MedicalResearch.com - Medical Research Interviews Week in Review

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 13 2014
For Informational Purposes Only: Not for Specific Medical Advice.

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Study Finds No Link Between HPV Vaccine and Blood Clots
MedicalResearch.com Interview with:
Nikolai Madrid Scheller
Department of Epidemiology Research
Statens Serum Institut, Copenhagen
• Medical Research: What are the main findings of the study?
• Answer: In a large and comprehensive study of more than 1.5 million women including more than
500,000 HPV vaccinated there was no association between HPV vaccination and blood clots.
Medical Research: What should clinicians and patients take away from your report?
• Answer: The HPV vaccines are now included in immunization programs around the world and
emerging safety issues need to be addressed in thorough and well-designed studies to inform
policymakers, caregivers, and the public. Our study adds to the body of data that support a
favorable overall safety profile of the qHPV vaccine and expands this knowledge by providing
comprehensive analyses of the risk of VTE after qHPV vaccination.
• Medical Research: What recommendations do you have for future research as a result of this
study?
• Answer: It is essential that other severe adverse events reported in temporal association with HPV-
vaccination are investigated in detail in controlled and well-powered studies to either confirm or
refute an association with the vaccine in question, as earlier experiences have demonstrated that
such safety concerns might compromise vaccine acceptance and uptake.
• Citation:
• Scheller N, Pasternak B, Svanström H, Hviid A. Quadrivalent Human Papillomavirus Vaccine and the
Risk of Venous Thromboembolism. JAMA. 2014;312(2):187-188. doi:10.1001/jama.2014.2198.
•
Read the rest of the interview on MedicalResearch.com
Content Not Intended as Specific Medical Advice

Childhood Obesity: Sibling Influence May Be Greater Than Parents
MedicalResearch:.com Interview with: Mark C. Pachucki, PhD
Senior Scientist, Mongan Institute for Health Policy
Affiliated Faculty, MGHfC Division of General Academic Pediatrics
Instructor in Medicine and Pediatrics, Harvard Medical School Boston, MA 02114
• MedicalResearch: What are the main findings of the study?
• Dr. Pachucki: We found that in in one-child families, having an obese parent made a child
about twice as likely to be obese themselves. However, in two-child families, a child’s obesity status
was more strongly related with their sibling than with their parent. Even more interesting, in the
case of the younger sibling, the parent’s obesity status was not related with that child’s obesity
status at all. These findings matter because family members are primary sources of social influence
for children – understanding how health status is correlated within a family gives us a better
foothold on possible intervention strategies.
• MedicalResearch: Were any of the findings unexpected?
• Dr. Pachucki: We’ve known from prior research that there’s a strong parent-child obesity link, and
separate studies have shown that there’s a strong sibling-sibling obesity correlation as well. Parents
model healthy and unhealthy behaviors for their children through their own actions; siblings do this
as well. So it wasn’t immediately clear which kind of obesity relationship would be stronger. I went
into this with a hunch that given parents’ oversize roles in their kids’ lives, parent-child obesity
would be stronger than sibling-sibling obesity, but I was surprised that it was the opposite. What’s
also interesting is that if siblings were of the same gender, it made a big difference in their
shared obesity status. Having an older brother who is obese makes it more likely that a younger
brother will also be obese. For girls, the pattern was the same – having an obese older
sister increases the odds that the younger sister will be obese.

Childhood Obesity: Sibling Influence May Be Greater Than Parents
MedicalResearch:.com Interview with: Mark C. Pachucki, PhD
Senior Scientist, Mongan Institute for Health Policy
Affiliated Faculty, MGHfC Division of General Academic Pediatrics
Instructor in Medicine and Pediatrics, Harvard Medical School Boston, MA 02114
• MedicalResearch: What should clinicians and patients take away from your report?
• Dr. Pachucki: Our health is often more connected with the other people in our lives than we
commonly recognize. Clinicians should continue to pay close attention to the health status and
behaviors of other people in a child’s family. For adult patients who have children, our message
isn’t that your health doesn’t matter to your child’s health, but that during a child’s development,
their siblings may play a greater role in their health behaviors and health outcomes. For child
patients, our message is that if they make efforts to eat healthy food and get enough exercise, it
can also improve the health of their brother or sister.
• MedicalResearch: What recommendations do you have for future research as a result of this
study?
• Dr. Pachucki:: This was a relatively modest study concerned with reported behaviors, and it would
be great to replicate it on a larger scale with more detailed information on family members’
measured food intake, physical activity and weight status. We also recognize that obesity is a result
of a mix of behavioral, social, and genetic factors, and we could only look at part of the puzzle. Our
study was a cross-sectional snapshot at one point in time, and we examined correlations, not causal
relationships. Longitudinal data could provide stronger evidence of sibling or parental responsibility
for a child’s health. More concrete knowledge in this area would help us use information about
relationships to improve family-based obesity interventions.
• Citation:
• Within-Family Obesity Associations
Pachucki, Mark C. et al. American Journal of Preventive Medicine

Hypoxia Associated With Improved Insulin Sensitivity
Eric Ravussin, Ph.D., Boyd Professor Director Nutrition Obesity Research Center
Douglas L. Gordon Chair in Diabetes and Metabolism
Associate Executive Director for Clinical Science Baton Rouge LA
• Medical Research: What is the background of this study?
• Dr. Ravussin: It has long been postulated that hypoxia is bad for metabolic health.
• Hypoxia of adipose tissue has been thought to cause oxidative stress, resulting in the
recruitment of macrophages with resultant secretion of cytokines and
inflammation. However, repeated bouts of hypoxia induced during vigorous exercise results
in increased glucose uptake and vascularization of muscle tissue. In addition, living at high
altitude is associated with a lower prevalence of impaired fasting glucose and type 2 diabetes
compared with living at low altitude.
• Therefore, we asked the question, “What is the balance between the beneficial effects of
hypoxia in muscle tissue and ‘bad’ effects in adipose tissue”? We devised a study in eight
healthy men of different ethnicities, put into a hypoxic environment for 10 consecutive nights
for 10 hours. The subjects slept in a hypoxic tent, using nitrogen dilution.
• Dr. Ravussin: The main findings of this study included:
• Adipose tissue hypoxia was confirmed;
• Subjects lost an average of 1.2 kg;
• This study reports for the first time a reduced fasting glucose level and improved whole-body
(skeletal muscle) and hepatic insulin sensitivity after nightly exposure to moderate hypoxia.

Hypoxia Associated With Improved Insulin Sensitivity
Eric Ravussin, Ph.D., Boyd Professor Director Nutrition Obesity Research Center
Douglas L. Gordon Chair in Diabetes and Metabolism
Associate Executive Director for Clinical Science Baton Rouge LA
• Medical Research: Were any of the findings unexpected?
• Dr. Ravussin: Insulin sensitivity increased a surprising 23%, with a significant improvement in the
glucose disposal rate (measured using a hyper-insulinemic euglycemic clamp)
• Medical Research: What should clinicians and patients take away from your report?
• Dr. Ravussin: Our study suggests that while hypoxia may be bad for adipose tissue, it may not be
bad overall in terms of metabolic health. The impact on appetite in particular is interesting, as it is
known that individuals often lose weight when exposed to high altitudes. At this point, we can
speculate that occasional hypoxia may be somewhat protective against diabetes.
study?
Dr. Ravussin:
• First, we have applied for a grant to do a similar study in diabetics, using an oral glucose tolerance
test instead of a clamp.
• Second, we would like to examine alternatives to a hypoxic tent, perhaps using a CPAP type mask.
• Third, we would like to study whether less frequent hypoxic exposure, perhaps 1-2 nights per week,
would have a beneficial effect on insulin sensitivity and fasting glucose.
• Citation:
• Ten Nights of Moderate Hypoxia Improves Insulin Sensitivity in Obese Humans
• Virgile Lecoultre, Courtney M. Peterson, Jeffrey D. Covington, Philip J. Ebenezer, Elizabeth A. Frost,
Jean-Marc Schwarz, and Eric Ravussin
Diabetes Care December 2013 36:12 e197-e198; doi:10.2337/dc13-1350 1935-5548

Best Way To Avoid Repeat ACL Injury Is To Avoid Cutting Activities
Christoher C. Kaeding M.D. Judson Wilson Professor, Department of Orthopaedics
Executive Director, Sports Medicine Center
Head Team Physician, Department of Athletics The Ohio State University
Dr. Kaeding:
• Younger age and high activity level were predictors off another ACL injury after an ACL
Reconstruction.
• Allograft use in younger more active patients Had an increased risk of re-injury.
•
MedicalResearch: Were any of the findings unexpected?
• Dr. Kaeding: That gender was not a risk factor for re-injury may surprise some people.
• Dr. Kaeding: The best WAY TO AVOID ANOTHER ACL INJURY IS TO NOT RETURN TO AGGRESSIVE
CUTTING ACTIVITIES
study?
• Dr. Kaeding: We need do more research into Allograft use in ACL surgery..
• Citation: Abstract Presented at the AOSSM 2014 Annual Meeting abstract discussing:
• Paper 24: Risk Factors and Predictors of Subsequent ACL Injury after ACL
Reconstruction: Prospective Analysis of 2801 Primary ACL Reconstructions
Christopher C. Kaeding MD, Angela Pedroza MPH, Emily Reinke PhD, Laura J. Huston MS, on behalf
of MOON Group, The Ohio State University, Columbus, OH
• Vanderbilt University, Nashville, TN

