Fat Hormone Influences Baseline Dopamine Levels And Our Motivation To Eat

As we all know from experience, people eat not only because they are hungry, but also because the food just simply tastes too good to pass up. Now, a new study in the August 6th Cell Metabolism, helps to explain how leptin, a hormone produced by fat tissue, influences that motivation to eat.

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The researchers describe for the first time a new bunch of leptin-responsive (LepRb) neurons in the brain's lateral hypothalamic area (LHA). Those LHA neurons feed directly into the mesolimbic dopamine system seated in the ventral tegmental area (VTA) of the brain, which controls the rewarding properties we assign to things.

"Dopaminergic neurons in the VTA and their downstream targets represent the site of action for drugs of abuse, and also control motivation for food, sex or a fancy car," explained Martin Myers, Jr., of the University of Michigan, Ann Arbor. Put simply, "they control our wanting of stuff."

The study therefore adds to growing evidence that leptin doesn't turn the appetite on and off just by controlling satiety – for instance, whether we feel hungry or full.

"Most who have studied leptin in the brain have focused on an important circuit in the ARC," and the leptin-responsive neurons there, Myers said. ARC stands for arcuate nucleus and is an area in the brain's hypothalamus that controls energy balance by controlling satiety. "It has been assumed that leptin action in the ARC – if not the be all and end all – was responsible for the vast majority of leptin's effect on appetite."

But in fact, neurons bearing leptin receptors exist in many other parts of the brain too. Earlier studies revealed the role of leptin action on the VTA and its influence on dopamine. The new findings show that leptin also has direct effects on the LHA, which in turn exerts greater influence on the dopamine system of the VTA.

The new study shows that leptin injected in the LHAs of rats causes the animals to eat less and lose weight. Leptin action in the LHA also raises dopamine content in the brains of otherwise leptin-deficient animals.

While in general higher dopamine release tends to be associated with wanting things – food or something else – Myers said he suspects the higher dopamine at baseline may in fact dampen the response to food temptations, making them easier to resist.

"Some people may over-eat rewarding food because of a perceived 'reward deficit,'" Myers suggested. "When leptin is turned up, it might fix that deficit and make us feel better about a lot of things."

It's not yet clear how the leptin-responsive neurons in the LHA and VTA work together to control dopamine and with it our motivations, according to the researchers.

"The unique roles played by these subpopulations of LHA LepRb neurons, as well as those played by VTA LepRb neurons, remain unclear, but could include the requirement for leptin to differentially regulate specific populations of midbrain dopamine neurons and/or to distinctly modulate the incentive for feeding relative to other behaviors. Going forward, it will be important to determine how these various populations of mesolimbic dopamine system-interacting LepRb neurons differ in terms of their wiring and the control of different aspects of mesolimbic dopamine signaling."

The new findings do highlight the LHA neurons as a major link between leptin's anorectic action and the mesolimbic dopamine system, they conclude. "These findings reveal important mechanisms that underlie the regulation of the mesolimbic dopamine system by a crucial signal of energy stores. In the future, it will be crucial to address the potential dysregulation of these neurons in states of obesity."

The researchers include Gina M. Leinninger, University of Michigan, Ann Arbor, MI; Young-Hwan Jo, Albert Einstein College of Medicine, Bronx, NY; Rebecca L. Leshan, University of Michigan, Ann Arbor, MI; Gwendolyn W. Louis, University of Michigan, Ann Arbor, MI; Hongyan Yang, University of Michigan, Ann Arbor, MI; Jason G. Barrera, University of Cincinnati, Cincinnati, OH; Hilary Wilson, University of Cincinnati, Cincinnati, OH; Darren M. Opland, University of Michigan, Ann Arbor, MI; Miro A. Faouzi, University of Michigan, Ann Arbor, MI; Yusong Gong, University of Michigan, Ann Arbor, MI; Justin C. Jones, University of Michigan, Ann Arbor, MI; Christopher J. Rhodes, University of Chicago, Chicago, IL; Streamson Chua, Jr., Albert Einstein College of Medicine, Bronx, NY; Sabrina Diano, Yale University, New Haven, CT; Tamas L. Horvath, Yale University, New Haven, CT; Randy J. Seeley, University of Michigan, Ann Arbor, MI; Jill B. Becker, University of Michigan, Ann Arbor, MI; Heike Munzberg, University of Michigan, Ann Arbor, MI; and Martin G. Myers Jr., University of Michigan, Ann Arbor, MI.

Source : http://www.sciencedaily.com/releases/2009/08/090805133009.htm

Clinical Factors Predict Risk of Complicated Community-Acquired Pneumonia

Seven clinical factors can predict the risk of complicated parapneumonic effusion or empyema in patients presenting with community-acquired pneumonia (CAP), researchers report in the July issue of the journal Thorax.

Pneumonia severity scores have been used to predict 30-day mortality in patients presenting with CAP, the authors explain, but their utility to predict the development of complicated parapneumonic effusion or empyema has not been studied.

Dr. James D. Chalmers and colleagues from the Royal Infirmary of Edinburgh in Scotland set out to identify key factors predicting the development of these complications in patients admitted with CAP.

They report that recognized severity scores poorly predicted complicated parapneumonic effusion and empyema in these patients.

However, seven clinical factors emerged as independent risk factors for these complications on multivariate logistic regression, including serum albumin below 30 g/L, C-reactive protein above 100 mg/L, platelet count above 400 billion/L, sodium below 130 mmol/L, intravenous drug use, and chronic alcohol abuse. A history of chronic obstructive pulmonary disease (COPD) was associated with a lower risk.

When each risk factor was given a value of 1 (except the history of COPD, which was given a value of negative 1), a cutoff of 2 or more points accurately separated patients with a high and low risk of developing complicated parapneumonic effusion and empyema, the investigators say.

The 2-point cut-off was 87.0% sensitive and 68.3% specific and gave a positive predictive value of 17.7% and a negative predictive value of 98.5%. This score was superior to all pneumonia severity scores in predicting complicated parapneumonic effusion or empyema.

"This study," the investigators say, "has provided proof of the concept that complicated parapneumonic effusion and empyema can be predicted by deriving a scoring system with good predictive value."

"Independent validation studies are needed," they add.

"Exactly which biomarker is most appropriate and what cut-off levels should be used to affect the management decisions requires further clarification," writes Dr. Jeremy S. Brown from University College Medical School, London, UK, in a related editorial.

"Furthermore," Dr. Brown concludes, "any changes to CAP guidelines to include the use of biomarkers along the lines described above would ideally need support from prospective trials."

Thorax 2009;64:556-558,592-597.

Source : http://www.medscape.com/viewarticle/706328?sssdmh=dm1.503531&src=nldne

Successful New Treatment For Hodgkin's Lymphoma, Reduces Long-term Risks

New research led by Cindy Schwartz, MD, of Hasbro Children's Hospital has identified a new chemotherapy regimen for pediatric Hodgkin lymphoma (HL) patients. The new treatment enhances efficacy through dose-dense drug delivery while simultaneously reducing the long-term risks presented by high cumulative dose chemotherapy. Schwartz and the researchers of the Children's Oncology Group have published their findings in the journal Blood (posted in an online first edition).

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The Children's Oncology Group's Hodgkin Lymphoma Committee, led by Schwartz, director of pediatric hematology/oncology at Hasbro Children's Hospital, recognized that treatment for HL in the United States was not being treated with the most modern treatment models, in large part because it was one of the first malignancies for which a curative chemotherapy regimen was developed.

Schwartz says, "For decades, the chemotherapy regimens known as MOPP and ABVD had been the standard treatment options for these patients. However, while they yielded excellent survival rates, they often resulted in long-term effects from toxicity, including infertility, second malignancy and cardiopulmonary toxicity. With the new treatment paradigm we've developed, in essence, we've been able to cure the cancer while reducing the risk of long-term effects on our patients."

The group designed a new chemotherapy treatment known as ABVE-PC, combining six different drugs into one "dose-dense" regimen that could limit the cumulative doses of each drug below the recognized thresholds known for resulting in long-term toxicity. Their goal was to reach a rapid early response (RER) in order to further reduce cumulative therapy and to thereby increase event-free survival (EFS). They also combined the chemotherapy treatment with low dose radiation following the completion of the ABVE-PC cycles.

The treatment developed by the researchers was unique given that its focus was on early response after nine weeks, measuring to detect primary chemosensitivity – a favorable response to chemotherapy, indicating that the therapy is working. This approach differs from the traditional evaluation of the response at the end of chemotherapy. Schwartz notes that this is important, because, "This early detection allows for a reduction in therapy for those who respond well to the dose-dense treatment, and therefore, individual response can be tailored for maximum efficacy."

Schwartz, who is also a professor of pediatrics at The Warren Alpert Medical School of Brown University, believes that the study represents a new treatment model for patients with HL. She states, "Our treatment paradigm for advanced HL relied on two treatment principles: dose density enhances therapeutic efficacy and rapid early response is evidence of chemosensitivity and can serve as a basis for reduction of therapy."

The researchers conducted a trial of 216 eligible patients under 22 years of age, with intermediate or high risk HL; there were 76 females and 140 males. The median time from initial treatment to completion of the third cycle was approximately 8.7 weeks, and completion of the fifth cycle was approximately 16 weeks. While the dose densities of the chemotherapy agents exceeded those of the most commonly used regimens, cumulative doses of the chemotherapy were significantly lower, particularly in those with RER. The study was conducted at Children's Oncology Group sites between 1997 and 2001.

