Medical Research Interviews on Cancer, Heart Disease

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
August 8 2015
For Informational Purposes Only: Not for Specific Medical Advice.

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7 Cancers May Occur More Frequently In LGBTQ Community
MedicalResearch.com Interview with:
Gwendolyn P. Quinn, Ph.D.
Moffitt Cancer Center
University of South Florida
• MedicalResearch: What is the background for this study? What are the main findings?
• Dr. Quinn: Our research group has been conducting studies of the LGBTQ community and
their healthcare experiences combined with providers knowledge and attitudes about LGBTQ
and cancer care. This led us to examine the literature on cancer and LGBTQ. The main
findings point to the lack of rigorous data about cancer in the LGBTQ community. Our
review revealed that 7 cancers (anal, breast, cervical, colorectal, colon and rectal,
endometrial, lung and prostate cancers) may occur more frequently in the community due to
elevated prevalence of risk factors and behaviors such as obesity and substance use;
however, there are limited data on outcomes, morbidity and mortality. The lack of data
makes it difficult for providers to fully inform patients about early detection, prevention, and
treatment options and outcomes. Further, the lack of psychosocial data makes it difficult to
provide supportive care recommendations and other forms of support.
Read the rest of the interviews on MedicalResearch.com
Content NOT an endorsement of efficacy and NOT intended as specific medical advice.

• MedicalResearch: What should clinicians and patients take away from your report?
• Dr. Quinn: There is great need to collect information on sexual orientation and gender
identity so that we can build larger databases to track incidence and outcomes of cancer in
the LGBTQ community. Further research is also needed in the psychosocial realm. For
example, we hear anecdotal reports that lesbian women with breast cancer are less
interested in reconstruction and more interested in having educational materials that are
not heteronormative, yet there are no empirical studies to support this. Clinicians
should understand that sexual orientation and gender identity are important pieces of
information to collection about their patients – they should not be treating everyone the
same or assuming everyone is gender aligned and heterosexual. Patients should expect to be
asked and provide this information – it is an important part of their health history.

• MedicalResearch: What recommendations do you have for future research as a result of
this study?
• Dr. Quinn: Collection of gender identity and sexual orientation should be part of the health
record with strict confidentiality applied and large databases established so the research and
clinical community can provide the best cancer prevention and cancer treatment care for the
LGBTQ community.
• Citation:
• Quinn, G. P., Sanchez, J. A., Sutton, S. K., Vadaparampil, S. T., Nguyen, G. T., Green, B. L.,
Kanetsky, P. A. and Schabath, M. B. (2015), Cancer and lesbian, gay, bisexual,
transgender/transsexual, and queer/questioning (LGBTQ) populations. CA: A Cancer Journal
for Clinicians. doi: 10.3322/caac.21288

How To Handle ICD If Patient’s Heart Function Improves?
Alan Cheng, MD, FACC, FAHA, FHRS
Associate Professor of Medicine and Pediatrics Director, Arrhythmia Device Service
Johns Hopkins University School of Medicine Baltimore, MD
• Medical Research: What is the background for this study? What are the main findings?
• Dr. Cheng: Sudden cardiac death (SCD) has been the most common way in which people in
the United States die. While it’s hard to accurately identify who is a higher risk for SCD, we
have learned from a number of studies over the past 30-40 years that people with
significant reductions in their heart function (measured as the ejection fraction (EF)) is one
group of individuals at high risk for Sudden cardiac death. In fact, the current American
College of Cardiology and American Heart Association guidelines state that people with an
EF below 35% are at high enough risk for Sudden cardiac death that these patients should
undergo implantation of an implantable cardioverter defibrillator (or ICD for short), a device
capable of monitoring the heart 24/7 and shocking the heart out of any arrhythmias that
could lead to Sudden cardiac death. The data they cite for this recommendation are so
compelling that they currently recommend implanting ICDs in patients not only among those
who already experienced an Sudden cardiac death event, but also those who have not.
Implanting an ICD to prevent Sudden cardiac death before they have had Sudden cardiac
death is known as primary prevention and this accounts for about 70-80% of all ICD implants
in the United States.

• While the EF is the best metric out there to determine if a patient should get an ICD, it has its
limitations. Because of these limitations, we have been interested for a long time in better
understanding how the EF and other metrics affect a patient’s risk for Sudden cardiac death.
• In this study, we followed 538 patients who were recipients of a primary prevention ICD who
underwent repeat assessment of their EF during followup in order to determine if changes in
their EF over time altered their risk for ICD shocks for ventricular arrhythmias or death. Over
a median of almost 5 years of followup, we found that 40% of the cohort had improvements
in their EF. And when the EF does improve, the risk goes down for ICD shocks for ventricular
arrhythmias as well as for death.

• Medical Research: What should clinicians and patients take away from your report?
• Dr. Cheng: Since changes in Ejection Fraction can affect a patient’s risk for ICD shocks and
death, it is important that patients and their doctors are doing everything possible to
maximize the chances of EF improvement or at the very least avoid a worsening of the EF.
Heart failure medications are the most important interventions in trying to accomplish this
and therefore, it is important that patients and their doctors are constantly looking at ways to
maximize and optimize their heart failure medication regimen.

• Medical Research: What recommendations do you have for future research as a result of
this study?
• Dr. Cheng: In most patients, getting an ICD was based on the fact that the EF was <35%. One
natural question from this study is whether patients with ICDs who later show improvement
in their heart function to >35% and whose ICDs are due for a generator exchange (because
the battery is expiring) benefit from having their generators replaced. This is a very important
question that many patients and their doctors are facing. Our study may seem to suggest that
a generator exchange is not necessary, but it’s important to point out that while we found
that the risk of ICD shocks goes down when the EF improves, the risk was not zero. I think it’s
premature to say that patients with improvements in their EF >35% no longer need a
generator exchange. Our data doesn’t support this assertion and larger studies will be
needed to confirm our findings and further tease out who can and cannot avoid a generator
exchange.
• Citation:
• Zhang Y, Guallar E, Blasco-Colmenares E, et al. Changes in Follow-Up Left Ventricular Ejection
Fraction Associated With Outcomes in Primary Prevention Implantable Cardioverter-
Defibrillator and Cardiac Resynchronization Therapy Device Recipients. J Am Coll Cardiol.
2015;66(5):524-531. doi:10.1016/j.jacc.2015.05.057.

Mild Increase in Daily Sodium Increases Risk of Hypertension
Tomonori Sugiura, MD, PhD
Department of Cardio‐Renal Medicine and Hypertension
Nagoya City University Graduate School of Medical Sciences
Nagoya Japan
• Dr. Sugiura: Although there is a close relationship between dietary sodium and hypertension,
the concept that individuals with relatively high dietary sodium are at increased risk of
developing hypertension compared to those with relatively low dietary sodium, has not been
intensively studied in a cohort. Therefore, the present observational study was designed to
investigate whether individual levels of dietary sodium critically affect future increases in
blood pressure in the general population.
• The main findings of this study were that a relatively high level of dietary sodium intake and
also a gradual increase in dietary sodium, estimated by urinary sodium excretion, are
associated with a future increase in blood pressure and the incidence of hypertension in the
general population.

Nagoya Japan
• Dr. Sugiura: A mild increase in sodium intake within the range observed in usual daily life, but
not a drastic sodium load as observed in interventional studies, increases the chance of
developing hypertension.

