From Therapeutic Advances in Gastroenterology
Thomas H. Frazier, MD; Abigail M. Stocker, MD; Nicole A. Kershner, MD; Luis S. Marsano, MD; Craig J. McClain, MD
Abstract
Alcoholic liver disease (ALD) remains a major cause of liver-related mortality in the US and worldwide.
The correct diagnosis of ALD can usually be made on a clinical basis in conjunction with blood tests, and a liver biopsy is not usually required.
Abstinence is the hallmark of therapy for ALD, and nutritional therapy is the first line of therapeutic intervention.
The role of steroids in patients with moderate to severe alcoholic hepatitis is gaining increasing acceptance, with the caveat that patients be evaluated for the effectiveness of therapy at 1 week.
Pentoxifylline appears to be especially effective in ALD patients with renal dysfunction/hepatorenal syndrome.
Biologics such as specific anti-TNFs have been disappointing and should probably not be used outside of the clinical trial setting.
Transplantation is effective in patients with end-stage ALD who have stopped drinking (usually for ≥6 months), and both long-term graft and patient survival are excellent.
Introduction
Alcoholic liver disease (ALD), which ranges from simple steatosis to cirrhosis and hepatocellular carcinoma (HCC), continues to represent a major health issue in the United States and abroad.
Despite significant advances in the understanding of the pathogenesis of alcohol-related liver injury, there are no FDA-approved treatments for ALD.
The purpose of this review is to examine the diagnosis and current modalities of treatment for ALD.
At present, abstinence remains the cornerstone for successful treatment of ALD. Aside from treatment of the underlying addiction, aggressive nutritional intervention and 'off-label' use of various pharmacotherapies aimed at the underlying mechanisms of injury (e.g., cytokine dysregulation, endotoxin translocation and oxidative stress) represent our approach to treating ALD.
for rest of article:
http://www.medscape.com/viewarticle/739272?src=mp&spon=17
Wednesday, April 6, 2011
Exercise and T2DM—Move Muscles More Often!
From Nature Reviews Endocrinology
David Dunstan
Abstract
New guidelines from the American College of Sports Medicine and the American Diabetes Association provide specific exercise advice for individuals with type 2 diabetes mellitus, while new research emphasizes the importance of getting people off the couch and moving more often throughout the day.
Introduction
"If we could give every individual the right amount of nourishment and exercise, not too little and not too much, we would have found the safest way to health." Hippocrates's profound view of the importance of regular exercise has been brought to the fore in a joint position statement released in December 2010 by the American College of Sports Medicine and the American Diabetes Association, which provides new guidelines on exercise for people with type 2 diabetes mellitus (T2DM).
In the eyes of some, this position statement may conjure thoughts that we already know: that physical activity is a cornerstone in the prevention and management of T2DM.
However, these guidelines provide patients with T2DM, and those who care for them, with a timely update on new evidence generated from numerous high-quality studies conducted over the past decade on what works for people with or at risk of developing T2DM.
The recommendations call for at least 150 min a week of aerobic exercise of at least moderate intensity—brisk walking is a moderate-intensity aerobic exercise that is appropriate for most people with T2DM.
This amount of exercise should be spread over at least 3 days during the week, with no more than two consecutive days between bouts of aerobic activity.
The recommendations also acknowledge that aerobic activity alone cannot deliver the full benefits of exercise to individuals with T2DM.
Numerous recent studies have shown that resistance exercise (strength training) is a highly effective type of exercise in diabetes management and is the only type of exercise that offers some protection against the loss of muscle mass (sarcopenia) and muscle strength and physical function that occurs with advancing age.
As such, the recommendations state that, in addition to the aerobic activity requirements, resistance exercise of at least moderate or vigorous intensity should be undertaken at least twice weekly on nonconsecutive days, but more ideally three times a week.
Although these new guidelines recommend both aerobic and resistance training, few studies have directly examined the effects of combined training in individuals with T2DM.
Combined training offers the capacity to achieve the unique health benefits of both types of exercise and has the potential to be more time efficient, as the benefits of aerobic and resistance exercise can be derived from the one session rather than two separate sessions.
This consideration is important, given that lack of time is one of the most frequently cited reasons for nonparticipation in regular exercise.
A large Canadian study published in 2007 was the first to report that combined training may be of greater benefit for glycemic control than either aerobic or resistance exercise alone in patients with T2DM.
However, the additional benefit observed might have been due to the extra exercise time in the combination group (approximately double that in the single-exercise groups).
At a similar time to the release of the new exercise guidelines, Church et al. published a randomized controlled trial that sought to address this uncertainty by comparing aerobic training, resistance training and a combination of both on glycemic control in adults with T2DM; importantly, in this trial, duration of weekly training was similar across groups (approximately 150 min per week).
The main finding of the study by Church and co-investigators was that significantly improved glycemic control was observed only in the combination group, which supports the guideline recommendation that optimal physical activity programs consist of regular aerobic activity combined with resistance training. Intriguingly, combination training did not alter lean body mass, whilst the resistance training alone led to nearly a 1.0 kg increase after 9 months.
This result suggests that finding the optimal balance of resistance training and aerobic training is an area that still deserves research attention to optimize not only glycemic control but also the beneficial effects of preserving or halting the decline in lean muscle mass.
Finally, are we really addressing the full extent of the problem that exists in modern society?
Even if a person with T2DM is doing the right thing and engaging in at least 2.5 h of moderate-intensity aerobic activity and at least 1.5 h of moderate-vigorous intensity resistance activity per week, what about the remaining 164 h in the week?
To further illustrate this point, let's take a hypothetical person with T2DM who engages in the recommended levels of physical activity, who rises from their bed at 0700 h and takes a 30 min brisk walk and performs 45 min of resistance exercise prior to breakfast.
This person then sits for 15 min to eat breakfast followed by a car trip to work that takes 45 min. The next 8 h of the day is spent sitting at the office desk or sitting to eat during the lunch break. At the end of the work day, the person travels in the car for another 45 min before sitting down at the dining table to consume the evening meal. The day concludes with the individual watching their favorite television shows for the next 4 h while seated on the sofa.
If this person achieves at least 2.5 h of brisk walking and at least 1.5 h of resistance exercise during the week, according the new guidelines, this person is meeting the minimum recommended amount of exercise.
Yet, for this individual, up to 92% of waking hours may be spent in sitting activities.
The new joint guidelines highlight the emerging importance of sedentary behaviors in determining metabolic risk.
In the past decade, numerous epidemiological studies have reported inverse associations between sedentary behaviors (for example, television viewing, computer and console use, workplace sitting and time spent in automobiles) and mortality and chronic disease risk, with many showing these associations to be independent of reported exercise.
As acknowledged in the joint guidelines, these new insights on sedentary behavior suggest that consideration should also be given to decreasing sitting time and prolonged periods of sedentary behavior.
Feasible steps to break up prolonged sitting with light-intensity activity include walking down the hall to speak to coworkers instead of e-mailing, extending walking distance during trips to the break room or bathroom, and standing or even pacing when on the phone.
Since recent data from NHANES 2003–2004, obtained by objective activity monitoring (accelerometer), indicate that sedentary behaviors account for 55% of an American's typical day, reducing sedentary time (namely, avoiding prolonged periods of sitting) may provide an important adjunct health message, alongside the well-established recommendation for regular participation in exercise.
David Dunstan
Abstract
New guidelines from the American College of Sports Medicine and the American Diabetes Association provide specific exercise advice for individuals with type 2 diabetes mellitus, while new research emphasizes the importance of getting people off the couch and moving more often throughout the day.
Introduction
"If we could give every individual the right amount of nourishment and exercise, not too little and not too much, we would have found the safest way to health." Hippocrates's profound view of the importance of regular exercise has been brought to the fore in a joint position statement released in December 2010 by the American College of Sports Medicine and the American Diabetes Association, which provides new guidelines on exercise for people with type 2 diabetes mellitus (T2DM).
In the eyes of some, this position statement may conjure thoughts that we already know: that physical activity is a cornerstone in the prevention and management of T2DM.
However, these guidelines provide patients with T2DM, and those who care for them, with a timely update on new evidence generated from numerous high-quality studies conducted over the past decade on what works for people with or at risk of developing T2DM.
The recommendations call for at least 150 min a week of aerobic exercise of at least moderate intensity—brisk walking is a moderate-intensity aerobic exercise that is appropriate for most people with T2DM.
This amount of exercise should be spread over at least 3 days during the week, with no more than two consecutive days between bouts of aerobic activity.
The recommendations also acknowledge that aerobic activity alone cannot deliver the full benefits of exercise to individuals with T2DM.
Numerous recent studies have shown that resistance exercise (strength training) is a highly effective type of exercise in diabetes management and is the only type of exercise that offers some protection against the loss of muscle mass (sarcopenia) and muscle strength and physical function that occurs with advancing age.
As such, the recommendations state that, in addition to the aerobic activity requirements, resistance exercise of at least moderate or vigorous intensity should be undertaken at least twice weekly on nonconsecutive days, but more ideally three times a week.
Although these new guidelines recommend both aerobic and resistance training, few studies have directly examined the effects of combined training in individuals with T2DM.
Combined training offers the capacity to achieve the unique health benefits of both types of exercise and has the potential to be more time efficient, as the benefits of aerobic and resistance exercise can be derived from the one session rather than two separate sessions.
This consideration is important, given that lack of time is one of the most frequently cited reasons for nonparticipation in regular exercise.
A large Canadian study published in 2007 was the first to report that combined training may be of greater benefit for glycemic control than either aerobic or resistance exercise alone in patients with T2DM.
However, the additional benefit observed might have been due to the extra exercise time in the combination group (approximately double that in the single-exercise groups).
At a similar time to the release of the new exercise guidelines, Church et al. published a randomized controlled trial that sought to address this uncertainty by comparing aerobic training, resistance training and a combination of both on glycemic control in adults with T2DM; importantly, in this trial, duration of weekly training was similar across groups (approximately 150 min per week).
The main finding of the study by Church and co-investigators was that significantly improved glycemic control was observed only in the combination group, which supports the guideline recommendation that optimal physical activity programs consist of regular aerobic activity combined with resistance training. Intriguingly, combination training did not alter lean body mass, whilst the resistance training alone led to nearly a 1.0 kg increase after 9 months.
This result suggests that finding the optimal balance of resistance training and aerobic training is an area that still deserves research attention to optimize not only glycemic control but also the beneficial effects of preserving or halting the decline in lean muscle mass.
Finally, are we really addressing the full extent of the problem that exists in modern society?
Even if a person with T2DM is doing the right thing and engaging in at least 2.5 h of moderate-intensity aerobic activity and at least 1.5 h of moderate-vigorous intensity resistance activity per week, what about the remaining 164 h in the week?
To further illustrate this point, let's take a hypothetical person with T2DM who engages in the recommended levels of physical activity, who rises from their bed at 0700 h and takes a 30 min brisk walk and performs 45 min of resistance exercise prior to breakfast.
This person then sits for 15 min to eat breakfast followed by a car trip to work that takes 45 min. The next 8 h of the day is spent sitting at the office desk or sitting to eat during the lunch break. At the end of the work day, the person travels in the car for another 45 min before sitting down at the dining table to consume the evening meal. The day concludes with the individual watching their favorite television shows for the next 4 h while seated on the sofa.
If this person achieves at least 2.5 h of brisk walking and at least 1.5 h of resistance exercise during the week, according the new guidelines, this person is meeting the minimum recommended amount of exercise.
Yet, for this individual, up to 92% of waking hours may be spent in sitting activities.
The new joint guidelines highlight the emerging importance of sedentary behaviors in determining metabolic risk.
In the past decade, numerous epidemiological studies have reported inverse associations between sedentary behaviors (for example, television viewing, computer and console use, workplace sitting and time spent in automobiles) and mortality and chronic disease risk, with many showing these associations to be independent of reported exercise.
As acknowledged in the joint guidelines, these new insights on sedentary behavior suggest that consideration should also be given to decreasing sitting time and prolonged periods of sedentary behavior.
Feasible steps to break up prolonged sitting with light-intensity activity include walking down the hall to speak to coworkers instead of e-mailing, extending walking distance during trips to the break room or bathroom, and standing or even pacing when on the phone.
Since recent data from NHANES 2003–2004, obtained by objective activity monitoring (accelerometer), indicate that sedentary behaviors account for 55% of an American's typical day, reducing sedentary time (namely, avoiding prolonged periods of sitting) may provide an important adjunct health message, alongside the well-established recommendation for regular participation in exercise.
What the New Food Allergy Guidelines Offer to Clinicians
From Medscape Allergy & Clinical Immunology
Expert Interview at AAAAI 2011
Matthew J. Fenton, PhD; Hugh A. Sampson, MD
Editor's Note:
Although the exact prevalence of food allergy in the United States is not known, it is estimated that 10-12 million Americans are affected. To address this growing public health problem, the National Institute of Allergy and Infectious Diseases (NIAID) in conjunction with professional organizations including the American Academy of Allergy, Asthma & Immunology (AAAAI), federal agencies, and patient advocacy groups worked together to develop clinical guidelines for healthcare professionals on the diagnosis and management of food allergy.
The Guidelines for the Diagnosis and Management of Food Allergy in the United States were released in December 2010.
At the AAAAI 2011 meeting, Medscape taped this discussion between Matthew J. Fenton, PhD, from NIAID, and Hugh A. Sampson, MD, past president of AAAAI, both of whom were involved in the guideline development process.
Dr. Fenton: Hello. My name is Dr. Matthew Fenton. I'm Chief of the Asthma, Allergy, and Inflammation Branch at NIAID. I led the Institute's effort to create clinical guidelines for the diagnosis and management of food allergy.
Here with me today is my colleague Dr. Hugh Sampson, Professor of Pediatrics and Dean for Translational Biomedical Sciences at the Mount Sinai School of Medicine in New York City where he serves as the Director of the Jaffe Food Allergy Institute. Dr. Sampson is past president of AAAAI. Dr. Sampson made the food allergy guidelines one of his presidential initiatives, and he chaired an expert panel writing group and served on the guidelines coordinating committee.
The food allergy guidelines were released in December 2010; with their release how should they now guide clinical practice? That's the topic we're going to discuss today for Medscape Allergy & Clinical Immunology.
Although the exact prevalence of food allergy in the United States is not known, it's estimated that 10-12 million Americans are affected.
A number of different diseases with similar symptoms are shared with food allergy, so there is a real potential for over diagnosis of food allergy.
Current increases in the prevalence of food allergy match the increases in prevalence that we see with other allergic diseases such as asthma. Hugh?
Dr. Sampson: Yes. Many food allergies are also outgrown as children get older. Several food allergies such as milk, eggs, wheat, and soy are outgrown in about 80% of the cases, whereas allergies to other foods such as peanuts, tree nuts, fish, and shellfish are typically not outgrown. Only about 20% of children will outgrow allergies to these foods.
Of interest, when individuals develop food allergy as adults those allergies also tend to be very persistent.
Dr. Fenton: Sensitization to food is not the same thing as clinical food allergy. That's a key point that the guidelines bring up.
In the case of allergic sensitization, an individual who is sensitized may not go on to proceed to clinical disease.
In the case of people with multiple allergen sensitivities, only one of those allergens may be responsible for the symptoms of food allergy, and that's one of the challenges in diagnosis -- to identify the particular allergen in multisensitized patients.
The guidelines provide a consensus definition for food allergy: one of the major goals of the initiative. They also provide best clinical practice recommendations. The key here is to provide recommendations for healthcare professionals across a variety of specialties ranging from allergists to dermatologists and pulmonologists all the way to family practice specialists and rural healthcare providers.
Dr. Sampson: Right. The guidelines were created by a variety of experts, so we really have good opinions from all the different areas.
With respect to how to diagnose food allergy, all of the appropriate methods were carefully reviewed.
History and physical exam are believed to be very good for helping direct the evaluation of food allergy, but history alone is not adequate to make the diagnosis.
Many allergists will do tests such as the skin prick, which is very good for helping identify potential foods that could be causing the problem, but by themselves these tests are not adequate.
There are also in vitro tests such as serum IgE [immunoglobulinE] levels to different foods.
Those can be also quite useful in identifying potential sources of the allergy, but by themselves are really not adequate to make the diagnosis.
The writing panel believed that the elimination diet was potentially useful for helping make the diagnosis, especially with some of the non-IgE-mediated type of allergies, but the only direct way to make the diagnosis is with the oral food challenge.
The committee believed that the double-blind, placebo-controlled food challenge is the gold standard for making such a diagnosis.
However, they also believed that the open food challenge or the single-blind challenge could be diagnostic if the challenge was negative or if the symptoms that were provoked by the challenge looked the same as what was described in the history and were supported by laboratory studies.
The writing group also looked at a number of other tests that are potentially used such as IgG levels, IgG4 levels to foods, and several others and believed that no other tests were really of value.
The group also looked at recommendations for proper treatment of food allergies, and that starts with the appropriate diagnosis.
Once the specific food allergy is diagnosed, then avoidance diets are recommended. At this point in time, avoidance is the only effective way to treat a food allergy. There has been a lot of excitement about oral immunotherapy and sublingual immunotherapy, but at this point in time it was believed that that information is inadequate to support these measures as forms of therapy going forward.
They also reviewed potential medications that people might use to try to prevent food allergic reactions and basically came to the conclusion that no medications can be used to prevent either the IgE-mediated or the non-IgE-mediated food allergy.
Finally, they believed that in children it was really necessary to have nutritional evaluations done on a periodic basis as well as weight checks, especially in children who are on very restrictive diets.
Going forward, because many food allergies are outgrown (depending on the food) these children should be re-evaluated on a regular basis.
Recommendations were made about trying to prevent food allergy, and there has been a lot of discussion about whether we can actually prevent it.
The guidelines assert that there is no reason for mothers to be eliminating foods either during pregnancy or during breast-feeding in an attempt to prevent food allergy. The information out there just does not support that as a potential way to prevent allergy.
The committee does recommend breast-feeding for the first 4-6 months of life, but the literature doesn't suggest any reason to avoid any particular foods -- even allergenic foods -- beyond that 4- to 6-month period.
Some people have also tried to avoid allergy by avoiding cross-reacting foods.
For example, somebody who is allergic to milk may have a positive skin test for something like beef, but it's very unlikely that beef would also be a cause of food allergy. The idea of trying to avoid foods by association was not recommended.
Several recommendations were made about treatment of anaphylaxis.
The main thing was that children or adults with food allergies should be cared for by physicians who are familiar with anaphylactic reactions, types of symptoms, and timing; and that rapid treatment was necessary and the use of intramuscular epinephrine was really the treatment of choice.
If the individual has a reaction, it's recommended that the patient be observed for about 4-6 hours afterward because a biphasic reaction can occur even after the patient looks to be well along the way to recovery.
It was believed to be very important to educate patients about recognizing early signs of anaphylaxis, how to avoid the offending foods, and prior to discharge making sure that they have a prescription for some form of injectable epinephrine as well as a follow-up appointment with their physician to get an appropriate evaluation of their food allergies.
Dr. Fenton: The recommendations in the guidelines are evidence based, but the expert clinical opinion by the writing groups was key in making the final wording of the recommendation especially in cases in which the evidence was weak. In preparing the evidence report, more than 12,000 papers were evaluated for inclusion in the evidence report. Each guideline describes the strength of the evidence that was used in making the guideline recommendation in addition to the contribution that was made by expert clinical opinion.
Each chapter of the guidelines concluded with a section on knowledge gaps. That points out future directions for research efforts on the basis of the paucity of knowledge in these particular areas. As the major funding agency for food allergy research in the United States, these knowledge gaps will guide the NIAID in developing new research funding opportunities.
Dr. Sampson: The guidelines don't present radically new information, but they do evaluate, in a very thorough fashion, all the literature that is out there and come up with recommendations as well as point out some common mistakes that are made by physicians.
For example, one thing that was stressed in the section on therapeutics was the tendency to use antihistamines first in treatment of an anaphylactic reaction, and so the guidelines stress that epinephrine given intramuscularly is the treatment of choice for anaphylaxis.
Also, many physicians have a tendency to take the results of skin tests or serum IgE levels and then tell patients that they are allergic to that particular food. As you pointed out when we first started talking, these tests tell us that the patient is sensitized but do not necessarily tell us that the patient is going to have clinical symptoms.
The guidelines also stress the issue of mothers trying to avoid particular allergens while they're pregnant or breast-feeding. As pointed out by the American Academy of Pediatrics guidelines about a year ago, the evidence is insufficient to support that approach as a way to try to prevent their offspring from having particular food allergies.
Dr. Fenton: In addition to the guidelines, the NIAID created multiple resources for healthcare professionals, patients, and families. These resources include a summary version of the guidelines that highlight the guidelines but don't go into all of the details behind the rationale that supports those guidelines.
Also, we've just generated a patient- and family-friendly synopsis of the guidelines that patients and their families can use to educate themselves prior to visiting the physician, and help them better understand how the physician will go about treating and managing the disease.
These resources are freely and publicly available from the NIAID Website.
Expert Interview at AAAAI 2011
Matthew J. Fenton, PhD; Hugh A. Sampson, MD
Editor's Note:
Although the exact prevalence of food allergy in the United States is not known, it is estimated that 10-12 million Americans are affected. To address this growing public health problem, the National Institute of Allergy and Infectious Diseases (NIAID) in conjunction with professional organizations including the American Academy of Allergy, Asthma & Immunology (AAAAI), federal agencies, and patient advocacy groups worked together to develop clinical guidelines for healthcare professionals on the diagnosis and management of food allergy.
The Guidelines for the Diagnosis and Management of Food Allergy in the United States were released in December 2010.
At the AAAAI 2011 meeting, Medscape taped this discussion between Matthew J. Fenton, PhD, from NIAID, and Hugh A. Sampson, MD, past president of AAAAI, both of whom were involved in the guideline development process.
Dr. Fenton: Hello. My name is Dr. Matthew Fenton. I'm Chief of the Asthma, Allergy, and Inflammation Branch at NIAID. I led the Institute's effort to create clinical guidelines for the diagnosis and management of food allergy.
Here with me today is my colleague Dr. Hugh Sampson, Professor of Pediatrics and Dean for Translational Biomedical Sciences at the Mount Sinai School of Medicine in New York City where he serves as the Director of the Jaffe Food Allergy Institute. Dr. Sampson is past president of AAAAI. Dr. Sampson made the food allergy guidelines one of his presidential initiatives, and he chaired an expert panel writing group and served on the guidelines coordinating committee.
The food allergy guidelines were released in December 2010; with their release how should they now guide clinical practice? That's the topic we're going to discuss today for Medscape Allergy & Clinical Immunology.
Although the exact prevalence of food allergy in the United States is not known, it's estimated that 10-12 million Americans are affected.
A number of different diseases with similar symptoms are shared with food allergy, so there is a real potential for over diagnosis of food allergy.
Current increases in the prevalence of food allergy match the increases in prevalence that we see with other allergic diseases such as asthma. Hugh?
Dr. Sampson: Yes. Many food allergies are also outgrown as children get older. Several food allergies such as milk, eggs, wheat, and soy are outgrown in about 80% of the cases, whereas allergies to other foods such as peanuts, tree nuts, fish, and shellfish are typically not outgrown. Only about 20% of children will outgrow allergies to these foods.
Of interest, when individuals develop food allergy as adults those allergies also tend to be very persistent.
Dr. Fenton: Sensitization to food is not the same thing as clinical food allergy. That's a key point that the guidelines bring up.
In the case of allergic sensitization, an individual who is sensitized may not go on to proceed to clinical disease.
In the case of people with multiple allergen sensitivities, only one of those allergens may be responsible for the symptoms of food allergy, and that's one of the challenges in diagnosis -- to identify the particular allergen in multisensitized patients.
The guidelines provide a consensus definition for food allergy: one of the major goals of the initiative. They also provide best clinical practice recommendations. The key here is to provide recommendations for healthcare professionals across a variety of specialties ranging from allergists to dermatologists and pulmonologists all the way to family practice specialists and rural healthcare providers.
Dr. Sampson: Right. The guidelines were created by a variety of experts, so we really have good opinions from all the different areas.
With respect to how to diagnose food allergy, all of the appropriate methods were carefully reviewed.
History and physical exam are believed to be very good for helping direct the evaluation of food allergy, but history alone is not adequate to make the diagnosis.
Many allergists will do tests such as the skin prick, which is very good for helping identify potential foods that could be causing the problem, but by themselves these tests are not adequate.
There are also in vitro tests such as serum IgE [immunoglobulinE] levels to different foods.
Those can be also quite useful in identifying potential sources of the allergy, but by themselves are really not adequate to make the diagnosis.
The writing panel believed that the elimination diet was potentially useful for helping make the diagnosis, especially with some of the non-IgE-mediated type of allergies, but the only direct way to make the diagnosis is with the oral food challenge.
The committee believed that the double-blind, placebo-controlled food challenge is the gold standard for making such a diagnosis.
However, they also believed that the open food challenge or the single-blind challenge could be diagnostic if the challenge was negative or if the symptoms that were provoked by the challenge looked the same as what was described in the history and were supported by laboratory studies.
The writing group also looked at a number of other tests that are potentially used such as IgG levels, IgG4 levels to foods, and several others and believed that no other tests were really of value.
The group also looked at recommendations for proper treatment of food allergies, and that starts with the appropriate diagnosis.
Once the specific food allergy is diagnosed, then avoidance diets are recommended. At this point in time, avoidance is the only effective way to treat a food allergy. There has been a lot of excitement about oral immunotherapy and sublingual immunotherapy, but at this point in time it was believed that that information is inadequate to support these measures as forms of therapy going forward.
They also reviewed potential medications that people might use to try to prevent food allergic reactions and basically came to the conclusion that no medications can be used to prevent either the IgE-mediated or the non-IgE-mediated food allergy.
Finally, they believed that in children it was really necessary to have nutritional evaluations done on a periodic basis as well as weight checks, especially in children who are on very restrictive diets.
Going forward, because many food allergies are outgrown (depending on the food) these children should be re-evaluated on a regular basis.
Recommendations were made about trying to prevent food allergy, and there has been a lot of discussion about whether we can actually prevent it.
The guidelines assert that there is no reason for mothers to be eliminating foods either during pregnancy or during breast-feeding in an attempt to prevent food allergy. The information out there just does not support that as a potential way to prevent allergy.
The committee does recommend breast-feeding for the first 4-6 months of life, but the literature doesn't suggest any reason to avoid any particular foods -- even allergenic foods -- beyond that 4- to 6-month period.
Some people have also tried to avoid allergy by avoiding cross-reacting foods.
For example, somebody who is allergic to milk may have a positive skin test for something like beef, but it's very unlikely that beef would also be a cause of food allergy. The idea of trying to avoid foods by association was not recommended.
Several recommendations were made about treatment of anaphylaxis.
The main thing was that children or adults with food allergies should be cared for by physicians who are familiar with anaphylactic reactions, types of symptoms, and timing; and that rapid treatment was necessary and the use of intramuscular epinephrine was really the treatment of choice.
If the individual has a reaction, it's recommended that the patient be observed for about 4-6 hours afterward because a biphasic reaction can occur even after the patient looks to be well along the way to recovery.
It was believed to be very important to educate patients about recognizing early signs of anaphylaxis, how to avoid the offending foods, and prior to discharge making sure that they have a prescription for some form of injectable epinephrine as well as a follow-up appointment with their physician to get an appropriate evaluation of their food allergies.
Dr. Fenton: The recommendations in the guidelines are evidence based, but the expert clinical opinion by the writing groups was key in making the final wording of the recommendation especially in cases in which the evidence was weak. In preparing the evidence report, more than 12,000 papers were evaluated for inclusion in the evidence report. Each guideline describes the strength of the evidence that was used in making the guideline recommendation in addition to the contribution that was made by expert clinical opinion.
Each chapter of the guidelines concluded with a section on knowledge gaps. That points out future directions for research efforts on the basis of the paucity of knowledge in these particular areas. As the major funding agency for food allergy research in the United States, these knowledge gaps will guide the NIAID in developing new research funding opportunities.
Dr. Sampson: The guidelines don't present radically new information, but they do evaluate, in a very thorough fashion, all the literature that is out there and come up with recommendations as well as point out some common mistakes that are made by physicians.
For example, one thing that was stressed in the section on therapeutics was the tendency to use antihistamines first in treatment of an anaphylactic reaction, and so the guidelines stress that epinephrine given intramuscularly is the treatment of choice for anaphylaxis.
Also, many physicians have a tendency to take the results of skin tests or serum IgE levels and then tell patients that they are allergic to that particular food. As you pointed out when we first started talking, these tests tell us that the patient is sensitized but do not necessarily tell us that the patient is going to have clinical symptoms.
The guidelines also stress the issue of mothers trying to avoid particular allergens while they're pregnant or breast-feeding. As pointed out by the American Academy of Pediatrics guidelines about a year ago, the evidence is insufficient to support that approach as a way to try to prevent their offspring from having particular food allergies.
Dr. Fenton: In addition to the guidelines, the NIAID created multiple resources for healthcare professionals, patients, and families. These resources include a summary version of the guidelines that highlight the guidelines but don't go into all of the details behind the rationale that supports those guidelines.
Also, we've just generated a patient- and family-friendly synopsis of the guidelines that patients and their families can use to educate themselves prior to visiting the physician, and help them better understand how the physician will go about treating and managing the disease.
These resources are freely and publicly available from the NIAID Website.
Monday, April 4, 2011
More Data on Diabetes Risk With Statins
From Heartwire
Sue Hughes
March 31, 2011 (San Francisco) —
A new analysis of three major trials with atorvastatin (Lipitor, Pfizer) has suggested that the risk of new-onset diabetes with statins appears to be dose dependent and related to the strength of cholesterol lowering achieved with the statin--ie, the more powerful the statin, the higher the risk of diabetes.
But the authors, as well as other experts, stress that the benefits of statin treatment still clearly outweigh the risks in patients with coronary or cerebrovascular disease.
This latest analysis, published in the April 5, 2011 issue of the Journal of the American College of Cardiology, was conducted by a team led by Dr David Waters (San Francisco General Hospital, CA).
He explained to heartwire that last year's meta-analysis of statin studies showed a small increase (HR 1.09) in new-onset diabetes in patients taking statins vs those on placebo. But other clinical predictors were not examined, and only one of the 13 trials in this analysis involved atorvastatin, compared with six with pravastatin and three with rosuvastatin (Crestor, AstraZeneca).
Waters et al wanted to look at the risk of diabetes specifically with atorvastatin, and they did this with data from three large studies–-TNT (comparing 80 mg and 10 mg/day of atorvastatin in patients with stable coronary disease), IDEAL (atorvastatin 80 mg vs simvastatin 20 mg/day in post-MI patients) and SPARCL (atorvastatin 80 mg/day vs placebo in patients with a recent stroke or transient ischemic attack).
Results showed that atorvastatin 80 mg was associated with an increased risk of new-onset diabetes compared with placebo in the SPARCL study, and in the other two trials atorvastatin 80 mg was associated with a trend toward more diabetes than lower doses of either atorvastatin or simvastatin.
Frequency of New Onset Diabetes (%) in SPARCL, TNT, and IDEAL
Trial Atorvastatin 80 mg Control HR (95% CI) P
SPARCL 8.71 6.06 1.37 (1.08–1.75) 0.011
TNT 9.24 8.11 1.10 (0.94–1.29) 0.226
IDEAL 6.40 5.59 1.19 (0.98–1.43) 0.072
Waters commented: "We verified what was seen in the Lancet meta-analysis. We found a small increase in risk of developing diabetes with atorvastatin vs placebo, and a trend toward a greater effect with higher doses or more powerful statins."
But he noted that they could also predict which patients would develop diabetes from traditional risk factors--fasting blood sugar, body-mass index, hypertension, and elevated triglycerides.
"If patients had all four of these risk factors, they had a 25% risk of developing diabetes. If they had none of these risks factors, their risk was just 2%. That is not surprising, as we know these factors predict new onset diabetes."
"Not a Big Deal"
Waters told heartwire : "The biggest point I want to emphasize about this study is that patients should not stop taking statins because they are afraid of developing diabetes. I do not think this is a big deal.
If they have a history of heart disease or stroke, statins will reduce their risk of a new event by a huge amount. Compared with their risk of a cardiovascular event, their risk of developing diabetes is paltry."
He continued: "I would advise patents to keep taking their statins and do other things to lower their risk of diabetes--lose weight, control blood pressure, and exercise.
The risk of diabetes with these drugs is quite low--lower than with beta blockers, diuretics, niacin, and steroids."
In the paper, Waters et al note that the authors of the recent meta-analysis calculated that treating 255 patients with a statin for four years would induce one case of new-onset diabetes but would prevent 5.4 coronary deaths or MIs for each mmol/L reduction in LDL cholesterol.
"This benefit would be greater if strokes and coronary revascularizations were included. The benefits of statin treatment thus far outweigh the risks, particularly because it is uncertain as to whether new-onset diabetes itself increases risk," they write.
"This Will Not Alter My Use of Statins"
Commenting on the study for heartwire , Dr Roger Blumenthal (Johns Hopkins Medical Institute, Baltimore, MD) was not overly concerned about these latest results.
"The important point to emphasize is that the event rate in persons with new-onset diabetes on atorvastatin was considerably less than those patients who had diabetes at the start of the trial and was essentially no different from those who did not develop diabetes during the trial.
Similarly, those subjects in ALLHAT who developed diabetes on a thiazide did not experience a higher CVD event rate," he said. "I emphasize to patients that the benefits of statins far outweigh their risks. If patients do a better job at increasing their exercise and improving their exercise habits, their glucose levels likely will improve. This will not alter my use of statins," Blumenthal added.
Metabolic-Syndrome Patients Need Aggressive Statin Treatment
Dr William Boden (University at Buffalo Schools of Medicine and Public Health) also said he would not read too much into this study. "At most, there is an association--not causality--of high-dose atorvastatin and new-incident type 2 diabetes. To me, what really comes across is that the substrate for developing new-onset diabetes is the existence of metabolic syndrome."
Boden further pointed out that the NCEP ATP III guidelines advocate aggressive treatment with statins in patients with metabolic syndrome. "We usually seek to achieve the optional, more aggressive LDL target of <70 mg/dL in these patients. Thus, one would expect that more patients with metabolic syndrome would be treated with high-dose atorvastatin to achieve this more stringent LDL target. So, then, it shouldn't be surprising that there is an association between high-dose atorvastatin and the development of diabetes in these patients--because they are at much higher risk for developing diabetes in the first place."
He added: "All this means to me is that one needs to be vigilant for observing whether patients with metabolic syndrome go on to develop type 2 diabetes. Given the robust findings across multiple primary- and secondary-prevention trials of statins showing that these agents decrease death, MI, stroke, and vascular disease, I would strongly argue the net clinical benefit of statins in such patients far, far outweighs the <10% risk of developing diabetes, and such patients are even more compelling candidates for aggressive risk-factor control and intervention with aggressive statin therapy."
Sue Hughes
March 31, 2011 (San Francisco) —
A new analysis of three major trials with atorvastatin (Lipitor, Pfizer) has suggested that the risk of new-onset diabetes with statins appears to be dose dependent and related to the strength of cholesterol lowering achieved with the statin--ie, the more powerful the statin, the higher the risk of diabetes.
But the authors, as well as other experts, stress that the benefits of statin treatment still clearly outweigh the risks in patients with coronary or cerebrovascular disease.
This latest analysis, published in the April 5, 2011 issue of the Journal of the American College of Cardiology, was conducted by a team led by Dr David Waters (San Francisco General Hospital, CA).
He explained to heartwire that last year's meta-analysis of statin studies showed a small increase (HR 1.09) in new-onset diabetes in patients taking statins vs those on placebo. But other clinical predictors were not examined, and only one of the 13 trials in this analysis involved atorvastatin, compared with six with pravastatin and three with rosuvastatin (Crestor, AstraZeneca).
Waters et al wanted to look at the risk of diabetes specifically with atorvastatin, and they did this with data from three large studies–-TNT (comparing 80 mg and 10 mg/day of atorvastatin in patients with stable coronary disease), IDEAL (atorvastatin 80 mg vs simvastatin 20 mg/day in post-MI patients) and SPARCL (atorvastatin 80 mg/day vs placebo in patients with a recent stroke or transient ischemic attack).
Results showed that atorvastatin 80 mg was associated with an increased risk of new-onset diabetes compared with placebo in the SPARCL study, and in the other two trials atorvastatin 80 mg was associated with a trend toward more diabetes than lower doses of either atorvastatin or simvastatin.
Frequency of New Onset Diabetes (%) in SPARCL, TNT, and IDEAL
Trial Atorvastatin 80 mg Control HR (95% CI) P
SPARCL 8.71 6.06 1.37 (1.08–1.75) 0.011
TNT 9.24 8.11 1.10 (0.94–1.29) 0.226
IDEAL 6.40 5.59 1.19 (0.98–1.43) 0.072
Waters commented: "We verified what was seen in the Lancet meta-analysis. We found a small increase in risk of developing diabetes with atorvastatin vs placebo, and a trend toward a greater effect with higher doses or more powerful statins."
But he noted that they could also predict which patients would develop diabetes from traditional risk factors--fasting blood sugar, body-mass index, hypertension, and elevated triglycerides.
"If patients had all four of these risk factors, they had a 25% risk of developing diabetes. If they had none of these risks factors, their risk was just 2%. That is not surprising, as we know these factors predict new onset diabetes."
"Not a Big Deal"
Waters told heartwire : "The biggest point I want to emphasize about this study is that patients should not stop taking statins because they are afraid of developing diabetes. I do not think this is a big deal.
If they have a history of heart disease or stroke, statins will reduce their risk of a new event by a huge amount. Compared with their risk of a cardiovascular event, their risk of developing diabetes is paltry."
He continued: "I would advise patents to keep taking their statins and do other things to lower their risk of diabetes--lose weight, control blood pressure, and exercise.
The risk of diabetes with these drugs is quite low--lower than with beta blockers, diuretics, niacin, and steroids."
In the paper, Waters et al note that the authors of the recent meta-analysis calculated that treating 255 patients with a statin for four years would induce one case of new-onset diabetes but would prevent 5.4 coronary deaths or MIs for each mmol/L reduction in LDL cholesterol.
"This benefit would be greater if strokes and coronary revascularizations were included. The benefits of statin treatment thus far outweigh the risks, particularly because it is uncertain as to whether new-onset diabetes itself increases risk," they write.
"This Will Not Alter My Use of Statins"
Commenting on the study for heartwire , Dr Roger Blumenthal (Johns Hopkins Medical Institute, Baltimore, MD) was not overly concerned about these latest results.
"The important point to emphasize is that the event rate in persons with new-onset diabetes on atorvastatin was considerably less than those patients who had diabetes at the start of the trial and was essentially no different from those who did not develop diabetes during the trial.
Similarly, those subjects in ALLHAT who developed diabetes on a thiazide did not experience a higher CVD event rate," he said. "I emphasize to patients that the benefits of statins far outweigh their risks. If patients do a better job at increasing their exercise and improving their exercise habits, their glucose levels likely will improve. This will not alter my use of statins," Blumenthal added.
Metabolic-Syndrome Patients Need Aggressive Statin Treatment
Dr William Boden (University at Buffalo Schools of Medicine and Public Health) also said he would not read too much into this study. "At most, there is an association--not causality--of high-dose atorvastatin and new-incident type 2 diabetes. To me, what really comes across is that the substrate for developing new-onset diabetes is the existence of metabolic syndrome."
Boden further pointed out that the NCEP ATP III guidelines advocate aggressive treatment with statins in patients with metabolic syndrome. "We usually seek to achieve the optional, more aggressive LDL target of <70 mg/dL in these patients. Thus, one would expect that more patients with metabolic syndrome would be treated with high-dose atorvastatin to achieve this more stringent LDL target. So, then, it shouldn't be surprising that there is an association between high-dose atorvastatin and the development of diabetes in these patients--because they are at much higher risk for developing diabetes in the first place."
He added: "All this means to me is that one needs to be vigilant for observing whether patients with metabolic syndrome go on to develop type 2 diabetes. Given the robust findings across multiple primary- and secondary-prevention trials of statins showing that these agents decrease death, MI, stroke, and vascular disease, I would strongly argue the net clinical benefit of statins in such patients far, far outweighs the <10% risk of developing diabetes, and such patients are even more compelling candidates for aggressive risk-factor control and intervention with aggressive statin therapy."
New Doubts on Value of Prostate Cancer Screening
From WebMD Health News
Salynn Boyles
April 1, 2011 — A study from Sweden raises new questions about the value of screening average-risk men for prostate cancer.
In the study, screening did not significantly reduce prostate cancer deaths over two decades of follow-up, but it did result in the detection of more cases of the cancer and more treatment.
The study is not as large as several other recent trials suggesting that routine screening leads to the over-detection and overtreatment of prostate cancer, but it is the longest.
Starting in 1987, some study participants received routine screening for prostate cancer while others did not. Twenty years later, the two groups had similar prostate cancer death rates.
“We found no survival advantage for screening, but this may have been influenced by the fact that the screening test we used when the trial started is not as sensitive as the tests we use today,” study researcher Gabriel Sandblom, MD, of Stockholm’s Karolinska Institute, tells WebMD.
PSA Screening Debate
The men in the screening study group did not receive prostate specific antigen (PSA) blood testing until their third or fourth screenings.
PSA is now the screening method of choice, but it remains controversial.
The American Cancer Society stopped recommending routine PSA screening more than a decade ago. Last year the group came out even more strongly against routine testing, stating that men should not be screened without first discussing the risks and limitations of screening with their doctors.
Two major studies published in 2009, one from the U.S. and another from Europe, added to the concerns about the PSA screening.
The U.S. trial, supported by the National Cancer Institute, failed to show a reduction in prostate cancer deaths associated with PSA screening over an average of seven years of follow-up.
The European study showed a modest reduction in prostate cancer deaths associated with screening, but the researchers concluded that an estimated 1,400 men would have to be screened and 48 men would have to be treated to prevent one death from prostate cancer.
A separate analysis involving Swedish participants in the European trial lowered that number to 293 men screened and 12 men treated to prevent one death.
“The 48 number is probably an overestimate and it is not clear if the 12 is an underestimate,” ACS Director of Prostate and Colorectal Cancers Durado Brooks, MD, MPH, tells WebMD. “What we can say is that there is significant over-diagnosis and overtreatment associated with screening.”
Prostate cancer is most often treated with surgery and radiation, which can result in erectile dysfunction and bladder and bowel incontinence.
Screening for Prostate Cancer
The newly published study included close to 1,500 Swedish men randomly selected for prostate cancer screening every three years from 1987 to 1999 and about 7,500 men who were not screened.
Digital rectal examinations were the only screening method used until 1993, when PSA testing was added to the screening protocol.
Between January 1987 and the end of 1999, 85 screened study participants (5.7%) and 292 men who were not screened (3.9%) received a diagnosis of prostate cancer.
The tumors detected in the screening group tended to be smaller and more localized than those found in the men who were not screened.
But the death rate did not differ significantly between the two groups.
Sandblom says PSA testing is beneficial for men with symptoms suggestive of prostate cancer or men with a high risk for the disease due to family history.
He agrees that the test is not appropriate for other men unless they fully understand the benefits and limitations of screening.
Because some men in the study did not have a PSA test at all and none had more than two tests, Brooks says the study adds little to the PSA debate.
“We know from other studies that PSA is far from a perfect tool,” he says. “While it has certainly had some value for some men, questions remain about its long-term impact on whether or not men die from prostate cancer.”
Salynn Boyles
April 1, 2011 — A study from Sweden raises new questions about the value of screening average-risk men for prostate cancer.
In the study, screening did not significantly reduce prostate cancer deaths over two decades of follow-up, but it did result in the detection of more cases of the cancer and more treatment.
The study is not as large as several other recent trials suggesting that routine screening leads to the over-detection and overtreatment of prostate cancer, but it is the longest.
Starting in 1987, some study participants received routine screening for prostate cancer while others did not. Twenty years later, the two groups had similar prostate cancer death rates.
“We found no survival advantage for screening, but this may have been influenced by the fact that the screening test we used when the trial started is not as sensitive as the tests we use today,” study researcher Gabriel Sandblom, MD, of Stockholm’s Karolinska Institute, tells WebMD.
PSA Screening Debate
The men in the screening study group did not receive prostate specific antigen (PSA) blood testing until their third or fourth screenings.
PSA is now the screening method of choice, but it remains controversial.
The American Cancer Society stopped recommending routine PSA screening more than a decade ago. Last year the group came out even more strongly against routine testing, stating that men should not be screened without first discussing the risks and limitations of screening with their doctors.
Two major studies published in 2009, one from the U.S. and another from Europe, added to the concerns about the PSA screening.
The U.S. trial, supported by the National Cancer Institute, failed to show a reduction in prostate cancer deaths associated with PSA screening over an average of seven years of follow-up.
The European study showed a modest reduction in prostate cancer deaths associated with screening, but the researchers concluded that an estimated 1,400 men would have to be screened and 48 men would have to be treated to prevent one death from prostate cancer.
A separate analysis involving Swedish participants in the European trial lowered that number to 293 men screened and 12 men treated to prevent one death.
“The 48 number is probably an overestimate and it is not clear if the 12 is an underestimate,” ACS Director of Prostate and Colorectal Cancers Durado Brooks, MD, MPH, tells WebMD. “What we can say is that there is significant over-diagnosis and overtreatment associated with screening.”
Prostate cancer is most often treated with surgery and radiation, which can result in erectile dysfunction and bladder and bowel incontinence.
Screening for Prostate Cancer
The newly published study included close to 1,500 Swedish men randomly selected for prostate cancer screening every three years from 1987 to 1999 and about 7,500 men who were not screened.
Digital rectal examinations were the only screening method used until 1993, when PSA testing was added to the screening protocol.
Between January 1987 and the end of 1999, 85 screened study participants (5.7%) and 292 men who were not screened (3.9%) received a diagnosis of prostate cancer.
The tumors detected in the screening group tended to be smaller and more localized than those found in the men who were not screened.
But the death rate did not differ significantly between the two groups.
Sandblom says PSA testing is beneficial for men with symptoms suggestive of prostate cancer or men with a high risk for the disease due to family history.
He agrees that the test is not appropriate for other men unless they fully understand the benefits and limitations of screening.
Because some men in the study did not have a PSA test at all and none had more than two tests, Brooks says the study adds little to the PSA debate.
“We know from other studies that PSA is far from a perfect tool,” he says. “While it has certainly had some value for some men, questions remain about its long-term impact on whether or not men die from prostate cancer.”
Depression Independent Risk Factor for Pain With Knee Arthritis
From Medscape Education Clinical Briefs
News Author: Norra MacReady
CME Author: Désirée Lie, MD, MSEd
March 25, 2011 — Coexisting depression is an independent predictor of pain among people with radiographic evidence of mild to moderate osteoarthritis of the knee, researchers in South Korea have found.
"The contribution of comorbid depression to knee osteoarthritis symptoms [KOAS] is almost equal to that of radiographic severity," senior author Tae Kyun Kim, MD, told Medscape Medical News.
"As this finding is particularly important for mild to moderate knee osteoarthritis, due consideration for the presence of depression should be given to patients who suffer irrationally severe or persistent symptoms from mild to moderate knee osteoarthritis."
Dr. Kim and his colleagues at Seoul National University Bundang Hospital in Seongnam, South Korea, decided to conduct their study after observing that elderly people with knee arthritis show a substantial disparity between radiographic findings and reported pain levels.
This suggests that "the perception of pain in arthritis is influenced by factors other than the degree of osteoarthritic joint damage," they explain in an article published online March 16 and in the March issue of the Journal of Bone and Joint Surgery. Because depression is common in elderly people, the researchers suspected it might account for some of that discordance.
The patients were participants in the Korean Longitudinal Study on Health and Aging, a population-based, prospective cohort study on health, aging, and common geriatric illnesses seen in elderly Koreans.
Of the 1000 study volunteers, 660 (368 women and 292 men) had completed a radiographic examination of the knee, symptom evaluation using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and diagnostic interviews for depression. The patients all were aged 65 years or older, with a mean age of 71.5 years and a mean body mass index of 24.3 kg/m2.
The WOMAC system consists of a 24-item questionnaire that evaluates pain, stiffness, and function. The highest possible score is 96; symptomatic knee osteoarthritis is defined as a score of at least 39. Patients also completed a short-form 36 scale that assessed health-related quality of life.
Of the 660 patients, 556 were KOAS-positive, and 104 were KOAS-negative. KOAS-positive patients were older (P < .001), more likely to be female (P < .001), and had a higher body mass index (P < .05) than their KOAS-negative counterparts. Their prevalence of depressive disorders was 26.9% compared with 5.8% in the KOAS-negative patients (P < .001). KOAS-positive patients also had a poorer health-related quality of life on the short-form 36, and more depressive symptoms (P < .001 for both).
On logistic regression analysis, the presence of depressive symptoms was associated with an odds ratio of 5.87 (95% confidence interval [CI], 3.01 - 11.44) of being KOAS-positive, the authors report. "However, the influence of a depressive disorder was limited to subjects with a radiographic severity of minimal to moderate; the odds ratio for the presence of a depressive disorder was 2.97 (95% CI, 1.04 to 8.47) in patients with a Kellgren-Lawrence grade [a measure of radiographic severity] of 0 or 1, and 72.08 (95% CI, 8.88 to 584.77) in those with a Kellgren-Lawrence grade of 2 or 3." Depressive disorders were not associated with an increased risk of being KOAS-positive in participants with a Kellgren-Lawrence grade of 4.
"Our findings support the hypothesis that comorbid depression explains the discordance between radiographic severity and symptomatic severity," Dr. Kim said.
"Depression is common in patients with arthritis, and much more prevalent than in the general population," said Mary Margaretten, MD, assistant professor of medicine in the Division of Rheumatology at the University of California–San Francisco.
"It is surprising that more severe [KOA] is not associated with depression, but perhaps patients with severe radiographic [KOA] have developed coping mechanisms over time that the patients with more mild and recent arthritis have not yet learned."
"The relationship between arthritis and depression can certainly go both ways," said Dr. Margaretten, who was not involved in this study.
"The pain and disability associated with arthritis can contribute to depressive symptoms, and just as possible, depression can contribute to a patient's perception of pain." She warned that "since this is a cross-sectional study, causality between depression and knee pain from arthritis cannot be determined."
Clinicians should suspect comorbid depression in patients with KOA whenever the symptoms seem unaccountably severe or persistent, especially when the arthritis is mild to moderate, Dr. Kim concluded. "For those patients, screening for the presence of comorbid depression or consultation with a psychiatrist to determine optimal treatment should be considered."
This study was supported by grants from Pfizer Global Pharmaceuticals and Seongnam City Government in Korea. One or more authors received funding support from Pfizer Global Pharmaceuticals and from the Seongnam City Government in Korea. Dr. Margaretten has disclosed no relevant financial relationships.
J Bone Joint Surg. 2011;93:556-563. Abstract
Clinical Context
KOA is a common cause of impairment and disability, and the prevalence increases with age and is expected to further increase in the coming years. Depression is also highly prevalent and contributes further to knee pain in osteoarthritis, but few studies have examined the association between KOA severity by radiographic assessment, symptoms, and depression, and how these factors are related.
This is a population-based prospective cohort study conducted in Korea within the Korean Longitudinal Study on Health and Aging to examine the association between KOA severity by radiographic assessment, clinical assessment, and depression.
News Author: Norra MacReady
CME Author: Désirée Lie, MD, MSEd
March 25, 2011 — Coexisting depression is an independent predictor of pain among people with radiographic evidence of mild to moderate osteoarthritis of the knee, researchers in South Korea have found.
"The contribution of comorbid depression to knee osteoarthritis symptoms [KOAS] is almost equal to that of radiographic severity," senior author Tae Kyun Kim, MD, told Medscape Medical News.
"As this finding is particularly important for mild to moderate knee osteoarthritis, due consideration for the presence of depression should be given to patients who suffer irrationally severe or persistent symptoms from mild to moderate knee osteoarthritis."
Dr. Kim and his colleagues at Seoul National University Bundang Hospital in Seongnam, South Korea, decided to conduct their study after observing that elderly people with knee arthritis show a substantial disparity between radiographic findings and reported pain levels.
This suggests that "the perception of pain in arthritis is influenced by factors other than the degree of osteoarthritic joint damage," they explain in an article published online March 16 and in the March issue of the Journal of Bone and Joint Surgery. Because depression is common in elderly people, the researchers suspected it might account for some of that discordance.
The patients were participants in the Korean Longitudinal Study on Health and Aging, a population-based, prospective cohort study on health, aging, and common geriatric illnesses seen in elderly Koreans.
Of the 1000 study volunteers, 660 (368 women and 292 men) had completed a radiographic examination of the knee, symptom evaluation using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and diagnostic interviews for depression. The patients all were aged 65 years or older, with a mean age of 71.5 years and a mean body mass index of 24.3 kg/m2.
The WOMAC system consists of a 24-item questionnaire that evaluates pain, stiffness, and function. The highest possible score is 96; symptomatic knee osteoarthritis is defined as a score of at least 39. Patients also completed a short-form 36 scale that assessed health-related quality of life.
Of the 660 patients, 556 were KOAS-positive, and 104 were KOAS-negative. KOAS-positive patients were older (P < .001), more likely to be female (P < .001), and had a higher body mass index (P < .05) than their KOAS-negative counterparts. Their prevalence of depressive disorders was 26.9% compared with 5.8% in the KOAS-negative patients (P < .001). KOAS-positive patients also had a poorer health-related quality of life on the short-form 36, and more depressive symptoms (P < .001 for both).
On logistic regression analysis, the presence of depressive symptoms was associated with an odds ratio of 5.87 (95% confidence interval [CI], 3.01 - 11.44) of being KOAS-positive, the authors report. "However, the influence of a depressive disorder was limited to subjects with a radiographic severity of minimal to moderate; the odds ratio for the presence of a depressive disorder was 2.97 (95% CI, 1.04 to 8.47) in patients with a Kellgren-Lawrence grade [a measure of radiographic severity] of 0 or 1, and 72.08 (95% CI, 8.88 to 584.77) in those with a Kellgren-Lawrence grade of 2 or 3." Depressive disorders were not associated with an increased risk of being KOAS-positive in participants with a Kellgren-Lawrence grade of 4.
"Our findings support the hypothesis that comorbid depression explains the discordance between radiographic severity and symptomatic severity," Dr. Kim said.
"Depression is common in patients with arthritis, and much more prevalent than in the general population," said Mary Margaretten, MD, assistant professor of medicine in the Division of Rheumatology at the University of California–San Francisco.
"It is surprising that more severe [KOA] is not associated with depression, but perhaps patients with severe radiographic [KOA] have developed coping mechanisms over time that the patients with more mild and recent arthritis have not yet learned."
"The relationship between arthritis and depression can certainly go both ways," said Dr. Margaretten, who was not involved in this study.
"The pain and disability associated with arthritis can contribute to depressive symptoms, and just as possible, depression can contribute to a patient's perception of pain." She warned that "since this is a cross-sectional study, causality between depression and knee pain from arthritis cannot be determined."
Clinicians should suspect comorbid depression in patients with KOA whenever the symptoms seem unaccountably severe or persistent, especially when the arthritis is mild to moderate, Dr. Kim concluded. "For those patients, screening for the presence of comorbid depression or consultation with a psychiatrist to determine optimal treatment should be considered."
This study was supported by grants from Pfizer Global Pharmaceuticals and Seongnam City Government in Korea. One or more authors received funding support from Pfizer Global Pharmaceuticals and from the Seongnam City Government in Korea. Dr. Margaretten has disclosed no relevant financial relationships.
J Bone Joint Surg. 2011;93:556-563. Abstract
Clinical Context
KOA is a common cause of impairment and disability, and the prevalence increases with age and is expected to further increase in the coming years. Depression is also highly prevalent and contributes further to knee pain in osteoarthritis, but few studies have examined the association between KOA severity by radiographic assessment, symptoms, and depression, and how these factors are related.
This is a population-based prospective cohort study conducted in Korea within the Korean Longitudinal Study on Health and Aging to examine the association between KOA severity by radiographic assessment, clinical assessment, and depression.
Hepatotoxicity Related to Antirheumatic Drugs
From Nature Reviews Rheumatology
Guruprasad P Aithal, BSc, MBBS, MD, PhD, FRCP
Abstract
Antirheumatic agents are among commonly used drugs associated with adverse hepatic reactions. Sulfasalazine and azathioprine are among the most important causes of acute hepatotoxicity. Because such a large number of people take NSAIDs, even the rare occurrence of hepatotoxicity from these agents might contribute substantially to the total burden of drug-induced liver disease. A wide spectrum of hepatotoxic effects is described with antirheumatic drugs. Studies investigating genetic susceptibility to diclofenac hepatotoxicity have expanded our understanding of the potential drug-specific, class-specific and general factors involved in its pathogenesis, and methotrexate-associated liver disease demonstrates the interaction between drug, host and environmental factors that determines the likelihood and magnitude of liver disease. Infliximab therapy is associated with typical drug-induced autoimmune hepatitis. Although validated causality assessment methods have been used to objectively assess the strength of the association between a drug and a clinical event, in practice the diagnosis of drug-induced liver injury (DILI) involves a clinical index of suspicion, pattern recognition, the establishment of a temporal relationship between drug exposure and the adverse event, and the exclusion of alternative explanations for the clinical presentation. Detailed understanding of genetic and environmental factors underlying an individual's susceptibility would enable risk reduction and potentially primary prevention of hepatotoxicity.
Introduction
Idiosyncratic hepatotoxicity is best described as an adverse hepatic reaction; that is, unexpected on the basis of the pharmacological action of a drug, hence unpredictable in its nature. During drug development, concordance between detection of hepatotoxic effects in animal studies and human trials remains poor (about 55%).[1] In addition, the frequency of clinically relevant liver injury is too low to assess accurately in clinical trials;[2] this difficulty is compounded by trial rules that mandate discontinuation of the medication at a point when 'self-resolving liver enzyme elevations' cannot be distinguished from drug-induced liver injury (DILI). Therefore, unexpected adverse hepatic reactions continue to account for the withdrawal of drugs from the market. Reports of acute liver failure associated with the NSAID bromfenac led to its withdrawal in 1998. Marketing of another NSAID, nimesulide, was suspended in Finland and Spain due to concerns regarding hepatotoxicity,[3] and the drug has never been approved in several other countries owing to similar concerns. Lumiracoxib, a selective inhibitor of cyclooxygenase-2, has been associated with serious liver injury at a rate of 6.39 incidents per 100,000 users (C. Paulding, personal communication). This association has led to the drug's widespread withdrawal or non-approval.[4] Such post-marketing withdrawals add to the overall cost of drug development.
Antirheumatic agents as a group are commonly associated with hepatotoxicity. A population-based case-control study that included 1.64 million subjects found sulfasalazine and azathioprine to be among the most hepatotoxic drugs of any class, both associated with an incidence of liver injury of about 1 per 1,000 users.[5] NSAIDs are among the most widely used medications worldwide. In the USA, 6% of the adult population reported using a prescription NSAID in a month and 24% non-prescription ibuprofen.[6] Therefore, even if rare, the occurrence of NSAID hepatotoxicity would contribute substantially to the total burden of drug-induced liver disease because of the large number of people taking these drugs.
A variety of terms has been used to define and characterize adverse hepatic reactions attributable to drugs ( Box 1 ). Despite clarification of these terms, case definitions and descriptions of hepatotoxicity are applied inconsistently in the literature. This Review includes a description of the spectrum of hepatotoxic effects related to antirheumatic agents, and the current understanding of the pathogenesis underlying these adverse reactions, which could point to opportunities for risk reduction.
http://www.medscape.org/viewarticle/736129?src=cmemp
Guruprasad P Aithal, BSc, MBBS, MD, PhD, FRCP
Abstract
Antirheumatic agents are among commonly used drugs associated with adverse hepatic reactions. Sulfasalazine and azathioprine are among the most important causes of acute hepatotoxicity. Because such a large number of people take NSAIDs, even the rare occurrence of hepatotoxicity from these agents might contribute substantially to the total burden of drug-induced liver disease. A wide spectrum of hepatotoxic effects is described with antirheumatic drugs. Studies investigating genetic susceptibility to diclofenac hepatotoxicity have expanded our understanding of the potential drug-specific, class-specific and general factors involved in its pathogenesis, and methotrexate-associated liver disease demonstrates the interaction between drug, host and environmental factors that determines the likelihood and magnitude of liver disease. Infliximab therapy is associated with typical drug-induced autoimmune hepatitis. Although validated causality assessment methods have been used to objectively assess the strength of the association between a drug and a clinical event, in practice the diagnosis of drug-induced liver injury (DILI) involves a clinical index of suspicion, pattern recognition, the establishment of a temporal relationship between drug exposure and the adverse event, and the exclusion of alternative explanations for the clinical presentation. Detailed understanding of genetic and environmental factors underlying an individual's susceptibility would enable risk reduction and potentially primary prevention of hepatotoxicity.
Introduction
Idiosyncratic hepatotoxicity is best described as an adverse hepatic reaction; that is, unexpected on the basis of the pharmacological action of a drug, hence unpredictable in its nature. During drug development, concordance between detection of hepatotoxic effects in animal studies and human trials remains poor (about 55%).[1] In addition, the frequency of clinically relevant liver injury is too low to assess accurately in clinical trials;[2] this difficulty is compounded by trial rules that mandate discontinuation of the medication at a point when 'self-resolving liver enzyme elevations' cannot be distinguished from drug-induced liver injury (DILI). Therefore, unexpected adverse hepatic reactions continue to account for the withdrawal of drugs from the market. Reports of acute liver failure associated with the NSAID bromfenac led to its withdrawal in 1998. Marketing of another NSAID, nimesulide, was suspended in Finland and Spain due to concerns regarding hepatotoxicity,[3] and the drug has never been approved in several other countries owing to similar concerns. Lumiracoxib, a selective inhibitor of cyclooxygenase-2, has been associated with serious liver injury at a rate of 6.39 incidents per 100,000 users (C. Paulding, personal communication). This association has led to the drug's widespread withdrawal or non-approval.[4] Such post-marketing withdrawals add to the overall cost of drug development.
Antirheumatic agents as a group are commonly associated with hepatotoxicity. A population-based case-control study that included 1.64 million subjects found sulfasalazine and azathioprine to be among the most hepatotoxic drugs of any class, both associated with an incidence of liver injury of about 1 per 1,000 users.[5] NSAIDs are among the most widely used medications worldwide. In the USA, 6% of the adult population reported using a prescription NSAID in a month and 24% non-prescription ibuprofen.[6] Therefore, even if rare, the occurrence of NSAID hepatotoxicity would contribute substantially to the total burden of drug-induced liver disease because of the large number of people taking these drugs.
A variety of terms has been used to define and characterize adverse hepatic reactions attributable to drugs ( Box 1 ). Despite clarification of these terms, case definitions and descriptions of hepatotoxicity are applied inconsistently in the literature. This Review includes a description of the spectrum of hepatotoxic effects related to antirheumatic agents, and the current understanding of the pathogenesis underlying these adverse reactions, which could point to opportunities for risk reduction.
http://www.medscape.org/viewarticle/736129?src=cmemp
Subscribe to:
Posts (Atom)