MedicalResearch.com: Medical Research Interviews January 2014

MedicalResearch.com
Exclusive Interviews with Medical Research and
Health Care Researchers
Editor: Marie Benz, MD
info@Hemodialysis.com
January 6 2014
For Informational Purposes Only: Not for Specific Medical Advice.

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Sleep Deprivation: Blood Markers of Brain Injury
MedicalResearch.com Interview with:
Jonathan Cedernaes PhD
Department of Neuroscience
Uppsala University Sweden
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MedicalResearch.com: What are the main findings of this study?
Dr. Cedernaes: We found that two peripheral blood markers were modestly but significantly increased in healthy young participants
after a single night of sleep deprivation, as compared with a normal night of sleep. These two markers, S-100B and NSE, are for example
used as markers of acute ischemic injury in the brain, and are also increased following concussions. S-100B is produced mainly by glial
cells and also increases after injury to the blood brain barrier. NSE is instead produced by neurons and is regarded as being more
specific for neuronal damage, although it can also be produced by peripheral cells.

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MedicalResearch.com: Were any of the findings unexpected?
Dr. Cedernaes: It was unexpected that a single night could increase these two markers, elevations of which have previously been
associated with acute brain trauma. It was also interesting that this occurred in healthy young men, all younger than 30 years of age. It
was furthermore interesting that both markers increased as this could indicate damage to cells of the brain. This combination could
therefore imply that sleep deprivation, if chronic, may be harmful to the brain. A single night of sleep loss is most likely however not
harmful, and it is important to remember that the levels of these markers, i.e. the increase after sleep deprivation, were much lower
than what is typically seen after for example acute head trauma and brain infections.
MedicalResearch.com: What should patients and providers take away from this report?
Dr. Cedernaes: As previous research has shown, getting enough and good sleep is important for many different reasons, for example
metabolic regulation including body weight control, mood, memory and both physical and cognitive performance. Both clinicians and
patients should therefore ideally discuss this issue regularly, especially as maintaining good sleep patterns is important for common
conditions such as type-2 diabetes, depression and cardiovascular disease. As epidemiological studies have also shown a link between
poor sleep habits and the development of neurodegenerative diseases such as dementia and multiple sclerosis, our research
emphasizes the importance of addressing sleep from the perspective of maintaining a healthy brain.
MedicalResearch.com: What further research do you recommend as a result of your study?
Dr. Cedernaes: Future studies are needed to verify our preliminary findings, and to resolve whether they indicate damage to cells of
the brain, increased synthesis by peripheral sources, or damage to the blood brain barrier. The latter would also be of significant
relevance as this could be important for drug delivery and how drugs reach the brain under different states of acute or chronic sleep
deprivation. As we studied one single night of acute total sleep deprivation, it is also important to investigate how these markers are
affected by partial sleep deprivation, especially under chronic conditions.
Citation:
Acute sleep deprivation increases serum levels of neuron-specific enolase (NSE) and S100 calcium binding protein B (S-100B) in
healthy young men
Benedict C; Cedernaes J; Giedraitis V; Nilsson EK; Hogenkamp PS; Vågesjö E; Massena S; Pettersson U; Christoffersson G; Phillipson M;
Broman JE; Lannfelt L; Zetterberg H; Schiöth HB. Acute Sleep Deprivation Increases Serum Levels of Neuron-Specific Enolase (NSE) and
S100 Calcium Binding Protein B (S-100B) in Healthy Young Men. SLEEP 2014;37(1):195-198.

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Read the rest of the interview on MedicalResearch.com

ARDS: IV Interferon-beta-1a Effect on Mortality
Prof Sirpa Jalkanen MD, PhD
MediCity Research Laboratory and Department of Medical Microbiology
University of Turku Turku, Finland
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MedicalResearch.com: What are the main findings of the study?
Answer: Pulmonary vascular leakage occurs early in acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Mortality is high (35-45%), but
no effective pharmacotherapy exists. Production of anti-inflammatory adenosine by ecto-5’-nucleotidase (CD73) maintains endothelial barrier
function. Interferon-beta-1a (IFN-beta) increases CD73 synthesis and might thus reduce vascular leakage and mortality in ALI/ARDS. We tested this
hypothesis and the findings were as follows:
1.IFN-beta increased the number of CD73-positive vessels in human lung culture (4- and 14.3-fold on days 1 and 4 respectively, p=0.04 and 0.004).
2. The optimal tolerated FP-1201 dose (a unique intravenous formulation of interferon-beta 10 μg /day for six days) caused a significant rise in serum
MxA (a marker for interferon response) and CD73 levels and a fall in interleukin-6 (an inflammatory cytokine) concentration.
3. Most importantly, odds of 28-day mortality was 81% lower in the treated than untreated subjects (8% vs 32%, OR[95% CI]0.19[0.03 to 0.72],
p=0.01).

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Answer: Although preclinical studies with mouse models suggested a good effect of interferon-beta in acute lung injury, the beneficial effect in the
clinical trial was surprisingly strong. This is especially encouraging in the light that no effective specific pharmacotherapy is available for ARDS.
MedicalResearch.com: What should clinicians and patients take away from your report?
Answer: Our human ex-vivo data are consistent with those from cell lines and animal studies, suggesting that IFN-beta-1a increases CD73 synthesis
in pulmonary tissue and results in decrease of pulmonary vascular leak. This mechanism is most likely behind the reduced mortality in patients with
ARDS. Although conclusive proof of efficacy needs to be obtained from randomised controlled trials, our human in-vivo data suggest a beneficial
effect. If proven to be effective in future trials, IFN-beta-1a would be the first clinically effective mechanistically targeted and disease-specific
treatment for ARDS. Until the results of future trials are available, clinicians should continue with best practice in supportive care.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Answer: Therapeutic potential must be substantiated in large-scale prospective randomised trials. FP-1201 has been granted an orphan drug status
for the treatment of ALI/ARDS with interferon-beta by the European Commission and European Medicines Agency (EMA) and is waiting for EMA
advise to start phase III studies. We are also currently evaluating the role of CD73 as a marker for disease severity and therapeutic response in ARDS.
Citation:
The effect of intravenous interferon-beta-1a (FP-1201) on lung CD73 expression and on acute respiratory distress syndrome mortality: an openlabel study
The effect of intravenous interferon-beta-1a (FP-1201) on lung CD73 expression and on acute respiratory distress syndrome mortality: an open-label
study
Geoff Bellingan MD,Mikael Maksimow PhD,David C Howell MD,Martin Stotz MD,Richard Beale MB,Monika Beatty MD,Timothy Walsh MD,Alexander
Binning MD,Alan Davidson MD,Martin Kuper MD,Sanjoy Shah MD,Jackie Cooper MSc,Matti Waris PhD,Gennady G Yegutkin PhD,Juho Jalkanen
PhD,Prof Marko Salmi MD,Ilse Piippo MD,Markku Jalkanen PhD,Prof Hugh Montgomery MD,Prof Sirpa Jalkanen MD
The Lancet Respiratory Medicine – 23 December 2013
DOI: 10.1016/S2213-2600(13)70259-5


Osteoporosis: Improving Bone Mineral Density Postmenopause with Monoclonal Antibody Romosozumab
MedicalResearch.com Interview with
Michael McClung, MD
Founding Director, Oregon Osteoporosis Center
5050 NE Hoyt Street, Suite 626
Portland, OR 97213

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Dr. McClung: In this Phase 2 trial, each of five romosozumab dose regimens significantly increased BMD compared with
pooled placebo groups at the lumbar spine, total hip and femoral neck regions (all p<0.001). The largest increases were
observed with the romosozumab 210 mg once-monthly dose, with mean increases, compared with baseline, of 11.3 percent
at the lumbar spine, 4.1 percent at the total hip and 3.7 percent at the femoral neck.

