MedicalResearch.com: Medical Research Interviews September12 2014

MedicalResearch.com
Exclusive Interviews with Medical Research and
Health Care Researchers from Major and Specialty Medical
Research Journals and Meetings
Editor: Marie Benz, MD
info@medicalresearch.com
Sept. 12 2014
For Informational Purposes Only: Not for Specific Medical Advice.

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Ebola: Each Primary Infection Resulting In Spread To More Than One Additional Case
MedicalResearch.com: Interview with:
Dr. Gerardo Chowell-Puente Ph.D.
Associate Professor School of Human Evolution and Social Change
College of Liberal Arts and Sciences Arizona State University
• Medical Research: What are the main findings of the study?
• Dr. Chowell-Puente:
• 1.We estimated the effective reproduction number of Ebola virus disease, i.e. average number of
secondary cases produced by a single primary case at calendar time t (Rt), for the ongoing epidemic in
West Africa from March to August 2014. Estimates of Rt for the Guinea, Sierra Leone and Liberia, countries
that are experiencing sustained community transmission were consistently above 1.0 since June 2014.
• 2.Country-specific estimates of the reproduction number for Liberia and Sierra Leone lied between 1.0 and
2.0, reflecting continuous growth of cases in these countries
• 3. Effective reproduction number below 2 indicate that control could be attained by preventing over half
of the secondary transmissions per primary case (e.g. by means of effective case isolation and contact
tracing).
• Medical Research: What recommendations do you have for future research as a result of this study?
•
• Dr. Chowell-Puente: Our statistical analysis of the reproduction number of Ebola virus disease in West
Africa has demonstrated that the continuous growth of cases from June to August 2014 signaled a major
epidemic, which is in line with estimates of the Rt above 1.0. Our estimated reproduction numbers,
broadly ranging from 1 to 2, are consistent with published estimates from prior outbreaks in Central Africa
(e.g. the reproduction number for Ebola virus disease has been estimated at 1.83 for an outbreak in Congo
in 1995 and 1.34 in Uganda in 2000 prior to the implementation of control intervention). Our estimates of
Rt below 2 indicate that the outbreak could be brought under control if more than half of secondary
transmissions per primary case are prevented. Uncontrolled cross-border transmission could fuel a major
epidemic to take off in new geographical areas (e.g. as seen in Liberia). Close monitoring of this evolving
epidemic should continue in order to assess the status of the outbreak in real time and guide control
interventions in the region.
Read the rest of the interview on MedicalResearch.com
Content Not Intended as Specific Medical Advice

Increased Ectopic Heart Beats Linked to Less Effective Pacing with CRT Therapy
MedicalResearch.comInterview with:Martin Huth Ruwald, MD, PhD
Post doctoral research fellow Heart Research Follow-up Program
University of Rochester Medical Center Rochester, NY, US
• Dr. Ruwald: A high percentage of biventricular pacing is required for optimal outcome in
patients treated with cardiac resynchronization therapy (CRT), but the influence of ectopic
beats on the success of biventricular pacing has not been well established.
• We found that patients with increasing amount of ectopic beats (the ectopic burden) (≥0.1%)
were more likely to achieve low biventricular pacing <97% and had higher risk of heart failure
or death and ventricular arrhythmias. Similarly the study identified patients with a very low
amount of ectopic beats, less than 1 in 1000, who are very likely to obtain high biventricular
pacing and who have very low risk of adverse outcomes.
Medical Research: Were any of the findings unexpected?
• Dr. Ruwald: It was unexpected that such a relatively low burden of ectopic beats
independently influenced and reduced the biventricular pacing percentage and resulted in
adverse outcomes to such a degree.

Increased Ectopic Heart Beats Linked to Less Effective Pacing with CRT Therapy
MedicalResearch.comInterview with:Martin Huth Ruwald, MD, PhD
Post doctoral research fellow Heart Research Follow-up Program
University of Rochester Medical Center Rochester, NY, US
• Dr. Ruwald: A 24-hour Holter recording can help identify both patients who are less likely to
obtain high biventricular pacing percentage and those who will achieve improved clinical
outcome based on evaluation of pre-implantation ectopic beats. This information can help
guide clinicians selecting patients who potentially will not respond to cardiac
resynchronization therapy or alternatively identify patients who require additional therapies
such as ablations or antiarrhythmic therapy in order to benefit from this device
• Medical Research: What recommendations do you have for future research as a result of
this study?
Dr. Ruwald: Studies establishing a threshold of ectopic burden where CRT treatment is no
longer beneficial because of ineffective biventricular pacing is needed. Further we need a
trial or documentation of whether or not aggressive treatment with ablation or anti-arrhythmic
drugs can actually improve outcome for these patients with CRT indication and a
burden of ectopic beats above 0.1% of all beats.
• Citation:
• Ruwald MH, Mittal S, Ruwald A, et al. Association Between Frequency of Atrial and
Ventricular Ectopic Beats and Biventricular Pacing Percentage and Outcomes in Patients With
Cardiac Resynchronization Therapy. J Am Coll Cardiol. 2014;64(10):971-981.
doi:10.1016/j.jacc.2014.06.1177.
•

How Does Prednisone Affect TB Infections in Patients With and Without HIV?
MedicalResearch.comInterview with:
Bongani M. Mayosi, M.B., Ch.B., D.Phil.
Department of Medicine, Old Groote Schuur Hospital
Cape Town, South Africa
• Medical Research: What are the main findings of this study?
• Dr. Mayosi: In those with definite or probable tuberculous pericardial effusion:
• (1) Prednisolone for 6 weeks and Mycibacterium indicus pranii for three months had no
significant effect on the combined outcome of death from all causes, cardiac tamponade
requiring pericardiocentesis or constrictive pericarditis.
(2) Both therapies were associated with an increased risk of HIV-associated malignancy.
(3) However, use of prednisolone reduced the incidence of constrictive pericarditis and
hospitalization.
(4) The beneficial effects of prednisolone on constriction and hospitalization were similar
in HIV-positive and HIV-negative patients
•
• Dr. Mayosi: The two findings that were unexpected were
(1) The neutral effect of steroids on death, and
(2) The increase in incidence of cancer in HIV infected patients.

How Does Prednisone Affect TB Infections in Patients With and Without HIV?
Bongani M. Mayosi, M.B., Ch.B., D.Phil.
Department of Medicine, Old Groote Schuur Hospital
Cape Town, South Africa
• Medical Research: What should clinicians and patients take away from your report?
• Dr. Mayosi: A selective approach to the use of adjunctive steroids in tuberculous pericarditis is required,
as follows:
(1) Adjunctive steroids should be avoided in patients with HIV-associated tuberculous pericardial effusion
because of the risk of cancer;
(2) Adjunctive steroids may be used in HIV negative patients for the beneficial effect on constrictive
pericarditis and hospitalization.
• There is no role for M. indicus pranii in patients with tuberculous pericardial effusion.
• Dr. Mayosi: The impact of adjunctive steroids in HIV positive patients on anti-retroviral therapy is
unknown.
Citation:
• Prednisolone and Mycobacterium indicus pranii in Tuberculous Pericarditis
• Bongani M. Mayosi, M.B., Ch.B., D.Phil., Mpiko Ntsekhe, M.D., Ph.D., Jackie Bosch, Ph.D., Shaheen Pandie,
M.Med. (Med.), Hyejung Jung, M.Sc., Freedom Gumedze, Ph.D., Janice Pogue, Ph.D., Lehana Thabane,
Ph.D., Marek Smieja, M.D., Ph.D., Veronica Francis, R.N., Laura Joldersma, B.Sc., Kandithalal M. Thomas,
M.B., B.S., Baby Thomas, M.B., B.S., Abolade A. Awotedu, M.B., B.S., Nombulelo P. Magula, M.B., Ch.B.,
Datshana P. Naidoo, M.B., Ch.B., Ph.D., Albertino Damasceno, M.D., Ph.D., Alfred Chitsa Banda, M.B.,
Ch.B., Basil Brown, M.B., Ch.B., Pravin Manga, M.B., B.Ch., Bruce Kirenga, M.B., Ch.B., Charles Mondo,
M.B., Ch.B., Ph.D., Phindile Mntla, M.B., Ch.B., Jacob M. Tsitsi, M.B., B.Ch., Ferande Peters, M.B., B.Ch.,
Mohammed R. Essop, M.B., B.Ch., James B.W. Russell, M.B., Ch.B., James Hakim, M.D., Jonathan Matenga,
M.B., Ch.B., Ayub F. Barasa, M.B., Ch.B., Mahmoud U. Sani, M.B., B.S., Taiwo Olunuga, M.B., B.Ch.,
Okechukwu Ogah, M.B., Ch.B., Victor Ansa, M.B., Ch.B., Akinyemi Aje, M.B., Ch.B., Solomon Danbauchi,
M.B., Ch.B., Dike Ojji, M.B., B.S., Ph.D., and Salim Yusuf, M.B., B.S., D.Phil. for the IMPI Trial Investigators
• September 2, 2014DOI: 10.1056/NEJMoa140738

Faster Resting Heart Rate Linked To Metabolic Syndrome
DrWeiguo Zhang, MD PhD
Cardiovascular and Neurological Institute 6771 San Fernando,
Irving, TX 75039, USA
• Dr. Zhang: The main finding is a strong and positive association between Resting heart rate
and metabolic syndrome (MetS) in a large population, that is the faster the resting heart rate,
the higher prevalence of metabolic syndrome.
• More importantly, higher heart rate also predict the incidence of metabolic syndrome in
future in people who don’t have metabolic syndrome now, that is the faster the resting heart
rate the higher likelihood of developing metabolic syndrome in future. The study suggests
that metabolic syndrome is likely one of the mechanisms by which higher resting heart rate
causes higher cardiovascular and all cause mortality.
Medical Research: What should clinicians and patients take away from your report?
Dr. Zhang: Clinicians and patients should pay more attention to resting heart rate. Physicians
should routinely check and record resting heart rate of clinic visitors. Those healthy and
asymptomatic subjects with higher resting heart rate should be under medical surveillance.

