MedicalResearch.com: Medical Research Exclusive Interviews October 27 2014

MedicalResearch.com
Exclusive Interviews with Medical Research and
Health Care Researchers from Major and Specialty Medical
Research Journals and Meetings
Editor: Marie Benz, MD
info@medicalresearch.com
October 27 2014
For Informational Purposes Only: Not for Specific Medical Advice.

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Patients With Severe Mental Illness Find Supportive Community On YouTube
MedicalResearch.comInterview with:
John A. Naslund, MPH – PhD Student at The Dartmouth Institute for Health Policy and Clinical Practice, Dartmouth College, Hanover, NH
Stuart W. Grande, PhD, MPA – Post–doctoral fellow at The Dartmouth Center for Health Care Delivery Science, Dartmouth College, Hanover,
NH
• Medical Research: What are the main findings of the study?
• Naslund: In this study we explored whether people with severe mental illness such as schizophrenia,
schizoaffective disorder, or bipolar disorder, use a popular social media website like YouTube to
naturally provide and receive peer support. We found that people with severe mental illness use
YouTube to feel less alone and to find hope, to support and to defend each other, and to share
personal stories and strategies for coping with day-to-day challenges.
• Dr. Grande: They also sought to learn from the experiences of others about using medications and
seeking mental health care. YouTube appears to serve as a platform that helps these individuals to
overcome fears associated with living with mental illness, and it also creates a sense of community
among them.
Medical Research: What was most surprising about the results?
• Naslund: What we found most surprising about our findings was that people with severe mental
illness were so open about their illness experiences on a public social media website like
YouTube. We saw that people with severe mental illness did not appear to be concerned about the
risks of openly sharing their personal illness experiences because they really wanted to help others
with similar mental health problems. There was a strong imperative for them to share their
personal stories in order to help others with mental health concerns cope with their illness and to
build an online community based on shared experience.
• Dr. Grande: We also saw that many individuals with severe mental illness immediately defended
each other’s responses and comments on YouTube when “outsiders” made negative or
inflammatory remarks. This seemed to reflect a sense of camaraderie, letting each other know they
would be supported to speak their minds and share highly personal stories.

Patients With Severe Mental Illness Find Supportive Community On YouTube
John A. Naslund, MPH – PhD Student at The Dartmouth Institute for Health Policy and Clinical Practice, Dartmouth College, Hanover, NH
Stuart W. Grande, PhD, MPA – Post–doctoral fellow at The Dartmouth Center for Health Care Delivery Science, Dartmouth College, Hanover,
NH
• Medical Research: What should clinicians and patients take away from your report
• Naslund: We caution clinicians and patients that our research is exploratory, and therefore we cannot draw firm conclusions
about the benefits or harms of naturally occurring peer support on YouTube. Nonetheless, we believe that it is important for
clinicians to be aware that a social media website like YouTube can serve as a platform for naturally occurring peer support
among their patients. Clinicians should also realize that our findings are consistent with how peer support is viewed in mental
health research and practice, which suggests that YouTube or other social media websites might even help to extend the
reach of informal peer support activities between people with severe mental illness.
• Dr. Grande: For patients, YouTube and other social media websites may serve as a community for seeking support, validation,
sharing experiences, or learning from others. It is also important to consider that while many patients may find these social
media websites useful and supportive, they should not substitute the informal advice from peers on YouTube for professional
advice.
• Medical Research: What recommendations do you have for future research as a result of this study?
• Naslund: At this point, our work is exploratory, and it is not possible for us to determine whether YouTube can provide the
benefits of peer support to a wider community of individuals with severe mental illness. We believe that future research is
necessary to better understand what motivates people with severe mental illness to openly share their experiences with
others on YouTube, given the stigma and discrimination associated with mental illness.
• Dr. Grande: We also want to learn whether YouTube might serve as a valuable resource that clinicians could point patients to,
and whether it should become part of regular services recommended for this at-risk population group.
• Naslund: Our research team is currently working on extending this work to better understand the benefits of peer
interactions on social media websites like YouTube among a wider group of people with severe mental illness, and to learn
whether YouTube could be used to deliver services to this patient population.
• Citation:
• Naturally Occurring Peer Support through Social Media: The Experiences of Individuals with Severe Mental Illness Using
YouTube
• John A. Naslund, Stuart W. Grande, Kelly A. Aschbrenner, Glyn Elwyn
PLOS ONE
Published: October 15, 2014 DOI: 10.1371/journal.pone.0110171

Canadian Universal Health Insurance Reduces Racial Disparities in Primary Care Access
Arjumand Siddiqi, Sc.D., Assistant Professor
Departments of Epidemiology and Social and Behavioral Sciences Dalla Lana School of Public Health
University of Toronto Toronto, Ontario Canada
• MedicalResearch: What are the main findings of the study?
• Dr. Siddiqi: The main finding of the study is that, in a society with universal health insurance (Canada),
racial disparities in access to primary care are drastically reduced, with some important exceptions.
•
MedicalResearch: What was most surprising about the results?
• Dr. Siddiqi: We didn’t expect as much parity in access to care across racial groups as our results indicated.
• MedicalResearch: What should clinicians and patients take away from your report?
• Dr. Siddiqi: Our study suggests that clinicians and patients (and indeed, society at large) should support
the implementation of universal access to health care – meaning, a unified system of health care in which
everyone is equally insured – in societies where this has not yet been realized.
• MedicalResearch: What recommendations do you have for future research as a result of this study?
•
• Dr. Siddiqi: Future research should investigate the process through which such universal systems can be
supported and brought about. Future research should also investigate the factors that would lead to
better access amongst sub-populations (most notably, First Nations/Aboriginal groups) who, even in the
face of universal health insurance, experience reduced access to basic primary care.
•
• Citation:
• Racial Disparities in Access to Care Under Conditions of Universal Coverage
• Siddiqi, Arjumand A. et al.
American Journal of Preventive Medicine
Published Online: October 17, 2014
• DOI: http://dx.doi.org/10.1016/j.amepre.2014.08.004

Sleep Apnea Increases Risk of Atrial Fibrillation After Bypass Surgery
Adrian BaranchukMD FACC FRCPC
Associate Professor of Medicine
Director, EP Training Program Queen’s University Kingston, Ontario, Canada
• Dr. Baranchuk: In this study, we investigated whether obstructive sleep apnea increases the
risk of atrial fibrillation after coronary artery bypass surgery. We found the risk to increase by
approximately two-fold for patients with obstructive sleep apnea, suggesting that this disease
is a strong predictor of atrial fibrillation after coronary artery bypass surgery.
• We also found that the risk increases in patients with more severe obstructive sleep apnea.
• This is an important association to explore since atrial fibrillation after coronary artery bypass
surgery increases patient mortality, the risk of stroke, hospital stay, healthcare costs, and has
substantial burden on patients and their families. It is also a common complication of the
surgery, occurring in up to half of the patients. Knowing which factors increase its risk gives
us a better understanding of how to manage it and mitigate its negative consequences.
• Medical Research: What was most surprising about the results?
• Dr. Baranchuk: Factors like age, obesity, and many others can influence the risk of atrial
fibrillation after coronary artery bypass surgery. Some studies we investigated in our
systematic review controlled for these factors, and obstructive sleep apnea became a
stronger risk factor when these study results were pooled.
• This suggests that obstructive sleep apnea independently predicts which patients are more
likely to have atrial fibrillation after coronary artery bypass surgery.

Sleep Apnea Increases Risk of Atrial Fibrillation After Bypass Surgery
Adrian BaranchukMD FACC FRCPC
Associate Professor of Medicine
Director, EP Training Program Queen’s University Kingston, Ontario, Canada
• Medical Research: What should clinicians and patients take away from your report?
• Dr. Baranchuk: Healthcare specialists of multiple disciplines, including cardiologists,
anesthesiologists, and cardiac surgeons should equip themselves with the necessary knowledge
and tools to both recognize and optimally manage obstructive sleep apnea. This can include
screening patients for obstructive sleep apnea using questionnaires, as well as following up to date
guidelines and using the best available evidence to manage it.
• Medical Research: What recommendations do you have for future research as a result of this
study?
• Dr. Baranchuk:We were not able to identify any studies that investigated the effectiveness of
obstructive sleep apnea management strategies on reducing the risk and negative consequences of
atrial fibrillation following coronary artery bypass surgery. This is an appealing research topic to
explore, since it can inform whether managing obstructive sleep apnea, such as using continuous
positive airway pressure, has a positive impact for outcomes in this patient population.
• Citation:
• Obstructive Sleep Apnea as a Predictor of Post Coronary Artery Bypass Graft Atrial Fibrillation: A
Systematic Review and Meta-analysis
Qaddoura, Amro et al.
• Canadian Journal of Cardiology
• Received: September 23, 2014; Received in revised form: October 10, 2014; Accepted: October 13,
2014; Published Online: October 14, 2014
• DOI: http://dx.doi.org/10.1016/j.cjca.2014.10.014

