HMS - Countway Library of Medicine - Director's Blog

Let's bring genome-scale sequencing into the clinic—safely and responsibly

2012-01-23T10:05:00.000-05:00

Children's Hospital Boston today announced the launch of the CLARITY Challenge, a $25,000 competition intended to advance standards for genomic analysis and interpretation and the reporting of clear, actionable results to clinicians and patients. The competition marks the first time a healthcare institution has sent out a broad call for the development of consistent and clear ways of applying genomic insights to everyday pediatric and adult patient care.

CLARITY (Children’s Leadership Award for the Reliable Interpretation and appropriate Transmission of Your genomic information) competitors will be tasked with discovering the unknown genetic basis of the disorders faced by three pediatric patients and, in the process, create best practices for interpreting and presenting genomic sequence results to patients and their families and physicians in meaningful ways that can help guide healthcare decisions.

Ancestral betrayal

2012-01-10T10:36:00.000-05:00

We share many things with our ancestors, including a fraction of their genetic code. This genetic link to the past has further invigorated an already large industry and hobby in the exploration of genealogy and historical provenance. This piece from today's news, shows how these same records can be used to leverage your ancestors to identify you. In this instance, a murder suspect is potentially fingered by his ancestors from the Mayflower.

Hat tip: Ben Reis

Costly questions

2012-01-03T21:22:00.001-05:00

Mark Twain once said "Only one thing is impossible for God: To find any sense in any copyright law on the planet."

I was reminded of this upon reading this brief but highly illuminating article describing the delayed but then aggressively pursued commercialization of a widely taught and adopted mental health questionnaire. A newer, perhaps even superior (but free and public domain) questionnaire with a few overlapping questions has been "de-rezzed" after a copyright dispute with the vendor of the earlier questionnaire.

The right questions may help disrupt the progress of disease, but not as effectively as a well-timed exercise of copyright on questions can disrupt progress (with apologies to Mark Twain).

Hat tip: Atul Butte

Crystallizing Methods for Drug Effects

2011-12-21T21:29:00.001-05:00

Yet another powerful example of the novel syntheses in which the aggregation of individual knowledge sources becomes a lot more than the sum of its parts: Using only the most well accepted and conventional of compedia of drug characteristics, Cami et al. demonstrate the power of integrative reasoning and systematic applications of "guilt-by-association" to predict accurately, across an interval of 5 years, hundreds of novel adverse events across more than 800 drugs. This performance is likely to improve further as they proceed to integrate healthcare data from electronic health records from consumers. The addition of molecular characterizations are also anticipated to provide further precision and individualization of these predictions.

These developments will be further accelerated if we can liberate data gathered with public funding for the public good.

Alternative Senior Rounds 2011

2011-12-14T12:33:00.000-05:00

Let us re-imagine senior rounds for the 21st century.

What I am about to describe does not require any new technologies or biomedical insights; it requires merely a different use of existing resources, different emphases in training and a national focus on the real-time use of clinical data as the evidentiary basis for clinical decision-making.

Senior rounds, in which the department chair meets with the senior residents to review the cases and processes of the prior day, are a decades-old tradition in medicine, and a valuable one. But as currently practiced in most residency programs, each senior resident reporting from their written notes or electronic health record system, the rounds fall far short of what they could be. Here, I offer an “alternative reality” for senior rounds, in hopes of catalyzing a discussion about why it is not the standard of care today. As the citations attest, the findings and techniques described here are all already available. So what are the principal obstacles then to the realization of this scenario?

Soma looked around the table, picking out the Seniors whom he would ask to give reports. He glanced at the screen to the side of the conference table listing the admissions and discharges of the prior day, wait times in the emergency department, diagnoses, and laboratory work ups.

He turned to Charles. “I see you admitted a 2-month-old for ‘rule-out’ meningitis but those laboratory results don’t look particularly worrisome.” Charles nodded but directed his tablet to throw up a local map with 5 red “X”s on the room’s screen¹.

“I thought so too,” Charles said, “but the intern pointed out to me the 5 cases of N. meningitis detected in the last week by the State Department of Public Health, including one case in the same day-care center as this infant, so we thought it was prudent. We’re going to wait for culture results.” ²

Soma grunted non-committedly and moved on to Dolores: “I heard you had a little argument with the diabetes service over the discharge of Mr. Smith. Care to share what happened?”

Dolores gave him a quizzical look for this ‘softball.’ “Yes, they were quite emphatic about switching Mr. Smith to a different oral hypoglycemic agent. I argued that its safety profile was far from as well established as the generics in the same structural drug class, and shared several publications with them that made the same point. But it’s only when I showed them that the risk for myocardial infarction, over the last four years, at our hospital was 50% higher for that drug as compared to others that they relented,” ³.

Soma looked at the curve of the myocardial infarction incidence of the drug in question, portrayed in red, and the six green lines showing the myocardial infarction incidence in the same hospital for the other oral hypoglycemic agents. The red curve rose above the green curves, well beyond the reach of their error bars.

He surveyed the seniors and returned to Dolores with a conspiratorial raised eyebrow. “You might want to share with the diabetes service that the FDA just reviewed these data and 20 data sets like it from other academic health centers. They all pointed in the same direction, and when they then reviewed the post-marketing data from the pharmaceutical company manufacturing the drug, the same trend was apparent. Chalk one up for evidence-based medicine. Speaking of which, Harvey, Mrs. Jones’ s headache ended up looking like a glioma on imaging. What are you telling her and her primary care provider about prognosis?”

Harvey directed the screen to replace the map with three graphs. “We’re scheduling the biopsy but it does look like Glioblastoma Multiforme (GBM), less than 2 cm in its largest dimension. The graph on the right shows the outcomes obtained at this hospital over the last 15 years for patients presenting with headaches not attributable to mass effect, like Mrs. Jones. The graph in the middle shows the other patients with GBM at this hospital without this ‘incidental’ presentation. The graph on the right suggests a better outcome but this might be due to the location of these incidental tumors. ⁴Regardless, it’s a tough prognosis but I shared this perspective with Mrs. Jones and her doctor. By the way, for reference you can see the national outcomes on the leftmost graph and you can see that ours are on average about 20% better as measured by survival times.”

Soma shared the slightest of winks and gestured towards Virginia.

“What about the infant you had discharged from the newborn service a week ago? I see that she was readmitted last night.” Virginia, looked up from the muffin that she had been steadily deconstructing, “Yes, that was unfortunate but not completely unexpected. We had not found any cause for the earlier episode of ventricular tachycardia in the first day of life. Because the tachycardia resolved spontaneously within 20 minutes, we decided to observe for another 72 hours. As there was no recurrence and no structural anomalies of the heart on imaging, we discharged the infant with a follow-up appointment with cardiology for a month from now. The ventricular tachycardia event did trigger an automatic rule from our electronic health record system (EHR) ⁵^,⁶ which recommended a genetic screen for mutations in the depolarizing sodium and/or calcium channels. We checked the genotyping results on readmission and they are positive for a mutation in a calcium channel—CaCNB2b⁷—that was found in over one hundred children with ventricular tachycardia as per the National Registry and in no control cases. And by the way, as per our EHR data warehouse this is the fifth case in the last decade in our hospital alone. Although we were able to convert the infant back to sinus rhythm within 10 minutes, the cardiology service is considering use of an implantable cardioverter-defibrillator because of the chanelopathy.”

Soma interjected “Wasn’t the QRS interval abnormal after the first episode?” Virginia flicked the ECG from the EHR view on her tablet to the conference room screen. “No, as you can see, it was not, and there are several similar reports from the literature.” She followed by displaying several PubMed abstracts describing cases of normal ECG in infants with a chanelopathy.

Soma, turned towards the Chief Resident, “Mary Lee, are we going to have enough beds to keep up with all the activity in the ED?”

This question was asked so often that Mary Lee had already displayed the current bed census, as well as the projected lengths of stay based on several morbidity indices and predictors, on the conference room’s screen. “We’re in good shape. Worst case scenario still gives us 32 free beds by noon today⁸^,⁹. Even with seasonal adjustment for influenza ¹⁰ we have at least 8 free beds including 2 in the ICU by the time the evening shift ends. That’s within the 95% confidence interval.”

Charles was glancing repeatedly at the smartphone he kept mostly hidden under the conference table.

“Is there a problem?” Soma asked, girding himself to deliver his well-worn diatribe on the distractions of modern communications.

Charles, stood up, pointing at the smartphone “Actually, there is. The ventilation requirements for one of the preemies is trending higher and the attending pediatrician is suggesting a caffeine infusion but I don’t think it is warranted based on the data. I had better go and check in with the team to see if they are on top of it.” ¹¹

Soma leaned back with a smile. “I should warn you against ‘dismissing long-established clinical opinions without understanding the basis for their existence’¹². But go ahead, rounds are over.”