Kidney Stone Risk Rises With the Temperature
Gregory Tasian, MD, MSc, MSCE
Attending Urologist
The Children’s Hospital of Philadelphia
• Dr. Tasian: The risk of developing kidney stones increased during the study period in all the cities except
Los Angeles when mean daily temperatures rose above 50°F (10°C). Mean daily temperatures reaching
86°F (30°C) were associated with risk increases of 38% in Atlanta, 37% in Chicago, 36% in Dallas, and 47%
in Philadelphia compared with 50°F (10°C). Kidney stone risk peaked within 3-5 days of exposure to high
temperatures but then decreased within 7 to 10 days afterward.
• Dr. Tasian: The risk of kidney stone presentation also increased at low temperatures in Atlanta, Chicago,
and Philadelphia. One possible explanation is that patients were spending more time inside and thus have
a risk of stones associated with warmer indoor temperatures.
• Dr. Tasian: For patients who are susceptible to stone formation, the risk of seeking care for kidney stones
increases as daily temperatures risk.
• Medical Research: What recommendations do you have for future research as a result of this study?
• Dr. Tasian: These findings need to be validated in other populations, including the un or underinsured.
Additionally, further studies to determine whether, race, age, or sex modifies the effect of temperature
will help elucidate particular groups of patients particularly vulnerable to heat-mediated
nephrolithiasis. Ultimately, it is necessary to develop strategies to increase water intake, which mitigates
the effect of dehydration on heat-mediated stone risk, among patients who have a history of kidney
stones.
Citation:
• Daily Mean Temperature and Clinical Kidney Stone Presentation in Five U.S. Metropolitan Areas: A Time-
Series Analysis
Gregory E. Tasian,1,2,3 Jose E. Pulido,2 Antonio Gasparrini,4 Christopher S. Saigal,5,6 Benjamin P. Horton,7,8 J.
Richard Landis,9 Rodger Madison,6 and Ron Keren3,9,10 for the Urologic Diseases in America Project
Environ Health Perspect; DOI:10.1289/ehp.1307703

Psychiatric Medications Linked To High Number of ER Visits
MedicalResearch.com interview with:
Lee M. Hampton, MD, MSc: Division of Healthcare Quality Promotion
Centers for Disease Control and Prevention Atlanta, Georgia
• Dr. Hampton: The study, which used CDC’s national outpatient adverse drug event surveillance
system (NEISS-CADES), found that there are almost 90,000 estimated annual emergency
department visits by adults for adverse drug events from therapeutic use of antipsychotics,
antidepressants, sedatives and anxiolytics, lithium salts or stimulants between 2009 and 2011.
Almost one in five of those emergency department visits (19.3%) resulted in hospitalization.
Sedatives and anxiolytics, antidepressants, and antipsychotics each caused 20,000 to 30,000
emergency department visits annually. However, relative to how often each of these types of
medications was prescribed at outpatient visits, antipsychotics and lithium salts were more likely to
cause emergency department visits for adverse drug events than were sedatives, stimulants, and
antidepressants. Antipsychotics caused 3.3 times more emergency department visits for adverse
drug events than sedatives, 4.0 times more emergency department visits than stimulants, and 4.9
times more emergency department visits than antidepressants relative to their outpatient use.
• Out of the 83 specific drugs the study looked at, ten drugs were implicated in nearly 60% of the
emergency department visits for ADEs from therapeutic use of antipsychotics, antidepressants,
sedatives and anxiolytics, lithium salts or stimulants. Zolpidem was implicated in nearly 12% of all
such emergency department visits and 21% of such emergency department visits involving adults
aged 65 years or older, more than any other antipsychotic, antidepressant, sedative or anxiolytic,
lithium salt or stimulant.

• Dr. Hampton: We were surprised that almost half (49.4%) of adult emergency department
visits for adverse events from the psychiatric drugs we looked at involved patients who were
19-44 years old. That means patients who were 19-44 years old had almost as many
emergency department visits for ADEs from therapeutic use of antipsychotics,
antidepressants, sedatives and anxiolytics, lithium salts or stimulants as did adults who were
45 years old or older. Even when you take the different age group’s use of these drugs into
account, the adults who were 19 to 44 years old had more ED visits for antipsychotic,
sedative and anxiolytic, and antidepressant adverse events than did adults 45 to 64 years old
or adults who were 65 years old or older.
• We are not certain why that was the case, but younger adults may be more likely to visit an
ED if they have a problem and ED doctors may be more likely to think a younger patient’s
problem was due a drug, in part because a younger patient usually has fewer chronic medical
conditions that could also have caused his or her problem. Nevertheless, the large number of
ED visits for adverse events from psychiatric drugs among young people shows that adverse
events from these drugs are a problem for all age groups, not just the elderly.

• Dr. Hampton: Last year, the leaders of the American Psychiatric Association, psychiatrists’
professional organization, urged doctors to use antipsychotics cautiously and only after exploring
the feasibility of using alternate treatments. Our report reinforces that it is important for doctors
and patients to heed the warning from the American Psychiatric Association to be cautious in their
use of antipsychotics.
• Doctors and patients should also be cautious in using zolpidem and other sedatives, particularly
because there are many treatment options for insomnia, the condition which zolpidem is intended
to treat.
study?
• Dr. Hampton: There have been many developments over the last few years that could influence
how many adverse events from psychiatric medication use occur, ranging from the warnings from
the American Psychiatric Association to revisions to the Diagnostic and Statistical Manual used to
make psychiatric diagnoses to some of these medications going off patent. It will be useful to track
the number of emergency department visits for adverse events from psychiatric drugs changes over
time in response to those developments.
• Citation:
• Hampton LM, Daubresse M, Chang H, Alexander G, Budnitz DS. Emergency Department Visits by
Adults for Psychiatric Medication Adverse Events. JAMA Psychiatry. Published online July 09, 2014.
doi:10.1001/jamapsychiatry.2014.436.

End Stage Kidney Disease: Does Peritoneal Dialysis Offer A Survival Advantage?
Victoria A. Kumar, M.D. Internal Medicine/Nephrology
Division of Nephrology Department of Internal Medicine
Southern California Permanente Medical Group Los Angeles, California, USA
• Dr. Kumar: There was over a 2 fold increase in patient survival in incident peritoneal dialysis
patients in the first year on dialysis compared to propensity matched incident hemodialysis
patients. We excluded any patients who utilized a central dialysis catheter at any point
during the first 90 days on hemodialysis in an effort to reduce the mortality bias associated
with hemodialysis patients who start with a catheter. All hemodialysis patients had pre-
dialysis care by a nephrologist prior to starting dialysis.
• The 2+ fold increase in survival among peritoneal dialysis patients resulted in a 2-3 year
cumulative survival advantage for peritoneal dialysis patients, using both intent to treat and
as-treated analyses.
Medical Research: Were any of the findings unexpected?
• Dr. Kumar: Given that a couple of recent reports had attributed the initial 1-2 year survival
advantage seen in PD patients in several large studies to the early use of central venous
catheters among matched hemodialysis patients, our findings were surprising. Other authors
have attributed the initial 1-2 year survival advantage seen in other studies to lack of pre-
dialysis care, but all of our study patients were managed by a nephrologist prior to starting
PD/HD.

