyzed data on more than 4,000 hospitals over the 2006-2011 period and
ranked hospitals by their performance on evidence-based process of care measures, with a
quality score of 100 being equal to perfect performance. Over this period, hospital
performance on all measures improved. There was a decreasing difference between the
quality scores of hospitals ranked at the 90th percentile and those of hospitals ranked 10th
percentile. The variation between hospitals at these percentiles decreased from a 9% to 2%
absolute difference for AMI, a 25% to 8% difference for congestive heart failure, and a 20% to
7% difference for pneumonia in 2006 and 2011, respectively.

Quality
• Medical Research: What recommendations do you have for future research as a result of
this study?
• Dr. Heslin: Future research to better ascertain the reasons for these reductions in inpatient
mortality could inform not only improvements in the clinical management of these
conditions, but also the development and modification of relevant health policies. Given the
dramatic decline in the number of Americans without health insurance since 2013 (Cohen
and Martinez, 2015), one of the most important areas for future research is to assess the
impact of the insurance coverage expansions made possible by the Affordable Care Act on
hospitalization rates and outcomes for these four conditions.
• References
• Cohen RA, Martinez ME. Health Insurance Coverage: Early Release of Estimates from the
National Health Interview Survey, January–March 2015. Centers for Disease Control and
Prevention, National Center for Health Statistics, National Health Interview Survey, 2010–
2015.

MMR Vaccination May Not Be Reliable in HIV+ Children
MedicalResearch.com Interview with: George K Siberry, MD, MPH, Medical Officer
Maternal and Pediatric Infectious Disease (MPID) Branch
Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health
Bethesda, MD
• Medical Research: What is the background for this study?
• Dr. Siberry: Vaccines may not work as reliably in children with HIV infection, especially when
their HIV is not under effective treatment. Today, most children in the United States who
were born with HIV infection are receiving effective HIV treatment and have reached school
age or even young adulthood. However, many received their childhood vaccines before they
got started on their HIV treatment (because modern HIV treatments weren’t available when
they were very young or their HIV infection was diagnosed late). So we wanted to see if these
older children still had immunity from the vaccines they received when they were much
younger.

Bethesda, MD
• Medical Research: What are the main findings?
• Dr. Siberry: We looked specifically at whether older children with HIV since birth were
protected against measles, mumps, and rubella, the three viral infections covered by the
measles-mumps-rubella (or MMR) vaccine. We found that 1/3 up to almost 1/2 of these
children were not protected against these viruses, even though nearly all of the children had
received at least 2 MMR doses, as recommended. And even if their HIV was currently under
excellent control. When we analyzed factors that were linked to being protected, we found
that one of the most important factors was whether you got your MMR vaccine
doses after you got on good treatment for your HIV infection. For instance, over 85% of
children who had gotten at least 2 MMR vaccine doses after being on effective HIV treatment
were protected against measles compared to less than half of those who didn’t get both of
their MMR vaccine doses while on effective HIV treatment.

Bethesda, MD
• Dr. Siberry: For clinicians caring for people (children and young adults) who were born with
HIV infection, it is important to review each patient’s medical record to determine the dates
the MMR vaccines were given and the date when effective HIV treatment was started. If 2
MMR vaccines were given at least 3 months after effective HIV treatment was started, then
that patient should be protected against measles, mumps and rubella. But MMR vaccine
doses given prior to at least 3 months of effective HIV treatment should be repeated now
(while the patient is on effective HIV treatment) to make sure the patient is protected against
these viral infections. This practice is consistent with the current recommendations from the
CDC for measles immunization in people born with HIV infection.

Bethesda, MD
this study?
• Dr. Siberry: We noted that the levels of protection were much higher (e.g., 85% for measles)
in HIV-infected children who got their MMR doses while on effective HIV treatment but still
not as high as the >95% of healthy children protected after 2 doses of MMR. We would like to
find strategies that further improve MMR vaccine response in HIV-infected children.
• We are also interested in determining if this approach for determining which HIV-infected
children need additional MMR vaccine doses may also apply to other childhood vaccines.
• Citation:
• George K. Siberry, Kunjal Patel, William Bellini, Brad Karalius, Murli Purswani, Sandra K.
Burchett, William A. Meyer III, Sun Bae Sowers, Angela Ellis,and Russell B. Van Dyke For the
Pediatric HIV AIDS Cohort Study (PHACS)
• Immunity to Measles, Mumps and Rubella in US Children with Perinatal HIV Infection or
Perinatal HIV Exposure without Infection
• Clin Infect Dis. 2015 Jun 9. pii: civ440. [Epub ahead of print]

Biopolymers from Algae May Provide Broad Spectrum Photoprotection
Susana C. M. Fernandes, PhD Researcher (Individual Marie Curie Fellowship – IEF) and
Professor Vincent Bulone
• MedicalResearch: What is the background for this study? What are the main findings?
• Response: We have exploited unique properties of natural compounds to develop novel
materials that are capable of absorbing both UV-A and UV-B radiations. The active UV-
absorbing molecules are known as mycosporines and mycosporines like-amino acids and they
occur in different organisms such as algae, photosynthetic bacteria (cyanobacteria) and some
fish species that thrive in, e.g., the tropical waters of the Great Barrier Reef. These
compounds were combined with a carbohydrate polymer found in the shells of crustaceans,
the exoskeleton of insects and the cell walls of fungi. Chitosan provided a matrix on which
mycosporines were attached using a simple chemical method already used for other
purposes in, e.g., the pharmaceutical industry. Chitosan can typically be extracted from food
waste such as the shells of shrimps. The immobilization of mycosporines on chitosan allowed
the development of unique materials that have many potential applications relevant to a
wide range of sectors, including cosmetics, sunscreen creams, wound dressings, plasticizers
in paints and varnishes, coatings of outdoor furniture and other materials such as fabrics for
shades, textiles, car dashboards, etc. In addition to being highly efficient for protection
against UV-A and UV-B, the materials were shown to be photostable, thermoresistant and
biocompatible. Compared to existing sunblock formulations, the materials have no
detrimental effects on health and the environment. They are also fully recyclable.

• MedicalResearch: What should clinicians and patients take away from your report?
• Response: The materials we have generated can be applicable to different biomedical areas.
They are compatible with cell proliferation and adhesion with no cytotoxic or allergenic
effect. They are therefore ideal for human use and can be exploited for tissue regeneration in
humans. Biomedical applications comprise the engineering of artificial skin, contact lenses,
artificial cornea, and so on. They can be further modified by other bioactive compounds to
generate multifunctional materials in different forms, that is, films, sprays, solutions,
hydrogels and 3D scaffolds. The materials we have generated are highly relevant to patients
with photopathologies (e.g., albinos) in which the lack of skin pigmentation makes the
organism more susceptible to sunburn and skin cancers.