(Thanks to Carey Goldberg for very constructive comments)

1. Brownstein JS, Freifeld CC, Madoff LC. Digital disease detection--harnessing the Web for public health surveillance. N Engl J Med 2009;360:2153-5, 7.

2. Fine AM, Nizet V, Mandl KD. Improved diagnostic accuracy of group a streptococcal pharyngitis with use of real-time biosurveillance. Annals of internal medicine 2011;155:345-52.

3. Brownstein JS, Murphy SN, Goldfine AB, et al. Rapid identification of myocardial infarction risk associated with diabetes medications using electronic medical records. Diabetes Care 2010;33:526-31.

4. Potts MB, Smith JS, Molinaro AM, Berger MS. Natural history and surgical management of incidentally discovered low-grade gliomas. J Neurosurg 2011.

5. Ullman-Cullere MH, Mathew JP. Emerging landscape of genomics in the Electronic Health Record for personalized medicine. Human mutation 2011;32:512-6.

6. Overby CL, Tarczy-Hornoch P, Hoath JI, Kalet IJ, Veenstra DL. Feasibility of incorporating genomic knowledge into electronic medical records for pharmacogenomic clinical decision support. BMC bioinformatics 2010;11 Suppl 9:S10.

7. Kanter RJ, Pfeiffer R, Hu D, Barajas-Martinez H, Carboni MP, Antzelevitch C. Brugada-Like Syndrome in Infancy Presenting with Rapid Ventricular Tachycardia and Intraventricular Conduction Delay. In: Circulation; 2011.

8. Mackay M, Lee M. Choice of models for the analysis and forecasting of hospital beds. Health Care Manag Sci 2005;8:221-30.

9. Littig SJ, Isken MW. Short term hospital occupancy prediction. Health Care Manag Sci 2007;10:47-66.

10. Reis BY, Pagano M, Mandl KD. Using temporal context to improve biosurveillance. Proceedings of the National Academy of Sciences of the United States of America 2003;100:1961-5.

11. Larkin H. mHealth. Hosp Health Netw 2011;85:22-6, 2.

12. Weiss S, Hatcher RA. Tincture of digitalis and the infusion of therapeutics. JAMA 1921;76:508-13.

Publisher bypass

2011-12-09T11:38:00.001-05:00

This piece from the WSJ ("How I Became a Best-Selling Author: Self-publishing is upending the book industry. One woman's unlikely road to a hit novel.") points to a model that academia (except the physics and a few other quantitative science communities) has been slow to embrace. Who will serve the role of Amazon.com to disrupt the current, expensive model? Will it be the open access journals? The current large science publishers? Or a new platform? Or Amazon.com?

Hat tip: Victor Zak

Insignificant significance

2011-12-09T10:37:00.000-05:00

An amusing look at correlation. Less amusing when you realize that this kind of analysis is often used to drive public debate. Hat tip: Carey Goldberg

Time to protect lawful sharing of information on the Internet.

2011-11-16T11:18:00.001-05:00

This post: http://www.mozilla.org/sopa/ is a timely reminder of the risk to untrammeled sharing of communications (including those that are scholarly) that a blunt and overstepping use of the law is likely to pose. Unless we act now.

Hat tip: Ben Adida.

Genesis of citations

2011-11-16T09:32:00.001-05:00

I was just reminded of an excellent review of the various forms of transmission of authoritativeness and outright falsehoods through citations by Steve Greenberg when I saw this all too accurate portrayal of citogenesis.

Conflicts of interest and the need for expertise.

2011-11-04T12:41:00.001-04:00

Ben Adida reflects here on Lessig and makes an interesting point about what might be lost if we do not listen to experts (in vaccine efficacy in this instance) even if they are in conflict of interest.

You are not the boss of me!

2011-10-10T10:24:00.001-04:00

This assertion, made by millions of children with respect to their siblings, has its echos in many contemporary conversations about scholarship and authoritativeness. Whether it is the dominance of genetic or environmental effects in child development, or the value of a prostate specific antigen test, or the meaning of a genetic mutation, one group's truth is another's discredited hypothesis or outdated approximation. Of course, there some facts whose authoritativeness are beyond doubt, such as the speed of light. Well, maybe. Certainly, until that eschatological moment when we will all know the absolute truth, those of us who are entrusted with the curation and dissemination of knowledge, in its various guises, will have to provide tools to manage the growing multiplicity of perspectives.

In that spirit, I have unearthed a piece I wrote with Russ Altman over a decade ago about authoritativeness in the peer review process and how it could be managed ecumenically. We'll see if our futurology was authoritative.

Faster, cheaper and in control

2011-10-09T11:55:00.001-04:00

Let's say you have a problem (e.g aligning the world's literature to defining the phylogenesis of the components of the current world-wide written corpus for scholarly attribution and automatic detection of plagiarism) that requires a computational solution. But it's taking days for the software to run. Buying a faster, bigger computer might provide some speed up, but what if you could get a 1000 fold improvement through a better implementation of the algorithm at the core of your software? Here's your chance to see if it can be done through a contest hosted by the Harvard Catalyst. Will the Overmind answer your most difficult computational questions?

Out in the Open

2011-09-27T15:35:00.000-04:00

This impressive compilation from GOOD (the data issue) documents the impressive growth of Application Programming Interfaces that provide third party software developers with access to, and the ability to repurpose, large and very useful data sets. This growth is driven both by altruism and self-interest and represents a dramatic refutation of the skepticism towards the open data movement of merely a decade ago.

Hat tip David Kreda

Take two aspirin and an algorithm and call me in the morning.

2011-09-26T14:41:00.001-04:00

This note from the American Medical Association nicely summarizes the recent approval of certification in Clinical Informatics by the American Board of Medical Specialties. It represent the closest encounter between clinical training and librarianship to date. We'll see what it portends for relative compensation.

Augmenting library reality

2011-09-19T15:56:00.001-04:00

Much has been written about the importance (or lack of it ) of happenstance in browsing through books on shelves and what we have lost with web-borne search. Thanks to Juliane Schneider, we are exploring how to augment the moment of serendipity using QR codes that students armed with a common "smart phone" can scan and thereby scoop up more information at a glance. Check out our 3rd floor for these codes printed on cards inserted in shelves. Paper chase now has web hints.

Weighty searches

2011-09-08T17:43:00.000-04:00

Billions of Google searches may seem to be evanescent, ephemeral, electronic abstractions but this article suggests that they leave a weighty, grimy residue. The company’s electrical consumption (mostly the data centers) is said to create a carbon footprint of one million five hundred thousand tons in a single year. That is possibly much less than the footprint left by the car/bus trips and phone calls that have been made unnecessary by web searches. But it does suggest that search engines that will be better (i.e provide the sought for answer in fewer searches) will also be greener, even without more efficient computational hardware.

Serious secret keeping

2011-08-10T11:13:00.001-04:00

This instance of the xkcd comic strip explains much of what is wrong with our current password systems and why, for example, the passwords protecting clinical information systems are hard to remember and easy to crack. Hat tip: Sam Volchenboum

The unbearable effectiveness of data

2011-07-22T15:39:00.000-04:00

Researchers in artificial intelligence (AI) of the 1980’s, librarians and aficionados of the Semantic Web have a shared faith: The unique value of human-designed knowledge structures whether they be taxonomies, ontologies or metadata. These knowledge representations are seen as providing important leverage in information retrieval, knowledge discovery, and decision-support. In this context, I was recently reminded by Alal Eran of an article by researchers at Google about the value of BIG data. These researchers (one of whom wrote a wonderful book on Common Lisp—Paradigms of Artificial Intelligence Programming: Case Studies in Common Lisp—widely appreciated by the AI community, which includes applications for expert systems) describe how statistical methods applied to trillion-word corpora can automatically support the aforementioned information tasks without requiring human annotation/categorization. It may be that the combination of human-derived annotations (whether crowd-sourced from the web or carefully curated in the monasteries of the ivory tower) can be used synergistically with the purely statistic-learning methods, but that has yet to be convincingly demonstrated. Until then, those of us working on genomic research will see how far we can get just with data, particularly those obtained in the course of healthcare.

For those of us in libraries and those of us who are librarians, there is now an active debate that has yet to achieve resolution on what value there is in human annotations and metadata. If there is value, at what cost? And if it is cost-effective, how do we demonstrate the efficacy? Our Universities' leaders will be interested in the answers and so will our colleagues at Google.

Bibliography of Clinical Genomics

2011-06-17T15:22:00.001-04:00

Recently, we held a summit on the topic of clinical grade reporting of full genomic sequence. Given the growth in the number of papers (likely to grow hyperexponentially in the near future) David Osterbur has followed up with a very nice bibliographic guide to this emerging literature. Feel free to contact him if you would like other such articles added to the guide.

Libraries are going to the dogs

2011-05-31T20:48:00.001-04:00

Yale Law School has gone for the full monty, so if your medicolegal liability is getting you down, we are pleased to present Cooper as a prescribed cure. Please observe the maximum dose of 30 minutes.

