Medical research slideshare_feb-24_2015

MedicalResearch.com
Exclusive Interviews with Medical Research and
Health Care Researchers from Major and Specialty Medical
Research Journals and Meetings
Editor: Marie Benz, MD
info@medicalresearch.com
February 24 2015
For Informational Purposes Only: Not for Specific Medical Advice.

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After Age 2, Daytime Naps May Interfere With Nightime Sleep
MedicalResearch.com Interview with: Karen Thorpe PhD
Professor, Developmental Psychology
Program Leader, Early Education and Development Group
Program leader, Sleep in Early Childhood Group
• MedicalResearch: What is the background for this study?
• Professor Thorpe: Sleep is undoubtedly important not only for how well we think, feel and behave
in our daily lives but also for longer-term health. In childhood, the quantity and quality of night-
time and 24 hour sleep have consistently been identified as predictor of health. For example, night
sleep predicts weight status. These findings have led to the hypothesis that increasing quantity of
sleep through promoting daytime sleep would benefit child health. We sought to look for evidence
on the independent effects of daytime sleep on child health, learning and behavior to assess
whether this hypothesis was supported.
• MedicalResearch: What are the main findings?
• Professor Thorpe: We conducted a systematic review of the literature for children aged 0-5 years.
We focus on early childhood as a period of significant sleep transition in which sleep consolidates
into the nighttime and naps cease. We found 26 papers that provided data on the independent
effects of daytime sleep. Outcomes included quantity and quality of night sleep, accidents, weight
status, memory and learning, and behavior. The most consistent evidence related to night sleep.
The evidence suggests that beyond the age of 2 years when cessation of napping becomes more
common, daytime sleep is associated with shorter and more disrupted night sleep. Those studies
examining direction of effect all report that daytime sleep is not a response to poor night sleep but
rather precedes poor night sleep. Evidence relating to cognitive functioning, accidents, weight
status and behavior were less conclusive. More research and higher quality research that can
provide evidence on causality was advocated.
Read the rest of the interviews on MedicalResearch.com
Content NOT an endorsement of efficacy and NOT intended as specific medical advice.

After Age 2, Daytime Naps May Interfere With Nightime Sleep
MedicalResearch.com Interview with: Karen Thorpe PhD
Professor, Developmental Psychology
Program Leader, Early Education and Development Group
Program leader, Sleep in Early Childhood Group
• MedicalResearch: What should clinicians and patients take away from your report?
• Professor Thorpe: The age of cessation of napping varies considerably. The age of 2 years should not be
seen as definitive point from which napping should be discouraged. Rather, clinicians and parents of young
children should respond to their child’s sleep need. Provision of opportunity to nap for those who have
not yet consolidated their sleep into the nighttime is likely important. However, there is not evidence of
benefit through prolonging and promoting napping beyond the period when children cease to need a
regular nap. For children presenting to clinicians with night sleep difficulties napping behaviours should be
considered as a potential factor.
• MedicalResearch: What recommendations do you have for future research as a result of this study?
• Professor Thorpe: Sleep studies to date focus on 24 hour or night sleep. There is little high quality
evidence regarding the independent effects of daytime sleep on child health. Considerably more studies
are required. This is particularly important to guide parents and non-parental carers of young children in
determining sleep practices. Studies providing physiological measurement of sleep and long-term follow-
up of child outcomes are particularly important. Children attending daycare are particularly of interest
because naptime is typically a standard practice regardless of individual variation in point of transition to
monophasic sleep.
• Citation::
• Napping, development and health from 0 to 5 years: a systematic review
Karen Thorpe, Sally Staton, Emily Sawyer, Cassandra Pattinson, Catherine Haden,
Simon Smith
• Arch Dis Child archdischild-2014-307241Published Online First: 17 February 2015 doi:10.1136/archdischild-
2014-307241

JAMA Study Confirms Better Anticoagulation Choice After Myocardial Infarction
MedicalResearch.com Interview with:
Karolina Szummer, MD, PhD
Section of Cardiology, Department of Medicine
Karolinska Institutet Karolinska University Hospital Stockholm, Sweden
Please note: This work is comparing the anticoagulant fondaparinux with low-molecular-
weight heparin (not heparin).
• Medical Research: What is the background for this study? What are the main findings?
Dr. Szummer: Since the publication of the OASIS-5 trial in 2006, many hospitals chose to
change their medical practice and start using fondaparinux instead of low-molecular-weight
heparin in the treatment of myocardial infarctions. In this study from the nation-wide near-
complete myocardial infarction registry we were able to follow how the use of fondaparinux
instead of low-molecular-weight heparin translated in clinical life was associated to a
reduction in bleeding events and death. It is a very satisfying study, that confirms that the
randomized clinical trial results are transferred with improvements in outcome to the treated
patients.
• Medical Research: What should clinicians and patients take away from your report?
• Dr. Szummer:
• Firstly, if fondaparinux is not used in the treatment of myocardial infarction, it is a good time
to consider its use.
• Secondly, it is highly relevant to follow what happens in real-life when new treatments are
implemented and confirm the good results seen in a selected trial.

JAMA Study Confirms Better Anticoagulation Choice After Myocardial Infarction
Karolina Szummer, MD, PhD
Section of Cardiology, Department of Medicine
Karolinska Institutet Karolinska University Hospital Stockholm, Sweden
Please note: This work is comparing the anticoagulant fondaparinux with low-molecular-
weight heparin (not heparin).
• Medical Research: What recommendations do you have for future research as a result of
this study?
• Dr. Szummer: A recommendation would be to keep a current updated registry which enables
to assess how new treatments are implemented and how they affect outcome when it
reaches a wider clinical use.
• Citation:
• Szummer K, Oldgren J, Lindhagen L, et al. Association Between the Use of Fondaparinux vs
Low-Molecular-Weight Heparin and Clinical Outcomes in Patients With Non–ST-Segment
Elevation Myocardial Infarction. JAMA. 2015;313(7):707-716. doi:10.1001/jama.2015.517.

Personalized Advice May Help Risky Drinkers Reduce Alcohol
Sean M. Murphy, Ph.D.
Assistant Professor Department of Health Policy & Administration
Washington State University
Medical Research: What is the background for this study? What are the main findings?
Dr. Murphy: Professional healthcare advice regarding excessive alcohol consumption has been
shown to reduce demand in a controlled setting. However, success in a clinical trial isn’t always
indicative of an intervention’s effectiveness in everyday use. Studies testing the effect of provider
advice on alcohol demand in a non-controlled environment are few, and have failed to control for
non-moderate drinkers. Therefore, it is possible that the estimated effect of professional-health
advice primarily reflected moderate-drinkers’ responses. The distinction between moderate and
non-moderate drinkers is an important one, as society bears a large cost for those who consume
above-moderate quantities, while moderate drinkers have been shown to be relatively
productive and healthy. Excise taxes may not be efficient given that they impose negative
externalities on moderate drinkers, while excessive drinkers have been shown to be relatively
unresponsive to price increases. We found that personalized information from a healthcare
professional was negatively associated with reported alcohol consumption among both
“risky” and “binge” drinkers. Moreover, we found that personalized drinking advice may have an
impact on those who are reluctant to state that they were given such advice.

Personalized Advice May Help Risky Drinkers Reduce Alcohol
Sean M. Murphy, Ph.D.
Assistant Professor Department of Health Policy & Administration
Washington State University
• Dr. Murphy: The ability to target risky drinkers with advice will improve their health and
reduce costs without negatively affecting moderate drinkers. Those reluctant to state that
they were given drinking advice may also be less likely to properly inform their healthcare
provider about their alcohol intake. If so, our findings indicate that a blanket statement to
patients regarding behaviors to avoid to control their hypertension may be effective.
•
Medical Research: What recommendations do you have for future research as a result of
this study?
• Dr. Murphy: The cross-sectional nature of our data limited our ability to make causal
inferences. Future studies that are able to longitudinally assess the effectiveness of targeted
healthcare advice on excessive alcohol consumption would be valuable.
• Citation:
• Does Individualized Health Information Regarding Alcohol Consumption Affect Consumption
Among Risky Drinkers?
• Berning J, Murphy SM.
Am J Health Promot. 2014 Jan 24. [Epub ahead of print]

Drug May Reverse Childhood Asthma Caused By Maternal Smoking
Virender K. Rehan, MD
LA BioMed Lead Researcher
• Medical Research: What are the main findings?
• Dr. Rehan: A new study holds hope for reversing asthma caused by smoking during
pregnancy. The study, published online by the American Journal of Physiology
– Lung Cellular and Molecular Physiology, reported that a medication that
stimulates certain proteins in the body reversed airway damage in disease
models of asthma caused by prenatal exposure to nicotine.
• This is the first study to indicate that the damage caused by exposure to
nicotine during pregnancy could actually be reversed. Earlier studies found
this medication could prevent nicotine-induced asthma when given during
pregnancy. Researchers at Los Angeles Biomedical Research Institute (LA
BioMed) conducted the study to determine if the lung and airway damage
caused by nicotine could be reversed and found it could be.