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Additionally, in exploratory analyses, BMD gains were significantly greater than active comparators (oral FOSAMAX 70 mg
weekly and subcutaneous FORTEO 20 ?g daily) at month 12, with romosozumab treatment achieving a mean increase of
11.3 percent at the lumbar spine compared to increases of 4.1 percent and 7.1 percent at the same region achieved with
FOSAMAX and FORTEO, respectively. At the total hip, romosozumab treatment increased BMD 4.1 percent, while observed
gains with FOSAMAX were 1.9 percent and FORTEO were 1.3 percent (all p<0.001).
Dr. McClung: To me, the magnitude of the increase in BMD with the largest dose of romosozumab was unexpected.
Additionally, the transient nature of the increase in markers of bone formation with values returning to baseline by 6
months was unexpected.
Dr. McClung: These results provide promise that this new approach to treatment will be of value in the future to patients
with severe osteoporosis.
Dr. McClung: More evidence is needed including understanding what happens with longer treatment, what happens when
treatment is stopped, the effects of therapy on fracture risk in women with osteoporosis and the safety and tolerability of
the treatment in a much larger group of patients. All of these studies are already underway.
Romosozumab in Postmenopausal Women with Low Bone Mineral Density
Michael R. McClung, M.D., Andreas Grauer, M.D., Steven Boonen, M.D., Ph.D., Michael A. Bolognese, M.D., Jacques P.
Brown, M.D., Adolfo Diez-Perez, M.D., Ph.D., Bente L. Langdahl, Ph.D., D.M.Sc., Jean-Yves Reginster, M.D., Ph.D., Jose R.
Zanchetta, M.D., Scott M. Wasserman, M.D., Leonid Katz, M.D., Judy Maddox, D.O., Yu-Ching Yang, Ph.D., Cesar Libanati,
M.D., and Henry G. Bone, M.D.
January 1, 2014DOI: 10.1056/NEJMoa1305224

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CANHEART: Cardiovascular Health Measurement Tool
Laura Maclagan, MSc.
Epidemiologist, Cardiovascular Program ICES Central
Toronto, Ontario M4N 3M5

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Answer: We developed the CANHEART health index in order to measure the cardiovascular
health of the Canadian population. The index is based on the prevalence of six health factors
and behaviours known to be associated with cardiovascular health; being a non-smoker,
being physically active, consuming at least 5 fruits and vegetables per day, having a low body
mass index (BMI <25 kg/m²) and being free of diabetes and hypertension. The factors were
summed to create an index ranging from 0 (worst) to 6 (best/ideal). We found that only 9.4%
of Canadian adults age 20 and older met our definition of ideal cardiovascular health. 53.3%
of adults were in intermediate cardiovascular health (4-5 healthy behaviours/factors) and
37.3% were in poor cardiovascular health (0-3 healthy behaviours). We found that the
cardiovascular health of Canadians was stable over the 2003-2011 study period.
Answer: Previous research has focused on the burden of cardiovascular disease in the
population. This is the first effort to quantify the cardiovascular health of Canadians using a
single metric. The findings of our study indicate that there is room for improvement in the
cardiovascular health of Canadians, particularly by improving levels of modifiable health
behaviours. Too many Canadians are at an increased risk of cardiovascular events due to
unhealthy behaviours and factors.

CANHEART: Cardiovascular Health Measurement Tool
Laura Maclagan, MSc.
Epidemiologist, Cardiovascular Program ICES Central
Toronto, Ontario M4N 3M5

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Answer: For clinicians, findings from our study can be used to identify areas where patients may be
counselled or encouraged to improve their heath behaviours. For example, smoking cessation should be
offered to patients who are smokers in order to reduce their risk of cardiovascular events. Encouraging
patients to improve other health behaviours such as being more physically active and eating more fruits
and vegetables will help individuals to maintain healthy body weights and reduce their risk of developing
diabetes, hypertension, and cardiovascular events.
For patients, the index can be used to identify areas for individual improvement in health behaviours. For
individuals who already have diabetes and hypertension, making improvements in health behaviours may
help to better manage their conditions. Small individual improvements in health behaviours and factors
can add up to large population-level changes in cardiovascular health if individuals take initiative to
improve even just one behaviour or factor.
Answer: We should continue to monitor population trends in health behaviours and factors in order to
identify appropriate targets for interventions that will have the most impact in reducing the burden of
cardiovascular disease in the population. Changing individual health behaviours is very difficult, and
successful interventions to improve the cardiovascular health of Canadians will require support and
collaboration from many groups including government, policy makers, disease and other organizations,
clinicians, patients, and the general public.
Citation:
The CANHEART health index: a tool for monitoring the cardiovascular health of the Canadian population
Laura C. Maclagan, Jungwee Park, Claudia Sanmartin, Karan R. Mathur, Doug Roth, Douglas G. Manuel,
Andrea Gershon, Gillian L. Booth, Sacha Bhatia, Clare L. Atzema, and Jack V. Tu
The CANHEART health index: a tool for monitoring the cardiovascular health of the Canadian population
CMAJ cmaj.131358; published ahead of print December 23, 2013, doi:10.1503/cmaj.131358


Obstructive Sleep Apnea: Outcomes in Hospitalized Pneumonia Patients
MedicalResearch.com Interview Invitation with:
Dr. Peter Lindenauer MD MS
Director, Center for Quality of Care Research
Baystate Medical Center, Springfield, MA, US

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Answer: Among a cohort of 250,000 patients hospitalized for pneumonia at 347 US hospitals,
those with a diagnosis of obstructive sleep apnea were twice as likely to be intubated at the
time of hospital admission than patients without sleep apnea. In addition, patients with
sleep apnea had approximately 50% higher risk of needing to be transferred to the ICU after
initial admission to a regular bed, and a 70% increased risk of requiring intubation later in the
hospital stay. Patients with sleep apnea stayed longer in the hospital and incurred higher
costs than those without sleep apnea.

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MedicalResearch.com:Were any of the findings unexpected?
Answer: Despite the increased requirement for mechanical ventilation at admission and
deterioration later in the hospital stay, sleep apnea was not associated with an increased risk
of in-hospital mortality. If anything, even after multivariable adjustment for differences
between the patients with and without sleep apnea, sleep apnea was associated with a
modestly lower or equivalent risk of mortality. This raises a number of interesting questions,
such as whether the clinical significance of intubation among patients with and without sleep
apnea differed – perhaps as a result of differences in the pathophysiology driving respiratory
failure.


Obstructive Sleep Apnea: Outcomes in Hospitalized Pneumonia Patients
MedicalResearch.com Interview Invitation with:
Dr. Peter Lindenauer MD MS
Director, Center for Quality of Care Research
Baystate Medical Center, Springfield, MA, US

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Answer: Patients with sleep apnea make up a large fraction of the US adult population. Our results
suggest that these patients are at increased risk of respiratory failure when they develop
pneumonia. Patients should probably seek medical attention early in the course of lower
respiratory tract illnesses like pneumonia, and physicians should be aware of the increased risk of
deterioration and may wish to consider placing these patients in setting with greater monitoring
capability (like a step-down unit).
MedicalResearch.com: What recommendations do you have for future research as a result of this
study?
Answer: Additional research is needed to determine whether increased levels of monitoring (as
suggested above) will prevent episodes of deterioration that lead to late intubation. More
importantly, while intuitively appealing, we don’t know whether routine use of positive airway
pressure devices (e.g. CPAP machines) during the hospitalization would be an effective strategy to
avoid complications among patients with sleep apnea.
Citation:
Lindenauer PK, Stefan MS, Johnson KG, Priya A, Pekow PS, Rothberg MB.
Prevalence, treatment and outcomes associated with obstructive sleep apnea among patients
hospitalized with pneumonia
Published online December 26, 2013.
doi:10.1378/chest.13-1544.


