MedicalResearch.com: Medical Research Interviews September 22 2014

MedicalResearch.com
Exclusive Interviews with Medical Research and
Health Care Researchers from Major and Specialty Medical
Research Journals and Meetings
Editor: Marie Benz, MD
info@medicalresearch.com
Sept. 22 2014
For Informational Purposes Only: Not for Specific Medical Advice.

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Longer Shifts and Overtime May Lead To Lower Quality and Safety of Nursing Care
MedicalResearch.comInterview with:
Dr. Peter Griffiths PhD, RN
Centre for Innovation and Leadership in Health Sciences
University of Southampton, Southampton, U
• Medical Research: What are the main findings of the study?
• Dr. Griffiths: This study found that hospital nurses who are working on a 2 shift system,
where care is provided by nurses working long shifts of 12-13 hours, report lower quality and
safety of care than nurses who work a traditional three shift system where nurses typically
work shifts of 8 hours. We also found that nurses who were working overtime reported lower
quality and safety of care. We found that these shifts are common in some European
countries – most notably Poland, Ireland and England.
•
Medical Research: What was most surprising about the results?
• Dr. Griffiths: One of the most surprising results was that long shifts and overtime were also
associated with nurses reporting that they were more likely to have necessary nursing care
care undone. Also, while it seems obvious after the fact that longer working hours and
overtime give poorer quality of care, arguments have been made that the 2 shift system can
improve quality and safety and one would expect that overtime working would, if anything,
be used to finish necessary care. The results weren’t simply a product of staffing differences
as we controlled for that in our analyses.
Read the rest of the interview on MedicalResearch.com
Content Not Intended as Specific Medical Advice

Longer Shifts and Overtime May Lead To Lower Quality and Safety of Nursing Care
Dr. Peter Griffiths PhD, RN
Centre for Innovation and Leadership in Health Sciences
University of Southampton, Southampton, U
• Medical Research: What should clinicians and patients take away from your report?
• Dr. Griffiths: Long shifts are probably a fact of life where they have been implemented. It seems
that nurses might prefer them because the compressed 4-day working week means that they have
more days off. Working three shifts of 12-13 hours means that a nurse can have 4 whole days off.
However, hospitals that have not yet implemented them should consider that any anticipated
benefits and savings might not be delivered. Hospitals that use them should recognise the risk and
pay close attention to ensuring that other aspects of shift work – rest periods between shifts,
cumulative hours worked and other factors – are optimised.
• Medical Research: What recommendations do you have for future research as a result of this
study?
• Dr. Griffiths: This research only looked at nurse reported quality. Research from the United States
also suggests negative impacts on patient experience and possibly even hospital death rates.
However, the context of care in Europe is quite different and we certainly need more research to
see if these other outcomes are adversely affected and whether it is a result of long shifts and
overtime or because these working patterns are associated with hospitals that are failing in other
ways.
• Citation:
• Nurses’ Shift Length and Overtime Working in 12 European Countries: The Association With
Perceived Quality of Care and Patient Safety
Griffiths P1, Dall’Ora C, Simon M, Ball J, Lindqvist R, Rafferty AM, Schoonhoven L, Tishelman C, Aiken
LH; For the RN4CAST Consortium.
• Med Care. 2014 Sep 15. [Epub ahead of print]

Sleep Apnea Predisposes To Impaired Brain Blood Flow With Physical Activity
Paul M. Macey, Ph.D. Assistant Professor in Residence
Associate Dean for Information Technology and Innovations,
Chief Innovation Officer UCLA School of Nursing and Brain Research Institute
• Dr. Macey: People with sleep apnea are less able to control the blood flowing to their brain,
in particular when they grip tightly, or have their foot put in cold water. We measured
changes in blood flowing through the brain using an MRI scanner while people gripped hard,
had their foot placed in cold water, and breathed out hard into a tube with a very small hole
in it. These activities all lead to more blood flowing to the brain in healthy people, which
probably helps protect the cells from being starved of blood and oxygen. However, people
with sleep apnea send less blood that the healthy participants during the gripped and cold
foot activities.
• A further important finding is that women with sleep apnea are worse off than men. The
female patients showed much weaker blood flow than the males, even accounting for normal
differences between men and women.
Medical Research: Were any of the findings unexpected?
Dr. Macey: We did not expect that breathing very hard into a small tube would lead to similar
changes in brain blood flow in the sleep apnea and healthy people; we had expected the
sleep apnea patients to show problems, as they did during the gripping and cold foot
activities. We now believe the hand and foot activities need to use more higher brain areas,
but that these areas are injured in people with sleep apnea, and so the brain processing is
weaker. The breathing into the tube on the other hand works mostly of higher pressure in the
chest squeezing the heart and blood vessels, and only uses lower brain areas, which appear
to mostly be working in people with sleep apnea.

Sleep Apnea Predisposes To Impaired Brain Blood Flow With Physical Activity
Paul M. Macey, Ph.D. Assistant Professor in Residence
Associate Dean for Information Technology and Innovations,
Chief Innovation Officer UCLA School of Nursing and Brain Research Institute
• Dr. Macey: The brain in people with sleep apnea is at risk of being starved of blood and
oxygen, especially as people go about their daily activities using their body for lifting or
holding. Women seem to be even more at risk than men with sleep apnea. This weaker blood
flow may tie in to the changes in brain function we see in people with sleep apnea, including
memory problems, depression and anxiety, and “stress- like” symptoms
• Medical Research: What recommendations do you have for future research as a result of
this study?
• Dr. Macey: The question is what treatments can improve the brain blood flow. Perhaps the
usual treatment, CPAP, will help, but until we do more research we won’t know. Other
possible treatments may be needed to complement CPAP.
Citation:
• Global Brain Blood-Oxygen Level Responses to Autonomic Challenges in Obstructive Sleep
Apnea
• Paul M. Macey , Rajesh Kumar, Jennifer A. Ogren, Mary A. Woo,
Ronald M. Harper Published: August 28, 2014
• PLoS DOI: 10.1371/journal.pone.0105261

Diabetes: Vascular Complications Vary By Duration of Disease
Dr. Sophia Zoungas:
Faculty of Medicine, Nursing & Health Sciences
Monash University, Clayton
• Medical Research: What are the main findings of the study
• Dr. Zoungas: Our study shows that age (or age at diagnosis) and duration of diabetes disease
are linked to the risk of death and marcovascular complications (those in larger blood vessels)
whereas only diabetes duration is linked to the risk of microvascular complications (in smaller
blood vessels such as those in the kidney and eyes)
• Dr. Zoungas: We were surprised to find that people diagnosed with type 2 diabetes at a
younger age were more at risk of microvascular complications than those diagnosed at an
older age.

Diabetes: Vascular Complications Vary By Duration of Disease
Dr. Sophia Zoungas:
Faculty of Medicine, Nursing & Health Sciences
Monash University, Clayton
• Dr. Zoungas: We believe a refocus towards intensive management of hyperglycaemia at
diagnosis of type 2 diabetes, particularly in younger people, may be warranted if the long-term
risk of microvascular complications is to be minimised.
• With respect to macrovascular complications, our findings indicate that effective prevention
requires vigilance at all stages of the disease and across all age groups. However, as the
absolute event rates were highest in the older age groups, surveillance for macrovascular
complications should be intensified with increasing age.”
this study?
• Dr. Zoungas: Future research into the best strategies for achieving and maintaining optimal
glucose control in people with diabetes diagnosed at a young age are required.
• With the increasing number of non-pharmacological and pharmacological approaches to
improve glycaemic control this objective should be achievable.
• Citation:
• Impact of age, age at diagnosis and duration of diabetes on the risk of macrovascular and
microvascular complications and death in type 2 diabetes
Diabetologia Sept 2014

Diabetes: Incretin-Based Drugs Not Linked To Congestive Heart Failure
MedicalResearch.comInterview with: Kristian Filion, PhD FAHA
Assistant Professor of Medicine
Division of Clinical Epidemiology Jewish General Hospital/McGill University
Montreal, Quebec H3T 1E2 Canada
• Dr. Filion: Previous studies have raised concerns that the use of incretin-based drugs, a type
of medication used to treat diabetes, may increase the risk of congestive heart failure. We
therefore examined this potential drug safety issue using a large, population-based database,
which allowed us to study the safety of these medications in a real world setting. In doing so,
we found that the use of incretin-based drugs was not associated with an increased risk of
congestive heart failure among patients with type 2 diabetes. Similar results were obtained
among both classes of incretin-based drugs (glucagon like peptide-1 [GLP-1] analogs and
dipeptidyl peptidase-4 [DPP-4] inhibitors), and no duration-response relationship was
observed.
• Medical Research: Were any of the findings unexpected?
• Dr. Filion: In a previous clinical trial called SAVOR-TIMI 53, patients who were randomized to
the incretin-based drug saxagliptin had an increased risk of congestive heart failure. For this
reason, our hypothesis was that these drugs were associated with an increased
risk. However, no increased risk was identified, making our results somewhat
unexpected. The discrepancy is likely due to the difference in study setting, with clinical trials
involving highly controlled settings with highly selected patient populations and our study
conducted using data from everyday clinical practice.