• Medical Research: What is the background for this study?
Dr. Rehan: Despite the many warnings about the dangers of smoking while pregnant, 12% of
women in the U.S. continue to smoke during pregnancy, resulting in the
births of at least 400,000 smoke-exposed infants in the U.S. alone. In
addition, pregnant women who try to give up smoking may continue to be
exposed to nicotine through nicotine replacement therapies and the use of
electronic cigarettes.
• The researchers noted that cigarette smoke contains more than 4,000 known
chemicals, so determining which ones are responsible for asthma in the
children of mothers who smoked is problematic. However, they said, previous
research has conclusively determined nicotine affects fetal lung
development, resulting in asthma, so they used nicotine for this study to
replicate the effects on the fetus of maternal smoking during pregnancy.
• Researchers had previously found that nicotine exposure during pregnancy
altered certain key activities in specific lung cells of the developing
fetus, and this contributed to the development of asthma. For this study,
they administered a diabetes medication, rosiglitazone, which is known to
stimulate cellular activity related to lung development. The medication was
administered over the first 21 days of life in a perinatal nicotine
exposure-induced asthma model. When compared to a group given a placebo,
those treated with the medication showed a complete reversal of asthma.

• Dr. Rehan: First and foremost, pregnant women should not only avoid smoking but should avoid nicotine
in any form – including in e-cigarettes and nicotine
treatment programs that include the use of nicotine. While this study holds
hope for reversing damage caused by smoking during pregnancy, the best
method for preventing asthma is avoiding smoking and the use of nicotine
during pregnancy.
• Medical Research: What recommendations do you have for future research as a result of this study?
• Dr. Rehan: This study was conducted in disease models. Before using the class of drugs
investigated in this study to treat or reverse childhood asthma resulting
from smoke exposure during pregnancy, additional studies are needed to
determine the safety and effectiveness of these drugs in humans.
• Virender K. Rehan, MD, an LA BioMed lead researcher, has conducted numerous
studies on the effects of maternal smoking on offspring and on the impact of
second- and third-hand smoke.
• Editor’s Note: Virender K. Rehan, MD, an LA BioMed lead researcher, has conducted numerous studies on
the effects of maternal smoking on offspring and on the impact of
• Citation:
• PPARγ Agonist Rosiglitazone Reverses Perinatal Nicotine Exposure-Induced
Asthma in Rat Offspring
• Jie Liu , Reiko Sakurai , Virender K Rehan
• American Journal of Physiology – Lung Cellular and Molecular Physiology Published 6 February 2015 Vol.
no. , DOI: 10.1152/ajplung.00234.2014

Study Suggests Most Physicians Would Not Perform Euthanasia For Dementia or Psychiatric Disease
MedicalResearch.com Interview with: Eva E. Bolt MD
Physician researcher Dept. Public and Occupational Health
EMGO+ Institute for Health and Care Research (VU University Medical Center)
Medical Faculty Amsterdam, The Netherlands
Dr. Bolt: Three-quarter of all Dutch physicians have ever been asked by a patient to perform
euthanasia. Each request for euthanasia calls for careful deliberation. Firstly, the physician
needs to judge whether euthanasia would be possible within the limits of the law. Above
that, a physician needs to decide whether performing euthanasia is in line with his personal
believes and values. This study shows that cause of suffering is an important factor in this
decision.
• In the Netherlands, the euthanasia law gives physicians the possibility of performing
euthanasia, if they adhere to strict rules. The euthanasia law is not restricted to certain
diseases. However, this study shows that the attitude of physicians towards performing
euthanasia varies by condition. Most Dutch physicians would consider granting a request for
euthanasia in case of cancer (85%) or another severe physical disease (82%). In contrast, only
four out of ten physicians would consider granting a request for euthanasia in case of early-
stage dementia. One in three would consider it in case of advanced dementia or psychiatric
disease, and one in four in case of a person who is tired of living without suffering from a
severe disease.

Study Suggests Most Physicians Would Not Perform Euthanasia For Dementia or Psychiatric Disease
MedicalResearch.com Interview with: Eva E. Bolt MD
Physician researcher Dept. Public and Occupational Health
EMGO+ Institute for Health and Care Research (VU University Medical Center)
Medical Faculty Amsterdam, The Netherlands
• Dr. Bolt: Each physician needs to form his or her own standpoint on euthanasia, based on
legal boundaries and personal values. For patients with a wish for euthanasia, it is important
to realize that a physician’s decision on euthanasia is highly individual. The chance that a
physician refuses a request for euthanasia in case of dementia, psychiatric disease or tired of
living is high.
• We would advise people with a future wish for euthanasia to discuss this wish with their
physician in time, and we would advise physicians to be clear about their standpoint on the
matter. This can help to prevent disagreement and disappointment.
• Citation:
• Can physicians conceive of performing euthanasia in case of psychiatric disease, dementia or
being tired of living?
• Eva Elizabeth Bolt, Marianne C Snijdewind, Dick L Willems, Agnes van der Heide,
• Bregje D Onwuteaka-Philipsen
• J Med Ethics medethics-2014-102150Published Online First: 18 February 2015
doi:10.1136/medethics-2014-102150

• Dr. Rehan: First and foremost, pregnant women should not only avoid smoking but should
avoid nicotine in any form – including in e-cigarettes and nicotine
treatment programs that include the use of nicotine. While this study holds
hope for reversing damage caused by smoking during pregnancy, the best
method for preventing asthma is avoiding smoking and the use of nicotine
during pregnancy.

this study?
• Dr. Rehan: This study was conducted in disease models. Before using the class of drugs
investigated in this study to treat or reverse childhood asthma resulting
from smoke exposure during pregnancy, additional studies are needed to
determine the safety and effectiveness of these drugs in humans.
• Virender K. Rehan, MD, an LA BioMed lead researcher, has conducted numerous
studies on the effects of maternal smoking on offspring and on the impact of
• Editor’s Note: Virender K. Rehan, MD, an LA BioMed lead researcher, has conducted
numerous studies on the effects of maternal smoking on offspring and on the impact of
• Citation:
• PPARγ Agonist Rosiglitazone Reverses Perinatal Nicotine Exposure-Induced
Asthma in Rat Offspring
• Jie Liu , Reiko Sakurai , Virender K Rehan
• American Journal of Physiology – Lung Cellular and Molecular Physiology Published 6
February 2015 Vol. no. , DOI: 10.1152/ajplung.00234.2014

MAPT locus on Chromosome 17 Links Parkinson’s and Alzheimer’sDiseases
Dr. Rahul S. Desikan MD, PhD
Department of Radiologoy
University of California, San Diego School of Medicine
Dr. Desikan: The MAPT gene encodes the tau protein, which plays an integral role in
Alzheimer’s disease (AD) neurodegeneration. Though a number of studies have investigated
this issue, the role of the MAPT gene in Alzheimer’s disease is still unclear. In contrast, a
number of studies have found a robust association between MAPT and increased risk for
other ‘tauopathies’ like Parkinson’s disease (PD). In our study, rather than evaluating all
possible genetic loci, we only assessed shared genetic variants between Alzheimer’s disease
and PD. By using this type of approach, we were able to increase our statistical power for
gene discovery in Alzheimer’s disease.
• We found genetic overlap between Alzheimer’s disease and Parkinson’s disease at a locus on
chromosome 17 within the MAPT region. Our findings demonstrate that this MAPT
associated locus increases risk for Alzheimer’s disease, correlates with gene expression of
MAPT and is associated with brain atrophy of the entorhinal cortex and hippocampus on
longitudinal MRI scans.

