MedicalResearch.com Interviews on Latest Medical Findings

MedicalResearch.com
Exclusive Interviews with Medical Research and
Health Care Researchers from Major and Specialty Medical
Research Journals and Meetings
Editor: Marie Benz, MD
info@medicalresearch.com
April 8 2015
For Informational Purposes Only: Not for Specific Medical Advice.

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Osteoarthritis May Develop Early After ACL Rupture
MedicalResearch.com Interview with:
Adam Culvenor Ι B.Physio(Hons), PhD
Division of Physiotherapy
School of Health & Rehabilitation Sciences The University of Queensland
• Medical Research: What is the background for this study?
• Dr. Culvenor: Knee injury, such as anterior cruciate ligament (ACL) rupture, is a well-
recognised risk factor for the accelerated development of knee osteoarthritis (OA). Previous
studies report high rates of knee osteoarthritis with radiographs (x-rays) more than 5-10
years following ACL injury and reconstruction (ACLR). However, once OA becomes well-
established and visible on radiographs, management options are limited. Potential therapies
may be better placed to target the early stages of disease when management strategies, such
as optimising knee load, may be more efficacious. Magnetic resonance imaging (MRI) enables
the assessment of early osteoarthritis features affecting any joint tissue. Yet, MRI has not
previously been used to assess early knee OA within the first year following ACLR.
• Medical Research: What are the main findings?
• Dr. Culvenor: Of the 111 patients who were one year following an anterior cruciate
ligament rupture, the prevalence of early knee OA assessed with MRI was much higher than
previously recognised. Medial and lateral tibiofemoral osteoarthritis was observed in 6% and
11%, respectively, while 17% had patellofemoral OA. These patterns of early OA are similar to
previous radiographic findings; the patellofemoral joint is at particular risk of OA. Specifically,
the femoral trochlea was the region most affected by bone marrow lesions, cartilage lesions
and osteophytes. The prevalence of structural pathology was much higher than the uninjured
control group of similar age and activity level, highlighting the impact of knee trauma (injury
and/or surgery).
Read the rest of the interviews on MedicalResearch.com
Content NOT an endorsement of efficacy and NOT intended as specific medical advice.

Medical Research: What should clinicians and patients take away from your report?
Dr. Culvenor: Following anterior cruciate ligament (ACL) rupture, individuals demonstrating
features of early OA should be encouraged to address modifiable factors that increase the risk of
OA progression, such as elevated BMI, quadriceps weakness, and abnormal knee alignment. The
high rate of early OA features we observed may indicate that post-operative rehabilitation
programs need to shift away from their primary emphasis of an early return to sport, to include
more specific elements of maintain long-term joint health. Clinicians should be alert to
patellofemoral dysfunction following ACLR, as this compartment is at particular risk of early
degenerative disease.

• Medical Research: What recommendations do you have for future research as a result of
this study?
• Dr. Culvenor: This cohort of individuals, and others following ACL injury, need to be
prospectively followed to identify the natural history of the osteoarthritis features observed,
and to identify clinical and imaging risk factors for the accelerated progression of OA. The
ultimate goal is developing efficacious interventions that modify post-traumatic disease
progression. The identification of early OA following ACLR provides a good platform for this
to be pursued.
• Citation:
• Early Knee Osteoarthritis Is Evident One Year Following Anterior Cruciate Ligament
Reconstruction: A Magnetic Resonance Imaging Evaluation
Culvenor AG1, Collins NJ, Guermazi A, Cook JL, Vicenzino B, Khan KM, Beck N, van Leeuwen J,
Crossley KM.
Arthritis Rheumatol. 2015 Apr;67(4):946-55. doi: 10.1002/art.39005.

Study Links Whole Grains With Longer Life and Improved Health
Lu Qi, MD, PhD, FAHA
Assistant Professor of Medicine Harvard Medical School Assistant Professor of Nutrition
Harvard T. H. Chan School of Public Health
• Medical Research: What is the background for this study? What are the main findings?
Dr. Lu Qi: The previous data from population and animal studies have suggested intakes of
whole grain or its fiber (cereal fiber) might benefit improvement of metabolic status such as
lipids, inflammation, body weight, and blood pressure. Epidemiological studies have shown
high whole grain consumption lower risk of various diseases such as type 2 diabetes,
cardiovascular disease, and certain cancers.
• Medical Research: What should clinicians and patients take away from your report?
• Dr. Lu Qi: The study clearly supports to increase consumption of whole grain products to
longer life and improve health.

Study Links Whole Grains With Longer Life and Improved Health
Lu Qi, MD, PhD, FAHA
Assistant Professor of Medicine Harvard Medical School Assistant Professor of Nutrition
Harvard T. H. Chan School of Public Health
this study?
• Dr. Lu Qi: The supportive evidence for the protective effect of whole grain and cereal fiber on
human health from large prospective cohort are accumulating; however, data from clinical
trials are still lacking but highly needed to move one step closer to the final conclusion. In
addition, experimental studies are also essential to clarify the mechanisms.
• Citation:
• Consumption of whole grains and cereal fiber and total and cause-specific mortality:
prospective analysis of 367,442 individuals
Tao Huang, Min Xu, Albert Lee, Susan Cho and Lu Qi
Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave, Boston
02115, MA
BMC Medicine 2015, 13:59 doi:10.1186/s12916-015-0294-7

NEJM Research Discusses Right Antibiotic Strategy For Community-Acquired Pneumonia in Adults
Henri van Werkhoven
Onderzoeker in Opleiding | Julius Centrum
Universitair Medisch Centrum Utrecht Utrecht
Response: Community-acquired pneumonia is an important cause of hospitalization and
death worldwide. Recommendations for antibiotic treatment in patients hospitalized to a
non-ICU ward vary widely between guidelines, because the optimal antibiotic strategy is
unknown. Interpretation of the available evidence from clinical studies is complicated by the
heterogeneity in designs and findings. In our study, we hypothesized that the most
conservative strategy, beta-lactam monotherapy, would be non-inferior to strategies with a
broader range of antibiotic coverage. The latter strategies are potentially related to increased
antibiotic resistance.
• For this purpose, we randomized hospitals to follow three different strategies of preferred
antibiotic treatment in consecutive periods of four months. Physicians were allowed to
deviate from the preferred antibiotic treatment for medical reasons. We found that a
strategy with beta-lactam monotherapy (e.g. amoxicillin) as the preferred treatment was
non-inferior to the strategies with beta-lactam/macrolide combination therapy or
fluoroquinolone monotherapy for 30 and 90-day all-cause mortality. Also there was no
difference in length of hospitalization and rate of complications.

NEJM Research Discusses Right Antibiotic Strategy For Community-Acquired Pneumonia in Adults
Henri van Werkhoven
Onderzoeker in Opleiding | Julius Centrum
Universitair Medisch Centrum Utrecht Utrecht
• Response: Most patients hospitalized to a non-ICU ward with community-acquired pneumonia can
be safely treated with a beta-lactam without compromising patient outcome.
• Medical Research: What recommendations do you have for future research as a result of this
study?
• Response: Within the group of beta-lactam antibiotics used as beta-lactam monotherapy for
treating pneumonia, the spectrum of antimicrobial coverage is still very diverse (e.g. ceftriaxone vs.
amoxicillin). A new study from our institution (currently in design phase) will address whether an
antibiotic stewardship program in which penicillin and amoxicillin use is advised as the preferred
antibiotic treatment will be non-inferior on patient outcome compared to standard care.
• Citation:
•
• Antibiotic Treatment Strategies for Community-Acquired Pneumonia in Adults
• Douwe F. Postma, M.D., Cornelis H. van Werkhoven, M.D., Leontine J.R. van Elden, M.D., Ph.D.,
Steven F.T. Thijsen, M.D., Ph.D., Andy I.M. Hoepelman, M.D., Ph.D., Jan A.J.W. Kluytmans, M.D.,
Ph.D., Wim G. Boersma, M.D., Ph.D., Clara J. Compaijen, M.D., Eva van der Wall, M.D., Jan M. Prins,
M.D., Ph.D., Jan J. Oosterheert, M.D., Ph.D., and Marc J.M. Bonten, M.D., Ph.D. for the CAP-START
Study Group
• N Engl J Med 2015; 372:1312-1323
April 2, 2015DOI: 10.1056/NEJMoa1406330

Adolescents Risk Failing HIV Treatment If No Parent Attends Clinic Visits
Elizabeth Lowenthal, MD MSCE
Assistant Professor of Pediatrics
Children’s Hospital of Philadelphia
Dr. Lowenthal: Between 2005 and 2012, HIV related deaths declined by 30% worldwide.
However, during the same time period, HIV related deaths increased 50% among
adolescents. Over 90% of HIV-infected children and adolescents live in sub-Saharan Africa
and HIV is the leading cause of death among adolescents in Africa. Treatment is available that
can allow babies born with HIV to live to be healthy adults. However, strict adherence to
these medicines is necessary and often becomes a great challenge during adolescence. In our
study of 300 adolescents (ages 10-19) in Botswana, my team found that adolescents who
come to clinic without a parent or guardian have a 4.5X greater odds of failing their HIV
treatment.
• Dr. Lowenthal: Frequently, during early adolescence, patients with chronic diseases are
relatively good about taking their medications. Parents often give these adolescents more
autonomy over their own healthcare before they are truly ready to sustain excellent
adherence to their medicines long-term. Patients need to ask for help when they need it and
clinicians and parents need to provide as much support as they can in a nonjudgmental
manner, especially during the challenging late adolescent years. The lives of these young
people depend on this support.

