David L. Keller, MD

To the Editor: Thanks for the concise review of obstructive sleep apnea (OSA) in the January 2016 issue.¹ I offer the following comments and questions:

1. Risk factors for OSA include large neck circumference, which in Table 1 is defined as larger than 40 cm (15.75 inches), which would include shirt collar sizes 16 and above. In the second paragraph of the text, large neck circumference is defined as greater than 17 inches in men, which would include collar sizes above 17. The definition of a large neck as larger than 40 cm must obviously be more sensitive for predicting OSA, and the definition of greater than 17 inches more specific. Which do the authors use in clinical practice?

2. The American Academy of Sleep Medicine is quoted as recommending home OSA screening “if direct monitoring of the response to non-[continuous positive airway pressure] treatments for sleep apnea is needed.”² However, the need for direct monitoring would seem to be a contraindication to home testing rather than an indication. If this statement is correct as written, would the authors explain why and how specific non-CPAP treatments for OSA are more amenable to monitoring at home than in the sleep lab?

3. Patients with Parkinson disease are at risk for both OSA and hypotension, making them generally an exception to the association of OSA with hypertension.³

4. The home overnight OSA test often consists of a pulse oximeter worn for 8 hours at night, taped to a finger.⁴ This simple, inexpensive test for OSA detects episodes of apnea or hypopnea that result in arterial desaturation. Is it beneficial to also document episodes of apnea or hypopnea that do not result in arterial desaturation? These episodes are included in the 17% false-negative rate for home OSA testing mentioned in the text. Are these episodes important clinically, other than for prognosis in patients who may go on to develop apneic episodes severe enough to cause desaturation?

5. Lastly, the authors may wish to comment on the importance of diagnosing and treating OSA in patients who plan to have elective surgery under general anesthesia, which can lead to profound sleep apnea in the recovery room, with associated morbidity and death.⁵

To the Editor: Thanks for the concise review of obstructive sleep apnea (OSA) in the January 2016 issue.¹ I offer the following comments and questions:

1. Risk factors for OSA include large neck circumference, which in Table 1 is defined as larger than 40 cm (15.75 inches), which would include shirt collar sizes 16 and above. In the second paragraph of the text, large neck circumference is defined as greater than 17 inches in men, which would include collar sizes above 17. The definition of a large neck as larger than 40 cm must obviously be more sensitive for predicting OSA, and the definition of greater than 17 inches more specific. Which do the authors use in clinical practice?

2. The American Academy of Sleep Medicine is quoted as recommending home OSA screening “if direct monitoring of the response to non-[continuous positive airway pressure] treatments for sleep apnea is needed.”² However, the need for direct monitoring would seem to be a contraindication to home testing rather than an indication. If this statement is correct as written, would the authors explain why and how specific non-CPAP treatments for OSA are more amenable to monitoring at home than in the sleep lab?

3. Patients with Parkinson disease are at risk for both OSA and hypotension, making them generally an exception to the association of OSA with hypertension.³

4. The home overnight OSA test often consists of a pulse oximeter worn for 8 hours at night, taped to a finger.⁴ This simple, inexpensive test for OSA detects episodes of apnea or hypopnea that result in arterial desaturation. Is it beneficial to also document episodes of apnea or hypopnea that do not result in arterial desaturation? These episodes are included in the 17% false-negative rate for home OSA testing mentioned in the text. Are these episodes important clinically, other than for prognosis in patients who may go on to develop apneic episodes severe enough to cause desaturation?

5. Lastly, the authors may wish to comment on the importance of diagnosing and treating OSA in patients who plan to have elective surgery under general anesthesia, which can lead to profound sleep apnea in the recovery room, with associated morbidity and death.⁵

To the Editor: Thanks for the concise review of obstructive sleep apnea (OSA) in the January 2016 issue.¹ I offer the following comments and questions:

1. Risk factors for OSA include large neck circumference, which in Table 1 is defined as larger than 40 cm (15.75 inches), which would include shirt collar sizes 16 and above. In the second paragraph of the text, large neck circumference is defined as greater than 17 inches in men, which would include collar sizes above 17. The definition of a large neck as larger than 40 cm must obviously be more sensitive for predicting OSA, and the definition of greater than 17 inches more specific. Which do the authors use in clinical practice?

