Plasmodium parasite

infecting a red blood cell

Image courtesy of St. Jude

Children’s Research Hospital

Research published in PNAS helps explain how the malaria parasite Plasmodium falciparum undergoes the changes that enable transmission of the parasite from humans to mosquitoes.

Investigators determined how the parasite transforms its own structure and the structure of a host red blood cell so the parasite can hide from the body’s normal defenses and later re-enter the bloodstream for transmission via mosquito bite.

The team believes that, by understanding this process, it may be possible to inhibit the blood cell’s transformation.

“Once you understand the molecular mechanisms, it becomes easier to find drugs to target them,” said Sulin Zhang, PhD, of Pennsylvania State University in University Park.

Dr Zhang developed the computational methods used to understand the physical transformations in the infected red blood cells that allow them to avoid removal in the spleen and prepare for transmission to a mosquito host.

He and his colleagues knew that healthy red blood cells are able to squeeze through small slits in the spleen, but damaged and aging red blood cells cannot and are filtered out and removed from the circulation.

To avoid this fate, the sexual stage malaria parasite first makes the red blood cell rigid and hides out in deep tissue. Then, when the parasite is mature, the infected red blood cells become flexible and elastic, ready to be picked up by a mosquito for disease transmission.

To understand these changes, the investigators prepared samples of parasites at each stage and studied the changing microstructure using atomic force microscopy.

This revealed changes in the organization of a meshwork of tiny spring-like proteins in the blood cell membrane. When the parasite is ready for transmission, it reverses the structural changes.

The team then turned to Dr Zhang, who developed a model to explain how subtle changes to the molecular structure of the spring-like proteins were sufficient to make the red blood cell either rigid or flexible.

The investigators are continuing to use Dr Zhang’s model to simulate the overall shapes and the flow dynamics of infected red blood cells in the bloodstream, providing information that could aid researchers looking to inhibit the malaria parasite’s spread.

Plasmodium parasite

infecting a red blood cell

Image courtesy of St. Jude

Children’s Research Hospital

Research published in PNAS helps explain how the malaria parasite Plasmodium falciparum undergoes the changes that enable transmission of the parasite from humans to mosquitoes.

Investigators determined how the parasite transforms its own structure and the structure of a host red blood cell so the parasite can hide from the body’s normal defenses and later re-enter the bloodstream for transmission via mosquito bite.

The team believes that, by understanding this process, it may be possible to inhibit the blood cell’s transformation.

“Once you understand the molecular mechanisms, it becomes easier to find drugs to target them,” said Sulin Zhang, PhD, of Pennsylvania State University in University Park.

Dr Zhang developed the computational methods used to understand the physical transformations in the infected red blood cells that allow them to avoid removal in the spleen and prepare for transmission to a mosquito host.

He and his colleagues knew that healthy red blood cells are able to squeeze through small slits in the spleen, but damaged and aging red blood cells cannot and are filtered out and removed from the circulation.

To avoid this fate, the sexual stage malaria parasite first makes the red blood cell rigid and hides out in deep tissue. Then, when the parasite is mature, the infected red blood cells become flexible and elastic, ready to be picked up by a mosquito for disease transmission.

To understand these changes, the investigators prepared samples of parasites at each stage and studied the changing microstructure using atomic force microscopy.

This revealed changes in the organization of a meshwork of tiny spring-like proteins in the blood cell membrane. When the parasite is ready for transmission, it reverses the structural changes.

The team then turned to Dr Zhang, who developed a model to explain how subtle changes to the molecular structure of the spring-like proteins were sufficient to make the red blood cell either rigid or flexible.

The investigators are continuing to use Dr Zhang’s model to simulate the overall shapes and the flow dynamics of infected red blood cells in the bloodstream, providing information that could aid researchers looking to inhibit the malaria parasite’s spread.

Plasmodium parasite

infecting a red blood cell

Image courtesy of St. Jude

Children’s Research Hospital

Research published in PNAS helps explain how the malaria parasite Plasmodium falciparum undergoes the changes that enable transmission of the parasite from humans to mosquitoes.

Investigators determined how the parasite transforms its own structure and the structure of a host red blood cell so the parasite can hide from the body’s normal defenses and later re-enter the bloodstream for transmission via mosquito bite.

The team believes that, by understanding this process, it may be possible to inhibit the blood cell’s transformation.

“Once you understand the molecular mechanisms, it becomes easier to find drugs to target them,” said Sulin Zhang, PhD, of Pennsylvania State University in University Park.

Dr Zhang developed the computational methods used to understand the physical transformations in the infected red blood cells that allow them to avoid removal in the spleen and prepare for transmission to a mosquito host.

He and his colleagues knew that healthy red blood cells are able to squeeze through small slits in the spleen, but damaged and aging red blood cells cannot and are filtered out and removed from the circulation.

To avoid this fate, the sexual stage malaria parasite first makes the red blood cell rigid and hides out in deep tissue. Then, when the parasite is mature, the infected red blood cells become flexible and elastic, ready to be picked up by a mosquito for disease transmission.

To understand these changes, the investigators prepared samples of parasites at each stage and studied the changing microstructure using atomic force microscopy.

This revealed changes in the organization of a meshwork of tiny spring-like proteins in the blood cell membrane. When the parasite is ready for transmission, it reverses the structural changes.

The team then turned to Dr Zhang, who developed a model to explain how subtle changes to the molecular structure of the spring-like proteins were sufficient to make the red blood cell either rigid or flexible.

The investigators are continuing to use Dr Zhang’s model to simulate the overall shapes and the flow dynamics of infected red blood cells in the bloodstream, providing information that could aid researchers looking to inhibit the malaria parasite’s spread.

AMSTERDAM – Further evidence that acetaminophen has limited benefits in patients with osteoarthritis was presented at the World Congress on Osteoarthritis, with authors of a systematic review calling for reconsideration of guidelines recommending the common analgesic as a first-line option.

“[Acetaminophen] provides minimal short-term benefits for people with hip or knee OA,” said presenting author and rheumatologist Dr. David J. Hunter of the University of Sydney. The treatment effects for both pain relief and for improving physical function were smallest in people with knee OA, he said. “In general, the small effect sizes are unlikely to be clinically relevant,” Dr. Hunter observed.

“These are mean differences across large populations in the clinical trials, and there may be certain individuals with knee or hip osteoarthritis that this may not necessarily apply to,” he conceded during a discussion following his presentation, “but I think from the perspective of the recommendations that come from guidelines, we have got to think about what would be do-able in the general population.”

The findings come shortly after the publication of a large meta-analysis of 74 trials evaluating pain-relieving medications that highlighted the ineffectiveness of acetaminophen for OA pain, particularly when compared against diclofenac and other nonsteroidal anti-inflammatory drugs (Lancet. 2016 Mar 17. doi: 10.1016/S0140-6736(16)30002-2).

Dr. Hunter and coworkers searched clinical trial and medical databases from inception to September 2015 for records relating to acetaminophen use in patients with hip or knee OA. Only placebo-controlled, randomized trials were included, and nine records were found that reported 10 trials involving 3,541 patients. Part of the analysis was published in the BMJ last year (BMJ. 2015;350:h1225. doi: 10.1136/bmj.h1225). The last prior systematic review on the topic was published in 2004 (Ann Rheum Dis. 2004;Aug;63[8]:901–7).

Pain scores were converted to a common 0-100 scale with 0 signifying no pain or disability and 100 the worst possible pain or disability and then expressed as a mean difference between the acetaminophen and placebo groups. Physical function scores were pooled to give a standardized mean difference.

There was high-quality evidence that acetaminophen given at a dose of 3-4 g per day had a significant effect on pain and physical function during a short period of more than 2 weeks to less than 3 months and a more immediate time frame of 2 weeks or less, but it was unlikely to be clinically significant, with a mean difference of just –3.14 for pain and a standardized mean difference of –0.12 to –0.15 for physical function. Differences would need to be at least 9 points for pain and greater than 0.2 for physical function to be clinically significant, Dr. Hunter explained.

Four of the trials considered knee OA only. The mean and standardized mean differences between the acetaminophen and placebo groups in those trials was just –1.09 for pain and –0.06 for physical function.

Similar numbers of patients reported being adherent to their assigned treatment group, with less rescue analgesic use in the acetaminophen-treated patients. Although no differences in adverse events, serious adverse events, or withdrawals because of adverse events were seen, there was a higher risk of liver function test (LFT) abnormalities in the acetaminophen-treated patients. The relative risk for abnormal LFTs was 3.79, but the clinical significance of this is uncertain according to the review’s authors.

“Current guidelines consistently recommend [acetaminophen] as the first line of analgesic medication for this condition,” Dr. Hunter said at the meeting, sponsored by the Osteoarthritis Research Society International. “But these results call for reconsideration of these recommendations.”

The results highlight the importance of using other, nonpharmacologic means to manage pain and physical function, the authors conclude, such as lifestyle changes, weight control, and regular physical exercise.

Dr. Hunter had no disclosures relevant to his comments.

AMSTERDAM – Further evidence that acetaminophen has limited benefits in patients with osteoarthritis was presented at the World Congress on Osteoarthritis, with authors of a systematic review calling for reconsideration of guidelines recommending the common analgesic as a first-line option.

“[Acetaminophen] provides minimal short-term benefits for people with hip or knee OA,” said presenting author and rheumatologist Dr. David J. Hunter of the University of Sydney. The treatment effects for both pain relief and for improving physical function were smallest in people with knee OA, he said. “In general, the small effect sizes are unlikely to be clinically relevant,” Dr. Hunter observed.

“These are mean differences across large populations in the clinical trials, and there may be certain individuals with knee or hip osteoarthritis that this may not necessarily apply to,” he conceded during a discussion following his presentation, “but I think from the perspective of the recommendations that come from guidelines, we have got to think about what would be do-able in the general population.”

The findings come shortly after the publication of a large meta-analysis of 74 trials evaluating pain-relieving medications that highlighted the ineffectiveness of acetaminophen for OA pain, particularly when compared against diclofenac and other nonsteroidal anti-inflammatory drugs (Lancet. 2016 Mar 17. doi: 10.1016/S0140-6736(16)30002-2).