Texting, Phone Use Especially Dangerous for Novice Drivers
Sheila G. Klauer, Ph.D
Virginia Tech Transportation Institute
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Sheila G. Klauer, Ph.D
Virginia Tech Transportation Institute

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Dr.Klauer: We found that novice drivers are especially at risk of crash/near-crash involvement when engaging in secondary
tasks that take their eyes off of the forward roadway. This includes tasks with wireless devices such as texting, dialing, and
reaching for the device as well as reaching for any object, eating, and looking at objects along the roadway. We also found
that the prevalence of engaging in these high risk tasks increases over time which concerns traffic safety researchers. This is
particularly concerning with the proliferation of highly capable smart phones where teens can do not only texting but also
sending pictures, watching video, skype, etc.

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Dr.Klauer: While we were not surprised that these tasks increased risk, we were surprised at how much higher risk these
tasks are for novice drivers. We are hoping that parents and teenagers hear about this study and take note.
Dr.Klauer: Secondary tasks that take the drivers eyes off the forward roadway increase crash/near-crash involvement. To
keep our teens and drivers of all ages safe, it is important to keep your eyes forward and minimize the time taken to engage
in secondary activities.
Dr.Klauer: We are hoping to further assess the impact of roadway context on distraction and how this affects novice
drivers. While we believe that hands-free devices could be safer, these devices must be well-designed and truly hands free
to achieve this goal.
Citation:
Distracted Driving and Risk of Road Crashes among Novice and Experienced Drivers
Sheila G. Klauer, Ph.D., Feng Guo, Ph.D., Bruce G. Simons-Morton, Ed.D., M.P.H., Marie Claude Ouimet, Ph.D., Suzanne E. Lee,
Ph.D., and Thomas A. Dingus, Ph.D.
N Engl J Med 2014; 370:54-59January 2, 2014DOI: 10.1056/NEJMsa1204142


Sugar-Sweetened Beverage Intake and Health Related Knowledge
Sohyun Park, PhD, Division of Nutrition, Physical Activity, and Obesity
National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention
Atlanta, GA 30341

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Dr. Park: Nearly 1 out of 3 U.S. adults (30.5%) consumed sugar-sweetened beverages at least
1 time per day; 20% consumed sugar-sweetened beverages at least 2 times per day. About 8
out of 10 adults agreed that drinking sugar-sweetened beverages can contribute to weight
gain. However, 8 of 10 adults also did not know the actual calorie content of a 24-oz fountain
soda. After controlling for sociodemographic factors, adults who were neutral (neither
agreed nor disagreed) that drinking sugar-sweetened beverages can contribute to weight
gain were more than 1-and-a-half times more likely to consume sugar-sweetened beverages
at least 2 times per day. Conversely, knowledge about the calorie content of a 24-oz fountain
soda was not associated with sugar-sweetened beverage intake.
Dr. Park: We hypothesized that correct knowledge about the calorie content of a 24-oz
fountain soda would be associated with a lower sugar-sweetened beverage intake. However,
unlike our hypothesis, knowledge about the calorie content of regular soda was not
significantly associated with consuming sugar-sweetened beverage at least 2 times daily
among U.S. adults after controlling for sociodemographic factors.


Sugar-Sweetened Beverage Intake and Health Related Knowledge
Sohyun Park, PhD, Division of Nutrition, Physical Activity, and Obesity
National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention
Atlanta, GA 30341

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Dr. Park: Knowledge about the adverse effects of sugar-sweetened beverage intake is significantly
associated with sugar-sweetened beverage intake among U.S. adults. Thus, clinicians should
consider counseling their patients about the potential contribution of excess energy intake from
sugar-sweetened beverages to weight gain, as this counseling could potentially contribute to
lowered intake and lower prevalence of obesity.
Also, while knowledge about the calorie content of a 24-oz fountain soda was not associated with
sugar-sweetened beverage consumption, health education on the calorie content of sugarsweetened beverages may still be valuable because most adults did not know the actual calorie
content of sugar-sweetened beverages.
study?
Dr. Park: The associations from our study are one point in time (cross-sectional), so studies that
follow the same individuals over time (longitudinal) are needed to explore whether changes in
knowledge about sugar-sweetened beverage calorie content modify sugar-sweetened beverage
intake and to further explore what other knowledge might be associated with sugar-sweetened
beverage consumption.
Citation:
The Relationship between Health-Related Knowledge and Sugar-Sweetened Beverage Intake among
US Adults
Journal of the Academy of Nutrition and Dietetics – 23 December 2013
(10.1016/j.jand.2013.11.003)
Sohyun Park, Stephen Onufrak, Bettylou Sherry, and Heidi M. Blanck


High LDL, Low HDL Levels and Elevated Brain Amyloid
Dr. Bruce Reed PhD
Professor of Neurology,
Associate Director UC Davis Alzheimer’s Disease Center Davis, CA 95616

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Dr. Reed: We found that high LDL cholesterol and low HDL cholesterol in blood were both associated with
higher amyloid deposition in the brain. This is potentially very important because the deposition of
amyloid seems to be a critical step that kicks off a whole chain of events that eventually lead to
Alzheimer’s disease. It is widely believed (although not proven) that if this deposition of amyloid could be
blocked that we could greatly decrease the incidence of Alzheimer’s. The connection to cholesterol is
exciting because we know a fair amount about how to change cholesterol levels. A great deal more
research needs to be done, but this does suggest a potential new path toward trying to prevent AD.
Dr. Reed: People had looked before at total cholesterol levels and amyloid and had not found any
relationship (nor did we). What we did differently was to look at the different types of cholesterol (HDL,
LDL) and that is where we found a pattern. An interesting thing about this is that the pattern we found is
the same pattern that has been observed between cholesterol and heart disease.
Dr. Reed: First, understand that our findings need to be confirmed and that much research needs to be
done to tease out exactly what is going on here. In the meantime, this is another reason to really pay
attention to cholesterol levels. Try to get the LDL levels down, and the HDL levels up.
Dr. Reed: We need to replicate our basic findings in a larger group. But the really interesting work will be
on basic biological mechanisms by which cholesterol might change amyloid levels. That work could lead to
new approaches to heading off Alzheimer‘s before it starts.
Citation:
Reed B, Villeneuve S, Mack W, DeCarli C, Chui HC, Jagust W. Associations Between Serum Cholesterol
Levels and Cerebral Amyloidosis. JAMA Neurol. 2013;():. doi:10.1001/jamaneurol.2013.5390.

Pneumonia: Improved Antibiotic Strategies and Decreased Mortality
Dr Simone Gattarello
Vall d’Hebron Hospital, Critical Care Department
Universitat Autonoma de Barcelona and Medicine Department, Spai

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Dr. Gattarello: The main findings from the present study are a 15% decrease in ICU mortality due to severe communityacquired pneumonia caused by Streptococcus pneumoniae in the last decade; moreover, several changes in antibiotic
prescription practices were detected and an association between improved survival and both earlier antibiotic
administration and increased combined antibiotic therapy were identified. In summary, in severe pneumococcal
pneumonia combined antibiotic therapy and early antibiotic administration are associated with lower mortality.
Dr. Gattarello: In the last years various studies were published about infection and mortality, but, the majority of them were
realized in the whole population without differentiation between mild infection versus sepsis or sepsis shock. The majority
of those previous studies didn’t find a decrease in mortality. Otherwise, in the present study, where only patients with
severe sepsis and septic shock due to pneumonia were included, we discover a significant decrease of mortality. In that way,
our results were unexpected.
Dr. Gattarello: In the last decade, ICU mortality due to severe pneumococcal pneumonia has significantly decreased; an
improved survival was associated with earlier antibiotic prescription and an increased use of combined antibiotic therapy.
Dr. Gattarello: It would be interesting to investigate if the use of different antibiotic regimens or doses are associated with
lower mortality.
Citation:
Gattarello S, Borgatta B, Solé-Violán J, et al.
Decrease in mortality in severe community-acquired pneumococcal pneumonia: impact of improving antibiotic strategies
(2000-2013)
doi:10.1378/chest.13-1531