2. The American Academy of Sleep Medicine is quoted as recommending home OSA screening “if direct monitoring of the response to non-[continuous positive airway pressure] treatments for sleep apnea is needed.”² However, the need for direct monitoring would seem to be a contraindication to home testing rather than an indication. If this statement is correct as written, would the authors explain why and how specific non-CPAP treatments for OSA are more amenable to monitoring at home than in the sleep lab?

3. Patients with Parkinson disease are at risk for both OSA and hypotension, making them generally an exception to the association of OSA with hypertension.³

4. The home overnight OSA test often consists of a pulse oximeter worn for 8 hours at night, taped to a finger.⁴ This simple, inexpensive test for OSA detects episodes of apnea or hypopnea that result in arterial desaturation. Is it beneficial to also document episodes of apnea or hypopnea that do not result in arterial desaturation? These episodes are included in the 17% false-negative rate for home OSA testing mentioned in the text. Are these episodes important clinically, other than for prognosis in patients who may go on to develop apneic episodes severe enough to cause desaturation?

5. Lastly, the authors may wish to comment on the importance of diagnosing and treating OSA in patients who plan to have elective surgery under general anesthesia, which can lead to profound sleep apnea in the recovery room, with associated morbidity and death.⁵

To the Editor: Regarding the excellent review on reducing the risk of injurious falls in older adults,¹ I would like to inquire whether the authors believe that fall-prone patients might benefit by wearing a bicycle helmet during some or all routine activities. Bicycle helmets are comfortable and lightweight, allow air circulation, and are designed to reduce the severity of head injury sustained in a fall or collision.

To the Editor: Regarding the excellent review on reducing the risk of injurious falls in older adults,¹ I would like to inquire whether the authors believe that fall-prone patients might benefit by wearing a bicycle helmet during some or all routine activities. Bicycle helmets are comfortable and lightweight, allow air circulation, and are designed to reduce the severity of head injury sustained in a fall or collision.

To the Editor: Regarding the excellent review on reducing the risk of injurious falls in older adults,¹ I would like to inquire whether the authors believe that fall-prone patients might benefit by wearing a bicycle helmet during some or all routine activities. Bicycle helmets are comfortable and lightweight, allow air circulation, and are designed to reduce the severity of head injury sustained in a fall or collision.

To the Editor: I enjoyed the dermatology update in the May 2015 issue.¹ I would like to inquire about the clinical management of the patient in case 3, a 58-year­old man with biopsy-proven malignant melanoma surrounded by intense inflammatory infiltrate. The tumor was excised with standard margins, but distal metastases developed 2 years later. The depth of invasion of the primary tumor was not revealed, but could this patient have benefited from sentinel lymph node biopsy immediately after the initial excision?

To the Editor: I enjoyed the dermatology update in the May 2015 issue.¹ I would like to inquire about the clinical management of the patient in case 3, a 58-year­old man with biopsy-proven malignant melanoma surrounded by intense inflammatory infiltrate. The tumor was excised with standard margins, but distal metastases developed 2 years later. The depth of invasion of the primary tumor was not revealed, but could this patient have benefited from sentinel lymph node biopsy immediately after the initial excision?

To the Editor: I enjoyed the dermatology update in the May 2015 issue.¹ I would like to inquire about the clinical management of the patient in case 3, a 58-year­old man with biopsy-proven malignant melanoma surrounded by intense inflammatory infiltrate. The tumor was excised with standard margins, but distal metastases developed 2 years later. The depth of invasion of the primary tumor was not revealed, but could this patient have benefited from sentinel lymph node biopsy immediately after the initial excision?

To the Editor: Question 1 of the December 2013 CME test “Can an ARB be given to patients who have had angioedema on an ACE inhibitor?” presents the case of a 73-year-old woman with angioedema thought to be due to her taking enalapril; in addition, she takes hydrochlorothiazide. Her blood pressure is 118/72 mm Hg, and her heart rate is not specified. The question is what the next best step would be to manage her blood pressure medications. The “correct” answer is given as “substitute metoprolol for enalapril in her regimen.”

