MedicalResearch.com - Medical Research Interviews Week in Review

MedicalResearch.com
Interviews on contemporary Medical Research with medical
researchers from major and specialty medical journals.
Editor: Marie Benz, MD
info@medicalresearch.com
November 1 2013
For Informational Purposes Only: Not for Specific Medical Advice.

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Food Consumed by Children in School Surprising High in Fat, Empty Calories
MedicalResearch.com Interview
Jennifer M. Poti
PhD Candidate, Nutritional Epidemiology
University of North Carolina at Chapel Hill

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MedicalResearch.com: What are the main findings of the study?
Answer: Consumption of solid fat and added sugar (SoFAS) by children exceeds
recommendations, but it was not known where kids obtain these “empty calories.” Analyzing
data from over 22,000 US children, we found that children consumed about 1/3 of their
calories as solid fat and added sugar for foods consumed from retail food stores (including
grocery stores and supermarkets), schools, or fast food restaurants in 2009-2010, despite
significant decreases from 1977 to 2010 at each location. These mean levels of empty calorie
intake greatly exceeded recommended amounts not just for fast foods, but also for foods
consumed from schools and from stores. For all survey years, foods consumed by children
from schools were higher in solid fat content than foods obtained and consumed from retail
food stores.
MedicalResearch.com: Were any of the findings unexpected?
Answer: In our study, milk consumed by children from schools was higher in total solid fat
and added sugar content than milk consumed from stores, likely because of the shift to
chocolate milk at schools. We also observed that French fries consumed by children from
schools were higher in solid fat than store-bought versions, and pizza consumed from schools
was not different than fast food pizza in SoFAS content.
Read the rest of the interview on MedicalResearch.com

Food Consumed by Children in School Surprising High in Fat, Empty Calories
MedicalResearch.com Interview
Jennifer M. Poti
PhD Candidate, Nutritional Epidemiology
University of North Carolina at Chapel Hill

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MedicalResearch.com: What should clinicians and patients take away from your report?
Answer: While fast foods are more widely recognized as having lower nutritional quality,
foods from schools and supermarkets can also be large contributors to solid fat and added
sugar consumption among children. Efforts to reduce children’s consumption of empty
calories should be made at all locations, not just fast food restaurants.
MedicalResearch.com: What recommendations do you have for future research as a result
of this study?
Answer: Further studies are needed to determine whether declines in solid fat and added
sugar by children are driven by product reformulations by food manufacturers, changes in
availability of products with lower SoFAS content, or shifts in consumers’ choices. Future
research should evaluate changes in SoFAS consumption as schools implement new nutrition
standards for school meals and competitive foods, food manufacturers and retailers carry out
their commitments to improve nutritional quality of store-bought foods, and menu-board
labeling at fast food restaurants becomes mandatory.
Citation:
Poti JM, Slining MM, Popkin BM. Solid fat and added sugar intake among U.S. children: the
role of stores, schools, and fast food, 1994-2010. Am J Prev Med 2013;45(5):551-9.

Autism and Language Impairment: Possible Common Genetic Link
MedicalResearch.com Interview with:
Linda Brzustowicz, M.D.
Professor and Chair Department of Genetics
Rutgers University,Piscataway, NJ 08854

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Dr. Brzustowicz: The objective of this study was to search for locations in the human genome that
impact language ability in individuals with autism as well as in their family members without
autism. To do this, we recruited families with an individual with autism and at least one other
family member without autism but with a language learning impairment. We identified two
locations in the human genome that are linked to language ability in these families. Importantly,
these locations do not appear to be specific to language impairment in the individuals with autism,
but are related to language ability in other family members as well. This suggests that while
individuals with autism may have new, or de novo, genetic variations that are important for risk of
illness, they may also carry inherited genetic variation that influence the expression of their
illness. The effects of these inherited variants can also be seen in the language performance of
family members without autism.

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Dr. Brzustowicz: Although we did not select these families for other members with impairments in
social responsiveness or for the presence of obsessive or compulsive thought or behaviors, we
were able to identify several additional locations in the genome that were linked to these
traits. This means that this one study has identified regions in the genome that are linked to all
three of the behavioral domains that are commonly impaired in autism. Furthermore, we have
identified these regions as being related to the expression of milder, but related, behavioral traits in
family members without autism.


Autism and Language Impairment: Possible Common Genetic Link
Linda Brzustowicz, M.D.
Professor and Chair Department of Genetics
Rutgers University,Piscataway, NJ 08854

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Dr. Brzustowicz: While much of the recent work on the genetics of autism has focused on de novo variants
that appear to be involved in risk of illness, our study reaffirms that there are also important inherited
genetic factors that are involved. Understanding the relative contributions of de novo and inherited risk
factors in the population and in specific families is very important for clinicians to be able to provide
accurate risk assessments for future pregnancies in families with one child with autism. We are also
hopeful that this and other genetic studies will further inform us about the biology of autism, potentially
providing new insights that may help in the development of new treatments.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Dr. Brzustowicz: Our study identified regions of the genome that are linked to these various components
of autism, but did not identify the specific genes that are involved. We are currently sequencing DNA from
individuals in our study as a method to identify the specific genes and variants that are involved in
increasing risk. It will also be important to replicate this work in additional families. Our group is currently
recruiting new families from New Jersey and surrounding regions to participate in such a replication
study. Any family who might be interested in participating can visit our study
website http://njlags.dls.rutgers.edu/ for more information about how to get involved with our research.
Citation:
A Genome Scan for Loci Shared by Autism Spectrum Disorder and Language Impairment
Christopher W. Bartlett, Ph.D., Liping Hou, Ph.D., Judy F. Flax, Ph.D., Abby Hare, B.S., Soo Yeon Cheong,
Ph.D., Zena Fermano, M.A., Barbie Zimmerman-Bier, M.D., Charles Cartwright, M.D., Marco A. Azaro,
Ph.D., Steven Buyske, Ph.D., Linda M. Brzustowicz, M.D.
American Journal of Psychiatry, Oct 2013; (); . doi: 10.1176/appi.ajp.2013.12081103


Lung Cancer: Breath Test Detection
Dr. Peter Mazzone MD, MPH
Pulmonary, Allergy and Critical Care Medicine
Cleveland Clinic Main Campus Cleveland, OH 44195

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MedicalResearch.com: What are the main findings of this study?
Dr. Mazzone: There were 2 parts to this study:
In the first part we looked at how the breath collection instrument and sensor were performing and
made adjustments to both in order to optimize its performance. In the second part we used the
improved device and sensor to see if we could accurately separate a sensor signal of our patients
with lung cancer from those without lung cancer. We found good separation of lung cancer from
non-cancer breath signals, and very good separation of signals of one type of lung cancer from
another.
We have concluded that a colorimetric sensor array based breath test is capable of separating those
with lung cancer from those without.
We learned about ways that we can enhance the sensor and breath collection instrument, and
showed enough promise that this can be an accurate test, that we plan to design a larger study with
an improved system in hopes that this will be the final step towards having a clinically useful test.
Citation:
The Analysis of Volatile Organic Compound Profiles in the Breath as a Biomarker of Lung Cancer
Peter Mazzone, MD; Xiaofeng Wang, PhD; Paul Rhodes, PhD; Ray Martino, PhD; Sung Lim, PhD;
Mary Beukeman; Meredith Seeley; Humberto Choi, MD; James Jett, MD
Chest. 2013;144(4_MeetingAbstracts):645A. doi:10.1378/chest.1703380


How much would Sugary Drink Tax Reduce Obesity?
Adam D M Briggs
Academic Clinical Fellow
British Heart Foundation Health Promotion Research Group
, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK

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Answer: For the first time this study estimates the impact of a
sugary drinks tax in the UK on obesity. We estimate the
tax would reduce the number of adults with obesity by
around 180,000 or just over 1% of all adults who are
obese, and the number of adults who are either overweight
or obese by 285,000. The greatest reductions are seen in
young adults. We also estimate that the effects of the tax
will be similar across all income groups.
Answer: There is some debate as to what the effect of such a tax
may have on different income groups with some researchers,
and commentators, suggesting that the health gains would
be greatest in lower income groups due to higher levels of
soft drink consumption and a greater prevalence of
obesity. However, our estimates indicate that in the UK,
changes in obesity will be similar across all income
groups. Although perhaps this is not wholly unexpected as
some other research groups have also estimated similar
outcomes, it does go against much of the perceived wisdom.


