Epidemiology 2015

FROM THE DEPARTMENT OF EPIDEMIOLOGY 2015 ANNUAL REPORT MAILMAN SCHOOL OF PUBLIC HEALTH – COLUMBIA UNIVERSITY Guohua Li, DrPH, MD Interim Chair Department of Epidemiology

EDITORS Barbara Aaron Administrative Director

Kathryn Gerlach Assistant Manager for Communications

CONTRIBUTING EDITOR/WRITER Dana March, PhD Assistant Professor of Epidemiology Editor-in-Chief, the 2x2 project

CONTRIBUTING WRITERS Emily Augustini Communication in Health and Epidemiology Fellow MPH Student; Class of ‘16

Prativa Baral Communication in Health and Epidemiology Fellow MPH Student; Class of ‘16

Stephanie Berger Director of Communications for Media Relations, Mailman School of Public Health

Elaine Meyer Timothy S. Paul Associate Director for Strategic Communications, Science Editor, Mailman School of Public Health

Amy Schellenbaum Freelance Health Writer

DESIGNER Kristen Byers Web Developer / Graphic Designer table of contents

Research highlights Features

4 New clues into cognitive dysfunction in chronic 16 Ending publication bias fatigue syndrome 21 Tuberculosis through the looking glass 5 People conceived during Dutch famine have altered regulation of growth genes 28 Gentrification and public health: Opportunities and challenges in change 6 Seals harbor Hepatitis A-like virus

7 Anxious? depressed? Blame it on your middle- Symposium reports management position 33 The vaccine conundrum 8 The law of epidemics: Heroin, prescription 35 Injury control through collaboration painkillers, and the addiction dilemma

10 As America inhales, scientists raise health concerns Epidemiology by the numbers

12 Children of older parents and May–December 38 Selected faculty awards couples at increased risk for autism 39 Recent alumni statistics

Databytes 40 Global reach 13 Relative risk for autism spectrum disorder by joint paternal and maternal age Bibliography

14 Spotty on measles? 42 Faculty publications

1 letter from the chair

Colleagues,

It is my great pleasure and distinct honor to present the 2015 Annual Report of the Department of Epidemiology. This past year was the most productive year in the history of our Department, with over 800 peer- reviewed articles published by our faculty in the first ten months alone. While we cannot do justice to this extraordinary volume of research in these pages, we hope to provide, through a few examples, a snapshot of the scientific advances and their impact on public health made by our stellar faculty.

In 2015, we explored how gentrification affects population health in communities, elucidated how famine exposure can change gene regulation, and delved deeper into the etiology of autism spectrum disorders. We looked under the hood at how publication bias in clinical trials limits the availability of critical data. We examined the broad health consequences of marijuana’s growing ubiquity, and the deadly opioid epidemic that touches every walk of life and every community in the United States.

Our faculty engaged in research around the globe and garnered numerous notable awards. And the value of our master’s and doctoral degree programs was once again borne out by our graduates’ robust employment statistics.

The arrival of the New Year brings a new journey. Among the many exciting academic programs we have planned for 2016 is a year-long seminar series on the future of epidemiology. This special seminar series will engage our faculty and students in a vigorous discussion about the challenges and opportunities facing our field and help us to forge a shared vision and roadmap for ensuring our Department’s successful transformation and continuing growth in the years to come.

Sincerely yours,

Guohua Li, MD, DrPH Finster Professor and Interim Chair

3 research highlight

esearchers in epidemiology have Implications for diagnosis and identified a unique pattern of treatment Rimmune molecules in the cere- brospinal fluid of people with myalgic “Diagnosis of ME/CFS is now based encephalomyelitis/chronic fatigue on clinical criteria. Our findings offer syndrome (ME/CFS) that provides the hope of objective diagnostic tests insights into the basis for cognitive for disease as well as the potential for dysfunction—frequently described by therapies that correct the imbalance patients as “brain fog”—as well as new in cytokine levels seen in people with hope for improvements in diagnosis ME/CFS at different stages of their and treatment. disease,” says Dr. W. Ian Lipkin, John In the study published in Molecu- Snow Professor of Epidemiology and lar Psychiatry, Dr. Mady Hornig, and director of the Center for Infection and colleagues used immunoassay test- Immunity. ing methods to measure levels of 51 There is precedent for use of immune biomarkers called cytokines human monoclonal antibodies that in the cerebrospinal fluid of 32 people regulate the immune response in with ME/CFS for an average of seven a wide range of disorders from years, 40 with multiple sclerosis, rheumatoid arthritis to multiple scle- and 19 non-diseased controls. The rosis. However, the researchers note, researchers found that levels of most additional work will be needed to cytokines, including the inflammatory assess the safety and efficacy of this immune molecule interleukin 1, were approach. depressed in individuals with ME/CFS compared with the other two groups, Hornig M, Gottschalk G, Peterson DL, Knox matching what was seen in a blood KK, Schultz AF, Eddy ML, Che X, Lipkin WI. study in patients who had the disease Cytokine network analysis of cerebrospinal for more than three years. One cyto- fluid in myalgic encephalomyelitis/chronic New clues kine—eotaxin—was elevated in the fatigue syndrome. Mol Psychiatry. 2015 Mar ME/CFS and MS groups, but not in the 31. doi: 10.1038/mp.2015.29. [Epub ahead of into cognitive control group. print] PubMed PMID: 25824300. “We now know that the same dysfunction in changes to the immune system that we recently reported in the blood of chronic fatigue people with ME/CFS with long-stand- ing disease are also present in the syndrome central nervous system,” says Dr. Hornig, professor of epidemiology and director of translational research at the Center for Infection and Immunity at the Mailman School. “These immune related media coverage differences may contribute to symp- toms in both the peripheral parts of Yahoo Health the body and the brain, from muscle yhoo.it/1MxQ8aI weakness to brain fog.”

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ndividuals conceived in the severe development showed a different gene Dutch Famine, also called the Hunger activity setting. The Hunger Winter chil- IWinter, may have adjusted to this dren were all approximately 60 years horrendous period of World War II of age when they gave blood for DNA by making adaptations to how active research. their DNA is. Genes involved in growth “The potential for a gene to become and development were differentially active is mainly determined in the regulated, according to researchers at crucial weeks after fertilization. This the Leiden University Medical Center, master regulatory system that deter- Harvard University, and Columbia mines which genes are on and which University’s Mailman School of Public are off is called epigenetics and can be Health. Findings are published in the compared to a sound technician making journal Nature Communications. adjustments during a recording to get During the winter of 1944–1945 the that perfect sound. Environmental fac- Western part of The Netherlands was tors during development can make a struck by a severe 6-month famine, the lasting imprint on this system,” says Dr. result of a German blockade. During Heijmans. this Hunger Winter the available rations The authors point out that a wealth provided as low as a quarter of the of past epidemiological studies daily energy requirements. Children suggests that early development is conceived—but not born—during the important for later health. “Thanks to famine were delivered with a normal the willingness of the Hunger Winter birth weight. Extensive research on the children and their families to contribute DNA of these Hunger Winter children to our studies, we can pinpoint which shows that the regulatory systems of phases of development are especially their growth genes were altered, which sensitive to the environment. We are may also explain why they appear to be currently extending our inquiries not at higher risk for metabolic disease in only to those conceived during the People conceived later life. famine, but also to those exposed during other gestation periods,” says Decades later growth genes during Dutch co-author Dr. Elmar W. Tobi. seemed different “These findings are exciting and famine have “The different setting of the growth provide tremendous opportunities for genes may have helped the Hunger epidemiologists,” says Dr. L.H. Lumey, altered regulation Winter children to withstand the Famine associate professor of epidemiology at conditions as compared with their unex- Columbia University’s Mailman School of growth genes posed siblings, but these changes may of Public Health and senior author who likewise be unfavorable for their metab- collected the analyzed blood samples. olism as adults,” says Leiden University “Looking at the human genome we see principal investigator Dr. Bas Heijmans. systematic changes in gene regulation For example, the altered settings were during early human development in associated with LDL cholesterol at age response to the environment. The epi- 60, according to the authors. genetic revolution has given us the tools The research team in Leiden com- to investigate these changes and look at pared the DNA of the Hunger Winter the impact for later life.” children, now aged 60, at 1.2 million CpG methylation sites comparing them Tobi EW, Goeman JJ, Monajemi R, Gu H, with same-sex siblings not exposed Putter H, Zhang Y, Slieker RC, Stok AP, Thijssen to famine. They were able to see how PE, Müller F, van Zwet EW, Bock C, Meissner the genes were differentially regu- A, Lumey LH, Slagboom PE, Heijmansa BT. lated in the Hunger Winter children, DNA methylation signatures link prenatal as compared with their siblings with a famine exposure to growth and metabolism. similar genetic and familial background. Nat Commun. 2014 Nov 26. doi: 10.1038/ Groups of genes involved in growth and ncomms6592. [Epub ahead of print]

DEPARTMENT OF EPIDEMIOLOGY 5 research highlight

cientists in the Center for there is no evidence that it causes Infection and Immunity at them any harm. However, they cau- SColumbia University’s Mailman tion that further research is needed School of Public Health have in mature seals, because if it acts discovered a new virus in seals that anything like hepatitis A it might only is the closest known relative of the cause disease in adults. human hepatitis A virus. The finding In the natural history of phopivirus provides new clues on the emergence and hepatitis A, it is unclear whether a of hepatitis A. The research appears common ancestor (virus) spilled over in the July/August issue of mBio, the from humans to seals, vice versa, or online open-access journal of the from a third unrelated host that has not American Society for Microbiology. yet been identified. The researchers “Until now, we didn’t know that next plan to look at species that have hepatitis A had any close relatives, close interactions with seals to see if and we thought that only humans and they can find other wildlife reservoirs other primates could be infected by of hepatitis A-like viruses. “Coyotes such viruses,” says lead author Dr. regularly scavenge dead seals along Simon Anthony, assistant professor of the coast, so it would be very interest- epidemiology at Columbia. ing to examine coyotes to see if they Hepatitis A viral infection, which have any similar viruses,” says Katie impacts 1.4 million people worldwide Pugliares, a senior biologist at the New annually, can cause mild to severe England Aquarium in Boston who was illness. It is a highly contagious dis- also involved in the study. Another ease that is usually transmitted by project might study humans who eat the fecal-oral route, either through seal meat to see if the seal virus has person-to-person contact or through ever spilled over. consumption of food or water. “Our data The vast majority of emerging suggest that hepatitis A and this new infectious diseases in humans have Seals harbor virus share a common ancestor, which origins in wildlife. In recent years, sci- means that a spillover event must have entists in the Center for Infection and hepatitis A-like occurred at some point in the past,” Immunity led by Dr. Simon Anthony says Dr. Anthony. “It raises the ques- have been working with partners at virus tion of whether hepatitis A originated the EcoHealth Alliance, University of in animals, like many other viruses that California Davis, and others under the are now adapted to humans.” auspices of the United States Agency The researchers discovered the for International Development’s PRE- related media coverage new virus while investigating a deadly DICT program to identify potential strain of avian influenza that killed over zoonotic viral threats to human health. NBC News 150 harbor seals off the coast of New “Our goal”, says Dr. W. Ian Lipkin, nbcnews.to/1LvCHXY England in 2011. In an effort to deter- director of the Center and John Snow mine what viruses might co-occur with Professor of Epidemiology, is “to try Infection Control Today influenza, researchers performed deep to understand drivers of infectious bit.ly/1Nh9tOb sequencing of all the viruses present disease emergence thereby enhancing in three of the marine mammals. They pandemic preparedness.” Drug Development & Discovery discovered a new virus that was genet- bit.ly/1VBG8NN ically similar to hepatitis A and named Anthony SJ, St Leger JA, Liang E, Hicks AL, it phopivirus. An analysis of additional Sanchez-Leon MD, Jain K, Lefkowitch JH, animals living off the coast of New Navarrete-Macias I, Knowles N, Goldstein England (29 harbor seals, 6 harp seals T, Pugliares K, Ip HS, Rowles T, Lipkin WI. and 2 grey seals) identified phopivirus Discovery of a Novel Hepatovirus (Phopivi- in 7 more animals. The researchers say rus of Seals) Related to Human Hepatitis A the virus appears to be fairly common Virus. MBio. 2015 Aug 25;6(4). pii: e01180-15. in seals based on the juvenile animals doi: 10.1128/mBio.01180-15. PubMed PMID: examined for their study, and so far 26307166.

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ndividuals near the middle of the Disorder and Associated Disabilities social hierarchy suffer higher rates Interview Schedule was used to assess Iof depression and anxiety than those DSM-IV psychiatric disorders. at the top or bottom, according to The researchers estimated the researchers at Columbia University’s prevalence and odds of any lifetime Mailman School of Public Health. and previous 12-month depression Nearly twice the number of super- and anxiety by occupational class visors and managers reported they categories, income, and education. suffered from anxiety compared to Class designations were made by workers. Symptoms of depression sorting respondents into three cat- were reported by 18 percent of super- egories: owners, who identified as visors and managers compared to self-employed and earned greater than 12 percent for workers. Findings are $71,500; managers and supervisors, online in the journal Sociology of who occupied executive, adminis- Health & Illness. trative or managerial positions; and While social disadvantage related workers, who were defined by various to income and educational attain- occupation categories in the NESARC ment is associated with a higher risk including farmers and laborers. of most adverse mental health out- “We chose to focus on depression comes, these latest findings show that and anxiety because the average age people towards the middle of social of onset is older than age 18, and hierarchies suffered higher rates of these disorders are likely to arise after depression and anxiety based on their entry in the workforce,” says Dr. Kath- social class and position of power in erine Keyes, assistant professor of the labor market. epidemiology. “Contradictory class locations are Prior research has shown that work those that embody aspects of both stress and job strain are important Anxious? ownership and labor, and using this risk factors in developing depres- construct we found patterns of depres- sion. Workers with little opportunity depressed? sion and anxiety that are not easily for decision-making and greater job detected or explained with standard demands show higher rates of depres- Blame it on approaches,” says first author Seth sive symptoms. J. Prins, MPH, a doctoral student in “Our findings highlight the need your middle- epidemiology at the Mailman School for population health research to of Public Health and fellow in the both conceptualize and measure management Psychiatry Epidemiology Training social class in ways that go beyond Program. “We explored how social the standard measures of socioeco- position class might influence depression and nomic status,” says Dr. Lisa M. Bates, anxiety in ways that may be masked assistant professor of epidemiology, or incompletely explained by standard “Standard measures are most readily socioeconomic status measures.” available, but can mask important related media coverage The researchers based their find- complexity in the relationship between ings on the largest representative social class and population health.” The Atlantic population data set ever used to test theatln.tc/1JsDkyJ these hypotheses directly: the 2001– Prins SJ, Bates LM, Keyes KM, Muntaner C. 2002 National Epidemiologic Survey Anxious? Depressed? You might be suffering Washington Post on Alcohol and Related Conditions from capitalism: contradictory class locations wapo.st/1MDjzXC (NESARC), a nationally representative and the prevalence of depression and anxiety survey of the U.S. population age 18 in the USA. Sociol Health Illn. 2015 Aug 3. ScienceDaily and older, interviewed in person. This doi: 10.1111/1467-9566.12315. [Epub ahead of bit.ly/1NDlyJX study used data on the 21, 859 partici- print] PubMed PMID: 26385581. pants who were full-time workers. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) Alcohol Use

