Medical research slideshare_june_18_2015

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
June 18 2015
For Informational Purposes Only: Not for Specific Medical Advice.

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Weekend Discharge Not Associated With Higher Rate of Readmission
MedicalResearch.com Interview with:
Jordan M. Cloyd, MD
Department of Surgery
Stanford University
Stanford, California
• Medical Research: What is the background for this study? What are the main findings?
Dr. Cloyd: The motivation for the study was that, anecdotally, we had noticed that several of
our patients who had been discharged on a weekend required readmission for potentially
preventable reasons. We wanted to investigate whether the data supported the idea that
weekend discharge was associated with a higher risk of hospital readmission.
• Medical Research: What should clinicians and patients take away from your report?
• Dr. Cloyd: Among patients undergoing abdominal aortic aneurysm repair, colorectal surgery,
pancreatectomy and total hip replacement, discharge on a weekend was not associated with
a higher rate of hospital readmission. We also found that a significant proportion of patients
who required readmission were readmitted to a different hospital than the discharging one.
Read the rest of the interviews on MedicalResearch.com
Content NOT an endorsement of efficacy and NOT intended as specific medical advice.

Weekend Discharge Not Associated With Higher Rate of Readmission
Jordan M. Cloyd, MD
Department of Surgery
Stanford University
Stanford, California
• Medical Research: What recommendations do you have for future research as a result of
this study?
• Dr. Cloyd: Additional research into hospital level factors that reduce the need for readmission
will be critical. Furthermore, based on an unexpected finding of our study, we are currently
investigating which factors are associated with readmission to a hospital other than the
initial, discharging hospital.
• Citation:
• Cloyd JM, Chen J, Ma Y, Rhoads KF. Association Between Weekend Discharge and Hospital
Readmission Rates Following Major Surgery. JAMA Surg. Published online June 03, 2015.
doi:10.1001/jamasurg.2015.1087.

Spring Babies Have Highest Lifetime Risk of Cardiovascular Disease
MedicalResearch.com Interview with: Nicholas Tatonetti, PhD
Department of Biomedical Informatics
Department of Systems Biology, Department of Medicine
Columbia University
New York, NY
Medical Research: What is the background for this study? What are the main findings?
Dr. Tatonetti: For decades, researchers have studied the link between disease incidence and the
seasons. We’ve known, for example, that those born when the dust mite population is highest
(summer) will have an increased chance of developing asthma. Traditionally, diseases have been
studied one at a time to identify these seasonal trends. Because of the rapid adoption of
electronic health records, it is now possible to study thousands of diseases, simultaneously. That
is what we did in this study. We evaluated over 1,600 diseases and discovered 55 that showed
this seasonal trend. Many of these had been studied previously, but several are new discoveries
— most prominently, we found that the lifetime risk of developing cardiovascular disease is
highest for those born in the spring.

Columbia University
New York, NY
• Dr. Tatonetti: This is from the press release:
• “It’s important not to get overly nervous about these results because even though we found
significant associations the overall disease risk is not that great,” notes Dr. Tatonetti. “The risk
related to birth month is relatively minor when compared to more influential variables like
diet and exercise.”

Columbia University
New York, NY
this study?
• Dr. Tatonetti: Probably the most exciting aspect of this study is that it opens up new avenues
of research into the environmental causes of disease. In particular, we are interested in
identify what the exposures are that drive the association we found between birth month
and cardiovascular disease. If we can identify these environmental mechanisms we may be
able to mitigate risk in the future or design new therapies.
• Citation:
• Birth Month Affects Lifetime Disease Risk: A Phenome-Wide Method
• Mary Regina Boland , Zachary Shahn , David Madigan , George Hripcsak , Nicholas P.
Tatonetti
• Journal of the American Medical Informatics Association
• DOI: http://dx.doi.org/10.1093/jamia/ocv046
First published online: 3 June 2015

Preoperative Pulmonary Function Testing Decreased After ACP Guidelines
Louise Sun, MD SM FRCPC
Assistant Professor Department of Anesthesiology,
University of Ottawa Staff | Division of Cardiac Anesthesiology
University of Ottawa Heart Institute
• Dr. Sun: Preoperative testing provides important information for perioperative
planning and decision-making. However, given the rapid increase in health
care costs, there has been growing emphasis on the more rational use of
resources and thus the need to better understand the utilization patterns
of specific tests. Preoperative pulmonary function tests (PFTs) are
important in helping perioperative physicians identify patients at risk
for postoperative pulmonary complications, but few appropriate use
guidelines exist for this test. We conducted a population-based study
using linked administrative databases in Ontario, Canada to describe
temporal trends in preoperative pulmonary function tests
and assess whether the recent 2006 American College of Physicians (ACP) guidelines on risk
assessment and prevention of postoperative pulmonary complications for non-cardiothoracic
surgery influenced these trends.

• We examined 511,625 individuals undergoing non-cardiothoracic surgery, amongst whom
3.6% underwent preoperative pulmonary function tests while 3.3% had non-operative PFTs.
• Preoperative pulmonary function tests rates decreased over the study period and following
the 2006 ACP guidelines while non-operative rates remained stable. By 2013,
preoperative pulmonary function tests were performed in fewer than 8% of Ontario patients
with risk factors for pulmonary complications, while preoperative testing
rates among individuals without known respiratory disease had approached
rates seen in the non-operative setting. The decreasing preoperative pulmonary function
tests rates contrast starkly against concurrent increases in rates of other
perioperative interventions such as preoperative anesthesia consultations
and stress testing.

• Dr. Sun: Given the low overall rate of preoperative pulmonary function tests, large-scale
efforts to reduce this testing are likely unnecessary. Also, the decreasing
preoperative pulmonary function tests rates were unlikely to have been solely due to the
2006 ACP guidelines and may in part be explained by increased use of bedside
spirometry, which is not captured by provincial administrative databases.
While less costly and possibly more accessible at some hospitals, these
alternative tests have limitations such as measurement error.

this study?
• Dr. Sun: We believe that our findings point to the need for more research to
identify which select group of surgical patients most benefit from
preoperative pulmonary function tests.
• Citation:
• Smetana GW. The Conundrum of Unnecessary Preoperative Testing. JAMA Intern Med.
Published online June 08, 2015. doi:10.1001/jamainternmed.2015.2106.
• Louise Sun, MD SM FRCPC, Assistant Professor Department of Anesthesiology,, University of
Ottawa Staff | Division of Cardiac Anesthesiology, & University of Ottawa Heart Institute
(2015). Preoperative Pulmonary Function Testing Decreased After ACP Guidelines

Defects in DNA Repair Could Underlie Cognitive Decline
Dr. Li-Huei Tsai Ph.D.
Professor and Director – Picower Institute For Learning and Memory
Department of Brain and Cognitive Sciences
Massachusetts Institute of Technology
Dr. Tsai: For a while now, we have been interested in observations made by many labs,
including our own, that the accumulation of DNA lesions is a hallmark of the aging brain, and
that mutations in DNA repair factors manifest in congenital and neurodegenerative disorders.
However, the precise contribution of unrepaired DNA lesions to the development of
neurological disorders remains poorly understood. A major confounding factor is that the
sources that generate DNA lesions in the brain are not well characterized, and it is not known
whether damage accumulates non-specifically throughout the genome, or whether there are
certain regions that are more prone to accumulate DNA damage.
• In this regard, our study reports three major findings:
• (1) Physiological neuronal activity itself results in the formation of DNA breaks;
• (2) Neuronal activity-induced DNA breaks form at highly specific locations, including within
the promoters of a subset of immediate early genes, including Fos, Npas4, and Egr1. These
genes are also rapidly expressed in response to neuronal stimulation, and play crucial roles in
experience-driven changes to synapses, and learning and memory;
• (3) Neuronal activity-induced breaks are generated by a topoisomerase, Topo IIβ, and Topo
IIβ-generated DNA breaks facilitate the rapid expression of these immediate early genes
following neuronal stimulation.