How much would Sugary Drink Tax Reduce Obesity?
Adam D M Briggs
Academic Clinical Fellow
British Heart Foundation Health Promotion Research Group
, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK

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MedicalResearch.com: What should clinicians and patients take away from your
report?
Answer: Our results indicate that a 20% tax on sugar sweetened
drinks is a promising population measure to target
population obesity in the UK, particularly among younger
adults. However, it should not be seen as a panacea and
could instead form part of a holistic approach to tackle
obesity.
Answer: The next steps will be to investigate the potential impact
of such a tax by population groups defined by the level of
consumption of sugar sweetened drinks (something we have
not been able to do here). It would also be important to
try to characterize the effect of any negative publicity
surrounding sugar sweetened drinks arising from a tax.
Finally, the response from industry of this type of tax is
unclear. Ideally, a government will introduce a tax of
this nature allowing for proper population level
evaluation as a natural experiment.
Overall and income specific effect on prevalence of
overweight and obesity of 20% sugar sweetened drink tax
in UK: econometric and comparative risk assessment
modeling study.
Citation:
Overall and income specific effect on prevalence of overweight and obesity of 20% sugar sweetened drink tax in UK:
econometric and comparative risk assessment modelling study
BMJ 2013; 347 doi: http://dx.doi.org/10.1136/bmj.f6189 (Published 31 October 2013)
Cite this as: BMJ 2013;347:f6189

Diabetes: Renoprotective Effects of ACE Inhibitors
Hon-Yen Wu, Lecturer
Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan

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Answer: We used the Bayesian network meta-analysis to evaluate the efficacy of different
antihypertensive treatment strategies on survival and major renal outcomes for diabetic
patients. We found that angiotensin converting enzyme (ACE) inhibitor therapy is the only
treatment that significantly prevents the doubling of serum creatinine levels compared with
placebo. Our analysis also shows the significant inferiority of β blockers in all cause mortality.
The available evidence is not able to show a significant difference between angiotensin
receptor blockers (ARBs) and ACE inhibitors. Although the protective effect of ACE inhibitor
plus calcium channel blocker compared with placebo was not statistically significant, yet this
combination therapy showed the greatest probability of being the best treatment option in
reducing mortality.
Answer:
A number of included studies showed low event rates or even no events in one or both
treatment arms, and those studies increase the uncertainty in the comparisons of multiple
treatments within a network meta-analysis, giving rise to wide credible intervals for several
treatment comparisons with low event rates.

Diabetes: Renoprotective Effects of ACE Inhibitors
Hon-Yen Wu, Lecturer
Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan

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Answer:
Our study shows the renoprotective effects of ACE inhibitors for diabetic patients. As the available
evidence does not show a better protective effect of ARBs compared with ACE inhibitors, our
findings support the use of ACE inhibitors to reduce the cost. Calcium channel blockers in
combination with ACE inhibitors may be an alternative, if adequate blood pressure control cannot
be achieved by the use of ACE inhibitors alone.
MedicalResearch.com: What recommendations do you have for future research as a result of this
study?
Answer:
Some patient characteristics and methodological quality, such as age, sex, cardiovascular diseases,
as well as selection bias or performance bias, might be potential confounders for our analyses.
However, metaregression or subgroup analysis in network meta-analysis is very complex and its
statistical power is relatively low. Whether those potential confounders have substantial influences
on treatment outcomes in patients with diabetes deserves further studies in the future.
Citation:
Comparative effectiveness of renin-angiotensin system blockers and other antihypertensive drugs
in patients with diabetes: systematic review and bayesian network meta-analysis
Wu H ,Huang J ,Lin H ,Liao W ,Peng Y ,Hung K ,et al. Comparative effectiveness of renin-angiotensin
system blockers and other antihypertensive drugs in patients with diabetes: systematic review and
bayesian network meta-analysis. BMJ 2013;347:f6008


Psoriatic Arthritis: Tight Control Improves Arthritis, Skin Disease
Dr. Laura Coates
Division of Rheumatic and Musculoskeletal Disease
Chapel Allerton Hospital Chapeltown Road Leeds
NIHR Clinical Lecturer at the University of Leeds

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Answer: The TICOPA study showed that treating patients with early psoriatic
arthritis to an objective target with regular review improved
patient’s clinical outcome both in terms of arthritis and skin
psoriasis. There was an increase in adverse events in the tight
control arm but only 4 serious infections seen in the tight control
arm that were thought to be related to treatment (2 cases of
cellulitis, 2 cases of chest infection).

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Answer: The findings are not totally unexpected as previous observational
studies have suggested that inflammation in joints is linked to longterm outcome. However this is the first study to assess treatment to
target in PsA and show such a direct improvement in outcome.
Answer: The study suggests that clinicians should be more aggressive with
treatment of psoriatic arthritis and assess all of the different
facets of the disease when considering treatment options. Using the
minimal disease activity (MDA) criteria to assess patients can assist
in treatment decisions ensuring that both the physician’s and
patient’s opinions are taken into account.
Answer: Further studies are now needed to test alternative treatment
strategies with different therapies as we have little evidence in PsA
about which drugs to use in which order. We also need to do further
research about predictors of response and disease severity so that we
can personalise treatment and identify which patients need more
aggressive therapy.
Citation:
ACR 2013 presentation:
Results of a randomized controlled trial comparing tight control of
early psoriatic arthritis (TICOPA) with standard care: Tight control
improves outcome

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Neglected Diseases: Research and Development Landscape
MedicalResearch.com Interview with :
Dr Belén Pedrique
Epidemiologist
Drugs for Neglected Diseases initiative, DNDi, 15 Chemin Louis Dunant
1202 Geneva, Switzerland

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MedicalResearch.com : What are the main findings of the study?
Dr. Pedrique: Of the 850 new drugs and vaccines approved for all diseases in 2000-2011, 4%
(37) were for neglected diseases, defined broadly as those prevalent primarily in poor
countries: malaria, tuberculosis, 17 neglected tropical diseases (NTDs) as defined by the
World Health Organization (WHO), 11 diarrheal diseases, and 19 other diseases of poverty,
excluding HIV/AIDS. Globally these neglected diseases represent an 11% health burden,
based on a recent assessment of 2010 disability-adjusted life-years (DALYs).
Most newly developed therapeutic products were repurposed versions of existing drugs. Of
the 336 brand-new drugs (new chemical entities, or NCEs) approved for all diseases in 20002011, only four, or 1%, were for neglected diseases; three were for malaria, and one for
diarrheal disease. None were for any of the 17 WHO-listed NTDs
Of 148,445 phase I-III clinical trials registered as of Dec 31, 2011, only 1% (2,016) were for
neglected diseases.


Dr Belén Pedrique
Epidemiologist

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Other study highlights:
New drugs for neglected diseases have a measurable medical benefit: Using inclusion on the WHO
Essential Medicines List (EML) as a proxy measure for medical benefit, 48% of all new therapeutic products
(excluding vaccines/biological products) approved 2000-2011 for neglected diseases were on the EML,
compared with 4% for all other diseases.
Most new candidates in development are vaccines: 123 new products are currently in development for
neglected diseases, with over half (55%; 68) being vaccines or biological products, including 21 for malaria.
A little over a quarter (28%; 34) are for the 17 NTDs, with only 3 NCEs (for onchocerciasis, Chagas disease,
sleeping sickness).
Drug repurposing and NCEs are further along in development than vaccines: 56% (38/68) of
vaccine/biological product candidates are in Phase I clinical trials, whereas 85% (29/34) of repurposeddrug products and 63% (10/16) of NCEs are in Phases II-III.
Nearly 80% of neglected diseases have R&D gaps: Based on selected evaluation criteria, of the 49
neglected diseases included in the study, 11 (22%) had no R&D gaps; 25 (51%) had R&D gaps and some
ongoing R&D; and 13 (27%) had R&D gaps and no ongoing R&D.
Public sponsorship leads R&D: Clinical trial sponsors were 54% public (governments, academia, public
research institutes), 23% private industry (pharma/biotech), and 15% private non-for-profit (product
development partnerships, charities, foundations). Remaining 8% were mixed. These results suggest that
public and not-for-profit organizations are largely involved in these clinical trials for neglected diseases.
Neglected-disease R&D has accelerated somewhat over the past 35 years: Previous studies reported 0.61.3 new products/year for neglected diseases for 1975-1999. This study reports a slight increase of 2.4
new products/year for 2000-2011 and predicts 4.7 new products/year through 2018 with a higher
proportion of vaccines over brand new drugs.