Faster Resting Heart Rate Linked To Metabolic Syndrome
DrWeiguo Zhang, MD PhD
Cardiovascular and Neurological Institute 6771 San Fernando,
Irving, TX 75039, USA
this study?
• Dr. Zhang: From a cardiovascular and metabolic perspective, the significance of Resting heart
rate in making therapeutic decisions and evaluating treatment outcomes cannot be
overlooked. From a public health perspective, Resting heart rate measurement constitutes a
simple and inexpensive approach in monitoring cardiovascular and metabolic health (or risks)
in the population.
• Citation:
• Metabolic syndrome is associated with and predicted by resting heart rate: a cross-sectional
and longitudinal study
• Xiongjing Jiang, Xiaoxue Liu, Shouling Wu, Gus Q Zhang, Meng Peng, Yuntao Wu, Xiaoming
Zheng, Chunyu Ruan, Weiguo Zhang
• Heart heartjnl-2014-305685Published Online First: 1 September 2014 doi:10.1136/heartjnl-
2014-305685

High Estrogen, Low Testosterone Linked To Sudden Cardiac Arrest
Sumeet S. Chugh MD
Pauline and Harold Price Endowed Professor Associate Director, the Heart Institute
Section Chief, Clinical Cardiac Electrophysiology Cedars-Sinai Medical Center, Los Angeles, CA
• Dr. Chugh: Our study, conducted in the community, showed that there are unique alterations in sex
hormone levels identified among patients who have sudden cardiac arrest. Male victims have lower
testosterone and both males and females have higher estrogren levels.
•
• Dr. Chugh: As you know there are multiple studies that link hormonal imbalances to increased risk of
cardiovascular conditions and mortality; and this is a subject that has been hotly debated as well.
However, a link between sex hormones and sudden cardiac arrest had not been evaluated previously.
There is one aspect of our findings that we were quite surprised by: higher levels of estrogen in men
correlating with higher risk of sudden cardiac arrest. While this hormone is present in men, finding of high
levels are quite unexpected. However, there are potential mechanisms that could explain the
phenomenon and need to be investigated further.
• Dr. Chugh: Sudden cardiac arrest remains a major health problem and 95% of patients who suffer this
condition will die within 10 minutes. Especially since sudden cardiac arrest accounts for 1000 US lives lost
on a daily basis, we have no choice but to discover novel methods of prediction and prevention. While
further research is warranted, these findings indicate the sex hormone levels can potentially be used to
predict sudden cardiac arrest in the future.
• Citation:
• Sex Hormone Levels in Patients with Sudden Cardiac Arrest
Kumar Narayanan, Rasmus Havmoeller, Kyndaron Reinier, Katherine Jerger, Carmen Teodorescu, Audrey
Uy-Evanado, Jo Navarro, Adriana Huertas-Vazquez, Karen Gunson, Jonathan Jui, Sumeet S. Chugh.
Heart Rhythm, 2014; DOI: 10.1016/j.hrthm.2014.08.031

BPH Symptoms May Be Reduced By Exercise
Kate Wolin, ScD, FACSM Associate Professor
Departments of Surgery & Public Health Sciences
Loyola University Chicago, Stritch School of Medicine
• Answer: Men who are physically active are less likely to experience nocturia.
• Medical Research: Were any of the findings unexpected?
• Answer: Few other LUTS were associated with physical activity, in contrast with previous
reports. However, most of these reports relied on prevalent data, suggesting future studies
should also focus on incident BPH-related outcomes.
• Answer: Promoting physical activity may be an effective nocturia management strategy for
men.
this study?
• Answer: Research into the dose of activity necessary to reduce nocturia risk and into the
dose necessary to reduce nocturia symptoms among men with nocturia is certainly
warranted.
• Citation:
• Physical Activity and Benign Prostatic Hyperplasia-Related Outcomes and Nocturia
Wolin KY1, Grubb RL 3rd, Pakpahan R, Ragard L, Mabie J, Andriole GL, Sutcliffe S.
Med Sci Sports Exerc. 2014 Jul 9. [Epub ahead of print]

Poor Sleep Linked To Missed Work Days
Tea Lallukka, PhD
Finnish Institute of Occupational Health &
University of Helsinki, Hjelt Institute, Department of Public Health University of Helsinki, Finland
• Dr. Lallukka: Our study used nationally representative survey data linked with
register data on medically certified sickness absence among working
-aged Finnish women and men. We showed consistent associations between
insomnia symptoms, sleep duration, and being tired and sickness
absence. The follow-up lasted around 7 years.
Sickness absence days were derived from comprehensive registers from
the Social Insurance Institution of Finland. The associations were
broadly similar among women and men. Furthermore, they remained even
after considering key correlates of sleep and sickness absence
including socioeconomic position, working conditions, health
behaviors, obesity, and mental and physical health. Health data were
derived from physical examination conducted by field physicians. These
data are more objective, and help provide more robust evidence. We
further covered all key sleep disturbances and sleep duration for more
comprehensive understanding about the contribution of sleep to
sickness absence. Finally, a novel method developed by the authors
(Härkänen & Kaikkonen) allowed us to estimate the difference in
sickness absence days per working year among those reporting and not
reporting different sleep disturbances. Using the difference in days
absent from work, we were further able to estimate the hypothetical
direct costs of sickness absence highlighting notable societal
significance of sleep. Thus, a large part of all costs of sickness
absence are attributable to poor sleep. For example, those sleeping 5
hours or less or 10 hours or more, were absent from work ca 5-9 days
more, as compared to those with optimal sleep length. The optimal
sleep length with the lowest risk of sickness absence was 7 hours 46
minutes for men and 7 hours 38 minutes for women.

Tea Lallukka, PhD
• Dr. Lallukka: The lack of an association between daytime sleepiness, apnea, and
seasonal variation in sleep duration and sickness absence could be
seen as unexpected.
• Dr. Lallukka: Insomnia symptoms should be detected early. This could help prevent
them from becoming chronic, and could help prevent decline in work
ability and subsequent sickness absence. Sufficient quantity and
quality of sleep likely promotes health, well-being, and functioning
among women and men.

Tea Lallukka, PhD
• Medical Research: What recommendations do you have for future research as a result
of this study?
• Dr. Lallukka: As insomnia symptoms are highly prevalent, and increase particularly
after middle-age, it is vital to be able to tackle them early in
efforts to promote employee well-being, wealth and work ability. It
would be important to conduct further research on whether early
detection and prevention of insomnia would lead to less sickness
absence. Mechanisms on how sleep affects work ability and health also
need further elaboration, as the effects remain even after considering
health and working conditions, for example.
• Work disability is also a major public health and societal challenge,
bearing huge costs for the employers and society, alongside individual
suffering related to ill- health and economical consequences.
• Citation:
• Tea Lallukka, Risto Kaikkonen, Tommi Härkänen, Erkki Kronholm, Timo Partonen, Ossi
Rahkonen, Seppo Koskinen. Sleep and Sickness Absence: A Nationally Representative
Register-Based Follow-Up Study
SLEEP, 2014; DOI: 10.5665/sleep.3986

New Ionic Liquids May Disrupt Pathogenic Biofilms, Enhance Antibiotic Delivery
MedicalResearch.com Interview with: David T. Fox
Bioenergy and Biome Science Group, Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87545 and
Prof. Samir Mitragotri
Center for Bioengineering and Department of Chemical Engineering
University of California, Santa Barbara, CA 93106
• Answer: Our research team identified a molten salt, choline-geranate, that possessed multiple
beneficial biological traits. Specifically, when mixed in a 1:2 ratio (choline:geranate) this solvent is
able to effectively disrupt and neutralize 72-hour biofilms formed by both Pseudomonas aeruginosa
and Salmonella enterica. Further, our studies demonstrated the same solvent exhibited minimal
cytotoxicity effects to normal human bronchial epithelial (NHBE) cells and was able to deliver an
antibiotic, cefadroxil, through the stratum corneum into the epidermis and dermis. Most
importantly, the research culminated in demonstrating the molten salt was able to neutralize ~95%
of the bacteria found within a 24-hour P. aeruginosa biofilm when grown on a skin wound model
(MatTek) and ~98% of the bacteria when formulated with the antibiotic, ceftazidime. When the
biofilm was treated with only antibiotic in a saline solution, less than 20% of the bacteria were
neutralized.
• Medical Research: Were any of the findings surprising?
• Answer: The most surprising finding was the observation the neat ionic liquids were quite effective
antimicrobial agents in the absence of the antibiotic. We built a hypothesis that the ionic liquids
would serve as a carrier of the antibiotic either to the bacteria or for facile penetration through the
skin for subsequent antibiotic delivery. This was a serendipitous finding that ultimately opened the
door for use of molten salts as both a standalone therapy and as a formulation with broad-spectrum
antibiotics. Further, some of the ionic liquids were more effective than a 10% bleach
solution on the microbes tested when applied for the same period of time yet did not exhibit the
prototypical cytotoxicity effects that bleach had on the cell lines tested.