DEPARTMENT OF EPIDEMIOLOGY 7 research highlight

rug abuse spreads within a for controlled substances. They’re community, sometimes quickly. designed to make it more difficult DIt devastates. And it kills. for patients to shop around, getting But unlike diseases such as HIV or multiple doctors to prescribe opioid Ebola, drug abuse is not, technically, painkillers or using multiple pharma- infectious. cies to fill a single prescription. (Some So, is talking about an epidemic of states even make the information drug abuse—the surge in opioid and available in neighboring states, to pre- heroin abuse reported this summer by vent a New Yorker, for example, from the Centers for Disease Control and scoring a duplicate prescription in Prevention, for example—just a sloppy New Jersey or Connecticut.) metaphor? Or can we actually use epi- Meanwhile, drug companies have demiological tools to predict its course been reformulating opioid painkill- and figure out ways to stop it? ers to make them harder to abuse. Epidemiologist Dr. Guohua Li thinks And increasing access to overdose we can. According to Farr’s law, infec- treatment—by having police carry the tious outbreaks follow a predictable antidote naloxone, for example—has and symmetrical path—a steady rise in helped. cases to a peak, followed by a decline. But, as the fairy tales caution, The 19th-century model has been beware what you wish for. The current applied to cattle plague, smallpox, heroin epidemic is a result, at least in even the aids epidemic. In a January some measure, of the success states article in the journal Injury Epidemi- have already had in limiting access to ology, Dr. Li, the Finster Professor of opioid painkillers. As pharmaceuticals Epidemiology, and his research team become less accessible, people turn to applied it to drug use in the United heroin. “We call this the substitution States. If Dr. Li’s resulting predictions effect,” Dr. Li says. “It’s going to make The law of are correct, the number of drug over- control of this drug overdose epidemic doses will keep rising until 2017, then more challenging.” epidemics: begin to fall. “One of the contentious Between 2002 and 2013, the points,” he says, “is to apply Farr’s law number of people in the U.S. dying Heroin, to a noninfectious epidemic like opioid from heroin overdose quadrupled. abuse.” As with infectious diseases, And in 2013, more than half a million prescription he says, environmental factors play Americans said they had used heroin a part in drug abuse trends. Addic- in the past year, an increase of almost painkillers, and tion—like other “social contagions” 150 percent from 2008. such as behavioral disorders and obe- It’s gotten so bad that, in the last the addiction sity—spreads through social networks, three years, drug overdose has been much like a pathogenic outbreak. If overtaking motor vehicle crashes as dilemma his projections are borne out, says Dr. the leading cause of accidental death Li, they “may help to gauge whether in the U.S.; in 34 states, it already has. interventions are working and guide For Dr. Li, much of whose earlier work long-term planning and management focused on traffic injuries, turning his of public health resources and preven- attention to drug abuse and preven- tion efforts.” tion was a logical shift. And, he points In the last two years, the increase out, there is even overlap between the in overdoses of opioid painkillers— two, since driving under the influence Demerol, Dilaudid, Vicodin, and the is (obviously) dangerous. like—has begun to slow, likely because Beyond vehicular risks—public multiple ongoing interventions are health scholars know them as “unin- starting to work. Prescription monitor- tentional injury mortality”—opioid ing programs, as the name suggests, injection poses additional hazards. are statewide databases that track the Heroin use has been implicated in the dates and details of all prescriptions spread of HIV, hepatitis C, and other

8 2015 ANNUAL REPORT blood-borne diseases. Earlier this year, for psychological problems, rather than the governor of Indiana declared a public trying to self-medicate. (In another study, Then there’s the question of how people health emergency in rural Scott County published in Psychological Medicine, Dr. end an addiction. Only a small number of after health officials there noticed a surge Martins documented a higher incidence of those with a drug problem seek treatment, in the number of new HIV infections tied to opioid drug use among people with mental says Dr. Martins. Others just quit using on intravenous use of opioid painkillers. The illnesses like bipolar disorder and anxiety their own. Certainly, we need monitoring county had already recorded an increase in and mood disorders.) programs and other interventions to avert hepatitis C and endocarditis, an infection Equally important, Dr. Martins says, overuse and addiction. But that won’t be of the lining of the heart that can be spread is targeting the right audience with those enough. “It’s complicated,” she says. “We through the use of dirty needles. The gov- drug abuse prevention programs. Many need policies to regulate this, but we also ernor, who had previously been opposed to universities emphasize the dangers of need to make sure that people who need harm reduction programs, quickly stepped opioid abuse in their drug prevention pro- medications can get them.” in to implement a temporary needle grams. Dr. Martins’ study published last Regardless how difficult the work may exchange program. year in Social Psychiatry and Psychiatric be, says Dr. Li, public health has a duty to Given the geographic concentration of Epidemiology showed that people who help turn the tide. “A decline in overdose the painkiller abuse, the intervention focused don’t have a college education are more deaths shouldn’t be used as justification to narrowly on Scott County. That approach likely than those with a degree to abuse pull back,” he says. “That would be wrong. exemplifies one of the first steps in figuring opioid painkillers. It would probably be If there is no intervention, then the epi- out how to stop an epidemic: Understand more effective, she says, to find ways to demic will last much longer. who’s involved. Dr. Silvia Martins, associate engage a non–college educated audience professor of epidemiology, uses data from to talk about opioid drug abuse and per- the federal government’s National Survey haps refocus college programs to address on Drug Use and Health to analyze who is stimulants, which her studies show are a using opioid painkillers and heroin and how bigger problem among people with a col- those patterns have changed over the last lege education. few years. The U.S., Dr. Martins says, has the In a report this year for Drug and Alco- highest rate of opioid painkiller use in the hol Dependence, Dr. Martins documented world; medical professionals here use the critical differences in drug abuse across drugs not just to manage the extreme pain racial and other lines. Between 2002 and caused by, say, cancer but also to manage 2011, for example, heroin use rose 75 per- much less serious complaints, like the dis- cent among non-Hispanic whites. Among comfort following a tooth extraction. blacks, on the other hand, use increased So healthcare providers and policymak- Certainly, only among those who had taken opioid ers will have to do their part. This summer, painkillers within the prior year, particularly the U.S. Senate debated the Safe Prescrib- we need those who had used them frequently—at ing of Controlled Substances Act, which least once daily for between 100 and 365 would impose new continuing education monitoring days. “We need to better delineate who is requirements on prescribers (already at higher risk,” Dr. Martins says, and target required in New York and nine other programs prevention programs to those populations. states), while the White House boosted That means updating old-fashioned training for federal healthcare providers. and other “Just Say No”–style drug abuse prevention At the state level, prescription monitor- programs to promote harm reduction, the ing programs vary widely. While 49 states interventions drug use equivalent of teaching safe sex have laws in place, Missouri legislators rather than abstinence only. have wrangled for years over compet- to avert In an age of Google and the increased ing bills. Nationwide, Dr. Martins sees information—and misinformation—the room for improvement. Physicians could overuse and internet affords, we need comprehensive inquire about prior drug use and mental public education, Dr. Martins says. With health history, for example, to identify addiction. But prescription drugs, that means explaining patients for whom opioids might become not only the benefits of the medication but a problem, then monitor those individuals that won’t be also its side effects, not stigmatizing pre- more closely or offer them alternatives scription opioid use, and reminding people such as physical therapy or non-narcotic enough. that it’s important to get professional help painkillers.

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IMAGE: DIANA GAZZIA

arijuana is going mainstream. of teenagers, published by Dr. Hasin As America So far, 23 states have legal- in Lancet Psychiatry, found teen use Mized medical use of the drug of pot was elevated in states with or effectively decriminalized it. Ohio medical marijuana laws, but because inhales, scientists recently voted against legalization, the rates of use were higher in these but another 17 states will consider the states before they even passed the raise health issue next year. As laws and societal laws, some other factor seems to be mores around marijuana are rewritten, responsible for both the higher rates concerns public health scientists at the Mail- of use and the laws. man School are taking a close look at As director of the Substance a range of issues, from who is using Dependence Research Group at the it and how widely to its long-term New York State Psychiatric Institute, consequences. Dr. Hasin sees considerable evidence Epidemiology professor Dr. Debo- that using marijuana involves some rah Hasin has written more than 350 risk. “Our studies show there are dan- papers on the epidemiology of drug gers from using marijuana,” she says. and alcohol use disorders. In October, “Others have shown lasting impair- she published a study in JAMA Psy- ments in brain functioning among chiatry finding marijuana use among adolescents who are heavy, regular adults more than doubled between users, while adults with marijuana use 2001 and 2012. The numbers of people disorders show impairments across diagnosed as abusing the drug or various areas of functioning.” dependent on it also climbed, reaching Dr. Silvia Martins, associate profes- nearly 7 million, or nearly three in ten sor of epidemiology, points to a wealth users. Was legalization of marijuana of data on the health risks of regular for medical purposes a factor? Among marijuana use. Using it this way over one group, at least, it wasn’t. A study the long-term is associated with

10 2015 ANNUAL REPORT reduced IQ, and with hallucinations, Driving high Regular schizophrenia, and major depression, particularly if adults started using it It’s well known that alcohol and and heavy heavily as teenagers. “Research shows automobiles are a deadly combination. that about one in eleven users can According to the Centers for Disease marijuana use become addicted,” she says. “Regu- Control, almost 30 people in the United lar and heavy marijuana use during States die in motor vehicle crashes that during the the adolescent years can affect brain involve an alcohol-impaired driver development and may reduce thinking, every day. What about pot? While adolescent memory, and learning.” driving under the influence of marijuana Some of us are more attune to the is illegal no matter what state you live years can risks than others. A study by Dr. Mar- in, growing numbers of marijuana users tins published in Drug and Alcohol are getting behind the wheel. affect brain Dependence earlier this year found In an analysis of toxicology reports women were twice as likely to see from fatal car accidents published in development regular use of cannabis as potentially the American Journal of Epidemiol- harmful, although that number had ogy, Dr. Guohua Li, Finster Professor and may dropped from 59 percent in 2002 to 27 of Epidemiology and Anesthesiology, percent in 2012. found that one in eight drivers tested reduce positive for the drug—up three-fold What Is the evidence for medical from a decade ago. A study published marijuana? thinking, in the journal Accident Analysis & Three-quarters of Americans favor Prevention, found that relative to memory, and using marijuana for medicinal drivers who tested positive for neither purposes. Many in the medical com- alcohol nor drugs, the odds of a fatal learning. munity too favor its use for pain, as crash climbed 13-fold for drivers test- muscle relaxer, appetite enhancer, and ing for alcohol alone, but 24 times for for other reasons. Yet there has been those positive for both alcohol and very little careful research to back marijuana. Whether or not the driver up this and other potential upsides. was high was unknown—marijuana “We see segments on the news about lingers in the system for days—but it children with epilepsy showing tre- does point to the fact that the driver mendous improvement from taking uses marijuana. In the future Dr. Li the drug,” says Dr. Hasin. “Yet while it says, a breathalyzer-type device might does help some, it could harm others, provide more accurate information on and we still need rigorous studies intoxication. and data to guide our decisions about But the notion that alcohol is more medical marijuana.” dangerous than marijuana should One significant hurdle to research: be subjected to rigorous scrutiny marijuana is still classified as a and requires important qualification, Schedule I drug. This could change. argues Dr. Li. “Although alcohol is Recently presidential hopeful Hillary more addictive and more impairing to Clinton echoed the sentiment of the cognitive functions than marijuana, American Medical Association by moderate alcohol consumption may saying she would like to see marijuana confer significant health benefits,” he reclassified so it can be more easily says. Whether marijuana has a similar studied. “I want to move from Sched- upside remains to be seen. And there ule 1 to Schedule 2 so researchers can is always potential for its misuse. Says research what’s the best way to use it, Dr. Li, “There is no such thing as safe dosage, and how it works with other substance abuse, regardless of the medications,” she says. drugs involved.”

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Drs. Ezra Susser, professor of mothers were 25-35 years old, fathers epidemiology and psychiatry; Michae- were 29-39 years old, and the parents Children of older line Bresnahan, assistant professor were closely matched in age. of epidemiology; and Mady Hornig, “Comparing fathers and mothers parents and associate professor of epidemiology over the same age range, the RRs [rel- and Director of Translational Research ative risks] with advancing age were May–December of the Center for Infection and Immu- of similar magnitude,” the authors say nity at Columbia’s Mailman School of in the article. This “. . . suggests that couples at Public Health, analyzed data from more advancing paternal age may contrib- than 5.7 million children born in Israel, ute more to the risk than advancing increased risk for Western , Denmark, Norway, maternal age overall, due to the longer and Sweden between 1985 and 2004. male child-bearing potential.” autism Children born to older parents or to In other words, advancing maternal couples who differ in age by ten years age and paternal age both increase chil- or more appear to be at an increased dren’s risk for autism, but because men risk for autism spectrum disorders are fertile longer than women, older related media coverage (ASD), according to a largest-of-its- dads may actually contribute more to kind, multinational study in Molecular overall autism risk than older moms. Medical News Today Psychology. In Denmark, Norway, and Sweden bit.ly/1F6zeXn “This is the first major result from (but not in Israel or Western Australia), a historic collaboration among epide- the association between mother’s age miologists that combines registry data and child’s autism risk was U-shaped: from many countries to study autism Teen moms were, much like older spectrum disorders,” says Dr. Susser. moms, more likely to give birth to chil- Obtaining and analyzing data dren with autism. The “safest” age for from millions of children allowed the giving birth among women in these researchers to ask important questions Scandinavian countries was just over about parental age and children’s rela- 30 years old. tive risk for autism that were, until now, The study “. . . raises a number of impossible to examine. new puzzles for future research,” says “Since maternal and paternal age Dr. Susser. tend to be highly correlated, very large No previous research has been numbers are required to clearly differ- able to examine autism trends in such entiate their effects,” says Dr. Susser. great detail. This article provides new Using this extremely large data set, directions for scholarly inquiry on the the researchers separated out the influ- subject of parental age and children’s here is a substantial body of ence of mother’s age versus father’s autism risk. research associating paren- age, while adjusting for the potential Ttal age with autism spectrum influence of the other parent’s age. Sandin S, Schendel D, Magnusson P, Hul- disorders, although not all studies Results show that “older maternal tman C, Surén P, Susser E, Grønborg T, agree with each other and it has age and paternal age at conception are Gissler M, Gunnes N, Gross R, Henning M, been a challenge to pinpoint the each independently related to the risk Bresnahan M, Sourander A, Hornig M, Carter shape of the relationship. A recent of ASD,” says Dr. Susser. K, Francis R, Parner E, Leonard H, Rosanoff study co-authored by epidemiology Kids born to older moms, older M, Stoltenberg C, Reichenberg A. Autism faculty members sheds new light on dads, or parents who differ in age by risk associated with parental age and with the nature of the risk relationship by a decade or more had an elevated risk increasing difference in age between the examining the ages of both parents to for autism. parents. Mol Psychiatry. 2015; Figure 3, determine if paternal age and maternal While it’s important to note that Retrieved June 23, 2015 from Nature. doi: age contribute independently or jointly most children developed normally— 10.1038/mp.2015.70 Used with permission to the likelihood of autism spectrum even those in high-risk groups—the from Nature Publishing Group. disorders in offspring. chances of autism were lowest when

12 2015 ANNUAL REPORT databyte

Relative risk for autism spectrum disorder by joint paternal and maternal age

Relative risk (RR) for autism spectrum disorder by joint paternal and maternal age (referent parental ages 25 years). RR’s adjusted for offspring sex, birth year, and country of birth. Color Code: dark greens indicate RR < 1; blue indicates RR ≈1; lime green, yellow, oranges and reds indicate increasing RR’s >1.