Dr. Hunter and coworkers searched clinical trial and medical databases from inception to September 2015 for records relating to acetaminophen use in patients with hip or knee OA. Only placebo-controlled, randomized trials were included, and nine records were found that reported 10 trials involving 3,541 patients. Part of the analysis was published in the BMJ last year (BMJ. 2015;350:h1225. doi: 10.1136/bmj.h1225). The last prior systematic review on the topic was published in 2004 (Ann Rheum Dis. 2004;Aug;63[8]:901–7).

Pain scores were converted to a common 0-100 scale with 0 signifying no pain or disability and 100 the worst possible pain or disability and then expressed as a mean difference between the acetaminophen and placebo groups. Physical function scores were pooled to give a standardized mean difference.

There was high-quality evidence that acetaminophen given at a dose of 3-4 g per day had a significant effect on pain and physical function during a short period of more than 2 weeks to less than 3 months and a more immediate time frame of 2 weeks or less, but it was unlikely to be clinically significant, with a mean difference of just –3.14 for pain and a standardized mean difference of –0.12 to –0.15 for physical function. Differences would need to be at least 9 points for pain and greater than 0.2 for physical function to be clinically significant, Dr. Hunter explained.

Four of the trials considered knee OA only. The mean and standardized mean differences between the acetaminophen and placebo groups in those trials was just –1.09 for pain and –0.06 for physical function.

Similar numbers of patients reported being adherent to their assigned treatment group, with less rescue analgesic use in the acetaminophen-treated patients. Although no differences in adverse events, serious adverse events, or withdrawals because of adverse events were seen, there was a higher risk of liver function test (LFT) abnormalities in the acetaminophen-treated patients. The relative risk for abnormal LFTs was 3.79, but the clinical significance of this is uncertain according to the review’s authors.

“Current guidelines consistently recommend [acetaminophen] as the first line of analgesic medication for this condition,” Dr. Hunter said at the meeting, sponsored by the Osteoarthritis Research Society International. “But these results call for reconsideration of these recommendations.”

The results highlight the importance of using other, nonpharmacologic means to manage pain and physical function, the authors conclude, such as lifestyle changes, weight control, and regular physical exercise.

Dr. Hunter had no disclosures relevant to his comments.

AMSTERDAM – Further evidence that acetaminophen has limited benefits in patients with osteoarthritis was presented at the World Congress on Osteoarthritis, with authors of a systematic review calling for reconsideration of guidelines recommending the common analgesic as a first-line option.

“[Acetaminophen] provides minimal short-term benefits for people with hip or knee OA,” said presenting author and rheumatologist Dr. David J. Hunter of the University of Sydney. The treatment effects for both pain relief and for improving physical function were smallest in people with knee OA, he said. “In general, the small effect sizes are unlikely to be clinically relevant,” Dr. Hunter observed.

“These are mean differences across large populations in the clinical trials, and there may be certain individuals with knee or hip osteoarthritis that this may not necessarily apply to,” he conceded during a discussion following his presentation, “but I think from the perspective of the recommendations that come from guidelines, we have got to think about what would be do-able in the general population.”

The findings come shortly after the publication of a large meta-analysis of 74 trials evaluating pain-relieving medications that highlighted the ineffectiveness of acetaminophen for OA pain, particularly when compared against diclofenac and other nonsteroidal anti-inflammatory drugs (Lancet. 2016 Mar 17. doi: 10.1016/S0140-6736(16)30002-2).

Dr. Hunter and coworkers searched clinical trial and medical databases from inception to September 2015 for records relating to acetaminophen use in patients with hip or knee OA. Only placebo-controlled, randomized trials were included, and nine records were found that reported 10 trials involving 3,541 patients. Part of the analysis was published in the BMJ last year (BMJ. 2015;350:h1225. doi: 10.1136/bmj.h1225). The last prior systematic review on the topic was published in 2004 (Ann Rheum Dis. 2004;Aug;63[8]:901–7).

Pain scores were converted to a common 0-100 scale with 0 signifying no pain or disability and 100 the worst possible pain or disability and then expressed as a mean difference between the acetaminophen and placebo groups. Physical function scores were pooled to give a standardized mean difference.

There was high-quality evidence that acetaminophen given at a dose of 3-4 g per day had a significant effect on pain and physical function during a short period of more than 2 weeks to less than 3 months and a more immediate time frame of 2 weeks or less, but it was unlikely to be clinically significant, with a mean difference of just –3.14 for pain and a standardized mean difference of –0.12 to –0.15 for physical function. Differences would need to be at least 9 points for pain and greater than 0.2 for physical function to be clinically significant, Dr. Hunter explained.

Four of the trials considered knee OA only. The mean and standardized mean differences between the acetaminophen and placebo groups in those trials was just –1.09 for pain and –0.06 for physical function.

Similar numbers of patients reported being adherent to their assigned treatment group, with less rescue analgesic use in the acetaminophen-treated patients. Although no differences in adverse events, serious adverse events, or withdrawals because of adverse events were seen, there was a higher risk of liver function test (LFT) abnormalities in the acetaminophen-treated patients. The relative risk for abnormal LFTs was 3.79, but the clinical significance of this is uncertain according to the review’s authors.

“Current guidelines consistently recommend [acetaminophen] as the first line of analgesic medication for this condition,” Dr. Hunter said at the meeting, sponsored by the Osteoarthritis Research Society International. “But these results call for reconsideration of these recommendations.”

The results highlight the importance of using other, nonpharmacologic means to manage pain and physical function, the authors conclude, such as lifestyle changes, weight control, and regular physical exercise.

Dr. Hunter had no disclosures relevant to his comments.

New Codes for 2016

In 2016, noninvasive imaging in dermatology finally received recognition at the Current Procedural Terminology (CPT) level with the publication of 6 new Category I codes for reflectance confocal microscopy.¹ These new codes are classified under the “Special Dermatological Procedures” section of CPT where codes do not have technical and professional payment splits, unlike pathology codes (Table). Currently, the new codes for reflectance confocal microscopy can only be implemented when using the VivaScope 1500 (Caliber I.D.) reflectance confocal imaging system and not with any other devices. At present, these codes are priced by each insurer and should be payable, as they are Category I codes that meet all criteria for widely used procedures that are well supported by strong evidence.

Additionally, MelaFind (MELA Sciences) has received 2 Category III CPT codes in 2016: 0400T, multispectral digital skin lesion analysis of clinically atypical cutaneous pigmented lesions for detection of melanomas and high-risk melanocytic atypia [1–5 lesions]; 0401T, multispectral digital skin lesion analysis of clinically atypical cutaneous pigmented lesions for detection of melanomas and high-risk melanocytic atypia [≥6 lesions]).

The CPT Professional Edition notes that Category III codes are a set of temporary codes for emerging technology, services, and procedures that allow data collection for these services and procedures.¹ Inclusion implies nothing about safety, efficacy, frequency of use, or payment. These codes are used to differentiate emerging technology from the widely accepted Category I codes and use of alphanumeric characters instead of 5-digit codes. If reading this paragraph makes you giddy all over, pay a visit to the American Medical Association website to learn more about the process by which CPT codes come to life.²

Policy and Coding Changes

Last year saw much sturm and drang with the passage of the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA).³ The MACRA repealed the Sustainable Growth Rate formula and established annual positive or flat-fee updates for 10 years. A 2-tracked fee update was instituted afterward. It also established the Merit-Based Incentive Payment System, which consolidates existing Medicare fee-for-service physician incentive programs, establishes a pathway for physicians to participate in alternative payment models including the patient-centered medical home, and makes a bunch of other changes to existing Medicare physician payment statutes. It is too early to say if and how it will work and if it will change dermatology. It could fail miserably or it could be a brave new world; stay tuned.³

On the coding front, MACRA prohibits across-the-board elimination of global periods that the Centers for Medicare & Medicaid Services (CMS) had previously announced.⁴ Instead, the CMS must develop and implement a process to gather data on services furnished during global periods based on a representative sample of physician data. The CMS can delay up to 5% of payments if it does not get the data it asks for and must work through the rulemaking process, which will impact medicine in 2019. Among our codes with nonzero global periods, the premalignant destruction codes 17000 and 17004, each of which contains the value of a 99212 established patient visit, are at the very apex of the hit list. It is not clear if the CMS will retrospectively pull medical records to evaluate the occurrence of the global visit or will prospectively have us use 99024, the code for a “[p]ostoperative follow-up visit, normally included in the surgical package, to indicate that an evaluation and management service was performed during a postoperative period for a reason(s) related to the original procedure.”¹ This code is not used unless your practice needs a “filler” code for nonreportable visits but that may change. Is this another unfunded mandate? Yes.

Clarifications also have been made for reporting superficial radiation therapy.¹ Treatment delivery using energies below 1 MV are to be reported with CPT code 77401 and cannot be combined with radiation treatment delivery codes (77402, 77407, 77412), clinical treatment planning codes (77261–77263), treatment device development codes (77332–77334), isodose planning codes (77306, 77307, 77316–77318), radiation treatment management codes (77427, 77431, 77432, 77435, 77469, 77470, 77499), continuing medical physics consultation code (77336), and special physics consultation code (77370). Evaluation and management services may still be reported separately, when appropriate, in cases in which only superficial radiation therapy services (ie, 77401) are provided.¹

Electronic brachytherapy for skin cancer has a new Category III tracking code (0394T [high-dose-rate electronic brachytherapy, skin surface application, per fraction, includes basic dosimetry, when performed]) that is priced by the insurer. Noridian Healthcare Solutions pulled the plug on what many perceived as astronomical payments, but changes may be afoot, as its URL for their new policy was down at the time of publication, and there is still great variability in how payment is being made for these codes. For those interested in learning about perception, a visit to http://forums.studentdoctor.net/threads/electronic-brachy.1132531/ is in order, as the economic drivers to the utilization of this therapy are discussed in detail from the perspective of students and young physicians.

Although there are new telehealth codes for inpatient services and end-stage renal disease management, there are still none that are relevant to dermatology.

Place of service codes have been updated. Place of service code 19 refers to “off campus outpatient hospital” settings while place of service code 22 has been revised to “on campus outpatient hospital.” If your practice is a facility, consult the Medicare Claims Processing Manual (20.4.2) on the site of service payment differential for further enlightenment.⁵ Do note that CMS is increasingly interested in physicians who use wrong place of service codes.