Adolescents Risk Failing HIV Treatment If No Parent Attends Clinic Visits
Elizabeth Lowenthal, MD MSCE
Assistant Professor of Pediatrics
Children’s Hospital of Philadelphia
this study?
• Dr. Lowenthal: Developing strategies to improve communication between adolescents and
their parents and adolescents and their healthcare providers is important for the support of
adolescents with HIV and other chronic diseases. In resource-limited settings, where the vast
majority of HIV-infected adolescents live, we need to investigate strategies that can be
sustainable with limited financial support.
• Citation:
• Lowenthal ED, Marukutira T, Tshume O, et al. Parental Absence From Clinic Predicts Human
Immunodeficiency Virus Treatment Failure in Adolescents. JAMA Pediatr. Published online
March 30, 2015. doi:10.1001/jamapediatrics.2014.3785.
• MedicalResearch.com Interview with:Elizabeth Lowenthal, MD MSCE (2015). Adolescents
Risk Failing HIV Treatment If No Parent Attends Clinic Visits

Laparoscopic Surgery Found Safe For Rectal Cancer
Dr. H. Jaap Bonjer, PhD, FRCSC
Professor of Surgery Chair Department of Surgery
VU University Medical Center Amsterdam Amsterdam
Dr. Bonjer: Laparoscopic surgery for colon cancer is widely used after sufficient evidence was
collected in various trials demonstrating similar long term cancer outcomes as open surgery.
However, solid evidence that laparoscopic surgery for rectal cancer has similar outcomes as
open surgery was lacking
Dr. Bonjer: Laparoscopic surgery for rectal cancers which have not invaded adjacent organs
has similar cancer outcomes as open surgery. There are indications that disease free survival
after laparoscopic surgery is better in patient with lymph node positive disease and that
fewer locoregional recurrences of rectal cancer occur after laparoscopic resection of low
rectal cancer.

Laparoscopic Surgery Found Safe For Rectal Cancer
Dr. H. Jaap Bonjer, PhD, FRCSC
Professor of Surgery Chair Department of Surgery
VU University Medical Center Amsterdam Amsterdam
• Dr. Bonjer: Long term studies in patients with colonic cancer who were randomized to either open
or laparoscopic surgery have provided evidence that cancer outcomes after laparoscopic resection
of colonic cancer are similar to those of open surgery. However, robust evidence for laparoscopic
resection of rectal cancer was lacking. This study in more than 1,000 patients assures patients and
medical doctors that laparoscopic surgery is safe for rectal cancer, and offers short term benefits
such as less pain and faster postoperative recovery. Therefore, laparoscopic surgery should be
offered to patients with rectal cancer.
study?
• Dr. Bonjer: Further research need to focus on survival rates in patients with lymph node positive
disease (stage III) and patients with low rectal cancer. The COLOR II study group is initiating a new
study, the COLOR III trial, to evaluate a new minimally invasive technique, the Transanal Total
Mesorectal Excision (TaTME) to remove low rectal cancer.
• Citation:
• A Randomized Trial of Laparoscopic versus Open Surgery for Rectal Cancer
• H. Jaap Bonjer, M.D., Ph.D., Charlotte L. Deijen, M.D., Gabor A. Abis, M.D., Miguel A. Cuesta, M.D.,
Ph.D., Martijn H.G.M. van der Pas, M.D., Elly S.M. de Lange-de Klerk, M.D., Ph.D., Antonio M. Lacy,
M.D., Ph.D., Willem A. Bemelman, M.D., Ph.D., John Andersson, M.D., Eva Angenete, M.D., Ph.D.,
Jacob Rosenberg, M.D., Ph.D., Alois Fuerst, M.D., Ph.D., and Eva Haglind, M.D., Ph.D. for the COLOR
II Study Group
• N Engl J Med 2015; 372:1324-1332
• April 2, 2015 DOI: 10.1056/NEJMoa1414882

Short Cardiac Biomarker Protocols May Underestimate Heart Damage
Anne Vorlat MD
Department of Cardiology Antwerp University Hospital
Department of Cardiology, Edegem, Belgium
• MedicalResearch: What is the background for this study? What are the main findings?
• Dr. Vorlat: Early diagnosis of myocardial infarction is critical for optimal treatment and
prognosis of the patient. The third universal definition of myocardial infarction states that a
rise and/or fall of cardiac biomarkers (preferably troponin) with at least one value above the
99th percentile of the upper reference limit is mandatory with symptoms and or ST segment
changes on the ECG. Since the development of more sensitive assays for cardiac troponins,
myocardial injury can be detected earlier. This has permitted to shorten the timing of the
second sampling of cardiac biomarkers from 6h to 3h after the first sampling. Recent studies
have tested biomarker protocols with a very short delay (e.g., 1 hour) or with a single
measurement of troponin and copeptin (a marker of endogenous stress, not cardiac specific)
to rule in or to rule out myocardial injury in a population with chest pain. Although these
newer protocols appear to be promising, early presenters (chest pain for less than 2 hours)
are underreported. The present study evaluated the usefulness of early rule-in and rule-out
biomarker protocols to estimate ischemia-induced myocardial injury in an early presenter
model. The “early presenter” model was tested in 107 stable patients after a short period of
myocardial ischemia, induced by stenting of a significant coronary artery stenosis. High-
sensitivity troponin T (hsTnT), hsTnI and copeptin were measured at the start, and 90, 180
and 360 minutes after stent implantation. We confirmed our hypothesis that short
biomarkers protocols underestimate myonecrosis in early presenters.

Anne Vorlat MD
• MedicalResearch: What should clinicians and patients take away from your report?
• Dr. Vorlat: The ongoing efforts to minimize the delay between diagnosis and treatment of
acute coronary syndromes encourages fast track protocols. The use of point of care assays in
the emergency department and the pre-hospital setting, to minimize the delay between
diagnosis and treatment of acute coronary syndromes will increase. Moreover, the ongoing
efforts to improve the awareness of the general public for acute coronary syndromes, the
early presenters will increase at the emergency departments. Therefore a better knowledge
about the diagnostic accuracy of troponin assays and fast track biomarker protocols for
detecting ischemia induced myocardial injury in early presenters is crucial . We confirmed our
hypothesis that short biomarkers protocols underestimate myonecrosis in early presenters.
At present, the best approach for the diagnosis of myocardial injury in early presenters is a
standard assessment of high-sensitivity troponin after 3 hours.

Anne Vorlat MD
• MedicalResearch: What recommendations do you have for future research as a result of
this study?
• Dr. Vorlat: For future research, the study of the slope of troponin rise over shorter time
intervals (e.g. between 30 and 60 min) could be of interest for recognizing early myocardial
injury in early presenters. Moreover, the search for even more specific markers with an
earlier release/detection is ongoing.
• Citation:
• Usefulness of Early Rule-in and Rule-out Biomarker Protocols to Estimate Ischemia-induced
Myocardial Injury in Early Chest Pain Presenters
• Anne Vorlat, MD ,Viviane O. Van Hoof, MD, PhD, Rania Hammami, MD, Stephanie van
Kerckhoven, MD,Catharina M. Van der Heijden, MD, Dries Coenen, MSPharm, Johan M.
Bosmans, MD, PhD, Steven Haine, MD, PhD Tom R. Vandendriessche, MD MD Christiaan J.
Vrints, PhD Marc J. Claeys, MD, PhD
The American Journal of Cardiology
• Available online 23 March 2015
• Received 14 January 2015, Revised 25 February 2015, Accepted 1 March 2015,
Available online 23 March 2015

Coronary Heart Disease: CT Scans May Reduce Tests, Procedures and Radiation Exposure
Pamela S. Douglas, M.D.
Duke University School of Medicine
Duke University Medical Center Durham, NC 27715
Medical Research: What is the background for this study?
Dr. Douglas: The primary objective of the PROMISE study was to compare the health outcomes
of people who went to the doctor with new symptoms such as shortness of breath and/or chest
pain that were suggestive of coronary artery disease and that required additional evaluation. This
was an important investigation because no large research trial has ever been conducted to help
guide the care of such patients. Instead, the selection of tests for such patients—which
constitutes at least 4 million patients in the United States each year—has been largely left up to
physician and patient preference rather than proven results.