• Dr. Tsai: First, that DNA breaks are an important component of normal physiological activity
in neurons.
• Second, because activity-induced DNA breaks form at the promoters of genes that mediate
experience-driven changes in the brain, any change in a neuron’s ability to repair such lesions
is likely to have important physiological and pathological implications. Our observations
underscore the importance of mechanisms that ensure that neuronal activity-induced DNA
breaks are repaired accurately. Defects that compromise these repair mechanisms could
underlie cognitive decline with age and in neurodegenerative disorders.

this study?
• Dr. Tsai: An exciting avenue of future research would be to identify the mechanisms that
ensure that neuronal activity-induced DNA breaks are accurately repaired. This information
could then be used to address the important question of whether the formation and repair
of activity-induced DNA breaks underlie cognitive decline with age or during the
development of neurodegenerative disorders. Identification of mechanisms that affect these
processes are also likely to provide new targets for therapeutic intervention.
• Citation:
• Li-Huei Tsai et al. Activity-Induced DNA Breaks Govern the Expression of Neuronal Early-
Response Genes. Cell, June 2015 DOI: 10.1016/j.cell.2015.05.032

Some Prostate Cancer Patient Decision Aids Need Updating
Prajakta Adsul, MBBS, MPH, PhD; Ricardo Wray, PhD, and Sameer Siddiqui, MD
Center for Cancer Prevention, Research and Outreach
Saint Louis University
• MedicalResearch: What is the background for this study? What are the main findings?
• Response: Patient decision aids are interventions designed to help patients engage in shared
decision making with their providers when multiple choices with more or less equivalent
efficacy are available for a particular medical decision. Several patient decision aids exists for
numerous medical conditions and previous research has demonstrated them to be effective
in improving the patient’s knowledge and understanding of treatment options and their
relative efficacy and side-effects and resulting in a higher proportion of decision that are
consistent with patient’s values and personal preferences.

• In the context of prostate cancer treatment, the practice of shared decision making is vital as
highlighted by recent calls from the American Urological Association and the American
Cancer Society. To aid with this process, several patient decision aids exist. However, the
content presented, the format and presentation styles of decision aids can be variable and
can have an influence on the choice made by the patients. The purpose of this study was to
assess the characteristics of the patient decision aids designed for men facing prostate cancer
treatment. We used the widely accepted International Patient Decision Aids Standards
(IPDAS) for the assessment, supplemented with implementation criteria to strategize
successful future improvement and promotion of decision aids in routine urological practice.
• The main findings of the review were that none of the decision aids reviewed met all
standards. The aids had variable content, format and presentation of prostate cancer
treatment information. Several decision aids were outdated and critical issues such as the risk
of overtreatment and active surveillance as a treatment option for prostate cancer were not
always covered in decision aids.

• MedicalResearch: What should clinicians and patients take away from your report?
• Response: Clinicians, especially urologists, should continue using and recommending their
patients to use decision aids when engaging in shared decision making for treatment of
prostate cancer. When doing so, they need to choose decision aids with characteristics that
are best suited to their patient populations and their personal practice styles. The review
highlights these characteristics of currently available decision aids.
• For newly diagnosed prostate cancer patients, it is important to engage in shared decision
making using decision aids and this review can help point out currently available decision aids
and their characteristics.

•
• MedicalResearch: What recommendations do you have for future research as a result of
this study?
• Response: Decision aid developers need to address the IPDAS criteria more stringently and
update decision aids to reflect the current medical evidence or lack thereof. Pre-testing
decision aids and feasibility of use with both patients and the clinicians can also improve
decision aid efficacy and further our understanding of how to promote widespread adoption
of these aids in routine practice.
• Citation:
• Systematic Review of Decision Aids for Newly Diagnosed Prostate Cancer Patients Making
Treatment Decisions
• Prajakta Adsul, MBBS, MPH, PhD Ricardo Wray, PhD Kyle Spradling, BA Oussama Darwish,
MD,Nancy Weaver, PhD, MS,Sameer Siddiqui, MD
• Accepted: May 28, 2015; Published Online: June 05, 2015
• Journal of Urology Publication stage: In Press Accepted Manuscript

Women and Men Have Similar Colon Cancer Recurrence-Free Death Risk
Prof. Catherine Quantin
Clinical Epidemiology/Clinical Trials Unit, Dijon, France and
Dr Michal Abrahamowicz Ph.D
Department of Epidemiology, Biostatistics and Occupational Health
McGill University, Montreal, Canada
• Medical Research: What is the background for this study?
Response: One difficulty, common to prognostic studies of cancer, concerns the need to
separate the effects of prognostic factors on different clinical endpoints, such as disease
recurrence vs recurrence-free death. Some published prognostic studies used a Cox
regression model that included recurrence as a time-dependent covariate, to assess the
impact of recurrence on mortality, and to adjust for recurrence when estimating the effects
of other prognostic factors on mortality. However, the Cox model is limited to the assessment
of the effects of covariates on a single endpoint, such as death. This limitation is overcome by
multi-state models, that make it possible to model alternative pathways of disease
progression and to assess the impact of prognostic factors on both recurrence-free death vs
death after recurrence, and recurrence followed by death.
• Another difficulty, is that the cause of death is not available or not accurately coded. Yet,
some patients are likely to die of causes not related to the disease of primary interest,
especially in cancers with longer survival and in those that affect older subjects. The effects
of prognostic factors estimated with Cox model, or classic multi-state models, are not able to
discriminate between their effects on the mortality due to cancer of primary interest vs
natural mortality. However, age is a very strong predictor of overall mortality, but is not
systematically associated with higher cancer-specific mortality.
• To deal with this difficulty, many prognostic studies use relative survival methods.
The general idea is to use the mortality tables for the relevant general population to estimate
survival corrected for the expected natural mortality, due to other causes of death.

Women and Men Have Similar Colon Cancer Recurrence-Free Death Risk
Prof. Catherine Quantin
Clinical Epidemiology/Clinical Trials Unit, Dijon, France and
Dr Michal Abrahamowicz Ph.D
Department of Epidemiology, Biostatistics and Occupational Health
McGill University, Montreal, Canada
• Medical Research: What are the main findings?
Response: Relative survival multistate model provides more information on prognosis and expected
outcomes of patients with different characteristics than usual models (Cox or non multi-state
relative survival models).
• Response:
• Women with colorectal cancer have a similar risk of recurrence-free death to men.
• Almost all deaths among patients who had recurrence were due to colorectal cancer.
• Many deaths among patients without recurrence may be due to natural causes, not related to
colorectal cancer.
• Medical Research: What recommendations do you have for future research as a result of this
study?
• Response: Future prognostic registry-based studies of different cancers should consider the relative
survival multi-state Markov analyses.
• Citation:
• Cancer Epidemiol. 2015 Jun;39(3):447-55. doi: 10.1016/j.canep.2015.03.005. Epub 2015 Mar 25.
• Multi-state relative survival modelling of colorectal cancer progression and mortality.
• Gilard-Pioc S1, Abrahamowicz M2, Mahboubi A1, Bouvier AM3, Dejardin O4, Huszti E5, Binquet C6,
Quantin C7.