Nagoya Japan
this study?
• Dr. Sugiura: As a result of this study, we strongly suggests that appropriate methods of
effective education need to be developed to reduce dietary sodium intake in hypertensive
patients, as well as the general population.
• Citation:
• Dietary Sodium Consumption Predicts Future Blood Pressure and Incident Hypertension in
the Japanese Normotensive General Population
• Hiroyuki Takase, Tomonori Sugiura, Genjiro Kimura, Nobuyuki Ohte, and Yasuaki Dohi
• J Am Heart Assoc. 2015;4:e001959, originally published July 29, 2015,
doi:10.1161/JAHA.115.001959

Insulin Resistance Linked to Poor Memory Performance
Auriel A. Willette, M.S., Ph.D.
Food Science and Human Nutrition Neuroscience Interdepartmental Graduate Program
Gerontology Interdepartmental Graduate Program
Iowa State University, Ames
• Response: Obesity is a major health concern around the world. Obesity causes insulin
resistance, defined in this case as the inability of insulin to bind to its receptor and mediate
glucose metabolism. Other researchers and I have recently found that higher insulin
resistance is associated with less glucose metabolism in the brains of patients with
Alzheimer’s disease. This relationship is found primarily in medial temporal lobe, an area
necessary for generating new memories of facts and events. This is important because
Alzheimer’s disease is characterized by progressive decreases in glucose metabolism over
time, and partly drives worse memory performance. Insulin resistance in midlife also
increases the risk of developing Alzheimer’s disease.
• We wanted to determine if insulin resistance is linked to similar effects in cognitively normal,
late middle-aged participants decades before Alzheimer’s disease typically occurs. If so,
insulin resistance might be an important biological marker to track from middle-age onwards.
Thus, we examined the association between insulin resistance, regional glucose metabolism
using FDG-PET, and memory function in 150 middle-aged participants, many of whom had a
mother or father with Alzheimer’s disease.

• We found that higher insulin resistance was strongly associated with less glucose metabolism
throughout many brain regions, predominantly in areas that are affected by Alzheimer’s
disease. The strongest statistical effects were found in left medial temporal lobe, which again
is important for generating new memories. This relationship, in turn, predicted worse
memory performance, both immediately after learning a list of words and a 20-minute delay
thereafter.
• The take-home message is that insulin resistance has an Alzheimer’s-like association with
glucose metabolism in middle-aged, cognitively normal people at risk for Alzheimer’s, an
association which is related to worse memory.

• Response: It is important to prevent, reduce, or reverse insulin resistance. This is not only
relevant to people with type 2 diabetes but also those with “pre-diabetes,” metabolic
syndrome, or even obese participants without glycemic control problems but who have
hyperinsulinemia.
• Moderate exercise is the most important intervention to consider. Moderate exercise is
defined here as 30 total minutes on a given day for at least 3 times a week. Activities include
brisk walking, yard work, house work, yoga, and other motor movement that is not
strenuous. Somatic muscle conditioning is critical for ameliorating or preventing insulin
resistance. It is especially important for older participants, who may have muscle atrophy
(i.e., sarcopenia) and tend to be less active.

• Weight loss interventions should also be considered. Standard recommendations include
fewer calorie-heavy drinks and avoiding diet soft drinks, as well as eating one light meal and
usually moderating portions for other meals in a given day. For patients who strongly desire
to lose weight, intermittent calorie restriction has in clinical trials been shown to reduce
weight by 6-8% over an 8-week period and significantly reduce insulin resistance.
• For patients with type 2 diabetes, aggressive management is required. Beyond diet and
exercise recommendations, controlling the disease with metformin, other drugs, and later if
necessary insulin may be best at reducing Alzheimer’s disease risk. Clinical trials using
intranasal insulin, which provide insulin directly to the brain, seem to maintain glucose
metabolism in the brain and also maintain memory function. Further studies are needed to
see if normal methods of controlling type 2 diabetes, or intranasal insulin or other new
therapies, will reduce or eliminate risk for Alzheimer’s disease, or the development of
Alzheimer’s-like pathology or effects in the brain.

this study?
• Response: It is important to longitudinally follow middle-aged participants as they begin to
age. Longitudinal studies will allow us to see who develops clinically relevant memory
impairment and who does not. One will then be able to see if changes in insulin resistance
predicts less glucose metabolism over time, and if that has meaningful predictive power for
determining who does and does not go on to have memory problems and eventually
Alzheimer’s disease.
• Our previous work has also implicated insulin resistance in predicting Alzheimer’s-like
pathology in middle-age, such as amyloid deposits in the brain. It will be imperative to
examine any links with regional deposits of tau filament, a hallmark of Alzheimer’s disease,
when tau imaging becomes more commonplace. This will be critical in both Alzheimer’s
disease and in middle-age.
• Citation:
• Willette AA, Bendlin BB, Starks EJ, et al. Association of Insulin Resistance With Cerebral
Glucose Uptake in Late Middle–Aged Adults at Risk for Alzheimer Disease. JAMA Neurol.
Published online July 27, 2015. doi:10.1001/jamaneurol.2015.0613.

Biomarker S100B Can Help Rule Out Hemorrhage After Minor Head Injury
Dr. Heinrich Thaler
Trauma Hospital Meidling
Vienna Austria
• Medical Research: What is the background for this study?
• Dr. Thaler: An increased prevalence of minor head injuries in elderly patients combined with
the frequent use of platelet aggregation inhibitors resulted in increased hospital admissions
and cranial computed tomography. We undertook the study with the aim to reduce the
workload of medical staff and costs as well as the radiation burden in the management of
patients with mild head injuries.

Dr. Heinrich Thaler
Vienna Austria
• Medical Research: What are the main findings?
• Dr. Thaler: S 100B is a reliable negative predictor in elderly patients and/or in patients on
platelet aggregation inhibitors to rule out an intracranial hemorrhage after minor head injury
(S100B is an astroglial derived protein detectable in serum in the case of cerebral tissue
damage). The negative predictive value of S100B is 99,6%. We conclude that S100B levels
below 0.105 µg/L can accurately predict a normal cranial computed tomography after minor
head injury in older patients and those on antiplatelet medication. Additionally we found no
increased risk for intracranial hemorrhage in older patients or in patients receiving
antiplatelet therapy.

Dr. Heinrich Thaler
Vienna Austria
• Dr. Thaler: Using S100B physicians can safely reduce the number of admissions and cranial
computed tomography in older patients with minor head injuries and in patients with minor
head injuries receiving platelet aggregation inhibitors.

Dr. Heinrich Thaler
Vienna Austria
this study?
• Dr. Thaler: We only evaluated platelet aggregation inhibitors (low dose aspirin, clopidogrel)
in this patient group. However, the direct oral anticoagulants (DOACs) are yet to be
evaluated.
• Citation:
• Evaluation of S100B in the diagnosis of suspected intracranial hemorrhage after minor head
injury in patients who are receiving platelet aggregation inhibitors and in patients 65 years of
age and older
• Thaler HW1, Schmidsfeld J2, Pusch M1, Pienaar S1, Wunderer J1, Pittermann P1, Valenta R3,
Gleiss A4, Fialka C1, Mousavi M2.
• J Neurosurg. 2015 Jul 7:1-7. [Epub ahead of print]

Modern Wireless Devices May Cause Excessive Oxidative Stress In Humans
Prof. Igor Yakymenko
Laboratory of Biophysics, Institute of Experimental Pathology, Oncology and Radiobiology NAS of Ukraine
• Prof. Yakymenko: We know a lot about both health effects and metabolic effects of
radiofrequency radiation (RFR) today, including mutagenic and carcinogenic effects. For
example, epidemiological studies over the world indicate that 5 years of cell phone use 20
min per day increase risk of acoustic neuroma 3 times. Or, for example, 4 years of cell phone
use 1 hour or more per day increase risk of some kinds of brain tumors, including glioma, 3-5
times. But it was not understandable the primary mechanisms of such effects. In our study
we had analyzed about 100 recent studies on metabolic effects of radiofrequency radiation,
including our own experimental data, and demonstrated that oxidative/free radical effects
are mandatory feature of RFR exposure of living cells. Moreover, the chronic radiofrequency
radiation exposure can produce chronic oxidative stress in living cells as a first step for
possible development of bulk of hazardous health effects.

