How I Became Interested in Pain

I am often asked about the origins of my interest in pain and pain research. It’s a complex question and it fits in with my past experience: I tend to be interested in issues that both intrigue me intellectually, and that I have, in some way, experienced.

We have all experienced acute pain unless we’re one of those few unlucky people who are born with congenital insensitivity to pain. Since acute pain is in part adaptive–a warning–it makes sense that acute pain is common. Moreover, acute pain is, in most cases, easy to treat, though it still appears to be underrated, at least in hospitals in the US, as survey data demonstrate. As colleague and co-author John Loeser, MD (Neurosurgery/Anesthesia and Pain Med, U Washington) puts it, no other group of medications are as effective as opioids in the context of acute pain.

Chronic pain–as currently define, pain that lasts more than 3 months or past the point of tissue healing–is far more difficult to both understand and to treat. And that is one of the things that has drawn me in.

Back to the central question, though. How did my interest develop? There aren’t many pain epidemiologists, so the niche is relatively unoccupied, which is fortuitous for me, and for anybody who wishes to enter the field.

Two things happened almost at once. I was asked to join a team of researchers at Washington who wanted to investigate small area variations in the rates of lumbar spinal surgeries.  It was a project that drew me in. We documented the fact that even after adjusting for demographic and epidemiological variables, there was an 11-fold difference between counties in Washington State in the frequency with which a set of low back procedures were performed. And this was interesting. John Loeser, who is one of the founders of pain medicine as a field of study and of treatment, drew me in a way that intrigued me, enticed me, and stimulated me. In addition John is one of the most well rounded people intellectually whom I have ever met, as well as being passionate and enthusiastic about understanding and treating pain, and spreading his knowledge to practitioners around the world. This combination appealed deeply to my intellect and to my love of learning, and learn I did. And so history went…..the topic, and John’s charismatic mind and compassion for his patients, both attracted me.

There was a personal dimension, too. I became the team guinea pig for acute pain and for low back procedures–and for under treatment and neglect of acute pain. At the time, I experienced significant pain from nerve root compression from a herniated disc. The distribution of my symptoms, and the appearance of the MRI were consistent with one another. After about 8 months of acute and limiting pain, with conservative care, including PT not working, I decided that the condition was impacting my life and my activities in a way that was sapping me of energy, sleep, fitness, and verve. Thus, I decided to explore surgical options, and, after talking to a few spine surgeons, I decided to proceed with one of the earliest minimally invasive decompression procedures. This turned into a nightmare, though I do not think that it was the wrong decision. The surgery was done under deep sedation in one of the main operating rooms. I remember one point during the surgery in which my left leg did its own screaming, because apparently it was being assaulted, but I have no memory of the procedure after that. Within a few hours after the procedure, I was in the most severe agony that I could imagine–the classical 10/10 patient on the “what’s your pain level from 0 to 10?” This was far worse than any pain that I had experienced in the prior year, and  in addition, I had lost some sensory and motor function in part of the affected leg in a distribution consistent with the area that was being addressed by the surgery. And that is where the real trouble began.

It was a week of nightmares and unbearable pain,  and some attendant fear. I was discharged home within a couple of hours after the end of the outpatient procedure. And the pain got worse and worse and worse. The neurological compromise did not resolve. It was obvious to me that the surgery itself had done some damage.

This damage, however, was not the most disconcerting part. The truly disconcerting part was the insensitivity of the medical staff to my acute pain. I could not turn over in bed at home without going into severe spasm, and without the hottest rod or sword that you can imagine penetrating deeply into my sciatic nerve. I contacted resident after resident, and all that they could say was that it would probably go away, and just take some acetaminophen with codeine–one of the so called “weak opioids.” And I lived like this for a week until I could no longer go to the bathroom without crawling–literally– for an hour and shrieking in real agony. I remember sleeping in the bathroom one night to avoid having to crawl It was hell. I felt that it would be inappropriate to call colleagues from our research team for advice and help, so I just tried to meditate, breathe, hope. Music gave me hope–especially Bach and Mozart.