Enterovirus infection Linked to Increased Risk of Childhood Diabetes
MedicalResearch.com Interview with: Dr Tsai Chung-Li
Graduate Institute of Biostatistics, College of Management, China Medical University,Taichung, Taiwan and
Dr. Hsiao-Chuan Lin Department of Public Health, College of Public Health, and Department of Pediatrics,
China Medical University, Taichung , Taiwan
• Response: We conducted a nationwide population-based cohort study that included two groups.
Children with enterovirus infection (aged < 18 years) during 2000-2007 were identified and
followed up until December 31, 2008 or until first occurrence of type 1 diabetes. The group without
enterovirus infection comprised half of all insured children of the same age and without a diagnosis
of enterovirus infection. By use of frequency-matching with sex and birth year, children in the group
with enterovirus were selected from those eligible. This nationwide retrospective cohort study
found:
• type 1 diabetes is positively correlated with enterovirus infection in patients younger than 18 years.
• the incidence rate of type 1 diabetes was lower in the non-enterovirus than the enterovirus group
(4 vs 6 per 100,000 person-years; incidence rate ratio 1.48 [95% CI 1.19, 1.83]).
• children that have been infected with enterovirus are 48% more likely to have developed type 1
diabetes.
• the risk of developing type 1 diabetes is 2.18 times greater among children aged 10 years and older
than among those aged younger than 1 year.
• Response: As this is first epidemiological cohort study examined the association between
enterovirus infection and type 1 diabetes, we were unsure as to whether this association remains
similar among children with atopic diseases. Specifically we postulated that in atopic groups,
deviation of the immune system toward the T helper 2 pathway may confer protective effects that
prevent these patients from developing type 1 diabetes (which is a T helper 1 pathway autoactivity
disease). Because in our study the sample size for children in atopic groups is much smaller
compared with that in non-atopic group and the incidence rate of type 1 diabetes is low, our data
did not have enough power to answer this question.

Enterovirus infection Linked to Increased Risk of Childhood Diabetes
MedicalResearch.com Interview with: Dr Tsai Chung-Li
Graduate Institute of Biostatistics, College of Management, China Medical University,Taichung, Taiwan and
Dr. Hsiao-Chuan Lin Department of Public Health, College of Public Health, and Department of Pediatrics,
China Medical University, Taichung , Taiwan
• Response: The prevention strategy for enterovirus infection should be taken in children who
are likely to be exposed to enterovirus agents.
• Medical Research: What recommendations do you have for future research as a result of
this study?
• Response: To provide experimental evidence, a well-run vaccine trial demonstrating whether
a reduction in EV infection will lead to lower type 1 diabetes is warranted. In addition, our
study have had limited power to detect the association between enterovirus infection and
type 1 diabetes in children with atopic diseases. Future studies need to be well-powered to
determine this association in children with atopic diseases.
• Citation:
• Tsai-Chung Li et al. Enterovirus infection is associated with an increased risk of childhood type
1 diabetes in Taiwan: a nationwide population-based cohort study. Diabetologia, October
2014 DOI: 10.1007/s00125-014-3400-z

PCV13 Vaccine Markedly Protects Elderly Against Community Acquired Pneumonia
Dr. Susanne Huijts – Pulmonary resident
UMC Utrecht | Research physician
UMCU Julius Center for Health Sciences and Primary Care Netherlands
• Medical Research:What are the main findings of the study?
• Dr. Huijts: The CAPiTA trial evaluated the efficacy of the 13-valent pneumococcal conjugate vaccine (PCV13) in adults of 65
years and older. In the per protocol analysis vaccine efficacy of 45.6% was demonstrated for the first episode vaccine type
(VT) pneumococcal community acquired pneumonia (CAP); 45.0% for the first episode of non-bacteremic/ non-invasive
(NB/NI) VT-CAP, and 75.0% for the first episode of VT-invasive pneumococcal disease.
• Dr. Huijts: CAPiTA is the first study to demonstrate the efficacy of pneumococcal vaccination for prevention of VT NB/NI
pneumococcal community acquired pneumonia in older adults.
• Dr. Huijts: PCV13 immunization in patients of 65 years and older prevents 45% against vaccine-type community acquired
pneumonia (VT-CAP) and 75% against VT-IPD.
• Dr. Huijts: The population evaluated in the CAPiTA trial concerned a relatively healthy population, so further evaluation of
the impact of vaccinating less healthy subjects would be interesting. Furthermore there’s much discussion about the impact
of vaccinating young children with PCV13 on the epidemiology of circulating PCV13-serotypes because this might influence
the overall impact of immunizing (all) adults with PCV13. This will vary per country and therefore every country should
monitor the local serotype-distribution.
• Citation:
Community Acquired Pneumonia Immunization Trial In Adults (CAPITA)
• Marc Bonten, MD PhD1,2, Susanne M Huijts, MD2, Marieke Bolkenbaas, MD2, Chris Webber, MD, PhD3, Samantha Gault,
Msc3, William Gruber, MD4, Scott D. Patterson, PhD5, Diederick E. Grobbee, MD, PhD2,6 and CAPiTA study team,
(1)Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, Netherlands, (2)Julius Center for Health
Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands, (3)Pfizer Vaccine Clinical Research,
Maidenhead, United Kingdom, (4)Pfizer Vaccine Clinical Research, Pearl River, NY, (5)Pfizer Vaccine Clinical Research,
Collegeville, PA, (6)Julius Clinical, Zeist, Netherlands
• ID Week 2014
Session: Oral Abstract Session: Adult Vaccines
• Friday, October 10, 2014: 8:30 AM

In Home Medication Errors Common Among Young Children
MedicalResearch.com: Interview with:
Dr. Huiyun Xiang, MD, MPH, PhD Center for Injury Research and Policy The Ohio State University College of Medicine, Columbus, Ohio
Jeb Phillips, BA
Project Specialist, Injury Research and Policy Staff Nationwide Children’s Hospital, Columbus, Ohio
• Response: From 2002-2012, a child younger than 6 years old experienced an out-of-hospital
medication error every 8 minutes. That’s a total of 696,937 during the study period, or
63,358 per year. Almost all happened at the child’s residence. The rate and number of errors
decreased with increasing age.
• Analgesics were the mostly commonly involved medications (25.2%), followed by cough and
cold medications (24.6%). More than 1 in 4 (27%) of the errors happened when a child
inadvertently took or was given medication twice. Errors also happened when children took
or were given an incorrect dose, when medication measurements were confused, and when
the wrong medication was taken or given.
•
• Response: I am not sure about surprising, but the sheer number and frequency of errors was
very interesting.

In Home Medication Errors Common Among Young Children
Dr. Huiyun Xiang, MD, MPH, PhD Center for Injury Research and Policy The Ohio State University College of Medicine, Columbus, Ohio
Jeb Phillips, BA
Project Specialist, Injury Research and Policy Staff Nationwide Children’s Hospital, Columbus, Ohio
• Response: First, it’s possible to reduce these errors. The combined efforts of manufacturers,
the U.S. Food and Drug Administration and groups like the American Academy of Pediatrics to
recommend against the routine use of cough and cold medication in young children greatly
reduced those errors. The same action may be warranted with other medication categories,
including analgesics.
• Parents and caregivers can work to reduce the errors, too. Using measuring cups provided
with liquid medicine instead of kitchen spoons and sticking to a consistent medication
schedule are a good start.
this study?
• Response: Further research should obtain parent and caregiver feedback about the ways
packaging, labeling and dosing devices contribute to errors and address health care provider
communication to low-literacy and non-English speaking caregivers.
• Citation:
• Out-of-Hospital Medication Errors Among Young Children in the United States, 2002–2012
Maxwell D. Smith, Henry A. Spiller, Marcel J. Casavant, Thiphalak Chounthirath,
Todd J. Brophy, and Huiyun Xiang
• Pediatrics peds.2014-0309; published ahead of print October 20, 2014,
doi:10.1542/peds.2014-0309

Alopecia Areata: Enbrel May Improve, or Worsen, Hair Loss
MedicalResearch.comInterview with
Marie C. Leger,MD, PhD
Ronald O. Perelman Department of Dermatology
New York University School of Medicine, New York
• Dr. Leger: Alopecia areata is a T-cell mediated autoimmune disease. As such, there was initially hope that
inhibiting the helper T cell cytokine TNF-α could effectively treat this condition. This has not been shown
to be the case—in fact, one open-label study of etanercept in 17 patients with moderate to severe
alopecia showed no hair regrowth and even worsening of alopecia in several subjects. There have been
many other case reports in the dermatologic literature of TNF-α inhibitors causing alopecia areata. In
contrast, our case report presents a patient who very clearly grew hair on adalimumab—its strength lies in
the fact that her hair loss and regrowth were replicated on withdrawal and rechallenge with the
medication.
• Our patient’s paradoxical response to adalimumab complements other literature suggesting that there are
genetic variations in the way a patient’s immune system responds to TNF-α inhibitors. In different
individuals, these medications can either treat or cause conditions such as psoriasis or lupus. It seems that
this is also the case with alopecia areata.
Medical Research: What recommendations do you have for future research as a result of this study?
• Dr. Leger: Our patient suggests that the inflammatory mechanism involved in alopecia areata is complex
and can vary on an individual level. It is known that single gene polymorphisms in the TNF-α gene region
have been associated with alopecia areata and that genetic polymorphisms can also affect an individual’s
response or non-response to therapy. More research is needed to clarify the inflammatory pathways
involved in alopecia areata as well as to predict which patients may respond to therapy.
• It is notable that our patient also had extensive eczema. Recently it was reported that a patient with
plaque psoriasis and alopecia universalis grew hair on the JAK kinase inhibitor tofacitinib. The efficacy of
tofacitinib to treat alopecia remains to be established via clinical trials. But could the presence of eczema
or psoriasis in a patient predict the way that their immune system responds to biologic therapies?