Many happy returns

2011-05-20T10:21:00.001-04:00

This twitter feed of returns of items borrowed from the Countway Library provides a glimpse of the vibrant engagement of our community with the scholarship of the present and past. These include The Anatomy of madness : essays in the history of psychiatry, Calories don't count by Herman Taller, Tachycardias--mechanisms, diagnosis, treatment, and Observed brain dynamics by Partha Mitra. One could presume that these were not all borrowed by the same patron, but if they were, what questions were they asking?

Stuffed full of information

2011-05-13T10:54:00.000-04:00

That bird rendered by taxidermy in a museum is not only of visual interest. This report by an enterprising undergraduate points to some unexpected public health insights gleaned from the feathers of these museum specimens about the trajectory over centuries of mercury contamination in seabirds. Perhaps needless to say, this could not be done with a purely virtual collection.

Master of your information domain

2011-04-12T11:04:00.001-04:00

A nice appreciation for National Librarian Week can be found here.

Hat tip: Daniel Masys

Deadly Medicine

2011-04-05T11:37:00.001-04:00

We are hosting a sobering exhibit about what happens when medical science loses its moral compass. More details can be found here.

Write the Future

2011-04-03T11:54:00.001-04:00

A very creative approach to impactful scholarship. Worth the try even if if fails.

Hat tip: Christopher Erdmann

Let the games begin!

2011-03-08T08:42:00.001-05:00

Do you think that you can create the new software app that will revolutionize healthcare? Do you agree that substitutability will allow us all to innovate healthcare practice? As detailed on the challenge.gov website, there is now a very short term opportunity to "walk the talk" for a modest prize and immodest glory.

Neat or scruffy?

2011-03-03T16:57:00.001-05:00

Is your desk topped by the monumental accreta of your work or does it retain it's pure sheen of Scandinavian simplicity? It turns out that the dichotomy between the "Neats" and the "Scruffies" cuts across several broad swathes of the human condition. Among these are the archane arts of taxonomization and representation so well known to librarians, botanists, and engineers working on electronic health record interoperability. On the latter topic, the President's Council of Advisors on Science and Technology, (PCAST) report has issued a report on how health information technology will or will not be effectively used to improve healthcare. Given the work we are pursuing on substitutability, our own Ben Adida shared a perspective on the report.

Hall or House of Mirrors? The citation perspective.

2011-02-21T12:31:00.001-05:00

Kudos to the analysts at SCImago. They have provided an outstanding, entertaining and educational perspective on worldwide academic publishing. I'll focus here on only one aspect: citations. Although the United States is the leader in citations at 87M citations, it is a surprising laggard in self-citation (32% citations are self-citations). The leaders are China (62%), Lithuania (38%), and Iran (37%). However, in the domain of medicine, authors in the United States are considerably less reticent and rack up a self-citation rate of 47%, earning them second place. The map below of the subject areas of the USA publications indicates where the action is.

Hat tip: Peter Park

We, the librarians

2011-02-12T19:53:00.001-05:00

As Harvard University reorganizes its extensive library system, it is worth reconsidering where library activity occurs and who drives it. This effort in Finland (hat tip David Osterbur) is a reminder that although professionally trained librarians with a mission and institutional memory are central to the curation, preservation and dissemination of scholarly materials, there is no sharp demarcation as to where expertise, time and effort can be found in our collective efforts. If individual scholars do not curate their own, increasingly electronic, notes, their messages, and other residua of the scholarly process, there will be very little for institutional librarians to work wit and a gaping hole in the scholarly record. But first, academic institutions will have to provide them with a easy to use process that can last their entire careers. This is a first class opportunity for entrepreneurial, techno-librarians who can think at the scale of the Internet. Conversely, libraries must reach out the to network of distributed expertise in all areas of academic endeavors which is populated by experts often well outside the walls of organized academe. Literally tens of thousands of precious modern and ancient scholarly archives remain in the dark, queued up, waiting for an overworked archivist to provide even the most cursory cataloguing. Shotgun mass annotation, leveraging external expertise will have to become the norm and, again, there is a large opportunity for those who are able to provide such capabilities at scale and with the appropriate legal and institutional framework.

Graduation in Five Years

2011-01-26T16:02:00.001-05:00

from a doctoral program in the life sciences is a reasonable goal, under most circumstances. For some unfortunates, it is not. Prospective students should make sure that they have the key bits of information required to decide if and where to proceed with a specific graduate program. If you are already in graduate school at Harvard University, you might want to consult with some of the faculty who are knowledgeable mentors.

Genome-wide clinical-grade interpretation

2010-11-02T13:43:00.000-04:00

We are getting very close to the point that genome-scale sequence is available for clinical use. But will we know how to process and interpret it for such clinical applications?

Harvard Medical School, Children’s Hospital Informatics Program, and Harvard Medical’s School Center for Biomedical Informatics, the Partners Center for Genetics and Genomics, and the Harvard Medical School Center for Computational Genetics will hold a working meeting on December 7th and 8th, 2010 at the Countway Library on the Harvard Medical School campus. The purpose of this meeting is to directly address the challenges of providing consistent and clinically useful information to physicians and their patients based on large-scale genome sequencing. This meeting will focus on developing a "pre-competitive space" where industry collaborates earlier and more often to accelerate the clinical benefit from next-generation sequencing. Attendees are from clinical laboratory, sequencing, electronic health record companies as well as governmental and academic groups. This is a free but limited attendance meeting so please contact me if you are interested.

Holding our breath for this diabetes risk

2010-10-04T20:50:00.000-04:00

A recent study exemplifies the leverage that can be obtained from mining existing, public data sets to further our national healthcare agenda. As described by the NY Times, our colleague John Brownstein obtained data from the Centers for Disease Control and Prevention (CDC) and U.S. Environmental Protection Agency (EPA) and found a consistent relationship between the amount of air pollution (particulate matter in the air) and population risk for diabetes (after correcting for the usual suspects such as income and ethnicity). This and other large-scale populations studies such as the one we recently reported by Atul Butte suggest that we might be insufficiently including the larger environment in our study of the diabetic plague that has afflicted us.

It also suggests that we have insufficiently taken advantage of freely available public data to pursue relevant and timely medical research.

What does a Harvard Medical or School of Public Health student think when she first tours the library?

2010-08-31T15:49:00.001-04:00

Circulation and reference staff gave tours and orientations to the incoming medical and public health students and just wrote down every question that the students asked. The students volunteered these questions, and they were not prompted. The word cloud below represents their questions. It will be interesting to see if this cloud will change with time for this group. (Hat tip Wendy Brown)

Do you get to read your own genetic data?

2010-08-03T13:13:00.000-04:00

My distinguished colleague Patrick Taylor and genetics/bioethics researchers Wylie Burke and Laura Beskow engaged in an interesting debate that can be listened to at TheScientist.

What are they checking out at Harvard Medical School?

2010-07-08T15:04:00.001-04:00

Enterprising souls at the circulation desk of the Countway Library of Medicine have provided this Twitter feed on the books being checked out (http://twitter.com/hrvrd_med_out). See how studious your colleagues are?

Marco Ramoni

2010-06-16T15:38:00.001-04:00

My dear and brilliant colleague, Marco Ramoni, died unexpectedly last week. This is not the venue for personal recollections, so I provide the academic sketch here as well as an invitation for contributions to a prize in his honor.

Marco Ramoni, PhD, Associate Professor and Medicine at Harvard Medical School and research faculty at Children’s Hospital, Boston and Brigham and Women’s Hospital. Most recently the Director, Biomedical Cybernetics Laboratory, Harvard Medical School, Director, NLM Fellowship in Biomedical Informatics, Children's Hospital Informatics Program., and Associate Director of Bioinformatics, Harvard - Partners Center for Genetics and Genomics. He was also the Director of the course “Biomedical Informatics” at the Harvard-MIT Division of Health Sciences and Technology, core faculty of the course Genomic Medicine at Harvard Medical School and a member of the curriculum committee of the Cellular and Molecular Medicine track of the Medical Physics and Medical Engineering graduate program at Harvard-MIT Division of Health Sciences and Technology. He was co-founder of Bayesware LLC, a software company developing machine-learning programs based on Bayesian methods.

He received a PhD in Biomedical Engineering and a BA in Philosophy (Epistemology) from the University of Pavia (Italy) and his postdoctoral training from McGill University, Montreal (Canada). He held academic and visiting positions at the University of Massachusetts, the University of London (United Kingdom), the Knowledge Media Institute (United Kingdom), and the University of Geneva (Switzerland). He was author of well over 100 publications in genetics, biomedical informatics, statistics and artificial intelligence.