New Ionic Liquids May Disrupt Pathogenic Biofilms, Enhance Antibiotic Delivery
MedicalResearch.com Interview with: David T. Fox
Bioenergy and Biome Science Group, Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87545 and
Prof. Samir Mitragotri
Center for Bioengineering and Department of Chemical Engineering
University of California, Santa Barbara, CA 93106
• Medical Research: What should patients and clinicians take away from this report?
• Answer: Clinicians and patients should embrace the potential for reexamining previously discarded
antibiotics due to either poor bioavailability or where antibiotic resistance was observed. In
addition, there is potential a new arsenal of therapeutic agents was added to an ever shrinking
repertoire of current effective treatments on resilient bacteria both on the surface of skin and the
underlying tissue layers.
• Medical Research: What future research do you suggest as a result of this study?
• Answer: Two major routes of future research should be undertaken in order to further develop use
of this class of materials in a clinical setting.
• First, a more exhaustive set of pathogens (both Gram positive and Gram negative) need to be
examined in order to assess the broad-spectrum ability of the ionic liquids for pathogen
neutralization in conjunction with the molecular mechanism for biofilm disruption and/or skin
penetration.
• The second, a more immediate, direction is to translate this research to in vivo studies to assess the
effect of ionic liquids and their antibiotic formulations on the treatment of open wounds.
• Citation:
• Ionic liquids as a class of materials for transdermal delivery and pathogen neutralization
• Michael Zakrewsky, Katherine S. Lovejoy, Theresa L. Kern, Tarryn E. Miller, Vivian Le, Amber Nagy,
Andrew M. Goumas, Rashi S. Iyer, Rico E. Del Sesto, Andrew T. Koppisch, David T. Fox, and Samir
Mitragotri
• PNAS 2014 ; published ahead of print August 25, 2014, doi:10.1073/pnas.1403995111

How Well Do Fetal Ultrasound Measurement Predict Infant and Childhood Outcomes?
Dr. Steve Turner
Child Health, Royal Aberdeen Children’s Hospital Aberdeen,UK
• Dr. Turner: There is evidence that being small for a given gestational age is associated with a
broad range of what could be loosely considered “disadvantageous” outcomes in early
childhood, eg increased risk for wheeze, increased blood fat levels, increased blood pressure
and low bone mineral density. Many of these outcomes are subclinical – ie unless they were
measured no-one would be any the wiser – and what remains to be determined is whether
as these individuals grow up these subclinical measurements become important. Follow up
may take many years, decades for outcomes such as coronary artery disease and type II
diabetes.
• Dr. Turner: Yes, we had expected to find that fetuses who became smaller were at increased
risk for “disadvantageous” outcomes but fetuses who grew fast were spared these. What we
found was that both faltering and accelerated growth were associated with
“disadvantageous” outcomes. This is consistent with the concepts of developmental
plasticity and predictive adaptive responses where the fetus anticipates the environment in
which it will be born and, rather like the weather forecast, it can be wrong. If the fetus is too
big this might be bad in one environment but not another, similarly a fetus which is too small
may not be able to make the most of a “good” environment. Ultimately, as identical twin
studies have shown, a given individual is initially “plastic” and might or might not go on to
develop a number of illnesses.

How Well Do Fetal Ultrasound Measurement Predict Infant and Childhood Outcomes?
Dr. Steve Turner
Child Health, Royal Aberdeen Children’s Hospital Aberdeen,UK
• Dr. Turner: At this stage, nothing. Our conclusions are based on observations and it is possible that
the same factor influencing fetal growth also leads to risk for disease and therefore manipulating
fetal size may well not be helpful (and may paradoxically make risk for disease higher). This work
gives some insight into the mechanisms leading/pre programming non-communicable diseases
such as asthma, type II diabetes and hypertension. Mothers who are pregnant should continue to
follow public health advice and eat and drink healthily, avoid cigarette smoke and exercise as much
as they can.
• Medical Research: What recommendations do you have for future research as a result of this
study?
• Dr. Turner: The results are based on observations made in young children and we need to replicate
these findings in older children and even adults. It seems highly likely that the antenatal and post
natal environment are important in predicting future health and wellbeing (the first 1000 days
following conception is probably very important) so it is important to link up growth in both the
antenatal and postnatal periods to health and wellbeing.
• Citation:
• Fetal ultrasound measurements and associations with postnatal outcomes in infancy and
childhood: a systematic review of an emerging literature
• Farah Alkandari, Awaiss Ellahi, Lorna Aucott, Graham Devereux, Steve Turner
• J Epidemiol Community Health jech-2014-204091Published Online First: 4 September 2014
doi:10.1136/jech-2014-204091

Bowel Cancer Screening May Have Small Unwanted Lifestyle Effect
MedicalResearch.comInterview Invitation
Paula Berstad, PhD, postdoc
Telemark Hospital
Oslo, Norway
• Dr. Berstad: In general population of age 50-55 years, both those invited to bowel cancer
screening in year 2001 by flexible sigmoidoscopy and those not invited improved their
lifestyle from year 2001 to 2012. Lifestyle was measured as adherence to public health
guidelines; non-smoking, daily physical exercise, healthy diet and normal body weight.
However, the 11-year improvement was smaller in those who were screened for bowel
cancer compared to those not screened. Further, among those who attended the screening,
the improvement was smaller in those with findings at screening (positive screening result)
compared to those without findings (negative screening result). Our interpretation of the
findings is that bowel cancer screening may have a small unwanted effect on lifestyle.
Particularly, attention should be given to lifestyle among those testing positive at screening.
• Dr. Berstad: It was surprising that the differences in lifestyle change between the screened
and non-screened, first were observed three years after screening, still were observable eight
years later.

Bowel Cancer Screening May Have Small Unwanted Lifestyle Effect
MedicalResearch.comInterview Invitation
Paula Berstad, PhD, postdoc
Telemark Hospital
Oslo, Norway
• Dr. Berstad: Cancer screening may have a small “health certificate” effect which reduces
individual’s own incentives for healthy lifestyle choices. Although this effect is modest and
without clinical importance, it may have impact on long-term health on the population level.
Combining cancer screening with lifestyle counselling might be considered.
this study?
• Dr. Berstad: Future research should pursue to find an optimal way to do cancer screening,
which motivates the participant for favorable health behaviour.
• Citation:
• Long-term lifestyle changes after colorectal cancer screening: randomised controlled trial
• Paula Berstad, Magnus Løberg, Inger Kristin Larsen, Mette Kalager, Øyvind Holme, Edoardo
Botteri, Michael Bretthauer, Geir Hoff
• Gut gutjnl-2014-307376Published Online First: 2 September 2014 doi:10.1136/gutjnl-2014-
307376

Multiple Sclerosis: Slower Walking Speed Associated With Decreased Quality of Life
Jeffrey Cohen MD
Department of Neurology
Cleveland Clinic
• Dr. Cohen: This study assessed the relationship between walking speed, as measured by the Timed
25-foot Walk test, and patient-reported quality of life, as measured by the Physical Component
Summary score of the 36-Item Short Form Health Survey (SF-36), in a pooled dataset from the
AFFIRM, SENTINEL, and IMPACT multiple sclerosis Phase 3 trials. It showed that slowed walking
speed is associated with decreased quality of life. It also showed that 20-25% slowing of walking
speed is a clinically meaningful change.
• Dr. Cohen:Waling ability is an important aspect of multiple sclerosis and the Timed 25-Foot Walk is
an appropriate way to assess it.
study?
Dr. Cohen:
• 1) Determine whether other walking tests capture walking ability in multiple sclerosis better
than the Timed 25-Foot Walk.
• 2) Assess other neuroperformance measures of e.g. the 9-Hole Peg Test of upper extremity
function using a similar approach.
• Citation:
• Cohen JA, Krishnan AV, Goodman AD, et al. The Clinical Meaning of Walking Speed as Measured by
the Timed 25-Foot Walk in Patients With Multiple Sclerosis. JAMA Neurol. Published online
September 01, 2014. doi:10.1001/jamaneurol.2014.1895.
•

MedicalResearch.com Interview with:
Sylvia Wassertheil-Smoller, PhD
Department of Epidemiology and Population Health
Albert Einstein College of Medicine
Bronx, NY 10461.
• Dr. Wassertheil-Smoller: We found in study of nearly 100,000 postmenopausal women in the
Women’s Health Initiative that a high intake of dietary potassium was associated with a lower
risk of ischemic stroke and death from all causes.
• Dr. Wassertheil-Smoller: The unexpected finding was that this effect was strongest in women
without hypertension (those whose blood pressure was normal and who were not on any
medications for high blood pressure). In these women there was a 27% lower risk of ischemic
stroke and a 21% % lower risk of all stroke types. There was no association with hemorrhagic
stroke.