Schwartz says, "The results of the study indicate that through this new chemotherapy treatment we have been able to effectively deliver dose-dense chemotherapy while reducing the cumulative exposure to our patients." There are other, more immediate outcomes of the new treatment paradigm that are also of note. Schwartz also adds, "Our patients truly appreciate the rapidity of treatment. Regimens traditionally used for intermediate and advanced disease require six to eight months of chemotherapy, instead of two to three and a half months. A major benefit of this new approach is that children and young adults are able to more quickly return to school and work."

Of the 216 eligible patients, 209 were able to be evaluated for response. Of those patients, 63 percent (132 patients) showed RER, and only two of the patients showed evidence of progressive disease. RER was achieved in 67 percent of intermediate HL patients and 61 percent of high risk HL patients. The five-year event-free survival for intermediate risk HL patients was 84 percent and 85 percent for high risk HL patients. Few relapses occurred beyond three years after enrollment.

Schwartz concludes, "We have successfully achieved five-year event free survival in 84 percent of the patients and overall survival in 95 percent of our patients with this dose-dense, early-response based treatment algorithm. Only nine weeks of chemotherapy were required in 63 percent of our patients. This study has shown conclusively that the new chemotherapeutic treatment of ABVE-PC simultaneously provides high efficacy and reduces the cumulative doses of chemotherapy and radiation. We believe this represents a significant advance in the treatment of HL."

Other researchers involved in the study with Schwartz include Louis S. Constine of the University of Rochester Medical Center in Rochester, NY; Doojduen Villaluna of Children's Oncology Group - Operations Center in Arcadia, CA; Wendy B. London of Children's Oncology Group – Statistics and Data Center, University of Florida in Gainesville, FL; Robert E. Hutchison of SUNY Upstate Medical University in Syracuse, NY; Richard Sposto of Children's Hospital Los Angeles in Los Angeles CA; Steven E. Lipshultz of University of Miami Miller School of Medicine in Miami, FL; Charles S. Turner of Wake Forest University School of Medicine in Winston-Salem, NC; Pedro A. deAlarcon of St. Jude Midwest Affiliate in Peoria, IL; and Allen Chauvenet of West Virginia University HSC in Charleston, WV.

Source : http://www.sciencedaily.com/releases/2009/07/090713160521.htm

One Secret To How TB Sticks With You

Mycobacterium tuberculosis is arguably the world's most successful infectious agent because it knows how to avoid elimination by slowing its own growth to a crawl. Now, a report in the July 10 issue of the journal Cell, a Cell Press publication, offers new insight into the bugs' talent for meager living.

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"Tuberculosis can resist the host immune system and remain latent for decades," said Michael Glickman of the Memorial Sloan-Kettering Cancer Center. To do so, the mycobacterium responsible must resist an arsenal of DNA-damaging mutagens produced within the macrophage, the immune cell in which it lives. "It's incompletely understood how it can do that. We've identified one such mechanism."

The discovery could lead to new drugs that might eliminate strains of TB that have grown resistant to those that are currently available.

A whopping 30% of the world's population is infected with latent TB, the researchers said. In some people, the Tuberculosis bacterium will reactivate, causing an estimated 1.3 million deaths a year, according to the World Health Organization.

One secret to TB's success is a protein that the researchers call CarD, the new study shows. That protein ratchets down transcription of the genes encoding ribosomal RNA (rRNA) by directly binding RNA polymerase, the cellular machinery that transcribes DNA into RNA. rRNA is the central component of the ribosomes that serve as the cell's protein factories, and, Glickman explained, its production accounts for some 90 percent of all transcription.

"The mycobacterium tailors its translational machinery in response to stress within the host and we have identified CarD as a critical mediator of this response" he said.

Loss of CarD is fatal to M. tuberculosis living in cell culture, Glickman and his colleague Christina Stallings show. CarD depletion leaves the pathogen sensitive to killing by oxidative stress, starvation, and DNA damage as it fails to cut its transcription of rRNA.

Importantly, Glickman said, they were able to show in infected mice that the mycobacterium depends on CarD not just when it is in its early, most active phase of growth, but also later in the course of infection. Drugs that target CarD's interaction with RNA polymerase could therefore lead to sorely needed, new TB drugs, the researchers said.

"The TB health crisis is exacerbated by the alarming emergence of multidrug- and extensively drug-resistant strains," Glickman said. "The development of new chemotherapeutic strategies is imperative, which requires insight into the pathways involved in M. tuberculosis infection, persistence, and drug resistance. CarD is one such pathway that we plan on targeting for therapeutic development. "

The findings might also prove to be clinically important for other disease-causing microbes.

Scientists knew before how some bacteria adapted to stress by limiting rRNA transcription, Glickman said. But the new study is the first to show how this is done in a mycobacterium, which lack a key gene responsible in other bugs like E. coli.

CarD is widely distributed in the bacterial world, he said, for instance it is found in Bacillus anthracis, the bacterium that causes anthrax. "This finding may have broader application to other important pathogens," he said.

The researchers include Christina L. Stallings, Sloan-Kettering Institute, New York, NY; Nicolas C. Stephanou, Sloan-Kettering Institute, New York, NY; Linda Chu, Sloan-Kettering Institute, New York, NY; Ann Hochschild, Harvard Medical School, Boston, MA; Bryce E. Nickels, Rutgers University, Piscataway, NJ; and Michael S. Glickman, Sloan-Kettering Institute, New York, NY, Memorial Sloan-Kettering Cancer Center, New York, NY.

Source : http://www.sciencedaily.com/releases/2009/07/090709124741.htm

Current Perspectives on Pneumonia in Clinical Practice

Introduction to Perspectives on Pneumonia

The increased concerns of drug resistance in managing lung disease affects both hospitalized and outpatient populations. In this expert interview with Michael Niederman, MD, of State University of New York and Winthrop University Hospital conducted by Medscape editor Jennifer Brown, PhD, the risks for pneumonia in special populations are considered. The current management trends to prevent and treat pneumonia caused by ever-evolving pathogens are put into a clinical perspective in the following commentary.

Patients at Risk for Pneumonia

Medscape: Welcome, Dr. Niederman, and thank you for sharing your perspectives on pneumonia. What patient populations are currently considered to be at increased risk for bacterial, viral, or fungal pneumonia?

Dr. Niederman: All 3 forms of pneumonia can affect virtually any individual, but in general the paradigm for any type of pneumonia is the balance between the patient's host defenses, the virulence of the potential pathogen, and the size of the exposure to the pathogen. So in theory, pneumonia can develop even in healthy individuals if they encounter particularly virulent pathogens or very large inoculum. So for example, an individual who gets severe acute respiratory syndrome (SARS) encounters a virus so virulent that it is impossible to have host defenses against it. On the other hand you can have a large inoculum of bacteria, which could overwhelm a healthy defense system. A good example is a young, otherwise healthy individual who gets drunk, vomits, and aspirates such a large quantity of bacteria that pneumonia develops. The majority of the patients we see in the hospital who have pneumonia tend to be individuals with impaired host defenses, either as a result of advanced age, underlying comorbid medical conditions, or medications. Because of their impaired immune systems not only are these individuals more prone to infection, but when pneumonia develops, it is a more severe infection.

Comorbid conditions could be congestive heart failure, chronic obstructive pulmonary disease (COPD), cigarette smoking, or underlying malignancy. A variety of medications that we routinely use increase the risk for infection. Even something as simple as aspirin has been shown to interfere with immune defenses and can predispose some patient populations to pneumonia. Certainly advanced age is also an important factor. There is some controversy about whether it is the age itself or the diseases that develop as a result of getting older. It is probably to some extent the combination of both.

Medscape: Are there special concerns for the immunocompromised, for example, those who take medications that are immunosuppressive?

Dr. Niederman: There are concerns, and the most common immunosuppressive drugs of concern used in clinical practice are probably corticosteroids. Individuals who are chronically treated with corticosteroids, as might be the case in those with COPD, rheumatoid arthritis, or other inflammatory diseases, are more prone to bacterial and viral infections as a result of their steroid therapy. Chemotherapy immune-related suppression can develop in individuals receiving chemotherapy, which particularly predisposes them to bacterial and fungal infections. With the biologic therapies that interfere with cell-mediated immunity, particularly the anti-tumor necrosis factor types of therapies, there has been a much greater concern about tuberculosis than pneumonia. Anything that interferes with immune defenses can predispose a patient to both bacterial and fungal infections.

Medscape: In patients with, for example HIV or a disease that has made them immunocompromised, what are the particular risks for pneumonia?

Dr. Niederman: There is a risk for immunocompromised patients. The way to evaluate that risk is to look at the abnormality the patient has to know, for example, what that does to the immune system. Then you can better predict what types of pathogens are likely to cause infection. So for example, people who are infected with HIV can have predominantly abnormalities of cell-mediated immunity but they can also have antibody formation abnormalities. Therefore, they are on the one hand predisposed to things like tuberculosis and atypical microbacteria and unusual fungal infections. In addition, they're also greatly at risk for pneumococcal pneumonia.

If you look for example at patients who have neutropenia because of cancer and chemotherapy, they are particularly predisposed to Gram-negative bacteria. So if you can define the nature of the immunosuppression and where specifically it affects the immune system, this can help you better predict which specific types of pathogens are likely to be problematic.

Evaluating Causes of Pneumonia

Medscape: In patients with cystic fibrosis in particular, what are the most common causes of pneumonia you see?

