MedicalResearch.com: Medical Research Exclusive Interviews July 16 2015

MedicalResearch.com
Exclusive Interviews with Medical Research and
Health Care Researchers from Major and Specialty Medical
Research Journals and Meetings
Editor: Marie Benz, MD
info@medicalresearch.com
July 16 2015
For Informational Purposes Only: Not for Specific Medical Advice.

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Most Young Cancer Patients Receive Intensive Measures At End of Life
MedicalResearch.com Interview with:
Jennifer Mack, MD, MPH
Pediatric oncologist
Dana-Farber/Boston Children’s Cancer and Blood Disorders Center
Medical Research: What is the background for this study? What are the main findings?
Dr. Mack: This study evaluated the intensity of end-of-life care received by adolescents and
young adults (AYAs) with cancer. Little was previously known about the kind of end-of-life care
these young patients receive. We evaluated the care of 663 Kaiser Permanente Southern
California patients who died between the ages of 15 and 39 between the years 2001 and 2010.
We found that more than two-thirds of adolescents and young adults received at least one form
of intensive end-of-life care before death. This includes chemotherapy in the last two weeks of
life (11%), more than one emergency room visit in the last month of life (22%), intensive care unit
care in the last month of life (22%), and hospitalization in the last month of life (62%).
Read the rest of the interviews on MedicalResearch.com
Content NOT an endorsement of efficacy and NOT intended as specific medical advice.

• Medical Research: What should clinicians and patients take away from your report?
• Dr. Mack: A majority of dying young people with cancer receive intensive measures at the
end of life. Older patients who know they are dying usually do not want to receive intensive
measures, which are associated with a poorer quality of life near death. High rates of
intensive measures raise the concern that young people may experience unnecessary
suffering at the end of life. However, it is also important to recognize that adolescents and
young adult patients may have different priorities than older patients, and may be more
willing to accept intensive measures in order to live as long as possible. Clinicians, patients,
and family members should talk about what is most important to patients at the end of life
so that their values can be upheld, whether patients prioritize doing everything possible to
live as long as possible or focus on quality of life.

• Medical Research: What recommendations do you have for future research as a result of
this study?
• Dr. Mack: Future research should further examine end-of-life decision-making for
adolescents and young adults, including the reasons for receipt of intensive measures.
• Citation:
• Mack JW, Chen LH, Cannavale K, Sattayapiwat O, Cooper RM, Chao CR. End-of-Life Care
Intensity Among Adolescent and Young Adult Patients With Cancer in Kaiser Permanente
Southern California. JAMA Oncol. Published online July 09, 2015.
doi:10.1001/jamaoncol.2015.1953.
•

Pupil Response To Sad Faces Linked To Increased Risk of Depression In Children
Katie Burkhouse, Graduate Student and
Dr. Brandon Gibb Ph.D Professor of Psychology
Director of the Mood Disorders Institute and Center for Affective Science
Binghamton University
Dr. Gibb: One of the strongest risk factors for depression is a family history of the
disorder. However, even among this at-risk group, the majority of children of depressed parents
do not develop depression themselves. For those who do become depressed, the depression can
severely and negatively affect their social and academic functioning, become chronic or recurrent
over the lifespan, and increase risk for suicide. What is needed therefore, is a good indicator of
which children may be at greatest risk for depression so that interventions can be targeted to
these individuals. We believe that pupil dilation may represent one such marker. Changes in
pupil dilation are associated with activity in the brain’s emotional circuits and have been linked in
previous research to the presence of depression. What my graduate student Katie Burkhouse
found is that, even among children who are not currently experiencing symptoms of depression,
the degree to which their pupil dilates when they look at pictures of sad faces predicts their risk
for developing clinically significant episodes of depression over the next two years. The findings
were specific to pupil responses to sad faces and were not observed when children looked at
happy or angry faces suggesting that there is something specific to how the children were
processing sad images.

• Dr. Gibb: This study adds to a growing body of research suggesting that subtle changes in
pupil dilation can provide a window into how the brain processes emotional information and
can help us determine which individuals are at greatest risk for depression themselves. We
believe that one day these types of tests could be included as part of children’s regular
pediatrician visits and help identify which children may be at risk for depression.

this study?
• Dr. Gibb: Katie’s study is exciting because it’s the first to show that pupillary reactivity to
images of sad faces predicts the onset of depression. However, before we can develop a
standardized test of depression risk based on these findings, more research is needed to
make sure that the findings replicate and to determine whether pupil dilation can be used to
predict depression risk in children even if they do not have a family history of the
disorder. We are optimistic about this research and hope that we will be able to standardize
the test so that it can be used as a general screen for depression risk.
• Citation:
• Katie L. Burkhouse, Greg J. Siegle, Mary L. Woody, Anastacia Y. Kudinova, Brandon E. Gibb.
Pupillary Reactivity to Sad Stimuli as a Biomarker of Depression Risk: Evidence From a
Prospective Study of Children.. Journal of Abnormal Psychology, 2015; DOI:
10.1037/abn0000072

3-Drug Combination May Better Reduce Nausea-Vomiting During Chemotherapy
Junichi Nishimura MD, PhD
Assistant professor
Osaka University in Japan
Dr. Nishimura: Oxaliplatin is classified as moderately emetogenic chemotherapy and 2-drug
combination antiemetic therapy is recommended for Oxaliplatin based chemotherapy including
FOLFOX and XELOX in all guidelines for antiemesis. Nausea and vomiting are still frequent adverse
events which decrease the patient’s QOL. However, there was no study investigating whether 3-
drug combination antiemetic therapy (5HT3 receptor antagonist+dexamethasone+aprepitant)
reduce chemotherapy-induced nausea and vomiting. In this study, we conducted a multicentre,
randomized phase III study to evaluate the usefulness of the combined use of aprepitant in
colorectal cancer patients treated with Oxaliplatin based chemotherapy. In this phase III study, 3-
drug combination therapy significantly increased the inhibition rate of vomiting which was the
primary endpoint of this study. Moreover, the inhibition rate of nausea, complete response (no
vomiting and no rescue medication use), and complete protection (no vomiting , no rescue
medication use and no moderate or worsened nausea) was significantly higher in aprepitant
group in overall and delayed phase. We, next, compared the inhibition of vomiting and nausea
between males and females in delayed phase. When patients were grouped by sex regardless of
the assigned treatment group, females were more affected by nausea and vomiting than males.
Finally, in female, aprepitant did significantly prevent nausea and vomiting as well as increased
chance of complete protection.

Assistant professor
• Dr. Nishimura: The 3-drug combination antiemetic therapy might be an antiemetic treatment
option for oxaliplatin based chemotherapy in colorectal patients who were not controlled
their vomiting and nausea.