Dr Belén Pedrique
Epidemiologist

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MedicalResearch.com : Were any of the findings unexpected?
Dr. Pedrique:
Few new chemical entities (NCEs) have been developed in the last decade for most neglected diseases, including for all
NTDs, and few NCEs are in the current pipeline.
We found a consistently low proportion of 1% allocated to R&D for neglected diseases in different areas of analysis: only 1%
of approved NCEs (2000-2011), 1% of clinical trials (December 2011), and, in a recent report by other authors (Lancet 2013;
382: 1286-1307), 1% of global health investment.
MedicalResearch.com : What should clinicians and patients take away from your report?
Dr. Pedrique:
Major advances were achieved in the last decade in the treatment and prevention of some neglected diseases (i.e. malaria,
leishmaniasis, sleeping sickness, diarrhoeal diseases)
Nevertheless, new therapeutic products are still needed for many neglected diseases in order to treat patients at the field
level.
MedicalResearch.com : What recommendations do you have for future research as a result of this study?
Researchers should conduct further analyses of patient and R&D needs for prevention, treatment, and diagnosis of
neglected diseases and set R&D priorities to address these unmet needs.
Researchers should provide regular updates of ongoing clinical trials and timelines, successes, and hurdles for new
therapeutics in development for neglected diseases.
Citation:
The drug and vaccine landscape for neglected diseases (2000–11): a systematic assessment
Dr Belen Pedrique MD,Nathalie Strub-Wourgaft MD,Claudette Some PharmD,Piero Olliaro MD,Patrice Trouiller
PharmD,Nathan Ford PhD,Bernard Pécoul MD,Jean-Hervé Bradol MD
The Lancet Global Health – 24 October 2013
DOI: 10.1016/S2214-109X(13)70078-0


Proton Therapy Radiation: Decreased Need for Feeding Tubes in Oropharnygeal Cancer Patients
Steven J. Frank, M.D., associate professor of Radiation Oncology at
The University of Texas MD Anderson Proton Therapy Center discusses the findings of his latest study, “Gastrostomy Tubes Decrease by Over
50% with Intensity Modulated Proton Therapy during the Treatment of Oropharyngeal Cancer Patients.”

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Dr. Frank: The study found that the use of feeding tubes in oropharyngeal carcinoma (OPC) cancer
patients treated with intensity modulated proton therapy (IMPT) decreased by more than 50%
percent compared to patients treated with intensity modulated radiation therapy (IMRT). This
suggests that proton therapy may offer vital quality of life benefits for patients with tumors
occurring at the back of the throat.
Of the 50 OPC patients enrolled in the study:
Twenty-five patients were treated with IMPT and 25 received IMRT.
Five patients treated with IMPT required the use of feeding tubes (20%) compared to 12 patients
treated with IMRT (48%).
IMPT patients were spared from serious side effects, usually a result of IMRT, such as loss of taste,
vomiting, nausea, pain, mouth and tongue ulcers, dry mouth, fatigue, and swallowing difficulty.
IMPT patients could better sustain their nutrition and hydration levels, often leading to faster
recovery during and after treatment.
IMPT is an advanced form of proton radiation therapy and a treatment currently only offered in
North America at The University of Texas MD Anderson Proton Therapy Center. It delivers protons
to the most complicated tumors by focusing a narrow proton beam and essentially “painting” the
radiation dose onto the tumor layer by layer. Unlike IMRT, which destroys both cancerous and
healthy cells, IMPT has the ability to destroy cancer cells while sparing surrounding healthy tissue
from damage. Therefore, important quality of life outcomes such as neurocognitive function, vision,
swallowing, hearing, taste and speech can be preserved in head and neck patients.



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Dr. Frank: It is known that using IMPT vs. IMRT in this critical head and neck area achieves less
radiation dose to the surrounding tissues. What the study found was that the low doses of radiation
therapy have truly measurable acute effects and the feeding tube rate in itself is simply a metric of
the symptom burden that is infused by all the additional radiation of IMRT. However, the fact that
the feeding tube rate in IMPT patients was reduced by over 50% was very surprising.
This finding guided MD Anderson to initiate a Phase II/III randomized trial to truly better appreciate
if the reduction of feeding tubes by 50% is a replicable finding that will perhaps change the
standard of care (more details below).
MedicalResearch.com: What should clinicians and patients take away from this report?
Dr. Frank: Clinicians and patients should realize that HPV associated head and neck tumors are
rising in epidemic proportions in the United States and most patients are young, non-drinkers and
non-smokers. Patients with HPV+ tumors will likely be cured and efforts are underway to reduce
the toxicity of the treatment. Proton therapy might offer another tool to provide one measurable
solution, and, in addition, since it reduces the toxicity, it can potentially increase patient’s quality of
life both during and after treatment.
The clinicians should realize that there are new capabilities at their disposal for head and neck
patients with proton therapy treatment.
Patients should be aware that proton therapy may effectively treat their head and neck cancer
while decreasing the toxicity that will allow the patients to continue to work and function during
and after treatment.



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of this study?
Dr. Frank: More studies are needed to better understand how improving the delivery of
radiation therapy, the main tool to treat OPC in this fairly young group of patients, can
provide additional value to those afflicted with HPV associated head and neck cancer. Based
on the results of this study, a Phase II/III randomized trial of IMPT vs. IMRT for the treatment
of advanced stage oropharyngeal cancer of the head and neck is underway at MD Anderson.
Over the next five years, the trial will enroll up to 400 patients. This randomized trial will aim
to demonstrate that proton therapy can improve treatment outcomes in a cost effective
manner.
Citation:
Gastrostomy Tubes Decrease by Over 50% With Intensity Modulated Proton Therapy (IMPT)
During the Treatment of Oropharyngeal Cancer Patients: A Case–Control Study
S.J. Frank, D.I. Rosenthal, K. Ang, E.M. Sturgis, M.S. Chambers, G.B. Gunn, K.A. Hutcheson,
X.R. Zhu, M.B. Palmer, A.S. Garden
International Journal of Radiation Oncology * Biology * Physics – 1 October 2013 (Vol. 87,
Issue 2, Supplement, Page S144, DOI: 10.1016/j.ijrobp.2013.06.371)

Prostate Cancer: Obesity at Diagnosis Increases Mortality Risk
Reina Haque, PhD, MPH
Research scientist, Kaiser Permanente Department of Research & Evaluation

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Answer: The main study findings are that men who are overweight or obese when they are
diagnosed with prostate cancer are more likely to die from the disease than men who are of
healthy weight. In patients with more aggressive forms of prostate cancer, the researchers also
found an even stronger correlation between obesity and mortality.
The study was restricted to patients undergoing surgical treatment for prostate cancer, rather than
other treatments such as radiation or hormone therapy.

Answer: The link between obesity and prostate cancer mortality remains controversial. Although
the connection between men’s weight at prostate cancer diagnosis and likelihood of survival has
been examined, many previous studies were limited by self-reported body weight data or it was
unclear when the BMI data were obtained.
The methodology of this study was improved because the researchers used BMI collected from
medical records, instead of self-reported data. The researchers identified men who died of prostate
cancer and compared their BMI at time of diagnosis to controls to determine if body weight is
related prostate cancer death. The biological relationship between obesity and prostate cancer
prognosis is still not understood, and is an active area of research.