SANDIN S, SCHENDEL D, MAGNUSSON P, HULTMAN C, SURÉN P, SUSSER E, GRØNBORG T, GISSLER M, GUNNES N, GROSS R, HENNING M, BRESNAHAN M, SOURANDER A, HORNIG M, CARTER K, FRANCIS R, PARNER E, LEONARD H, ROSANOFF M, STOLTENBERG C, REICHENBERG A. AUTISM RISK ASSOCIATED WITH PARENTAL AGE AND WITH INCREASING DIFFERENCE IN AGE BETWEEN THE PARENTS. MOL PSYCHIATRY. 2015; FIGURE 3, RETRIEVED JUNE 23, 2015 FROM NATURE. DOI: 10.1038/MP.2015.70 USED WITH PERMISSION FROM NATURE PUBLISHING GROUP.

DEPARTMENT OF EPIDEMIOLOGY 13 databyte

Spotty on measles? Everything you need to know about the virus and its vaccine

In 2000, the Centers for Disease Control and Prevention (CDC) announced that measles was eliminated from the United States. The highly contagious infection was no longer ever-present on home soil, thanks to an effective Measles, Mumps, and Rubella (MMR) vaccine, licensed in 1971, and a vaccination program refined to emphasize two doses over one. Between 2001 and 2011, the CDC reported 63 outbreaks, with a median number of six cases per outbreak. The majority of these outbreaks were concentrated in communities with low MMR vaccination rates, primarily affecting those who were not vaccinated or had unknown vaccination status.

Measles cases reached a 20-year high in May 2014 and came to the fore of national news with an outbreak at California’s Disneyland theme park in December 2014. By February 13, 2015, 141 cases had been reported across 17 states, 80 percent of which stemmed from the Disneyland outbreak.

Whither measles? What does it look like, and how does the MMR vaccine work? From basic reproductive rates to herd immunity, this infographic has got you covered.

Originally published at the2x2project.org

14 2015 ANNUAL REPORT DEPARTMENT OF EPIDEMIOLOGY 15 feature

Ending publication bias

How much do we actually know about our medical treatments?

BY ELAINE MEYER

the2x2project.org

2x2.ph/publication-bias

16 2015 ANNUAL REPORT ost of us who take a Even studies that are published may “We cannot know the true effects of the medication expect our over-emphasize positive results—a kind of medicines we prescribe if we do not have spin that we are conditioned to expect from access to all the information,” Dr. Ben Gol- doctor has prescribed politicians but not from clinical research- dacre, a physician and science writer said M ers. These are just some of the many in a 2012 TedMed Talk, which became an it based on evidence. But it misleading practices known as publication opening salvo for a science transparency turns out that basic assump- bias, and they can seriously skew the evi- group he founded called AllTrials that goes tion is often incorrect. dence doctors and patients use to make after this problem. health decisions. In recent years, a variety of govern- In fact, many clinical trials of medical treat- “People are rewarded for publishing in mental and nongovernmental groups are ments—particularly negative ones—never well known, high impact journals, not for forming or stepping up efforts to bring make it to publication in academic journals, producing well designed, well reported, transparency to medical research. What which doctors consult to make medical well conducted papers,” Dr. Simera remains to be seen is whether these efforts decisions and the media publicize in their acknowledges. can attack a problem that has persisted for health reporting. According to a 2014 sys- Yet in addition to misleading the public decades. tematic review in PLoS, more than half of and doctors, publication bias has a whole Tamiflu and antidepressants trial results are not published, and those other cascade of negative effects. It betrays that are published are three times more the trust of the patients who participate in The story of Tamiflu is perhaps one of likely to come out with positive rather than clinical trials. And it skews the findings of the most headline grabbing cases of negative results. systematic reviews, analyses of all available publication bias. This anti-influenza drug, “I think your average consumer thinks research on medical treatments. Indeed, also known as oseltamivir—along with a that their treatment is based on data or systematic reviews are conducted precisely similar drug called zanamivir, marketed research—that it’s odd that it is not,” to do what publication bias prevents: pro- as Relenza—came under scrutiny by the says Dr. Kay Dickersin, the director of the vide the most accurate information about Cochrane Collaboration, an independent Center for Clinical Trials at Johns Hopkins how effective and safe a treatment is based NGO that works to acquire data to conduct Bloomberg School of Public Health. on all of the available evidence. accurate systematic reviews.

DEPARTMENT OF EPIDEMIOLOGY 17 After engaging in a drawn out battle for the regulatory documents that formed the basis for approval of the two drugs, Cochrane “came to the conclusion that there were substantial problems with the design, conduct, reporting and availability of information from many of the trials,” according to a statement published last year. Cochrane concluded from its analysis of the trials that the drugs did little to prevent flu symptoms beyond reducing the duration of the virus by half a day. The report called into question the billions of dollars governments including the U.S. have spent stockpiling Tamiflu to prevent a flu outbreak and the lack of easy access to important regulatory data. In another widely covered story, a 2008 New England Journal of Medicine study of 74 FDA-registered studies of a dozen positive results. (One unpublished trial was have known what data was being collected popular antidepressant drugs, like Prozac, positive). The study was led by Dr. Erick as part of a trial,” says Dr. Ross. Zoloft, and Paxil, found 94 percent in the Turner, a former FDA medical officer who In theory, academic journals could medical literature were positive. But when had begun to question the veracity of the now use the registry to double check the the researchers filed freedom of informa- medical literature while working on the veracity of an article they were planning to tion requests for FDA review documents, drug approval process at the agency. publish—to make sure a trial reported on they found a good chunk of those trials In 2012, GlaxoSmithKline, the maker of what it originally set out to measure. were not published. Of 33 trials the FDA Paxil, even pled guilty and paid a $3 billion In 2007, Congress went even farther, had perceived as having negative or ques- fraud settlement in part for concealing neg- passing the FDA Amendments Act, which tionable results, 22 were not published, ative information about the effects of the mandated reporting final study results of a and 11 were published but communicated drug on children and teens. drug, biological product, or device to Clin- “If you start to dig down…you sort of icalTrials.gov within a year after the trial wonder what this is like for every drug. Is concluded. The rules apply to drugs that this really a problem across all classes of all are being studied, manufactured or seeking drugs? What can we really believe? And very new drug status in the U.S. quickly you’re sort of down a rabbit hole,” Today, over 178,000 clinical trials are says Dr. Joseph Ross, an associate professor registered in ClinicalTrials.gov—the largest of internal medicine at Yale University. registry in the world—and 15,000 report results, according to the National Institutes Trial registries ‘We cannot know of Health. To the 2007 law’s credit, trials As the problem has become more evident, registered increased significantly from the true effects of the U.S. government has tried to catch three years before that year to three years up by passing regulations requiring more after, according to a 2012 study in JAMA, the medicines we transparency. In 1997, Congress passed a and the number of missing data elements law requiring all trials file public informa- declined overall. prescribe if we do tion at their outset. In 2000, the National Dr. Dickersin, an early advocate for Institutes of Health launched a web site trial registries, believes ClinicalTrials. not have access to called ClinicalTrials.gov where this infor- gov has provided a good picture of where mation would be made available. “Before the problems are. “It’s clear that there is all the information.’ clinical trial registration, no editor could failure to report,” she says. For instance,

18 2015 ANNUAL REPORT ‘People are rewarded for publishing in well known, high impact journals, not for producing well designed, well reported, well conducted papers.’

fewer than half of registered studies made that are not being reported are more nega- written by experts in study design. it to a journal publication, according to a tive studies. “We try to improve the quality of report- study published in 2012 by Dr. Ross and Even a little bit of enforcement—such as ing after the submission of the papers. We colleagues in the BMJ. Another BMJ study an email reminder—could improve report- ask editors to check if the papers follow the from 2013 found that nearly 30 percent of ing. Dr. Ravaud and his team put this to the reporting guidelines,” says Dr. Ravaud. trials of at least 500 participants registered test when they sent emails to investigators While most journals endorse the guide- in ClinicalTrials.Gov remained unpublished in 190 studies that had not posted results lines, only a few require authors to submit three years after they were completed. on ClinicalTrials.gov. The researchers dis- a checklist ensuring they have met them. ClinicalTrials.gov also may be providing guised the reminders as surveys notifying “If a journal is going to be really tough, a check on spin. A study published last year recipients of their lateness and querying they’ve actually got to pay a technical in JAMA found cardiovascular trials that them about why they had not posted their editor to do that. Some people say, can had registered were less likely to report results. They compared them to a control peer reviewers do that? But peer reviewers positive findings than those not registered. group that did not receive emails. After are not paid,” says Dr. Elizabeth Wager, According to a 2013 study in PLoS, “serious three months of receiving the email, there who consults editors, scientists, and writ- adverse events,” were reported only 63 was little difference in number of studies ers on medical publishing and is a visiting percent of the time in journal articles com- posted by the control versus intervention professor at the University of Split School pared to 99 percent on the registry. group, but after six months, there had been of Medicine in Croatia. And studies published last year in an increase in those who posted their study Dr. Wager suggests journals require arti- Annals of Internal Medicine and JAMA results among the intervention group. The cles to follow a very structured template, found more accurate information in Clini- authors noted that the message might be similar to trial registry requirements, but calTrials.gov than published papers. “This more powerful if it came from regulators and she acknowledges it would not be popular is a problem,” says Dr. Philippe Ravaud, threatened some kind of fine or sanction. with academics. “I think [journals] know director of the Centre of Epidemiology at authors don’t like that. [Authors have] got a Targeting the journals the Hotel-Dieu in , adjunct professor funny idea that academic writing should be of epidemiology at Columbia University’s Because journals are the gateway through like creative writing,” she says. Mailman School of Public Health, and the which medical research is publicized, some Targeting the investigators senior author of the PLoS study. experts believe they are the best hope for Several sources interviewed for this cracking down on publication bias. “The Dr. Simera, who heads program develop- article say they are not aware of the FDA best enforcement is really going to be ment for EQUATOR based at the Centre ever fining an organization for failing to the journals refusing to publish,” says Dr. for Statistics in Medicine at Oxford Uni- report trial results, even though the agency Dickersin. versity, believes the push for accuracy and is authorized to collect civil penalties for The goal of the international EQUATOR transparency should take place at research violation of the regulations. network, short for “Enhancing quality and institutions. “At the end it’s researchers, One deterrent to posting on Clinical- transparency of health research,” is to scientists who are ultimately responsible Trials.gov may be that it is a challenging improve the standards of what is published for what they produce. You can say: edi- website to use. A 2011 study found it takes in medical journals. EQUATOR helps jour- tors, peer reviewers, they should spot the about 38 hours to submit basic results on nals and medical researchers use what are mistake. But it’s the manuscript that should the site, and an additional 22 hours to col- called reporting guidelines in the writing be already good enough that things are not lect the data and information required to and editorial process. The guidelines, cre- missing,” she says. register. Still, one wonders whether studies ated for many different kinds of studies, are

DEPARTMENT OF EPIDEMIOLOGY 19 Dr. Ravaud, who directs the French There are many barriers to sharing of EQUATOR Center says that to ensure better clinical trial data, such as issues surround- publications “we have to move to be able ing privacy of patient health information to intervene during the process of writing and the extensive technology infrastruc- the first draft of the manuscript.” ture it may require. But as suggested by There realities of the current incentive an Institute of Medicine report released in structure to publish positive results in top January, clinical trial data sharing is the journals that make spending time improv- future. The report outlines a framework for ing manuscripts a tall order. Academics developing “a culture, infrastructure, and may be at work on multiple studies as well policies” to foster data sharing among the Bias, bias as trying to write new grants. It may not multiple stakeholders involved. “We think make sense for them to spend their time responsible sharing of clinical trial data everywhere trying to publish a negative study when will advance the science that underlies as positive studies are more likely to get pub- the foundation of good clinical care,” says A biased interpretation, aka “spin,” lished in journals. Dr. Simera acknowledges Dr. Bernard Lo, president of the Greenwall was evident in 84 percent of journal as much: “Competitiveness in research is Foundation and the chair of the commit- articles’ abstracts and 88 percent of rising. People are rushing a lot more.” tee that published the report, at a press the stories found on Google Health Sometimes, Dr. Wager points out, briefing. News in recent studies by adjunct medical researchers are also ignorant, “Fake fixes” epidemiology professor Dr. Philippe especially those who may not have been Ravaud. trained in a discipline like epidemiology Dr. Goldacre of AllTrials to refer to journal that emphasizes study design. “I do a lot of guidelines and trial registries as “fake More research is needed to determine training with doctors and it surprises me fixes,” a term he used in his 2012 TedTalk if the spin found in health-related how unaware they are of reporting guide- and still stands by today. news stories originates from the lines,” she says. “There’s still no routine audit of whether scientific articles themselves or if jour- Universities lack a single compliance office registration and reporting are enforced, nalists misinterpret the information that can guide medical academics—some so there’s no accountability, and no way they read in press releases and aca- of whom may not be trained in study design, of knowing the levels of compliance,” Dr. demic journal articles. says Dr. Ross. “No one has the resources to do Goldacre wrote in an email in January. More on publication bias it, but academics are worse off.” He also points out that ClinicalTrials.gov only requires registration of trials that Incentivizing data sharing were ongoing during or after the 2007 FDA ff Classification and prevalence of Clinical trial registries require publication Amendments Act was passed. spin in abstracts of non-randomized of the results of studies, but a large portion He doesn’t have much faith that stepped studies evaluating an intervention of data from clinical trials is never pub- up enforcement of registry requirements 1.usa.gov/1QMgoNq lished or made available. Concerns about will happen anytime soon. Thus, his orga- ff Interpretation of results of studies publication bias, among other things, has nization AllTrials has tried to “take the bull evaluating an intervention driven a movement toward data sharing. by the horns” and directly audit company’s highlighted in Google Health News: A “Almost all other professions share a lot public statements and their actions. They cross-sectional study of news more data under much more liberal cir- plan to publish the results. 1.usa.gov/1PCgrgo cumstances than we do,” says Dr. Andrew “That way,” he writes “doctors, Vickers, an attending research methodol- patients, researchers, journalists and pol- ogist at Memorial Sloan Kettering Cancer icymakers can all see for themselves who Center, during a Columbia University are the worst offenders, but also, crucially, Epidemiology Scientific Symposium about who is showing leadership.” health research outcomes in February.