End Stage Kidney Disease: Does Peritoneal Dialysis Offer A Survival Advantage?
Victoria A. Kumar, M.D. Internal Medicine/Nephrology
Division of Nephrology Department of Internal Medicine
Southern California Permanente Medical Group Los Angeles, California, USA
• Dr. Kumar: The survival advantage afforded by peritoneal dialysis in the first couple years on
dialysis should be emphasized when patients are in the process of choosing a dialysis
modality.
• Medical Research: What recommendations do you have for future research as a result of
this study?
• Dr. Kumar: RCT comparing peritoneal dialysis to hemodialysis is probably not feasible. Future
studies might address the issue of baseline residual renal function and changes in residual
renal function over time when comparing survival among well matched PD/HD patients.
• Citation:
Survival of propensity matched incident peritoneal and hemodialysis patients in a United
States health care system
Victoria A Kumar1, Margo A Sidell2, Jason P Jones2 and Edward F Vonesh3
Kidney International advance online publication 2 July 2014; doi: 10.1038/ki.2014.224

Reducing Overuse of Cardiac Biomarkers Generates Substantial Health Care Savings
Jeff Trost, MD
Assistant Professor of Medicine
Johns Hopkins Medicine
• Dr. Trost: In our study, we reported the use of two relatively simple tactics to significantly reduce the number of unnecessary
blood tests to assess symptoms of heart attack and chest pain and to achieve a large decrease in patient charges.
• Specifically, we
• 1) Provided information and education to physicians about proven testing guidelines and
• 2) Made changes to the computerized provider order entry system at the medical center, part of the Johns Hopkins Health
System. The guidelines call for more limited use of blood tests for so-called cardiac biomarkers. A year after implementation,
our intervention led to an estimated $1.25 million reduction in laboratory charges.
•
• Dr. Trost: No, based on a small sample of our pre-intervention utilization pattern, we estimated that there was a significant
amount of “overuse” of this testing and that reducing the “overuse” would lead to a significant reduction in laboratory
charges.
• Dr. Trost: We believe that clinicians should consider eliminating the use of CK-MB if troponin is available at their institutions,
because CK-MB adds no incremental value over troponin in the evaluation and diagnosis of patients with chest pain. CK-MB
is an example of a low-value (and some would argue, zero-value) test for patients.
• We would also add that clinicians need to consider appropriate use of serial troponin values – typically, it only takes 2 or 3
values at most to make or exclude a diagnosis of acute coronary syndrome.
• Dr. Trost: Future research could center on applying our intervention – provider education and EMR changes – to the
appropriate ordering practice of other tests that are deemed to have little or no value in clinical practice.
• Citation:
• Reducing Excess Cardiac Biomarker Testing at an Academic Medical Center
Marc R. Larochelle MD,Amy M. Knight MD,Hardin Pantle MD, Stefan Riedel MD, PhD, Jeffrey C. Trost MD
Journal of General Internal Medicine June 2014

Smoking Plus Mental Illness Leads To Substantial Economic Burden
MedicalResearch.com Interview with: Ms Qi Wu:
Mental Health and Addiction Research Group, Department of Health Sciences
University of York, Heslington
York UK
• Ms Qi Wu: At any time in the UK about one in six adults has a mental health problem, the
prevalence of smoking in this group is over 33%, which is around 50% higher than in the general
population. It is estimated that 3 million adults with mental disorders were smokers in 2009-10.
Meanwhile, people with mental health disorders are also more likely to smoke heavily, this group
accounts for as much as 42% of the total national tobacco consumption. In this study, we
calculated the avoidable economic burden of smoking in people with mental disorders.
• The main finding was that people with mental disorders who smoke cost the UK economy £2.34
billion a year. The total costs are more or less equally divided among losses sustained from
premature death, lost productivity, and healthcare costs to treat smoking related diseases such as
lung cancer, cardiovascular disease and chronic obstructive pulmonary disease (COPD) in this
group. An estimated £719 million (31% of the total cost) was spent on treating diseases caused by
smoking. Productivity losses due to smoking-related diseases were about £823 million (35%) for
work- related absenteeism and £797 million (34%) was associated with premature mortality.
• Ms Qi Wu: Smokers with mental disorders using primary and secondary care services should be
identified and provided with specialist smoking cessation support. Professionals working with or
caring for people with mental disorders should be trained in awareness of smoking as a major
health issue, to deliver brief cessation advice, to provide or arrange further support to those who
want to quit. Smoke-free policy is crucial to promoting smoking cessation in mental health settings.

Smoking Plus Mental Illness Leads To Substantial Economic Burden
MedicalResearch.com Interview with: Ms Qi Wu:
Mental Health and Addiction Research Group, Department of Health Sciences
University of York, Heslington
York UK
this study?
• Ms Qi Wu: The result of this study showed that smoking in people with mental disorders
imposes a significant economic burden and therefore that development and implementation
of smoking cessation interventions in this group is a particularly high priority. Research
funding agencies should consider encouraging and investing in research to address this major
cause of ill-health. Further research is needed to develop tailored smoking cessation support
to increase cessation in people with mental disorders. For those smokers who can’t quit
smoking, it is important to integrate harm reduction and temporary abstinence strategies
into mental healthcare delivery to reduce the harm of smoking.
• Citation:
• Economic cost of smoking in people with mental disorders in the UKQi Wu,Lisa
Szatkowski,John Britton, Steve Parrott
• Tob Control tobaccocontrol-2013-051464Published Online First: 9 July 2014
doi:10.1136/tobaccocontrol-2013-051464

Childhood Tuberculosis Likely Under-diagnosed and Under-reported
Pete Dodd (BA, BSc, MMath, PhD)
Research associate in health economic modelling
Health Economics and Decision Science ScHARR Regent Court Sheffield
• Dr. Dodd: We found that over 650,000 children under the age of 15 developed tuberculosis in the
22 highest burden countries in 2010, with around 7.6 million becoming infected with the bacillus
and more than 50 million harboring latent infection.
Our work points to a much larger gap between notifications and incidence in children compared to
adults.
• Dr. Dodd: It is known that tuberculosis in children is often under-diagnosed and under-reported.
However, traditional burden estimates start from notification figures, and it is challenging to
determine how much to scale up these figures in children to arrive at incidence. Our approach used
mathematical modelling to start from the estimated tuberculosis burden in adults, which
introduces more uncertainty, but circumvents this problem.
• Dr. Dodd: Tuberculosis in children is a major health problem globally, and wider use of isoniazid
preventive therapy in eligible children exposed to tuberculosis should be facilitated. Improving
diagnosis and reporting of tuberculosis in children should be on the public health agenda.
• Citation:
• Burden of childhood tuberculosis in 22 high-burden countries: a mathematical modelling study
The Lancet Global Health – 9 July 2014
DOI: 10.1016/S2214-109X(14)70245-1

Regular Use of Some NSAIDs May Increase Adverse Cardiovascular Events.
Anthony Bavry, MD MPH
Interventional Cardiology, North Florida/South Georgia Veterans Health System
Associate Professor of Medicine, University of Florida Gainesville, FL 32610
Dr. Bavry:
1) Among post-menopausal women, the regular use of NSAIDs was associated with an increased
risk of cardiovascular death, myocardial infarction, or stroke.
2) Cardiovascular risk was observed among users of celecoxib, naproxen, but not ibuprofen.
• Dr. Bavry: The finding of naproxen being associated with risk was consistent with our initial study
hypothesis. This finding may be unexpected to many readers. We hypothesized that naproxen
would be associated with harm because this agent is a non-selective NSAID with more cox-2 than
cox-1 inhibition.
• Dr. Bavry: Regular use of NSAIDs (celecoxib and naproxen) can increase adverse cardiovascular
events.
study?
• Dr. Bavry: Future studies are needed to define risks of NSAIDs in men and the role of dose and
duration in determining adverse cardiovascular risk of these agents.
• Citation:
Nonsteroidal Anti-Inflammatory Drugs and Cardiovascular Outcomes in Women: Results From the
Women’s Health Initiative Circ Cardiovasc Qual Outcomes.
2014;CIRCOUTCOMES.113.000800published online before print July 8 2014

Pancreatic Cancer: Combination Chemotherapy Increases Survival
Andrea Wang-GillamMD, PhD
Assistant Professor, Department of Medicine
Oncology Division, Medical Oncology Section Washington University School of Medicine in St. Louis
• Dr. Wang-Gillam: This is a global randomized phase III trial of MM398 plus 5FU/LV vs. MM398 vs.
5FU/LV in patients with metastatic pancreatic cancer who had received prior gemcitabine-based
therapy. The primary endpoint was overall survival (OS). The secondary endpoints included
progression-free survival (PFS), response rate (RR), biochemical response and safety. The trial
achieved its primary endpoint. The median overall survival was statistically longer with the
combination of MM398 plus 5FU/LV compared with 5FU/LV alone (6.1 months vs 4.2 months; HR of
0.67; p=0.0122). A superior progression-free survival was also seen in the MM398 plus 5FU/LV
group compared with the 5FU/LV alone group (3.1 months vs 1.5 months; HR of 0.56; p=0.0001). A
higher response rate was observed in the combination regimen compared with the 5FU/LV group
(16% vs 1%). There were no differences in overall survival or PFS between the MM 398
monotherapy and 5FU/LV groups.
• Dr. Wang-Gillam: Some unexpected findings appeared in the MM398 monotherapy arm.
• First, in terms of efficacy, although MM398 monotherapy resulted in a higher RR and biochemical
response compared with 5FU/LV, there was no difference in OS and PFS between MM 398
monotherapy and 5FU/LV treatment.
• Second, regarding toxicity, the study reported a higher incidence of grade 3 or above adverse
events in the GI tract such as diarrhea, vomiting and hypokalemia in the MM398 monotherapy
group compared with the MM398 plus 5FU/LV group.