Prostate Cancer: Obesity at Diagnosis Increases Mortality Risk

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Answer: Clinicians and patients should be aware of the growing body of evidence that
associates weight and prostate cancer mortality. In addition, they should be vigilant for future
studies that provide information regarding whether weight loss or other lifestyle changes
could prolong a prostate cancer patient’s life
of this study?
Answer: Moving forward, we are hoping future studies will examine the effect of weight loss
and other lifestyle modifications on prostate cancer mortality. Further investigation also is
needed to determine if the findings of this study, which looked at men who had prostate
cancer surgery, apply to men who received other treatments such as radiation or hormone
therapy.
Citation:
Weight at time of diagnosis linked to prostate cancer mortality
Reina Haque, Stephen K. Van Den Eeden, Lauren P. Wallner, Kathryn Richert-Boe, Bhaskar
Kallakury, Renyi Wang, Sheila Weinmann
Obesity Research & Clinical Practic
06 August 2013


Diabetes: Are Antioxidants Really a Good Idea?
Kumar Sharma, M.D. Professor of Medicine
Director, Institute of Metabolomic Medicine
Director, Center for Renal Translational Medicine
University of California, San Diego La Jolla, CA 92093-0711

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Dr. Sharma: Main findings are that diabetes is associated with reduced superoxide production in the kidney and heart and
that stimulation of superoxide production with AMPK led to improvement in organ function.

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Dr. Sharma: Yes, these were the first in vivo imaging studies to look at real time superoxide production. As per the prevailing
theory we expected to see an increase in mitochondrial superoxide production with diabetes, but we saw the opposite.
Dr. Sharma: Our data, coupled with other reports, suggest that anti-oxidants may not be a good idea for chronic disease
such as diabetic kidney disease. We need to understand individual sources of reactive oxygen species much better before we
could identify if any anti-oxidants are useful.
Dr. Sharma: New treatments to improve mitochondrial function may be beneficial. The challenge will be to identify the
right drugs and the best way to monitor response in patients.
Dr. Sharma: Use of real time imaging approaches will be very revealing in many disease states linked to reactive oxygen
species. We will also need to better understand how and why mitochondrial function is reduced in diabetes and what is the
best method to regulate function and protect organs.
Citation:
AMPK dysregulation promotes diabetes-related reduction of superoxide and mitochondrial function.
Dugan LL, You YH, Ali SS, Diamond-Stanic M, Miyamoto S, Decleves AE, Andreyev A, Quach T, Ly S, Shekhtman G, Nguyen W,
Chepetan A, Le TP, Wang L, Xu M, Paik KP, Fogo A, Viollet B, Murphy A, Brosius F, Naviaux RK, Sharma K.
J Clin Invest. 2013 Oct 25. pii: 66218. doi: 10.1172/JCI66218. [Epub ahead of print]

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Venous Blood Clots: Sex Difference in Risk Explained
Dr. W.M. Lijfering, MD, PhD
Department of Clinical Epidemiology, C7-P-89
Leiden University Medical Center 2300 RC Leiden

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Dr. Lijfering: In this study we found that the risk of a first venous thrombosis* is two-fold
higher in men than in women once female reproductive risk factors for venous thrombosis
are taken into account (odds ratio 1.9, 95% CI 1.7-2.2). These results were found in all age
categories (18-70 years) and were not affected by adjustment for body mass index and
smoking, or by excluding participants with malignancy.

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Dr. Lijfering: This is the first study that explains why the crude annual risk of first venous
thrombosis is equal in men and women, yet the crude annual risk for a recurrent event is
twice as high in men as compared with women. Women often stop taking oral contraceptives
after a first venous thrombotic event or receive thromboprophylaxis when being pregnant.
Hence, they are no longer prone to recurrent thrombotic events that are due to these
reproductive factors. For a first event this is very different. Approximately 50% of women of
reproductive ages experience a first venous thrombosis while being exposed to reproductive
risk factors. Therefore our hypothesis was that a risk difference between the sexes is masked
by female exposure to reproductive factors, which we confirmed in our study.

Venous Blood Clots: Sex Difference in Risk Explained
Dr. W.M. Lijfering, MD, PhD
Department of Clinical Epidemiology, C7-P-89
Leiden University Medical Center 2300 RC Leiden

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Dr. Lijfering: This finding, which is in line with the findings of previous studies that showed that venous
thrombosis recurs twice as often in men as in women, suggests that the intrinsic risk of venous thrombosis
is higher in men than in women. Prediction models for recurrent venous thrombosis already advocate
differential treatment strategies for men and women after a first venous thrombosis. From our results it
seems that a differential approach to the prevention of first venous thrombosis in men and in women
without reproductive risk factors may also be indicated. For instance, men may benefit from a lower
threshold for prophylactic treatment than women without reproductive risk factors when encountering
high risk situations for venous thrombosis. Male sex could be included in a prediction model in the same
way as, for example, oral contraceptive use in women is sometimes included now. Alternatively, men may
require a higher dose of prophylactic anticoagulation therapy than women without reproductive risk
factors in order to reduce their venous thrombosis risk to the same extent.
Dr. Lijfering: It is important that future studies focus on the sex-specific risk and prevention of first venous
thrombosis in order to identify which factors can be targeted to reduce the higher risk of venous
thrombosis in men.
Citation:
Sex Difference in Risk of Second but not of First Venous Thrombosis: Paradox Explained
Rachel E. J. Roach, Willem M. Lijfering, Frits R. Rosendaal, Suzanne C. Cannegieter, and Saskia le Cessie
Circulation. 2013;CIRCULATIONAHA.113.004768published online before print October 21 2013,
doi:10.1161/CIRCULATIONAHA.113.004768


Epicardial Fat, Fatty Liver Linked
MedicalResearh.com Interview with:
Gianluca Iacobellis MD PhD
Professor of Clinical Medicine
Division of Diabetes, Endocrinology and Metabolism, Department of Medicine,
University of Miami Miller School of Medicine, Miami, Florida, USA

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Dr. Iacobellis: Our study suggests that epicardial fat, the fat pad in direct contiguity to the heart, is a
good predictor of liver steatosis in obese subjects

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Dr. Iacobellis: Our findings were consistent with the study hypothesis. However, we showed for the
first time that cardiac and liver fat are clinically correlated, independently of the BMI.
MedicalResearch.com: What should clinicians and patients take away from this study?
Dr. Iacobellis: Excessive accumulation of fat within and around the heart and the liver is a
modifiable risk factor for diabetes and heart diseases. Ultrasound-measured cardiac and liver
steatosis are accurate, non invasive and easily accessible markers of intra-organ fat accumulation.
MedicalResearch.com: What recommendations do you have for future research as a result of your
study?
Dr. Iacobellis: Ultrasound-measured epicardial fat predicts fatty liver better than BMI or waist
circumferences does. Future studies looking at the clinical use of the echocardiographic epicardial
fat as predictor of organ-specific adiposity and cardiometabolic risk are warranted.
Citation:
Epicardial fat thickness and nonalcoholic fatty liver disease in obese subjects.
Obesity 2013 Sep 30.[Epub ahead of print]

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Rheumatoid Arthritis and Increased Risk of Heart Disease
Eric Matteson, M.D.
Rheumatology Chair
Mayo Clinic in Rochester, Minn.

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MedicalResearch.com: What are the main findings of the studies?
Dr. Matteson: “The main finding is that patients with severe rheumatoid arthritis have a
higher risk of heart disease. Further, women who experience early menopause also have a
higher risk of heart disease.”

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Dr. Matteson: “We suspected that patients with worse disease would have higher risk, but
did not actually know this. As well, we thought that early menopause might suggest lower
estrogen exposure which could be a risk factor for heart disease, but we were not clear if this
would increase or decrease risk.”


Rheumatoid Arthritis and Increased Risk of Heart Disease
Eric Matteson, M.D.
Rheumatology Chair
Mayo Clinic in Rochester, Minn.