The AMIA Board of Directors, at the urging of Dr. Ramoni’s colleagues, devoted friends and family, this week established the Marco Ramoni Fund, to support an award in Marco’s honor to be presented each year at the AMIA Summit on Translational Bioinformatics (TBI). The award will be presented to the author who submits a paper at the meeting that best exemplifies the spirit and scholarship of Marco F. Ramoni, PhD. To read more about Dr. Ramoni and the new Marco F. Ramoni Fund, click here.

Let our data go

2010-06-15T11:06:00.001-04:00

In principle we have access to our own healthcare data. In practice, it is frequently laborious, costly and at least inconvenient and sometimes impossible. In that context as noted by my colleague Keith Strier, we have some good news from the federal government.

In the very first PCHRI conference, when I facilitated the business section, one of the few truly memorable take-aways for me was coming to the conclusion that what we really needed was a “download” button on EHRs. It seemed so simple, but unachievable. Yet, here we are, the first major public initiative to install a download button. It’s nice to see if come full circle.

http://govhealthit.com/newsitem.aspx?nid=73961

Perhaps the government will mandate that all developers and vendors of electronic health records must follow suit.

Should your email be archived?

2010-06-07T22:06:00.001-04:00

Who will make sure that the pearls of your scholarship, scattered throughout your email and other electronic files will survive and be studied? Or should such digital ephemera be allowed to be composted in the big electronic bit bucket in the sky? These and other questions will be addressed June 9th at the Harvard Digital Scholarship Summit.

What about the environment?

2010-05-31T11:29:00.000-04:00

Hundreds of millions of dollars have been spent on comparing the frequencies of genetic variants in disease-afflicted and control populations to suss out the genetic basis of diseases, common or rare. The results for diseases with diabetes have been mixed which despite the high concordance of this disease in identical twins raises yet again the question of the role of the environment in the etiology of diabetes. Of course, we know that the inherited component of diabetes risk is contingent on environmental factors (notably diet) but these are much harder to quantify and moreover there is a universe of environmental risks that is potentially much larger than the entirety of the genome. So how to go about capturing more of the environmental risk as it pertains to real human beings (as opposed to petri dish or rodent studies)?

Atul Butte at Stanford shows us how, through the lens of informatics, systematic approaches can be taken to understand the environmentally-borne determinants of our disease burden. He leverages one of the most admirable public national studies of US citizens, the NHANES study. Butte and colleagues performed analyses analoguously to genome wide association studies but instead examined each of the chemicals (e.g. pesticides, heavy metals, vitamin metabolites) measured in the urine and blood of the members of the NHANES groups comparing cases of diabetes vs. controls. As summarized in the figure below, after comparing multiple groups they found a consistent increased risk of diabetes with PCB and pesticide derivatives and a decreased risk with some carotene derivatives (related to vitamin A). Although, just as for their genome-wide analogues, the results of this Environment Wide Association Study (EWAS) should be taken with due caution, they add to a growing array of methodologies that provide a complement to conventional randomized and controlled studies.

Looking SHARPly at electronic health records

2010-04-13T08:49:00.001-04:00

Earlier, I commented about some concerns about current implementations of electronic health records and aspirations for a very different model that would be far more nurturing of innovation. John Halamka was kind enough to craft a summary of a recent award we just received for a proposal to bring these aspirations to practice.

Science Meets Nature

2010-04-01T13:55:00.001-04:00

Who's Gonna Pay for these Journals?

2010-03-24T11:06:00.001-04:00

Town Hall Meeting: Who’s Gonna Pay for these Journals?

2:00-3:30 PM

Thurs., April 8, 2010

TMEC, Walter Amphitheater

Harvard Medical School

Scholarly Communication is broken.

Your access to articles in Brain Research, Tetrahedron Letters, Cell, Nature publications, and other leading journals in every discipline is paid for to the tune of millions of dollars per year by Harvard libraries.

Journal costs are skyrocketing and free market processes are failing to control costs--STM publishers can charge what they want without regard to value because they have a monopoly on the content that you have given them. More and more you will be seeing "This article is not included in your organization's subscription " because libraries can no longer afford to buy back the content that has been freely given to the publishers. Commercial publishers make up to 40% profit on work produced here at Harvard and other research institutions. How can we establish some control over these costs and at the same time make it easier for you to regain control of your rights to use your own work?

Come to a Town Meeting and discuss what we can do to fix scholarly communication!

Free access app for open access content

2010-03-22T22:11:00.000-04:00

We have just released a new iPhone application in collaboration with PloS Medicine and with the leadership of the Healthmap team (particularly John Brownstein) that allows you to read, browse and share content from PLoS Medicine including their features such as "collections". More to come in this vein from this and other knowledge sources in the near future.

Libraries can be catalysts for translational research

2010-03-12T09:07:00.001-05:00

It's an open secret that most major academic health centers are lagging in providing their researchers with state of the art knowledge in the computational techniques required to analyze data sets with tens of thousands of variables. The exponential growth of the generation of these data sets over the last decade has far outstripped the ability of the average post-doctoral student to analyze them. With the advent of libraries whose curatorial taste and reference expertise now extends to vast biomedical data sets and their analysis, we are well positioned to catalyze the diffusion of bioinformatics expertise through the research community. One such example is heralded here at the Harvard Clinical and Translational Science Center.

Making new the old

2010-03-11T12:17:00.001-05:00

In this era of fungible electronic sources of data, there remain unique sources of scholarly materials developed in the course of the conduct of biomedical research. One of these is the Countway's Center for the History of Medicine (CHoM) which has just inaugurated its new electronic public face. There, you can learn which of CHoM's holding have been recently featured in the Smithsonian Magazine, a new initiative for digitizing rare books, or the availability of a new important collection.

We will miss our book-filled bookshelves (at least for a while)

2010-03-11T12:06:00.001-05:00

This article on the proliferation of incompatible electronic book formats and digital rights management (DRM) standards for book content is a stark reminder that much of what is digital is incompletely archived, if at all. This is particularly the case for our personal collections. I have some favorite novels and text books which I can still pick off my shelves in my office months or decades after I first purchased them. Until that unlikely day that all digital books are sold without DRM or that one DRM/encoding is adopted by all electronic book vendors, I will have to hope against hope that the vendor of the e-book I also use will remain in business. Otherwise, I will have to regularly repurchase all the books I purchased in electronic form every few years. Or just reread those older and less evanescent paper-based books.

the new conditions of the Harvard Medical School promise to be as nearly ideal as the forethought of man can plan

2010-03-08T10:18:00.001-05:00

or so it says in this 1905 article from Popular Science now available to all through the Popular Science archive viewer (courtesy of Google). Worth reading also for many wonderful quotes including "A medical student so trained [ in regularly reading selected up-to-date publications] in the use of medical literature can hardly be content to depend on antiquated text-book knowledge in his practise in after years." Amen. But do our students currently know how to (and have the culture) get up to date genetic and genomic relevant knowledge from the web? Perhaps our libraries can continue to lead in this regard.

What the Tell-Tale Heart Tells Us About Healthcare

2010-02-21T11:54:00.001-05:00

At the end of his short story, Edgar Allen Poe's haunted murderous protagonist lets loose in front of the unsuspecting police officers:

"Villains!" I shrieked, "dissemble no more! I admit the deed! -- tear up the planks! -- here, here! -- it is the beating of his hideous heart!"

It is this story that inspired the title of a paper we published a few years ago on how we could detect the increase (and subsequent decrease) of myocardial infarctions coincident with the rise and fall of the use of Vioxx. This investigation relied solely on the informational byproducts of healthcare delivery. This weekend a Senate report on the risk of Avandia and what was known by GSK came to light. This resonated because we had recently published an article in Diabetes Care about the rapid identification of an increased risk of myocardial infarction with Avandia in patients with diabetes mellitus as compared to other drugs, even drugs in the same class, such as Pioglitazone. Whereas the current headlines are about what the pharmaceutical company knew or dissimulated, there is a broader question that needs addressing: Should every healthcare system not be instrumented so that the clinical leaders of these systems should know whether there are unexpected changes in the risks and health status of their patient populations?

Often, the state of clinical practice is compared unfavorably to the practice of commercial air travel, but what remains underemphasized is that as a system, we are flying blind. There is no local, regional or national air-traffic-controller-equivalent for the healthcare system. Should not the local hospital, and Department of Public Health be the first to know if there is about to be a local health collision or crash? Should not such local surveillance systems run in parallel to regional and national systems? Do we not need multi-level redundancy and open communication to avoid tens of thousands of unnecessary deaths? Further, even as the federal government becomes more aware of the need of such instrumentation, we all expect that our local healthcare systems and health authorities should know of any untoward health trends. Perhaps healthcare systems will start to compete on being able to provide timely and localized health trend data to their customers. Unfortunately right now, the major investments in such health market intelligence is to the payors (i.e. the insurers) who quite reasonably want to know what are the local risks, performance and trends for each of their contracts. Will it take regulation or market competition to make such data extraction and return to patients a matter of course? Let's hope we do not have to wait for a post-mortem Poe'esque orgy of recrimination to find out.