Diabetes: Incretin-Based Drugs Not Linked To Congestive Heart Failure
MedicalResearch.comInterview with: Kristian Filion, PhD FAHA
Assistant Professor of Medicine
Division of Clinical Epidemiology Jewish General Hospital/McGill University
Montreal, Quebec H3T 1E2 Canada
• Dr. Filion: When deciding to prescribe or take a medication, it is important to weigh the
potential benefits versus the potential harms for each individual patient. In this study, we
found that incretin-based drugs appear to be safe with respect to heart failure. However, the
potential risk for other adverse events was not assessed in our study and should be
considered when deciding the most appropriate treatment choice.
this study?
• Dr. Filion: While this study examined the risk of heart failure associated with incretin-based
drugs as a class, future studies are needed to conclusively examine this association among
the individual incretin-based drugs. Furthermore, these anti-diabetic drugs only entered the
market recently, and there remains a need for long-term post-marketing surveillance.
• Citation:
• Incretin-Based Drugs and the Risk of Congestive Heart Failure
Yu OH1, Filion KB2, Azoulay L3, Patenaude V4, Majdan A5, Suissa S6.
Diabetes Care. 2014 Sep 9. pii: DC_141459. [Epub ahead of print]

Researcher Discusses TOPAS Mesh System For Patients Suffering From Accidental Bowel Leakage
Dr. Dee Fenner, M.D.
Professor of Obstetrics and Gynecology
Director of Gynecology University of Michigan
• MedicalResearch.com Editor’s note: American Medical Systems Inc. (AMS), a subsidiary of
Endo International plc (Nasdaq: ENDP) (TSX: ENL), released top-line results from its
TRANSFORM study that show the investigational TOPAS™ System improves fecal incontinence
in women.
• The results show that over a 12 month period, 69% of women suffering from fecal
incontinence who were implanted with the TOPAS™ System experienced at least a 50%
reduction in weekly incontinence episodes and experienced a durable, consistent effect
across the study period. The results were presented in Cape Town, South Africa at the
International Society of University Colon & Rectal Surgeon (ISUCRS) Congress.
• Dr. Fenner, a primary investigator of the study, kindly answered the questions below:
• Medical Research: How common/prevalent is the problem of fecal incontinence in women?
• Dr. Fenner: Fecal incontinence, also known as accidental bowel leakage (ABL), is estimated to
affect nearly 11 million women and 10% of women over the age of 20 in the United States.1,2
Additionally, nearly one in five women over the age of 45 experience ABL at least once a
year.3

•
Medical Research: What medical/surgical conditions contribute to this incidence?
• Dr. Fenner: Contributing factors to the development of accidental bowel leakage may include childbirth,
trauma, obesity, diabetes, multiple sclerosis and inflammatory bowel disease. Patients may have one or
several of these factors and sometimes it is difficult to identify which one is most important. ABL is most
commonly associated with damage to the pelvic floor muscles caused during childbirth.
• Medical Research: Can you describe the TOPAS™ System and how it aids in reducing fecal
incontinence? Are there side effects associated with this new procedure?
• Dr. Fenner: The TOPAS™ System supports a woman’s natural anatomy and is designed for use when
conservative therapies like dietary changes, anti-diarrheal medicine and pelvic floor muscle training are
not effective. It is a permanently implanted mesh strip designed to naturally support and maintain pelvic
floor muscles. The strip of surgical mesh is passed between two incisions, beneath the puborectalis muscle
(not inside the anal canal) and each end of the mesh is then pulled up through corresponding thigh
incisions using specially designed instruments. The mesh is then adjusted to the proper tension. Top-line
data showed the TOPAS™ System provided an early and durable decline in the number of accidental bowel
leakage episodes and has a favorable safety profile.
• The procedure typically takes about 30 minutes and patients usually can return home on the same day.
After the procedure patients are advised to abstain from heavy lifting, exercise and intercourse for a
minimum of six weeks, which is typical for other urogynecologic surgical procedures.
• The most common side effects observed in the TRANSFORM study (>5%) were pain (primarily buttock,
pelvic or groin pain) and incision site infection. In the TRANSFORM study no patients experienced erosions,
extrusions, organ perforations, bowel obstructions, or device revisions but these are potential risks any
time a mesh is implanted and it is important that they are discussed with the patient.

• Medical Research: What further research do you plan regarding fecal incontinence and
the TOPAS™ System in particular?
• Dr. Fenner: The TRANSFORM study will continue to follow patients for up to five years to fully
understand the long-term patient outcomes and the impact of the TOPAS™ System on
accidental bowel leakage. AMS will be conducting post-market studies that will be either part
of their approval requirements or will be studies that AMS elects to conduct to evaluate
safety and efficacy in a broader base of implanters.
• Future data releases will include additional endpoints and details that were collected as part
of TRANSFORM.
• References:
• S. Census Bureau, Current Population Survey, Annual Social and Economic Supplement, 2012.
Internet release date Dec 2013
• Wu JM, Vaughan CP et al, Prevalence and trends of symptomatic pelvic floor disorders in U.S.
women. Obstet Gynecol. 2014; 123(1):141–148). DOI: 10.1097/AOG.0000000000000057
• Manchio JV, Sanders BM, Fecal incontinence: Help for patients who suffer silently. J of Family
Practice. 2013; 62(11):640-650

Inflammation May Explain Why Glycemic Control Alone May Not Prevent Diabetic Heart Disease
Carlos F. Sánchez-Ferrer, M.D., Ph.D.
Professor of Pharmacology
Universidad Autónoma de Madrid, Spain.
• Dr. Sánchez-Ferrer: We were studying the possible ways of interaction between high glucose levels, which
are found in diabetes mellitus, with vascular damage,
which is the most common and devastating consequence of this disease.
An intriguing fact is that a very strict control of blood sugar in
diabetic patients is not sufficient to avoid the development of such
diabetes-induced cardiovascular diseases. We think our results can
explain why this is happening.
• Using cultured smooth muscle cells from the main human artery (aorta)
in the presence of high concentrations of extracellular glucose, we
observed:
1. In the absence of inflammation, excess glucose in the culture fluid
didn’t enter the cells.
2. When extra glucose was forced into the cells, no harm was done in
the absence of inflammation.
3. When the inflammation-stimulating protein interleukin-1 (IL-1) was
introduced, more glucose entered the cells.
4. With IL-1, the glucose entering the cells was metabolized via
chemical pathways that spur escalating inflammation, overwhelming the
cells’ ability to counteract it.
5. In the presence of the anti-inflammatory drug anakinra, which blocks
the activity of IL-1, the deleterious changes didn’t occur.
•
• Dr. Sánchez-Ferrer: These results were rather consistent with previous work from our laboratory. Perhaps
we had some surprise after observing how “healthy” non-inflamed cells could metabolize excess glucose
without developing any damage.

Inflammation May Explain Why Glycemic Control Alone May Not Prevent Diabetic Heart Disease
Carlos F. Sánchez-Ferrer, M.D., Ph.D.
Professor of Pharmacology
Universidad Autónoma de Madrid, Spain.
• Dr. Sánchez-Ferrer: An important message for the clinicians and patients is to explain why glycemic
control, which is of course very important, can be not enough to prevent diabetic-induced cardiovascular
diseases.
• We should look for other therapeutic targets, aimed to reduce
inflammatory environment associated to diabetes. Therefore, changes in
life style, physical exercise, and weight reduction, can be important
not only because reduce blood glucose but because reduce inflammation.
• Medical Research: What recommendations do you have for future research as a result of this study?
• Dr. Sánchez-Ferrer: Our data indicates that, in addition to glycemic control, we likely
need to find new pharmacological targets focused to reduce diabetic
inflammatory environment. We think this will be a very important
future therapeutic approach.
• For example, there are some preliminary data indicating that IL 1
receptor antagonist can reduce the development of diabetic vascular
complications. Antagonists for other inflammatory cytokines could be
also be useful. This is only the beginning of a research line and more
research is needed to obtain conclusive results.
• Citation:
• Study presented at the American Heart Association’s High Blood Pressure Research Scientific Sessions
2014.
INFLAMMATION MAY BE KEY TO DIABETES/HEART DISEASE LINK
• American Heart Association Meeting Report Abstract 560
Concepción Peiró, Ph.D.; Tania Romacho, Ph.D.; Verónica Azcutia, Ph.D.; Laura Villalobos, Ph.D.; Enrique
Fernández, Ph.D.; Juan P. Bolaños, Ph.D.; and Salvador Moncada, M.D., Ph.D.

VA Hospitals CART Program Provides Quality Oversight Of All VA Heart Cath Labs
Thomas M. Maddox, MD MSc FACC FAHA
Cardiology, VA Eastern Colorado Health Care System Associate Director, VA CART Program
Associate Professor, Department of Medicine, University of Colorado School of Medicine
• Dr. Maddox: We were curious to know if the VA, as a provider of PCI at centers without on-site
CT surgery, was providing better access to its veterans without compromising their
safety. We were pleased to find that there was evidence of better access, with patients
reducing their drive time to PCI facilities by, on average, 90 minutes. In addition, there was
no compromised safety. Rates of both peri-procedural and 1-year adverse outcomes were
low and no different between centers with and without on-site CT surgery.
•
• Dr. Maddox: None were unexpected, but the questions about access and safety were
unknown, so it was gratifying to see the results. We were happy to see that access improved
without causing any harm. We were also pleased to see that the VA CART program – a
national clinical quality program with oversight of all VA cath labs – appears to be providing
effective quality supervision. We believe that quality oversight programs like CART may be an
example of how effective quality management for cardiac services can be provided nationally
and internationally.