Alopecia Areata: Enbrel May Improve, or Worsen, Hair Loss
Marie C. Leger,MD, PhD
Ronald O. Perelman Department of Dermatology
New York University School of Medicine, New York
• Dr. Leger: In a patient who has failed first line treatments for alopecia universalis or who has
contraindications to first line therapy it may be worth considering a short trial of
adalimumab. Our patient responded very quickly with very impressive regrowth within 2
months of initiating therapy suggesting that an extensive trial may not be necessary. Of
course patients and physicians need to understand both the risks of immunosuppressant
therapy as well as the possibility that adalimumab may worsen the alopecia.
• Citation:
• Gorcey L, Spratt E, Leger MC. Alopecia Universalis Successfully Treated With Adalimumab.
JAMA Dermatol. Published online October 08, 2014. doi:10.1001/jamadermatol.2014.1544.

Health Insurance, Regular Healthcare Visits Linked To Hypertension Control
Dr. Brent M. Egan MD
Adjunct Professor
Medical University of South Carolina
• Dr. Egan: The study was undertaken to determine progress toward the Healthy People 2020
goals of controlling hypertension or high blood pressure in 61.2% of all adults with the
condition. What we found is that hypertension control has changed very little from 2007
through 2012. In 2011-2012, an estimated 51.2% of all hypertensive adults were controlled,
which is 10% below the 2020 goal. The analysis indicated that healthcare insurance and at
least two healthcare visits yearly were related to both the likelihood that hypertension would
be treated and controlled.
• Dr. Egan: Control of high blood pressure generally requires that individuals are aware of the
hypertension and that aware individuals are treated and treated adults are controlled. All of
these measures showed steady progress from 1999-2000 to 2007-2008 with some
continuation of the upward trend in 2009-2010. However, the 2011-2012 data broke the
upward trend line and were more similar to the 2007-2008 than the 2009-2010 data for
percentage of adults treated and percentage of treated adults controlled. The findings
strongly suggest that new strategies are required to attain the Healthy People 2020 goal for
hypertension control.

Health Insurance, Regular Healthcare Visits Linked To Hypertension Control
Dr. Brent M. Egan MD
Adjunct Professor
• Medical Research: Medical Research: What should clinicians and patients take away from your report?
• Dr. Egan: Among all adults with hypertension, approximately 20% are unaware that they have high blood pressure and
approximately 30% are not treated. Among adults on treatment for high blood pressure approximately 30% are not
controlled.
• The single factor that most strongly predicted treatment and control of hypertension was having at least two medical visits
yearly. In other words, a single annual healthcare check-up is generally not sufficient to properly treat and control
hypertension.
• Healthcare insurance was also positively associated with treatment and control of hypertension.
• Individuals who reported taking treatment for high cholesterol and high blood pressure also more likely to have the
hypertension controlled than individuals who reported taking medication only for their high blood pressure. While this does
not prove that cholesterol treatment lowers blood pressure, the majority of people with high blood pressure also have high
cholesterol. Treatment of both risk factors reduces risk for heart attack and stroke more than treatment for only one of the
risk factors. And, as an added benefit, blood pressure control also appears to be better.
• What recommendations do you have for future research as a result of this study?
Dr. Egan:
• Additional research, especially patient-centered research, is needed to find the best ways to engage more adults in regular
health care, to understand their health risk factors, and to take an active role in receiving health care and medications, when
necessary, to effectively manage risk.
• More research is needed to understand how best to engage more adults with high blood pressure in making lifestyle
changes and taking medications needed to control their hypertension.
• More research is needed to better understand various options for improving blood pressure control without traditional visits
to the doctor’s or another clinician’s office, and to determine which of the options are best for certain groups of patients.
• Citation:
• Hypertension in the United States 1999-2012: Progress toward Health People 2020 GoalsBrent M. Egan, Jiexiang Li, Florence
N. Hutchison, and Keith C. Ferdinand
• Circulation. 2014; published online before print October 20 2014, doi:10.1161/CIRCULATIONAHA.114.010676

No Adverse Effects of Short-Term Daily Egg Ingestion in Coronary Artery Disease
David L. Katz, MD, MPH, FACPM, FACP
Director, Yale University Prevention Research Center
Griffin Hospital
• Dr. Katz: We did not see any adverse effects of short-term, daily egg ingestion in adults with established coronary artery
disease.
• Dr. Katz: Eggs are routinely banned from ‘heart healthy diets.’ in particular eggs are always absent from cardiac care units,
with egg beaters substituting. However, these same units routinely serve products with refined starch and added sugar. The
scientific basis for excluding eggs from diets to improve cardiac health has long been suspect. Here, we show that in the
short term at least, there are no discernible harms of daily egg ingestion even in adults with heart disease.
Medical Research: What should clinicians and patients take away from your report?
• Dr. Katz: Our motivation for this line of research- which includes two prior studies- was that people don’t just remove foods
from their diets; they replace them. So people eating fewer eggs might wind up eating more oatmeal, which might improve
their cardiac health. But they also might wind up eating more donuts and danish, which clearly would not. Our findings, in
context, suggest that eggs can certainly be included in a heart-healthy diet by those so inclined. We have no evidence that
eating eggs reduces cardiac risk, but excluding them might increase it if poor substitutions are made. If eggs are
incorporated into diets as a high-quality protein source, they might replace other foods, such as fatty meats, that are less
heart-healthy. Our on-going work looks at egg inclusion vs. Egg exclusion, and the effects on overall diet quality in general.
• Dr. Katz: That failure to consider food substitutions is a prevailing blind spot in nutritional epidemiology. We need more
research exploring the notion that when we advise people to stop eating x, they may eat more y. So- what is y?- matters a
lot. Similarly, when we tell people to eat y, they may stop eating x. What was x?
• As for eggs, as noted, there is no clear evidence they reduce cardiac risk per se. But the idea that their cholesterol content
means they need to be banished from cardiac-conscious diets is obsolete.
• Citation:
• Effects of egg ingestion on endothelial function in adults with coronary artery disease: a randomized, controlled, crossover
trial
• David Lawrence Katz, Yingying Ma, Yasemin Kavak and Valentine Njike
• (The FASEB Journal. 2013;27:225.6)

Comorbiditites Contribute To Unplanned Hospitalizations Among GI Cancer Patients
Joanna-Grace M. Manzano, MD Assistant Professor Department of General Internal Medicine
Maria E. Suarez-Almazor, MD, PhD Barnts Family Distinguished Professor Chief, Section of Rheumatology &
Deputy Chair, Dept. of General Internal Medicine UT MD Anderson Cancer Center Houston, TX
• Response: Our study established that unplanned hospitalization among elderly patients with
GI cancer are very common – 93 events per 100-person years.
• Certain characteristics were found to have an increased risk for an unplanned hospitalization
in our cohort, namely: older age, black race, advanced disease, higher comorbidity score,
residing in poor neighborhoods and dual eligibility for Medicare and Medicaid. Esophageal
and gastric cancer had the highest risk for unplanned hospitalization among all GI cancer
types.
• Some of the observed reasons for unplanned hospitalization were potentially preventable
and related to the patient’s comorbid illness.
• Response: We found the high rate of unplanned hospitalizations very surprising. We
anticipated that unplanned hospitalizations would be common in our cohort, but 93 events
per 100 person-years is a striking number.

Comorbiditites Contribute To Unplanned Hospitalizations Among GI Cancer Patients
Joanna-Grace M. Manzano, MD Assistant Professor Department of General Internal Medicine
Maria E. Suarez-Almazor, MD, PhD Barnts Family Distinguished Professor Chief, Section of Rheumatology &
Deputy Chair, Dept. of General Internal Medicine UT MD Anderson Cancer Center Houston, TX
• Response: Patients, caregivers and treating physicians (oncologists, primary care physicians and other
treating specialists) should recognize that elderly patients who have GI cancer are vulnerable to unplanned
hospitalizations.
• A high comorbidity score is associated with the highest risk for unplanned hospitalization in our
cohort, and some of the top reasons for unplanned hospitalization are potentially preventable. This
should promote efforts at improving coordination of care among all health care providers involved in a
cancer patient’s care. Patients would likely benefit from continued close follow-up with primary care
physicians and other treating specialists during the initial years after cancer diagnosis.
• Response: Future research should explore if the same patterns we have observed in our cohort hold true
among elderly patients with GI cancer outside of Texas.
• It would be interesting to find out also if regular follow-up with both oncologists and non-cancer providers
during the first years after cancer diagnosis can modify the risk for unplanned hospitalization among
patients with high comorbidity scores.
• Citation:
• Patterns and Predictors of Unplanned Hospitalization in a Population-Based Cohort of Elderly Patients with
GI Cancer
Joanna-Grace M. Manzano, Ruili Luo, Linda S. Elting, Marina George, and Maria E. Suarez-Almazor
• JCO.2014.55.3131; published online on October 6, 2014;
•

Opioid Dependence: Buprenorphine Maintenance May Be Better Than Taper for Treatment Retention
David A. Fiellin, M.D.
Professor of Medicine, Investigative Medicine and Public Health
Yale University School of Medicine
• Dr. Fiellin: The main finding of our randomized clinical trial, conducted in primary care, was that among
prescription opioid dependent patients, ongoing buprenorphine therapy resulted in better treatment
retention and reduced illicit opioid use when compared to buprenorphine taper (detoxification).
•
• Dr. Fiellin: Only 11% of the patients who under went the buprenorphine taper completed the 14 weeks of
treatment. Only 2 of these patients went on to receive naltrexone.
• Dr. Fiellin: Primary care and office-based physicians who are providing buprenorphine treatment to
prescription opioid dependent patients should advise their patients of the superior outcomes with
ongoing maintenance treatment and be cautious about considering or offering tapering doses in the first
2-3 months of treatment. Prescription opioid dependent patients and there family members should be
aware that this condition often requires combined on-going medication, counseling and monitoring in
order to be treated safely and successfully.
• Dr. Fiellin: Future research should focus on improving retention and illicit drug use outcomes among
patients receiving buprenorphine in primary care and office-based settings, and focus on implementation
strategies to increase the uptake of this treatment among a greater number of providers.
Citation:
• Fiellin DA, Schottenfeld RS, Cutter CJ, Moore BA, Barry DT, O’Connor PG. Primary Care–Based
Buprenorphine Taper vs Maintenance Therapy for Prescription Opioid Dependence: A Randomized Clinical
Trial. JAMA Intern Med. Published online October 20, 2014. doi:10.1001/jamainternmed.2014.5302.