While this answer is the best choice given, I would take issue with it for two reasons. First, many elderly hypertension patients are overmedicated. With a blood pressure of 118/72 on two medications, it is entirely possible that she may not need to replace the enalapril with any other medication to maintain her pressure below the new JNC 8 threshold of 150/90 for the elderly, or even the 140/90 level specified in other guidelines.

I would recheck her pressure daily on her diuretic alone before adding back a second medication. If she does require a second blood pressure medication, JNC 8 (in agreement with other recent guidelines) recommends adding a calcium channel blocker. Beta-blockers are not recommended by any recent guidelines for first-line or second-line treatment of hypertension for elderly patients without special indications, such as tachyarrhythmias or history of myocardial infarction. No special indications for a beta-blocker were mentioned in this case. Indeed, elderly hypertensive patients often have slow-normal heart rates, or even mild resting bradycardia, which would make the addition of metoprolol contraindicated and potentially dangerous.

To the Editor: Question 1 of the December 2013 CME test “Can an ARB be given to patients who have had angioedema on an ACE inhibitor?” presents the case of a 73-year-old woman with angioedema thought to be due to her taking enalapril; in addition, she takes hydrochlorothiazide. Her blood pressure is 118/72 mm Hg, and her heart rate is not specified. The question is what the next best step would be to manage her blood pressure medications. The “correct” answer is given as “substitute metoprolol for enalapril in her regimen.”

While this answer is the best choice given, I would take issue with it for two reasons. First, many elderly hypertension patients are overmedicated. With a blood pressure of 118/72 on two medications, it is entirely possible that she may not need to replace the enalapril with any other medication to maintain her pressure below the new JNC 8 threshold of 150/90 for the elderly, or even the 140/90 level specified in other guidelines.

I would recheck her pressure daily on her diuretic alone before adding back a second medication. If she does require a second blood pressure medication, JNC 8 (in agreement with other recent guidelines) recommends adding a calcium channel blocker. Beta-blockers are not recommended by any recent guidelines for first-line or second-line treatment of hypertension for elderly patients without special indications, such as tachyarrhythmias or history of myocardial infarction. No special indications for a beta-blocker were mentioned in this case. Indeed, elderly hypertensive patients often have slow-normal heart rates, or even mild resting bradycardia, which would make the addition of metoprolol contraindicated and potentially dangerous.

To the Editor: Question 1 of the December 2013 CME test “Can an ARB be given to patients who have had angioedema on an ACE inhibitor?” presents the case of a 73-year-old woman with angioedema thought to be due to her taking enalapril; in addition, she takes hydrochlorothiazide. Her blood pressure is 118/72 mm Hg, and her heart rate is not specified. The question is what the next best step would be to manage her blood pressure medications. The “correct” answer is given as “substitute metoprolol for enalapril in her regimen.”

While this answer is the best choice given, I would take issue with it for two reasons. First, many elderly hypertension patients are overmedicated. With a blood pressure of 118/72 on two medications, it is entirely possible that she may not need to replace the enalapril with any other medication to maintain her pressure below the new JNC 8 threshold of 150/90 for the elderly, or even the 140/90 level specified in other guidelines.

I would recheck her pressure daily on her diuretic alone before adding back a second medication. If she does require a second blood pressure medication, JNC 8 (in agreement with other recent guidelines) recommends adding a calcium channel blocker. Beta-blockers are not recommended by any recent guidelines for first-line or second-line treatment of hypertension for elderly patients without special indications, such as tachyarrhythmias or history of myocardial infarction. No special indications for a beta-blocker were mentioned in this case. Indeed, elderly hypertensive patients often have slow-normal heart rates, or even mild resting bradycardia, which would make the addition of metoprolol contraindicated and potentially dangerous.

To the Editor: In a recent CCJM review of canagliflozin,¹ this novel antihyperglycemic medication was noted to be associated with a dose-dependent increase in low-density lipoprotein (LDL) cholesterol, with an increase in LDL of 8.3 mg/dL (0.215 mmol/L) seen with the 300-mg/day dose of canagliflozin.

The Cholesterol Treatment Trialists’ (CTT) meta-analysis² showed a significant 21% proportional reduction in major vascular events per 1.0 mmol/L reduction in LDL cholesterol in people with diabetes treated with statins over an average of 4.3 years. If we assume that raising LDL cholesterol by 1.0 mmol/L has the opposite effect, then patients taking 300 mg per day of canagliflozin would be expected to suffer an increase in major vascular events of about 4.5% over 4.3 years. Put another way, for every 22 diabetic patients treated with canagliflozin over 4.3 years, one additional major vascular event would be expected on the basis of the associated increase in LDL cholesterol.