20 2015 ANNUAL REPORT feature

Tuberculosis through the looking glass

A prismatic view of novel research to combat an ages-old disease

BY EMILY AUGUSTINI, MPH ‘16 PRATIVA BARAL, MPH ‘16 EDITED BY DANA MARCH, PHD

DEPARTMENT OF EPIDEMIOLOGY 21 hite plague. Phthisis. Consumption. Depicted in early W One third of the world’s population is TRACKING TRANSMISSION Egyptian art and referenced infected with TB. In 2014 alone, 9.6 million The majority of people who are infected people fell ill with the disease. Across the in the Bible, tuberculosis with TB do not have the disease—the bac- globe, TB kills over 1.5 million people each terium remains dormant in 90–95 percent (TB) has been called many year. Cases of multi-drug resistant (MDR) of people, kept in check by their immune and extreme drug resistant (XDR) TB are different names since it systems. rising at an alarming rate. Moreover, TB Latent TB can turn into active disease began infecting humans long and HIV have developed into a co-epidemic, years after a person is infected, which with 1.2 million people infected by both the before recorded history. obscures transmission. From a clinical per- TB bacterium and HIV virus worldwide. Of spective, the “when,” “where” and “how” For centuries, its cause was those living with both diseases, one in three don’t necessarily matter: regardless of the people are never notified that they have TB elusive. Ever since the 1882 means by which an individual becomes and do not receive treatment for it. infected, treatment is much the same. discovery of Mycobacterium Now, the scientific community is more Those seeking to control the spread of this focused than ever on finding innovative tuberculosis, the infecting infectious disease, however, must concern methods to combat this chronic infectious themselves with such details. agent, we have been disease. searching for new ways Together, a passionate, dedicated core “People lie but bugs don’t” of faculty in Columbia’s Department of Epi- From an epidemiological perspective, to track the bacterium and demiology are imagining new approaches an epidemic demands a systemic—and to TB that span the spectrum of the minimize its effects. In the systematic—approach: households, indi- challenges it presents. Their innovative viduals and their respective contacts all mid-20th century, antibiotics research ranges from tracking the molecu- need to be investigated, which requires lar messages that TB sends to better detect seemed to promise an end to tracing and verification. But memories are the disease, and telling the tale of transmis- unreliable at times—especially given that the disease, but the microbe sion dynamics through the tubercule itself, infection may have occurred years ago and to a more humane way of delivering what has become stubbornly drug doesn’t even require direct physical contact historically has been one of the more puni- (the bacterium that causes TB is airborne). resistant in the 21st century. tive population-level treatment protocols.

22 2015 ANNUAL REPORT Understanding the pathogen through molecular genetics and mechanisms of characterization is essential to painting a bigger picture of TB transmission and consequentially, global epidemics.

What’s more, individuals may not want “The bug innately wants to survive—it’s because transmission is complex and at to share information because of stigma a very well-adapted human pathogen, a times, perplexing. Distinctive strains may or social constraints. All of these factors product of hundreds of thousands of years be observed within the same household, hinder TB control because they make it of evolution, and fine-tuning. And in that which suggests a non-linear method of difficult to paint a clear picture of how the process, it adapts, spreads and mutates,” transmission. A father, for example, may bacterium is being spread using traditional says Dr. Mathema. contract TB from someone at work, while epidemiological methods. Dr. Mathema uses data to understand this his children pick up a different variant of the A pathogen-centric approach can lead to evolution and to observe the natural changes bacterium at school. a much deeper understanding of TB trans- that occur over time. “Over the years, the Tracking this non-linear transmission mission because while, with respect to their organism has gone through a Darwinian requires spatial and social network analy- exposure, people might forget, or may even process of selection and adaptation such that sis. Understanding the pathogen through be compelled to lie, bugs simply don’t. the pathogen has learned to co-adapt and molecular genetics and mechanisms of survive with us as a host,” he says. characterization is essential to painting a From microorganism to macro Tracking the evolution of the bug is bigger picture of TB transmission and con- movements one way to control the epidemic because sequentially, global epidemics. Historically, the pathogen responsible for the specific changes and mutations that Social medium TB, the Mycobacterium tuberculosis bac- occurred during evolution can indicate pos- terium, has been observed superficially: sible targets that can be used to develop Indeed, poverty and TB are closely asso- we started out by recognizing its shape, more effective drugs. Furthermore, analysis ciated, where the poorest and most texture, and growth characteristics. In of the strains can demonstrate similari- vulnerable communities are most at risk of other words, basic microbiology relied on ties and differences, and allow for early developing the disease. In an ideal world, the phenotype of the organism for classi- detection of mutations that may result in eradicating poverty and the discrepancies fication purposes. Modern methods are multi-drug-resistance. in the wider societal structures would more granular, relying on genotyping, a All of this is vital to public health’s eliminate TB. But until then, Dr. Mathema laboratory-based method that analyzes and ongoing efforts to control the epidemic: says, hotspot mapping, a visualization of recognizes the genetic configuration of the the pathogen-centric lens leads to a more high-density occurrences, is a valuable organism, to detect outbreaks earlier and nuanced understanding of transmission. public health tool that can advance our recognize unsuspected relationships. The pathogen doesn’t just tell us who gave understanding of the disproportionate prev- Dr. Barun Mathema is an assistant TB to whom. It provides insight into specific alence and the population dynamics of TB. professor of epidemiology at Columbia mutations that affect the ease of transmis- South African gold miners, for instance, University’s Mailman School of Public sibility from one person to the next and have an extremely high TB prevalence. We Health. He uses a combination of molecular drug resistance. Such examination is the now know that this is a consequence of genotyping and epidemiological methods, key to identifying chinks on the microbe’s their exposure to silica dust in the mines. such as surveillance, spatial analysis, and armor, which helps clinicians select appro- But it was through spatial analysis and gen- network analysis in order to understand priate treatment protocols and researchers otype analysis of the strains prevalent in the spread of TB epidemics. He says TB is to avoid wasting time on pharmaceutical that population that led public health scien- fascinating because it has endured years of dead-ends. tists to conclude that TB emerged from the insults by the host’s immune system and It should be noted that simply recog- gold mines. Recognizing the strain-specific constant attacks by a slew of antibiotics. nizing the pathogen is alone inadequate catalysts of TB transmission, mapping the

DEPARTMENT OF EPIDEMIOLOGY 23 highly prevalent locations and finally, prior- measures a patient’s antibody levels to Disease signals itizing interventions tailored towards these determine if they’ve been exposed to TB highly dense areas is key for TB control. bacteria. While relatively cheap and easy, The term “biomarker” is reminiscent Merging the fields of public health the skin test has a high false positive rate. of other buzzwords like “synergy” and and biomedicine can lead to a better The Interferon-Gamma Release Assay, or “empowerment”—trendy, catchall terms understanding of the complexities of TB IGRA, is more reliable but far too expensive with many meanings. This is because transmission for the prevention and control for resource-poor settings. These are the “biomarkers” aren’t just one thing; they of the disease. This way, a more targeted two most common diagnostic tests for TB. comprise a vast array of molecular signals. implementation of public health strate- The tests available for assessing When a person is infected with TB, these gies can occur, kick-started by a thorough treatment outcomes are even more molecular messages sound off. understanding of the pathogen and its inadequate. The “gold standard” for drug According to Dr. O’Donnell, “A biomarker transmission. trials is merely determining whether subjects is a surrogate that’s close to the disease According to Dr. Mathema, “Transmis- are still infected with TB after two years. process and reflects disease activity.” These sion is a real Achilles heel of TB—we really The emphasis now is on a worldwide surrogates are biochemical signals that are need to knock down the incidence. And the hunt for biomarkers of TB that can be used given off by either the bacterium itself or the best way for us to do that is to understand to precisely determine disease status, and human host, and can be quantified in order the pathogen and then concentrate on therefore improve the diagnosis and prog- to determine disease status and progression. hotspots.” nosis of TB patients. Dr. Max O’Donnell, an Host-derived biomarkers are often anti- assistant professor in the Division of Pulmo- bodies that the immune system creates to THE BIOCHEMICAL ILLUMINATI nary, Allergy, and Critical Care Medicine and fight the infection. These antibodies are an For a disease as ancient as TB, we have the Department of Epidemiology at Colum- attractive target because of our knowledge shockingly few tools with which to fight it. bia, described his search for new methods of the human immune system, but may Most people who have attended college of assessing and optimizing treatment out- provide an imperfect measure of disease have had the tuberculin skin test, which comes through the use of biomarkers. activity. Instead of monitoring the bacteria,

Transmission electron microscopy image of mycobacterium tuberculosis

24 2015 ANNUAL REPORT IMAGE: U.S. NATIONAL LIBRARY OF MEDICINE

the results are filtered through the immune health care workers must witness patients Predicting resistance response of the host. taking their medications, because treat- Dr. O’Donnell’s research focuses on The uses for this modified virus are vir- ment non-adherence is expected. And biomarkers derived from the TB bacterium tually limitless. One of Dr. O’Donnell’s patients not completing their six-month itself. His lab has created a virus that feeds priorities is examining whether treatments regimens are labeled defaulters. Never on TB. It releases a fluorescent green pro- are likely to generate drug-resistant strains mind the toxic side effects. tein when it finds a snack. of TB. The treatment for TB is arduous, lengthy, Researchers collect a sputum sample “Almost all of our data on rates of muta- and unaided by its impersonal, rather puni- from the patient and add the modified virus. tion come from a petri dish. How frequently tive nature. If the sample glows green under a fluores- the bug mutates is based on in vitro data, A perfect storm for paternalism cent microscope, TB bacteria are present. If and it may be that some of the second-line the sample glows in a well when antibiotics drugs we’re giving have mutagenic poten- TB is something of a perfect storm for are added, the TB is drug resistant. tial. Because they interfere with…enzymes paternalistic public health interventions. The virus created by Dr. O’Donnell’s that are involved in DNA replication, it’s The disease is airborne, so it is spread team only infects TB bacteria, making it totally plausible that the rates of mutation simply by breathing; there’s no deliberate more accurate than the traditional tests, are quite different. We’re trying to use deep action required on the part of the exposed. and it can detect extremely small concen- sequencing and this phage, this modified There aren’t any corporate stakeholders to trations of bacteria. When the procedure virus, to detect subpopulations that are push back against TB control, like tobacco was tested in a clinic in , it was drug resistant as they emerge,” says Dr. companies do with smoking. Those infected found to be more sensitive but less spe- O’Donnell. are usually of lower socioeconomic status cific for detection of TB—meaning it was and, in the United States, are often for- PRIORITIZING PATIENTS better at detecting true cases of TB than it eign-born, limiting their ability to access was weeding out the non-cases—than an For individuals, a diagnosis of TB is unlike services and complete treatment. expensive, sophisticated PCR machine. It any other. Quarantine is common. Treat- The standards for TB treatments were did not make a difference if the patient also ment is laced with mistrust, precisely developed originally with sound reasoning had HIV, which is critical in the developing because of concerns regarding trans- and no intent to demean patients. Directly world, where co-infection is extremely mission and treatment resistance. Often, observed therapy, or DOT, for TB treatment is common. not an inherently bad idea, just an outdated

DEPARTMENT OF EPIDEMIOLOGY 25 Swaziland National TB Center IMAGE: ICAP AT COLUMBIA UNIVERSITY one. As medicine and public health become the three pillars of the End TB strategy for transportation to the clinic, educational pro- more technologically advanced and the 2015–2030. grams to improve patients’ understanding biology of disease is better understood, the This shifting mentality is due in part of their treatment, job aides for nurses, and importance of humanity—human factors, to the relative failure of current TB con- an SMS reminder system for appointments. humane engagement—is starting to emerge. trol methods. Though TB deaths have Each of the interventions is extremely decreased markedly since 1990, there were inexpensive, and together they stand to From punitive to patient-centered still 1.5 million TB deaths worldwide in improve treatment completion and survival Dr. Yael Hirsch-Moverman, an assistant 2014. Dr. Hirsch-Moverman says, “That’s rates. The team is doing a similar study in professor of epidemiology at Colum- unacceptable. It’s a preventable, curable Ethiopia, but with the goal of enabling HIV bia, focuses on a holistic, empowering disease. We’re not doing well, and we need positive patients to complete preventive approach to TB treatment known as to fix it.” treatment regimens for TB. The packages patient-centered care, which is gaining There are myriad reasons for these gaps are tailored to the region in which they’re traction worldwide. in TB management, including absence of used. For example, in Ethiopia literacy rates According to Dr. Hirsch-Moverman, funding, lack of visibility, and the latent are lower than in Lesotho, so the SMS text patient-centered care is “Basically the way nature of the disease. Dr. Hirsch-Moverman reminders are replaced by automated voice it sounds, which is putting the patient at the and many others hope that patient-centered reminders. center of the treatment.” In patient-centered care for TB will not only empower patients Scaling up these culturally and locally care, providers consider the barriers that but also improve their ultimate outcomes, specific interventions presents a grand prevent patients from seeking and complet- all while being cost effective. challenge. However, Dr. Hirsch-Moverman ing treatment, including social, educational, is confident that it can be done in a cost Packaged for patients psychological, and structural factors. effective manner. “We designed these This approach isn’t new, though. It has In a trial that Dr. Hirsch-Moverman is interventions to be sustainable. Not too long roots is patient advocacy—activists for working on in Lesotho with the Columbia expensive, nothing super fancy, because diseases like HIV/AIDS have been champi- University organization ICAP, a patient-cen- at the end of the day we’re going to have to oning patients’ rights for years. However, tered approach means combining multiple depend on the local ministries of health to patient-centered care only recently made interventions that have been shown to be deliver these things,” she says. its way into TB treatment. The WHO just effective into a comprehensive package. The high level of acceptance and buy-in adopted patient-centered care as one of This package includes reimbursement for achieved in the communities will usher