Both Gastric Banding and Bypass Surgery Reduce Medical Costs
Kristina H. Lewis, MD, MPH, SM
Kaiser Permanente Georgia, Center for Clinical and Outcomes Research, Atlanta
Department of Population Medicine
Harvard Medical School/Harvard Pilgrim Health Care Institute, Boston, Massachusetts
Dr. Lewis: The prevalence of severe obesity (BMI ≥40 kg/m2) in the U.S. is rising. This is
concerning, because patients with severe obesity tend to be sicker and have higher
healthcare costs. Bariatric surgery produces substantial weight loss and remission of a
number of obesity-related comorbidities, but there have been very few studies directly
comparing current procedure types. This leaves patients, providers and insurers with little
information to help them decide about the pros and cons of different surgeries.
• We wanted to compare outcomes after two of the most common bariatric surgeries in the US
– laparoscopic adjustable gastric banding (band) and laparoscopic roux-en-y gastric bypass
(bypass). To do this, we examined commercial claims data from almost 10,000 U.S. band and
bypass patients who were very similar with respect to age, gender, and medical conditions.
We looked at what happened to these patients from one year before their surgeries through
3 years after surgery. We compared changes in medical costs and use of healthcare services
before and after surgery.

• Medical Research: What are the main findings?
• Dr. Lewis: When performed laparoscopically, both gastric bypass and adjustable gastric
banding appear to result in lower total medical costs after surgery. Bypass patients see a
greater immediate drop in prescription drug costs than band patients – this is not surprising
given that we know that this surgery is more likely to induce weight loss and diabetes
remission. Unfortunately, bypass patients also have an initial increase in emergency
department visits after surgery that is not present for banding patients.
• When we compared total annual medical costs between band and bypass, we found no
difference between procedures in the first 2 years after surgery. But, by year 3, bypass
patients’ total annual medical costs are about 16% lower than those for band patients.

• Dr. Lewis: Patients and clinicians considering one of these procedures should see these
findings as good news. On balance, it looks like, for a group of very sick patients whose
annual medical costs are trending upwards before surgery, these procedures result in overall
lower levels of healthcare use after they are performed. Deciding between the two
procedures, or opting for even newer procedure types, such as sleeve gastrectomy, would
require a conversation between patients and their providers about their specific medical
needs and their personal health goals.

this study?
• Dr. Lewis: Studies are needed that examine the newer “vertical sleeve gastrectomy”
procedure in a similar fashion. That procedure has become very popular in the U.S. recently
but very little is known about longer-term outcomes after it. Also – formal cost effectiveness
studies that weigh the costs of the procedures against any potential benefits to patients
would be important to conduct.
• Citation:
• Lewis KH, Zhang F, Arterburn DE, Ross-Degnan D, Gillman MW, Wharam J. Comparing Medical
Costs and Use After Laparoscopic Adjustable Gastric Banding and Roux-en-Y Gastric Bypass.
JAMA Surg. Published online June 03, 2015. doi:10.1001/jamasurg.2015.1081.
• Kristina H. Lewis, MD, MPH, SM, Kaiser Permanente Georgia, Center for Clinical and
Outcomes Research, Atlanta, Department of Population Medicine, Harvard Medical
School/Harvard Pilgrim Health Care Institute, Boston, Massachusetts (2015). Both Gastric
Banding and Bypass Surgery Reduce Medical Costs

Diet and Supervised Exercise May Be Helpful In Preventing Excessive Pregnancy Weight Gain
Theresa A Lawrie
World Health Organization
Department of Reproductive Health and Research
Geneva, Switzerland
• MedicalResearch: What is the background for this study?
• Response: Excessive weight gain in pregnancy is associated with various undesirable
outcomes in pregnancy. The aim of the review was to assess data from all relevant clinical
trials in the field, to determine whether diet and/or exercise interventions during pregnancy
were effective in reducing the chance of excessive weight gain in pregnancy. We also wanted
to know whether these interventions could reduce the chance of having large babies
(macrosomia), as this is associated with difficult labor, c/section, postpartum hemorrhage,
birth injuries and other complications.

Theresa A Lawrie
Geneva, Switzerland
• MedicalResearch: What are the main findings?
Response: Altogether 49 trials contributed data to the review. Approximately half the trials
recruited women of any pre-pregnancy weight, the other half recruited women who were
overweight or obese at the start of pregnancy. Most of the trials were conducted in high
income countries. Interventions varied, some involved individual counseling, others group
sessions, some were counseling interventions only, other programs were actively supervised
by fitness trainers. Health outcomes for women receiving the intervention programs in
addition to routine antenatal care (the intervention group) were compared with those of
women receiving the routine antenatal care only (the control group).
• We found that diet or exercise or combined interventions led to an average 20% reduction in
the number of women gaining excessive weight in pregnancy. This reduction was fairly
consistent across the different types of interventions, although the largest effect was
observed for combined diet and supervised exercise interventions. Overall findings suggested
a small reduction in caesarean section (of about 5%) and in large babies (of about
7%). However, a bigger reduction in large babies (in the region of a 19% reduction) was
noted for exercise-only interventions, which were more likely to be supervised interventions.

Theresa A Lawrie
Geneva, Switzerland
• Other findings: We also found no difference in the risk of preterm birth between groups.
Fewer women in the intervention group were assessed as having high blood pressure during
pregnancy (although we assessed this as low quality evidence). Low quality evidence also
suggested that women in the intervention group were likely to retain less weight at six
months postpartum compared with the control group. Interestingly, data from two studies
suggested that women receiving diet and exercise interventions were less likely to have
babies with breathing difficulties at birth. These findings will hopefully be corroborated by
other studies. A limitation of the review, is that we did not include gestational diabetes as an
outcome as this is partly covered in a separate Cochrane review. Our exploratory analyses,
however, suggested that there may be a reduction in gestational diabetes for certain types of
interventions, and we hope to include these data in future review updates.
• In general, we did not find differences in outcomes for women according to pre-pregnancy
weight or BMI.

Theresa A Lawrie
Geneva, Switzerland
• Response: Pregnancy is a good time to establish or reinforce healthy lifestyle choices, which
have measurable benefits for mother and child. Regular, moderate-intensity exercise is an
important component of this healthy lifestyle. Refer to the RCOG guidelines on exercise in
pregnancy for guidance.
• For clinicians: Consider how your service is geared towards consistently supporting pregnant
women to make healthy lifestyle choices. Diet and/or exercise interventions need not be
hugely resource intensive; the review shows that counseling interventions alongside routine
care can lead to improvements in health outcomes.
• For clinicians: Consider how your service is geared towards consistently supporting pregnant
women to make healthy lifestyle choices. Diet and/or exercise interventions need not be
hugely resource intensive; the review shows that counseling interventions alongside routine
care can lead to improvements in health outcomes.
• For women: Talk to your doctor or midwife about your ideal weight gain in pregnancy and
find out what guidance, support and antenatal activities are available in your area to help you
monitor and attain it.