Bipolar Disorder: Protective Genetic Discovery May Lead To New Drug Treatment
MedicalResearch.com: Interview with: Edward I. Ginns, MD, PhD, Director
Program in Medical Genetics and
Lysosomal Disorders Treatment and Research Program University of Massachusetts Medical School
Reed Rose Gordon Building, Room 137
Shrewsbury, MA 01545
• Dr. Ginns: Our study identified that sonic hedgehog signaling, an important brain pathway, is
involved in bipolar affective disorder.
• This finding shows a mechanism and provides new targets for drug development. It suggests that
sonic hedgehog signaling can be modulated to help manage bipolar symptoms in adults by using
drugs already being studied in clinical trials for other medical conditions.
• The new findings were uncovered by decades of translational research in the Old Order Amish
families of Pennsylvania, where in a few special families in the Amish Study there is a high incidence
of both bipolar disorder and a rare genetic dwarfism, Ellis van‐Creveld (EvC) syndrome. No person
with EvC had bipolar disorder despite forty years of documented research across multiple
generations, suggesting that the genetic cause of this rare dwarfism was protective of bipolar
affective disorder.
• Dr. Ginns:We connected bipolar disorder to the sonic hedgehog pathway that is known to be
important to brain function and that contains druggable targets.
• Our discovery was essential to integrating pieces of the molecular puzzle. The overriding protective
effect of the genetic mutation in Ellis van‐Creveld syndrome in the Amish led us to an important
brain signaling pathway with potential novel targets for drug development for bipolar disorder. Our
study went beyond finding associations with risk genes. Even though the symptoms of bipolar
affective disorder can be quite varied and complicated, the underlying genetics might actually have
a more simple cause than we could have imagined.

Bipolar Disorder: Protective Genetic Discovery May Lead To New Drug Treatment
MedicalResearch.com: Interview with: Edward I. Ginns, MD, PhD, Director
Program in Medical Genetics and
Lysosomal Disorders Treatment and Research Program University of Massachusetts Medical School
Reed Rose Gordon Building, Room 137
Shrewsbury, MA 01545
• Dr. Ginns: There is hope for bipolar patient that new drugs may be available sooner. For those of us
searching for new ways to treat mood disorders, such as bipolar disorder, the finding of novel
potentially druggable sonic hedgehog pathway targets is very exciting. There hasn’t been a really
new drug treatment for bipolar disorder in decades. Our findings could revolutionize the way we
diagnose and treat the disease.
study?
• Dr. Ginns: This breakthrough should help bipolar disorder research and the search for new
treatments. We are already working with collaborators to unravel more details of the puzzle to
identify changes in the sonic hedgehog signaling and related pathways that correlate with disease
symptoms. We anticipate that additional studies of sonic hedgehog signaling in model systems and
humans will help us gain a better understanding of the underlying biology and more effective
treatments for bipolar and related disorders.
• Citation:
• Disruption of sonic hedgehog signaling in Ellis-van Creveld dwarfism confers protection against
bipolar affective disorder
• E I Ginns, M Galdzicka, R C Elston, Y E Song, S M Paul and J A Egeland
• Molecular Psychiatry , (14 October 2014) | doi:10.1038/mp.2014.118

Even Thin Melanomas Can Be Fatal
Prof. David Whiteman
Group leader, Cancer Control Group QIMR Berghofer
Herston, Queensland
• Dr. Whiteman: Mortality from melanoma has continued to rise in Queensland, Australia, the jurisdiction
with the world’s highest incidence of this disease. We analysed more than 4000 deaths from melanoma
over the last 2 decades, and calculated mortality rates according the thickness of the primary lesion.
• Dr. Whiteman:We found that, contrary to widespread perception, thin melanomas (i.e. those with a good
prognosis) actually accounted for more deaths overall than thick melanomas. This reflects the huge
increases in the incidence of thin melanomas in Queensland, so that even though the individual case
fatality rates for thin melanomas are relatively low, the frequency of these thin cancers means that they
contribute to many deaths.
• Dr. Whiteman: These findings serve to remind us that, as a strategy to reduce melanoma mortality, early
detection of melanoma has its limits. These data confirm that even thin melanomas (i.e. those detected
early) contribute to substantial numbers of deaths from melanoma. A comprehensive melanoma control
strategy must also include primary prevention advice to reduce the incidence of melanomas.
• Dr. Whiteman:We need to identify the genetic and molecular characteristics of those thin melanomas
that are destined to metastasize, as these need to be targeted for higher surveillance and new therapeutic
approaches.
• Citation:
• More people die from thin melanomas (<1mm) than thick melanomas (>4mm) in Queensland, Australia
David C Whiteman, Peter D Baade & Catherine M Olsen
• Journal of Investigative Dermatology doi:10.1038/jid.2014.452

Metformin May Be Protective Against Cancer
Dr. Iris L. Romero MD MS
Associate Professor of Obstetrics & Gynecology, Section of General Gynecology
The University of Chicago Medicine Chicago, IL
• Dr. Romero: There is increasing epidemiologic and preclinical data indicating that the commonly
used diabetic drug, metformin, may have anticancer effects. In ovarian cancer, in 2011 in Obstetrics
& Gynecology we reported that in a retrospective cohort ovarian cancer patients that were using
metformin had increased survival compared to those not using mefomrin. In this study, we expand
on those findings by testing whether metformin can prevent ovarian cancer or improve response to
chemotherapy in mouse models.
• In a prevention study, we found that mice treated with metformin before cancer was initiated
developed less tumor than those treated with placebo. In a treatment study, in vitro, metformin
increased the cytotoxic effect of paclitaxel. In addition, using a genetic mouse model we show that
the combination of paclitaxel plus metformin results in a greater tumor reduction than either drug
used alone.
• Dr. Romero: The molecular mechanism by which metformin protects against cancer is not entirely
clear. An early hypothesis was that metformin activates AMPK, a critical regulator of metabolism in
the cell. When activated AMPK inhibits energy-consuming processes such as fatty acid and protein
synthesis, ultimately resulting in cell death. In this study, like others before us, we show that in
ovarian cancer metformin activates AMPK and alters metabolism in the cancer cell.
• In addition, we report two new effects of metformin in ovarian cancer:
• First, metformin treatment reduced levels of several important receptor tyrosine kinases (RTKs).
Second, metformin inhibited expression of fatty acid binding protein 4 (FABP4). Metformin’s
inhibition of FABP4 was particularly exciting as we reported in 2011 in Nature Medicine that FABP4
plays a key role in ovarian cancer metastasis.

Metformin May Be Protective Against Cancer
Dr. Iris L. Romero MD MS
Associate Professor of Obstetrics & Gynecology, Section of General Gynecology
The University of Chicago Medicine Chicago, IL
• Dr. Romero: Clinicians and patients should be aware of the increasing preclinical research indicating
that metformin may have anticancer effects in several cancer types, including ovarian cancer. The
protective effect of metformin has been reported in the context of prevention as well as adjuvant
treatment. However, while promising, the findings to date do not include prospective clinical trial
testing in patients and therefore do not justify use of metformin as a cancer treatment.
study?
• Dr. Romero: The study reported here adds to the sum of preclinical and epidemiologic data
supporting the hypothesis that metformin may have a protective effect in ovarian cancer and
prospective testing in patients is warranted. In fact, a randomized phase 2 clinical trial is ongoing at
University of Chicago during which newly diagnosed ovarian cancer patients are treated with
metformin or placebo plus standard chemotherapy. After completion of chemotherapy, patients
will continue on metformin or placebo for two years and progression free survival will be evaluated
(PI: S.D Yamada, NCT02122185).
• Citation:
• Metformin inhibits ovarian cancer growth and increases sensitivity to paclitaxel in mouse models
Lengyel, Ernst et al.
• American Journal of Obstetrics & Gynecology
Received: July 20, 2014; Received in revised form: September 25, 2014; Accepted: October 16,
DOI: http://dx.doi.org/10.1016/j.ajog.2014.10.026

CHEST 2014: ECMO CPR May Improve Patient Recovery
MedicalResearch.com Interview with:
Graham Peigh, BA
Thomas Jefferson University
• Response: The main findings of our study show that extracorporeal cardiopulmonary resuscitation
(E-CPR) can provide recovery when a patient is unresponsive to conventional CPR. In our sample of
24 patients, 13 survived ECMO, and 7 were successfully discharged from the hospital. Major meta
analytic studies have shown that in-hospital CPR yields a discharge rate of under 20%, and our
study presents results which demonstrate that E-CPR provides a method by which those survival
figures can be increased. Importantly, our study also showed that vital organ function among ECMO
survivors was maintained. All13 patients had improved or unchanged kidney and liver function, and
12/13 had improved or unchanged metabolic function. After using standard hypothermia protocols,
all seven hospital survivors had full neurological recovery. This study differs from the majority of
other studies on E-CPR because our institution does not have a dedicated E-CPR/Code team
available to perform E-CPR 24/7. We believe that our results are thus generalizable to other
institutions, which, like ours, have the capability to perform E-CPR, but are only able to do so during
on-hours when physicians, perfusionists, and ECMO materials are available.
• Response: We were surprised that the length of CPR did not correlate with ECMO or hospital
survival. A longer duration of CPR tends to be correlated with undesirable outcomes, but this trend
was not observed in our sample. We were also pleasantly surprised with the impressive solid organ
recovery among ECMO survivors, and 100% neurological recovery among hospital survivors. Even
among the patients who died of an anoxic brain injury, two were able to donate organs for
transplant.