Medical Research: What are the main findings?
Dr. Douglas: 10,003 patients from 193 different medical facilities across the US and Canada
agreed to be part of the PROMISE study and were randomized to a functional stress test or an
anatomic test Using CT angiography. The study found that the clinical outcomes of participants
with suspected coronary artery disease were excellent overall, and were similar in terms of death
and major cardiac conditions regardless of whether patients had a functional stress test or a
computed tomographic scan. However, the CT scan may be better at ruling out the need for
subsequent tests and procedures in patients who are free of heart disease, and involved a lower
radiation exposure relative to a stress nuclear study. We also found, in a separately reported
study, that the costs of the two diagnostic strategies were similar.

• Dr. Douglas: Patients undergoing testing for suspected coronary artery disease have an excellent
outcomes overall. The choice of test does not affect that outcome, but may provide a more efficient
triage to the use of the cath lab, and lower radiation if the alternate choice is nuclear testing.
Ultimately, the choice of test will depend on many factors, including clinical judgment and local
expertise, but not cost.
study?
• Dr. Douglas: Although the excellent outcomes were achieved with all patients undergoing testing,
events were so infrequent that a strategy of watchful waiting, or no testing, should be further
examined. However this should be carefully investigated as we did not test this approach.
• Citation:
• Outcomes of Anatomical versus Functional Testing for Coronary Artery Disease
• Pamela S. Douglas, M.D., Udo Hoffmann, M.D., M.P.H., Manesh R. Patel, M.D., Daniel B. Mark, M.D.,
M.P.H., Hussein R. Al-Khalidi, Ph.D., Brendan Cavanaugh, M.D., Jason Cole, M.D., Rowena J. Dolor,
M.D., Christopher B. Fordyce, M.D., Megan Huang, Ph.D., Muhammad Akram Khan, M.D., Andrzej S.
Kosinski, Ph.D., Mitchell W. Krucoff, M.D., Vinay Malhotra, M.D., Michael H. Picard, M.D., James E.
Udelson, M.D., Eric J. Velazquez, M.D., Eric Yow, M.S., Lawton S. Cooper, M.D., M.P.H., and Kerry L.
Lee, Ph.D. for the PROMISE Investigators
• N Engl J Med 2015; 372:1291-1300
April 2, 2015
•

Sitting, Watching TV Increases Diabetes Risk In Predisposed Individuals
Bonny Rockette-Wagner, Ph.D. Director of physical activity assessment,
University of Pittsburgh Graduate School of Public Health and
Andrea Kriska, Ph.D. Professor of epidemiology, University of Pittsburgh Graduate School of Public Health
• Researchers’ Note:
• Drs. Kriska and Rockette-Wagner: It should be noted that this study looked at adults at high risk for
diabetes. Not everyone in the general population would be at high risk. We would hypothesis that
the risk increase from TV watching may be lower in those not at high risk for diabetes, but obviously
could not test that in our study population.
• MedicalResearch: What is the background for this study?
• Response: In this research effort focused on participants in the Diabetes Prevention Program (DPP)
study (published in 2002 and funded by the National Institute of Digestive and Diabetes and Kidney
Diseases [NIDDK] section of the US National Institutes of Health [NIH]). That study enrolled 3,234
overweight US adults (1996–1999) of at least 25 years of age with the goal of delaying or
preventing type 2 diabetes in high risk individuals with either a metformin drug or lifestyle
intervention. The DPP demonstrated that the lifestyle intervention was successful at reducing the
incidence of diabetes and achieving its goals of 150 minutes per week of moderate intensity activity
(such as brisk walking) and a 7% weight loss (New England Journal of Medicine, 2002). There was
no goal to reduce sitting in the Diabetes Prevention Program.
• Results from other studies suggest that it is unclear if interventions focusing on increasing physical
activity also reduce time spent sitting. This current investigation examined whether the Diabetes
Prevention Program lifestyle intervention, which was shown to be effective at increasing physical
activity, also decreased self-reported sitting time. The effect of sedentary behavior on diabetes
development was also examined.

• MedicalResearch: What are the main findings?
• Response: For the lifestyle participants, a reduction in reported TV watching alone and the
combination of TV watching and work sitting was observed. This reduction was significantly
greater than any changes seen in the other two randomized groups, who did not receive the
intervention. Because these reductions were accomplished without an explicit program goal
to reduce sitting we feel optimistic that with better awareness of sitting behaviors and goal
setting to reduce sitting it may be possible to have an even greater impact than what was
achieved in this cohort.
• Additionally, our results showed that for every hour spent watching TV there was a 3.4%
increased risk of developing diabetes during the 3 year follow-up period in individuals at high
risk for diabetes. This finding means that reductions in sitting can translate into a positive
health effect separate from improvements in moderate-vigorous activity.

• Response: We have always known that increasing physical activity is beneficial. This new
effort suggests that individuals also need to be aware of how much time they spend sitting,
as demonstrated in this group of individuals at high risk for diabetes.

this study?
• Response: We feel it is important to investigate what happens when sedentary goals are
added to interventions that already focus on increasing physical activity and reducing weight.
Additionally, it will be beneficial to measure activity and sedentary behavior in these
interventions both with subjective questionnaires that can provide information on specific
behaviors, such as TV watching, and objective electronic activity monitors that can provide a
better assessment of total activity and sedentary behavior.
• As a next step in the effort to determine the impact of decreasing sedentary behavior, we (Dr.
Kriska and her colleagues at the University of Pittsburgh) have just received a $3 million grant
from NIH to test the efficacy of a community-based lifestyle intervention program in
sedentary, overweight adults that focuses on sitting less. The study involves modifying our
existing, highly successful translation of the DPP, the Group Lifestyle Balance Program by
reducing the amount of time spent sitting rather than starting with an emphasis on
increasing the amount of time they spend exercising.
• Citation:
• The impact of lifestyle intervention on sedentary time in individuals at high risk of diabetes
• http://www.diabetologia-journal.org/

Melanoma: Study Examines Metastases in Nonhottest Sentinel Nodes
MedicalResearch.com Interview with: Lyn McDivitt Duncan, MD
Professor of Pathology, Harvard Medical School Chief, Dermatopathology Unit and
Su Luo, MD Dermatology Resident
Massachusetts General Hospital Boston, MA 02114
Medical Research: What is the background for this study? What are the main findings?
Response: We studied 475 patients with cutaneous melanoma diagnosed at the Massachusetts
General Hospital (MGH) who also had a sentinel lymph node biopsy procedure performed. There
is a practice gap in the sentinel lymph node biopsy procedure ranging from removal of one
“sentinel” lymph node to removing the hottest lymph node and any lymph nodes with
radioactive tracer of 10% or more of the hottest lymph node’s counts (with an average of three
lymph nodes removed). At the MGH we use this latter method. We examined the sentinel lymph
nodes in each case to determine whether the positive cases with microscopic melanoma
metastases had metastases only in the most radioactive, or “hottest”, node or whether tumor
was also present in the less hot nodes. We found that in 19% of positive cases there were
metastases present only in the less hot nodes. We also performed survival analysis and showed
that the less hot nodal positive cases are of equivalent prognostic significance. We found that
removal of only the hottest lymph node would have led to under-staging of 19% of patients with
melanoma.