Theresa A Lawrie
Geneva, Switzerland
• What recommendations do you have for future research as a result of this study?
• Response: There is currently a lot of research interest in this area – we identified 40
registered ongoing trials which have not yet published results. Incorporating data from these
trials, once completed, into future versions of this review will hopefully shed more light on
the relative benefits or risks of the different types of interventions. Longer term follow-up
data from trials are needed to assess postpartum and childhood outcomes relevant to these
interventions. In addition, economic evaluation of different types of interventions is needed,
as is more research on diet and exercise interventions in low-income countries.
• Citation:
• Muktabhant B, Lawrie TA, Lumbiganon P, Laopaiboon M. Diet or exercise, or both, for
preventing excessive weight gain in pregnancy. Cochrane Database of Systematic Reviews
2015, Issue 6. Art. No.: CD007145. DOI: 10.1002/14651858.CD007145.pub2

Despite Guidelines, Many Physicians Still Ordering Routine PreoperativeTests
Joseph A. Ladapo, MD, PhD
Assistant Professor of Medicine
Section on Value and Effectiveness
Department of Population Health
NYU School of Medicine
Dr. Ladapo: Routine tests before elective surgery are largely considered to be of low value, and
they may also increase costs. In an attempt to discourage their use, two professional societies
released guidance on use of routine preoperative testing in 2002. We sought to examine the
long-term national effect of these guidelines from the American College of Cardiology/American
Heart Association and the American Society of Anesthesiologists on physicians’ use of routine
preoperative testing. While we found that overall rates of routine testing declined across several
categories over the 14-year study period, these changes were not significant after accounting for
overall changes in physicians’ ordering practices. Our findings suggest that professional guidance
aimed at improving quality and reducing waste has had little effect on physician or hospital
practice.

• Dr. Ladapo: While it’s important to ensure patients can safely undergo surgical procedures,
many of these procedures are low-risk, and the tests rarely improve patient management.
Clinicians are responsible for reducing these low-value tests, and this harkens all the way
back to residency training.

this study?
• Dr. Ladapo: While the evidence suggests that physicians are not readily adopting the
published guidelines, we don’t know why. Research that informs how to facilitate greater
adherence to evidence-based guidelines should significantly improve quality of care.
• Citation:
• Sigmund AE, Stevens ER, Blitz JD, Ladapo JA. Use of Preoperative Testing and Physicians’
Response to Professional Society Guidance . JAMA Intern Med. Published online June 08,
2015. doi:10.1001/jamainternmed.2015.2081.

Dual Hormone Artificial Pancreas Reduces Nocturnal Hypoglycemia in Type 1 Diabetes
Dr. Ahmad Haidar Ph.D
Division of Experimental Medicine, Department of Medicine
McGill University, Montreal, QC, Canada
Dr. Haidar: This is the first head-to-head-to-head comparison in outpatient setting of dual-
hormone artificial pancreas, single-hormone artificial pancreas, and conventional pump
therapy in children and adolescents with type 1 diabetes.
• The main finding is that the dual-hormone artificial pancreas seems to outperform the other
two systems in reducing nocturnal hypoglycemia in camp settings when the patients are very
physically active during the day.
• Dr. Haidar: Glucagon has the potential to reduce nocturnal hypoglycemia if added to the
artificial pancreas. However, this needs to be confirmed in larger and longer studies as the
single-hormone artificial pancreas might be sufficient in home settings (this study was
conducted at a camp, which is an environment different that home).

Dual Hormone Artificial Pancreas Reduces Nocturnal Hypoglycemia in Type 1 Diabetes
Dr. Ahmad Haidar Ph.D
Division of Experimental Medicine, Department of Medicine
McGill University, Montreal, QC, Canada
this study?
• Dr. Haidar: We need to conduct longer and larger day-and-night outpatient studies (our
study was for only 3 nights per intervention).
• Citation:
• Outpatient overnight glucose control with dual-hormone artificial pancreas, single-hormone
artificial pancreas, or conventional insulin pump therapy in children and adolescents with
type 1 diabetes: an open-label, randomised controlled trial
• DOI: http://dx.doi.org/10.1016/S2213-8587(15)00141-2
• Haidar, Ahmad et al.
• The Lancet Diabetes & Endocrinology Published Online: 08 June 2015

Antibiotic Impregnated Sponges Reduced Chest Wound Infections After Heart Surgery
Mariusz Kowalewski, MD
Department of Cardiac Surgery, Dr Antoni Jurasz Memorial University Hospital Bydgoszcz,
Systematic Investigation and Research on Interventions and Outcomes
Medicine Research Network, Poland
Dr. Kowalewski: Sternal wound infections occurring after heart surgery performed via median
sternotomy, and in particular, after coronary artery bypass grafting (CABG), although rare, still
pose serious postoperative complications that increase the length of hospital stay and healthcare
costs. One of many ways to prevent them from happening, except from optimal glucose control,
tight-fixed closure of the sternum at the end of surgery and perioperative iv. antibiotics, is to
insert a gentamicin collagen sponge between two sternal edges, just before wiring them together.
High local concentrations of gentamicin were shown to eliminate any microbial growth in the
area, in the same time, not affecting the kidneys, as would be the case with systemic
administration. Gentamicin sponges are widely used in orthopadic, gastro-intestinal and vascular
surgery and were shown to reduce postoperative infection rates. Although extensively tested in
the field of heart surgery, findings of one recent multicenter study have questioned their true
benefit. We aimed to perform a comprehensive meta-analysis of studies assessing the efficacy of
implantable gentamicin-collagen sponges in sternal wound infection prevention.

After screening multiple databases, a total of 14 studies (N = 22,135 patients, among them 4
randomized controlled trials [N = 4,672 pts]) were included in the analysis. Implantable
gentamicin-collagen sponges significantly reduced the risk of sternal wound infection by
approximately 40% when compared with control (risk ratio [RR], 0.61; 95% confidence interval
[CI], 0.39-0.98; P = .04 for randomized controlled trials and RR, 0.61; 95% CI, 0.42-0.89; P = .01 for
observational studies). A similar, significant benefit was demonstrated for deep sternal wound
infection (RR, 0.60; 95% CI, 0.42-0.88; P = .008) and superficial sternal wound infection (RR, 0.60;
95% CI, 0.43-0.83; P = .002). The overall analysis revealed a reduced risk of mediastinitis (RR,
0.64; 95% CI, 0.45-0.91; P = .01). The risk of death was unchanged.

In addition, we investigated, by means of meta-regression, the correlation between sternal
wound infections and extent to which the bilateral internal thoracic artery (BITA) was
harvested. We found that the benefit provided by the gentamicin sponge was attenuated when
BITA was harvested; these results suggest that another potentially preventive measure must be
taken in such patients, as with severely reduced blood supply to the sternum (as is the case with
BITA), sponge itself might not be enough to prevent wound infection.