Pancreatic Cancer: Combination Chemotherapy Increases Survival
Andrea Wang-GillamMD, PhD
Assistant Professor, Department of Medicine
Oncology Division, Medical Oncology Section Washington University School of Medicine in St. Louis
• Dr. Wang-Gillam: There are a couple of important take home messages from this study.
• First, the study has met its primary endpoint demonstrating that the combination of MM398 plus 5FU/LV
resulted in a superior overall survival compared with 5FU/LV alone.
• The combination could be another treatment option for metastatic pancreatic cancer patients who have
previously received gemcitabine-based regimens. Second, the toxicities of the combination of MM398 plus
5FU/LV were acceptable and manageable.
• Third, the study accrued 417 patients globally in less than 2 years, reflecting a desperate need for novel
therapy in this patient population.
• Dr. Wang-Gillam: MM398 is a novel delivery system for irinotecan. Because of the delivery system,
MM398 can linger in circulation longer compared with the conventional irinotecan. Furthermore, this
nanoliposomal delivery system allows a higher uptake of the drug at the tumor site and possible
subsequent local conversion to its active metabolite SN-38. In light of these favourable features, I
anticipate MM398 will be studied for the treatment of many different kinds of tumors, especially those for
which conventional irinotecan has already demonstrated its clinical efficacy. As a GI oncologist, I would like
see large clinical studies using regimens containing MM398 in several GI cancers including colorectal
cancer and gastric cancer.
• Last but not least, in light of the efficacy of FOLFIRINOX, I personally would advocate for a study
investigating MM398 combined with 5FU/LV and oxaliplatin in the front-line setting for locally advanced or
metastatic pancreatic cancer.
• Citation: Abstract
• MM-398 Added to Standard Treatment Shows Survival Benefit in Mets Pancreatic Cancer Published: June
25, 2014. By European Society for Medical Oncology
http://www.esmo.org

Premenopausal Breast Cancer: Exemestane Found Superior to Tamoxifen in Estrogen Positive Disease
Dr. Olivia Pagani
Clinical Director of the Breast Unit of Southern Switzerland
Ospedale San Giovanni, Switzerland
• Dr. Pagani: The study showed that the aromatase inhibitor Exemestane is superior to Tamoxifen (both given together with
ovarian function suppression) in preventing breast cancer recurrence in premenopausal women with oestrogen receptor
positive early breast cancer.
• Dr. Pagani: We designed the 2 studies (SOFT and TEXT) to confirm the results achieved with aromatase inhibitors in
menopausal women and in fact the benefit, in terms of disease free survival, is in the same range of that seen in
postmenopausal women with aromatase inhibitors.
• Dr. Pagani: The combination of an aromatase inhibitor (in our study Exemestane) and ovarian function suppression is a very
effective treatment option in this population of patients. In women for whom ovarian function is indicated, Exemestane
should be preferred to Tamoxifen. In addition, overall survival at 5 years is excellent in both treatments groups, and also in
women who do not receive chemotherapy, which is a very important information for young women with oestrogen receptor
positive breast cancer.
• Dr. Pagaini: The SOFT trial will also answer (by the end of the year) the pending question of the added benefit of ovarian
suppression in patients receiving tamoxifen. All these data will allow to better tailor treatment decisions in our individual
patients. We will also deeply analyse our data to see if any patients’ or disease characteristics are associated with better
outcome or different toxicity profile.
• Citation:
• Adjuvant Exemestane with Ovarian Suppression in Premenopausal Breast Cancer
• Olivia Pagani, M.D., Meredith M. Regan, Sc.D., Barbara A. Walley, M.D., Gini F. Fleming, M.D., Marco Colleoni, M.D., István
Láng, M.D., Henry L. Gomez, M.D., Carlo Tondini, M.D., Harold J. Burstein, M.D., Edith A. Perez, M.D., Eva Ciruelos, M.D.,
Vered Stearns, M.D., Hervé R. Bonnefoi, M.D., Silvana Martino, D.O., Charles E. Geyer, Jr., M.D., Graziella Pinotti, M.D., Fabio
Puglisi, M.D., Diana Crivellari, M.D., Thomas Ruhstaller, M.D., Eric P. Winer, M.D., Manuela Rabaglio-Poretti, M.D., Rudolf
Maibach, Ph.D., Barbara Ruepp, Pharm.D., Anita Giobbie-Hurder, M.S., Karen N. Price, B.S., Jürg Bernhard, Ph.D., Weixiu Luo,
M.S., Karin Ribi, Ph.D., Giuseppe Viale, M.D., Alan S. Coates, M.D., Richard D. Gelber, Ph.D., Aron Goldhirsch, M.D., and
Prudence A. Francis, M.D. for the TEXT and SOFT Investigators and the International Breast Cancer Study Group
• N Engl J Med 2014; 371:107-118July 10, 2014DOI: 10.1056/NEJMoa1404037

ICU Admission For Pulmonary Embolism Varies By Hospital
Dr. Colin Cooke MD, MSc, MS
Assistant Professor, Department of Internal Medicine University of Michigan
Center for Healthcare Outcomes and Policy Ann Arbor, MI
• Dr. Cooke: We determined that when patients who are hospitalized for pulmonary embolism (PE), a
blood clot in the lung, approximately 1 in 5 will be admitted to an intensive care unit (ICU).
However, the chances that a patient will go to an ICU is highly dependent upon which hospital they
are admitted to. For example, some hospitals admitted only 3% of patients with pulmonary
embolism to an ICU while others admitted almost 80%.
• Importantly, the differences in how hospitals use their ICU for patients with pulmonary embolism
was not entirely related to the patient’s need for life support measures, the things that the ICU is
designed to deliver. For example, the ICU patients in high ICU-use hospitals tended to receive fewer
procedures, including mechanical ventilation, arterial catheterization, central lines, and
medications to dissolve blood clots. This suggest that high utilizing hospitals are admitting patients
to the ICU with weaker indications for ICU admission.
• Dr. Cooke: We know from prior research that care delivered in an ICU is often quite expensive
relative to the care provided in other areas of the hospital. We expected that hospitals that
admitted more of their patients with pulmonary embolism to the ICU would also be the higher cost
hospitals. However, this was not the case. In fact, we observed no differences in either the costs for
other outcomes, such a patient’s risk of death or their risk for hospital readmission, in hospitals
using more ICU care. This may be because hospitals that admit more patients with pulmonary
embolism to the ICU are admitting those with fewer needs for ICU therapies, thereby negating
some of the excess costs of care in an ICU.

ICU Admission For Pulmonary Embolism Varies By Hospital
Dr. Colin Cooke MD, MSc, MS
Assistant Professor, Department of Internal Medicine University of Michigan
Center for Healthcare Outcomes and Policy Ann Arbor, MI
• Dr. Cooke: Clinicians should recognize that in many patients with pulmonary embolism the ICU is an
appropriate location within the hospital to best care for patients. In particular, those who require
life support measures as well as those who are at risk of rapid decompensation certainly benefit
from ICU care. However, there are also likely a subset of low risk patients with PE who could
effectively be managed in alternative locations. Doing so may free up ICU beds for more acutely ill
patients, and ultimately reduce the costs of care for patients with this condition.
study?
• Dr. Cooke: The most important next steps will require a better understanding of why ICU admission
practice varies so dramatically across hospitals. Because we observed no differences in outcomes
in pulmonary embolism patients across hospitals with differing ICU use, this suggests that there
may be great opportunities to improve the efficiency in use of the ICU.
• Citation:
• Hospital-level variation in intensive care unit admission and critical care procedures for patients
hospitalized for pulmonary embolism
• Andrew J. Admon, MD, MPH; Christopher W. Seymour, MD, MSc; Hayley B. Gershengorn, MD;
Hannah Wunsch, MD, MSc; Colin R. Cooke, MD, MSc, MS
• Chest. 2014. doi:10.1378/chest.14-0059

Opioid Deaths Particularly High Among Young People
Tara Gomes
St Michael’s Hospital
Toronto, ON, Canada
• Tara Gomes: We found that rates of opioid overdose in Ontario have increased more than 3-
fold over the past 2 decades. Furthermore, these deaths are clustered among younger
Ontarians; in 2010, 1 in 8 deaths among those aged 25 to 34 years were related to opioids.
This has led to considerable burden due to loss of life.
• Tara Gomes: Although past research suggested that the mean age at time of opioid-overdose
death was fairly low, we didn’t expect such a pronounced clustering of these deaths among
those aged 25 to 44 years old. Furthermore, the substantial impact of this early loss of life
was surprising. In 2010, 21,927 years of life lost were attributable to opioid-related death,
which is more than that attributable to alcohol use disorders, pneumonia, or influenza.