The CTT data also showed a significant 9% decrease in all-cause mortality for every 1.0 mmol/L decrease in LDL cholesterol. Again, assuming that raising LDL has the opposite effect of lowering it, then we should expect an additional death for each 52 diabetic patients treated with 300 mg/day of canagliflozin per day for 4.3 years.

The hypotensive side effect of canagliflozin might tend to mitigate some of the above adverse effects, as might its antihyperglycemic effect. Still, it would seem prudent to use this novel agent only as a second- or third-line choice, particularly in diabetic patients who have already suffered a major vascular event.

To the Editor: In a recent CCJM review of canagliflozin,¹ this novel antihyperglycemic medication was noted to be associated with a dose-dependent increase in low-density lipoprotein (LDL) cholesterol, with an increase in LDL of 8.3 mg/dL (0.215 mmol/L) seen with the 300-mg/day dose of canagliflozin.

The Cholesterol Treatment Trialists’ (CTT) meta-analysis² showed a significant 21% proportional reduction in major vascular events per 1.0 mmol/L reduction in LDL cholesterol in people with diabetes treated with statins over an average of 4.3 years. If we assume that raising LDL cholesterol by 1.0 mmol/L has the opposite effect, then patients taking 300 mg per day of canagliflozin would be expected to suffer an increase in major vascular events of about 4.5% over 4.3 years. Put another way, for every 22 diabetic patients treated with canagliflozin over 4.3 years, one additional major vascular event would be expected on the basis of the associated increase in LDL cholesterol.

The CTT data also showed a significant 9% decrease in all-cause mortality for every 1.0 mmol/L decrease in LDL cholesterol. Again, assuming that raising LDL has the opposite effect of lowering it, then we should expect an additional death for each 52 diabetic patients treated with 300 mg/day of canagliflozin per day for 4.3 years.

The hypotensive side effect of canagliflozin might tend to mitigate some of the above adverse effects, as might its antihyperglycemic effect. Still, it would seem prudent to use this novel agent only as a second- or third-line choice, particularly in diabetic patients who have already suffered a major vascular event.

To the Editor: In a recent CCJM review of canagliflozin,¹ this novel antihyperglycemic medication was noted to be associated with a dose-dependent increase in low-density lipoprotein (LDL) cholesterol, with an increase in LDL of 8.3 mg/dL (0.215 mmol/L) seen with the 300-mg/day dose of canagliflozin.

The Cholesterol Treatment Trialists’ (CTT) meta-analysis² showed a significant 21% proportional reduction in major vascular events per 1.0 mmol/L reduction in LDL cholesterol in people with diabetes treated with statins over an average of 4.3 years. If we assume that raising LDL cholesterol by 1.0 mmol/L has the opposite effect, then patients taking 300 mg per day of canagliflozin would be expected to suffer an increase in major vascular events of about 4.5% over 4.3 years. Put another way, for every 22 diabetic patients treated with canagliflozin over 4.3 years, one additional major vascular event would be expected on the basis of the associated increase in LDL cholesterol.

The CTT data also showed a significant 9% decrease in all-cause mortality for every 1.0 mmol/L decrease in LDL cholesterol. Again, assuming that raising LDL has the opposite effect of lowering it, then we should expect an additional death for each 52 diabetic patients treated with 300 mg/day of canagliflozin per day for 4.3 years.

The hypotensive side effect of canagliflozin might tend to mitigate some of the above adverse effects, as might its antihyperglycemic effect. Still, it would seem prudent to use this novel agent only as a second- or third-line choice, particularly in diabetic patients who have already suffered a major vascular event.

To the Editor: I was somewhat confused by the Clinical Picture case in the May 2013 issue.¹ The caption for Figure 1 stated that the MRI showed erosions and marrow edema, which were “asymmetrical compared with the other wrist, a finding highly suggestive of rheumatoid arthritis.” However, rheumatoid arthritis is generally considered to be symmetrical.² Was this a typographical error, or did I miss a crucial concept somewhere?