VA Hospitals CART Program Provides Quality Oversight Of All VA Heart Cath Labs
Thomas M. Maddox, MD MSc FACC FAHA
Cardiology, VA Eastern Colorado Health Care System Associate Director, VA CART Program
Associate Professor, Department of Medicine, University of Colorado School of Medicine
• Dr. Maddox: Clinicians and patients in the VA system should be comforted by the knowledge
that they will receive safe care in any of the VA cath labs that provide PCI.
this study?
• Dr. Maddox: Keeping a close eye on outcomes in all labs going forward will be
important. Fortunately, the CART program is designed to do just that. We should also
explore what specific factors are leading to such a safe environment. Is it highly trained
interventional cardiologists? Good patient selection? Excellent cath lab staff? By answering
these sorts of questions, we can make sure that all cath labs, both within and outside of the
VA, have the essential elements to provide safe and effective cardiac care.
• Citation:
Patient Access and 1-Year Outcomes of Percutaneous Coronary Intervention Facilities with
and without On-Site Cardiothoracic Surgery: Insights from the VA CART Program
• Thomas M. Maddox, Maggie A. Stanislawski, Colin O’Donnell, Mary E. Plomondon, Steven M.
Bradley, P. Michael Ho, Thomas T. Tsai, Adhir R. Shroff, Bernadette Speiser, Robert J. Jesse,
and John S. Rumsfeld
• Circulation. 2014;CIRCULATIONAHA.114.009713published online before print September 4
2014, doi:10.1161/CIRCULATIONAHA.114.009713

Multiple Sclerosis: Sleep Disorders Both Common and Underdiagnosed
MedicalResearch.com Interview with:
Steven D. Brass, M.D., M.P.H., M.B.A. PI and Lead Author on the study
Director of Neurology Sleep Clinical Program Co-Medical Director of Sleep Medicine Laboratory
Associate Clinical Professor in the Department of Neurology UC Davis Health System 4860 Y Street — Suite 3700
Sacramento, CA 95817
• Medical Research: What was the primary finding of your study?
• Dr. Brass : Among the 11,400 surveys mailed out to all members of the Northern California
Chapter of the National Multiple Sclerosis Society, 2,810 (24.6%) were returned. Of these,
2,375 (84.5%) met the inclusion criteria. Among the completed surveys, 898 (37.8%)
screened positive for obstructive sleep apnea, 746 (31.6%) for moderate to severe insomnia,
and 866 (36.8%) for restless legs syndrome. In contrast, only 4%, 11%, and 12% of the cohort
reported being diagnosed by a health care provider with obstructive sleep apnea, insomnia,
and restless legs syndrome, respectively. Excessive daytime sleepiness was noted in 30% of
respondents based on the Epworth Sleepiness Scale. More than 60% of the respondents
reported an abnormal level of fatigue based on the Fatigue Severity Scale. There was also an
increased risk between complaints of Fatigue based on screening positive for the Fatigue
Severity Scale and screening positive for Obstructive Sleep Apnea (1.850, with a 95% p-value
< 0.001).
•
• Dr. Brass : This survey demonstrates there is a significant burden of sleep disorders that are
likely undiagnosed and unrecognized in the MS population. The number that was the most
shocking was the large discrepenancy in the survey between being screened positive for
OSA (37.8%) and being diagnosed with OSA by a provider (4%).

Multiple Sclerosis: Sleep Disorders Both Common and Underdiagnosed
MedicalResearch.com Interview with:
Steven D. Brass, M.D., M.P.H., M.B.A. PI and Lead Author on the study
Director of Neurology Sleep Clinical Program Co-Medical Director of Sleep Medicine Laboratory
Associate Clinical Professor in the Department of Neurology UC Davis Health System 4860 Y Street — Suite 3700
Sacramento, CA 95817
• Medical Research: Why are these results important?
• Dr. Brass : The vast majority of these sleep disorders were undiagnosed in this MS population
and the presence of a sleep disorders may be contributing to the most disabling multiple
sclerosis symptom fatigue. This may support that further attention on the diagnosis and
management of sleep disorders in this MS population is needed. Greater attention to the
sleep of MS patients is needed by providers who care for these MS patients especially those
complaining of fatigue with a special focus on obstructive sleep apnea. Not only does
undiagnosed obstructive sleep apnea lead to fatigue but it can put the subjects at higher risk
for cognitive problems, emotional problems, hypertension, diabetes, stroke and car accidents
from falling asleep at the wheel.
• Citation:
• The Underdiagnosis of Sleep Disorders in Patients with Multiple Sclerosis
Brass SD, Li CS, Auerbach S.
J Clin Sleep Med. 2014 Sep 15;10(9):1025-31. doi: 10.5664/jcsm.4044.

ER Visits For Hypertension Complications Rise
Sourabh Aggarwal, MD
University College of Medical Sciences
Western Michigan University School of Medicine in Kalamazoo.
• Dr. Aggarwal: The main findings were that from 2006 to 2011:
• ER visits for essential hypertension increased by 25 percent, while the admission percentage for these
patients fell by 15 percent.
• ER visits for hypertension with complication and secondary hypertension increased by 19 percent, while
the admission percentage for these patients fell by 12 percent
• Dr. Aggarwal:Well, we did not expect these results especially the increase in relative rate of number of
visits with hypertension as first listed diagnosis.
• Dr. Aggarwal: The takeaway message would be that there is large unmet need for better control of blood
pressure in outpatient/ambulatory setting. These visits to ER, with some resulting in admission leading to
high cost to healthcare can potentially be avoided by better outpatient control of blood pressure.
• Dr. Aggarwal:We need to identify the demographics and risk factors of these patients with visit to ER for
hypertension. Identifying at-risk patients can help us channelize resources better to prevent morbidity and
associated healthcare cost.
• Citation:
• Sourabh Aggarwal, M.D., chief resident, internal medicine, Western Michigan University School of
Medicine, Kalamazoo, Mich.; Stephen Pitts, M.D., M.P.H., associate professor, medicine, Emory University
School of Medicine, Atlanta; Sept. 9, 2014, presentation, American Heart Association High Blood Pressure
Research Scientific Sessions 2014, San Francisco

Specific Brain Circuit Permanently Switched On In Patients With Anxiety Disorders
Dr Oliver J Robinson Ph.D. Section on Neurobiology of Fear and Anxiety,
National Institute of Mental Health, NIH, Bethesda, MD, Institute of Cognitive Neuroscience
University College London, London, UK
• Dr. Robinson: This study is looking at a symptom of anxiety disorders known as “negative
affective bias”. This describes the tendency of people with anxiety disorders to focus on
negative or threatening information at the expense of positive information.
• We completed a number of previous studies looking at so called “adaptive” anxiety in healthy
individuals – this is the normal, everyday anxiety that everyone experiences; walking home in
the dark, for instance (in these prior studies we used unpredictable electrical shocks to make
people anxious and stressed). When we made healthy people transiently anxious in this way
we showed that this was also associated with negative affective bias and driven by a specific
brain circuit: the dorsal medial prefrontal (anterior cingulate) cortex—amygdala aversive
amplification circuit.
• In this study we showed that the same circuit that was engaged by transient anxiety in our
healthy sample was actually engaged ‘at baseline’ (i.e. without stress) in our patient group.
This suggests that this mechanism which can be temporarily activated in healthy controls
becomes permanently ‘switched on’ in our patient group. This might explain why people with
anxiety disorders show persistent ‘negative affective biases’.
• Furthermore, the extent to which this circuit was turned on correlated with self-reported
anxiety. That is to say the more anxious an individual said they were, the greater the activity
in this circuit. Therefore, there seems to be more of a dimension or scale of anxiety, rather
than a simple well/unwell diagnosis.