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Dr. Matteson: “Patients with rheumatoid arthritis should have a heightened awareness of their risk
of heart disease over and above the usual risk factors such as smoking, high blood pressure and
high cholesterol. Particularly patients with more severe disease should be aware of this risk and
together with their physicians take steps to evaluate the risks. This is perhaps true also for women
with RA who have undergone early menopause. The latter is of interest also because in the past
estrogen replacement had been suggested to reduce the risk of heart disease, but because of side
effects is not pursued today as a general recommendation.”
study?
Dr. Matteson: “We need to better understand how therapy for rheumatoid arthritis may influence
the long-term risk of heart disease, by reducing the burden of the rheumatoid arthritis itself. We
also need to find better predictors including biomarkers which might be predictive of heart disease
risk in patients with rheumatoid arthritis who have no apparent other risk factors.”
Citation:
Presented at the American College of Rheumatology Annual Meeting Fall, 2014
Mayo Clinic (2013, October 27). Dangerous connection between rheumatoid arthritis, heart
disease. ScienceDaily. Retrieved October 29, 2013, from http://www.sciencedaily.com/releases/2013/10/131027123153.htm


Depression: Physical Activity and Prevention
George Mammen, PhD Candidate
Health & Exercise Psychology Unit
University of Toronto

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Answer:
25 out of the 30 studies found PA to protect against depression; majority of these were of high methodological quality
Decreasing PA overtime can increase the risk of developing depression; increasing PA overtime can reduce the risk of
developing depression
In terms of dosage, the review highlighted studies that showed even low levels, such as 20 mins of walking a day, can prevent the onset
of depression.
Answer:
It was promising to see so many studies finding a similar protective relationship while they controlled for an array of confounders that
relate to either PA or depression (e.g., SES, age, smoking, alcohol use)
Answer:
Clinicians should explain to patients that not only will PA help prevent future chronic diseases such as heart disease, type II diabetes,
cancer and stroke; but it can also prevent depression and help sustain positive mental health
Patients and the general public, should take this seriously and realize that being active throughout the day goes far beyond the physical
benefits generally associated with PA. Everyone should make it a goal to try and be active for at least 20-30 minutes a day.
Answer:
Future research should now look at the exact mechanisms of ‘how’ this protective effect occurs.
future research should take into account genetic factors that may play a strong role in this relationship
Additionally, a standardized way to subjectively and objectively measure PA is needed in order to decipher the exact dosage of how
much PA is needed to help prevent depression.
Citation:
Physical Activity and the Prevention of Depression: A Systematic Review of Prospective Studies
George Mammen, Guy Faulkner
American Journal of Preventive Medicine – November 2013 (Vol. 45, Issue 5, Pages 649-657, DOI: 10.1016/j.amepre.2013.08.001)


Rheumatoid Arthritis: Heart Disease and Biologics
Lotta Ljung, MD, PhD
Umeå University, Umeå and Karolinska Institute
Stockholm, Sweden

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Dr. Ljung: In this observational study we observed a lower risk of acute coronary syndromes in a
cohort of patients with rheumatoid arthritis (RA) exposed to tumor necrosis factor inhibitors (TNFi)
compared with the risk among patients without this exposure. The adjusted relative risk (HR) was
0.73-0.82 among TNFi exposed patients compared with the biologics-naive RA cohort, depending
on the time frame evaluated, which can be concluded as a moderately lower risk.
Compared with the risk in the general population, the risk in RA patients was higher, whether
exposed to TNFi or not.

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Dr. Ljung: A number of previous studies have shown an increased risk of cardiovascular events,
especially ischemic heart disease, among patients with RA. Treatment that lower the inflammatory
activity, such as methotrexate, has often been associated with lower cardiovascular risk. Regarding
treatment with TNFi, previous studies have shown conflicting results and there has been a need for
more evidence. This study supports the hypothesis of the inflammation in RA having an impact on
the cardiovascular risk. It also adds to the evidence that treatment with TNFi is safe regarding the
development of ischemic heart disease. The size of the study and its population based, nation-wide
setting implicates a high probabililty of the results being generalizable to other populations.


Rheumatoid Arthritis: Heart Disease and Biologics
Lotta Ljung, MD, PhD
Umeå University, Umeå and Karolinska Institute
Stockholm, Sweden

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Dr. Ljung: That treatment with TNFi are safe regarding the development of acute coronary syndrome in
patients with RA, and that the treatment actually might lower the risk. As the over risk, compared with the
risk in the general population, was not abolished, identification and management of traditional
cardiovascular risk factors are needed for patients with RA also under treatment with TNFi.
Dr. Ljung: It would be valuable to evaluate if response to treatment is associated with the risk of
cardiovascular disease in treated patients, if treatment is associated with a modified risk in specific
subpopulations, and if there are any differences between the different TNFi drugs that are under use, as
well as risk modifications for other cardiovascular outcomes. Studies on cardiovascular risk with other
biological treatment options are also needed in the future.
Citation:
Tumour Necrosis Factor Inhibitors and The Risk Of Acute Coronary Syndrome In Rheumatoid Arthritis – A
National Cohort Study –
Lotta Ljung, Umeå University, Umeå, Sweden
AMERICAN COLLEGE OF RHEUMATOLOGY
77th Annual Meeting
ASSOCIATION OF RHEUMATOLOGY HEALTH PROFESSSIONALS
48th Annual Meeting
October 26-30, 2013
San Diego, Calif.


Celiac Disease: Association with Iron Supplement during Pregnancy?
MedicalResearch.com Interview with
Dr. Ketil Stordal
Researcher/consultant paediatrician
National Institute of Public Health Norway

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Dr. Stordal: Mothers who used iron supplementation during pregnancy had an increased risk for having children with a
diagnosis of celiac disease. This association was not caused by maternal anemia during pregnancy, anemia was not a
predictor of celiac disease in the offspring. The risk for celiac disease when the mother had used the highest doses and for
the longest period.
Dr. Stordal: The findings were unexpected, and to our knowledge, the association has not been investigated before.
However, studies have shown pro-inflammatory effects in the placenta after iron supplementation, and programming effects
on the fetal immune system could be hypothesized.
The effect was not present for other kinds of nutritional supplements commonly used in health-conscious mothers as folic
acid and multivitamins, and is unlikely to be driven by care-seeking behavior.
Dr. Stordal: Our findings are preliminary, and iron should be taken when deficiencies are present during pregnancy because
of other beneficial effects on the fetal health. However, indiscriminant use of iron supplements should not be
recommended.
Dr. Stordal: Biomarkers of iron overload or excess would be of interest in observational studies to study if the association
between celiac disease and iron exposure in early life could be reproduced.
Citation:
Maternal iron supplement intake during pregnancy and risk of celiac disease in children
Clin Gastroenterol Hepatol. 2013 Oct 7. pii: S1542-3565(13)01509-7. doi: 10.1016/j.cgh.2013.09.061. [Epub ahead of print]
Størdal K, Haugen M, Brantsæter AL, Lundin KE, Stene LC.
Norwegian Institute of Public Health, Oslo, Norway; Østfold Hospital Trust, Fredrikstad, Norway


Smoking: Monday Most Popular Day to Quit
MediclResearch.com Interview with:
John W. Ayers, PhD, MA
Graduate School of Public Health
San Diego State University, San Diego, California

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Dr. Ayers: Our study, published today in the Journal of the American Medical Association, Internal
Medicine was the first to describe daily rhythms in health behaviors.
Because trends in quitting contemplations are usually described annually using telephone surveys,
we had to use a novel data source that could capture daily patterns. By monitoring aggregate
Internet search queries we can see precisely what the population is thinking about by the content
of their queries and that the population is engaged in the issue by searching. We therefore analyzed
daily search volumes for smoking cessation queries (e.g., “quit smoking”) in six languages across
the entire globe.
We found that people search about quitting smoking more often early in the week, with the highest
query volumes on Mondays, using a daily measure representing the proportion of quit smoking
searches to all searches. This pattern was consistent across all six languages, suggesting a global
predisposition to thinking about quitting smoking early in the week, particularly on Mondays.
English searches, for example, showed Monday query volumes were 11 percent greater than on
Wednesdays, 67 percent greater than on Fridays, and 145 percent greater than on Saturdays. In
total for all six languages, Monday query volumes were 25 percent higher than the combined mean
number of searches for Tuesday through Sunday.
Practically these findings are very meaningful. For example, in English alone there are about
150,000 more quit smoking queries on Monday than on a typical day; about 8,000,000 over an
entire year.



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Dr. Ayers: Popular belief has been that the decision to quit smoking is unpredictable with one
recently published study from BMJ’s Tobacco Control calling the decision to quit “chaotic.” By
taking a bird’s-eye view of Google searches, however, we find anything but chaos. Instead,
Google search data reveal interest in quitting is part of a larger collective pattern of behavior
dependent on the day of the week.
Dr. Ayers: Our first message is for smokers: If you’re a smoker, just remember: quit this
Monday. Everyone else is doing it.
For clinicians and health advocates: We believe our results provide important evidence that
can improve the delivery of existing anti-smoking measures. Whether it’s scheduling staff
hours or buying media time, you are better off reaching people when they’re thinking about
their smoking habit, and early in the week, especially Monday, seems to be an ideal time.