• MedicalResearch: What recommendations do you have for future research as a result of
this study?
• Response: Development toward commercialization requires the actual assessment of more
developed materials for their specific targeted applications. For instance, in the next phase,
we will prepare physical creams, hydrogels and other forms of the materials, and evaluate
the potential for commercialization by further assessing their advantages over existing
materials through experiments specifically relevant to the desired applications.
• The concept will be extended to the modification of other biopolymers and to the generation
of multifunctional materials, thereby increasing the range of products and potential areas of
application.
• Citation:
• Exploiting Mycosporines as Natural Molecular Sunscreens for the Fabrication of UV-
Absorbing Green Materials ACS Appl. Mater. Interfaces, 2015, 7 (30), pp 16558–16564
• DOI: 10.1021/acsami.5b04064
• Susana C. M. Fernandes, Ana Alonso-Varona , Teodoro Palomares , Verónica Zubillaga , Jalel
Labidi ‡, and Vincent Bulone

Hospital Mortality Outcomes Differ After Lung Cancer Surgery Complications
MedicalResearch.com Interview with: Tyler Grenda, MD House Officer VI Section of General Surgery Department of Surgery
University of Michigan
• Medical Research: What is the background for this study? What are the main findings?
• Dr. Grenda: The main purpose for this study was to better understand the factors underlying
differences in mortality rates for hospitals performing lung cancer resection. The
methodology we used included only the highest and lowest mortality hospitals (Commission
on Cancer accredited cancer programs) so the sampling frame was specific. There are wide
variations in mortality rates across hospitals performing lung cancer resection (overall
unadjusted mortality rates were 10.8% vs. 1.6%, respectively.

• Dr. Grenda: To better understand the factors that may underlie differences in mortality rates,
we examined adherence to perioperative processes of care (e.g. adherence to venous
thromboembolism prophylaxis) and outcomes following surgery between high mortality
hospitals (HMHs) and low mortality hospitals (LMHs). While there were variations in
adherence to some evidence-based perioperative processes of care, those variations did not
translate to differences in directly related complications. In fact, there was no significant
difference in complication rates between HMH and LMHs. However, we found that failure to
rescue rates (or case fatality rates—deaths that occur after complications) explain much of
the differences in mortality rates between HMHs and LMHs.

this study?
• Dr. Grenda: Further investigation is needed to better understand the main factors related to
the development of complications with a focus on their subsequent management. We need
to improve our understanding of why there are differences in rates of failure to rescue.
• Citation:
• Grenda TR, Revels SL, Yin H, Birkmeyer JD, Wong SL. Lung Cancer Resection at Hospitals With
High vs Low Mortality Rates JAMA Surg. Published online August 12, 2015.
doi:10.1001/jamasurg.2015.2199.

Increased Indoor Tanning Among Gay/Bisexual Men Raises Skin Cancer Risk
MedicalResearch.com Interview with: Howa Yeung, MD PGY3, Emory Dermatology
Emory University
• Dr. Yeung: Indoor tanning is a well-established and preventable cause for melanomas and
non-melanoma skin cancers. Public health efforts in curbing indoor tanning have focused on
known high-risk populations, such as young, college-aged, White women. However, other
demographic risk factors for indoor tanning remain unknown.
• As our nation increasingly focuses on addressing and improving the health of lesbian, gay,
bisexual, and transgender (LGBT) individuals, more and more evidence demonstrates that
various LGBT subpopulations face higher rates of cancer-related behavior risk factors, such as
smoking, alcohol use, obesity, etc. We wanted to find out whether risk factors for skin cancer,
such as indoor tanning, disproportionately affected LGBT populations.
• Our study showed higher rates of indoor tanning among gay and bisexual men, with 1.8-fold
and 3.6-fold higher odds of tanning bed use within the past year, compared to straight men,
after adjusting for sociodemographic factors. Disparities in frequent tanning, defined as using
tanning bed 10 or more times within the past year, are even more prominent among gay and
bisexual men. In contrast, no significant sexual orientation disparities were noted among
women after adjusting for sociodemographic factors.

Emory University
• Dr. Yeung: Indoor tanning among gay and bisexual men is significant and underappreciated
problem, with rates approaching those among other known high-risk demographic groups.
These results call for critically needed clinical a

Emory University
this study?
• Dr. Yeung: We hope our study will encourage further research on skin health among LGBT
individuals. Future studies should delineate the burden of skin cancer and its modifiable risk
factors among LGBT individuals. In addition, specific mediators for indoor tanning among gay
and bisexual men should be examined, in order to develop targeted interventions that
address the root causes of disparities.
• Citation:
• Yeung H, Chen SC. Sexual Orientation and Indoor Tanning Device Use: A Population-Based
Study. JAMA Dermatol. Published online August 05, 2015.
doi:10.1001/jamadermatol.2015.2038.

Several Modifiable Risk Factors for Alzheimer’s Disease Identified
MedicalResearch.com Interview with: Jin-Tai Yu MD, PhD
Memory and Aging Center, Department of Neurology University of California San Francisco
San Francisco, CA 94158
• Response: The number of dementia cases in the whole world was estimated to be 35.6
million in 2010 and this number was expected to almost double every 20 years, to 65.7
million in 2030 and 115.4 million in 2050. The global prevalence of dementia was 5-7% and
Alzheimer’s disease accounts for roughly 60%. This data means that we are facing an
increasing number of global populations of this specific neurodegenerative disease and also
the heavy burden brought by it.
• Data from the website of global clinical trials (http://clinicalTrials.gov) showed that a total of
1,732 clinical trials for Alzheimer’s disease were under way. However, the previous results are
not so optimistic, possibly due to the complex etiological mechanisms. In one word, we had
currently no effective drugs for this disease. Figuring out how to effectively prevent its
occurrence is increasingly attracting people’s attentions.Therefore, we have done the most
extensive and comprehensive systematic review and meta-analysis to date, which employs a
full-scale search of observational studies to calculate effect sizes and grade the evidence
strength of various modifiable risk factors for this disease. We hope these results will be
informative and instructive.

We systematically searched PubMed and the Cochrane Database of Systematic Reviews from
inception to July 2014, and the references of retrieved relevant articles. We included prospective
cohort studies and retrospective case–control studies. 16,.906 articles were identified of which
323 with 93 factors met the inclusion criteria for meta-analysis. In addition, we assigned three
grades of evidence in support of the conclusion according to two elements including the pooled
sample size and heterogeneity: ‘grade I evidence’ was defined as both pooled population >5000
and lower heterogeneity (I2<50%); ‘grade II-A evidence’ was defined as pooled population >5000
but with higher heterogeneity (I2≥50%); ‘grade II-B evidence’ was defined as lower heterogeneity
(I2≥50%) but with pooled population <5000; ‘grade III evidence’ was defined as both pooled
population <5000 and higher heterogeneity.

Eleven risk factors with grade I evidence included heavy smoking, low DBP, high BMI in midlife,
carotid atherosclerosis, DM-2 in Asian population, low BMI, low educational attainment, high
tHcy level, depression, SBP > 160mmHg and frailty; and 2 risk factors with grade II-A evidence
included current smoking in Asian population and neuroticism. Our study also found that 23
protective factors for Alzheimer’s Disease (Grade I evidence: coffee/caffeine drinking, high folate
intake, cognitive activity, high vitamin E intake, high vitamin C intake, current statin use, arthritis,
light-to-moderate drinking, ever use of estrogens, anti-hypertensive medications, NASIDs use,
high BMI in late-life, et al.; Grad II-A evidence: healthy dietary pattern, fish consumption, high
education and physical activity). Given that most of the studies included in the meta-analysis are
case-control studies, what is seen here is an association rather than a direct cause and effect
relationship between any one factor and Alzheimer’s risk.