Opioid Deaths Particularly High Among Young People
Tara Gomes
St Michael’s Hospital
Toronto, ON, Canada
• Tara Gomes: Clinicians should carefully consider when to prescribe opioids to their patients
and should avoid escalating to high dose therapy which has been shown to be associated
with increased risk of opioid overdose. Furthermore, patients need to become informed
about the risks of addiction and overdose when using opioids so that they can ensure that
they do not accidentally misuse these drugs, which can lead to serious – and life threatening
– consequences.
this study?
• Tara Gomes: Since 2010, several changes have occurred in the opioid landscape. There have
been new policies implemented in Ontario that attempt to address the issue of opioid misuse
and abuse, as well as several new products introduced (including both a tamper deterrent
formulation and a generic formulation of long-acting oxycodone). Future research should
explore the potential impact of these changes on the trends observed in this study.
Citation:
• Gomes, T., Mamdani, M. M., Dhalla, I. A., Cornish, S., Paterson, J. M. and Juurlink, D. N.
(2014), The burden of premature opioid-related mortality. Addiction. doi: 10.1111/add.12598

Diabetes, Age and Obesity Drive Demand for Endocrinologists
Robert A. Vigersky, MD
Walter Reed National Military Medical Center Bethesda, MD
• Medical Research: What type of patients do endocrinologists typically treat and why is the
demand for their services anticipated to grow?
• Dr. Vigersky: Endocrinologists are physicians trained in managing, diagnosing, and treating
disorders of the endocrine system: thyroid, parathyroid, adrenal glands, hypophyseal and
hypothalamic axes, ovaries, testes, and pancreas. Their role involves controlling diabetes
mellitus, menopause, hyperthyroidism and other conditions involving metabolism.
• A major factor affecting the anticipated demand for health care services is the aging
population. In 2010, there were 37.5 million people age 65 or over, constituting about 12.7
percent of the total population, and by 2025 the population age 65 or over will number 62.5
million (17.9 percent of the population). Due to the greater prevalence of many of the
diseases in older age groups, like osteoporosis, diabetes, obesity, and thyroid nodules, the
growth in the population age 65 or over will exert a major influence on the demand for
endocrine services.
• Diabetes, by itself, is a major driver of demand. The incidence of Type 2 diabetes rises
dramatically with age, and with obesity. In an increasingly overweight population an
estimated 22.3 million people in the U.S. are diagnosed with diabetes as of 2012,
representing about 7 percent of the population. This estimate is higher than but consistent
with those published by the CDC for 2010. The percentage of the population with diagnosed
diabetes continues to rise, with one study projecting that as many as one in three U.S. adults
could have diabetes by 2050 if current trends continue.

• Medical Research: How large is the projected shortfall of adult endocrinologists?
• Dr. Vigersky: Our baseline projections indicate that there is a substantial gap, about 1,484 full-time
equivalent endocrinologists between the adult endocrinology services demanded, measured in
terms of the services that an adult endocrinologist can provide when working full time in patient
care, and the amount that can be supplied by the current and projected numbers of clinically active
adult endocrinologists, in 2015. The gap between the supply and demand of full-time equivalent
endocrinologists is likely to persist through 2025, where we estimate it to fall slightly to 1,344. That
is the best case scenario. If the prevalence of diabetes rises from a current rate of 7.4 percent to 12
percent by 2025, there will be a shortage of nearly 2,900 endocrinologists serving adults. Without a
concerted effort to recruit more endocrinologists, the gap between the number of endocrinologists
and the demand for their care will increase even further and patients will struggle to get the care
they need.
• Medical Research: What factors contribute to the relative lack of endocrinologists?
• Dr. Vigersky: A significant proportion of the adult endocrinologist workforce is Baby Boomers (born
between 1946 and 1964). Those physicians who are over age 60 will leave the workforce or will
greatly reduce hours of clinical work, over the next decade. The next generation of endocrinologists
also are working fewer hours and seeing fewer patients in an average week than their
predecessors. Although the number of fellowship positions in the field is increasing, the modest
growth is not sufficient to keep pace with the growing demand.
• Another factor that discourages physicians from specializing in endocrinology is compensation
rates. Since much of the care they provide is not based around specific procedures,
endocrinologists tend to earn less than their counterparts in specialties such as noninvasive
cardiology and gastroenterology.

• Medical Research:
What recommendations do you have to increase the number and productivity of
endocrinologists, in order to meet the current and anticipated demand for their
services?
• Dr. Vigersky: The creation of additional fellowship positions would help ensure an adequate
supply of endocrinologists to serve patients for years to come. The Endocrine Society’s
workforce analysis found the number of new entrants to the workforce must grow at a rate
of 14 percent a year to close the gap in five years.
• In addition, improved reimbursement rates that reflect the true value of endocrinologists’
care are required to encourage more physicians to choose endocrinology as a specialty.
Meaningful salary increases may incentivize medical school graduates to select endocrinology
as a specialty rather than the higher paying procedural-based specialties.
• Citation:
• The Clinical Endocrinology Workforce: Current Status and Future Projections of Supply and
Demand
Vigersky RA1, Fish L, Hogan P, Stewart A, Kutler S, Ladenson PW, McDermott M, Hupart KH.
J Clin Endocrinol Metab. 2014 Jun 18:jc20142257. [Epub ahead of print]

Venous Thromboembolism Associated With Short and Long Term Increase In Mortality
Kirstine Kobberøe Søgaard, MD
Department of Clinical Epidemiology,
Aarhus University Hospital, Denmark
• Response: Venous thromboembolism (VTE) is mainly considered an acute illness with a high
mortality right after the event, whereas knowledge on the impact on long-term survival has
been sparse. In our study, we used nationwide data on VTE since 1977, and included 128,223
patients with VTE and 640,760 individuals from the general population without a VTE
diagnosis. We had complete follow-up data on individual patient level and were able to link
information from other hospital admissions and thereby obtain each patient’s entire hospital
history, as well as death statistics with specific cause of death. We confirmed the high
mortality immediately after the thromboembolic event, but more interestingly, we found
that mortality remained increased during the entire follow-up period of 30 years, with
venous thromboembolism as an important cause of death among patients with deep venous
thrombosis and/or pulmonary embolism.
• Response: During the study period, we observed no decrease in mortality in patients with
deep venous thrombosis, whereas 1-year mortality in patients with pulmonary embolism was
markedly reduced over the last three decades. This reduction may reflect an improvement in
the treatment of venous thromboembolism, but it is also likely that enhanced diagnostic
procedures (identifying less serious embolisms) had an impact. While deep venous
thrombosis and pulmonary embolism were likely to be the cause of death in the short term,
this finding persisted even 11-30 years after diagnosis.

Venous Thromboembolism Associated With Short and Long Term Increase In Mortality
Kirstine Kobberøe Søgaard, MD
Department of Clinical Epidemiology,
Aarhus University Hospital, Denmark
• Response: VTE is not only an acute disease, but is also associated with an increased mortality
in the long term. Some of these deaths may be prevented if we learn more about optimizing
the treatment of venous thromboembolism, as well as reducing the risk of venous
thromboembolism recurrence.
this study?
• Response: The mechanism behind the increased long-term mortality risk in venous
thromboembolism patients needs to be further investigated. We believe it is crucial to find
out more about which diseases predict and/or mediate long-term mortality, and to gain more
knowledge on how treatment may need to be personalized according to patient
characteristics.
• Citation:
• 30-Year Mortality Following Venous Thromboembolism: A Population-Based Cohort Study
Kirstine Kobberøe Søgaard,Morten Schmidt,Lars Pedersen,Erzsébet Horváth-Puhó,and Henrik
Toft Sørensen
• Circulation. 2014;CIRCULATIONAHA.114.009107published online before print June 26 2014,
doi:10.1161/CIRCULATIONAHA.114.009107

Biomarker BNP Linked To Severity of Aortic Stenosis
MedicalResearch.com Interview with :
Philippe Pibarot, DVM, PhD, FAHA, FACC, FESC, FASE
Chair, Canada Research Chair in Valvular Heart Diseases
–
• Dr. Pibarot: The optimal timing of aortic valve replacement (AVR) in asymptomatic patients
with severe aortic stenosis (AS) remains a matter of debates. Both the American and
European guidelines recommend AVR for patients with severe AS who present with
symptoms or left ventricular (LV) systolic dysfunction. However, patients with aortic stenosis
are often older, less physically active and have more comorbidities, which make the
assessment of AS-related symptoms challenging and unreliable. In this study by Capoulade et
al, plasma levels of brain natriuretic peptide (BNP) were obtained in 157 patients with severe
asymptomatic aortic stenosis and preserved LV ejection fraction at peak of exercise-stress
echocardiography. Patients in the upper (>95 pg/ml) and mid (>45 pg/ml) tertiles of exercise
BNP respectively had a 5- and 3- fold increase in the risk of events (i.e. AVR or death)
compared to those in the lower tertile. Similar results were obtained in the subset of patients
with low resting BNP.
• Dr. Pibarot: These findings provide strong impetus for systematic measurement of BNP
during exercise test in asymptomatic patients with severe AS. Patients who display a marked
increase in BNP during exercise require more frequent and closer clinical and
echocardiographic follow-up and may potentially benefit from earlier intervention (i.e. aortic
valve replacement)