Finally, on the 8th postoperative day, I called a neurosurgeon colleague at home who served with me on the Ethics Consult Service (I headed it) at one of the community hospitals in Seattle. And he told me to come right into the ER, by medic unit, if necessary, and he would admit me to his service. I learned that it is possible to think of a hospital stay as a healing and a positive experience, you can understand the essence of what post op week number 2 was like. I was admitted for pain control and for neurologic assessment. I had patient controlled analgesia with either morphine or hydromorphone (Dilaudid). I cannot remember which. And within a few hours, I felt relief. Not total, and I could control how much–I went for enough so that I was uncomfortable, quite conscious of and responsive to my surroundings, but with much attenuated pain.  The CEO of the hospital even sent me a champagne brunch while I was in-house. I thought that mixing champagne with morphine and diazepam (Valium) would probably not be the best idea, even though the code cart was right outside my room, but my visitors enjoyed the champagne. Imaging showed that there was very recent damage to my L-5 nerve root consistent with what was done during my procedure at The Other Hospital. Living the experience was interesting, in a way, because I got to feel what I was writing intellectually about–lived experience has some value. By the end of the week, I was presented with the option of proceeding with further surgery, or going home and opting for conservative care. I chose the latter. By the next week I had chosen a physiatrist, entered physical therapy, continued a gentle and “graded” gym program, and doing things that were meaningful to me. One of those was to continue learning from our surgery project.

The whole experience was deeply disturbing, and felt existentially threatening. I went home 8 days after I was admittedq, and I cried when I got home. I had become very thankful for what I had. But the experience changed me, and angered me. It seemed to threaten my integrity, my autonomy, and my existence. What made me angry was not the adverse surgical outcome. That is what informed consent is all about, and there is always the risk of damage. I could accept that, and did from the beginning. What shook me profoundly, though–I think that it caused a pseudo, loosely defined PTSD–was the indifference to and ignorance pain by the service at the hospital in which I had the surgery. The attitude was the classical “it’s only pain. You can live with it. Nobody dies from pain (which is not true).” I experienced what I hope nobody experiences again: uncontrolled post-surgical pain from inadequate treatment due to indifference, due to an underlying cause of ignorance of pain. I was told that I could not possibly be experiencing the pain that I was relating. I will write more about the inherently subjective nature of pain in a subsequent blog post. The attending and the residents were more interested in operating than in treating the pain of a post op patient.

Once word got out Original Hospital that I had been admitted to The Other Hospital, I began getting cover your ass phone calls. Apologies from the chief of service. Deep regrets from several attendings at The Original Hospital. And I think that these well meaning individuals were indeed sorry that I had experienced an underbelly of the system. I accepted these calls gracefully and suggested that had their service been this concerned in the first place, all might have benefitted. The one person who did not call was the attending who had performed the surgery, though everybody told me that he was “very worried” about me. I just wanted to get better, though. I did not care who called me or who did not. And I also wanted to understand. To learn. And to share that learning. I have no doubt that these well meaning individuals truly were sorry that I went through the experiences that I have related here. I also know that they never really understood the underlying cause: systemic lack of knowledge of the nature of pain, and the importance of treating pain adequately.

So, it was partly because of this experience, and to honor the enthusiasm that I had developed for a new and intriguing health issue catalyzed by a brilliant, charismatic, compassionate,  and productive co-founder of interdisciplinary pain medicine that I vowed I would become deeply involved in pain research. And through that research, I not only found a mid-career mentor, but also a close friend. The wonder about pain–its causes, context, treatment, understanding–is still there. It’s mysterious. And mysteries draw me in almost inevitably. In the end, I have come to think of my own suffering during that period as something without which my career and passions would be different.

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Patient outcomes and medical/health geography

Nearly 40 years ago, Ross Mullner and Jack Goldberg published “Toward an outcome-oriented medical geography: an evaluation of the Illinois trauma/emergency medical services system” (Soc Sci Med 1978;12(2D):103-110). The underlying question was whether regionalization and optimal location of services actually made a difference in patient outcome, and the answer was “yes.” This led me, in some of my early research in the 1980s, to ask a similar question. I was interested in whether location of emergency medical service units (either BLS or ALS–that is, either EMT or paramedic units) made a difference in patient survival from cardiac arrest, and, in particular, ventricular fibrillation. My answer, too, using the Seattle Medic I program as an example, was also “yes.” Survival from out of hospital cardiac arrest dropped for each additional minute of delay. Thus, choosing the best strategic locations for these units actually mattered to survival.

In retrospect, both of these sets of articles were harbingers of the evidence-based medicine/comparative outcomes movements. I wanted to know whether the selection of location, in order to minimize aggregate response times, would benefit patients. In other words, did geography matter to outcomes?

