Descriptions and commentary about what's in the news and your digestive health.
- IBS is No Joking Matter
- Misunderstood Functional GI Disorders
- It Takes Action to get Results
- Is there an association between abuse history and IBS?
- Fibromyalgia and IBS: How real must they be?
- Interpreting pain sensitivity in irritable bowel syndrome: what's the cause?
- Post-infectious IBS study: Are overly anxious people prone to IBS?
- Long-term PPI therapy safety study: Is there an increased risk of hip fracture?
(December 28, 2009) Of all the disorders of digestive function, irritable bowel syndrome (IBS) is the most studied and among the most frequently occurring. For that reason, it effectively serves as the model for dozens of chronic, painful disorders that occur in segments throughout the entire digestive tract.
That is one reason it was so distressing when U.S. Senator John McCain singled out as being wasteful, federal support earmarked for an IBS research center. He seemingly is ill informed on the topic.
Senator McCain is far from alone in his lack of knowledge about IBS and digestive conditions. His very public statements are a symptom of a much broader problem – a huge lack of public awareness. That lack of awareness has made it difficult to garner support for research funding for many digestive disorders. Lack of research increases the risk that persons with these disorders will not receive adequate care and treatment.
IFFGD met with a staff member in Senator McCain’s Washington DC office and hand-delivered a packet of information which will help inform the Senator and his staff on this issue. We will continue to follow-up with Senator McCain and other federal legislators and regulators.
You can help. You can take effective action. Go to our legislative alerts web page to find out how.
(February 4, 2008) News reports about a study conducted at UNC Center for Functional GI and Motility Disorders and UCLA, recently published in the medical journal Gastroenterology*, contain a glaring factual error about abuse and IBS.
The study of the effect of abuse history on pain reports and brain responses to unpleasant stimulation (rectal distention) looked at 10 women with IBS and 10 controls; 5 in each group reported abuse. Using fMRI brain imaging the researchers found greater activation in a region of the brain associated with increased pain perception in the 5 women with IBS reporting severe abuse. This small limited study is merely suggestive, but may contribute to better understanding how to better care for patients with severe IBS who have a history of abuse.
Unfortunately, news reports of the study have included a statement that, “More than 50 percent of patients with IBS have been physically or sexually abused at some time in their lives.” This is incorrect. Past studies have found that up to 50% of women with IBS and other functional GI disorders referred to specialty GI centers report past abuse experiences. But this represents a very small proportion of patients with IBS. Less than half of people with IBS ever consult with a doctor, and of those only a small percentage are seen at referral GI clinics. These referral clinics, or tertiary facilities, are specialty GI centers where the physician specialists (gastroenterologists) refer their most severe patients – those who have not responded to conventional treatments.
No studies on abuse in IBS patients, or other GI disorders, have ever suggested that abuse causes their disorders. Rather, past abuse experience may worsen symptoms, leading to a lower pain threshold, greater severity and increased challenges to the person trying to manage their recurring symptoms.
In fact, the study reported merely showed the way in which abuse history can make pain more severe, not that it is more common in these disorders. Abuse exists in people throughout society including those with illnesses and those who are healthy. The UNC investigator who looked at abuse in the study, Douglas A. Drossman, MD, previously reported there is no greater frequency of abuse history in IBS than in any other gastrointestinal disorder.
Given the lack of effective treatments for IBS, it follows that a higher percentage of women with IBS who have past abuse experiences that worsens symptoms would be seen in referral clinics compared to in the general population. That’s not news. Improving the understanding of why it worsens symptoms – possibly because of alterations in brain regions that regulate pain as this study suggests – is news and should have been the focus of news reports about the study.
– William F. Norton, Publications Editor, IFFGD
(January 27, 2008) Two weeks ago the New York Times published a front page story about a new drug approval for the treatment of fibromyalgia that questioned the validity of functional disorders and implied that both fibromyalgia and irritable bowel syndrome (IBS) are not “real.” In response, IFFGD joined a group of internationally recognized clinicians and scientists in sending a Letter to the Editor at the New York Times. The letter is intended to provide perspective and balance to the article, which was entitled “Drug Approved. Is Disease Real?” We believe it to be a disservice to leave the millions of sufferers with fibromyalgia and IBS with the thought that their medical disorder is not legitimate. The newspaper has not published our response. We present it to you here.