• Dr. Desikan: I think the main contribution of our work is showing the importance of tau and
the need to focus additionally on tau-based diagnostic and therapeutic approaches.
• A tremendous amount of prior work is being undertaken to identify and treat amyloid
dysmetabolism. Comparatively little is known about the early involvement of tau in the
Alzheimer’s cascade. Our findings suggest that individuals who are carriers of the deleterious
MAPT allele may be at increased risk for developing Alzheimer’s neurodegeneration.
Clinically, it will be important to identify and follow these individuals.

this study?
• Dr. Desikan: I think it will be very important to have a better understanding of the entire
MAPT region on chromosome 17. There are a number of loci within the larger MAPT region,
including the CRHR locus that we identify, that demonstrate a strong correlation (linkage
disequilbrium) with MAPT and it will be important to decipher whether these signals just tag
MAPT or represent independent signals. It will also be important to see what happens
functionally if you knockout/knockdown our identified locus: how does this correlate with
tangle formation or memory decline? does this have any relationship with amyloid
pathology? does possessing this locus increase the rate of progressing to Alzheimer’s disease
in a survival analysis? finally, what is the relationship between MAPT carrier status and APOE
carrier status?
• Citation:
• R S Desikan, A J Schork, Y Wang, A Witoelar, M Sharma, L K McEvoy, D Holland, J B Brewer, C-
H Chen, W K Thompson, D Harold, J Williams, M J Owen, M C O’Donovan, M A Pericak-Vance,
R Mayeux, J L Haines, L A Farrer, G D Schellenberg, P Heutink, A B Singleton, A Brice, N W
Wood, J Hardy, M Martinez, S H Choi, A DeStefano, M A Ikram, J C Bis, A Smith, A L
Fitzpatrick, L Launer, C van Duijn, S Seshadri, I D Ulstein, D Aarsland, T Fladby, S Djurovic, B T
Hyman, J Snaedal, H Stefansson, K Stefansson, T Gasser, O A Andreassen, A M Dale. Genetic
overlap between Alzheimer’s disease and Parkinson’s disease at the MAPT locus. Molecular
Psychiatry, 2015; DOI: 10.1038/mp.2015.6

Improved Survival with Combination Therapy for HER2- Positive Metastatic Breast Cancer
Sandra M Swain, MD, FACP, FASCO
Medical Director, Washington Cancer Institute
MedStar Washington Hospital Center Washington DC 20010
• MedicalResearch: What take-home message would you like the general public to
understand about this new analysis from the Cleopatra study?
• Potential Key Message Options:
• Updated results from the CLEOPATRA study showed that people treated with the
combination of pertuzumab, trastuzumb and chemotherapy lived 15.7 months longer than
those who received trastuzumab and chemotherapy alone (median survival of 56.5 months
versus 40.8 months).
• The survival improvement of nearly 16 months observed in CLEOPATRA is unprecedented
among studies of metastatic breast cancer. This is the kind of survival improvement that
those of us who treat breast cancer strive for, and this data will be incredibly meaningful to
patients and their families.
• Furthermore, the median survival of nearly five years observed in CLEOPATRA patients
treated with the pertuzumab regimen is the longest ever observed in a clinical study of
people with HER2-positive metastatic breast cancer, once one of the most aggressive forms
of breast cancer.
• Patients who responded with shrinkage of their tumor had a response that was 8 months
longer with the pertuzumab regimen compared to the trastuzumab and chemotherapy
regimen.

• MedicalResearch: In simple terms could you explain why the Cleopatra study was
undertaken?
• CLEOPATRA was the pivotal, Phase III study where we evaluated the safety and efficacy of the
pertuzumab regimen in people with previously untreated HER2-positive metastatic breast
cancer. HER2-positive metastatic breast cancer has historically been one of the most
aggressive forms of the disease.
• In CLEOPATRA we evaluated whether dual HER2 blockade by combining the antibody
pertuzumab with trastuzumab and chemotherapy, would help people live longer (overall
survival, OS) or live longer without their disease worsening (progression-free survival, PFS).
• MedicalResearch: For a non-specialist reader, how would you describe the significance of
the new data presented at ESMO 2014? (We need to be clear about what is new compared
to previously published or reported data.)
• We previously reported that the pertuzumab regimen significantly extended the time before
patients’ disease got worse (PFS) and improved survival.
• We are now reporting results of the final analysis of survival in CLEOPATRA after long term
follow-up of patients in the study (longest follow up was approximately 6 years).
• What’s new about these results is that we can now see that the magnitude of survival
improvement in CLEOPATRA is nearly 16 months.

• MedicalResearch: Are there any important caveats or limitations to the new analysis that I should
mention in a press release?
• The survival benefit observed with the pertuzumab regimen in CLEOPATRA was consistent across
patient subgroups.
• The previously observed benefit in progression free survival was maintained after long ter follow
up.
• The long-term safety profile of the pertuzumab regimen was unchanged from previous analyses
and the long-term cardiac safety profile was maintained
• MedicalResearch: Are there any subtleties in the data that you particularly want to emphasise in
the press release? (For example, should we elaborate on the patients who crossed over into the
pertuzumab arm after the previous report of OS benefit?)
• Overall survival was analyzed using all randomized patients, with no adjustments for cross over.
• Patients who crossed over from the placebo arm to the pertuzumab arm were analyzed as part of
the placebo arm.
• As such, this is a very conservative final analysis of survival.
• Pertuzumab, Trastuzumab, and Docetaxel in HER2-Positive Metastatic Breast Cancer
• Sandra M. Swain, M.D., José Baselga, M.D., Sung-Bae Kim, M.D., Jungsil Ro, M.D., Vladimir
Semiglazov, M.D., Mario Campone, M.D., Eva Ciruelos, M.D., Jean-Marc Ferrero, M.D., Andreas
Schneeweiss, M.D., Sarah Heeson, B.Sc., Emma Clark, M.Sc., Graham Ross, F.F.P.M., Mark C.
Benyunes, M.D., and Javier Cortés, M.D. for the CLEOPATRA Study Group
• N Engl J Med 2015; 372:724-734
February 19, 2015
DOI: 10.1056/NEJMoa1413513

Radioactive Iodine Treatment for Thyroid Cancer
MedicalResearch.com Interview with: Sanziana Roman MD FACS
Professor of Surgery Duke University Section of Endocrine Surgery
Director of the Endocrine Surgery Fellows and Scholars Program
Duke University School of Medicine
• Medical Research: What is the background for this study?
Dr. Roman: Adjuvant radioactive iodine (RAI) is commonly used in the management of
differentiated thyroid cancer. The main goals of adjuvant RAI therapy are to ablate remnant
thyroid tissue in order to facilitate long-term follow-up of patients, decrease the risk of
recurrence, or treat persistent and metastatic lesions.
• On the other hand, Adjuvant radioactive iodine ( therapy is expensive, with an average cost
per patient ranging between $5,429.58 and $9,105.67. It also carries the burden of several
potential complications, including loss of taste, nausea, stomatitis with ulcers, acute and/or
chronic sialoadenitis, salivary duct obstruction, dental caries, tooth loss, epiphora, anemia,
neutropenia, thrombocytopenia, acute radiation pneumonitis, pulmonary fibrosis, male
infertility, and radiation-induced malignancies. Therefore, Adjuvant radioactive iodine (
should be used only for appropriately selected patients, for whom the benefits would
outweigh the risks.
• Based on current guidelines, adjuvant RAI is not recommended for patients with papillary
thyroid cancers confined to the thyroid gland when all foci are ≤1 cm (papillary thyroid
microcarcinoma, or PTMC). Similarly, Adjuvant radioactive iodine ( does not have a role in the
treatment of medullary and anaplastic thyroid cancer. Given the fact that variation in
treatments exist, our goal was to analyze patterns of inappropriate adjuvant RAI use in the
U.S. in order to identify potential misuses leading to an increase of costs for the healthcare
system and unnecessary patients’ exposure to risks of complications.