To the Editor: I was somewhat confused by the Clinical Picture case in the May 2013 issue.¹ The caption for Figure 1 stated that the MRI showed erosions and marrow edema, which were “asymmetrical compared with the other wrist, a finding highly suggestive of rheumatoid arthritis.” However, rheumatoid arthritis is generally considered to be symmetrical.² Was this a typographical error, or did I miss a crucial concept somewhere?

To the Editor: I was somewhat confused by the Clinical Picture case in the May 2013 issue.¹ The caption for Figure 1 stated that the MRI showed erosions and marrow edema, which were “asymmetrical compared with the other wrist, a finding highly suggestive of rheumatoid arthritis.” However, rheumatoid arthritis is generally considered to be symmetrical.² Was this a typographical error, or did I miss a crucial concept somewhere?

To the Editor: The discussion by Gennari and colleagues¹ on how to obtain certification from the National Committee for Quality Assurance (NCQA) for a geriatric patient-centered medical home was very timely and instructive. The great effort that must be put into getting one’s practice certified was thoroughly documented.

Some community-based physicians will not require financial incentives to undertake this laborious process, finding sufficient reward in continuous quality improvement. However, economic reality dictates that time spent on certification must be taken away from other, productive (ie, income-generating) activities. Therefore, it is reasonable to ask what kind of financial incentives will be provided to physicians who obtain NCQA certification, and which organization or entity will pay for these incentives.

To the Editor: The discussion by Gennari and colleagues¹ on how to obtain certification from the National Committee for Quality Assurance (NCQA) for a geriatric patient-centered medical home was very timely and instructive. The great effort that must be put into getting one’s practice certified was thoroughly documented.

Some community-based physicians will not require financial incentives to undertake this laborious process, finding sufficient reward in continuous quality improvement. However, economic reality dictates that time spent on certification must be taken away from other, productive (ie, income-generating) activities. Therefore, it is reasonable to ask what kind of financial incentives will be provided to physicians who obtain NCQA certification, and which organization or entity will pay for these incentives.

To the Editor: The discussion by Gennari and colleagues¹ on how to obtain certification from the National Committee for Quality Assurance (NCQA) for a geriatric patient-centered medical home was very timely and instructive. The great effort that must be put into getting one’s practice certified was thoroughly documented.

Some community-based physicians will not require financial incentives to undertake this laborious process, finding sufficient reward in continuous quality improvement. However, economic reality dictates that time spent on certification must be taken away from other, productive (ie, income-generating) activities. Therefore, it is reasonable to ask what kind of financial incentives will be provided to physicians who obtain NCQA certification, and which organization or entity will pay for these incentives.

To the Editor: I have the following comments and questions regarding the excellent Medical Grand Rounds article on Parkinson disease by Dr. Fernandez in your January 2012 issue.¹

The author mentions that when “cost may be of concern, levodopa is the preferred starting drug.”¹ Generic versions of pramipexole and ropinirole are now available and have made these medications more affordable. For example, the cash price of generic ropinirole 5 mg was recently $66 for 100 tablets, comparable with generic carbidopa/levodopa (25/100 mg priced at $46 for 100 tablets.² And even though the price of generic pramipexole was $240 for 90 tablets, seniors with Medicare Part D drug coverage can usually get any generic medication for a low copay.

When choosing a dopamine agonist, how does Dr. Fernandez decide between ropinirole and pramipexole (aside from the price difference noted above)? Pramipexole has a longer elimination half-life (8 to 12 hours) compared with ropinirole (6 hours).³ Does this imply a significantly longer effective dosing interval for pramipexole? Are there other significant clinical differences between these agents?

Isradipine (DynaCirc CR), a dihydropyridine calcium channel blocker, has shown promise as a neuroprotective agent for slowing the progression of Parkinson disease in epidemiologic and laboratory studies, as noted by the author. In addition, immediate-release isradipine, with its relatively short elimination half-life of 8 hours,³ may be well suited for treating Parkinson patients whose essential hypertension is complicated by episodes of orthostatic hypotension. It should be noted that dihydropyridines that do not cross the blood-brain barrier (such as amlodipine [Norvasc]) have shown no evidence of neuroprotection.