Sylvia Wassertheil-Smoller, PhD
Department of Epidemiology and Population Health
Albert Einstein College of Medicine
Bronx, NY 10461.
• Dr. Wassertheil-Smoller: Clinicians should recommend a diet that includes potassium-rich foods. The
current recommendations for dietary intake of potassium from the Institute of Medicine and the U.S.
Department of Agriculture are 4700 mg per day. The World Health Organization’s recommendations are
for about 3500 mg per day. The average intake for Americans is considerably below that at about 2640 per
day and in our study the women consumed on average 2611 mg per day so increasing potassium in the
diet is important. There are many foods rich in potassium including the well-known banana, but also
baked potatoes, orange juice, spinach, fruits and green vegetables in general, salmon, yogurt – it is quite
ubiquitous. People should read the labels on processed foods they buy.
• Dr. Wassertheil-Smoller: Since it is unlikely there will a randomized clinical trials of this issue due to
excessive costs and feasibility, we need to get the best information we can from observational,
longitudinal studies. There are quite a few cohorts, nationally and internationally, that have dietary data
and these studies should be analyzed with regard to potassium intake so that we get more information on
different population groups, people of different ethnicities, ages, sex. A collaborative effort should be
undertaken to pool data. Also, it is important to consider sodium intake as we are not clear about the
balance of sodium and potassium that is best. Our next paper will deal with sodium intake.
• Citation:
• Potassium Intake and Risk of Stroke in Women With Hypertension and Nonhypertension in the Women’s
Health Initiative
• Arjun Seth, Yasmin Mossavar-Rahmani, Victor Kamensky, Brian Silver, Kamakshi Lakshminarayan, Ross
Prentice, Linda Van Horn, and Sylvia Wassertheil-Smoller
• Stroke. 2014;STROKEAHA.114.006046published online before print September 4 2014,
doi:10.1161/STROKEAHA.114.006046

Isabelle Bedrosian, M.D., F.A.C.S.
Associate Professor, Department of Surgical Oncology, Division of Surgery
Medical Director, Nellie B. Connelly Breast Center
The University of Texas MD Anderson Cancer Center, Houston, TX
Dr. Bedrosian:
• National BCT (breast conserving therapy) rates have increased during the last two
decades.
• Disparities based on age, geographic facility location and type of cancer treatment
facility have lessened over time.
• Insurance type and travel distance remain persistently associated with underutilization
of breast conserving therapy.
• Annual income of less than $35K may be emerging as a new association with
underutilization of breast conserving therapy.
• Dr. Bedrosian: The extent to which socio-economic factors were associated with breast
conserving therapy utilization and that in the most recent year of analysis, these socio-economic
factors appear to be the greatest source driving the disparity in breast conserving
therapy utilization.

Isabelle Bedrosian, M.D., F.A.C.S.
Associate Professor, Department of Surgical Oncology, Division of Surgery
Medical Director, Nellie B. Connelly Breast Center
The University of Texas MD Anderson Cancer Center, Houston, TX
• Dr. Bedrosian: Clinicians should recognize that they have made significant strides in
democratizing care for breast cancer patients- these gains are reflecting in the reduction in
practice based disparities. However, to address the socio-economic factors that currently
appear to be behind the disparities in the surgical treatment of breast cancer will likely
require policy level interventions.
this study?
• Dr. Bedrosian: To better define identify the factors behind the socio-economic disparities.
These socio-economic factors are likely surrogates for a broad range of considerations such as
child care, transportation challenges, time of work, cultural beliefs, etc. Better clarity on
these fronts is needed in order to implement strategies to overcome these socio-economic
disparities.
• Citation:
• 2014 Breast Cancer Symposium abstract:
• Abstract 63:
Late axillary recurrence after negative SLNB.
•

How Much Caffeine Should Kids and Teens Ingest?MedicalResearch.com Interview with:
Naman Ahluwalia, PhD, DSc, FACN
Nutrition Monitoring Advisor Office of the Director
Division of Health and Nutrition Examination Surveys, NCHS, CDC
Hyattsville, MD 20782
• Dr. Ahluwalia: Health Canada has put forth caffeine intake guidelines for children and
adolescents in absolute amounts (mg) and in mg/kg body weight for teens. The maximal
caffeine intakes of 45, 63, and 85 mg/day are suggested for children ages 4-6, 7-9, and 10-12
years and for teens (13 y and over) Health Canada suggests that caffeine intake be no more
than 2.5 mg/kg body weight/day. Although no such recommendations have been set in the
US, the American Academy of Pediatrics (AAP) underlines that “caffeine and other stimulant
substances contained in energy drinks have no place in the diet of children.”
• This study provides national estimates of dietary caffeine intake in US children 2-19 y of age,
both in absolute amounts (mg) and in relation to body weight (mg/kg), to update estimates
that were published in another study in 2005 based on older data from the Continuing
Survey of Food Intakes by individuals in 1994-96 and 1998.

• The key findings were:
• 1. Majority (71%) of children in the survey reported consuming caffeine on a given day; over
one-half of US children aged 2-5 y and 3 in 4 children ages 6 y and over consumed caffeine on
a given day.
• 2. Certain socio-demographic patterns in caffeine intake were observed. More non-Hispanic
white and Mexican American children reported consuming caffeine than non-Hispanic black
children; in addition, the amount of caffeine consumed by non-Hispanic white and Mexican
American children was higher than that consumed by non-Hispanic black children. Caffeine
intake increased with age. For instance, 2-5 year-old caffeine consumers reported 5 mg of
caffeine intake on a given day, compared to 9 mg for 6-11 y olds and ~ 40 mg for teens (12-19
y). For reference, a 8 fl oz can of soda contains about 24-50 mg of caffeine.
• 3. Another finding was that on a given day one in ten children (6-19 y) had caffeine intakes
that exceeded the Canadian maximal guidelines.
• 4. Caffeine intake (mg or mg/kg) stayed relatively constant among teens over the last decade,
but trends towards decreased intake were noted in younger (2-11 y old) children.

• Dr. Ahluwalia: The common prevailing thought is that caffeine intake particularly in teens may be
high and that it is likely to have increased over the last decade; our results did not support these.
• Dr. Ahluwalia: Although caffeine intake in younger children is small, a large percentage of children
do consume caffeine and this does not fit well with the AAP. About one in ten children 6 y of age
and above reported intakes that exceeded the Canadian maximal guidelines; thus clinicians and
health care-providers should stay vigilant to follow children closely regarding their caffeine
consumption, so as to identify children that may be “heavy consumers” of caffeine and provide
appropriate counselling on potential adverse effects.
study?
• Dr. Ahluwalia: Dietary sources of caffeine intake among children should be examined more closely,
and analysis of newer data from NHANES this year should be undertaken particularly among older
children who were the highest consumers of caffeine. There is a need to continue monitoring
caffeine intake (and sources) of children.
• Citation:
• Caffeine intake in children in the United States and 10-y trends: 2001–2010
Namanjeet Ahluwalia, Kirsten Herrick, Alanna Moshfegh, and Michael Rybak
• Am J Clin Nutr 2014 ajcn.082172; First published online August 27, 2014.
doi:10.3945/ajcn.113.082172

Blood Transfusions: Stored Blood Becomes Less Functional With Time
Gabriel Popescu Associate Professor
Department of Electrical and Computer Engineering & Bioengineering
University of Illinois at Urbana-Champaign
Beckman Institute for Advanced Science Urbana, IL
• Prof. Popescu:We used a new imaging method, which combines microscopy and interferometry, to
measure nanoscale fluctuations in the red blood cell membrane. We found that the fluctuations, known to
be due to thermal or Brownian motion, decrease with blood storage time. These results indicate that the
deformability of the cells degrades with time. It means that blood functionality is lower the longer the
blood is stored.
• Prof. Popescu: One surprising aspect we found was that this stiffening of the cells appears without chance
in morphology or hemoglobin concentration.
• Prof. Popescu: Following blood transfusions, visual inspection by a hematologist involves smearing a
droplet of blood between on a glass slide and studying the cells using optical microscopy. Abnormalities in
cell shapes can be easily identified by this procedure. However, our results show that, even if the cells
exhibit a normal, discocyte shape, they may function improperly due to the limited deformability. We
believe that our test can be added to the menu of assays at the hematologist’s disposal.
• Prof. Popescu:We would like to follow up with studies dedicated to understanding the molecular
mechanism responsible for the cell stiffening during storage. Also, it would be very useful in clinical
practice to come up with a drug that will restore the cell deformability, before it is administered to the
patient.
• Citation:
Optical Assay of Erythrocyte Function in Banked Blood
Basanta Bhaduri,Mikhail Kandel,Carlo Brugnara , Krishna Tangella & Gabriel Popescu
• Scientific Reports 4, Article number: 6211
• doi:10.1038/srep06211 Received 28 April 2014 Accepted 04 August 2014 Published 05 September 2014