Medical Research: What are the main findings?
Dr. Roman: We demonstrated in two separate U.S. national databases, which encompassed >85%
of all incident thyroid cases in the U.S. and more than 28% of the population, that nearly 16% of
patients with papillary thyroid microcarcinoma, 4% of those with medullary thyroid cancers, and
2% of those with anaplastic thyroid cancers undergo unnecessary RAI therapy, with an estimated
cost burden of $9,599,497-16,098,824 per year for papillary thyroid microcarcinoma treatment
only. This cost is likely an underestimation, since we could not include in our analysis costs
associated with possible RAI complications and quality of life changes, and that our reported
costs are based on Medicare reimbursements, which are likely to be lower than private
insurances rates. Additionally, we identified that certain patient factors, such as having low
income, receiving care in non-academic facilities, and having multifocal and larger thyroid tumors
were associated with an increased risk of receiving inappropriate RAI after a papillary thyroid
microcarcinoma diagnosis.

• Dr. Roman: There is good evidence that practice guidelines have a positive impact on the
outcome of patients with thyroid cancer; guidelines regarding the appropriate use
of Adjuvant radioactive iodine are important in providing a platform for improved care. This
study highlights the importance of better dissemination of national practice guidelines
among health care providers and centers, especially in areas who serve vulnerable patients
populations.
this study?
• Dr. Roman: Future research should be oriented towards identifying reasons for non-
adherence to guidelines and determining better ways of disseminating knowledge on
adjuvant radioactive iodine therapy recommendations for non-academic health care teams,
in order to improve patient care.
• Citation:
• Goffredo P, Thomas SM, Dinan MA, Perkins JM, Roman SA, Sosa JA. Patterns of Use and Cost
for Inappropriate Radioactive Iodine Treatment for Thyroid Cancer in the United States: Use
and Misuse. JAMA Intern Med. Published online February 16, 2015.
doi:10.1001/jamainternmed.2014.8020.

Physical Activity in Elders Increased By Pedometers and Nursing Input
Tess Harris
St George’s University of London
• MedicalResearch: What is the background for this study?
• Response: Physical activity is vital for both physical and mental health in older people,
preventing at least 20 common health problems. Yet the majority of older people do not
achieve the World Health Organisation physical activity guidelines for health of at least 150
minutes every week of at least moderate-to-vigorous intensity physical activity in bouts that
each last at least 10 minutes. Brisk walking is a good way to achieve moderate intensity
physical activity, with a low risk of harm. Pedometers can give you direct feedback on your
step-count and accelerometers record both step-counts and the intensity of physical activity
achieved. The PACE-Lift trial assessed whether an intervention to increase walking,
comprising pedometer and accelerometer feedback, combined with physical activity
consultations provided by practice nurses over a 3 month period, based on simple behaviour
change techniques, could lead to sustained increases in physical activity in 60-75 year olds.

Tess Harris
• MedicalResearch: What did the researchers do and what are the main findings?
• Response: The researchers enrolled 298 people aged 60-75 years from 3 different UK general
practices and randomised them by household to receive either standard care or the above
intervention aimed to increase physical activity. At 3 months, the intervention group’s
average daily step-counts were 1037 steps higher than the control group’s and participants in
the intervention group spent 63 more minutes per week in moderate-to-vigorous physical
activity of 10 minutes or more than those in the control group. At 12 months, those
differences were 609 steps per day and 40 minutes per week. Adverse effects, such as falls or
injuries, were similar between groups, and qualitative interviews and a focus group
conducted at the end of the study revealed that participants and practice nurses were very
positive about the intervention.

Tess Harris
• MedicalResearch: What should clinicians and patients take away from your report
• Response: This study demonstrates that practice nurses can safely deliver an intervention to
increasing walking, as demonstrated by both increased steps and increased time in moderate
intensity physical activity. The intervention had a lasting effect, with demonstrable differences at 12
months (9 months after the intervention was over). If sustained, this level of increased physical
activity is estimated to decrease risk of heart disease by 5.5% and type 2 diabetes by 9.1%, with
additional reductions in risk in other common diseases too. The main advantages that primary care
offers are an ideal setting for delivering physical activity interventions in this age group and the
opportunity to integrate this into routine care.
• MedicalResearch: What recommendations do you have for future research as a result of this
study?
• Response: Further trials are needed to distinguish which aspects of the intervention were most
effective, whether the intervention will be effective in more socio-economically diverse
populations, and to determine the costs of implementing a program like this on a larger scale.
• A Primary Care Nurse-Delivered Walking Intervention in Older Adults: PACE (Pedometer
Accelerometer Consultation Evaluation)-Lift Cluster Randomised Controlled Trial
• Tess Harris , Sally M. Kerry, Christina R. Victor, Ulf Ekelund, Alison Woodcock, Steve Iliffe, Peter H.
Whincup, Carole Beighton, Michael Ussher, Elizabeth S. Limb, Lee David, Debbie Brewin, Fredrika
Adams, Annabelle Rogers, Derek G. Cook
Published: February 17, 2015
DOI: 10.1371/journal.pmed.1001783

Illicit Marketing Practices of UK, Swedish Pharmaceutical Companies Outlined
Shai Mulinari Researcher, PhD
Sociology, Lund University
Dr. Mulinari : Over the past decade, several so-called whistleblower cases have spotlighted
the illicit marketing practices of pharmaceutical companies in the US but relatively few
similar cases have been brought in Europe. The reason for this discrepancy is unclear but one
possibility is that the wider use of self-regulation in Europe encourages companies to comply
with drug promotion rules and deters illicit conduct. But to date self-regulation of medicines
promotion has been poorly studied.
• We therefore investigated pharmaceutical industry self-regulation in the UK and Sweden.
These are two countries often cited as places where self-regulation is effective. One of things
that we found was that between 2004 and 2012 the Swedish and UK self-regulatory bodies
ruled that 536 and 597 cases, respectively, were in breach of the country’s rules on medicines
promotion; many of the violations in both countries concerned misleading claims about a
drug’s effects. This equates to an average of more than one case per week in each country.
• Charges incurred by companies because of these violations were equivalent to about 0.014%
and 0.0051% of annual sales revenue in Sweden and the UK, respectively. Notably, nearly
20% of the cases in breach of the code of conduct in both countries were serious breaches.

Illicit Marketing Practices of UK, Swedish Pharmaceutical Companies Outlined
Shai Mulinari Researcher, PhD
Sociology, Lund University
• Dr. Mulinari : The prevalence and severity of breaches testifies to a discrepancy between the
ethical standard codified in industry codes of conduct and the actual conduct of the industry.
Clinicians and patients should therefore always take a critical stance regarding pharmaceutical
industry marketing practices. I also want to stress the importance of reporting potential industry
misconduct to the regulatory bodies responsible for the oversight of marketing activities.
• Medical Research: What recommendations do you have for future research as a result of this
study?
• Dr. Mulinari : Future studies need to assess the effectiveness of various policies for improving
industry behaviour, such as larger fines for violations and giving greater publicity to rulings. There is
also a need to investigate promotion and its regulation in other countries.
• Citation:
• Complaints, Complainants, and Rulings Regarding Drug Promotion in the United Kingdom and
Sweden 2004–2012: A Quantitative and Qualitative Study of Pharmaceutical Industry Self-
Regulation
• Anna V. Zetterqvist, Juan Merlo, Shai Mulinari
•
• Published: February 17, 2015
• DOI: 10.1371/journal.pmed.1001785

Study Finds No Link Between Head Injuries and Parkinson’s Disease
Line Kenborg, MSc, PhD
Survivorship Unit Danish Cancer Society Research Center
Copenhagen
this study?
• Response: Future studies need to examine head injuries in combination with genetics or
environmental risk factors for Parkinson disease such as pesticides, which we did not include
in our study. Further, the studies need to include a proper time window between head
injuries and the diagnosis of Parkinson disease to exclude head injuries that might be due to
the undiagnosed movement disorder.
• Citation:
• Head injury and risk for Parkinson disease
• Results from a Danish case-control study
• Kenborg L1, Rugbjerg K2, Lee PC2, Ravnskjær L2, Christensen J2, Ritz B2, Lassen CF2.
• Neurology. 2015 Feb 13. pii: 10.1212/WNL.0000000000001362. [Epub ahead of print]

Study Finds No Link Between Head Injuries and Parkinson’s Disease
Line Kenborg, MSc, PhD
Survivorship Unit Danish Cancer Society Research Center
Copenhagen
Response: The hypothesis that head injuries increase the risk for Parkinson disease has been
examined in many studies during the past decades, but the findings have been highly
inconsistent. We have previously examined the hypothesis in a study based on information
on head injuries and Parkinson disease from the Danish National Hospital Registry. In this
study, we found a positive association between a hospital contact for a head injury in middle
or late adulthood and a diagnosis of Parkinson disease. The reported association, however,
was almost entirely due to injuries that occurred during the months preceding the first
hospital contact for Parkinson disease. Because we used information from registries, we
lacked detailed diagnostic information to distinguish Parkinson disease from other types of
parkinsonism, and we had no information on milder head injuries and head injuries in early
life. So we wanted to study whether head injuries throughout life increased the risk for
Parkinson disease in the largest interview-based case-control study to date including patients
with a verified diagnosis of Parkinson disease. The main finding of our study is that we do not
find any association between head injuries and Parkinson disease.
• Response: Our study is observational so we cannot say anything about causality. Based on
our results, however, it seems that one or several mild or severe head injuries do not
increase the risk for Parkinson disease.