• Response: Our study found that individuals would benefit from addressing the related
potentially modifiable factors. Effective interventions in diet, medications, biochemical
exposures, psychological condition, preexisting disease and lifestyle might decrease new
incidence of Alzheimer’s Disease.

this study?
• Response: Given that, as yet, there is no cure forAlzheimer’s Disease. Our study indicates that
Alzheimer’s Disease might be preventable by effectively addressing the identified modifiable
factors. More prospective cohort studies are necessary for clearing the exact direct
relationship between the related modifiable risk factors and Alzheimer’s risk and exploring
the possibility of preventing Alzheimer’s Disease by effectively addressing the identified
modifiable factors.
• Citation:
• J Neurol Neurosurg Psychiatry. 2015 Aug 20. pii: jnnp-2015-310548. doi: 10.1136/jnnp-2015-
310548. [Epub ahead of print]
• Meta-analysis of modifiable risk factors for Alzheimer’s disease.
• Xu W1, Tan L2, Wang HF3, Jiang T3, Tan MS1, Tan L4, Zhao QF1, Li JQ1, Wang J1, Yu JT5.

Research Into Many Skin Diseases Receives Too Little NIH Funding
MedicalResearch.com Interview with: Erika Hagstrom, M.D., M.A. Preliminary Internal Medicine PGY-1
Loyola University Medical Center
• Dr. Hagstrom: Allocation of funding dollars to research is a critical and daunting task. While
many factors may impact research-funding decisions, establishing a transparent priority-
setting exercise is paramount. This is particularly important for the National Institutes of
Health, which invests over $30 billion for medical research each year. Diseases that have the
greatest impact on our population warrant increased research dollars to reduce disease
burden. The Global Burden of Disease Study (GBD) is an epidemiological effort to quantify
the global burden of disease in a universal metric called disability-adjusted life years (DALYs).
Focusing on our particular interest of dermatology, we investigated the 2012-2013 NIH
funding for 15 skin diseases and matched this to the corresponding DALY metrics.

Research Into Many Skin Diseases Receives Too Little NIH Funding
MedicalResearch.com Interview with: Erika Hagstrom, M.D., M.A. Preliminary Internal Medicine PGY-1
Loyola University Medical Center
this study?
• Dr. Hagstrom: We hope that our investigation demonstrates the usefulness of high-quality
disease burden metrics to inform priority-setting decisions for any funding center.
• Citation:
• J Am Acad Dermatol. 2015 Sep;73(3):383-391.e1. doi: 10.1016/j.jaad.2015.04.039. Epub
2015 Jun 4.
• Comparing cutaneous research funded by the US National Institutes of Health (NIH) with the
US skin disease burden.
• Hagstrom EL1, Patel S2, Karimkhani C3, Boyers LN4, Williams HC5, Hay RJ6, Weinstock
MA7, Armstrong AW8, Dunnick CA9, Margolis DJ10, Dellavalle RP11.

Spinach Bleach Contours May Prevent Adequate Decontamination
MedicalResearch.com Interview with: Nichola Kinsinger, Ph.D Postdoctoral Researcher, Chemical & Environmental Engineering
University of California, Riverside
USDA National Institute for Food and Agricultural Postdoctoral Fellow
DoD Office of Naval
• Dr. Kinsinger: Outbreaks observed in produce are becoming increasing common possibly due
to contaminated irrigation waters or contaminated waters used during processing. In 2006
California had spinach-borne E. coli outbreak that impacted 26 states and 200 confirmed
sickened. Leafy greens account for 20% of the outbreaks alone and are of increased concern
since they are frequently consumed raw. These outbreaks drew our attention over the past
few years and we started applying methods originally developed for studying bacterial
adhesion on engineered surfaces to the issue of food safety. Although food safety is a new
area of study for our lab, the project is based upon the concept of pathogen adhesion
transport which has been the focus of my advisor’s lab for many years previously. Rather
than the previous scenario looking at pathogen interaction with engineered or mineral
surfaces, we are looking at a spinach leaf instead.

DoD Office of Naval
We are using a parallel plate flow chamber system developed by Professor Sharon Walker to
evaluate the real time attachment and detachment of the pathogens to the spinach epicuticle
layer (surface layer of the leaf) in realistic water chemistries and flow conditions. Subsequently
we can evaluate the efficacy of the rinsing process to kill the bacteria that may remain on the
leaf. Initially we were finding that at low concentrations of bleach, bacteria will detach from the
leaf surface allowing for potential cross-contamination later in the process. However above
500ppb we observed 100% of the attached bacterial cells are killed.

DoD Office of Naval
So how in commercial rinsing operations that use bleach concentration ranging from 50-200ppm
result in outbreaks? Through this study we analyzed the topography of the leaf and modeled the
concentration gradient across the surface of a leaf based on commercial rinsing practices. We
found that even at high bleach concentrations within rinse water result in low bleach
concentrations at the leaf surface on the order of 5-1000 ppb bleach, which in our study has
shown to that the bacteria can survive when attached to the leaf and/or detach causing concern
for cross-contamination. In this case the very disinfection processes intended to clean, remove,
and prevent contamination was found to be a potential pathway to amplifying foodborne
outbreaks.

DoD Office of Naval
this study?
• Dr. Kinsinger: The work presented at the conference is part of an ongoing effort in my
advisor’s lab. The work will continue to look at a broader range of foods, engineered
surfaces, and pathogen types.
• Citation:
• 250th American Chemical Society National Meeting & Exposition discussing:
• “Is our salad safe? Efficacy of disinfection techniques to decontaminate spinach leaves and
reduce cross-contamination”

Early Life Intelligence Linked To Better Physical Fitness in Middle Age
MedicalResearch.com Interview with: Rikke Hodal Meincke PhD student
Center for Healthy Aging and the Department of Public Health
University of Copenhagen
• Response: A sufficient level of physical capability is a precondition for maintaining
independence and quality of life. Physical capability can be assessed objectively by tests of
physical performance, for instance handgrip strength, chair-rising and postural balance.
Physical performance is associated with mortality and disability in late life, so gaining insights
into the variance in physical performance is important to promote sustained physical
capability and prevent disability. Research has previously found physical activity, health status
and socioeconomic position to be associated with physical performance. In addition, early life
factors, such as childhood SEP, have been found to be associated with measures of physical
performance later in life. The objective of our study was to examine the association between
intelligence in early adulthood and midlife physical performance in Danish men.

If an association between intelligence in early life and midlife physical performance exists it may
indicate that cognitive abilities and physical performance share some of the same
neurodevelopmental processes, but may also indicate that intelligence has an independent effect
on later physical performance through various pathways.

• Response: In our study of more than 2800 Danish men, we found positive associations
between intelligence in early adulthood and five objective measures of physical performance
in midlife independent of other early life factors. A one standard deviation increase in
intelligence score resulted in 1.1 more chair-rises in 30 seconds, a 1 cm higher jump, a 3.7%
smaller balance area, a 0.7 kg increase in handgrip-strength, and a 0.5 kg increase in lower
back force.