Dr. Niederman: The 2 pathogens that have been a problem in cystic fibrosis are Staphylococcus aureus, which tends to be a pathogen earlier in the disease and Pseudomonas aeruginosa, which tends to be a pathogen later in the disease. But there are a variety of unusual Gram-negative bacteria that have been a problem with cystic fibrosis as the disease gets more advanced. Here the factors that predispose patients to infection tend to be the cystic fibrosis itself, which leads to alterations in production of mucous, quality of the mucous, and clearance of the mucous. All of these can predispose to specific bacteria. Inevitably because of their disease, patients with cystic fibrosis are frequently treated with antibiotics. The treatment can then predispose to emergence of particularly resistant forms of Gram negative bacteria that tend to be problematic later in the disease.

Medscape: How would you determine the cause in a patient who has symptoms of pneumonia, whether bacterial, viral, or fungal?

Dr. Niederman: I think one of the issues that people are struggling with right now is this question, is it possible to look at a patient and know whether their infection is bacterial or viral? Efforts in the past included can you tell by the clinical syndrome, can you tell by the radiographic patterns, by the fever, by the white cell count? Many studies have been done but they have not yet shown that clinical features can separate bacterial from viral infections. One of the reasons this is important is if you can predict who has a viral infection with some accuracy, then you could say that this person doesn't need antibacterial therapy. Since we are concerned about the overuse of antibiotics and how that could be driving resistance, it would be helpful in theory to be able to predict who has which.

A particularly promising approach right now involves serum measurements of procalcitonin.^[1] When procalcitonin measurements are low, they exclude bacterial disease, as low procalcitonin levels seem to occur in viral infection. Studies in patients who have x-ray-positive pneumonia and low procalcitonin levels who have been randomized to observation without antibiotics have done very well without antibiotic therapy. This is one potential measurement for the future.

Today, for most patients, we look at their clinical features. If there is any chance that it is bacterial, we treat them with antibiotics and we try to identify the bacterial pathogen. Sputum samples are used if patients are intubated and the tracheal aspirates or bronchoscopic samples are cultured. We examine them microscopically to identify suspicious bacterial infections, and to identify what bacteria.

Medscape: Are agent-specific tests recommended for regular use?

Dr. Niederman: Generally agent-specific tests are not routinely used. Agent-specific tests widely available right now include urinary antigen testing for Legionella and Pneumococcus species. The problem with specific-agent tests in community-acquired pneumonia (CAP) is that it's difficult to know when the test is positive and how it should affect your approach to treatment. There are some new-onset cases and complexities of treatment. For example, there is a dataset of patients who have been in infected with Pneumococcus, who have pneumococcal bacteremia, who seem to benefit by the addition of a second antibiotic. If that is reproducible, then it would be hard to imagine how doing a specific test for Pneumococcus that was positive might change the antibiotic therapy. It might narrow it if you have a broad-spectrum therapy because of the possibility of needing a second antibiotic. But Legionella and Pneumococcus urinary antigen tests are probably the most specific tests in use.

The other common approach is to culture sputum, tracheal aspirates, bronchoscopic samples, or lower respiratory tract samples in patients who have suspected or confirmed pneumonia.

Current Practice for Treating Pneumonia

Medscape: What are the current medications of choice and how is the therapy selection individualized for the patient newly diagnosed with pneumonia?

Dr. Niederman: Guidelines for treating patients with CAP, with healthcare-associated pneumonia (HAP), and with nosocomial pneumonia depend on the severity of illness, the comorbidities of the patients, and the time of onset of the illness in the case of nosocomial infection. There are a variety of different algorithms for therapy, but no single best therapy. The 2005 guidelines for nosocomial pneumonia were a joint effort of American Thoracic Society and the Infectious Disease Society of America, as were the 2007 guidelines for CAP.^[2,3]

In general, with CAP, we treat for pneumococcus and generally the possibility of atypical pathogen co-infection. Some subpopulations are treated for Gram-negative bacteria. For patients who have HAP, coming from a nursing home or the hospital in the previous 3 months, they are at much greater risk for drug-resistant Gram negative infections and methicillin-resistant S aureus, and these patients need therapies directed to those pathogens. In nosocomial pneumonia it depends on how late in the course of the hospital stay pneumonia developed. Have they recently been on antibiotics? What are the pathogens that are common in a given hospital? All of these factors then get considered in terms of choosing an antibiotic therapy.

Strategies for Preventing Pneumonia

Medscape: Considering care of the elderly, could you please comment on strategies to prevent pneumonia in this population?

Dr. Niederman: I think in the elderly, 3 factors may play a role in their increased risk for infection. One is aging itself, and there is some controversy whether that really plays a role. The medications that the elderly get, and also the comorbidities that they have both play a role. For the elderly, many medications and comorbidities are associated with the risk for pneumonia. In terms of prevention, prevention of pneumonia generally involves smoking cessation and vaccination for patients outside of the hospital setting. For the elderly individual who is residing outside of the hospital, whether it's in the nursing home or at home, vaccination, including both pneumococcal and influenza vaccines, are probably the 2 most important preventive strategies that we have right now. In the hospital a whole series of preventive measures is undertaken.

Medscape: A recent report indicated vaccinating even the young had a positive effect for preventing pneumonia in others with HIV in the population.

Dr. Niederman: This is an interesting observation, the concept of herd immunity. When the 7-valent conjugant vaccine for Pneumococcus ^[4] (PCV7) was widely used in children, it had a benefit in elderly individuals, particularly the ones caring for the children. It seemed that if you eliminated the reservoir of Pneumococcus in young children, you might then eliminate the distribution source, if you will, of the Pneumococcus to older individuals who came in contact with the children. Very compelling data showed that with the early use of the vaccine in children there was a decline in the frequency of those strains of Pneumococcus in elderly individuals. This paralleled the decline in children, and the speculation was that they were therefore not transmitting the Pneumococcus at the same rate to the elderly caregivers around them.

Another twist to that data on vaccinating the young should be watched very closely. There have now been reports that with continued use of PCV7, there appears to be a decline in the frequency of the strains covered in that vaccine. They have been replaced at a higher frequency by other strains that aren't covered. In particular there are some very severe, necrotizing strains of Pneumococcus that aren't covered by the current vaccine that have emerged at higher frequency in vaccinated individuals. The concern is that the Pneumococcus being able to adapt to this vaccination strategy has now replaced some of the vaccine strains with other strains, some of which are more virulent, and that effect may be that there is more severe pneumonia occurring in certain populations than was appearing before the vaccine was introduced.^[5] So if that turns out to be true and can be confirmed in other populations, it may negate some of that herd immunity benefit that has been seen in the nonvaccinated individuals.

Medscape: What preventive measures would you say are helpful in the hospital setting to reduce HAP?

Dr. Niederman: Well the big issue right now in the hospital is the focus on mechanically ventilated patients, and there a lot of efforts have revolved around something that has been referred to as a "ventilator bundle." It's a bundling of interventions that many hospitals do in an effort to reduce the frequency of pneumonia. The typical bundle most widely promoted and used involves 5 elements, two of which are part of the bundle but really are good patient care that can help reduce intensive care unit stay and may indirectly reduce pneumonia but don't directly interfere with pneumonia pathogenesis. Those are gastrointestinal bleeding prophylaxis and deep venous thrombosis prophylaxis.

The other 3 interventions in the bundle are much more pneumonia-specific. One is elevation of the head of the bed with the idea of minimizing gastric reflux into the oropharynx and then aspiration into the lung. Keeping the head of the bed elevated can reduce gastric transmission of bacteria to the lungs. The 2 others are a daily interruption of sedation -- you wake the patient up every day, and when you do that there is a daily effort of weaning. That is the fifth element. So the bundle is: daily interruption of sedation and daily weaning trials, head of the bed elevation, deep vein thrombosis and gastrointestinal bleeding prophylaxis.

Although these bundles are probably effective, their advent has led to some interesting discussions and controversies. Some individuals are reporting that with the use of ventilator bundles they have eliminated pneumonia from their hospital. Some hospitals have even said we have gone as long as 2 years without an episode of ventilator associated pneumonia because of how valuable these bundles are and how successful we've been in implementing them.

The problem with those reports has been that many studies report a lower frequency of pneumonia in ventilated patients, but don't seem to report secondary benefits, meaning overall reduction in use of antibiotics, reduction in mortality, reduction in length of stay -- the known consequences of VAP. The diagnosis of VAP can often be subjective, and it's an elusive, difficult diagnosis. The worry is that people are now saying they don't have pneumonia in their hospital, but it isn't as credible as you would like because the secondary consequences of pneumonia are not also disappearing.

All of this has become increasingly more controversial because Medicare has proposed, and it's unclear what the final decision will be, that VAP should be considered a potential medical error that should not be given additional reimbursement. If so, the concern is that many hospitals would report very low rates of pneumonia. However, it's not clear to me that they're really eliminating the problem. It seems like there are populations of patients who are at such high risk because of their underlying comorbidities, chronic illness, and acute illness that they can't possibly have a zero-risk for pneumonia, even in the best hands and in the best hospitals.

Medscape: That really leads us directly into the Hospital Compare Web site. What impact will public reporting have on practice, or how will it change how patients choose hospitals?

Dr. Niederman: The Hospital Compare Web site right now is looking at CAP, but it may become part of the Medicare database that they'll be publicly reporting on VAP rates, and I would make the distinction. I think that in general it is good that pneumonia has become a target of public reporting, that people are aware of the importance of pneumonia. It is the number one cause of death from infectious diseases in the United States, and we are doing everything we can to reduce the frequency of pneumonia.

But you have to wonder whether the public reporting can have some unintended consequences that are not positive. One worry in the VAP side is if we have public reporting of very low VAP rates, that sort of strains credibility. There are populations where it's impossible to get the rates as low as some people report; you wonder if they are simply redefining the illness and haven't really made progress. What I worry about personally is that if we say pneumonia is a medical error, VAP, and it really is not eliminated, it will really, I think, hamper future research in this area. It would be very difficult for people to want to investigate a disease that when it occurs, it is considered bad medical care. So I think we have to get very accurate and honest in defining how low we can reduce these rates.