•
• Dr. Robinson: This was part of a programmatic sequence of studies following up from healthy
control studies. As such our findings were as hypothesized. However, the idea that the same
mechanism might be involved in so called healthy anxiety and anxiety disorders may be
surprising to many (given how different the two experiences can be).
• Dr. Robinson: The first thing to note is that this will not actually have an immediate effect. It
will need to be replicated and a number of follow up studies are needed. However, one key
thing is that we have previously shown that this circuit is modulated by serotonin.
Specifically, if you lower serotonin in healthy individuals using a dietary manipulation, you
actually see increase in activity of this circuit – in the same way that it is recruited in patients.
This suggests that serotonin may be involved in ‘inhibiting’ this so called ‘aversive
amplification circuit’. As such, selective serotonin reuptake inhibitors (SSRIs – the first line
pharmacological treatment for anxiety disorders e.g prozac) may work by dampening down
and restoring balance in this circuit. This is important, firstly because – surprising as it may be
– we do not actually know how these drugs work. At the moment for the majority of people
with a mood or anxiety disorder, the first treatment they try does not work. Anything we can
do to improve this hit rate would be enormously beneficial. It would avoid unnecessary
suffering and wasted time

this study?
• Dr. Robinson: Firstly, we need to replicate these findings. I am currently about to explore this
same circuit in people with depression – who also show negative biases – to see if this
mechanism may cut across diagnoses. We are also going to directly look at the effects of
SSRIs on this circuit and see if it is possible to start using this technique to stratify patients
into those who will respond to SSRIs and those who wont. Ultimately can we use this
understanding to improve the diagnosis and treatment of anxiety disorders, because at the
end of the day that is all that matters. Can we improve the lives of people who suffer from
these problems? Can we translate this to clinical relevance?
• Citation:
• The dorsal medial prefrontal (anterior cingulate) cortex—amygdala aversive amplification
circuit in unmedicated generalised and social anxiety disorders: an observational study
• Dr Oliver J Robinson PhD,Marissa Krimsky BA,Lynne Lieberman BA,Phillip Allen BA,Katherine
Vytal PhD,Christian Grillon PhD
The Lancet Psychiatry – 1 September 2014 ( Vol. 1, Issue 4, Pages 294-302 )
DOI: 10.1016/S2215-0366(14)70305-0
• Sep 2014

Your Parietal Brain Size May Predict Your Financial Risk Tolerance
Agnieszka Tymula PhD
School of Economics, University of Sydney
Sydney, New South Wales Australia
• Dr. Tymula:We found that the grey matter volume in the posterior parietal cortex, a region long known to
be involved in decision-making, correlates with individual tolerance for financial risks.
•
• Dr. Tymula: Previous research has demonstrated associations between brain structure and cognitive and
personality traits so we expected to find a similar relationship with economic preferences.
• Dr. Tymula: Our findings suggest that clinical structural brain scans could be used to infer something about
patient’s decision making. More research is needed to establish whether structural changes in the brain
lead to changes in risk tolerance or whether the structure of the brain is affected by our everyday risky
choices.
• Dr. Tymula: We would like to establish a causal link between financial risk taking and brain structure and
understand how this relates to aging which is associated with changes in both brain structure and
preferences for risk.
• Citation:
• Neuroanatomy Predicts Individual Risk Attitudes
• Sharon Gilaie-Dotan, Agnieszka Tymula, Nicole Cooper, Joseph W. Kable, Paul W. Glimcher, Ifat Levy
The Journal of Neuroscience, 10 September 2014, 34(37): 12394-12401; doi: 10.1523/JNEUROSCI.1600-
14.2014

Back Pain? Which Sex Position is Best?
Natalie Sidorkewicz, MSc (Kin) PhD (HSG) Student
Spine Biomechanics Laboratory
School of Public Health and Health Systems, Faculty of Applied Health Sciences University of Waterloo Waterloo, ON
• Answer: First, we successfully documented male spine motion and muscle activity during sex — this
biomechanics study was the first of its kind.
• Second, we used this data to develop general recommendations for low back pain patients whose pain is
worsened by motions and postures. The general recommendations focus on changing how people move,
and position themselves during sex. To make any sex position more spine-sparing, we recommend that the
individual controlling the movement use their hips and knees more than their spine and that the
individual not controlling the movement maintain a more neutral-spine position. An excellent working
example is one of the sex positions that we studied: the missionary position. The man, who is controlling
the movement with pelvic thrusting, is recommended to do so with more hip and knee movement than
spine movement. The women, who is lying on her back, is recommended to use a back support placed
underneath the natural curve of her spine to maintain a more neutral spine position. The general
recommendations can be applied to any sex position for both men and women.
• Finally, we developed specific guidelines for men whose back pain is worsened by two specific types of
motion: flexion and extension. If a man’s low back pain is worsened by spine flexion movements, such as
touching their toes or sitting for long periods of time, we would consider them to be flexion-motion-intolerant.
The ideal sex position for a flexion-motion-intolerant patient would then be one that uses
minimal spine flexion, so as not to worsen that patient’s pain. When we compared the five sex positions,
we found that men used the least amount of spine flexion in doggy-style as well as the missionary position
as long as the male was propped up on his hands (as opposed to his elbows).
• If a man’s low back pain is worsened by spine extension movements, such as arching their back or lying on
their stomach, we would consider them to be extension-motion-intolerant. The ideal sex position for an
extension-motion-intolerant patient would then be one that uses minimal spine extension, so as not to
worsen the patient’s pain. When we compared the five sex positions, we found that men used the least
amount of spine extension in spooning and the missionary position as long as the male was propped up on
his elbows (as opposed to his hands).

• Answer: Considering the fact that spooning was the commonly-recommended position for both men and women with any
type of low back pain, we did not expect it to find men using the most spine flexion in that position out of the five positions
that we studied.
• This unexpected finding highlighted the importance of recognizing that there are many types of back pain that are triggered
by different motions, postures, and loads, rather than assuming there is one position that will be suitable for all — a patient
with one type of back pain may find a sex position to be quite comfortable while another patient with back pain worsened
by different triggers may find that same sex position exacerbates their pain. Once the clinician determines which motions,
postures, and/or loads elicit low back pain during the physical examination and provocative testing, the specific
recommendations that we have outlined can be utilized.
• Answer: Clinicians are very familiar with the fact that four in every five people will have one disabling low back pain episode
at least once in their lifetime. It is our hope that we have now brought a common struggle among this population to the
forefront and shed light on the potential mechanical causes for their increase in pain during sex; many men and women with
chronic low back pain are having to severely reduce the amount of sex they are having with their partners — if they are able
to continue to have sex at all — because it exacerbates their pain.
• Now that awareness has been raised about this issue and we have started to explore why low back pain patients may
experience elevated levels of pain during sex, it is also important for clinicians and patients to know that both parties often
feel uncomfortable discussing the potential difficulties that someone with low back pain may encounter when trying to have
sex. Until now, recommendations that were being provided to patients with low back pain were based on conjecture, clinical
experience, or popular media resources. Clinicians may feel more comfortable discussing their patient’s sexual problems
now that their recommendations are supported by scientific evidence. Patients may also feel more comfortable discussing
their sexual problems not only with their clinician, but also their partner, now that researchers are working towards the
development of a complete atlas of sex positions for many categories of low back pain.
• There are movement and position strategies that can make any sex position more spine-sparing. These general
recommendations are in keeping with advice that clinicians give to their low back pain patients on a regular basis: avoid the
motions, postures, and loads that worsen your back pain. Our specific recommendations for flexion- and extension-intolerant
male low back pain patients are simply building upon those general principles and emphasizing the importance of
the identification of pain triggers during the physical examination. One recommendation cannot be given to all low back pain
patients regardless of their pain triggers.

this study?
• Answer: In the coming months, we will be publishing similar data that focuses on
recommendations for women with low back pain, as well as spine motion and muscle activity
during male orgasm. The next phase of our research will include more sex positions and low
back pain patients whose back pain is triggered by a variety of motions, postures, and loads.
Our intent is to test the effectiveness of our initial recommendations on these patients to
further develop the guidelines into a complete atlas for clinicians and patients to use. We
hope our body of work will improve the quality of life of many low back pain patients who
have been struggling with this issue for quite some time.
• Citation:
Male Spine Motion during Coitus: Implications for the low back pain patient.
• Sidorkewicz, Natalie MSc; McGill, Stuart M. PhD
• Spine: 15 September 2014 – Volume 39 – Issue 20 – p 1633–1639
doi: 10.1097/BRS.0000000000000518
•

Lung Cancer Survival Improved By Thoracic Radiotherapy
MedicalResearch.comInterview wth:
Prof. dr. B.J. Slotman
VU University Medical Center Cancer Center
Amsterdam Netherlands
• Medical Research: What are the main findings of this study?
• Prof. Slotman: This randomized trial showed that the use of thoracic radiotherapy in patients with
extensive stage small cell lung cancer reduces the risk of intrathoracic progression by about 50%
and improves 2 years survival from 3 to 13%.
•
• Prof. Slotman:We anticipated both the reduction in intrathoracic progression and the survival
improvement. However, in the first year, the survival curves overlapped and only after the first year,
the benefit of thoracic radiotherapy became evident.
• Medical Research: What should patients and clinicians take away from this report?
• Prof. Slotman: Thoracic radiotherapy should now be considered in addition to. PCI in all patients
with ES-small-cell lung cancer who respond to chemotherapy.
• Medical Research: What further research do you recommend as a result of this report?
• Prof. Slotman: A logical next step would be to evaluate the effect of radiotherapy to other sites of
residual disease after chemotherapy.
• Citation:
• Use of thoracic radiotherapy for extensive stage small-cell lung cancer: a phase 3 randomised
controlled trial
Ben J Slotman MD,Harm van Tinteren PhD,John O Praag MD,Joost L Knegjens MD,Sherif Y El
Sharouni MD,Matthew Hatton FRCR,Astrid Keijser MSc,Suresh Senan FRCR,Corinne Faivre-Finn PhD
The Lancet – 14 September 2014
DOI: 10.1016/S0140-6736(14)61085-0

VOMS Test Better Identifies Symptoms and Impairment Following Concussion
MedicalResearch.comInterview with: Anthony P. Kontos, Ph.D.
Assistant Research Director UPMC Sports Medicine Concussion Program Associate Professor
Department of Orthopaedic Surgery
University of Pittsburgh
• Dr. Kontos: Our new Vestibular/Ocular Motor Screening (VOMS) examination was able to
accurately identify nearly 90% of patients with a concussion. In our study of 64 concussed
patients approximately five days post-injury and 78 healthy control-group patients who were
administered VOMS by trained clinicians, we also found that more than 60% of patients with
a concussion reported symptoms or had impairment on the VOMS following their injury. The
VOMS, which was developed in conjunction with an interdisciplinary team of experts,
assesses five areas of the vestibular ocular system: smooth pursuits, saccades (rapid eye
movement), horizontal vestibular ocular reflex (VOR), visual motion sensitivity (VMS), and
near-point-of-convergence (NPC) distance.
•
• Dr. Kontos: We were somewhat surprised that over 60% of the patients reported symptoms
or had impairment on the VOMS. This is an important finding, as other tests that do not
include vestibular or oculomotor components might miss impairment in these patients.