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of this study?
Dr. Ayers: Clearly, these results are not intended to be definitive as more research is needed,
especially for understanding the mechanisms linking the days of the week with search
patterns. For instance, just what is it about the days of the week and how ubiquitous are
these patterns?
However, intuition suggests that these results are reflective of an important link between the
days of the week and population health that goes well beyond our previous understanding.
Circaseptan (Weekly) Rhythms in Smoking Cessation Considerations
John W. Ayers, PhD, MA; Benjamin M. Althouse, ScM, PhD; Morgan Johnson, MPH; Joanna
E. Cohen, MHSc, PhD
JAMA Intern Med. Published online October 28, 2013.
doi:10.1001/jamainternmed.2013.11933


Physicians in Training and Basic Etiquette: Room for Improvement
Lauren Block, MD
Assistant Professor, North Shore–LIJ Hofstra School of Medicine
2001 Marcus Ave., Suite S160 Lake Success, NY 11042

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Dr. Block: Our goal was to look at how often doctors in training were performing basic niceties with their
patients, such as introducing themselves and sitting down. We found that while the doctors usually asked
open-ended questions and touched patients, resident physicians were unlikely to introduce themselves,
explain their role, or sit down when talking to patients.
Dr. Block: Yes, we were surprised to note that resident doctors estimated performing these behaviors
more frequently than was observed.
Dr. Block: Basic etiquette in patient care is associated with higher patient satisfaction, and has been shown
to impact the patient-doctor relationship. Resident physicians are not commonly performing these
behaviors, which speaks to an opportunity for education and role-modeling in the clinical setting.
Dr. Block: We believe the next step is to perform an intervention looking at whether simple curricula in
communication skills or environmental changes such as providing chairs in patient rooms can encourage
doctors to perform these behaviors more commonly.
Citation:
Do internal medicine interns practice etiquette-based communication? A critical look at the inpatient
encounter
Block, L., Hutzler, L., Habicht, R., Wu, A. W., Desai, S. V., Novello Silva, K., Niessen, T., Oliver, N. and
Feldman, L. (2013), Do internal medicine interns practice etiquette-based communication? A critical look
at the inpatient encounter. J. Hosp. Med.. doi: 10.1002/jhm.2092


Heart Attack: Evaluation of Bioabsorbable Drug Eluting Stents
Lorenz Raber, MD
University Hospital Bern
Bern, Switzerland

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Dr. Raber: The main finding of the clinical study is that the benefit of a biolimus-eluting stent using
a biodegradable polymer (Biomatrix, BES) regarding MACE (cardiac death, target vessel MI, TLR)
continued to accrue during the second year of follow-up, actually with a similar relative risk
reduction as observed during the first year. After one year, the timepoint at which most patients
stopped dual antiplatelet therapy (DAPT), no difference in safety (cardiac death, myocardial
infarction, stent thrombosis) was observed between BES and the control group (bare metal stent,
BMS). This largely confirms the principle concept of biodegradable polymer stent platforms.
The results of the imaging substudy provide a mechanistic explanation for the observed benefit
with BES. Specifically, BES showed a lower neointimal thickness, a low frequency of uncovered and
malapposed stent struts (OCT) and the absence of positive remodeling (IVUS) at 13 months followup.
Dr. Raber: The favorable arterial healing profile following BES implantation in culprit lesions of
STEMI patients was not anticipated. Early generation DES were associated with a substantial delay
in arterial healing, particularly in STEMI lesions. The finding of a lower frequency of atherothrombotic material in BES as compared to BMS after stent implantation came as a surprise and
offers a potential explanation for the lower thrombotic risk observed with newer generation DES
compared with BMS.

Heart Attack: Evaluation of Bioabsorbable Drug Eluting Stents
Lorenz Raber, MD
University Hospital Bern
Bern, Switzerland

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Dr. Raber: The use of BES appears more safe and efficient as compared to a BMS, even after
cessation of DAPT. In concert with data on the safety and efficacy of other newer generation
DES used for primary PCI, there is not much air left for BMS in primary PCI. Guidelines will
sooner or later acknowledge this paradigm shift.
of this study?
Dr. Raber: Newer generation DES appear as the new safety and efficacy benchmark for any
future stent comparisons, including fully bioabsorbable scaffolds. Following primary PCI,
there is a need to improve early outcomes (e.g. <2 days after stent placement). This might be
achieved with the use of novel antithrombotic drugs. The ideal DAPT duration following
primary PCI with newer generation DES also remains to be investigated.
Citation:
Insights into the unique capabilities of bioabsorbable polymer-based drug-eluting stents in
high-risk scenarios: 2-year clinical and imaging data from COMFORTABLE AMI
http://www.tctconference.com


Hip Fracture Surgery: Hand Grip Strength and Recovery Prediction
Stefano Volpato MD MPH
Department of Medical Sciences, University of Ferrara
Ferrara, Italy

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Dr. Volpato: In this study we evaluated clinical value of handgrip strength assessment in
older patients admitted to the hospital for hip fracture. We observed 504 older patients
admitted to 4 Italian hospitals for hip surgery, able of walking independently before fracture,
and we found a strong, graded and independent association of grip strength, assessed before
hip surgery, and the likelihood of functional recovery over the one-year follow-up. The
findings reported in our manuscript can be summarized as:
a. handgrip strength significantly correlated with several prognostic factors traditionally
considered in clinical practice, such as age, gender, neuro-psychological and functional status,
comorbidity level, vitamin D plasma levels, and time before the surgical procedure;
b. logistic regression models showed that handgrip strength was directly associated with
higher probability of walking recovery, both at any follow-up (incident walking recovery), and
for at least 2 consecutive follow-ups (persistent walking recovery);
b. Kaplan-Meier survival estimates showed that lower grip strength was related to increased
mortality after hip surgery;
c. the association between grip performance and walking recovery was clinically relevant and
statistically independent of potential confounders.

Ferrara, Italy

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Dr. Volpato: In spite of Kaplan-Meier curves, we could not confirm a statistically significant
association between low handgrip strength and probability of death in fully adjusted Cox
proportional hazard models, this was probably due to the effects of other covariates.
Dr. Volpato: Grip strength is a simple clinical parameter, assessable at bedside before hip
surgery, and it captures the integrated and multi-systemic effects of aging, comorbidity,
disease severity, malnutrition, motivation, cognition, and body resilience on the health status
of older persons. It might provide important prognostic information in order to better
identify high-risk individuals who could benefit the most from intensive multi-domain
intervention programs, including but not limited to earlier surgery strategy, intensive
nutritional support, and rehabilitation programs.


Ferrara, Italy

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of this study?
Dr. Volpato: and different populations. Second, to fully translate these results in clinical
practice we need to establish and validate sex and age-specific cut-points to identify patients
with low hand grip strength. Third, we need further studies to demonstrate that clinical and
rehabilitation interventions based upon grip strength assessment might improve the
functional recovery of older persons with hip fracture.
Citation:
Handgrip Strength Predicts Persistent Walking Recovery After Hip Fracture Surgery.
Savino E, Martini E, Lauretani F, Pioli G, Zagatti AM, Frondini C, Pellicciotti F, Giordano A,
Ferrari A, Nardelli A, Davoli ML, Zurlo A, Lunardelli ML, Volpato S.
Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
Am J Med. 2013 Sep 17. pii: S0002-9343(13)00482-8. doi: 10.1016/j.amjmed.2013.04.017.
[Epub ahead of print]


Flu and Pediatric Deaths
Karen K. Wong, MD MPH
Community Interventions for Infection Control Unit
Division of Global Migration & Quarantine
Centers for Disease Control and Prevention

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Dr. Wong: There were 830 pediatric influenza-associated deaths reported to CDC during the 2004–2005
through 2011–2012 seasons; deaths occurred in children of all ages, and 43% had no high-risk medical
conditions. Of children 6 months of age or older whose vaccination status was known, only 16% had been
fully vaccinated with seasonal influenza vaccine.