Incident to billing rules are somewhat clearer. The physician or other practitioner who bills must be the supervising physician or practitioner. Services cannot be provided by individuals who have been excluded from Medicare, Medicaid, or other federal programs, nor can they be provided by an individual who has had Medicare enrollment revoked. State laws that are more restrictive take precedence.

Of course, the Relative Value Scale Update Committee (RUC) process moves on as always and you likely will receive 1 or more surveys in the near future. If you get one of these surveys, do not delete it. The surveys are the currency of the RUC, and if you give your RUC team bad or no data, the specialty will suffer cuts in valuation of what we do. If you have questions about the survey, contact the American Academy of Dermatology staff as listed in the survey. If you want to learn more about RUC, visit the American Medical Association website.⁶ To see the current relative value units for what dermatologists do and the typical time for these procedures, visit the CMS website, which provides resources that supply tremendous amounts of data on code valuation including documents detailing relative value units for every CPT code.⁷ You also can access current time values for preservice work, intraservice work, and postservice work times for all CPT codes in the entire CPT Professional Edition. They are based on typical times and are the major determinants of what you get paid. Happy reading.

New Codes for 2016

In 2016, noninvasive imaging in dermatology finally received recognition at the Current Procedural Terminology (CPT) level with the publication of 6 new Category I codes for reflectance confocal microscopy.¹ These new codes are classified under the “Special Dermatological Procedures” section of CPT where codes do not have technical and professional payment splits, unlike pathology codes (Table). Currently, the new codes for reflectance confocal microscopy can only be implemented when using the VivaScope 1500 (Caliber I.D.) reflectance confocal imaging system and not with any other devices. At present, these codes are priced by each insurer and should be payable, as they are Category I codes that meet all criteria for widely used procedures that are well supported by strong evidence.

Additionally, MelaFind (MELA Sciences) has received 2 Category III CPT codes in 2016: 0400T, multispectral digital skin lesion analysis of clinically atypical cutaneous pigmented lesions for detection of melanomas and high-risk melanocytic atypia [1–5 lesions]; 0401T, multispectral digital skin lesion analysis of clinically atypical cutaneous pigmented lesions for detection of melanomas and high-risk melanocytic atypia [≥6 lesions]).

The CPT Professional Edition notes that Category III codes are a set of temporary codes for emerging technology, services, and procedures that allow data collection for these services and procedures.¹ Inclusion implies nothing about safety, efficacy, frequency of use, or payment. These codes are used to differentiate emerging technology from the widely accepted Category I codes and use of alphanumeric characters instead of 5-digit codes. If reading this paragraph makes you giddy all over, pay a visit to the American Medical Association website to learn more about the process by which CPT codes come to life.²

Policy and Coding Changes

Last year saw much sturm and drang with the passage of the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA).³ The MACRA repealed the Sustainable Growth Rate formula and established annual positive or flat-fee updates for 10 years. A 2-tracked fee update was instituted afterward. It also established the Merit-Based Incentive Payment System, which consolidates existing Medicare fee-for-service physician incentive programs, establishes a pathway for physicians to participate in alternative payment models including the patient-centered medical home, and makes a bunch of other changes to existing Medicare physician payment statutes. It is too early to say if and how it will work and if it will change dermatology. It could fail miserably or it could be a brave new world; stay tuned.³

On the coding front, MACRA prohibits across-the-board elimination of global periods that the Centers for Medicare & Medicaid Services (CMS) had previously announced.⁴ Instead, the CMS must develop and implement a process to gather data on services furnished during global periods based on a representative sample of physician data. The CMS can delay up to 5% of payments if it does not get the data it asks for and must work through the rulemaking process, which will impact medicine in 2019. Among our codes with nonzero global periods, the premalignant destruction codes 17000 and 17004, each of which contains the value of a 99212 established patient visit, are at the very apex of the hit list. It is not clear if the CMS will retrospectively pull medical records to evaluate the occurrence of the global visit or will prospectively have us use 99024, the code for a “[p]ostoperative follow-up visit, normally included in the surgical package, to indicate that an evaluation and management service was performed during a postoperative period for a reason(s) related to the original procedure.”¹ This code is not used unless your practice needs a “filler” code for nonreportable visits but that may change. Is this another unfunded mandate? Yes.

Clarifications also have been made for reporting superficial radiation therapy.¹ Treatment delivery using energies below 1 MV are to be reported with CPT code 77401 and cannot be combined with radiation treatment delivery codes (77402, 77407, 77412), clinical treatment planning codes (77261–77263), treatment device development codes (77332–77334), isodose planning codes (77306, 77307, 77316–77318), radiation treatment management codes (77427, 77431, 77432, 77435, 77469, 77470, 77499), continuing medical physics consultation code (77336), and special physics consultation code (77370). Evaluation and management services may still be reported separately, when appropriate, in cases in which only superficial radiation therapy services (ie, 77401) are provided.¹

Electronic brachytherapy for skin cancer has a new Category III tracking code (0394T [high-dose-rate electronic brachytherapy, skin surface application, per fraction, includes basic dosimetry, when performed]) that is priced by the insurer. Noridian Healthcare Solutions pulled the plug on what many perceived as astronomical payments, but changes may be afoot, as its URL for their new policy was down at the time of publication, and there is still great variability in how payment is being made for these codes. For those interested in learning about perception, a visit to http://forums.studentdoctor.net/threads/electronic-brachy.1132531/ is in order, as the economic drivers to the utilization of this therapy are discussed in detail from the perspective of students and young physicians.

Although there are new telehealth codes for inpatient services and end-stage renal disease management, there are still none that are relevant to dermatology.

Place of service codes have been updated. Place of service code 19 refers to “off campus outpatient hospital” settings while place of service code 22 has been revised to “on campus outpatient hospital.” If your practice is a facility, consult the Medicare Claims Processing Manual (20.4.2) on the site of service payment differential for further enlightenment.⁵ Do note that CMS is increasingly interested in physicians who use wrong place of service codes.

Incident to billing rules are somewhat clearer. The physician or other practitioner who bills must be the supervising physician or practitioner. Services cannot be provided by individuals who have been excluded from Medicare, Medicaid, or other federal programs, nor can they be provided by an individual who has had Medicare enrollment revoked. State laws that are more restrictive take precedence.

Of course, the Relative Value Scale Update Committee (RUC) process moves on as always and you likely will receive 1 or more surveys in the near future. If you get one of these surveys, do not delete it. The surveys are the currency of the RUC, and if you give your RUC team bad or no data, the specialty will suffer cuts in valuation of what we do. If you have questions about the survey, contact the American Academy of Dermatology staff as listed in the survey. If you want to learn more about RUC, visit the American Medical Association website.⁶ To see the current relative value units for what dermatologists do and the typical time for these procedures, visit the CMS website, which provides resources that supply tremendous amounts of data on code valuation including documents detailing relative value units for every CPT code.⁷ You also can access current time values for preservice work, intraservice work, and postservice work times for all CPT codes in the entire CPT Professional Edition. They are based on typical times and are the major determinants of what you get paid. Happy reading.

New Codes for 2016

In 2016, noninvasive imaging in dermatology finally received recognition at the Current Procedural Terminology (CPT) level with the publication of 6 new Category I codes for reflectance confocal microscopy.¹ These new codes are classified under the “Special Dermatological Procedures” section of CPT where codes do not have technical and professional payment splits, unlike pathology codes (Table). Currently, the new codes for reflectance confocal microscopy can only be implemented when using the VivaScope 1500 (Caliber I.D.) reflectance confocal imaging system and not with any other devices. At present, these codes are priced by each insurer and should be payable, as they are Category I codes that meet all criteria for widely used procedures that are well supported by strong evidence.

Additionally, MelaFind (MELA Sciences) has received 2 Category III CPT codes in 2016: 0400T, multispectral digital skin lesion analysis of clinically atypical cutaneous pigmented lesions for detection of melanomas and high-risk melanocytic atypia [1–5 lesions]; 0401T, multispectral digital skin lesion analysis of clinically atypical cutaneous pigmented lesions for detection of melanomas and high-risk melanocytic atypia [≥6 lesions]).

The CPT Professional Edition notes that Category III codes are a set of temporary codes for emerging technology, services, and procedures that allow data collection for these services and procedures.¹ Inclusion implies nothing about safety, efficacy, frequency of use, or payment. These codes are used to differentiate emerging technology from the widely accepted Category I codes and use of alphanumeric characters instead of 5-digit codes. If reading this paragraph makes you giddy all over, pay a visit to the American Medical Association website to learn more about the process by which CPT codes come to life.²

Policy and Coding Changes

Last year saw much sturm and drang with the passage of the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA).³ The MACRA repealed the Sustainable Growth Rate formula and established annual positive or flat-fee updates for 10 years. A 2-tracked fee update was instituted afterward. It also established the Merit-Based Incentive Payment System, which consolidates existing Medicare fee-for-service physician incentive programs, establishes a pathway for physicians to participate in alternative payment models including the patient-centered medical home, and makes a bunch of other changes to existing Medicare physician payment statutes. It is too early to say if and how it will work and if it will change dermatology. It could fail miserably or it could be a brave new world; stay tuned.³

On the coding front, MACRA prohibits across-the-board elimination of global periods that the Centers for Medicare & Medicaid Services (CMS) had previously announced.⁴ Instead, the CMS must develop and implement a process to gather data on services furnished during global periods based on a representative sample of physician data. The CMS can delay up to 5% of payments if it does not get the data it asks for and must work through the rulemaking process, which will impact medicine in 2019. Among our codes with nonzero global periods, the premalignant destruction codes 17000 and 17004, each of which contains the value of a 99212 established patient visit, are at the very apex of the hit list. It is not clear if the CMS will retrospectively pull medical records to evaluate the occurrence of the global visit or will prospectively have us use 99024, the code for a “[p]ostoperative follow-up visit, normally included in the surgical package, to indicate that an evaluation and management service was performed during a postoperative period for a reason(s) related to the original procedure.”¹ This code is not used unless your practice needs a “filler” code for nonreportable visits but that may change. Is this another unfunded mandate? Yes.