26 2015 ANNUAL REPORT the process along. Although the research “It’s a way of detecting way early if [the team won’t know the final results for a few patient] has two populations of bacteria, Tuberculosis now months, the trials have already had a signifi- one’s antibiotic resistant and one’s suscep- cant effect on the patients that participated. tible. As you get antibiotics that kill down world’s deadliest “What’s been really interesting is to the drug-susceptible, the drug resistant will see them feeling like somebody cares emerge. As it’s emerging, we want to detect infectious about them,” Dr. Hirsch-Moverman says. it at say, one part in 100,000 rather than “Through the messages, they feel cared waiting until it’s 50-50.” disease for. They feel that someone in the clinic is COMING FULL CIRCLE thinking about them. It’s automated, but to About 1.5 million people died from TB them it’s not necessarily.” Emphasizing the If we have half a chance of fighting this in 2014, which means that tuberculosis humanity of this approach, Dr. Hirsch-Mov- disease that causes so much morbidity is now causing more deaths than any erman adds, “It’s beautiful.” and mortality globally, it’s going to take other infectious disease. HIV/AIDS, no the complimentary, coordinated efforts of longer the world’s deadliest infection, Precision medicine researchers represented by this Columbia killed 1.2 million globally during the Indeed, the human touch is a focal point thought collective. This group’s unique same time period, according new data for patient-centered care. However, with set of perspectives, which encompasses released by the World Health Organi- his work on biomarkers, Dr. O’Donnell is the micro and the macro, the local and the zation (WHO) in late October, 2015. interested in yet another dimension of indi- global, offers fresh hope for one day ade- The WHO and the White House have vidualized treatment for TB. He’s striving to quately addressing this ages-old killer. both created new plans for addressing foster a shift towards the use of precision tuberculosis. Beginning in 2016, WHO medicine for the disease. The current drug will shift its focus from just controlling regimens for TB are highly standardized, TB to eliminating the disease alto- and often don’t detect when patients have gether with the launch of The End TB drug-resistant strains until several treat- Strategy. ment programs have failed. Dr. O’Donnell’s work with the TB-detecting virus his lab The WHO’s goal is “to reduce TB developed, as well as biomarker research in deaths by 95% and to cut new cases general, has the potential to change those by 90% between 2015 and 2035, and to outcomes. ensure that no family is burdened with catastrophic expenses due to TB.” › bit.ly/VMb6tX

More on tuberculosis

ff Tuberculosis surpasses HIV/AIDS as leading cause of global death: WHO bit.ly/1ZNVv9H Scaling up these culturally and ff TB surpasses HIV/AIDS as top killer: Drug quality control needs to change locally specific interventions fxn.ws/1jX7m66 ff White House releases plan to fight presents a grand challenge. multidrug-resistant tuberculosis huff.to/1NM4LDM

ff New plan to fight tuberculosis nyti.ms/1TgKaep

DEPARTMENT OF EPIDEMIOLOGY 27 feature

Gentrification and public health: Opportunities and challenges in change

BY AMY SCHELLENBAUM AND DANA MARCH, PHD

28 2015 ANNUAL REPORT IMAGE: TIMOTHY KRAUSE IMAGE: ANDREAS KAMBANIS

IMAGE: MATTHEW RUTLEDGE IMAGE: RACHEL KRAMER BUSSEL

ongtime residents Officials neglected the area for decades— residents from greater Austin started unless, of course, something undesirable, moving in. The effect snowballed until, by consider East Austin, like a power plant, needed a home. 2014, housing prices were 70 to 80 times Texas a victim of its Fast-forward to the mid-2000s. The what they were even in the 1990s. L neighborhood boasts the farmers’ markets, “We cleaned it all up,” Ms. Almanza own success. It’s a narrative coffee shops, and food trucks required of says, “just so the new [residents] can come locals in transforming a blooming hipster haven. Land value has in and take over the barrio.” skyrocketed, and so have rents and down Grappling with gentrification neighborhoods across payments. Much of the old community America would recognize: can’t afford to live here. Indeed, when people or institutions with For decades the community came more money decide land is valuable, the As recently as the 1990s, together to protect its neighborhood, many onrush of wealth drives up housing prices, East Austin’s population was times to great success. For example, in squeezing out the neighborhood’s original the 1990s, community leaders combated dwellers. around 90 percent Latino; the what activist and longtime resident Susana The effects of such a shift can be severe: area’s families having carved Almanza called “environmental racism,” researchers have long established the demanding the closure of the Holly Street health woes of people whose lives have homes here in the decades Power Plant. Eventually, in 2009, the gov- been uprooted. People leave their jobs following a 1928 law that ernment ceased the plant’s operations. and move into lesser-quality housing, life This is where the victim-of-its-own-suc- events are often paid for by working more segregated Texas’ capital. cess moniker comes into play. As blights hours or avoiding medical care. The psy- and polluting structures were demolished, chological effects are long-lasting and dire.

DEPARTMENT OF EPIDEMIOLOGY 29 IMAGE: STUART MCALPINE IMAGE: SEE-MING LEE

IMAGE: TONY FISCHER IMAGE: JOE NICKOL

The term gentrification dates back What causes gentrification? How detri- from minority affairs, and Dr. Gina Lovasi, more than five decades—and its socio-po- mental are its effects? How do we facilitate assistant professor of epidemiology, first litical causes back much further—but the development that isn’t harmful for resi- outlined the problem. Policies dating back task of understanding this process has dents? The department of epidemiology before The New Deal set the stage for taken on a new urgency. Researchers recently convened a symposium to ask urban renewal, gentrification, and other endeavor to parse its context, causes, and these questions, investigating themes that forms of forced displacement. consequences. resonate here-and-now, despite having In all, some one million Americans in Researchers have focused on the extent been gnarled by decades. Scholars and 993 cities have been forced out of their of gentrification in U.S. cities. A 2013 activists discussed the origins and implica- communities. Some 75 percent of those analysis by economist Daniel Hartley, for tions of gentrification, calling upon a spate displaced were people of color. example, shows the most pronounced of tools from the academic’s arsenal. The narrative begins with Jim Crow effects of this complex social process in the The task at hand was not to pin down laws, which allowed banks and real estate nation’s largest urban areas—New York, a solution to the displacement of poor companies to limit where blacks could live Boston, Washington, DC, Seattle, and San communities—though many were dis- and open businesses, and continues into Francisco. In Hartley’s investigation, the cussed—but rather to inform researchers the aftermath of the Great Depression, percent of gentrified urban neighborhoods and organizers, inspire new collaborations, when the government decided where ranged substantially, from 61 percent in and reiterate the importance of studying to invest New Deal money based on the Boston to less than five percent in other the topic. number of foreign-born residents and major metro areas, such as San Diego. To introduce the symposium, its hosts people of color. Neighborhoods that were Meanwhile, advocates strive to keep Dr. Mindy Fullilove, professor of clinical already neglected were given the lowest neighborhoods from disintegrating or, bar- psychiatry and clinical sociomedical sci- scores, furthering disinvestment. ring that, mitigate the potentially negative ences, Dr. Robert E. Fullilove, professor of Fast-forward a few decades, and the effects of community dissolution. sociomedical sciences and associate dean city labels some of these neighborhoods

30 2015 ANNUAL REPORT Because new residents are also more likely to make noise complaints, gentrification too threatens place- based culture, one defined in Tremé by parades, bars, and live jazz.

“slums,” using eminent domain to demol- fewer parks, and poorer public schools. A “second-most gentrified” in the country. ish housing and community buildings in dearth of housing code enforcement and Mr. Padilla interviewed community lead- favor of university infrastructure or shiny tenants’ rights contributed to the slum-like ers last year, uncovering a troublesome cultural centers. conditions the federal government tried to narrative: the more success community Gentrification is often viewed as a nat- eradicate in the ‘50s and ‘60s. members had expelling unsightly struc- ural process, although its history indicates Vulnerability to gentrification today, says tures the government imposed, the more otherwise. Dr. Lovasi, is “the legacy of segregation.” the community became endangered. But gentrification is both dynamic and Twenty years ago a house “would cost The eve of mass displacement complex—and contextually dependent. you maybe about $18,000,” an interviewee Dr. Richard Marciano from the University It doesn’t always rupture communities of noted. In 2015, a new house goes for $1.3 of Maryland and his co-authors examined color. Research using Census data from million. data from the Home Owners’ Loan Corpo- the 1990s led by University of Colorado For decades, a local environmental group ration, a New Deal program FDR created economist Terra McKinnish indicates that worked to rid the neighborhood of power to refinance mortgages and prevent mass gentrification of low-income black neigh- plants and other undesirable structures. By foreclosures post-Depression. (Over the borhoods, in fact, renders them more the 2000s, they had found a lot of success, next three decades, the U.S. government attractive to middle-class black families. but success meant people from “Anglo” financed over $120 billion in new housing, Austin wanted to live on the other side. A vulgar, criminal intrusion though less than two percent of that real As Mr. Padilla put it, “We cleaned it up, estate was available to non-white families.) To showcase the detrimental effects of gen- but the last cleanup is us leaving.” The HOLC put in place appraisal meth- trification, Dr. Trushna Parekh from Texas Housing instability as brain poison ods that kick-started a practice known as Southern University presented vignettes redlining, or the institutionalized denial of from the New Orleans Tremé neighbor- Dr. Angela A. Aidala, associate research services. hood. One interviewee, George, described scientist in Sociomedical Sciences, points The appraisals are painful to read, the changes in terms of police activity, and out that politicians and developers tend to describing neighborhoods in terms of racial how he “couldn’t move about the neighbor- focus on things like the increased sense of makeup and the immigration status of hood freely without being stalked by the safety, property values, tax revenues, and their inhabitants. Documents discouraged police,” Dr. Parekh says. “He was routinely even social mix, meaning poverty is less realtors from “introducing any individuals harassed without any reason.” concentrated. “Yes, it facilitates mixing,” whose presence will clearly be detrimental Because new residents are also more she says. “For a time.” to property,” according to Dr. Marciano, likely to make noise complaints, gentrifi- Impacts for the original residents, how- with the capacity for detriment based cation also threatens place-based culture, ever, are hard to ignore: rent increases are largely on “race or nationality.” one defined in Tremé by parades, bars, and often financed by cutting back on healthy Using these appraisals, HOLC cate- live jazz. food and medical care, or by working more gorized neighborhoods into colors, with hours. Residents may need to double-up ‘The last clean up is us leaving.’ “red” neighborhoods being the most in apartments or seek poorer-quality “detrimental.” Redlining is how the govern- Andrew J. Padilla, a filmmaker, documents housing. They may also experience some ment noted where it wasn’t going to send changing neighborhoods like his own, East unexpected boosts as well, like credit score money—again, based on race and ethnicity. Harlem. At the symposium, he spoke about increases of 1.5 to 8 points, depending on Perhaps unsurprisingly, the red areas of how communities fight to determine their whether they are staying or going. these maps “fit like a glove” with maps of own fate. Rapid gentrification, in particular, may urban renewal projects decades later. It’s That quest for self-determination result in serious short- and long-term con- not hard to see why. Systematic neglect had duplicitous effects for East Austin, sequences that “undermine the resilience translates to less federal mortgage aid, Texas, whose zip code is considered the of communities,” according to Dr. Lovasi.

DEPARTMENT OF EPIDEMIOLOGY 31 When gentrification breaks down social What remains clear is that the changes ties, says Dr. Lovasi, it “ultimately contrib- inherent in gentrification can deeply affect utes to a sense of futility and cynicism.” communities that have forged meaningful lives despite a lack of financial resources. Another yoga studio is not the solution Families that are confined to lower socio- “Things are really, really bad,” Dawn Phil- economic positions are likely to retain that lips, a 20-year activist in California’s Bay status across generations, living in dis- Area, says. To live in Oakland on minimum advantaged neighborhoods regardless of wage, one must work 165 hours a week. their geographic mobility, as work by NYU Now is the time, she says, to figure out sociologist Patrick Sharkey shows in his Higher rates of community-driven development. award-winning 2014 book, Stuck In Place. So what exactly are the key components Residential neighborhoods are but one axis incarceration of establishing a community-driven model along which the staggering social inequality of development? Quite simply, a major in the U.S. manifests itself. The complexi- related to paradigm shift. Development, she says, is ties of gentrification demand sophisticated very different when the government is not epidemiological, social, and economic neighborhood planning for wealthier residents. “We have research that can parse out its many causes never heard people say ‘we need another and consequences. Such research should depression and yoga studio.’” involve communities themselves, because The solution begins by stabilizing the there is no simple solution, especially when anxiety community with tenant protections that the challenges hit home. keep rents affordable. As Ms. Phillips says, There is “significant collateral damage “Organizing for tenant protection is some for the mental health of people left of the least popular forms of organizing, behind in neighborhoods where but we’ve got to.” incarceration rates are unusually high,” says a New Republic article that reports on a study by Dr. Katherine Keyes, Dr. Sandro Galea, Ms. Ava Hamilton, and colleagues.

Read more in New Republic. › bit.ly/1KjVwdM

32 2015 ANNUAL REPORT symposium report

The vaccine conundrum Are immunization programs victims of their own successes?

hen vaccines work, Unlike 60 years ago when diseases like measles and polio were commonplace and the discovery of vaccines celebrated, Dr. Offit said, vaccines today are nothing happens. To essentially a “matter of faith.” some extent vaccines This situation has led some parents to skip inoculations for their children, W leading to outbreaks. Earlier this year, a case of measles at Disneyland spread have become victims of their across six states and infected 147 people. In the aftermath, Dr. Offit said, even own successes, explained Paul some doctors who had been vocal about purported risks of vaccines were now giving more measles vaccines than ever before “because parents were scared of Offit, a pediatrician and infec- measles.” tious disease expert, at a recent Vaccines date back to the 1790s when English physician Edward Jenner suc- cessfully immunized people against smallpox by injecting them with pus from a symposium on vaccines hosted cow infected with a similar disease. As Dr. Stephen Morse, professor of epide- by the Mailman School Depart- miology, noted, the word “vaccine” derives from the Latin vaccinus, meaning “from cows.” ment of Epidemiology. Smallpox was responsible for an estimated 300–500 million deaths in the 20th Century alone. But, after a vigorous inoculation campaign, the disease was finally eliminated in 1980. As Dr. Morse noted, smallpox remains the only infectious disease to be completely eliminated through human intervention. Inoculation programs have also brought rates of rubella, polio, and diphtheria infection down to negligible levels in most countries. The fight against global infectious disease, however, is not over. Bird flu, Middle East Respiratory Syndrome Coronavirus (MERS) and, most notably, Ebola have emerged or flared up in the last decade or so. Combating these diseases relies on scientific ingenuity to develop vaccines and a society that embraces vaccination. “With microbes, it’s our wits versus their genes,” Dr. Morse said. Fear of vaccines is nearly as old as vaccines themselves. A British political cartoon published in 1802, for example, shows recipients of smallpox inoculation morphing into cows. One hundred year later, the Anti-Vaccination Society of America published flyers and actively recruited followers. Some of the earliest anti-vaxxers were ministers who warned that God sends illness as a punishment for sin and any interference by humans borders on blasphemy: diseases, they maintained, should be allowed to run their course. The latest iteration of anti-vaccine rhetoric isn’t rooted in fire-and-brimstone, but may be just as difficult to uproot. The 1998 vaccine-autism connection, based on one poorly designed (now retracted) study in The Lancet, is persistent. The Columbia University “There aren’t two sides to this story,” Dr. Offit assured the audience. “Vac- Epidemiology Scientific Symposium cines simply don’t cause autism.” (CUESS) series brings the best Media coverage of outspoken celebrities’ opinions on the matter, most nota- minds in epidemiology and other bly, a focus on Jenny McCarthy’s misdirected outrage over her son’s health disciplines together for a day of problems, has pushed the anti-vaccine movement into the popular conscious- discussion on the most pressing ness in recent years, Dr. Offit said. Unfortunately, in the interest of balanced health questions of our time. journalism, or perhaps higher ratings, the news media has highlighted anecdotes and given science rather short shrift, he said.