Obsessive-Compulsive Disorder Increases Risk Of Schizophrenia
Sandra M. Meier, PhD
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH,
National Centre for Register-Based Research Aarhus University, Aarhus, Denmark
• Dr. Meier: People with an obsessive-compulsive disorder are at a 6 to 7 times higher risk of developing
schizophrenia than people without an obsessive-compulsive disorder. If the parents are diagnosed with an
obsessive-compulsive disorder, their offspring experience a 3 to 4 times higher chance to develop
schizophrenia.
• Dr. Meier: The findings fit with observations in clinical practice linking obsessive-compulsive disorder to
schizophrenia.
• Dr. Meier: Although only a small proportion of patients with obsessive-compulsive disorder will
subsequently develop schizophrenia, clinicians should be more aware of the associations of obsessive-compulsive
disorder with schizophrenia. Treating comorbid obsessive-compulsive disorder may prevent
and improve the symptoms of schizophrenia. Even if this association is not causal—and instead an
epiphenomenon due to genetics or environmental factors—psychiatric patients with comorbid diseases
would most likely still benefit through greater quality of life and improved survival.
• Dr. Meier: Our findings indicate that obsessive-compulsive disorder and schizophrenia might share
etiologic risk factors. Future research is needed to disentangle which genetic and environmental risk
factors are truly common to both disorders.
• Citation:
• Obsessive-Compulsive Disorder as a Risk Factor for Schizophrenia: A Nationwide Study
• Meier SM, Petersen L, Pedersen MG, et al. Obsessive-Compulsive Disorder as a Risk Factor for
Schizophrenia: A Nationwide Study. JAMA Psychiatry. Published online September 03, 2014.
doi:10.1001/jamapsychiatry.2014.1011.

Young Eyes Should Be Protected From UV Light
MedicalResearch.comInterview with: Louis R. Pasquale, MD
Channing Division of Network Medicine Department of Ophthalmology
Harvard Medical School, Massachusetts Eye and Ear Infirmary
Boston, Massachusetts
• Dr. Pasquale: We found that more time spent outdoors in summer was associated with
increased risk of exfoliation syndrome.
• Dr. Pasquale: The eye is a seeing organ but is is also vulnerable to climatic elements.
Protection from reflected UV rays during young adulthood could contribute to better ocular
health in the elder years.
this study?
• Dr. Pasquale: A gene for exfoliation syndrome has been identified called LOXL1. A specific
polymorphism in LOXL1 is found in 99% of exfoliation syndrome cases and 80% of
controls. Why do 80% of people with the polymorphism NOT get the disease? It will be
important to determine if increased ocular UV exposure modifies the relation between LOXL1
gene variants and the development of exfoliation syndrome.
• Citation:
Pasquale LR, Jiwani AZ, Zehavi-Dorin T, et al. Solar Exposure and Residential Geographic
History in Relation to Exfoliation Syndrome in the United States and Israel. JAMA Ophthalmol.
Published online September 04, 2014. doi:10.1001/jamaophthalmol.2014.3326.

Going Braless Doesn’t Increase Risk of Breast Cancer
MedicalResearch.com Interview with: Lu Chen, MPH
Researcher in the Public Health Sciences Division
Fred Hutchinson Cancer Research Center
Doctoral student in the Department of Epidemiology
University of Washington School of Public Health
• Dr. Chen: We found no evidence that wearing a bra is associated with breast cancer risk. Further, breast cancer risk was not
impacted by bra wearing frequency, wearing a bra with an underwire, or starting to wear a bra at a young age.
• Dr. Chen: The biological plausibility for a relationship between bra wearing and breast cancer risk when we began this study
was quite weak, but since no other studies have really addressed this question in depth we were uncertain what we would
find. The potential mechanism through which bra wearing could influence breast health is that bras could impair lymphatic
drainage particularly in the lymph nodes located under a woman’s arm leading to compromised filtration of accumulated
waste products. Given the very limited biologic evidence supporting a potential link between bra wearing and breast cancer
risk, our results were not surprising.
Dr. Chen: With our findings there is no published scientific evidence that bra wearing is related to breast cancer risk.
• Dr. Chen: Like all studies, our study had limitations. The main limitation was that almost every woman in our study wore a
bra, therefore we could not directly compare those who never wore a bra to those who wore. Alternatively, we compared
how long they wore a bra every day, whether the bra had an underwire and when they began wearing a bra. Based on these
factors we evaluated, the results were consistent that all these aspects of bra wearing were not relevant to breast cancer. If
future studies can include women who never wore a bra in her lifetime and directly compare those who wore versus those
who did not, it would strengthen the existing evidence.
• Citation:
• Lu Chen, Kathleen E. Malone, and Christopher I. Li. Bra Wearing Not Associated with Breast Cancer Risk: A Population-Based
Case–Control Study. Cancer Epidemiology, Biomarkers & Prevention, September 2014 DOI: 10.1158/1055-9965.EPI-14-0414

SSRIs May Increase Risk Of Dental Implants Failure
Faleh Tamimi, BDS, PhD Assistant Professor,
Faculty of Dentistry Strathcona Anatomy & Dent,
Montreal, Quebec Canada
• Dr. Tamimi: The main finding was that SSRIs usage was associated with an increased risk of dental
implants failure.
• Dr. Tamimi: SSRIs are widely used all over the world, but their impact on the oral health was
unknown.
• Dr. Tamimi: Our findings indicate that treatment with SSRIs is associated with an increased failure
risk of osseointegrated implants, which might suggest a careful surgical treatment planning for
SSRIs users.
study?
• Dr. Tamimi: We suggest further studies investigating the influence of SSRIs on oral and dental
health. As well as on other biomedical devices such as hip prosthesis and knee prosthesis.
• Citation:
• SSRIs and the Risk of Osseointegrated Implant Failure – A Cohort Study
X. Wu, K. Al-Abedalla, E. Rastikerdar, S. Abi Nader, N.G. Daniel, B. Nicolau, and F. Tamimi
• J DENT RES, 0022034514549378, first published on September 3, 20

Poor Access To SSRIs May Result In Suicide Inequalities
MedicalResearch.comInterview with: Sean Clouston Ph.D. Assistant Professor
Core Faculty, Program in Public Health
Department of PreventiveMedicine
Stony Brook University Health Sciences Center Stony Brook, NY 11794
• Medical Research: What is the background for this study:
• Dr. Clouston: A number of epidemiological studies have found that suicide rates have decreased rapidly with the widespread
distribution of SSRI antidepressants. Our group has found that proliferation of preventive medicine has, with regard to other causes of
death, tended to occur unequally. We hypothesized that if SSRI antidepressants prevent suicide by treating depression, then suicide
might also be susceptible to such inequality. Our study used mortality data to show that decreases in suicide were concentrated in
regions with higher socioeconomic status.
• Dr. Clouston We used the best available data from the US and found that socioeconomic inequalities have increased dramatically in
conjunction with the proliferation of SSRI antidepressants.
•
• Dr. Clouston: There were two surprising results:
• Suicide has not historically been associated with socioeconomic inequality, so the main finding was quite surprising.
• We were also somewhat surprised to have found that suicide has not decreased to the same extent in states within the U.S. where
NAMI has rated the mental health system as failing, suggesting perhaps that there is more that we can do to improve public health and
prevent suicide.
• Dr. Clouston: Socioeconomic inequalities are both inequitable and inefficient. It is unlikely that SSRIs will effectively prevent all suicides,
but many suicides may be preventable. Depression is a key determinant of suicide, and most individuals who commit suicide have
sought help in the months prior to taking action. However, once individuals decide to take action they often act quickly and without
warning. Prevention is therefore of primary importance, so clinicians and patients should be aware that if patients seem suicidal, they
should seek immediate help from a trained mental health professional.
• Dr. Clouston: Suicide is somewhat rare, so studying cause and effect can be difficult. Further research is needed to ensure that SSRIs
have caused reductions in suicide, as well as identifying for whom such treatments may not work. Furthermore, suicide reductions
have been reported in the United Kingdom, Sweden, Denmark, and Canada, among others; international researchers should also be
aware that socioeconomic inequalities may also be evident in suicide internationally.
• Citation:
• Social Inequalities in Suicide: The Role of Selective Serotonin Reuptake Inhibitors
Am J Epidemiol. 2014 Aug 28. pii: kwu191. [Epub ahead of print]
• Clouston SA, Rubin MS, Colen CG, Link BG.

Contrast Media: PPIs One Of Risk Factors For Hypersensitivity Reaction
Elena Ramírez, MD, PhD
Clinical Pharmacology Department
Hospital Universitario la Paz, IdiPaz School of Medicine, U.A.M.
• Dr. Ramirez: We found that the presence of a past history of allergy, the use of proton pump
inhibitors (PPI), the number of times of previous administration of contrast media , and high
values of creatinine are significant factors to hypersensitivity reactions to contrast media
(CM). We found a low, but relevant, number of positive skin tests. The tolerability of an
alternative skin test-negative contrast media or different contrast media was confirmed in all
cases.
• Dr. Ramirez: To our knowledge, this is the first time that PPI are described as a specific factor
related hypersensitivity reactions to contrast media . The mechanisms by PPI may cause
reactions to contrast media are hypothetical. The presence of undigested oligopeptides by
treatment with PPI may induce a T-helper (Th)-2 response and immunoglobulin (Ig)-E
sensitization of the immune system. This allergic status of the patient might be facilitating the
reactions to intravenous contrast media .