Clarifications also have been made for reporting superficial radiation therapy.¹ Treatment delivery using energies below 1 MV are to be reported with CPT code 77401 and cannot be combined with radiation treatment delivery codes (77402, 77407, 77412), clinical treatment planning codes (77261–77263), treatment device development codes (77332–77334), isodose planning codes (77306, 77307, 77316–77318), radiation treatment management codes (77427, 77431, 77432, 77435, 77469, 77470, 77499), continuing medical physics consultation code (77336), and special physics consultation code (77370). Evaluation and management services may still be reported separately, when appropriate, in cases in which only superficial radiation therapy services (ie, 77401) are provided.¹

Electronic brachytherapy for skin cancer has a new Category III tracking code (0394T [high-dose-rate electronic brachytherapy, skin surface application, per fraction, includes basic dosimetry, when performed]) that is priced by the insurer. Noridian Healthcare Solutions pulled the plug on what many perceived as astronomical payments, but changes may be afoot, as its URL for their new policy was down at the time of publication, and there is still great variability in how payment is being made for these codes. For those interested in learning about perception, a visit to http://forums.studentdoctor.net/threads/electronic-brachy.1132531/ is in order, as the economic drivers to the utilization of this therapy are discussed in detail from the perspective of students and young physicians.

Although there are new telehealth codes for inpatient services and end-stage renal disease management, there are still none that are relevant to dermatology.

Place of service codes have been updated. Place of service code 19 refers to “off campus outpatient hospital” settings while place of service code 22 has been revised to “on campus outpatient hospital.” If your practice is a facility, consult the Medicare Claims Processing Manual (20.4.2) on the site of service payment differential for further enlightenment.⁵ Do note that CMS is increasingly interested in physicians who use wrong place of service codes.

Incident to billing rules are somewhat clearer. The physician or other practitioner who bills must be the supervising physician or practitioner. Services cannot be provided by individuals who have been excluded from Medicare, Medicaid, or other federal programs, nor can they be provided by an individual who has had Medicare enrollment revoked. State laws that are more restrictive take precedence.

Of course, the Relative Value Scale Update Committee (RUC) process moves on as always and you likely will receive 1 or more surveys in the near future. If you get one of these surveys, do not delete it. The surveys are the currency of the RUC, and if you give your RUC team bad or no data, the specialty will suffer cuts in valuation of what we do. If you have questions about the survey, contact the American Academy of Dermatology staff as listed in the survey. If you want to learn more about RUC, visit the American Medical Association website.⁶ To see the current relative value units for what dermatologists do and the typical time for these procedures, visit the CMS website, which provides resources that supply tremendous amounts of data on code valuation including documents detailing relative value units for every CPT code.⁷ You also can access current time values for preservice work, intraservice work, and postservice work times for all CPT codes in the entire CPT Professional Edition. They are based on typical times and are the major determinants of what you get paid. Happy reading.

The Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) have jointly released evidence-based guidelines for implementing an inpatient antibiotic stewardship program.

The guidelines, published April 13 online in Clinical Infectious Diseases, address the optimal use of antibiotics in inpatient populations, and were prepared by a multidisciplinary expert panel of the IDSA and the SHEA, which included representation from the specialties of internal medicine, emergency medicine, microbiology, critical care, surgery, epidemiology, pharmacy, and adult and pediatric infectious diseases.

Antibiotic stewardship has been defined by IDSA, SHEA, and the Pediatric Infectious Diseases Society as “coordinated interventions designed to improve and measure the appropriate use of [antibiotic] agents by promoting the selection of the optimal [antibiotic] drug regimen including dosing, duration of therapy, and route of administration.” The new guidelines discuss a broad range of possible interventions, but the authors emphasize the need “for each site to assess its clinical needs and available resources and individualize its [antibiotic stewardship program] with that assessment in mind.”

The process used in the development of the guidelines included a systematic weighting of the strength of recommendation and quality of evidence using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system, according to Dr. Tamar F. Barlam of the section of infectious diseases at Boston University, and her colleagues.

“The benefits of antibiotic stewardship include improved patient outcomes, reduced adverse events including Clostridium difficile infection, improvement in rates of antibiotic susceptibilities to targeted antibiotics, and optimization of resource utilization across the continuum of care,” Dr. Barlam and her coauthors wrote.

A complete list of any potential conflicts of interest for the multiple coauthors is provided with the full stewardship guidelines, which can be reviewed in Clinical Infectious Diseases (doi: 10.1093/cid/ciw118).

rpizzi@frontlinemedcom.com

On Twitter @richpizzi

The Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) have jointly released evidence-based guidelines for implementing an inpatient antibiotic stewardship program.

The guidelines, published April 13 online in Clinical Infectious Diseases, address the optimal use of antibiotics in inpatient populations, and were prepared by a multidisciplinary expert panel of the IDSA and the SHEA, which included representation from the specialties of internal medicine, emergency medicine, microbiology, critical care, surgery, epidemiology, pharmacy, and adult and pediatric infectious diseases.

Antibiotic stewardship has been defined by IDSA, SHEA, and the Pediatric Infectious Diseases Society as “coordinated interventions designed to improve and measure the appropriate use of [antibiotic] agents by promoting the selection of the optimal [antibiotic] drug regimen including dosing, duration of therapy, and route of administration.” The new guidelines discuss a broad range of possible interventions, but the authors emphasize the need “for each site to assess its clinical needs and available resources and individualize its [antibiotic stewardship program] with that assessment in mind.”

The process used in the development of the guidelines included a systematic weighting of the strength of recommendation and quality of evidence using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system, according to Dr. Tamar F. Barlam of the section of infectious diseases at Boston University, and her colleagues.

“The benefits of antibiotic stewardship include improved patient outcomes, reduced adverse events including Clostridium difficile infection, improvement in rates of antibiotic susceptibilities to targeted antibiotics, and optimization of resource utilization across the continuum of care,” Dr. Barlam and her coauthors wrote.

A complete list of any potential conflicts of interest for the multiple coauthors is provided with the full stewardship guidelines, which can be reviewed in Clinical Infectious Diseases (doi: 10.1093/cid/ciw118).

rpizzi@frontlinemedcom.com

On Twitter @richpizzi

The Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) have jointly released evidence-based guidelines for implementing an inpatient antibiotic stewardship program.

The guidelines, published April 13 online in Clinical Infectious Diseases, address the optimal use of antibiotics in inpatient populations, and were prepared by a multidisciplinary expert panel of the IDSA and the SHEA, which included representation from the specialties of internal medicine, emergency medicine, microbiology, critical care, surgery, epidemiology, pharmacy, and adult and pediatric infectious diseases.

Antibiotic stewardship has been defined by IDSA, SHEA, and the Pediatric Infectious Diseases Society as “coordinated interventions designed to improve and measure the appropriate use of [antibiotic] agents by promoting the selection of the optimal [antibiotic] drug regimen including dosing, duration of therapy, and route of administration.” The new guidelines discuss a broad range of possible interventions, but the authors emphasize the need “for each site to assess its clinical needs and available resources and individualize its [antibiotic stewardship program] with that assessment in mind.”

The process used in the development of the guidelines included a systematic weighting of the strength of recommendation and quality of evidence using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system, according to Dr. Tamar F. Barlam of the section of infectious diseases at Boston University, and her colleagues.

“The benefits of antibiotic stewardship include improved patient outcomes, reduced adverse events including Clostridium difficile infection, improvement in rates of antibiotic susceptibilities to targeted antibiotics, and optimization of resource utilization across the continuum of care,” Dr. Barlam and her coauthors wrote.

A complete list of any potential conflicts of interest for the multiple coauthors is provided with the full stewardship guidelines, which can be reviewed in Clinical Infectious Diseases (doi: 10.1093/cid/ciw118).

rpizzi@frontlinemedcom.com

On Twitter @richpizzi

Patients with severe psoriasis were nearly 70% more likely to develop abdominal aortic aneurysms compared with the general population, according to a Danish population-based cohort study.

The findings augment existing evidence linking psoriasis and cardiovascular diseases, wrote Dr. Usman Khalid of Copenhagen University Herlev and Gentofte Hospital, Denmark. The report was published online April 14 in Arteriosclerosis, Thrombosis, and Vascular Biology.

While the mechanisms for the link are unclear, “emerging evidence suggests that AAA is a focal representation of a systemic disease with a distinct inflammatory component, rather than a mere consequence of atherosclerosis,” wrote Dr. Khalid and his associates.

Several case series have linked AAA with other autoimmune disorders, including systemic lupus erythematosus and rheumatoid arthritis, they noted. Their study comprised nearly 5.5 million adults in Denmark between 1997 and 2011. The researchers identified 59,423 patients with mild psoriasis and 11,566 patients with severe psoriasis (Arterioscler Thromb Vasc Biol. 2016 April 14. doi: 10.1161/ATVBAHA.116.307449).

The incidence of AAA in the reference population was 3.72 cases per 10,000 person-years, with an average follow-up period of 14.4 years. In contrast, the incidence of AAA in patients with mild psoriasis was 7.30 cases per 10,000 person-years, and the rate in patients with severe psoriasis was 9.87 cases of per 10,000 person-years, with average follow-up periods of 5.7 years. Both mild and severe psoriasis were significantly associated with AAA after the researchers accounted for age, sex, comorbidities, medications, socioeconomic status, and smoking, with adjusted incidence rate ratios of 1.20 (95% confidence interval, 1.03-1.39) and 1.67 (95% CI, 1.21-2.32), respectively.

The historical view that AAA is caused mainly by atherosclerosis has largely been upended, the researchers noted. Instead, AAA appears to be a multifactorial process involving inflammation, matrix degradation, thrombosis, and aortic wall stress. Furthermore, inflammation in both AAA and psoriasis is centrally mediated by T-helper-17 cells and interleukin-17. Together, the data suggest that shared inflammatory mechanisms link psoriasis and AAA, especially because the association correlates with psoriatic disease activity, they said. “This finding clearly requires independent replication, and the clinical consequences are unclear at present.”

The LEO Foundation and the Novo Nordisk Foundation funded the study. Dr. Khalid had no disclosures. Four coinvestigators reported financial ties with Abbott, Pfizer, AstraZeneca, Bayer, and several other pharmaceutical companies.

Patients with severe psoriasis were nearly 70% more likely to develop abdominal aortic aneurysms compared with the general population, according to a Danish population-based cohort study.