The Hospital Compare Web site, which compares different hospitals and their compliance with CAP, in general has been helpful. The one area that I think it still controversial is the antibiotic timing measure that Medicare has instituted. Originally that was looking at the frequency with which antibiotics were given within 4 hours and that has now been changed to 6 hours. But the concern has been that if it becomes publicly reported that 4 hours is the standard, then hospitals will inevitably try to get that rate to 100%. I think that many experts believe that 100% compliance with the 4-hour rule isn't necessarily good medical care. There may be cases of medical uncertainty, and so as another modification they have introduced medical uncertainty as an exemption to this 4-hour rule.

Published reports have raised concern about the 4-hour antibiotic timing rule. There are now 2 retrospective studies that show that when hospitals try to comply with the 4-hour rule, in general they give antibiotics to more patients, but the frequency with which the antibiotics were used for a final discharge of CAP actually dropped. In other words, many more patients got antibiotics but some of them got antibiotics when they didn't really have pneumonia.

Another consequence is at least one report of a hospital with very bad episodes of infection with Clostridium difficile. The majority of the episodes occurred in patients who were treated with antibiotics for pneumonia, but half of those patients who were treated for pneumonia didn't, in retrospect, have pneumonia. This occurred at a time period when the hospital was trying to be more compliant with the antibiotic timing measure.

I think that the Hospital Compare Web site is generally a good idea, but the goals that are set in comparison have to be accurate and realistic. What I worry about is that when the data get published publicly, everyone is going to look for the hospital that has the highest number. You have to recognize that it might be possible for some of these measures, that the highest number may not necessarily equal the desired goal. The desired goal might be 85% rather than 100% for some of these measures. It might be that there is a bell-shaped curve where the best care occurs when the compliance rate for a hospital is 80% to 85%. People below that and above that might not be providing the best possible care.

Source : http://www.medscape.com/viewarticle/577190

Greater Soy Consumption Appears to Lower COPD Risk

The results of a study conducted in Japan and published in Respiratory Research suggest there is an association between high soy consumption and low risk of COPD and breathlessness.

Cigarettes are known to be the principle risk factor for COPD, Dr. Andy H. Lee of the Curtin University of Technology, Perth, Australia, and colleagues point out. "Other factors such as dietary and environmental exposures may protect against, or contribute to, disease development."

In a case-control study, the investigators examined the association between soy consumption and the risk of COPD and respiratory symptoms in 278 COPD patients (244 men and 34 women) between the ages of 50 and 75 years who were diagnosed within the past 4 years. A total of 340 controls (272 men and 68 women) were recruited from the community.

The study participants underwent spirometric measurements of respiratory function and structured questionnaires were used to collect information on demographics, lifestyle characteristics, and habitual food consumption. Control subjects had significantly higher mean soy intake than COPD patients (59.98 g/day versus 44.84 g/day, respectively, (p <>

A positive correlation was found between total soy consumption and lung function measures. The risk of COPD was significantly reduced among those with the highest versus the lowest quartile of daily total intake of total soybean products (p for trend = 0.001).

Similar decreases in the risk of COPD were observed with higher intakes of tofu and bean sprouts. An inverse association was found between high consumption of soy foods and respiratory symptoms, especially breathlessness.

"Habitual intake of soy foods offer a new prevention which can have an important impact on the cost to health care systems associated with the morbidity and death from this disease," Dr. Lee said in an interview with Reuters Health. "Long-term follow-up studies are recommended to ascertain whether soy consumption can lengthen the survival of patients already diagnosed with COPD."

Respir Res 2009;10.

Source : http://www.medscape.com/viewarticle/705630?sssdmh=dm1.497700&src=nldne

Statin-Induced Myopathy Reflects Structural Muscle Damage, New Study Shows

Persistent muscle pain in patients taking statins reflects structural muscle damage, and this microscopic damage can occur in the absence of elevated creatine phosphokinase levels, according to the results of a new study [1].

"It's clear that a patient with statin-induced myopathy can have microscopic muscle damage, but the damage is not sufficient to break the cell open, and that means that it doesn't release creatinine phosphokinase into the blood," said study investigator Dr Richard Karas (Tufts-New England Medical Center, Boston, MA). "So to say that the other way around, we have clear evidence that there is ongoing damage to the muscle at the microscopic level, but it's not revealed in the blood tests that we use to check for muscle damage."

Speaking with heartwire , Karas said that muscle-related adverse effects limit statin use, despite the drugs being part of the foundation of cardiovascular risk reduction. He added that although these muscular side effects are well documented, little is known about the mechanisms of myopathy.

In this study, which is published online July 7, 2009 in the Canadian Medical Association Journal, Karas, along with lead investigator Dr Marcus Mohaupt (University of Bern, Switzerland), obtained biopsy samples from the vastus lateralis muscle of 83 patients. Overall, 44 subjects had clinically diagnosed statin-associated myopathy, and of these, 29 were currently taking a statin, while 15 had discontinued statin therapy for at least three weeks. Among the 83 patients, 19 were currently taking a statin but had no myopathy and 20 patients served as healthy controls.

Among the 44 individuals with myopathy, 57% had muscle injury defined by structural abnormalities in the muscle fibers, as did one patient without clinically diagnosed myopathy. Interestingly, just one patient with structural muscle injury had circulating creatine phosphokinase levels that exceeded 10 times the upper limit of normal, or >1950 U/L.

"This is clinically relevant because when a patient is on a statin and they come in complaining that their muscles hurt, we check the blood test for creatinine phosphokinase," said Karas. "If it's normal we tell them not to worry about it, that it's not the statin. This study tells us that in this group of patients, that clinical assumption is not true."

Not Your Average Patient on a Statin

Karas stressed that the patients included in this study are not typical patients on statins, but rather individuals with clinically identified statin-related myopathy. This distinction is important because patients treated with statins who feel fine and who have normal creatine phosphokinase levels should not worry they are damaging their muscles with the LDL-cholesterol-lowering medications.

The researchers point out, however, that patients with clinically diagnosed statin-induced myopathy who had stopped their statins for at least three weeks also had persistent microscopic evidence of muscle damage. Although he is cautious in interpreting results, saying it needs further study, Karas said that muscle problems might not go away among individuals with persistent muscle pain.

The researchers also performed a gene-expression analysis in 57 patients to look for association between muscle damage and genes that encode proteins located in T-tubule membrane or the adjacent sarcoplasmic reticulum and that are involved in the release of intracellular calcium. One of those proteins, ryanodine receptor 3, was significantly upregulated among patients with structural muscle damage when compared with individuals without muscle damage.

"The problem is that we don't know if this was elevated in the first place, and then this makes people susceptible to statin-induced myopathy, or whether it is elevated as a result of them having statin-induced myopathy," Karas explained to heartwire . "This is the first step, as it tells us that it's a gene that should be focused on in studies going forward. What we'd like to do is take a huge group of people and get their levels of expression and see if it predicts them getting myopathy."

Source : http://www.medscape.com/viewarticle/705429?src=mpnews&spon=34&uac=133298AG

Gluten and Glucose Management in Type 1 Diabetes

Abstract

The prevalence of coeliac disease in patients with type 1 diabetes is significantly increased when compared to the general population. An explanation of the association between the development of both diseases may be explained by the inheritance of common major histocompatibility complex immunogenotypes that influence the presentation of auto antigens to CD4+ T-Cells. The subsequent loss of self tolerance results in destruction of the small bowel villi and pancreatic β-cells in coeliac and type 1 diabetes respectively. The diagnosis of coeliac disease in type 1 diabetic patients occurs commonly as a result of screening of individuals with subclinical coeliac disease. Recent studies have demonstrated the clinical benefit of treating subclinical coeliac disease in children with improvement in growth parameters, resolution of anaemia and fewer hypoglycaemic episodes. There is no current clinical evidence supporting routine screening of adult type 1 diabetic patients for coeliac disease. After the diagnosis of coeliac disease, type 1 diabetic patients should be commenced on a gluten-free diet with care co-ordinated between a dietician, gastroenterologist and diabetologist.

Introduction

Coeliac disease is a complex multifactorial autoimmune disease that is influenced by both genetic and environmental factors. Environmental exposure to gluten present in wheat, barley protein and rye results in immune mediated injury of the mucosa of the small intestine. Coeliac disease may be classified as symptomatic (diarrhoea with or without malabsorption) or subclinical (without gastrointestinal symptoms but may have extra-intestinal symptoms). Symptomatic coeliac disease is relatively rare occurring with a clinical frequency of one in 3,345 people worldwide, while asymptomatic coeliac disease detected on serological screening affects one of every 120–300 persons worldwide.^[1,2]

Type 1 diabetes is a relatively common disease accounting for 5–10% of all diabetes and is increasing in prevalence. It is a complex multifactorial autoimmune mediated disease characterised by the destruction of pancreatic β-cells leading to absolute insulin deficiency and subsequent ketoacidosis. The environmental antigen(s) has not been conclusively identified in type 1 diabetes though recent reports suggest that insulin may be the causative agent.^[3,4]

The association between coeliac disease and type 1 diabetes is estimated at 2–10% in European populations.^[5,6] In addition, both diseases are known to cluster with other organ specific autoimmune disorders such as autoimmune thyroid disorder and Addison's disease giving rise to Autoimmune Polyendocrine Syndrome type II.^[7.8] In this review we explore the common immune pathology between coeliac disease and type 1 diabetes, the role of screening for coeliac disease in individuals with type 1 diabetes and finally the clinical management of patients affected by both diseases.