There is other evidence that it does, at least in some contexts. Regionalization of specialized services can affect outcome, because of the well known volume-outcome relationships for procedures as diverse as coronary artery bypass grafting, aortic aneurysm surgery, the Whipple procedure for pancreatic cancers, burn services, neonatal intensive care, and others. In most centrally planned systems, regionalization is mandated and is taken for granted: complex procedures and services should be centralized and consolidated to maximize outcome and, sometimes, to minimize cost. In the US, these arrangements have been more haphazard. It is the norm for high level services for severe burns to be regionalized, as it is for highest order trauma, the most specialized neonatal intensive care units, and some organ transplantation services (cardiac transplantation and lung transplants are more consolidated than kidney transplant services). This regionalization is through a patchwork quilt of cooperative and voluntary arrangements, as well as some statutes. On the other hand, there is far less centralization and consolidation of cardiac surgery. Why? Because cardiac surgery tends to be a money maker for hospitals. Thus, in the Seattle metropolitan area, cardiac surgery is performed in between 6 and 8 hospitals, depending on the definition of the metropolitan area. This region has approximately 2.5 million people. In the UK, a similar area would be served by 1-2 institutions.

Logically, one would hope that services would be configured in a manner that best serves the patient–and not the hospitals. This is not always the case in the US–in fact, this happens far less frequently than one would hope. Of course, “benefit the patient” is a slippery term, because it can mean anything from “be most convenient for the patient” to “maximizes survival probability for the patient.” This is the case when considering whether a given service should be more dispersed, and therefore more accessible, or more centralized, which is less convenient to those at more distant locations. In the case of services for which the outcome depends in part on volume–the “practice makes perfect” orientation, a strong ethical argument can be made for greater centralization. That arrangement would be most beneficent, or at least non-maleficent, and these considerations are basic to contemporary medical ethics. In fact, it was exactly this set of considerations that led me to do a fellowship in medical ethics that led to my serving as Chief of the Clinical Ethics Consult Service at one of the Seattle area hospitals.

I see an ethically grounded outcome-orientation all too rarely in geographic studies of health services. I hope that one of our goals is to benefit “the patient” which, in the aggregate, means “to beneficent as many patients as possible.” In other words, this is the utilitarian philosophy that one sees in distributive justice considerations in medical ethics: to do the greatest good for the greatest number.

I hope that we can return to this outcome orientation in which the greatest good for the greatest number is a strong priority.

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Evidence based medicine and “in my experience.”

As an epidemiologist with interests in many clinical questions, I have naturally gotten drawn into the realm of evidence-based medicine. If you ask almost any clinician, he or she will state that they practice evidence-based medicine. But I wonder if this is actually true? In other words, what is the evidence that clinicians actually practice evidence-based medicine? I am doing a project on this now in the contexts of infectious disease practice, and in pain medicine and related specialties. To begin with, though, I have observed a dearth of research on this topic.

“In My Experience Medicine”

I’ve observed that in the surgical specialties especially, it’s very common to hear “in my experience I’ve found…” type reasoning. This has both strengths and weaknesses that are too extensive to note here. Consider the following scenario, though.

An acquaintance at the gym had hip replacement surgery 3 weeks ago. There are two major approaches to this surgery: the traditional approach, which involves a long incision laterally, and the newer anterior approach, which involves a short incision on the front of the hip area. This does not involve much muscle destruction, and the recovery times are far shorter than with the lateral approach. When I asked this person about his experience, I found that he had had the lateral approach done, not because of any clinical indication, but because his surgeon said “in my experience, it works.” The evidence is clear, though. In the hands of skilled clinicians, the outcomes from these two approaches after 1 year are identical, yet the anterior approach–the newer approach–involves less pain, less time off of normal activities, and shorter rehab. This is an example of “in my experience” medicine. To be fair, since the anterior approach is newer, there is a learning curve, and some retraining that is involved. Yet by saying that this is how he does things, this surgeon was impacting the patient’s recovery. This “in my experience medicine” cuts both ways. On the one hand, it may have sub-optimal outcomes, yet we don’t want to completely discount the importance of personal experience and the patient-physician relationship.

There are reasons to suspect “in my experience medicine”. Cognitively, there is selective memory, so that clinicians remember their patients who have done well with a given practice. This is backed up firmly by multiple studies. This introduces bias. Just as significant is the fact that that there is a dearth of data on whether or not clinicians actually practice EBM. This is what is getting me into much intriguing territory.

Consider, too, the case of spine surgery. There are a multiplicity of approaches to and indications for surgery. We can take the case of spinal stenosis, or narrowing of the spinal canal due to osteoarthritic changes, or of the foramina–areas through which spinal nerve roots exit the canal to the periphery.