No iTunes-equivalent for Google

2010-02-05T15:24:00.001-05:00

Google and the Authors Guild and the Association of American Publishers had hoped to create a one-stop shop for a wide array of published works. The Department of Justice has just ruled that the current proposal does not pass muster. Whether or not this helps or hinders dissemination or scholarship appears to be a matter of some controversy.

Biomedical science is not a game for the young?

2010-01-26T11:14:00.001-05:00

The National Institutes of Health have helpfully posted summary information about their funding patterns. It is much more revealing of the training patterns and mentoring of young investigators at our academic centers than any specific NIH policy. It is evident that whatever your terminal degree, your age at first R01 is 42-44, a full 10 years older than the age of first R01 in 1970. PhD's only are 2 years younger on average than MD's and MD-PhD's are remarkably no older than the MD's (which was not the case in 1970). What does this say about the capability of our research workforce to be energetically innovative? Are we drawing from the right pool of investigators or is there something fundamentally wrong in the institutionalized career path leading to an R01?

Who are the right practictioners of medicine?

2010-01-25T11:06:00.001-05:00

This report from Haiti is a reminder that doctors are not always the answer to a healthcare need. We might be well-served by a national discussion of what are the properties of healthcare practitioners that we believe we are seeking to maximize and whether these are well matched to our needs as a society and as patients. It is a discussion which will also inform budgets.

Positive Peer Pressure

2010-01-15T10:24:00.001-05:00

Can we use Internet-borne viral messages to counter biological viruses? Our very own Ben Reis is recognized by HHS Secretary Kathleen Sebelius for his Facebook application:

The “I’m a Flu Fighter” Facebook application takes users through four steps. In the first step, “Choose My Character,” users choose between a superhero, a doctor, a virus behind bars, or a cartoon syringe to represent themselves as a flu fighter. Then, users set their status by sharing whether they got the flu vaccine or plan to, and how it was (Could be better, Fine, Good, Great!). Next, users can send invites to their friends challenging them to get vaccinated. Lastly, users are taken to a page with resources about flu such as the flu vaccine locater. The visibility of users’ information as Flu Fighters is controlled by users through their privacy settings.

When is obesity as infectious as tuberculosis (or even more)?

2009-11-24T13:26:00.001-05:00

As part of our Notable Books series, Nicholas Christakis will be reviewing the interesting relationship between our social networks and disease burden (and related phenomena). This is in context of his recently published book:Connected: The Surprising Power of Our Social Networks and How They Shape Our Lives. Time: December 10th, 4pm. Place: Countway Library of Medicine, 5th floor, Ballard auditorium.

Open Source Changing Medicine

2009-11-13T16:19:00.000-05:00

Just as Open Access is a threat to an unsustainable publishing model, so it seems are open source medical applications to the most of the closed-source offerings of the for-profit sector. In conjunction with the development of substitutable platforms, there is a new and widening opportunity for independent developers to innovate and disseminate their solutions and to let a larger and more diverse ecosystem of solutions to be adopted. What is most promising in this regard is the growing acceptance of open source solutions for implementation

Addendum: It's rewarding to see our efforts listed here as among the top 10 open source software projects changing medicine (i2b2 and indivohealth).

Normality, expertise and fairness.

2009-11-12T15:15:00.000-05:00

Who is more knowledgeable? The physician who remembers more diagnostic tests than any other physician or the physician who is the quickest and most savvy at online searching for the relevant tests? Who is the most technically expert surgeon? The one who has the most nimble fingers and the sharpest eyes or the one who can make herself most comfortable with robotically assisted micromanipulators? This story taken from athletics suggests that we are going to be uncomfortable with some of the answers to these questions for many years to come.

Screening to distraction: Greater focus on the incidentalome

2009-10-26T11:03:00.001-04:00

Last week, Gina Kolata of the New York Times summarized a growing controversy around the value of some of the types of medical screening tests currently employed.The salutory effect of this and related articles is a growing awareness of the tradeoff between increased sensitivity and specificity. It also is a shot across the bow as we contemplate the growth in the number of incidental findings that are going to occur as we test hundreds if not thousands of genetic variants today and in the future. Also, today, Gina Kolata reviewed how little we know about diseases as extensively studied as cancer. Some of them do disappear. Do these spontaneously regressed tumors contribute to the surprisingly high false positive rates for screening?

A physician of distinction: Oliver Wendell Holmes

2009-10-23T10:35:00.001-04:00

An invitation to celebrate the life, the accomplishments, and the continuing relevance of the literary and scientific contributions of Dr. Oliver Wendell Holmes.

Oliver Wendell Holmes (1809–1894) spent parts of the nineteenth century as America’s best-known physician and best-selling author. Sir William Osler praised him as “the most successful combination which the world has ever seen, of the physician and man of letters.” Henry James, Sr., called him “intellectually the most alive man I ever knew.” Today, he is remembered as a physician for his investigation of the contagiousness of puerperal fever (two decades before the advent of the germ theory), his advocacy for therapeutic skepticism and rationalism, and for coining such terms as “anesthesia.” He is celebrated as a literary and cultural figure for such poems as “Old Ironsides” (considered responsible for saving the U.S.S. Constitution), for his early forays into what would be considered a new depth psychology, and for terming Boston the “Hub of the solar system” and describing its “Brahmin” caste.

Join us to help celebrate the life, the accomplishments, and the continuing relevance of the literary and scientific contributions of Dr. Oliver Wendell Holmes.

Dr. Oliver Wendell Holmes and the Spirit of Skepticism:

November 17, 2009, 1:00 PM- 5:00 PM, reception 5:00-6:30

Location: Countway Library, 10 Shattuck St., Boston

You could be an information spigot

2009-10-13T09:38:00.001-04:00

Even if you are not an information altruist, there are those who would like to just plug you in and take it from there.

Hat tip: Ken Mandl

Where is the consumer in healthcare?

2009-10-12T09:58:00.001-04:00

Prof. Regina Herzlinger, with the Harvard Business School, will be teaching a free intensive seminar course, Innovations in Consumer-Driven Health Care, in January 2010. This is a one week class, beginning on 1/11/10 and ending on 1/15/10.

She welcomes students from the various Harvard and MIT graduate schools as well as both undergraduate universities to submit their resumes to her for consideration if they wish to enroll . These can be to jlopez@hbs.edu. The class itself will be held on the Harvard Business School campus and will likely run from 9.00am until 3.30pm with a lunch period from 11.30am-1.00pm. Students chosen to take part in this class will be notified in November.

Innovations in Consumer-Driven Health Care

Monday, January 11-Friday, January 15; 9-11:30am and 1-3:30pm
Aldrich 211

Career Focus

Health care industry

Educational Objectives

This seminar will focus on the creation of innovations in health care that
better meet consumer needs.

Content and Organization

In the first two sessions on day one, students will examine three different
national models for achieving universal coverage:

*   Consumer-driven health care in Switzerland, in which consumers use their
own funds to purchase insurance
*   Single payer health care in the UK, in which the government controls the
health care system
*   Managed competition system in the Netherlands, in which the government
creates a national health care market

On day two, the second two sessions will delineate the entrepreneurial
opportunities and obstacles created by a consumer-driven health care system.

On days three, four, and five, students will discuss case studies of
entrepreneurial, consumer-driven ventures in the following fields:

*   Health insurance - innovative efforts that support health promotion and
reward efficiency (two cases)
*   Health services - focused, integrated care for chronic diseases; specialty
hospitals; retail health care outlets; medical travel (four cases)
*   Personalized diagnostics tests for mutated genes; companies that offer
genetic maps (two cases)
*   Personalized medical devices - Proteous; Chronicle (two cases)
*   Personalized drugs (one case)
*   Personalized information (one case)

Not so knotty genomes

2009-10-09T08:37:00.001-04:00

Erez Lieberman, of the HST Bioinformatics and Integrative Genomics program has just published a provocative paper which uses moderate resolution mapping (1 megabase) of the 3 dimensional structure of the genome. The results are consistent with prior work suggesting that DNA maintains its function by packaging itself into a structure that is free of knots. Now, if I could only apply this to my collection of wires in my drawer.

Information Technology is Central to the Conduct of Medicine

2009-10-01T08:58:00.000-04:00

Medicine always was a discipline of information processing. We took data (signs and symptoms) from the patient, matched them against our knowledge-base (the hopefully updated residue of medical school) and then came up with a interwoven diagnostic and therapeutic plan. We then understood that this information processing could be automated. But then, there were no electronic medical record systems that could truly provide the data that such automation required. Decades later, the federal government is trying to make a concerted push into this arena, one that explicitly includes the patient (us) as an active participant in this information processing enterprise. Yesterday, we wrapped up an interesting meeting attended by representatives of the government, academia, and industry to address some specific opportunities to catalyze successful deployment.

Regulating Curators?