Immunogenetics

A partial explanation for the association between type 1 diabetes and coeliac disease is their similarities in immunogenotype, with both diseases being associated with inheritance of the MHC genes located on the short arm of Chromosome 6 (6p21.31). The MHC class II genes encode for a cell surface HLA class II molecule (MHC class II molecule) that is expressed on APC. The HLA class II molecule is a heterodimer composed of an alpha and a beta subunit and the latter may be encoded by the alleles of the DP, DQ or DR genes.^[9,10]

Type 1 Diabetes

Type 1 diabetes has a concordance rate of 30–50% in monozygotic twins indicating a significant environmental contribution to the development of the disease phenotype. The average risk to siblings of an affected individual is estimated at 6%. Inheritance of one of the MHC class II haplotypes DR4 DQA1*0301/DQB1*0302 or DR3 DQA1*0502/DQB1*0201 increases the risk of type 1 diabetes. One of these haplotypes is found in 90% of children affected. The DR4 DQA1*0301/DQB1*0302 and DR3 DQA1*0502/DQB1*0201 haplotypes encode genes to form HLA-DQ8 and HLA-DQ2 class II molecules respectively. The combination heterozygous genotype DR4 DQA1*0301-DQB1*0302/DR3 DQA1*0502- DQB1*0201 confers the greatest susceptibility to the development of type 1 diabetes which commonly presents as diabetic ketosis in infancy. The MHC class II locus is estimated to confer 50% of the genetic susceptibility to type 1 diabetes with the remainder from genes outside the MHC.^[11,12]

Coeliac Disease

The total genetic contribution to development of coeliac disease has been estimated from monogenetic twin concordance data as 70% compared with 30% in HLA-identical siblings, indicating a contribution from loci outside the MHC genes such as 5q31-33. The most common MHC class II haplotypes inherited in coeliac disease are the HLA DR3 DQA1* 0502/DQB1*0201 encoding the HLA DQ2 class II molecule. The HLA DQ2 cell surface receptor is expressed in 90% of coeliac patients. The DR4 DQA1*0301/DQB1*0302 haplotype encoding the HLA-DQ8 class II molecule is also found in individuals with coeliac disease but more rarely. It is important to note that inheritance of these haplotypes confers susceptibility to coeliac disease but additional environmental triggers are necessary for disease development.^[13,14]

The HLA DR4 and DR3 loci occur frequently in type 1 diabetes and coeliac disease ( Table 1 ). The similar genetic background is the likely explanation for the common clinical concurrence of both conditions.^[15,16]

Pathogenesis

Coeliac Disease

The key event in the development of coeliac disease in genetically susceptible individuals is the ingestion of gluten – the storage protein of wheat. Gliadin is the alcohol soluble fraction of gluten and this has been investigated extensively. The current disease model for coeliac disease involves the deamidation of gliadin by tissue transglutaminase to glutamic acid peptides (Figure 1). Specifically a 33-amino-acid (33-mer) peptide that resists digestion by gastric and intestinal proteolytic enzymes, in vitro and in vivo, is immunogenic in coeliac patients. The 33-mer peptide is deaminated by transglutaminase on the subepithelial layer of the intestine. The deaminated peptide residues are then processed by APC to three epitopes that bind to the HLA DQ2 or DQ8. The T-cell receptor on intestinal CD4+ T-cells in the lamina propria recognise the epitopes displayed on the HLA DQ2/DQ8 as foreign and initiates the production of proinflammatory cytokines. This inflammatory environment results in immune deregulation and loss of tolerance with activation of CD8+ T-cells and B-cells in the intestinal epithelium. The pathophysiological result is intraepithelial lymphocytosis, villous atrophy and the production of transglutaminase antibodies.^[13,17]

Figure 1. Activation of the immune system by gluten in coeliac disease. Gluten is degraded by gastrointestinal enzymes to a 33 amino acid (33-mer) peptide. The 33-mer peptide is absorbed across the small bowel epithelium to the subepithelial layer in the lamina propria. Tissue transglutaminase deaminates the 33-mer peptide. The deaminated peptides are processed by APC to three epitopes that bind to the HLA-DQ2 or DQ8 molecules. The T-cell receptor on T-cells then cross-react with the HLA molecule leading to the initiation of an autoreactive immune response with subsequent activation of B-cells, CD4+ Th1 cells and NK cells. The resultant proinflammatory environment results in further immune activation and migration of lymphocytes resulting in the characteristic pathological finding of increased intraepithelial lymphocytes and villous atrophy. APC = antigen presenting cells; HLA = human leukocyte antigen; NK = natural killer cells.

Figure 1.

Activation of the immune system by gluten in coeliac disease. Gluten is degraded by gastrointestinal enzymes to a 33 amino acid (33-mer) peptide. The 33-mer peptide is absorbed across the small bowel epithelium to the subepithelial layer in the lamina propria. Tissue transglutaminase deaminates the 33-mer peptide. The deaminated peptides are processed by APC to three epitopes that bind to the HLA-DQ2 or DQ8 molecules. The T-cell receptor on T-cells then cross-react with the HLA molecule leading to the initiation of an autoreactive immune response with subsequent activation of B-cells, CD4+ Th1 cells and NK cells. The resultant proinflammatory environment results in further immune activation and migration of lymphocytes resulting in the characteristic pathological finding of increased intraepithelial lymphocytes and villous atrophy. APC = antigen presenting cells; HLA = human leukocyte antigen; NK = natural killer cells.

Type 1 Diabetes

Overt symptoms of diabetes do not occur until approximately 80% of the β-cells have been destroyed, making it difficult to identify the precipitating environmental event.^[18] It has recently been suggested that insulin may be the primary auto antigen.^[19,20] In vivo, this auto antigen may be displayed on APC activating CD4+ T cells to initiate an immune response (Figure 2). Evidence to support this disease model of type 1 diabetes mainly originates from clinical trials involving administration of cyclosporin to achieve T-cell suppression. This treatment induced remission with enhanced insulin secretion. However the significant side effects of cyclosporin prevented the widespread use of this therapeutic strategy. Of late more targeted therapy with an anti T-cell monoclonal antibody (hOKT3gamma)Ab improved C-peptide responses with a single treatment lasting up to one year.^[21] The anti T-cell monoclonal antibody (ChAglyCD3) has been shown to maintain β-cell function for at least 18 months.^[22] These clinical trials demonstrate the pivotal role of T-cells in the development of symptomatic disease.

Figure 2. Proposed autoimmune mechanism of the development of type 1 diabetes. An auto-antigen, proposed to be insulin, is presented to an APC. The antigen is processed to epitopes which are bound and displayed on HLA DQ2/DQ8. Cross-reaction occurs between CD4+ T-cell and APC to initiate autoimmune reaction directed at the β-cells of the pancreatic islets. A component of the T-cell mediated immune response involves the activation of B-cells to produce autoreactive antibodies. The ultimate result is immune mediated destruction of pancreatic β-cells with concomitant insulin deficiency and subsequent ketoacidosis. APC = antigen presenting cells; HLA = human leukocyte antigen

Figure 2.

Proposed autoimmune mechanism of the development of type 1 diabetes. An auto-antigen, proposed to be insulin, is presented to an APC. The antigen is processed to epitopes which are bound and displayed on HLA DQ2/DQ8. Cross-reaction occurs between CD4+ T-cell and APC to initiate autoimmune reaction directed at the β-cells of the pancreatic islets. A component of the T-cell mediated immune response involves the activation of B-cells to produce autoreactive antibodies. The ultimate result is immune mediated destruction of pancreatic β-cells with concomitant insulin deficiency and subsequent ketoacidosis. APC = antigen presenting cells; HLA = human leukocyte antigen

In summary the development of both coeliac disease and type 1 diabetes share a similar immunopathogenesis requiring the activation of auto reactive T-cells in genetically susceptible individuals. Coeliac disease however differs from type 1 diabetes in that the environmental antigenic trigger gliadin (a component of gluten) has been identified and avoidance leads to remission of the disease.

Screening

The diagnosis of coeliac disease in individuals with type 1 diabetes is most commonly due to screening since most affected patients have subclinical disease. A minority will present with overt classical coeliac disease characterised by growth failure, muscle wasting, pallor, oedema and rickets. Screening for coeliac disease involves testing for circulating endomysial or transglutaminase antibodies, with diagnosis being confirmed by small bowel biopsy demonstrating infiltration of the intestinal mucosa by lymphocytes and the development of crypt hyperplasia and villous atrophy.^[2]

Many clinicians have suggested that all children with type 1 diabetes should be screened for coeliac disease and treated. However, others have questioned the potential benefits of treatment and the risks of screening. Support for the effectiveness of screening is provided by the facts that coeliac disease is known to be more common in type 1 diabetic patients (mean 4.1%, range 0–10.4%) than the general population (0.3–0.5%) and is usually subclinical. A highly effective treatment is available, withdrawal of gluten from the diet. Studies of non-diabetic coeliac children suggest that treatment may avoid the complications of growth failure, low bone density and potential neurological abnormalities. Glycaemic control may also be improved by a reduction in hypoglycaemic episodes caused by erratic absorption of glucose. Finally it is speculated that treatment of coeliac disease in type 1 diabetes could reduce the likelihood of the development of other autoimmune diseases such as Grave's or Addison's disease or non-Hodgkin's lymphoma of the small bowel.^[23]