• Response: This knowledge can be used in the development of interventions which should be
designed to address people with different cognitive abilities. Furthermore, policy-makers and
scientists should bear in mind that the prevention of mobility limitations in midlife might
need to start early in life.

this study?
• Response: Future research should look into the mechanisms behind the association between
intelligence and physical performance, for instance if physical activity or other lifestyle factors
mediate the relationship. When the mechanisms are better understood, interventions aiming
to prevent mobility limitations should incorporate this knowledge.
• Citation:
• H. Meincke, M. Osler, E. L. Mortensen, A. M. Hansen. Is Intelligence in Early Adulthood
Associated With Midlife Physical Performance Among Danish Males?Journal of Aging and
Health, 2015; DOI:10.1177/0898264315594139

Extent of Liver Damage May Be Underestimated In Hepatitis C Patients
MedicalResearch.com Interview with: Stuart Gordon, M.D.
Director of Hepatology at Henry Ford Hospital
Detroit, Michigan
• Dr. Gordon: The U.S. Centers for Disease Control and Prevention’s Division of Viral Hepatitis
estimates 2.7 to 3.9 million people in the United States currently suffer from chronic hepatitis
C. But, unfortunately, many of these patients may be unaware of the severity of their liver
damage. We looked at evidence of cirrhosis among hepatitis C patients by examining four
different parameters: ICD9 codes; liver biopsy reports; evidence of liver failure; and the FIB-4
test, an easily calculated biomarker. By using all four indicators of cirrhosis, we found a far
higher prevalence of cirrhosis than would be indicated by any one method.

Detroit, Michigan
• Dr. Gordon: Presence of cirrhosis in hepatitis C may be hidden or not easily recognizable; is
often asymptomatic in its early form; and may require a high degree of suspicion in order to
diagnose.

Detroit, Michigan
this study?
• Dr. Gordon: Studies that rely on diagnostic codes or biopsies performed in routine care for
evidence of cirrhosis may be underestimating the extent of cirrhosis, which is a leading cause
of death in the United States. Future research should investigate the value of indirect markers
of cirrhosis. This could result in earlier diagnosis and prevention of liver disease
complications.
• Citation:
• Stuart C Gordon, Lois E Lamerato, Loralee B Rupp, Scott D Holmberg, Anne C Moorman,
Philip R Spradling, Eyasu Teshale, Fujie Xu, Joseph A Boscarino, Vinutha Vijayadeva, Mark A
Schmidt, Nancy Oja-Tebbe, Mei Lu. Prevalence of Cirrhosis in Hepatitis C Patients in the
Chronic Hepatitis Cohort Study (CHeCS): A Retrospective and Prospective Observational
Study. The American Journal of Gastroenterology, 2015; 110 (8): 1169
DOI: 10.1038/ajg.2015.203

Protein Irisin Linked to Muscle Wasting and Atherosclerosis in Dialysis Patients
MedicalResearch.com Interview with: Tae-Hyun Yoo MD PhD
Department of Internal Medicine, College of Medicine
Severance Biomedical Science Institute, Brain Korea 21 PLUS
Yonsei University, Seoul, Korea
• Dr. Tae-Hyun Yoo: Sarcopenia, reduction in muscle mass, is frequently observed in PEW and
is prevalent in chronic kidney disease (CKD) patients. In ESRD patients, sarcopenia is
significantly associated with greater mortality. Skeletal muscles produce and release
myokines, which suggested to mediate their protective effects. Irisin, a novel myokine, has
been introduced to drive brown-fat-like conversion of white adipose tissue and has beneficial
effects of skeletal muscle on energy homeostasis and glucose metabolisms. Therefore, we
hypothesized that irisin had significant association with sarcopenia and cardiovascular
disease in dialysis patients. In peritoneal dialysis patients, serum irisin was positively
correlated with mid-arm muscle circumference and thigh circumference. In addition, serum
irisin was a significant independent predictor for carotid atherosclerosis even after
adjustment for high-sensitivity C-reactive protein in these patients. This study demonstrated
that serum irisin was significantly associated with sarcopenia and carotid atherosclerosis in
peritoneal dialysis patients.

• Dr. Tae-Hyun Yoo: Malnutrition and chronic inflammation have been proposed to explain the
significant association between sarcopenia and cardiovascular disease in (end stage renal
disease) ESRD population. Lower muscle mass might reflect poor nutritional status and
higher degrees of unopposed inflammation. In addition to these factors, a myokine could be
a contributor. In this study, irisin as a myokine could be helpful for stratifying risk of
sarcopenia and carotid atherosclerosis in peritoneal dialysis patients. In addition, present
study suggested muscle is an another important organ for protection and modulating
cardiovascular diseases in dialysis population.

this study?
• Dr. Tae-Hyun Yoo: A study with follow-up carotid ultrasound and measurement of
anthropometric indices and serum irisin is necessary to clarify the association of irisin,
sarcopenia, and cardiovascular disease. Therefore, the impact of irisin on future
cardiovascular outcomes should be clarified in the future study. The effect of the intervention
using exercise training on irisin, sarcopenia, and cardiovascular disease might be also worth
investigating in dialysis patients.
• Citation:
• Irisin, a novel myokine is an independent predictor for sarcopenia and carotid atherosclerosis
in dialysis patients
• Lee, Mi Jung et al. Atherosclerosis
• Received: February 20, 2015; Received in revised form: July 7, 2015; Accepted: August 6,
2015; Published Online: August 13, 2015
• Publication stage: In Press Accepted Manuscript
• DOI: http://dx.doi.org/10.1016/j.atherosclerosis.2015.08.002

Factors Identified For Lasting Total Hip Replacement
MedicalResearch.com Interview with: Sandrine Colas, MSc, MPH Department of Epidemiology of Health Products
French National Agency for Medicines and Health Products Safety (ANSM)
Saint-Denis, France
• Response: Total hip replacement (THR) is to replace a damaged coxofemoral joint with a
prosthetic implant. Primary or secondary degenerative osteoarthritis of the hip joint is the
main indication for THR (other indications are essentially trauma, which is more common in
the elderly and mostly affects women over 80 years of age). The number of THR has
increased in all industrialized countries, particularly on account of the ageng population.Total
hip replacement is one of the most common and successful surgical procedures in modern
practice. Although results are generally good, revision (consisting in changing one or all
components of the implant) is sometimes necessary (about 1% per year). Prosthetic revision
is a longer and more complex operation than primary implantation and it has a higher
incidence of post-surgical complications.

Saint-Denis, France
• Several prosthetic revision risk factors have been highlighted recently in published studies,
but results relating to prosthetic and/or patient characteristics and total hip replacement
survivorship tend to vary. The existence of an association between the fixation technique
and/or bearing surface and prosthetic survivorship has yet to be established.
• The main aim of our work was therefore to compare total hip replacement short-term
survivorship according to cement type and bearing surface, in a large population of subjects
who have undergone total hip replacement for reasons other than trauma (25%) and bone
tumor (<0.1%), taking prosthetic revision risk factors (age, gender, comorbidities,
concomitant medication, implanting center, etc.) into account.
• Total hip replacement characteristics are related to early implant survivorship. After 33
months of follow-up, antibiotic-impregnated cemented THRs have a better prognosis. MoM
total hip replacemenst have a slightly worse prognosis.