Decompression surgery involves removing some of the disc that may exert pressure on the nerve roots, and “shaving” or removing some of the areas affected by the osteoarthritis, thereby minimizing nerve root compression, and therefore pain and neurologic deficit. Another approach that is sometimes followed is decompression plus fusion (which can be accomplished in a host of different ways.) Despite some definitive studies–some randomized clinical trials–that show that in the absence of instability, the outcomes from the less extensive decompression surgery are equal to or superior to fusion surgery. The latter involves much greater risk of post infection, and involves greater pain, more blood loss, more anesthesia time,  and longer recovery. Despite this, fusions are among the fastest growing surgical procedures in the US. Why?

The cynical view holds that surgeons like to operate, and that medicine in general and surgery in particular in the US is a business, with psychological and economic incentives to enhance revenue. Surgeons (neurosurgeons, orthopedic surgeons, with or without spine fellowships) are paid far more for the more procedure. In addition, fellowship trained surgeons (1-2 years post neurosurgery or orthopaedic surgery residencies) are well trained in “complex spine operations” which include fusion. Thus, this begins to invoke the “in my experience” scenario, which may operate to the detriment of patients if they are not among those few for whom fusion is really indicated.

So…we don’t really know how frequently surgeons and interventionists actually practice evidence based medicine. Yes, experience counts for something–I cannot and will not deny this. However, there are many other things at work here.

I think–I argue–that medicine is undergoing some growing pains moving from a fairly subjective base of evidence that is based upon experience and case series, to the 30 year old evidence based medicine paradigm. And, on top of that is the fact (ironically based upon “in my experience” on my part) that clinicians do not have sufficient training in critically reading and understanding clinical research and clinical trials, with a strong ability to identify a study’s strengths and weaknesses, which include biases. Put this together with the tremendous time demands of physicians, and we find that much knowledge is based upon what others say about the existing studies in various formats–and in reading abstracts, and the proliferation of publications that summarize the findings of original research, with varying accuracy.

So back to my gym acquaintance. He is doing remarkably well 3 weeks post op. I asked him if he had consulted additional surgeons before making his decision about he operation, and the answer was the all too common “no” because of his trust in the surgeon, and in his primary care physician who was the source of the referral. Yet we are in Seattle, where there is no shortage of excellent orthopedic surgeons, including many world leaders in hip replacement surgery at the University of Washington. Without going off on a tangent here at the end, was it not the responsibility of the referring physician to suggest speaking to–“interviewing” as I call it, at least one other surgeon prior to the decision of how to proceed? Was this person served best by speaking to only one surgeon–the one who performed the more extensive surgery?

As I said, he is doing well and recovering nicely. In his case, the lateral approach went fine. But epidemiology, and all clinical studies as well, are concerned with populations. Would selecting the less invasive approach make a difference in a population of 1,000 patients and surgeries? Probably yes–though the evidence may be lacking to back up this contention.

In the end, we need a solid base of evidence on whether evidence-based guidelines are followed, and whether they make a difference to patient outcomes.

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Pain seminar approaching

Each year, I get excited as the beginning of our seminar on multidisciplinary approaches to pain draws near. I teach this undergraduate honors seminar with my friend and colleague, John Loeser, of UW’s Department of Neurological Surgery, and also Anesthesiology and Pain Medicine. John is my “mentor” in pain–as one of the true founders of scientific and clinical approaches to pain, he has been a true inspiration.

We approach pain, especially chronic pain, as a phenomenon that is a multidimensional experience. By this, I mean that chronic pain is as much social and psychological as it is biological. It is depicted scientifically, but also in the rich depths of the arts, of literature, of behavioral and depth psychology. We can understand the epidemiologic approaches to pain, and clinical approaches. but unless we can understand the personal meaning of the experience of pain, perhaps we understand little.

Acute pain is a symptom and a warning: it serves an adaptive function, and is a symptom of tissue damage. Persistent pain, however, alters brain structure, brain physiology, and neurologic processes. In other words, it alters the very structure of the nervous system. Chronic pain seems to develop a life of its own, and serves no adaptive function. It becomes a disease unto itself. Approximately 100 million Americans report that they experience chronic pain at any one time. It is the top cause of disability adjusted life years globally.

Treatments are improving, but they are far from satisfactory in that treatment failures are common. The approaches that seem best–and data bear this out–are multidisciplinary approaches to pain treatment. These typically involve a combination of medication (esp tricyclic and SNRI antidepressants), antieptilectic medications (esp gabapentin and pregabalin), cognitive-behavioral therapy, relaxation, visualization and mindfulness meditation, and “graded”, or gradual, increases in physical activity, geared to the individual and to not exacerbating underlying pathology.