Atrial Fibrillation: Impact of Kidney Function
Dr Amitava Banerjee
NIHR Clinical Lecturer in Cardiovascular Medicine
University of Birmingham UK

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This was the first long-term study in individuals with atrial fibrillation to consider the impact
of renal function, as measured by eGFR, on stroke/thromboembolism, mortality and bleeding
in the same population concurrently.
Answer: There were three main findings of our study.
First, patients with worsening renal function had more severe risk factor profiles and had
higher rates of stroke/thromboembolism, mortality and bleeding.
Second, individuals receiving oral anticoagulation had lower rates of
stroke/thromboembolism and mortality than those not receiving anticoagulation at all levels
of renal function measured by eGFR, suggesting that anticoagulation has benefit in even
patients with low eGFR.
Third, renal function was not an independent predictor of stroke/thromboembolism at 1 year
after adjustment for baseline characteristics.
Answer: Given the fact that patients with poor renal function had increased rates of
stroke/thromboembolism, it was surprising that renal function, as measured by eGFR was not
independently associated with stroke/thromboembolism after adjustment for other risk
factors. Our findings suggest that the risk associated with poor renal function, is already
captured by other risk factors such as age, diabetes mellitus, hypertension and heart failure.

Atrial Fibrillation: Impact of Kidney Function
Dr Amitava Banerjee
NIHR Clinical Lecturer in Cardiovascular Medicine
University of Birmingham UK

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Answer: Although renal function was not an independent predictor of stroke/thromboembolism in
individuals with atrial fibrillation, these patients are still at high risk, and regular checking of renal
function (as measured by eGFR) would be recommended, especially because normal or mild renal
impairment at baseline does not preclude some patients from deteriorating to severe renal
impairment. Full anticoagulation is recommended in patients with at least moderate renal
impairment.
study?
Answer: Net clinical benefit weighs up the risk of stroke/thromboembolism versus the risk of
bleeding. Our data suggested that oral anticoagulation may have the greatest net clinical benefit in
individuals with atrial fibrillation and renal failure. However, our data are observational data and
not clinical trial data. Trials of oral anticoagulation are urgently required in patients with renal
impairment to determine the balance between efficacy and safety of anticoagulation in this patient
group. This is especially important because the majority of trials in patients with atrial fibrillation
have excluded patients with renal impairment.
Citation:
A prospective study of estimated glomerular filtration rate and outcomes in patients with atrial
fibrillation: The Loire Valley Atrial Fibrillation Project
Banerjee A, Fauchier L, Vourc’h P, et al.
A prospective study of estimated glomerular filtration rate and outcomes in patients with atrial
fibrillation: the loire valley atrial fibrillation project


Lung Cancer: Annual CT Screening for High Risk Patients
Harry J de Koning, MD PhD
Professor of Public Health & Screening Evaluation
Rotterdam, The Netherlands.

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Dr. de Koning: Annual CT screening for lung cancer has a favorable benefit-to-harm ratio for
individuals ages 55 through 80 years with 30 or more pack-years’ exposure to smoking. It
would lead to 50% (model ranges, 45% to 54) of cases of cancer being detected at an early
stage (stage I/II), 575 screenings examinations per lung cancer death averted, a 14% (range,
8.2% to 23.5%) reduction in lung cancer mortality, 497 lung cancer deaths averted, and 5250
life-years gained per the 100 000-member (1950-) cohort. Harms would include 67 550 falsepositive test results, 910 biopsies or surgeries for benign lesions, and 190 overdiagnosed
cases of cancer (3.7% of all cases of lung cancer [model ranges, 1.4% to 8.3%]), again for a
100 000-member (1950-) cohort.
Dr. de Koning: Yes and no; the NLST (National Lung Screening Trial) had shown benefits from
3 annual CT screens in a specific volunteer population aged 55-74.
Inviting asymptomatic individuals for screening and implementing a large-scale screening
program should be considered only when the benefits clearly outweigh the harms. Our
analysis provides a detailed account of the balance between harms and benefits of annual
lung cancer screening to inform individuals, clinicians, and policymakers. This analysis
estimated life-time benefits and harms of different screening scenarios, and found a set of
efficient scenarios, that included continuing screening through age 80. It estimated life-years
gained, but also important harms like over diagnosis, false positives and radiation-related
lung cancer deaths, that was not available yet.

Lung Cancer: Annual CT Screening for High Risk Patients
Harry J de Koning, MD PhD
Professor of Public Health & Screening Evaluation
Rotterdam, The Netherlands.

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Dr. de Koning: First of all, to try to stop smoking and discourage starting smoking.
Secondly, the USPSTF recommends, partly based on our results, yearly screening with LDCT in
adults aged 55 through 80 years who have at least a 30 pack-year history of smoking and who
continue to smoke or who have quit less than 15 years ago.
Thirdly, I think it is important to realize that over diagnosis in lung cancer screening is relatively
limited.
study?
Dr. de Koning: The NEderlands-Leuven Screening Onderzoek (NELSON) trial, which enrolled 15 822
individuals age 50 to 75 years and compared CT screening with no screening in Europe is still
missing mortality results. But, the NELSON trial has primarily used volume-doubling times and
volume measurements of lung nodules to define its referral strategy, thereby substantially reducing
the number of positive and false-positive results: About 60% of referrals were for false-positive
results, and the percentage of referrals was about 2%. It may therefore be feasible to reduce one of
the important harms of lung cancer screening via changes in follow-up guidelines.
In the coming years it may also be possible to improve eligibility criteria for screening and adapt our
models to incorporate broader eligibility criteria based on more complex measures of risk.
Citation:
Harry J. de Koning, Rafael Meza, Sylvia K. Plevritis, Kevin ten Haaf, Vidit N. Munshi, Jihyoun Jeon,
Saadet Ayca Erdogan, Chung Yin Kong, Summer S. Han, Joost van Rosmalen, Sung Eun Choi, Paul F.
Pinsky, Amy Berrington de Gonzalez, Christine D.


Colon Cancer and Diverticular Disease
Chia-Hung Kao, MD
Graduate Institute of Clinical Medicine Science and School of Medicine
College of Medicine, China Medical University, Taiwan.

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Answer: Colonic diverticular disease and colorectal cancer shared certain characteristics.
Some previous studies aimed to identify their epidemiological correlation. However, their
results were discrepant and insufficiently strong to draw firm conclusion. In our nationwide
population-based retrospective cohort study, we found that the previously diagnosed colonic
diverticular disease is not associated with an elevated risk of colorectal cancer after the first
year of a diagnosis of colonic diverticular disease (adjusted HR, 0.96). The increased risk in
the first year may be due to misclassification and screening effect.
Answer: Hypertension, hyperlipidemia, and diabetes mellitus were very common chronic
disease. They were also risk factors for colorectal cancer. We expected they had more
significant impact on increased colorectal cancer in patients with diverticular disease than
those without. However, in our current study, the risk of colorectal cancer was not further
enhanced by the comorbidities. While no previous studies addressed this issue, the
interaction among these chronic diseases, diverticular disease and colorectal cancer was still
unknown.


Colon Cancer and Diverticular Disease
Chia-Hung Kao, MD
Graduate Institute of Clinical Medicine Science and School of Medicine
College of Medicine, China Medical University, Taiwan.