The findings augment existing evidence linking psoriasis and cardiovascular diseases, wrote Dr. Usman Khalid of Copenhagen University Herlev and Gentofte Hospital, Denmark. The report was published online April 14 in Arteriosclerosis, Thrombosis, and Vascular Biology.

While the mechanisms for the link are unclear, “emerging evidence suggests that AAA is a focal representation of a systemic disease with a distinct inflammatory component, rather than a mere consequence of atherosclerosis,” wrote Dr. Khalid and his associates.

Several case series have linked AAA with other autoimmune disorders, including systemic lupus erythematosus and rheumatoid arthritis, they noted. Their study comprised nearly 5.5 million adults in Denmark between 1997 and 2011. The researchers identified 59,423 patients with mild psoriasis and 11,566 patients with severe psoriasis (Arterioscler Thromb Vasc Biol. 2016 April 14. doi: 10.1161/ATVBAHA.116.307449).

The incidence of AAA in the reference population was 3.72 cases per 10,000 person-years, with an average follow-up period of 14.4 years. In contrast, the incidence of AAA in patients with mild psoriasis was 7.30 cases per 10,000 person-years, and the rate in patients with severe psoriasis was 9.87 cases of per 10,000 person-years, with average follow-up periods of 5.7 years. Both mild and severe psoriasis were significantly associated with AAA after the researchers accounted for age, sex, comorbidities, medications, socioeconomic status, and smoking, with adjusted incidence rate ratios of 1.20 (95% confidence interval, 1.03-1.39) and 1.67 (95% CI, 1.21-2.32), respectively.

The historical view that AAA is caused mainly by atherosclerosis has largely been upended, the researchers noted. Instead, AAA appears to be a multifactorial process involving inflammation, matrix degradation, thrombosis, and aortic wall stress. Furthermore, inflammation in both AAA and psoriasis is centrally mediated by T-helper-17 cells and interleukin-17. Together, the data suggest that shared inflammatory mechanisms link psoriasis and AAA, especially because the association correlates with psoriatic disease activity, they said. “This finding clearly requires independent replication, and the clinical consequences are unclear at present.”

The LEO Foundation and the Novo Nordisk Foundation funded the study. Dr. Khalid had no disclosures. Four coinvestigators reported financial ties with Abbott, Pfizer, AstraZeneca, Bayer, and several other pharmaceutical companies.

Patients with severe psoriasis were nearly 70% more likely to develop abdominal aortic aneurysms compared with the general population, according to a Danish population-based cohort study.

The findings augment existing evidence linking psoriasis and cardiovascular diseases, wrote Dr. Usman Khalid of Copenhagen University Herlev and Gentofte Hospital, Denmark. The report was published online April 14 in Arteriosclerosis, Thrombosis, and Vascular Biology.

While the mechanisms for the link are unclear, “emerging evidence suggests that AAA is a focal representation of a systemic disease with a distinct inflammatory component, rather than a mere consequence of atherosclerosis,” wrote Dr. Khalid and his associates.

Several case series have linked AAA with other autoimmune disorders, including systemic lupus erythematosus and rheumatoid arthritis, they noted. Their study comprised nearly 5.5 million adults in Denmark between 1997 and 2011. The researchers identified 59,423 patients with mild psoriasis and 11,566 patients with severe psoriasis (Arterioscler Thromb Vasc Biol. 2016 April 14. doi: 10.1161/ATVBAHA.116.307449).

The incidence of AAA in the reference population was 3.72 cases per 10,000 person-years, with an average follow-up period of 14.4 years. In contrast, the incidence of AAA in patients with mild psoriasis was 7.30 cases per 10,000 person-years, and the rate in patients with severe psoriasis was 9.87 cases of per 10,000 person-years, with average follow-up periods of 5.7 years. Both mild and severe psoriasis were significantly associated with AAA after the researchers accounted for age, sex, comorbidities, medications, socioeconomic status, and smoking, with adjusted incidence rate ratios of 1.20 (95% confidence interval, 1.03-1.39) and 1.67 (95% CI, 1.21-2.32), respectively.

The historical view that AAA is caused mainly by atherosclerosis has largely been upended, the researchers noted. Instead, AAA appears to be a multifactorial process involving inflammation, matrix degradation, thrombosis, and aortic wall stress. Furthermore, inflammation in both AAA and psoriasis is centrally mediated by T-helper-17 cells and interleukin-17. Together, the data suggest that shared inflammatory mechanisms link psoriasis and AAA, especially because the association correlates with psoriatic disease activity, they said. “This finding clearly requires independent replication, and the clinical consequences are unclear at present.”

The LEO Foundation and the Novo Nordisk Foundation funded the study. Dr. Khalid had no disclosures. Four coinvestigators reported financial ties with Abbott, Pfizer, AstraZeneca, Bayer, and several other pharmaceutical companies.

The best diagnosis is:

a. bronchogenic cyst
b. dermoid cyst
c. epidermal inclusion cyst
d. hidrocystoma
e. steatocystoma

H&E, original magnification ×40.

H&E, original magnification ×100.

Continue to the next page for the diagnosis >>

Dermoid Cyst

Dermoid cysts often present clinically as firm subcutaneous nodules on the head or neck in young children. They tend to arise along the lateral aspect of the eyebrow but also can occur on the nose, forehead, neck, chest, or scalp.¹ Dermoid cysts are thought to arise from the sequestration of ectodermal tissues along the embryonic fusion planes during development.² As such, they represent congenital defects and often are identified at birth; however, some are not noticed until much later when they enlarge or become inflamed or infected. Midline dermoid cysts may be associated with underlying dysraphism or intracranial extension.^3,4 Thus, any midline lesion warrants evaluation that incorporates imaging with computed tomography or magnetic resonance imaging.^4,5 Histologically, dermoid cysts are lined by a keratinizing stratified squamous epithelium (quiz image A), but the lining may be brightly eosinophilic and wavy resembling shark teeth.^1,3 The wall of a dermoid cyst commonly contains mature adnexal structures such as terminal hair follicles, sebaceous glands, apocrine glands, and/or eccrine glands (quiz image B).¹ Smooth muscle also may be seen within the lining; however, bone and cartilage are not commonly reported in dermoid cysts.² Lamellar keratin is typical of the cyst contents, and terminal hair shafts also are sometimes noted within the cystic space (quiz image B).^1,2 Treatment options include excision at the time of diagnosis or close clinical monitoring with subsequent excision if the lesion grows or becomes symptomatic.^4,5 Many practitioners opt to excise these cysts at diagnosis, as untreated lesions are at risk for infection and/or inflammation or may be cosmetically deforming.^6,7 Surgical resection, including removal of the wall of the cyst, is curative and reoccurrence is rare.⁵

Figure 1. Bronchogenic cyst demonstrating a ciliated pseudostratified epithelial lining encircled by smooth muscle (H&E, original magnification ×200).
Figure 2. Epidermal inclusion cyst containing loose lamellar keratin and a lining that closely resembles the surface epidermis (H&E, original magnification ×40).

Bronchogenic cysts demonstrate an epithelial lining that often is pseudostratified cuboidal or columnar as well as ciliated (Figure 1). Goblet cells are present in the lining in approximately 50% of cases. Smooth muscle may be seen circumferentially surrounding the cyst lining, and rare cases also contain cartilage.¹ In contrast to dermoid cysts, other types of adnexal structures are not found within the lining. Bronchogenic cysts that arise in the skin are extremely rare.² These cysts are thought to arise from respiratory epithelium that has been sequestered during embryologic formation of the tracheobronchial tree. They often are seen overlying the suprasternal notch and occasionally are found on the anterior aspect of the neck or chin. These cysts also are present at birth, similar to dermoid cysts.³

Epidermal inclusion cysts have a lining that histologically bears close resemblance to the surface epidermis. These cysts contain loose lamellar keratin, similar to a dermoid cyst. In contrast, the lining of an epidermal inclusion cyst will lack adnexal structures (Figure 2).¹ Clinically, epidermal inclusion cysts often present as smooth, dome-shaped papules and nodules with a central punctum. They are classically found on the face, neck, and trunk. These cysts are thought to arise after a traumatic insult to the pilosebaceous unit.²

Hidrocystomas can be apocrine or eccrine.³ Eccrine hidrocystomas are unilocular cysts that are lined by 2 layers of flattened to cuboidal epithelial cells (Figure 3). The cysts are filled with clear fluid and often are found adjacent to normal eccrine glands.¹ Apocrine hidrocystomas are unilocular or multilocular cysts that are lined by 1 to several layers of epithelial cells. The lining of an apocrine hidrocystoma will often exhibit luminal decapitation secretion.³ Apocrine and eccrine hidrocystomas are clinically identical and appear as blue translucent papules on the cheeks or eyelids of adults.^1-3 They usually occur periorbitally but also can be seen on the trunk, popliteal fossa, external ears, or vulva. Eccrine hidrocystomas can wax and wane in accordance with the amount of sweat produced; thus, they often expand in size during the summer months.²

Steatocystomas, or simple sebaceous duct cysts, histologically demonstrate a characteristically wavy and eosinophilic cuticle resembling shark teeth (Figure 4) similar to the lining of the sebaceous duct where it enters the follicle.¹ Sebaceous glands are an almost invariable feature, either present within the lining of the cyst (Figure 4) or in the adjacent tissue.² In comparison, dermoid cysts may have a red wavy cuticle but also will usually have terminal hair follicles or eccrine or apocrine glands within the wall of the cyst. Steatocystomas typically are collapsed and empty or only contain sebaceous debris (Figure 4) rather than the lamellar keratin seen in dermoid and epidermoid inclusion cysts. Steatocystomas can occur as solitary (steatocystoma simplex) or multiple (steatocystoma multiplex) lesions.^1,3 They are clinically comprised of small dome-shaped papules that often are translucent and yellow. These cysts are commonly found on the sternum of males and the axillae or groin of females.²

Figure 3. Eccrine hidrocystoma with clear contents and lined by 2 layers of cuboidal epithelial cells (H&E, original magnification ×100).		Figure 4. Steatocystoma with a red wavy cuticle, sparse sebaceous contents, and sebaceous glands within the lining (H&E, original magnification ×100).