Letter to the Editor, New York Times
We are writing to you as academic gastroenterologists with careers in the scientific investigation and clinical care of patients with gastrointestinal disorders, as well as the executive directors from an international patient advocacy group for the functional gastrointestinal disorders, including irritable bowel syndrome. We are compelled to address the comments made by Alex Berenson in his recent article “Drug Approved. Is Disease Real?” (Jan. 14, 2008). We do understand his concerns that massive direct to consumer marketing efforts for common medical disorders may be a thinly veiled strategy for a pharmaceutical company to obtain a quick profit. Certainly this is an important issue to study. However to adequately explore this question would require attention to the specific features of the therapeutic agent and its risk/benefit ratio, the type of disorder being treated and its health care impact, and the needs and interests of the patient.
The more critical issue we want to address is the impact of Mr. Berenson’s statements which seek to make these points by relegating fibromyalgia or as stated, IBS to a “nebulous” state, something not real. With innuendo, and alleged statements of fact, the story is constructed in a way to influence the reader’s thinking, but in a discriminatory fashion. The very nature of the title which challenges the necessity of treating symptoms not considered legitimate is a disservice to the patients; those who experience the distressing and at times disabling effects of fibromyalgia, IBS or other so-called “functional” disorders. Yet epidemiological surveys and clinical investigations find these disorders to be real: they “breed true” when using standard diagnostic criteria and the results harmonize across all cultures and clinical populations. To deny their legitimacy as medical entities is unacceptable. Since the time of Descartes, scientists and clinicians have had to wrestle with the deficiencies and flaws of the dualistic concepts of illness and disease that permeates Western thinking, and which is so evident in this article: Is the patient’s illness or dis-ease (i.e., the personal perception of ill health) “real” in the absence of currently observable disease pathology or laboratory tests, or not real (i.e, non-existent or possibly “psychiatric”) as implied by Mr. Berenson? Was King George’s madness imagined before we discovered the chemical basis of porphyria?
Mr. Berenson quotes experts to convey “truths.” First, he states that some doctors believe: “...that the disease (fibromyalgia) does not exist, and Lyrica and other drugs will be taken by millions of people who do not need them.” Most of the reasons that patients see physicians are for treatment of specific clusters of symptoms, not diseases. In a recent study (Shaheen et al. Am J Gastroenterology, 2006), the top 6 gastrointestinal diagnoses made in outpatient clinics were heartburn, abdominal pain, gastroenteritis, constipation, dyspepsia (gastritis) and IBS, accounting for 20 million annual visits (followed by hemorrhoids, 1.5 million visits). In fact the most common symptom that patients report, accounting for 12 million visits was abdominal pain followed by diarrhea (3.8 million visits). These symptoms-based diagnoses, much like migraine headache are not characterized by disease pathology; presently, no x-ray or blood test will diagnose them, though medical science may eventually change this. For the individual experiencing these symptoms, their impaired daily function and reduced health related quality of life is very real and requires treatment. To say they don’t have a real disease is a disservice to the patient, and to withhold treatment refutes the basic tenets of medicine: to care for patients.
Second is the concept that these disorders are “nebulous” or poorly defined. Over the last two decades there has been an explosion in research in brain-body science, neurotransmitter function, and brain imaging that is precisely defining the location and mechanisms that explain these symptoms. This is probably the most exciting area in modern medical investigation, and many new drugs are being targeted to treat these mechanisms.
Third, is the presumption that making a diagnosis (for example of fibromyalgia) worsens the condition by encouraging people to think of themselves as sick. Experience shows that providing a diagnostic label usually reduces health care utilization. Patients who suffer from a chronic disorder are relieved to know that a diagnosis exists, rather than have to go through numerous expensive studies that are always negative, or to be stigmatized by family, friends and physicians who tell them “nothing is wrong” or that it’s “psychiatric” or in the least to be freed from the burden of wondering if indeed they really are “crazy” (to experience what they do and to have nothing found).
Finally, there is the statement that the condition is: “...a physical response to stress, depression and economic and social anxiety.” The issue here is not whether or not this is true, but the implied intent that such an association makes the condition less real. Modern science has substantiated over and over that the onset and exacerbations of “real” diseases like tuberculosis, HIV disease, colitis and even certain cancers can occur in response to all these factors.
We are joined by many colleagues committed to the care of patients with functional somatic syndromes and functional gastrointestinal disorders to request that you please put this issue in its proper perspective. We treat real people with real diagnoses.
