MedicalResearch.com - Medical Research Week in Review

MedicalResearch.com
Exclusive Interviews with Medical Research and
Health Care Researchers from Major and Specialty Medical
Research Journals and Meetings
Editor: Marie Benz, MD
info@medicalresearch.com
April 20 2014
For Informational Purposes Only: Not for Specific Medical Advice.

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For Whiplash Treatment: Education and Advice As Good As Prolonged PT
MedicalResearch.com Interview with: Zoe Michaleff
PhD Student, Musculoskeletal Division
The George Institute for Global Health
Sydney NSW 2000 Australia
MedicalResearch.com: What are the main findings of the study?
Answer: Our study showed that a 30 minute advice session with two phone call follow ups was as
effective for chronic whiplash as the comprehensive physiotherapy exercise program in which
participants received twenty, one-hour individually-tailored and supervised exercise sessions over
a 12-week period. While people’s pain and activity improved in both treatment groups, the most
important finding is that there were no differences between groups. This finding held true for all
outcome measures except for two secondary outcome measures of self rated recovery (global
perceived effect) and functional ability (patient specific functional scale) which were in favour of
the comprehensive exercise program however the size of these effects were too small to be
considered clinically meaningful.
There is evidence to suggest that whiplash patients are not all the same and that their response
to treatment may differ depending on individual patient characteristics for example the presence
of symptoms suggestive of sensory hypersensitivity or post traumatic stress and the duration of
injury. Our secondary analyses did not reveal a differential response to treatment based on these
factors nor did a longer duration of symptoms affect participant’s response to treatment.
Read the rest of the interview on MedicalResearch.com

• MedicalResearch.com: Were any of the findings unexpected?
• Answer: Yes, the results of our randomised controlled trial were definitely unexpected. The primary
hypothesis of our study was that the comprehensive exercise program would be more effective than a
single advice session in reducing pain, disability and improving quality of life for people with chronic
whiplash. This hypothesis was supported by a strong biological and theoretical rationale and confirmed by
the results of a small pilot study. We were therefore quite surprised with the finding that that the
comprehensive exercise program was equally effective as one advice session with the option of two phone
call follow ups.
• MedicalResearch.com: What should clinicians and patients take away from your report?
• Answer: The results of our study suggest that more treatment is not necessarily better for people with
chronic whiplash and that people can have just as good an outcome by attending only one session of
physiotherapy and learning how to self manage their condition. Our study actually adds to the growing
body of literature that suggests that we need to rethink how we deliver treatment to people with a
chronic whiplash injury, and perhaps for these people intensive treatment is not required. Traditionally
physiotherapy involved long courses of one-to-one care. More recently, it’s become clear that to deliver
physiotherapy more efficiently traditional treatments need to be reconfigured from long programs of care
to effective, simple and shorter treatments where the patient is actively involved.
• Patient’s expectations of treatment and their health practitioner need to be better aligned with current
evidence and this study highlights the importance of getting patients actively involved in treatment.
Clinicians have an important role in educating and empowering patients with the information required to
allow them to self manage their condition and therefore become more self reliant. This information must
include educating patients about whiplash, the principles of progressing activity, the identification of
patient specific functional goals and teaching patients simple neck and shoulder exercises aimed at
improving posture, range of motion, coordination and strength.

• MedicalResearch.com:What recommendations do you have for future research as a result of this
study?
• Answer: For the future we need to identify the best ways in which to deliver simple self
management advice and education. Education and advice has been shown to be as effective as
more costly interventions and yet we need to better understand how to deliver these to patients in
the most effective manner. This may involve the development and use of verbal, written, or
multimedia approaches that reflect the cultural diversity within Australia.
• In general, we need to identify effective and affordable strategies to prevent and treat
musculoskeletal conditions, as these are one of the leading causes of disability and chronic pain in
the latest Global Burden of Disease study. This is especially true for those with chronic whiplash-
associated disorders because most have tried and failed previous treatments and their continuing
symptoms mean they would be unlikely to pursue more of the same approaches.
• Citation:
• Comprehensive physiotherapy exercise programme or advice for chronic whiplash (PROMISE): a
pragmatic randomised controlled trial
• Dr Zoe A Michaleff PhD,Prof Chris G Maher PhD,Chung-Wei Christine Lin PhD,Trudy Rebbeck
PhD,Prof Gwendolen Jull PhD,Prof Jane Latimer PhD,Prof Luke Connelly PhD,Prof Michele Sterling
PhD
The Lancet – 4 April 2014
DOI: 10.1016/S0140-6736(14)60457-8

Chronic Hepatitis C: RESTORE Study Results
MedicalResearch.com Interview with: Christophe Moreno, MD, PhD
Directeur clinique, clinique d’Hépatologie
Service de Gastroentérologie
Hépatopancréatologie et Oncologie Digestive
• MedicalResearch.com: What are the main findings of the study?
• Dr. Moreno: The RESTORE study is an open label, phase 3 study, evaluating Simeprevir in
combination with PegIFN and ribavirin in genotype 4 Chronic Hepatitis C patients, either
naïve or treatment experienced. Results of this study demonstrated high efficacy of this
combination, with an overall SVR rate of 65.4%. Efficacy is particularly high in treatment naïve
and prior relapsers patients, with SVR rate of 82.9% and 86.4%, respectively.
• Moreover, treatment naïve patients and prior relapsers were eligible to a shorter treatment
duration of 24 weeks if they met response-guided therapy (RGT) criteria (defined by an HCV
RNA below 25 at week 4 and undetectable at week 12). 89.5% met RGT criteria. Of those,
94.1% achieved a SVR.
• Dr. Moreno: No unexpected finding was observed in the RESTORE trial. In particular, the
safety profile was good, and comparable to the one observed in studies of Simeprevir in
combination with PegIFN and ribavirin in Chronic Hepatitis C (CHC) genotype 1 patients.

Chronic Hepatitis C: RESTORE Study Results
MedicalResearch.com Interview with: Christophe Moreno, MD, PhD
Directeur clinique, clinique d’Hépatologie
Service de Gastroentérologie
Hépatopancréatologie et Oncologie Digestive
• Dr. Moreno: Simeprevir in combination with PegIFN and ribavirin become one of the new standard
of care for Chronic Hepatitis C genotype 4 patients. This regimen offers a particularly high chance of
SVR with a shorter treatment duration of 24 weeks in treatment naïve and experienced patients.
• MedicalResearch.com: What recommendations do you have for future research as a result of this
study?
• Dr. Moreno: An ongoing trial is evaluating Simeprevir in combination with PegIFN and ribavirin
in Chronic Hepatitis C genotype 4 naïve patients with mild or moderate fibrosis, with a very rapid
virological response.
• Future research would evaluate Simeprevir in combination with another DAA (with antiviral activity
against genotype 4), in order to propose an IFN-free regimen to this group of patients in the future.
• Citation:
• ONCE-DAILY SIMEPREVIR (TMC435) WITH PEGINTERFERON/RIBAVIRIN IN TREATMENT-NAÏVE OR
TREATMENT-EXPERIENCED CHRONIC HCV GENOTYPE 4-INFECTED PATIENTS: SVR12 RESULTS OF A
PHASE III TRIAL
• MORENO ET AL. ONCE-DAILY SIMEPREVIR (TMC435) WITH PEGINTERFERON/RIBAVIRIN IN
TREATMENT-NAÏVE OR TREATMENT-EXPERIENCED CHRONIC HCV GENOTYPE 4-INFECTED PATIENTS:
SVR12 RESULTS OF A PHASE III TRIAL. ABSTRACT PRESENTED AT THE INTERNATIONAL LIVER
CONGRESS™ 2014

Evaluating Pulmonary Nodules for Cancer: Patients May Receive Too Much, Too Little Care
MedicalResearch.com Interview with: Renda Soylemez Wiener, MD, MPH
Assistant Professor of Medicine The Pulmonary Center
Boston University School of Medicine Center for Healthcare Organization & Implementation Research
Edith Nourse Rogers Memorial VA Hospital
• Dr. Soylemez Wiener: The main finding is that evaluation of pulmonary nodules to determine
whether or not they are cancerous is inconsistent with clinical practice guideline recommendations
in almost half of cases, suggesting there is room for improvement in clinical care of these patients.
Patients with pulmonary nodules are sometimes evaluated more aggressively than they should be
(18%), which can cause harms to patients from unnecessary invasive tests (biopsies or surgery) or
unneeded radiation exposure from imaging studies. Still more patients (27%) are followed less
aggressively than they should be, which in the worst case scenario could lead to delays in the
diagnosis and treatment of cancer. It is particularly important to improve care of these patients
now, because new guidelines from the US Preventive Services Task Force recommend CT screening
for lung cancer screening, which often finds pulmonary nodules that require evaluation.
• Dr. Soylemez Wiener: I was surprised that almost half of patients with a pulmonary nodule received
care that was inconsistent with guidelines. I was also surprised by the extent of overevaluation we
observed in some cases, with some patients with very small nodules subjected to testing for years
for an incidentally detected radiographic finding with a very low likelihood of cancer. Unfortunately,
I was not surprised that many patients with pulmonary nodules received underevaluation. Given
how many pulmonary nodules are detected with today’s highly sensitive CT scans, it is difficult to
ensure all patients receive appropriate evaluation unless there are systems in place to track
patients with pulmonary nodules.