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Answer: Clinicians should be aware that patients with colorectal cancer might be
misclassified as colonic diverticular disease at first. We suggested that these patients should
be closely followed and carefully selected for colonoscopy. For patients with colonic
diverticular disease, regular follow up is recommended for at least 1 year.
MedicalResearch.com: What recommendations do you have for future research as a result
of this study?
Answer: The incidence rates of colonic diverticular disease and colorectal cancer varies
worldwide. Our result is from Taiwan and may be different from those in other countries.
Further research on different races is recommended.
Citation:
Association Between Colonic Diverticular Disease and Colorectal Cancer: a Nationwide
Population-Based Study
Wen-Yen Huang, Che-Chen Lin, Yee-Min Jen, Yen-Jung Chang, Cheng-Wen Hsiao, Muh-Hwa
Yang, Chun-Shun Lin, Fung-Chang Sung, Ji-An Liang, Chia-Hung Kao
Clinical Gastroenterology and Hepatology – 19 December 2013 (10.1016/j.cgh.2013.11.039)


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Hypothyroidism and Mild Cognitive Impairment Risk?
Ajay K Parsaik, MD, MS
Department of Psychiatry and Behavior Sciences
The University of Texas Medical School, Houston
Department of Neurology and Mayo Alzheimer’s Disease Research Center, Mayo Clinic, Rochester, Minnesota

Dr. Parsaik: Main findings of our study are that clinical and subclinical hypothyroidism is not
associated with mild cognitive impairment in an elderly population after accounting for possible
confounding factors and interactions.
Dr. Parsaik: Yes, these findings were unexpected as there is limited previous evidence supporting
it.
Dr. Parsaik:
For patients – Clinical and subclinical hypothyroidism is not associated with mild cognitive
impairment among elderly.
For cliniciansMain message for clinician is that they should reassure the patients with hypothyroidism and sub
clinical hypothyroidism that none of them are associated with mild cognitive impairment. While
evaluating the patients with mild cognitive impairment for underlying etiologies, they should focus
more on other causes.
study?
Dr. Parsaik: Our results should be validated in longitudinal cohort study.
Citation:
Parsaik AK, Singh B, Roberts RO, et al. Hypothyroidism and Risk of Mild Cognitive Impairment in
Elderly Persons: A Population-Based Study. JAMA Neurol. 2013;():.
doi:10.1001/jamaneurol.2013.5402.

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Hospital Readmissions: Many Caused by Co-Morbid Diseases, Infections
Dr. Jacques Donzé MD PhD
Research Associate
Division of General Internal Medicine and Primary Care, Brigham and Women’s Hospital
Harvard Medical School, Boston, MA 02115,

Dr. Donzé: In a large retrospective cohort study, we identified the primary diagnoses of 30-day potentially
avoidable readmissions in medical patients according to the most common comorbidities. Interestingly,
almost all of the top five diagnoses of potentially avoidable readmissions for each comorbidity were
possible direct or indirect complications of that comorbidity. Patients with cancer, heart failure, and
chronic kidney disease had a significantly higher risk of potentially avoidable readmission than those
without those comorbidities. Also, when readmitted, patients with chronic kidney disease had a 20%
higher risk of having the readmission be potentially avoidable.
Dr. Donzé: As much of the existing literature on readmissions focuses on heart failure, it is worth noting
that potentially avoidable readmissions were most often due to infections in this study.
Dr. Donzé: Transitions of care should not only focus on the acute condition responsible for the
hospitalization, but also on patients’ underlying chronic comorbidities that may increase the risk of new,
acute complications.
Dr. Donzé: Transition care interventions that include consideration of the patients’ underlying chronic
comorbidities should be proven to the reduce readmission risk. Also, further work is needed to explore the
nature of infections causing potentially avoidable readmission and to identify possible ways in which they
could be avoided in the future.
Citation:
Causes and patterns of readmissions in patients with common comorbidities: retrospective cohort study
Donzé J ,Lipsitz S ,Bates DW ,Schnipper JL. Causes and patterns of readmissions in patients with common
comorbidities: retrospective cohort study. BMJ 2013;347:f7171


Improving Suceess of Corneal Transplantation
MedicalResearch.com Interview with: Dr. Jerry Y. Niederkorn, Ph.D. George A. and Nancy P. Shutt Professorship in Medical Sciences
Royal C. Miller Chair in Age-Related Macular Degeneration Research Professor of Ophthalmology and Microbiology
Vice Chair, Research (Department of Ophthalmology)
Department of Ophthalmology, University of Texas Southwestern Medical Center Dallas, TX

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Dr. Niederkorn: These findings indicate that a combination of two simple maneuvers increases the
acceptance of corneal transplants. In the past, there was no clear benefit in performing tissue
matching of the cornea donor’s major histocompatibility complex (MHC) with the recipient of the
corneal transplant. However, our study in experimental animals revealed that blocking a single
immune system molecule called interferon-gamma (IFN-γ) combined with matching the corneal
transplant donor with the transplant recipient’s MHC gene complex reduced the risk of rejection to
less than 10% in the total absence of anti-rejection drugs. This study revealed that blocking this
single immune system molecule promoted the development of immune system cells called T
regulatory cells (Tregs) that suppressed the lymphocytes that are responsible for attacking organ
transplants.

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Dr. Niederkorn: Two aspects of this study were especially unexpected.
First, the prevailing theory in in the field of transplantation immunology has assumed that a key
immune system molecule called IFN-γ was necessary for and facilitated the immune rejection of
organ transplants. Our study showed that blocking this molecule (IFN-γ) in recipients of corneal
transplants in which tissue typing for the MHC compatibility was performed resulted in an
exacerbation, rather than a prevention of corneal graft rejection.
The second unexpected finding was that tissue matching of the MHC of the cornea donor and the
corneal graft recipient did not enhance graft survival. However, MHC matching and blocking IFN-γ
with a monoclonal antibody prevented graft rejection.

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Improving Suceess of Corneal Transplantation
MedicalResearch.com Interview with: Dr. Jerry Y. Niederkorn, Ph.D. George A. and Nancy P. Shutt Professorship in Medical Sciences
Royal C. Miller Chair in Age-Related Macular Degeneration Research Professor of Ophthalmology and Microbiology
Vice Chair, Research (Department of Ophthalmology)
Department of Ophthalmology, University of Texas Southwestern Medical Center Dallas, TX

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Dr. Niederkorn: Matching the corneal transplant donor and the graft recipient alone offers no
benefit for long-term corneal graft survival. In the absence of MHC tissue matching, blocking IFN-γ
alone not only fails to enhance graft survival, but in fact exacerbates immune rejection.
However, the combination of the two maneuvers guarantees corneal graft acceptance in rodents. It
remains to be determined if the same condition occurs in patients, especially “high risk” transplant
recipients who have rejected a previous corneal transplant.
study?
Dr. Niederkorn: It will be important to determine if a blocking antibody against IFN-γ can be
administered in eye drops as a simple application that has minimal systemic effects.
There is evidence that the immune systems of hosts with long-term surviving corneal transplants
become “tolerant” of the foreign histocompatibility molecules on the transplant and remain in a
dormant or quiescent state. Therefore, it will useful to ascertain if the immune systems of hosts
who have received MHC-matched corneal grafts and have been treated with anti-IFN-γ antibody
become reprogrammed and as a result, the administration of antibodies against IFN-γ can be
tapered and eventually terminated.
Citation:
Cunnusamy, K. and Niederkorn, J. Y. (2013), IFN-γ Blocks CD4+CD25+ Tregs and Abolishes Immune
Privilege of Minor Histocompatibility Mismatched Corneal Allografts. American Journal of
Transplantation, 13: 3076–3084. doi: 10.1111/ajt.12466


Peanut Allergy: Does Eating Peanuts During Pregnancy Reduce Allergies in Children?
Michael C. Young, M.D.
Associate Clinical Professor of Pediatrics Harvard Medical School
Division of Allergy & Immunology Children’s Hospital Boston

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Dr. Young: We found an association between increased maternal peripregnancy consumption of peanuts/ tree nuts and
reduced risk of nut allergies in the offspring.
Dr. Young: These data support similar findings in recents studies of early infant diets, that early exposure to food allergens
reduces risk of developing allergies to those foods, whereas avoidance of food allergens in early childhood may increase risk
of food allergies. Ours is the first to examine peripregnancy diets with reduction of risk to a food allergy in the offspring.
Dr. Young: While our data shows an association, because of our study design as an observational study, we do NOT show a
causal relationship between maternal diet during peripregnancy and the offspring’s risk of nut allergy. Therefore specific
dietary recommendations for the pregnant woman cannot be made from this study. However, this study does dispel the
notion that pregnant women should avoid eating nuts to prevent sensitization and development of nut allergies; if a
pregnant woman wishes to eat peanuts and tree nuts, she can feel free and safe in doing so.
Dr. Young: To prove a cause-and-effect relationship between maternal diet during pregnancy and risk of nut allergies in the
offspring, a prospective randomized interventional study is required. Only then can definitive evidence-based dietary
recommendations for pregnant women be formulated, for the prevention of food allergies in offspring.
Citation:
Frazier A, Camargo CA, Jr, Malspeis S, Willett WC, Young MC.
Prospective Study of Peripregnancy Consumption of Peanuts or Tree Nuts by Mothers and the Risk of Peanut or Tree Nut
Allergy in Their Offspring. JAMA Pediatr. 2013;():. doi:10.1001/jamapediatrics.2013.4139.