Biomarker BNP Linked To Severity of Aortic Stenosis
Philippe Pibarot, DVM, PhD, FAHA, FACC, FESC, FASE
Chair, Canada Research Chair in Valvular Heart Diseases
–
this study?
• Dr. Pibarot: Further studies are needed to determine if the present findings obtained with
semi-supine exercise test can be transposed to the setting of upright exercise test.
• Citation:
• Prognostic value of plasma B-type natriuretic peptide levels after exercise in patients with
severe asymptomatic aortic stenosis
• Romain Capoulade, Julien Magne, Raluca Dulgheru, Zeineb Hachicha, Jean G Dumesnil, Kim
O’Connor, Marie Arsenault, Sébastien Bergeron, Luc A Pierard, Patrizio Lancellotti, Philippe
Pibarot
• Heart heartjnl-2014-305729Published Online First: 3 July 2014 doi:10.1136/heartjnl-2014-
305729

Do Antibiotics Improve Post-Op Course Following Cholecystectomy?
Pr. Jean-Marc Regimbeau
Service de Chirurgie Digestive Oncologique et Métabolique,
CHU d’Amiens
• Medical Research : What are the main findings of the study?
• Answer: In our study we found that the absence of postoperative administration of amoxicillin plus clavulanic acid did not
improve the occurrence of postoperative infections in patients with mild or moderate acute calculous cholecystitis. The bile
cultures were pathogen free in 60.9% of case. Moreover we show that less than 2 percent of the overall population
presented a major complication defined according to the Clavien Dindo Classification (Clavien score ≥3a). After
cholecystectomy the readmission rate was 6%.
Medical Research : Were any of the findings unexpected?
• Answer: All of the surgical results (operative time, conversion rate…) were concordant with the literature. Nevertheless we
reported a perforation rate around 40%. This data, never reported in the articles, represents the daily practice. Moreover
the patients with pathogens resistant to Amoxicillin plus clavulanic acid had similar length of stay and postoperative course.
• Medical Research : What should clinicians and patients take away from your report?
• The main data taken away from our study are :
• Postoperative administration of amoxicillin plus clavulanic acid after mild or moderate acute calculous cholecystitis lasting
for less than 5 days is not necessary (the treatment of this condition should include preoperative antibiotic and
cholecystectomy)
• Whatever the treatment course the readmission rate is around 6%.
• Medical Research : What recommendations do you have for future research as a result of this study?
• Answer: To improve the quality of the report some methodological aspects should be scheduled.
• First the use of the placebo as a comparator (preferably a double placebo : one for the IV administration and one for the per
os administration).
• Secondly to schedule an alternative for antibiotic regimen in case of amoxicillin plus clavulanic acid allergy. Finally to obtain
the reason of non inclusion as soon as the study begins.
• Citation :
• Regimbeau J, Fuks D, Pautrat K, et al. Effect of Postoperative Antibiotic Administration on Postoperative Infection Following
Cholecystectomy for Acute Calculous Cholecystitis: A Randomized Clinical Trial. JAMA. 2014;312(2):145-154.
doi:10.1001/jama.2014.7586.
• Views vs UniqueViews2014-06-182014-06-232014-06-282014-07-032014-07-08

Smoking Cessation: Odds Improved By Combining Chantix With Nicotine Patches
Coenie Koegelenberg, MBChB, MMed (Int), FCP (SA), MRCP (UK), Cert Pulm (SA), PhD
Associate Professor: Pulmonology
Stellenbosch University & Tygerberg Academic Hospital
• Dr. Koegelenberg: The aim of this study was to evaluate the efficacy of combining varenicline and a
nicotine patch versus varenicline alone as an aid to smoking cessation in a double-blind study
design in a larger group and with a longer assessment period than has been studied to date. It was
found that the combination treatment was associated with a statistically significant and clinically
important higher continuous abstinence rate at 12 weeks (55.4% vs. 40.9%; P=.007) and 24 weeks
(49.0% vs. 32.6%; P=.004), and point prevalence abstinence rate at 6 months (65.1% vs. 46.7%;
P=.002). The present study was not adequately powered to fully assess safety and tolerability
endpoints, but the results suggest that adverse events were balanced across treatment arms,
except for mild skin reactions that were more frequently observed in the nicotine patch group
(14.4% vs. 7.8%, P=.03).
• Dr. Koegelenberg: Both varenicline and nicotine acts on the nicotinic cholinergic receptor,
specifically the α4β2 receptor subtype, which is believed to be the principal mediator of nicotine
dependence. The additive efficacy of combining the two drugs therefore cannot be readily
explained. It is possible that neither varenicline nor nicotine alone fully saturate all nicotine
receptors in the brain, leaving room for the action of the other. Nicotine replacement may also bind
to additional receptors involved in nicotine dependency. A further possibility is that the different
pharmacokinetics of the two components provides a more favorable onset of receptor agonism.
Moreover, it is possible that the introduction of varenicline one week after Nicotine replacement
therapy, or tapering of varenicline might in some way have improved the effectiveness of the
combination.

Smoking Cessation: Odds Improved By Combining Chantix With Nicotine Patches
Coenie Koegelenberg, MBChB, MMed (Int), FCP (SA), MRCP (UK), Cert Pulm (SA), PhD
Associate Professor: Pulmonology
Stellenbosch University & Tygerberg Academic Hospital
• Dr. Koegelenberg: It was shown that in relatively healthy smokers, the odds of achieving
successful smoking cessation after 12 and 24 weeks were significantly increased by using a
combination of varenicline and nicotine patches compared to varenicline alone. The
combination appeared to be safe, although further studies are needed to confirm this.
this study?
• Dr. Koegelenberg: The study population was limited to relatively healthy smokers. Future
studies should include a broader range of smokers (including those with significant
cardiovascular and/or respiratory diseases), other forms of nicotine replacement therapy and
assessments of tolerability and cost/benefit comparisons with alternative therapies.
• Citation:
• Koegelenberg CN, Noor F, Bateman ED, et al. Efficacy of Varenicline Combined With Nicotine
Replacement Therapy vs Varenicline Alone for Smoking Cessation: A Randomized Clinical
Trial. JAMA. 2014;312(2):155-161. doi:10.1001/jama.2014.7195.

Nurse Visitation During Pregnancy and Infancy Reduced Maternal and Child Mortality
MedicalResearch.com Interview with: David Olds, Ph.D.
Professor of Pediatrics and Director
Prevention Research Center for Family and Child Health
University of Colorado Department of Pediatrics Aurora, Colorado 80045
• Dr. Olds: We’ve conducted a randomized controlled trial of a program of nurse home visiting for
low-income women with no previous live firths during pregnancy and the first two years of the
child’s life, with randomization of participants beginning in 1990. In our most recent follow-up of
mothers and children in Memphis, those who received nurse-visitation were less likely to have died
over a 2-decade period following the child’s birth than those in the control group. Death among
mothers and children in these age ranges in the US is rare and extraordinarily important for what it
tells us about the health of the population studied in this trial.
• For children, the reduction in death was present for preventable causes, that is, sudden infant
death syndrome, injuries, and homicide. All of the child deaths for preventable causes were in the
control group, for whom the rate was 1.6%. None of the nurse-visited children died of preventable
causes.
• The reductions in maternal mortality were found for two nurse-visited groups combined for this
report: one received prenatal and newborn visitation and a second received visitation during
pregnancy and through child age two. Overall, mothers assigned to the control group were nearly 3
times more likely to die than those assigned to the two nurse-visited conditions. The relative
reduction in maternal mortality was particularly pronounced for deaths linked to maternal
behaviors — suicide, drug overdose, injuries, and homicide; for these external causes of death,
1.7% of the mothers in the control group had died, compared to 0.2% of those visited by nurses.
•
• Dr. Olds: All of these findings were unexpected as we thought that the rates of maternal and child
mortality for women and children in these age ranges would be too infrequently occurring to
discern program effects.

Nurse Visitation During Pregnancy and Infancy Reduced Maternal and Child Mortality
MedicalResearch.com Interview with: David Olds, Ph.D.
Professor of Pediatrics and Director
Prevention Research Center for Family and Child Health
University of Colorado Department of Pediatrics Aurora, Colorado 80045
• Dr. Olds: Nurse visitation during pregnancy and the early years of the child’s life among low-
income mothers with no previous live births is a promising means of improving maternal and
child health and reducing maternal and child mortality.
this study?
• Dr. Olds: These findings need to be replicated with other highly disadvantaged low-income
families.
• Citation:
• Olds DL, Kitzman H, Knudtson MD, Anson E, Smith JA, Cole R. Effect of Home Visiting by
Nurses on Maternal and Child Mortality: Results of a 2-Decade Follow-up of a Randomized
Clinical Trial. JAMA Pediatr. Published online July 07, 2014.
doi:10.1001/jamapediatrics.2014.472.