Assistant professor
this study?
• Dr. Nishimura: Casopitant, which is another NK1 receptor antagonist, were reported to have
no significant effects in colorectal patients receiving oxaliplatin based chemotherapy
compared with recommended 2-drug combination antiemetic therapy. We need more data
about the effectiveness of 3-drug combination therapy in colorectal patients treated with
Oxaliplatin to conclude whether aprepitant is recommended antiemetic therapy for
Oxaliplatin based chemotherapy.
• Citation:
• Nishimura J, Satoh T, Fukunaga M, et al, et al. A phase III trial of aprepitant in colorectal
cancer patients receiving oxaliplatin-based chemotherapy (SENRI Trial). Ann Oncol. 2015;26
(suppl 4; O-001). – See more at: http://www.onclive.com/conference-coverage/2015-world-
GI/adding-aprepitant-improves-control-of-oxaliplatin-related-nausea-vomiting-in-
crc#sthash.0gjjzcCI.dpuf

Novel Anti-Metabolite Offers New Therapeutic Option For Resistant Colon Cancer
Howard S. Hochster, MD
Associate Director, Yale Cancer Center
Professor of Medicine, Yale School of Medicine
New Haven, CT 06520
• Medical Research: What is the background for this study? What are the main findings?
Dr. Hochster: TAS-102 is a novel anti-metabolite, recently combined with a metabolic
inhibitor to make it orally bioavailable and active in the treatment of cancer. In pre-clinical
studies, it is non-cross reactive with 5FU. What this means practically is that we have
another chemotherapy agent that can be used for patients with colon cancer. This drug will
be an addition to the approved chemotherapy agents 5FU, oxaliplatin and irinotecan. It may
be combinable with these and with targeted agents to provide new active regimens.
• The main findings of the study were published in NEJM, May 15, 2015. The study enrolled
800 patients randomized (2:1 ratio) to drug vs placebo. Patients with advanced colon cancer
who had been treated with all the previously approved drugs were eligible. The drug was
active in reducing time to tumor growth (Progression Free Survival) by 50% and improved
overall survival for treated patients by about 25%.

New Haven, CT 06520
The data I presented at ESMO included a further analysis on specific genomic subsets of patients
within the 800 patient study. All patients were tested locally for RAS mutations and about 50%
had such mutations (as expected). There was no differences in benefit or toxicity for those with
RAS wild-type tumors or RAS mutated tumors. We also looked at those with BRAF mutations, but
only 15% of patients were tested and this mutation occurs in about 8% of colon cancer, so we had
very few patients with BRAF mutation. Given this limitation, it appeared that this did not make a
difference for benefit or toxicity either.

New Haven, CT 06520
• Medical Research What should clinicians and patients take away from your report?
• Dr. Hochster: TAS-102 is currently under review at the FDA and will receive a decision this
year. I expect it should be approved based on approval of other agents with similar benefits
in such studies. This will give patients a new therapeutic option after they have exhausted all
others and possibly newer treatment options for earlier lines of therapy in the future.

New Haven, CT 06520
this study?
• Dr. Hochster: The next steps include combinations with irinotecan, with oxaliplatin and with
biologics including bevacizumab. These regimens can be eventually incorporated into the
new treatment paradigms and guidelines. We will be working on how this drug works after
patients have been receiving 5FU and when tumors are resistant to 5FU.
• Citation:
• Presented at 2015
• European Society for Medical Oncology | ESMO
• Hochster H, Hager S, Pipas JM, et al. KRAS and BRAF gene subgroup analysis in the Phase 3
RECOURSE trial of TAS-102 versus placebo in patients with metastatic colorectal cancer. Ann
Oncol. 2015;26 (suppl 4; O-010) – See more at: http://www.onclive.com/conference-
coverage/2015-world-GI/improved-os-pfs-demonstrated-by-tas-102-regardless-of-kras-
status#sthash.GYh8XDQX.dpuf

Substance Abuse and Tobacco Linked To Longer Term Opioid Use
W. Michael Hooten, M.D
Professor of Anesthesiology
Mayo Clinic
• Medical Research: What is the background for this study?
• Dr. Hooten: The purpose of the study was to investigate a gap in knowledge related to the
progression of short-term opioid use to longer-term use.
• Medical Research: What are the main findings?
Dr. Hooten: The main findings are that a history of substance abuse or tobacco use is
associated with the progression from short-term to a longer-term pattern of opioid
prescribing.

Substance Abuse and Tobacco Linked To Longer Term Opioid Use
W. Michael Hooten, M.D
Professor of Anesthesiology
Mayo Clinic
• Dr. Hooten: Physicians and patients should be aware that a history of substance abuse and
smoking may be risk factors for longer patterns of opioid use.
this study?
• Dr. Hooten: In future research, we plan to focus on the potential effects that the initial opioid
dose may have on longer-term patterns of opioid use.
• Citation:
• Incidence and Risk Factors for Progression From Short-term to Episodic or Long-term Opioid
Prescribing: A Population-Based Study.
• Hooten WM, St Sauver JL, McGree ME, Jacobson DJ, Warner DO.
• Mayo Clin Proc. 2015 Jul;90(7):850-6. doi: 10.1016/j.mayocp.2015.04.012.

Postmenopausal Hormones Linked To Decreased Colon Cancer Risk
Dr. Hannah Arem Ph.D. M.H.S. Postdoctoral Fellow
Nutritional Epidemiology Branch
Division Cancer Epidemiology and Genetics
National Cancer Institute
• MedicalResearch: What is the background for this study?
• Dr. Arem: In the United States, men are more likely to develop colorectal cancer (CRC) than
women. In large prospective studies, researchers observed that women who reported taking
menopausal hormone therapy (MHT) containing estrogen had a 30-40% lower risk of
colorectal cancer, compared to women who did not report menopausal hormone therapy
use, suggesting an anti-carcinogenic role for estrogen.
• We investigated the relationship between estrogen exposure (hormonal and reproductive
factors) in relation to survival (risk of death) among women diagnosed with colorectal cancer.

• MedicalResearch: What are the main findings?
• Dr. Arem: We found a 20% lower risk of death overall among women who reported current
menopausal hormone therapy use at study entry (HR=0.79, 95% CI 0.66-0.94) and a 24%
lower risk of death from colorectal cancer (0.76, 0.59-0.99), compared to women who
reported never using menopausal hormone therapy.
• Among women in our study, we observed no statistically significant associations for
colorectal cancer mortality with oral contraceptive use, menarche age, age at first birth,
parity, or menopausal age.
• MedicalResearch: What should clinicians and patients take away from your report?
• Dr. Arem: Our study was designed to investigate a mechanistic role for estrogen on
carcinogenesis for research purposes. We do not expect these findings to influence clinical
practice or behavior.

• MedicalResearch: What recommendations do you have for future research as a result of
this study?
• Dr. Arem: Future studies should focus on the mechanisms by which exogenous estrogen
exposure might affect tumor progression and colorectal cancer survival.
• Citation:
• Reproductive and hormonal factors and mortality among women with colorectal cancer in
the NIH-AARP Diet and Health Study
• H Arem, Y Park, A S Felix, A Zervoudakis, L A Brinton, C E Matthews and M J Gunter
• British Journal of Cancer , (23 June 2015) | doi:10.1038/bjc.2015.224

Clinical Trial of Ultraviolet Blood Irradiation For Resistant Infectious Disease
Dr. J. Todd Kuenstner MD
Clinical Laboratories
Charleston Area Medical Center, Charleston, Virginia
West Virginia School of Medicine, Charleston, West Virginia
Dr. Kuenstner: Prior to the advent of recent antiviral therapies with sustained virologic response
rates (SVR) of 94%, ultraviolet blood irradiation (UVBI) was proposed as a method to improve the
outcome of treatment with interferon and ribavirin which had an virologic response rates of 50%.
This therapy was invented by Dr. Emmett Knott in 1928 and used to treat viral and bacterial
infectious disease in the 1930s through the 1950s and an estimated 60,000 treatments were
conducted in the United States by 1948. The AVIcure hemo-irradiator is a modification of the
Knott Hemo-irradiator and meets contemporary safety standards.