VOMS Test Better Identifies Symptoms and Impairment Following Concussion
MedicalResearch.comInterview with: Anthony P. Kontos, Ph.D.
Assistant Research Director UPMC Sports Medicine Concussion Program Associate Professor
Department of Orthopaedic Surgery
University of Pittsburgh
• Dr. Kontos: The VOMS is a consistent and valid brief screening tool for clinicians to use to identify
patients with vestibular and oculomotor symptoms and impairment following concussion. The
VOMS can help clinicians to better identify patients with these issues so that they can be referred
for appropriate specialized rehabilitation and treatment strategies. The VOMS complements
current symptom, computerized neurocognitive, and balance assessments for concussion and
provides another tool for clinicians to use as part of a comprehensive approach to assessing this
heterogeneous injury.
study?
• Dr. Kontos:We plan to examine potential age and sex difference on the VOMS. We also want to
compare the VOMS to established tests such as the Gaze Stability Test, Dynamic Visual Acuity Test,
Functional Gait Assessment and Dynamic Gait Index. Finally, we think the VOMS might be a useful
as a sideline assessment, but further research is needed in this area.
• Citation:
• A Brief Vestibular/Ocular Motor Screening (VOMS) Assessment to Evaluate Concussions:
Preliminary Findings.
• Mucha A1, Collins MW2, Elbin RJ3, Furman JM4, Troutman-Enseki C1, DeWolf RM2, Marchetti G5,
Kontos AP6.
• Am J Sports Med. 2014 Aug 8. pii: 0363546514543775. [Epub ahead of print]
• Views vs UniqueViews2014-08-212014-08-262014-08-312014-09-052014-09-10

“Biospleen” Acts Like Dialysis To Remove Pathogens From Bloodstream
MedicalResearch.com Interview with:Michael Super M.Sc., PhD
Senior Staff Scientist Advanced Technology Team Wyss Institute at Harvard
Center for Life Science, 2nd Floor Boston MA 02115
• Medical Research: What is the background for this study? How big a problem is sepsis?
Dr. Super:
• Sepsis is a major problem and is the primary cause of death from infection. The incidence of
sepsis is rising.
• Sepsis affects more than 18 M people each year and at least 1/3 ( 6 million) die every year of
sepsis.
• Sepsis is a disease that affects the very young and old and it is estimated that 60-80% of
childhood deaths in the developing world are due to sepsis.
• Medical Research: How does the ‘biospleen’ cleanse the blood of pathogens?
• Dr. Super: The patient’s blood is passed through tubing and an external device and back to
another vein in their body, much like in dialysis. Once the blood has been removed from the
body, Nanometer-sized magnetic beads coated with a genetically engineered version of a
natural blood protein, called MBL (Mannose Binding Lectin) that is part of the innate
(primitive) immune system are injected into the blood. The MBL binds to sugars on the
surface of the microbes and on toxins they release that are present in the blood. The
magnetic beads and bound microbes and toxin are then removed by magnets in the device,
outside the body, and the cleansed blood is returned to the patient.

“Biospleen” Acts Like Dialysis To Remove Pathogens From Bloodstream
MedicalResearch.com Interview with:Michael Super M.Sc., PhD
Senior Staff Scientist Advanced Technology Team Wyss Institute at Harvard
Center for Life Science, 2nd Floor Boston MA 02115
• Dr. Super: This is a technology that can bind many types (>90) of different live and dead
pathogen cells as well as toxins released by these cells. Thus, this technology can be used to
treat patients with systemic microbial infection without having to first identify the type of
pathogen. The technology also works equally well with antibiotic-resistant pathogens, and it
can be used in combination with current therapies, such as antibiotics and fluid therapy.
• Medical Research: What further research is required before the system is ready for human
clinical evaluation?
• Dr. Super: We need to validate the ability of this technology to work equally well in large
animal trials of the therapy.
• Citation:
• An extracorporeal blood-cleansing device for sepsis therapy
Joo H Kang, Michael Super, Chong Wing Yung, Ryan M Cooper,Karel Domansky et al.
Nature Medicine doi:10.1038/nm.3640 14 September 2014
•

Telemedicine Supported For Chronic Disease Management Except For In Frail, Elderly Patients
Rashid Bashshur, PhD Senior Advisor for eHealth
Professor Emeritus, Department of Health Management and Policy
Executive Director, UMHS eHealth Center University of Michigan Health System
• Medical Research: What are the Main findings of the study?
• Dr. Bashshur: The main findings can be summarized as follows:
• The prevalence of chronic disease is increasing due to the changing demographic composition of the population and
unhealthy life styles. Chronic diseases are expensive, accounting for about 70% of health care expenditures; but they are
amenable to telemedicine interventions. These interventions consist of ongoing monitoring of patients living in their own
home environments, engaging them in managing their health, providing them with educational materials and the necessary
tools to manage their life style mostly by avoiding risky behaviors and adopting healthy ones.
• Telemedicine interventions consist of various configurations of technology (telephone, video, wired or wireless, automated
or manual) , human resources (physicians, nurses, combinations, and patient populations at various levels risk levels or
severity of illness, The interventions investigated to date also vary in terms of study design, duration of application (during
the study period), and frequency of administration of the intervention. Hence, the findings must be viewed from the
perspective of the specific methodological attributes of the studies that were performed.
• Using only robust studies from 2000 to the near present, and limited to congestive heart failure, stroke and COPD. With
notable exceptions, overall there is substantial and fairly consistent evidence of:
• A decrease in use of service, including hospitalization, rehospitalization, and emergency depart visits as a result of the
telemedicine intervention.
• Improved health outcomes.
• Improved event timing for stroke patients.
• Reduced exacerbations of symptoms for COPD patients
• Some interesting trends to be considered:
• Frail and elderly patients, those with co-morbid conditions, and those in advanced stages of illness are not likely to benefit
from telemedicine interventions, as compared to their counterparts.
• Visual information as in videoconferencing proved superior to telephone only connection for the diagnosis and treatment of
stroke patients.
• There could be a tradeoff between extra nursing time versus reduced physician time in some settings, but the net effect is
cost savings.
• There seems to be a paradoxical telemedicine effect in terms of increasing longevity but no reduction in hospitalization,
reported in few studies.

• Medical Research: Are there unexpected findings?
• Dr. Bashshur: Yes, we did not expect to find this level of consistency and strength in findings
among studies conducted in some 14 countries over the span of about 14 years. The
evidence supporting the use of telemedicine in chronic disease management is strong,
consistent and based on valid research (randomized clinical trials and large samples). There
were exceptions. In a minority of studies, there was no evidence of reductions in
hospitalization/hospitalization but a definite improvement in health outcomes. But here
again, one study that recruited frail and elderly patients with multiple comorbidities
observed a negative health effect in the telemedicine intervention.

• Medical Research: What should clinician and patients take away from this report?
• Dr. Bashshur: I think clinicians need to know that:
• (1) the acute care model that has been in practice for the past century has outlived its utility
or usefulness, and the revolving door arrangement in treating the chronically ill is clinically
ineffective and costly. A new model for on-going management of chronic illness is needed,
and telemedicine offers a viable and effective alternative.
• (2) it would be folly to hold physician’s and other clinicians accountable for the health of the
population, when their domain (or their service) can account for less than 30% of a
population’s health.
• Hence, (3) patients have to be fully engaged in managing their own health, including the
adoption of a healthy life style, medication management, and informed decision making in
health matters. Patients must assume more responsibility for managing their health,
especially when they are afflicted with chronic diseases, singly or in some
combination. When given good information on their health status, symptoms and
appropriate courses of action, they must embrace this new modality of care and participate
in managing their care as a partner with their provider. Patients can be heartened to learn
that the symptoms and severity of most chronic conditions can be alleviated, even prevented
in few instances. The merit of “shared decision making’ between patient and provider is well
validated by research evidence.