CHEST 2014: ECMO CPR May Improve Patient Recovery
Graham Peigh, BA
Thomas Jefferson University
• Response: E-CPR provides a good alternative for patients who require resuscitation and are
unresponsive to conventional CPR. E-CPR can improve the prognosis for these patients who
would otherwise face undesirable outcomes.
this study?
• Response: The majority of E-CPR associated deaths in our sample were neurological in
nature. Further research to determine how to protect a patient’s brain during E-CPR could
improve prognoses. Continuing to look at survival trends with a larger sample size will also be
beneficial.
• Citation:
• Saving Life and Brain With Extracorporeal Cardiopulmonary Resuscitation (E- CPR)
Graham Peigh, BA
Presenter CHEST 2014

CHEST 2014: Breath Test May Become Accurate Enough For Lung Cancer Detection
Peter J. Mazzone, MD, FCCP MPH
Director of the Lung Cancer Program for the Respiratory Institute
Cleveland Clinic
• Medical Research: What are the main findings of this study?
• Dr. Mazzone: There were 2 parts to this study. In the first part we looked at how the breath
collection instrument and sensor were performing and made adjustments to both in order to
optimize its performance.
• In the second part we used the improved device and sensor to see if we could accurately
separate a sensor signal of our patients with lung cancer from those without lung cancer. We
found good separation of lung cancer from non-cancer breath signals, and very good
separation of signals of one type of lung cancer from another.
• We have concluded that a colorimetric sensor array based breath test is capable of
separating those with lung cancer from those without.
• Medical Research: What should patients and clinicians take away from this report?
• Dr. Mazzone: We learned about ways that we can enhance the sensor and breath collection
instrument, and showed enough promise that this can be an accurate test, that we plan to
design a larger study with an improved system in hopes that this will be the final step
towards having a clinically useful test.
• Citation:
The analysis of volatile organic compound profiles in the breath as a biomarker of lung cancer
• CHEST 2014

HER2+ Breast Cancer: Trastuzumab Increased Survival
Edith A. Perez, MD
Mayo Clinic Jacksonville, FL 32224
• Dr. Perez: Our joint analysis of two large prospective trials showed that adding one year of
Trastuzumab to otherwise standard adjuvant chemotherapy significantly improved long term
survival in women with resected HER2+ breast cancer.
• Dr. Perez: Although the Trastuzumab was given for only a year starting around the middle of
chemotherapy, the benefits are long lasting with very few significant side effects.
• Dr. Perez: Science and clinical trials helped us identify a treatment regimen that helps improve
survival for patients who had undergone surgery for HER2+ breast cancer.
study?
• Dr. Perez: Continue to identify biomarkers to best predict efficacy and tolerability.
• Citation:
• Trastuzumab Plus Adjuvant Chemotherapy for Human Epidermal Growth Factor Receptor 2–Positive
Breast Cancer: Planned Joint Analysis of Overall Survival From NSABP B-31 and NCCTG N9831
• Edith A. Perez, Edward H. Romond, Vera J. Suman, Jong-Hyeon Jeong, George Sledge, Charles E.
Geyer Jr, Silvana Martino, Priya Rastogi, Julie Gralow, Sandra M. Swain, Eric P. Winer, Gerardo Colon-
Otero, Nancy E. Davidson, Eleftherios Mamounas, Jo Anne Zujewski, and Norman Wolmark
• JCO JCO.2014.55.5730; published online on October 20, 2014;

Flu Mutations Led To More Disease Among Middle-Aged Adults
Scott E. Hensley, Ph.D.
Assistant Professor, The Wistar Institute
Philadelphia, PA 19104
Dr. Hensley: We found that H1N1 viruses recently acquired a mutation that abrogates binding of influenza antibodies that
are present in a large number of middle-aged adults. We propose that this mutation lead to increased disease among
middle-aged adults during the 2013-2014 influenza season.
• Dr. Hensley: We were surprised this antigenic H1N1 mutation has been largely overlooked and that most surveillance
laboratories have labeled this mutation as ‘antigenically neutral’. Most influenza antigenic studies utilize animal anti-sera,
which fails to recapitulate the types of antibodies that are present in some humans.
• Dr. Hensley: We identified an antibody signature that is present in some middle-aged individuals and we propose that this
type of antibody does not proper fight off recently mutated influenza strains. At this point, our human studies are
correlative in nature, and the overall contribution of this type of antibody to influenza susceptibility still needs to be
determined. Without a doubt, patients should continue to receive the seasonal influenza vaccine this year. Studies have
shown that the current vaccine formulation is effective.
• Dr. Hensley: Each year surveillance laboratories make suggestions for which influenza strains to include in the seasonal
vaccine. Our current work is focused on creating reference animal anti-sera that is representative of human immunity. This
type of anti-sera could potentially be useful when deciding which vaccine strains to include in the seasonal influenza vaccine
each year.
• Citation:
• Potential antigenic explanation for atypical H1N1 infections among middle-aged adults during the 2013–2014 influenza
season
Susanne L. Linderman, Benjamin S. Chambers, Seth J. Zost, Kaela Parkhouse, Yang Li, Christin Herrmann, Ali H. Ellebedy,
Donald M. Carter, Sarah F. Andrews, Nai-Ying Zheng, Min Huang, Yunping Huang, Donna Strauss, Beth H. Shaz, Richard L.
Hodinka, Gustavo Reyes-Terán, Ted M. Ross, Patrick C. Wilson, Rafi Ahmed, Jesse D. Bloom, and Scott E. Hensley
PNAS 2014 ; published ahead of print October 20, 2014, doi:10.1073/pnas.1409171111

CHEST 2014: Obstructive Sleep Apnea Linked To Cognitive Difficulties in Postmenopausal Women
Chitra Lal, MD. Assistant Professor
• Dr. Lal: We studied the prevalence of cognitive problems in early postmenopausal women (age 45-60 years) with obstructive
sleep apnea syndrome (OSAS+) and without obstructive sleep apnea syndrome (OSAS-) using a questionnaire called the
Mail-In Cognitive Function Screening Instrument (MCFSI).
• We found that the mean MCFSI scores after adjusting for depression were significantly higher in obstructive sleep apnea
syndrome+ then the OSAS- group, indicating more self-reported cognitive difficulty in OSAS+ women
•
• Dr. Lal: Preliminary results on functional MRI scanning showed differences in brain activation patterns in obstructive sleep
apnea syndrome+ women with greater self-reported cognitive difficulty as compared to women with less cognitive difficulty.
Dr. Lal:
• 1. Our findings indicate that early postmenopausal women with obstructive sleep apnea syndrome report more cognitive
problems than those without obstructive sleep apnea syndrome.
• Cognitive dysfunction and OSAS may modulate brain activation patterns on fMRI.
•
• Dr. Lal: Given the association of obstructive sleep apnea syndrome with cognitive problems, future large studies should fully
evaluate the impact of obstructive sleep apnea syndrome on cognition in postmenopausal women.
• Citation:
CHEST 2014.
• Cognitive Impairment and Obstructive Sleep Apnea Syndrome in Early Postmenopausal Women
• Poster Number: 2944 CHEST 2104

Recommended Osteoporosis Screening May Not Effectively Screen Younger Patients
Carolyn J. Crandall, MD, MS Professor of Medicine
David Geffen School of Medicine at University of California
UCLA Medicine/GIM Los Angeles, CA 90024
• Dr. Crandall: Clinical guidelines recommend that women aged ≥ 65 years should be screened
for osteoporosis. However, for younger postmenopausal women aged between 50 and 64
years, the United States Preventive Services Task Force (USPSTF) recommends osteoporosis
screening for women who have a 10-year predicted risk of osteoporosis fracture that is
≥9.3%. We tested the ability the USPSTF strategy, and two other strategies (called OST and
SCORE), to distinguish between women who did and did not experience a fracture in the
subsequent 10 years. We found that the USPSTF strategy did not identify the majority of
who experienced osteoporotic fracture in the subsequent 10 years. Especially in women
aged 50-54 years, the USPSTF strategy identified fewer than 5% of women who experienced
fracture over 10-year follow-up.
•
• Dr. Crandall: The strategy that is recommended by current USPSTF clinical guidelines does
not perform well among these younger postmenopausal women in terms of distinguishing
which women will, and will not, experience a fracture in the subsequent 10 years. In fact, in
these women aged between 50 and 64 years, the ability to discriminate between women
with and without fractures was not substantially better than chance alone for all 3 strategies
that we examined.