Melanoma: Study Examines Metastases in Nonhottest Sentinel Nodes
MedicalResearch.com Interview with: Lyn McDivitt Duncan, MD
Professor of Pathology, Harvard Medical School Chief, Dermatopathology Unit and
Su Luo, MD Dermatology Resident
Massachusetts General Hospital Boston, MA 02114
• Response: Clinically significant metastases may occur in lymph nodes other than the primary
draining or “hottest” lymph node. Our study reinforces the practice of removing all the
sentinel nodes down to 10% of the most radioactive, thus capturing these less hot nodes.
this study?
• Response: We hope that our study can drive further research into developing practice
standards for sentinel lymph node biopsy and also provide the basis for additional studies
that investigate sentinel lymph node metastases and prognosis in patients with primary
cutaneous melanoma.
• Citation:
• Luo S, Lobo AC, Tanabe KK, et al. Clinical Significance of Microscopic Melanoma Metastases in
the Nonhottest Sentinel Lymph Nodes. JAMA Surg. Published online April 01, 2015.
doi:10.1001/jamasurg.2014.3843.

Permethrin-Impregnated Mattress Liner Found Effective Against Bedbugs
MedicalResearch.com Interview with: Susan C. Jones, Ph.D.
Professor, The Ohio State University
Department of Entomology
Rothenbuhler Research Lab. Columbus, OH 43210
Response: Bed bugs are important public health pests that have made a huge comeback in
developed countries throughout the world. Human health effects from bed bugs include
allergic reactions, secondary bacterial infections, asthma, anaphylactic shock, sleeplessness,
agitation, and anxiety. Bed bugs require multiple integrated pest management (IPM)
strategies such as extremely thorough inspections, sanitation, a wide variety of nonchemical
and chemical measures, and follow-up monitoring. Evaluating the effectiveness of various
bed bug products is an ongoing effort of my research lab.
Response: In this study, we provide data demonstrating decreased feeding and fecundity (egg
production) of bed bugs after just 10 minutes of exposure to ActiveGuard fabric as compared
to untreated fabric. The ActiveGuard Mattress Liner, which is impregnated with 550 mg
permethrin per m2, was effective even against bed bug populations that were resistant to
pyrethroids.

Permethrin-Impregnated Mattress Liner Found Effective Against Bedbugs
MedicalResearch.com Interview with: Susan C. Jones, Ph.D.
Professor, The Ohio State University
Department of Entomology
Rothenbuhler Research Lab. Columbus, OH 43210
• Response: Based on our findings, ActiveGuard Mattress Liners have sublethal effects against
bed bugs even when bedbugs have only brief contact with the treated fabric. The
ActiveGuard Mattress Liners are intended for use as a preventive tool or as the final
treatment step within an integrated pest management (IPM) program. Note, however, to
avert potential issues concerning insecticide resistance, ActiveGuard Mattress Liners should
not be used as a front-line tool, which is one that is used against heavy bed bug infestations.
this study?
• Response: Future research is needed to elucidate the mode of action of the formulated
ActiveGuard product. Furthermore, additional field trials should be conducted to further
assess and refine their use as part of an IPM program.
• Citation:
• Susan C. Jones , Joshua L. Bryant , Frances S. Sivakoff. Sublethal Effects of ActiveGuard
Exposure on Feeding Behavior and Fecundity of the Bed Bug (Hemiptera: Cimicidae). Journal
of Medical Entomology, March 2015 DOI: 10.1093/jme/tjv008

Genital Psoriasis Negatively Impacts Quality of Life and Sexual Function
Caitriona Ryan, MD
Baylor University Medical Center, Dallas
• Dr. Ryan: Psoriasis is a common, chronic, inflammatory disorder of the skin which has a
considerable impact on social functioning and personal relationships. Genital involvement
can have devastating psychosexual implications for psoriasis patients. In a study examining
the stigmatization experience in psoriasis patients, involvement of the genitalia was found to
be the most relevant, regardless of the overall psoriasis severity. Although sexual function is
an integral component of quality of life, dermatology-specific and psoriasis-specific scales
largely neglect the impact of disease on sexual health. Despite major advances in other
aspects of psoriasis research, there has been little emphasis in recent times on the
identification and treatment of genital psoriasis and few studies have examined predisposing
risk factors, phenotypical associations or its impact on quality of life and sexual functioning.
• This study was designed to examine the prevalence and nature of genital involvement in
patients with psoriasis, to ascertain risk factors for the development of genital psoriasis, to
determine the impact of genital disease on quality of life and sexual functioning, and to
assess patient satisfaction with current topical treatments for genital psoriasis.

Caitriona Ryan, MD
• Dr. Ryan: Genital psoriasis in our patient cohort contributed significantly to the burden of
disease. The prevalence of current genital psoriasis was high at 38%, while approximately
two-thirds of patients reported ever having genital involvement. A significant proportion of
patients reported itch, pain, dyspareunia, worsening of their genital psoriasis after
intercourse and a decreased frequency of intercourse. Patients with genital psoriasis had
more impairment in quality of life and sexual health as determined by the Dermatology Life
Quality Index, the Center for Epidemiological Studies-Depression Scale and the Relationship
and Sexuality Scale .
• It has been shown that few dermatologists routinely examine for the presence of genital
disease, and if present, patients are seldom questioned or counseled about its effect on their
quality of life. Likewise, a significant number of patients “hide” their genital psoriasis from
both their dermatologist and their sexual partner.
• Hopefully the important findings of this study will heighten awareness about the prevalence
of genital involvement together with the considerable psychosocial and psychosexual
morbidity associated with genital disease. Dermatologists should systematically screen all
psoriasis patients in a sensitive fashion for the presence of genital involvement and its impact
on their sexual health and relationships, while tailoring appropriate therapy to their patients.

Caitriona Ryan, MD
• MedicalResearch: What recommendations do you have for future research as a result of this
study?
• Dr. Ryan: There is a great need for more effective therapies for genital psoriasis. Controlled studies
are necessary to adequately assess the impact of topical, systemic and biologic treatments on
genital psoriasis. We have shown the value of the genital PASI and the RLSS scale in quantifying the
objective severity of genital disease and the patient-reported psychosexual burden of genital
involvement. These could be valuable instruments for use in drug trials of new targeted psoriasis
therapies, which, to date, have failed to specifically measure efficacy in treating genital disease. We
hope that the results of this study will encourage drug companies and drug regulatory agencies to
assess the efficacy of psoriasis therapies in the genital area when designing future clinical trials.
• Citation:
• Genital psoriasis is associated with significant impairment in quality of life and sexual functioning
• Caitriona Ryan, Muriel Sadlier, Edward De Vol, Mahir Patel, Amanda Abramson Lloyd, Antoinette
Day, Aoife Lally, Brian Kirby, Alan Menter
• Publication stage: In Press Corrected Proof
Journal of the American Academy of Dermatology
Accepted: February 18, 2015; Published Online: March 30, 2015
• http://dx.doi.org/10.1016/j.jaad.2015.02.1127

RNA Sequencing Helps Unravel Disease Pathology In Atopic Dermatitis
Emma Guttman-Yassky, MD, PhD
Department of Dermatology
Icahn School of Medicine at Mount Sinai MedicalCenter New York, NY 10029
Dr. Guttman-Yassky: Atopic dermatitis/AD is the most common inflammatory skin disease. Increased
knowledge about the molecular phenotype of atopic dermatitis has contributed to development of
novel therapeutics, including trials with targeted therapeutics. Genomic skin data from these trials
largely rely on microarrays that are based on hybridization of labeled RNA/cDNA to single stranded DNA
sequences that translate to expression levels. We have recently shown that the atopic dermatitis
transcriptome (defined as differentially expressed genes [DEGs] between lesional and non-lesional skin)
is reversible with broad and specific therapeutics. For future mechanistic studies within clinical trials, it
is important to determine the agreement between microarrays and RNA-seq and to evaluate whether
RNA-seq offers additional benefits. This is the first report of the lesional atopic dermatitis phenotype by
RNA-seq, and the first direct comparison between the microarray and RNA-seq platforms in this disease.
Both platforms robustly characterize the AD transcriptome. Through RNA-seq, we unraveled novel
atopic dermatitis disease pathology, including increased expression of the novel TREM-1 signaling
pathway and IL-36 cytokine, which might have a pathogenic role in atopic dermatitis. Importantly, good
agreement with real time PCR, which serves as the “gold standard” for detection of gene expression was
observed for both technique. Overall good agreement was observed with RT-PCR for both RNA-seq and
microarrays, but key atopic dermatitis immune cytokines (such as interleukin 13, and interleukin 22),
which are highly elevated in atopic dermatitis lesions were only detected by RT-PCR. Overall, both RNA-
seq and microarrays can similarly characterize the lesional AD transcriptome and serve as valuable tools
for molecular tissue studies within large clinical trials and a core atopic dermatitis pathology is common
to microarray and the RNA-seq transcriptomes. RNAseq might play a complementary role for unravelling
novel disease pathology, although analyses tools for RNAseq are still being developed.