Contrast Media: PPIs One Of Risk Factors For Hypersensitivity Reaction
Elena Ramírez, MD, PhD
Clinical Pharmacology Department
Hospital Universitario la Paz, IdiPaz School of Medicine, U.A.M.
• Dr. Ramirez: The incidence of hypersensitivity reactions to contrast media is low. A new risk
factor is PPI. The impaired renal function, in patients with history of allergy, and PPI use can
significantly increase the risk of hypersensitivity reactions to contrast media , especially
allergic reactions. Skin tests are useful for the diagnostic workup in patients with allergic
reactions.
this study?
• Dr. Ramirez: Test the tolerability of an alternative skin test-negative contrast media different
contast media before avoiding all contast media. However, there is still room for caution on
the reliability of skin test for diagnosis of hypersensitivity reactions to contast media and for
the choice of safe alternative CMcontast media.
• Citation:
• Hypersensitivity reactions to contrast media injections: a nested case–control study
Ramírez, Elena et al.
Annals of Allergy, Asthma & Immunology
Published Online: August 22, 2014
DOI: http://dx.doi.org/10.1016/j.anai.2014.07.016

Sleep Difficulties Linked To Shrinking Brain
Dr. Claire Sexton Ph.D.
University of Oxford
• Dr. Sexton:We found that sleep difficulties (which can include trouble falling asleep, waking up during the
night, or waking up too early) were associated with an increased rate of decline in brain volumes over 3-5
years.
•
• Dr. Sexton: Previous studies have linked a diagnosis of insomnia to reduced performance in cognitive tests
and reduced brain volumes in certain regions, so our results weren’t completely unexpected. However, it
was striking to find that sleep quality was associated with increased rate of decline in brain volumes across
widespread brain regions in community-dwelling adults.
• Dr. Sexton: Previous studies have linked a number of factors with an increased rate of decline in brain
volumes, such as physical inactivity, high blood pressure and high cholesterol. Our research indicates that
sleep is also an important factor that needs to be examined in more detail in future studies. Since there
are a number of effective treatments for sleep disorders, it could be an exciting avenue through which to
promote brain health, but more research needs to be done to determine if poor sleep is a cause or
consequence of increased decline in brain volumes.
• Dr. Sexton: In future, it will be important to examine if improving sleep quality can help slow rates of
decline in brain volume.
• Citation:
• Poor sleep quality is associated with increased cortical atrophy in community-dwelling adults
Sexton CE1, Storsve AB2, Walhovd KB2, Johansen-Berg H2, Fjell AM2.
Neurology. 2014 Sep 3. pii: 10.1212/WNL.0000000000000774. [Epub ahead of print]

US Life Expectancy Varies By Sex, Race/Ethnicity and Geography
Dr. Benedict Truman
Associate Director for Science
CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention
• Dr. Truman: In 2008, healthy life expectancy, which isthe number of years a person is expected to live in
good or better health after a particular age, varied by sex, race/ethnicity and geographical regions in the
United States. In each of four U.S. census regions, females were expected to live longer and healthier lives
than males; non-Hispanic whites were expected to live shorter but healthier lives than Hispanics; and non-
Hispanic whites were expected to live longer and healthier lives than non-Hispanic blacks.
• Dr. Truman: Expected years of life at any age is greater for Hispanic persons than for non-Hispanic white
persons. Therefore, a surprising finding of this study is that for people who are the same age, the expected
years of healthy life remaining for Hispanics was less than that for Non-Hispanic white persons (Fig. 3).
• Dr. Truman: Clinicians should encourage patients to make healthier lifestyles choices, get recommended
preventive services, and use high quality health care when needed. Patients should follow this advice to
live longer and healthier lives.
• Dr. Truman: Future research should identify the factors that lead to differences in healthy life expectancy
based on sex, race/ethnicity, and geography. The effectiveness of interventions to address these factors
also should be determined.
• Citation:
• Chang MH1, Molla MT2, Truman BI1, Athar H3, Moonesinghe R4, Yoon PW3.
J Public Health (Oxf). 2014 Aug 30. pii: fdu059. [Epub ahead of print]

Tuberculosis: Moxifloxacin Likely To Be Cornerstone Of New Treatment Regimen
Stephen H. Gillespie, M.D., D.Sc
University of St. Andrews Medical School, St. Andrews
• Dr. Gillespie: REMox TB was a pioneering trial that has shown that a large-scale trial can be
run efficiently in resource-poor settings with a high TB burden, adhere to the highest
standards of good clinical trial practices, and deliver a clear, unequivocal result. REMoxTB was
among the most rigorous Tuberculosis drug trials ever conducted in the modern era of TB
treatment and among the largest ever conducted for a new TB treatment. It enrolled 1,931
patients at 50 sites in nine countries, mostly in Africa and Asia. Previously, there were
thought to be regional differences in way in which patients’ response to treatment across the
world but we showed that a rigorous approach to trial conduct there was no evidence for
that difference.
• The study confirmed that daily moxifloxacin was safe over four months of therapy and the
moxifloxacin containing arms were more bactericidal initially. Despite its substantial anti-TB
activity it did not prove possible to shorten therapy to four months. .
• These findings, with the safety of moxifloxacin, and its activity against TB, support the
continued clinical testing of moxifloxacin as a component of other novel regimens.

Tuberculosis: Moxifloxacin Likely To Be Cornerstone Of New Treatment Regimen
Stephen H. Gillespie, M.D., D.Sc
University of St. Andrews Medical School, St. Andrews
• Dr. Gillespie: We undertake clinical trials because we don’t know the answer. What might have
been unexpected is that a trial of this scope and rigor could be conducted or completed. We have
shown that it is possible to conduct high quality clinical trials for new Tuberculosis treatments using
state of the art diagnostic methods in countries that have a high TB burden. More importantly, it is
possible for clinicians and scientists in resource-poor nations to play a critical role in finding
innovative solutions to this disease.
• Dr. Gillespie: Our report shows that moxifloxacin is safe over extended periods for tuberculosis and
that it is likely to be the cornerstone of a new regimen. It also shows that finding a better regimen is
challenging, but when clinicians, scientists and health professionals across the world work together
much can be achieved as REMoxTB has brought a four month regimen closer to reality.
study?
• Dr. Gillespie: REMoxTB paved the way for future progress by showing us that effective, markedly
shorter and safer treatments are just within our grasp. It is likely that we will need to build novel
regimens that combine multiple novel agents to make a more bactericidal regimen. Moxifloxacin
most certainly looks like it can play a role in such future treatments.
• Citation:
• Four-Month Moxifloxacin-Based Regimens for Drug-Sensitive Tuberculosis
Stephen H. Gillespie, M.D., D.Sc., Angela M. Crook, Ph.D., Timothy D. McHugh, Ph.D., Carl M.
Mendel, M.D., Sarah K. Meredith, M.B., B.S., Stephen R. Murray, M.D., Ph.D., Frances Pappas, M.A.,
Patrick P.J. Phillips, Ph.D., and Andrew J. Nunn, M.Sc. for the REMoxTB Consortium
• September 7, 2014DOI: 10.1056/NEJMoa1407426

US Hospitals Spend At Least Double Other Countries on Billing and Administration
Steffie WoolhandlerMD MPH
Professor School of Public Health and Hunter College, CUNY;
Professor of Medicine Harvard Medical School Cambridge Hospital
• Dr. Woolhandler: In 2011, U.S. hospitals spent $215 billion on
billing and administration. Meanwhile, other
countries spent far less. None of the other
seven countries we studied spent even half as
much as the U.S., and they all have modern, high
quality hospitals. While we spent nearly
$700 per capita on hospital paperwork, Scotland
and Canada spent less than $200. This means
that if U.S. hospitals ran as efficiently as
Canada’s, the average family of four would save
$2,000 annually on health care.
Medical Research: How was the study done?
• Dr. Woolhandler: We put together an international team of hospital
experts to obtain official hospital cost data
from eight nations. We then aligned the hospital
accounting categories to do an apples to apples
comparison of hospital administrative spending in
8 nations: the U.S., Canada, England, Scotland,
Wales, the Netherlands, France and Germany.

• Medical Research:Were any of the findings unexpected?
• Dr. Woolhandler: The conventional wisdom is that market breed
efficiency. We found the reverse to be true.
Nations with the most market oriented systems,
like the U.S. and increasingly the Netherlands,
had much higher administrative costs that
countries with single payer systems, like Canada
and Scotland. Another unexpected finding was
the explosion of administrative spending by US
hospitals in the past decade. In 2000 hospital
administration consumed 0.98% of total US GDP.
By 2011, hospital administration costs had more
than doubled in inflation adjusted dollars, and
were consuming a whopping 1.43% of
GDP. Meanwhile, hospital administrative costs were falling in Canada.