– Douglas A. Drossman, MD, Professor of Medicine and Psychiatry, Co-Director UNC Center for Functional GI and Motility Disorders, Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, USA
– Lin Chang, MD, Professor of Medicine in Residence, UCLA Department of Medicine,
Division of Digestive Diseases, at the David Geffen School of Medicine, UCLA, Co-Director, UCLA Center for Neurovisceral Sciences and Women’s Health (CNS/WH), Los Angeles, CA, USA
– Enrico Corazziari, MD, Professor of Gastroenterology, Dipartimento di Scienze Cliniche, Universita degli Studi “La Sapienza”, Rome, Italy
– John E. Kellow, MD, FRACP, Associate Professor of Medicine, University of Sydney, Royal North Shore Hospital, Sydney, Australia
– Robin Spiller, MD, Professor of Gastroenterology, Wolfson Digestive Diseases Centre, University Hospital, Nottingham, UK
– Nicholas J. Talley, MD, PhD, MMSc (Clin Epi), Chair, Department of Internal Medicine, Mayo Clinic Jacksonville, Professor of Medicine, Mayo Clinic College of Medicine, Professor of Epidemiology, Mayo Clinic College of Medicine, Jacksonvilee, FL USA
– W. Grant Thompson, MD, FRCPC, Emeritus Professor of Medicine, Division of Gastroenterology, University of Ottawa, Ottawa, Canada
– William E. Whitehead, PhD, Professor of Medicine and Adjunct Professor of OBGYN, Co-Director of the Center for Functional GI & Motility Disorders, University of North Carolina, Chapel Hill, NC, USA
– Nancy J. Norton, President & Founder, International Foundation for Functional Gastrointestinal Disorders, Milwaukee, WI USA
– William F. Norton, Vice President & Co-Founder, International Foundation for Functional Gastrointestinal Disorders, Milwaukee, WI USA
What causes pain sensitivity in IBS patients?
An article by Spencer D. Dorn, M.D. et al published in the journal Gut (2007;56;1202-1209) entitled, “Increased colonic pain sensitivity in IBS is the result of an increased tendency to report pain rather than increased neurosensory sensitivity” was reported by Reuters, the world’s largest international multimedia news agency, under the headline, “Pain sensitivity in IBS patients may be psychological.” But is this interpretation correct; and if not, how should we interpret these findings?
In this summary and commentary, clinician and researcher Emeran A. Mayer, M.D. offers a different perspective. Following Dr. Mayer’s comments, Spencer D. Dorn, M.D. and William E. Whitehead, Ph.D., two authors of the study, respond. Finally, we add an editorial comment.
Summary and Commentary by Emeran A. Mayer, M.D.
The study by Dorn and a group of experienced investigators is a well designed and executed research study of 121 patients with irritable bowel syndrome (IBS) and 28 healthy control subjects. The goal of the study was to determine if the characteristic increased perception of experimental colorectal distension (“visceral hypersensitivity”) reported by many laboratories around the world is due to “physiological or psychological factors.”
The authors studied the patient’s subjective response to inflation of a balloon placed into the lower part of the bowel/colon, according to two well established distension protocols. One of these is thought to measure the “objective” sensitivity of the neural pathways, and the other to measure the respective tendency of an individual to “report” pain, regardless of actual neural sensitivity.
The authors confirmed previous reports that IBS patients as a group report pain and urgency (feeling the need to have a bowel movement) at significantly lower colonic distension pressures than healthy control subjects. However, using a technique called sensory decision theory (SDT) analysis, they failed to demonstrate differences in “objective” sensitivity; IBS patients and control subjects showed similar sensitivity of the neural pathways mediating the sensations of pain and urgency. The authors provide evidence that the observed lower perception thresholds for pain and urgency are fully accounted for by “an increased tendency to report pain.” In addition, they show that this increased reporting tendency is weakly, but statistically significantly, correlated with psychological measures, such as somatization (frequently described as the physical expression of psychological problems) and general psychological distress.
Based on their findings the authors conclude that the increased perception of colonic distension in IBS patients is strongly influenced by a greater psychological tendency to report pain rather than a “real” physiological hypersensitivity.
Even though this is an interesting and important study, the conceptual model and hypotheses on which the study is based are very limited and result in a message to investigators and physicians, to the public, and particularly to affected patients, which is highly problematic. I would like to point out the most striking of these problems.