• Medical Research: What recommendations for future research do you have as a result of this work?
• Dr. Bashshur: Recommendations for future research include:
• Research is a scientific enterprise that has many tools for uncovering the truth, or what we call evidence. As everyone knows, the rules
of scientific discovery are explicit and rigid. But they are there to assure both internal and external validity, namely that what we
observe cannot be explained by a rival hypothesis, and also not limited to the setting where the research is conducted. Therefore,
researchers have the obligation of considering all validi threats in designing their studies, both internal and external. The telemedicine
literature is inundated with inferior or flawed studies. Their sheer volume, by itself, has not advanced the science behind telemedicine
nor accounted for advancing the adoption of telemedicine by mainstream medicine. We don’t need more feasibility , pilot or
acceptance studies, except when exploring brand new areas. Sample size must provide adequate statistical power to test
hypotheses. Typically, samples of less than 150 may not yield adequate statistical power. Randomization of subjects is far superior to
“cluster randomization.” And importantly, we must be very cautious and frugal in utilizing the “intent to treat’ escape valve. As in
sample surveys, missing data can introduce bias into estimates to be made. Data imputation is used sparingly in sample surveys’,
and good researchers tend to do their best in assessing its effect on bias. If used improperly, data imputation is a palatable term for
data fabrication. In other words, when we incur the potential for bias as a result of loss of cases or non-participation, we should do
our best to exercise extreme caution in data imputation, and we must attempt to estimate its effect on introducing bias into the
findings. In sample surveys, calculating statistical or sampling error while ignoring bias is hazardous at best. In experimental studies,
ignoring the loss of cases as a result of non-participation is similarly egregious. The percentage of “intent to treat” must be quite small,
and some effort must be made to ascertain the nature of the bias it might introduce.
• Finally, the sheer large volume of studies that we ignored to report on in this analysis suggests perhaps philosophical questions that
must be addressed:
• Should we go ahead and continue to conduct small and inconclusive studies from which we can get a publication or two but whose
results we cannot trust?
• Is flawed research better than no research ?
• It seems to be that if we are trying to build the science behind telemedicine, the answer is clear.
• Citation:
• The Empirical Foundations of Telemedicine Interventions for Chronic Disease Management
• Bashshur RL1, Shannon GW, Smith BR, Alverson DC, Antoniotti N, Barsan WG, Bashshur N, Brown EM, Coye MJ, Doarn CR, Ferguson S,
Grigsby J, Krupinski EA, Kvedar JC, Linkous J, Merrell RC, Nesbitt T, Poropatich R, Rheuban KS, Sanders JH, Watson AR, Weinstein RS,
Yellowlees P.
Telemed J E Health. 2014 Sep;20(9):769-800. doi: 10.1089/tmj.2014.9981.
Epub 2014 Jun 26.

Should Routine Breast Cancer Screening Stop At Age 70?
Nienke de Glas, MD PhD-student
Leiden University Medical Center Department of Surgery
Leiden The Netherlands
• Dr. de Glas: It remains unclear whether mass breast cancer screening has a beneficial effect
in older women. In the Netherlands, the upper age limit of the breast cancer screening
program was extended from 69 to 75 years in 1998. If a screening program is effective, it can
be expected that the incidence of early stage tumours increases, while the incidence of
advanced stage tumours decreases. The aim of this study was to assess the incidence of early
stage and advanced stage breast cancer before and after the implementation of mass
screening in women aged 70-75 years in the Netherlands. We showed that the extension of
the upper age limit to 75 years has only led to a small decrease of advanced stage breast
cancer, while the incidence of early stage tumours has strongly increased. For every advanced
stage tumour that was prevented, 20 “extra” and early stage tumours were diagnosed.
• Dr. de Glas: These findings were to some extend unexpected, as previous observational
studies showed beneficial effects of breast cancer screening in terms of survival outcomes.
However, it must be noted that these previous studies often suffered from lead time bias,
length time bias and selection bias, which may explain the discrepancy between these
studies and the present study.

Should Routine Breast Cancer Screening Stop At Age 70?
Nienke de Glas, MD PhD-student
Leiden University Medical Center Department of Surgery
Leiden The Netherlands
• Dr. de Glas: Since we have shown that each “prevented” advanced stage tumour resulted in
20 “extra” and therefore overdiagnosed early stage tumours, this implies that mass screening
in women aged 70-75 leads to a considerable proportion of overdiagnosis. Overdiagnosis and
overtreatment could have a great impact on quality of life and physical function of older
breast cancer patients, as they are at increased risk of adverse outcomes of breast cancer
treatment. Consequently, unfavourable effects of screening may outweigh the benefits from
a certain age. Moreover, the additional costs of treating overdiagnosed tumours could result
in a tremendous increase in health expenditure due to the screening program, while no
actual health benefits are being obtained.
this study?
• Dr. de Glas: We propose that routine breast cancer screening in women over the age of 70
should not be performed on a large scale. Instead, the harms and benefits of screening
should be weighed on a personalized basis, taking remaining life expectancy, breast cancer
risk, functional status and patients’ preferences into account.
• Citation:
• Breast cancer screening offers few benefits to women over 70, finds study
• BMJ 2014; 348 doi: http://dx.doi.org/10.1136/bmj.g2333 (Published 25 March 2014) Cite this
as: BMJ 2014;348:g2333

Chiropractic Spinal Manipulation Therapy May Be Helpful For Uncomplicated Sciatica
Gert Bronfort, DC, PhD
Professor, Integrative Health and Wellbeing Research Program
Center for Spirituality & Healing University of Minnesota
Were any of the findings unexpected?
• Dr. Bronfort: Our study found that spinal manipulative therapy SMT coupled with home exercise and advice (HEA) appears
to be helpful compared to home exercise and advice alone (especially in the short term) for patients with sub-acute and
chronic back-related leg pain (BRLP). BRLP was defined as radiating pain originating from the lumbar spine, which travels
into the proximal or distal lower extremity, with or without neurological signs. Patients with progressive neurological
deficits, cauda equina syndrome, spinal fracture, and other potentially serious causes of BRLP (and often candidates for
surgery) were EXCLUDED.
• There were a few things we did find to be quite interesting. First, it is notable that the spinal manipulative therapy & home
exercise and advice group experienced less self-reported medication use after one year than the home exercise and advice
alone group (SMT&HEA was 2.6 times more likely to experience fewer medication days than HEA alone at 1 year). Given the
growing concerns of overuse of pain medications (and the potential for adverse events and addiction), this is a finding that
has important public health consequence.
• Another interesting and important finding is that the adverse events observed in this study were only mild to moderate and
self-limiting. No serious adverse events occurred that were related to the study interventions. Mild to moderate adverse
events (e.g. temporary aggravation of pain, muscle soreness, etc.) were reported by 30% of the patients in the SMT&HEA
group, and 42% in the HEA group. This is important as few studies have systematically recorded the side effects and adverse
events related to SMT&HEA and HEA alone; this is one of the first, larger clinical trials to do so. These findings are especially
notable because SMT is often not recommended for patients with leg symptoms because of safety concerns (which might be
related to the previous absence of robust scientific data to support its use).
• Finally, while an advantage of SMT& HEA versus HEA was found (especially in the short term), we do find the findings of the
HEA alone group to also be of interest. Almost half of the HEA patients experienced a 50% reduction in leg pain symptoms in
both the short (at 12 weeks) and long term (at 52 weeks). That’s an important improvement and warrants future
investigation. Self-management strategies (like home exercise) that emphasize the importance of movement and fitness,
restoration of normal activities, and allow patients to care for themselves embrace important principles for promoting
overall health and wellbeing that could have a big impact if routinely put into practice.

• Dr. Bronfort: Consider trying conservative and simple strategies first before medications,
injections and surgery for patients with radiating leg pain.
• This is one of the first sufficiently powered studies to investigate spinal manipulative therapy
for BRLP. We hope this new knowledge will inspire clinicians to think differently about how
they treat patients with sub-acute and chronic BRLP. Prior to this study, SMT was considered
a viable treatment option for what is known as ‘uncomplicated low back pain’, that is low
back pain without radiating pain to the leg. This study shows that for patients WITH radiating
leg pain, but without progressive neurological deficits and serious identifiable causes (e.g.
spinal fracture, etc.) spinal manipulative therapy, coupled with home exercise and advice,
may be helpful for these types of patients as well. This has potentially substantial implications
for improving the overall quality of life and wellbeing of BRLP patients, and also for
decreasing the overall socio-economic burden of BRLP as a condition.