• Dr. Soylemez Wiener: It is important for clinicians and patients alike to recognize that there is
a real gap between care that is currently being delivered to patients with pulmonary nodules
and what clinical practice guidelines consider optimal care. I would like both clinicians and
patients to understand the harms that inappropriate evaluation of pulmonary nodules can
cause, including both harms of overly aggressive evaluation (unneeded radiation exposure
with the associated risk of radiation-induced tumors, physical complications from
unnecessary biopsies and surgeries) and harms of under-evaluation (potential for delays in
cancer diagnosis and treatment). Part of the solution will be drawing attention to the fact
that a problem exists, which may prompt clinicians to be more attentive to nodule evaluation
and to educate patients about the importance of adherence to evaluation. Clinicians should
educate patients about what a pulmonary nodule is, the likelihood of cancer, and what the
evaluation process will entail. If patients understand the process better and why it is
important, I believe they will be more likely to follow through with the necessary testing and
advocate for themselves.

study?
• Dr. Soylemez Wiener: I believe our work makes it clear that systems must be implemented to
improve quality of care of pulmonary nodule evaluation. For example, in some cases, there were
delays in evaluation because of failures of communication between providers (such as the primary
care provider not being informed of a pulmonary nodule that was detected during a hospitalization
or on a pre-operative chest x-ray). In other cases, radiologists recommended evaluation strategies
that were not consistent with guideline recommendations, and the treating clinician simply
followed the radiologist’s recommendations. A logical next step for future research is to study the
impact of different systems designed to improve pulmonary nodule evaluation. Some possible
quality improvement strategies to be tested include better flagging of clinicians when a nodule is
identified, templated radiographic reporting of pulmonary nodules that include a summary of
relevant guideline recommendations, registries to track patients with pulmonary nodules to make
sure they are receiving evaluation in a timely fashion, improved communication and educational
materials explaining to patients what pulmonary nodules are and why it is important to complete
the evaluation process, and dedicated nurse coordinators to facilitate evaluation of patients with
pulmonary nodules
• Citation:
• Resource Use and Guideline Concordance in Evaluation of Pulmonary Nodules for Cancer: Too
Much and Too Little Care
• Wiener R, Gould MK, Slatore CG, Fincke BG, Schwartz LM, Woloshin S. Resource Use and Guideline
Concordance in Evaluation of Pulmonary Nodules for Cancer: Too Much and Too Little Care. JAMA
Intern Med. 2014;():. doi:10.1001/jamainternmed.2014.561

Rhematoid Arthritis: Treatment with Traditional Chinese Remedy
MedicalResearch.com Interview with:
Zhang, Xuan MD Professor of Medicine Dept. of Rheumatology Peking Union Medical College Hospital Beijing,China,100730 and
Dr. Peter E. Lipsky, MD Formerly National Institute of Arthritis and Musculoskeletal and Skin Diseases
National Institutes of Health, Bethesda, MD,
• Prof. Zhang & Lipsky--The results of this study indicate that TwHF is effective for the
treatment of active rhematoid arthritis (RA). Importantly, these are the first data indicating
that TwHF is effective in DMARD-naïve patients with active rheumatoid arthritis. At week 24,
TwHF monotherapy resulted in significant improvement of disease activity, including pain
assessment, the patient’s and physician’s global assessment, tender joint counts, swollen
joint counts, ESR, CRP, and HAQ and SF-36 scores. MTX monotherapy and TwHF monotherapy
had similar efficacy as shown by ACR20, ACR50 and ACR70 response criteria, EULAR and cDAI
good response criteria, as well as DAS28 remission criteria and low disease activity(LDA) rate.
The efficacy of TwHF was not inferior to that of MTX, and MTX +TwHF combination therapy
was more effective than MTX monotherapy in treating active rhematoid arthritis. A safety
evaluation of the study demonstrated that the frequency of total adverse events and severe
adverse events of TwHF monotherapy was not significantly higher than that of MTX
monotherapy, except for a slightly increased frequency of irregular menstruation.

Rhematoid Arthritis: Treatment with Traditional Chinese Remedy
Zhang, Xuan MD Professor of Medicine Dept. of Rheumatology Peking Union Medical College Hospital Beijing,China,100730 and
Dr. Peter E. Lipsky, MD Formerly National Institute of Arthritis and Musculoskeletal and Skin Diseases
National Institutes of Health, Bethesda, MD,
• Prof. Zhang & Lipsky: In Peking Union Medical College Hospital (PUMCH), the tertiary referral centre in China, we treat over
30 000 patients with rhematoid arthritis each year and more than half of them are treated with TwHF, in most cases in
combination with MTX, because of the low cost of TwHF. Importantly, in ‘real-world’ clinical practice, we have observed the
considerable effectiveness of the MTX+TwHF combination, so we are not surprised at the findings of this RCT in which all
patients were assessed by trained investigators who were unaware of the therapeutic regimen.
• Prof. Zhang & Lipsky: TwHF could be a promising approach to the treatment of active rheumatoid arthritis, particularly as
not all patients respond to DMARDs, and because these drugs are expensive.
• MedicalResearch.com: What recommendations do you have for future research as a result of this study?
• Prof. Zhang & Lipsky: We will continue to follow-up this cohort of patients and compare the radiological progression when
the patients have completed 2 years of treatment. We are looking forward to the results and will share our findings in the
near future.
• Citation:
• Comparison of Tripterygium wilfordii Hook F with methotrexate in the treatment of active rheumatoid arthritis
• Qian-wen Lv,Wen Zhang,Qun Shi,Wen-jie Zheng,Xin Li,
Hua Chen,Qing-jun Wu,Wan-lan Jiang,Hong-bin Li,Lu Gong, Wei Wei,Hui Liu,Ai-jing Liu,
Hong-tao Jin,Jun-xiang Wang,Xiu-mei Liu,
Zhen-bin Li,Bin Liu,Min Shen,Qian Wang,Xiang-ni Wu,Di Liang,Yu-feng Yin,
Yun-yun Fei,Jing-mei Su,Li-dan Zhao,Ying Jiang,Jing Li,Fu-lin Tang,Feng-chun Zhang,Peter E Lipsky,Xuan Zhang
• Ann Rheum Dis annrheumdis-2013-204807Published Online First: 14 April 2014 doi:10.1136/annrheumdis-2013-204807

Pregnancy Complications Increase With Obesity
Dagfinn Aune MS Department of Epidemiology and Biostatistics
School of Public Health Imperial College London St. Mary’s Campus
Norfolk Place, Paddington, London W2 1PG, UK
• Answer: We conducted a systematic review and meta-analysis of studies examining the
association between maternal body mass index (BMI) and risk of fetal death, stillbirth,
neonatal, perinatal and infant death. We found that the risk of all these outcomes increased
with greater BMI in a dose-response fashion. For example even within the high end of what is
considered the normal BMI range (BMI of 24-25) there was a 10-20% increase in the relative
risk, but the strongest relations were seen for those who were obese and morbidly obese
with 30-60% and 2-3 fold increases in the relative risk respectively (depending on the
outcome examined).
• Answer: We knew that many studies had previously reported increased risk so in that sense
we were not surprised. The findings are consistent with an increasing number of pregnancy
complications that are related to overweight and obesity.

Pregnancy Complications Increase With Obesity
Dagfinn Aune MS Department of Epidemiology and Biostatistics
School of Public Health Imperial College London St. Mary’s Campus
Norfolk Place, Paddington, London W2 1PG, UK
• Answer: The findings show that excess body weight is an important risk factor for fetal death,
stillbirth and infant death and suggest that being quite lean within the normal BMI range is
associated with the lowest risk. As the BMI increases the risk increases with a dose-response
relationship. Although these are quite rare outcomes in high-income countries and the absolute
risk is low, they are devastating for the parents that are affected. In addition, there are a number of
other more common pregnancy complications that are strongly linked to overweight and obesity,
including gestational diabetes, preeclampsia, gestational hypertension, and macrosomia, so it’s an
important issue that needs to be addressed.
study?
• Answer: We need more data regarding the optimal gestational weight gain in relation to stillbirths
and studies of weight change between pregnancies and risk of stillbirths in the latter pregnancy. In
addition, studies are needed to clarify whether physical activity could reduce the risk. There are
some data showing reduced risk of other obesity-related pregnancy complications such as
gestational diabetes and preeclampsia in women who are physically active compared to inactive
women, but we need to expand those investigations into stillbirths and other pregnancy outcomes
as well.
• Citation:
• Aune D, Saugstad O, Henriksen T, Tonstad S. Maternal Body Mass Index and the Risk of Fetal Death,
Stillbirth, and Infant Death: A Systematic Review and Meta-analysis. JAMA. 2014;311(15):1536-
1546. doi:10.1001/jama.2014.2269.