Recommended Osteoporosis Screening May Not Effectively Screen Younger Patients
Carolyn J. Crandall, MD, MS Professor of Medicine
David Geffen School of Medicine at University of California
UCLA Medicine/GIM Los Angeles, CA 90024
• Dr. Crandall: To optimally predict fractures in younger postmenopausal women, we probably
have to consider risk factors that are not included in the available risk assessment tools.
this study?
• Dr. Crandall: Clearly new approaches will have to be developed to fill this critical knowledge
gap, in order to have at-risk women and their clinicians feel empowered to take measures
prior to the occurrence of a fracture.
• Citation:
• Comparison of Fracture Risk Prediction by the US Preventive Services Task Force Strategy and
Two Alternative Strategies in Women 50–64 Years Old in the Women’s Health Initiative
• JCEM: Carolyn J. Crandall, Joseph C. Larson, Nelson B. Watts, Margaret L. Gourlay, Meghan G.
Donaldson, Andrea LaCroix, Jane A. Cauley, Jean Wactawski-Wende, Margery L. Gass, John A.
Robbins, and Kristine E. Ensrud
• DOI: http://dx.doi.org/10.1210/jc.2014-2332
• Received: May 13, 2014 Accepted: September 09, 2014 Published Online: October 16, 2014

Shared Savings May Promote Lower Costs With Equally Effective Health Care
MedicalResearch.comInterview with Dr. Harald Schmidt, MA, PhD
Assistant Professor, Department of Medical Ethics and Health Policy , Research Associate, Center for Health Incentives and Behavioral
Economics, Perelman School of Medicine
University of Pennsylvania Philadelphia, PA 19104-3308
• Dr. Schmidt: We reviewed currently available policies for aligning cost and quality of care. We
focused on interventions are similar in their clinical effectiveness, have modest differences in
convenience, but pose substantial cost differences to the healthcare system and patients. To control
health care costs while ensuring patient convenience and physician burden, reference pricing
would be the most desirable policy. But it is currently politically unfeasible. Alternatives therefore
need to be explored. We propose the novel concept of Inclusive Shared Savings, in which
physicians, the healthcare system, and, crucially, patients, benefit financially in moving more
patients to lower cost but guideline concordant and therapeutically equivalent interventions.
•
• Dr. Schmidt: Inclusive Shared Savings offers financial incentives to physicians and patients to
promote the use of lower-cost, but equally effective interventions. The approach has promising
potential to undercut the significant budgetary impact of supply-induced demand resulting from
the prescribing of no- or low-value interventions. Moreover, it can shield patients financially by
eliminating or reducing their copayments and providing a positive financial incentive to opt for
lower cost tests and treatments. Inclusive Shared Savings also encourages patient reflection on
value for money and promotes culture change. Emotionally, Inclusive Shared Savings helps patients
to appreciate that they receive adequate care, offering reassurance in a situation where many feel
vulnerable in their exposure to a bewildering array of interventions that—knowingly or
unknowingly—exploit the politics of hope.

Shared Savings May Promote Lower Costs With Equally Effective Health Care
MedicalResearch.comInterview with Dr. Harald Schmidt, MA, PhD
Assistant Professor, Department of Medical Ethics and Health Policy , Research Associate, Center for Health Incentives and Behavioral
Economics, Perelman School of Medicine
University of Pennsylvania Philadelphia, PA 19104-3308
this study?
• Dr. Schmidt: Strategies for gaining broader acceptability of reference pricing need to be
identified. In the meantime, Inclusive Shared Savings should be evaluated in a rigorous trial
or demonstration project as the current policy options are unsatisfactory.
• Citation:
• Schmidt H, Emanuel EJ. Lowering Medical Costs Through the Sharing of Savings by Physicians
and Patients: Inclusive Shared Savings. JAMA Intern Med. Published online October 20, 2014.
doi:10.1001/jamainternmed.2014.5367.
• Views vs UniqueViews2014-09-272014-10-022014-10-072014-10-122014-10-17

Exercise Improves Brain Blood Flow Up To About Age 70
Professor Emrah Düzel
Director, Institute of Cognitive Neuroscience
University College London
• Professor Düzel:We found that even in old age, intensive and long-term (3 months) aerobic
exercise can improve blood flow in the hippocampus, a brain structure that is of critical importance
for memory. The increase in blood flow is evident during a resting state and this means that the
exercise improves the overall perfusion of the hippocampus. Such effects had previously only been
reported in young adults. As previously observed in young adults, the change in blood flow after
exercise is related to the improvement of specific memory skills. We found the closest relationship
between improved blood flow and recognition memory for complex objects. This is interesting
because this type of memory is likely to benefit from “pattern separation”, a process that in animal
studies of exercise is tightly associated with hippocampal neurogenesis.
• However, we also found that the exercise-related improvement in hippocampal blood flow and in
recognition memory was absent in the older seniors of our study cohort. Those who were beyond
70 did not show any improvement. We reasoned that this may have been due to higher levels of
stress in the older seniors. Therefore, we investigated whether elevated serum cortisol levels
dampened the benefits of exercise in the older seniors. But this was not the case making it unlikely
that stress levels can account for these findings.
• Professor Düzel: The absence of a benefit of exercise on hippocampal blood flow and recognition
memory beyond the age of 70 was surprising. This is certainly something we need to replicate and
investigate further in the future.

Exercise Improves Brain Blood Flow Up To About Age 70
Professor Emrah Düzel
Director, Institute of Cognitive Neuroscience
University College London
• Professor Düzel: This was a proof-of-concept study looking at the effects of long-lasting
exercise on resting blood flow in brain structures that are important for memory faculties
that decline in Alzheimer’s Disease. Our study indicates that the positive benefits of exercise
on blood flow and recognition memory are preserved in old age but starting exercising before
the age of 70 may be more effective. It is well possible, however, that even starting regular
exercise beyond the age of 70 may be beneficial. That benefit may not be an enhancement of
brain function but rather a preservation of it. However, it is too early to make conclusive
recommendations along these lines.
this study?
• Professor Düzel: Future research should have a stronger focus on the effects of advancing
age on brain plasticity. We need to understand the physiological and molecular brakes on
vascular plasticity in the hippocampus that emerge with advancing age. There may be
potential for pharmacologically enhancing plasticity in response to exercise.
• Citation:
• Vascular hippocampal plasticity after aerobic exercise in older adults
• A Maass, S Düzel, M Goerke, A Becke, U Sobieray, K Neumann, M Lövden, U Lindenberger, L
Bäckman, R Braun-Dullaeus, D Ahrens, H-J Heinze, N G Müller and E Düzel
Molecular Psychiatry , (14 October 2014) | doi:10.1038/mp.2014.114

Smokers’ Homes Have High Air Pollution Levels
Dr. John Cherrie PhD
Honorary Professor in Occupational Hygiene
Institute of Applied Health Sciences Aberdeen, UK
•
Medical Research: What are the main findings of the study?
• Dr. Cherrie:We set out to bring together measurements of fine particle levels in homes where
smoking takes place, to compare these with smoke-free homes and then to estimate how much of
these fine particles are inhaled by people at different stages in their life. We also wanted to look at
the exposure to particles of non-smokers living with smokers and compare this with the exposure
of people living in heavily polluted major cities around the world.
• Dr. Cherrie: The levels of fine particles, called PM2.5, in homes where smoking takes place were, on
average, three times higher than the World Health Organisation (WHO) recommends and in a
quarter of the smoking homes where we measured the concentrations were more than 11 times
higher than recommended levels. A considerable proportion of smokers’ homes had air pollution
levels that were the same or higher than the annual average PM2.5 concentration measured in
Beijing. What is surprising is that, the mass of these fine particles inhaled over a lifetime is not that
great. A non-smoker living with a smoker will only inhale about 5g more than a non-smoker living in
a smoke-free home in Scotland, that’s just a little more than a teaspoon of fine smoke particles.
However, we know from epidemiological evidence that these small amounts of inhaled particles
can have a substantial effect on the risk of developing diseases of the cardiovascular and
respiratory systems.