These mutldisciplinary programs have the best outcomes, and it is not surprising. Unfortunately, because they are few and far between, much of the population in the US does not have access to them. This is compounded by the fact that clinicians typically have poor understanding of pain, its underlying mechanisms, and its optimal treatments. The average medical school curriculum has less than one half day devoted to pain. Knowledge of how to treat acute pain is more common than knowledge of how to treat chronic pain–a much more complex phenomenon–a psychosocial phenomenon. It is more than acute pain that lasts longer than usual.

Narrative medicine–understanding the story, the narrative behind each patient’s experience–is helpful in understanding the subjective experiences of those who are caught in the cycles of chronic pain. We read one novel and one personal narrative: Philip Roth’s The Anatomy Lesson, and Reynolds Price’s A Whole New World. The former deals with a protagonist with a chronic pain problem that comes to dominate his life, and the latter is written by an author and novelist recounting his own experience with a devastatingly painful spinal tumor. Both books are eloquent narratives by 2 of the country’s greatest writers.

I can understand my excitement as we approach the beginning of the pain seminar. We expose the students to something that transcends easy diagnostic categories, and that remains mysterious, and frequently dreaded. While there are epidemiology courses on cardiovascular, cancer, and infectious disease epidemiology, or neuroepidemiology, or psychiatric epidemiology, we know of no course on pain epidemiology.

Thus, as we approach the beginning of our pain course–the only such course that we have been able to find in the US–there is good reason for our excitement. If we can get a few students to think about pain in novel ways, or to enter clinical or research careers with foci in pain, our efforts will be successful.

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Reproducibility: Or Not?

A study that demonstrated a disappointing lack of reproducibility in studies in psychology has recently received much publicity in scientific journals as well as popular media, including the New York Times. Without going into the details of the study, only 39% of the effect sizes in 100 articles could be reproduced. In other words, an admittedly overly simple interpretation is that 39% of the findings in psychological science journals could be reproduced [citation is at the end of this post]

There are all sorts of potential explanations. However, one of the tenets of scientific research is that the findings in a study should be reproducible (or replicable). If this is not the case, then the validity of the study is called into question. Putatively, sometimes something as simple as an error in data entry or faulty use of a statistical package such as STATA, SAS, or SPSS could be at fault.

How much research in scientific psychology is in fact “true?” More generally, how much research in medical, epidemiologic, and social science research is reproducible? In clinical studies, the ability to replicate findings using the actual original data is still difficult, but it is becoming easier because Congressionally mandated NIH funded data collection needs to be shared. A data sharing plan is mandatory in NIH proposals. However, replicability is all too rare and cumbersome.

The public is frequently confused when apparently conflicting results in clinical studies are publicized in the press. There are all sorts of examples, ranging from the relative contributions of diet and exercise in prevention of cardiovascular disease; the relative benefits of medication and therapy in treating affective disorders such as depression; and whether or not vitamin D supplementation attenuates the risk of diseases ranging from coronary heart disease to multiple sclerosis to affective disorders. Because vitamin D may have some effect on immune modulation, some studies have demonstrated that vitamin D deficiency may attenuate the immune response to a variety of pathogens. I am sure that all of you can think of examples.

The most downloaded paper in the PLoS journals, published years before the replicability study in Science is titled “Why most research findings are false”. [citation below] This paper is written mostly about clinical research findings–of fundamental importance in medicine and public health–but it can be extended to many of the empirical biological and social sciences. Some of the reasons for false findings include inadequate study design and statistical power, sampling and study bias, chasing statistical significance rather than a priori specifying the study power and therefore calculating, a priori, the necessary sample size, and low pre and post test probabilities for positive predictive values( aptly called by my colleague Noel Weiss, “the predictive value of a positive test”).

Despite the fundamental need for replication, it is all too difficult to accomplish. My own experience, and the experiences of innumerable colleagues in the social sciences, epidemiology, and clinical sciences is that it is difficult to obtain funding to replicate prior research, and it is equally difficult to publish research that replicates earlier research. I have seen this as a member of many NIH study sections (funding panels), National Academy of Sciences and Institute of Medicine committees, and membership on journal editorial boards. I have experienced this in submitting research papers for publication, and most colleagues with whom I have spoken repeat the same story. A damning critique of research, sometimes regarded as a fatal flaw, is that the research is “derivative” and unoriginal. In other words, it has been done before. This bias makes replication virtually impossible, even though it is fundamentally important in science and social science.

It is equally dismaying that a subpopulation of researchers who are wedded only to open qualitative interviews even deny the importance of replicability and generalizability, stating that the whole point of the effort is not to generalize, but to understand the subjective experiences of perhaps 10-20 research respondents. While I do not deny that there is much to be learned by in depth understanding of subjective experience, a denial of the importance of generalizability is almost proudly publicized as being virtually 0. This will be the subject of a subsequent post.