Salt Reduction Program Led To Population Drop In Blood Pressure, Stroke and Heart Disease Deaths
MedicalResearch.com Interview with: Dr. Feng He
Wolfson Institute of Preventive Medicine
Barts and The London School of Medicine and Dentistry
Queen Mary University of London, London, UK
• Dr. He:
• The UK salt reduction program has led to a fall in population blood pressure and thereby
contributed to the reduction in stroke and heart disease deaths.
• In 2003, the UK Food Standards Agency and CASH (Consensus Action on Salt & Health)
developed a salt reduction program. As approximately 80% of the salt in the diet is added to
food by the food industry i.e. in processed foods, fast foods, canteen and restaurant foods
etc, the public have no choice about eating it. Therefore progressive incremental targets to
limit the amount of salt for each food category were set, which the industry had to achieve in
a specified time. Reductions first started in 2003 and are continuing to this day.
• The salt reduction program has been very successful and led to a 15% reduction in the
average salt intake of the population, from 9.5g per day in 2003 to 8.1g per day in 2011
(P<0.05).
• Over the same time period, blood pressure fell in the adult population by 3 mm Hg systolic
and 1.4 mm Hg diastolic (P<0.0001). Stroke and heart disease deaths fell by 42% (P<0.0001)
and 40% (P<0.0001) respectively.
• It is possible that these falls in blood pressure and deaths from stroke and heart disease were
attributable to various factors such as changes in diet, lifestyles and the improvement in the
treatment of cardiovascular disease and its risk factors. Our further analysis showed that the
reduction in salt intake played an important role, particularly in the falls in blood pressure.

In a further analysis, we looked at individuals who were not on any drug treatment for blood
pressure and a correction was made for all other variables that could have influenced blood
pressure, apart from salt. There was still a fall in adult population blood pressure of 2.7mm Hg
systolic/ 1.1mm Hg diastolic, (P <0.0001). This reduction in blood pressure could therefore be
largely attributed to the fall in salt intake. It is well established that raised blood pressure
throughout its range is a major cause of stroke and heart disease. The reduction in salt intake that
led to a fall in blood pressure would have played an important role in both stroke and heart
disease deaths. Despite considerable progress being made on salt reduction, the average salt
intake in England is still high. In 2011, it was 8.1 g/day which is over a third more salt than the
recommended level of 6g/day. Therefore continuing and much greater efforts are needed to
achieve further reductions in salt intake to prevent the maximum number of stroke and heart
disease deaths.

Dr. He:
• Patients should reduce their salt intake.
• Do not add salt at the table;
• Do not add salt or ˜flavor enhancers” made from salt such as stock cubes, soy sauce, when
preparing food or during cooking; use herbs, ginger, garlic, pepper, vinegar, lemon or lime
juice to add flavor instead;
• When eating at restaurants, ask the chef to add less salt to your meals;
• Importantly, check food labels for salt, compare products, brands and varieties, and choose
lower salt options.
• FoodSwitch, a free and easy to use health app, lets you scan the barcode of a product and
provides you with clear nutritional information with colour-coded ratings for the four key
food components – total fat, saturated fat (saturates), sugars and salt. It also gives you a list
of healthier choices.
• FoodSwitch is available as a free, UK-only download from iTunes and Google Play. – See more
at: http://www.actiononsalt.org.uk/foodswitch/#sthash.zoB8DYAa.dpuf
• SaltSwitch is a feature of the app, which focusses on the salt content of the food, and gives
you a list of less salty alternatives
http://www.actiononsalt.org.uk/foodswitch/FAQ/119965.html#AboutSaltSwitch

• MedicalResearch.com: What recommendations do you have for future research as a result
of this study?
Dr. He:
• The evidence for the benefit of salt reduction is very clear. The results of our study indicate
that we need to redouble our efforts in the UK, in particular to get the food industry to act
faster and more aggressively to save the maximum number of people from suffering and
dying from stroke and heart disease.
• Other countries should follow the UK’s lead. All countries should adopt a coherent and
workable strategy to reduce salt intake.
• Citation:
• Salt reduction in England from 2003 to 2011: its relationship to blood pressure, stroke and
ischaemic heart disease mortality.
Feng J He, Sonia Pombo-Rodrigues, Graham A MacGregor
• BMJ Open 2014;4:4 e004549 doi:10.1136/bmjopen-2013-004549

Collaborative Treatment of Depression and Anxiety Feasible in Hospitalized Cardiac Patients
Dr. Jeffery C. Huffman, M.D.
Harvard Medical School Department of Psychiatry
Massachusetts General Hospital, Boston
• Dr. Huffman: Depression and anxiety in cardiac patients are associated with adverse cardiac
outcomes. We completed a very low-intensity care management intervention to identify
depression and anxiety disorders during a cardiac admission and then to assist in the
monitoring and management of the condition over the next 24 weeks. There have been
other care management trials in cardiac patients, but ours was the first to co-manage
depression and anxiety, the first to initiate treatment in the hospital, the first to take a broad
population of cardiac patients rather than a single diagnosis, and the first to use such a low-
resource strategy with only a single part-time social worker to coordinate care.
• We found that the care management intervention was associated with significant
improvements in mental health treatment, mental health related quality of life, depression,
and function at 24 weeks compared to enhanced treatment as usual. We did not find
differences in anxiety, adherence, or cardiac readmissions.

• Dr. Huffman: It was certainly quite a pleasant surprise to see that such an intervention had
significant effects—with moderate effect sizes—on these key clinical outcomes, given the
very pragmatic and inclusive approach to enrollment and the low-intensity intervention. It
suggests that this may be the right time to intervene and that a relatively lighter touch—if
correctly targeted—may have real effects.
• At the same time, this was not a “home run.” There were not effects on some key outcomes
, like anxiety or adherence, and the intervention did not impact readmissions. So more work
needs to be done to get to those important outcomes.
• The other unexpected thing is that our “treatment as usual” arm ended up having nearly 50%
of patients getting treatment for their condition because we continually informed patients
and treaters about the condition and ongoing symptoms in this arm, which is not really
treatment as usual—so we ended up giving oursevles a very high bar to get over.

• Dr. Huffman: That treatment of depression and anxiety disorders in hospitalized cardiac
patients is feasible, and when paired with a collaborative care model that facilitates ongoing
monitoring and care, can be associated with improvements in key outcomes that are
important to patients and physicians. And it may not take a giant overhaul of existing
systems to do so.
of this study?
• Dr. Huffman: As I noted, I don’t think this is yet something that is ready for immediate
implementation, especially if the goal is cardiac outcomes or readmissions. I think we have
found something that may improve function and quality of life, but to have something that is
both more powerful and might impact “bigger” outcomes, it may be worth having a slightly
more intensive intervention post-admission or using a blended care management model in
which the case manager monitors both psychiatric and medical symptoms, as in Wayne
Katon’s TEAMCare study.
• Citation:
• Huffman JC, Mastromauro CA, Beach SR, et al. Collaborative Care for Depression and Anxiety
Disorders in Patients With Recent Cardiac Events: The Management of Sadness and Anxiety in
Cardiology (MOSAIC) Randomized Clinical Trial. JAMA Intern Med. 2014;():.
doi:10.1001/jamainternmed.2014.739.

Irregular Menses Linked to High Risk of Ovarian Cancer
Barbara A. Cohn, Ph.D.
Director, Child Health and Development Studies
A Project of the Public Health Institute Berkeley, CA 94709
• Women with irregular menses had a statistically significant 2.4 fold increase in risk of death
due to any form ovarian cancer, and a statistically significant 3-fold increase in risk of death
due to late stage serous disease. Consistent with these findings, the incidence of late stage
disease at diagnosis, and late stage serous cancer was increased about 2-fold in women with
irregular menses.
• Irregular menses was defined as irregular cycles (variation of 10 days or more) or infrequent
cycles (>35 days) or history of annovulatory cycles identified during an in-person interview
with women at an average age of 26 years or mentioned in their medical records.

• MedicalResearch.com: What are the strengths of the study?
• Irregular menses was defined by women’s own report of usual cycle length when women
were an average age of 26 years, during an in-person interview. Errors of recall would be
minimal at that age and interviewers could probe for correct classification of irregular
menses.
• The study design was a prospective 50+ year follow-up of 14,403 pregnant women recruited
from 1959-1967 to the Child Health and Development Studies (www.chdstudies.org). There
were 103 incident cases and 65 ovarian cancer deaths in this study.
• We ruled out the contribution of infertility, the use of fertility drugs, or the use of birth
control bills as explanations of study findings. All women in this study had a live birth, and
medical records recorded pharmaceuticals prescribed 6 months prior to pregnancy.
Clomiphene was rarely used prior to 1967, nor were current methods of assisted
reproduction in use in the 1960’s. During this period, birth control pill use was also
infrequent, and pill formulations were very different from those currently in use.
• Women with irregular menses constituted 13% of this large pregnancy cohort, and so
findings are relevant to many women. Given the lack of information about risk factors,
screening or biomarkers for ovarian cancer in young life, our findings offer an opportunity for
prevention and for understanding the 90% of ovarian cancer cases that occur in women who
do not have rare heritable germline mutations or family history in a first degree relative.