Using Clinical Databases to Monitor Drug Side Effects and Performance
Leo Anthony Celi, MD, MS, MPH
Massachusetts Institute of Technology
Cambridge, MA 02139

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Dr. Celi: The main take home point from the paper is that we know little about how drug
perform in the real world. Which patients truly benefit? Which patients are harmed? How do
drugs interact with different acute (such as critical illness) and chronic conditions? These
questions are almost never answered during pre-marketing research due to cost. We need a
better system of following the life cycle of drugs post-marketing. Clinical databases provide us
with this opportunity.

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Dr. Celi: Note that the findings of the study would need to be validated in other databases
given that the analysis was only performed using a clinical database from a single center.
Retrospective analyses are quite complicated to perform. A significant caveat is that the
analysis may be marred by residual confounding and bias by indication. The goal is to identify
patient records in the database that are as similar as possible to the patient in terms of the
variables that can confound the relationship between the drug and the outcome, and then to
compare the outcomes of those who receive the drug versus those who did not. Residual
confounding means that the outcome difference might not be due to the drug but rather due
to something inherent to those patients who receive the drug, or their condition.


Using Clinical Databases to Monitor Drug Side Effects and Performance
Leo Anthony Celi, MD, MS, MPH
Massachusetts Institute of Technology
Cambridge, MA 02139

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Dr. Celi: Obtaining new information about a drug’s benefits and risks should not stop after market
authorization. In recent years, highly-publicized post-marketing crises like those of Vioxx and
Avandia have raised FDA’s awareness of the shortcomings of the Adverse Event Reporting System
(AERS), a passive surveillance system for collecting spontaneous reports of drug safety by providers
and researchers. We propose modernizing and extending this surveillance system through
systematic aggregation of safety and efficacy information.
study?
Dr. Celi: Electronic Medical Records that include detailed clinical information provide researchers
an opportunity to accumulate safety and efficacy evidence, to discover patient subpopulations that
experience increased efficacy or unanticipated delayed adverse effects, and to uncover interactions
between simultaneous treatments as drugs become used in wider, more diverse patient
populations than those possible during pre-market approval clinical studies. We recommend the
FDA partner with representative clinics and hospitals across the country for access to their clinical
databases, to better represent minority and vulnerable patient populations. Such an active national
surveillance system would allow drugs to be monitored longitudinally over the entire market
life, providing the FDA timely access to new information for evaluating a drug’s benefit-risk profile.
Citation:
SSRI use prior to ICU admission is associated with increased hospital mortality
Ghassemi M, Marshall J, Singh N, Stone DJ, Celi L.
Ssri Use Prior To Icu Admission Is Associated With Increased Hospital Mortality
doi:10.1378/chest.13-1722.

Antibiotic May Treat Dry Eye Disorder
Dr. Yang Liu Preceptor and Dr. David A. Sullivan, MS, PhD, FARVO
Senior Scientist, Schepens Eye Research Institute, Associate Professor, Department of Ophthalmology Harvard Medical School
Boston, MA, USA 02114

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MedicalResearch.com: What is the main finding of the study?
Answer: We discovered that azithromycin (AZM) can directly stimulate the function of human meibomian gland epithelial
cells. Given this finding, it is possible that this antibiotic may prove beneficial as a treatment for meibomian gland
dysfunction (MGD), which is the leading cause of dry eye disease in the world.
Answer: No. We hypothesized that azithromycin could act directly on human meibomian gland epithelial cells to stimulate
their differentiation, enhance the quality and quantity of their lipid production, and promote their holocrine secretion.
Answer: The ability of AZM to stimulate the differentiation, and apparently secretion, of human meibomian gland epithelial
cells is clinically very significant. This action could explain why the off-label use of topical AZM is the most commonly used
pharmaceutical treatment for MGD in the United States. This antibiotic’s efficacy has been presumed to be due to its antiinflammatory and anti-bacterial actions, which may suppress the MGD-associated posterior blepharitis and growth of lid
bacteria. However, our data indicate that AZM also has the capability to enhance directly the function of human meibomian
gland epithelial cells, and thereby possibly ameliorate the pathophysiology of MGD.
Answer: This study was made possible by our previous immortalization of human meibomian gland epithelial cells. This cell
line is an ideal human preclinical model to permit the discovery of drugs to treat MGD. Such research in the future will allow
the creation of a portfolio of therapeutic options to treat the underlying disease and improve the quality of life of MGD
patients.
Citation:
Effect of Azithromycin on Lipid Accumulation in Immortalized Human Meibomian
Liu Y, Kam WR, Ding J, Sullivan DA. Effect of Azithromycin on Lipid Accumulation in Immortalized Human Meibomian Gland
Epithelial Cells. JAMA Ophthalmol. 2013;():. doi:10.1001/jamaophthalmol.2013.6030. Gland Epithelial Cells
Tear Film & Ocular Surface Society
www.TearFilm.org<https://outlook.meei.harvard.edu/owa/redir.aspx?C=tQH4PkVqm0up5gbb4EOinz4pVxcnPtAI0LTEjlc50iRk5dk8G_JRK6-o_3jrstFV9FrO798GSI.&URL=http%3a%2f%2fwww.tearfilm.org%2f>


Clinical Trial Enrollment: Racial & Ethnic Enrollment Differences
Aisha T. Langford, PhD, MPH Postdoctoral Fellow
VA Health Services Research and Development Service & U-M Center for Bioethics and Social Sciences in Medicine
Ann Arbor, MI 48109

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Dr. Langford: The main and perhaps most interesting finding was that there were no racial/ethnic differences in cancer
clinical trial enrollment, refusal rates, or “no desire to participate in research” as the reason given for clinical trial refusal;
however, patients over the age of 65 had lower odds of being enrolled in a clinical trial. Additionally, higher odds of having
physical/medical conditions were associated with older age, males, and non-Hispanic blacks.