Delayed School Entry May Disadvantage Preterm Children
Julia Jaekel PhD
Department of Developmental Psychology
Ruhr-University Bochum in Germany
Dr. Jaekel: Recent reports suggest that delayed school entry (DSE) may be beneficial for
children with developmental delays. However, studies of the effects of DSE are inconclusive.
Our study investigated the effects of delayed school entry versus age-appropriate entry (ASE)
in a large sample after minimizing selection bias and accounting for confounding effects of
preschool knowledge. We found that delayed school entry has no effect on Year 1 teacher
ratings of academic performance. In contrast, DSE children’s standardized mean test scores of
mathematics, reading, writing and attention at 8 years of age were lower than ASE children’s
mean scores.
• Dr. Jaekel: These findings are particularly applicable to preterm children who are born up to
four months before their due date and may enter school less mature compared with their
peers. Parents of preterm children often inquire whether they can delay entry into school as
they believe it would benefit their child. This may arise from an expectation that preterm
children will developmentally catch-up with their peers over time. However, parents and
professionals should be aware that delayed school entry may not promote preterm children’s
academic performance. Thus decisions to delay school entry should be taken with due
caution as there may be disadvantages arising from missing one year of learning
opportunities or not receiving special educational support. Effectively, delayed school entry
may mean that children miss out on learning opportunities during the critical early years.

Delayed School Entry May Disadvantage Preterm Children
Julia Jaekel PhD
Department of Developmental Psychology
Ruhr-University Bochum in Germany
this study?
• Dr. Jaekel: There are two implications for future research:
• Firstly, we need studies investigating how to best provide specific educational support for
children who have failed their school entry exams. Researchers, clinicians, teachers, and
parents need to work together in order to ensure that children with developmental delays
receive the specific help they need to thrive in school.
• Secondly, future research is needed to determine the long-term impact of delayed school
entry on academic performance and attainment at the end of formal schooling.
• Citation:
• Julia Jaekel, Vicky Yu-Chun Strauss, Samantha Johnson, Camilla Gilmore, Dieter Wolke.
Delayed school entry and academic performance: a natural experiment. Developmental
Medicine & Child Neurology, 2015; DOI: 10.1111/dmcn.12713

For Moderate or Severe Diabetic Macular Edema, Eylea Is Best
Adam Glassman, M.S.
Director, DRCRnet Coordinating Center Jaeb Center for Health Research
Tampa, FL 33647
Response: Diabetic macular edema (DME) is the most common cause of vision loss in patients with
diabetes, impairing the vision of approximately 750,000 people in the United States. The most
common treatment involves the injection into the eye of one of 3 drugs that inhibit vascular
endothelial growth factor (VEGF). The relative effectiveness and safety of these 3 drugs, Eylea,
Avastin and Lucentis were unknown. We compared the 3 drugs by randomly assigning 660 patients
with center-involved Diabetic macular edema and vision loss to receive injections of either Eylea,
Avastin, or Lucentis as often as every 4 weeks (according to protocol defined retreatment criteria)
for one year. The results showed that all three drugs, on average, improved vision in eyes with
Diabetic macular edema. However, in eyes with moderate or worse vision loss, Eylea was more
effective, on average, at improving vision than the other two drugs. In eyes with mild vision loss at
baseline (20/32 to 20/40), the average gain in vision was similar with all 3 drugs.
• Response: This study should help doctors and patients make informed treatment decisions
regarding the management of diabetic macular edema. The results are reassuring in that all drugs
have been shown to be effective at improving vision and that all 3 drugs are equally safe, so doctors
can confidently use any one of the drugs to treat diabetic macular edema. All drugs performed
similarly, on average, when baseline vision loss was mild. Eyes with worse initial vision improved
more with Eylea than the other drugs. However, the choice of drug in an individual patient requires
consideration of cost, insurance coverage and other factors not addressed in our study.

For Moderate or Severe Diabetic Macular Edema, Eylea Is Best
Adam Glassman, M.S.
Director, DRCRnet Coordinating Center Jaeb Center for Health Research
Tampa, FL 33647
this study?
• Response: The current study is continuing for a second year for each participant to assess the
longer term comparative effectiveness of the three drugs. Previous studies using
ranibizumab showed a smaller number of injections in the second year of diabetic macular
edema treatment than in the first, so it will be interesting to see if this the current study
shows similar results for all three drugs. In addition, in all three treatment groups there was
a proportion of eyes in which diabetic macular edema did not completely resolve within the
first year of treatment. It would be interesting to know why DME sometimes persists in
particular eyes even with anti-VEGF therapy and what other treatment options may be
available for this unique cohort.
• Citation:
• Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema
• The Diabetic Retinopathy Clinical Research Network
• February 18, 2015DOI: 10.1056/NEJMoa141426

Reassurance After False Alarms May Delay Future Cancer Screenings
Dr Cristina Renzi
Department of Epidemiology and Public Health, University College London, Health Behaviour Research Centre, London, UK
• MedicalResearch: What is the background for this study? What are the main findings?
• Dr. Renzi: Only a minority of symptomatic individuals undergoing cancer investigations are
diagnosed with cancer and more than 80% receive an ‘all-clear’ or non-cancer diagnosis (here
called a ‘false alarm’). This makes it important to consider the possible unintended consequences of
a false alarm.
• Several studies have shown that investigations for a suspected cancer can have negative
psychological effects, even for individuals ultimately diagnosed with a benign condition. In addition,
an association between false alarms and subsequent delayed diagnosis has been reported for
various cancers, with both patients and healthcare providers contributing to delays.
• Our review published by BMJ Open focused on 19 research papers which reported information on
false alarms and subsequent symptom attribution or help-seeking. By integrating the available
evidence from qualitative, quantitative and mixed methods studies this review allowed us to
identify areas that need to be addressed in order to reduce the risk of delayed help-seeking after a
previous false alarm. In particular, over-reassurance and under-support of patients can be an
unintended consequence of a false alarm leading to delays in help-seeking, even years later, if
patients notice possible symptoms of the disease again.
• The review, funded by Cancer Research UK, looked only at adult patients who had a false alarm
after raising concerns about their symptoms; the effect of a false alarm might be different in
patients who are investigated for suspected cancer following cancer screening.

Dr Cristina Renzi
• MedicalResearch: What should clinicians and patients take away from your report?
• Dr. Renzi: Our study suggested that patients may delay seeking help for new or recurrent symptoms
if they feel over-reassured following a previous false alarm or felt under-supported at the time by
the healthcare system. In particular, over-reassurance from the previous ‘all-clear’ diagnosis can
lead to subsequent symptoms being interpreted as benign. Our review has also shown that under-
supporting patients receiving an all-clear diagnosis can negatively impact future symptom
interpretation and help-seeking. The perception that symptoms were previously dismissed as
unimportant was a relevant theme explaining subsequent delays, most often because of not
wanting to appear hypochondriacal. Several studies also reported that insufficient explanation or
advice at the time of the false alarm, on possible causes of the symptoms or the next steps, left
patients feeling that doctors could not help them, and unsure about what to do next. Many of the
studies reported on prolonged delays, suggesting that the effects of a false alarm can be long-
lasting, and may generalize beyond recurrence of the original symptom to new symptoms
appearing some time later. In the case of breast symptoms, a benign diagnosis appeared to give
some women a false sense of security persisting for many years.
• Providing appropriate, balanced information to patients who have a cancer false alarm, including
making sure they don’t feel foolish about having sought help, might encourage them to check out
any future symptoms earlier. A clinical encounter providing information before and after diagnostic
investigations may be valuable to ensure that bodily sensations are not dismissed following
negative examinations, and to discuss next steps in the case of recurrent or new symptoms. It’s
important that patients don’t have a false sense of security and understand they should still seek
help if they notice any potential cancer symptoms even after an all-clear diagnosis.