• MedicalResearch.com: What are the weaknesses of the study?
• This study does not include infertile women (approximately 10 percent of all women) and
therefore findings are not relevant to risk of ovarian cancer in infertile women.
• There were some tumors with missing data on histology and stage, although there was no
evidence that missing data was correlated with irregular menses.
• Other than serous tumors, the most common form of ovarian cancer, the sample size for
other tumor types was too small for study. However, there was a suggestive finding that risk
of death due to endometroid tumors was also elevated (p=0.14).
• We estimate that about 80% of women with irregular menses may have polycystic ovarian
syndrome (PCOS). However women without significant clinical symptoms (e.g. hirsutism,
infertility, obesity) may never be diagnosed with PCOS, even today. Still we cannot determine
with certainty whether it is predominantly women with PCOS who were at increased risk of
ovarian cancer in our study.

• Findings were unexpected. The “incessant ovulation hypothesis” predicts that women with
less frequent cycles or more annovulatory cycles would be at lower risk of ovarian cancer. We
observed the opposite.
• Physicians may wish to obtain and record a history of usual menstrual cycle length; preferably
during women’s early reproductive years, when recall is more accurate. Even though there
are no known effective screening strategies for early detection of ovarian cancer, results of
clinical trials in progress, or other advances could provide an opportunity to offer women
with irregular cycles screening options in the future.
• Physicians may wish to begin a conversation with women who have irregular menses about
both the personal benefits and personal risks of oral contraceptives/hormonal
contraception. There is good evidence that oral contraceptive use correlates with lower risk
of ovarian cancer. It is important to emphasize that there is no known effective screening
strategy for ovarian cancer at this time, so this strategy may be a reasonable opportunity for
prevention until there are alternatives.

of this study?
• It would be of interest to replicate our findings with studies of similar design: prospective,
with assessment of cycle length during the reproductive years when errors of classification
are less likely. I am hopeful that our findings will stimulate interest in more research among
those with access to such data.
• Human pathology studies of tissues available from women with a history of irregular cycles
(but not infertility) in comparison to controls, and similarly designed endocrine studies could
yield clues about the etiology of ovarian cancer, and opportunities for prevention, early
detection and treatment for the 90% of ovarian cancers that occur in women without
evidence of heritable risk.
• Experimental studies in appropriate animal models where phenotypes correlated to “long or
irregular cycles” could be simulated would also advance understanding, similar to the
strategy of investigating the functional consequences of BRCA1 mutations in animal models.
• Citation:
• Abstract Presented at the AACR 2014 Irregular Menses and Ovarian Cancer

Sleeping Pills: Education Leads to Dose Reduction By Older Adults
MedicalResearch.com Interview with: Cara Tannenbaum, MD, MSc
The Michel Saucier Endowed Chair in Geriatric Pharmacology, Health and Aging,Professor of Medicine and Pharmacy
University of Montreal Centre de Recherche
Institut Universitaire de Gériatrie de Montréal Montreal, QC
• Dr. Tannenbaum: The EMPOWER study showed that providing older patients with
information about the harms of sleeping pill use led to discontinuation or dose reduction in
1-in-every 4 patients with longstanding use of benzodiazepines. Receipt of evidence-based
information about drug harms resulted in a 8-fold higher likelihood of benzodiazepine
cessation. Many physicians think that patients become too dependent on sedative-hypnotics
to successfully discontinue. Regardless of age, sex, and duration of use, 27% of patients aged
65-95 in this study successfully completed the recommended 20-week tapering protocol
during a 6-month time period and another 11% were in the process of tapering.
EMPOWERing patients with evidence-based information therefore results in appropriate risk
reduction.
• Dr. Tannenbaum: What was surprising was the number of physicians and pharmacists who
counseled patients NOT to discontinue benzodiazepine therapy. There is growing evidence
that even p.r.n use of sedative hypnotics – including classic benzodiazepines and the newer Z-
drugs – increases the risk of falls by 57%, with a two-fold greater risk of fractures. Use of
sleeping pills has also been conclusively associated with cognitive impairment and motor
vehicle accidents in older adults. De-prescribing at any age should be attempted, with
substitution of non-pharmacologic strategies for the treatment of insomnia or anxiety.

Sleeping Pills: Education Leads to Dose Reduction By Older Adults
MedicalResearch.com Interview with: Cara Tannenbaum, MD, MSc
The Michel Saucier Endowed Chair in Geriatric Pharmacology, Health and Aging,Professor of Medicine and Pharmacy
University of Montreal Centre de Recherche
Institut Universitaire de Gériatrie de Montréal Montreal, QC
• Dr. Tannenbaum: The main message is that older adults can actively participate in safer
medication management and should be included in decisions around continued use of
medications that increase the risk of harm.
of this study?
• Dr. Tannenbaum: It would be interesting to better understand the deterrents physicians face
in de-prescribing inappropriate prescriptions. Judicious prescribing for older adults involves
elimination of medications such as sedative hypnotics that increase the risk of harm. Why
then, do so many physicians and pharmacists continue to renew prescriptions for these
offending medications? Especially when both the American Board of Internal Medicine and
the American Geriatrics Society asks then to “Choose Wisely”.
• Citation:
• Reduction of Inappropriate Benzodiazepine Prescriptions Among Older Adults Through Direct
Patient Education: The EMPOWER Cluster Randomized
• Tannenbaum C, Martin P, Tamblyn R, Benedetti A, Ahmed S. Reduction of Inappropriate
Benzodiazepine Prescriptions Among Older Adults Through Direct Patient Education: The
EMPOWER Cluster Randomized Trial. JAMA Intern Med. 2014;():.
doi:10.1001/jamainternmed.2014.949.

Delirium: New Scoring System Relates Severity To Hospital Outcomes
MedicalResearch.com Interview with: Sharon K. Inouye, MD, MPH
Professor of Medicine, Harvard Medical School
Director, Aging Brain Center, Institute for Aging Research Hebrew SeniorLife both in Boston, MA
Study Co- Authors Cyrus Kosar, Douglas Tommet, Eva Schmitt, Margaret Puelle, Jane Saczynski, Edward Marcantonio and Richard Jones.
• Dr. Inouye: In this study, we developed and validated a new scoring system for delirium
severity. Delirium (acute confusional state) is a common and morbid complication of
hospitalization for older persons, which often goes undetected. Our new scoring system
indicates that the severity of delirium is directly related to hospital outcomes, such as length
of stay, nursing home placement, death, and healthcare costs.
MedicalResearch.com: Were any of the findings unexpected?
• Dr. Inouye: None of the findings were unexpected, but the strength of the associations were
more striking than we had anticipated. Thus, delirium was an important and independent
prognostic predictor.

Delirium: New Scoring System Relates Severity To Hospital Outcomes
MedicalResearch.com Interview with: Sharon K. Inouye, MD, MPH
Professor of Medicine, Harvard Medical School
Director, Aging Brain Center, Institute for Aging Research Hebrew SeniorLife both in Boston, MA
Study Co- Authors Cyrus Kosar, Douglas Tommet, Eva Schmitt, Margaret Puelle, Jane Saczynski, Edward Marcantonio and Richard Jones.
• Dr. Inouye: The main take-away message is that delirium is an incredibly important condition
that should not be missed. It carries the same mortality as acute myocardial infarction, which
is rarely missed. Yet delirium is routinely missed. We hope that this article will provide tools
to help increase the diagnosis of delirium and rating of its severity as a guide to clinical care.
of this study?
• Dr. Inouye: We believe that the CAM-S will be an important tool to help with future research
on delirium. The CAM-S should be used as an outcome measure for intervention trials and
management interventions, prognostic studies, and mechanistic studies. It provides a means
to quantify changes in and recovery from delirium over time. In addition, the availability of a
standardized measure can help to compare results across studies more readily.
• Citation:
• The CAM-S: Development and Validation of a New Scoring System for Delirium Severity in 2
Cohorts

Traumatic Stress Effects In Early Life Can Be Transmitted To Offspring
Prof Dr Isabelle Mansuy Lab of Neuroepigenetics
University/ETH Zürich Brain Research Institute
Zürich Switzerland
• Prof. Mansuy: The mains findings are that the transmission of the effects of traumatic stress
in early life involves small non-coding RNAs in sperm. The study shows that some microRNAs
are in excess in the sperm of adult males subjected to trauma during early postnatal life, but
are also altered in the brain and in blood, and that these alterations are associated with
behavioral and metabolic symptoms including depressive behaviors, reduced risk assessment
and altered glucose/insulin metabolism. Injecting sperm RNA in fertilized oocytes reproduces
these symptoms and confirm that RNA are the responsible factors.
•
• Prof. Mansuy: It was unexpected that sperm RNA is sensitive to trauma and can be a
mediator of the transmission of its effects across generations.
MedicalResearch.com: What should clinicians and patients take away from your report?