• Dr. Guttman-Yassky: Using RNAseq we identified pathogenic models of inflammatory
cytokines as atopic dermatitis disease drivers, with potential new therapeutic targets.
Overall, both RNA-seq and microarrays can similarly characterize the core transcriptome of
atopic dermatitis lesions and serve as valuable tools for molecular tissue studies within large
clinical trials. Although there is currently no major benefit to using RNA-seq instead of
microarrays in clinical settings, it might play a complementary role for unraveling novel
disease pathology.

this study?
• Dr. Guttman-Yassky: I believe that there is currently no major benefit to using RNA-seq
instead of microarrays in clinical (including clinical trial) settings. However, RNA-seq might
play a complementary role for unraveling novel disease pathology in research settings as we
detected in this manuscript.
• Citation:
• RNA sequencing atopic dermatitis transcriptome profiling provides insights into novel disease
mechanisms with potential therapeutic implications
• Mayte Suárez-Fariñas, Benjamin Ungar, Joel Correa da Rosa, David A. Ewald, Mariya
Rozenblit, Hui Xu, Xiuzhong Zheng, Xiangyu Peng, Yeriel D. Estrada, Stacey R. Dillon, James G.
Krueger, Emma Guttman-Yassky
• DOI: http://dx.doi.org/10.1016/j.jaci.2015.03.003
• Journal of Allergy and Clinical Immunology
Publication stage: In Press Corrected Proof
• Published online: March 31, 2015

Sunsmart Mass Media Campaign Encourages Sun Protection
Suzanne Dobbinson PhD
Senior Research Fellow
Centre for Behavioural Research in Cancer
Cancer Council Victoria Melbourne Australia
• Dr. Dobbinson: Australia has one of the highest skin cancer rates in the world due to the
country’s high levels of ultraviolet (UV) radiation and a population with susceptible skin
types. Two in three Australians will be diagnosed with skin cancer by the age of 70, with
more than 40,000 new cases annually in the state of Victoria alone.
• Since the 1980s there have been broad public education programs to raise awareness of skin
cancer. Television campaigns have been central to these multi-component prevention
programs, including SunSmart, which is the longest-running program in Victoria.
• This study examined SunSmart television advertisements broadcast over summers between
1987 to 2011 to determine what effect – if any – these advertisements had on people’s sun
protection attitudes and behaviours.
• Cross-sectional weekly telephone surveys of Melbourne residents were conducted over
summers during the study period. Population exposure to campaign TV advertisements was
also measured as cumulated weekly target audience rating points (TARPs) for 4 weeks prior
to interview. Using multiple logistic and linear regression models, we examined whether
there was a relationship between the TARPs and responses of the surveys.
• We found that increasing TARPs were related to an increased preference for no tan, increased
sunscreen use and overall reduced mean percentage of skin exposed to the sun. Also of note
was that this behavioural impact was consistent across all age groups.

• Dr. Dobbinson: The study shows that after more than two decades of exposure to SunSmart
television advertising these campaigns have not yet reached a saturation point, and continue
to have a strong impact on improving people’s sun protection behaviours. These effects were
seen population-wide despite the campaigns being largely developed for a youth audience.
Thus delivery of SunSmart messages in a timely manner during summer months can provide
important prompts for sun protection behaviours among both adolescents and adults.
• Given the long-term already significant public health burden of skin cancer in Australia, this
study highlights the potential benefits of advertising campaigns in contributing to population-
wide reductions in skin cancer incidence.

this study?
• Dr. Dobbinson: A number of areas for future research are of interest. We would like to
examine the effects of campaign advertising exposure alongside measures of potentially
competing sun-related messages, such as news stories on vitamin D.
• Secondly, we would also like to better understand the relationship between change in sun
protection behaviours and sunburn outcomes, given this study found no benefits for sunburn
outcomes, despite the improvements in sunscreen use and reduced body exposure.
• Finally, to fully ascertain the cost-effectiveness of mass media campaigns, we would like to
examine their impact compared to other media, policy and environmental approaches.
• Citation:
• Continued Impact of SunSmart Advertising on Youth and Adults’ Behaviors
• Dobbinson SJ1, Volkov A2, Wakefield MA2.
Am J Prev Med. 2015 Mar 7. pii: S0749-3797(15)00031-8. doi:
10.1016/j.amepre.2015.01.011. [Epub ahead of print]

High-Dose Flu Vaccine Prevented More Influenza Infections In Elderly Than Standard Dose
Dr Richard Forshee PhD
Associate Director for Research in the Office of Biostatistics and Epidemiology Center for Biologics Evaluation and Research
U.S. Food and Drug Administration Silver Spring, MD On behalf of the study authors
Dr. Forshee: Influenza continues to be a major public health concern causing illness, hospitalization, and
death. The elderly are at highest risk for seasonal influenza complications, including hospitalization and
death. As people grow older their ability to raise a strong protective immune response can weaken. The
availability of a vaccine that uses a higher dose to induce a stronger immune response could reduce the
serious impact of influenza in this age group. The purpose of this study was to determine whether a high-
dose inactivated influenza vaccine was more effective for prevention of probable influenza infections and
influenza-related hospital admissions, compared to standard-dose inactivated influenza recipients.
• In December 2009, the U.S. Food and Drug Administration (FDA) licensed Fluzone High Dose, an injectable
inactivated trivalent seasonal influenza vaccine for people ages 65 years and older. This high-dose vaccine
contains four times more hemagglutinin—the active ingredient in influenza vaccines that cause the human
body to produce antibodies against the influenza viruses—than the standard-dose vaccine. The FDA
approved the high-dose vaccine using the accelerated approval regulatory pathway, which allows the
agency to approve products for serious or life-threatening diseases based on reasonable evidence of a
product’s effectiveness. This pathway reduces the time it takes for needed medical products to become
available to the public. Studies conducted prior to licensure showed an enhanced immune response to
the high-dose vaccine compared with the standard-dose vaccine in individuals 65 years of age and older
indicating that the high-dose vaccine was reasonably likely to be more effective in preventing influenza
disease.
• As part of the accelerated approval process, the manufacturer, Sanofi Pasteur, was required to conduct a
randomized clinical study post-licensure to confirm that the high-dose vaccine decreased seasonal
influenza disease after vaccination relative to standard dose vaccine. This confirmatory study
demonstrated that the high–dose vaccine prevented 24% more cases of laboratory-confirmed influenza
illness compared to standard-dose vaccines in people 65 years of age and older. However, the study was
not large enough to determine efficacy of the vaccine against severe disease.

• A team of scientists from FDA, the Centers for Disease Control and Prevention, Centers for
Medicare and Medicaid Services, and Acumen LLC ( an independent research organization)
studied the relative effectiveness of the high-dose influenza vaccine in the U.S. population
ages 65 years and older. The observational study, which covered the 2012-2013 influenza
season, found a significant reduction both in influenza-associated illness and in influenza-
related hospitalizations among individuals who received the high-dose vaccine, compared to
those receiving the standard dose.
• Additional background about this study: “Comparative effectiveness of high-dose versus
standard-dose influenza vaccines in US residents aged 65 years and older from 2012 to 2013
using Medicare data: a retrospective cohort analysis” is available at:
• http://dx.doi.org/10.1016/S1473-3099(14)71087-4
• A commentary on the study titled “Novel observational study designs with new influenza
vaccines” is available at:
• http://dx.doi.org/10.1016/S1473-3099(15)70020-4

Dr. Forshee: The scientists found that the high-dose influenza vaccine was 22% more
effective at preventing influenza-associated illness than standard-dose vaccine among
individuals ages 65 years and older. They also found a similar effect for the more serious
outcome of influenza-associated hospital admissions and emergency department visits in this
age group.
this study?
Dr. Forshee: The results of this study were consistent with relative efficacy estimates
reported in the manufacturer’s research, “Efficacy of High-Dose versus Standard-Dose
Influenza Vaccine in Older Adults,” and demonstrated that this study design could be used in
the future to estimate the benefits of newer influenza vaccines. The methods may also be
used to study more rare events, such as hospitalizations. In addition, future studies based on
this design could also enable rapid evaluation of the life-saving effectiveness of other
vaccines, including those protecting against pandemics.
• Further information about the manufacturer’s study is available at:
• http://www.nejm.org/doi/full/10.1056/NEJMoa1315727