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Dr. Langford: It was a bit surprising to find that a higher grade level score for consent form readability (OR = 0.9, 95%
CI = 0.83-0.97) was significantly associated with lower refusal rates and that consent page length ≥ 20 was significantly
associated with lower odds of “no desire to participate in research” among clinical trial decliners (OR = 0.75, 95% CI = 0.580.98).
Dr. Langford: Better management of physical/medical conditions before and during treatment may increase the pool of
eligible patients for clinical trials. Additionally, we should be cautious about assuming that racial/ethnic minorities are less
willing to participate in cancer clinical trials. The racial/ethnic disparity in clinical trial participation overall may be due to
logistical factors such as the characteristics of a clinical trial, patients being excluded because of co-morbidities, and
clinicians not offering clinical trials to all patients.
Dr. Langford: Future work should examine the role of comorbidities, sex, age, and consent form characteristics on clinical
trial participation. Additionally, future work should evaluate the impact of provider preferences and biases in the context of
offering clinical trials. Although we did not fully explore physician characteristics and patient clinical trial participation, the
primary reasons that MDs declined offering a trial to an eligible patient were preference for standard of care and concerns
about the patient?s ability to tolerate a clinical trial due comorbidities/ frailty.
Citation:
Racial/ethnic differences in clinical trial enrollment, refusal rates, ineligibility, and reasons for decline among patients at sites
in the National Cancer Institute’s Community Cancer Centers Program
Langford, A. T., Resnicow, K., Dimond, E. P., Denicoff, A. M., Germain, D. St., McCaskill-Stevens, W., Enos, R. A., Carrigan, A.,
Wilkinson, K. and Go, R. S. (2013), Racial/ethnic differences in clinical trial enrollment, refusal rates, ineligibility, and reasons
for decline among patients at sites in the National Cancer Institute’s Community Cancer Centers Program. Cancer.
doi: 10.1002/cncr.28483

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Bacteria Can Survive Longer In Environment Than Previously Thought
Anders P. Hakansson, Ph.D.
Assistant Professor of Microbiology
Department of Microbiology and Immunology Buffalo, NY 14214

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MedicalResearch.com: What are the main findings of the study:
Dr. Hakansson: During the last couple of years we have shown that Streptococcus pneumoniae, a common
colonizer of the nasopharynx in small children and elderly that sometimes cause respiratory infections such as
middle ear infections and pneumonia, and Streptococcus pyogenes, a common colonizer of the oropharynx and
also the cause of strep throat and skin infections, colonize us humans by forming biofilms; intricate bacterial
communities. Biofilms have been studied for a long time but these specific organisms have not been shown to
form biofilms during colonization until recently. As biofilms are much more resistant to environmental stresses and
antibiotics, we were interested to see whether biofilms formed by these organisms could survive in the
environment. The main reason for doing the experiments was that CDC guidelines indicate that spread of these
organisms between individuals occur solely by inhalation of bacteria-containing droplets after coughing or
sneezing. The risk of spread through surfaces has been estimated to be very low as laboratory experiments over
the last 40 years have shown that these bacteria die very rapidly on surfaces. These studies were
not, however, done with biofilm bacteria. Laura Marks in the laboratory with help from Ryan Reddinger therefore
first tested how long biofilm bacteria could survive on plastic surfaces and found that rather than hours these
bacteria were alive even after a month and could be used to successfully colonize animals. This made us
interested in understanding if these bacteria survive better on hands, a common way to spread bacteria. And just
as on inanimate surfaces, the biofilms survived much better on hands than bacteria grown in laboratory media.
Based on these results, we were allowed to sample bacteria from stuffed toys, books, crib linens and others
surfaces in a day care center early in the morning before the children arrived, and found both S. pneumoniae and
S. pyogenes on these items. The results of the study indicate that these bacteria can survive in the environment
longer than we have previously thought and may therefore play a role in spread between individuals.
Dr. Hakansson: Although we hypothesized that biofilms would survive longer than bacteria grown in laboratory
medium, we were a little surprised that they survived for so long. We were also a little surprised initially that it
was so easy to culture these bacteria from inanimate objects in the day care center.


Bacteria Can Survive Longer In Environment Than Previously Thought
Anders P. Hakansson, Ph.D.
Assistant Professor of Microbiology
Department of Microbiology and Immunology Buffalo, NY 14214

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Dr. Hakansson: These studies add a piece to the puzzle of how these bacteria may spread between
individuals, and could be potentially important in preventing spread. The studies are initial and they
only suggest that spread of these two bacterial species may occur through surfaces. Other studies
will be needed to understand how important this type of spread is. If it is common, it may be worth
revisiting the recommendations for handling colonization and infection with these bacteria in
health care settings and in environments dealing with children, such as schools and day care
centers. As always, good hand hygiene, and keeping surfaces clean goes a long way to prevent
spread both for those bacteria and other microorganisms in our environment.
study?
Dr. Hakansson: As mentioned above, future studies should investigate the level of spread that
occurs through surfaces and fomites for these two bacteria. If it is substantial, new
recommendations limiting the spread of these bacteria can be implemented in the environments
these bacteria are most often found, such as hospitals, day care centers and schools.
Citation:
Biofilm Formation enhances Fomite Survival of S. pneumoniae and S. pyogenes
Laura R. Marks, Ryan M. Reddinger, and Anders P. Hakansson
Infect. Immun. IAI.01310-13; published ahead of print 26 December 2013, doi:10.1128/IAI.01310-13

Gastroparesis: Nortriptyline Found Ineffective
MedicalResearch.com Interview Invitation with
Henry P. Parkman, MD Professor, Medicine
Director, GI Motility Laboratory
Temple University, Philadelphia, Pennsylvania

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Dr. Parkman: Gastroparesis remains a challenging syndrome to manage with few effective treatments and a lack of
rigorously controlled trials. Tricyclic
antidepressants are often used to treat refractory symptoms of nausea,
vomiting, and abdominal pain. Evidence from well-designed studies for this
is lacking.
However, in this study, among patients with idiopathic gastroparesis, the
use of nortriptyline compared with placebo for 15 weeks did not result in
improvement in overall symptoms. These findings do not support the use of
nortriptyline for idiopathic gastroparesis.
Dr. Parkman: Yes, we expected this might help the symptoms of abdominal pain, nausea, vomiting.
Dr. Parkman: This study shows that among patients with idiopathic gastroparesis, the use of nortriptyline compared with
placebo for 15 weeks did not result in
improvement in overall symptoms. Our results raise general doubts about the
utility of tricyclic antidepressants in low doses as a strategy for the
treatment of idiopathic gastroparesis.
Dr. Parkman: Other neuromodulators should be assessed in patients with gastroparesis. Specifically, those that target
nausea and vomiting.
Citation:
Effect of Nortriptyline on Symptoms of Idiopathic Gastroparesis
The NORIG Randomized Clinical Trial
Parkman HP, Van Natta ML, Abell TL, et al. Effect of Nortriptyline on Symptoms of Idiopathic Gastroparesis: The NORIG
Randomized Clinical Trial. JAMA. 2013;310(24):2640-2649. doi:10.1001/jama.2013.282833.


Pediatric Migraines: Cognitive Therapy Plus Amitriptyline
Scott W. Powers, PhD APBB
Division of Behavioral Medicine and Clinical Psychology and
Division of Neurology, Cincinnati Children’s Hospital Medical Center Department of Pediatrics,
University of Cincinnati College of Medicine, Cincinnati, Ohio

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Dr. Powers: Cognitive behavioral therapy plus amitriptyline resulted in greater reductions in days
with headache and migraine-related disability compared with the use of headache education plus
amitriptyline. Children and adolescents with chronic migraine began the study with an average of
21 days with headache per 28 days and disability measured in the severe range. After 20 weeks of
treatment, 2 out of 3 participants in the CBT group had a 50% or greater reduction in headache
days and 3 out of 4 had a reduction in disability to the mild to none range.

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Dr. Powers: Cognitive behavioral therapy works, children and adolescents like it and stick with it,
and the impact of treatment is durable. CBT should be discussed with families at the time a
diagnosis of chronic migraine is made. It is helpful to describe the treatment in a way that focuses
on the active, coaching in coping skills nature of CBT and how it is based on a biopsychosocial
model and when used along with preventive medication, may change the neurobiological
mechanisms that generate and maintain chronic migraine. Because of the clinically meaningful
impact we demonstrated in our trial, CBT should now be recommended as a first line treatment for
chronic migraine in youth along with medication from the onset of an initial treatment plan and not
as as add-on therapy once medication is found to be less than optimally effective. The major
transformation of practice would be to incorporate into treatment from the time of diagnosis and
advocate for access, reimbursement, and training of health care providers in this specific form of
biopsychosocial treatment.