Recalled Yogurt Harbored Harmful Fungus
Soo Chan Lee, PhD Senior Research Associate,
Center for Microbial Pathogenesis, Department of Molecular Genetics and Microbiology,
Duke University Medical Center, Durham, N.C. 27710
• Dr. Soo Chan Lee: Mucor circinelloides strain isolated from recalled Chobani yogurt was found to be the
most virulent subspecies M. circinelloides forma circinelloides that is commonly associated with human
infections. When mice were infected with this fungus through the tail-vein, 80% mortality was observed 5
days post infection. When mice were fed with spores, the fungus survived passage through the GI tract as
many as 10 days, indicating the fungus can colonize to cause infections. Whole genome sequence analysis
revealed the possibility that this fungus could produce harmful secondary metabolites that are unknown
in this fungal species.
• Dr. Soo Chan Lee: Mucor circinelloides is already known as one of the causal agents for mucormycosis,
which is rare but aggressive with high mortality in case of disseminated infections. So virulence of the
fungus in mouse is kind of expected.
• However, one interesting finding was that the fungus survived the passage through the mouse GI tract.
• Dr. Soo Chan Lee: When people think about food-borne pathogens, normally they list bacteria, viruses,
and parasites. Fungal pathogens are not considered food-borne pathogens. However, this incidence
(Chobani yogurt recalled after customer complaints of discomfort and their products were contaminated
by Mucor circinelloides) indicates that we need to pay more attention to fungi. Fungal pathogens can
threaten our health systems as food-borne pathogens.
• The immunocompromised population is increasing as a result of HIV-AIDS infection, diabetes, and other
medical conditions. Elderly populations are increasing too. Those people are especially susceptible to
fungal infections. As mentioned above, specific attention needs to be given to fungi. It may be time to
consider developing sound regulations about fungi in food products and factories that manufacture them.

Recalled Yogurt Harbored Harmful Fungus
Soo Chan Lee, PhD Senior Research Associate,
Center for Microbial Pathogenesis, Department of Molecular Genetics and Microbiology,
Duke University Medical Center, Durham, N.C. 27710
this study?
• Dr. Soo Chan Lee: It is less evident so far that this fungus really causes food-borne illness
through infection or production of toxic compounds. Our study evaluated the potential risks
of this fungal infection. Further study could include examination of whether this fungus can
produce any secondary metabolites because its genome tells us it would be possible.
• Citation:
• Analysis of a foodborne fungal pathogen outbreak: virulence and genome of a Mucor
circinelloides isolate from yogurt,” Soo Chan Lee, R. Blake Billmyre, Alicia Li, Sandra Carson,
Sean M. Sykes, Eun Young Huh, Piotr Mieczkowski, Dennis C. Ko, Christina A. Cuomo, and
Joseph Heitman. mBio, July 8, 2014. DOI:10.1128/mBio.01390-14

Sleep Deprivation Can Induce Symptoms Resembling Schizophrenia
Prof. Dr. Ulrich Ettinger Departments of Psychology
University of Bonn
Bonn, Germany
• Prof. Ettinger: We found that 24-hour sleep deprivation induced subjective cognitive, perceptual and
emotional alterations resembling the symptoms of schizophrenia. We also observed that sleep deprivation
led to a deficit in a sensorimotor filter mechanism called prepulse inhibition (PPI), similar to the
disturbance seen in schizophrenia.
• Prof. Ettinger: The magnitude of the impairment in prepulse inhibition was quite astonishing.
• Prof. Ettinger: We believe that our findings support the validity of sleep deprivation as an experimental
model system of schizophrenia. This means, that future antipsychotic drug development studies may build
upon our findings by testing new compounds for their efficacy on PPI following sleep deprivation.”
• Prof. Ettinger: We would like to replicate and extend these findings by combining our design with the
administration of an established, clinically effective antipsychotic. It will be intriguing to find out whether a
drug with known antipsychotic effects will prevent and/or reverse the prepulse inhibition deficit that is
produced by sleep deprivation.
• Citation:
• Sleep deprivation disrupts prepulse inhibition and induces psychosis-like symptoms in healthy humans
• Petrovsky N1, Ettinger U2, Hill A1, Frenzel L1, Meyhöfer I1, Wagner M3, Backhaus J1, Kumari V4.
• J Neurosci. 2014 Jul 2;34(27):9134-40. doi: 10.1523/JNEUROSCI.0904-14.2014.

Painful Diabetic Neuropathy Linked To Higher Nocturnal Blood Pressure
Vincenza Spallone MD PhD
Endocrinology and Neurology
Department of Systems Medicine Tor Vergata University, Rome, Italy
• Dr. Spallone:To investigate a possible relationship between painful diabetic polyneuropathy (PDPN) and the circadian
pattern of blood pressure (BP), we performed ambulatory blood pressure monitoring in 113 diabetic patients with PDPN,
with painless diabetic polyneuropathy (DPN) and without DPN. In addition, we evaluated neuropathic pain, sleep, risk for
obstructive sleep apnoea (OSA), autonomic function, and in a subgroup of patients, depressive symptoms.
• The main finding was that patients with painful diabetic polyneuropathy displayed impaired nocturnal fall in BP compared to
those without neuropathy, and higher nocturnal systolic blood pressure than the other two groups. Although the day-night
change (∆) in blood pressure failed to reach a significant difference between painful diabetic polyneuropathy and DPN
groups, nondipping (the loss of nocturnal fall in systolic BP) was more strictly associated with painful diabetic
polyneuropathy than DPN and in multivariate analysis, including comorbidities and most potential confounders, neuropathic
pain was an independent determinant of ∆ BP and nocturnal systolic blood pressure.
• In summary, we showed a novel association of peripheral diabetic neuropathic pain with nondipping and higher systolic
nocturnal blood pressure, which was not entirely explained through pain dependent sleep problems or other pain- or
diabetes-related comorbidities, like CAN, OSA and depression.
• Dr. Spallone: Pain-dependent sleep disturbances were a rather expected finding, even though previous studies lacked a
comparison between patients with painful and painless DPN. Here, we confirmed the negative impact of neuropathic pain
on sleep and provided the finding of a peculiar link between diabetic peripheral neuropathic pain and sleep behaviour
independently on possible influences of neuropathy and diabetes per se.
• Nondipping and reverse dipping patterns have been reported to be associated with CAN and linked to a disruption of the
circadian variation in sympathovagal activity, i.e. a diminished increase in vagal activity during the night with a consequent
sympathetic predominance. Nondipping has also been associated with short sleep duration in patients with diabetes and
with OSAS in the general population. Thus, it was not obvious that the PDPN was related to nondipping and night-time BP
independently from CAN influence and from the presence of sleep problems and high OSA risk. This finding possibly
suggests that, in patients with painful diabetic polyneuropathy, nocturnal pain itself acts as a stressor by inducing a
sympathetic response during the night with a consequent exacerbation of the pre-existent sympathovagal unbalance
(associated with autonomic dysfunction secondary to diabetes and to chronic pain) and thus inhibiting BP fall during the
night.

Painful Diabetic Neuropathy Linked To Higher Nocturnal Blood Pressure
Vincenza Spallone MD PhD
Endocrinology and Neurology
Department of Systems Medicine Tor Vergata University, Rome, Italy
• Dr. Spallone: We think that the finding of an association between painful diabetic polyneuropathy and
both nondipping and higher night-time BP could be of clinical relevance given the independent prognostic
value of these two BP features for end-organ damage and cardiovascular morbidity and mortality in the
general population and even more in diabetic population. The prognostic burden represented by
nondipping and higher night-time BP increases the negative prognostic value already constituted by
diabetic neuropathy itself and other comorbidities of chronic neuropathic pain, as sleep loss and
disturbance.
• Painful diabetic polyneuropathy is common (with a prevalence of about 18%), and exerts a deep impact on
sleep, mood, and quality of life. It is, however often undiagnosed and under-treated. This study indicates
one more reason to pay attention to this diabetic complication and supports the view that diabetic
peripheral neuropathic pain should increasingly be regarded as a condition of high cardiovascular risk.
Chronic neuropathic pain in diabetic patients should be promptly recognized and properly managed to
offer relief to patients and improve their cardiovascular risk profile.
• Dr. Spallone: A logical development of this study would be to verify whether effective pain treatment can
correct the abnormal BP findings, i.e. lowering night-time BP and restoring dipping status, and to ascertain
whether and to what degree the potential beneficial effect on BP of pain relief is direct or mediated
through sleep or mood changes.
• Citation:
• A Novel Association Between Nondipping and Painful Diabetic Polyneuropathy
Cinzia D’Amato, Roberto Morganti, Federica Di Gennaro, Carla Greco, Girolama A. Marfia, and Vincenza
Spallone
Diabetes Care published ahead of print June 26, 2014, doi:10.2337/dc14-0528 1935-5548