• Citation:
• Comparative effectiveness of high-dose versus standard-dose influenza vaccines in US
residents aged 65 years and older from 2012 to 2013 using Medicare data: a retrospective
cohort analysis
• Izurieta, Hector S et al.
• The Lancet Infectious Diseases , Volume 15 , Issue 3 , 293 – 300

Night Owls May Have Increased Risk of Metabolic Syndrome and Diabetes
MedicalResearch.com Interview with: Nan Hee Kim M.D., Ph.D., Professor
Korea University Ansan Hospital,
Gojan1-dong, Danwon-gu, Gyunggi-do, Korea
• MedicalResearch: What is the background for this study?
• Dr. Nan Hee Kim: Many individuals in modern society experience a discrepancy between
social and biological time. Especially during the work or school week, we are often forced to
be awake against our preferred time. In addition, the increase of light, TV, computer and
internet make people stay up late at night. However, night owls (evening persons) have been
reported to have more health and behavioral problems than morning persons. Evening
persons experience eating disorders, negative mood and insufficient sleep compared to
morning persons. They initiate sleep later in the night but need to wake up earlier than their
biologic morning due to social demands. There is abundant evidence that short sleep
duration and insomnia are significant risk factors for obesity and diabetes. Therefore, we feel
the necessity to reveal whether evening persons are associated with metabolic abnormalities
in the general population.
• MedicalResearch: What are the main findings?
• Dr. Nan Hee Kim: In middle-aged adults, people who stayed up late had a 1.7-fold increased
risk for type 2 diabetes and metabolic syndrome, and a 3.2-fold increase in risk for sarcopenia
as compared with morning persons, independent of sleep duration and lifestyle. Evening
persons were associated with reduced muscle mass in men and increased fat mass including
visceral fat in women.

• Dr. Nan Hee Kim: Many things of modern environment make people stay up late. In this
study, we found that evening persons were associated with a higher prevalence of diabetes,
metabolic syndrome and sarcopenia in middle-aged adults, independent of sleep duration
and lifestyle. Evening persons had poor sleep quality and unhealthy behavior patterns such as
smoking, lack of exercise and eating late at night, which possibly contribute to the adverse
metabolic outcomes of them. Considering evening type is more prevalent in the younger age
groups, these findings are important major health issue since they are at high risk for
diabetes or metabolic syndrome in the relatively young age. Furthermore, this finding may
become more severe due to the increasing social pressure.

this study?
• Dr. Nan Hee Kim: In the future, it remains to be seen whether young people with evening
type will have the early development of metabolic disorders such as diabetes and metabolic
syndrome compared with morning types, though a randomized prospective long-term follow-
up study. And also, basic and genetic research will have to be performed to reveal the
mechanism of adverse metabolic outcomes in evening persons.
• Citation:
• Evening Chronotype Is Associated With Metabolic Disorders and Body Composition in
Middle-Aged Adults.
• Yu JH1, Yun CH, Ahn JH, Suh S, Cho HJ, Lee SK, Yoo HJ, Seo JA, Kim SG, Choi KM, Baik SH, Choi
DS, Shin C, Kim NH.
J Clin Endocrinol Metab. 2015 Apr 1:jc20143754. [Epub ahead of print]

Biomarkers May Lead to Breath Test For Malaria
Amalia Z. Berna
CSIRO Food and Nutrition Flagship
Acton ACT 2601
• Response: Globally an estimated 3.2 billion people in 97 countries are at risk of malaria and, in
2013, an estimated 198 million cases and 584,000 deaths were attributed to this infection. Accurate
diagnosis of malaria is important to provide adequate treatment, conserve valuable drugs, and help
prevent the emergence of resistant strains of the parasite. It is becoming important to be able to
diagnose low level and asymptomatic cases, to support the drive towards local and/or global
eradication.
• Detection of volatile chemicals in expired breath has been used to diagnose or monitor a small
number of diseases, including Helicobacter pylori infection, diabetes and lung inflammation but, if
breath analysis is to be more broadly useful, we need to identify reliable biomarkers for a wider
range of diseases and to develop more robust methods for breath analysis.
• In collaboration with Professor James McCarthy of the QIMR Berghofer Institute and Associate
Professor Kevin Saliba of the ANU, we found:
• Four specific thioether biomarkers in the breath of volunteers with experimentally induced blood
stage Plasmodium falciparum
• That the levels of the volatiles strongly correlate with the levels of malaria parasitaemia.
• That the thioethers are not produced by in vitro cultures of falciparum.
• That although we do not know the metabolic origin of the thioethers, our results suggest that
interplay between host and parasite metabolic pathways is involved in their production.
• We think it is important to emphasise that no volunteer was infected with malaria primarily for the
purpose of this study. Our research was entirely piggy-backed on pre-existing trials of malaria
therapeutics.

Amalia Z. Berna
Acton ACT 2601
• Response: This publication describes the first analysis of human breath specimens for
biomarkers of malaria. From a practical point of view, providing breath samples could be
simpler and more convenient for patients than giving blood samples.
• The fact that changes in VOC levels in infected volunteers’ breath occurred at low parasitemia
indicates that the biomarkers have promise for diagnosing malaria with unprecedented
sensitivity. The breath biomarkers may be applicable below the threshold of detection (100
parasite µL-1) of rapid diagnostic tests, which target the circulating PfHRP2 biomarker.

Amalia Z. Berna
Acton ACT 2601
this study?
• Response:
• Investigate whether the same thioethers can be detected in patients suffering from naturally-
acquired falciparum infections.
• Investigate whether similar volatiles are found with other species of malaria.
• Identify a suitable animal model of malaria to enable studies of the metabolic origins of the
thioethers.
• Develop cheap and reliable methods to sense these compounds in expired breath.
• Citation:
• Biomarkers of infection with Plasmodium falciparum detected in human breath.
• Berna AZ1, McCarthy JS2, Wang XR3, Saliba KJ4, Bravo FG5, Cassells J5, Padovan B5, Trowell SC5.
• J Infect Dis. 2015 Mar 25. pii: jiv176. [Epub ahead of print]

Gene Expression Links Gastric Absorption and Bone Mass
MedicalResearch.com Interview with: Ricardo Battaglino, Ph.D.
Department of Mineralized Tissue Biology The Forsyth Institute, Cambridge, Massachusetts
Department of Oral Medicine, Infection, and Immunity Harvard School of Dental Medicine,
Boston, Massachusetts
Dr. Battaglino: Mutations in sorting nexin 10 (Snx10) have recently been found to account for
roughly 4% of all human malignant osteopetrosis, some of them fatal. To study the disease
pathogenesis, we investigated the expression of Snx10 and created mouse models in which Snx10
was knocked down globally or knocked out in osteoclasts. We found that Snx10, a molecule
expressed in osteoclasts, was also expressed in the stomach. Studies in tissue specific or global
knock-down mice showed that Snx10 deficiency resulted in a phenotype that was a consequence
of deficiencies in both osteoclasts and gastric zymogenic cells. Our studies add to a growing list of
genes, including atp6i (Tcirg1), whose expression is required both in bone and stomach to
maintain normal gastric acidification and calcium absorption.

• Dr. Battaglino: Our work provides additional insight into the mechanisms governing the
regulation of bone accrual by the gastrointestinal tract. Because osteopetrorickets has not
been described clinically in Snx10-related osteopetrosis, these findings highlight the
importance of considering impaired acidification in both stomach and bone in osteopetrotic
patients with mutations in SNX10 and other genes with similar patterns of expression and
activities. Reliance solely on hematopoietic stem cell transplantation can leave hypocalcemia
uncorrected with sometimes fatal consequences. Because defects in gastric differentiation
and/or gastric acidification may cause or contribute to hypocalcemia, bone insufficiency, and
early death, our results suggest that dietary calcium supplementation could be a life-saving
intervention in these patients.

study?
• Dr. Battaglino: The skeleton is one of the largest tissues of the vertebrate body plan and as such
cannot function in isolation. Instead, there is a complex system of cross-regulation that exists
between bone and most other organs. The ability to perform tissue or cell-specific gene ablation
has afforded us the experimental tools to understand how organs signal to one another and has
revitalized the concept of whole-organism physiology. The regulation of bone mass by the
gastrointestinal tract represents a remarkable example of an unexpected and novel relationship
between these two systems that is only now becoming fully appreciated. Our work is expected to
elucidate the role of SNX10 in early endosomal formation and subsequent OC function. In addition,
we anticipate that expression of Snx10 in stomach regulates calcium bioavailability by controlling
gastric pH.
• This work will lay the foundation for future studies that may address the following questions:
• 1) can we use analysis of expression patterns of gene networks across systems to identify novel
regulatory functions between bone and gut (and/or other systems) and
• 2) does Snx10 partner with different proteins in OCs and stomach? This all may be important for
the development of therapies that preferentially target Snx10 in OCs but not stomach.
• Citation:
• Osteopetrorickets due to Snx10 Deficiency in Mice Results from Both Failed Osteoclast Activity
and Loss of Gastric Acid-Dependent Calcium Absorption
• PLoS Genet. 2015 Mar 26;11(3):e1005057. doi: 10.1371/journal.pgen.1005057. eCollection 2015.
• Ye L1, Morse LR2, Zhang L3, Sasaki H4, Mills JC5, Odgren PR6, Sibbel G5, Stanley JR7, Wong G7,
Zamarioli A8, Battaglino RA1.