Smokers’ Homes Have High Air Pollution Levels
Dr. John Cherrie PhD
Honorary Professor in Occupational Hygiene
Institute of Applied Health Sciences Aberdeen, UK
• Medical Research: Medical Research: What should clinicians and patients take away from
your report?
• Dr. Cherrie: The message is pretty simple really. Smoking in your home leads to really poor air
quality and results in concentrations of fine particles – that you can’t see – and that would
cause real concern to us if they were found outside. Making your home smoke-free is key to
reducing your exposure to PM2.5; for non-smokers who live with a smoker the impact of
implementing smoke-free house rules where smoking is only done in the garden or some
other outdoor place would reduce their daily intake of PM2.5 by 70% or more.
• What recommendations do you have for future research as a result of this study?
• Dr. Cherrie: We need to better understand how to help smokers make their homes smoke-free.
Smokers want to do what is best for the health of their families and those they love.
Providing air quality feedback can help to educate and motivate smokers on how they can
improve the air in their home. Developing low cost, easy to understand feedback to
households with smokers would be a step forward to reducing population levels of exposure
to PM2.5 and second-hand smoke. We are actively working on this type of approach.
• Citation:
S. Semple, A. Apsley, T. Azmina Ibrahim, S. W. Turner, J. W. Cherrie. Fine particulate matter
concentrations in smoking households: just how much secondhand smoke do you breathe in
if you live with a smoker who smokes indoors? Tobacco Control, 2014; DOI:
10.1136/tobaccocontrol-2014-051635

Vitamin D Levels Lower In Children Who Drink Non-Cow’s Milk
Jonathon Maguire MD MSc FRCPC
Pediatrician and Scientist Department of Pediatrics Li Ka Shing Knowledge Institute
St. Michael’s Hospital University of Toronto
•
• Medical Research: What is the background for this study? What are the main findings?
• Dr. Maguire: One of the main health benefits of cow’s milk is vitamin D. We were interested
to know if non-cow’s milk supports children’s vitamin D blood levels as well as cow’s milk.
• Dr. Maguire: It appears that children drinking non-cow’s milk have lower vitamin D levels
than children drinking cow’s milk.
this study?
• Dr. Maguire: Identify strategies for children who consume non-cow’s milk to have the same
vitamin D levels as children who consume cow’s milk.
• Citation:
• Consumption of non–cow’s milk beverages and serum vitamin D levels in early childhood
Grace J. Lee, Catherine S. Birken, Patricia C. Parkin, Gerald Lebovic ,Yang Chen, Mary R.
L’Abbé, Jonathon L. Maguire, and for the TARGet Kids! Collaboration
CMAJ cmaj.140555; published ahead of print October 20, 2014, doi:10.1503/cmaj.140555

Air Pollution Exposure During Pregnancy Linked To Childhood Lung Function Risk
Medical Research Interview with:
Eva Morales, MD, PhD, MPH
Centre for Research in Environmental Epidemiology (CREAL)
Barcelona Biomedical Research Park Barcelona, Spain
Dr. Morales: We aimed to assess the consequences of exposure to outdoor air pollution
during specific trimesters of pregnancy and postnatal lifetime periods on lung function in
preschool children. We conducted a longitudinal study by using data from 620 mother-child
pairs participating in the INfancia y Medio Ambiente (INMA) Project – a population-based
cohort study set up in several geographic areas in Spain. We found that exposure to outdoor
air pollution during the second trimester of pregnancy in particular raises the risk of harm to
a child’s lung function at preschool age.
• Dr. Morales: We did not find significant associations between exposure to outdoor air
pollution during early postnatal (the first year of life), recent (last 12 months) and current
(last week) and lung function at preschool age.

Air Pollution Exposure During Pregnancy Linked To Childhood Lung Function Risk
Medical Research Interview with:
Eva Morales, MD, PhD, MPH
Centre for Research in Environmental Epidemiology (CREAL)
Barcelona Biomedical Research Park Barcelona, Spain
• Dr. Morales: The results highlight the importance of early-life environmental exposures
acting during in utero development on programming respiratory health later in life. Prenatal
respiratory health promotion and disease prevention should be in the agenda of clinicians
and pregnant women to guarantee that offspring attain maximal lung function during early
childhood, a critical period in lung function development. In addition, public policies to
reduce exposure to traffic-related air pollution may avoid harmful effects on lung
development and function with substantial public health benefits.
this study?
• Dr. Morales: Future studies investigating the effect of early-life experiences on lung function
during childhood should assess lung function as early as preschool age to understand the full
impact on lung development and growth.
• Citation:
• E. Morales, R. Garcia-Esteban, O. Asensio de la Cruz, M. Basterrechea, A. Lertxundi, M. D.
Martinez Lopez de Dicastillo, C. Zabaleta, J. Sunyer. Intrauterine and early postnatal exposure
to outdoor air pollution and lung function at preschool age. Thorax, 2014; DOI:
10.1136/thoraxjnl-2014-205413

CT Angiograms Improve Outcomes and Save Lives
Dr. Matthew Budoff, M.D.
Los Angeles Biomedical Research Institute
Torrance California
• Dr. Budoff: We evaluated whether patients undergoing coronary CT angiography (non-invasive
angiography) had better outcomes than those treated without the test. We found
survival was better with CT angiography. Finding atherosclerosis allows cardiologists and
primary care doctors to treat the patient better, including more statin therapy, more anti-platelet
therapy, more lifestyle modifications. Several small studies showed similar results,
but this was by far the most significant and largest study of it’s kind.
• Dr. Budoff: The magnitude of benefit. Patients were MUCH less likely to die if they
underwent a CT angiogram.

CT Angiograms Improve Outcomes and Save Lives
Dr. Matthew Budoff, M.D.
Los Angeles Biomedical Research Institute
Torrance California
• Dr. Budoff: Finding the plaque in the coronaries directly is much better for doctors to make decisions
about medications, stents, bypass and lifestyle. The old methods of evaluating coronary artery disease, by
looking at stress tests and only identifying patients with high grade stenosis (more than 50% or 70%
blockages) is not adequate. Many plaques that rupture and cause MI and death are only 20-50% in
severity, and these would be missed by treadmill, nuclear scan or echocardiography. We know from the
COURAGE trial that we can successfully treat atherosclerosis with aggressive medical therapy, but we need
to make the diagnosis to know who to treat. This is what CT angiography allows.
• Dr. Budoff: Prospective studies of CT angiography vs standard of care need to be undertaken, especially in
regard to compliance and findings of subclinical atherosclerosis.
• Our hypothesis of why people live longer undergoing cardiac CT is both more accurate diagnosis and
identification of subclinical (<50% blockages) atherosclerosis, but also better adherence to
medications. Patients who see the plaque are more likely to stay on medications, but what is the long
term adherence rates of those undergoing CTA vs standard of care, and does this influence outcomes.
• Citation:
• Coronary CT angiography Versus Standard of Care Strategies to evaluate patients with potential coronary
artery disease; Effect on long term clinical outcomes
Budoff, Matthew J. et al
• Atherosclerosis
• Received: February 10, 2014; Received in revised form: September 13, 2014; Accepted: September 22,
• DOI: http://dx.doi.org/10.1016/j.atherosclerosis.2014.09.038

Cow’s Milk May Be Protective Against Childhood Infections
MedicalResearch.comInterview with: Georg Loss, PhD
Dr. von Hauner Children’s Hospital
Ludwig Maximilians University of Munich
Munich, Germany
• Dr. Loss: In this large population based cohort study we observed that consumption of fresh
unprocessed cow’s milk protected from respiratory infections, febrile illness and inflammation of
the middle ear during the first year of life. The risk of developing these conditions was reduced by
up to 30%, and the effect was diminished if the milk was heated at home before consumption.
Conventionally pasteurized milk retained the ability to reduce the risk of febrile illness, while
exposure to the higher temperatures used in UHT (Ultra-heat-treatment) processing eliminated the
effect altogether. Importantly, the positive impact of fresh milk could be clearly separated from the
confounding effects of other elements of the children’s nutrition. Furthermore, infants fed on
unprocessed milk were found to have lower levels of the C-reactive protein, which is a measure of
inflammation status.
•
• Dr. Loss: Before this study there was no evidence supporting the idea of fresh milk protecting
against respiratory infections in early life. In fact, pediatricians recommend against consuming
cow’s milk during the first six months of life, especially against the consumption of
unprocessed milk in infancy due to a possible contamination with harmful bacteria. We knew from
previous studies that breast feeding protects from respiratory infections. We thought it could be
possible to observe a similar effect in our rural population by consumption of cow’s milk in its
native state given the similarities of breast milk and cow’s milk. It was surprising, however, to
observe such a clear protection against infections and that ingestion of unprocessed milk reduced
the levels of inflammation markers.

Cow’s Milk May Be Protective Against Childhood Infections
MedicalResearch.comInterview with: Georg Loss, PhD
Dr. von Hauner Children’s Hospital
Ludwig Maximilians University of Munich
Munich, Germany
• Medical Research: What should clinicians, patients and health officials take away from your
report?
• Dr. Loss: Middle ear inflammation and respiratory infections are common during the first year of
life. The latter has been hypothesized to be involved in the development of asthma later on.
Reducing these infections reduces their direct burden and may be beneficial in the onset of
asthmatic disease. A microbiologically safe milk with minimal processing to preserve beneficial
components might be a novel basic food with an enormous public health value. A prevention
strategy based on a well-accepted food of everyday nutrition might succeed without profound
changes in life-style.
study?
• Dr. Loss:We would like to see an intervention study with a microbiologically safe but minimally
processed cow’s milk to substantiate our findings. Moreover, we plan to identify exact components
responsible for the health effects.
• Citation:
Consumption of unprocessed cow’s milk protects infants from common respiratory infections
• Loss, Georg et al.
• Journal of Allergy and Clinical Immunology
Received: May 16, 2014; Received in revised form: July 15, 2014; Accepted: August 6, 2014;
Published Online: October 19, 2014
• DOI: http://dx.doi.org/10.1016/j.jaci.2014.08.044