study?
• Dr. Bronfort: Future studies should examine patients’ preferences regarding these treatments
(especially what motivates them to be engaged in their own self-care, and how SMT might add to
the SMT&HEA treatment experience from the patients’ vantage point). The cost-effectiveness of
SMT and HEA also needs to be rigorously investigated. We conducted qualitative interviews with all
patients in the study, and also collected cost-effectiveness and utility data; these data are currently
being analyzed and will be published at a later date.
• Also, there is interest in looking more closely at the HEA group used in this study, and how it could
be further optimized to meet patients’ preferences and increase the use of self-management. As
noted above there is great interest in empowering patients to embrace simple tips and techniques.
• Finally, this study did not address the effectiveness of home exercise versus usual medical
treatment and/or no treatment at all; future large studies are required to answer these questions.
• Citation:
• Spinal Manipulation and Home Exercise With Advice for Subacute and Chronic Back-Related Leg
Pain: A Trial With Adaptive Allocation
• Gert Bronfort, DC, PhD; Maria A. Hondras, DC, MPH; Craig A. Schulz, DC, MS; Roni L. Evans, DC, PhD;
Cynthia R. Long, PhD; and Richard Grimm, MD, PhD
Ann Intern Med. 2014;161(6):381-391. doi:10.7326/M14-0006

Pediatric Cancer More Common In White, Male Adolescents from Northeast
Dr. Jun Li, MD, PhD, MPH
Epidemiology and Applied Research Branch Division of Cancer Prevention and Control
National Center for Chronic Disease Prevention and Health Promotion
• Dr. Li: Using the 2001 to 2009 National Program of Cancer Registries (NPCR) and Surveillance,
Epidemiology, and End Results (SEER) data, which represent 94.2% of the US population, we
identified 120,137 pediatric cancer cases with an incidence rate of 171 cases per million
children and adolescents.
• Overall cancer incidence rates were stable from 2001-2009. However, we found rates were
increasing significantly at 1.3% per year in African American children and adolescents. This
increase might be partially attributed to the rise among renal tumors and thyroid cancer. We
also found rising incidence in thyroid cancer and renal carcinoma among children and
adolescents.
• As has been previously established, pediatric cancer is more common in males, in white, in
adolescents, and in the Northeast. Leukemia is the most common pediatric cancer, followed
by central nervous system (CNS) neoplasms, and then lymphomas.
• Dr. Li: A decreasing trend of melanoma incidence in the US pediatric population was
unexpected. That finding may be largely due to late-reporting of melanoma cases. As we
were not able to use the delay-adjustment method for NPCR and SEER combined data, the
decreasing rates of melanoma must be interpreted critically.

Pediatric Cancer More Common In White, Male Adolescents from Northeast
Dr. Jun Li, MD, PhD, MPH
Epidemiology and Applied Research Branch Division of Cancer Prevention and Control
National Center for Chronic Disease Prevention and Health Promotion
• Dr. Li: First, although the incidence of some pediatric cancer types is increasing, the chances for
developing these cancers are very small.
• Second, we are hopeful that our findings could help clinicians and researchers generate research
hypotheses to better understand the reasons behind the increase in these cancers.
• Finally, while not a focus of the study itself, it bears mentioning that no population-based cancer
screening is recommended for children and adolescents.
study?
• Dr. Li: Our study suggests areas for further investigation such as examination of epidemiology of
cancer in African Americans children and adolescents, and in thyroid cancer and renal carcinoma
among all children and adolescents. Associations of obesity with thyroid cancer and renal
carcinoma have been reported in the literature, and more research is warranted for this younger
population. The associations between thyroid cancer and radiation exposures including medical
radiation merit further investigations in this area, as well.
• Citation:
• Cancer Incidence Rates and Trends Among Children and Adolescents in the United States, 2001-
2009
David A. Siegel, Jessica King, Eric Tai, Natasha Buchanan, Umed A. Ajani, and Jun Li
• Pediatrics peds.2013-3926; published ahead of print September 8, 2014, doi:10.1542/peds.2013-
3926

Heart Failure: Serum Uric Acid As Predictor Of Poor Outcome
Muthiah Vaduganathan, MD MPH
Department of Medicine
Massachusetts General Hospital Boston, Mass
• Dr. Vaduganathan: Based on data from a large, multinational randomized controlled trial of patients hospitalized for heart
failure and reduced ejection fraction (HFrEF), we conducted a retrospective analyses of the clinical profiles associated with
baseline serum uric acid levels. Serum uric acid was commonly elevated in patients hospitalized for heart failure and
reduced ejection fraction (mean ~9 mg/dL), especially in men and black patients. Higher uric acid levels were associated
with lower systolic blood pressure and EF, higher natriuretic peptides, and more impaired renal function. After accounting
for 24 known baseline covariates, serum uric acid was independently predictive of post-discharge mortality and
rehospitalization in patients with relatively preserved renal function, but not in those with poor renal function.
• Medical Research: What was most surprising about the results?
• Dr. Vaduganathan: The prognostic utility of serum uric acid differs by baseline renal function, suggesting different biologic
and pathophysiologic significance of serum uric acid among those with and without significant renal dysfunction.
• Dr. Vaduganathan: A single baseline measurement of serum uric acid can help identify patients at high risk of poor post-discharge
prognosis after hospitalization for heart failure and reduced ejection fraction, even beyond traditional markers and
known predictors of adverse events.
• Dr. Vaduganathan: We eagerly await the results of the recently completed EXACT-HF (Xanthine Oxidase Inhibition for
Hyperuricemic Heart Failure Patients; NCT00987415) trial, which is a multicenter randomized, 24-week trial of allopurinol in
hyperuricemic (sUA ≥9.5 mg/dL) chronic heart failure and reduced ejection fraction.
• Citation:
• Relation of Serum Uric Acid Levels and Outcomes among Patients Hospitalized for Worsening Heart Failure with Reduced
Ejection Fraction (From the EVEREST Trial)
• Muthiah Vaduganathan, Stephen J. Greene, Andrew P. Ambrosy, Robert J. Mentz, Haris P. Subacius, Ovidiu Chioncel, Aldo P.
Maggioni, Karl Swedberg, Faiez Zannad, Marvin A. Konstam, Michele Senni, Michael M. Givertz, Javed Butler, Mihai
Gheorghiade, EVEREST trial investigators
• DOI: http://dx.doi.org/10.1016/j.amjcard.2014.09.008
• Publication stage: In Press Accepted Manuscript
•
• American Journal of Cardiology Published online: September 14, 2014

Abdominal Obesity Continues To Increase, Particularly in Women
Earl S. Ford, MD, MPH
Medical officer, U.S Public Health Service
Centers for Disease Control and Prevention Atlanta, GA 30341
• Dr. Ford: The main finding of the study is that mean waist circumference and the prevalence of abdominal
obesity in US adults have increased since 1999-2000 and that these increases are being driven primarily by
trends in women. Mean waist circumference and the percentage of abdominal obesity in men has been
relatively stable since 2003-2004.
• Dr. Ford: The steady increase in mean waist circumference in women was unanticipated.
• Dr. Ford: In light of our study’s finding that waistlines are still expanding, particularly in women, clinicians
should consider measuring waist circumference to evaluate abdominal obesity in their patients. In
addition to their weight, patients should also keep track of their waist circumference. Expanding
waistlines, even in the presence of stable weight, should cause patients to evaluate their lifestyle
behaviors such as physical activity/sedentary behavior and diet and possibly consult their physicians.
• Dr. Ford: Continued monitoring of trends in mean waist circumference and the prevalence of abdominal
obesity should be conducted. Possible drivers for the gender divergence in the trend patterns in waist
circumference warrant examination.
• Citation:
• Trends in Mean Waist Circumference and Abdominal Obesity Among US Adults, 1999-2012
Earl S. Ford MD, MPH, Leah M. Maynard PhD, Chaoyang Li MD, PhD
JAMA. 2014;312(11):1151-1153. doi:10.1001/jama.2014.8362
doi:10.1001/jama.2014.8362

Multiple Sclerosis: Generic Copaxone Demonstrates Equivalent Safety and Efficacy
MedicalResearch.com: Interview with:
Jeffrey A. Cohen, MD Hazel Prior Hostetler Endowed Chair
Professor, Cleveland Clinic Lerner College of Medicine Director, Mellen Center for MS Treatment and Research
Neurological Institute Cleveland Clinic Cleveland, OH 44195
• Dr. Cohen: The primary objective of the GATE trial was to compare the efficacy and safety of generic
glatiramer acetate to the approved form (Copaxone) in relapsing-remitting multiple sclerosis. The
study demonstrated equivalent efficacy of generic glatiramer acetate and Copaxone measured by
gadolinium enhancing brain MRI lesions at months 7, 8, and 9 and a number of additional measures
of MRI lesion activity. The study also showed comparable safety (measured by adverse events) and
injection site tolerability.
• Dr. Cohen: Medications contribute significantly to the high cost of multiple sclerosis care. As the
patents expire for MS disease medications, there is the opportunity to develop generic versions
with potential cost savings for patients and payors. However, since MS disease medications are
biologics, large molecules, or complex molecular mixtures, adequate testing probably will include
not only extensive chemical, physicochemical, toxicological, and immunological testing but also
clinical trials.
study?
• Dr. Cohen: Ongoing studies of generic glatiramer acetate include an open label extension study to
provide additional efficacy and safety data on generic glatiramer acetate up to two years and data
on switching from Copaxone to generic glatiramer acetate. Immunogenicity studies also are in
progress.
• Citation:
• ACTRIMS-ECTRIMS 2014 abstract: MSBoston 2014
• Generic glatiramer acetate is equivalent to Copaxone on efficacy and safety: results of the
randomized double-blind GATE trial in multiple sclerosis

