Medical Complexity Drives Child Readmissions

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
February 10 2015
For Informational Purposes Only: Not for Specific Medical Advice.

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Gut Bacteria Link Between Heart and Kidney Disease Strengthened
MedicalResearch.com Interview with:
W. H .Wilson Tang, M.D., F.A.C.C., F.A.H.A.
Professor in Medicine, Cleveland Clinic Lerner College of Medicine
Cleveland Clinic, Cleveland, OH 44195.
• Medical Research: What is the background for this study? What are the main findings?
Dr. Tang: Our group has previously demonstrated that TMAO is linked to future cardiac risks
in both humans and in animal models. We now show that long-term exposure to higher
levels of TMAO promotes renal functional impairment and fibrosis in animal studies. We also
show that in humans, as the kidneys lose function, TMAO isn’t eliminated as easily, and their
blood levels further rise, thereby increasing cardiovascular and kidney disease risks
further. This newly discovered TMAO link offers further insight into the relationship between
cardiovascular disease and chronic kidney disease.
• Medical Research: What should clinicians and patients take away from your report?
• Dr. Tang: Our studies raise the exciting prospects of nutritional interventions to help retard
development and progression of chronic kidney disease and associated cardiovascular
disease by modulating gut bacteria metabolism of dietary nutrients.
Read the rest of the interviews on MedicalResearch.com
Content NOT an endorsement of efficacy and NOT intended as specific medical advice.

Gut Bacteria Link Between Heart and Kidney Disease Strengthened
W. H .Wilson Tang, M.D., F.A.C.C., F.A.H.A.
Professor in Medicine, Cleveland Clinic Lerner College of Medicine
Cleveland Clinic, Cleveland, OH 44195.
• Medical Research: What recommendations do you have for future research as a result of
this study?
• Dr. Tang: This research strongly implies the need to focus preventive efforts on dietary
interventions and therapeutic targeting of gut microbiota-dependent TMAO pathways
particularly in those with impaired kidney function, potentially to halt development and
progression of chronic kidney disease, as well as cardiovascular disease risks.
• Citation:
• Gut Microbiota-Dependent Trimethylamine N-oxide (TMAO) Pathway Contributes to Both
Development of Renal Insufficiency and Mortality Risk in Chronic Kidney Disease
• WH Wilson Tang, Zeneng Wang, David J Kennedy, Yuping Wu, Jennifer Buffa, Brendan Agatisa-
Boyle, Xinmin S Li, Bruce S Levison, and Stanley L Hazen
• Circulation Research. 2014;CIRCRESAHA.114.305360published online before print November
5 2014, doi:10.1161/CIRCRESAHA.116.305360

PHOTON-2 Study Addresses Combination Hepatitis C Pill For HIV+ Patients
Prof Jean-Michel Molina
Maladies Infectieuses et Tropicales, Hôpital
Saint-Louis, Paris France
Prof. Molina: Treatment of co-infected patients is complicated by drug drug interactions with HIV
drugs, and the news DAAs are not very potent on HCV G2 and 3 infections.
• Prof. Molina: The simple combination of sofosbuvir plus ribavirin (available as a generic drug)
provides potent response rates above 80% for co-infected patients with all genotypes, with
limited drug drug interactions with HIV drugs.
• Medical Research: What recommendations do you have for future research as a result of this
study?
• Dr. Prof. Assess new combinations of DAAs, also with pangenotypic activity and limited drug drug
interactions with HIV drugs, better tolerated and allowing shorter treatment duration.
• Citation:
• Sofosbuvir plus ribavirin for treatment of hepatitis C virus in patients co-infected with HIV
(PHOTON-2): a multicentre, open-label, non-randomised, phase 3 study
• Sofosbuvir plus ribavirin for treatment of hepatitis C virus in patients co-infected with HIV
(PHOTON-2): a multicentre, open-label, non-randomised, phase 3 study
• Prof Jean-Michel Molina, MD Chloe Orkin, MDb,David M Iser, MBBSc,Francisco-Xavier Zamora,
MDd,Mark Nelson, MBBSe,Prof Christoph Stephan, MDf,Benedetta Massetto, MDg, Anuj Gaggar,
MDg,Liyun Ni, MAg,Evguenia Svarovskaia, PhDg,Diana Brainard, MDg, G Mani Subramanian,
MDg,John G McHutchison, MDg,Prof Massimo Puoti, MDh, Prof Jürgen K Rockstroh, MDi, for the
PHOTON-2 study team
• The Lancet Available online 4 February 2015†

Simple Information Sheet Improves Contraception Knowledge In Isotretinoin Study
Dr. Eleanor B. Schwarz, M.D., M.S
University of California, Davis
Sacramento, CA
• MedicalResearch.com: What is the background for this study? What are the main findings?
• Dr. Schwarz: The background for this study is that…
• Women treated with Isotretinoin receive a lot of scary information about this medication’s risk of
causing birth defects, but few receive clear information on the most effective ways to protect
themselves from undesired pregnancy and the risks of medication-induced birth defects.
• Our main finding is that women who spent less than a minute reviewing a simple information sheet
were significantly more likely to be aware that some contraceptives are considerably more effective
than others.
• MedicalResearch.com: What should clinicians and patients take away from your report?
• Dr. Schwarz: Clinicians who prescribe medications that can cause birth defects should make sure
their patients are aware of the fact that women using a birth control pill are typically twenty times
more likely to experience a contraceptive failure than those using a subdermal contraceptive
implant (e.g. Nexplanon) or intrauterine contraceptive (e.g. Mirena, ParaGard).
• MedicalResearch.com: What recommendations do you have for future research as a result of this
study?
• Dr. Schwarz: The next step is to prove that this simple information sheet improves contraceptive
knowledge and use in a range of other clinical settings.
• Citation:
• Promoting Safe Use of Isotretinoin by Increasing Contraceptive Knowledge
• Carly A. Werner MD, Melissa J. Papic BS, Laura K. Ferris MD, PhD, Eleanor B. Schwarz MD, MS
• JAMA Dermatol. 2015;151(4):-. doi:10.1001/jamadermatol.2014.4171

Childhood Hospital Readmissions Linked to Chronic, Complex Conditions
Mark Brittan MD MPH
Assistant Professor, Pediatric Hospital Medicine Children’s Hospital Colorado
University of Colorado School of Medicine
• MedicalResearch: What is the background for this study? What are the main findings?
• Dr. Brittan: As hospitals face reimbursement penalties for excess readmissions, clinicians are
increasingly focused on improving care transitions in order to reduce readmissions. We are
interested in learning about feasible ways to reduce pediatric readmissions so that we can
improve the quality of care and experience of children and families who are being discharged
from the hospital. The purpose of this study was to assess whether outpatient follow-up
visits after hospital discharge can help to prevent readmissions. We chose to examine this
question in a population of medically complex children enrolled in Medicaid. Children with
medical complexity account for a growing proportion of pediatric hospitalizations and
inpatient costs. These children are often dependent on technology (for example, ventilator
machines, feeding tubes, and chronic indwelling catheters), and can have very complex care
plans and medication regimens. Publically insured children are also vulnerable to increased
hospital utilization and may not always have optimal or easy access to outpatient services.
Showing a relationship between post-discharge outpatient visits and fewer readmissions
would suggest that improvements in coordination of care or access to outpatient follow-up
care may help to reduce readmissions in these children. To assess this relationship, we
retrospectively analyzed 2006-2008 Colorado Medicaid claims data from which we were able
to gather demographic, clinical, and visit information for all enrollees.

Mark Brittan MD MPH
In our study, we excluded children who were readmitted within 3 days of hospital discharge so
that we could evaluate children who had a chance to follow-up. The study cohort included 2415
medically complex children aged 6 months to 18 years who were hospitalized at least once. Of
these children, 6.3% were readmitted on days 4 – 30 after hospital discharge. Almost 22% of the
children had an outpatient follow-up visit within 3 days of discharge, and 40% had a visit on days
4-29 after discharge. In the final analysis, we found expected associations between readmission
and previously described risk factors, including number of patient comorbidities and longer initial
hospital length of stay. Examining the relationship between outpatient follow-up and
readmission, we found that children with later outpatient follow-up visits (days 4-29) were
significantly less likely to be readmitted than those who did not have an outpatient visit on days
4-29 after discharge.