This study describes the FDA phase II controlled clinical trial that was conducted before the
advent of sofosbuvir and ledipasvir with the AVIcure hemo-irradiator using ultraviolet blood
irradiation (UVBI) for the treatment of 10 patients infected with the hepatitis C virus (HCV). This
study is significant because of the potential of this device for treating other infectious diseases
with few treatment options. This therapy was safe and beneficial in the 10 patients that were
studied. At the nadir of the viral load, the mean reduction of hepatitis C viral load was 45%
(p=0.0048) or 0.35 log viral load (p=0.015). Three of the patients in the group achieved a greater
than 0.5 log viral load reduction at some point in the trial. The phase I controlled clinical trial of
UVBI in patients with HCV infection on 10 patients (submitted for publication) showed that 7 of
10 patients had a greater than 0.5 log reduction in viral load and a mean viral load reduction of
56% and a mean log viral load reduction of 0.60 (p=0.039).

In the phase II clinical trial, 8 of 10 patients also showed a concurrent reduction in their serum
transaminase levels, mean reduction in AST of 15% (p=0.0069) and mean reduction in ALT of 19%
(p=0.0031). The above phase II trial results were achieved in spite of two therapeutic “holidays”
of 7 weeks duration during the trial and during these therapeutic “holidays” the patients did not
receive any treatments.

• Dr. Kuenstner: This controlled clinical trial in a viral infection, combined with two controlled
trial reports in the Russian medical literature on the use of combination UVBI and antibiotics
for more rapid resolution of tuberculosis and the extensive United States medical literature
on the Knott Hemo-irradiator from 1930 through 1950 indicate that this therapy is useful for
the treatment of infectious diseases. In recent years, increasing resistance to existing
antimicrobial agents indicates the need for alternative strategies in combating infectious
diseases.

• Medical Research: What recommendations do you have for future research as a result of this
study?
• Dr. Kuenstner: This device should be evaluated for the treatment of infectious diseases with few or
no treatment options. Such diseases include multidrug resistant Mycobacterium tuberculosis,
multidrug resistant Salmonella typhi, Mycobacterium avium complex, and dengue, chikungunya,
Ebola, Marburg, West Nile and influenza viruses. Studies of patients who have failed existing
therapies for other infections including malaria, human immunodeficiency virus and hepatitis B
virus are also indicated.
• We also believe that this device will be very useful in the treatment of Crohn’s disease and other
diseases traditionally considered “autoimmune” but in our view caused by Mycobacterium avium
paratuberculosis (MAP). We recently published a series of case reports describing the resolution of
Crohn’s disease and complex regional pain syndrome in two patients who were treated with
combination UVBI and antibiotics following demonstration of MAP positive blood cultures.
Controlled clinical trials of UVBI are planned in these diseases.
• Citation:
• The treatment of infectious disease with a medical device: results of a clinical trial of ultraviolet
blood irradiation (UVBI) in patients with hepatitis C infection
• J. Todd Kuenstnera, b, , ,Shanker Mukherjeec,Stuart Wegd,Trish Landrye,
Thomas Petrie
• International Journal of Infectious Diseases
• Volume 37, August 2015, Pages 58–63
• doi:10.1016/j.ijid.2015.06.006

Intestinal Microbiome May Contribute To Burn Pathology
Mashkoor A. Choudhry, PhD
Professor of Surgery, Microbiology & Immunology Burn & Shock Trauma Research Institute
Stritch School of Medicine Loyola University Chicago Health Sciences Division
Maywood, IL 60153
Dr. Choudhry: Intestine is the major reservoir of bacteria in the body. We observed that gut
bacterial composition is altered after burn injury. We found that burn causes a significant
increase in Enterobacteriaceae, a group of bacteria that has the potential to be harmful for
the host. Dysbiosis of the healthy intestinal microbiome is associated with a number of
inflammatory conditions.
Dr. Choudhry: Although based on limited number of patients, our findings suggest that
changes in the intestinal microbiome can potentially contribute to pathology associated with
burns, however more studies are required to establish this link.

Intestinal Microbiome May Contribute To Burn Pathology
Mashkoor A. Choudhry, PhD
Professor of Surgery, Microbiology & Immunology Burn & Shock Trauma Research Institute
Stritch School of Medicine Loyola University Chicago Health Sciences Division
Maywood, IL 60153
this study?
Dr. Choudhry: As I indicated above that our current study is based on limited number of
patients, so more studies are needed to confirm these findings with large burn patient
population. Additionally more research is also needed to investigate the mechanism by which
burn injury results in the dysbiosis of normal gut microbiota.
• Citation:
• Burn Injury Alters the Intestinal Microbiome and Increases Gut Permeability and Bacterial
Translocation.
• Zachary M. Earley, Suhail Akhtar, Stefan J. Green, Ankur Naqib, Omair Khan, Abigail R.
Cannon, Adam M. Hammer, Niya L. Morris, Xiaoling Li, Joshua M. Eberhardt, Richard L
Gamelli, Richard H. Kennedy, Mashkoor A. Choudhry
• Published: July 8, 2015
DOI: 10.1371/journal.pone.0129996

Phthalate Replacements May Contribute to High Blood Pressure in Youth
Leonardo Trasande, MD, MPP
Associate Professor, Department of Pediatrics;Associate Professor, Department of Environmental Medicine;Associate Professor, Department
of Population Health
NYU Langone Medical Center
• Dr. Trasande: Phthalates are environmental chemicals widely used in consumer and personal
care products, and often found in plastic to increase flexibility. Di-2-ethylhexylphthalate
(DEHP) is of particular interest because industrial processes to produce food frequently use
plastic products containing DEHP. Because recognition of potential health risks related to
DEHP exposure has increased, DEHP is being replaced by di-isononyl phthalate (DINP) and di-
isodecyl phthalate (DIDP), two phthalates with similar chemical properties. Specifically, DINP
is used in plastic products for food packaging, and DIDP is used in furnishings, cookware,
medications, and several other consumer products. These alternatives have not been
substantially studied for toxicity in laboratory studies because these studies are not required
for regulatory approval: unlike the EU, in the US the current regulatory framework assumes
that chemicals are safe until proven toxic.

• Dr. Trasande: We examined DINP and DIDP levels in urine samples from children and
adolescents (6 to 19 years old) who participated in the National Health and Nutrition
Examination Survey between 2009 and 2012, to assess if these levels were associated with
blood pressure measurements. Diet, physical activity, gender, race/ethnicity, income, and
other factors that can contribute to increased blood pressure were also included in the
analysis. A significant association was found between high blood pressure and DINP/DIDP
levels in study participants. This is not a cause-and-effect relationship but it suggests that
phthalates may contribute to increased blood pressure.

• Dr. Trasande: Children and adolescents exposed to DIDP and DINP, currently used as DHEP
replacements, have significantly increased blood pressure. This adds to the increasing body
of evidence on the harmful effects of these environmental chemicals. Simple steps that could
be taken to limit exposure include not microwaving food in plastic containers or covered by
plastic wraps, and avoiding using the dishwasher for plastic food containers: high
temperatures make more likely for these chemicals to leach into food. Plastic containers
labeled with the numbers 3, 6 or 7 (inside the recycle symbol usually at the bottom of the
container) should also be avoided, as these codes indicate the presence of phthalates.

this study?
• Dr. Trasande: Further studies are required to identify the underlying mechanisms and to
investigate the long-term effects of exposure to these chemicals. This is particularly
important during pregnancy and early childhood, and might reveal different and/or more
persistent effects on health. There are ample opportunities for policy prevention in the
current regulatory void, and these studies will form the basis for much needed regulatory
interventions to limit exposure to ubiquitous environmental chemicals with the potential to
increase cardiovascular risk.
• Citation:
• Leonardo Trasande and Teresa M. Attina. Association of Exposure to Di-2-Ethylhexylphthalate
Replacements With Increased Blood Pressure in Children and Adolescents. Hypertension, July
2015 DOI: 10.1161/HYPERTENSIONAHA.115.05603