Does Magnesium Help Prevent Cerebral Palsy?
MedicalResearch.comInterview with: LexW Doyle MD BS MSc FRACP
Professor of Neonatal Paediatrics
Department of Obstetrics and Gynaecology The Royal Women’s Hospital
Parkville, Victoria, Australia
• Dr. Doyle: From collectively pooling data from five large trials carried out around the world over the
past 20 years, we know that magnesium sulfate given under strict medical protocols in hospital to
women threatening to deliver preterm reduces the risk of cerebral palsy in their children in early
childhood. Following from this knowledge, magnesium sulfate is now given routinely to women,
under strict medical conditions, who are threatening to deliver very early in Australia, and in other
parts of the world, to try to prevent cerebral palsy in their child. What we do not know is if
magnesium sulfate used this way has any longer-term effects on the brain or on other important
outcomes.
• One of the initial studies that contributed to the overall evidence about cerebral palsy was carried
out in Australia and New Zealand and completed more than 10 years ago. Over 1000 women and
their babies were enrolled in that study and although the rate of cerebral palsy was not
substantially reduced by magnesium sulfate in our study, we showed that there were fewer
children at 2 years of age who were not walking in the group whose mothers were given
magnesium compared with those whose mothers were given placebo. With this knowledge, and
given the unknown longer-term benefits or risks, we re-evaluated the children from our study at
school-age, between 6-11 years of age. We thoroughly evaluated their brain function, including
movement and co-ordination, thinking ability, behaviour, and school progress, as well as general
health and well-being. The basic message from our longer-term study is that magnesium sulfate, as
used in our trial, does not have any substantial benefits or harms on brain or cognitive function, or
any other outcome at school age.

Does Magnesium Help Prevent Cerebral Palsy?
MedicalResearch.comInterview with: LexW Doyle MD BS MSc FRACP
Professor of Neonatal Paediatrics
Department of Obstetrics and Gynaecology The Royal Women’s Hospital
Parkville, Victoria, Australia
• Dr. Doyle: Given that walking was improved at 2 years, we hoped that magnesium sulfate might
improve motor function or co-ordination at school-age, but it did not do so.
• Dr. Doyle: What this means for those who are currently using magnesium sulfate to prevent
cerebral palsy in very preterm infants is that there is no evidence for longer-term harm to the
children from this practice, so they should continue. On the other hand, for those who are yet to
decide to use magnesium sulfate to prevent cerebral palsy, the longer-term data does not help to
convince them otherwise.
study?
• Dr. Doyle: What is required now is for all of the original trials to try to re-evaluate the children
enrolled in their studies at school-age. Then the total amount of data can be combined, as we did
when the outcomes in early childhood were available, to try to establish any longer-term outcomes
that may be important for the children and their families.
• Citation:
• Doyle LW, Anderson PJ, Haslam R, Lee KJ, Crowther C, for the Australasian Collaborative Trial of
Magnesium Sulphate (ACTOMgSO4) Study Group. School-age Outcomes of Very Preterm Infants
After Antenatal Treatment With Magnesium Sulfate vs Placebo. JAMA. 2014;312(11):1105-1113.
doi:10.1001/jama.2014.11189.
•

Venous Thromboembolism: Review Compares Eight Treatment Options
MedicalResearch.com Interview with: Dr. Marc Carrier, MD MSc
Scientist, Clinical Epidemiology, Ottawa Hospital Research Institute
Physician, Hematology (Thrombosis), The Ottawa Hospital
Associate Professor, Department of Medicine, Faculty of Medicine, and Research Chair in Venous Thromboembolism and Cancer (Tier 2) at
the University of Ottawa
• MedicalResearch.com: What are the main findings of this study?
Dr. Carrier: Venous thromboembolism (VTE), comprised of deep vein thrombosis and
pulmonary embolism, is the third leading cause of cardiovascular death. There are many
anticoagulant treatments available but there is little guidance about which treatment is most
effective and safe. This systematic review and network meta-analysis evaluated eight
different treatment options for acute Venous thromboembolism. Forty-five trials were
included in the analysis and there were no significant differences in clinical or safety
outcomes associated with most treatment options when compared to the combination of
LMWH-VKA..
• Dr. Carrier: The combination of UFH-VKA was the least effective treatment with 1.84% of
patients experiencing recurrent VTE in the first 3 months, compared to 1.3% for patients
treated with LMWH-VKA combination. Rivaroxaban and apixaban were associated with the
lowest risk of bleeding compared to LMWH-VKA combination, 0.49%, 0.29% and 0.89%,
respectively, in the first 3 months of treatment. All other treatment options demonstrated
similar efficacy and safety as the combination of LMWH-VKA.

Venous Thromboembolism: Review Compares Eight Treatment Options
MedicalResearch.com Interview with: Dr. Marc Carrier, MD MSc
Scientist, Clinical Epidemiology, Ottawa Hospital Research Institute
Physician, Hematology (Thrombosis), The Ottawa Hospital
Associate Professor, Department of Medicine, Faculty of Medicine, and Research Chair in Venous Thromboembolism and Cancer (Tier 2) at
the University of Ottawa
• Dr. Carrier: These data provide clinicians with much needed information regarding which
anticoagulation regimens are effective and safe for treatment of acute Venous
thromboembolism. While all treatment options, with the exception of UFH-VKA combination,
demonstrated no difference in rates of recurrent venous thromboembolism events or
bleeding risk compared to LMWH-VKA combination, these data should be interpreted
cautiously given the lack of direct comparison between treatments. Patient preferences for
treatment options should also be considered.
this study?
• Dr. Carrier: Areas for future study including direct comparison trials, patient-level network
meta-analyses, or high quality non-randomized studies, are needed to confirm our findings.
Future studies are also needed to determine which treatment options are most cost
effective.
• Citation:
• Castellucci LA, Cameron C, Le Gal G, et al. Clinical and Safety Outcomes Associated With
Treatment of Acute Venous Thromboembolism: A Systematic Review and Meta-analysis.
JAMA. 2014;312(11):1122-1135. doi:10.1001/jama.2014.10538.

Carotid Stenosis: Using Cerebrovascular Reserve To Assess Stroke Risk
MedicalResearch.comInterview with: Ankur Pandya, PhD
Assistant Professor of Healthcare Policy and Research
Departments of Healthcare Policy and Research
Weill Cornell Medical College New York, NY 10065.
• Dr. Pandya: Asymptomatic carotid stenosis is a highly prevalent condition that can lead to
ischemic stroke, which is a leading cause of death and healthcare costs in the U.S.
Revascularization procedures are often performed on asymptomatic carotid stenosis
patients, but experts have questioned whether the stroke prevention benefits outweigh the
risks and costs of revascularization in these patients. Imaging-based stroke risk assessment
has traditionally focused on the degree of artery narrowing, but there has been growing
interest in using cerebrovascular reserve (CVR) assessment to stratify these patients into
those that are more likely to have a stroke, and thus better candidates for revascularization,
and those that would be better off with less invasive management strategies (such as medical
therapy). We therefore developed a simulation model to evaluate whether the CVR-based
decision rule could be used efficiently select the right patients for revascularization. We
found that the CVR-based strategy represented the best value for money compared to
immediate revascularizations or medical therapy-based treatment for all patients.
• Dr. Pandya: Interestingly, we found that there were combinations of certain variables (such
as baseline stroke risk and risk of complications during revascularization) that led to the
immediate revascularization or medical therapy-based strategies being optimal.

Carotid Stenosis: Using Cerebrovascular Reserve To Assess Stroke Risk
MedicalResearch.comInterview with: Ankur Pandya, PhD
Assistant Professor of Healthcare Policy and Research
Departments of Healthcare Policy and Research
Weill Cornell Medical College New York, NY 10065.
• Dr. Pandya: (from the paper): “Assessment of CVR with transcranial Doppler ultrasound can allow
identification of patients with carotid stenosis who are at higher baseline risk for stroke, and thus,
are better candidates for revascularization procedures.
• The optimal decision on performance of revascularization procedures in asymptomatic patients
with carotid stenosis depends on baseline risk of stroke and the likelihood of procedure
complications, factors that can vary according to patient, provider, and institution.”
study?
• Dr. Pandya: We are currently using our simulation model to explore whether other imaging tests,
like MRI, could be efficiently employed to look at the composition and stability of plaque which
may give greater insight into those plaques most likely to rupture and cause symptoms.
• Citation:
• “Carotid Artery Stenosis: Cost-effectiveness of Assessment of Cerebrovascular Reserve to Guide
Treatment of Asymptomatic Patients.” Collaborating with Dr. Pandya at Weill Cornell Medical
College were Ajay Gupta, M.D., Hooman Kamel, M.D., Babak B. Navi, M.D., Pina C. Sanelli, M.D.,
M.P.H., and Bruce R. Schackman, Ph.D.
DOI: http://dx.doi.org/10.1148/radiol.14140501
Journal Radiology Sept 2014 Ahead of Print

MedicalResearch.com: Medical Research Interviews September 22 2014

MedicalResearch.com: Medical Research Interviews September 22 2014

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