2009-10-01T06:29:00.001-04:00

This article suggests that a new bill in introduced in California may regulate how the modern curators and interpreters of biomedical data (bioinformaticians) may end up being regulated and tarred by the same brush as direct-to-consumer genetics testing companies.

“This law doesn’t just cover companies, it covers what’s done in academic institutions, too,” Butte said. “Nothing in this bill blocks that.”

More evidence, in any case, of the centrality of information processing to the biomedical enterprise.

Never Ending STories

2009-09-23T13:10:00.001-04:00

In preparation for a conference on substitutable platforms in health IT, I was directed to an instance of a growing form of self-publication that we call the Never Ending STory (NEST). This instance of NEST is the knol which has become an increasingly popular venue for publications including ones that look a lot like standard peer reviewed journals. More generally, a NEST starts as an embryonic paper. With iteration and with the help of co-author and reader suggestions, it incubates a mature manuscript. Unlike a blog, it is not just a snapshot of a narrative perspective in a sequence of snapshots, but a single integrated document. Unlike a wikipedia article it does not claim encyclopedic authoritativeness (or at least sole authoritativeness so that disagreeing contributors have to battle it out) but only the moderated perspective of the authors. Unlike a standard peer review article, it's publication does not signify the end of its incubation and the hatching of a fully mature narrative. And it is timely and time efficient to make NEST's more prevalent. How often, have you read a scientific article from five years ago and wondered if more recent developments had influenced the authors' perspective on their prior results and/or conclusions? Would it not be more effective to allow the author to update their articles (while maintaining an archival history of all prior versions) so that they continue to be current? Or if there were additional data that bolstered the case of the original article, the author could add these data to that article without having to go through an entire process of a new publication just for the incremental data. That would reduce unnecessary publication noise and increase the value of the article to the reader.

Although, right now, we are using the knol as the infrastructure for our NESTs, we can hope that academic publishers will provide vehicles of similar functionality. Until, then we will just have to incubate our own.

Once we have electronic medical records implemented, what then?

2009-09-18T10:17:00.001-04:00

We, as nation, are in the process of investing several billion dollars into the implementation of electronic health records. If all goes well, there will be a lot of individual data buried in these care systems. This begs the question of what utility, if any, this data has for research whether for genomics, comparative effectiveness research, pharmacovigilance, or public health. The NIH is hosting a conference at the end of October (entitled “Widening the Use of Electronic Health Record Data for Research”) to attempt to answer the question. All are interested parties are invited.

Evolution of Evolution

2009-09-09T11:38:00.001-04:00

In a mashup of bioinformatics methods and historical scholarship Ben Fry provides an artistic rendering of the evolution of Darwin's work. Watch it evolve for a few minutes.

Hat tip: Ben Adida

The Least Publishable Unit

2009-08-31T11:45:00.001-04:00

This might explain why we have so many journals too.

Hat tip: Ben Adida

What are medical libraries expected to do?

2009-08-26T22:35:00.001-04:00

This is not an abstract question about the future of libraries, although that is also an interesting question. It is a question about what the medical school accrediting organizations have determined. "The Liaison Committee on Medical Education (LCME) is the nationally recognized accrediting authority for medical education programs leading to the M.D. degree in U.S. and Canadian medical schools. The LCME is sponsored by the Association of American Medical Colleges and the American Medical Association." and this is what they had to say (the bold face is mine for emphasis):

D. Information Resources and Library Services
ER-11 The medical school must have access to well-maintained library and information facilities,
sufficient in size, breadth of holdings, and information technology to support its education and
other missions.

There should be physical or electronic access to leading biomedical, clinical, and
other relevant periodicals, the current numbers of which should be readily
available. The library and other learning resource centers must be equipped to
allow students to access information electronically, as well as to use self-instructional
materials.

ER-12 The library and information services staff must be responsive to the needs of the faculty, residents
and students of the medical school.

A professional staff should supervise the library and information services, and
provide training in information management skills. The library and information
services staff should be familiar with current regional and national information
resources and data systems, and with contemporary information technology.
[Revised annotation approved by the LCME in October 2007 and effective immediately.]
Both school officials and library/information services staff should facilitate access
of faculty, residents, and medical students to information resources, addressing
their needs for information during extended hours and at dispersed sites.

(This is taken from:
http://www.lcme.org/functions2008jun.pdf found at:http://www.lcme.org/standard.htm
Hat tip David Osterbur.)

These are important recommendations and ones which foreshadow trends from the very near future. We have embraced this educational mission from access of electronic resources to teaching biomedical researchers how to perform bioinformatics-enabled research (see the bioinformatics nanocourses offered to all by Reddy Galli— details here ). The central question is whether librarian training will embrace the information technology that will be required to keep libraries current and relevant to their patrons. The answer to that question will determine where the future librarians are trained and that will in turn determine how central libraries remain to the academic mission.

The alien within and other tales of curatorial genetic mishap

2009-08-26T21:51:00.001-04:00

As reported by the New Scientist.

Another quality improvement challenge for the genomically-knowledgeable librarian.

Different cell, different story

2009-08-05T21:37:00.001-04:00

A Swiss-American collaboration makes vivid just how specific the effect of cellular/tissue context is upon the impact of genetic variation. We have understood for several years that each tissue has a different (if highly overlapping) mix of expressed genes (mRNA). However this study shows, in a study of three different cell types in 75 individuals, that the variation in expression between individuals that is attributable to genetic variation in control elements (i.e. regulatory SNP's) is highly tissue dependent. That is, over half of the regulatory variants only have impact in particular tissues. This suggests that understanding the impact of human genetic variation will take a lot more detailed study and not only in one tissue (usually blood).

[Dimas, A.S., Deutsch, S., Stranger, B.E., Montgomery, S.B., Borel, C., Attar-Cohen, H., Ingle, C., Beazley, C., Arcelus, M.G., Sekowska, M., Gagnebin, M., Nisbett, J., Deloukas, P., Dermitzakis, E.T. and Antonarakis, S.E. (2009) Common Regulatory Variation Impacts Gene Expression in a Cell Type-Dependent Manner, Science.]

Distortions, biases, amplification and invention in the biomedical literature.

2009-07-22T21:58:00.001-04:00

The telephone game that many of us played as children showed the amusing side of how indirect communication can lead to distortion of the original message. Steve Greenberg has written an eye opening article in the British Medical Journal describing how he followed the entire citation network for a particular claim (that β amyloid, a protein accumulated in the brain in Alzheimer’s disease, is produced by and injures skeletal muscle of patients with inclusion body myositis) that in a medical analog of the telephone game resulted in the subsequent adoption of questionable "facts" as medical conventional wisdom. He also shows how, much like websites trying to increase their Google Pagerank, there arise mutual citation networks that will increase the acceptance of their joint claims. One of the lasting contributions of this study is the development of a vocabulary of citation distortions (reproduced below) that Greenberg used to taxonomize the citation network. It also is a vocabulary that other conscientious reviewers and readers can use in their own disciplines to identify and name these distortions.

Vocabulary of citation distortions

Citation

Both scholarly and social forms: the scholarly form connects statements to the broader

medical literature, the social form (social citation) includes self serving and persuasive

subtypes

Citation distortions

Self serving citation is always a distortion

Persuasive citation may be necessary to communicate new, sound claims to the scientific

community; it may, however, have distorted uses—citation bias, amplification, and

invention

Citation bias

Systematic ignoring of papers that contain content conflicting with a claim

Bolster claim; justifying animal models to provide opportunities to amplify claim

Amplification

Expansion of a belief system without data

Citation made to papers that don’t contain primary data, increasing the number of

citations supporting the claim without presenting data addressing it

Invention

Citation diversion—citing content but claiming it has a different meaning, thereby diverting

its implications

Citation transmutation—the conversion of hypothesis into fact through the act of citation

alone

Back door invention—repeated misrepresentation of abstracts as peer reviewed papers to

fool readers into believing that claims are based on peer reviewed publishedmethods and

data

Dead end citation—support of a claim with citation to papers that do not contain content

addressing the claim

Title invention—reporting of “experimental results” in a paper’s title, even though the paper

does not report the performance or results of any such experiments

Accidental Neurosurgery

2009-07-16T18:15:00.001-04:00

An interesting footnote for one of the more famous inhabitants of the Countway's Warren Museum.

Another perspective from the Boston Globe.

Celebrity-driven education

2009-06-25T12:40:00.001-04:00

Here's an interesting angle in promoting health literacy by two of my colleagues.

When does an electronic medical record look like an iPhone?

2009-06-17T16:44:00.001-04:00

Almost never. But it could be a lot more, as articulated by several of us who recently gathered at the Countway to discuss the matter.