Saint-Denis, France
• Response: These findings are useful in helping surgeons select a total hip replacement
fixation technique and bearing surface, and helpful for both patient and surgeon in the
decision-making process.
• Citation:
• Colas S, Collin C, Piriou P, Zureik M. Association Between Total Hip Replacement
Characteristics and 3-Year Prosthetic Survivorship : A Population-Based Study.JAMA Surg.
Published online August 19, 2015. doi:10.1001/jamasurg.2015.1325.

Noninvasive FFR Study Superior to CT Angiography In Patients With Highly Calcified Coronary Disease
MedicalResearch.com Interview with: Bjarne Linde Norgaard, MD PhD Department of Cardiology, Aarhus University Hospital
Skejby
Aarhus, Denmark
• Dr. Norgaard: Noninvasive fractional flow reserve derived from standard acquired coronary
CT angiography (CTA) (FFRct) in patients with suspected coronary artery disease exhibits high
and superior diagnostic performance when compared to coronary CTA alone in identifying
lesion-specific ischemia (which is the established metric for decision-making on coronary
revascularization). As the presence of coronary calcification may compromise the
diagnostic accuracy and specificity of coronary CTA, this study was performed in order to
investigate the influence of calcification on the diagnostic performance of FFRct in patients
(214) and vessels (333) with suspected coronary artery disease. The main finding in this study
was that FFRct provides high and superior diagnostic performance and discrimination of
ischemia compared with coronary CTA interpretation alone in patients and vessels with high
levels of calcification.

Noninvasive FFR Study Superior to CT Angiography In Patients With Highly Calcified Coronary Disease
MedicalResearch.com Interview with: Bjarne Linde Norgaard, MD PhD Department of Cardiology, Aarhus University Hospital
Skejby
Aarhus, Denmark
• Dr. Norgaard: In the event of good CT image quality, which can be established in most
patients by careful attention to pre-acquisition heart-rate control and use of nitroglycerin,
noninvasive FFRct provides high diagnostic performance in identifying lesion-specific
ischemia in patients and vessels over a wide range of coronary calcification.

Novel DNA Vaccine Provides Protection Against MERS Virus
MedicalResearch.com Interview with: David B. Weiner, Ph.D.
Professor, Department of Pathology and Laboratory Medicine
Chair, Gene Therapy and Vaccine Program, CAMB
Co-Leader Tumor Virology Program, Abramson Cancer Program
University of Pennsylvania, Perelman School of Medicine
• Dr. Weiner: MERS, like the Severe Acute Respiratory Syndrome (SARS), is characterized by
high fever and severe cough from pneumonia. MERS is caused by an emerging human
coronavirus, which is distinct from the SARS coronavirus. Since its identification in 2012,
MERS has been linked to over 1,300 infections and close to 400 deaths. It has occurred in the
Arabian Peninsula, Europe, and in the US and in Asia. It can be spread in a hospital setting.
• Scientists now report that a novel synthetic DNA vaccine can, for the first time, induce
protective immunity against the Middle EastRespiratory Syndrome (MERS) coronavirus in
animal species. Researchers from the Perelman School of Medicine at the University of
Pennsylvania. The NIH, the Public Health agency of Canada, and from a leading company in
the development of synthetic DNA vaccine technology, Inovio described the results in a
paper published their work in Science Translational Medicine (STM) this
week. The experimental, preventive vaccine, given six weeks before exposure to the MERS
virus, fully protects rhesus macaques from disease. The vaccine also generated potentially
protective antibodies in blood drawn from camels, the purported source of MERS
transmission in the Middle East.

• Response: Dr David Weiner, of the Perelman School of Medicine, senior author of the study
described “The significant recent increase in MERS cases, coupled with the lack of effective
antiviral therapies or vaccines to treat or prevent this infection, have raised significant
concern,” Weiner said. “Accordingly the development of a vaccine for MERS remains a high
priority. and the results reported here in this regard are encouraging.”
• The STM study describes a vaccine to prevent disease and control virus replication in an
important primate model of MERS pathogenesis, which was developed by the National
Institutes of Health (NIH). The vaccine was able to prevent MERS disease and offered benefit
to 100 percent of the animals in this study. In addition, the vaccine induced antibodies that
are linked with protection in camels, a species that is thought to be a major source of
transmission to humans from the Middle East, showing that this vaccine could be deployed to
break this this link in the MERS transmission cycle. In the field, say the researchers, this
vaccine could decrease person-to-person spread of infection in the event of an outbreak and
help to protect health care workers or exposed individuals.
• Dr. Muthumani first author of the study described “This simple synthetic vaccine has the
potential to overcome important production and deployment limitations, and what’s more,
the vaccine is non-live, so does not pose a risk of spreading to unintended individuals.”

this study?
• Dr. Weiner: Most importantly the corportate collaborator for this study, Inovio, will move this
program into human testing. Under a previously announced collaboration agreement with
GeneOne Life Science Inc. (KSE: 011000), Inovio’s MERS vaccine product will advance into a
clinical trial in healthy volunteers before the year end. In addition studies of the use of such a
vaccine in a formulation specific for Camels, the animal species associated with transmission
to humans, is continuing.
• Citation:
• Muthumani, D. Falzarano, E. L. Reuschel, C. Tingey, S. Flingai, D. O. Villarreal, M. Wise, A.
Patel, A. Izmirly, A. Aljuaid, A. M. Seliga, G. Soule, M. Morrow, K. A. Kraynyak, A. S. Khan, D. P.
Scott, F. Feldmann, R. LaCasse, K. Meade-White, A. Okumura, K. E. Ugen, N. Y. Sardesai, J. J.
Kim, G. Kobinger, H. Feldmann, D. B. Weiner. A synthetic consensus anti-spike protein DNA
vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in
nonhuman primates. Science Translational Medicine, 2015; 7 (301): 301ra132
DOI:10.1126/scitranslmed.aac7462

Single Vaccine Can Protect Against Six Common Childhood Diseases
MedicalResearch.com Interview with: Gary S. Marshall, M.D. Professor of Pediatrics
Chief, Division of Pediatric Infectious Diseases
Director, Pediatric Clinical Trials Unit
University of Louisville School of Medicine
• Dr. Marshall: The infant immunization schedule has become crowded. That’s great news, in a
sense, because it means that our children have become better protected against more
diseases. At the same time, this has led to well child visits during which many shots are
recommended, and some parents want to limit the number of injections their children
receive at one time. This leads to deferrals, poor timeliness and decreased coverage rates, all
of which could impair protection. This study shows that a hexavalent vaccine—one that
combines diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type b, and hepatitis
B vaccines in one syringe—is safe and just as immunogenic as the currently used component
vaccines.