Dr Cristina Renzi
• MedicalResearch: What recommendations do you have for future research as a result of
this study?
• Dr. Renzi: The evidence on the effects of a false alarm is limited as the majority of studies are
based on qualitative data collection methods and are limited by small sample size,
retrospective design and lack of control groups. More prospective studies are needed, also
including information provided by healthcare professionals.
• The majority of studies were conducted in English-speaking countries, mainly the UK and the
USA, with a few from Northern Europe. More international comparisons, including central
and southern European countries could provide a different perspective on common issues.
• Prospective studies are needed to identify the appropriate forms of patient-information to
avoid unintended consequences of false alarms on subsequent symptom attribution and
help-seeking.
• Citation:
• Renzi, K. L. Whitaker, J. Wardle. Over-reassurance and undersupport after a ‘false alarm': a
systematic review of the impact on subsequent cancer symptom attribution and help
seeking. BMJ Open, 2015; 5 (2): e007002 DOI: 10.1136/bmjopen-2014-007002

Arsenic in Drinking Water Linked to Increased Risk Of Heart Disease and Diabetes
Katherine A James, PhD, MSPH, MSCE
Colorado School of Public Health
University of Colorado Denver, Aurora, Colorado
Dr. James: Exposure to inorganic arsenic in drinking water has been associated with several
chronic diseases including cardiovascular disease and diabetes mellitus in areas with high
levels of exposure. Our study is one of the first to show association with cardiovascular
disease and diabetes mellitus in a low-moderately exposed population. Our results show that
for every 15 micrograms per liter of inorganic arsenic in drinking water the risk for CHD
disease increased 38% and for diabetes it increases 27%.
• Dr. James: Both patients and clinicians should be aware of potential exposure to inorganic
arsenic and make effort to reduce or eliminate exposure especially in children and
adolescents.

Arsenic in Drinking Water Linked to Increased Risk Of Heart Disease and Diabetes
Katherine A James, PhD, MSPH, MSCE
Colorado School of Public Health
University of Colorado Denver, Aurora, Colorado
this study?
• Dr. James: Recommendations are to continue to characterize the risk at various stages in life
(prenatal vs. child vs adolescent vs adult) and also determine what the biologically relevant
exposure period is for chronic diseases including cancer. Other areas of research to pursue
are co-exposures to other naturally occurring metals with similar adverse effects such as
cadmium or lead.
• Citation:
• Association between Lifetime Exposure to Inorganic Arsenic in Drinking Water and
Coronary Heart Disease in Colorado Residents
• Katherine A. James,1 Tim Byers,1 John E. Hokanson,1 Jaymie R. Meliker,2 Gary O. Zerbe,1 and
Julie A. Marshall1
• Environ Health Perspect; DOI:10.1289/ehp.1307839
• MedicalResearch.com Interview with:, & Katherine A James, PhD (2015). Arsenic in Drinking
Water Linked to Increased Risk Of Heart Disease and Diabetes

Sugar May Add To Excessive Gestational Weight Gain
MedicalResearch.com Interview with: Ekaterina Maslova PhD
Doctor of Science in Nutrition and Epidemiology
Center for Fetal Programming
Copenhagen, Denmark
Response: From prior studies we know that excessive gestational weight gain (GWG) in pregnancy is
associated with complications for both the mother and the child, including gestational diabetes,
hypertension, and high birth weight. Understanding the factors that determine gestational weight
gain would allow for interventions early on to improve pregnancy outcomes. Dietary intake has
been found to influence gestational weight gain in other studies, but evidence is conflicting and still
quite limited. In non-pregnant populations a high-protein diet was shown to decrease weight and
improve weight maintenance. We therefore hypothesized that a similar relation may exist
for gestational weight gain in pregnant women.
• In this study we had data on dietary intake of more than 45,000 Danish women who were pregnant
between 1996 and 2002. We examined the relation between their intake of protein and
carbohydrates and the rate of gestational weight gain (in grams per week). We found that women
who consumed a high protein-to-carbohydrate (PC) ratio gained less gestational weight gain
compared to women with a lower PC ratio in their diet. The results was stronger in women who
started their pregnancy already overweight compared to normal weight women.
• Since a high PC ratio may result from either a high protein intake or low carbohydrate intake, we
decided to focus on a component of carbohydrates that may increase gestational weight gain:
added sugar. We found that pregnant women with higher intake of sugar gained more weight in
pregnancy compared to those who consumed less added sugar. This averaged out to about 1.4 kg
(or 7%) higher weight gain across the entire pregnancy.

Copenhagen, Denmark
• Response: Dietary interventions in pregnant women many have clinically relevant effects on
gestational weight gain, especially in overweight women. Any recommendations on protein
and carbohydrate intake need to consider not only the quantity of intake but also the quality
of the dietary sources (e.g. animal, vegetable) as well as address substitution foods. For
example, a decrease in added sugar may lead to an increase in artificial sweeteners, which
may carry their own risks. These findings need also to be regarded in the context of other
research findings, nutrient requirements in pregnancy, and the patient’s own situation and
needs.

Copenhagen, Denmark
this study?
• Response: It will, first of all, be important to have these findings replicated in other large
cohorts and such studies need to include overweight and obese women in addition to normal
weight women. Evaluating the diet-gestational weight gain relation separately in these
groups of pregnant women would tell us whether they may benefit more (or less) from a
change in their macronutrient intake. If more conclusive evidence is needed these dietary
changes could be evaluated in a randomized clinical trial.
• Citation:
• Maslova E,
• Halldorsson TI, Astrup A, Etal Dietary protein-to-carbohydrate ratio and added
sugar as determinants ofexcessive gestational weight gain: a prospective cohort study.
• BMJOpen 2015;: e005839. doi:10.1136/
bmjopen-2014-005839

High DNA Mutation Rate In Teenage Dads May Lead To More Birth Defects
Dr. Peter Forster PhD
Fellow of Murray Edwards College and
McDonald Institute at the University of Cambridge
•
• Dr. Forster: As a result of our paternity testing work at the Institute for Forensic Genetics in
Munster (Germany), we have accumulated a pool of over 24,000
parents and their children, of whom we know for certain that they are
biologically related. Occasionally we observe a new mutation in these
children, which must have come either from the sperm or the egg of one
of the parents. As we analyse highly variable microsatellite DNA (a
repetitive type of DNA, also know as STR DNA, which stands for “short
tandem repeat” DNA), we can fairly easily find out whether the mutation
has come from the mother or the father. It turns out that the fathers
contribute 6-7 times more mutations to the children than the mothers do.
This has long been known. What is new is that we have observed that the
male and female teenagers at puberty do NOT set out with the same low
mutation load, but instead, the teenage boys already have a sixfold
higher mutation load in their sperm than the girls in their oocytes.