•
Medical Research: What should clinicians and patients take away from your report?
• Prof. Yakymenko: I think it’s extremely important for clinicians and patients to realize that
excessive radiofrequency radiation exposure from modern wireless devices is a risk factor for
human health with particular molecular/metabolic effects, which include oxidative/free
radical damages in living cell. One should avoid excessive exposure to RFR from wireless
devices (cell phones, Wi-Fi, smart meters). The precautionary principle says the less, the
better. To that in case of prophylactic and/or therapy science-based antioxidant approaches
should be accepted as logical keeping in mind the recent experimental findings.

this study?
• Prof. Yakymenko: The future research perspective should include deep analysis of molecular
mechanisms of hazardous effects of RFR. And may be the most intriguing part of the research
would be the elaboration of effective antioxidant approaches under such kinds of medical
conditions.
• Citation:
• Oxidative mechanisms of biological activity of low-intensity radiofrequency radiation
• Posted online on July 7, 2015. (doi:10.3109/15368378.2015.1043557)
Electromagnetic Biology and Medicine Posted online on July 7, 2015

Cancer Drug Can Activate HIV Reservoirs To Target For Eradication
Dr. Satya Dandekar PhD
Professor and Chair
Department of Medical Microbiology and Immunology
UC Davis
Medical Research: What is the background for this study? What are the main findings?
Dr. Dandekar: Current anti-retroviral therapy is effective in suppressing HIV replication and
enhancing immune functions in HIV infected individuals. However, it fails to eradicate the latent
HIV reservoirs. Therapy interruption leads to a rapid viral rebound in these patients. Eradication
of latent HIV reservoirs is essential to achieve HIV cure. A “shock and kill” strategy for HIV cure
has been proposed that involves reactivation of latent viral reservoirs using latency reversal
agents (LRA) and eradication by the immune response. This highlights the need to identify potent
LRAs to optimally activate latent HIV reservoirs so that immune surveillance and clearance
mechanisms can be effectively engaged in the process of viral eradication. We have found that
ingenol-3-angelate (PEP005), an anti-cancer drug can effectively reactivate latent HIV. It is a
protein kinase C agonist that activates NF-kB and stimulates HIV expression. In combination with
another compound, JQ1, a previously known p-TEFb agonist, the efficacy of PEP005 for HIV
reactivation is markedly increased. In addition, ingenol-3-angelate decreases the expression of
HIV co-receptors on immune cells, which potentially will help preventing further spread of the
virus. The use of ingenol-3-angelate in combination with other latency reversal agents provides
an excellent opportunity to optimally activate latent HIV reservoirs and target them for
eradication.

Professor and Chair
UC Davis
• Dr. Dandekar: With the availability of suppressive anti-retroviral therapy, it is now possible to
explore innovative approaches for HIV eradication. Identification of potent latency reversal
agents and optimization of the combination of LRAs will be important to achieve full
activation of the latent HIV reservoirs.

Professor and Chair
UC Davis
this study?
• Dr. Dandekar: Ingenol-3-angelate is a potential candidate for advancing to clinical HIV cure
studies based on its ability to activate latent HIV, act synergistically with other candidate LRAs
and to potentially protect immune targets by down-modulation of HIV co-receptor
expression. Future studies can be focused on pharmacokinetic evaluations in vivo and proof
of concept experiments in the experimental models.
• Citation:
• Synergistic Reactivation of Latent HIV Expression by Ingenol-3-Angelate, PEP005, Targeted
NF-kB Signaling in Combination with JQ1 Induced p-TEFb Activation
• Guochun Jiang, Erica A. Mendes, Philipp Kaiser, Daniel P. Wong, Yuyang Tang, Ivy Cai, Anne
Fenton, Gregory P. Melcher, James E. K. Hildreth, George R. Thompson, Joseph K. Wong,
Satya Dandekar
• Published: July 30, 2015 DOI: 10.1371/journal.ppat.1005066

Epigenetic Biomarker May Improve Cervical Cancer Screening
Christos Nikolaidis Ph.D.
Laboratory of Pharmacology
Medical School, Democritus University of Thrace
Dragana, Alexandroupolis Greece
Medical Research: What is the background for this study?
Response: Epigenetic changes are part of the natural history of cervical neoplasia. Tracking these
changes at the molecular level is necessary for understanding disease progression, response to
treatment and prognosis. Epigenetic biomarkers can potentially assess the stage of cervical
intraepithelial neoplasia (CIN). This information can be used for screening purposes, to improve
the overall quality of cervical cancer diagnostics.

Medical Research: What are the main findings?
Response: Paired boxed 1 (PAX1) gene methylation status has been widely used as a biomarker
for cervical cancer screening. We have conducted a meta-analysis of the diagnostic test accuracy
of PAX1 methylation, on moderate cervical dysplasia or worse (CIN2+) versus normal epithelium,
and severe cervical dysplasia or worse (CIN3+) versus normal epithelium, for a total population of
1385 women. The results of this assay were generally satisfactory for CIN2+ vs normal, and
extremely satisfactory for CIN3+ vs normal (Sensitivity=0.77, Specificity=0.92, AUC=0.931). This
raises the possibility of utilizing this biomarker to improve current diagnostic protocols.

• Response: The incorporation of HPV-DNA analysis into clinical practice has greatly improved
cervical cancer screening. However, despite its higher sensitivity, a notable compromise in
specificity is often observed, due to the transient nature of most HPV infections. Currently,
most patients with second (CIN2) or third degree (CIN3) lesions undergo corrective surgery
by ablation or excision of the intraepithelial anomaly. Being able to accurately distinguish
between benign infections, and those requiring more intensive treatment is of paramount
importance. Numerous unnecessary referrals could be avoided, preventing iatrogenic
discomfort to patients and significantly reducing healthcare costs.

this study?
• Response: The fact that certain genes are found methylated at precancerous stages, suggests
that methylation-specific biomarkers have an important role to play in secondary cancer
prevention. Research in the field of cancer epigenetics can greatly improve diagnostic
practices in the near future. Further studies are required, in order to identify the best
candidate gene/s for clinical application and test their efficacy.
• Citation:
• PAX1 methylation as an auxiliary biomarker for cervical cancer screening: A meta-analysis
• Nikolaidis, Christos et al.
Cancer Epidemiology Published Online: July 30, 2015
DOI: http://dx.doi.org/10.1016/j.canep.2015.07.008

Genes May Explain Why Smarter People Live Longer
Dr. Rosalind Arden
Centre for Philosophy of Natural & Social Science
London School of Economics
London
• MedicalResearch: What is the background for this study? What are the main findings?
• Dr. Arden: We’ve known for a while that people who score higher on IQ-type tests tend to
live longer. A study published in the British Medical Journal (Whalley & Deary, 2001)
examined intelligence in childhood and later survival. People born in Scotland in 1921 took an
IQ-type test at age 11 in 1932. Those with higher test scores were more likely to survive to
age 76.
• What we haven’t known is ‘why?’ One possibility is that advantages from being raised in a
wealthier family may enhance intelligence and health – leading to brighter people living
longer. Another possibility is that many genes that influence brains also influence bodies. If
well-built brains co-occur with well-built bodies, that could also explain the link. These are
only two of several possible explanations. We aimed to test whether genes caused the link
between intelligence and life-expectancy.

Dr. Rosalind Arden
London
• We found
• 1) the link between intelligence and life expectancy is positive but small.
• 2) The cause of the link is almost all genetic.
• We found this by examining differences within twin pairs. Twins offer a quasi-natural
experiment because they share many features of the environment that are often thought
(mistakenly) to cause differences between people. And marvelously, for science there are
two kinds of twins, with known genetic relatedness (100 % or 50%). This give us a means to
test questions about the cause of differences in a population, as well as the causes of
correlations among traits within a population.