Single Vaccine Can Protect Against Six Common Childhood Diseases
MedicalResearch.com Interview with: Gary S. Marshall, M.D. Professor of Pediatrics
Chief, Division of Pediatric Infectious Diseases
Director, Pediatric Clinical Trials Unit
University of Louisville School of Medicine
• Dr. Marshall: Pending FDA approval, pediatric practices should have a new option for infant
immunization, one that will allow for fewer shots without compromising protection.
this study?
• Dr. Marshall: The more vaccine antigens that can be combined into single injections the
better, as long as safety and protection are preserved. The performance of higher-valency
combination vaccines cannot be predicted a priori, so the formulations have to be prepared
and the clinical studies have to be done to assess reactogenicity, safety and immunogenicity.
• Citation:
• Immunogenicity, Safety, and Tolerability of a Hexavalent Vaccine in Infants
• Gary S. Marshall, Gregory L. Adams, Michael L. Leonardi, Maria Petrecz,Sheryl A.
Flores, Angela L. Ngai, Jin Xu, Guanghan Liu, Jon E. Stek, Ginamarie Foglia, and Andrew W. Lee
• Pediatrics peds.2014-4102; published ahead of print July 27, 2015,doi:10.1542/peds.2014-
4102

How Do Female Cells Inactivate One X Chromosome?
MedicalResearch.com Interview with: Hendrik Marks Ph.D Group leader Epigenetics of Stem Cells
Radboud University, Department of Molecular Biology, RIMLS
Nijmegen, The Netherlands
• Dr. Marks: In mammals, sex is determined by two so-called “sex” chromosome: males have a
single X chromosome as well as a Y chromosome, whereas females have two copies of the X
chromosome. However, if both X chromosomes were to be active in female cells, these cells
would have a double dosis of X-chromosomal gene products as compared to male cells. As
this is lethal for almost all cells, female cells shut off one X chromosome in every cell in a
process called X inactivation. This process occurs during early embryonic development.

A lot is known about how this process is turned on, but is was unclear how such a silencing
process spreads along a full chromosome. In order to further study this, we used female mouse
embryonic stem cells (mESCs) as a model system and initiated X inactivation by means of
differentiation. With the latest technologies, we were able to keep the two X chromosomes apart
and measure one of them – with its 166 million base pairs (Mbs) – in detail. Every day we
checked which parts of the chromosome had been switched off. The whole process took about
eight days, and the inactivation spreads out from the centre of the X chromosome towards the
ends. That doesn’t happen gradually but moves jumpwise from domain to domain. Domains are
long pieces of DNA (of around 1Mb) that cluster together in knots. As it seems that X inactivation
jumps from domain to domain, we now know that these domains are co-regulated. Also, we
collected strong evidence that the same process is occurring in human.

• Dr. Marks: Our study is very fundamental in nature. It shows how a full chromosome gets
silenced, and it also points towards a very important role of the recently-discovered domains
it this process. However, It is not unlikely that some diseases that are linked to the X
chromosome in female, the so-called X linked diseases, are due to improper spreading across
domains. Thus, in some of these diseases it might turn out very helpful investigating the
domain structure of the X chromosomes, and/or SNPs that present at the borders of the
domains.

this study?
• Dr. Marks: After one of the X chromosomes has been inactivated, it will stay inactive forever.
It would be very interesting to discover why sometimes the one while in other cases the
other X chromosome is inactivated during development. That could help in treating X-linked
diseases – like Rett syndrome and fragile X syndrome in females. Reactivating (part of) the
‘right’ X chromosome could be a potential treatment for these diseases. So one of the next
steps that the field is aiming at is to figure out how to do that, and our current studies
provide new clues for potential strategies.
• Citation:
• ‘Dynamics of gene silencing during X inactivation using allele-specific RNA-seq’
• Hendrik Marks, Hindrik H. D. Kerstens, Tahsin Stefan Barakat, Erik Splinter, René A. M. Dirks,
Guido van Mierlo, Onkar Joshi, Shuang-Yin Wang, Tomas Babak, Cornelis A. Albers, Tüzer
Kalkan, Austin Smith, Alice Jouneau, Wouter de Laat, Joost Gribnau and Hendrik G.
Stunnenberg
• Genome Biology; doi:10.1186/s13059-015-0698-x

Florida’s Drug and Pill Mills Law Reduced Opioids Prescriptions
MedicalResearch.com Interview with: Lainie Rutkow, JD, PhD, MPH Associate Professor
Department of Health Policy and Management
Johns Hopkins Bloomberg School of Public Health
• Dr. Rutkow: Rates of prescription drug diversion and misuse, as well as overdose deaths,
have increased throughout the United States. CDC estimates that each day, 44 people die
from a prescription drug overdose. In the mid-2000s, Florida was viewed as the epicenter of
this epidemic, with prescription drug overdose deaths increasing more than 80% from 2003
to 2009. In response, Florida enacted several laws to mitigate prescription drug abuse and
diversion. Its pill mill law required pain management clinics to register with the state and
prohibited physician dispensing of certain drugs. Florida’s Prescription Drug Monitoring
Program (PDMP) collects data about dispensing of prescription drugs and can be accessed by
physicians and pharmacists. Little is known about how these laws have affected prescribing
of opioids.

We applied comparative interrupted time series analyses to pharmacy claims data to examine
four outcomes related to opioid prescribing in Florida, with Georgia as a comparison state. We
found that in the first year of implementation, Florida’s Prescription Drug Monitoring
Program and pill mill law were associated with modest reductions in prescription opioid volume,
prescriptions written, and the dose per prescription. These declines were statistically significant
among the highest volume prescribers and patients at baseline.

• Dr. Rutkow: Our findings suggest that policy responses to the prescription drug epidemic –
such as Prescription Drug Monitoring Program and pill mill laws – are viable options. Most
prescribers are supportive of policies that limit access to opioids. Given this support, along
with our findings, other states may want to consider implementing both a PDMP and a pill
mill law.

this study?
• Dr. Rutkow: While our study looked at the first year of implementation for these laws, future
research should consider their longer-term effects.
• Citation:
• Rutkow L, Chang H, Daubresse M, Webster DW, Stuart EA, Alexander G. Effect of Florida’s
Prescription Drug Monitoring Program and Pill Mill Laws on Opioid Prescribing and Use. JAMA
Intern Med.Published online August 17, 2015. doi:10.1001/jamainternmed.2015.3931.

Polygenetic Score Predicts Educational Attainment
Ben Domingue
Assistant Professor (starting 9/2015)
Stanford Graduate School of Education
• Response: Earlier research has started to illuminate which genetic variants are associated
with educational attainment. Subsequent work has taken these variants, combined them into
a “polygenic score”, and studied how that polygenic score predicts educational attainment.
Our research continues this line of inquiry by examining the predictive performance of that
polygenic score in a representative sample of US adults who are now in their 30s. A few
notable findings include that:
• (A) the polygenic score predicts educational attainment in the African Americans in our
sample and
• (B) that the polygenic score is associated with neighborhood characteristics. As with earlier
research, we are able to show that the higher score sibling from within a family will complete
more years of schooling (on average) than their lower score co-sib.

Ben Domingue
• Response: Our study adds to the growing body of knowledge about how genetics predict
outcomes that we care about. Although it is unlikely that this score would be used as a basis
for intervention, our results may serve as a useful basis for comparison for those polygenic
scores (e.g., for cardiovascular disease) which may be of clinical utility.