• Medical Research: What should clinicians and patients take away
from your report?
• Dr. Woolhandler: The major take-away point is
that doctors and patients need to be working to
go beyond Obamacare to a single paper
reform. The current payment systems is wasteful
because every hospital has to negotiate rates
schedules with hundreds of different insurance
plans, each with its own set of billing and
documentation requirements. And hospitals
need staff to collect deductibles, co-payments
and co-insurance from every patient who comes
through the door. Single payer systems (like
Canada’s or Scotlands) can give hospitals
simple lump sum budgets, the way we fund local
fire houses. And like fire departments
hospitals in single payer systems don’t need to
collect from each victim of misfortune. In
Scotland, even hospital parking is free.
• Medical Research: What recommendations do you have for future
research as a result of this study?
• Dr. Woolhandler: Research is needed on how we can minimize
administrative waste in payment of hospitals, physicians, and
other health providers, and use the savings to
provide excellent care to every American.
• Citation:
• A Comparison Of Hospital Administrative Costs In
Eight Nations: US Costs Exceed All Others By Far:
David U. Himmelstein, Miraya Jun, Reinhard Busse, Karine Chevreul, Alexander Geissler, Patrick Jeurissen, Sarah Thomson,
Marie-Amelie Vinet, and Steffie Woolhandler
Health Aff September 2014 33:91586-1594; doi:10.1377/hlthaff.2013.1327

Osteoporosis Medications Differ in Joint Fracture Reduction, Adverse Effects
Carolyn J. Crandall, MD, MS Professor of Medicine
David Geffen School of Medicine at University of California,
Los Angeles
Dr. Crandall:
• 1. We found high-strength evidence that several medications decrease fracture risk when
used by persons with bone density in the osteoporotic range and/or with pre-existing hip or
vertebral fracture. While many of the medications (alendronate, risedronate, zoledronic acid,
ibandronate, denosumab, teriparatide, and raloxifene) reduce vertebral fractures, a
reduction in the risk of hip fracture is not demonstrated for all of the medications. In
particular, hip fracture reduction is only demonstrated for alendronate, risedronate,
zoledronic acid, and denosumab. Unfortunately, due to a lack of head-to-head trials, the
comparative effectiveness of the medications is unclear.
• 2. The adverse effects of the medications vary. For example, raloxifene is associated with
an increased risk of thromboembolic events, whereas denosumab and the bisphosphonate
medications have been associated with increased risk of osteonecrosis of the jaw and
atypical subtrochanteric femoral fractures.
• Dr. Crandall: Many physicians and patients are likely to be surprised to know that there is
such a tremendous lack of direct head-to-head comparisons of these medications, both for
fracture reduction and for adverse effects.

Osteoporosis Medications Differ in Joint Fracture Reduction, Adverse Effects
Carolyn J. Crandall, MD, MS Professor of Medicine
David Geffen School of Medicine at University of California,
Los Angeles
• Dr. Crandall: Clinicians and patients should realize that many agents are efficacious for
decreasing fracture risk, but they differ as to their adverse effect profiles, and not all of them
are demonstrated to decrease hip fractures. Also, the absolute risk for atypical
subtrochanteric femoral fractures during bisphosphonate use is low, ranging from about 2
per 100,000 for women receiving bisphosphonates for less than 2 years to 100 per 100,000
for women receiving bisphosphonates for 8 years or more.
this study?
• Dr. Crandall: We need more head-to-head (direct) comparisons of these medications to
clarify how their anti-fracture and adverse effects differ. Also, there is only sparse
information regarding anti-fracture efficacy of the medications in men, so we desperately
need randomized controlled trials to be performed in men with osteoporosis. Finally, we
don’t know the optimal treatment duration for these medications.
• Citation:
• Crandall CJ, Newberry SJ, Diamant A, Lim Y, Gellad WF, Booth MJ, et al. Comparative
Effectiveness of Pharmacologic Treatments to Prevent Fractures: An Updated Systematic
Review. Ann Intern Med. [Epub ahead of print 9 September 2014] doi:10.7326/M14-0317

Dignified Death Still Elusive On Many Cancer Wards
Karin Jors MA
Department of Palliative Care, Comprehensive Cancer Center,
University Medical Center Freiburg, Freiburg, Germany
• Answer: The findings of our study shed light on the current circumstances for dying in cancer
centers. Physicians and nurses in our study reported that they rarely have enough time to
care for dying patients. In addition, only a minority of staff members felt that they had been
well-prepared during their training to care for dying patients and their families. Overall, only
56% of participants indicated that it is usually possible for patients to die in dignity on their
ward. This is likely the result of various factors such as: inadequate rooms for dying patients
and their families (i.e. shared rooms), poor communication with patients regarding
burdensome treatments, an overuse of life-prolonging measures, etc. Striking differences
were found between the responses of palliative care staff and staff from other wards (e.g.
general care, oncology, intensive care). For example, palliative care staff reported that they
usually have enough time to care for dying patients. In addition, 95% of palliative care staff
indicated that it is usually possible for patients to die in dignity on their ward. Overall, nurses
perceived the situation for dying patients more negatively than physicians. Whereas 72% of
physicians reported that patients can usually die a dignified death on their ward, only 52% of
nurses shared this opinion. Although only slightly more than half of participants believed that
patients can usually die in dignity on their ward, this is a considerable improvement to the
situation 25 years ago. In a similar study published in 1989, researchers found that 72% of
physicians and nurses experienced the situation for patients dying on their hospital ward as
undignified.

Karin Jors MA
• Answer: Over the last 25 years, considerable improvements in the care of patients dying in the
hospital setting have taken place. Patients can be comforted by the knowledge that the
overwhelming majority of physicians and nurses in our study recognized the importance of
honestly informing patients about their prognosis as well as all potential treatment options, even
potentially burdensome ones. This stands in contrast to the study from 25 years ago, which found
that 58% of physicians and nurses believed that patients did not wish to be informed about their
prognosis, and 54% from the prior study were of the opinion that knowledge of a negative
prognosis could be harmful to the patient. Furthermore, it can be viewed positively that the
majority of physicians and nurses in our study expressed a desire for more training in end-of-life
care, which suggests that they recognize the importance of this aspect of their work.
• The results of this study also have important implications for practicing physicians and nurses. Our
study found that 72% of physicians believe it is usually possible for patients to die a dignified death
on their ward, but only 52% of nurses shared this opinion. This difference in perception suggests
that physicians and nurses may need to communicate more effectively with each other about the
needs of dying patients in order to provide the best possible care. According to our results,
physicians and nurses on palliative care wards work together more closely, and this appears to
correspond with an overall more positive experience for dying patients. A majority of participants in
this study also complained that they rarely have enough time to care for dying patients. Working in
a team may also help to alleviate this burden by distributing responsibility among several people.

Karin Jors MA
this study?
• Answer: Although we aimed at a comprehensive investigation of the situation for patients
dying in cancer centers, there are still other issues that should be explored, such as the role
of other health care professionals including psychologists, social workers and chaplains.
• Our findings indicate that future research should be conducted to establish feasible, patient-oriented
standards for end-of-life care. In addition, further research is necessary to develop
comprehensive palliative care curricula and training for health care staff. To encourage such
research, the Palliative Care Center of Excellence in Baden-Württemberg (KOMPACT) was
established in 2014. This center combines the expertise of five academic, specialist palliative
care departments. We believe that this cooperation is a valuable tool for improving patient
care in the end-of-life setting.
• Citation:
• Dying in cancer centers: Do the circumstances allow for a dignified death?
• Jors, K., Adami, S., Xander, C., Meffert, C., Gaertner, J., Bardenheuer, H., Buchheidt, D.,
Mayer-Steinacker, R., Viehrig, M., George, W. and Becker, G. (2014), Dying in cancer centers:
Do the circumstances allow for a dignified death?. Cancer. doi: 10.1002/cncr.28702

Prediabetes Associated With Increased Cancer Risk
Professor Yuli Huang
The First People’s Hospital of Shunde, Daliang Town, China, and colleagues
• Professor Huang: In this meta-analysis of 16 prospective cohort studies comprising more
than 890,000 individuals, we found that the presence of prediabetes at baseline associated
with a 15% increased risk of cancer overall. The results were consistent across cancer
endpoint, age, duration of follow-up and ethnicity. There was no significant difference for the
risk of cancer with different definitions of prediabetes (impaired fasting glucose [IFG] and/or
impaired glucose tolerance [IGT]).
• Professor Huang: Although the difference of risk of cancer was not significant
between impaired glucose tolerance defined as 5.6-6.9 mmol/l or 6.1-6.9mmol/l. I think it is
very interesting that the risks of cancer were increased even when a lower fasting plasma
glucose value of 5.6–6.9 mmol/l was used, according to the current American Diabetes
Association definition of IFG. These findings support the lower threshold definition impaired
glucose tolerance proposed by the ADA, and highlight the clinical value of the early
management of hyperglycemia to prevent cancer.