Diabetes: Even High Risk Patients May Have Modifiable Risk Factors
MedicalResearch.com: Interview with:
Interview with Professor Donald W Bowden and Dr. Amanda J Cox
Center for Diabetes Research,
Center for Genomics and Personalized Medicine Research
Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC
• Answer: The study examined modifiable cardiovascular disease (CVD) risk factors and risk for mortality in a subset of
individuals from the Diabetes Heart Study who were at high risk based for cardiovascular disease based on burden of
subclinical CVD assessed by coronary artery calcified plaque scores greater than 1000. Even among this high risk group,
known CVD risk factors were still useful in assessing ongoing risk for mortality. Use of cholesterol-lowering medication was
one factor identified to be protective against mortality.
•
• Answer: It was assumed that risk for mortality would be consistently high among this subgroup given the individual histories
(and duration) of type 2 diabetes and the presence of subclinical cardiovascular disease. However, 60% of this high-risk
subset were still living after, on average, more than eight years of follow-up supports the potential for variable and
modifiable risk, even in the presence of multiple existing risk factors.
• Answer: The findings from this study indicate that even among type 2 diabetes patients identified to be at high risk of
adverse outcome, modifiable risk factors exist that should be targeted for early and continued intervention.
• Answer: Identification of multiple modifiable risk factors supports the multifactorial nature of cardiovascular disease and the
need for concurrent risk reduction strategies. Future research should aim to further resolve the seemingly episodic events
that lead to adverse outcome and which may explain the variable risk noted in this subset.
• Citation:
• Contributors to Mortality in High-Risk Diabetic Patients in the Diabetes Heart Study
• Diabetes Care published ahead of print July 2, 2014, doi:10.2337/dc14-0081 1935-5548
Amanda J. Cox, Fang-Chi Hsu, Barry I. Freedman, David M. Herrington, Michael H. Criqui, J. Jeffrey Carr, and Donald W.
Bowden

Treating Psychogenic Nonepileptic Seizures With Psychotherapy Workbook Approach
MedicalResearch.com Interview with: W Curt LaFrance Jr MD, MPH
Assistant Professor of Psychiatry and Neurology, Alpert Medical School, Brown University
Director of Neuropsychiatry and Behavioral Neurology, Rhode Island Hospital Providence RI 02903-4923
• Dr. LaFrance: Patients treated with the 12 session, 1 hour, individual psychotherapy seizure
treatment workbook had significant reductions in their seizures and improvement in their
comorbid symptoms, quality of life and functioning. In contrast, treatment as usual /standard
medical care (TAU/SMC) showed no improvement in seizures, comorbid symptoms or other
outcomes.
• Dr. LaFrance: Showing such a significant treatment effect size in the two psychotherapy
treated groups (with and without sertraline) with the small sample was unexpected. The
robust results are an indicator of the impact of this intervention.

Treating Psychogenic Nonepileptic Seizures With Psychotherapy Workbook Approach
MedicalResearch.com Interview with: W Curt LaFrance Jr MD, MPH
Assistant Professor of Psychiatry and Neurology, Alpert Medical School, Brown University
Director of Neuropsychiatry and Behavioral Neurology, Rhode Island Hospital Providence RI 02903-4923
• Dr. LaFrance: In our research, we have worked to demystify the challenging neuropsychiatric
population with Psychogenic Nonepileptic Seizures and to equip patients and clinicians with
effective treatment for a disorder that has largely been avoided by mental health providers. The
results show that treatment as usual / standard medical care is not helpful for Psychogenic
Nonepileptic Seizures (PNES). That all of the outcomes for the TAU/SMC group showed
no improvement underscores that what is being done now with supportive therapy and routine
followup is not enough to help these patients. The seizure treatment workbook is a new, targeted
treatment option for clinicians that has been used successfully for Psychogenic Nonepileptic
Seizures and other conversion disorders. The workbook will be published later this year.
study?
• Dr. LaFrance: Examining the impact of the workbook with other providers trained in delivering the
intervention across the country will be important, as the treatment is being disseminated to other
seizure centers. Many experts have noted that approaching the disorder from a combined
neurologic and psychiatric perspective, with the collaboration of Neurological and Mental Health
Institutes will be important for moving the field forward.
• Citation:
• LaFrance W, Jr, Baird GL, Barry JJ, et al. Multicenter Pilot Treatment Trial for Psychogenic
Nonepileptic Seizures: A Randomized Clinical Trial. JAMA Psychiatry. Published online July 02, 2014.
doi:10.1001/jamapsychiatry.2014.817.

Brain Imaging Of Psychedelic State Shows Resemblance To REM Sleep
Dr. Enzo Tagliazucchi:
Goethe University, Germany
• Dr. Tagliazucchi: The main finding of the study is the objective discovery of an “expanded
mind” and a more “unpredictable mind” after the ingestion of a psychedelic (in this case
psilocybin, a compound found in “magic mushrooms”). We say that this discovery is objective
since it comes from a brain imaging experiment (using magnetic resonance imaging) instead
from reports of drug users, which could be unreliable or exaggerated.
• Also, comparing our results with those obtained in brain imaging experiments of REM sleep
(the phase of sleep when we dream), we found a remarkable resemblance between both
brain states. Thus, the psychedelic state perhaps has more to do with a “dream-like” state
than with normal, resting wakefulness.
• Dr. Tagliazucchi: In part, yes. The psychedelic state is strongly associated with visual and
auditory hallucinations and distortions (such as geometric patterns, for instance) and other
sensory alterations (such as mixing of the senses or synesthesia). However, all our results
point to “high-level” alterations in brain activity, this is, not alterations in the way we perceive
the world around us, but deeper alterations in the way we put our thoughts together over
time. Thus, psychedelics allow us not only to see or hear differently but also to “think
differently”.

Brain Imaging Of Psychedelic State Shows Resemblance To REM Sleep
Dr. Enzo Tagliazucchi:
Goethe University, Germany
• Dr. Tagliazucchi: Psilocybin is currently being explored as a treatment for depression, anxiety and
other related disorders. Our results reveal a general effect of psilocybin on brain activity during rest
(which is perhaps shared by other psychedelics). By understanding better the influence of
psilocybin on the functional architecture of the human brain, we will be closer to revealing the
specific effects involved in its role as anti-depressant.
study?
• Dr. Tagliazucchi: It is necessary to study the human brain as a dynamic entity continuously evolving
over time. Most studies to date treat the brain as a static object whose properties (such as
connectivity) remain unchanged over several minutes. It is only by defining “brain states” and
studying the temporal succession of states (a “train of thought”) that we can reveal some specific
effects of psilocybin on the human brain. Otherwise, the effects would remain hidden.
• Citation:
• Enhanced Repertoire of Brain Dynamical States During the Psychedelic Experience
Tagliazucchi, E. et al.
• http://onlinelibrary.wiley.com/doi/10.1002/hbm.22562/abstract.
• Tagliazucchi, E., Carhart-Harris, R., Leech, R., Nutt, D. and Chialvo, D. R. (2014), Enhanced repertoire
of brain dynamical states during the psychedelic experience. Hum. Brain Mapp..
doi: 10.1002/hbm.22562

Diabetes: Combining Resistance with Aerobic Exercise May Be More Effective For Glucose Control
MedicalResearch.com: Interview with: Lukas Schwingshackl, MSc
Department of Nutritional Sciences
University of Vienna Vienna, AUSTRIA
• Lukas Schwingshackl: The results of the present meta-analyses showed that, in patients with
established diabetes, aerobic training might be more effective in reducing glycosylated
haemoglobin and fasting glucose when compared with resistance training. Combined aerobic and
resistance training was more powerful in reducing glycosylated haemoglobin compared with
aerobic training, and more effective in reducing glycosylated haemoglobin, fasting glucose and
tricylglycerols when compared with resistance training. However, these results could not be
confirmed when only low risk of bias studies were included.
•
• Lukas Schwingshackl: Combined aerobic and resistance training can be recommended as part of a
lifestyle programme in the management of type 2 diabetes wherever possible. However, the
interpretation of these findings with respect to their clinical relevance is limited by the overall low
to moderate quality of the studies included, the lack of information on clinically important
outcomes.
• With respect to the potential side effects, 8/14 trials in the present meta-analysis reported adverse
events such as hypoglycaemia, back pain, shoulder pain, musculoskeletal injury, tendonitis and
other musculoskeletal discomforts following exercise, with no significant differences between the
intervention groups. However, it remains possible that the number of adverse events will increase
with the duration and intensity of exercise. There is evidence that supervised exercise is more
effective than unsupervised training, but in practice it seems unlikely that most patients would
have access to supervised exercise regimens of this intensity. It is possible that either aerobic
training, resistance training or combined training may be easier to perform effectively without
supervision, thus affecting the external validity of these results since only studies with supervised
training were included.

Diabetes: Combining Resistance with Aerobic Exercise May Be More Effective For Glucose Control
MedicalResearch.com: Interview with: Lukas Schwingshackl, MSc
Department of Nutritional Sciences
University of Vienna Vienna, AUSTRIA
this study?
• Lukas Schwingshackl: Further high quality with long-term exercise interventions including
hard clinical endpoints (i.e. cardiovascular disease, mortality) are needed to develop
definitive recommendations.
• Citation:
Lukas Schwingshackl, Benjamin Missbach, Sofia Dias, Jürgen König, Georg Hoffmann. Impact
of different training modalities on glycaemic control and blood lipids in patients with type 2
diabetes: a systematic review and network meta-analysis. Diabetologia, 2014; DOI:
10.1007/s00125-014-3303-z

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