Traumatic Stress Effects In Early Life Can Be Transmitted To Offspring
Prof Dr Isabelle Mansuy Lab of Neuroepigenetics
University/ETH Zürich Brain Research Institute
Zürich Switzerland
• Prof. Mansuy: That environmental factors involving traumatic events and chronic stress in
early life can be responsible for severe psychiatric disorders not only in exposed individuals
but also in their progeny. In turn, that parents and children of affected people may need to
be considered. Also, that such negative events affect not only the brain but other parts of the
body and other functions not directly linked to the brain i.e. metabolism.
of this study?
• Prof. Mansuy: That environmental factors play a more important role than thought and that
people have to reconsider the importance of the genome in perspective of non-genomic and
epigenetic factors.
Citation:
• Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in
mice
• Nature Neuroscience (2014) doi:10.1038/nn.3695
• Published online 13 April 2014
Katharina Gapp, Ali Jawaid, Peter Sarkies, Johannes Bohacek, Pawel Pelczar, Julien
Prados, Laurent Farinelli, Eric Miska , Isabelle M Mansuy

After Stroke: Pharmacist Led Case Management Improved Blood Pressure Control
Finlay A McAlister MD
University of Alberta, Edmonton, Canada
• Dr. McAlister: We tested 2 systems of case management on top of usual care (note that at
baseline more than 3/4 of our study patients were already taking medications to lower blood
pressure (BP) and/or cholesterol but none were at guideline-recommended targets).
• The first (our “control” group) was a nurse seeing patients monthly x 6 months, measuring
their blood pressure and LDL cholesterol, counseling them about risk factor reduction
strategies (including lifestyle and medication adherence), and faxing results of BP/cholesterol
to their primary care physicians with advice to patients who had blood pressure or
cholesterol above guideline-recommended targets to see their primary care physician.
• The second (our “intervention” group) was a pharmacist seeing patients monthly x 6 months,
measuring their blood pressure and LDL cholesterol, counseling them about risk factor
reduction strategies (including lifestyle and medication adherence), and faxing results of
BP/cholesterol to their primary care physicians. However, if patients had blood pressure or
cholesterol above guideline-recommended targets instead of just recommending that the
patient see their primary care physician the pharmacist provided them with a prescription for
medication (or up-titration of their current medications) to address the uncontrolled risk
factor.
• Both groups improved substantially over usual care, but the intervention group improved
even more (13% absolute improvement in control of BP/cholesterol levels compared to the
nurse-led control arm) .

After Stroke: Pharmacist Led Case Management Improved Blood Pressure Control
Finlay A McAlister MD
University of Alberta, Edmonton, Canada
• MedicalResearch.com What should clinicians and patients take away from your report?
• Dr. McAlister:Stroke/TIA (minor stroke) is a warning sign for future cardiovascular events
including bigger strokes, heart attacks, or death.
• Current system of care results in more than 3/4 of patients who’ve had a stroke/TIA still
having inadequately controlled vascular risk factors even 6 months later.
• I think our study shows that case management by non-physician health care providers can
improve vascular risk factor management for at-risk patients, and that case management is
more effective if the case manager can actively modify medications rather than just feedback
risk factor levels to patients and/or their primary care physicians.
• MedicalResearch.com What recommendations do you have for future research as a result
of this study?
• Dr. McAlister: Future studies should test whether active case management works for other
“at risk” populations and to evaluate different “doses” of active case management – are
monthly visits required or could less frequent visits confer the same benefits?
• Citation:
• Case management for blood pressure and lipid level control after minor stroke:
Finlay A. McAlister, Sumit R. Majumdar, Raj S. Padwal, Miriam Fradette, Ann Thompson, Brian
Buck, Naeem Dean, Jeffrey A. Bakal, Ross Tsuyuki, Steven Grover, and Ashfaq Shuaib
• CMAJ cmaj.140053; published ahead of print April 14, 2014, doi:10.1503/cmaj.140053

Stroke: Fragmentation of Care Leads To More CT Scans, Higher Costs
Kimon Bekelis, MD
Department of Neurosurgery
Dartmouth-Hitchcock Medical CenterDr. Bekelis
• Dr. Bekelis: We demonstrated extensive regional and racial variation in the utilization of
head CT scans in the first year after ischemic stroke. Increased use paralleled spending in
corresponding Hospital Referral Regions. Greater fragmentation of care was associated with
high intensity head CT utilization. African-Americans were associated with increased
fragmentation of care and utilization of head CT.
• Dr. Bekelis: The extensive regional variation in the use of head CT for ischemic stroke has not
been demonstrated before. In addition, the racial disparities in these practices are striking
and are also reported for the first time. We identified that a major component of these
utilization patterns is fragmentation of care, an issue not addressed previously
through health care reforms. Hopefully the implementation
of Accountable Care Organizations will minimize disparities and maximize continuity of care,
with potential impacts in cost and overultilization.

Kimon Bekelis, MD
Dartmouth-Hitchcock Medical CenterDr. Bekelis
• Dr. Bekelis: We demonstrated that fragmentation of care is associated with overutilization of
costly and potentially hazardous imaging modalities. From a physician’s perspective, every
effort should be made to maintain continuity of care and enhance communication between
providers in order to minimize this dangerous practice. Patients should avoid seeing multiple
providers and be critical of unnecessary use of CT scans. Initiatives such as the “Choosing
Wisely Campaign” can assist patients with decision-making.
of this study?
• Dr. Bekelis: The best performing Hospital Referral Regions in terms of utilization and cost
should be studied further. The particular practice patterns in these areas, and their methods
of ensuring continuity of care should be identified. They can be used as examples that can be
mirrored in order to maximize efficiency and minimize cost in the constantly changing health
care landscape.
• Citation:
• Fragmentation of Care and the Use of Head Computed Tomography in Patients With
Ischemic Stroke.
• Bekelis K1, Roberts DW, Zhou W, Skinner JS.
Circ Cardiovasc Qual Outcomes. 2014 Apr 8. [Epub ahead of print]

Kimon Bekelis, MD
Dartmouth-Hitchcock Medical CenterDr. Bekeli
• Dr. Bekelis: We demonstrated extensive regional and racial variation in the utilization of
head CT scans in the first year after ischemic stroke. Increased use paralleled spending in
corresponding Hospital Referral Regions. Greater fragmentation of care was associated with
high intensity head CT utilization. African-Americans were associated with increased
fragmentation of care and utilization of head CT.
• Dr. Bekelis: The extensive regional variation in the use of head CT for ischemic stroke has not
been demonstrated before. In addition, the racial disparities in these practices are striking
and are also reported for the first time. We identified that a major component of these
utilization patterns is fragmentation of care, an issue not addressed previously
through health care reforms. Hopefully the implementation
of Accountable Care Organizations will minimize disparities and maximize continuity of care,
with potential impacts in cost and overultilization.

Kimon Bekelis, MD
Dartmouth-Hitchcock Medical CenterDr. Bekeli
• Dr. Bekelis: We demonstrated that fragmentation of care is associated with overutilization of
costly and potentially hazardous imaging modalities. From a physician’s perspective, every
effort should be made to maintain continuity of care and enhance communication between
providers in order to minimize this dangerous practice. Patients should avoid seeing multiple
providers and be critical of unnecessary use of CT scans. Initiatives such as the “Choosing
Wisely Campaign” can assist patients with decision-making.
of this study?
• Dr. Bekelis: The best performing Hospital Referral Regions in terms of utilization and cost
should be studied further. The particular practice patterns in these areas, and their methods
of ensuring continuity of care should be identified. They can be used as examples that can be
mirrored in order to maximize efficiency and minimize cost in the constantly changing health
care landscape.
• Citation:
• Fragmentation of Care and the Use of Head Computed Tomography in Patients With
Ischemic Stroke.
• Bekelis K1, Roberts DW, Zhou W, Skinner JS.
Circ Cardiovasc Qual Outcomes. 2014 Apr 8. [Epub ahead of print]

Antibiotics and Growth in Children From Low Income Countries
Ethan K Gough, PhD candidate Department of Epidemiology
Biostatistics and Occupational Health
McGill University, Montreal, QC, Canada
• Answer: Antibiotic use produces significant gains toward expected growth in children, for
their age and sex, from low- and middle-income countries. Children included in our study
were generally smaller in height and weight than adequately nourished children of the same
age, reflecting the spectrum of stunting and wasting malnutrition seen in low- and middle-
income countries. Antibiotic use had a larger impact on weight than height, and the effect on
weight was larger in populations who may be at greater risk of infections and early mortality,
such as populations with a high prevalence of HIV infection or exposure, and a high
prevalence of severe acute malnutrition.
• Answer: Not completely, no. Or hypothesis was that there would be a significant effect of
antibiotic use on growth in low- and middle-income countries, and that the antibiotic growth
promoting effect would vary by the characteristics of the children being treated.