- The human pain experience is multidimensional. It is influenced by a variety of factors, including input from sensory nerve pathways, cognitive and emotional factors, the general homeostatic state of the organism, and by recall of past memories and experiences. This “deconstruction” of the human pain experiences into its multiple neurobiological dimensions has only recently become possible using sophisticated neuroimaging techniques of the brain. At the level of the brain, there is no distinction between psychological and physiological mechanisms (a main hypothesis of the authors is that there is such a distinction). Even though some aspects of the pain experience are generated in the brain by limbic circuits (such as arousal or anxiety) and others by cortical pathways (such as belief systems and coping skills) all pain dimensions are generated by neurobiological activity.
- Unless one measures the electrical activity of sensory nerves during a painful stimulus, or looks directly at the brain activity using electroencephalographic (EEG) or neuroimaging techniques it is difficult to measure objective “neurosensory sensitivity” from subjective stimulus ratings. Any time a pain measure relies on the subjective response of a subject, it is the product of the multiple dimensions outlined in the paragraph above. Thus the study by Dorn is based on the debatable concept that any objective, neurological assessment of pain or non-painful sensations can be derived from subjective patients’ responses (as opposed to direct neurological recordings of nerve or brain activity).
- The conclusion that IBS patients don’t have “real” hypersensitivity but that their subjective discomfort and ultimately symptoms are to blame on their “greater tendency to report pain” is also a problematic interpretation of their findings. Convincing evidence has been provided by several research groups that IBS patients show greater anxiety in expectation of potentially aversive stimuli to the gut or to the lower abdomen, and that this so called symptom related anxiety may play an important role in central pain amplification [increasing the pain sensation in the central nervous system] and ultimately in symptoms. Recent brain imaging studies, which visualize brain activity, have identified the biological brain circuits and mechanisms that play a role in this anticipatory anxiety, and in its role in central pain amplification. This is not a psychological (e.g., non-physiological) phenomenon, but is a dysregulation in neurobiological mechanisms related to pain sensitivity.
In summary, this is an interesting and well executed paper, which puts into serious question the concept that the enhanced perception (commonly referred to as “visceral hyperalgesia”) is related to the peripheral sensitization of visceral afferent pathways (nerve pathways from the gut), for example by some type of immune activation in the gut. However, it is unfortunate that the main findings and conclusions of this article are likely to nurture the still prevailing prejudice, that IBS patients like to complain about symptoms that are not real, and that this tendency is a reflection of their psychological problems. As long as we continue to divide symptoms into those that are psychological in nature, and therefore not as real as those that are physiological and organic, we will never understand some of the most common and burdensome chronic illnesses such as IBS, depression, and chronic pain syndromes.
– Emeran A. Mayer, M.D., Professor of Medicine, Physiology, Psychiatry & Biobehavioral Sciences; Director, Center for Neurovisceral Sciences & Women’s Health, David Geffen School of Medicine at UCLA, Los Angeles, CA
Authors’ Reply to Dr. Mayer: Better Understanding of the Pain Experience May Lead to Better Treatment
Dr. Mayer is critical of the methods we used to study the pain experiences of IBS patients and suggests that neuroimaging of the brain may have advantages over our techniques. We will give our views of these alternative methods for studying pain below. However, the most important issue, as the last paragraph of Dr. Mayer’s commentary makes clear, is his concern that our study findings might harm IBS patients by reinforcing the prejudices of some physicians that IBS is “only” a psychological disorder. We share the concern that readers might jump to simplistic conclusions rather than trying to understand the complexity of the pain experience. However, we carried out and published our study in the belief that, in the long run, well conducted research will benefit IBS patients by leading to more appropriate treatments, even though the research findings may seem unpopular at first.
Dr. Mayer acknowledges that the human pain experience is influenced by a variety of factors that include sensory nerve pathways, cognitive and emotional factors, and past memories and experiences. However, he argues that this complexity cannot be studied by techniques such as sensory decision theory which analyze the ways patients describe their subjective experiences in response to pain stimuli; he argues that only sophisticated neuroimaging of the brain can achieve this. While we agree that functional brain imaging (i.e., identifying which areas of the brain become more active in response to pain sensations from the bowel) is an important new method for increasing our understanding of visceral pain, we do not believe it has achieved the precision of methods such as sensory decision theory as yet. Not enough is known about what specific parts of the brain do, and it is clear that brain activation reflects a mixture of sensory, cognitive, and emotional influences. This makes it difficult to disentangle different influences on the pain experience. Sensory decision theory and other techniques of cognitive science, on the other hand, have a long developmental history, and the meaning of the findings is well worked out.