Ejaculatory Issues Common and Not Helped By Testosterone Treatment
Darius A. Paduch, MD, PhD Associate Professor of Urology and Reproductive Medicine
Director Sexual Health and Medicine Research Director of Male Infertility Fellowship
Co-Director Male Infertility Genetics Laboratory Weill Cornell Medical College Dept of Urology
New York, NY 10065
Dr. Paduch: Ejaculatory dysfunction, inability to ejaculate or delayed ejaculation affects 10-
8% of men. Inability to ejaculate either intravaginally or at all is independent of erectile
function.
• Men with normal erection may take very long time to ejaculate (>30 min) or not able to
ejaculate at all. The men in our study had either normal erections or minimal erectile
dysfunction.
• Men of all ages have spontaneous erections but don’t ejaculate just from erection, it is
progression of arousal and activation of spinal cord motor generator for ejaculation which is
necessary for ejaculation.
• One of important factors in our ability to ejaculate is testosterone (T), testosterone allows for
normal function of CNS centers for ejaculation, it is a modulator and is necessary;
preadolescent boys don’t ejaculate because their spinal cord centers for ejaculations are not
mature – process dependent on testosterone. However testosterone is just one of many
neurotransmitters and hormones needed of normal ejaculation.

New York, NY 10065
• Actually our study showed that in men who achieved normal levels of testostosterone the
ejaculatory function have improved. As this was first double blinded and randomized clinical
trial we had to report our results based on radomization to testosterone treatment or
placebo. Unfortunately only 70-80% of men treated with topical testosterone preparation
will achieve normal testosterone level , we simply didn’t reach statistical significance based
on randomization and considering relatively low number of patients in each group. But in
men who achieved normal testosterone levels the difference was statistically significant.
• Testosterone should not be used to treat any conditions, including ejaculatory dysfunction, in
absence of low testosterone level.
• EjD is very common but it bares significant embarrassment stigma, it is difficult for the couple
to bear fact that male partner can’t ejaculate, it also creates issues within couple and
question about attraction and fidelity.
• We have previously showed that treatment with tadalafil improves ejaculatory and orgasmic
dysfunction and these data has been published.

New York, NY 10065
• This study was focused on effect of testosterone, but its main significance was it’s design: we
developed new tools to assess ejaculatory function and learned a lot about when patients or
their partners start to be bothered by EjD. If time to ejaclate takes > 30 min
• We are now looking into novel and available pharmacotherapy modulating dopaminergic and
canabioid signaling and reward mechanisms. I am also very excited about our potential work
in direct spinal cord motor generator nano stimulator, this could be very useful for men with
spinal cord injuries and diabetic patients. We paved the road for others and I am sure new
treatments are just a matter of time.

New York, NY 10065
• Dr. Paduch: Message to clinician: in 2015 we need to understand that sexual experience is
much more than just having rigid penis, disorders of ejaculation, orgasm, desire and arousal
are common but poorly understand in men.
• For centuries we were thought that only women fail to achieve orgasm . The work of my
team at WCMC and our collaborators at Eli LillY has shown that not only EJD is common,
but failure of orgasm affects men same as women. We hope that by sharing our research we
will stimulate further interest in this area and bring more funding from pharma and federal
sources to treat this common yet not understood condition.

New York, NY 10065
this study?
• Dr. Paduch: We are focusing in my lab on identifying if genetic mutations and single
nucleotide polymorphisms modulate delayed ejaculation and how small RNAs affect nerve
and vascular function in the penis and modulate sensory processing in the spinal cord and
brain. This research would uncover completely novel pathways of treatment of male sexual
dysfunction
• Citation:
• Paduch DA, Polzer PK, Ni X, Basaria S. Testosterone Replacement in Androgen-Deficient Men
With Ejaculatory Dysfunction: A Randomized Controlled Trial. Journal of Clinical
Endocrinology & Metabolism. 2015.

Type 2 Diabetes Linked to Decreased Brain Blood Flow and CognitiveAbility
Vera Novak, MD PhD Associate Professor of Neurology Dept. of Neurology, Stroke Division
Director Syncope and Falls in the Elderly Laboratory
Beth Israel Deaconess Medical Center
Boston, MA
• Dr. Novak: Diabetes mellitus (DM) is a major contributor to morbidity and mortality.
Type 2 diabetes mellitus affects more than 44 million people in the U.S., and its numbers are
growing rapidly, affecting up to 27% of older adults. Diabetes mellitus accelerates brain aging
by about 5 years1, manifests as a widespread generalized atrophy2, and promotes earlier
onset of vascular dementia and Alzheimer’s disease (AD).3,4 Diabetes mellitus -related
atrophy manifests as worse cognitive function, memory, and gait, especially during a dual
task, 5,6 and even a tight glycemic control did not improve cognitive function in participants of
the large clinical trials 7.

Boston, MA
• Dr. Novak: Sixty-five participants (aged 66± 9.2 years) 35 with T2DM and 30 non-diabetic
controls participated in this study. After 2 years of follow-up, participants with T2 Diabetes
mellitus had diminished vascular reactivity in the brain (an ability to increase blood flow in
responses to a task or metabolic demands) and performed worse on multiple cognitive tasks
(in particular verbal learning and memory). In T2DM group, lower cerebral vasoreactivity
correlated with worse performance on daily living activities. Specifically, the lower
vasodilatation (ability to increase blood flow) was associated with worse mental functions. In
addition, those with higher markers of inflammation had greater decline in vascular function
in the brain.

Boston, MA
• Dr. Novak: Impaired blood flow regulation in the brain may accelerate brain aging and
functional decline. Worse performance on daily activities, worse memory or slower gait
speed 8 in older diabetic adults may thus hallmark a decline in ability to regulate blood flow
in the brain.

Boston, MA
• MedicalResearch: What recommendations do you have for future research as a result of
this study?
• Dr. Novak: There is a need for new therapies focused on prevention of T2 Diabetes mellitus
related decline in older population that would be focused on improving vascular control and
reducing the impact of T2DM on the brain. Our pilot study has shown that insulin
administered sprayed into the nose may have potential benefits for learning and memory 9,
10. We will test this approach in our new clinical trial. Maintaining optimal T2DM control in
combination with exercise and active healthy lifestyle regimen is very important for T2DM
adults.

Boston, MA
• Reference List
• Franke,K., Gaser,C., Manor,B., & Novak,V. Advanced BrainAGE in older adults with type 2
diabetes mellitus. Front Aging Neurosci. 5, 90 (2013).
• Cui,X., Abduljalil,A., Manor,B., Peng,C.K., & Novak,V. Multi-Scale glycemic variability: A link to
gray matter atrophy and cognitive decline in type 2 diabetes. PLoS. One. 9, E86284E (2014).
• Xu,W.L., Qiu,C.X., Wahlin,A., Winblad,B., & Fratiglioni,L. Diabetes mellitus and risk of dementia
in the Kungsholmen project: a 6-year follow-up study. Neurology 63, 1181-1186 (2004).
• Korf,E.S., White,L.R., Scheltens,P., & Launer,L.J. Brain aging in very old men with type 2
diabetes: the Honolulu-Asia Aging Study. Diabetes Care 29, 2268-2274 (2006).
• Last,D. et al. Global and regional effects of type 2 diabetes mellitus on brain tissue volumes and
cerebral vasoreactivity . Diabetes Care 30, 1193-1199 (2007).
• Novak,V. et al. Adhesion molecules, altered vasoreactivity, and brain atrophy in type 2 diabetes.
Diabetes Care 34, 2438-2441 (2011).
• Launer,L.J. et al. Effects of intensive glucose lowering on brain structure and function in people
with type 2 diabetes (ACCORD MIND): a randomised open-label substudy. Lancet Neurol. 10, 969-
977 (2011).
• Jor’dan,A., Manor,B., & Novak ,V. Slow gait speed-an indicator of lower cerebral vasoreactivity
in type 2 diabetes mellitus. Frontiers in Aging Neuroscience Frontiers in Aging Neuroscience 6,135
(2014).
• Novak,V. et al. Enhancement of Vasoreactivity and Cognition by Intranasal Insulin in Type 2
Diabetes. Diabetes Care 3, 751-759 (2014).
• Zhang,H. et al. Intranasal insulin enhanced resting-state functional connectivity of hippocampal
regions in type 2 diabetes. Diabetes 64:687-688 (2015).