• Dr. Forster: In recent years clinical research has accumulated showing that children
from older fathers (above 35) but also from teenage fathers have an
increased risk for conceiving children with birth defects. The incidence
for birth defects in the general population is 1.5 percent, and the
increased rate for teenage fathers might be on the order of 2 percent.
Also, these children seem to be at a higher risk of low birth weight,
low IQ, schizophrenia and autism. It appeared logical to those
researchers that older fathers may have a less than pristine genome in
their germline, which would explain the higher incidence of defects. But
they were puzzled by the teenage effect, and suggested that other
explanations need to be sought. Our study removes this complication by
showing that teenage fathers already set off with a high DNA mutation
load.

this study?
• Dr. Forster: So our main message is to clinical researchers to continue looking for
genetic explanations for birth defects and cognitive disorders in
children of teenagers, especially where the father is young. As the
individual risk of an abnormal child is still relatively low, expectant
teenage couples should not be too anxious. But as a policy matter, even
half a percent of additional cases of birth defects in a population is
worrying and teenage parenthood should therefore continue to be
discouraged. I caution however I say this as a geneticist, and ideally
the epidemiologists should now embark on quantitative risk assessments
which can be implemented as guidelines.
• Citation:
• Peter Forster, Carsten Hohoff, Bettina Dunkelmann, Marianne Schürenkamp, Heidi Pfeiffer,
Franz Neuhuber, Bernd Brinkmann. Elevated germline mutation rate in teenage fathers.
Proceedings of the Royal Society B, February 2015 DOI: 10.1098/rspb.2014.2898

Model Show Lucentis Markedly Reduces Blindness From Diabetes
Rohit Varma, MD, MPH
Professor and Chair, Department of Ophthalmology USC Eye Institute, Keck School of Medicine
University of Southern California, Los Angeles, Calif
Dr. Varma: The Centers for Disease Control and Prevention estimates that 4.4% of adults with
diabetes aged 40 and older have advanced diabetic retinopathy that may result in severe
vision loss. Clinical trials have shown that intravitreal injections of anti-VEGFs, such as
ranibizumab, can reduce visual impairment and even in some cases improve visual acuity
outcomes in patients with diabetic macular edema. We developed a model, based on data
from the RIDE and RISE clinical trials, to estimate the impact of ranibizumab treatment on
the number of cases of vision loss and blindness avoided in non-Hispanic white and Hispanic
persons with diabetic macular edema in the United States.Results from the model suggest
that, compared with no treatment, every-4-week ranibizumab 0.3 mg reduces legal blindness
between 58%-88% and reduces vision impairment between 36%-53% over 2 years in this
population.
• Dr. Varma: Our results emphasize the importance of treating diabetic macular edema (DME)
and the role of anti-VEGFs in the prevention of vision loss. These data are particularly
important given the large number of individuals with diabetic retinopathy in the United
States, including those in the workforce

Model Show Lucentis Markedly Reduces Blindness From Diabetes
Rohit Varma, MD, MPH
Professor and Chair, Department of Ophthalmology USC Eye Institute, Keck School of Medicine
University of Southern California, Los Angeles, Calif
this study?
• Dr. Varma: At this time, we do not yet know how well this diabetic macular edema model
translates to clinical practice. Therefore, future research should include examining the impact
of the use anti-VEGFs on visual impairment and blindness prevalence in individuals
with diabetic macular edema in the real world setting of clinical practice. Additionally, as
this analysis was limited to a population of Hispanic and non-Hispanic white individuals in the
United States, it would be important to expand the research to include other racial/ethnic
groups.
• Citation:
• Visual impairment and blindness avoided with ranibizumab in Hispanic and non-Hispanic
whites with diabetic macular edema in the United States
• Varma, Rohit et al. Ophthalmology

Less Than Half of Adolescents Report Getting Enough Sleep
Katherine M. Keyes, Ph.D.
Assistant Professor of Epidemiology Columbia University
Mailman School of Public Health New York, NY 10032
Dr. Keyes: The Monitoring the Future study is an annually conducted survey of 8th, 10th, and
12th grade high school students in the United States, covering a wide range of adolescent health
behaviors. The same questions on adolescent sleep were queried every year since 1991, allowing
us to examine historical trends in the amount of sleep adolescents report. We found that there
have been substantial decreases in the proportion of adolescents who report 7 or more hours of
sleep on a regular basis, across all age groups and across all demographic groups. In the most
recent years, after age 15, less than half of adolescents report regularly getting 7 or more hours
of sleep every night. Given the importance of sleep in both the short and the long term for
adolescent health, these findings suggest substantial public health concern.

• Dr. Keyes: We encourage parents, educators, clinicians and public health professionals to talk
with adolescents about the recommended guidelines for sleep, 8-10 hours a night, and how
obtaining adequate sleep and help adolescents achieve goals, both academically and socially.
Sleep is critical to adolescent health, and reinforcing the benefits of sleep to adolescents may
improve outcomes.

this study?
• Dr. Keyes: We found that the majority of the decreases in adolescent sleep occurred in the
1990s, before smart phones and social media became embedded in most adolescent lives.
Health outcomes that changed across that time include major increases in pediatric and
adolescent overweight and obesity – given that such health outcomes are linked to sleep
problems, we speculate that such changes may be linked to the historical trends in sleep that
we have observed. Future studies should examine the extent to which changes in obesity and
other health problems may be linked to adolescent sleep patterns, and continued monitoring
and surveillance of adolescent sleep is critical to ongoing public health efforts.
• Citation:
• The Great Sleep Recession: Changes in Sleep Duration Among US Adolescents, 1991–2012
Katherine M. Keyes, Julie Maslowsky, Ava Hamilton, and John Schulenberg
• Pediatrics peds.2014-2707; published ahead of print February 16, 2015,
doi:10.1542/peds.2014-2707
• MedicalResearch.com Interview with: Katherine M. Keyes, Ph.D. (2015). Less Than Half of
Adolescents Report Getting Enough Sleep

Minority Patients With Lupus Kidney Disease May Have Suboptimal Care
Laura Plantinga, PhD Assistant Professor
Division of Renal Medicine, Department of Medicine
Emory University School of Medicine Atlanta, GA 30322
Dr. Plantinga: Quality of care for end-stage renal disease (ESRD), which is treated with dialysis or
kidney transplantation, is a high priority for the U.S. healthcare system, given universal coverage
of these services. However, quality of ESRD care remains relatively unexplored in lupus patients,
who have multiple providers and may have greater access to care. We found that, overall, nearly
three-quarters of U.S. ESRD patients with lupus had pre-ESRD nephrology care and about 20% of
lupus patients on dialysis were waitlisted for kidney transplant per year; however, fewer than
one-quarter of those who started on dialysis had a permanent vascular access in place, which is
associated with better outcomes than a temporary catheter. Furthermore, patients who were
black or Hispanic were nearly a third less likely to have pre-ESRD care and were also less likely to
be placed on the kidney transplant waitlist in the first year of dialysis than white patients. Having
Medicaid or no insurance at the start of ESRD were both associated with lower likelihood of
quality ESRD care by all measures, despite universal Medicare coverage after the start of ESRD.
While there was geographic variation in quality of ESRD care, patterns were not consistent across
quality measures.

• Dr. Plantinga: Despite multiple national and regional quality-of-care initiatives and incentives
aimed at improving care in the overall ESRD population, care for lupus patients with ESRD
remains suboptimal, particularly with respect to permanent vascular access placement.
Minority patients and those with Medicaid or no insurance—who represent the majority of
the young, predominantly female lupus population—were even less likely to access quality
care than their white, privately insured counterparts. Better patient-provider, as well as
provider-provider communication, could improve quality of ESRD care in this population.

this study?
• Dr. Plantinga: Further study regarding the potential barriers to improving quality of ESRD
care in this population at the levels of the health system, ESRD Networks, providers (including
rheumatologists, nephrologists, and transplant and vascular access surgeons), and patients is
warranted. Our results also identify specific targets for potential intervention studies to
improve the translation of quality-of-care measures in this population (particularly,
permanent vascular access placement) and the patient subpopulations that are least likely to
receive high-quality care.
• Citation:
• Sociodemographic and geographic predictors of quality of care in U.S. patients with end-
stage renal disease due to lupus nephritis
• Laura C. Plantinga, Cristina Drenkard, Rachel Patzer, Mitchel Klein, Michael R. Kramer,
Stephen Pastan, S. Sam Lim and William M. McClellan
• Accepted manuscript online: Arthritis and Rheumatology 18 FEB 2015 09:53AM EST | DOI:
10.1002/art.38983
• MedicalResearch.com Interview with:, & Laura Plantinga, PhD Assistant Professor (2015).
MedicalResearch.com

Diet and Exercise Offer Some Protection Against Knee Pain in Obese Diabetics
Dan White PT , ScD, Msc
University of Delaware
• Dr. White: We know that diet and exercise are beneficial to reduce knee pain, however it is
not known whether diet and exercise can actually prevent the development of knee pain in
people at high risk. We found that an intensive program of diet and exercise had a small but
statistically significant protective effect with preventing the development of knee pain in
overweight and obese people with diabetes.
• Dr. White: Diet and exercise are effective are important to recommend to people who are
overweight and obese in order to prevent the onset of knee pain.
this study?
• Dr. White: We need to figure out how much physical activity and weight loss is necessary to
start to be protected from developing knee pain.
• Citation:
• Can an intensive diet and exercise program prevent knee pain among overweight adults at
high risk?
• White DK1, Neogi T, Rejeski WJ, Walkup MP, Lewis CE, Nevitt MC, Foy CG, Felson DT, And The
Look Ahead Research Group.
• Arthritis Care Res (Hoboken). 2015 Feb 18. doi: 10.1002/acr.22544. [Epub ahead of print]