The best diagnosis is:

a. bronchogenic cyst
b. dermoid cyst
c. epidermal inclusion cyst
d. hidrocystoma
e. steatocystoma

H&E, original magnification ×40.

H&E, original magnification ×100.

Continue to the next page for the diagnosis >>

Dermoid Cyst

Dermoid cysts often present clinically as firm subcutaneous nodules on the head or neck in young children. They tend to arise along the lateral aspect of the eyebrow but also can occur on the nose, forehead, neck, chest, or scalp.¹ Dermoid cysts are thought to arise from the sequestration of ectodermal tissues along the embryonic fusion planes during development.² As such, they represent congenital defects and often are identified at birth; however, some are not noticed until much later when they enlarge or become inflamed or infected. Midline dermoid cysts may be associated with underlying dysraphism or intracranial extension.^3,4 Thus, any midline lesion warrants evaluation that incorporates imaging with computed tomography or magnetic resonance imaging.^4,5 Histologically, dermoid cysts are lined by a keratinizing stratified squamous epithelium (quiz image A), but the lining may be brightly eosinophilic and wavy resembling shark teeth.^1,3 The wall of a dermoid cyst commonly contains mature adnexal structures such as terminal hair follicles, sebaceous glands, apocrine glands, and/or eccrine glands (quiz image B).¹ Smooth muscle also may be seen within the lining; however, bone and cartilage are not commonly reported in dermoid cysts.² Lamellar keratin is typical of the cyst contents, and terminal hair shafts also are sometimes noted within the cystic space (quiz image B).^1,2 Treatment options include excision at the time of diagnosis or close clinical monitoring with subsequent excision if the lesion grows or becomes symptomatic.^4,5 Many practitioners opt to excise these cysts at diagnosis, as untreated lesions are at risk for infection and/or inflammation or may be cosmetically deforming.^6,7 Surgical resection, including removal of the wall of the cyst, is curative and reoccurrence is rare.⁵

Figure 1. Bronchogenic cyst demonstrating a ciliated pseudostratified epithelial lining encircled by smooth muscle (H&E, original magnification ×200).
Figure 2. Epidermal inclusion cyst containing loose lamellar keratin and a lining that closely resembles the surface epidermis (H&E, original magnification ×40).

Bronchogenic cysts demonstrate an epithelial lining that often is pseudostratified cuboidal or columnar as well as ciliated (Figure 1). Goblet cells are present in the lining in approximately 50% of cases. Smooth muscle may be seen circumferentially surrounding the cyst lining, and rare cases also contain cartilage.¹ In contrast to dermoid cysts, other types of adnexal structures are not found within the lining. Bronchogenic cysts that arise in the skin are extremely rare.² These cysts are thought to arise from respiratory epithelium that has been sequestered during embryologic formation of the tracheobronchial tree. They often are seen overlying the suprasternal notch and occasionally are found on the anterior aspect of the neck or chin. These cysts also are present at birth, similar to dermoid cysts.³

Epidermal inclusion cysts have a lining that histologically bears close resemblance to the surface epidermis. These cysts contain loose lamellar keratin, similar to a dermoid cyst. In contrast, the lining of an epidermal inclusion cyst will lack adnexal structures (Figure 2).¹ Clinically, epidermal inclusion cysts often present as smooth, dome-shaped papules and nodules with a central punctum. They are classically found on the face, neck, and trunk. These cysts are thought to arise after a traumatic insult to the pilosebaceous unit.²

Hidrocystomas can be apocrine or eccrine.³ Eccrine hidrocystomas are unilocular cysts that are lined by 2 layers of flattened to cuboidal epithelial cells (Figure 3). The cysts are filled with clear fluid and often are found adjacent to normal eccrine glands.¹ Apocrine hidrocystomas are unilocular or multilocular cysts that are lined by 1 to several layers of epithelial cells. The lining of an apocrine hidrocystoma will often exhibit luminal decapitation secretion.³ Apocrine and eccrine hidrocystomas are clinically identical and appear as blue translucent papules on the cheeks or eyelids of adults.^1-3 They usually occur periorbitally but also can be seen on the trunk, popliteal fossa, external ears, or vulva. Eccrine hidrocystomas can wax and wane in accordance with the amount of sweat produced; thus, they often expand in size during the summer months.²

Steatocystomas, or simple sebaceous duct cysts, histologically demonstrate a characteristically wavy and eosinophilic cuticle resembling shark teeth (Figure 4) similar to the lining of the sebaceous duct where it enters the follicle.¹ Sebaceous glands are an almost invariable feature, either present within the lining of the cyst (Figure 4) or in the adjacent tissue.² In comparison, dermoid cysts may have a red wavy cuticle but also will usually have terminal hair follicles or eccrine or apocrine glands within the wall of the cyst. Steatocystomas typically are collapsed and empty or only contain sebaceous debris (Figure 4) rather than the lamellar keratin seen in dermoid and epidermoid inclusion cysts. Steatocystomas can occur as solitary (steatocystoma simplex) or multiple (steatocystoma multiplex) lesions.^1,3 They are clinically comprised of small dome-shaped papules that often are translucent and yellow. These cysts are commonly found on the sternum of males and the axillae or groin of females.²

Figure 3. Eccrine hidrocystoma with clear contents and lined by 2 layers of cuboidal epithelial cells (H&E, original magnification ×100).		Figure 4. Steatocystoma with a red wavy cuticle, sparse sebaceous contents, and sebaceous glands within the lining (H&E, original magnification ×100).

The best diagnosis is:

a. bronchogenic cyst
b. dermoid cyst
c. epidermal inclusion cyst
d. hidrocystoma
e. steatocystoma

H&E, original magnification ×40.

H&E, original magnification ×100.

Continue to the next page for the diagnosis >>

Dermoid Cyst

Dermoid cysts often present clinically as firm subcutaneous nodules on the head or neck in young children. They tend to arise along the lateral aspect of the eyebrow but also can occur on the nose, forehead, neck, chest, or scalp.¹ Dermoid cysts are thought to arise from the sequestration of ectodermal tissues along the embryonic fusion planes during development.² As such, they represent congenital defects and often are identified at birth; however, some are not noticed until much later when they enlarge or become inflamed or infected. Midline dermoid cysts may be associated with underlying dysraphism or intracranial extension.^3,4 Thus, any midline lesion warrants evaluation that incorporates imaging with computed tomography or magnetic resonance imaging.^4,5 Histologically, dermoid cysts are lined by a keratinizing stratified squamous epithelium (quiz image A), but the lining may be brightly eosinophilic and wavy resembling shark teeth.^1,3 The wall of a dermoid cyst commonly contains mature adnexal structures such as terminal hair follicles, sebaceous glands, apocrine glands, and/or eccrine glands (quiz image B).¹ Smooth muscle also may be seen within the lining; however, bone and cartilage are not commonly reported in dermoid cysts.² Lamellar keratin is typical of the cyst contents, and terminal hair shafts also are sometimes noted within the cystic space (quiz image B).^1,2 Treatment options include excision at the time of diagnosis or close clinical monitoring with subsequent excision if the lesion grows or becomes symptomatic.^4,5 Many practitioners opt to excise these cysts at diagnosis, as untreated lesions are at risk for infection and/or inflammation or may be cosmetically deforming.^6,7 Surgical resection, including removal of the wall of the cyst, is curative and reoccurrence is rare.⁵

Figure 1. Bronchogenic cyst demonstrating a ciliated pseudostratified epithelial lining encircled by smooth muscle (H&E, original magnification ×200).
Figure 2. Epidermal inclusion cyst containing loose lamellar keratin and a lining that closely resembles the surface epidermis (H&E, original magnification ×40).

Bronchogenic cysts demonstrate an epithelial lining that often is pseudostratified cuboidal or columnar as well as ciliated (Figure 1). Goblet cells are present in the lining in approximately 50% of cases. Smooth muscle may be seen circumferentially surrounding the cyst lining, and rare cases also contain cartilage.¹ In contrast to dermoid cysts, other types of adnexal structures are not found within the lining. Bronchogenic cysts that arise in the skin are extremely rare.² These cysts are thought to arise from respiratory epithelium that has been sequestered during embryologic formation of the tracheobronchial tree. They often are seen overlying the suprasternal notch and occasionally are found on the anterior aspect of the neck or chin. These cysts also are present at birth, similar to dermoid cysts.³

Epidermal inclusion cysts have a lining that histologically bears close resemblance to the surface epidermis. These cysts contain loose lamellar keratin, similar to a dermoid cyst. In contrast, the lining of an epidermal inclusion cyst will lack adnexal structures (Figure 2).¹ Clinically, epidermal inclusion cysts often present as smooth, dome-shaped papules and nodules with a central punctum. They are classically found on the face, neck, and trunk. These cysts are thought to arise after a traumatic insult to the pilosebaceous unit.²

Hidrocystomas can be apocrine or eccrine.³ Eccrine hidrocystomas are unilocular cysts that are lined by 2 layers of flattened to cuboidal epithelial cells (Figure 3). The cysts are filled with clear fluid and often are found adjacent to normal eccrine glands.¹ Apocrine hidrocystomas are unilocular or multilocular cysts that are lined by 1 to several layers of epithelial cells. The lining of an apocrine hidrocystoma will often exhibit luminal decapitation secretion.³ Apocrine and eccrine hidrocystomas are clinically identical and appear as blue translucent papules on the cheeks or eyelids of adults.^1-3 They usually occur periorbitally but also can be seen on the trunk, popliteal fossa, external ears, or vulva. Eccrine hidrocystomas can wax and wane in accordance with the amount of sweat produced; thus, they often expand in size during the summer months.²

Steatocystomas, or simple sebaceous duct cysts, histologically demonstrate a characteristically wavy and eosinophilic cuticle resembling shark teeth (Figure 4) similar to the lining of the sebaceous duct where it enters the follicle.¹ Sebaceous glands are an almost invariable feature, either present within the lining of the cyst (Figure 4) or in the adjacent tissue.² In comparison, dermoid cysts may have a red wavy cuticle but also will usually have terminal hair follicles or eccrine or apocrine glands within the wall of the cyst. Steatocystomas typically are collapsed and empty or only contain sebaceous debris (Figure 4) rather than the lamellar keratin seen in dermoid and epidermoid inclusion cysts. Steatocystomas can occur as solitary (steatocystoma simplex) or multiple (steatocystoma multiplex) lesions.^1,3 They are clinically comprised of small dome-shaped papules that often are translucent and yellow. These cysts are commonly found on the sternum of males and the axillae or groin of females.²

Figure 3. Eccrine hidrocystoma with clear contents and lined by 2 layers of cuboidal epithelial cells (H&E, original magnification ×100).		Figure 4. Steatocystoma with a red wavy cuticle, sparse sebaceous contents, and sebaceous glands within the lining (H&E, original magnification ×100).