If 1) much psychological science is not reproducible; 2) much to most research findings are wrong; 3) it is very difficult to obtain funding for “derivative research” or to publish such research, this makes me wonder if our very understanding is misplaced. In clinical epidemiology and in clinical trials, how many of the findings are so false that treatment at the individual levels, or community based public health interventions are fundamentally incorrect? How many medications are administered based upon faulty research, how much surgery is performed out of misplaced trust in the scientific basis for the surgery, and how much public health policy and intervention is based upon findings that cannot be replicated and that may, in fact, be “false”? How much evidence based medicine is based upon incorrect and faulty evidence?

This questioning might be extended to the policy sciences in general. For example, economic and fiscal policies strive to based upon trusted understanding of the factors underlying inflation, unemployment, and economic growth?

In short, how much of our understanding in general is incorrect? Unfortunately that remains unknown.

[Open Science Collaboration, Estimating the reproducibility of psychological science. Science 2015;349:943; DOI: 10.1126/science.aac4716]

[Ioannidis JPA (2005) Why most published
research findings are false. PLoS Med 2(8): e124]

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Ebola: No Surprise

Media sources, politicians, and others have treated the current Ebola outbreak in several countries in West Africa as a complete surprise, and therefore, as an unpredictable threat. This “surprise” was not surprising at all. “Unprecedented is a moniker that I seldom saw prior to 9/11. Since then, it has become a cliche. The Ebola epidemic has been described as “unprecedented.” However, it was not unprecedented.

Had it not been Ebola, it would have been Lassa Fever, Marburg, or other hemorrhagic fevers. It could have been many diseases. In fact, the conditions have been ripe for this sort of outbreak for decades–and something like this happened before: SARS. “Emerging infectious diseases” or EIDs have been so notable in infectious diseases and epidemiology that a monthly journal of that title is already in volume 20. It has become one of the most influential journals in the field, with an impact factor of over 7, and has the third highest impact of all infectious disease journals (ISI). The first Institute of Medicine (IOM) report on emerging infectious diseases was published in 1992, and had a tremendous effect on the scientific community, on public health agencies ranging from the local to the WHO, and on policymakers and legislators throughout the world. Laurie Garrett’s well known book, “The Coming Plague,” was published in 1994–twenty years ago. For at least the past 25 years, EIDs have been prominent in my own thinking. The spread of a virus such as Ebola virus was inevitable.

Why the inevitability? Because of social, economic, and demographic changes in societies around the world. Because of economic globalization, and intensifying transportation ties worldwide. The 1992 IOM report identified the “factors in emergence,” and 5 out of the 6 that were identified were social. The sixth, “microbial adaptation and change,” is also social. What the IOM was referring to was the proliferation of antimicrobial resistance, which I will write about in a subsequent blog. The decision to use antimicrobials has a strong social dimension–public expectations of receiving a prescription, lack of public knowledge that these molecules are useless against bacteria, and the spread of antimicrobials to small pharmacies in developing countries, and, indeed, to street markets, where they may be bought freely. And, of course, the use of antibiotics to promote growth in livestock and poultry accounts for 70% of antibiotic use by volume.

Against this backdrop, where viruses and other microbes have existed in micro-foci in isolated portions of rainforest in many tropical areas, and where increasing connectivity with urban areas has constituted a demographic revolution, pathogenic viral and bacterial agents have had a rapidly increasing chance of spreading. It was entirely predictable, and many of us wrote and spoke of this near certainty. Any uncertainty concerned which agent, and where, and when. Predictive epidemiology is not yet at the point where the when and the where could be pinned down.

So was the spread of Ebola a real surprise? Not to those of us in the field. Indeed, not to those of us who saw the movie “Contagion” and realized the scientific basis for that excellent film, which I use as a teaching tool. And not to those of us who realize that the regular and periodic emergence of new influenza strains also represent disease emergence.

The current epidemic was not a surprise. In most ways, it is not even “unprecedented”–a word that I hope to never use in my writing! Not an unpredictable threat: just a threat to health, and, indeed, to economies. Once this outbreak diminishes, and it will, there will be other Ebolas in the future. Because of this, we will need novel public health interventions, and we will need to apply an old intervention on occasion: quarantine, or, the more palatably named “social distancing.” It points to the importance of the public health disciplines to society, and the importance of funding basic and applied epidemiology. I will write more about this issue of funding in the coming weeks.

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Wild polio virus has been detected in Israel. Routine environmental/water sampling in southern Israel (Rahat) detected the virus in May. It has now spread to the north. Since the first week of August, the Israeli government has mounted a campaign to administer oral vaccine (OPV) to all children under the age of 10. As of this week, over 180,000 children have been (re)vaccinated.