Public Proponents Proliferating

2009-06-16T10:42:00.001-04:00

I was recently reviewing research on the costs of recruiting subjects for population studies. I found that even with several million dollars of subscription costs paid by the University per year, about 1/3 of the articles I had identified were not covered by our subscriptions. These articles then required an additional $20 to $35 personal investment each if I wanted to see their details. For less well-endowed institutions, the challenge is even more significant for their faculty and students. In this context, it is heartening to read this report from the Public Library of Science organization. Not only have they published high quality articles but they have 5.4 million readers, 26,000 authors, 13,000 peer reviewers, over 11,000 articles submitted in 2008 and they project that 90% of operating expenses will be covered by the PLoS funding model by the end of 2009. Hats off to a daring and creative act of social and academic organization.

A statistical cure for the voodoo

2009-06-16T00:19:00.001-04:00

A recent issue of Perspectives in Psychological Science demonstrates the kind of full-throated give and take that makes for better science. An article by Ed Vul et al, questions the results of functional magnetic resonance imaging (fMRI) studies that relate imaged changes to personality traits, emotional states, and social interactions. The heart of the critique is how the correlations are calculated and how their statistical significance is reported. Their analysis is backed up with a very substantial survey of the investigators of the studies in question. In the same issue, the supporters and detractors of the critique are given their say. Most impressive is the statistical perspective of Lindquist and Gelman. It is even-handed and informative and should be required reading for any student about to engage in research of the increasingly familiar "high dimensionality" data sets (e.g. in genomics and imaging) that allow a multiplicity of questions to be asked or hypotheses to be tested.

Update: 7/7/2009: Nice piece on this topic from NPR.

Minting a new medical record

2009-06-07T15:46:00.002-04:00

Early on in the development of personal health records, we had many discussions about how to jump-start the critical first step to adoption: populating that personally controlled record with clinical data. We recognized that, especially in the early years (i.e. 1994) healthcare institutions might be loathe to share data of their patients with these same patients (in electronic form) and even less so with other institutions delivering health care. So, it was with a slightly evil gleam that we considered the following opportunity when some of the local healthcare institutions developed patient portals to their healthcare systems (e.g. PatientSite and Patient Gateway). If patients could access their own medical record at one or more institutions, then a program working on their behalf (using their credentials) could then automatically log in and scrape up whatever HTML-formatted data was available and then reformat it into a standardized data model within a truly portable and personally controlled health record. This solution would not require that any institution hew to a particular data standard or communication protocol (beyond HTTP and HTML) but it would require us to be very nimble to update our translation programs. Specifically, if one of the hospitals would change the formatting of the screens on the patient portal, we would have to change the program that transforms those screens into a useable personal health database. That would certainly have been possible and legal but we decided not to proceed out of a sense of collegiality with our medical informatics colleagues and instead worked to cultivate more explicit data sharing governance and agreements.

Recently, however, I was reminded by my colleague Jeff Behrens, of a very successful model of data sharing in a personally controlled financial record: Mint.com. It's a remarkable site that allows anybody (and without additional cost) to develop a cohesive view of their finances drawn from myriad information sources including: your bank account(s), your retirement accounts (e.g. 401K plan), your investment brokerage account, your credit/debit card(s), and your mortgage account. To just name a few. This in the absence of any data interchange model across this multiplicity of institutions and functions. Once this aggregation is performed for you, many services are available such as alerts for over-budget spending, due dates of credit card bills, changes in your spending mix, and decision support for improved financial performance (e.g. switching to lower interest credit cards—Mint.com knows the interest rates on each card). There are a few remarkable properties of this site that may be quite instructive for healthcare information technology.

Some of us are quite comfortable passing along all our account information, user names, and passwords to a third party given a basic level of confidence in their privacy policy, as backed up by their explicitly state policies.
- Essential to this comfort however, is the immediate value that the user obtains by participating. Not in the distant future but today.
Hundreds of data sources of relevance are unified without a single standard data model (unless you consider Mint.com's model the standard).
The data source institutions did not enter into an agreement for data sharing. Only the consumer had to agree to let Mint.com automatically access these data sources with their borrowed credentials.
A national data sharing infrastructure was created in 1 year from a startup-sized technology development and marketing budget.

Mint.com now has over a million users and is tracking over $50 billion in transactions. Can healthcare organizations, or the government or healthcare entrepreneur catalyze an analoguous success?

iPhone vs. Blackberry

2009-05-26T10:22:00.001-04:00

So many of our colleagues appear to be doing their daily work holding onto an electronic device carefully positioned below eyesight (barely) that this direct comparison of two leading mobile platforms may be useful. Alternatively, there are ways to make meetings more efficient and personal.

Open Source Software Not So Evil

2009-05-07T11:55:00.001-04:00

I recall several earnest conversations with colleagues who insisted that by making all the projects I was involved in (e.g. i2b2 and Indivo) adhere to an Open Source license, I was being both naive and counterproductive. There was no way, I was told (as recently as last year) that "real" companies would get anywhere close to supporting products that had an Open Source license. This story about Microsoft's use of Open Source software in its search engine developments should settle those concerns, at least for the next few days.

More here.

Masters of Sex

2009-05-07T08:54:00.002-04:00

When studies that helped fuel the sexual revolution become the subject of scholarly retrospectives, one has to wonder what is the current social aphrodisiacal locus?

Critically acclaimed biographer Thomas Maier will be at the Countway Library of Medicine for a presentation and signing of his newest release, The Masters of Sex, offering an unprecedented look at William Masters and Virginia Johnson, the nation’s top experts on sex; their pioneering studies of intimacy, and the sexual revolution they inspired.
Thursday, May 14, 2009, Minot room, Countway Library
4:30 pm: PRESENTATION
5:30 pm: BOOK SIGNING
(The Harvard Medical Coop will be selling the book at Countway)
5:30 RECEPTION: Lahey Room

What Open Access Might Be Competing With

2009-05-04T11:26:00.001-04:00

There has been some concern articulated about the bias that could arise from author-fee-driven publications (which is one flavor of open access). Here is an example of bias within the closed access framework that can arise almost completely undetected (thanks to The Scientist for the pointer) and enabled by an industry:industry collaboration

The Australasian Journal of Bone and Joint Medicine, which was published by Exerpta Medica, a division of scientific publishing juggernaut Elsevier, is not indexed in the MEDLINE database, and has no website (not even a defunct one). The Scientist obtained two issues of the journal: Volume 2, Issues 1 and 2, both dated 2003. The issues contained little in the way of advertisements apart from ads for Fosamax, a Merck drug for osteoporosis, and Vioxx. (Click here and here to view PDFs of the two issues.)

Hat tip Josh Parker

Addendum 5/8/2009 here.

5/10/2009 More from The Scientist.

From Moss to Autism to Skateboarding

2009-05-01T11:02:00.001-04:00

Our very own Dennis Wall, demonstrates some of his impressive extracurricular "skillz."

The price of knowledge is worth knowing

2009-04-28T15:57:00.001-04:00

We all pay a lot of money for the product of our own collective academic enterprise. With 2.5 million downloads of pdf's by Harvard University patrons from our top three publisher packages, I wondered what the costs might be. Well, thanks to Betsy Eggleston, we now have a better idea:

Elsevier package 2008 article downloads: ($.76/download)
Wiley package 2008 article downloads: ($1.52/download)
Springer package 2008 article downloads: ($2.98/download)

That is a lot of money per click but several questions pose themselves:

a) Do all libraries have a similar cost per download?

b) Is the relative cost per download similarly ordered for each of these three publishers in other libraries?

c) What is the equivalent cost for a circulated book/monograph per patron-use? Is that a fair comparator?

d) What is the equivalent cost per download for open access publications (including the author cost)?

I suspect that knowing the answers to these questions is a source of leverage and power. How can we make decisions with and on behalf of our researchers, faculty and public without knowing these answers? Should we not insist on greater transparency of the relationship of academic value and cost. If you have any additional data, feel free to enter a comment regarding this post or send me an email and I will add it to this post.

Electronic Medical Nags are Largely Ignored

2009-04-28T12:43:00.001-04:00

First there was the machine that went ping. Then there were a lot of pings because of all the machines around patients and it became clear that most of them were not relevant (94% of alarms in the pediatric intensive care unit). Although there was some work done to attempt to reduce the noise, a lot of the monitors now have their alarms silenced. So, perhaps it is not too surprising that a recent study has shown that many of the electronic health record-driven advice, reminders, and warnings regarding medication are now being ignored. This begs the question whether the solution is primarily addressable by technology or really a matter of re-engineering the process of patient care.

(hat tip Ted Shortliffe)

Influenza in Massachusetts

2009-04-27T17:37:00.004-04:00

aegis.4.27.2009 Originally uploaded by kohane

Time will tell whether this picture is due to a lot of worried individuals with influenza-like symptoms showing up in emergency rooms or an actual uptick in cases. Nonetheless, there is something compelling about observing, live, the distribution of cases of influenza across this state.

An equally compelling global perspective is provided by my colleague John Brownstein.