Dr. Rosalind Arden
London
• Dr. Arden: Intelligence has links with health, and for genetic reasons. Intelligence may be
something of a ‘canary in the mine’. It is a faint signal of how well a body is put together. Yet
as clinicians already know, while intelligence is a useful indicator, its correlation with health
outcomes is probabilistic and small. It is helpful to know about at the population or actuarial
level, but not predictive at the individual level. The high intelligence of the poet (and doctor)
Keats did not prevent his early death.
• The importance of genes to health outcomes is clear; yet none of us know the full extent of
the tricks and treats hidden in our own personal allocation of genetic ‘lottery tickets’. Taking
care of ourselves in all the usual ways is a good plan because it works to give us the best odds
regardless of genetic background. Anyone who is worried that a loved one is not the sharpest
knife in the drawer need not be concerned.

Dr. Rosalind Arden
London
this study?
• Dr. Arden: Easy – replication! We hunted around for data that would serve our purposes, but
it would be smashing to have genetically-informative data (data where there are known
differences in relatedness within the sample) on a population where IQ-type test scores had
been collected in youth, and where data on illness and mortality data had also been
collected.
• Another critical design would be to test the same link (intelligence and lifespan) with other
mammals (see Lou Matzel’s marvellous mouse lab for example (L D Matzel et al., 2003; L. D.
Matzel, Sauce, & Wass, 2013). It would be wonderful to learn whether (and if so, why) this
link exists in say, mice and dogs. There are several reasons to choose these animals. Mice and
dogs are both reasonably tractable species; they have a lot to offer human studies of ageing
and longevity, and they do not experience the diversity of socio-economic conditions that
people do. Mice and dogs could help us learn whether being bright is a) a fitness benefit in
the evolutionary sense, b) positively correlated with other health outcomes (such as lifespan)
that we care about. Who said going to the dogs was a bad thing?

Dr. Rosalind Arden
London
• @Rosalind_Arden_ on Twitter
• Our open access paper:
• http://ije.oxfordjournals.org/cgi/reprint/dyv112?
ijkey=qx3WNCwOm8puV38&keytype=ref
• Citation and Referencs:
• Matzel, L. D., Han, Y. R., Grossman, H., Karnik, M. S., Patel, D., Scott, N., … Gandhi, C. C.
(2003). Individual differences in the expression of a “general” learning ability in mice. Journal
of Neuroscience, 23, 6423–6433.
• Matzel, L. D., Sauce, B., & Wass, C. (2013). The Architecture of Intelligence: Converging
Evidence From Studies of Humans and Animals. Current Directions in Psychological Science,
22(5), 342–348. doi:10.1177/0963721413491764
• Whalley, L. J., & Deary, I. J. (2001). Longitudinal cohort study of childhood IQ and survival up
to age 76. British Medical Journal, 322(7290), 819–822. doi:10.1136/bmj.322.7290.819

Blood Pressure Dippers May React Differently to Morning Blood Pressure Surge
Prof. Sante D. Pierdomenico
Associate Professor of Internal Medicine
University “Gabriele d’Annunzio”
Chieti-Pescara – Italy
• Dr. Pierdomenico: Though a peak incidence of cardiovascular events in the morning has
been observed, the independent prognostic value of morning surge (MS)
of blood pressure (BP) is not yet clear. We investigated the
association between morning surge of systolic blood pressure and risk of coronary events in
elderly treated hypertensive patients. Subjects were divided according
to tertiles of MS of systolic blood pressure of the population as a whole, by
dipping status (nondippers are at increased risk than dippers) and by
group-specific tertiles of morning surge of systolic blood pressure in dippers and nondippers
because these groups have different MS of blood pressure. In elderly treated
hypertensive patients, high MS of systolic BP predicts coronary events
in dippers but not in nondippers. Nondippers, however, show higher
risk of coronary events independently of morning surge in systolic blood pressure.

Patient-Derived Stem Cells May Be Able To Reverse Hemophilia A
Dong-Wook Kim
Center for Genome Engineering, Institute for Basic Science
Yonsei University College of Medicine
Seoul, Korea
Response: Hemophilia A is an X-linked genetic disorder caused by mutations in the F8 gene,
which encodes the blood coagulation factor VIII. Almost half of all severe hemophilia A cases
result from two gross (140-kbp or 600-kbp) chromosomal inversions. We derived induced
pluripotent stem cells (iPSCs) from patients with these inversion genotypes and used CRISPR-
Cas9 nucleases to revert these chromosomal segments back to the WT situation.
Response: We isolated inversion-corrected iPSCs with frequencies of up to 6.7% without
detectable off-target mutations based on whole-genome sequencing or targeted deep
sequencing. Endothelial cells differentiated from corrected iPSCs expressed the F8 gene and
functionally rescued factor VIII deficiency in an otherwise lethal mouse model of hemophilia.

Patient-Derived Stem Cells May Be Able To Reverse Hemophilia A
Dong-Wook Kim
Center for Genome Engineering, Institute for Basic Science
Yonsei University College of Medicine
Seoul, Korea
• Response: Our results provide a proof of principle for functional correction of large
chromosomal inversions in Hemophilia patient-derived induced pluripotent stem cells and
suggest potential therapeutic applications in the future.
this study?
• Response: We need to prove the safety of patient-derived iPSCs before we move towards
clinics.
• The safety of iPSCs means to prevent teratoma formation when we do clinical trials.
• For that purpose, we need to develop good differentiation protocols into EC cells and to
purify the cells as well. In addition, we need much more animal study.
• Citation:
• Functional Correction of Large Factor VIII Gene Chromosomal Inversions in Hemophilia A
Patient-Derived iPSCs Using CRISPR-Cas9
• Chul-Yong Park Duk Hyoung Kim Jeong Sang Son Jin Jea Sung Jaehun Lee Sangsu Bae Jong-
Hoon Kim Dong-Wook Kim Jin-Soo Kim
• Cell Stem Cell Available online 23 July 2015
• doi:10.1016/j.stem.2015.07.001

Primary Care Study: Screening Women For Partner Violence Did Not Improve Health
Joanne Klevens, MD, PhD
Division of Violence Prevention
US Centers for Disease Control and Prevention
Atlanta, Georgia
Dr. Klevens: The United States Preventive Services Task Force recommends women of
reproductive age be screened for partner violence but others, such as the World Health
Organization and the Cochrane Collaborative conclude there is insufficient evidence for this
recommendation. Our randomized clinical trial allocated 2700 women seeking care in outpatient
clinics to 1 of 3 study groups: computerized partner violence screening and provision of local
resource list, universal provision of partner violence resource list without screening, or a no-
screen/no resource list control group. No differences were found in women’s quality of life, days
lost from work or housework, use of health care and partner violence services, or the recurrence
of partner violence after 1 year. In this three-year follow-up, no differences were found in the
average number of hospitalizations, emergency room visits or ambulatory care visits.

Atlanta, Georgia
• Dr. Klevens: This is one study and does not rule out asking women about their experiences of
violence; however, among women attending primary care clinics, the findings indicate that
just providing a list of partner violence resources, with or without asking questions about
partner violence, did not result in improved health. More intensive interventions may be
necessary to see health benefits. Other studies suggest that screening coupled with multiple
sessions of counseling may be effective among some groups of women (e.g., pregnant
women) and on other types of outcomes (e.g., preterm birth).