Antibiotics and Growth in Children From Low Income Countries
Ethan K Gough, PhD candidate Department of Epidemiology
Biostatistics and Occupational Health
McGill University, Montreal, QC, Canada
• Answer: Our study demonstrates that in addition to the recognized benefits of antibiotics for
saving the lives of children at high risk for early mortality due to infections, antibiotics can
also improve the growth and development of these children. This has positive implications
for their development and future well-being. Unfortunately, in many low- and middle-income
countries, these select children are a meaningful proportion of the population. However, our
findings are NOT to be taken as evidence for wide-spread use of antibiotics to treat
malnutrition, due to concerns about antibiotic resistance. What is important, is that there is
some mechanism through which antibiotic use promotes growth in these children, and we
need to understand what that mechanism is.
of this study?
• Answer: Antibiotic treatment for undernourished children is not the best solution and more
research is needed to better understand the underlying reasons for improved growth so that
safer treatments can be developed.
• Citation:
• Gough EK ,Moodie EEM ,Prendergast AJ ,Johnson SMA ,Humphrey JH ,Stoltzfus RJ ,et al. The
impact of antibiotics on growth in children in low and middle income countries: systematic
review and meta-analysis of randomised controlled trials. BMJ 2014;348:g2267

Colon Cancer Surgical Outcomes in Elderly Improve
MedicalResearch.com Interview Invitation
Dorna Jafari, M.D. and Michael J Stamos, MD
Professor of Surgery John E. Connolly Chair, Department of Surgery
University of California, Irvine Orange, CA 92868
• Answer: Surgeons are faced with an aging population and data regarding outcomes is rare given
that many studies preclude the elderly from the study population. Therefore, it is difficult to
accurately discuss risk of surgical resection given the lack of data. Therefore we aimed to report the
national trends and outcomes of colorectal cancer treatment in the elderly population.
• We demonstrated that the majority of resections are performed in patients >65yeras old. There is a
trend towards a decrease in incidence of colorectal resection and a decrease in rate of mortality
during 2001-2010. However, the unique physiological changes associated with aging contribute to
increase morbidity and morality as demonstrated by our findings. In fact patients >85 years have a
472% increase in risk-adjusted mortality during a hospital admission compared to younger patients.
However, despite the substantially higher mortality and morbidity associated with age, there has
been a marked improvement in surgical outcomes in the elderly population.
• Answer: We encountered multiple interesting findings including the rate of decrease in surgical
resections for colorectal cancer, the improved rates of mortality and substantially higher rates of
mortality and complications in the elderly population.
• Perhaps the most unexpected finding was that the highest rate of decrease in the number of
resections was in the elderly, specifically 7% compared to 2% in the younger population. This would
lead us to believe that cancer screening may in fact be contributing to the decreased rate of elderly
patients requiring resection compared to younger population.
• We also discovered that despite the fact that age independently effected outcomes, over the past
10 years overall mortality rates improved. This improvement was seen mainly in the elderly. In fact
as patients aged, the rate of mortality improved.

Colon Cancer Surgical Outcomes in Elderly Improve
MedicalResearch.com Interview Invitation
Dorna Jafari, M.D. and Michael J Stamos, MD
Professor of Surgery John E. Connolly Chair, Department of Surgery
University of California, Irvine Orange, CA 92868
• Answer: We hypothesize that the improvement in mortality is attributable to improved surgical
technique and intra-operative and post-operative care of this subset of patients. We believe that
given this substantial improvement, we should strive to continue this trend given our aging
population. Social factors, increased rates of morbidity and mortality should be addressed with
patients so that there are realistic goals and expectations post-operatively.
study?
• Answer: This study demonstrates that we have had an overall improvement in mortality; therefore
future research should focus on specific areas where further improvements can be made. Given the
increased mortality in the elderly and the overall incidence in this population, we should also look
into our practices regarding screening in this subgroup and further consider the risk and benefit of
continued screening and surgical management based on patient life expectancy. Octogenarians and
beyond vary greatly in their physiologic condition and frailty tests have recently been shown to
predict outcome and recovery. Further analysis of the elderly based on such an index might allow
us to direct resources to the correct subset of the elderly population to garner the greatest rewards
in improved outcomes.
• Citation:
• Jafari MD, Jafari F, Halabi WJ, et al. Colorectal Cancer Resections in the Aging US Population: A
Trend Toward Decreasing Rates and Improved Outcomes. JAMA Surg. 2014;():.
doi:10.1001/jamasurg.2013.4930.

Obstructive Sleep Apnea Raises Risk of Osteoporosis
MedicalResearch.com Interview with: Kai-Jen Tien, MD
Division of Endocrinology and Metabolism,
Department of Internal Medicine, Chi Mei Medical Center Assistant Professor, Center of General Education
Chia Nan University of Pharmacy and Science Tainan, Taiwan
• Answer: We conducted the first and largest population-based cohort study to evaluate the
association of obstructive sleep apnea (OSA) and osteoporosis in a 6-year follow-up
investigation of an Asian population. OSA is characterized by repetitive episodes of
apnea/hypopnea and hypoxia in tissue, which might impact the bone metabolism. The results
of the study showed that patients with obstructive sleep apnea had 2.74 times the risk of
osteoporosis than patents without obstructive sleep apnea after adjustment for the patient`s
characteristics and comorbidities. Across all age groups and sex groups, individuals with OSA
had higher incidence rate of osteoporosis than individuals without obstructive sleep apnea.
Subgroup analysis showed that older patients and female patients had a higher risk for
osteoporosis than their younger and male counterparts.
• Answer: None of the findings were unexpected. Although most of those previous studies
were of small sample size and cross-sectional designs with inconsistent results, they indicated
that obstructive sleep apnea should have impact on bone metabolism. Our results further
confirmed that OSA would deteriorate bone health.

Division of Endocrinology and Metabolism,
Department of Internal Medicine, Chi Mei Medical Center Assistant Professor, Center of General Education
Chia Nan University of Pharmacy and Science Tainan, Taiwan
• Answer: As we know, the prevalence of obstructive sleep apnea is increasing in the world and it
raises the risk of many associated diseases, especially cardiovascular diseases. We find that OSA
also increases the risk for subsequent osteoporosis. Osteoporosis increases the risk of fracture,
medical expenditure, mortality and reduces the quality of life. So we need to pay more attention to
the relationship between obstructive sleep apnea and osteoporosis and construct some strategies
to prevent the disease in the future.
study?
• Answer: In the present study, we could not evaluate the impact of the family history of
osteoporosis, daily activity, eating habits, alcohol and tobacco use, that were known as risk factors
for osteoporosis. The exact mechanism that link OSA and osteoporosis were also unknown. The
future researches may need to cover these issues. In addition, studies are needed to clarify
whether early treatment of the OSA could reduce the risk of osteoporosis later in life.
• Citation:
• Obstructive Sleep Apnea and Risk of Osteoporosis: A Population-Based Cohort Study in Taiwan
• Yu-Li Chen, Shih-Feng Weng, Yuan-Chi Shen, Chien-Wen Chou, Chwen-Yi Yang, Jhi-Joung Wang, and
Kai-Jen Tien
• JCEM DOI: http://dx.doi.org/10.1210/jc.2014-1718

Low-Calorie Menu Categories Reduce Calorie Posting Benefits
Jeffrey R. Parker
Assistant Professor of Marketing
Robinson College of Business – Georgia State University
• Mr. Parker: Recently, there has been quite a bit of debate about the effectiveness of providing dish-
specific calorie information (a practice called “calorie posting”) on restaurant menus in terms of the
healthiness of consumers’ food choices. Some results suggest that such labels lead to lower-calorie
choices, while other research shows that there is no effect. We examined one factor that might impact the
effectiveness of calorie posting: the practice of grouping low-calorie options on a menu and labeling this
category accordingly (i.e., incorporating a low-calorie menu/category in the menu)—which we call “calorie
organizing”—as opposed to simply allowing them to appear in their natural categories with the caloric
content appearing in the dish descriptions (e.g., Sandwiches, Salads, Pastas, etc.).
• On the surface it seems obvious that making low-calorie options easier to find—by giving them their own
labeled category on the menu—would bolster the positive effects of calorie posting. However, we found
the opposite: additionally calorie organizing an already calorie-posted menu regularly eliminates the
benefits that calorie posting can have.
• We argued and found evidence indicating that the underlying cause of this effect stems from how
consumers make decisions. Restaurant menus are often too large for a consumer to seriously consider all
of the dishes. Some consumers typically eliminate large portions of the menu on the basis of simple
criteria (e.g., “I don’t like seafood.”, “It’s too early to eat pasta.”, etc. ). Since consumers generally make
negative inferences about low-calorie dishes (e.g., “They don’t taste good.”, “They are small dishes.”, etc.)
they are likely to summarily dismiss all of the low-calorie options early in the decision process when the
menu is calorie-organized (i.e., has grouped the low-calorie dished and labeled the new category
accordingly). Thus, they are likely to choose as poorly as they would were they given no calorie
information. In contrast, when the menu is just calorie-posted, and the low-calorie dishes appear in their
natural categories, these dishes are unlikely to be dismissed in the early choice-simplification stages. Thus,
low-calorie dishes are likely to be seriously considered in the final decision process, during which the pros
and cons of dishes can be more comprehensively traded off, and are therefore more likely to be chosen.