DEPARTMENT OF EPIDEMIOLOGY 33 Anti-vaccine cartoon published in 1802

“Media’s job is to entertain,” Dr. Offit said. “As long as people enjoy ‘vaccines “Vaccine inventors cause autism stories,’ we’ll have them.” Whether and to what extent vaccines are compulsory is worthy of serious were once celebrated consideration. In the view of Dr. Ronald Bayer, “a very small number of people should be allowed to forgo vaccines,” including those with weakened immune with ticker-tape systems. Vaccinating children not only protects them, but the kids they interact with parades. Now they get at school every day. “The unvaccinated are free-riders, which [also] violates jus- tice,” Dr. Bayer said. hate mail.” Dr. Offit, who co-invented the lifesaving RotaTeq vaccine that protects against rotavirus, maintains that vaccines are vastly underappreciated considering how many lives they’ve saved. “Vaccine inventors were once celebrated with ticker-tape parades,” he lamented. “Now they get hate mail.”

34 2015 ANNUAL REPORT symposium report

Injury control through collaboration

ttendees at the third “To just treat trauma and not try to prevent it is just absolutely immoral,” said Dr. Barbara A. Barlow, executive director of the Injury Free Coalition for Kids and annual Innovations professor emerita of surgery epidemiology at Columbia University. in Translating Injury The daylong symposium on May 22, sponsored by Columbia’s Center for A Injury Epidemiology and Research, drew scholars and policy experts from across Research into Effective Pre- the country to examine and debate best practices for injury prevention. vention Seminar are passionate More than 60 people attended the event, which covered a wide range of topics, including traffic fatalities, prescription drug overdoses, gun violence, falls about protecting community from windows, sudden infant death syndrome, and techniques for geographic health in the United States and injury mapping. The average person encounters numerous situations every day that involve a abroad. significant, preventable risk for injury, and, according to estimates by the Centers for Disease Control and Prevention (CDC), injuries are the number-one killer of Americans between the ages of one and 44. In the U.S. alone, injuries result in 2.8 million hospitalizations and 29 million emergency room visits annually. Dr. Joyce C. Pressley, associate professor of epidemiology and health policy and management at Columbia, served as course director and was one of ten speakers to present new findings. Attendees also had the opportunity to partici- pate in several roundtable discussions. Dr. Pressley gave a talk on window falls, illustrating how the New York City initiative to prevent them via legislation alone and legislation combined with vary- ing types of enforcement led to incremental improvements in window fall injury and mortality. More broadly, she also highlighted the roles that mandatory injury reporting systems for tracking the impact of health regulations/injury prevention legislation and various legal actions, such as complaints, citations, civil fines, criminal prosecution, and expanded liability, can play in safeguarding health. In 1976, when New York’s window guard regulations were first enacted, 24 children died and 217 were injured in window falls. Since that time, falls from windows have significantly decreased: In 2013, only one child died and just six were injured in such incidents. Children Can’t Fly, the pioneering window guard campaign that inspired the formal health code requirement, was created by Democratic politician and civic leader Charlotte Spiegel who passed away on April 27 in Manhattan at age 92. Kim Wiley-Schwartz, Assistant Commissioner for Education and Outreach at the NYC Department of Transportation, provided an update on Vision Zero, the City’s initiative to reduce traffic fatalities and injuries, especially among pedestri- ans. By 2024, the goal is to completely eliminate traffic fatalities in New York City. In October 2014, Mayor Bill de Blasio signed local legislation reducing the default speed limit on New York City streets from 30 to 25 miles per hour. The Department of Transportation also recently installed more than 400 new speed bumps, five miles of protected bike paths, and 45 leading pedestrian interval signals (which show a walk sign for pedestrians before showing a green light to car traffic).

DEPARTMENT OF EPIDEMIOLOGY 35 IMAGE: VICTORIA DINIELLI

Twenty-three percent fewer pedestrians social cohesion and making the local com- 100 Americans, according to the 2007 Small lost their lives in 2014 compared to 2013 munities better places to live. Arms Survey conducted by the Gene- (138 deaths vs. 180 deaths), and pedestrian Dr. Steven C. Rogers, assistant pro- va-based Graduate Institute of International fatalities in NYC are at their lowest levels fessor at the University of Connecticut’s Studies. The United States Bureau of Jus- since 1910. The City’s Vision Zero Task School of Medicine, attending physician tice Statistics found that firearm violence Force plans to concentrate on reducing at Emergency Mental Health Services, and accounted for about 70 percent of all homi- truck- and bus-related pedestrian deaths in co-principal investigator for the Injury Free cides in the U.S. between 1993 and 2011. the coming year. Coalition for Kids of Hartford, described Garry Lapidus, Injury Prevention Center Dr. Hillary V. Kunins, Assistant Commis- the Pediatric E-Network, a pilot program for Director at Connecticut Children’s Medical sioner at the New York City Department providing injury prevention education. He Center/Hartford Hospital and associate of Health and Mental Hygiene and head of and his research team offered 101 patients professor of pediatrics and public health the Department’s Bureau of Alcohol and a tablet pre-loaded with a mobile app that at the University of Connecticut School Drug Use - Prevention, Care and Treatment, contains information about teen driving of Medicine, reviewed the epidemiology spoke about prescription drug initiatives safety. The vast majority of patients, 81 and prevention of motor vehicle crashes in New York City. The City’s multi-pronged percent, accepted the tablet when it was among teen drivers, spotlighting risk fac- approach includes: monitoring and surveil- handed to them, suggesting that par- tors for crashes and evidence that favors lance; raising public awareness; promoting ents and children would be receptive to graduated driver licensing (GDL) systems, judicious opioid prescribing; distributing receiving injury prevention information at which place restrictions on underage driv- naloxone; and promoting access to effec- outpatient clinics when presented in this ers. Per mile driven, teen drivers are three tive treatment for opioid addiction. digital format. times more likely to crash than drivers Dr. Pina Violano, co-principal investi- Dr. Michael P. Hirsh, professor of surgery aged 20 years and older. Many studies in gator of the Injury Free Coalition for Kids and pediatrics at University of Massachu- the U.S. and Canada have shown that GDL at New Haven, presented on a framework setts Medical School and Surgeon-in-Chief reduces motor vehicle crashes and fatali- to mitigate gun violence, using the city at UMASS Memorial Children’s Medical ties by 20–40 percent. Since North Carolina of New Haven, New York as a test case. Center, made a compelling case for gun implemented comprehensive graduated Informed by survey data collected from buyback programs using the Pittsburgh licensing laws, crashes involving 16-year- people in the area, she and her colleagues and Worcester gun buyback projects and olds have decreased by 25 percent. formed two Community Resilience Teams their track records as successful examples. Beverly Miller, Associate Director of in the neighborhoods of West River and The U.S. is the most heavily armed country Research at Arkansas Children’s Hospital Newhallville, which will focus on building in the world with about 90 guns for every Injury Prevention Center and Program

36 2015 ANNUAL REPORT ‘To just treat trauma and not try New study will to prevent look at elderly it is just driving patterns Researchers in injury epidemiology are now recruiting people between absolutely the ages of 65-79 to participate in an unprecedented 3,000-person study of immoral’ elderly drivers, funded by AAA Foun- dation of Traffic Safety. They will fit cars with GPS to monitor driving pat- terns and accidents and do check-ups of participants’ cognition and physical health, Dr. Guohua Li, principal investi- gator of the study, told Reuters Health.

Read more on Reuters. Coordinator at the Injury Free Coalition health events and detect trends, which › reut.rs/1yNQ5fG for Kids of Arkansas, enumerated the helps inform decision making and priority American Academy of Pediatrics’ recom- setting. Injury maps are also useful for mendations for safe sleep environments to storytelling, as they enhance commu- reduce infant mortality and described four nication. The tool can play a key role in specific interventions. Sudden Infant Death health-related program development, Syndrome (SIDS) is 133 percent higher implementation, and evaluation. It can also in Arkansas than in the U.S. as a whole, inspire community members, motivate according to Ms. Miller’s presentation. public leaders, and engage stakeholders. Forty-three babies would be saved in just Support and collaboration were among one year if the incidence of SIDS in Arkan- the seminar’s most prominent themes: sas could be brought down to the national Participants eagerly shared new-found level. knowledge while seeking to benefit from Arkansas experiences excess SIDS in others’ wealth of experience. part because caregivers are unaware of “If you go into injury prevention and you the risk factors. Fewer than half of teen feel like you are alone doing this, it gets mothers in Arkansas place their infants on overwhelming” said Dr. Kitty Gelberg, New appropriate sleep surfaces and 75 of these York State Department of Health Bureau teen moms report occasional bed sharing. of Occupational Health and Injury Director, Finally, Dr. Wendy J. Pomerantz, pro- who attended the event. She added that fessor of pediatrics at the University of seminars like this one provide a reminder Cincinnati, showed how attractive data that “you are not alone; you don’t have to presentation is crucial to injury preven- recreate the wheel. The template is there tion efforts. A Geographic Information and you can follow it.” System (GIS) is a critical tool for visualizing spatial or geographical data, including public health data, such as incidence rates and factors contributing to local inju- ries. Researchers can use GIS to monitor

DEPARTMENT OF EPIDEMIOLOGY 37 epidemiology by the numbers

As epidemiologists we believe that numbers can speak volumes. Here are just a few:

In 2015, our faculty published over 800 peer-reviewed papers in the first ten months alone. The bibliography at the end of this report demonstrates the scope and influence of their path-breaking research.

This past year, our faculty, along with our students, engaged in public health work around the globe—in 68 countries, at last count.

We are training a total of 406 students in our MPH, MS, Executive MS, PhD and DrPH programs.

Upon graduation, these students will be much in demand, locally and internationally. The graphic on the opposing page shows the jobs the class of 2014 entered into within six months of graduation. selected faculty awards

Over the last calendar year, our faculty Dr. Wafaa El-Sadr was named the inaugural Dr. Guohua Li received an Excellence in garnered numerous awards and honors. recipient of the Dr. Mathilde Krim-amfAR Science Award from the American Public Here is a select (incomplete) list: Chair of Global Health, a professorship Health Association (APHA) for his for his endowed through the generosity of the Hess outstanding contribution to the science of Dr. Quarraisha Abdool Karim received an Foundation and of amfAR The Foundation injury epidemiology and prevention and for A-Rating from the National Research for AIDS Research. › epi.is/1kD3ebA his leadership in advancing the academic Foundation (NRF) for her seminal scientific field of injury control and prevention contributions in HIV prevention research; Dr. Linda Fried was selected as the 2015 through his pioneering research and A-rated scientists are recognized by their Lorraine and Ralph Lubin Distinguished training programs. › epi.is/1P9kBuD peers as leading international scholars Visiting Professor at Weill Cornell Medical in their fields.› epi.is/1UFmJwg. She Center; the Dean Fried of the Mailman Dr. Jose Luchsinger became Editor-in-Chief was also named a Laureate of the 2016 School of Public Health, she was chosen of the journal Alzheimer’s Disease and L’Oréal-UNESCO for Women in Science because of her achievements in the field Associated Disorders. › epi.is/1IWNqv4 Award for her “remarkable contribution to of epidemiology and because she is a role the prevention and treatment of HIV and model for students › epi.is/1RrrtHg. Dr. Dr. Alfredo Morabia became Editor of the associated infections, greatly improving the Fried was also named one of Next Avenue’s American Journal of Public Health. quality of life of women in Africa.” 2015 Influencers in Aging. These 50 thought › epi.is/1ZejKh5 › epi.is/1mq0H59 leaders, innovators, writers, advocates, experts and others are changing how we Dr. Andrew Rundle was presented with an Dr. Salim Abdool Karim is the recipient age and think about aging. › epi.is/1QvVFk6 Excellence in Leadership Award from the of a new endowed Chair, the CAPRISA Mailman School of Public Health; these Professorship of Global Health in the Dr. Grace Hillyer was awarded a Calderone awards recognize efforts by the School’s Department of Epidemiology, which was Junior Faculty Prize from the Mailman senior leaders that exceed the expectations announced by Mailman School Dean Linda School of Public Health; these prizes provide of any individual role. › epi.is/1JeGjJh P. Fried. › bit.ly/1hpekj1 financial support to further research with significant scientific merit.› epi.is/1lTLI3H Dr. Ryan Demmer earned a Junior Faculty Teaching Award from the Mailman School Dr. Katherine Keyes was awarded a Calderone of Public Health; these awards recognize Junior Faculty Prize from the Mailman assistant professors who are making a School of Public Health; these prizes provide remarkable impact on education. financial support to further research with › epi.is/1T4gjFO significant scientific merit.› epi.is/1lTLI3H

38 2015 ANNUAL REPORT recent alumni statistics

2014 graduates: Where do they work?

Our graduates from the class of 2014 have accepted a wide variety of jobs: 27 percent work at universities; 17 percent work for government entities; 13 percent work for nonprofits; 11 percent work for pharma/biotech—the remainder work for research organizations, hospitals/ healthcare facilities, insurance companies, etc. Government (U.S. federal) Government (international) Managed care/insurance

Nonpro t (international)

University Nonpro t (domestic)

Hospital/health care Consulting

Research organization

Pharmaceutical/biotech Government (state/local)

2014 graduates: What are their job functions?

More than half (52 percent) of our alumni from the class of 2014 are employed as researchers, 11 percent are in management/administrative roles, and 10 percent are public health practitioners.

Marketing/communication

Other Consulting

Educator

Physician/clinician Researcher

Public health practitioner

Management/administration

DEPARTMENT OF EPIDEMIOLOGY 39 epidemiology by the numbers

global reach Our faculty members and students are doing public health work in more than 60 countries around the world.