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Dr. Wong: Some parents might not think of influenza as being a very serious illness; however, this study
shows that even previously healthy children can have severe influenza complications. Also, most of the
children died within a week of their first symptoms, emphasizing the importance of prevention, especially
with annual influenza vaccination.
Dr. Wong: Any child may be at risk for severe influenza complications, even if they are otherwise healthy,
and children can get very sick very quickly. Getting vaccinated against influenza every year is the best way
to protect your family. Speak to your healthcare provider about whether antiviral medications may be
recommended if your child does show flu symptoms. Finally, everyday precautions like washing hands and
covering coughs will also help protect your household against influenza and other viruses.
Citation:
Influenza-Associated Pediatric Deaths in the United States, 2004–2012
Karen K. Wong, Seema Jain, Lenee Blanton, Rosaline Dhara, Lynnette Brammer, Alicia M. Fry, and Lyn
Finelli
Pediatrics peds.2013-1493; published ahead of print October 28, 2013, doi:10.1542/peds.2013-1493

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C.diff and Obesity
Nahid Bhadelia, MD, MALD Assistant Professor
Associate Hospital Epidemiologist, Section of Infectious Diseases Director, Infection Control
National Emerging Infectious Diseases Laboratory (NEIDL)
Boston Medical Center, Boston, MA

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Summary of Findings:
Dr. Bhadelia:
Clostridium difficile infections (CDI) are a growing problem related to healthcare exposure and antibiotic
use. Over the last decade, these infections have been noted to present in patients from the community
without traditional risk factors. We examined 132 patients over a six month period presenting to our
medical center with CDI to explore the association between obesity and CDI. We hypothesized that in a
group without exposure to health care facilities, the statistical significance of other risk factors such as
obesity and IBD may be increased. Our results showed that patients with community onset CDI without
known health exposure were 4 times more likely to be obese than their counterparts (OR, 4.06 95% CI
1.15–14.36) with known healthcare exposure. Furthermore, this former group was also statistically more
obese than the general population of Massachusetts (34% vs 23%, OR 1.7, 95% CI 1.02–2.99).
We did not note a similar difference between community onset patients without healthcare exposure and
patients who developed CDI in the hospital. This may be due to limitations of sample size or because
obesity maybe a confounder in hospitalized patients and a marker for other conditions requiring
admission.
Obesity has not previously been considered a risk factor for CDI but given the similarities in the
derangement of gut microbiome in obese patients and that of patients with inflammatory bowel disease
and recurrent antibiotic use, there is biological plausibility for this finding. Further prospective and
translational research is required to elucidate the pathogenesis behind this observation. These findings
may contribute to improved clinical surveillance of those at highest risk of disease.
Citation:
Possible Association between Obesity and Clostridium difficile Infection


Diabetes and Heart Attack Mortality in Women
Marcin Sadowski
Świętokrzyskie Cardiology Center, Kielce, Poland

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Dr. Sadowski: In multivariable analysis, diabetes was an independent risk factor of in-hospital
and 1-year mortality in women treated for STEMI.
In women with STEMI and diabetes one-year mortality was significantly lower in those
treated with primary percutaneous coronary intervention than in those on optimal medical
therapy.
Early and long-term prognoses after STEMI were the worst in diabetic women, compared
with non-diabetic women and diabetic men.
Dr. Sadowski: Although primary angioplasty improves long-term prognosis in diabetic
women, it is less frequently implemented as compared to diabetic men and non-diabetic
women.


Diabetes and Heart Attack Mortality in Women
Marcin Sadowski
Świętokrzyskie Cardiology Center, Kielce, Poland

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Dr. Sadowski: Poor short- and long-term prognosis in diabetic women with STEMI is related to the
high-risk clinical profile, the longest symptom onset-to-door time, and high in-hospital complication
rate. This should encourage both primary care physicians and all specialists to manage the patients
strictly according to guidelines and not to neglect referring for immediate revascularization.
Regardless of the good system of STEMI management some educational programs targeted on
patients with diabetes are crucial to improve results of primary angioplasty as the rule “time is
muscle” is still valid.
study?
Dr. Sadowski: Ongoing similar registries in all countries are mandatory to monitor the guidelines
implementation and the results of STEMI management in diabetic patients. This may help to
optimize local STEMI networks.
Citation:
ST-Segment Elevation Myocardial Infarction in Women With Type 2 Diabetes.
Radomska E, Sadowski M, Kurzawski J, Gierlotka M, Polonski L.
Corresponding author: Marcin Sadowski, emsad@o2.pl.
Diabetes Care. 2013 Nov;36(11):3469-75. doi: 10.2337/dc13-0394. Epub 2013 Oct 2.


Memory Performance: Negatively Impacted by Higher Glucose, even in Non-Diabetics
Lucia Kerti MA
From the Departments of Neurology
Charité–University Medicine, Berlin

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Answer: The results of our study on 141 healthy older people suggest that chronically higher
blood glucose levels may have a negative influence on memory performance even in the
absence of type 2 diabetes or even pre-diabetes. Moreover, our findings indicate that
elevated blood glucose levels impair the functioning of brain areas like the hippocampus, a
structure particularly relevant for memory. An important novel aspect in our study was the
additional analysis of diffusion tensor imaging-based mean diffusivity within the
hippocampal, which allowed us to obtain information on microstructure. We here provided
first-time data of an association between higher blood glucose levels and lower hippocampal
microstructure. Decreased hippocampal microstructure as measured by mean diffusivity may
reflect a disruption of neuronal membranes and increased extracellular water content,
leading to decreased signaling within and between hippocampal cells. Thus, information
transfer between cells, indispensable for memory encoding, storage and retrieval, would be
compromised. In sum, our data suggest that chronically higher blood glucose levels even
within the “normal range” may decrease memory functions, possibly in part mediated by
microstructural changes within the hippocampus.


Lucia Kerti MA

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Answer: Our findings were in line with previous studies that were able to demonstrate
associations between non diabetic glucose levels and memory performance and hippocampal
volume. Yet, we here provided first-time results showing not only an association between
higher glucose levels and poorer memory performance, but also a partial mediation of these
effects by hippocampal volume and microstructure.
Answer: As a general recommendation, several lifestyle choices tend to lower blood glucose
levels in young and old individuals. These include avoidance of obesity (particularly in midlife), consuming a diet rich in fibers, vegetables, fruit, fish, and whole-grain products
(sometimes referred to as “Mediterranean foods”), and undertaking physical activity on a
regular basis. Moreover, in individuals at risk – e. g., those presenting with obesity -, and in
everyone from age 55 onwards, regular health checks at the primary care physician should
include fasting glucose and HbA1c levels for early detection and treatment of elevated
glucose levels.


Lucia Kerti MA

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of this study?
Answer: Future interventional trials should elucidate whether specific lifestyle changes aimed
at long-term improvement of glucose control actually prevent cognitive decline in aging. One
strategy to be assessed would be lower dietary caloric intake, or dietary supplementation
that “mimic” the effects of caloric restriction. Another important strategy would be to regular
physical activity. Smaller interventional trials are currently running at our site and others
around the world, but larger international collaborative initiatives will be needed as well.
Citation:
Higher glucose levels associated with lower memory and reduced hippocampal
microstructure
Lucia Kerti, A. Veronica Witte, Angela Winkler, Ulrike Grittner, Dan Rujescu, and Agnes Flöel
Article | Neurology 10.1212/01.wnl.0000435561.00234.ee; published ahead of print October
23, 2013


Drug Hypersensitivity to Dapsone HLA Association
Dr. Jian-Jun Liu
Shangdong Provincial Institute of Dermatology and Venereology

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Answer:
· HLA-B*13:01 is associated with the development of dapsone hypersensitivity syndrome.
· Carrying one copy of HLA-B*13:01 increases one’s risk by 34 times of getting DHS, while
carrying two copies increases risk by 100 times as compared to not carrying this allele.
· HLA-B*13:01 has a sensitivity and specificity of above 85% in predicting the risk of DHS,
theoretically reducing the risk of DHS by 7 fold when implemented in clinical screening.

Answer:
· Many drug-adverse hypersensitivity reactions are immunologically mediated, whose risks
have been reported to be associated with HLA molecules. Hence, the association between
HLA-B*13:01 and dapsone hypersensitivity syndrome is not completely unexpected.
· However, we found that certain patients with DHS (about 14%) do not carry the HLAB*13:01, which is unexpected and suggests that other genetic variants might also play an
important role in DHS development. Further study will be needed to identify these
additional genetic risk variants for DHS.