• Dr. Kowalewski: Current report is the largest to date database analyzed to assess the role of
gentamicin sponge in sternal wound prevention after heart surgery. While international
guidelines are not conclusive regarding topical antibiotic administration after heart surgery,
findings of the present report, suggest reduced infection rates in patients in whom,
gentamicin sponge was implanted. The evidence was strikingly consistent across randomized
and observational studies.

this study?
• Dr. Kowalewski: We would encourage cardiac surgeons to introduce the gentamicin sponge
to their institutional protocols, at least in patients at high risk of developing sternal wound
infections (BMI >30, type 2 DM, COPD, BITA). What remains to be ascertained is the best
combination of gentamicin sponge and iv. antibiotic. Also the results of 2×2 study comparing
pedicled vs skeletonized internal thoracic artery and gentamicin sponge vs control could shed
a new light to the topic.
• Citation:
• J Thorac Cardiovasc Surg. 2015 Jun;149(6):1631-1640.e6. doi: 10.1016/j.jtcvs.2015.01.034.
Epub 2015 Jan 23.
• Gentamicin-collagen sponge reduces the risk of sternal wound infections after heart surgery:
Meta-analysis.
• Kowalewski M1, Pawliszak W2, Zaborowska K3, Navarese EP4, Szwed KA5, Kowalkowska ME6,
Kowalewski J7, Borkowska A5, Anisimowicz L2.

Craniofacial Anomalies Provide More Evidence Pedophilia DevelopsPrenatally
Fiona Dyshniku, M.A.
Ph.D. Candidate, Clinical Psychology – Adult Clinical track
Department of Psychology
University of Windsor
• MedicalResearch: What is the background for this study?
• Response: This study was conducted in the context of previous research that has found other
evidence that pedophilia has biological roots that start before birth, such as shorter stature
and left-handedness. Both of these correlates have prenatal origins, meaning that their
development necessarily precedes the onset of more socially oriented correlates, such as
parenting styles, sexual abuse during childhood, etc. Moreover, these neurodevelopmental
correlates appear permanent and immune to later psychosocial influences. Much like
handedness and stature, minor physical anomalies (MPA) develop prenatally, are permanent,
and remain immune to psychosocial influences. There are additional benefits to examining
minor physical anomalies, including the fact that they tend to develop in a set sequence, are
actually formed from the same tissue that gives rise to the central nervous system, and have
been widely studied in other well-established neurodevelopmental disorders, such as
schizophrenia.

• MedicalResearch: What are the main findings?
• Response: We found that individuals simultaneously possessing more craniofacial anomalies
and fewer peripheral anomalies scored higher on several well-established pedophilia indices,
including phallometric testing, possession of child pornography, and number of child victims.
We also found that craniofacial anomalies on their own were more prevalent among
individuals classified as pedophiles through phallometric testing. Taken together, these
results suggest that there is further evidence for a biological cause of pedophilia. Moreover,
since craniofacial anomalies develop around week 5 of gestation, it would appear that
biological differences occur quite early on during foetal developmental.

• Response: The take way message for clinicians and patients is that there is now a good
amount of evidence to suggest that pedophilia or at least a propensity for it develops
prenatally.
• The differences are merely statistical, however. None of these correlates, be it shorter
stature, left handedness, or craniofacial anomalies, together or separately, should be
interpreted as tell-tale signs that someone is a pedophile. What a still-broadening field of
evidence is suggesting is that people do not choose to be sexually interested in children: They
discover that they are aroused by children. The best means of preventing child sexual abuse
may therefore be to assist such people to deal with their sexual interests. Instead, most
current policies drive these people underground and make it impossible for them to get sex-
drive-reducing medications or other treatments.

this study?
• Response: We hope other researchers, especially researchers from other fields, try not only
to replicate this finding, but also to identify other markers of developmental perturbations.
Each of these findings is a clue to when and how pedophilia develops. We need more clues
like these to narrow down the possibilities and, potentially, find a means of reducing the
probability of developing pedophilia in the first place.
• Citation:
• Minor Physical Anomalies as a Window into the Prenatal Origins of Pedophilia
• Fiona Dyshniku,Michelle E. Murray,Rachel L. Fazio,Amy D. Lykins,James M. Cantor
Archives of Sexual Behavior June 2015 Date: 10 Jun 2015

JAK1-2 inhibitor Baricitinib May Limit Progression of Diabetic Kidney Disease
Frank C. Brosius, MD
Professor, Internal Medicine and Physiology
Chief, Division of Nephrology
University of Michigan Ann Arbor, MI
Response: Our University of Michigan team had found that JAK-STAT gene expression was
increased in kidneys in patients with diabetic kidney disease and that these changes
correlated with progression of kidney disease. We subsequently substantiated these changes
in other studies and have found that by increasing expression of just one of these genes,
JAK2, in a single kidney cell type (podocytes) in mice that we can make their diabetic kidney
disease much worse.
• At around the same time, investigators at Eli Lilly and Co. had FDA approval to test a JAK1-2
inhibitor, baricitinib, in patients with rheumatoid arthritis. The Lilly scientists saw our human
results and thought about using baricitinib in patients with diabetic kidney disease. After
initial discussions with Dr. Kretzler and myself they concluded that there was good reason to
move ahead with this study and just 14 months after the initial meeting the phase 2 clinical
trial of baricitinib in the treatment of patients with diabetic kidney disease was initiated.

• Medical Research: What are the main findings? What should clinicians and patients take
away from your report?
• Response: This is an initial report and so there will need to be further testing of the
effectiveness and safety of baricitinib before it is a new treatment to prevent progression of
diabetic kidney disease. However, the results are very encouraging. The drug reduced
abnormal losses of protein in the urine, a marker of kidney injury, by about 40
percent. Furthermore, it reduced levels of compounds in the blood and urine that are
markers of inflammation in the kidneys and elsewhere in the body. This result strongly
suggests that baricitinib is tamping down the inflammation that is very important in causing
progressive kidney injury in diabetes. There were no major side effects except a modest and
expected reduction in the hemoglobin in patients on the highest dose of baricitinib.

this study?
• Response: Discussions are ongoing about next steps, but we are very hopeful that Lilly will
move ahead with further definitive trials of baricitinib in diabetic kidney disease. Positive
results in bigger and longer trials could set the stage for FDA approval of baricitinib in the
treatment of the millions of patients worldwide that have this disease. We hope that other
investigators look carefully at the JAK-STAT pathway to determine its role in other kidney
diseases and to potentially find other methods to inhibit this pathway to increase the
likelihood of finding new, safe and effective agents for all individuals with chronic kidney
disease.
• Citation: Presented at American Diabetes Association June 2015
• Baricitinib in Diabetic Kidney Disease: Results from a Phase 2, Multicenter, Randomized,
Double-Blind, Placebo-Controlled Study. Katherine R. Tuttle et al. American Diabetes
Association 75th Scientific Sessions (2015):

Children With Traumatic Brain Injuries Can Have Poor Sleep Quality
Kimberly Allen PhD, RN Assistant Professor
Center for Narcolepsy, Sleep and Health Research
Department Women Children and Family Health Science
Chicago, IL 60612
• Dr. Allen: Pediatric traumatic brain injuries (TBI) are a leading cause of morbidity and
mortality worldwide.Each year in the United States over 1Ž2 million children are admitted to
the hospital for traumatic brain injuries (TBIs). Depending on the severity of the injury and
how the individual child responds to the primary injury, a range of medical care may be
necessary from an overnight hospital admission for observation to admission in the intensive
care unit (ICU) and inpatient rehabilitation facility to re-teach and help to recover skills
children once knew. The short- and long-term consequences of traumatic brain injuries
include: motor and sensory impairments; cognitive, emotional, psychosocial impairments;
headaches, and sleep disruptions.