I must emphasize that no clinical cases of polio have been detected, despite enhanced surveillance. Rather, polio virus has been detected in water samples. That nonetheless poses a risk to any individual with inadequate immunity to the virus: either the non-immunized, or those whose immunity resulting from childhood vaccination has dwindled. And, the troubling question is how virus got into the water supply? This is because there is no known animal reservoir for the virus, and there are likely unsymptomatic carriers in the country.

Heightened wastewater surveillance has detected virus in 67 samples and 24 locations in Israel, according to the Global Polio Eradication Initiative (

It is not unheard to find polio virus isolates in the environment in developed countries with high vaccination rates (Israel’s is 94%). Indeed, there are sporadic reports of polio cases in developed countries. I remember that this was the case right before I left for a conference in Finland in 1985–and I quickly got a polio booster prior to departure. There was a well documented outbreak of clinical cases in the Netherlands in 1992.

A possible scenario explaining this unusual occurrence of polio in Israel is as follows. There are two polio vaccines that are available–the killed virus, injectable vaccine (IPV), and the oral vaccine (OPV), which is a live, attenuated virus vaccine. IPV, which was the standard vaccine given to children in Israel until roughly 1 decade ago, provides good protection to the individual, but still allows people to be adequate carriers of virus–poliovirus is an enteric virus, so the virus, when present, in the gastrointestinal system. The OPV provides mucosal immunity, and decreases shedding of the attenuated virus. To put it another way, IPV provides good protection for the individual, but, to oversimplify, does nothing to prevent passage of the virus from the individual to the environment. OPV, on the other hand, makes this far less likely because of its intestinal immunity. The current vaccination campaign uses only OPV.

The particular strain detected in Israel is identical to a strain detected in Egypt.

There is hope that polio will be eradicated in the near future. The only countries with clinical cases regularly detected are Afghanistan, Pakistan, and Nigeria. Recently, over 100 cases have been detected in Somalia. These are all countries where the public health infrastructure is chaotic, making it difficult to attain high immunization rates.

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H7N9: Source and origins identified

More of the H7N9 mystery has been solved (or almost solved) in an article published online in Nature today (Wed. Aug. 21, 2013). Let’s remember that H7N9 was first noted earlier this year in China; so far there have been >130 human cases reported, and 40 deaths, for a case fatality ratio of approx. 31%. The public health community–and I–have been concerned about this strain not because of the actual morbidity and mortality, but because of its potential for spread and increase.


Today’s article, published online in Nature (Lam, Wang, Shen et al, The genesis and source of the H7N9 influenza viruses causing human infections in China, doi:10.1038/nature12515) consists of a painstaking process of sampling from the environment as well as oropharyngeal and cloacal swabs from a variety of avian spp., including ducks, geese, and chickens. Phylogenies were then identified using quantitative reverse transciptase PCR (qRT-PCR). Based upon phylogenetic similarity, some of the article’s conclusions are:

1) Transfer of H7 viruses from domestic duck to chicken populations probably occurred at least twice in China;

2) Enzootic H9N2 viruses combined with the H7 viruses to produce H7N9, and a novel H7N7 virus that had not previously been identified. This was in chicken populations, and the novel virus has been shown, experimentally, to infect mammals.

3) Live poultry markets which are found widely in parts of China and other areas of Asia were implicated as potential foci of spread because of the presence of H7N9 in these markets. The authors caution that the H7N9 virus, and H7N7 viruses may be widespread in chickens, and therefore have the possibility of widespread species transfer to humans in these foci.


Echoing so many similar calls and observations, the authors warn that “Long-term influenza surveillance remains essential for early warning of novel reassortant viruses and interspecies transmission.”


This article is the latest of a series of articles on the molecular epidemiology of this novel virus. I argue that a big challenge is to combine two types of analysis: 1) molecular epidemiology identifying “clusters” of similar genomic configurations; and 2) geospatial analysis using GIS, spatial statistics, and spatial modeling, in combination with molecular epidemiology to understand patterns of spread of variants, and, indeed, to serve as early warning and surveillance instruments as new strains of flu and other viruses spread from localized foci, and threaten a more widespread population.

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H5N7: A problem in the making?

A new strain of avian influenza, H5N7, has been in the news recently, and every day brings with it reports of more cases and more deaths, principally in China. I am frequently asked: is this something to worry about?
It depends on the interpretation of the question. Any new strain of influenza is something for concern. Considering the mortality rates and the case fatality ratios of newly reassorted strains of influenza, we could see widespread and significant mortality and morbidity. At the same time, we must be circumspect before declaring a new strain as a potential public health emergency.