Acetaminophen May Not Be Effective For Osteoarthritis, Low Back Pain
Gustavo C Machado, PhD student
The George Institute for Global Health, Sydney Medical School
University of Sydney Sydney Australia
• (Editor’s note: Paracetamol isalso known as acetaminophen)
• Response: Back pain and osteoarthritis are the two major musculoskeletal conditions
affecting people worldwide, and paracetamol is the most used over the counter medicine to
treat these conditions. Recent debates on the efficacy and safety of paracetamol prompted
us to conduct a systematic review of literature on the efficacy of this medication. In our study
we included all available clinical trials that compared paracetamol to placebo, and our
conclusions are based on data from more than 5,300 patients with low back pain and hip or
knee osteoarthritis. We found that paracetamol is ineffective for low back pain and provides
small and not clinically important benefits to patients with osteoarthritis.

•
MedicalResearch: What should clinicians and patients take away from your report?
• Response: Given the clear results of our study we would recommend that patients use other
treatments; and there are quite a few options outlined in evidence-based guidelines. For
people with low back pain, clinical guidelines include advising patients to remain active and
avoid bed rest, avoiding routine imaging, physical therapies, and psychological therapies such
as cognitive behavioural therapy. For people with osteoarthritis, recommendations include
land- or water-based aerobic exercise, strength training and weight management.

this study?
• Response: Our results provide high quality evidence on the efficacy of paracetamol for low
back pain and osteoarthritis, so future research on this topic is unlikely to change our
conclusions. We however suggest future research to investigate the long-term effects of this
medication.
• Citation:
• Efficacy and safety of paracetamol for spinal pain and osteoarthritis: systematic review and
meta-analysis of randomised placebo controlled trials
• Gustavo C Machado, PhD student, Chris G Maher, director,Paulo H Ferreira, senior lecturer,
Marina B Pinheiro, PhD student, Chung-Wei Christine Lin, associate professor, Richard O Day,
professor, Andrew J McLachlan, professor, Manuela L Ferreira, associate professor
• BMJ 2015; 350 doi: http://dx.doi.org/10.1136/bmj.h1225 (Published 31 March 2015) Cite this
as: BMJ 2015;350:h1225

No Matter How It’s Applied, Eyeliner Often Gets Into The Eyes
Alison Ng PhD, BSc(Hons), MCOptom
Post-Doctoral Fellow
Centre for Contact Lens Research School of Optometry & Vision Science
University of Waterloo Waterloo, Ontario Canada
Dr. Ng: Eye care practitioners often see patients coming into our clinics with eyeliner
“floating” in the tears or adhered to the surface of contact lenses during our routine
examinations. When products such as eyeliner enters and contaminates the tear film, some
patients complain of temporary discomfort, and if they wear contact lenses, they may report
blurred vision if the lenses become spoiled. Specifically in this pilot study, we wanted to look
at how differently eyeliner migrated into the tear film when applied in two different ways:
inside the lash line and outside of the lash line.
• Dr. Ng: Whichever way eyeliner is applied, a certain quantity will get into your eyes (even if
applied outside of the lash line). This study found there is a 30% increase in eyeliner
contamination when it is applied within the lash line.

No Matter How It’s Applied, Eyeliner Often Gets Into The Eyes
Alison Ng PhD, BSc(Hons), MCOptom
Post-Doctoral Fellow
Centre for Contact Lens Research School of Optometry & Vision Science
University of Waterloo Waterloo, Ontario Canada
this study?
• Dr. Ng: This study was the first of a series of studies examining the effects of eye cosmetics
on the tear film. Future reports will be available in the near future.
• Citation:
• Migration of Cosmetic Products into the Tear Film
• Ng A1, Evans K, North RV, Purslow C.
• Eye Contact Lens. 2015 Mar 3. [Epub ahead of print]

‘Heart To Heart’ Aims To Improve Adherence to HIV Medications
Marya Viorst Gwadz, Ph.D Senior Research Scientist Director,
Transdisciplinary Methods Core Center for Drug Use and HIV Research (CDUHR) New York University College of Nursing
New York, NY 10010
Dr. Gwadz: HIV is a major success story in that the tolerability, convenience, and efficacy of
antiretroviral medications have improved dramatically over the last decade. A number of years
ago in the course of another research study with vulnerable individuals infected with HIV in New
York City, and we noticed that a substantial proportion of study participants were medically
eligible for HIV medications, and had access to medications, but had declined or stopped taking
them. We then turned our attention to understanding why this is the case, that is, to identify the
individual, social, and structural barriers that persons living with HIV/AIDS (PLHA) experience to
antiretroviral therapy. We focused in particular on African American/Black and Latino/Hispanic
PLHA, because the overall emphasis of our research group at the NYU College of Nursing is the
development and evaluation of culturally targeted intervention approaches to address health
disparities. Around 2011, studies of the “HIV cascade of care” began to emerge, which
highlighted the problem of poor engagement in HIV care and antiretroviral therapy nationally.
The ultimate goal of HIV treatment is viral suppression, but at present, the Centers for Disease
Control and Prevention (CDC) estimates that we have achieved that goal with only 30% of PLHA.

New York, NY 10010
• Medical Research: What kind of intervention approach that emerged from these
background findings?
• Dr. Gwadz: We found that barriers to HIV medication are complex and multi-faceted for PLHA
from African American/Black and Latino/Hispanic backgrounds. In particular, PLHA
experience serious emotional barriers to the uptake of HIV medications, such as fear of side
effects, stigma, and disclosure of HIV status. Further, high rates of substance use and mental
health distress, and barriers to accessing services for these concerns, impede medication
uptake. Moreover, PLHA who are wary of HIV medication tend to avoid HIV primary care,
often because they do not want to feel pressured to take medications, or explain to their
providers why they are not taking them. So poor engagement in HIV care, which is very
common among PLHA, and low uptake of HIV medication are actually related problems.

New York, NY 10010
With funding from the National Institute of Mental Health (grant #R34MH093352), and in
collaboration with Mount Sinai Beth Israel and Mount Sinai St. Luke’s-Roosevelt Hospital Center,
we developed a multi-component culturally targeted intervention grounded in the Motivational
Interviewing approach that included three individual sessions, 12-24 weeks of patient navigation
(as needed), up to five support groups with other PLHA who had declined medication, which
were co-led by a “successful” peer who was engaged in HIV care and were taking HIV medication
with good adherence. One novel aspect of the intervention was its focus on emotional barriers to
HIV medication, and the program’s “no pressure, no judgment” stance, congruent with the
Motivational Interviewing approach, was key to engaging participants into the study to talk about
these difficult issues.

New York, NY 10010
• Dr. Gwadz: This was a small and exploratory study to develop and evaluate the acceptability,
feasibility, and evidence of efficacy of the intervention, called “Heart to Heart.” Nonetheless,
we found that the intervention was quite promising compared to a control arm. Eight months
post-baseline, intervention participants tended to be more likely to evidence “good” (that is,
7 day a week) adherence assessed via hair sample analysis (60% among intervention arm
participants vs. 26.7% among controls), and also had lower HIV viral load levels based on the
medical record than controls, at a statistically significant level (a difference of 0.88 log10 viral
load), both large effect sizes. Adherence to HIV medication is considered the “Achilles’ heel”
of treatment. The field has produced a lot of good adherence interventions, but their effects
do not tend to last once the intervention ends. One hypothesis we have is that the Heart to
Heart intervention was successful in fostering high quality, durable intrinsic motivation for
behavior change among participants. However, we need a study with a longer follow-up
period to explore that issue.