Chicago, IL 60612
Medical Research: What are the main findings?
Dr. Allen: The main finding from this pilot study with two groups with 15 children in each group:
one of children with traumatic brain injuries and one of typically, developing healthy children was
that children with traumatic brain injuries have significantly more daytime sleepiness and worse
sleep quality compared to the control group. Additionally, children with TBI also had
lower overall functional scores (e.g, school, social) compared to the controlled children. All of the
surveys were completed by the child’s parent.

Chicago, IL 60612
• Dr. Allen: This study has a small number of children and must be interrupted with caution.
We can recommend that clinicians continue asking questions about sleep to this population,
as we continue to explore who is most a risk and eventually determine if treatment is
necessary.

Chicago, IL 60612
this study?
• Dr. Allen: Future research needs to identify the trajectory to the sleep symptoms in
larger populations, and determine if severity and other medical factors effect sleep problems.
Additionally, more objectively and subjective data are need in conduction to determine the
whole picture of what changes are necessary for the child and family.
• Citation:
• SLEEP 2015 abstract: June 2015
• Allen K, et al “Sleep after pediatric traumatic brain injury: a survey study” SLEEP 2015;
Abstract 1050.

Your Smartphone May Help You Control Your Blood Pressure
MedicalResearch.com Interview with: Neetika Garg, MD
Fellow in Nephrology
Beth Israel Deaconess Medical Center
Division of Nephrology, Department of Medicine
Boston, MA 02215
• MedicalResearch: What is the background for this study? What are the main findings?
• Dr. Garg: One in every three Americans suffers from hypertension. Since high blood pressure
(BP) frequently does not cause any symptoms, self-blood pressure monitoring at home and
patient education are critical components of patient management. With more than 58% of
the US adults owning a smartphone, mobile-based health technologies (most commonly in
the form of applications or “apps”) can serve as useful adjuncts in diagnosis and management
of hypertension. At the same time, several smartphone-based applications are advertised as
having blood pressure measurement functionality, which have not been validated against a
gold standard. In this cross-sectional study, we analyzed the top 107 hypertension related
apps available on the most popular smartphone platforms (Google Android and Apple
iPhone) to analyze the functional characteristics and consumer interaction metrics of various
hypertension related apps.

Boston, MA 02215
Nearly three-quarters of the apps record and track blood pressure, heart rate, salt intake, caloric
intake and weight/body mass index. These app features can facilitate patient participation in
hypertension management, medication adherence and patient-physician communication.
However, it was concerning to find that 6.5% of the apps analyzed could transform the
smartphone into a cuffless BP measuring device. None of these had any documentations of
validation against a gold standard. Furthermore, number of downloads and favorable user ratings
were significantly higher for these apps compared to apps without blood pressure measurement
function. This highlights the need for greater oversight and regulation in medical device
development.

Boston, MA 02215
• Dr. Garg: Physicians should incorporate use of mobile-based health technology into
discussions at patient visits for various reasons:
• First, tracking their blood pressure can motivate patients to participate in their own care.
• Secondly, many apps allow patients to transmit data entered over a period of time directly
and conveniently to their physicians, thereby facilitating patient-physician communication
and health management.
• Thirdly, our study highlights the need for cautioning patients regarding use of very popular,
but as yet unvalidated use of smartphone-based apps as blood pressure measuring devices.
• Similarly, patients should use smartphone-based applications for tracking their blood
pressure as these data can help with diagnosis and management of chronic health conditions
such as hypertension. At the same time, patients should be aware of the presence of popular
yet potentially misleading resources. They should look for information/methodologies that
are approved/validated by reliable professional organizations. Also, if they are using any
smartphone-based technologies for blood pressure measurement, they should discuss the
same with their physicians.

Boston, MA 02215
this study?
• Dr. Garg: There is an unmet need in mobile-based health technologies that can effectively
and conveniently assist with management of chronic health conditions such as hypertension.
Future research should focus on development and validation of various blood pressure
measurement devices that can facilitate management of this chronic health condition.
• Many groups are in fact working on smartphone-based devices that can measure blood
pressure without use of the traditional cuff.
• Secondly and more importantly, it would be important to determine the actual impact of use
of these resources on hypertension management and related outcomes.
• Citation:
• J Am Soc Hypertens. 2015 Feb;9(2):130-6. doi: 10.1016/j.jash.2014.12.001. Epub 2014 Dec
11.
• A content analysis of smartphone-based applications for hypertension management.
• Kumar N1, Khunger M2, Gupta A3, Garg N4.

Wei Zheng, MD, PhD, Professor of Medicine
Anne Potter Wilson Chair in Medicine Director, Vanderbilt Epidemiology Center and
Danxia Yu, PhD Research Fellow
Vanderbilt Epidemiology Center Vanderbilt University School of Medicine
Nashville, TN, 37203
• Response: The Dietary Guidelines for Americans (DGA) provide the most authoritative advice
in the US about healthy eating. Higher adherence to the DGA, reflected by a higher Healthy
Eating Index (HEI) score, has been found to be associated with lower risk of developing or
dying from chronic diseases (e.g. diabetes, cardiovascular disease, and certain cancers) in
several US studies. However, these studies recruited mostly non-Hispanic white individuals
and middle to high income Americans. It has been reported that racial/ethnical background
and socioeconomic status may influence food choices and diet quality. However, no previous
study has adequately evaluated the association between adherence to the DGA and risk of
death due to diseases in racial/ethnical minorities and low-income Americans. Therefore, it is
uncertain whether the health benefits of adherence to the current DGA can be generalized to
these underserved populations.

• We analyzed diet and mortality data from the Southern Community Cohort Study (SCCS), a
large, prospective cohort study including approximately 85,000 American adults, 40-79 years
old, enrolled from 12 southeastern states between 2002 and 2009. Two-thirds of the SCCS
participants were African-American and more than half reported an annual household
income <$15,000.
• During a mean follow-up of 6.2 years, we identified 6,906 deaths in the SCCS, including 2,244
from cardiovascular disease, 1,794 from cancer, and 2,550 from other diseases. Using
multivariate analysis methods, we found that participants in the top 20% of the HEI score
(highest adherence to the DGA) had only about 80% of the risk of death due to any diseases
compared with those in the bottom 20% of the HEI score. This protective association was
found regardless of sex, race and income levels.