Atlanta, Georgia
this study?
• Dr. Klevens: There are at least 4 interventions for women experiencing partner violence with
some evidence of health impacts. However, these interventions have been evaluated among
specific groups of women (e.g., pregnant women, women in or exiting domestic violence
shelters). Future research could determine whether these interventions are utilized by and
have benefits for women seeking primary care for reasons other than pregnancy. Future
research also is needed to see if more intensive interventions such as screening plus
counseling sessions or case management to actively help women access services might
improve health outcomes for women experiencing or at risk for intimate partner violence.
• Citation:
• Klevens J, Sadowski LS, Kee R, Garcia D, Lokey C. Effect of Screening for Partner Violence on
Use of Health Services at 3-Year Follow-up of a Randomized Clinical Trial. JAMA.
2015;314(5):515-516. doi:10.1001/jama.2015.6755.

Hospitals Vary in Rates of Missed Acute Myocardial Infarction Diagnosis
Philip G. Cotterill PhD
Centers for Medicare & Medicaid Services
Baltimore, MD
• Dr. Cotterill: Chest pain is one of those elusive complaints where patients can seem initially
low-risk based on symptoms or risk factors, and subsequently have an acute myocardial
infarction (AMI) or die in a short period of time. Using combinations of history and physical
examination findings to discriminate patients with serious causes of chest pain is often not
possible. In our study, we demonstrated wide variation in the decision to hospitalize
Medicare beneficiaries with chest pain – nearly two fold between the lowest (38%) and
highest (81%) quintile of hospitals – and that patients treated in hospitals with higher
admission rates for chest pain are less likely to have an acute myocardial infarction within 30-
days of the index event and less likely to die.

Baltimore, MD
While the findings were statistically significant – differences in outcomes were small: 4 fewer
AMIs and 3 fewer deaths per 1,000 patients comparing the highest and lowest admission
quintiles. Stated differently, these numbers suggest that if low admitting hospitals were to behave
more like high admitting hospitals, 250 patients would need to be admitted to prevent one AMI
and 333 cases to prevent one death.

Baltimore, MD
• Dr. Cotterill: A main reason for hospital admission of patients with a symptom of chest pain,
but who do not have an objective diagnosis during the first few hours of emergency
department (ED) care, is to assess the presence of serious causes that are not initially
detected – such as acute coronary syndrome and other conditions. Factors such as risk
tolerance and malpractice fear have been identified as important explanatory factors
associated with the wide variation in admission rates among emergency physicians. Patients
who are treated and released, but subsequently return with serious causes for chest pain, are
a particular concern because patients with “missed” acute myocardial infarction (AMI) have
worse outcomes. The rate of “missed” AMI has been estimated at around 2% of patients with
AMI. Missed acute myocardial infarction is the leading cause for ED medical malpractice
litigation. Although there have been attempts to create decision rules for Missed acute
myocardial infarction is the leading cause for ED medical malpractice litigation-based chest
pain, there are currently no broadly validated or accepted instruments that suitably identify
patients as safe for ED discharge.

Baltimore, MD
this study?
• Dr. Cotterill: We did not have detailed information on the specific processes of care that
might explain our results; however, we can hypothesize that higher admission rates allow
more time for patient evaluation and assessment for serious causes of chest pain. If our
findings can be interpreted as meaning that a more intensive approach to risk-stratification
and observation for chest pain is more effective, and comparable to other recommended
screening interventions in terms of effectiveness, the ultimate clinical question is how we can
achieve this goal in the context of national health policy that is pushing toward lower use of
expensive resources such as inpatient admissions.

Baltimore, MD
• Additional studies will be required to reassess how risk-stratification in the ED is conducted
as the diagnostic technology to detect occult coronary syndromes– such as high sensitivity
troponins and CT coronary angiograms — and other serious diagnoses evolves. Specifically,
future work should focus on how to appropriately exclude serious diagnoses with either
advanced technology in the ED, in hospital-based observation units, or alternatively for
patients to have short-term follow-up with specialists such as cardiologists for outpatient
stress testing. As new payment models emerge, finding cost-effective alternatives to identify
occult serious causes for chest pain will be increasingly important in an era with an increasing
focus on the value of the healthcare dollar.
• Citation:
• Variation in Chest Pain Emergency Department Admission Rates and Acute Myocardial
Infarction and Death Within 30 Days in the Medicare Population
• Philip G. Cotterill PhD Partha Deb PhD William H. Shrank MD, MSHS3 and Jesse M. Pines MD,
MBA, MSCE4
• Academic Emergency Medicine 2015;22:000–000 © 2015 by the Society for Academic
Emergency Medicine

Mindfulness-Based Stress Therapy May Reduce PTSD Symptoms in Veterans
Melissa A. Polusny, PhD, LP
Staff Psychologist/Clinician Investigator
Core Investigator, Center for Chronic Disease Outcomes Research
Associate Professor, University of Minnesota Medical School
Dr. Polusny: VA has invested heavily in the dissemination of prolonged exposure therapy and
cognitive processing therapy as first-line treatments for PTSD; however, 30% to 50% of Veterans
do not show clinically significant improvements and dropout rates are high. Evidence suggests
that mindfulness-based stress reduction – an intervention that teaches individuals to attend to
the present moment in a non-judgmental, accepting manner – can reduce symptoms of anxiety
and depression. This randomized clinical trial compared mindfulness-based stress reduction with
present-centered group therapy – sessions focused on current life problems. We randomly
assigned 116 Veterans with PTSD to receive nine sessions of mindfulness-based stress reduction
therapy (n=58) or nine sessions of present-centered group therapy (n=58). Outcomes were
assessed before, during and after treatment, and at two-month follow-up. Exclusion criteria
included: substance dependence (except nicotine), psychotic disorder, suicidal or homicidal
ideation, and/or cognitive impairment or medical illness that could interfere with treatment. The
primary outcome was a change in self-reported PTSD symptom severity over time. Secondary
outcomes included interview-rated PTSD severity scores, self-reported depression symptoms,
quality of life, and mindfulness skills.

Mindfulness-based stress reduction therapy – compared with present-centered group therapy –
resulted in a greater decrease in self-reported PTSD symptom severity. Veterans in the
mindfulness-based stress reduction group were more likely to show clinically significant
improvement in self-reported PTSD symptom severity (49% vs. 28%) at two-month follow-up, but
they were no more likely to have loss of PTSD diagnosis (53% vs. 47%). Veterans participating in
mindfulness-based stress reduction therapy reported greater improvement in quality of life and
depressive symptoms than those in present-centered group therapy; however improvement in
depressive symptoms scores did not reach the level of significance. Improvements in quality of
life made during treatment were maintained at 2-month follow-up for Veterans in the
mindfulness-based stress reduction group, but reports of quality of life returned to baseline
levels for those in present-centered group therapy. The dropout rate observed for mindfulness-
based stress reduction therapy (22%) in this study was lower than dropout rates reported in
previous studies for PE (28.1% to 44%) and CPT (26.8% to 35%).

• Dr. Polusny: Several effective treatments for PTSD are available, and veterans and others with
PTSD should be encouraged to seek help for their problems with PTSD. Mindfulness-based
stress reduction therapy – an intervention that teaches individuals to attend to the present
moment (immediate emotional and physical states, including discomfort) in a non-
judgmental, accepting manner – shows promise as a treatment for PTSD. While clinicians
should continue to encourage Veterans to engage in existing evidence-based treatments for
PTSD, mindfulness-based stress reduction therapy may be acceptable to veterans who have
poor adherence to existing evidence-based treatments for PTSD.

this study?
• Dr. Polusny: While mindfulness-based stress reduction therapy shows promise as a treatment
for PTSD among Veterans, replication of findings from this study with more diverse samples
and additional centers is needed.
• Citation:
• Polusny MA, Erbes CR, Thuras P, et al. Mindfulness-Based Stress Reduction for Posttraumatic
Stress Disorder Among Veterans: A Randomized Clinical Trial. JAMA. 2015;314(5):456-465.
doi:10.1001/jama.2015.8361.
• Email *

Vitamin D Did Not Improve Bone or Muscle Health in Post-Menopausal Women
Karen E. Hansen, M.D., M.S.
Associate Professor of Medicine
University of Wisconsin School of Medicine and Public Health
Madison, WI 53705-2281
Medical Research: What is the background for this study?
Dr. Hansen: The USPTF says to older community dwelling adults, “don’t bother taking vitamin D”,
the Endocrine Society says “take 2,000-4,000 IU daily” and the Institute of Medicine gave an RDA
of 600-800 IU daily. The Endocrine Society argues that optimal vitamin D levels are 30 ng/mL and
higher, while the Institute of Medicine concludes that 20 ng/mL and higher indicates optimal
vitamin D status. The disagreement between experts prompted my study.