Ibuprofen is another drug that has fairly strong epidemiologic and laboratory evidence that it might be neuroprotective,⁴ although the other nonsteroidal anti-inflammatory drugs (NSAIDs) have proven disappointing as a class.⁵ Lacking any prospective randomized trials, the evidence is not strong enough to recommend ibuprofen solely for neuroprotection. Does Dr. Fernandez, however, consider it reasonable to suggest ibuprofen to Parkinson patients who need to take an NSAID for an approved indication (such as pain)?

Dexpramipexole has recently demonstrated great promise in a phase 3 clinical trial as a neuroprotective agent in amyotrophic lateral sclerosis.⁶ How does this compound relate to pramipexole, and does the author believe it may offer neuroprotection in other neurodegenerative diseases like Parkinson disease?

The author discusses the use of catechol-O-methyltransferase (COMT) inhibitors (such as Comtan and Tasmar) and the monoamine oxidase (MAO) type-B inhibitors rasagiline (Azilect) and selegiline (Eldepryl, Zelapar) for prolonging the effects of levodopa by slowing the breakdown of dopamine. However, it is important to note that it is contraindicated to prescribe both a COMT inhibitor and an MAO-B inhibitor, because these agents also inhibit the breakdown of other catecholamines and can lead to adrenergic crisis when taken concomitantly.

To the Editor: I have the following comments and questions regarding the excellent Medical Grand Rounds article on Parkinson disease by Dr. Fernandez in your January 2012 issue.¹

The author mentions that when “cost may be of concern, levodopa is the preferred starting drug.”¹ Generic versions of pramipexole and ropinirole are now available and have made these medications more affordable. For example, the cash price of generic ropinirole 5 mg was recently $66 for 100 tablets, comparable with generic carbidopa/levodopa (25/100 mg priced at $46 for 100 tablets.² And even though the price of generic pramipexole was $240 for 90 tablets, seniors with Medicare Part D drug coverage can usually get any generic medication for a low copay.

When choosing a dopamine agonist, how does Dr. Fernandez decide between ropinirole and pramipexole (aside from the price difference noted above)? Pramipexole has a longer elimination half-life (8 to 12 hours) compared with ropinirole (6 hours).³ Does this imply a significantly longer effective dosing interval for pramipexole? Are there other significant clinical differences between these agents?

Isradipine (DynaCirc CR), a dihydropyridine calcium channel blocker, has shown promise as a neuroprotective agent for slowing the progression of Parkinson disease in epidemiologic and laboratory studies, as noted by the author. In addition, immediate-release isradipine, with its relatively short elimination half-life of 8 hours,³ may be well suited for treating Parkinson patients whose essential hypertension is complicated by episodes of orthostatic hypotension. It should be noted that dihydropyridines that do not cross the blood-brain barrier (such as amlodipine [Norvasc]) have shown no evidence of neuroprotection.

Ibuprofen is another drug that has fairly strong epidemiologic and laboratory evidence that it might be neuroprotective,⁴ although the other nonsteroidal anti-inflammatory drugs (NSAIDs) have proven disappointing as a class.⁵ Lacking any prospective randomized trials, the evidence is not strong enough to recommend ibuprofen solely for neuroprotection. Does Dr. Fernandez, however, consider it reasonable to suggest ibuprofen to Parkinson patients who need to take an NSAID for an approved indication (such as pain)?

Dexpramipexole has recently demonstrated great promise in a phase 3 clinical trial as a neuroprotective agent in amyotrophic lateral sclerosis.⁶ How does this compound relate to pramipexole, and does the author believe it may offer neuroprotection in other neurodegenerative diseases like Parkinson disease?

The author discusses the use of catechol-O-methyltransferase (COMT) inhibitors (such as Comtan and Tasmar) and the monoamine oxidase (MAO) type-B inhibitors rasagiline (Azilect) and selegiline (Eldepryl, Zelapar) for prolonging the effects of levodopa by slowing the breakdown of dopamine. However, it is important to note that it is contraindicated to prescribe both a COMT inhibitor and an MAO-B inhibitor, because these agents also inhibit the breakdown of other catecholamines and can lead to adrenergic crisis when taken concomitantly.