Ben Domingue
this study?
• Response: As a social scientist, my attention will now be shifting towards research focusing
on how the predictive performance of this score may function as a product of the
environment in which a focal individual resides.
• Citation:
• W. Domingue, D. W. Belsky, D. Conley, K. M. Harris, J. D. Boardman.Polygenic Influence on
Educational Attainment: New Evidence From the National Longitudinal Study of Adolescent
to Adult Health. AERA Open, 2015; 1 (3) DOI: 10.1177/2332858415599972

Extreme Obesity Can Cause Kidney Disease Especially In Elderly
MedicalResearch.com Interview with: Dr. Csaba P. Kovesdy, MD
Professor of Medicine University of Tennessee Health Science Center Chief of Nephrology
Memphis Veterans Affairs Medical Center
• Dr. Kovesdy: Obesity has reached epidemic proportions in modern societies, and has been
linked to adverse outcomes such as diabetes mellitus, hypertension, cardiovascular disease
and mortality. In addition, obesity is also associated with chronic kidney disease through a
variety of mechanisms. Our population is ageing, and previous studies have suggested that
the effect of obesity on certain outcomes like mortality may be different in older vs. younger
individuals, but this has not been previously examined for chronic kidney disease. We have
this examined the association of granular BMI categories with progressive loss of kidney
function in a very large cohort of patients with normal estimated GFR in patients of different
ages. We found that the association of a BMI of >30 kg/m2 with progressive loss of kidney
function was not present in younger individuals (< 40 years of age), and increased as people
aged, with >80 years old displaying the strongest associations between obesity and loss of
kidney function. In addition to this we also examined the association of BMI with mortality in
different age groups, and found uniform U-shaped associations that did not vary by age.

Professor of Medicine University of Tennessee Health Science Center
Chief of Nephrology
• Dr. Kovesdy: These results reinforce the widely held notion that extreme obesity can cause
kidney damage. The novelty of these data is that it seems that oldest patients are most prone
to such damage. This may be because ageing kidneys are more vulnerable to any kind of
insult, or because older individuals have been exposed to the ill-effects of obesity for a much
longer time, experiencing cumulative damage.

Professor of Medicine University of Tennessee Health Science Center
Chief of Nephrology
• Medical Research: What recommendations do you have for future research as a result of this
study?
• Dr. Kovesdy: The observational nature of our data does not allow us to make concrete practice
recommendations; that would require clinical trials of weight loss. Our data raises interesting
questions about when weight loss interventions should commence: if the kidney damage in older
individuals is due to the combined effects of age-related changes and obesity-related
pathophysiology, then interventions could be effective at any age, and especially when started in
the oldest individuals. If, on the other hand, kidney damage is more of a function of cumulative
damage experienced over many decades, then interventions started at earlier ages, and maintained
for a long time would be most effective. This dilemma will have to be answered by future
interventional studies.
• Another important practical point is the ideal BMI which is associated with the best clinical
outcomes. In our population this was a BMI of 25-30 kg/m2. This range has been supported by
several other studies in the recent past, and suggests that current guidelines about what an ideal
BMI should be may need to be re-evaluated in certain groups of patients.
• Citation:
• Association of age and BMI with kidney function and mortality: a cohort study
• Jun Ling Lu, MD, Miklos Z Molnar, MD, Adnan Naseer, MD,Margit K Mikkelsen, Prof Kamyar
Kalantar-Zadeh, MD,ProfCsaba P Kovesdy, MD
• The Lancet Diabetes & Endocrinology Published Online: 30 July 2015
• DOI: http://dx.doi.org/10.1016/S2213-8587(15)00128-X

Mental and Physical Health Issues Common In Caregivers of Stroke Survivors
MedicalResearch.com Interview with: Josefine Persson Doctoral student
Institute of Neuroscience and Physiology Sahlgrenska Academy
University of Gothenburg
• Response: Stroke is a major global disease that requires extensive care and support from the
society and the family. We know from previous research that a stroke often has a wide-
spread impact on the daily life of the family. To provide support to a partner is often
perceived as natural and important, but can be demanding and have an impact on the
spouses own health. The situation for spouses as caregivers is well studied during the first
two years after the stroke, while the long-term effects are less well known. By this, we
studied the physical and mental health of 248 spouses of stroke survivors, below age 70 at
stroke onset, seven years after the stroke event and compared our result with 245 spouses of
non-stroke, age- and sex-matched controls.

• Response: The main finding of our study is that caregiver spouses of stroke survivors are at
an increased risk of mental and physical health issues even seven years after stroke onset.
This is the first study with this long period of follow up and the results show that the
restriction on the spouses own activity and social relationships studied in shorter follow up is
also obvious for a large proportion of the spouses in a very long perspective. Spouses’ quality
of life was most adversely affected by their partners’ level of disability, cognitive difficulties
and depressive symptoms.

• Response: The findings of this study suggest the importance for long-lasting, target societal
support to the spouses to prevent or reduce the burden, perceived stress and strain which
might contribute to health benefits, strength to fulfil goals in work and education reduced
risk of disease. In addition, our study indicates that the level of depression and level of
disability of the stroke survivor is associated with the spouses’ physical and mental health,
which strengthens the need for adequate workarounds for rehabilitation and follow-up
including spouses.
• Furthermore, our results also show that the spouses of stroke survivors reported lower
general health than the spouses of controls, which might be due to perceived stress or strain
for a long period, or due to shared lifestyle factors. Hence, it is important for the society to
provide support to prevent or reduce the burden on spouses and health promotion to
prevent unhealthy lifestyle. A societal effort could be aimed to reduce the burden on spouses
and to provide health promotion against an unhealthy lifestyle.

this study?
• Response: The spouses who are at risk are those who experience a supporting role towards
the stroke survivors, especially if the spouses have experienced lack of social support. Further
research is needed to explore the demanding situation for the supporting spouses and to
investigate the quantity of time spent on providing support as well as which components it
contains. A key question is to understand how the caregiver role impacts the spouses own
health and how information and support can positively affect their own health and
cohabitation.
• Citation:
• Spouses of Stroke Survivors Report Reduced Health-Related Quality of Life Even in Long-Term
Follow-Up: Results From Sahlgrenska Academy Study on Ischemic Stroke
• Josefine Persson, Lukas Holmegaard, Ingvar Karlberg, Petra Redfors,Katarina Jood, Christina
Jern, Christian Blomstrand, and Gunilla Forsberg-Wärleby
• Stroke. 2015;STROKEAHA.115.009791published online before print August 20
2015, doi:10.1161/STROKEAHA.115.009791

Fortunately, Good Moods Are Contagious But Depression Is Not
Edward Hill PhD student Centre for Complexity Science
Member of the Warwick Infectious Disease Epidemiology Research Centre (WIDER)
at the University of Warwick
• Response: Depression is a major public health concern worldwide. We know social factors,
such as living alone, can influence whether someone becomes depressed. We also know that
social support (having people to talk to) is important for recovery from depression.
• Our study is slightly different as we looked at the effect of being friends with people on
whether you are likely to develop depression or recover from being depressed. To do this, we
looked at over 2,000 adolescents in a network of US high school students to see how their
mood influenced each other.

• Response: Our study revealed that having mentally healthy friends can help someone recover
from depression or even remain mentally healthy in the first place. But crucially, having
depressed friends does not make you more likely to become depressed yourself. In other
words, it is healthy mood that spreads through social networks but depression does not.
• In particular, an individual with healthy mood having five or more friends with a healthy
mood can halve their probability of developing depression over a six-to-12 month period,
compared to those with no friends with healthy mood. Over a similar time period, a
depressed individual having ten healthy-mood friends doubles their probability of recovering
from depression compared to those who have just three such friends.