Mark Brittan MD MPH
• MedicalResearch: What should clinicians and patients take away from your report?
• Dr. Brittan: It is important for clinicians and patients/families to be aware that children with
chronic and complex conditions are more likely to experience readmission than otherwise
healthy children who are hospitalized with acute illnesses. Our study suggests that rates of
post-discharge outpatient follow-up may be lower than expected. Ensuring that medically
complex children follow-up after hospitalization can help clinicians to identify and mitigate
hospital-related problems before they become serious enough to require readmission.
Increasing rates of outpatient follow-up may help to prevent readmissions for these children
and their families.

Mark Brittan MD MPH
• MedicalResearch: What recommendations do you have for future research as a result of
this study?
• Dr. Brittan: It would be important to replicate these findings for other pediatric patient
populations, and for children in other regions of the country. Our study had several
limitations related to its retrospective design. A prospective study examining the impact of an
intervention to increase post-discharge outpatient follow-up may help to provide additional
evidence for the importance of transitional care continuity in reducing hospital readmissions
for children with medical complexity.
• Citation:
• Outpatient Follow-Up Visits and Readmission in Medically Complex Children Enrolled in
Medicaid
• Mark S. Brittan, MD, MPH Marion R. Sills, MD1, 2,David Fox, MD1, 2,Elizabeth J. Campagna,
MS2,Doron Shmueli, MS2,James A. Feinstein, MD, MPH1, 2,Allison Kempe, MD, MPH1, 2
• The Journal of Pediatrics Available online 29 January 2015

Healthy Diet May Lower COPD Risk
Raphaëlle Varraso
INSERM U1168, VIMA (Aging and chronic diseases. Epidemiological and public health approaches), 16 avenue Paul Vaillant Couturier
Villejuif, France
• Response: Respiratory health and lung function, strongly predict general health status and
all-cause mortality. Chronic obstructive pulmonary disease (COPD) is currently ranked the
third leading cause of death worldwide. The predominant risk factor for COPD in the
developed world is cigarette smoking, but up to one-third of COPD patients have never
smoked, suggesting that other factors are involved. Besides smoking, relatively little attention
has been paid to other modifiable risk factors that might decrease risk of developing COPD,
including diet. The Alternate Healthy Eating Index (AHEI)-2010, a new measure of diet quality
based on current scientific knowledge, has been linked to risk of major chronic diseases, such
as cardiovascular disease, diabetes and cancer. However, the role of dietary scores on risk of
COPD is unknown.
• We examined this issue among >120,000 US female and male health professionals (Nurses’
Health Study and Health Professionals Follow-up Study), and we reported that a high AHEI-
2010 dietary score score (reflecting high intakes of whole grains, vegetables, fruit,
polyunsaturated fatty acids, nuts and legumes, and long-chain omega-3 fats, a moderate
intake of alcohol, and low intakes of red/processed meats, trans fat, sodium and sugar-
sweetened beverages) was associated with a lower risk of COPD in both women and men.
This novel finding supports the importance of diet in COPD pathogenesis.

Healthy Diet May Lower COPD Risk
Raphaëlle Varraso
INSERM U1168, VIMA (Aging and chronic diseases. Epidemiological and public health approaches), 16 avenue Paul Vaillant Couturier
Villejuif, France
Response: Although COPD prevention efforts should continue to focus on smoking cessation,
these prospective findings support the importance of a healthy diet in multi-interventional
programs to prevent COPD. Our results encourage clinicians to consider the potential role of
the combined effect of foods in a healthy diet in promoting lung health. While one study is
unlikely to change clinical practice, our paper provides further support for non-traditional risk
factors for COPD.
this study?
• Response: Our two cohorts are comprised of health professionals and, as such, are not
necessarily generalizable to the general population. For example, differences in health
awareness, socio-economic status, and smoking behavior might differ significantly between
our study population and the general population. Moreover, our study population was mainly
non-Hispanic white, which might limit generalizability of our results to other racial/ethnic
populations. We encourage replication of our prospective findings on AHEI-2010 and COPD in
other populations.
• Citation:
• Varraso Raphaëlle, Chiuve Stephanie E, Fung Teresa T, Barr R Graham, Hu Frank B, Willett
Walter C et al. Alternate Healthy Eating Index 2010 and risk of chronic obstructive pulmonary
disease among US women and men: prospective study BMJ 2015; 350:h286

Live Longer…Don’t Reproduce?
John Tower, PhD
Professor, Molecular and Computational Biology Program Department of Biological Sciences
USC Dana and David Dornsife College of Letters, Arts and Sciences University of Southern California
Los Angeles, CA 90089-2910
Response: One of the main causes of aging is thought to be the trade-off between reproduction
and life span – in other words, the body uses its resources for mating and producing offspring
instead of repairing and maintaining its tissues and organs. What exactly these resources are and
how this works is not yet known.
• The drug mifepristone inhibits reproduction in human females. Mifepristone antagonizes (inhibits)
the activity of the female hormone progesterone, which is required for normal reproduction. We
found that mifepristone could also inhibit reproduction in the laboratory fruit fly Drosophila
melanogaster, and could increase the life span of mated female flies by up to +68%. Drosophila are
not thought to contain progesterone, but the results suggest that some similar steroid hormone
may be functioning in Drosophila to regulate the trade-off between reproduction and life span. We
found that many of the genes that were altered by mifepristone in the fly are genes that also exist
in humans; these genes are therefore promising targets for future interventions in aging.
• One exciting possibility suggested by our results is that mifepristone might be able to favor the life
span of human females. This could be tested using mice and/or in human clinical trials.
• Citation:
• The progesterone antagonist mifepristone/RU486 blocks the negative effect on life span caused
by mating in female Drosophila.
• Landis GN1, Salomon MP1, Keroles D1, Brookes N1, Sekimura T1, Tower J1.
• Aging (Albany NY). 2015 Jan 15. [Epub ahead of print]

Study Addresses Factors Prolonging ED Visits For Psychiatric Patients
Michael Wilson, MD, PhD, FAAEM
Attending Physician, UCSD Department of Emergency Medicine
Director, Department of Emergency Medicine Behavioral Emergencies Research (DEMBER) lab UC San Diego Health System
• Dr. Wilson: Emergency departments (EDs) nationwide are crowded. Although psychiatric
patients do not make up the largest proportion of repeat visitors to the emergency
department, psychiatric patients stay longer in the ED than almost any other type of patient.
So, it’s really important to find out things about these patients that may predict longer stays.
• In this study, we looked at patients on involuntary mental health holds. The reasoning is
simple: patients on involuntary mental health holds aren’t free to leave the ED. So, the only
thing that should really matter is how quickly an Emergency department can release them
from the involuntary hold. Surprisingly, though, this wasn’t the only thing that correlated
with longer stays.

• Dr. Wilson: Unlike other research which has focused solely on the structure of the ED and
community resources, this study focused on what things that both the emergency department and
the Emergency department physician did that seem to make disposition faster for patients on
involuntary mental health holds.
• This really is a new way to look at the problem. There are lots of things about the patient and about
the way that the psychiatry service is structured that seem to correlate with longer stays for these
patients. For instance, how quickly the psychiatry service can clear the hold really seems to matter
a lot, just as you’d expect. So, patients in this study stayed longer on the weekends when the
psychiatry attendings don’t round in our Emergency department.
• Patient complaint also seems to correlate with longer stays. So, for instance, patients with thoughts
of self-harm stay longer in the emergency department. Although we don’t know the reason for this,
it may be because these patients need longer evaluations by trained specialists.
• Most surprising was that medication by Emergency department physicians also seem to matter.
Although presence of agitation didn’t seem to correlate with longer stays, the fact that patients
received medications did. The reasons for this are unknown. It may be that the type of patients on
involuntary health holds who receive medication naturally need more workup in the emergency
department. It may also be that physicians in the emergency department tend to prescribe
medications that make people sleep longer, and so it is more difficult to evaluate and discharge
them. Or, it may be from some other combination of factors entirely.
• Either way, it suggests that even in patients on involuntary health holds, both what the emergency
department does and the type of working relationship the Emergency department has with
psychiatry, matter greatly. Although we might all wish for better community resources, the ED itself
can help speed evaluate and discharge these patients more quickly.