To the Editor: I have the following comments and questions regarding the excellent Medical Grand Rounds article on Parkinson disease by Dr. Fernandez in your January 2012 issue.¹

The author mentions that when “cost may be of concern, levodopa is the preferred starting drug.”¹ Generic versions of pramipexole and ropinirole are now available and have made these medications more affordable. For example, the cash price of generic ropinirole 5 mg was recently $66 for 100 tablets, comparable with generic carbidopa/levodopa (25/100 mg priced at $46 for 100 tablets.² And even though the price of generic pramipexole was $240 for 90 tablets, seniors with Medicare Part D drug coverage can usually get any generic medication for a low copay.

When choosing a dopamine agonist, how does Dr. Fernandez decide between ropinirole and pramipexole (aside from the price difference noted above)? Pramipexole has a longer elimination half-life (8 to 12 hours) compared with ropinirole (6 hours).³ Does this imply a significantly longer effective dosing interval for pramipexole? Are there other significant clinical differences between these agents?

Isradipine (DynaCirc CR), a dihydropyridine calcium channel blocker, has shown promise as a neuroprotective agent for slowing the progression of Parkinson disease in epidemiologic and laboratory studies, as noted by the author. In addition, immediate-release isradipine, with its relatively short elimination half-life of 8 hours,³ may be well suited for treating Parkinson patients whose essential hypertension is complicated by episodes of orthostatic hypotension. It should be noted that dihydropyridines that do not cross the blood-brain barrier (such as amlodipine [Norvasc]) have shown no evidence of neuroprotection.

Ibuprofen is another drug that has fairly strong epidemiologic and laboratory evidence that it might be neuroprotective,⁴ although the other nonsteroidal anti-inflammatory drugs (NSAIDs) have proven disappointing as a class.⁵ Lacking any prospective randomized trials, the evidence is not strong enough to recommend ibuprofen solely for neuroprotection. Does Dr. Fernandez, however, consider it reasonable to suggest ibuprofen to Parkinson patients who need to take an NSAID for an approved indication (such as pain)?

Dexpramipexole has recently demonstrated great promise in a phase 3 clinical trial as a neuroprotective agent in amyotrophic lateral sclerosis.⁶ How does this compound relate to pramipexole, and does the author believe it may offer neuroprotection in other neurodegenerative diseases like Parkinson disease?

The author discusses the use of catechol-O-methyltransferase (COMT) inhibitors (such as Comtan and Tasmar) and the monoamine oxidase (MAO) type-B inhibitors rasagiline (Azilect) and selegiline (Eldepryl, Zelapar) for prolonging the effects of levodopa by slowing the breakdown of dopamine. However, it is important to note that it is contraindicated to prescribe both a COMT inhibitor and an MAO-B inhibitor, because these agents also inhibit the breakdown of other catecholamines and can lead to adrenergic crisis when taken concomitantly.

To the Editor: In their thorough review of essential tremor,¹Drs. Abboud, Ahmed, and Fernandez make a statement that needs clarification. In their list of absolute contraindications to propranolol (Inderal), the authors include “concurrent use of a calcium channel blocker.” This warning applies only to the nondihydropyridine calcium channel blockers, which are diltiazem (Cardizem) and verapamil (Calan). These two medications slow the heart rate and generally should not be combined with beta-blockers such as propranolol unless the patient requires this combination to control tachycardia. Most calcium channel blockers are dihydropyridines, which include amlodipine (Norvasc), nifedipine (Procardia), felodipine (Plendil), nisoldipine (Sular), isradipine (DynaCirc CR), and nicardipine (Cardene). These agents do not slow the heart rate significantly and therefore can be used freely in combination with propranolol. Of course, the dose of the calcium channel blocker may need to be decreased because of the antihypertensive effect of propranolol.

To the Editor: In their thorough review of essential tremor,¹Drs. Abboud, Ahmed, and Fernandez make a statement that needs clarification. In their list of absolute contraindications to propranolol (Inderal), the authors include “concurrent use of a calcium channel blocker.” This warning applies only to the nondihydropyridine calcium channel blockers, which are diltiazem (Cardizem) and verapamil (Calan). These two medications slow the heart rate and generally should not be combined with beta-blockers such as propranolol unless the patient requires this combination to control tachycardia. Most calcium channel blockers are dihydropyridines, which include amlodipine (Norvasc), nifedipine (Procardia), felodipine (Plendil), nisoldipine (Sular), isradipine (DynaCirc CR), and nicardipine (Cardene). These agents do not slow the heart rate significantly and therefore can be used freely in combination with propranolol. Of course, the dose of the calcium channel blocker may need to be decreased because of the antihypertensive effect of propranolol.