Breastfeeding during the first 27 weeks of life had a risk-specific effect on reducing respiratory symptoms in healthy term infants, based on data from a prospective cohort study of 436 children in Switzerland.

“Breastfeeding is generally accepted to be protective against respiratory symptoms in early life,” but most published studies on this topic are cross-sectional and more likely biased, wrote Dr. Olga Gorlanova of the University of Basel (Switzerland) and her colleagues.

©Jupiterimages/ thinkstockphotos.com

The researchers studied infants enrolled in the Bern-Basel Infant Lung Development cohort via weekly telephone interviews during the first year of life. In addition, weekly measurements of environmental particulate matter were collected from local monitoring stations. Risk factors included maternal history of atopy, vaginal vs. cesarean delivery, parents’ level of education, smoking during and after pregnancy, number of older siblings, child care attendance, and housing conditions.

Overall, infants breastfed during the first 27 weeks of life had significantly reduced respiratory symptoms, compared with nonbreastfed infants (risk ratio, .70)

The study “suggests that breastfeeding attenuates the effects of risk factors such as sex, age, gestational age, cesarean delivery, and prenatal maternal tobacco smoking in healthy term infants,” Dr. Gorlanova and her associates wrote. No significant interaction was noted between breastfeeding and child care attendance, number of older siblings, maternal atopy, or environmental particulate matter.

Read the full study here (J Pediatr. 2016. doi: 10.1016/j.jpeds.2016.03.041).

Breastfeeding during the first 27 weeks of life had a risk-specific effect on reducing respiratory symptoms in healthy term infants, based on data from a prospective cohort study of 436 children in Switzerland.

“Breastfeeding is generally accepted to be protective against respiratory symptoms in early life,” but most published studies on this topic are cross-sectional and more likely biased, wrote Dr. Olga Gorlanova of the University of Basel (Switzerland) and her colleagues.

©Jupiterimages/ thinkstockphotos.com

The researchers studied infants enrolled in the Bern-Basel Infant Lung Development cohort via weekly telephone interviews during the first year of life. In addition, weekly measurements of environmental particulate matter were collected from local monitoring stations. Risk factors included maternal history of atopy, vaginal vs. cesarean delivery, parents’ level of education, smoking during and after pregnancy, number of older siblings, child care attendance, and housing conditions.

Overall, infants breastfed during the first 27 weeks of life had significantly reduced respiratory symptoms, compared with nonbreastfed infants (risk ratio, .70)

The study “suggests that breastfeeding attenuates the effects of risk factors such as sex, age, gestational age, cesarean delivery, and prenatal maternal tobacco smoking in healthy term infants,” Dr. Gorlanova and her associates wrote. No significant interaction was noted between breastfeeding and child care attendance, number of older siblings, maternal atopy, or environmental particulate matter.

Read the full study here (J Pediatr. 2016. doi: 10.1016/j.jpeds.2016.03.041).

Breastfeeding during the first 27 weeks of life had a risk-specific effect on reducing respiratory symptoms in healthy term infants, based on data from a prospective cohort study of 436 children in Switzerland.

“Breastfeeding is generally accepted to be protective against respiratory symptoms in early life,” but most published studies on this topic are cross-sectional and more likely biased, wrote Dr. Olga Gorlanova of the University of Basel (Switzerland) and her colleagues.

©Jupiterimages/ thinkstockphotos.com

The researchers studied infants enrolled in the Bern-Basel Infant Lung Development cohort via weekly telephone interviews during the first year of life. In addition, weekly measurements of environmental particulate matter were collected from local monitoring stations. Risk factors included maternal history of atopy, vaginal vs. cesarean delivery, parents’ level of education, smoking during and after pregnancy, number of older siblings, child care attendance, and housing conditions.

Overall, infants breastfed during the first 27 weeks of life had significantly reduced respiratory symptoms, compared with nonbreastfed infants (risk ratio, .70)

The study “suggests that breastfeeding attenuates the effects of risk factors such as sex, age, gestational age, cesarean delivery, and prenatal maternal tobacco smoking in healthy term infants,” Dr. Gorlanova and her associates wrote. No significant interaction was noted between breastfeeding and child care attendance, number of older siblings, maternal atopy, or environmental particulate matter.

Read the full study here (J Pediatr. 2016. doi: 10.1016/j.jpeds.2016.03.041).

CHICAGO – Six months of treatment with a proton pump inhibitor (PPI) is a safe way to cut the incidence of major gastrointestinal events in cardiovascular disease patients on dual-antiplatelet therapy regardless of whether they receive low-dose or high-dose aspirin, according to a post-hoc analysis of data from more than 3,700 patients enrolled in the multicenter, randomized COGENT trial.

“Short-term, prophylactic PPI therapy consistently reduced rates of adjudicated upper-gastrointestinal events without increasing cardiovascular events, regardless of the aspirin dose,” Dr. Muthiah Vaduganathan said while presenting his study at the annual meeting of the American College of Cardiology. “Gastroprotection with PPI therapy should be used in appropriately selected patients with coronary artery disease who require dual-antiplatelet therapy even if they are on low-dose aspirin.”

Mitchel L. Zoler/Frontline Medical News

In addition to documenting the safety and efficacy of 6 months of PPI treatment for patients at high risk for cardiovascular events and low or moderate risk for a GI event, the results from the analysis also documented how common GI events are in this population, even when patients receive low-dose aspirin. Nearly two-thirds of the 3,752 patients included in the analysis took low-dose aspirin, either 75 mg or 81 mg per day. Their incidence of an adjudicated upper GI bleed, the study’s primary GI endpoint, occurred in 3.1% of patients on placebo, and in 1.2% of patients taking a prophylactic PPI. Among the other 34% of patients on high-dose aspirin – a daily dosage of at least 150 mg – the rate of adjudicated upper-GI bleeds was 2.6% without a PPI and 0.9% in those on a PPI.

In other words, even among patients deemed to have a relatively low risk for upper GI complications from aspirin (because their entry into this study required no history of major GI bleeds or recent treatment with a gastroprotection agent), treatment with low-dose aspirin resulted in upper-GI bleeds at the same rate, about 3%, as high-dose aspirin. And in both of these aspirin subgroups 6 months of concurrent treatment with a PPI cut the incidence of major GI bleeds by more than half.

The findings are especially notable because the enrollment criteria stacked the deck toward patients with high cardiovascular disease risk and relatively low GI risk. The study enrolled “a unique population at high risk for cardiovascular disease – 71% had previously undergone a percutaneous coronary intervention, and 42% had a history of an acute coronary syndrome – and low GI risk, but even in this population enriched for cardiovascular disease risk, there was no increased rate of cardiovascular disease events” during a median follow-up while on PPI treatment of 110 days, Dr. Vaduganathan said.

Among patients on low-dose aspirin, the rate of cardiovascular death, MI, stroke, or coronary revascularization was 5.6% with PPI treatment and 5.5% without, and in the high-dose aspirin patients the rates were 4.2% with PPI treatment and 5.5% without. Neither of these differences between the subgroups taking or not taking a PPI were statistically significant.

Concurrent with Dr. Vaduganathan’s report at the meeting the results also appeared online (J Am Coll Cardiol. 2016 April 12;67[14]:661-71).

“There appeared to be no adverse clinical effect from PPI treatment. When used short-term, for up to 6 months, PPI treatment appears to be safe in patients with cardiovascular disease,” Dr. Vaduganathan concluded.

The analysis used data collected in COGENT (Clopidogrel and the Optimization of Gastrointestinal Events Trial), a phase 3 study designed to compare a single-pill formulation of 20 mg omeprazole and 75 mg clopidogrel taken orally once daily with 75 mg clopidogrel against a background of all patients taking aspirin. COGENT stopped prematurely in late 2008 as the company developing this formulation and sponsoring the trial, Cogentus Pharmaceuticals, filed for bankruptcy. Despite its abrupt conclusion, the trial had enrolled and followed enough patients to show that treatment with omeprazole plus clopidogrel and aspirin led to a significant reduction in upper GI bleeding without increasing the rate of cardiovascular disease events, compared with clopidogrel plus aspirin (N Engl J Med. 2010 Nov 11;363[20]:1909-17).

The new analysis focused on the greater than 99% of patients in the total COGENT cohort for whom information was available on whether they received high- or low-dose aspirin.

Although the primary findings from COGENT, reported in 2010, documented the safety and efficacy of concomitant PPI treatment during dual-antiplatelet therapy, and despite guidelines revised in 2010 that called for PPI treatment when appropriate, this strategy for preventing GI complications remains underused, Dr. Vaduganathan said. The most recent U.S. recommendations that address this issue called for assessing the potential risk and benefit from PPI treatment in patients receiving dual-antiplatelet therapy: “The risk reduction with PPIs is substantial in patients with risk factors for GI bleeding and may outweigh any potential reduction in the CV efficacy of antiplatelet treatment because of a drug-drug interaction (J Am Coll Cardiol. 2010 Dec;56[24]:2051-66).”

The only caveat Dr. Vaduganathan placed on PPI use was that the COGENT data addressed only 6 months of PPI use; the safety of longer-term use has not been studied. But “the trend is to use PPIs for as short a period as possible,” and the risk for adverse effects from PPI treatment on cardiovascular disease events is likely greatest during the first 6 months of PPI treatment, he noted. If PPI treatment needs to continue beyond 6 months, he suggested systematically reassessing the risk-benefit balance for individual patients from continued PPI treatment every 3 months.*

*Changes were made to this story on 4/20/2016.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

CHICAGO – Six months of treatment with a proton pump inhibitor (PPI) is a safe way to cut the incidence of major gastrointestinal events in cardiovascular disease patients on dual-antiplatelet therapy regardless of whether they receive low-dose or high-dose aspirin, according to a post-hoc analysis of data from more than 3,700 patients enrolled in the multicenter, randomized COGENT trial.