this study?
• Dr. Wilson: Further prospective research is badly needed, looking at 3 things:
• 1) Patient factors that might make a certain patient stay longer in the ED;
• 2) ED factors that might contribute to longer stays; and
• 3) Physician-specific factors that might contribute to the problem.
• In other words, perhaps Emergency department physicians could use different types of
medications that have been shown to calm patients but not put them to sleep. This might
allow patients to leave the Emergency department more quickly. We also don’t know much
about the optimum working relationship with psychiatry. How many mental health workers
are needed? How often should they see patients? These sorts of questions are important for
helping manage Emergency department overcrowding.
• Citation:
• Lengths of stay for involuntarily-held psychiatric patients in the emergency department are
affected both by patient characteristics and medication use
• Michael P. Wilson, MD, PhD Jesse J. Brennan, MA Lucia Modesti, MD James Deen, BA Laura
Anderson, BA Gary M. Vilke, MD Edward M. Castillo, PhD, MPH The American Journal of
Emergency Medicine Available online 20 January 2015

Cost-Effectiveness of CDC Recommended HIV Prevention Strategies
Ya-lin (Aileen) Huang, PhD.
Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and
Prevention Atlanta, GA, 30329
Dr. Huang: With an estimated 50,000 new HIV infections each year in this country, and no
vaccine or cure available yet, prevention is critical. Maximizing the impact of all available
prevention strategies could significantly reduce new infections in this country. The purpose of
this study is to provide evidence for the cost effectiveness of the interventions recommended
under the funding announcement and to highlight where more cost-effectiveness studies
may be needed. We limited our scope to the four interventions required under the health
department funding announcement, including HIV testing, prevention with HIV-positives and
their partners, condom distribution and efforts to align policies with optimal HIV prevention,
care and treatment.
• Our review provides an updated summary of the published evidence of cost-effectiveness of
four key HIV prevention interventions recommended by CDC: HIV testing, prevention with
HIV-positives and their partners, condom distribution and policy initiatives. Models suggest
that more than 350,000 HIV infections have been avoided because of the nation’s HIV
prevention efforts. In addition to lives saved, HIV prevention has also generated substantial
economic benefits. For every HIV infection that is prevented, an estimated $402,000
(http://www.ncbi.nlm.nih.gov/pubmed/23615000) is saved in the cost of providing lifetime
HIV treatment. It is estimated that HIV prevention efforts have averted more than $125
billion in medical costs since the beginning of the epidemic.

Cost-Effectiveness of CDC Recommended HIV Prevention Strategies
Ya-lin (Aileen) Huang, PhD.
Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and
Prevention Atlanta, GA, 30329
• Dr. Huang: By building upon progress to date and maximizing the impact of the range of proven
prevention tools now available, there is more hope than ever before of ending the HIV epidemic in
the United States. Through our report, health care providers and patients could learn the HIV
prevention activities that have been funded and advocated by the CDC, and where the economic
evaluation evidence are that supported those activities.
study?
• Dr. Huang: More cost-effectiveness evaluation research is needed in the US for interventions
related to prevention for HIV positives, condom distribution, and policy initiatives. However, this
descriptive assessment is helpful in supporting policymakers or those charged with HIV resource
allocation decisions in several ways.
• First, it identifies the body of evidence of cost effectiveness for the various interventions
considered. And, where lacking, this review encourages decision-makers to seek local data on the
costs and outcomes of HIV programs. These data could then be used to map out an evidenced-
based HIV intervention portfolio. Funding decisions are typically influenced by a myriad of factors
including historical spending, epidemic data, stakeholder pressures and other non-quantifiable
factors; with this study, we expect to further inform this decision-making process.
• Citation:
• A Systematic Review on Cost Effectiveness of HIV Prevention Interventions in the United States.
• Huang YA, Lasry A, Hutchinson AB, Sansom SL.
• Appl Health Econ Health Policy. 2014 Dec 25. [Epub ahead of print]
• PMID: 25536927 [PubMed – as supplied by publisher]

Hip Fractures: Comprehensive Geriatric Care Improved Outcomes and ReducedCosts
Ingvild Saltvedt PhD
Department of Neuroscience, Norwegian University of Science and Technology,
Medical Faculty Trondheim, Norway
Medical Research: What is the background for this study? What are the main findings?
Dr. Saltvedt: Hip fracture patients are often old, frail and have many comorbidities. When treated
with a traditional orthopaedic approach the outcomes are often poor, and many patients get
functionally impaired with reduced ability to walk independently and impairment in daily life
activities and with high costs for the society. In many ways these patients are geriatric patients
with hip-fractures. It has previously been shown that acutely sick geriatric patients benefit from
treatment in geriatric wards and different kind of orthogeriatric treatment models where
orthopaedic surgeons and geriatricians collaborate have been studied and have shown beneficial
results on short term outcomes. In the present study patients home-dwelling hip-fracture
patients were randomised to orthogeriatric treatment or traditional orthopaedic treatment from
admission to the hospital and during the entire stay except for the surgery that was performed
similar in both groups. The study focused on long-term outcomes and also on use of health care
services and cost-effectiveness. Patients in the orthogeriatric group got comprehensive geriatric
assessment and treatment performed by an interdisciplinary team that emphasised early
mobilisation and rehabilitation and started discharge planning early. In the orthopaedic group
traditional treatment according to national and international guidelines was offered.

The primary endpoint was mobility at four months, that was better in the orthogeriatric group
than in the orthopaedic group, the same difference was also shown at 12 months. In addition
there were differences in instrumental activities of daily living and personal activities of daily
living, quality of life and fear of falling, all differences were statistically and clinically significant
and in favour of the orthoegeriatric group. The length of hospital stay was 1,7 days longer in the
geriatric group, while there was no differences in days spent in hospital during one year of follow-
up. One of four orthogeriatric patients were discharged directly home as compared to one of ten
in the orthopaedic group. The orthopaedic group spent more days in nursing homes and
rehabilitation institutions during one year of follow-up. The treatment was cost-effective in
favour of the orthogeriatric group.

• Dr. Saltvedt: Outcomes can be improved when hip-fractures are treated with an
orthogeriatric approach from admission to hospital.
• Although we think that our results are valid also outside our hospital, the present study is a
single centre study that should be followed by a multicentre study to be sure that the results
are valid in other settings and other countries. There is also need of further research on how
to treat these patients both during the hospital stay and afterward in order to improve
outcomes for patients and save costs for the society.
• Citation:
• Comprehensive geriatric care for patients with hip fractures: a prospective, randomised,
controlled trial
• Anders Prestmo, MD Gunhild Hagen, MPhil Olav Sletvold, PhD
Prof Jorunn L Helbostad, PhD Pernille Thingstad, MSc Kristin Taraldsen, PhD Prof Stian
Lydersen, PhD Vidar Halsteinli, PhD Turi Saltnes, MScProf Sarah E Lamb, PhD Lars G
• Johnsen, PhD Dr Ingvild Saltvedt, PhD
• The Lancet Available online 5 February 2015

Brain’s Protective Blood Barrier Becomes Leaky With Age
V. Zlokovic, MD, PhD Professor and Chair
Department of Physiology and Biophysics
Keck School of Medicine of USC.
Dr. Zlokovic: Our team used high-resolution imaging of the living human brain to show for the first
time that the brain’s protective blood barrier becomes leaky with age, starting at the hippocampus,
a critical learning and memory center that is damaged by Alzheimer’s disease.
• Dr. Zlokovic: The study indicates it may be possible to use brain scans to detect changes in blood
vessels in the hippocampus before they cause irreversible damage leading to dementia in
neurological disorders characterized by progressive loss of memory, cognition and learning.
study?
• Dr. Zlokovic: In my humble opinion, individuals with symptoms of mild dementia on
neuropsychological tests, people at genetic risk who appear cognitively normal, and individuals
who may be at risk for familial Alzheimer’s should consider having a brain scan to detect leakage of
the blood brain barrier. Symptoms of mild dementia should raise a red flag, while those at genetic
risk may be asymptomatic APOE4 carriers for late onset Alzheimer’s, which is not so rare — APOE4
affects up to 25 percent of the population — or presenilin 1 mutants carriers.
• Citation:
• Berislav V. Zlokovic et al. Blood-Brain Barrier Breakdown in the Aging Human Hippocampus.
Neuron, January 2015 DOI: 10.1016/j.neuron.2014.12.032

Gut Bacteria in Infancy May Have Long Lasting Effects on Weight
Joanna Holbrook PhD
Senior Principal Investigator – Systems Biology Singapore Institute for Clinical Sciences
Brenner Centre for Molecular Medicine Singapore
• Medical Research: What is the background for this study?
Dr. Holbrook: Bacteria in the human gut may influence many aspects of our health; however,
it is not fully known what determines the composition of the gut microbiota. Rapid bacterial
colonisation of the infant gut could be influenced by the environment of the baby before
birth, and microbiota content has been associated with the development of obesity and
insulin resistance.
• Medical Research: What are the main findings?
• Dr. Holbrook: The rate of bacterial colonisation of the gut is influenced by external factors
such as the method of delivery and duration of gestation. Also, infants with a mature gut
bacteria profile at an early age gained normal levels of body fat, while infants with less
mature gut bacteria profiles displayed a tendency to gain lower levels of body fat at the age
of 18 months, indicating that gut bacteria could be related to normal development and
healthy weight gain.