Screening for coeliac disease was deemed inappropriate in children with type 1 diabetes by some clinicians since classical coeliac disease is easy to recognise. Screening therefore would only identify subclinical disease. The long-term outcome of subclinical coeliac disease in type 1 diabetes was unknown, as were the benefits of treatment. The definitive diagnosis of subclinical coeliac disease also requires invasive investigation with associated risk and treatment of coeliac disease in type 1 diabetes possibly leading to further complexity and psychological burden in patients. Screening of children with increased hypoglycaemic episodes for coeliac disease would be justified however.^[23,24]

Recent investigations have clarified many of the issues regarding the screening of children with type 1 diabetes for coeliac disease. An Italian multicentre study found the prevalence of biopsy proven coeliac disease in children with diabetes to be high (6.8%). Diabetes is usually diagnosed prior to the development of coeliac disease. The risk of the development of coeliac disease is correlated with earlier onset of type 1 diabetes, with three times the risk of onset at age less than four, than in children older than nine. The study also detected a trend of decreased prevalence of coeliac disease detection after 10 years duration of diabetes.^[25]

One group has shown that at diagnosis of type 1 diabetes raised EMA were predictive for the development of coeliac disease. In children who were negative for EMA antibodies at diagnosis seroconversion took place in the next 2.8–10.8 years in those who subsequently developed coeliac disease. All patients were asymptomatic at diagnosis. A recommendation of screening at two-year intervals for asymptomatic patients was suggested as a safe and cost-effective strategy.^[26]

A Danish study found the highest prevalence (10%) of coeliac disease in children (<16>1C remained unchanged in patients on a GFD though two patients experienced fewer hypoglycaemic episodes. Compliance with diet was good with 24 of the 31 patients having disappearance of the coeliac antibodies.^[27]

Clinical Management

The cornerstone of the treatment of coeliac disease is the initiation and maintenance of a GFD.^[28] However, commencement of a GFD in patients initially diagnosed with coeliac disease does not offer protection from the development of type 1 diabetes.^[27] Similarly, removal of gluten from the diet of individuals at high risk of the development of type 1 diabetes does reduce the incidence of coelic disease.^[29,30]

Care of type 1 diabetic patients with coeliac disease should be co-ordinated between a dietician, gastroenterologist and diabetologist. Patient compliance with treatment is highest in coeliac patients when the GFD is commenced as young children rather than as adolescents.^[31] Patient compliance with GFD may be monitored by self-reported diet, growth charts and/or transglutaminase antibody titres.^[32] Studies of GFD in type 1 diabetic patients with coeliac disease have demonstrated good compliance rates.^[33-36] However, it remains to be determined if these compliance rates can be achieved in a normal clinical setting.

The effect of GFD on glycaemic control in type 1 diabetic patients has been examined by a number of studies. Prior to treatment with GFD type 1 diabetic patients with coeliac disease have lower insulin requirements and BMI than type 1 diabetic (non coeliac) control patients. With treatment their insulin requirements increase as BMI increases. The overall effect on metabolic control remains unclear, one study has reported improvement in HbA_1C ^[35] while two others have reported that HbA_1C remains unchanged,^[27,33] and a reduction in microvascular complications or diabetic nephropathy has not been observed in type 1 diabetic patients affected with coeliac disease treated with GFD as when compared to diabetic patient controls.^[26,37] Standard glycaemic targets referenced to the patient's age should be pursued.^[38] As previously discussed there may be a reduction in hypoglycaemic episodes thereby allowing for tighter glycaemic control to be achieved.^[39]

Conclusions

Coeliac disease and type 1 diabetes may occur in patients as a result of their common immunogenotypes. Though both diseases differ in organ specificity they appear to share a similar pathogenic mechanism involving the deregulation of T-cell responses and the loss of self tolerance with resultant tissue damage to the small bowel (coeliac) and β-cells of the pancreatic islets (type 1 diabetes). Treatment of children, diagnosed first with coeliac disease with GFD does not provide subsequent protection from the development of type 1 diabetes.

Recent evidence has provided support for the screening of type 1 diabetic patients under the age of sixteen for subclinical coeliac disease given the resolution of gastrointestinal symptoms and improvement in growth parameters. Serological screening (EMA and tTGA with concurrent serum IgA) should be carried out every two years for a ten-year duration post diagnosis of type 1 diabetes. Positive serology should lead to formal small bowel biopsy to examine for partial or total villous atrophy ( Table 2 ). Treatment with a GFD may also reduce the number of hypoglycaemic episodes in patients, though overall glycaemic control remains unchanged.

Widespread screening for coeliac disease in adults with type 1 diabetes is not recommended since the clinical benefit is unknown. However, adult patients with type 1 diabetes with symptoms of coeliac disease or recurrent hypoglycaemic episodes or multiple endocrine diseases should be investigated for coeliac disease. Future screening studies of adult type 1 diabetic patients with subclinical coeliac disease should aim to demonstrate clinical benefit of initiation of GFD by improvement in metabolic control or possibly reduction in prevalence of non-Hodgkin's lymphoma of the small bowel.

References

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4. American Diabetes Association. Standards of Medical Care in Diabetes 2007. Diabetes Care 2007;30:S4-S41.
5. Collin P, Kaukinen K, Valimaki M et al. Endocrinological disorders and coeliac disease. Endocr Rev 2002;23:464-83.
6. Hansen D, Brennedbaek FN, Hansen LK et al. High prevalence of coeliac disease in Danish children with type 1 diabetes mellitus. Acta Paediatr 2001;90:1238-43.
7. Eisenbarth GS, Gottlieb PA. Autoimmune Polyendocrine Syndromes. N Engl J Med 2004;350:2068-79.
8. Cronin CC, Shanahan F. Insulin-dependant diabetes mellitus and coeliac disease. Lancet 1997;349:1096-7.
9. McDevitt HO. Discovering the role of the Major histocompatibility complex in the immune response. Ann Rev Immunol 2000;18:1-17.
10. Kumanovics A, Takada T, Lindahl KF. Genomic organisation of the mammalian MHC. Ann Rev Immunol 2003;21:629-57.
11. Jahromi MN, Eisenbarth GS. Genetic determinants of type 1 diabetes across populations. Ann N Y Acad Sci 2006;1079:289-99.
12. Lambert AP, Gillespie KM, Thomson G et al. Absolute risk of childhoodonset type 1 diabetes defined by human leukocyte antigen class II genotype: A Population-Based Study in the United Kingdom. J Clin Endocrinol Metab 2004;89:4037-43.
13. McManus R, Kelleher D. Celiac disease the villian unmasked? N Engl J Med 2003;348:2573-4.
14. Sollid LM. Coeliac disease: dissecting a complex inflammatory disorder. Nat Rev Immunol 2002;2:647-55.
15. Bao F, Yu L, Wang T et al. One third of HLA DQ2 homozygous patients with type 1 diabetes express coeliac disease-associated transglutminase autoantibiodies. J Autoimmun 1999;13:143-8.
16. Saukkonen T, Ilonen J, Akerblom HK, Savilahti E. Prevalence of coeliac disease in siblings of patients with Type 1 diabetes is related to the prevalence of DQB1*02 allele. Diabetologia 2001;44:1051-3.
17. Kagnoff MF. Overview and pathogenesis of celiac disease. Gastroenterology 2005;128:S10-S18.
18. Gillespie KM. Type 1 diabetes: pathogenesis and prevention. CMAJ 2006;175:165-70.
19. Kent SC, Chen Y, Bregoli L et al. Expanded T cells from pancreatic lymph nodes of type 1 diabetic subjects recognise an insulin epitope. Nature 2005;435:224-8.
20. Nakayama M, Abiru N, Moriyama H et al. Prime role for an insulin epitope in the development of type 1 diabetes in NOD mice. Nature 2005;535:220-3.
21. Herold KC. Treatment of type 1 diabetes mellitus to preserve insulin secretion. Endocrinol Metab Clin North Am 2004;33:93-111.
22. Keymeulen B, Vandemeulebroucke E, Zieger AG et al. Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes. N Engl J Med 2005;353:2598-608.
23. Freemark M and Levitsk LL. Screening for coeliac disease in children with type 1 diabetes. Diabetes Care 2003;26:1932-39.
24. Murray JA. Celiac disease in patients with an affected member, type 1 diabetes, iron deficiency, or osteoporosis. Gastroenterology 2005;128:S52-S56.
25. Ceritti F, Beuno G, Chiarelli F et al. Younger age at onset and sex predict celiac disease in children and adolescents with type 1 diabetes. Diabetes Care 2004;27:1294-8.
26. Glastras SJ, Craig ME, Verge CF et al. The Role of autoimmunity at diagnosis of type 1 diabetes in the development of thyroid and celiac disease and microvascular complications. Diabetes Care 2005; 28:2170-5.
27. Ludvigsson JF, J Ludvisson J, Ekbom A et al. Coeliac Disease and Risk of Subsequent Type 1 Diabetes. Diabetes Care 2006;29:2483-8.
28. Rewer M, Liu Edwin, Simmons J et al. Coeliac disease associated with type 1 diabetes mellitus. Endocrinol Metab Clin N Am 2004;33:197-214.
29. Hummel M, Bonifacio E, Naserke HE, Ziegler AG. Elimination of dietary gluten does not reduce titres of Type 1 diabetes-associated autoantibiodies in high risk subjects. Diabetes Care 2002; 25:1111-16.
30. Pastrone MR, Bazzigaluppi E, Belloni C et al. Six months of gluten-free diet do not influence autoantobody titres but improve insulin secretion in subjects at high risk for type 1 diabetes. J Clinical Endocrinology Metab 2003;88:162-5.
31. Cranney A, Rostom A, Sy R et al. Consequences of testing for celiac disease. Gastroenterology 2005;128:S109-S20.
32. Pieta MM. Follow-up of patients with coeliac disease: achieving compliance with treatment. Gastroenterology 2005;128:S135-S141.
33. Amin R, Murphy N, Edge J et al. Longitudinal study of the effects of a gluten-free diet on glycemic control and weight gain in subjects with type 1 diabetes and coeliac disease. Diabetes Care 2006; 25:1117-22.
34. Hansen D, Brock-Jacobben B, Lund E et al. Clinical benefit of glutenfree diet in type 1 diabetic children with screening-detected coeliac disease. Diabetes Care 2006;29:2452-6.
35. Sanhchez-Albisua I, Wolf J, Neu A et al. Coeliac disease in children with Type 1 diabetes mellitus; the effect of the gluten-free diet. Diabetic Medicine 2005;22:1079-82.
36. Saadah OI, Zacharin M, O'Callaghan A et al. Effect of gluten-free diet and adherence on growth and diabetic control in diabetics and coeliac disease. Arch Dis Child 2004;89:871-6.
37. Skovbjery H, Tarnow L, Locht H, Parving HH. The prevalence of coeliac disease in adult Danish patients with type 1 diabetes with and without nephropathy. Diabetologia 2005;48:1416-17.
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Source : http://www.medscape.com/viewarticle/574648

Anxiety, Depression Linked to Angina Frequency in Heart Patients

New research shows that ischemic heart disease patients who suffer significant anxiety have close to a 5-fold increased risk of experiencing frequent angina and those with depression have more than a 3-fold increased risk for these episodes.