Drug Hypersensitivity to Dapsone HLA Association
Dr. Jian-Jun Liu
Shangdong Provincial Institute of Dermatology and Venereology

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Answer:

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· Our findings have provided evidence that the risk for the adverse-effect of dapsone is largely influenced by HLA-B*13:01
and can be prevented in the future by testing the carrier status of HLA-B*13:01.
· By implementing clinical test for HLA-B*13:01, the effectiveness of dapsone in treating infection and inflammation can
be used to its maximum potential and at the same time with better assurance of patient’s safety.
Answer:

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· Development and clinical validation of a diagnostic kit for HLA-B*13:01 can be the next step of reducing the burden of
dapsone hypersensitivity reactions.
· Further studies will be needed for identifying additional genetic risk variants for dapsone hypersensitivity syndrome.
Citation:
HLA-B*13:01 and the Dapsone Hypersensitivity Syndrome
F.-R. Zhang, H. Liu, A. Irwanto, X.-A. Fu, Y. Li, G.-Q. Yu, Y.-X. Yu, M.-F. Chen, H.-Q. Low, J.-H. Li, F.-F. Bao, J.-N. Foo, J.-X. Bei, X.M. Jia, J. Liu, H. Liany, N. Wang, G.-Y. Niu, Z.-Z. Wang, B.-Q. Shi, H.-Q. Tian, H.-X. Liu, S.-S. Ma, Y. Zhou, J.-B. You, Q. Yang, C.
Wang, T.-S. Chu, D.-C. Liu, X.-L. Yu, Y.-H. Sun, Y. Ning, Z.-H. Wei, S.-L. Chen, X.-C. Chen, Z.-X. Zhang, Y.-X. Liu, S.L. Pulit, W.-B.
Wu, Z.-Y. Zheng, R.-D. Yang, H. Long, Z.-S. Liu, J.-Q. Wang, M. Li, L.-H. Zhang, H. Wang, L.-M. Wang, P. Xiao, J.-L. Li, Z.-M.
Huang, J.-X. Huang, Z. Li, J. Liu, L. Xiong, J. Yang, X.-D. Wang, D.-B. Yu, X.-M. Lu, G.-Z. Zhou, L.-B. Yan, J.-P. Shen, G.-C. Zhang,
Y.-X. Zeng, P.I.W. de Bakker, S.-M. Chen, and J.-J. Liu
N Engl J Med 2013; 369:1620-1628
October 24, 2013DOI: 10.1056/NEJMoa1213096


Alzheimer disease: Genetic Risk Mitigated by Good Sleep
Andrew S. Lim MD MMSc FRCPC DABPN
Assistant Professor and Clinician Scientist
Division of Neurology, Department of Medicine
Sunnybrook Health Sciences Centre University of Toronto

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Dr. Lim: Alzheimer disease (AD) is the result of a confluence of genetic, behavioral, and
environmental risk factors. The Apolipoprotein E (APOE) e4 allele is the most common and well
established genetic risk factor for Alzheimer Disease. 10-20% of the US population carries the high
risk APOE e4 allele, which confers up to a 30% lifetime risk of AD. Meanwhile, previous work had
suggested that poor sleep may be a risk factor for AD and that APOE genotype and poor sleep may
amplify each other’s negative cognitive effects.
We asked the question whether good sleep consolidation (i.e. sound sleep without repeated
awakenings) may reduce the effect of APOE on the risk of incident AD and the burden of AD
pathology. We studied 698 individuals without dementia participating in the Rush Memory and
Aging Project – a longitudinal cohort study of aging and risk factors for AD. We measured sleep
consolidation using wrist-watch like devices called actigraphs, and followed participants for up to 6
years, examining them annually for the development of AD. Autopsies were perfumed on 201
participants who died during the follow-up period and we quantified the burden of AD pathology.
During the follow-up period, 98 participants developed AD. As expected, carrying the APOE e4
allele was associated with a higher risk of AD, faster cognitive decline, and a higher burden of AD
pathology (amyloid plaques and neurofibrillary tangles) at death. However, better sleep at baseline
significantly reduced the negative impact of APOE e4 on the risk of AD, rate of cognitive decline,
and burden of neurofibrillary tangle pathology.


Alzheimer disease: Genetic Risk Mitigated by Good Sleep
Andrew S. Lim MD MMSc FRCPC DABPN
Assistant Professor and Clinician Scientist
Division of Neurology, Department of Medicine
Sunnybrook Health Sciences Centre University of Toronto

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Dr. Lim: These results highlight a heretofore unappreciated link between sleep, APOE, neurofibrillary
tangle biology, and dementia.
Dr. Lim: First, these results suggest that even among APOE e4 carriers, there is a subset of individuals with
excellent sleep consolidation who may be at a reduced risk of AD, and on the other hand, there is a subset
of individuals with very poor sleep who may be at a particularly high risk of AD. Second, these results raise
the possibility that interventions to enhance sleep consolidation (whether by diagnosing and treating
sleep disorders, using pharmacological interventions, or environmental interventions such as noise
reduction) may potentially be a useful way to decrease AD risk in APOE e4 carriers.
Dr. Lim: Future interventional studies will help to further define the appropriate role for genotyping, sleep
assessment, and sleep interventions in the clinical management of individuals at risk for AD.
Citation:
Modification of the Relationship of the Apolipoprotein E ε4 Allele to the Risk of Alzheimer Disease and
Neurofibrillary Tangle Density by Sleep
Lim AS, Yu L, Kowgier M, Schneider JA, Buchman AS, Bennett DA.
JAMA Neurol. 2013 Oct 21. doi: 10.1001/jamaneurol.2013.4215. [Epub ahead of print]
PMID: 24145819 [PubMed - as supplied by publisher]


Pediatric Anemia and Vitamin D Levels
Meredith Atkinson, MD, MHS
Assistant Professor of Pediatrics
Division of Pediatric Nephrology
Johns Hopkins University School of Medicine Baltimore, MD 21287

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Dr. Atkinson: First, among a healthy cross-section of U.S. children, vitamin D deficiency
defined as levels below 30 ng/mL (the currently accepted threshold for adequate vs.
inadequate vitamin D) were associated with nearly twice the risk for anemia compared to
those with sufficient vitamin D levels. Secondly, when we looked specifically at Caucasian
and African-American children, we found that children with the lowest vitamin D levels were
at increased risk for anemia in both groups, but that the specific vitamin D level below which
the anemia risk started to increase was much lower in the African-American children (12
ng/mL) than in the Caucasian children (20 mg/mL).

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Dr. Atkinson: Although not unexpected, this is the first time that vitamin D deficiency has
been associated with increased risk for anemia in otherwise healthy
children. Epidemiologically, we know that there is an increased prevalence of vitamin D
deficiency in African-American compared to Caucasian children. What was somewhat
surprising, however, was that the vitamin D levels where this risk is substantially increased
was so different by race.

Pediatric Anemia and Vitamin D Levels
Meredith Atkinson, MD, MHS
Assistant Professor of Pediatrics
Division of Pediatric Nephrology
Johns Hopkins University School of Medicine Baltimore, MD 21287

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Dr. Atkinson: Vitamin D deficiency may be associated with a variety of health effects beyond bone
health, and if these findings are confirmed, supplementation with vitamin D may be an easy way to
modify anemia risk. Our current clinical approach to the management of vitamin D deficiency takes
only the blood level into account. However, these results bring up the concern that what may be a
pathologically low level in one person may be adequate in another.
study?
Dr. Atkinson: Similar analyses should be conducted in other populations to confirm this finding, and
prospective studies would be needed to demonstrate that vitamin D supplementation is actually
beneficial in decreasing anemia risk. Additionally, further study will be required to examine
whether specific health outcomes associated with vitamin D deficiency vary between people by
race or ethnicity.
Citation:
Vitamin D, Race, and Risk for Anemia in Children
Meredith A. Atkinson, Michal L. Melamed, Juhi Kumar, Cindy N. Roy, Edgar R. Miller, Susan L. Furth,
Jeffrey J. Fadrowski
The Journal of Pediatrics – 10 October 2013 (10.1016/j.jpeds.2013.08.060)


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