Dr. Mayer is critical of our assumption that it is useful to distinguish between physiological and psychological contributions to pain. We believe that this distinction is important; we believe, for example, that it is important to distinguish the influence on pain of a recent attack of gastroenteritis from the effects of fear and expectancy because these different causes of pain are likely to require very different treatments. We agree with Dr. Mayer that psychological processes have a biological basis (namely the electrical impulses in neurons), and that psychological processes therefore influence which parts of the brain are most active. The problem, in our view, is that examining images of brain activation does not as yet allow us to distinguish between physiological factors such as gastroenteritis and psychological factors such as worrying about whether we have cancer. Such distinctions are important, and they are readily appreciated by asking patients to report about their subjective experiences.
Our findings are supportive of other recent research on visceral pain and how to go about relieving it. Dr. Mayer notes that several research groups including his own have shown that anxiety related to the expectation of abdominal pain plays an important role in central pain amplification and ultimately in symptoms. That is the conclusion of our study.
We do not believe, nor do we imply, that IBS patients are falsely reporting what they experience. However, our study shows that IBS patients are no better at telling the difference between two intensities of pain than anyone else, and they tend to label unpleasant sensations as painful at lower intensities than most other people. This is not unique to patients with IBS; it has been observed in patients with other chronic pain conditions. We believe this is important because it makes a difference in which treatments are likely to benefit patients with IBS. These observations may be difficult to understand or even uncomfortable to accept, but our conviction is that knowledge brings power for good.
– Spencer Dorn, M.D., and William E. Whitehead, Ph.D., University of North Carolina Center for Functional GI and Motility Disorders, Chapel Hill, NC
Editors’ Comment – a Final Note
We think it is important that any article about a study of the perception of pain in IBS be sensitive to the long history of negative attribution aimed at the IBS patient. That the disorder is “all in their head” remains a popular notion. Reuters reporting the Dorn study under the angle, “Pain sensitivity in IBS patients may be psychological,” helps perpetuate that notion.
Despite the educational efforts of professional groups such as the Rome committees and of advocacy groups such as IFFGD, misconceptions persist that IBS is not “legitimate.” Or that it’s a nuisance – or that the patients are a nuisance. The satirist/commentator Bill Maher, on a 2006 segment of the TV show, Real Time with Bill Maher, said: “I mean, it seems as if every time I turn on the TV these days, I see some ad for some drug I never heard of to treat some disease I never heard of. That’s not a stomach ache you have from eating the chili-cheese fries at Johnny Rockets, it’s Irritable Bowel Syndrome. Or IBS. Or as I call it, BS.” A similar opinion by Maher was published in an op-ed piece in the Los Angeles Times. Attitudes like this seem rooted in society. They spill over into the normal support channels for people with IBS, including their family members and even clinicians. What’s more, they affect attitudes among regulators and funding agencies.
Perhaps it should not be surprising that Bill Maher and others have never heard of IBS; it’s a disorder that most sufferers have a hard time talking about. But perpetuating misconceptions about the disorder will only reinforce the desire to keep silent about it, making it even harder for people with IBS to find proper care.
We know that pain is perceived in the brain, and that a host of emotional and cognitive factors interplay with stimulus to create that perception. It is important to keep in mind that these influences on pain may not distinguish individuals with IBS from those with other chronic pain conditions. (Published studies have compared IBS patients with control groups of healthy individuals.) As Drs. Dorn and Whitehead say in their response above, "(labeling) unpleasant sensations as painful at lower intensities than most other people is not unique to patients with IBS; it has been observed in patients with other chronic pain conditions."
Well designed studies avoid factors that would bias results. But when talking about IBS, it is the audience that is likely biased. We think researchers promoting understanding of the disorder need to consider that bias when reporting their findings. An explanation in the Dorn article of how humans, with or without IBS, process pain would have provided perspective that may have helped avoid, in effect, shining a spotlight on the IBS patient as if they are somehow different.
It is extraordinary that IBS researchers, pursuing scientific explanations to help a population of suffering people, must also explain that this suffering is real. But it seems to yet be necessary.