• Response: A potential way to tackle depression among young people would be to simply
encourage friendships.Having depressed friends does not put an individual at risk of getting
depression themselves, but having healthy friends is both protective and curative. If every
teenager had more friends it could go some way to providing them with a protective effect
against mental health problems. This also supports the idea that depression should be a
public health issue rather than an individual one and should be used to help counter the
stigma attached to the condition.

this study?
• Response: In the context of mood, it is important to stress that we do not believe that the
analogy with viral spreading is literally true, but rather that it emerges from the behaviour of
a complex social system. Future work could therefore try to look in more detail at how
different aspects of mood are influenced by friends to understand this phenomenon better.
• Furthermore, our methods could be used in other areas of public-health importance,
investigating if smoking or obesity spreads for example.
• Citation:
• Spreading of healthy mood in adolescent social networks
• E. M. Hill, F. E. Griffiths, T. House
• Published 19 August 2015. DOI: 10.1098/rspb.2015.1180

Chemotherapy and Radiation For Brain Cancer Lead To Brain Shrinkage
MedicalResearch.com Interview with: Jorg Dietrich, MBA MMSc MD PhD
Director, Cancer & Neurotoxicity Clinic and Brain Repair Research Program
Massachusetts General Hospital Cancer Center Assistant Professor of Neurology
Harvard Medical School
• Dr. Dietrich: Understanding the adverse effects associated with cancer therapy is an
important issue in oncology. Specifically, management of acute and delayed neurotoxicity of
chemotherapy and radiation in brain cancer patients has been challenging. There is an unmet
clinical need to better characterize the effects of standard cancer therapy on the normal
brain and to identify patients at risk of developing neurotoxicity. In this regard, identifying
novel biomarkers of neurotoxicity is essential to develop strategies to protect the brain and
promote repair of treatment-induced damage.
• In this study, we demonstrate that standard chemotherapy and radiation in patients treated
for glioblastoma is associated with progressive brain volume loss and damage to gray matter
– the area of the brain that contains most neurons.
• A cohort of 14 patients underwent sequential magnetic resonance imaging studies prior to,
during and following standard chemoradiation to characterize the pattern of structural
changes that occur as a consequence of treatment.

• Dr. Dietrich: The effects of chemotherapy and radiation on the brain remain poorly
understood. With an increasing number of long-term survivors, it is increasingly important to
better understand how cancer therapy affects the nervous system and to identify patients at
highest risk to develop neurotoxic symptoms.
• The findings from this study should not discourage the use of chemotherapy and radiation, as
these remain the standard of care to fight brain cancer. In contrast, the results from this
study should promote further investigations in this field to minimize the harmful effects of
existing treatments on the brain.
• Importantly, understanding the mechanisms of neurotoxicity will be the basis for
development of more selective therapies designed to avoid harmful effects on normal
tissues, and to improve quality of life of patients.

this study?
• Dr. Dietrich: It remains unclear whether the structural changes that we have observed in our
study are associated with neurocognitive symptoms, such as memory impairment. This is the
subject of ongoing investigations. Future studies will have to demonstrate how structural
changes in the brain are linked to functional outcomes, such as memory problems, cognitive
impairment and mood changes.
• Citation:
• Standard chemoradiation for glioblastoma results in progressive brain volume loss
• Morgan J. Prust, MD, Kourosh Jafari-Khouzani, PhD, Jayashree Kalpathy-Cramer, PhD, Pavlina
Polaskova, MD,Tracy T. Batchelor, MD, Elizabeth R. Gerstner, MD and Jorg Dietrich, MD, PhD
• Published online before print July 24, 2015,
• doi: http:/ / dx. doi. org/ 10. 1212/ WNL. 0000000000001861
• Neurology 10.1212/WNL.0000000000001861

Up to 70% of Marijuana Users Also Use Tobacco With Complex Results
Francesca M. Filbey PhD School of Behavioral and Brain Sciences
Center for Brain Health University of Texas at Dallas
Dallas, TX
• Dr. Filbey: Most studies exclude tobacco users from participating, but 70% of marijuana users
also use tobacco. We were interested in investigating the combined effects of marijuana and
tobacco. Our research targeted the hippocampus because smaller hippocampal size is
associated with marijuana use. We chose to study short term memory because the
hippocampus is an area of the brain associated with memory and learning. The main finding
was surprising. The smaller the hippocampus in the marijuana plus nicotine user, the greater
the memory performance. We expected the opposite, which was true of the non-using
control group.

Dallas, TX
• Dr. Filbey: It is important to note that substances interact with each other, and, therefore,
combined use could lead to complex effects. More research needs to be done to fully
understand the effects of marijuana on the brain. Very rarely are individuals using one type of
substance and it is very difficult to generalize findings from these studies across the board. It
is hard to know what the effects are of marijuana, for instance, if we don’t take into account
other substance use such as tobacco.

Dallas, TX
this study?
• Dr. Filbey: Future studies should consider directly examining the combined effects of these
highly prevalently co-used substances. More research is also needed to further characterize
the relationship between the hippocampus and memory in combined users – for instance
brain connectivity, and the role of other brain regions such as the prefrontal cortex.
• Citation:
• Francesca M. Filbey, Tim McQueeny, Shrinath Kadamangudi, Collette Bice, Ariel
Ketcherside. Combined effects of marijuana and nicotine on memory performance and
hippocampal volume. Behavioural Brain Research, 2015; 293: 46
DOI: 10.1016/j.bbr.2015.07.029

Commercial Brain Training Device Reduces Working Memory
MedicalResearch.com Interview with: Laura Steenbergen, MSc., PhD Candidate Cognitive Psychology at Institute of Psychology
Leiden University
• Response: A recent initiative supported by several eminent research institutes and scientists
calls for a more critical and active role of the scientific community in evaluating the
sometimes far-reaching, sweeping claims from the brain training industry with regard to the
impact of their products on cognitive performance. tDCS is a noninvasive brain stimulation
technique that has developed into a promising tool to boost human cognition. Previous
studies using medical tDCS devices have shown that tDCS promotes working memory (WM)
updating in healthy individuals and patients. The aim of the current study was to investigate
whether the commercial tDCS headset foc.us (v.1), which is easily and freely available to
anyone in the world, does in fact improve cognitive performance, as advertised in the media.
Results showed that active stimulation with the commercial device, compared to sham
stimulation, significantly decreased working memory performance. The device we tested is
just one example of a commercial device that can easily be purchased and, without any
control or expert knowledge, used by anyone. The results of our study are straightforward in
showing that the claims made by companies manufacturing such devices need to be
validated. Even if the consequences of long-term or frequent use of the device are yet to be
demonstrated, our findings provide strong support the important role of the scientific
community in validating and testing far reaching claims made by the brain training industry.

MedicalResearch.com Leading Medical Research Interviews August 24 2015

MedicalResearch.com Leading Medical Research Interviews August 24 2015

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MedicalResearch.com Leading Medical Research Interviews August 24 2015