Gut Bacteria in Infancy May Have Long Lasting Effects on Weight
Joanna Holbrook PhD
Senior Principal Investigator – Systems Biology Singapore Institute for Clinical Sciences
Brenner Centre for Molecular Medicine Singapore
• Dr. Holbrook: Epidemiological data has linked what happens to us very early in life with our
health later in life. The mechanisms for this are not yet known; how do our bodies
remember our earliest experiences in a way that impacts health issues like our weight? This
work suggests that one of the mechanisms for the transmission of early life experience to
later life health is the seeding of our gut microbiota.
this study?
• Dr. Holbrook: This study is an important example of how influences before and after birth
have a lasting effect on the growth and development of the child. The findings will help
design future interventions aimed at optimising early development, with benefits for lifelong
health.
• Citation:
• MBio. 2015 Feb 3;6(1). pii: e02419-14. doi: 10.1128/mBio.02419-14.
• Dynamics of infant gut microbiota are influenced by delivery mode and gestational
duration and are associated with subsequent adiposity.
• Dogra S1, Sakwinska O2, Soh SE3, Ngom-Bru C2, Brück WM2, Berger B2, Brüssow H2, Lee YS,
Yap F4, Chong YS, Godfrey KM5, Holbrook JD6.

Enzyme Critical to Non-Small Cell Lung Cancer Growth Identified
Teresa W-M. Fan PhD and Andrew N Lane, PhD
Markey Cancer Center, University of Kentucky
• Response: The study began about eight years ago at the University of Louisville as a collaboration
between thoracic surgeon Michael Bousamra II, immunologist Jun Yan and our metabolomics team
(T. Fan, R Higashi and A.N. Lane) now at the U. Kentucky. Lung cancer remains as the highest cancer
mortality in North America, and is unfortunately often not diagnosed until the most successful
treatment, surgery, is no longer an option. Furthermore although there are numerous subtypes of
the disease, the options for chemotherapy are quite limited. We wanted to know how the
biochemistry of early stage (resectable) lung cancer differs from that of healthy or at least non-
cancerous lung tissue from the point of view of basic tumor biology, and whether we might uncover
better option for therapeutic intervention.
• To this end, we applied our stable isotope resolved metabolomics (SIRM) technique directly to
patients who were diagnosed with resectable NSCLC. By this technique, the fate of individual atoms
from a non-radioactive enriched precursor (C-13 glucose in this instance) are traced as they are
taken up from the blood and metabolized in situ. This technique, along with model studies with
mice, isolated cell cultures, and so-called “Warburg” slices provides tremendous detail about the
functional biochemistry of a cancer within its natural microenvironments, compared with non-
cancerous tissue. The major finding published in this article is that the anaplerotic enzyme pyruvate
carboxylase is greatly upregulated in NSCLC compared with paired non-cancerous lung tissue,
whereas the other commonly utilized anaplerotic enzyme glutaminase was not. Interestingly, only
cancer cells showed strong staining for pyruvate carboxylase, whereas in the paired non-cancerous
lung tissue, only resident macrophages stained for PC. Pyruvate carboxylase was further shown to
be essential for tumor growth in both call culture and in mouse xenografts.

• Response: This study shows that high quality information can be obtained with stable
isotope tracing in human subjects, and that this provides unprecedented detail about the
workings of tumors- what nutrients are used, how they survive and/or proliferate. While still
years away from new treatments, we believe that this approach will hasten discovery of new
enzymes as anticancer drug targets, and that the Warburg slice approach may be an
important component in the preclinical drug discovery pipeline, ultimately accelerating the
bench to beside that is notoriously hampered by the high rate of attrition of oncodrugs in
Phase 2 /3 clinical trials.

this study?
• Response: This research is continuing under an NCI-funded program project grant on non-
small cell lung cancer, with a focus on the tumor microenvironment and metabolic
biochemistry that we call “Systems Biochemistry”. We aim to characterize in greater detail
the cellular consequences of pyruvate carboxylase expression, and other metabolic enzymes,
as well as modulating the activity of the tumor-infiltrating macrophages, with a view to
developing new therapeutics for this deadly cancer.
• Citation:
• Pyruvate carboxylase is critical for non–small-cell lung cancer proliferation
• Published in Volume 125, Issue 2 (February 2, 2015)
J Clin Invest. 2015;125(2):687–698. doi:10.1172/JCI72873.
• Katherine Sellers1,2, Matthew P. Fox3, Michael Bousamra, II3,4, Stephen P. Slone5, Richard
M. Higashi1,6,7, Donald M. Miller4, Yali Wang4, Jun Yan4, Mariia O. Yuneva2, Rahul
Deshpande7, Andrew N. Lane4,6,7 and Teresa W.-M. Fan1,4,6,7

Pesticide Exposure May Impact Development Of ADHD
MedicalResearch.com Interview with: Jason R. Richardson MS,PhD DABT Associate Professor
Department of Environmental and Occupational Medicine
Robert Wood Johnson Medical School and Resident Member
Environmental and Occupational Health Sciences Institute Piscataway, NJ
• Dr. Richardson: Although ADHD is often though of as a genetic disorder, no single gene can
explain more than a fraction of the cases. This suggests that environmental factors are likely
to interact with genetic susceptibility to increase risk for ADHD. Our study reports that
exposure of pregnant mice to relatively low levels of a commonly used pesticide reproduces
the behavioral effects of ADHD in their offspring. Because the study was in animals, we
wanted to see if there was any association in humans. Using data from the Centers for
Disease Control and Prevention we found that children and adolescents with elevated levels
of metabolites of these pesticides in their urine, which indicates exposure, were more than
twice as likely to be diagnosed with ADHD.
• Dr. Richardson: Parents and Clinicians should know that pregnant women and children may
be uniquely susceptible to pesticide exposure and that proper precautions should be taken
when using pesticides. Vegetables and fruits should be washed and alternative pest control
measures should be used in the home if possible if there are young children and pregnant
women residing in the household.

Pesticide Exposure May Impact Development Of ADHD
MedicalResearch.com Interview with: Jason R. Richardson MS,PhD DABT Associate Professor
Department of Environmental and Occupational Medicine
Robert Wood Johnson Medical School and Resident Member
Environmental and Occupational Health Sciences Institute Piscataway, NJ
this study?
• Dr. Richardson: Although we can’t change genetic susceptibility to ADHD, there may be
modifiable environmental factors, including exposures to pesticides, that we should be
examining in more detail. Additional studies are required to characterize exposure and effects
in a larger human population. Additionally, studies in mice may help to understand why
exposure during a brief period of life results in persistent, if not permanent, behavioral
changes.
• Citation::
• Jason R. Richardson, Michele M. Taylor, Stuart L. Shalat, Thomas S. Guillot III, W. Michael
Caudle, Muhammad M. Hossain, Tiffany A. Mathews, Sara R. Jones, Deborah A. Cory-Slechta,
and Gary W. Miller
• Developmental pesticide exposure reproduces features of attention deficit hyperactivity
disorder FASEB J fj.14-260901; published ahead of print January 28, 2015, doi:10.1096/fj.14-
260901

Genetic Predisposition to Psoriatic Arthritis Localized To Chromosome 5
Professor Anne Barton FRCP PhD and Dr John Bowes PhD
Centre for Musculoskeletal Research and Centre for Genetics and Genomics,
The University of Manchester, Manchester UK
Response: Psoriatic arthritis (PsA) is an inflammatory condition causing pain and stiffness in
joints and tendons. Approximately one third of patients with psoriasis will go on to develop
PsA resulting in a reduction in their quality of life caused by increasing disability and
additional health complications. A key area of research within the Arthritis Research UK
Centre for Genetics and Genomics in the Centre for Musculoskeletal Research is the
identification of risk factors for the development of Psoriatic arthritis; this will allow us to
understand the underlying cause of disease and ultimately help identify psoriasis patients at
high risk of PsA, allowing early treatment to be introduced to reduce the impact of PsA.
• Our study focuses on the identification of genetic risk factors for Psoriatic arthritis; we
compared the frequency of genetic variants, referred to as single nucleotide polymorphisms
(SNPs), between large numbers of DNA samples from patients with PsA and healthy control
samples. When the frequency of the SNP is significantly different between cases and
controls, the SNP is said to be associated with risk of developing Psoriatic arthritis and this
association is interpreted as being important in the disease process.

Response: When we analysed the data from the study we found a new association to SNPs
on chromosome 5, and when we investigated these SNPs for association with skin-only
psoriasis, we did not find any evidence for association. In addition, we also found SNPs that
were specifically associated with Psoriatic arthritis at a gene on chromosome 1. This gene is
known to be associated with psoriasis, but our results show that there are different SNPs
associated with PsA and psoriasis at this gene. Hence, our results identify new SNPs that are
specifically associated with PsA.
• In addition, identifying which cells are the key drivers of inflammation in Psoriatic arthritis
will help us to focus on how the genetic changes act in those cells to cause disease. Our
results show that many of the PsA associated SNPs occur in regions of the genome that are
important in the function of CD8+ cells, an important cell type in the immune system.
• Response: By identifying genes that predispose to Psoriatic arthritis but not psoriasis, we
hope in the future to be able to test patients with psoriasis to find those at high risk of
developing Psoriatic arthritis. Excitingly, it raises the possibility of introducing treatments to
prevent the development of PsA in those individuals in the future.

this study?
• Response: Our study has begun to reveal key insights into the genetics of PsA that explain
fundamental differences between psoriasis and Psoriatic arthritis. The results demonstrate
that future studies attempting to identify genes specifically associated with PsA would
benefit from directly comparing findings from patients with PsA and patients with psoriasis
alone approach. Our findings also highlight that CD8+ cells are likely to be the key drivers of
inflammation in PsA and identify this as the key cell type to focus on in future studies
investigating the biological impact of these SNPs.
• Citation:
• John Bowes, Ashley Budu-Aggrey, Ulrike Huffmeier, Steffen Uebe, Kathryn Steel, Harry L.
Hebert, Chris Wallace, Jonathan Massey, Ian N. Bruce, James Bluett, Marie Feletar, Ann W.
Morgan, Helena Marzo-Ortega, Gary Donohoe, Derek W. Morris, Philip Helliwell, Anthony W.
Ryan, David Kane, Richard B. Warren, Eleanor Korendowych, Gerd-Marie Alenius, Emiliano
Giardina, Jonathan Packham, Ross McManus, Oliver FitzGerald, Neil McHugh, Matthew A.
Brown, Pauline Ho, Frank Behrens, Harald Burkhardt, Andre Reis, Anne Barton. Dense
genotyping of immune-related susceptibility loci reveals new insights into the genetics of
psoriatic arthritis. Nature Communications, 2015; 6: 6046 DOI: 10.1038/ncomms7046

Staph Aureus Colonization Linked To Asthma Symptoms in Children and Young Adults
Meghan F. Davis, DVM MPH PhD
Assistant Professor Department of Environmental Health Sciences
Johns Hopkins Bloomberg School of Public Health
Dr. Davis: Asthma rates have been on the rise, particularly in children. Interventions targeted
at allergens and other environmental factors known to exacerbate asthma are only partially
successful, suggesting a role for novel drivers of morbidity among existing patients with
asthma. In this study, we evaluated associations between nasal colonization with the
bacterium Staphylococcus aureus and symptoms related to wheeze and asthma using data
from the nationally-representative NHANES database. We found that S. aureus nasal
colonization was associated with asthma symptoms in children and young adults, but not in
older adults.
• Dr. Davis: S. aureus colonizes about a third of the population at any given time and can
sometimes cause skin or soft tissue infections. Our findings suggest that this bacterium may
elicit respiratory health effects without causing infection. More work is needed to confirm
these results and understand the mechanisms underlying this observed association.

Staph Aureus Colonization Linked To Asthma Symptoms in Children and Young Adults
Meghan F. Davis, DVM MPH PhD
Assistant Professor Department of Environmental Health Sciences
Johns Hopkins Bloomberg School of Public Health
this study?
• Dr. Davis: Future research should evaluate S. aureus and respiratory outcomes in children
and young adults with asthma over time and should measure host factors, such as atopic
status, that could influence how people respond to S. aureus colonization. Further, since not
all strains of S. aureus share the same characteristics, virulence factors in the bacteria also
should be measured.
• Citation:
• Staphylococcus aureus colonization is associated with wheeze and asthma among US children
and young adults
• Journal of Allergy and Clinical Immunology (Impact Factor: 11.25). 12/2014;
DOI: 10.1016/j.jaci.2014.10.052

Black Mortality from HIV Declines But Still Higher Than Whites, Hispanics
MedicalResearch.com Interview with: Azfar-e-Alam Siddiqi, MD, PhD
Associate Chief of Science (Acting) HIV Incidence and Case Surveillance Branch Division of HIV/AIDS Prevention
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention
Centers for Disease Control and Prevention
Dr. Sidiqqi: African Americans remain the population most affected by HIV in the United
States — accounting for almost half (44 percent) of all new infections and more than a third
(41 percent) of people living with HIV, despite representing just 12 percent of the U.S.
population. We also know that far too many African Americans living with HIV do not get the
medical care and treatment they need to stay healthy and protect themselves and others. In
fact, less than half (40 percent) of African Americans living with HIV are engaged in care and
only one-quarter (28 percent) have the virus under control through treatment.
• To better understand mortality among African Americans with HIV, our team analyzed data
from the National HIV Surveillance System for 2008 through 2012. Because immune
suppression caused by HIV infection can result in fatal co-illnesses, our analysis estimated
deaths due to all causes, rather than limiting their analysis to deaths resulting directly from
HIV infection. This method allowed us to capture the fullest picture of mortality among
African Americans with HIV.
• According to our new analysis, from 2008-2012, the death rate per 1,000 blacks living with
HIV decreased 28 percent, more than the overall decline (22 percent) observed among all
persons living with HIV and more than declines observed among other races/ethnicities (13
percent for whites and 25 percent for Hispanics). Despite substantial declines in mortality,
the death rate per 1,000 blacks living with HIV in 2012 was 13 percent higher than the rate
for whites and 47 percent higher than the rate for Hispanics.

• Dr. Sidiqqi: To build on the progress we’ve already made and, one day, realize a future
without HIV and AIDS, we will have to confront this disease head on. Each of us has a critical
role to play.
• Individuals can start by getting tested. We need to ensure all people living with HIV know
they are infected. But, getting tested is just the first step – getting into – and staying in –
appropriate care and taking steps to prevent further transmission are also critical. People
who have HIV need to receive HIV treatment – it can help them live longer, healthier lives,
and recent studies have shown that it can dramatically reduce HIV transmission. People who
don’t have HIV should talk to their healthcare provider about all of the prevention options
available today, such as daily pre-exposure prophylaxis.
• Healthcare providers should test their patients for HIV according to CDC recommendations,
talk with their patients who may be at risk for infection about available prevention options,
and work closely with their patients who have HIV to be sure they’re continuing to receive
the treatment they need, as well as risk reduction counseling on how to protect their
partners.

this study?
• Dr. Sidiqqi: Continuing to track trends in mortality moving forward would allow us to monitor
progress. Additionally, research into ways to successfully engage people with HIV in care and
to keep them on medication will have far-reaching consequences.
• Citation:
• Mortality Among Blacks or African Americans with HIV Infection — United States, 2008–
2012
• MMWR Weekly February6 2015

Insurance Study Evaluates Emergency Room Imaging For Low Back Pain
Erin R. Schlemmer, MPH Health Care Manager / Epidemiologist
Department of Clinical Epidemiology & Biostatistics
Blue Cross Blue Shield of Michigan
• MedicalResearch: What is the background for this study?
• Response: Low back pain (LBP) is a common reason for emergency department (ED) visits.
Usually, uncomplicated acute LBP is a benign, self-limited condition that can be managed
without the need for imaging studies. However, national data have shown that a substantial
proportion of ED patients with LBP receive imaging studies, and that the use of advanced
imaging has increased considerably for this population in recent years.
• A number of groups (including specialty societies, a consortium of health plan medical
directors, and an expert panel of emergency medicine physicians) have offered
recommendations for the appropriate use of imaging for Low back pain. Within these
guidelines, there are a number of “red flag” conditions that serve as indications for Low back
pain imaging, and it is generally accepted that most patients do not require imaging to inform
treatment of their Low back pain unless they have one or more red flags.
• Our objective was to use claims data from a large commercial insurer to describe the imaging
indications and imaging status of patients presenting to the ED with Low back pain, and to
describe demographic and healthcare use characteristics associated with non-indicated
imaging.

• MedicalResearch: What are the main findings?
• Response: We found that over half (51.9%) of all patients presenting to the ED with low back pain
had no claims-based evidence of indications for imaging. Overall, 36.5% of patients received
imaging, and 10.2% received advanced imaging (CT or MRI). Among patients with imaging
indications, the most common indication was trauma (71.6%), followed by cancer (24.0%).
Although nearly a third of non-indicated patients received imaging, this population had a lower
prevalence of imaging compared to patients with imaging indications (30.1% vs. 43.5%), and were
also less likely to have prior healthcare use (such as ED visits) in the past year. Among non-indicated
patients who received imaging, 26.2% received advanced imaging (CT or MRI) and 4.3% had >1 type
of imaging.
• Response: Over half of patients presenting to the ED with Low back pain in our study did not have
claims evidence of indications to receive imaging, suggestive of uncomplicated low back pain and
potentially-avoidable ED visits. Further, according to our data, over 70% of patients with non-
indicated imaging saw a PCP in the past year. Greater communication among PCPs, ED physicians,
and patients may help prevent unnecessary imaging for LBP or reduce patient demand for imaging.
• It is important to note that the generalizability of our findings is limited in that our study population
was restricted to commercially insured residents of Michigan. While BCBSM covers about 40% of
the commercially insured adults in Michigan and is representative of that population, results should
not be generalized to those with public insurance or the uninsured. In addition, patients with
commercial health insurance may be more likely to receive imaging because they have third party
coverage.

this study?
• Response: Administrative claims data can provide us with useful information about a
patient’s medical history, but it is important to keep in mind that claims do not provide a
complete medical record. Our ability to characterize indications for imaging is therefore
limited. An important next step will be to conduct chart review studies to determine how
closely claims data and patient medical records align regarding Low back pain diagnosis,
imaging, and imaging indications. In addition, although relatively few patients in our study
had observation/treatment room use, non-indicated imaging (particularly MRI) was very
common for these patients. Further work could examine imaging in the observation unit to
better understand its role in the treatment of low backpain.
• Citation:
• Imaging During Low Back Pain Emergency Department Visits – A Claims-Based Descriptive
Analysis
• Erin Schlemmer, MPH, ,
• James C. Mitchiner, MD, MPH ,
• Michael Brown, MD, MSc, ,
• Elizabeth Wasilevich, PhD, MPH
• The American Journal of Emergency Medicine Available online 31 December 2014

Twin Study Shows Physical Activity May Decrease Dementia Mortality
Paula Iso-Markku, MD,
Department of Clinical Physiology and Nuclear Medicine, HUS Medical Imaging Center,
Helsinki University Central Hospital and University of Helsinki Helsinki , Finland
• Dr. Iso-Markku : The social, financial and humane burden of the dementia is extensive as the
worldwide prevalence of dementia is estimated around 35.6 million. Finding efficient
prevention strategies for dementia is crucial. Within the past decade vascular risk factors
have been recognized as very potential risk factors of dementia. As physical activity is known
to affect vascular risk factors, it might also be a potential preventive tool against dementia.
Few comprehensive epidemiological studies on physical activity in middle age and dementia
occurrence later in life have been conducted.
• The comprehensive Finnish Twin Study offers a unique approach to the subjects as the
shared growing up environment and genes can be taken into account. The study population is
extensive and a good representation of the Finnish population. In this study the association
of physical activity in adulthood and dementia mortality was investigated in a 29-year follow-
up.
• The main finding in this study was that persistent vigorous (i.e. more strenuous than walking)
physical activity was significantly associated with lower dementia mortality. The results in the
paired analysis, comparing twins to co-twins, were similar but remained non-significant. The
analyses of the volume of physical activity were, however, controversial.

Twin Study Shows Physical Activity May Decrease Dementia Mortality
Paula Iso-Markku, MD,
Department of Clinical Physiology and Nuclear Medicine, HUS Medical Imaging Center,
Helsinki University Central Hospital and University of Helsinki Helsinki , Finland
• Dr. Iso-Markku : Late onset Alzheimer’s disease and vascular dementia cause the majority of
dementia cases. The risk profile in these diseases is similar to that of cardiovascular diseases;
smoking, type 2 diabetes, hypertension and dyslipidemia have been associated to greater
dementia incidence. Our gives additional evidence on that also physical inactivity is a risk
factor for dementia.
this study?
• Dr. Iso-Markku : The evidence of the association of physical activity and dementia remains
still scarce. More good quality research on physical activity precisely in midlife and dementia
incidence later in life is needed.
• Citation:
• Ann Med. 2015 Jan 22:1-7. [Epub ahead of print]
• Physical activity and dementia: Long-term follow-up study of adult twins.
• Iso-Markku P, Waller K, Kujala UM, Kaprio J.

Pregnant Flight Attendants May Have Increased Risk of Miscarriage
Barbara Grajewski, Ph.D., M.S., Epidemiologist Elizabeth Whelan, Ph.D., Branch Chief Christina Lawson, Ph.D., Epidemiologist
Division of Surveillance, Hazard Evaluations and Field Studies
National Institute for Occupational Safety and Health
Response: The study, published January 5 online ahead of print in the journal Epidemiology, looked
at potential workplace reproductive hazards for flight attendants. While in flight, flight attendants
are exposed to cosmic radiation from space and, periodically, can be exposed to radiation from
solar particle events. Flight attendants can also experience circadian disruption (disruption to the
body’s internal time clock) from traveling across time zones and from working during hours when
they would normally be asleep.
• For this study, we analyzed 840 pregnancies among 673 female flight attendants and examined
company records of 2 million single flights flown by these women. From these data, we estimated a
marker of circadian disruption—working during normal sleeping hours—and exposure to cosmic
and solar particle event radiation for each flight. This gives us a much more specific estimate of the
exposures these workers face on the job every day. We also assessed the physical demands of the
job, such as standing and walking for more than 8 hours a day and bending at the waist more than
25 times a day. Cosmic radiation and circadian disruption among flight attendants are linked very
closely on many flights and are very difficult to look at separately when trying to understand what
causes miscarriage. This is the first study that has attempted to separate these two exposures to
determine which is potentially linked to miscarriage. This study is also an improvement over other
studies in its assessment of cosmic radiation for each individual flight flown and from
documentation of solar particle events. Earlier studies have looked at how many years a flight
attendant has worked or other ways to estimate exposures that are not as specific.

Response: Working during normal sleep hours, exposure to cosmic radiation and high
physical job demands may put pregnant flight attendants at higher risk for miscarriage.
• Results indicated that flight attendants who flew more than 15 hours during normal sleep
hours in the first trimester were at increased risk for miscarriage. Analysis of exposure to
background cosmic and solar particle event radiation suggested that exposure to 0.1mGy or
more may be associated with increased risk of miscarriage. Solar particle events were
infrequent, but during one of the solar particle events studied, radiation dose reached 0.44
mGy on a single flight. These data suggest that if a pregnant flight attendant were to work on
a flight that travels through a solar particle event, she could be exposed to more radiation
than is considered safe during pregnancy. Finally, from a questionnaire administered to the
flight attendants, we found that early miscarriage (in the first trimester) was about 2 times as
likely for a pregnant flight attendant with high physical job demands compared to those
without high physical job demands.

• Response: Flight attendants may want to consult their healthcare professional about the
potential for occupational hazards if they are pregnant or considering pregnancy. Our results
may also apply to those women who fly frequently for business or pleasure.
• Information from this study supports the need for clearer guidelines and additional research
on potential reproductive risks for flight attendants.
this study?
• Response: It will take a larger study of pregnant flight attendants and rigorous exposure
assessment to get beyond our findings with better focus. It might be possible to improve the
study’s insights by adding biomarker and monitoring methods, such as sleep and light
monitors, which have come a long way in the last few years
• Citation:
• Miscarriage Among Flight Attendants
• Grajewski B, Whelan EA, Lawson CC, Hein MJ, Waters MA, Anderson JL, MacDonald LA,
Mertens CJ, Tseng C, Cassinelli RT, Luo L
• Epidemiology. 2015 Mar;26(2): 192–203.
• PMID: 25563432

Risk of Rehospitalization After Cardiac Admission Remain Elevated For Protracted Period
Kumar Dharmarajan MD MBA
Section of Cardiovascular Medicine
Yale University School of Medicine, New Haven, CT 06510
Dr. Dharmarajan: We know that patients are at high risk for rehospitalization and death in
the month after hospital discharge. Yet little is known about how these risks dynamically
change over time for the full year after hospitalization. This information is needed for
patients and hospitals to set realistic goals and plan for appropriate care.
• We found that the risk of rehospitalization and death decline slowly following hospitalization
and remain elevated for many months. We also found that specific risk trajectories vary by
discharge diagnosis and outcome. For example, risk remains elevated for a longer period of
time following hospitalization for heart failure compared with hospitalization for acute
myocardial infarction. For all 3 conditions we studied (heart failure, heart attacks, and
pneumonia), risk of rehospitalization remained elevated for a longer period of time than the
risk of death.
• Dr. Dharmarajan: Patients should remain vigilant for deterioration in health for an extended
time after hospitalization. Health providers can use knowledge of absolute risks and their
changes over time to better align interventions designed to reduce adverse outcomes after
hospitalization with the highest risk periods for patients.

Risk of Rehospitalization After Cardiac Admission Remain Elevated For Protracted Period
Kumar Dharmarajan MD MBA
Section of Cardiovascular Medicine
Yale University School of Medicine, New Haven, CT 06510
this study?
• Dr. Dharmarajan: We will need to understand what other factors impact long-term
trajectories of risk after hospitalization besides the admitting condition. We will also need to
figure out how to integrate this information into care plans to make them more efficient and
effective.
• Citation:
• Trajectories of risk after hospitalization for heart failure, acute myocardial infarction,
or pneumonia: retrospective cohort study
• BMJ 2015; 350 doi: http://dx.doi.org/10.1136/bmj.h411 (Published 06 February 2015) Cite
this as: BMJ 2015;350:h411

Optogenetics Pinpoint Neurons That Drive REM Sleep
MedicalResearch.com Interview with: Christa Van Dort PhD
Department of Anesthesia, Critical Care, and Pain Medicine, Department of Brain and Cognitive Sciences,
Picower Institute for Learning and Memory,
Massachusetts General Hospital, Harvard Medical School
Dr. Van Dort: Sleep is crucial for survival and maintenance of health. Inadequate sleep and sleep
disorders impair many brain and body functions such as executive function, the immune system
and memory consolidation. The benefits of sleep are dependent on normal sleep physiology and
patterns. Natural sleep is composed of non-rapid eye movement (NREM) sleep and rapid eye
movement (REM) sleep alternating every 90 min in humans. Each stage provides different benefits,
for example deep NREM sleep is associated with feeling rested and REM sleep is important for
learning. Current sleep aids do not effectively restore normal sleep physiology or timing and as a
result do not fulfill the important functions of natural sleep. To develop new strategies for
reproducing natural sleep, we aimed to understand each component of sleep (NREM and REM
sleep) individually and then in combination. Cholinergic neurons have been hypothesized to control
REM sleep for many years but no one had been able to test this directly due to limited
methodology. Optogenetics solved this problem by giving us the ability to activate selectively the
cholinergic neurons in the pedunculopontine tegmentum (PPT) and laterodorsal tegmentum (LDT).
• The primary finding of this study was that cholinergic neurons in the PPT and LDT are sufficient to
drive REM sleep from NREM sleep. These cholinergic neurons were important for initiation of REM
sleep but not the duration of REM sleep. Understanding REM sleep control is an important first step
in reproducing normal sleep patterns and by itself could enhance learning and memory.

Optogenetics Pinpoint Neurons That Drive REM Sleep
MedicalResearch.com Interview with: Christa Van Dort PhD
Department of Anesthesia, Critical Care, and Pain Medicine, Department of Brain and Cognitive Sciences,
Picower Institute for Learning and Memory,
Massachusetts General Hospital, Harvard Medical School
• Dr. Van Dort: The long term goal of this research is to apply sleep state control to humans so
that we can reproduce normal sleep patterns in people with insomnia and improve their
overall health. While it’s not possible to control REM sleep via optogenetics in humans yet,
this research lays the foundation for discovery of future treatments for insomnia by telling us
which cell types and brain regions are important to regulate REM sleep.
this study?
• Dr. Van Dort: Future studies that carefully examine the role of crucial brain regions in control
of NREM and REM sleep will provide key steps to reproduce natural sleep patterns in
humans.
• Citation:
• Optogenetic activation of cholinergic neurons in the PPT or LDT induces REM sleep
• Christa J. Van Dort,a,b,c,1 Daniel P. Zachs,a,b,c Jonathan D. Kenny,a,b,c Shu Zheng,b Rebecca R.
Goldblum,b,c,d Noah A. Gelwan,a,b,c Daniel M. Ramos,b,c Michael A. Nolan,b,c,d Karen Wang,b,c
Feng-Ju Weng,b,e Yingxi Lin,b,e Matthew A. Wilson,b,c and Emery N. Browna,b,d,f,1
• Proc Natl Acad Sci U S A. 2015 Jan 13; 112(2): 584–589.
• Published online 2014 Dec 29. doi: 10.1073/pnas.1423136112

Asthma in White and Hispanic Women May Increase Risk of Adverse Outcomes
Pauline Mendola, PhD, Investigator
Epidemiology Branch Division of Intramural Population Health Research
Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH
Dr. Mendola: Asthma is the most common chronic disease in pregnancy and both asthma
and maternal race/ethnicity are associated with adverse pregnancy outcomes. Since the
prevalence of asthma also varies by race/ethnicity, we wanted to assess whether asthma was
an important contributor to racial/ethnic disparities in pregnancy outcomes. We examined
the joint impact of maternal race/ethnicity and asthma status on the risk of obstetric and
neonatal outcomes.
• In general, maternal asthma did not impact the risk of obstetric and neonatal complications
within racial/ethnic groups. However, compared to mothers of the same race/ethnicity
without asthma, White and Hispanic asthmatic mothers were more likely to have infants born
small-for gestational age or admitted to the NICU. White women with asthma were also at
increased risk of preeclampsia and maternal hemorrhage and Hispanic mothers with asthma
were more likely to have infants with apnea. Despite their increased risk of maternal asthma
and neonatal and obstetric complications, maternal asthma did not impact the risk of
complications among Black women or their infants.

• Dr. Mendola: Our analyses suggest that asthma is not a strong contributor to racial/ethnic
disparities in adverse pregnancy and birth outcomes. This is very reassuring, particularly for
Black women who have both high rates of asthma and of adverse outcomes. Careful
management of asthma is important in pregnancy since the literature suggests this improves
obstetric and neonatal outcomes. White and Hispanic mothers with asthma appear to
experience higher risk for some of the outcomes we studied.

this study?
• Dr. Mendola: We did not have information on asthma treatment or severity. Given the high
prevalence of asthma in Black women, future research is needed to understand if our null
findings are a result of greater asthma monitoring during pregnancy or unmeasured
competing risks. Additionally, future studies should be more inclusive with respect to racial
and ethnic groups studied. Our data did not contain information on Hispanic or Asian/Pacific
Islander subgroups or countries of origin. Both asthma prevalence and birth outcomes vary
for many subgroups, so further work is needed to determine if asthma contributes to other
perinatal health disparities among those groups.
• Citation:
• Does maternal asthma contribute to racial/ethnic disparities in obstetric and neonatal
complications?
• Katrina F. Flores Candace A. Robledo Beom Seuk. Hwang Kira Leishear Katherine Laughon
Grantz Pauline Mendola
• Annals of Epidemiology Available online 30 January 2015

Study Addresses Health Insurance Needs of Homeless Young Adults
MedicalResearch.com
Hailey Winetrobe, MPH, CHES
Project Manager NIDA Transitions to Housing Study School of Social Work
University of Southern California
• Response: Homeless young adults are a very vulnerable population with high healthcare
needs. However, because of their housing instability and very low income, many homeless
young adults may not have health insurance and/or access to healthcare services. Prior
research regarding this population’s health insurance coverage was mostly outdated.
Additionally, with the implementation of the Affordable Care Act (ACA), homeless young
adults may now qualify for health insurance coverage (i.e., if there is a relationship, by being
a dependent on their parent’s health insurance until 26 years old; and via Medicaid
expansion in states choosing to expand). As such, this study aimed to update homeless young
adults’ rates of health insurance coverage prior to the full implementation of the ACA (i.e.,
before Medicaid expansion) and to determine if there was an association between insurance
and use of healthcare services.
• We found that 70% of homeless young adults did not have health insurance in the prior year.
Of those with health insurance, 46% reported coverage through their parents, and 34%
through Medicaid (not mutually exclusive). Over half (52%) of the sample received healthcare
in the prior year. Furthermore, in a multivariable logistic regression model controlling for
demographic characteristics, homeless young adults with health insurance, compared to
their peers who did not have health insurance, had 11 times the odds of receiving healthcare
in the prior year.

MedicalResearch.com
• Response: Clinicians and other healthcare providers should encourage homeless young adult
patients without health insurance to enroll in coverage, as insurance coverage is the only
factor that is associated with receiving care. Common sources of healthcare for this
population include emergency departments, community clinics, hospitals, and private
doctors’ offices. These facilities should have referrals in place to assist uninsured homeless
young adults to enroll in health insurance. Moreover, because homeless young adults often
have difficulties in accessing care, clinicians should treat each visit as an opportunity to
provide comprehensive healthcare services while being mindful of the barriers associated
with any potential follow-up care.

MedicalResearch.com
this study?
• Response: As this study was conducted prior to the full implementation of the ACA and in a
state that has now expanded Medicaid, new studies should investigate the health insurance
coverage of homeless young adults nationwide. It would be interesting to see how coverage
rates vary in states that have opted to expand Medicaid versus those that chose not to
expand. Future research may utilize medical records to examine the specific healthcare
services (e.g., preventive care, chronic care) that homeless young adults are obtaining and
how their health insurance (or lack thereof) may be impacting their receipt of services.
• Citation:
• Health insurance coverage and healthcare utilization among homeless young adults in Venice,
CA
• Winetrobe, E. Rice, H. Rhoades, and N. Milburn
• J Public Health first published online January 28, 2015 doi:10.1093/pubmed/fdv001

MOVE! VA Lifestyle Program Linked To Lower Diabetes Incidence
Dr Sandra L Jackson PhD
Atlanta VA Medical Center, Decatur, GA, Nutrition and Health Sciences,
Graduate Division of Biological and Biomedical Sciences
Dr. Jackson: Lifestyle change programs are aimed to improve health, yet little is known about
their impact once translated into clinical settings. The Veterans Health Administration (VA)
MOVE! program is the largest lifestyle change program in the U.S. Participation is a key
challenge of the program, as only 13% of the eligible population participated. However,
among patients who did not have diabetes at baseline, we found that MOVE! participation
was associated with lower diabetes incidence.
• Dr. Jackson: Findings such as ours, indicating benefits of participation in a lifestyle change
program, may encourage physicians to recommend the program more frequently and more
strongly, and may encourage patients to participate.

MOVE! VA Lifestyle Program Linked To Lower Diabetes Incidence
Dr Sandra L Jackson PhD
Atlanta VA Medical Center, Decatur, GA, Nutrition and Health Sciences,
Graduate Division of Biological and Biomedical Sciences
this study?
• Dr. Jackson: Based on our findings, reaching a broader proportion of the eligible population
may help VA patients better manage their weight and may lower diabetes incidence in the
VA. However, further research would be needed to evaluate whether the MOVE! program
remains associated with benefits, as it grows to reach more of the population.
• Citation:
• Weight loss and incidence of diabetes with the Veterans Health Administration MOVE!
lifestyle change programme: an observational study
• Dr Sandra L Jackson, PhD Qi Long, PhDc,Mary K Rhee, MDa, e,Darin E Olson, MDa, e,Anne M
Tomolo, MDa, e,Solveig A Cunningham, PhDd,Prof Usha Ramakrishnan, PhDd,Prof K M Venkat
Narayan, MDd, Lawrence S Phillips, MDa, e
• The Lancet Diabetes and Endocrinology Available online 2 February 2015

Many Women Exceeding Gestational Weight Gain Recommendations
Jonetta L. Johnson, PhD, MPH
Epidemiologist
Division of Reproductive Health, CDC.
Dr. Johnson: Achieving adequate gestational weight gain (GWG) is important for optimal health of the
infant and mother. Women who gain below or above Institute of Medicine (IOM) recommendations are
more likely to experience maternal complications and negative infant birth outcomes. Realizing the
importance of gestational weight gain to maternal and infant health, the IOM established
recommendations for gestational weight gain based on a woman’s prepregnancy body mass index (BMI)
in 1990 and updated them in 2009. Trends in GWG are particularly of interest since prepregnancy BMI has
increased over time in the U.S and little data was available on how gestational weight gain has changed
over time.
Dr. Johnson: Our findings show that from 2000-2009, the majority of women did not gain weight within
IOM GWG recommendations and that women were more likely to gain outside recommendations in more
recent years. In fact, from 2000–2009, there was a gradual decrease (1.0 percentage point every 2 years)
in women gaining within IOM gestational weight gain recommendations and a gradual increase (0.8
percentage points every 2 years) in women gaining above IOM recommendations while the percentage of
women gaining weight below IOM recommendations remained relatively constant. Although there were
slight differences in mean gestational weight gain by BMI group, gestational weight gain was about 31
pounds on average. The decreasing percentage of women gaining within IOM recommendations during
our study period may be influenced by increases in prepregnancy BMI during the same time period
because women in higher BMI groups are recommended to gain less weight during pregnancy compared
to women in lower BMI groups. Thus, even with no change in gestational weight gain over time, an
increase in the proportion of women who are obese could result in a decrease in the proportion of women
gaining within gestational weight gain recommendations.

Epidemiologist
Dr. Johnson: Our study is the first to report gestational weight gain trends by obesity class
and to examine trends adjusted for demographic and health characteristics. Our results
demonstrate the need for more efforts to encourage and support women to enter pregnancy
at a healthy weight and gain within gestational weight gain recommendations. Although
surveys of obstetrician/gynecologists’ practices suggests that the majority counsel pregnant
women on gestational weight gain and nonpregnant women on weight control, these efforts
may not be sufficient. To help women achieve appropriate gestational weight gain, the IOM
has developed an evidence-based toolkit to help clinicians and pregnant women track and
meet weight gain goals (www.iom.edu/whattogaintoolkit).
• Enhanced cultural and social sensitivity training may be needed to improve communication
on weight gain during pregnancy. Increased public awareness of the consequences of excess
weight gain during pregnancy may also improve the effectiveness of gestational weight gain
counseling. Current 2009 IOM gestational weight gain recommendations for total weight gain
during pregnancy include: underweight women (<18.5 kg/m²) 28-40lbs, normal weight
women (18.5-24.9 kg/m²) 25-35lbs, overweight (25.0-29.9 kg/m²) women 15-25lbs and
obese women (≥30.0 kg/m²) 11-20lbs.

Epidemiologist
• Healthy lifestyle recommendations for pregnant women which may help with gestational
weight gain within recommendation include:
• Diet
• o Pregnancy does not equate to eating for two. The first trimester does not require any
extra calories. In general for all women, to meet the metabolic needs of pregnancy, women
need an additional 340 calories per day during the second trimester and 450 calories per day
during the third trimester.
• o Women should be encouraged to eat a balanced diet with an increase in fruits and
vegetables and to limit intake of added sugars and solid fats in foods like soft drinks, desserts,
fried foods, cheese, whole milk, and fatty meats.

Epidemiologist
• Physical Activity
• o Women should get at least 150 minutes per week of moderate-intensity aerobic activity
during and after pregnancy.
• o Healthy women who already engage in vigorous-intensity activity, such as running, can
continue doing so during and after pregnancy provided they stay healthy and discuss with
their health care professionals how and when activity should be adjusted over time.

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