Medical Research: What are the main findings?
Dr. Hansen: Among postmenopausal women whose vitamin D level was ~21 ng/mL at baseline,
there was no benefit of high-dose or low-dose vitamin D, compared to placebo, on
spine/hip/total body bone mineral density, muscle fitness by 5 sit to stand test or Timed Up and
Go, or falls. We did see a small 1% increase in calcium absorption in the high-dose vitamin arm,
but this small increase did not translate into clinically meaningful changes in bone density or
muscle tests.

• Dr. Hansen: the Institute of Medicine concluded that virtually all patients are vitamin D
replete, if their serum levels are 20 ng/mL or higher. Our study agreed with that conclusion,
since we found no clinical benefits from pushing levels from ~21 ng to above 30 ng/mL for
one year, with use of high-dose vitamin D.

this study?
• Dr. Hansen: We did not have many African American women in our study. Whether this
group of individuals has differing vitamin D requirements, due to racial variations in vitamin D
binding protein levels, or different calcium absorption efficiency and/or renal calcium
recycling, is an important future study.
• Citation:
• Hansen KE, Johnson R, Chambers KR, et al. Treatment of Vitamin D Insufficiency in
Postmenopausal Women: A Randomized Clinical Trial. JAMA Intern Med. Published online
August 03, 2015. doi:10.1001/jamainternmed.2015.3874.

Spicy Foods May Decrease Mortality From Chronic Health Conditions
Lu Qi, MD, PhD, FAHA
Harvard Medical School
Associate Professor of Nutrition and Epidemiology
Harvard T.H. Chan School of Public Health
Dr. Lu Qi: There are accumulating evidence from mostly experimental research to show the
benefit of spicy foods or their active components on human health. However, supportive data
from population based studies are sparse. The major findings are that high consumption of spicy
foods reduce risk of total mortality and death related to diseases such as cancer, heart disease
and cancer, ischamic heart diseases, and respiratory system diseases.
• Dr. Lu Qi: Eating spicy foods may benefit human health.

this study?
• Dr. Lu Qi:
• First, more studies in large, prospective cohorts are needed to validate our findings,
especially in populations with various ethnicity.
• Second, experimental analysis in animals and cells is essential to illustrate what is going on
underlying the observed associations.
• Intervention studies in humans would give more solid evidence, though conducting such
studies is not easy.

• Citation:
• Lv Jun, Qi Lu, Yu Canqing, Yang Ling, Guo Yu, Chen Yiping et al. Consumption of spicy foods
and total and cause specific mortality: population based cohort study 2015; 351 :h3942

Tenovir Gel May Reduce Risk of Both HIV and Herpes Simplex
Dr. Salim Abdool Karim at CAPRISA
Doris Duke Medical Research Institute
South Africa
•
Response: Globally, Herpes simplex virus type-2 (HSV-2) is among the most common sexually
transmitted infections and is the leading cause of genital ulcers. Available global estimates
indicate that approximately 417 million sexually active adults between the ages of 15 and 49
years had an existing prevalent HSV-2 infection in 2012. Current interventions to prevent
HSV-2 infection, including condoms, circumcision, and antiviral treatment among
heterosexual, HSV-2-discordant couples, have demonstrated protection levels ranging from
6% to 48%. This study showed that peri-coital tenofovir gel reduced HSV-2 acquisition in
women by 51%, rising to 71% in high gel-users.
•

South Africa
• Response: If licensed, tenofovir gel could potentially be used as a HSV-2 prevention strategy
for women unable to negotiate condom use. Tenofovir gel, when used, has also been shown
to be effective in reducing HIV risk. Given the close association between HSV-2 infection and
the increased risk of HIV acquisition in women, tenofovir gel has the potential to empower
women to control their risk of both HIV and HSV-2.

South Africa
this study?
• Response: Research on new long-acting formulations of tenofovir is needed. Since peri-coital
gel adherence can be challenging for women at high-risk, especially young women who are
not aware of their risk, improved long-acting formulations of tenofovir or other anti-HSV
drugs are needed to provide effective long-term protection.
• Citation:
• Tenofovir Gel for the Prevention of Herpes Simplex Virus Type 2 Infection
• Salim S. Abdool Karim, M.B., Ch.B., Ph.D., Quarraisha Abdool Karim, Ph.D., Ayesha B.M.
Kharsany, Ph.D., Cheryl Baxter, Ph.D., Anneke C. Grobler, Ph.D., Lise Werner, M.Sc., Angela
Kashuba, Pharm.D., Leila E. Mansoor, Ph.D., Natasha Samsunder, B.Tech., Adrian Mindel,
M.D., and Tanuja N. Gengiah, Ph.D. for the CAPRISA 004 Trial Group
• N Engl J Med 2015; 373:530-539
August 6, 2015 DOI: 10.1056/NEJMoa1410649

Majority of New HIV Infections Occur in Men Who Have Sex With Men
Adaora Adimora, MD, MPH
Chair of the HIV Medicine Association
Professor of Medicine School of Medicine
University of North Carolina, Chapel Hill.
• MedicalResearch: What is the current scope of the HIV epidemic?
• Dr. Adimora: The Centers for Diseases Control and Prevention (CDC) estimates that there are
1.2 million people living with HIV in the U.S. Nearly 13% are undiagnosed and unaware of
their status. Men who have sex with men represented 54% of all people living with HIV in
2011. While new infection rates are stable, a majority of new infections (63%) are occurring
among men who have sex with men. We have seen alarming increases among young black
men who have sex with men who account for 55% of new infections among men who have
sex with men. New infections among women have decreased slightly but black and
Hispanic/Latina women represent 62% and 17% of new infections respectively among
women.[i] While there have been decreases in new HIV infections among people who inject
drugs in recent years, the serious outbreak largely among injection drug users in Scott
County, Indiana identified this past spring[ii] puts us on high alert to improve access to
preventive services and substance use treatment, including access to sterile syringes and
equipment.

My responses will generally focus on the U.S. epidemic but want to acknowledge that globally an
estimated 36.9 million people were living with HIV at the end of 2014 with just 51% of them
being diagnosed and more than 34 million deaths were attributed to HIV-related causes.[iii]

• Dr. Adimora: On the scientific front, we have made great progress. The development of
antiretorivral drugs that are highly effective at suppressing HIV now allow people with HIV to
stay healthy and live near normal life spans.[iv] New research definitively shows that people
with HIV who start treatment earlier have significantly better health outcomes. [v] [vi] The
U.S. Department of Health and Human Services Panel on Antiretroviral Guidelines for Adult
and Adolescent recently strengthened their recommendation that all patients are offered HIV
treatment in light of this new data.[vii]
• Other critical developments include the overwhelming evidence that HIV treatment not only
benefits the patient with HIV, but also improves public health by reducing the HIV-infected
individual’s risk of transmitting the virus to zero when viral suppression is sustained.[viii] In
addition, antiretroviral drugs have proven highly effective at preventing transmission when
taken by individuals who are HIV negative – an important intervention, referred to as Pre-
exposure Prophylaxis (PrEP), for people who are at higher risk for contracting HIV.[ix] For care
delivery, the Ryan White HIV/AIDS Program (RWHAP) has been a leader in supporting a multi-
disciplinary team approach to providing high quality, comprehensive care to poor, uninsured
and underinsured individuals with HIV.[x] [xi] Celebrating its 25th anniversary this month, the
RWHAP serves two out of three people with HIV in care and continues to be vital to
responding to HIV in the U.S.