Boston, MA
• Citation:
• Chen-Chih Chung, Daniela Pimentel, Azizah J. Jor’dan, Ying Hao, William Milberg, and Vera
Novak. Inflammation-associated declines in cerebral vasoreactivity and cognition in type 2
diabetes. Neurology, July 2015 DOI: 10.1212/WNL.0000000000001820

Diabetic Severity May Predict Risk of Dementia
Wei-Che Chiu, MD, PhD
National Taiwan University College of Public Health,
Cathay General Hospital and Fu Jen Catholic University
Taipei, Taiwan
• Response: Diabetes mellitus is a common risk factor for dementia and accounts
for 6–8% of all cases of dementia in older populations. Cognitive
impairment is associated with the presence of diabetic complications
and diabetic severity, but the effects of diabetic severity on
dementia are unclear. Our study was to investigate the association
between the severity and progress of diabetes and the risk of
dementia.
• Response: The diabetic severity and progression reflected the risk
of dementia, and the early progress in diabetic severity could predict
the risk of dementia in new-onset diabetic patients.

Taipei, Taiwan
• Response:
• 1. The risk of dementia was increased from the diabetes onset and was
associated with the diabetic complication severity and progression.
• 2. Progress of the diabetic severity in the early years of diabetes
could predict the risk of dementia.
• 3. The prevention of diabetic progression is important to reduce the
risk of dementia.
• 4. The diabetic complication severity was another indicator of the
risk of dementia from the blood sugar.

Taipei, Taiwan
this study?
• Response: Because the etiology of dementia is varied, the mechanisms of
the diabetic severity and progression on the different types of
dementia should be further investigated.
• Citation:
• Wei-Che Chiu, MD, PhD et al. Progess of Diabetic Severity and Risk of Dementia. Journal of
Clinical Endocrinology & Metabolism, July 2015 DOI: 10.1210/jc.2015-1677

Anti-depressant Amitriptyline May Inhibit Adenovirus Infections
Prof. Urs Greber, PhD
Professor of Molecular Cell Biology
Institute of Molecular Life SciencesUniversity of ZurichZurich, Switzerland
Prof. Greber: This study has addressed two fundamental questions in virology – how do non-
enveloped viruses which are lipid-free penetrate through cell membranes, and how is this
process tuned by host lipids?
• We found that certain neutral lipids, ceramide lipids, were unregulated during the entry
process of human adenovirus into cells. The ceramide lipids enhanced the uptake of viruses
into cells by endocytosis, and they boosted the disruption of endosomal vesicles which
carried the virus,, and thereby enhanced infection.
• The ceramide lipids were found to be produced by the enzyme acid sphingomyelinase
(ASMase), which was secreted from lysosomes to the plasma membrane upon virus
attachment to cells.
• ASMase is a clinical target, and can be inhibited by the antidepressant amitriptyline, a small
chemical compound, which is widely used to treat mental disorders.

Anti-depressant Amitriptyline May Inhibit Adenovirus Infections
Prof. Urs Greber, PhD
Professor of Molecular Cell Biology
Institute of Molecular Life SciencesUniversity of ZurichZurich, Switzerland
• Prof. Greber: The anti-depressant amitriptyline inhibits infection of cells with human
adenovirus. This virus causes respiratory, ocular and intestinal disease.
this study?
• Prof. Greber: Future research will show if amitriptyline can be used to treat viral disease in
humans.
• Citation:
• Stefania Luisoni, Maarit Suomalainen, Karin Boucke, Lukas B. Tanner, Markus R. Wenk, Xue Li
Guan, Michał Grzybek, Ünal Coskun, Urs F. Greber. Co-option of Membrane Wounding
Enables Virus Penetration into Cells. Cell Host & Microbe, 2015; 18 (1): 75 DOI:
10.1016/j.chom.2015.06.006

Athletes With Shoulder Instability Better Able To Return To Sport After Arthroscopic Repair
Brett D. Owens, MD
Professor of Orthopaedic Surgery
Brown University Alpert Medical School
Providence, RI
Response: Last year at this meeting we presented the results of a prospective multicenter
study of collegiate contact athletes who experienced in-season shoulder instability events.
While most were able to return to sport within a week, only roughly one quarter were able
to successfully return without recurrent instability. We continued to follow this cohort and 39
athletes with additional eligibility the subsequent season. We found that 90% of the 29 who
underwent arthroscopic stabilization successfully returned the next season compared with
40% of the 10 underwent nonoperative treatment
• Response: Arthroscopic stabilization of shoulder instability events in collegiate athletes
results in a greater than 5 times increased likelihood of successful return to play in the
following season compared with nonoperative treatment.

Athletes With Shoulder Instability Better Able To Return To Sport After Arthroscopic Repair
Brett D. Owens, MD
Professor of Orthopaedic Surgery
Brown University Alpert Medical School
Providence, RI
this study?
• Response: This works underscores the importance of early arthroscopic stabilization of
shoulder instability in high risk patients.We need to continue to explore the incremental risk
associated with each recurrent instability event in athletes to provide optimal counseling.
• Citation:
• Abstract presented at the American Orthopaedic Society for Sports Medicine
• Treatment of shoulder instability helps return collegiate athletes to playing field

Shape Differences of Brain Important For Individualized Precision Medicine
Chun Chieh Fan Ph.D student USCD Cognitive Science and
Professor Anders M. Dale Ph.D Department of Cognitive Science,
University of California, San Diego School of Medicine
Response: The shape of human skull is closely associated with the ancestral background.
Forensics uses it for determining ethnicity. Anthropologists use it to infer neuroanatomical
change in human evolution. Yet it is unclear the inner content of skull, human brain, contains
how much information about individual’s ancestry.
• Our study found that different continental ancestries are associated with unique cortical
folding patterns. Even for contemporary populations in modern day USA, a melting pot of
ethnicities, cortical folding patterns are highly predictive of the percentage of each
continental ancestry, as determined based on the person’s genotype. These shape
differences between ancestral heritages are not necessarily related to brain function. It is
highly possible that the shape differences are resulting from a random process accumulated
along human history, without significant functional consequences.