Prediabetes Associated With Increased Cancer Risk
Professor Yuli Huang
The First People’s Hospital of Shunde, Daliang Town, China, and colleagues
• Professor Huang: First, as the risk of cancer increased in people with prediabetes, clinicians should
be aware that it is important to screening for prediabetes with a view to cancer prevention. Second,
lifestyle intervention (weight control, stop smoking and healthy diet etc.) should be suggested
earlier and recommended as the mainstay of treatment for prediabetes in the general population.
study?
• Professor Huang: First, future researches are needed to explore the underlying mechanisms
associated with prediabetes and cancer. Second, Future prospective cohort studies that include
testing of HbA1c may provide more information on the association between prediabetes and
cancer. Third，long-term, large-scale studies are urgently needed to explore the effects of
interventions (including lifestyle intervention and drug treatment) on the risk of cancer in people
with prediabetes.
• Citation:
• Prediabetes and the risk of cancer: a meta-analysis
Yi Huang & Xiaoyan Cai & Miaozhen Qiu & Peisong Chen &
Hongfeng Tang & Yunzhao Hu & Yuli Huang
Diabetologia
DOI 10.1007/s00125-014-3361-2
Received: 16 May 2014 /Accepted: 31 July 2014
# Springer-Verlag Berlin Heidelberg 2014

More Than $60 Billion Spent On Proton Pump Drugs In Just Four Years
Michael Johansen, MD MS
Assistant Professor Dept of Family Medicine
Ohio State University
• Dr. Johansen: Between 2007-2011, the United States spent $63.4 billion on high-cost proton pump inhibitors of which $47.1
billion was in excess of using generic omeprazole.
• Dr. Johansen: Yes and no. While the finding of excess expenditure was expected to be high, I was shocked by the level of the
excess.
• Medical Research: What should clinicians take away from your report?
• Dr. Johansen: As a clinician, it became clear that we need to be good steward of societal resources. Prescribing one person
an unnecessary high cost drug doesn’t seem like a big deal until you think about it on a societal level. We end up spending
more than $47.1 billion more over 5 years than needed within a single class of drugs. These billions are taken away from
other aspects of society such as for roads, schools, or high value medical interventions.
• Medical Research: What should patients take away from your report?
• Dr. Johansen: Patients were responsible for paying almost $7 billion more than if they had used omeprazole. It is a good idea
to ask your physician if there are cheaper options to branded medications (there normally are).
• What recommendations do you have for future research as a result of this study?
Dr. Johansen: We are at a point that we need to try different ways of decreasing unnecessary use of high cost drugs. It is
critical that policy makers intervene. Expecting different outcomes without changing the incentives and structures for
pharmaceutical companies, physicians, and patients is highly unlikely. The goals of change should focus on incentivizing
innovative new products, while decreasing the profitability of drugs that provide minimal value over cheaper alternative
drugs.
• Citation:
• Johansen ME, Huerta TR, Richardson CR. National Use of Proton Pump Inhibitors From 2007 to 2011. JAMA Intern Med.
Published online September 08, 2014. doi:10.1001/jamainternmed.2014.2900.

Post Stent: Delaying Non-Emergency Surgery Reduced Adverse Events
Laura A. Graham,MPH
Center for Surgical, Medical Acute Care Research, and Transitions Birmingham Veterans Affairs Medical Center
Section of Gastrointestinal Surgery, Department of Surgery
University of Alabama at Birmingham, Birmingham
• Answer: The main findings of the study are that the recommendations made in the guidelines
published by the American College of Cardiology / American Heart Association in 2007 were
effective at reducing postoperative major adverse cardiac events following noncardiac surgery in
patients with a cardiac stent.1 These guidelines recommended the delay of noncardiac surgeries in
patients with a drug-eluting stent for 365 days if the surgery was not emergent or the delay of
surgery for 4 to 6 weeks among patients with a bare metal stent.1 In addition to a 26% reduction in
postoperative major adverse cardiac events, we also found an increase in the time between drug-eluting
stent placement and non-cardiac surgery consistent with the guideline recommendations.
• Answer: In addition to our primary finding of a reduction in postoperative major adverse cardiac
events, we also found evidence of a shift in cardiac risk to patients with a bare metal stent for
surgeries occurring between 2006 and 2009. Previous studies have suggested that differences in
the outcomes of patients with a bare metal stent as compared to a drug-eluting stent are due to
confounding by indication, where sicker patients needing more urgent operations were more likely
to receive a bare metal stent and also more likely to experience adverse postoperative events. This
study provides evidence of a shift toward higher cardiac risk in patients with a bare metal stent
following the initial publication in 2006 of several case reports of postoperative stent thrombosis in
patients with a drug-eluting stent.

Post Stent: Delaying Non-Emergency Surgery Reduced Adverse Events
Laura A. Graham,MPH
Center for Surgical, Medical Acute Care Research, and Transitions Birmingham Veterans Affairs Medical Center
Section of Gastrointestinal Surgery, Department of Surgery
University of Alabama at Birmingham, Birmingham
• Answer: While the recommendations were effective at increasing time between drug-eluting stent
placement and surgery as well as reducing major adverse cardiac events, the trends in timing of surgery
following drug-eluting stent placement suggest a high level of awareness among healthcare professionals
treating patients with cardiac stents as well as an increased use of evidence-based practices. This resulted
in an increase in surgery timing for drug-eluting stent patients which can be seen prior to the publication
of the guidelines. While the publication of the guidelines marks a summary of this information into one
document, it does not necessarily mark the time at which the information was officially available to
healthcare providers in the field.
• Answer: Further study should be done to examine other factors influencing the management of patients
with cardiac stents in need of subsequent surgery and their effect on outcomes.
• Fleisher LA, Beckman JA, Brown KA, et al. ACC/AHA 2007 Guidelines on Perioperative Cardiovascular
Evaluation and Care for Noncardiac Surgery: Executive Summary: A Report of the American College of
Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise
the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery) Developed in
Collaboration With the American Society of Echocardiography, American Society of Nuclear Cardiology,
Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography
and Interventions, Society for Vascular Medicine and Biology, and Society for Vascular Surgery. J Am Coll
Cardiol. Oct 23 2007;50(17):1707-1732.
• Citation:
• Graham LA, Singletary BA, Richman JS, Maddox TM, Itani KF, Hawn MT. Improved Adverse Postoperative
Outcomes With Revised American College of Cardiology/American Heart Association Guidelines for
Patients With Cardiac Stents. JAMA Surg. Published online September 03, 2014.
doi:10.1001/jamasurg.2014.2044.

Breath Temperature Test May Help Diagnose Lung Cancer
Dr. Giulia Scioscia
Coauthor of this study with the Prof. Carpagnano
University of Foggia.
• Dr. Scioscia: The principal and newest findings of our study are:
• Airways inflammation and neoangionesis are critical component of the lung cancer pathogenesis
and they contribute to the regulation of airways temperature. They cause a regional hyperthermia
in the lung lesion.
• The exhaled Breath temperature has been proven to be the expression of the airways temperature
and for this reason of their inflammation and neoangionesis.
• For the first time we have measured this hyperthermia in lung cancer patients with the xhalo. The
patient with diagnosis of tumor shows an higher temperature than in healthy ones and this values
correlate with cigarette smoking and tumor progression.
• Medical Research: What further research do you recommend as a result of this study?
• Dr. Scioscia: Actually it is only a pilot study and the breath temperature in lung cancerogene
requires a standardization in large prospective studies. We could underline that our study opens up
a new application of this non-invasive biomarkers in the protocols of early diagnosis of the lung
cancer.
• Citation:
• Breath temperature test could identify lung cancer
• Abstract presented at the 2014 European Respiratory Society (ERS) International Congress
• Abstract: Exhaled breath temperature in NSCLC: Could be a new non-invasive marker?
Session: Advances in diagnosis and therapy of thoracic tumours
Date and time: Monday 8 September, 10.45–11.45

Long Term Benzodiazepines May Increase Alzheimer’s Disease Risk
Sophie Billioti de Gage PharmD
University of Bordeaux Segalen
France
• Answer: The risk of Alzheimer’s disease was found increased by 43-51% in persons (>65) having initiated a
treatment with benzodiazepines in the past (>5 years before). Risk increased with the length of exposure
and when long acting benzodiazepines were used.
• Answer: Benzodiazepines remain valuable tools for managing anxiety and insomnia. We did not found any
increase in the risk of Alzheimer’s disease in individuals using benzodiazepines in accordance with
international guidelines (short duration, not exceeding one month for hypnotics and three months for
anxiolytics).
• For people needing or using benzodiazepines, it seems crucial to encourage physicians to carefully balance
the benefits and risks when renewing the treatment. Abrupt discontinuation of long-term treatments with
benzodiazepines should be avoided because of the risk of withdrawal effects.
• Answer: Experimental animal or cellular models are needed to help in identifying a possible biological
mechanism linking benzodiazepines with risk of Alzheimer’s disease.
• Studies based on a long follow-up—that is, at least 20-30 years—would make it possible to evaluate the
risk of long term use of benzodiazepines in younger adults and to better assess the exact role of anxiety,
sleep disorders, and depression as putative early risk factors of future dementia.
• Citation:
Risk of Alzheimer’s disease in benzodiazepine users: a case-control study
BMJ 2014; 349 doi: http://dx.doi.org/10.1136/bmj.g5205 (Published 09 September 2014) Cite this as: BMJ
2014;349:g5205

MedicalResearch.com: Medical Research Interviews September12 2014

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