• MedicalResearch: What are the barriers to current HIV diagnosis and treatment?
• Dr. Adimora: Transferring the scientific advances in HIV medicine to the frontlines has been
complicated and challenging due to a number of multi-dimensional factors. The CDC
estimates that of the 1.2 million people living with HIV in the U.S. only 40% are engaged in
care; 37% are prescribed antiretroviral treatment and just 30% are virally suppressed – the
clinical definition of successful treatment.[xii] Stigma and discrimination play a large role in
discouraging people with HIV from getting tested and interferes with linking and keeping
patients with HIV in care. Many people living with HIV are dealing with other complex health
issues, such as hepatitis C, mental illness or substance abuse in addition to facing challenges
meeting other basic living needs, such as housing, stable employment and family care. HIV
infection also disproportionately affects people with lower incomes who – depending on
where they live – may not have any access to health care coverage. This is a major challenge
particularly in the Southeastern U.S. where the HIV rates are growing the fastest[xiii] and
where a majority of states have rejected the Medicaid expansion.[xiv]

• MedicalResearch: What suggestions do you have to implement wider HIV prevention,
diagnosis and treatment?
• Dr. Adimora: As detailed in the 2015 to 2020 National HIV/AIDS Strategy[xv], action is needed
at multiple levels to improve HIV prevention, diagnosis and treatment outcomes. Primary
care and other medical providers can play an important role by incorporating routine HIV
screening into their practice and developing relationships with the HIV providers in their
community to refer and link patients who are newly diagnosed with HIV. We must increase
access to delivery systems, like those supported by the Ryan White HIV/AIDS Program, that
take a comprehensive approach to health by not just treating HIV but also helping patients
address their other health, psychosocial and basic living needs. At the policy level, the
inequities in access to health care coverage need to be addressed to support early and
reliable access to HIV and other preventive and health care services for everyone regardless
of who they are or where they live. We need the 20 states that have not expanded Medicaid
to do so. We also must let the science drive our efforts and employ the range of tools proven
effective at preventing HIV infection, including allowing federal support for syringe access
programs and increasing access to Pre-exposure Prophylaxis for everyone who could benefit
from it.

• Citations:
• [i]Centers for Disease Control and Prevention. HIV in the United States: At A Glance. Online at
http://www.cdc.gov/hiv/statistics/basics/ataglance.html.
• [ii]CDC. MMWR 64(16);443-444. Community Outbreak of HIV Infection Linked to Injection Drug Use of Oxymorphone — Indiana, 2015.
Online at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6416a4.htm.
• [iii]World Health Organizations. HIV/AIDS. Fact Sheet. Online at: http://www.who.int/mediacentre/factsheets/fs360/en/.
• [iv]Schackman LE, et al. Racial and Sex Disparities in Life Expectancy Losses among HIV‐Infected Persons in the United States: Impact of
Risk Behavior, Late Initiation, and Early Discontinuation of Antiretroviral Therapy. Clin Infect Dis 2009;49(10):1570-8.
• [v] INSIGHT START Study Group. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med. Jul 20 2015.
Online at: http://www.ncbi.nlm.nih.gov/pubmed/26192873.
• [vi] Temprano ANRS 12136 Study Group. A trial of early antiretrovirals and isoniazid preventive therapy in Africa. N Engl J Med. Jul 20
2015. Online at: http://www.ncbi.nlm.nih.gov/pubmed/26193126.
• [vii] Statement by the HHS Panel on Antiretroviral Guidelines for Adults and Adolescents Regarding Results from the START and
TEMPRANO Trials. July 28, 2015. Online at: https://aidsinfo.nih.gov/news/1592/statement-from-adult-arv-guideline-panel—start-and-
temprano-trials
• [viii] Cohen, MS et al. Prevention of HIV-1 Infection with Early Antiretroviral Therapy, N Engl J Med. Aug 11 2011. Online at:
http://www.nejm.org/doi/full/10.1056/NEJMoa1105243.
• [ix] U.S. Public Health Service. Preexposure Prophylaxis for the Prevention of HIV Infection in the United States – 2014. A Clinical
Practice Guideline. Online at: http://www.cdc.gov/hiv/pdf/prepguidelines2014.pdf.
• [x] Gallant JE, et al. Essential Components of Effective HIV Care. Clin Infect Dis. 2011. Online at:
http://cid.oxfordjournals.org/content/early/2011/10/20/cid.cir689.full.
• [xi]Moore RD, Keruly JC and Bartlett JG. Improvement in the Health of HIV-Infected Persons in Care: Reducing Disparities. Clin Infect Dis.
2012 Nov 1; 55(9): 1242–1251.
• [xii]AIDS.gov. HIV/AIDS Care Continuum. Online at: https://www.aids.gov/federal-resources/policies/care-continuum/.
• [xiii] Prejean J, et al. HIV Diagnoses and Prevalence in the Southern Region of the United States, 2007-2010. J Community Health 2012.
• [xiv] Kaiser Family Foundation. Status of State Medicaid Expansion Decisions. Online at: http://kff.org/health-reform/slide/current-
status-of-the-medicaid-expansion-decision.
• [xv] White House Office of National HIV/AIDS Policy. National HIV/AIDS Strategy for the United States: Updated to 2020. July 2015.
Online at: https://www.aids.gov/federal-resources/national-hiv-aids-strategy/nhas-update.pdf.

Botulinum Toxin Reduces Pain of Skin Leiomyomas
Edward W. Cowen, MD, MHSc
Dermatology Branch, Center for Cancer Research
National Cancer Institute
Bethesda, Maryland
Dr. Cowen: Cutaneous leiomyomas are benign smooth muscle proliferations that are
associated with pain that is typically not well-controlled by topical remedies or systemic pain
medication. Hereditary leiomyomatosis and renal cell cancer is a rare syndrome in which
patients may have dozens or even hundreds of these painful tumors. We sought to determine
if botulinum toxin injected directly into leiomyomas may ameliorate discomfort and improve
quality of life in patients who experience significant pain from cutaneous leiomyomas.
Dr. Cowen: In a double-blinded placebo-controlled study, we found that injection of
botulinum toxin was associated with improved skin-related quality of life (p = 0.007) and
decreased skin-specific pain (p = 0.048) on the Dermatology Life Quality Index. A trend for
decreased pain (p = 0.06) by visual analog score was reported in the botulinum toxin treated
group compared to the placebo group.

Botulinum Toxin Reduces Pain of Skin Leiomyomas
Edward W. Cowen, MD, MHSc
Dermatology Branch, Center for Cancer Research
National Cancer Institute
Bethesda, Maryland
• Dr. Cowen: In this small pilot study, we provide preliminary evidence that botulinum toxin
improves quality of life and may exhibit analgesic qualities in patients with significant pain
related to cutaneous leimyomas. To our knowledge, this is the first clinical trial demonstrating
such a benefit with botulinum toxin for leimyoma skin-related pain.
this study?
• Dr. Cowen: The mechanisms underlying the benefit of botulinum toxin for this and other pain
disorders remains unclear. Botulinum toxin injection into cutaneous leimyomas is associated
with discomfort and, therefore, other routes of administration, such as topical formulation of
botulinum toxin, could potentially avoid the discomfort of intralesional injection.
• Citation:
• Naik HB, Steinberg SM, Middelton LA, et al. Efficacy of Intralesional Botulinum Toxin A for
Treatment of Painful Cutaneous Leiomyomas: A Randomized Clinical Trial. JAMA Dermatol.
Published online August 05, 2015. doi:10.1001/jamadermatol.2015.1793.