– William F. Norton, Publications Editor, IFFGD
Are "overly anxious" people prone to IBS?
(June 30, 2007) Recently, the results of a study published in Gut (2007 Feb 26 Epub) by Megan J. Spence and Rona Moss-Morris, “The Cognitive behavioural model of irritable bowel syndrome: a prospective investigation of gastroenteritis patients,” provoked news articles with headlines such as this: “Overly Anxious and Driven People Prone to Irritable Bowel Syndrome”
How accurate is that characterization? In this article, A. Sidney Barritt, MD, Division of Gastroenterology and Hepatology at the University of North Carolina in Chapel Hill reviews the study and comments on the findings.
The British medical journal Gut recently published a study of patients who developed criteria for irritable bowel syndrome (IBS) after being infected with a common bacterium that causes gastroenteritis. The aim of this study was to determine whether a combination of mood and personality factors together with illness beliefs and behaviors predict the onset of IBS after gastroenteritis, as suggested by the cognitive behavioral model of IBS.
This study followed 620 primary care patients, over age 16, with Campylobacter species gastroenteritis and no previous history of IBS or serious gastrointestinal problems over a period of six months. These patients were recruited from the largest provider of community clinical diagnostic services in Auckland, New Zealand, and were given a questionnaire at the time of infection and again three and six months later. Patients were determined to have IBS if they met an inclusive mix of Rome I and II criteria at both three and six months.
A total of forty-nine participants met the criteria for IBS at both follow-up points. According to the authors, those who developed IBS had significantly higher levels of perceived stress, anxiety, somatization, and negative illness beliefs at the time of infection than those who did not develop IBS. Patients with IBS were also significantly more likely to exhibit “all or nothing behavior,” a method of ignoring illness symptoms and forging ahead until the point of complete exhaustion and the inability to perform even basic tasks. Female gender was also associated with IBS. Depression and perfectionism were not associated with IBS. Illness severity, as defined by antibiotic use and certain symptoms, was not associated with IBS.
Post-infectious IBS (PI-IBS) occurs in about 10–20% of individuals who get a bacterial gastroenteritis, but continue to have symptoms consistent with IBS even after the infection is gone. Post-infectious IBS is thought to occur when the infection develops in an individual under high stress. This paper is one of the first to prospectively examine some of the psychological factors that may predispose to PI-IBS.
The authors highlight some interesting associations between IBS and some psychological traits. Nonetheless, the statistical significance of the results should not be overstated.
One of the intrinsic limitations in interpreting data from any survey study is selection bias. [Selection bias refers to error(s) in the design of a study involving how the participants are chosen.] Of 2,547 original patients identified with Campylobacter species infection, only about 1,500 received the survey. This number is based on the authors’ estimate that only about 60% of primary care physicians actually forwarded the survey to their patients. The worst case scenario of this initial selection bias is that only physicians who “believe” in IBS forwarded the survey. About one-half of these patients returned the survey, perhaps only those who identified with the psychological theme of the query; another event that may bias the results. In other words, the results may not represent all who got the infection. Rather, it may represent only those who were motivated to complete the survey, and that may select out those more likely to have the intended findings of the study.
The authors’ conclusions that patients with perceived stress, anxiety, somatization, and negative illness beliefs are more prone to developing post infectious IBS is based on odds ratios that are statistically significant; but the actual clinic significance, or whether the results have meaning in clinical practice, is debatable. In this cohort study of a common illness, odds ratios (the measure of the degree of significance) will overestimate the true effect. A more reliable statistical tool in this study would have been risk-ratio. As the odds ratios in this study are so small, the actual risk that stress, anxiety, somatization, and negative illness beliefs play in the development of IBS is minimal at best.
Multiple studies have demonstrated that IBS is more than just a gastrointestinal manifestation of psychological distress. While there is a “brain-gut” interaction, and gastrointestinal symptoms are modified for better or worse by neurotransmitters like serotonin and norepinepherine, there are also changes that take place within the gastrointestinal tract. There are macro and microscopic alterations in gut motility, inflammation, and neurotransmitter release in patients with IBS that are not explained by alterations in mood.
Just as there can be many variants of IBS symptoms, there can be many causes or contributing factors. There are likely specific organism-host interactions (flora such as bacteria in the gut) that alter symptoms in IBS as is thought in inflammatory bowel disease. The results of this study (and behavior of this organism) of post infectious IBS are not applicable to all IBS. The authors acknowledge this and suggest further studies of other patient groups.