• Response: Similar to what was reported previously in studies conducted in mostly non-
Hispanic white individuals and middle to high income Americans, our study suggests that
having a healthy diet, as described in the DGA, may help to reduce disease mortality in
African Americans and low-income populations.

this study?
• Response: African Americans and low-income populations experience a disproportionally
high disease burden. Future studies are needed in these underserved populations to directly
evaluate cost-effective disease prevention strategies to reduce the morbidity and mortality of
diseases in these populations.
• Citation:
• Yu D, Sonderman J, Buchowski MS, McLaughlin JK, Shu X-O, Steinwandel M, et al. (2015)
Healthy Eating and Risks of Total and Cause-Specific Death among Low-Income Populations of
African-Americans and Other Adults in the Southeastern United States: A Prospective Cohort
Study. PLoS Med 12(5): e1001830. DOI: 10.1371/journal.pmed.1001830

Simple and readily available patient characteristics predicts death and dialysis dependence
in critically ill patients with severe acute kidney injury
MedicalResearch.com Interview with: Raghavan Murugan MD, MS, FRCP, FCCP
and John Kellum, MD
Department of Critical Care Medicine
University of Pittsburgh Pittsburgh, PA
• Response: In our prior studies, we found that nearly one-half of critically ill patients in the
intensive care unit who receive dialysis die by 2 months after acute illness and more than
one-third of surviving patients are dialysis dependent. We sought to examine whether simple
patient characteristics and inflammatory biomarkers predicted death and non-recovery of
kidney function after severe acute kidney injury.
• We found that a combination of four simple and readily available patient characteristics
including older age, lower mean arterial pressure, need for mechanical ventilation, and
higher serum bilirubin levels predicted death and dialysis dependence. Higher plasma
concentration of interleukin (IL)-8 in combination with the clinical characteristics also
increased risk prediction. To our knowledge, this study is the first large study to examine risk
prediction for outcomes after severe acute kidney injury using a panel of biomarkers in a
large cohort of critically ill patients receiving dialysis.

and John Kellum, MD
• Response: Our findings have important implications for patients and clinicians. First, the four
clinical characteristics along with plasma IL-8 could be used to estimate patient prognosis and
clinical decision-making by nephrologists and intensivists. For instance, the clinical variables
and IL-8 marker levels measured on the day when dialysis initiation is being considered by a
clinician could be useful to better inform patients and families about prognosis. Because
patients who are older, are mechanically ventilated, and have lower mean arterial pressure,
high bilirubin, and IL-8 levels, are likely to have worse outcomes, they may not wish to
undergo dialysis and clinicians may treat those patients accordingly. Second, early prediction
of renal recovery is likely to be helpful with regard to post-discharge planning by
nephrologists after critical illness and monitoring for subsequent progression to chronic
kidney disease and end-stage renal disease in patients who are unlikely to have complete
renal recovery.

and John Kellum, MD
this study?
• Response: First, although IL-8 is not yet used in clinical practice to treat patients with acute
kidney injury, the assay is easy to perform and could easily be developed into a clinical test.
Second, identification of a homogeneous group of patients using biomarker-guided risk
assessment allows for examination of new interventions or interventions that have previously
failed in clinical trials that included a heterogeneous population of patients with severe acute
kidney injury. Third, although we did a cross-validation within our study, our findings require
external validation before they can be applied to other patient populations with severe acute
kidney injury.
• Citation:
• Biomarker Enhanced Risk Prediction for Adverse Outcomes in Critically Ill Patients Receiving
RRT
• Francis Pike, Raghavan Murugan, Christopher Keener, Paul M. Palevsky, Anitha Vijayan, Mark
Unruh, Kevin Finkel, Xiaoyan Wen, John A. Kellum, and for the Biological Markers for
Recovery of Kidney (BioMaRK) Study Investigators
• CJASN CJN.09911014; published ahead of print June 5, 2015, doi:10.2215/CJN.09911014

Biologics in Rheumatic Disease Reduce Missed Workdays
Cécile Gaujoux-Viala, MD, PhD
Université Montpellier I Chef de Service de Rhumatologie
CHU de Nîmes Carémeau
France
• Response: Chronic inflammatory rheumatic diseases – such as rheumatoid arthritis (RA),
ankylosing spondylitis (AS), and psoriatic arthritis (PsA) – confer significant patient and
economic burdens : 1/5 of people with rheumatic conditions has been forced to change
career, 1/3 will have stopped working within two years of onset and 1/2 will be unable to
work within ten years.
• The addition of biological agents in treatment strategies for rheumatic diseases have
improved the possibility of controlling disease activity and slowing the progression of joint
damage. But these treatments are very expensive and their effect on work participation
remains unclear.

France
Medical Research: What are the main findings?
Response: Our study demonstrates a positive effect of biological disease-modifying antirheumatic
drugs ( DMARDs) on work participation with reduction of absenteeism (missed work days and
number of patients losing workt ime due to rheumatic disease) and improvement of
presenteeism. The positive effect on job loss was nearly significant. Thus the high costs of these
treatments could be at least partly offset by the savings they deliver in indirect costs.

France
this study?
• Response: There is a real lack of published results especially for ankylosing spondylitis and
psoriatic arthritis, for recent rheumatic diseases and for some biological agents. Studies in
patients with shorter disease duration, longer follow-up periods and preferably adjusted for
secular trends using the general population as a control group to understand employment
outcome, are urgently needed. There is also a large heterogeneity in ‘Work evaluation’
scales. Hopefully, work impact is increasingly studied and standardized.
• Citation:
• Presented at European League Against Rheumatism. “Biologics improve productivity and
reduce missed workdays in rheumatic disease: Treatment could reduce economic burden on
patients and society.

ACA Medicaid Expansion Will Require More Primary Care Providers, Especially In Low Income Areas
Eric T. Roberts and Darrell Gaskin
Johns Hopkins University Bloomberg School of Public Health
Baltimore, MD
Response: This study looked at the implications of the Affordable Care Act’s expansion of
Medicaid on the need for additional physicians working in primary care. Since 2014, 11
million low-income adults have signed up for Medicaid, and this figure will likely increase as
more states participate in the expansion. Many new Medicaid enrollees lacked
comprehensive health insurance before, and will be in need of primary and preventive care
when their Medicaid coverage begins. In light of these questions, in this study, we projected
the number of primary care providers that are needed to provide care for newly-enrolled
adults.
• We forecast that, if all states expand Medicaid, newly-enrolled adults will make 6.1 million
additional provider visits per year. This translates into a need for 2,100 additional full time-
equivalent primary care providers. We conclude that this need for additional providers is
manageable, particularly if Congress fully funds key primary care workforce training
programs, such as the National Health Service Corps.

Baltimore, MD
• Response: Policies that focus on the recruitment of physicians to low-income areas that are
medically under-served can help to meet the health care needs of newly-insured adults.
Although training more health care workers – to meet the needs of an aging population and
workforce turnover – is important, clinicians and policy makers should also pay close
attention to the effects of workforce policies on where providers work.
• Physicians entering the workforce after completing their training may take a number of
factors into consideration when deciding where to practice. Young physicians should consider
the valuable opportunities for hands-on training and financial assistance paying off student
debt that are available through programs like the National Health Service Corps (NHSC).
Physicians should also work closely with policy makers to identify strategies that can improve
recruitment to the NHSC and promote the long-term retention of Corps members in the
communities they serve.