To the Editor: In their thorough review of essential tremor,¹Drs. Abboud, Ahmed, and Fernandez make a statement that needs clarification. In their list of absolute contraindications to propranolol (Inderal), the authors include “concurrent use of a calcium channel blocker.” This warning applies only to the nondihydropyridine calcium channel blockers, which are diltiazem (Cardizem) and verapamil (Calan). These two medications slow the heart rate and generally should not be combined with beta-blockers such as propranolol unless the patient requires this combination to control tachycardia. Most calcium channel blockers are dihydropyridines, which include amlodipine (Norvasc), nifedipine (Procardia), felodipine (Plendil), nisoldipine (Sular), isradipine (DynaCirc CR), and nicardipine (Cardene). These agents do not slow the heart rate significantly and therefore can be used freely in combination with propranolol. Of course, the dose of the calcium channel blocker may need to be decreased because of the antihypertensive effect of propranolol.

To the Editor: Drs. Lansang and Hustak¹ provide a comprehensive and useful review of steroid-induced diabetes and adrenal suppression.

In their section on local steroids, they discuss the side effects of topical and inhaled glucocorticosteroids. Much has been made of the fact that certain steroids, such as mometasone (Elocon, Nasonex) and fluticasone (Flonase), have a higher “therapeutic index” or ratio of local anti-inflammatory effect to systemic side effects, due to extensive hepatic first-pass metabolism, than older agents such as beclomethasone (Qvar) and betamethasone (Diprosone).² Ciclesonide (Alvesco, Omnaris), a newer inhaled steroid, is said to have an enhanced therapeutic index because it is a prodrug that is activated by metabolism in the lungs; it reportedly has an even less suppressive effect on hypothalamic-pituitaryadrenal axis function.³

Are the authors aware of any other evidence that clinical outcome, such as adrenal suppression or hyperglycemia, is improved by the use of steroids with a higher therapeutic index?

To the Editor: Drs. Lansang and Hustak¹ provide a comprehensive and useful review of steroid-induced diabetes and adrenal suppression.

In their section on local steroids, they discuss the side effects of topical and inhaled glucocorticosteroids. Much has been made of the fact that certain steroids, such as mometasone (Elocon, Nasonex) and fluticasone (Flonase), have a higher “therapeutic index” or ratio of local anti-inflammatory effect to systemic side effects, due to extensive hepatic first-pass metabolism, than older agents such as beclomethasone (Qvar) and betamethasone (Diprosone).² Ciclesonide (Alvesco, Omnaris), a newer inhaled steroid, is said to have an enhanced therapeutic index because it is a prodrug that is activated by metabolism in the lungs; it reportedly has an even less suppressive effect on hypothalamic-pituitaryadrenal axis function.³

Are the authors aware of any other evidence that clinical outcome, such as adrenal suppression or hyperglycemia, is improved by the use of steroids with a higher therapeutic index?

To the Editor: Drs. Lansang and Hustak¹ provide a comprehensive and useful review of steroid-induced diabetes and adrenal suppression.

In their section on local steroids, they discuss the side effects of topical and inhaled glucocorticosteroids. Much has been made of the fact that certain steroids, such as mometasone (Elocon, Nasonex) and fluticasone (Flonase), have a higher “therapeutic index” or ratio of local anti-inflammatory effect to systemic side effects, due to extensive hepatic first-pass metabolism, than older agents such as beclomethasone (Qvar) and betamethasone (Diprosone).² Ciclesonide (Alvesco, Omnaris), a newer inhaled steroid, is said to have an enhanced therapeutic index because it is a prodrug that is activated by metabolism in the lungs; it reportedly has an even less suppressive effect on hypothalamic-pituitaryadrenal axis function.³

Are the authors aware of any other evidence that clinical outcome, such as adrenal suppression or hyperglycemia, is improved by the use of steroids with a higher therapeutic index?