Overall, Spence and Moss-Morris, provide an interesting study about psychological factors that may contribute to IBS. However, because of the study methods and the statistical analysis used, the effect should not be overestimated.
Commentary By: A. Sidney Barritt, MD, Division of Gastroenterology and Hepatology, UNC in Chapel Hill. This article also appeared in the Summer 2007 issue IFFGD's print Publication Digestive Health Matters.
Is there an increased risk of hip fracture?
(March 2007) A study published in JAMA (2006;296:2947-2953) was conducted to determine whether there is an association between long-term proton pump inhibitor (PPI) therapy and the risk of hip fracture. The study concluded that long-term PPI therapy, particularly at high doses, is associated with an increased risk of hip fracture.
What does this study mean for people who benefit from taking a PPI? J. Patrick Waring, MD, a gastroenterologist at Digestive Healthcare of Georgia, Atlanta, GA and member of the Editorial Board of IFFGD comments.
Many patients were alarmed recently by news reports of a 44% increase in the risk of a hip fracture if they are taking a proton pump inhibitor (PPI). The currently available PPIs include omeprazole (Prilosec, Prilosec OTC, Zegerid), lansoprazole (Prevacid), pantoprazole (Protonix), rabeprazole (Aciphex) and esomeprazole (Nexium). This is the latest in a series of articles that have questioned the safety of these powerful, widely used medications. Worldwide, PPIs have been available for over 20 years. In the 1980’s there were concerns that, by profoundly decreasing stomach acid production, they might lead to other health problems such as serious infections, poor absorption of vitamins and minerals, even gastrointestinal cancers. However, by the mid-1990s, based largely on anecdotal experience, it was becoming clear that PPIs were remarkably safe. Formal studies looking at the use of PPIs in hundreds of patients showed virtually no long term side effects. As a result, new PPIs were developed, PPIs became generic and ultimately available over the counter without a prescription. This was a great advance in our ability to treat the millions of patients worldwide that have acid-peptic diseases.
In the last few years, researchers have been able to evaluate the side effects and complications of medications by using large databases of millions of patients. A recent report in the Journal of the American Medical Association (JAMA) looked at the medical records of over 9 million people in the United Kingdom. They were able to identify over 13,000 people with a hip fracture and compare them to over 135,000 people who did not have a hip fracture. They found that using a PPI for over 1 year increased the risk of a hip fracture by 44%. They also found that the risk increased further if the patients were taking the PPI a longer period of time, or at higher doses. This is probably due to impaired calcium absorption when there is less acid in the stomach. Now, it must be mentioned that the patients with hip fractures in this study were much more likely to be a cigarette smoker, be thin, be a diabetic, be alcoholic, have had a stroke, had dementia or had previous bone fractures. Studies like this talk about the risk per patient-year of follow up. For example if one follows 100 patients for 10 years, that is 1,000 patient-years of follow-up. This study suggests that the risk of a hip fracture that is specifically related to PPI use is about 2 per 1,000 patient-years.
There have been other reports over the past couple of years about the possible risk of pneumonia and infections of the colon with a bacterium called clostridium difficile in patients taking PPIs. Again, these articles looked at the medical records of hundreds of thousands of patients and found a small increase risk in patients using PPIs. Additionally, like the hip fracture study, other medical illness such as diabetes, heart, and lung disease were also important risk factors.
The Canadian Task Force for Preventative Health Care recently published recommendations for the prevention of osteoporosis in women. It mentioned major risk factors such as advanced age, family history of osteoporosis, early menopause, propensity to fall and minor risk factors such as being thin, smoking, excess alcohol or caffeine intake. We may learn that long-term PPI use will be considered a minor risk factor. If you need to take a PPI, you should talk with your doctor about your risk of osteoporosis. If you have other risk factors, you may need a bone density test. You may simply need to take exercise more or take calcium supplements. You may need to take one of the many excellent medicines for osteoporosis.
It has probably been wishful thinking that the long-term use of PPIs was perfectly safe. Like most medications, there are side-effects and complications. Fortunately the overall risk of long-term PPI use still seems to be relatively small. Common sense tells that if you don’t need to take a PPI, you should stop it. There any many people taking PPIs that could get away with using a less powerful medication. However, most people who need to take a PPI should be able to safely continue to take it without the fear of serious complications.