• Response: Our findings are particularly important for individualized, or “precision”, medicine.
If a clinician wants to know where an individual patient’s brain size or shape measures fall
relative to age- and sex-matched norms or growth charts, it is essential that these norms be
based on individuals with similar ancestral background. Otherwise, the comparisons can be
misleading, and confounded by irrelevant ancestry effects. Building on the approach
described in the Current Biology paper, we believe it will be possible to calculate personalized
norms or growth charts for a range of brain measures, incorporating genetic information
from each individual patient, which may enable earlier, and more sensitive detection of brain
pathology or abnormal development.

this study?
• Response: One natural extension of the study will be to investigate the specific genes and
gene variants involved in the shape differences among ethnic ancestry groups. This effort will
be greatly facilitated by ongoing large, multi-site studies involving brain imaging and
genotyping.
• When combined with large biobanking, precision medicine, and health outcomes research
initiatives, the “Big Data” approach described in the Current Biology paper may allow for
creation of personalized risk scores, incorporating quantitative measures from brain imaging,
genomic information, ethnicity, family history, and molecular biomarkers, with much greater
diagnostic and prognostic utility than current approaches.
• Citation:
• Modeling the 3D Geometry of the Cortical Surface with Genetic Ancestry
• Fan, Chun Chieh et al. Chun Chieh Fan ,Hauke Bartsch,Andrew J. Schork,Chi-Hua
Chen,Yunpeng Wang,Min-Tzu Lo,Timothy T. Brown,Joshua M. Kuperman,Donald J. Hagler
Jr.,Nicholas J. Schork,Terry L. Jernigan,Anders M. Dale
• the Pediatric Imaging, Neurocognition, and Genetics Study
• Current Biology (Cell Press)
• DOI: http://dx.doi.org/10.1016/j.cub.2015.06.006

Study Confirms Validity of Bova Score For Pulmonary Embolism Patients
David Jimenez PhD, FCCP
Respiratory Department and Medicine Department
Ramon y Cajal Hospital IRYCIS, and Alcala de Henares University
Madrid Spain
Dr. Jimenez: Normotensive patients that have an estimated high-risk for pulmonary
embolism (PE)-related complications (i.e., intermediate-risk PE) might benefit from
surveillance in an intensive care setting or from the administration of specific advanced
therapy. The Bova score was developed for identifying these patients. This study confirms the
validity and reproducibility of the Bova score.
• Dr. Jimenez: Clinicians should combine clinical variables, and markers of right ventricular
dysfunction and myocardial injury to identify the sickest normotensive patients with acute
symptomatic pulmonary embolism.

Study Confirms Validity of Bova Score For Pulmonary Embolism Patients
David Jimenez PhD, FCCP
Respiratory Department and Medicine Department
Ramon y Cajal Hospital IRYCIS, and Alcala de Henares University
Madrid Spain
this study?
• Dr. Jimenez: Prospective studies should further address the safety and efficacy of early
recanalization procedures for intermediate-risk pulmonary embolism patients who are
identified with the proposed criteria.
• Citation:
• Validation of a model for identification of patients at intermediate to high risk for
complications associated with acute symptomatic pulmonary embolism
• Fernández C, Bova C, Sanchez O, et al.
• Chest
• 2015;148(1):211-218. doi:10.1378/chest.14-2551.

Atrial Fibrillation Increase Leading To More Hospitalizations and Higher Costs
Azfar B. Sheikh, M.D.
Internal Medicine Resident Physician
Staten Island University Hospital
New York
• Dr. Sheikh: The background of this review article circles around the impact of
atrial fibrillation on epidemiology, trends in hospitalizations, costs
associated with hospitalization and outpatient care, in the United
States. This article also describes the benefits of newer treatment
modalities compared to the standard of care with regards to
symptomatic improvement and prevention of thromboembolism. These
findings are supported by several cost-utility analyses/

New York
• Dr. Sheikh: The main findings of the study are:
• The cost of hospitalization is three times higher for patients with
atrial fibrillation than those without atrial fibrillation.
• 5 million new cases are being reported annually.
• The incidence of atrial fibrillation is projected to increase from
1.2 million cases in 2010 to 2.6 million cases by 2030. Due to this
increase in incidence, the prevalence of atrial fibrillation is
projected to increase from 5.2 million cases to 12.1 million cases by
2030.
• The most common co-moribidites associated with atrial fibrillation
were hypertension, diabetes mellitus, and chronic obstructive lung
disease.
• According to the NIS database, the atrial fibrillation.
hospitalization rate has increased from 1552 to 1812 per one million
US residents per year from 2000 to 2010 (relative increase 14.4%).
• According to the NIS database, the mortality associated with atrial
fibrillation hospitalizations has decreased significantly from 1.2% in
2000 to 0.9% in 2010 (relative decrease 29.2%).
• The median length of stay in the hospital is 3 days and increases
proportionally with a rise in CHADS2 score.
• The largest source of direct healthcare costs associated with
atrial fibrillation is hospitalization. According to the NIS database,
the mean cost of inpatient atrial fibrillation hospitalization
increased significantly from $6401 in 2001 to $8439 in 2010 (relative
increase 24.0%). The mean cost of atrial fibrillation hospitalization
also increases proportionally with a rise in CHADS2 score.
• In the outpatient setting, the highest costs were associated with
physician office visits in comparison to emergency room and urgent
care visits.
• With regards to prevention of thromboembolism, the new oral
anticoagulant agents (dabigatran, rivaroxaban, and apixaban) have been
found to be more cost-effective compared to warfarin.
• Left atrial catheter ablation is more effective than rate control
and rhythm control. It is more cost-effective in younger patients who
are moderate risk for stroke.

New York
• Dr. Sheikh: Clinicians should pay strong attention to the risk factors associated
with atrial fibrillation. Their practice should emphasize on
preventing and limiting the progression of risk factors attributed to
the development of atrial fibrillation. Once the patients have
developed atrial fibrillation, the clinician should consider the use
of new oral anticoagulant agents over warfarin unless a
contradindication exists limiting their use. They should also consider
early referral to a cardiac electrophysiologist for ablation in a
younger patient population who are at moderate risk for stroke. Those
who are not candidates for ablation should be managed using the rate
control strategy.
• Patients also need to emphasize their attention towards the reversible
risk factors associated with atrial fibrillation. They should have
frequent follow up with their primary doctors to optimally manage each
condition associated with atrial fibrillation.

New York
this study?
• Dr. Sheikh: In the future, additional cost-utility analyses are required for
• comparing each of the new oral anticoagulants amongst each other.
• comparing cryoballoon ablation to radiofrequency ablation.
• comparing each device used for left atrial appendage closure amongst each other.
• Citation:
• Trends in Hospitalization for Atrial Fibrillation : Epidemiology, Cost, and Implications for the
Future
• Sheikh, Azfar et al.
Progress in Cardiovascular Diseases
• DOI: http://dx.doi.org/10.1016/j.pcad.2015.07.002

Heroin Addiction Most Often Preceded by Opioid Abuse
Christopher M. Jones, Pharm D., M.P.H.
Senior advisor, Office of Public Health Strategy and Analysis
Office of the Commissioner, Food and Drug Administration
Dr. Jones: Heroin use and overdose deaths have increased significantly in the United States
in recent years. Most heroin users have a history of nonmedical use of prescription opioid
pain relievers as well, and an increase in the rate of heroin overdose deaths has occurred
concurrently with an epidemic of prescription opioid overdoses.
• Although it has been postulated that efforts to curb opioid prescribing, resulting in restricted
prescription opioid access, have fueled heroin use and overdose, a recent analysis of 2010–
2012 drug overdose deaths in 28 states found that decreases in prescription opioid death
rates within a state were not associated with increases in heroin death rates; in fact,
increases in heroin overdose death rates were associated with increases in prescription
opioid overdose death rates.