Much of the uncertainty comes from the fact that we do not know H5N7’s transmission dynamics: its R(0), or average number of people whom an infected individual infects. We do not know how virulent and pathogenic the strain is in even moderate numbers of people. In short, the basic characteristics of contagion and transmission are unknown. At this point, it is fairly certain that there is no human to human trnsmission. Were there human to human transmission, it might be time to be more concerned. Rather, H5N7 appears to be the product of genetic reassortment involving commercial and domestic fowl, and probably pigs as well. The same complex,, therefore, is probably involved here as it has been with many novel strains.
H5N7 does not appear to be completely new, although the media suggests, in many places, that it is. H5N7 was recognized in Italy in 2007.
So what are we to make out of what we see with H5N7? At this point, it bears watching through various surveillance tools available, including Flu View, WHO, CDC, ProMED, and others. I always have a great deal of respect for the destructive potential of influenza. However, during the same week that CDC has declared our period of seasonal flu transmission to be over, let’s just keep an eye on H5N7.

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Chronic pain as a public health problem

Some estimates suggest that 120 million Americans suffer from chronic pain. However, the issue is how to improve access to state of the art pain treatment. It is becoming clearer that treatments that are effective in acute pain, such as opioids, are far less effective in treating chronic pain. Chronic pain is fundamentally different than acute pain since chronic pain involves the remodeling of the brain and CNS. Acute pain is adaptive; chronic pain is usually maladaptive, and serves little physiologic purpose, yet its prevalence is so high.

In the last few years, it has become clear how little we know about public health approaches to chronic pain. Even the epidemiology and risk factors of chronic pain have received little attention–perhaps 10 or 15 people globally have published the major research in pain epidemiology. It is repeated again and again, now, that there is no proof that the use of opioids in chronic pain is appropriate. They may help some people adapt to chronic pain. The ultimate test is whether these individuals are more able to go about activities of daily living, and lives that *they* consider to be happy and productive.

Multiple disciplinary pain research teams have found in the last 50 years that graded exercise is very helpful in most chronic pain states–exercise that is appropriate for the particular individual. This includes both aerobic/cardio exercise, and appropriate muscle training, such as core muscle strengthening exercises. More recently, it has been shown that the use of imagery, relaxation techniques, and mindfulness meditation help to down regulate pain. Movement, exercise, imagery, and mindful breathing all have their places.

In addition, for many types of pain, antiepileptic medication such as gabapentin (Neurontin) and pregabalin (Lyrica, in the US) can help. Even earlier, it became clear that tricyclic antidepressants are helpful. More recently, some of the newer antidepressants, such as venlafaxine (Effexor) and duloxetine (Cymbalta) may be helpful.

Medical intervention aside, might more walkable cities help in the treatment and even prevention of pain? Research has shown that walkable neighborhoods are associated with lower rates of obesity, and possibly lower rates of obesity-related disease, such as diabetes, and cardiovascular disease. Might these walkable neighborhoods–areas with sidewalks, good lighting, and parks, to name a few characteristics–help to prevent and treat chronic pain? A testable hypothesis is that such neighborhoods are associated with lower chronic pain prevalence, after adjusting for confounders and effect modifiers.

The fact that there is no central pain registry, and that it is nearly impossible to get geographically specific data from some of the national health survey data, such as the National Health Interview Survey, hinders pain research. Basically, it is necessary to collect primary data to address these questions, which poses logistical and financial difficulties.

The fact that chronic pain is viewed as a symptom rather than as a set of pathological conditions in themselves may hinder research. This is because most research is disease oriented rather than symptom oriented. For example, most departments of epidemiology have cancer epidemiologists, cardiovascular epidemiologists, neuroepidemiologists, and, going back to the origins of the field, infectious disease epidemiologists. Though there have been several books published on the epidemiology of pain, I know of no epidemiology departments that have pain epidemiologists (maybe I am the only one).

This poses a more fundamental question: is chronic pain a symptom or a disease? A disease in itself that hinders function and happiness. Pain researchers have begun to view chronic pain as a disease. I prefer to consider it as a phenomenon: it just *is*, but chronic pain hinders happiness and harms public health.

If one third of a population (such as in the US) reports that they have chronic pain, we are dealing with one of the most prevalent public health problems. It is time to increase funding for and research on chronic pain. It is time to address chronic pain as perhaps the most prevalent public health issues. And, once there is more understanding and more appreciation of chronic pain, it will be time to address it definitively from a public policy perspective.

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