Baltimore, MD
• result of this study?
• Response: Policy makers need evidence about the effectiveness of the Affordable Care Act’s
various workforce development programs in order to prioritize funding for future initiatives.
The ACA expanded support for the NHSC, in addition to Title VII funding for medical
education and clinic-based graduate medical education, in an effort to expand the pipeline of
professionals entering the primary care workforce in high-need communities. Evaluating the
effectiveness of these different programs, on both the short-term recruitment and the long-
term retention of professionals in primary care, will help policy makers invest in programs
that deliver care to populations that need it the most.
• Citation:
• Projecting Primary Care Use in the Medicaid Expansion Population Evidence for Providers and
Policy Makers
Eric T. Roberts and Darrell J. Gaskin
Med Care Res Rev 1077558715588435, first published on June 10, 2015
doi:10.1177/1077558715588435

Bone Marrow Receptor Opens Door To New Therapy For a Pediatric Leukemia
Susan Schwab, PhD
Assistant professor at NYU Langone
Skirball Institute of Biomolecular Medicine
• Dr. Schwab: T cell acute lymphoblastic leukemia (T-ALL) remains a devastating pediatric
disease. Roughly 20% of children do not respond to current therapies. Furthermore,
metastasis to the central nervous system is common in T-ALL, and intrathecal chemotherapy,
even when successful at eradicating the cancer, causes serious long-term cognitive side-
effects.
• Here we report that the chemokine receptor CXCR4 is essential for T cell acute lymphoblastic
leukemia progression in both mouse and human xenograft models of disease. Consistent
with sustained disease remission in the absence of CXCR4, loss of CXCR4 signaling results in
decreased levels of c-Myc, which is required for leukemia initiating cell activity. T-ALL cells
reside near cells generating the CXCR4 ligand CXCL12 in the bone marrow, and our data
suggest that vascular endothelial cells may be an important part of the T-ALL niche.

Susan Schwab, PhD
• Dr. Schwab: The importance of CXCR4 in T-ALL was unexpected because CXCR4 plays only
limited roles in normal T cell development and peripheral T cell maintenance. Yet because
several potent and well-tolerated CXCR4 antagonists are in clinical trials for other blood
cancers, this finding may be rapidly translated into improved therapy for T cell acute
lymphoblastic leukemia patients.

Susan Schwab, PhD
this study?
• Dr. Schwab: One very high priority is to perform further preclinical testing of CXCR4
antagonists in T-ALL, using a wider spectrum of patient samples.
• A second priority is to understand why CXCR4 is indispensable for T-ALL, which would help
identify patients who would most benefit from CXCR4 antagonism.
• Citation:
• CXCL12-Producing Vascular Endothelial Niches Control Acute T Cell Leukemia Maintenance
• Pitt, Lauren A. et al.
• Cancer Cell , Volume 27 , Issue 6 , 755 – 768

Parkinson’s Disease Can Be Stratified Into Three Distinct Groups
Ron Postuma, MD, MSc
Associate Professor Department of Neurology
Montreal General Hospital Montreal, Quebec
• Dr. Postuma: The background is that we often think about Parkinson’s Disease as a single
disease. However, every clinician knows that there is a great deal of variability from patient
to patient. If we can understand the main aspects that separate patients into groups, we can
target therapy better.
• The analysis used a semi-automated means to divide Parkinson’s patients into groups, using
extensive information about motor and non-motor aspects of disease. We found that the
non-motor symptoms, especially cognition, sleep disorders, and blood pressure changes
were the most powerful predictors of which group a patient would be in. Based on these
non-motor (and some motor aspects), the most accurate way to divide patients was into
three groups – diffuse (many non-motor symptoms), pure motor, and intermediate (halfway
between the other). We then followed patients over time. The diffuse group had, by far, the
worse prognosis. This was not only for the non-motor aspects, but the motor as well.

• Dr. Postuma: Most importantly, we can start to stratify patients into groups and predict their
prognosis, based especially upon non-motor aspects of disease.
• Not all patients are the same – if you are seeing mild cognitive changes, REM sleep behavior
disorder, orthostatic hypotension and predominant gait dysfunction, prepare for a
dramatically worse progression of disease, and be especially vigilant for cognitive changes.

this study?
• Dr. Postuma: The most critical thing is that these finding must be confirmed in other long
term studies. Any patient population can have its own individual characters (for example, we
think that because of the way we recruited patients, we may have had more of the ‘diffuse-
malignant’ patients than other groups might have (for example, if they select highly-
motivated cognitively well patients)). So, we have to see not only whether the classification
holds up, but what the proportions in each group are.
• Then, we have to start to understand why there is this variation. Is the underlying pathology
different. Does genetics play a role (we already know that certain genetic causes have
different phenotypes). Is it partially determined by the presence of other, even very early
stage neurologic disease (like prodromal Alzheimer’s)? And finally, should these patients
receive different types of therapy?
• Citation:
• Fereshtehnejad S, Romenets S, Anang JM, Latreille V, Gagnon J, Postuma RB. New Clinical
Subtypes of Parkinson Disease and Their Longitudinal Progression: A Prospective Cohort
Comparison With Other Phenotypes. JAMA Neurol. Published online June 15, 2015.
doi:10.1001/jamaneurol.2015.0703.

Dramatic Increase In Young Children Accidentally Exposed To Pot
Dr. Gary Smith MD, DrPH
Center for Injury Research and Policy
Nationwide Children’s Hospital
Columbus, Ohio
• Dr. Smith: As of January 2015, 23 states and Washington D.C. have legalized marijuana for
medical use. Four of those same states and Washington D.C. have also voted to legalize
marijuana for recreational use. The debate about legalization often focuses on health effects
among adults, economic benefits, and crime rates. Lost in the discussion is the potential
harm to young children from unintentional exposure to marijuana.
• The study found that the rate of marijuana exposure among children 5 years of age and
younger rose 147.5 percent from 2006 through 2013 across the United States. The rate
increased almost 610 percent during the same period in states that legalized marijuana for
medical use before 2000.
• In states that legalized marijuana from 2000 through 2013, the rate increased almost 16
percent per year after legalization, with a particular jump in the year that marijuana was
legalized. Even states that had not legalized marijuana by 2013 saw a rise of 63 percent in the
rate of marijuana exposures among young children from 2000 through 2013.
• Most children were exposed when they swallowed marijuana – that may be related to the
popularity of marijuana brownies, cookies and other foods.

Columbus, Ohio
• Dr. Smith: Marijuana exposure among young children is a growing problem. Most exposures
resulted in minor clinical effects, but some children experience coma, respiratory depression,
or seizures. Health care providers need to inform parents and other child caregivers of the
hazard, and talk to them about proper storage if marijuana is in the household.
• The same precautions used to protect children from medicines and dangerous household
chemicals need to be used with marijuana products – for example, keeping the products in
child-resistant, opaque containers and storing products up, away and out of sight of children,
preferably in a locked cabinet.

Columbus, Ohio
this study?
• Dr. Smith: Future research should be done to evaluate the effect of the safety requirements
included in marijuana legalization laws. Are additional child protections needed? What is the
most effective way to enforce child safety provisions? Study of future trends in marijuana
exposure among children should be done to continue to inform public policy and child safety
efforts.
• Citation:
• Bridget Onders, Marcel J. Casavant, Henry A. Spiller, Thiphalak Chounthirath, and Gary A.
Smith. Marijuana Exposure Among Children Younger Than Six Years in the United States. CLIN
PEDIATR, June 7, 2015 DOI: 10.1177/0009922815589912

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