• In addition, a study examining trends in opioid pain reliever overdose hospitalizations and
heroin overdose hospitalizations between 1993 and 2009 found that increases in opioid pain
reliever hospitalizations predicted an increase in heroin overdose hospitalizations in
subsequent years. Thus, the changing patterns of heroin use and overdose deaths are most
likely the result of multiple, and possibly interacting, factors. Moreover, there is a lack of
research examining recent trends in the prevalence of other substance use among persons
using heroin, especially among the high-risk population of heroin users who meet diagnostic
criteria for heroin abuse or dependence.
• We wanted to better understand how heroin use is changing and identify the demographic
and substance using groups that are at greatest risk for use. Knowing this information can
help prevention efforts.
• HHS Secretary Sylvia M. Burwell has made addressing opioid abuse, dependence, and
overdose a priority and work is underway within HHS on this important issue. The evidence-
based initiative focuses on three promising areas: informing opioid prescribing practices,
increasing the use of naloxone – a drug that reverses symptoms of a drug overdose, and
using medication-assisted treatment to slowly move people out of opioid addiction.
• The Obama Administration is also committed to tackling the prescription drug and heroin
epidemic, proposing significant investments to intensify efforts to reduce opioid misuse and
abuse.

Dr. Jones: Heroin use has increased significantly across most demographic groups. There
were significant increases in heroin use among demographic groups that have had historically
lower rates of heroin use, including women, the privately insured, and people with higher
incomes. In fact, the gap between men and women, low and high incomes, and people with
Medicaid and private insurance have narrowed in the past decade.
• Heroin use is occurring in the context of broader poly-substance use, including marijuana,
alcohol, cocaine, and prescription drugs. The use of heroin with other substances increases
the risk of overdose. Nearly all (96%) people who reported heroin use also reported using at
least one other drug in the past year. More than half (61%) used at least three other drugs.

• Among heroin users in 2011-2013:
• 45% had past-year prescription opioid painkiller abuse or dependence
• 36% had past-year alcohol abuse or dependence
• 25% had past-year cocaine abuse or dependence
• 24% had past-year marijuana abuse or dependence
• As heroin abuse and dependence have increased, so have heroin-related overdose deaths.
From 2002 through 2013, the rate of heroin-related overdose deaths nearly quadrupled.
• The strongest risk factor for heroin abuse or dependence was opioid pain reliever abuse or
dependence followed by cocaine abuse or dependence.

• Dr. Jones: Clinicians can follow best practices for responsible painkiller prescribing to reduce
opioid painkiller addiction, the strongest risk factor for heroin addiction. This entails
• 1) using state prescription drug monitoring programs and asking patients about past or
current drug and alcohol use prior to considering opioid treatment;
• 2) prescribing the lowest effective dose of an opioid and only the quantity needed for each
patient; and
• 3) linking patients with substance use disorders to effective substance abuse treatment
services, including the use of medication assisted treatment for people with opioid use
disorders.
• Patients and others can learn more about the risks of using heroin and other drugs and
become trained in how to recognize and respond to an opioid overdose. For people who are
struggling with substance abuse problems, they can call 1-800-662 HELP for assistance.

this study?
• Response: More research is needed to evaluate the impact of interventions designed to
reduce prescription opioid and heroin abuse. We also need to conduct additional research to
further understand the risk and protective factors for heroin initiation and heroin addiction.
• Citation:
• Vital Signs: Demographic and Substance Use Trends Among Heroin Users — United States,
2002–2013
• Weekly
• July 10, 2015 / 64(26);719-725

Clinically Silent Maternal Cancer Detectable By Prenatal Testing
Diana W. Bianchi, M.D.
Executive Director, Mother Infant Research Institute
Vice Chair for Research and Academic Affairs, Department of Pediatrics
Tufts Medical Center
Response: Noninvasive Prenatal Testing (NIPT) is the fastest growing genetic test. It has been
available since late 2011. Over 2 million tests have been performed worldwide. Cancer in
pregnancy is rare, and only occurs in 1 in 1,000 pregnant women. About 0.2 per cent of
noninvasive prenatal tests that use sequencing of maternal plasma DNA have a so-called “false
positive” result. In most cases this is not an error, but there is a biological explanation for the
discrepancy between the abnormal noninvasive prenatal test result and a normal fetal
chromosome result obtained from a diagnostic procedure, such as amniocentesis or chorionic
villus sampling (CVS). We are very interested in the underlying biological explanations for the
false positive cases, and it turns out that a clinically silent tumor in the mother is one of them.
The mother’s tumor is shedding DNA into her blood that is detected by the prenatal test.

• In a large clinical dataset of over 125,000 pregnant women who had a DNA sequencing
screen for fetal chromosome abnormalities there were 10 women who were subsequently
found to have cancer. We retrospectively analyzed the DNA sequencing results in 8 of these
women and found that they had abnormalities in multiple areas of the genome, suggesting
that it was DNA from the tumor that was shed into the maternal blood and being detected by
the prenatal screen.
• The noninvasive prenatal sequencing test result that was most suggestive of a cancer risk was
the presence of more than one aneuploidy. This finding was present in 7 of the 10 women
who had cancer.
• In three of the eight women we studied it was the abnormal prenatal test result that
triggered a subsequent work-up that led to the diagnosis of cancer.

• Response: Make sure that the patient knows that the noninvasive prenatal test sequences
both her own DNA and the DNA from the placenta, so an abnormal result does not
necessarily mean that something is wrong with the baby. All abnormal noninvasive prenatal
test (NIPT) results need to be confirmed with a fetal diagnostic karyotype. The patient should
not take irrevocable action until she has the results of the fetal karyotype. Cancer is only a
possible explanation if there is a discrepancy between the Noninvasive Prenatal Testing result
and a normal fetal karyotype (obtained by amniocentesis or CVS).

this study?
• Response: We need to do a prospective study to determine what is the pattern of genome
imbalance that is most closely associated with a risk of cancer. Furthermore, we need to
determine what is the appropriate subsequent medical work-up for pregnant women who
have highly unusual noninvasive prenatal testing results, such as the detection of multiple
aneuploidies.
• Citation:
• Bianchi DW, Chudova D, Sehnert AJ, et al. Noninvasive Prenatal Testing and Incidental
Detection of Occult Maternal Malignancies. JAMA. Published online July 13, 2015.
doi:10.1001/jama.2015.7120.

Women’s Out-of-Pocket Expenses For Contraceptives Drop After ACA
Nora V. Becker MD/PhD candidate
Department of Health Care Management and Economics
Wharton School, University of Pennsylvania, in Philadelphia.
Response: The Affordable Care Act mandates that private health insurance plans cover
prescription contraceptives with no consumer cost sharing. The positive financial impact of this
new provision on consumers who purchase contraceptives could be substantial, but it has not yet
been estimated. Using a large administrative claims data set from a national insurer, we
estimated out-of-pocket spending before and after the mandate. We found that mean and
median per prescription out-of-pocket expenses have decreased for almost all reversible
contraceptive methods on the market. The average percentages of out-of-pocket spending
for oral contraceptive pill prescriptions and intrauterine device (IUD) insertions by women using
those methods both dropped by 20 percentage points after implementation of the ACA mandate.
We estimated average out-of-pocket savings per contraceptive user to be $248 for the IUD
and $255 annually for the oral contraceptive pill.