Jeffrey R. Parker
•
• Mr. Parker: All of predictions derived directly from the intersection of previous theories and
findings. In that way, none of our findings were unexpected. In terms of intuitive beliefs and
expectations, these results deviate from most people’s expectations.
• MedicalResearch.com What should clinicians and patients take away from your report?
• Mr. Parker: We hope that our findings will help consumers make better decisions. Sometimes
big changes in behavior can come from simply pointing out behaviors consumers are
unaware they are in engaging. Further, our results suggest that the negative effects of calorie
organization diminish significantly when consumers take longer before selecting a dish (either
voluntarily or because they must wait before being able to order). Thus, simply requesting
that patients take their time in deciding which dish to order may lead to healthier choices.
Alternatively, specifically explaining our results might get some patients to realize that they
do tend to choose less healthy dishes when low-calorie menus are available.

Jeffrey R. Parker
of this study?
• Mr. Parker: We present some findings that the results reverse when the low-calorie dishes
are grouped but the category is given an appealing label (e.g., “Favorites”). Further research
in this direction will certainly be beneficial. Of particular importance, as is the case with all
research that hopes to help consumers make better decisions, will be replicating these
results in a variety of circumstances and contexts with an eye toward determining the
robustness of our results and identifying important boundary conditions.
• Citation:
• How and When Grouping Low-Calorie Options Reduces the Benefits of Providing Dish-
Specific Calorie Information
• Journal of Consumer Research April 2014

Calcium Scores: Predictive Of Heart Disease Death Even In Low Risk Adults
Rine Nakanishi, MD, PhD
Los Angeles Biomedical Research Institute
• Dr. Nakanishi: With growing evidence that a measurement of the buildup of calcium in
coronary arteries can predict heart disease risk, Los Angeles Biomedical
Research Institute (LA BioMed) researchers found that the process of
“calcium scoring” was also accurate in predicting the chances of dying among
adults with little or no traditional risk factor of heart disease.
• The study conducted by LA BioMed researchers examined 5,593 adults with no
known heart disease and zero or minimal risk factor of heart disease –
including hypertension, dyslipidemia, diabetes, current smoking and family
history of heart disease — who had undergone coronary artery calcium
screening by non-contrast cardiac computed tomography from 1991-2011.
• Among the adults in the study, even those with low coronary artery calcium
scores of 1-99 were 50% more likely to die of heart disease than adults with
a calcium score of zero. Adults with moderate scores of 100-399 were 80%
more likely to die from heart disease than those with a score of zero, and
those with scores of 400 or more were three times more likely to die from
heart disease, when compared to adults with no calcified plaque buildup, or
a score of zero.
• Dr. Nakanishi: Previous studies had found that calcium scores were effective in predicting future
cardiovascular risks among adults with low-intermediate or
intermediate risk of coronary artery disease. These finding, along with
other research presented at ACC.14, the annual scientific session of the
American College of Cardiology in March, found coronary artery calcium
screening accurately predicted the future mortality risk among subjects at
low risk of coronary artery disease.

Calcium Scores: Predictive Of Heart Disease Death Even In Low Risk Adults
Rine Nakanishi, MD, PhD
Los Angeles Biomedical Research Institute
• Dr. Nakanishi: Normally, calcium scoring is only recommended for patients with
low-intermediate or intermediate risk of coronary artery disease. These
findings suggest that calcium scoring can be an effective tool for assessing
heart disease risks in adults with no or minimal risk factors so that they
can make the lifestyle and other changes that can help them avoid heart
disease in the future.”
of this study?
• Dr. Nakanishi: We continue to evaluate calcium scoring as a tool for assessing heart
disease risks and for helping provide the needed incentive for patients to
make the lifestyle choices – such as an improved diet, smoking cessation and
increased exercise – that will increase their chances of avoiding heart
disease.
• Citation:
Coronary Artery Calcium Score Predicts the Long-Term Mortality amongPatients
with No or Minimal Coronary Artery Risk Factor during 20 Years Observation
• Rine Nakanishi; Michael Blaha; Suguru Matsumoto; Anas Alani; Panteha Rezaeian;
Christopher Dailing; Matthew Budoff
• J Am Coll Cardiol. 2014;63(12_S):. doi:10.1016/S0735-1097(14)60979-7

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chi Mei Medical Center
Assistant Professor, Center of General EducationChia Nan University of Pharmacy and Science
Tainan, Taiwan
• Answer: We conducted the first and largest population-based cohort study to evaluate the association of obstructive sleep
apnea (OSA) and osteoporosis in a 6-year follow-up investigation of an Asian population. OSA is characterized by repetitive
episodes of apnea/hypopnea and hypoxia in tissue, which might impact the bone metabolism. The results of the study
showed that patients with obstructive sleep apnea had 2.74 times the risk of osteoporosis than patents without obstructive
sleep apnea after adjustment for the patient`s characteristics and comorbidities. Across all age groups and sex groups,
individuals with OSA had higher incidence rate of osteoporosis than individuals without obstructive sleep apnea. Subgroup
analysis showed that older patients and female patients had a higher risk for osteoporosis than their younger and male
counterparts.
• Answer: None of the findings were unexpected. Although most of those previous studies were of small sample size and
cross-sectional designs with inconsistent results, they indicated that obstructive sleep apnea should have impact on bone
metabolism. Our results further confirmed that OSA would deteriorate bone health.
• Answer: As we know, the prevalence of obstructive sleep apnea is increasing in the world and it raises the risk of many
associated diseases, especially cardiovascular diseases. We find that OSA also increases the risk for subsequent
osteoporosis. Osteoporosis increases the risk of fracture, medical expenditure, mortality and reduces the quality of life. So
we need to pay more attention to the relationship between obstructive sleep apnea and osteoporosis and construct some
strategies to prevent the disease in the future.
• Answer: In the present study, we could not evaluate the impact of the family history of osteoporosis, daily activity, eating
habits, alcohol and tobacco use, that were known as risk factors for osteoporosis. The exact mechanism that link OSA and
osteoporosis were also unknown. The future researches may need to cover these issues. In addition, studies are needed to
clarify whether early treatment of the OSA could reduce the risk of osteoporosis later in life.
• Citation:
• Obstructive Sleep Apnea and Risk of Osteoporosis: A Population-Based Cohort Study in Taiwan
• Yu-Li Chen, Shih-Feng Weng, Yuan-Chi Shen, Chien-Wen Chou, Chwen-Yi Yang, Jhi-Joung Wang, and Kai-Jen Tien
• JCEM DOI: http://dx.doi.org/10.1210/jc.2014-1718

Google Glass In the Operating Room: Promising, With Room for Improvement
Dr. Oliver Muensterer MD Ph.D
Division of Pediatric Surgery New York Medical College
Maria Fareri Children’s Hospital of Westchester Medical Center Valhalla, NY 10595, USA
• Dr. Muensterer: We looked at the functionality of Google Glass, a novel head-mounted mobile computer with integrated
display, camera, microphone, and speaker, in the clinical environment. While the technology has a lot of promise to be
useful for pediatric surgeons, in its current version, it also has significant limitations. The most obvious utilities are hands-
free photo- and videodocumentation, looking up medical terminology on the internet, help with coding and billing activities,
and hands-free telecommunication.
•
• Dr. Muensterer: The way Glass handles information made us take certain steps to protect patient privacy. Usually, all
acquired images and videos are automatically uploaded to the Google cloud. Because we were concerned that this
information could potentially end up on an unsecured server, we disabled the internet connection when taking images of
patients.
• Also, the batteries did not last very long when we were using Glass to record movies or for videoconferencing.
• Dr. Muensterer: This is promising technology, but before it can become mainstream in clinical medicine, some drawbacks
must be addressed. More apps for medical purposes must be written, and the issue of data privacy must be solved.
• Dr. Muensterer: There are a number of applications that we can envision in the future where Glass would be very helpful.
These include procedural training, telementoring, having pertinent information projected on the head-mount display in real
time, for example. This technology has great potential to really impact positively on patient care in the future.
• Citation:
• Google Glass in pediatric surgery: An exploratory study
Oliver J. Muensterer, Martin Lacher, Christoph Zoeller, Matthew Bronstein, Joachim Kübler
International Journal of Surgery
Volume 12, Issue 4, 2014, Pages 281–289

Prophylactic Anticoagulation for Venous Thrombosis In Critically Ill Patients
Craig M. Lilly, M.D. Professor of Medicine
Departments of Medicine, Anesthesiology, and Surgery, University of Massachusetts Medical School, and Clinical and Population Health
Research Program, Graduate School of Biomedical Sciences, Worcester, MA
• Dr. Lilly: Critically ill adults with clinicians that chose to manage them with prophylactic
anticoagulation were more likely to survive their hospitalization than patients that received venous
thrombosis prophylaxis with mechanical devices or were not treated with venous thrombosis
prophylaxis.
• Dr. Lilly: Patients that were managed by clinicians who chose to use mechanical device venous
thrombosis prophylaxis had higher in hospital mortality risk than patients managed without
prophylaxis.
• Dr. Lilly: Critically ill adults that do not have contraindications to anticoagulation should
receive pharmacological prophylaxis for VTE.
study?
• Dr. Lilly: We recommend that a means of fostering a randomized interventional study of the
relation of the alternative forms of venous thrombosis prophylaxis to in hospital mortality for
critically ill adults be created.
Citation:
• Thrombosis Prophylaxis and Mortality Risk among Critically Ill Adults
Craig M. Lilly, M.D.; Xinggang Liu, M.D., Ph.D.; Omar Badawi, Pharm.D. MPH.; Christine S. Franey,
MPH; Ilene H. Zuckerman, Pharm. D, Ph.D
Chest. 2014. doi:10.1378/chest.13-2160