Even Low-Level Physical Activity Improves Cardiac Risk
Thomas W. Buford, PhD Assistant Professor, Division of Clinical Research
Department of Aging and Geriatric Research, University of Florida College of Medicine
Director, Health Promotion Center University of Florida Institute on Aging
• Dr. Buford: This study was a cross-sectional analysis of data collected from over 1000 older
adults upon their entry into the Lifestyle Interventions and Independence for Elders (LIFE)
study. Briefly, participants were recruited into the LIFE Study who were over 70 years of age,
sedentary, and had mobility limitations. The objective of this study was to examine, at
baseline prior to their participation in the study interventions, the association between daily
physical activity habits and risk of major cardiovascular events (i.e. heart attack and coronary-
related death). The study utilized accelerometers, devices designed to identify and quantify
human movement, to measure participant’s daily activity. Predicted risk of cardiovascular
events was determined using a risk score established in the Framingham Heart Study. As
identified by accelerometry measures, participants spent on average 70% of their waking
hours being sedentary. The major finding of the study, however, was that even extremely
low-level activity was associated with an improved cardiovascular risk profile. For every 25-30
minutes a participant was sedentary per day, predicted risk was 1 percent higher. Conversely,
But activity identified as slightly above sedentary — which could be light housework or slow
walking — was associated with higher levels of the more beneficial kind of cholesterol, HDL,
in people with no history of heart disease.

• Dr. Buford: A common refrain we hear is that all individuals should exercise at a moderate-
intensity for at least 30 minutes on at least 3 days/week. It’s important to note that for many
of these older individuals with mobility limitations, this goal may be unrealistic at least
initially. This study indicates that even low-levels of activity may have an important impact in
preventing cardiovascular events among older adults. As I mentioned, much of the emphasis
has recently been placed on engaging in structured physical exercise. It is becoming
increasingly evident, however, that encouraging individuals to at least reduce the amount of
time they spend being sedentary may have important cardiovascular benefits. Encouraging
people – particularly those with conditions which limit their mobility – to avoid sitting for
extend periods of time and taking short breaks to move may have important health
implications and be easier for many people to adhere to, at least initially.

• Medical Research: What recommendations do you have for future research as a result of this study?
• Dr. Buford: One of the limitations of this study was that all participants were sedentary so the range of
activity levels was quite narrow. We hope to follow-up on this study to see how changes in their activity
patterns as the study progressed may influence these outcomes. It will be interesting to see if low-
intensity activities have the same value once the participants overall level of activity increases. We also
hope to utilize these data to examine relationships with the actual occurrence of cardiovascular events, as
opposed to using a risk score. More broadly, I think we as scientists and practitioners need to think more
closely about the population we are working with in developing physical activity recommendations. We
tend to want one-size-fits-all recommendations, but physical activity recommendations may need to more
tailored to individual populations. This is an area which I have great interest. Finally, scientists in recent
years have become increasingly interested in identifying differences between the lack of exercise/higher
intensity activity and chronic engagement in sedentary activities. This is referred to by some as “sitting
science”. The idea is that, even if you exercise for an hour in the morning, if you go and sit for 8 hours the
rest of the day you have health risks that are independent of the fact that you exercised. I think continuing
to increase our understanding of the distinct benefits and limitations of both structured exercise and low-
intensity physical activity will have important health implications.
• Citation:
• Association of Objectively Measured Physical Activity with Cardiac Risk in Mobility-limited Older Adults
• Thomas W Buford Don G Hire Walter T Ambrosius Stephen D Anton Timothy S Church John A Dodson
Anthony P Marsh Mary M McDermott Joe R Nocera Daniel K White Veronica Yank Marco Pahor Todd M
Manini
• Circulation. 2014; 129: AMP01

Active Surveillance May Be Appropriate for Ill Patients With Prostate Cancer
Karim Chamie MD
Department of Urology Ronald Reagan UCLA Medical Center
UCLA Medical Center, Santa Monica
Response: Active surveillance has been shown to be safe and effective. There are multiple
longitudinal studies that have demonstrated the safety of active surveillance for men with
indolent prostate cancer. In this context, we sought out to determine national practice
patterns for localized prostate cancer. Moreover, we wanted to identify patient, tumor, and
physician factors that influence treatment decision. What we found was that the vast
majority of patients undergo radiation therapy, regardless of patient age and health or
severity of tumor. Instead, by far the most significant predictor of whether a patient
undergoes radiation therapy is whether they have been referred to a radiation oncologist. On
the other hand, surgeons significantly incorporate patient age and health and tumor severity
when considering radical prostatectomy (surgery).
• Response: If a patient with indolent prostate cancer is too ill to undergo surgery (because of
the risk of mortality or complications), then they are unlikely to benefit from radiation
therapy. Instead, these patients often times suffer serious side effects from the radiation (e.g.
incontinence, bowel dysfunction, and erectile dysfunction) in their limited life expectancy. In
other words, if a patient is too ill to undergo surgery for their low-risk prostate cancer, then
they and their physician should strongly consider active surveillance and watchful waiting
as a viable alternative.

Active Surveillance May Be Appropriate for Ill Patients With Prostate Cancer
Karim Chamie MD
Department of Urology Ronald Reagan UCLA Medical Center
UCLA Medical Center, Santa Monica
this study?
• Response: Our next objective is to identify the incidence of complications due to radiation
therapy among those with indolent disease and a limited life expectancy. Ideally, we would
measure their quality of life and determine if there are any treatment regrets.
• Citation:
• Prasad SM, Sartor A, Bennett CL. Population-Based Assessment of Determining Treatments
for Prostate Cancer. JAMA Oncol. Published online February 19, 2015.
doi:10.1001/jamaoncol.2014.183.
•
• MedicalResearch.com Interview with: Karim Chamie MD (2015). Who Receives Surgery or
Radiation for Prostate Cancer?
• MedicalResearch.com Interview with:, & Karim Chamie MD (2015). Active Surveillance May
Be Appropriate for Ill Patients With Prostate Cancer MedicalResearch.com

NIH Study Examines Links Between Breastfeeding Duration and ChildhoodObesity
Yeyi Zhu, PhD IRTA Postdoctoral Fellow Epidemiology Branch
Division of Intramural Population Health Research
Eunice Kennedy Shriver National Institute of Child Health and Human Development,
• MedicalResearch: What is the background for this study? What are the main findings?
• Dr. Zhu: Currently in the US, nearly two thirds of reproductive-aged women are overweight or
obese. Moreover, the amount of weight gained during pregnancy can have immediate and long-
lasting impacts on health of a woman and her infant. Previous evidence implicates that excessive
gestational weight gain above the Institute of Medicine guidelines is related to high birthweight
(>4000 g), a marker of intrauterine over-nutrition which may impose a greater risk of offspring’s
obesity and metabolic diseases in later life.
• Given that more than one third of children and adolescents are overweight or obese in the US, it is
of great public health significance to improve our understanding of determinants and mediators of
childhood obesity. The length of breast feeding and age at introduction of solid foods are infant
feeding practices that are potentially modifiable in early life. We therefore examined whether
birthweight and infant feeding practices, specifically length of breast feeding, mediate the
relationship between maternal gestational weight gain and childhood growth in the National
Children’s Study Formative Research in Anthropometry, a cross-sectional multi-ethnic study of 1387
mothers and their children aged 0-5.9 years in the US (2011-2012).
• We illustrated that the intergenerational relationship between maternal gestational weight gain
and early childhood growth (i.e., z scores for weight-for-age, weight-for-height, and body mass
index-for-age) largely acts through birthweight rather than directly on childhood growth. Further,
given the negative association of breastfeeding duration with childhood anthropometrics, longer
length of breastfeeding suppressed the positive associations of gestational weight gain and
birthweight with childhood growth. In addition, analysis by ethnicity revealed that these
associations were only significant in non-Hispanic White and non-Hispanic Black participants as
opposed to Hispanics and other ethnicities.

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