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Pediatric Migraines: Cognitive Therapy Plus Amitriptyline
Scott W. Powers, PhD APBB
Division of Behavioral Medicine and Clinical Psychology and
Division of Neurology, Cincinnati Children’s Hospital Medical Center Department of Pediatrics,
University of Cincinnati College of Medicine, Cincinnati, Ohio

MedicalResearch.com: Do you have recommendations for future research based upon your trial?
Dr. Powers: First off, migraines need to be recognized, treated, and considered a neurological
disorder that has a major impact on the lives of children, adolescents, and adults. To help
patients, we need to now take evidence from rigorous randomized clinical trials, and translate the
treatments into practice. Also, more research focused on determining the efficacy of medication
and behavioral treatments for migraines in youth is needed. Our team at the Cincinnati Children’s
Headache Center is leading a US based effort to test amitriptyline, topiramate, and placebo in
pediatric migraine. The CHAMP Study (Childhood and Adolescent Migraine Prevention Trial) is
funded by the National Institute of Neurological Disorders and Stroke and involves up to 40 sites
across the country. Currently enrolling, this trial will be the first to compare the effectiveness of
these two medications and to compare both to a placebo pill in a group of children and adolescents
ages 8 to 17 that are representative of those families that seek care for migraines. The University of
Iowa is the data coordinating center. For chronic migraine, we need to conduct health outcomes
research to demonstrate the effectiveness of CBT in the clinical care setting and to innovate in
terms of refining the treatment so it is more accessible for the most number of families
possible. We also need to conduct longitudinal research to examine how durable the impact of CBT
is as the youth move into adulthood. If early intervention can be shown to change a life-long
trajectory of outcomes for people who have migraines, then the public health impact of CBT and
active treatment of youth with migraine and chronic migraine could be quite remarkable.
Citation:
Cognitive Behavioral Therapy Plus Amitriptyline for Chronic Migraine in Children and Adolescents :A
Randomized Clinical Trial
Powers SW, Kashikar-Zuck SM, Allen JR, et al. Cognitive Behavioral Therapy Plus Amitriptyline for
Chronic Migraine in Children and Adolescents: A Randomized Clinical Trial. JAMA.
2013;310(24):2622-2630. doi:10.1001/jama.2013.282533.

Mortality Rates after Hip, Knee Surgery Fall
Arief Lalmohamed, PharmD
Utrecht Area, Netherlands
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Dr. Lalmohamed: In a nationwide cohort study, short-term survival following elective
hip and knee replacement surgery has greatly improved since the early
90s. Between 1989 and 2007, risk of death within 60 days has decreased
by 60% for hip surgery and 63% for knee surgery. This translates into
a 60-day mortality rate of 0.23% between 2003 and 2007.
Dr. Lalmohamed: The findings were somewhat unexpected when taking into account the
following observation: surgical patients tended to have more
co-morbidity over time (e.g. diabetes, COPD, and heart failure). Even
when not adjusting for this trend, the drop in mortality rates
remained present. This suggests that, despite surgical patients having
a more complex risk profile, this did not result into a higher rate of
short-term mortality.
Dr. Lalmohamed: For patients who are about to undergo elective hip or knee replacement surgery, the observed decline in mortality rates is
reassuring. For
clinicians, this might imply that changes in patient care, surgical
techniques, and the introduction of novel therapeutics may indeed have
improved short-term survival. As an example, we found a relationship
between the length of hospital stay and mortality, which supports
current common practice of mobilizing these surgical patients as fast
as possible.
Dr. Lalmohamed: Although this study showed that mortality rates were low on an overall
level, there may still be patients who are at substantially increased
risk of death (or non-fatal complications) following elective hip or
knee replacement surgery. We therefore promote the development of
clinical risk scores that can estimate the risk of these unwanted
outcomes in each individual patient who is thinking about undergoing
such an elective procedure.
Citation:
Changes in mortality patterns following total hip or knee replacement over
the past two decades: A nationwide cohort study
Lalmohamed A, Vestergaard P, de Boer A, Leufkens HG, van Staa TP, de Vries F.
Arthritis Rheum. 2013 Dec 18. doi: 10.1002/art.38232. [Epub ahead of print]


Sham Surgery as Effective as Meniscectomy for Degenerative Knee Mensicus Tear
Raine Sihvonen, M.D.
From the Department of Orthopedics and Traumatology
Hatanpää City Hospital, Tampere Finland

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Dr. Järvinen: The main finding of the study is that arthroscopic partial meniscectomy
is not superior over sham-surgery (placebo) when treated patients with knee
pain attributable to degenerative meniscus tear, even in the
`best-case-scenario, that is patients with no knee OA.

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Dr. Järvinen: The fact that meniscectomy was found to be no better than sham even 0 to
6 six months postoperatively.
Dr. Järvinen: Arthroscopic partial meniscectomy should not be offered to middle-aged
patients with degenerative knee disease, that is non-traumatic knee pain.
Middle-aged patients with non-traumatic knee pain, should not seek after
surgery, but rather do muscle exercise.
Dr. Järvinen: The possible benefit of partial meniscectomy should be investigated
among patients with a clear traumatic onset of symptoms.
Citation:
Arthroscopic Partial Meniscectomy versus Sham Surgery for a Degenerative
Meniscal Tear
Raine Sihvonen, M.D., Mika Paavola, M.D., Ph.D., Antti Malmivaara, M.D., Ph.D., Ari Itälä, M.D., Ph.D., Antti
Joukainen, M.D., Ph.D., Heikki Nurmi, M.D., Juha Kalske, M.D., and Teppo L.N. Järvinen, M.D., Ph.D. for the
Finnish Degenerative Meniscal Lesion Study (FIDELITY) Group

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Diabetes: Effect of Lifestyle Intervention on Weight Change
Prof. Raj S Bhopal
Bruce and John Usher Professor of Public Health
Edinburgh Ethnicity and Health Research Group, Centre for Population Health Sciences,
University of Edinburgh, Teviot Place, Edinburgh EH89AG

Prof. Bhopal: In a randomised controlled trial, a tailored, family orientated intervention whereby dietitians worked in the
family home to provide diet and exercise advice in people at high risk of developing diabetes, had a modest but potentially
important effect in reducing weight at the end of the three-year intervention, by 1.6 kg more than in the control group.
Prof. Bhopal: More than one fifth of the study population, including those in the intervention group, increased their weight
by 2.5 kg or more over three years. A remarkable 98% of the study population of 171 people completed the three-year trialthat may well be a record in the context of trials of this kind.
Prof. Bhopal: If people at high risk of developing diabetes e.g. because of impaired glucose tolerance or impaired fasting
glucose, family orientated health promotion provided by trained health professionals would be a reasonable addition to the
normal armamentarium of actions.
Prof. Bhopal: This is one of the first trials of its kind i.e. focused on ethnic minority populations in Europe. It shows that such
trials are feasible, and the very high retention rates are promising. We need to improve the impact of such interventions and
then evaluate how they work in routine clinical care.
Effect of a lifestyle intervention on weight change in south Asian individuals in the UK at high risk of type 2 diabetes: a
family-cluster randomised controlled trial
Prof Raj S Bhopal DSc,Anne Douglas MA,Sunita Wallia MSc,Prof John F Forbes PhD,Prof Michael E J Lean MD,Jason M R Gill
PhD,John A McKnight MD,Prof Naveed Sattar FRCP,Prof Aziz Sheikh MD,Prof Sarah H Wild PhD,Prof Jaakko Tuomilehto
MD,Anu Sharma MSc,Ruby Bhopal BSc,Joel B E Smith PhD,Isabella Butcher PhD,Prof Gordon D Murray PhD
The Lancet Diabetes & Endocrinology – 23 December 2013
DOI: 10.1016/S2213-8587(13)70204-3


MedicalResearch.com: Medical Research Interviews January 2014

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