Recommendation Allows Mother To Hold Newborn Immediately After Birth
MedicalResearch.com Interview with: Nestor E. Vain M.D.
Professor of Pediatrics, School of Medicine, University of Buenos Aires
Vice-President, FUNDASAMIN (Foundation for Maternal Infant Health), Argentina
Director, Neonatology, Hospital Sanatorio de la Trinidad Palermo and San Isidro, Buenos Aires
• MedicalResearch.com: What is the background of this study?
• Prof. Vain: Delayed umbilical cord clamping (DCC) is currently recommended by many
professional associations. The main reason is that it decreases the incidence of iron
deficiency in infancy, a very serious public health problem in developing countries, but also
prevalent in the USA and in western Europe. Besides it has other advantages in premature
infants such as better adaptation of the cardiovascular system to extra-uterine life. How
does Delayed umbilical cord clamping work?. Approximately 30% of the fetal blood volume is
in the placenta at the time of delivery. Waiting for a couple of minutes before clamping the
cord allows for a large part of that blood volume to return to the infant. (this process is
known as placental transfusion)
• Despite of these well known facts, and the absence of serious complications, the compliance
with the recommendation of delayed umbilical cord clamping is low. Why is that? There may
be a variety of reasons but we are certain that one very important one is that the majority of
obstetricians and neonatologists believe that to achieve an efficient placental transfusion and
to avoid a negative effect from gravity, it is necessary to hold the infant at or below the level
of the vagina during those 2 minutes. In that way the procedure is cumbersome and it
prolongs unwillingly a separation between the infant and the mother. The believe that the
infant needs to be at that low level is based on small studies performed more than 35 years
ago.

• Prof. Vain: The main finding of our randomized controlled trial including 391 infants is that
when the umbilical cord is clamped at 2 minutes, holding the infant on the mother’s
abdomen or chest, even when mother is in a semi-sitting position makes no difference in the
volume of placental transfusion compared to infants held at the level of the vagina. We
measured the volume of placental transfusion in the following way: we got an initial weight
in all infants immediately after birth with an electronic weight scale with its surface at the
level of the vagina. Then half of the infants were held at the level of the vagina by an
investigator and the other half were held by the mother on her abdomen or chest. In both
groups we clamped the cord at 2 minutes and obtained a second weight using the same
scale. Infants of both groups gained approximately 55g, which represents 50 cc of blood. The
total blood volume of a 3 kg infant is approximately 250 cc.
• Prof. Vain: We had no real bias as what the findings will be. We suspected that the results
would be that the volume of placental transfusion was going to be similar.

• Prof. Vain: The most important measure is that the recommendation of delaying cord
clamping can be respected by obstetricians and neonatologists while the infant is held by the
mother on her abdomen or chest, therefore enhancing maternal infant bonding and
facilitating the procedure. In this way the procedure may contribute to decrease anemia and
delayed neurodevelopment associated with iron deficiency in infancy.
of this study?
• Dr. Vain: We did not explore the effects of the position where the infant is held in premature
newborns or infants born by cesarean section. Perhaps that can be studied in the future.
• Citation:
Effect of gravity on volume of placental transfusion: a multicentre, randomised, non-
inferiority trial
• Prof Nestor E Vain MD,Daniela S Satragno MD,Adriana N Gorenstein MD,Juan E Gordillo
MD,Juan P Berazategui MD,M Guadalupe Alda MD,Prof Luis M Prudent MD
The Lancet – 17 April 2014
DOI: 10.1016/S0140-6736(14)60197-5

Hepatitis C: Triple DAA Plus Ribavirin Highly Effective for Genotype 1 Infections
MedicalResearch.com Interview with: Jordan Feld MD MPH
Toronto Western Hospital Liver Center
University Health Network Sandra Rotman Centre for Global Health
• Dr. Feld: The SAPPHIRE 1 study was an international, large (631 patients) Phase 3 study of 3 direct acting antivirals combined
with ribavirin for 12 weeks for the treatment of patients with genotype 1 hepatitis C virus (HCV) infection without
cirrhosis. The antivirals used were ABT-450, which is a protease inhibitor that is boosted with ritonovir to allow for once
daily dosing along with ombitasvir (formally ABT 267), a potent NS5A inhibitor and dasabuvir (formerly known as ABT 333), a
non-nucleoside polymerase inhibitor. The ABT-450, ritonovir and ombitasvir were all co-formulated into a single tablet and
dasabuvir was taken twice daily, as was ribavirin. The results of the study showed that the treatment is highly effective with
96% of patients achieving a sustained virological response (SVR) at 12 weeks after completing treatment. SVR is a cure of
HCV infection. Importantly, patients with genotypes 1a and 1b had similar results with a rate of SVR12 of 95% in genotype
1a and 98% in genotype 1b. These results were clearly superior to a historical control treatment with telaprevir combined
with peginterferon and ribavirin. Baseline factors were not predictive of outcome, including factors associated with non-
response to interferon such as the IL28B genotype, baseline HCV viral load and older age.
One unique thing about this study was the inclusion of a placebo arm. Patients were randomized (3:1) to active treatment
or a placebo for 12 weeks. All placebo-treated patients received active treatment for 12 weeks as soon as they completed
the placebo course. The inclusion of a placebo arm allows for a true evaluation of the safety and tolerability of the
treatment. The regimen proved to be very well tolerated. Although 87% of patients reported an adverse event of some
type on treatment, 73% of those treated with placebo also reported at least one side effect. The most common side effects,
fatigue and headache, were equally frequent in the placebo and active treatment groups. Nausea, pruritus (itch), diarrhea
and insomnia were reported more frequently in the treatment arm but side effects were generally very mild with only 3
patients (0.6%) stopping therapy due to an adverse event. Some of these side effects were likely due to the inclusion of
ribavirin in the regimen, however in general ribavirin was well tolerated without the addition of peginterferon, with only
5.8% of patients experiencing grade 2 anemia. Transient bilirubin elevations were seen in 2.8% of patients, likely related to
inhibition of a bile transporter by ABT-450. Overall, treatment was well-tolerated and 96% achieved SVR12 with just 12
weeks of therapy, irrespective of genotype 1 subtype.

• Dr. Feld: The low rate of virological failure in the trial and particularly in patients with
genotype 1a was somewhat surprising. In general, resistance to the 3 classes of drugs used is
more common in patients with genotype 1a infection than in those with genotype 1b
HCV. However, in the trial, only 1 patient experienced virological breakthrough on therapy,
meaning that the virus was undetectable and then became detectable with continued
treatment. In addition, 7 patients relapsed after completing therapy. All 8 patients with
virological failure had at least 1 HCV variant known to confer resistance to at least one of the
3 antivirals identified. The significance of these resistant variants is unknown but the fact
that a potent regimen of 3 moderate barrier drugs produces so little resistance, even in
genotype 1a, is very notable.

• Dr. Feld: This triple DAA regimen with ribavirin is highly effective for all genotype 1 infected patients. A
parallel study showed that the same regimen was equally effective in patients who had failed therapy with
peginterferon and ribavrin previously and another study showed that this regimen is effective in patients
with compensated cirrhosis. Collectively these data suggest that a ‘one size fits all’ approach is feasible,
with all patients, regardless of baseline characteristics, being very likely to achieve SVR with this
combination. Tolerability and safety look very reassuring and therefore this regimen offers a great option
for most genotype 1 infected patients. For those with genotype 1b infection, ribavirin does not appear to
be necessary, which would allow for a better-tolerated option with a lower pill burden.
• Dr. Feld: A question still remains about whether ribavirin is absolutely necessary and whether treatment
duration could be shortened. A study reported elsewhere clearly showed that ribavirin is not necessary
for patients with genotype 1b infection, with 99% of patients treated with the 3 DAA regimen with or
without ribavirin going on to achieve SVR. With such a high percentage of patients cured with 12 weeks of
therapy, one wonders whether a shorter duration of treatment might be feasible, particularly in a
genotype 1b population. The 1a vs 1b issue raises the question of whether it is better to opt for a ‘one size
fits all’ strategy, using the same regimen for all patients, or to customize therapy by HCV genotype 1
subtype. The simplicity of one regimen is appealing but will lead to over-treatment of a large number of
patients. Sorting out the optimal approach for tailoring therapy will need to be a high priority for future
research.
• Citation:
EASL – The International Liver Congress 2014
49th Annual Meeting of the European
Association for the Study of the Liver
London, United Kingdom April 9-13

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