This observed link between psychiatric symptoms and angina underlines the importance of treating anxiety and depression in cardiac patients, according to study coauthor Mark D. Sullivan, MD, PhD, from the department of psychiatry and behavioral sciences at the University of Washington School of Medicine, in Seattle.

Current cardiology care focuses almost exclusively on management of ischemia with medications and revascularization, said Dr. Sullivan. "We're saying that there's a very significant contribution of depression and anxiety to these symptoms." This is among the first studies to measure depression and anxiety in ischemic heart patients, he added.

The research is published online June 29 in the journal Circulation.

Significant Comorbidities

The study included patients with suspected ischemic heart disease who were scheduled for an outpatient stress test with myocardial perfusion imaging at 2 medical centers in Washington State between April 2004 and April 2006. Researchers focused on 191 patients with clearly established inducible ischemia on stress testing. The mean age of these subjects was 63 years. Many participants were middle-aged male veterans.

A significant portion of the study group had cardiac-related comorbidities. For example, 82% had hypertension, 81% had hyperlipidemia, 34% were smokers, and 14% had diabetes mellitus

Prior to the stress testing, patients completed the Seattle Angina Questionnaire. Researchers focused on the portion of this questionnaire that quantifies the frequency and burden of angina. Angina frequency was categorized as none, monthly, weekly, or daily; the last 2 frequencies were combined for the purposes of this analysis.

Angina pectoris was defined as discomfort, usually around the chest, jaw, shoulder, back, or arm, associated with atherosclerotic obstruction. Of the 191 patients with inducible ischemia on stress perfusion imaging, 68 (36%) reported no angina over the previous 4 weeks, 66 (35%) reported monthly symptoms, and 57 (30%) had weekly or daily angina.

Patients with more frequent baseline angina were much more likely to report chest pain during stress tests: 63% of patients with weekly or daily angina compared with 20% of patients with monthly angina and 11% of patients with no angina.

Psychosocial Factors

The researchers examined 5 psychosocial factors that might affect angina frequency: anxiety; depression; neuroticism (tendency to experience negative emotions such as sadness, anger, or guilt); alexithymia (impaired ability to express inner feelings); and somatosensory amplification (tendency to experience a somatic sensation as intense, noxious, and disturbing).

There was more anxiety and depression among patients with frequent angina. For instance, 22% of patients with no angina had clinically significant anxiety, defined as a score of 16 or greater on the Beck Anxiety Inventory scale, compared with 38% for patients with monthly angina and 64% for those with weekly or daily angina.

Other psychosocial factors were also increased among patients with more frequent angina. For example, 38% of patients with weekly or daily angina had a high level of alexithymia compared with 17% of patients with monthly angina and 14% of those without angina.

However, after adjustment for degree of myocardial ischemia, greater anxiety score (odds ratio, 1.39 per half–standard deviation increase in anxiety score) and greater depression score (OR, 1.51 per half–standard deviation increase in depression score) were the only psychosocial factors significantly associated with more frequent angina. As expected, previous coronary revascularization was also significantly associated with frequent angina.

Patients with at least moderate anxiety symptoms experienced a 4.7-fold increased risk of having more frequent angina (95% CI, 1.91 – 11.66; P = .001). Patients with clinically relevant depressive symptoms (16 or greater on the Center for Epidemiologic Studies Depression scale) had a 3.2-fold increased risk of experiencing more frequent angina (95% CI, 1.45 – 6.69; P = .004.)

Biological Factors

Not every patient with coronary artery disease develops angina. Up to 45% of these patients have asymptomatic ischemia. Several biological factors might explain the discrepancy between coronary artery disease and angina severity, according to the authors. For example, metabolic neuropathy or ischemic regional nerve injury may influence pain levels.

"Just as with other pain syndromes — for example, chronic back pain — the relationship between the injury or the disease severity and the pain severity is very loose," said Dr. Sullivan, who has an interest in chronic pain. "There are all sorts of things that modify it, but these have not been studied very much in angina. That's why we wanted to do this study."

While the study showed a link between psychosocial symptoms and angina frequency, there is no evidence yet that treating these symptoms would reduce angina, said Dr. Sullivan.

"In cardiology, we thought we knew exactly why people were having pain — because they've got plugged plumbing, and unplugging the plumbing was going to solve the problem," said Dr. Sullivan. And while revascularization often does relieve the pain, there is growing evidence that for stable angina, revascularization is not superior to medication, he noted.

Dr. Sullivan stressed that the study sample included heart patients, not psychiatric patients, and that most people with heart disease do not develop a clinical level of anxiety or depression. It is those who are vulnerable to begin with who are more susceptible to these psychological symptoms, said Dr. Sullivan.

Talk to Patients

Asked for his opinion, Gerald Fletcher, MD, professor of medicine and cardiology at the Mayo Clinic in Jacksonville, Florida, commended the authors for their innovative work.

The research underlines the need for doctors to talk to their patients more often to determine underlying psychological issues. "You can't determine sometimes if someone has anxiety, depression, or whatever without facing them in an exam room and talking to them."

Pursuing a healthy lifestyle, including exercising and not smoking, could make patients less prone to these psychological problems, he said. He added that psychotherapy and other treatment approaches may help to reduce stresses of everyday life.

Source : http://www.medscape.com/viewarticle/705085

ASMBS 2009: Gastric Banding Achieves Sustained Weight Loss, Improvement of Diabetes

Laparoscopic adjustable gastric banding has a sustained and substantial positive effect on metabolic parameters in morbidly obese patients with type 2 diabetes, according to data presented here at the annual meeting of the American Society of Metabolic and Bariatric Surgery.

Investigators assessed the 5-year outcomes of 95 morbidly obese patients with type 2 diabetes, recording age, sex, race, body mass index (BMI), diabetes history, fasting glucose level, hemoglobin A1c (HbA1c), and use of medications. The patients underwent laparoscopic adjustable gastric banding between January 2002 and June 2004.

Morbid obesity was defined as a BMI of 40 kg/m² or more or a BMI of 35 kg/m² with an obesity-related illness. The mean age of patients before surgery was 49.3 years, and mean duration of diabetes was 6.5 years. The mean preoperative BMI was 46.3 kg/m² (range, 35.1 – 71.9 kg/m²), which fell to 35.0 kg/m² (range, 21.1 – 53.7 kg/m²) at 5-year follow-up. Mean excess weight loss was 48.3%.

The mean fasting glucose level fell from 146 mg/dL to 118.5 mg/dL (P = .004). The mean HbA1c decreased from 7.53% to 6.58% at 5 years after banding (P < .0001).

Diabetes resolution was defined as the patient being medication-free with an HbA1c of less than 6% and/or a glucose level less than 100 mg/dL. Resolution occurred in 23 (39.7%) of 58 patients. Improvement, defined as fewer medications required and fasting glucose levels between 100 and 125 mg/dL, was seen in 41 (71.9%) of 57 patients.

The overall combined improvement/resolution rate was 80% (64 of 80 patients).

"Our study shows that for the vast majority of diabetic, morbidly obese patients, they will have improvement in their diabetes and often times a resolution of their diabetes, which extends out to 5 years," said Christine Ren, MD, FACS, an associate professor of surgery at New York University School of Medicine in New York City, and one of the study's senior authors.

"We saw [that] the only difference between those who had complete resolution of diabetes vs those who did not was their weight loss," said Dr. Ren.

"It appears that in gastric banding, the probability of a patient having improvement or resolution of diabetes depends on how much weight you lose and keep off."

Investigators did not find a statistically significant difference in remission of diabetes based on the duration of diagnosis prebanding. A total of 83 (88.3%) of 94 patients were on oral medications before gastric banding, and 14.9% were on insulin. Five years after gastric banding surgery, 33 (46.5%) of 71 patients were on oral medications and 8.5% were on insulin.

Evidence has been available on the efficacy of gastric bypass surgery on resolution of diabetes, but these results point to the efficacy of laparoscopic adjustable gastric banding in resolving diabetes and in controlling metabolic parameters in the morbidly obese patient with diabetes, said Alan Wittgrove, MD, FACS, a member of the executive council of the American Society of Metabolic and Bariatric Surgery and medical director of the Bariatric Surgical Program at Scripps Memorial Hospital in La Jolla, California.

"It's important because the study follows the patients for at least 5 years," said Dr. Wittgrove. "It shows the longevity of the procedure in resolving diabetes through weight loss and [its] impact on the metabolic syndrome."

Although the study did not reveal the duration of diagnosis to be a factor that influenced whether or not patients experienced improvement in their diabetes, duration of diagnosis may have emerged as a variable that affected outcomes in a larger study, according to Dr. Wittgrove.

"That is probably a function of the power of the study," he said, noting that several studies have found that the timing of surgery has an effect on resolving diabetes in this type of patient. Surgery performed earlier results in more durable resolution, he pointed out.

"Since [duration of disease] has been shown to be a factor in other studies, I would extrapolate that if [the researchers] get more numbers, it would reach [statistical] significance," Dr. Wittgrove said.

The study was independently conducted. Dr. Ren is a member of the Speaker's Bureau, sits on an advisory board, and receives research and educational grants from Allergan Inc. She receives research and educational grants from Ethicon Endo-Surgery Inc and is a consultant for Explora Med Development, LLC. Dr. Wittgrove is a consultant for Ethicon Endo-Surgery Inc and receives research funding from Stryker Corporation.

American Society of Metabolic and Bariatric Surgery 2009 Annual Meeting: Abstract PL-104. Presented June 24, 2009.

Source : http://www.medscape.com/viewarticle/705047?src=mpnews

The Art of Patient Care in Clinical Medicine

"... the secret of the care of the patient is in caring for the patient."
-Frances Peabody, 1925There was a time not long ago, when physicians and nurses didn’t have much else to offer patients other than personal attention, comfort, compassion and concern for their ailments. Medical professionals were revered and respected for that and for what little they could do in regard to symptomatic treatment for incurable conditions.

The Twenty-First Century has thrust health care into an era of modernization, precipitated by advances in medical technology and computerization of everything in sight. We have made fantastic strides in the diagnosis and treatment of many serious illnesses. Patients are living longer and more productive lives as a result of these wonderful advances.

However, concomitant with these changes, we have experienced the indisputable depersonalization of patient care. Patients are often treated as diseases or numbers. We often hear medical personnel referring to a patient as “the gallbladder in room 232” or “the COPDer in 476”. We order test after test instead of taking a history because if we don’t “prove” our diagnosis with a test, we may be subjected to a lawsuit later if something goes wrong.

Health care costs have spun out of control. Forty-three million people in the US can no longer afford health insurance. Access to care has deteriorated. Prenatal care and birth rates are suffering. Doctors’ salaries are restricted by insurance companies. Busy primary care physicians have to see 30-40 patients a day to make enough income to pay off their own expenses beginning with a $250,000 debt for medical training.

There is no time to spend 20 minutes with an 80 year-old patient with diabetes, arthritis, heart failure, and hypertension out of control who has just developed shortness of breath recently, and who needs 6 prescriptions rewritten. Other patients in the waiting room are feeling ignored.

These are very difficult challenges. Unfortunately, in the middle of it all, we often lose site of the fact that our patients are people – in many cases, very ill people - who are looking to us for support and guidance as well as medical care. There is an art to providing this support and to personalizing care for each and every patient in the midst of an imperfect environment.

Anyone who works in the health care profession knows there is a right way and a wrong way to approach patient care. They also know this is somewhat different for every patient they encounter due to multiple variables – type of illness, gender, age, background, etc. This is an art that we learn mostly by experience – both by our own personal experience and by observing the experiences of others. How well we assimilate the information from these experiences and how well we use that knowledge determines a very large part of how we interact with patients and how we are perceived as medical professionals.

The key word here is the art of patient care. For the purposes of this site, the reference is not so much on the science of medicine per se, but rather on how medical personnel can interact with patients to improve the healing process, rather than dismantle it.

This is not to say that science is unimportant; but rather that concern for the humanity of the patient should not be so overwhelmed by science as to be nonexistent at the bedside. Indeed, true clinical competence is a blend of knowledgeable application of medical science along with the recognition and understanding of the human condition. The art of this blend, the integration of these two disciplines, and how well it is done, is what determines the quality of patient care that we provide. One without the other is not sufficient.

This can be a science unto itself. One of the influences that this site will hopefully promote is more discussion and ultimately more research on how to practice this art in a more meaningful and fulfilling way for both ourselves and our patients alike. In addition, the more formal exploration and inclusion of these concepts into medical training programs would have a huge effect on the future of medicine in this country.

Some people say you have to be born with this talent. I don’t think so. I do think it comes easier to some than others; but, whatever the genetics and background of the individual, patient care is an art that can be learned and practiced and improved upon, just as drawing or painting a thoughtful picture can be learned and practiced to the point where it can be greatly appreciated by others.

So what kind of doctor or nurse or care partner do you want to be?

What is your approach to patient care?

How do patients perceive your approach to them and your overall competence?

If you long to be one of those caring, well-respected and revered medical professionals that patients (and even other professionals) admire and tell their friends and neighbors about, you’ve found the right place.

Read and study the pages on this site. You will become a much more people-oriented professional, knowledgeable about how to approach all kinds of patients and challenging situations, and who will at the very least be perceived as someone who cares and is concerned about his or her patients.

If you practice what you learn here, you may find yourself actually rediscovering virtues you didn’t know you had. If you already have the nurturing gene, these pages will help you hone that talent into something very special; and your patients will benefit from it in ways you never thought possible.

Source : http://www.art-of-patient-care.com/

EULAR 2009: New Diagnostic Recommendations for Knee Osteoarthritis

New EULAR recommendations for the diagnosis of knee osteoarthritis unveiled here focus on simple measures — clinical examination and plain radiography.

"These recommendations should be especially helpful for primary care physicians in providing them a firm foundation of diagnostic criteria," said lead author Weiya Zhang, associate professor at the University of Nottingham in the United Kingdom.

The guidance was released here during EULAR 2009: The Annual European Congress of Rheumatology.

Dr. Zhang pointed out that these EULAR recommendations differ from American College of Rheumatology (ACR) criteria by focusing on clinical diagnosis rather than classification, and they are more generalizable to different populations because they were based on a thorough evidence-based review of studies from 1950 to 2008 as well as expert consensus from different countries.

The task force was made up of 17 osteoarthritis experts from 12 countries. The expert panel developed 10 key recommendations, and then tested the diagnostic accuracy of these recommendations on 2 separate study populations: one from the United Kingdom and one from the Netherlands.

Three Recommendations Presented

At EULAR, Dr. Zhang presented 3 of the new recommendations — one on risk factors, one on clinical diagnosis, and one on radiography. The full document that includes all 10 recommendations will be published soon.

Risk factors for knee osteoarthritis were identified as follows: female sex, aging, overweight, joint injury, malalignment, joint laxity, occupational and recreational use, family history, and Heberden's nodes (bone overgrowth) at the distal finger joints.

The recommendation for clinical diagnosis focused on 3 symptoms (pain on use, short-lived morning stiffness, and functional limitation) and 3 signs (crepitus, restricted movement, and bony enlargement). The panel found that the 3 signs and 3 symptoms could correctly identify 99% of patients with knee osteoarthritis.

A validation study in the UK sample using the 6 criteria identified a prevalence of knee osteoarthritis of 44%. The probability of making the diagnosis increased with increasing use of the 6 features.

"This performance test tells us that the clinical diagnosis of knee osteoarthritis can be made with confidence based on these factors," Dr. Zhang said. "These 6 criteria apply even if the radiographs appear normal."

The third recommendation called for plain radiography of the knees, with a weight bearing, semi-flexed view, plus a lateral and skyline view. Classical features of osteoarthritis on radiography are space narrowing, osteophytes, and subchondral bone sclerosis.

"There is no gold standard for knee osteoarthritis, as there is for gout, but using the 3 views increases the probability of a correct diagnosis," Dr. Zhang explained. "Other imaging modalities, such as MRI [magnetic resonance imaging], sonography, and scintigraphy, are seldom needed.

"We call radiography a reference standard, not a gold standard," he pointed out. "Some patients with radiographic damage may not have symptoms, and some patients with symptoms may not have evidence of radiographic damage."

This is the first formal EULAR recommendation for diagnostic imaging for knee osteoarthritis. Imaging may also be needed for management, Dr. Zhang noted.

Consider Recommendations Within Context

The new EULAR recommendations should be considered within the context of the many new treatments available for osteoarthritis and the need to have a consensus for training purposes, according to Andrew Cope, MD, from King's College in London, United Kingdom.

"These are recommendations, not fixed guidelines. The idea is to guide clinicians according to the evidence base. There is no question that some patients won't fit the parameters, which is always a weakness of population-based recommendations. The long-term, far-off goal for rheumatologists is patient-specific targeted management," Dr. Cope said.

The recommendations should be helpful for primary care physicians, he continued. "Keep it simple, keep it safe," he said.

Dr. Zhang, the other panel members, and Dr. Cope have disclosed no relevant financial relationships.

EULAR 2009: The Annual European Congress of Rheumatology: Abstract OP-0209. Presented June 12, 2009.

Clinical Implications

• Risk factors for knee osteoarthritis include female sex, aging, overweight, joint injury, misalignment, joint laxity, occupational and recreational use, family history, and Heberden's nodes; plain radiography is recommended with a weight-bearing, semi-flexed view plus a lateral and skyline view.
• Clinical diagnosis should focus on 3 clinical symptoms (pain on use, short-lived morning stiffness, and functional limitation), and 3 signs (crepitus, restricted movement, and bony enlargement) with a prevalence of 44% in a UK sample using all 6 criteria.

Source : http://cme.medscape.com/viewarticle/704387?src=cmenews