New York, NY 10010
• Dr. Gwadz: Patients should know they are not alone: many PLHA are struggling with the issue
of whether to take HIV medication or not, and have stopped medication and are avoiding HIV
care because they don’t want to talk about that with their health care providers. We know
it’s a long and hard road. We know HIV is a roller coaster. On the other hand, there are
compassionate, evidence-based services in HIV clinics to help you achieve your health goals,
whether you choose to take medication or not. So come to your HIV care setting and talk
about it with a health care provider or social worker, whomever you feel most comfortable
with.
• Clinicians should know that interventions such as Heart to Heart can be implemented in clinic
settings to complement HIV primary care. Health care providers simply do not have the time
to address complex barriers to HIV medication in the course of treating a serious disease such
as HIV. That’s where behavioral interventions such as Heart to Heart can help. Further, clinical
settings can and should conduct active outreach efforts to engage patients who have
dropped out or who are avoiding HIV care, because they rarely present in clinical settings.
But we have found these patients can be reached though peers and outreach efforts. Last,
clinic settings may benefit from training in Motivational Interviewing and other similar
approaches to better engage fearful and wary patients.

New York, NY 10010
this study?
• Dr. Gwadz: We learned a great deal in the Heart to Heart intervention study. Modifications to
the intervention are needed for the next phase of this research program, and future studies
with a longer follow up period and a study of intervention mediators may shed light on
whether the Heart to Heart approach has enduring effects, and on its specific mechanisms of
action.
• Citation:
• Marya Gwadz, Charles M. Cleland, Elizabeth Applegate, Mindy Belkin, Monica Gandhi, Nadim
Salomon, Angela Banfield, Noelle Leonard, Marion Riedel, Hannah Wolfe, Isaiah Pickens, Kelly
Bolger, DeShannon Bowens, David Perlman, Donna Mildvan. Behavioral Intervention
Improves Treatment Outcomes Among HIV-Infected Individuals Who Have Delayed, Declined,
or Discontinued Antiretroviral Therapy: A Randomized Controlled Trial of a Novel
Intervention. AIDS and Behavior, 2015;
DOI: 10.1007/s10461-015-1054-6

Exclusive Breastfeeding Does Not Reduce Allergies by Age 7
Hans Bisgaard, MD, DMSc
Copenhagen Prospective Studies on Asthma in Childhood Faculty of Health and Medical Sciences,
University of Copenhagen & Danish Pediatric Asthma Center
Gentofte Hospital, Gentofte, Denmark.
• Dr. Bisgaard: Extended breast-feeding is recommended for
newborn children at risk of allergy-associated diseases, but the
evidence of a protective effect on sensitization and these diseases
remains elusive.
• Dr. Bisgaard: Exclusive breastfeeding does not affect
sensitization in early childhood or associated diseases at 7 years
of age in at-risk children.

Exclusive Breastfeeding Does Not Reduce Allergies by Age 7
Hans Bisgaard, MD, DMSc
Copenhagen Prospective Studies on Asthma in Childhood Faculty of Health and Medical Sciences,
University of Copenhagen & Danish Pediatric Asthma Center
Gentofte Hospital, Gentofte, Denmark.
• Dr. Bisgaard: Although it is generally acknowledged that
breastfeeding provides the most optimal source of food for
infants, these findings should be emphasized to prevent distress
and guilt in allergy-disposed mothers with breast-feeding
difficulties
study?
• Dr. Bisgaard: Our findings suggest that more complex pathways leads to allergy beyond genetics
and exposure. Some other factors appears critical and we are pursuing this in our research
• Citation:
• Breast-feeding does not protect against allergic sensitization in early childhood and allergy-
associated disease at age 7 years
• Ea Jelding-Dannemand, MSc,Ann-Marie Malby Schoos, MD ,Hans Bisgaard, MD, DMSc
• Copenhagen Prospective Studies on Asthma in Childhood, Faculty of Health and Medical Sciences,
University of Copenhagen & Danish Pediatric Asthma Center, Gentofte Hospital, University of
Copenhagen, Gentofte, Denmark
• Received: September 25, 2014; Received in revised form: February 14, 2015; Accepted: February
22, 2015; Published Online: April 02, 2015
Journal of Allergy and Clinical Immunology
• DOI: http://dx.doi.org/10.1016/j.jaci.2015.02.023

Study Show Close Link Between Leisure Time Exercise and Mortality
Hannah Arem, MHS, PhD
Division of Cancer Epidemiology and Genetics
National Cancer Institute, Bethesda, Maryland
Dr. Arem: The 2008 Physical Activity Guidelines for Americans recommend a minimum of 150
minutes of moderate-intensity or 75 minutes of vigorous-intensity activity per week for
“substantial” health benefit, and suggest “additional” benefit with more than double the
exercise minimum. However, the guidelines note that there is a lack of evidence for an upper
limit of health benefit. We set out to define the dose-response relationship between leisure-
time physical activity and mortality and to determine the upper limit of benefit associated
with higher levels of aerobic exercise.
Dr. Arem: We found that study participants who met the recommended minimum level of
leisure-time physical activity derived most of the mortality benefit, with a 31% lower risk of
death compared to inactive individuals. Study participants who engaged in three to five times
the recommended minimum level of leisure-time physical activity had a marginally increased
mortality benefit, with a 39% lower risk of death compared to inactive individuals. Three to
five times the recommended minimum is equivalent to a weekly minimum of walking 7 hours
or running 2 hours 15 minutes.

Study Show Close Link Between Leisure Time Exercise and Mortality
Hannah Arem, MHS, PhD
Division of Cancer Epidemiology and Genetics
National Cancer Institute, Bethesda, Maryland
• Dr. Arem: Clinicians should encourage inactive adults to follow the 2008 Physical Activity
Guidelines for Americans and should not discourage adults who already participate in high
levels of exercise.
this study?
• Dr. Arem: Future studies are needed to further explore mortality differences by exercise
intensity (light vs moderate or vigorous) and types of specific activities. Additional studies
might also look at very high levels of exercise and health outcomes other than mortality.
• Citation:
• Arem H, Moore SC, Patel A, et al. Leisure Time Physical Activity and Mortality: A Detailed
Pooled Analysis of the Dose-Response Relationship. JAMA Intern Med. Published online April
06, 2015. doi:10.1001/jamainternmed.2015.0533.

Mexican Study Links Health System Delays and Later Stage Of Breast Cancer Diagnosis
Dr. Karla Unger-Saldaña
Unit of Epidemiology
Instituto Nacional de Cancerología Mexico City, Mexico.
Dr. Unger-Saldaña: Even though Breast Cancer is most common in the developed world, most
cancer deaths actually occur in developing regions. This is mainly because patients are diagnosed
in advanced stages, with poor chances of survival. Most studies have shown that long times
between symptom discovery and treatment start (total delay) are associated with advanced
clinical stage. Like total delay, patient delay -a prolonged time between symptom discovery and
the first medical consultation- has also shown to be associated with advanced clinical stage. But
the impact of health system delay -the time between the first clinical consultation and the start of
cancer treatment- is less clear. Studies have shown contradictory findings. For example, studies in
developed countries have found the reverse association: advanced stages associated with short
times between first medical consultation and treatment start. This has been attributed to the
ability of doctors to quickly identify patients with advanced cancer and somehow accelerate their
care.

Medical Research: What are the main findings?
Dr. Unger-Saldaña: In this study, done among 886 patients, we found that the majority started
cancer treatment in advanced stages, with only 15% being diagnosed in stages 0 and I. Also, we
found long delays for breast cancer diagnosis and treatment in most cases. The median time
between symptom discovery and cancer treatment start was 7 months. The longest subinterval
was that between the first medical consultation and diagnosis confirmation, which had a median
of 4 months. The most relevant result was that not only was patient delay associated with
advanced stage, but also health system delay. For every additional month of health system delay,
the probability of starting treatment in advanced stage was increased by 1%.

• Dr. Unger-Saldaña: The most relevant take home message for clinicians is that time to
diagnosis, referral and cancer treatment does matter. So, we need to have audacious
clinicians suspecting the diagnosis in time and acting appropriately.
• For patients, our study also showed that patient delay increases the probability of starting
cancer treatment in advanced stages. So it is very important that they consult a doctor as
promptly as they can after discovering symptoms that could be due to breast cancer.
• The biggest challenge is at the health system level, where better defined referral routes from
first level health care facilities to cancer hospitals could shorten dramatically these delays.

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