“Short-term, prophylactic PPI therapy consistently reduced rates of adjudicated upper-gastrointestinal events without increasing cardiovascular events, regardless of the aspirin dose,” Dr. Muthiah Vaduganathan said while presenting his study at the annual meeting of the American College of Cardiology. “Gastroprotection with PPI therapy should be used in appropriately selected patients with coronary artery disease who require dual-antiplatelet therapy even if they are on low-dose aspirin.”

Mitchel L. Zoler/Frontline Medical News

In addition to documenting the safety and efficacy of 6 months of PPI treatment for patients at high risk for cardiovascular events and low or moderate risk for a GI event, the results from the analysis also documented how common GI events are in this population, even when patients receive low-dose aspirin. Nearly two-thirds of the 3,752 patients included in the analysis took low-dose aspirin, either 75 mg or 81 mg per day. Their incidence of an adjudicated upper GI bleed, the study’s primary GI endpoint, occurred in 3.1% of patients on placebo, and in 1.2% of patients taking a prophylactic PPI. Among the other 34% of patients on high-dose aspirin – a daily dosage of at least 150 mg – the rate of adjudicated upper-GI bleeds was 2.6% without a PPI and 0.9% in those on a PPI.

In other words, even among patients deemed to have a relatively low risk for upper GI complications from aspirin (because their entry into this study required no history of major GI bleeds or recent treatment with a gastroprotection agent), treatment with low-dose aspirin resulted in upper-GI bleeds at the same rate, about 3%, as high-dose aspirin. And in both of these aspirin subgroups 6 months of concurrent treatment with a PPI cut the incidence of major GI bleeds by more than half.

The findings are especially notable because the enrollment criteria stacked the deck toward patients with high cardiovascular disease risk and relatively low GI risk. The study enrolled “a unique population at high risk for cardiovascular disease – 71% had previously undergone a percutaneous coronary intervention, and 42% had a history of an acute coronary syndrome – and low GI risk, but even in this population enriched for cardiovascular disease risk, there was no increased rate of cardiovascular disease events” during a median follow-up while on PPI treatment of 110 days, Dr. Vaduganathan said.

Among patients on low-dose aspirin, the rate of cardiovascular death, MI, stroke, or coronary revascularization was 5.6% with PPI treatment and 5.5% without, and in the high-dose aspirin patients the rates were 4.2% with PPI treatment and 5.5% without. Neither of these differences between the subgroups taking or not taking a PPI were statistically significant.

Concurrent with Dr. Vaduganathan’s report at the meeting the results also appeared online (J Am Coll Cardiol. 2016 April 12;67[14]:661-71).

“There appeared to be no adverse clinical effect from PPI treatment. When used short-term, for up to 6 months, PPI treatment appears to be safe in patients with cardiovascular disease,” Dr. Vaduganathan concluded.

The analysis used data collected in COGENT (Clopidogrel and the Optimization of Gastrointestinal Events Trial), a phase 3 study designed to compare a single-pill formulation of 20 mg omeprazole and 75 mg clopidogrel taken orally once daily with 75 mg clopidogrel against a background of all patients taking aspirin. COGENT stopped prematurely in late 2008 as the company developing this formulation and sponsoring the trial, Cogentus Pharmaceuticals, filed for bankruptcy. Despite its abrupt conclusion, the trial had enrolled and followed enough patients to show that treatment with omeprazole plus clopidogrel and aspirin led to a significant reduction in upper GI bleeding without increasing the rate of cardiovascular disease events, compared with clopidogrel plus aspirin (N Engl J Med. 2010 Nov 11;363[20]:1909-17).

The new analysis focused on the greater than 99% of patients in the total COGENT cohort for whom information was available on whether they received high- or low-dose aspirin.

Although the primary findings from COGENT, reported in 2010, documented the safety and efficacy of concomitant PPI treatment during dual-antiplatelet therapy, and despite guidelines revised in 2010 that called for PPI treatment when appropriate, this strategy for preventing GI complications remains underused, Dr. Vaduganathan said. The most recent U.S. recommendations that address this issue called for assessing the potential risk and benefit from PPI treatment in patients receiving dual-antiplatelet therapy: “The risk reduction with PPIs is substantial in patients with risk factors for GI bleeding and may outweigh any potential reduction in the CV efficacy of antiplatelet treatment because of a drug-drug interaction (J Am Coll Cardiol. 2010 Dec;56[24]:2051-66).”

The only caveat Dr. Vaduganathan placed on PPI use was that the COGENT data addressed only 6 months of PPI use; the safety of longer-term use has not been studied. But “the trend is to use PPIs for as short a period as possible,” and the risk for adverse effects from PPI treatment on cardiovascular disease events is likely greatest during the first 6 months of PPI treatment, he noted. If PPI treatment needs to continue beyond 6 months, he suggested systematically reassessing the risk-benefit balance for individual patients from continued PPI treatment every 3 months.*

*Changes were made to this story on 4/20/2016.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

CHICAGO – Six months of treatment with a proton pump inhibitor (PPI) is a safe way to cut the incidence of major gastrointestinal events in cardiovascular disease patients on dual-antiplatelet therapy regardless of whether they receive low-dose or high-dose aspirin, according to a post-hoc analysis of data from more than 3,700 patients enrolled in the multicenter, randomized COGENT trial.

“Short-term, prophylactic PPI therapy consistently reduced rates of adjudicated upper-gastrointestinal events without increasing cardiovascular events, regardless of the aspirin dose,” Dr. Muthiah Vaduganathan said while presenting his study at the annual meeting of the American College of Cardiology. “Gastroprotection with PPI therapy should be used in appropriately selected patients with coronary artery disease who require dual-antiplatelet therapy even if they are on low-dose aspirin.”

Mitchel L. Zoler/Frontline Medical News

In addition to documenting the safety and efficacy of 6 months of PPI treatment for patients at high risk for cardiovascular events and low or moderate risk for a GI event, the results from the analysis also documented how common GI events are in this population, even when patients receive low-dose aspirin. Nearly two-thirds of the 3,752 patients included in the analysis took low-dose aspirin, either 75 mg or 81 mg per day. Their incidence of an adjudicated upper GI bleed, the study’s primary GI endpoint, occurred in 3.1% of patients on placebo, and in 1.2% of patients taking a prophylactic PPI. Among the other 34% of patients on high-dose aspirin – a daily dosage of at least 150 mg – the rate of adjudicated upper-GI bleeds was 2.6% without a PPI and 0.9% in those on a PPI.

In other words, even among patients deemed to have a relatively low risk for upper GI complications from aspirin (because their entry into this study required no history of major GI bleeds or recent treatment with a gastroprotection agent), treatment with low-dose aspirin resulted in upper-GI bleeds at the same rate, about 3%, as high-dose aspirin. And in both of these aspirin subgroups 6 months of concurrent treatment with a PPI cut the incidence of major GI bleeds by more than half.

The findings are especially notable because the enrollment criteria stacked the deck toward patients with high cardiovascular disease risk and relatively low GI risk. The study enrolled “a unique population at high risk for cardiovascular disease – 71% had previously undergone a percutaneous coronary intervention, and 42% had a history of an acute coronary syndrome – and low GI risk, but even in this population enriched for cardiovascular disease risk, there was no increased rate of cardiovascular disease events” during a median follow-up while on PPI treatment of 110 days, Dr. Vaduganathan said.

Among patients on low-dose aspirin, the rate of cardiovascular death, MI, stroke, or coronary revascularization was 5.6% with PPI treatment and 5.5% without, and in the high-dose aspirin patients the rates were 4.2% with PPI treatment and 5.5% without. Neither of these differences between the subgroups taking or not taking a PPI were statistically significant.

Concurrent with Dr. Vaduganathan’s report at the meeting the results also appeared online (J Am Coll Cardiol. 2016 April 12;67[14]:661-71).

“There appeared to be no adverse clinical effect from PPI treatment. When used short-term, for up to 6 months, PPI treatment appears to be safe in patients with cardiovascular disease,” Dr. Vaduganathan concluded.

The analysis used data collected in COGENT (Clopidogrel and the Optimization of Gastrointestinal Events Trial), a phase 3 study designed to compare a single-pill formulation of 20 mg omeprazole and 75 mg clopidogrel taken orally once daily with 75 mg clopidogrel against a background of all patients taking aspirin. COGENT stopped prematurely in late 2008 as the company developing this formulation and sponsoring the trial, Cogentus Pharmaceuticals, filed for bankruptcy. Despite its abrupt conclusion, the trial had enrolled and followed enough patients to show that treatment with omeprazole plus clopidogrel and aspirin led to a significant reduction in upper GI bleeding without increasing the rate of cardiovascular disease events, compared with clopidogrel plus aspirin (N Engl J Med. 2010 Nov 11;363[20]:1909-17).

The new analysis focused on the greater than 99% of patients in the total COGENT cohort for whom information was available on whether they received high- or low-dose aspirin.

Although the primary findings from COGENT, reported in 2010, documented the safety and efficacy of concomitant PPI treatment during dual-antiplatelet therapy, and despite guidelines revised in 2010 that called for PPI treatment when appropriate, this strategy for preventing GI complications remains underused, Dr. Vaduganathan said. The most recent U.S. recommendations that address this issue called for assessing the potential risk and benefit from PPI treatment in patients receiving dual-antiplatelet therapy: “The risk reduction with PPIs is substantial in patients with risk factors for GI bleeding and may outweigh any potential reduction in the CV efficacy of antiplatelet treatment because of a drug-drug interaction (J Am Coll Cardiol. 2010 Dec;56[24]:2051-66).”

The only caveat Dr. Vaduganathan placed on PPI use was that the COGENT data addressed only 6 months of PPI use; the safety of longer-term use has not been studied. But “the trend is to use PPIs for as short a period as possible,” and the risk for adverse effects from PPI treatment on cardiovascular disease events is likely greatest during the first 6 months of PPI treatment, he noted. If PPI treatment needs to continue beyond 6 months, he suggested systematically reassessing the risk-benefit balance for individual patients from continued PPI treatment every 3 months.*

*Changes were made to this story on 4/20/2016.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler