Letters To The Editor

To the Editor: I truly enjoyed the review by Drs. Senter and Francis in the March issue of the Journal,¹ and I marveled at the authors’ feat of encompassing so much essential information about the diagnose of acute myocardial infarction (MI) in so few pages!

Under the subheading “Electrocardiography: Necessary but not sufficient,” the authors clearly describe the vagaries in using standard 12-lead electrocardiography in the diagnosis of acute MI. Indeed, one is often unable to substantiate the diagnosis of acute MI using standard 12-lead electrocardiography, with occasionally devastating consequences (death, loss of cardiac muscle due to failure to implement thrombolysis or percutaneous coronary intervention). Troponin biomarkers, echocardiography, and frequent sequential recordings of standard 12-lead electrocardiography may provide additional aid, as the authors remark. However, quite frequently, even all the above do not suffice, and acute MI remains undiagnosed, or, if the correct diagnosis is made, we fail to subject some patients to the appropriate procedures for optimal management of their condition.

It is time to upgrade standard 12-lead electrocardiography! Many have proposed certain additional electrocardiographic leads, on extensive thoracic electrode arrays, which are cumbersome to use in an acute or emergency setting. Instead, I have recently proposed as the solution the “double electrocardiogram” for the diagnosis of acute MI in patients with suspected acute coronary syndromes and a nondiagnostic electrocardiographic result. The double electrocardiogram consists of supplementing the 12-lead electrocardiogram immediately by repeating it, with the V₁ to V₆ electrodes used to record leads V₃R, V₄R, V₇, V₈, and V₉ to the left of the spine, and V₉R to the right of the spine.

To the Editor: I truly enjoyed the review by Drs. Senter and Francis in the March issue of the Journal,¹ and I marveled at the authors’ feat of encompassing so much essential information about the diagnose of acute myocardial infarction (MI) in so few pages!

Under the subheading “Electrocardiography: Necessary but not sufficient,” the authors clearly describe the vagaries in using standard 12-lead electrocardiography in the diagnosis of acute MI. Indeed, one is often unable to substantiate the diagnosis of acute MI using standard 12-lead electrocardiography, with occasionally devastating consequences (death, loss of cardiac muscle due to failure to implement thrombolysis or percutaneous coronary intervention). Troponin biomarkers, echocardiography, and frequent sequential recordings of standard 12-lead electrocardiography may provide additional aid, as the authors remark. However, quite frequently, even all the above do not suffice, and acute MI remains undiagnosed, or, if the correct diagnosis is made, we fail to subject some patients to the appropriate procedures for optimal management of their condition.

It is time to upgrade standard 12-lead electrocardiography! Many have proposed certain additional electrocardiographic leads, on extensive thoracic electrode arrays, which are cumbersome to use in an acute or emergency setting. Instead, I have recently proposed as the solution the “double electrocardiogram” for the diagnosis of acute MI in patients with suspected acute coronary syndromes and a nondiagnostic electrocardiographic result. The double electrocardiogram consists of supplementing the 12-lead electrocardiogram immediately by repeating it, with the V₁ to V₆ electrodes used to record leads V₃R, V₄R, V₇, V₈, and V₉ to the left of the spine, and V₉R to the right of the spine.

To the Editor: I truly enjoyed the review by Drs. Senter and Francis in the March issue of the Journal,¹ and I marveled at the authors’ feat of encompassing so much essential information about the diagnose of acute myocardial infarction (MI) in so few pages!

Under the subheading “Electrocardiography: Necessary but not sufficient,” the authors clearly describe the vagaries in using standard 12-lead electrocardiography in the diagnosis of acute MI. Indeed, one is often unable to substantiate the diagnosis of acute MI using standard 12-lead electrocardiography, with occasionally devastating consequences (death, loss of cardiac muscle due to failure to implement thrombolysis or percutaneous coronary intervention). Troponin biomarkers, echocardiography, and frequent sequential recordings of standard 12-lead electrocardiography may provide additional aid, as the authors remark. However, quite frequently, even all the above do not suffice, and acute MI remains undiagnosed, or, if the correct diagnosis is made, we fail to subject some patients to the appropriate procedures for optimal management of their condition.

It is time to upgrade standard 12-lead electrocardiography! Many have proposed certain additional electrocardiographic leads, on extensive thoracic electrode arrays, which are cumbersome to use in an acute or emergency setting. Instead, I have recently proposed as the solution the “double electrocardiogram” for the diagnosis of acute MI in patients with suspected acute coronary syndromes and a nondiagnostic electrocardiographic result. The double electrocardiogram consists of supplementing the 12-lead electrocardiogram immediately by repeating it, with the V₁ to V₆ electrodes used to record leads V₃R, V₄R, V₇, V₈, and V₉ to the left of the spine, and V₉R to the right of the spine.

In Reply: We thank Dr. Madias for his letter. We agree that doing a second electrocardiogram to inspect V₃R, V₄R, and V₇ to the left of the spine and V₉ to the right of the spine may provide important additional information that supports the diagnosis of acute MI. When clinical suspicion is high and the standard 12-lead electrocardiogram shows only minimal changes, then additional lead placement may be useful. Some other situations were not covered in our paper but are worthy of consideration when looking for electrocardiographic evidence of acute MI, eg:

• Patients with left main disease may demonstrate modest ST-T elevation in lead AVR with diffuse ST-T depression when having an acute MI.
• Patients with only T-wave-flattening in AVL may be having an acute MI due to isolated circumflex coronary disease.

Again, we thank Dr. Madias for his interest in our paper. We welcome his suggestion and hope that our response will be of some value to physicians responsible for making the very important decision to send a patient urgently to the cardiac catheterization laboratory.

In Reply: We thank Dr. Madias for his letter. We agree that doing a second electrocardiogram to inspect V₃R, V₄R, and V₇ to the left of the spine and V₉ to the right of the spine may provide important additional information that supports the diagnosis of acute MI. When clinical suspicion is high and the standard 12-lead electrocardiogram shows only minimal changes, then additional lead placement may be useful. Some other situations were not covered in our paper but are worthy of consideration when looking for electrocardiographic evidence of acute MI, eg:

• Patients with left main disease may demonstrate modest ST-T elevation in lead AVR with diffuse ST-T depression when having an acute MI.
• Patients with only T-wave-flattening in AVL may be having an acute MI due to isolated circumflex coronary disease.

Again, we thank Dr. Madias for his interest in our paper. We welcome his suggestion and hope that our response will be of some value to physicians responsible for making the very important decision to send a patient urgently to the cardiac catheterization laboratory.

In Reply: We thank Dr. Madias for his letter. We agree that doing a second electrocardiogram to inspect V₃R, V₄R, and V₇ to the left of the spine and V₉ to the right of the spine may provide important additional information that supports the diagnosis of acute MI. When clinical suspicion is high and the standard 12-lead electrocardiogram shows only minimal changes, then additional lead placement may be useful. Some other situations were not covered in our paper but are worthy of consideration when looking for electrocardiographic evidence of acute MI, eg:

• Patients with left main disease may demonstrate modest ST-T elevation in lead AVR with diffuse ST-T depression when having an acute MI.
• Patients with only T-wave-flattening in AVL may be having an acute MI due to isolated circumflex coronary disease.

Again, we thank Dr. Madias for his interest in our paper. We welcome his suggestion and hope that our response will be of some value to physicians responsible for making the very important decision to send a patient urgently to the cardiac catheterization laboratory.

To the Editor: Kudos to Drs. Singh and Englund for their excellent article concerning the shingles vaccine in the January 2009 issue. However, I would like to know the authors’ thoughts about the purpose and cost-effectiveness of vaccinating patients who definitely have had shingles. I have heard that the recurrence rate is 3% to 5%, and the efficacy of the vaccine is only 50% to 65%. Though every article I have read states we can give the vaccine to these patients, should we?

To the Editor: Kudos to Drs. Singh and Englund for their excellent article concerning the shingles vaccine in the January 2009 issue. However, I would like to know the authors’ thoughts about the purpose and cost-effectiveness of vaccinating patients who definitely have had shingles. I have heard that the recurrence rate is 3% to 5%, and the efficacy of the vaccine is only 50% to 65%. Though every article I have read states we can give the vaccine to these patients, should we?

To the Editor: Kudos to Drs. Singh and Englund for their excellent article concerning the shingles vaccine in the January 2009 issue. However, I would like to know the authors’ thoughts about the purpose and cost-effectiveness of vaccinating patients who definitely have had shingles. I have heard that the recurrence rate is 3% to 5%, and the efficacy of the vaccine is only 50% to 65%. Though every article I have read states we can give the vaccine to these patients, should we?

In Reply: We thank Dr. Shaheen for his interesting comment. He has made an important point. The data on the use of shingles vaccine in patients with a history of zoster are insufficient. The main study of shingles vaccine¹ excluded patients who had already had shingles.

The US Centers for Disease Control and Prevention says: “Persons with a reported history of zoster can [emphasis added] be vaccinated. Repeated zoster has been confirmed in immunocompetent persons soon after a previous episode. Although the precise risk for and severity of zoster as a function of time following an earlier episode are unknown, some studies suggest it may be comparable to the risk in persons without a history of zoster. Furthermore, no laboratory evaluations exist to test for the previous occurrence of zoster, and any reported diagnosis or history might be erroneous.”²

Until more data are available for this patient population, current evidence and availability of shingles vaccine should be discussed with patients who report a history of shingles.

In Reply: We thank Dr. Shaheen for his interesting comment. He has made an important point. The data on the use of shingles vaccine in patients with a history of zoster are insufficient. The main study of shingles vaccine¹ excluded patients who had already had shingles.

The US Centers for Disease Control and Prevention says: “Persons with a reported history of zoster can [emphasis added] be vaccinated. Repeated zoster has been confirmed in immunocompetent persons soon after a previous episode. Although the precise risk for and severity of zoster as a function of time following an earlier episode are unknown, some studies suggest it may be comparable to the risk in persons without a history of zoster. Furthermore, no laboratory evaluations exist to test for the previous occurrence of zoster, and any reported diagnosis or history might be erroneous.”²

Until more data are available for this patient population, current evidence and availability of shingles vaccine should be discussed with patients who report a history of shingles.

In Reply: We thank Dr. Shaheen for his interesting comment. He has made an important point. The data on the use of shingles vaccine in patients with a history of zoster are insufficient. The main study of shingles vaccine¹ excluded patients who had already had shingles.

The US Centers for Disease Control and Prevention says: “Persons with a reported history of zoster can [emphasis added] be vaccinated. Repeated zoster has been confirmed in immunocompetent persons soon after a previous episode. Although the precise risk for and severity of zoster as a function of time following an earlier episode are unknown, some studies suggest it may be comparable to the risk in persons without a history of zoster. Furthermore, no laboratory evaluations exist to test for the previous occurrence of zoster, and any reported diagnosis or history might be erroneous.”²

Until more data are available for this patient population, current evidence and availability of shingles vaccine should be discussed with patients who report a history of shingles.

To the Editor: I would like to comment on the excellent review article on barium esophagography by Drs. Allen, Baker, and Falk in your February 2009 issue. In their opening clinical vignette, they describe a 55-year-old female patient with gastroesophageal reflux disease (GERD) and slowly worsening dysphagia for solids. The patient was sent for barium esophagography, which disclosed an obstructing mucosal ring in the distal esophagus. The patient was then sent for endoscopy so that the ring could be treated with dilation. The authors present this case as an example of the type of patient who could obtain benefit from barium esophagography as the initial study. I disagree. In this patient’s case, the barium procedure accomplished nothing, but it did unnecessarily cost the patient money, time, and radiation exposure. The patient would have been better served by being sent directly for endoscopy at the start of her workup, so that her condition could be diagnosed and treated with a single procedure. In her case, this would have spared her any need for the barium procedure. I believe that patients with dysphagia and GERD are best served by initial endoscopy, since GERD is associated with esophageal strictures, dysplasia, and cancer. Barium esophagography can be reserved for those who have had a normal or nondiagnostic endoscopy. For example, a patient with dysphagia and a normal endoscopy might then be sent for esophagography to diagnose a motility disorder.

To the Editor: I would like to comment on the excellent review article on barium esophagography by Drs. Allen, Baker, and Falk in your February 2009 issue. In their opening clinical vignette, they describe a 55-year-old female patient with gastroesophageal reflux disease (GERD) and slowly worsening dysphagia for solids. The patient was sent for barium esophagography, which disclosed an obstructing mucosal ring in the distal esophagus. The patient was then sent for endoscopy so that the ring could be treated with dilation. The authors present this case as an example of the type of patient who could obtain benefit from barium esophagography as the initial study. I disagree. In this patient’s case, the barium procedure accomplished nothing, but it did unnecessarily cost the patient money, time, and radiation exposure. The patient would have been better served by being sent directly for endoscopy at the start of her workup, so that her condition could be diagnosed and treated with a single procedure. In her case, this would have spared her any need for the barium procedure. I believe that patients with dysphagia and GERD are best served by initial endoscopy, since GERD is associated with esophageal strictures, dysplasia, and cancer. Barium esophagography can be reserved for those who have had a normal or nondiagnostic endoscopy. For example, a patient with dysphagia and a normal endoscopy might then be sent for esophagography to diagnose a motility disorder.

To the Editor: I would like to comment on the excellent review article on barium esophagography by Drs. Allen, Baker, and Falk in your February 2009 issue. In their opening clinical vignette, they describe a 55-year-old female patient with gastroesophageal reflux disease (GERD) and slowly worsening dysphagia for solids. The patient was sent for barium esophagography, which disclosed an obstructing mucosal ring in the distal esophagus. The patient was then sent for endoscopy so that the ring could be treated with dilation. The authors present this case as an example of the type of patient who could obtain benefit from barium esophagography as the initial study. I disagree. In this patient’s case, the barium procedure accomplished nothing, but it did unnecessarily cost the patient money, time, and radiation exposure. The patient would have been better served by being sent directly for endoscopy at the start of her workup, so that her condition could be diagnosed and treated with a single procedure. In her case, this would have spared her any need for the barium procedure. I believe that patients with dysphagia and GERD are best served by initial endoscopy, since GERD is associated with esophageal strictures, dysplasia, and cancer. Barium esophagography can be reserved for those who have had a normal or nondiagnostic endoscopy. For example, a patient with dysphagia and a normal endoscopy might then be sent for esophagography to diagnose a motility disorder.

In Reply: We thank Dr. Keller for his kind remarks and feedback. However, we do not necessarily agree that the case presented was a bad example of a patient to be evaluated with a barium study. While a significant distal mucosal ring was identified on the study as the cause of the patient’s symptoms, this was not known before the examination. This patient could easily have had a subtle peptic stricture as the cause of the dysphagia. It is well known that subtle strictures can be missed with endoscopy. Further, if we knew that the patient had a significant distal mucosal ring before any testing, one could argue that all that was necessary was a dilation. When one knows, after the fact, what the cause of a patient’s symptoms are, one can always retrospectively determine which tests were necessary and which tests were not.

In our experience, we find that a well-performed barium study can identify many abnormalities that further direct a patient’s care. This examination, when performed correctly, provides both functional and anatomic information about the esophagus. We believe that too many patients undergo unnecessary endoscopic procedures and that endoscopy is not necessarily the initial examination in patients with dysphagia. As a result, the barium examination of the esophagus is underused. Furthermore, we view the barium examination and endoscopy as complementary examinations. We realize this is in many respects a philosophy. But Dr. Keller is also expressing a philosophy when he states, “I believe that patients with dysphagia and GERD are best served by initial endoscopy.” We, including most of our gastroenterologists and esophageal surgeons, believe that the barium examination is an important and often the best initial examination in patients with dysphagia.

In Reply: We thank Dr. Keller for his kind remarks and feedback. However, we do not necessarily agree that the case presented was a bad example of a patient to be evaluated with a barium study. While a significant distal mucosal ring was identified on the study as the cause of the patient’s symptoms, this was not known before the examination. This patient could easily have had a subtle peptic stricture as the cause of the dysphagia. It is well known that subtle strictures can be missed with endoscopy. Further, if we knew that the patient had a significant distal mucosal ring before any testing, one could argue that all that was necessary was a dilation. When one knows, after the fact, what the cause of a patient’s symptoms are, one can always retrospectively determine which tests were necessary and which tests were not.

In our experience, we find that a well-performed barium study can identify many abnormalities that further direct a patient’s care. This examination, when performed correctly, provides both functional and anatomic information about the esophagus. We believe that too many patients undergo unnecessary endoscopic procedures and that endoscopy is not necessarily the initial examination in patients with dysphagia. As a result, the barium examination of the esophagus is underused. Furthermore, we view the barium examination and endoscopy as complementary examinations. We realize this is in many respects a philosophy. But Dr. Keller is also expressing a philosophy when he states, “I believe that patients with dysphagia and GERD are best served by initial endoscopy.” We, including most of our gastroenterologists and esophageal surgeons, believe that the barium examination is an important and often the best initial examination in patients with dysphagia.

In Reply: We thank Dr. Keller for his kind remarks and feedback. However, we do not necessarily agree that the case presented was a bad example of a patient to be evaluated with a barium study. While a significant distal mucosal ring was identified on the study as the cause of the patient’s symptoms, this was not known before the examination. This patient could easily have had a subtle peptic stricture as the cause of the dysphagia. It is well known that subtle strictures can be missed with endoscopy. Further, if we knew that the patient had a significant distal mucosal ring before any testing, one could argue that all that was necessary was a dilation. When one knows, after the fact, what the cause of a patient’s symptoms are, one can always retrospectively determine which tests were necessary and which tests were not.

In our experience, we find that a well-performed barium study can identify many abnormalities that further direct a patient’s care. This examination, when performed correctly, provides both functional and anatomic information about the esophagus. We believe that too many patients undergo unnecessary endoscopic procedures and that endoscopy is not necessarily the initial examination in patients with dysphagia. As a result, the barium examination of the esophagus is underused. Furthermore, we view the barium examination and endoscopy as complementary examinations. We realize this is in many respects a philosophy. But Dr. Keller is also expressing a philosophy when he states, “I believe that patients with dysphagia and GERD are best served by initial endoscopy.” We, including most of our gastroenterologists and esophageal surgeons, believe that the barium examination is an important and often the best initial examination in patients with dysphagia.

In Reply: We appreciate the interest and comments of Dr Hirsch. Due to space limitations of the Journal’s 1-Minute Consult format, we were unable to elaborate on the cost and reimbursement. Since shingles vaccine is not covered by Medicare part B, reimbursement and administration of this vaccine remains challenging, and resources like eDispense are helpful tools for the physician to simplify the process of reimbursement—with no charge to the physician.

In Reply: We appreciate the interest and comments of Dr Hirsch. Due to space limitations of the Journal’s 1-Minute Consult format, we were unable to elaborate on the cost and reimbursement. Since shingles vaccine is not covered by Medicare part B, reimbursement and administration of this vaccine remains challenging, and resources like eDispense are helpful tools for the physician to simplify the process of reimbursement—with no charge to the physician.

In Reply: We appreciate the interest and comments of Dr Hirsch. Due to space limitations of the Journal’s 1-Minute Consult format, we were unable to elaborate on the cost and reimbursement. Since shingles vaccine is not covered by Medicare part B, reimbursement and administration of this vaccine remains challenging, and resources like eDispense are helpful tools for the physician to simplify the process of reimbursement—with no charge to the physician.

To the Editor: In their 1-Minute Consult, Drs. Singh and Englund give a thorough review of Zostavax, the vaccine to prevent shingles.¹ Unfortunately, the information they provided on cost and reimbursement is incomplete.

As they noted, this vaccine is not covered by Medicare part B and is mandated to be covered by Medicare part D as a “prescription drug.” Furthermore, the vaccine administration charge cannot be billed to Medicare part B. Since physician offices do not bill prescription drug plans, physicians are permitted to administer the vaccine, charge the patient for the vaccine and administration, and have the patient submit the receipt to his or her prescription drug provider for reimbursement. There is no fee schedule for this vaccine, so physicians are free to charge a fee that they deem reasonable. For patients without part D, it is reasonable to ask them to call their prescription provider and inquire about coverage before vaccination, since many commercial plans will not cover the vaccine, and the $200 or more price may be unaffordable for many.

Alternatively, physician offices may enroll with a private vendor, eDispense Vaccine Manager, at enroll.edispense.com, and submit charges for Zostavax electronically to the patient’s Medicare part D provider; eDispense is contracted with most of the large part D providers. This service allows the physician to input the patient’s demographics and get an immediate response, showing the patient’s coverage and copayment, and allowing the physician to submit the claim electronically. There is no charge to the physician, and the reimbursement covers the cost of the vaccine, the administration cost, and a small profit. If the patient wishes to pay for the vaccine, the system can produce a receipt containing all the information needed for submission by the patient to the insurer. (Note: I have no financial or ownership interest in eDispense.com or Merck.)

Since recommending and administering Zostavax is soon to become the standard of care, the availability of these options will provide better care than the authors’ recommendation that patients pick up the vaccine and transport it back to the physician’s office on ice, which risks defrosting and inactivating the vaccine, or leaving patients to find a vaccine provider on their own.

To the Editor: In their 1-Minute Consult, Drs. Singh and Englund give a thorough review of Zostavax, the vaccine to prevent shingles.¹ Unfortunately, the information they provided on cost and reimbursement is incomplete.

As they noted, this vaccine is not covered by Medicare part B and is mandated to be covered by Medicare part D as a “prescription drug.” Furthermore, the vaccine administration charge cannot be billed to Medicare part B. Since physician offices do not bill prescription drug plans, physicians are permitted to administer the vaccine, charge the patient for the vaccine and administration, and have the patient submit the receipt to his or her prescription drug provider for reimbursement. There is no fee schedule for this vaccine, so physicians are free to charge a fee that they deem reasonable. For patients without part D, it is reasonable to ask them to call their prescription provider and inquire about coverage before vaccination, since many commercial plans will not cover the vaccine, and the $200 or more price may be unaffordable for many.

Alternatively, physician offices may enroll with a private vendor, eDispense Vaccine Manager, at enroll.edispense.com, and submit charges for Zostavax electronically to the patient’s Medicare part D provider; eDispense is contracted with most of the large part D providers. This service allows the physician to input the patient’s demographics and get an immediate response, showing the patient’s coverage and copayment, and allowing the physician to submit the claim electronically. There is no charge to the physician, and the reimbursement covers the cost of the vaccine, the administration cost, and a small profit. If the patient wishes to pay for the vaccine, the system can produce a receipt containing all the information needed for submission by the patient to the insurer. (Note: I have no financial or ownership interest in eDispense.com or Merck.)

Since recommending and administering Zostavax is soon to become the standard of care, the availability of these options will provide better care than the authors’ recommendation that patients pick up the vaccine and transport it back to the physician’s office on ice, which risks defrosting and inactivating the vaccine, or leaving patients to find a vaccine provider on their own.

To the Editor: In their 1-Minute Consult, Drs. Singh and Englund give a thorough review of Zostavax, the vaccine to prevent shingles.¹ Unfortunately, the information they provided on cost and reimbursement is incomplete.

As they noted, this vaccine is not covered by Medicare part B and is mandated to be covered by Medicare part D as a “prescription drug.” Furthermore, the vaccine administration charge cannot be billed to Medicare part B. Since physician offices do not bill prescription drug plans, physicians are permitted to administer the vaccine, charge the patient for the vaccine and administration, and have the patient submit the receipt to his or her prescription drug provider for reimbursement. There is no fee schedule for this vaccine, so physicians are free to charge a fee that they deem reasonable. For patients without part D, it is reasonable to ask them to call their prescription provider and inquire about coverage before vaccination, since many commercial plans will not cover the vaccine, and the $200 or more price may be unaffordable for many.

Alternatively, physician offices may enroll with a private vendor, eDispense Vaccine Manager, at enroll.edispense.com, and submit charges for Zostavax electronically to the patient’s Medicare part D provider; eDispense is contracted with most of the large part D providers. This service allows the physician to input the patient’s demographics and get an immediate response, showing the patient’s coverage and copayment, and allowing the physician to submit the claim electronically. There is no charge to the physician, and the reimbursement covers the cost of the vaccine, the administration cost, and a small profit. If the patient wishes to pay for the vaccine, the system can produce a receipt containing all the information needed for submission by the patient to the insurer. (Note: I have no financial or ownership interest in eDispense.com or Merck.)

Since recommending and administering Zostavax is soon to become the standard of care, the availability of these options will provide better care than the authors’ recommendation that patients pick up the vaccine and transport it back to the physician’s office on ice, which risks defrosting and inactivating the vaccine, or leaving patients to find a vaccine provider on their own.

To the Editor: I read with interest the article by Perkins and colleagues, “A young pregnant woman with shortness of breath” on pages 788–792 of the November 2008 issue of the Cleveland Clinic Journal of Medicine. An incorrect meaning occurs in the article. Thyrotoxicosis is the state of symptomatic thyroid hormone excess, of both endogenous and exogenous cause. It is not synonymous with hyperthyroidism, which is the result of excessive thyroid function.

To the Editor: I read with interest the article by Perkins and colleagues, “A young pregnant woman with shortness of breath” on pages 788–792 of the November 2008 issue of the Cleveland Clinic Journal of Medicine. An incorrect meaning occurs in the article. Thyrotoxicosis is the state of symptomatic thyroid hormone excess, of both endogenous and exogenous cause. It is not synonymous with hyperthyroidism, which is the result of excessive thyroid function.

To the Editor: I read with interest the article by Perkins and colleagues, “A young pregnant woman with shortness of breath” on pages 788–792 of the November 2008 issue of the Cleveland Clinic Journal of Medicine. An incorrect meaning occurs in the article. Thyrotoxicosis is the state of symptomatic thyroid hormone excess, of both endogenous and exogenous cause. It is not synonymous with hyperthyroidism, which is the result of excessive thyroid function.

To the Editor: I read with great interest Dr. Byron Hoogwerf’s summary¹ of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial² in your October issue.

I am curious as to your opinion, though. I previously e-mailed two other ACCORD investigators to ask if they planned to look at which subgroups were responsible for the higher death rate in the intensive-therapy group. They cannot get this data until after the lipid portion is unblinded next year.

The early release of data and discontinuation of one ACCORD arm is of concern but the data may shed light on the failure of previous trials. Muraglitazar was a failed dual peroxisome proliferator-activated receptor (PPAR) alpha and gamma agonist; it had outstanding effects on surrogate markers but was harmful regarding total mortality.³ The same outcomes were seen in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study: lower cardiovascular morbidity rate but higher total mortality rate,⁴ prompting an exchange between Dr. Steven Nissen and me in JAMA in 2006.^5,6

I think it would be prudent to evaluate the total mortality rate as well as cardiovascular morbidity in the study population receiving thiazolidinediones alone, fibric acid alone, both together, or neither. The group of patients most likely to receive both agents (those who are obese, with metabolic syndrome or diabetes) is a very large population. If the data analysis confirms that dual PPAR inhibition raises total mortality rates, that information should be made public as soon as it is available. It may be prudent to review those data before official publication in 2009.

To the Editor: I read with great interest Dr. Byron Hoogwerf’s summary¹ of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial² in your October issue.

I am curious as to your opinion, though. I previously e-mailed two other ACCORD investigators to ask if they planned to look at which subgroups were responsible for the higher death rate in the intensive-therapy group. They cannot get this data until after the lipid portion is unblinded next year.

The early release of data and discontinuation of one ACCORD arm is of concern but the data may shed light on the failure of previous trials. Muraglitazar was a failed dual peroxisome proliferator-activated receptor (PPAR) alpha and gamma agonist; it had outstanding effects on surrogate markers but was harmful regarding total mortality.³ The same outcomes were seen in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study: lower cardiovascular morbidity rate but higher total mortality rate,⁴ prompting an exchange between Dr. Steven Nissen and me in JAMA in 2006.^5,6

I think it would be prudent to evaluate the total mortality rate as well as cardiovascular morbidity in the study population receiving thiazolidinediones alone, fibric acid alone, both together, or neither. The group of patients most likely to receive both agents (those who are obese, with metabolic syndrome or diabetes) is a very large population. If the data analysis confirms that dual PPAR inhibition raises total mortality rates, that information should be made public as soon as it is available. It may be prudent to review those data before official publication in 2009.

To the Editor: I read with great interest Dr. Byron Hoogwerf’s summary¹ of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial² in your October issue.

I am curious as to your opinion, though. I previously e-mailed two other ACCORD investigators to ask if they planned to look at which subgroups were responsible for the higher death rate in the intensive-therapy group. They cannot get this data until after the lipid portion is unblinded next year.

The early release of data and discontinuation of one ACCORD arm is of concern but the data may shed light on the failure of previous trials. Muraglitazar was a failed dual peroxisome proliferator-activated receptor (PPAR) alpha and gamma agonist; it had outstanding effects on surrogate markers but was harmful regarding total mortality.³ The same outcomes were seen in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study: lower cardiovascular morbidity rate but higher total mortality rate,⁴ prompting an exchange between Dr. Steven Nissen and me in JAMA in 2006.^5,6

I think it would be prudent to evaluate the total mortality rate as well as cardiovascular morbidity in the study population receiving thiazolidinediones alone, fibric acid alone, both together, or neither. The group of patients most likely to receive both agents (those who are obese, with metabolic syndrome or diabetes) is a very large population. If the data analysis confirms that dual PPAR inhibition raises total mortality rates, that information should be made public as soon as it is available. It may be prudent to review those data before official publication in 2009.