• Response: Privately-insured patients should take away from our study that their financial
options for contraception have changed because of the ACA. More effective, longer-term
methods like IUD or the implant used to require a large up-front payment of several hundred
dollars, and now should be available without any copays and deductibles. Clinicians,
especially those who provide well-woman services, should mention this to their patients as
well. This is still a new law and many women may not realize that their insurance coverage
has changed.

this study?
• Response: The next big question for researchers is how will these changes in out-of-pocket
price affect the rates of birth control use in the U.S. There are two types of contraceptive use
that could be affected. Overall rates of use of any birth control method could increase, and
the distribution of methods chosen could also change. How women respond to these price
changes will depend on how price-sensitive they are to the out-of-pocket cost of
contraceptives. There is not much research on this in the U.S., but what little we have
suggests that women may be fairly price-insensitive, suggesting that perhaps overall rates of
use might not change substantially. I’d speculate that where we are more likely to see a
response is in the type of method chosen; women may choose longer-term methods at
higher rates now that the up-front cost of these methods has been lowered to zero. It’s too
soon to know for sure what the final effects will be; this is an area where it will be important
to continue studying the long-term impacts of the ACA.
• Citation:
• Women Saw Large Decrease In Out-Of-Pocket Spending For Contraceptives After ACA
Mandate Removed Cost Sharing
• Nora V. Becker and Daniel Polsky
• Health Aff July 2015 34:71204-1211; doi:10.1377/hlthaff.2015.0127

Lack of Sleep May Impair Memory Functions In Stressful Situations
Jonathan Cedernaes M.D., Ph.D.
Department of Neuroscience
Uppsala University
Sweden
• Dr. Cedernaes: Sleep is known to facilitate the formation of long-term memory in humans, by
transferring newly learned memories from short-term to long-term memory stores. Studies
however indicate that even shorter periods of sleep – including naps – can ensure access to
different types of memories under normal restful conditions. Furthermore, while some studies
have shown that acute sleep loss can exacerbate e.g. physiological responses to acute stress,
it it has not been studied whether shortened sleep in combination with acute cognitive stress
can have a negative impact on the retrieval of newly learned memories.
• With this background in mind, we conducted a study where we aimed to investigate how
nocturnal sleep duration impacts this memory transfer, and to what extent long-term
memories formed by sleep remain accessible after acute cognitive stress.

Uppsala University
Sweden
We recruited 15 participants who in each of two sessions first underwent a learning session in
the evening, during which they learned 15 card pair locations on a computer screen. Then, in one
of the two experimental session, subjects slept for half a night (4-hr), instead being able to sleep
for a full night (8-hr) in the other session. On the morning after each sleep condition, we had the
subjects try to recall as many card pair locations as possible. We found that following half a night
of sleep (4-hr), participants were equally able to recall memories for the learned card pair
locations, as after a full night of sleep (8-hr). However, we also showed that the ability to retrieve
memories following 30 minutes of acute stress, in the morning after these two sleep conditions,
was different depending on whether the participants had slept for 8 or 4 hours. Following short
sleep, the 30-min long stress exposure reduced the participants’ ability to recall the card pair
locations that the participants had learned the previous night by around 10%. In contrast, no such
stress-induced memory impairment was observed when the same men were allowed to sleep for
a full night.

Uppsala University
Sweden
• Dr. Cedernaes: On the basis of our study findings, we have two important take home
messages:
• First, even though losing half a night of sleep may not impair memory functions under
baseline conditions, the addition of acute cognitive stress may be enough to lead to
significant impairments. These impairments can possibly be detrimental in real-world
scenarios, e.g. for medical health professionals who often have to go without sleep for long
periods but also often face stressful situations in which they need to be able to access
information stored in their long-term memory.
Second, interventions that allow people who usually don’t get enough sleep to sleep
longer, including delaying school start times and greater use of flexible work schedules, may
improve their academic and occupational performance by ensuring optimal access to memories
under stressful conditions.

Uppsala University
Sweden
this study?
• Dr. Cedernaes: An important next step will be to investigate how chronic sleep loss and/or
more chronic stress may interact to impair the ability to retrieve memories that are
consolidated during sleep. It will also be interesting to study how individual factors such as
genetics may determine how vulnerable people are to the effects of acute or chronic stress
when they have not slept enough.
• Citation:
• Cedernaes et al. Short sleep makes declarative memories vulnerable to stress in humans.
Sleep, 2015

May Be Possible To Use Video Games To Block PTSD Intrusive Memories
MedicalResearch.com interview with
Dr. Ella James, Post-Doctoral Investigator Scientist
Medical Research Council Cognition and Brain Sciences Unit
Cambridge, UK.
• Dr. James: Post-traumatic stress disorder (PTSD) is experienced by some people after a
traumatic event. While many people who’ve been involved in traumatic events don’t
experience PTSD, those who do typically have repeated visual intrusive memories of certain
moments in vivid detail that pop back into mind, seemingly out of the blue. For example,
with PTSD after a car crash might repeatedly ‘see’ the moment the other car crashed into
them.
• The recommended treatment for PTSD is cognitive behaviour therapy, a talking therapy that
has been demonstrated to work well. But it is only delivered once intrusive memories have
become established and PTSD is diagnosable – i.e. at least one month after the traumatic
event occurred. At present, there is nothing readily available for use soon after trauma that
has been shown to prevent symptoms building up and PTSD becoming established.

Cambridge, UK.
• In previous laboratory work our research team showed that playing Tetris shortly after
viewing events with traumatic content (e.g. film footage of road safety campaigns – what we
call an experimental trauma) could reduce intrusive memories of those events in healthy
volunteers over the following week [2, 3] when played in a 4-hour time window after
viewing. We reasoned that this was because having to follow and track the shapes, colour
and movement of the coloured blocks in Tetris soon after seeing the experimental trauma
(the film) disrupted aspects of the visual memory of that event from being ‘laid down’ in the
sensory part of the brain, whilst leaving memory for the narrative and meaning of the events
unaffected.
• However, it is hard to reach people so soon after a traumatic event in the real world and
memories for events become ‘fixed’ in mind within hours after an event making them
difficult to change. Therefore it was important to show whether we can change older,
established memories of trauma.

Cambridge, UK.
• Dr. James: To our knowledge, this work is the first to show that it is theoretically possible to
disrupt involuntary intrusive memory for events that are ‘fixed’ in mind, in the current study
a memory for an experimental trauma that is 1 day old. The study addressed memory
‘reconsolidation’ and used a simple cognitive blockade procedure (rather than drugs or a
more complex task) involving 3 steps;
• 1) reactivation of the memory (volunteers viewed non-traumatic still images from the film
watched 24 hours earlier,
• 2) a wait period of 10 minutes to allow for memory for the experimental trauma to ‘become
malleable’, then
• 3) Tetris game play to interfere with the malleable memory, and reduce the occurrence of
subsequent intrusive memories over the week.

Cambridge, UK.
We showed that merely playing ‘Tetris’ (without prior reactivation) did not reduce intrusions – by
analogy, distraction by enjoyable computer games alone may not help. Further, just being
exposed to reminders of the event (without Tetris play afterwards) did not reduce subsequent
intrusion frequency – by analogy then, simply recalling/talking about a trauma in the absence of
the cognitive task, may not help reduce intrusive memories. Rather, it is the critical combination
of both reactivating the trauma memory followed by a short break and then playing ‘Tetris’ that is
necessary to reduce the occurrence of later intrusive memories.

Cambridge, UK.
• Dr. James: The first key take-home message is that these findings relate to experimental
research that is still in the early stages, so no immediate clinical implications can be drawn.
• Our research uses an experimental trauma to study intrusive, visual images that pop back to
mind involuntary as an analogue of intrusive memories that are the hallmark symptom of
post-traumatic stress disorder (PTSD).
• From a research perspective our findings indicate that it may be possible, under certain
conditions, to render old memory for emotional events as less intrusive, even for memories
have consolidated and are established in mind. Further research is needed to develop this
approach as a potential intervention to reduce intrusive memories. Again, we are keen to
emphasise that this research is still in the early stages, and careful steps need to be taken to
translate findings from the laboratory to the clinic.

MedicalResearch.com: Medical Research Exclusive Interviews July 16 2015

MedicalResearch.com: Medical Research Exclusive Interviews July 16 2015

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MedicalResearch.com: Medical Research Exclusive Interviews July 16 2015