Angola Haiti Rwanda Argentina Netherlands Saudi Arabia Australia Hong Kong Senegal Bangladesh Sierra Leone Belarus Israel South Africa Botswana Italy Spain Japan Swaziland Cambodia Jordan Sweden Cameroon Kazakhstan Switzerland Canada Kenya Tajikistan Chile Kyrgyz Republic Tanzania China Lebanon Thailand Colombia Lesotho Turkey Cote d’Ivoire Malawi Uganda Democratic Republic of the Congo Mali Ukraine Denmark Mexico United Kingdom Dominican Republic Mozambique United States Egypt Myanmar (Burma) Uzbekistan Ethiopia Nepal Venezuela Finland Norway Vietnam Oman Zambia Gabon Philippines Zimbabwe Germany Puerto Rico

40 2015 ANNUAL REPORT DEPARTMENT OF EPIDEMIOLOGY 41 faculty publications JANUARY 1–OCTOBER 31, 2015

Abdool Karim Q, Dellar RC, Bearnot B, FL, Kasner SE, Aletich VA, Caplan LR, Archary D, Liebenberg LJ, Werner L, Tulsi Bai JR, Befus M, Mukherjee DV, Lowy FD, Werner L, Frohlich JA, Kharsany AB, Abdool Derdeyn CP, Gorelick PB, Charbel FT; VER- S, Majola N, Naicker N, Dlamini S, Hope TJ, Larson EL. Prevalence and Predictors of Karim SS. HIV-Positive Status Disclosure iTAS Study Group. Hemodynamic Features Samsunder N, Abdool Karim SS, Morris Chronic Health Conditions of Inmates Newly in Patients in Care in Rural South Africa: of Symptomatic Vertebrobasilar Disease. L, Passmore JA, Garrett NJ. Randomized Admitted to Maximum Security Prisons. J Implications for Scaling Up Treatment and Stroke. 2015 Jul;46(7):1850-6. PubMed Cross-Sectional Study to Compare HIV-1 Correct Health Care. 2015 Jul;21(3):255- Prevention Interventions. AIDS Behav. 2015 PMID: 25977279. Specific Antibody and Cytokine Concentra- 64. PubMed PMID: 26084947; NIHMSID: Feb 13. tions in Female Genital Secretions Obtained NIHMS701389; PubMed Central PMCID: Ananth CV, Keyes KM, Hamilton A, Gissler by Menstrual Cup and Cervicovaginal Lavage. PMC4491502. Abdool Karim SS, Abdool Karim Q, M, Wu C, Liu S, Luque-Fernandez MA, PLoS One. 2015;10(7):e0131906. PubMed Kharsany AB, Baxter C, Grobler AC, Werner Skjærven R, Williams MA, Tikkanen M, Cnat- Baldin E, Hesdorffer DC, Caplan R, Berg PMID: 26147923. L, Kashuba A, Mansoor LE, Samsunder N, tingius S. An international contrast of rates AT. Psychiatric disorders and suicidal Mindel A, Gengiah TN; CAPRISA 004 Trial of placental abruption: an age-period-cohort Arnold KB, Burgener A, Birse K, Romas L, behavior in neurotypical young adults Group. Tenofovir Gel for the Prevention analysis. PLoS One. 2015;10(5):e0125246. Dunphy LJ, Shahabi K, Abou M, Westmacott with childhood-onset epilepsy. Epilepsia. of Herpes Simplex Virus Type 2 Infection. PubMed PMID: 26018653; PubMed Central GR, McCorrister S, Kwatampora J, Nyanga B, 2015 Oct;56(10):1623- 8. doi: 10.1111/ N Engl J Med. 2015 Aug 6;373(6):530-9. PMCID: PMC4446321. Kimani J, Masson L, Liebenberg LJ, Abdool epi.13123. Epub 2015 Sep 20. PubMed doi: 10.1056/NEJMoa1410649. PubMed Karim SS, Passmore JS, Lauffenburger PMID: 26387857; PubMed Central PMCID: Ananth CV, Lavery JA, Vintzileos AM, PMID: 26244306; PubMed Central PMCID: DA, Kaul R, McKinnon LR. Increased levels PMC4602170. Skupski DW, Varner M, Saade G, Biggio J, PMC4562018. of inflammatory cytokines in the female Williams MA, Wapner RJ, Wright JD. Severe Bangen KJ, Gu Y, Gross AL, Schneider BC, reproductive tract are associated with altered Abdool Karim SS. Overcoming Impedi- Placental Abruption: Clinical Definition and Skinner JC, Benitez A, Sachs BC, Shih R, expression of proteases, mucosal barrier ments to Global Implementation of Early Associations with Maternal Complications. Sisco S, Schupf N, Mayeux R, Manly JJ, proteins, and an influx of HIV-susceptible Antiretroviral Therapy. N Engl J Med. Am J Obstet Gynecol. 2015 Sep 19. pii: Luchsinger JA. Relationship Between Type target cells. Mucosal Immunol. 2015 Jun 2015 Aug 27;373(9):875-6. doi: 10.1056/ S0002-9378(15)01120-5. doi: 10.1016/j. 2 Diabetes Mellitus and Cognitive Change 24;PubMed PMID: 26104913. NEJMe1508527. Epub 2015 Jul 20. PubMed ajog.2015.09.069. [Epub ahead of print] in a Multiethnic Elderly Cohort. J Am Geriatr PMID: 26193047. PubMed PMID: 26393335. Aschebrook-Kilfoy B, Argos M, Pierce BL, Tong Soc. 2015 Jun;63(6):1075-83. PubMed L, Jasmine F, Roy S, Parvez F, Ahmed A, Islam PMID: 26096383; NIHMSID: NIHMS672564; Accordino MK, Wright JD, Buono D, Neugut Ananth CV, Skjaerven R, Klunssoyr K. T, Kibriya MG, Ahsan H. Genome-Wide Asso- PubMed Central PMCID: PMC4477832. AI, Hershman DL. Trends in Use and Safety Change in paternity, risk of placental ciation Study of Parity in Bangladeshi Women. of Image-Guided Transthoracic Needle Biop- abruption and confounding by birth interval: Barnes C, Boutron I, Giraudeau B, Porcher R, PLoS One. 2015;10(3):e0118488. sies in Patients With Cancer. J Oncol Pract. a population-based prospective cohort Altman DG, Ravaud P. Impact of an online 2015 Jan 20. pii: JOP.2014.001891. [Epub study in Norway, 1967-2009. BMJ Open. Aschebrook-Kilfoy B, James BC, Nagar writing aid tool for writing a randomized trial ahead of print] 2015 Feb 10;5(2):e007023. doi: 10.1136/ S, Kaplan S, Seng V, Ahsan H, Angelos P, report: the COBWEB (Consort-based WEB bmjopen-2014-007023. Kaplan E, Guerrero MA, Kuo JH, Lee JA, tool) randomized controlled trial. BMC Med. Accordino MK, Wright JD, Vasan S, Neugut Mitmaker EJ, Moalem J, Ruan DT, Shen 2015 Sep 15;13:221. doi: 10.1186/s12916- AI, Tergas A, Hu JC, Hershman DL. Serum Ananth CV. Paediatric and Perinatal Epide- WT, Grogan RH. Risk Factors for Decreased 015-0460-y. PubMed PMID: 26370288; Tumor Marker Use in Patients With Advanced miology: an Appreciation to our Impressive Quality of Life in Thyroid Cancer Survivors: PubMed Central PMCID: PMC4570037. Solid Tumors. J Oncol Pract. 2015 Sep 15. Referees. Paediatr Perinat Epidemiol. 2015 Initial Findings from the North American pii: JOP.2015.005660. [Epub ahead of print] Jan;29(1):93-5. doi: 10.1111/ppe.12170. Barr RG, Avilés-Santa L, Davis SM, Aldrich Thyroid Cancer Survivorship Study. Thyroid. PubMed PMID: 26374862. T, Gonzalez Ii F, Henderson AG, Kaplan RC, Ananth CV. Paediatric and perinatal epidemi- 2015 Oct 2. [Epub ahead of print] PubMed LaVange L, Liu K, Loredo JS, Mendes ES, Ni Ahmed S, Kim MH, Dave AC, Sabelli R, ology: past accomplishments and looking to PMID: 26431811. A, Ries A, Salathe M, Smith LJ. Pulmonary Kanjelo K, Preidis GA, Giordano TP, Chiao E, the future. Paediatr Perinat Epidemiol. 2015 Assi N, Fages A, Vineis P, Chadeau-Hyam Disease and Age at Immigration Among His- Hosseinipour M, Kazembe PN, Chimbwandira Jan;29(1):1-2. doi: 10.1111/ppe.12171. M, Stepien M, Duarte-Salles T, Byrnes G, panics: Results from the Hispanic Community F, Abrams EJ. Improved identification and Andersson NW, Gustafsson LN, Okkels Boumaza H, Knüppel S, Kühn T, Palli D, Health Study/Study of Latinos (HCHS/SOL). enrolment into care of HIV-exposed and N, Taha F, Cole SW, Munk-Jørgensen P, Bamia C, Boshuizen H, Bonet C, Overvad K, Am J Respir Crit Care Med. 2015 Oct 9. [Epub -infected infants and children following a Goodwin RD. Depression and the risk of Johansson M, Travis R, Gunter MJ, Lund E, ahead of print] PubMed PMID: 26451874. community health worker intervention in autoimmune disease: a nationally representa- Dossus L, Elena-Herrmann B, Riboli E, Jenab Lilongwe, Malawi. J Int AIDS Soc. 2015 Jan Barral S, Cheng R, Reitz C, Vardarajan B, tive, prospective longitudinal study. Psychol M, Viallon V, Ferrari P. A statistical framework 7;18(1):19305. doi: 10.7448/IAS.18.1.19305. Lee J, Kunkle B, Beecham G, Cantwell LS, Med. 2015 Dec;45(16):3559-69. doi: 10.1017/ to model the meeting-in-the-middle princi- eCollection 2015. Pericak-Vance MA, Farrer LA, Haines JL, S0033291715001488. Epub 2015 Aug 14. ple using metabolomic data: application to Goate AM, Foroud T, Boerwinkle E, Schel- Akinyemiju TF, Genkinger JM, Farhat M, PubMed PMID: 26271451. hepatocellular carcinoma in the EPIC study. lenberg GD, Mayeux R. Linkage analyses in Wilson A, Gary-Webb TL, Tehranifar P. Mutagenesis. 2015 Jun 30;PubMed PMID: Antelman G, Medley A, Mbatia R, Pals Caribbean Hispanic families identify novel Residential environment and breast cancer 26130468. S, Arthur G, Haberlen S, Ackers M, Elul loci associated with familial late-onset Alz- incidence and mortality: a systematic review B, Parent J, Rwebembera A, Wanjiku Atwoli L, Platt J, Williams DR, Stein DJ, heimer’s disease. Alzheimers Dement. 2015 and meta-analysis. BMC Cancer. 2015 L, Muraguri N, Gweshe J, Mudhune S, Koenen KC. Association between witnessing Sep 30. pii: S1552-5260(15)02650-3. doi: Mar 28;15:191. PubMed PMID: 25885593; Bachanas P, Prevention in Care and Treat- traumatic events and psychopathology in the 10.1016/j.jalz.2015.07.487. [Epub ahead of PubMed Central PMCID: PMC4396806. ment Settings Study Group. Pregnancy desire South African Stress and Health Study. Soc print] PubMed PMID: 26433351. Akinyemiju TF, McDonald JA, Lantz PM. and dual method contraceptive use among Psychiatry Psychiatr Epidemiol. 2015 Mar 15. Barral S, Vardarajan BN, Reyes-Dumeyer D, Health care access dimensions and cervical people living with HIV attending clinical care Atwoli L, Stein DJ, Koenen KC, McLaughlin Faber KM, Bird TD, Tsuang D, Bennett DA, cancer screening in South Africa: analysis in Kenya, Namibia and Tanzania. J Fam Plann KA. Epidemiology of posttraumatic stress Rosenberg R, Boeve BF, Graff-Radford NR, of the world health survey. BMC Public Reprod Health Care. 2015 Jan;41(1):e1. doi: disorder: prevalence, correlates and con- Goate AM, Farlow M, Lantigua R, Medrano Health. 2015 Apr 15;15:382. PubMed 10.1136/jfprhc-2013-100784. sequences. Curr Opin Psychiatry. 2015 MZ, Wang X, Kamboh MI, Barmada MM, PMID: 25886513; PubMed Central PMCID: Anthony SJ, Islam A, Johnson C, Navarre- Jul;28(4):307-11. PubMed PMID: 26001922; Schaid DJ, Foroud TM, Weamer EA, Ottman PMC4404041. te-Macias I, Liang E, Jain K, Hitchens PL, NIHMSID: NIHMS694673; PubMed Central R, Sweet RA, Mayeux R; NIA-LOAD/ Al-Naamani N, Palevsky HI, Lederer DJ, Che X, Soloyvov A, Hicks AL, Ojeda-Flores PMCID: PMC4452282. NCRAD Family Study Group. Genetic variants Horn EM, Mathai SC, Roberts KE, Tracy RP, R, Zambrana-Torrelio C, Ulrich W, Rostal MK, associated with susceptibility to psychosis Auld AF, Kamiru H, Azih C, Baughman AL, Hassoun PM, Girgis RE, Shimbo D, Post WS, Petrosov A, Garcia J, Haider N, Wolfe N, Gold- in late-onset Alzheimer’s disease families. Nuwagaba-Biribonwoha H, Ehrenkranz P, Kawut SM; ASA-STAT Study Group. Prognos- stein T, Morse SS, Rahman M, Epstein JH, Neurobiol Aging. 2015 Nov;36(11):3116. Agolory S, Sahabo R, Ellerbrock TV, Okello V, tic Significance of Biomarkers in Pulmonary Mazet JK, Daszak P, Lipkin WI. Non-random e9-3116.e16. doi: 10.1016/j.neurobio- Bicego G. Implementation and Operational Arterial Hypertension. Ann Am Thorac Soc. patterns in viral diversity. Nat Commun. 2015 laging.2015.08.006. Epub 2015 Aug 15. Research: Evaluation of Swaziland’s Hub- 2015 Oct 26. [Epub ahead of print] PubMed Sep 22;6:8147. doi: 10.1038/ncomms9147. PubMed PMID: 26359528; PubMed Central and-Spoke Model for Decentralizing Access PMID: 26501464. PubMed PMID: 26391192; PubMed Central PMCID: PMC4609604. to Antiretroviral Therapy Services. J Acquir PMCID: PMC4595600. Alvarez KJ, Kirchner S, Chu S, Smith S, Winn- Immune Defic Syndr. 2015 May 1;69(1):e1-12. Barthe J, Perrodeau E, Gilberg S, Ravaud P, ick-Baskin W, Mielenz TJ. Falls Reduction Anthony SJ, St Leger JA, Liang E, Hicks AL, PubMed PMID: 25942465. Ghasarossian C, Marchand-Buttin F, Deyra J, and Exercise Training in an Assisted Living Sanchez-Leon MD, Jain K, Lefkowitch JH, Falcoff H. Impact of a Doctor’s Invitation on Aviv A, Kark JD, Susser E. Telomeres, Ath- Population. J Aging Res. 2015;2015:957598. Navarrete-Macias I, Knowles N, Goldstein Participation in Colorectal Cancer Screening: erosclerosis, and Human Longevity: A Causal doi: 10.1155/2015/957598. Epub 2015 Aug 5. T, Pugliares K, Ip HS, Rowles T, Lipkin WI. A Cluster Randomized Trial. Am J Med. 2015 Hypothesis. Epidemiology. 2015 Mar 13. PubMed PMID: 26345431; PubMed Central Discovery of a Novel Hepatovirus (Phopivi- Apr 20;PubMed PMID: 25908395. PMCID: PMC4541005. rus of Seals) Related to Human Hepatitis A Aviv A, Kark JD, Susser E. Telomeres, Bayer R, Galea S. Public Health in the Virus. MBio. 2015 Aug 25;6(4). pii: e01180- atherosclerosis, and human longevity: a Amin-Hanjani S, Du X, Rose-Finnell L, Precision-Medicine Era. N Engl J Med. 15. doi: 10.1128/mBio.01180-15. PubMed causal hypothesis. Epidemiology. 2015 Pandey DK, Richardson D, Thulborn KR, 2015 Aug 6;373(6):499-501. doi: 10.1056/ PMID: 26307166; PubMed Central PMCID: May;26(3):295-9. PubMed PMID: 25774608; Elkind MS, Zipfel GJ, Liebeskind DS, Silver NEJMp1506241. PubMed PMID: 26244305. PMC4550696. PubMed Central PMCID: PMC4381978.