CHEST 2014: Electronic Stethoscope For Evaluation of Lung and Heart Disease
Ilina and Medha Krishen
• Medical Research: Ilina, please tell us a little about you and the background for your study.
• Ilina: I am a senior at Port Huron Northern High School in Fort Gratiot, Michigan. I was exploring the effects of air pollutants on lungs using frequency
analysis of lung recordings. My goal was to see if I could pick up early changes in healthy smokers and firefighters.
• Dr. Sridhar Reddy, a local pulmonologist and occupational medicine expert mentored me. He lent me his electronic stethoscope. I am a violinist and
a clarinet player, so initially had a lot of fun analyzing music frequencies. Later, I moved to lung sounds (a little more difficult!).
• I used a Thinklabs Electronic Stethoscope for recording lung sounds. The inventor, Mr. Clive Smith, helped me understand the stethoscope.
• I used the MATLAB program for analyzing frequencies. Mr. Charles Munson, a graduate student at the University of Michigan, helped me write the
software program for it.
• Medical Research: How did you become interested in this area?
• Ilina: Several members of my family have died from the effects of smoking.
I am interested in environmental issues, such as air pollution.
I wanted to perform meaningful community service.
• Ilina: I had 3 groups of volunteers: Never-smokers, current smokers and local firefighters.
• Frequency analysis revealed that smokers and firefighters had a broader range of frequencies and a greater proportion of frequency peaks above 125
Hz as compared to never-smokers. These differences are obvious on the frequency plots.
• For Patients: Lung damage occurs early, symptoms reveal an advanced stage of damage. Don’t smoke or quit smoking.
• For Physicians: These lung recordings can be used to demonstrate early signs of damage in order to encourage patients to stop smoking. This could
be a great educational tool for smoking cessation.
• Physicians have always listened to lung sounds and they use their trained ears and knowledge to analyze lung sounds. Now they can keep a graphic
record of this for future comparisons.
• Community Members: Environmental pollution as a cause of early lung damage is under-appreciated. All of my firefighter volunteers would wear
masks while performing their duties. I have presented my data to them and hopefully they can come up with some meaningful solutions.
• Three of my smoking volunteers have quit smoking after they saw the results of the study. They want me to come back and do a repeat analysis of
their lung sounds in the future.
• I am glad that I could be helpful to my community.
• I am doing a follow up study this year.

CHEST 2014: Electronic Stethoscope For Evaluation of Lung and Heart Disease
• Medical Research: Medha, please tell us a little about you and the background for your study.
• Medha: I am currently a junior at Port Huron Northern High School in Port Huron, MI.
• I was interested in finding a new way to screen high school athletes at risk of dying suddenly (Sudden Cardiac Death) from Hypertrophic
Cardiomyopathy (HCM). I analyzed heart sound frequencies in patients with Hypertrophic Cardiomyopathy and compared them to individuals with a
normal heart.
• I used a Thinklabs Digital Electronic Stethoscope to record heart sound frequencies while lying down and after a light exercise. Then, I performed a
frequency analysis on the sound recordings, using the MATLAB Software Program.
• Dr. Sridhar Reddy, my mentor, let me use his electronic stethoscope for this project.
• Mr. Clive Smith, the inventor of THINKLABS Digital Electronic Stethoscope, guided me through the program for recording heart sounds and
introducing me to the concepts of filters and noise reduction. It was his suggestion to practice recording sounds of musical instruments. I play the
piano and the bassoon.
• Mr. Charles Munson, a graduate student at the University of Michigan taught me how to write the software script for Fast Fourier Analysis on
MATLAB.
• Medical Research: What is the background for your study?
• Medha: In middle school, I wrote a research paper on “Sudden Death in Athletes” after a family friend collapsed and died while jogging. Since I am a
figure skater, I was very scared. The individual who died was my mentor’s brother-in-law.
• He had a genetic condition called Hypertrophic Cardiomyopathy (HCM). It is the most common cause of sudden cardiac arrest under the age of
30. Each year, at least 100 young athletes die suddenly in the US; 65% of these are high school athletes. A health questionnaire and examination at a
doctor’s office may miss HCM.
• Therefore, Dr. Reddy and I wanted to develop a new screening method for high school athletes.
• Medha: A significant difference was seen between the Hypertrophic Cardiomyopathy and the normal group with exercise. The frequency graphs
showed that the distribution of the frequency peaks was completely opposite in the two groups.
• Medha: In order to prevent Sudden Cardiac Arrest in young athletes, the screening process for Hypertrophic Cardiomyopathy must begin in high
school.
• My goal was to develop a technique that can be easily implemented by school staff to screen their athletes for Hypertrophic Cardiomyopathy.
• Medha: Find simple ways to screen for and detect HCM.
• Citation:
• An Electronic Stethoscope to detect lung and heart disease
CHEST 2014 presentation discussing

Metastatic Colon Cancer: Survival Improved With FOLFOXIRI and Evacizumab
Alfredo Falcone MD
Chiara Cremolini Fotios Loupakis
University of Pisa and Azienda-Ospedaliero Universitaria Pisana
Italy
• Dr. Falcone: In the TRIBE study the main findings are that the use of an initial more intensive
therapy with a triplet of cytotoxics (FOLFOXIRI) plus bevacizumab vs a doublet (FOLFIRI) +
bevacizumab improves the outcome of metastatic colorectal cancer patients with
unresectable metastases. In particular FOLFOXIRI + bevacizumab vs FOLFIRI+bevacizumab
improved RECIST response-rate (65% vs 53%, p=0.006), progression-free survival which was
the primary endpoint (median 12,1 vs 9,7 months, HR=0,75, p=0.003) and overall survival
(median 31,0 vs 25,8 months, HR=0.79, p=0.054). These results, also compared to those
reported in previous phase III studies in molecularly unselected patients, represent an
important advance in the treatment of this disease.
• Dr. Falcone: That the improvement in the outcome with FOLFOXIRI+bevacizumab was
observed despite the fact that no improvement in the secondary R0 resection rate of
metastases was observed (15% vs 12%, p=0.33). This indicates that FOLFOXIRI+bevacizumab
is a more effective therapy also in a palliative setting where secondary surgery of metastases
is not a reasonable objective of the treatment.

Metastatic Colon Cancer: Survival Improved With FOLFOXIRI and Evacizumab
Alfredo Falcone MD
Chiara Cremolini Fotios Loupakis
University of Pisa and Azienda-Ospedaliero Universitaria Pisana
Italy
• Dr. Falcone: To consider an initial intensive therapy with FOLFOXIRI+bevacizumab, followed by
maintenance with 5-FU/LV and bevacisumab, as a very good option for many metastatic colorectal cancer
patients with a good ECOG Performace-status (0-1), no relevant comorbidities and age < 70-75 yrs,
independently from the molecular characteristcs of the tumor. In patients with RAS mut or BRAF mut
tumors FOLFOXIRI+bevacizumab may represent today the best option.
• Dr. Falcone: First of all to update the overall survival of the TRIBE study to estimate the long-term benefit
of FOLFOXIRI+bevacizumab.
• In the meantime, to improve the tolerance of the regimen, and perhaps its efficacy, by reducing the
duration of the induction phase from 6 to 4 months, followed by a maintenance with bevacizumab and a
low toxic metronomic chemotherapy, followed by a re-treatment with FOLFOXIRI+bevacizumab at the first
progression (MOMA study).
• In the RAS-wt patients it is of great interest to study the triplet FOLFOXIRI in combination with anti-EGFR
mAbs and also these studies are ongoing with preliminary promising results (MACBETH study).
• Citation:
• Initial Therapy with FOLFOXIRI and Bevacizumab for Metastatic Colorectal Cancer
• Fotios Loupakis, M.D., Ph.D., Chiara Cremolini, M.D., Gianluca Masi, M.D., Sara Lonardi, M.D., Vittorina
Zagonel, M.D., Lisa Salvatore, M.D., Enrico Cortesi, M.D., Gianluca Tomasello, M.D., Monica Ronzoni, M.D.,
Rosella Spadi, M.D., Alberto Zaniboni, M.D., Giuseppe Tonini, M.D., Angela Buonadonna, M.D., Domenico
Amoroso, M.D., Silvana Chiara, M.D., Chiara Carlomagno, M.D., Ph.D., Corrado Boni, M.D., Giacomo
Allegrini, M.D., Luca Boni, M.D., and Alfredo Falcone, M.D.
• N Engl J Med 2014; 371:1609-1618
October 23, 2014

Mortality From Acute Respiratory Distress Syndrome Drops Dramatically
Jared Radbel MD
Staten Island, New York
• Dr. Radbel: Using ICD 9 coding from the largest all-payer inpatient health care database in the
United States, the National Inpatient Sample (NIS) database we identified 174,180 patients
with Acute Respiratory Distress Syndrome (ARDS) from 1996-2011. When expanded to
estimate country-wide discharges, our data represents 856,293 patients. We found a
decrease in case fatality rate from 46.8% in 1996 to 32.2% in 2011. This corresponds to an
absolute mortality reduction of 14.6% and relative reduction of 31%.
• Dr. Radbel: The most surprising finding in our study was the sharp decline in mortality from
2000-2005. Over this time frame we found an absolute reduction in case fatality rate of
8.9%. While mortality had been trending downward from 1996-2000, there was a
statistically significant drop in mortality beginning in 2000. Then in 2005, the decrease in
mortality returned to its pre-2000 trend. The ARDS Clinical Trials Network’s groundbreaking
study, “Ventilation with lower tidal volumes as compared with traditional tidal volumes for
acute lung injury and the acute respiratory distress syndrome,” published in 2000,
demonstrated an absolute mortality reduction of 8.8%. This absolute decrease is almost
identical to the drop we discovered from 2000-2005.

MedicalResearch.com: Medical Research Exclusive Interviews October 27 2014

MedicalResearch.com: Medical Research Exclusive Interviews October 27 2014

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MedicalResearch.com: Medical Research Exclusive Interviews October 27 2014