Doctors do not bill to make insurance companies smarter

2009-04-14T01:23:00.000-04:00

Those of us who have worked with electronic healthcare data have been long aware of the limitations of billing data (aka claims data, aka administrative data) for research. They are often too coarse grained for clinical research and are inherently biased to maximize income. It is motivated by these limitations that Natural Language Processing (NLP) has become increasingly important in mining clinical records for research. What a doctor writes in her notes is much more revealing of her patient's state than what she bills for. Notwithstanding there are some significant challenges in the de-identification of textual records and in transforming these records into standardized clinical categories (e.g. SNOMED). Yet the appeal of using the clinical narrative text rather than claims data is compelling. In our work in i2b2, we have seen significant overrepresentation of diagnostic codes where a diagnostic encounter to "rule out" a disease was codified as that disease in the claims data. For example, a radiologist asked to rule out rheumatoid arthritis based on an X-ray will often classify the X-ray with a billing code corresponding to rheumatoid arthritis when perusal of the full narrative text of the radiologist's notes that there were NO findings consistent with rheumatoid arthritis.

A recent article in the Boston Globe points out additional challenges in using claims data for personal medical records. The same limitations of claims data for research appear to impinge on their utility for clinical care. My colleague John Halamka makes several useful suggestions on how to improve the use of such data, including recruiting patients themselves as collaborators in refining the categorization of their clinical records or even removing gross errors. Notwithstanding, a small number of codes are likely to be quite limiting and it may be that codifying the patient's record by using the entirety of their clinical documentation (i.e. what their care providers wrote about them) will ensure the most nuanced and most faithful representation available of what the clinician was thinking about in each clinical encounter with that patient.

Medical Justice

2009-04-02T09:20:00.001-04:00

One of the many reasons healthcare records do not have broad adoption, is that they are burdened with a multitude of functions beyond "merely" serving as a communications vehicle among the members of the healthcare team. All these functions are then bundled into monolithic systems by single vendors. It is then typically arduous and expensive to substitute new functionality for existing functions. Perhaps one of the most onerous uses of these systems, one that is not tightly linked to quality of care, is clinical documentation for preemptive legal defense rather than for effective clinical communication and decision making. This brief article in the NY Times offers a path towards safety and rationality so that patients who are injured are justly compensated and those who are not, are not compensated. It also offers as an implicit side-effect, changes in physician behavior and use of electronic medical record systems that would be focused on improving quality of care and communications (to and from patient as well as physician).

Defining Core Competencies in Informatics

2009-03-29T15:46:00.007-04:00

If you ask two well-regarded experts in informatics as to the definition of their discipline, you are highly likely to get two different answers. It is for this reason that it is remarkable that there are now several maturing efforts to define a set of core competences. These include those that are primarily around the implementation and use of clinical information/decision support systems. Others emphasize probabilistic reasoning, formalized decision science, statistically informed knowledge-mining and expertise in different communications modalities. Whatever the truly most central core competencies, it is very clear that we don't have enough experts in any of them.

Just as the lack of sufficiently well-trained bioinformaticians is delaying our harvest of the fruit of the human genome project, the lack of well-trained clinical informaticians is likely to be a rate-limiting step in the Recovery Act's plan to broadly implement electronic health record systems.

Stimulomics—An informatics initiative

2009-03-24T17:32:00.001-04:00

This comes in somewhere between useful and cheeky.

Medical Museum on the Web

2009-03-20T15:05:00.001-04:00

(Originally uploaded by otisarchives1 )An interesting example of how historical medical data can be shared more widely for scholars worldwide. If all medical libraries followed this lightweight formula for dissemination, we could avoid repeating many mistakes of the past and learn how better to deal with old challenges revisited (e.g. epidemics). Kudos to the Medical Museum.

Search + Internet = Better Public Health?

2009-03-14T20:21:00.000-04:00

Our very own John Brownstein, has just published an article in the Canadian Medical Association Journal which demonstrates the consequences of removing information bottlenecks between the public and population-level analytics. Some have expressed skepticism regarding the value of mining web-activity for "objective" reporting but, in this instance at least, it seems that a distributed network of non-experts can be effective in detecting outbreaks earlier than through standard surveillance methods.

Disclosing to and educating patients about genetic risk

2009-03-11T00:17:00.001-04:00

We've read a lot about direct to consumer disclosure of genetic risk. Here is an opportunity to learn from Prof Robert Green about what he has learned from the methodological study of the disclosure process of the genetic risk for a serious disease.

Translational Genomics Seminar Series
"Genetic Risk Assessment for Alzheimer's Disease: The REVEAL Study."
Robert C. Green, MD, MPH
Duncan Reid Conference Room Brigham and Women's Hospital on Thursday, March 19th at 5pm.

Pushing open access at Harvard Medical School

2009-03-06T11:57:00.001-05:00

A very nice account here regarding the work of our very own Alexa McCray and Scott Lapinski in leading the medical school to implementation of an open access policy and compliance with the NIH's mandate for open access in for the publications funded by the NIH.

A cautionary note about electronic health records

2009-03-06T10:01:00.001-05:00

Those of us who are pediatricians cannot help but take this personal story (Hat tip Ted Shortliffe) about the effect of electronic health records very seriously. It does point out that we are still a long way from the day when the computer is not a distracting magic box but rather serves as an active vigilant partner in the healthcare of our patients.

Open access week

2009-03-05T16:10:00.000-05:00

The politics of openness are heating up. As per SPARC (Scholarly Publishing and Academic Resources Coalition):

"To accommodate widespread global interest in the movement toward Open Access to scholarly research results, October 19 – 23, 2009 will mark the first international Open Access Week. The now-annual event, expanded from one day to a full week, presents an opportunity to broaden awareness and understanding of Open Access to research, including access policies from all types of research funders, within the international higher education community and the general public.

Open Access Week builds on the momentum generated by the 120 campuses in 27 countries that celebrated Open Access Day in 2008. Event organizers SPARC (the Scholarly Publishing & Academic Resources Coalition), the Public Library of Science (PLoS), and Students for FreeCulture welcome key new contributors, who will help to enhance and expand the global reach of this popular event in 2009: eIFL.net (Electronic Information for Libraries), OASIS (the Open Access Scholarly Information Sourcebook); and the Open Access Directory (OAD).

For more information about Open Access Week and to register, visit http://www.openaccessweek.org."

Politics as Statistics

2009-03-02T10:10:00.001-05:00

Our very own Ben Reis appears to have touched the same nerve that turns baseball fans into obsessed statisticians. Speechwars is now generating secondary analyses about the meaning of presidential utterances from a purely lexical perspective. Who is to say this is any less insightful that allegedly semantically rich punditry? Some have argued that Google's success points to the strengths of this "low-level" data driven perspective, Can we be equally effective in mining our clinical health records?

Extreme Social Networking

2009-03-01T14:37:00.001-05:00

We already know that television viewing is associated with inactivity, obesity and a variety of other problems. Now, apparently Internet-borne social networking is being billed as a risk to cognitive development and a stable affect (or not). Yet, here is a stunning example of an extremely tight and productive social network. Most of us probably would not want to be this networked but some apparently do.

How do we know what works in medical informatics?

2009-03-01T09:42:00.000-05:00

In the context of all the hubbub around the monies for health care information technology in the stimulus package, how are we going to know whether we will be have any lasting value from this investment?

This reminded me to peruse again the best resource on how to think about evaluation: Friedman and Wyatt's book on the topic "Evaluation Methods in Biomedical Informatics". Particularly useful is the chapter that describes approaches to evaluating systems when the conventional outcome metrics are either unavailable, premature, or inappropriate. Given that Chuck is in the Office of the National Coordinator for Health Information Technology, it's not unreasonable to suppose that some thought will be given to selecting those proposals for the stimulus that include worthy evaluations.

American College of Physicians gets excited about Electronic Health Records

2009-02-26T09:59:00.001-05:00

The American College of Physicians is promoting the virtues of electronic health records. Contrast this offering with this.

Hat tip Ted Shortliffe.

Our Data Ourselves

2009-02-23T17:53:00.000-05:00

The American Recovery and Reinvestment Act has important medical privacy mandates which in theory should allow for increased "liquidity" of our own healthcare data. That is, it should allow patients to request an electronic copy of their record where there is one to be had. Specifically (thanks to AMIA for a very useful summary):

Privacy –Title XIII Subtitle D

•Sec. 13405

Provides individuals the right to obtain from a covered entity using an EHR a copy of their information in electronic format, allowing the individual to designate a 3rdparty, such as a PHR, to receive a copy

This has been a long time coming and it is a welcome development. It should further stimulate an industry working on the personal use of such data.

Boston University sets an important example

2009-02-20T08:51:00.001-05:00

Boston University in its entirety has adopted an open access policy that includes both the undergraduate and graduate schools. This move signals the continued tectonic shift in the awareness of faculty of the importance of providing more efficient access to their scholarly output, for themselves, for their colleagues and for their students. Details of the policy can be found here.