42 2015 ANNUAL REPORT Befus M, Lowy FD, Miko BA, Mukherjee DV, J, Feliubadaló L, Tornero E, Benítez J, Osorio Wappenschmidt B, Sutter C, Engel C, Nied- PMID: 26368008; PubMed Central PMCID: Herzig CT, Larson EL. Obesity as a Determi- A, Cajal TR, Nevanlinna H, Aittomäki K, Arun eracher D, Steinemann D, Plendl H, Kast K, PMC4569413. nant of Staphylococcus aureus Colonization BK, Toland AE, Karlan BY, Walsh C, Lester Rhiem K, Ditsch N, Arnold N, Varon-Mateeva Bourgarit A, Baron G, Breton G, Tattevin P, Among Inmates in Maximum-Security J, Greene MH, Mai PL, Nussbaum RL, Andru- R, Schmutzler RK, Preisler-Adams S, Markov Katlama C, Allavena C, Campa P, Ravaud Prisons in New York State. Am J Epidemiol. lis IL, Domchek SM, Nathanson KL, Rebbeck NB, Wang-Gohrke S, de Pauw A, Lefol C, P, Lortholary O, Carcelain G; IGRAVIH 2015 Sep 15;182(6):494-502. doi: 10.1093/ TR, Barkardottir RB, Jakubowska A,Lubinski Lasset C, Leroux D, Rouleau E, Damiola Study Group. Latent Tuberculosis Infection aje/kwv062. Epub 2015 Aug 19. PubMed J, Durda K, Jaworska-Bieniek K, Claes K, Van F; GEMO Study Collaborators, Dreyfus Screening and 2-Year Outcome in Antiret- PMID: 26292691; PubMed Central PMCID: Maerken T, Díez O, Hansen TV, Jønson H, Barjhoux L, Golmard L, Uhrhammer N, roviral-Naive HIV-Infected Patients in a PMC4564937. L, Gerdes AM, Ejlertsen B, de la Hoya Bonadona V, Sornin V, Bignon YJ, Carter J, Low-Prevalence Country. Ann Am Thorac M, Caldés T, Dunning AM,Oliver C, Fineberg Van Le L, Piedmonte M, DiSilvestro PA, de la Benjet C, Bromet E, Karam EG, Kessler Soc. 2015 Aug;12(8):1138-45. doi: 10.1513/ E, Cook M, Peock S, McCann E, Murray Hoya M, Caldes T, Nevanlinna H, Aittomäki RC, McLaughlin KA, Ruscio AM, Shahly AnnalsATS.201412-600OC. PubMed PMID: A, Jacobs C, Pichert G, Lalloo F, Chu K, Jager A, van den Ouweland AM, Kets CM, V, Stein DJ, Petukhova M, Hill E, Alonso J, 26213798. C, Dorkins H, Paterson J, Ong KR, Teixeira Aalfs CM, van Leeuwen FE, Hogervorst FB, Atwoli L, Bunting B, Bruffaerts R, Caldas- MR; Teixeira,Hogervorst FB, van der Hout Meijers-Heijboer HE; HEBON, Oosterwijk Bowman AS, Lerebours L, Amesty S, de la de-Almeida JM, de Girolamo G, Florescu S, AH, Seynaeve C, van der Luijt RB, Ligten- JC, van Roozendaal KE, Rookus MA, Devilee Rosa M, Gil E, Halpern M, Nicholas S, Lamb Gureje O, Huang Y, Lepine JP, Kawakami berg MJ, Devilee P, Wijnen JT, Rookus P, van der Luijt RB, Olah E, Diez O, Teulé A, MR. Evaluation of patient care cascade N, Kovess-Masfety V, Medina-Mora ME, MA, Meijers-Heijboer HE, Blok MJ, van Lazaro C, Blanco I, Del Valle J, Jakubowska for HIV-positive patients diagnosed in La Navarro-Mateu F, Piazza M, Posada-Villa den Ouweland AM, Aalfs CM, Rodriguez A, Sukiennicki G, Gronwald J, Lubinski J, Romana, Dominican Republic in 2011: a retro- J, Scott KM, Shalev A, Slade T, Ten Have GC, Phillips KA, Piedmonte M, Nerenstone Durda K, Jaworska-Bieniek K, Agnarsson spective cohort study. Int J STD AIDS. 2015 M, Torres Y, Viana MC, Zarkov Z, Koenen SR, Bae-Jump VL, O’Malley DM, Ratner BA, Maugard C, Amadori A, Montagna M, May 4;PubMed PMID: 25941055. KC. The epidemiology of traumatic event ES, Schmutzler RK, Wappenschmidt Teixeira MR, Spurdle AB, Foulkes W, Ols- exposure worldwide: results from the World Bradbury AR, Patrick-Miller L, Schwartz L, B,Rhiem K, Engel C, Meindl A, Ditsch wold C, Lindor NM, Pankratz VS, Szabo CI, Mental Health Survey Consortium. Psychol Egleston B, Sands CB, Chung WK, Glen- N, Arnold N, Plendl HJ, Niederacher Lincoln A, Jacobs L, Corines M, Robson M, Med. 2015 Oct 29:1-17. [Epub ahead of print] don G, McDonald JA, Moore C, Rauch P, D, Sutter C, Wang-Gohrke S, Steinemann Vijai J, Berger A, Fink-Retter A, Singer CF, PubMed PMID: 26511595. Tuchman L, Andrulis IL, Buys SS, Frost CJ, D, Preisler-Adams S, Kast K, Varon-Mateeva Rappaport C, Kaulich DG, Pfeiler G, Tea MK, Keegan TH, Knight JA, Terry MB, John Bernstein EJ, Peterson ER, Sell JL, D’Ovidio R, Gehrig A, Bojesen A, Pedersen IS, Sunde Greene MH, Mai PL, Rennert G, Imyanitov EM, Daly MB. Psychosocial Adjustment F, Arcasoy SM, Bathon JM, Lederer DJ. L, Jensen UB, Thomassen M, Kruse EN, Mulligan AM, Glendon G, Andrulis IL, in School-age Girls With a Family History Survival of adults with systemic sclerosis TA, Foretova L, Peterlongo P, Bernard Tchatchou S, Toland AE, Pedersen IS, Thom- of Breast Cancer. Pediatrics. 2015 Oct 19. following lung transplantation: A nationwide L, Peissel B, Scuvera G, Manoukian assen M, Kruse TA, Jensen UB, Caligo MA, pii: peds.2015-0498. [Epub ahead of print] cohort study. Arthritis Rheumatol. 2015 Jan S,Radice P, Ottini L, Montagna M, Agata Friedman E, Zidan J, Laitman Y, Lindblom PubMed PMID: 26482668. 7. doi: 10.1002/art.39021. [Epub ahead of S, Maugard C, Simard J, Soucy P, Berger A, Melin B, Arver B, Loman N, Rosenquist print] A, Fink-Retter A, Singer CF, Rappaport R, Olopade OI, Nussbaum RL, Ramus SJ, Bradshaw PT, Stevens J, Khankari N, C, Geschwantler-Kaulich D, Tea MK,Pfeiler Nathanson KL, Domchek SM, Rebbeck Teitelbaum SL, Neugut AI, Gammon MD. Bernstein EJ, Peterson ER, Sell JL, D’Ovidio G; BCFR, John EM, Miron A, Neuhausen TR, Arun BK, Mitchell G, Karlan BY, Lester Cardiovascular Disease Mortality Among F, Arcasoy SM, Bathon JM, Lederer DJ. SL, Terry MB, Chung WK, Daly MB, Goldgar J, Orsulic S, Stoppa-Lyonnet D, Thomas Breast Cancer Survivors. Epidemiology. 2015 Survival of adults with systemic sclerosis DE, Janavicius R, Dorfling CM, van Rensburg G, Simard J, Couch FJ, Offit K, Easton DF, Sep 23. [Epub ahead of print] PubMed PMID: following lung transplantation: a nation- EJ, Fostira F,Konstantopoulou I, Garber Chenevix-Trench G, Antoniou AC, Mazoyer 26414938. wide cohort study. Arthritis Rheumatol. J, Godwin AK, Olah E, Narod SA, Ren- S, Phelan CM, Sinilnikova OM, Cox DG. An 2015 May;67(5):1314-22. PubMed PMID: Brady JE, DiMaggio CJ, Keyes KM, Doyle nert G, Paluch SS, Laitman Y, Friedman original phylogenetic approach identified 25581250. JJ, Richardson LD, Li G. Emergency depart- E; SWE-BRCA, Liljegren A, Rantala J, Sten- mitochondrial haplogroup T1a1 as inversely ment utilization and subsequent prescription Betz RC, Petukhova L, Ripke S, Huang H, mark-Askmalm M, Loman N, Imyanitov associated with breast cancer risk in BRCA2 drug overdose death. Ann Epidemiol. 2015 Menelaou A, Redler S, Becker T, Heilmann EN, Hamann U; kConFab Investigators, Spur- mutation carriers. Breast Cancer Res. 2015 Aug;25(8):613-619.e2. PubMed PMID: S, Yamany T, Duvic M, Hordinsky M, Norris dle AB, Healey S, Weitzel JN, Herzog Apr 25;17(1):61. PubMed PMID: 25925750; 25935710. D, Price VH, Mackay-Wiggan J, de Jong J, Margileth D, Gorrini C, Esteller M, Gómez PubMed Central PMCID: PMC4478717. A, DeStefano GM, Moebus S, Böhm M, A, Sayols S, Vidal E, Heyn H; GEMO, Stop- Brady JE, DiMaggio CJ, Keyes KM, Doyle Bloemen EM, Rosen T, Clark S, Nash D, Blume-Peytavi U, Wolff H, Lutz G, Kruse R, pa-Lyonnet D, Léoné M, Barjhoux JJ, Richardson LD, Li G. Emergency depart- Mielenz TJ. Trends in Reporting of Abuse Bian L, Amos CI, Lee A, Gregersen PK, Blau- L, Fassy-Colcombet M, de Pauw A, Lasset ment utilization and subsequent prescription and Neglect to Long Term Care Ombudsmen: meiser B, Altshuler D, Clynes R, de Bakker C, Ferrer SF, Castera L, Berthet P,Cornelis drug overdose death. Ann Epidemiol. 2015 Data from the National Ombudsman Report- PI, Nöthen MM, Daly MJ, Christiano AM.Ge- F, Bignon YJ, Damiola F, Mazoyer S, Sinil- Aug;25(8):613-619.e2. doi: 10.1016/j. ing System from 2006 to 2013. Geriatr Nurs. nome-wide meta-analysis in alopecia areata nikova OM, Maxwell CA, Vijai J, Robson annepidem.2015.03.018. Epub 2015 Apr 2. 2015 Apr 30;PubMed PMID: 25936894. resolves HLA associations and reveals two M, Kauff N, Corines MJ, Villano D, Cunning- PubMed PMID: 25935710. new susceptibility loci. Nat Commun. 2015 ham J, Lee A, Lindor N,Lázaro C, Easton Boccardi V, Razdan N, Kaplunov J, Mundra Brady JE, DiMaggio CJ, Keyes KM, Li G. Jan 22;6:5966. doi: 10.1038/ncomms6966. DF, Offit K, Chenevix-Trench G, Couch JJ, Kimura M, Aviv A, Herbig U. Stn1 is Response to Letter to the Editor. Ann Epi- FJ, Antoniou AC, Pujana MA.. Assessing critical for telomere maintenance and long- Bhiman JN, Anthony C, Doria-Rose NA, demiol. 2015 Nov;25(11):881. doi: 10.1016/j. Associations between the AURKA-HMMR- term viability of somatic human cells. Aging Karimanzira O, Schramm CA, Khoza T, Kitchin annepidem.2015.07.014. Epub 2015 Aug 20. TPX2-TUBG1 Functional Module and Breast Cell. 2015 Feb 14. D, Botha G, Gorman J, Garrett NJ, Abdool PubMed PMID: 26350001. Cancer Risk in BRCA1/2 Mutation Carriers. Karim SS, Shapiro L, Williamson C, Kwong Bock NN, Emerson RC, Reed JB, Nkambule PLoS One. 2015;10(4):e0120020. Bray F, Jemal A, Torre LA, Forman D, Vineis PD, Mascola JR, Morris L, Moore PL. Viral R, Donnell DJ, Bicego GT, Okello V, Philip P. Long-term Realism and Cost-effectiveness: variants that initiate and drive maturation of Blaser N, Vizcaya LS, Estill J, Zahnd C, Kale- NM, Ehrenkranz PD, Duong YT, Moore JS, Primary Prevention in Combatting Cancer and V1V2-directed HIV-1 broadly neutralizing anti- san B, Egger M, Gsponer T, Keiser O. gems: Justman JE. Changing antiretroviral eligibility Associated Inequalities Worldwide. J Natl bodies. Nat Med. 2015 Oct 12. doi: 10.1038/ An R Package for Simulating from Disease criteria: impact on the number and proportion Cancer Inst. 2015 Sep 30;107(12). pii: djv273. nm.3963. [Epub ahead of print] PubMed Progression Models. J Stat Softw. 2015 of adults requiring treatment in Swaziland. doi: 10.1093/jnci/djv273. Print 2015 Dec. PMID: 26457756. Mar;64(10):1-22. PubMed PMID: 26064082; J Acquir Immune Defic Syndr. 2015 Sep PubMed PMID: 26424777. NIHMSID: NIHMS675170; PubMed Central 8. [Epub ahead of print] PubMed PMID: Bijwaard GE, van Poppel F, Ekamper P, PMCID: PMC4458858. 26361174. Brenner AB, Borrell LN, Barrientos-Gutierrez Lumey LH. Gains in Life Expectancy Asso- T, Diez Roux AV. Longitudinal associations ciated with Higher Education in Men. PLoS Blein S, Bardel C, Danjean V, McGuffog L, Boillot A, Demmer RT, Mallat Z, Sacco RL, of neighborhood socioeconomic character- One. 2015 Oct 23;10(10):e0141200. doi: Healey S, Barrowdale D, Lee A, Dennis J, Jacobs DR, Benessiano J, Tedgui A, Rundek istics and alcohol availability on drinking: 10.1371/journal.pone.0141200. eCollection Kuchenbaecker KB, Soucy P, Terry MB, T, Papapanou PN, Desvarieux M. Periodontal Results from the Multi-Ethnic Study of 2015. PubMed PMID: 26496647; PubMed Chung WK, Goldgar DE, Buys SS; Breast microbiota and phospholipases: The Oral Atherosclerosis (MESA). Soc Sci Med. Central PMCID: PMC4619701. Cancer Family Registry, Janavicius R, Infections and Vascular Disease Epidemiol- 2015 Sep 30;145:17-25. doi: 10.1016/j. Tihomirova L, Tung N, Dorfling CM, van ogy Study (INVEST). 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