ACE Level Lowered by ACE Inhibitors Can Falsely Rule Out Sarcoidosis
Matthew D. Krasowski MD, PhD
Department of Pathology
Response: Serum angiotensin converting enzyme (ACE) activity is commonly measured for
the diagnosis and management of sarcoidosis. It was well known several decades ago that
serum ACE activity is reduced in patients taking ACE inhibitors (e.g., captopril, enalapril,
lisinopril, etc.). However, providers ordering ACE levels may be unaware of this interaction
and not realize that ACE inhibitor therapy can dramatically lower serum ACE activity (and
thus resulting in a misleadingly low ACE level).
• The main goal of the study was to determine how often serum ACE levels were performed in
patients prescribed ACE inhibitors. Using electronic medical record review at an academic
medical center, it was determined that 8.4% of serum ACE levels were ordered on patients
currently on ACE inhibitors. The group of patients on ACE inhibitors had significantly lower
serum ACE activity than the other patients. Analysis of samples at a national reference
laboratory arrived at a similar estimate. This analysis included detection of lisinopril in a
subset of serum samples with very low ACE activity. At the academic medical center, the use
of targeted warning prompts and alerts greatly reduced the frequency of ordering serum ACE
activity in patients on ACE inhibitors.

• Response: Clinicians and patients should be aware that the serum ACE assay measures
enzyme activity and and is therefore lowered by ACE inhibitor therapy. Consequently, the
serum ACE activity assay is unreliable in patients currently prescribed ACE inhibitors such as
captopril or lisinopril. Failure to recognize this interaction can result in misleading test results
and potentially the erroneous exclusion of sarcoidosis as a possible diagnosis for a patient.

this study?
• Response: Future research can focus on interventions within electronic medical records to
help prevent situations such as ordering serum ACE assays in patients on ACE inhibitors.
• Citation:
• Krasowski MD, Savage J, Ehlers A, et al.
• Ordering of the serum angiotensin-converting enzyme (ace) test in patients receiving ace
inhibitor therapy: an avoidable but common error
• CHEST Published online July 30, 2015.
doi:10.1378/chest.15-1061.

NSAIDS Work For Menses Pain But Carry Risk of Side Effects
Jane Marjoribanks
Obstetrics and Gynaecology
University of Auckland, National Women’s Hospital,
Auckland, New Zealand,
• MedicalResearch: What is the background for this study?
• Response: This study is a systematic review of all randomised evidence published up to
January 2015 on the effectiveness and safety of non-steroidal inflamatory drugs (NSAIDs)
used to treat primary dysmenorrhoea (period pain). It includes 80 randomised controlled
trials (total 5820 participants), which compare 20 different NSAIDs versus placebo, other
NSAIDs or paracetamol.
• The review was prepared by researchers from the Cochrane Collaboration, which is a global
independent network of contributors (37,000 from more than 130 countries) who gather and
summarize the best evidence from research to produce credible, accessible health
information that is free from commercial sponsorship and other conflicts of interest.

Jane Marjoribanks
• MedicalResearch: What are the main findings?
• Response: The main findings are that NSAIDs appear to be very effective in relieving period
pain. The evidence suggests that if 18% of women taking placebo achieve moderate or
excellent pain relief, between 45% and 53% taking NSAIDs will do so. NSAIDs appear to work
better than paracetamol, but it is unclear whether any one NSAID is safer or more effective
than others.
• NSAIDs commonly cause adverse effects (side effects), including indigestion, headaches and
drowsiness. The evidence suggests that if 10% of women taking placebo experience side
effects, between 11% and 14% of women taking NSAIDs will do so.
• Based on two studies that made head-to-head comparisons, there was no evidence that
newer types of NSAID (known as COX-2-specific inhibitors) are more effective for the
treatment of dysmenorrhoea than traditional NSAIDs (known as non-selective inhibitors), nor
that there is a difference between them with regard to adverse effects.

Jane Marjoribanks
• Response: NSAIDs appear to be a very effective treatment for dysmenorrhoea, but women
using them need to be aware of the substantial risk of adverse effects. It is unclear which (if
any) individual NSAID is the safest and most effective for the treatment of dysmenorrhoea.
We rated the quality of the evidence as low for most comparisons, mainly due to poor
reporting of study methods.

Jane Marjoribanks
this study?
• Response: We suggest that a comparison of combination therapies versus NSAIDs alone
would be a useful topic for a further systematic review.
• Citation:
• Marjoribanks J, Ayeleke R, Farquhar C, Proctor M. Nonsteroidal anti-inflammatory drugs for
dysmenorrhoea. Cochrane Database of Systematic Reviews 2015, Issue 7. Art. No.:
CD001751. DOI: 10.1002/14651858.CD001751.pub3

Simple Internet Program Increased Handwashing and Reduced Infections
Paul Little MBBS, BA, MD, DLSHTM, MRCP, FRCGP, FMedSci
Professor of Primary Care Research
University of Southampton
Prof. Little: Hand washing has been recommended to help prevent respiratory infections (coughs,
colds flu, sore throats) – this can be important in normal winters but might be especially
important in pandemic flu years. However, there has been little evidence from randomised trials
to date to show that handwashing works.

Simple Internet Program Increased Handwashing and Reduced Infections
Paul Little MBBS, BA, MD, DLSHTM, MRCP, FRCGP, FMedSci
Professor of Primary Care Research
University of Southampton
• Prof. Little: A simple internet based intervention to support increasing handwashing
behaviour reduced the numbers of infections caught and the number of infections given to
family members, reduced diarrhoea and vomiting, reduced attendance at physicians offices
and reduced antibiotic use.
this study?
• Prof. Little: That anyone who has trouble with respiratory infections or wants to cut down
the number of infections should be advised to wash their hands, aiming for 10 times per day.
People might find it helpful to access the website from the study that supported
handwashing – which has been made available. In a pandemic widespread handwashing
should be recommended.
• Citation:
• An internet-delivered handwashing intervention to modify
influenza-like illness and respiratory infection transmission
(PRIMIT): a primary care randomised trial

Treatment of Patent Ductus Arteriosus Linked to Neurodevelopmental Risks in Infants
Prof. Abdel-Latif Mohamed
Discipline of Neonatology,
Medical School, College of Medicine, Biology & Environment
Australian National University
Acton, Canberra, ACT, Australia
• Prof. Mohamed: Despite decades of research and debate amongst neonatologists, consensus
regarding optimal management of Patent Ductus Arteriosus (PDA) in the premature infant is
yet to be established. The vast majority of premature infants are treated with oral or
intravenous medication and surgical ligation is usually reserved to severely ill infants.
• Our study demonstrated that treatment for Patent Ductus Arteriosus , particularly of a
surgical nature, maybe associated with a greater risk of adverse neurodevelopmental
outcome at 2-3 years of age. This was particularly so among infants born below 25 weeks
gestation. This result may support permissive tolerance of PDAs. However, reasons for this
association remain to be elucidated through carefully designed prospective trials.

Treatment of Patent Ductus Arteriosus Linked to Neurodevelopmental Risks in Infants
Prof. Abdel-Latif Mohamed
Discipline of Neonatology,
Medical School, College of Medicine, Biology & Environment
Australian National University
Acton, Canberra, ACT, Australia
• Medical Research: What should clinicians and parents take away from your report?
• Prof. Mohamed: Overall, our results may support permissive tolerance of PDAs. Treatment of
Patent Ductus Arteriosus should be individualised and decided on case by case basis.
Treatment, particularly of a surgical nature, should not be rushed unless absolutely indicated.
• Infants who undergo treatment for Patent Ductus Arteriosus should be monitored for early
detection of neurodevelopmental abnormalities.

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