Case Report

A healthy 17-year-old adolescent boy with an unremarkable medical history presented with an asymptomatic fixed rash on the abdomen, buttocks, and legs. The rash initially developed in a small area on the right leg 2 years prior and had slowly progressed. He was not currently taking any medications and did not participate in intense physical activity. Multiple biopsies had previously been performed by an outside physician, the most recent one demonstrating an interface and superficial perivascular lymphocytic infiltrate with extravasated red blood cells consistent with pigmented purpura. He did not respond to treatment with intralesional corticosteroids, high-potency topical steroids, or high-dose oral prednisone.

Clinical examination revealed multiple annular purpuric patches on the abdomen, buttocks, and legs that covered approximately 20% of the body surface area (Figure 1). Over several follow-up visits, a few of the lesions evolved from patches to thin plaques. There was no adenopathy or hepatosplenomegaly. Three additional biopsies taken over the next 4 months demonstrated a mixture of small mature lymphocytes with some atypical lymphocytes in the dermis and epidermis exhibiting diminished CD7 staining and lymphocytes lining up at the dermoepidermal junction. T-cell receptor g gene rearrangements demonstrated the same clonal population in all 3 specimens. The patient was diagnosed with stage IB mycosis fungoides (MF) of the pigmented purpura–like variant. Marked improvement of the lesions was noted after 6 weeks of psoralen plus UVA therapy 3 times weekly (Figure 2). Treatment was continued for 6 months but was discontinued due to the international shortage of methoxsalen. Two months after discontinuation, most of the lesions had completely resolved (Figure 3).

Figure 1. Multiple annular purpuric patches on the abdomen, anterior thighs (A), and right leg (B).

Comment

Mycoses fungoides is a rare cutaneous lymphoma that affects approximately 2000 patients in the United States.¹ Only 5% of all cases are known to occur in the first 2 decades of life,² and even fewer cases pre-sent with pigmented purpura, usually of the lichenoid variant.³ Although the patches and plaques of MF can masquerade as many other dermatoses (eg, dermatophytosis, psoriasis, dermatitis), there have been few reports of patients presenting with lesions with the clinical appearance of pigmented purpuric dermatosis (PPD).⁴ As with the many cases of early MF, which are histologically indistinguishable from dermatitis, the pigmented purpura–like variant of MF initially may have the histologic appearance of pigmented purpura and generally evolves to the histologic appearance of MF over time.

Similar to our case, there have been reports of clinical and histologic diagnosis of PPD preceding the histologic diagnosis of MF. In a small cohort study of 3 young men, Barnhill and Braverman⁵ first demonstrated the progression of PPD to MF over a 12-year period. The age of onset ranged from 14 to 30 years, with a mean age of 24.3 years. Biopsies in all 3 patients were consistent with PPD for many years prior to the diagnosis of MF, with an average length of time to diagnosis of 8.4 years. Atypical from most cases of PPD, the patients in this study demonstrated extensive involvement of the trunk, arms, and legs.⁵ It has been suggested that atypical PPD is a variant of PPD that evolves into MF over many years; however, we believe that PPD is a variant of MF, similar to the way an indolent dermatitis may evolve to classical MF over time. If characterized by a T-cell clone, this period preceding the diagnosis of cutaneous T-cell lymphoma could be characterized as a cutaneous T-cell lymphoid dyscrasia.

Guitart and Magro⁶ noted multiple chronic conditions that are associated with T-cell clones, including PPD. These conditions occurred without a known trigger, were unresponsive to topical therapies, and often did not meet diagnostic criteria for MF. The investigators felt the criteria that may indicate a cutaneous T-cell lymphoid dyscrasia include widespread distribution, lymphocytic infiltrate, diminished CD7 and CD62L expression, and clonality. Lymphocytes may be small without notable atypia.⁶

In a study of 43 patients with PPD, Magro et al³ found monoclonality and diminished CD7 expression in 18 participants, correlating with large surface area involvement. Approximately 40% of patients had histologic findings consistent with MF, suggesting that T-cell gene rearrangement studies should be obtained for prognostic evaluation in patients with widespread disease.³

Figure 2. Marked improvement of the lesions was noted after 6 weeks of psoralen plus UVA therapy 3 times weekly.

Figure 3. After 6 months of psoralen plus UVA therapy, most of the lesions had completely resolved.

To facilitate proper patient care, histopathology and molecular markers should be evaluated in conjunction with the clinical picture. A considerable increase in the size of the body surface area affected by purpuric patches combined with the presence of poikilodermatous changes and pruritus as well as disease lasting longer than 1 year should prompt an increased clinical suspicion of MF in patients with PPD.^4,5 Histologically, the presence of Pautrier microabscesses, large cerebriform lymphocytes, and intraepidermal lymphocytic atypia extending beyond the dermis also would support a diagnosis of MF.³ Given the morphologic appearance and distribution of the lesions in our patient combined with epidermotropism, diminished CD7 expression, and monoclonality seen on pathology, we favored a diagnosis of MF. It would not be unreasonable to call this clonal variant of PPD a T-cell lymphoid dyscrasia. We appreciate that both PPD and MF will respond to phototherapy.⁷

Conclusion

We propose that there is a spectrum of disease presenting as PPD or MF sitting at either end of that spectrum and an intermediate stage, where not all criteria for cutaneous lymphoma are met, characterized as cutaneous T-cell lymphoid dyscrasia. Until the potential for evolution of PPD to malignant disease is better understood, patients with unusual presentations of pigmented purpura should be further evaluated for MF.

Case Report

A healthy 17-year-old adolescent boy with an unremarkable medical history presented with an asymptomatic fixed rash on the abdomen, buttocks, and legs. The rash initially developed in a small area on the right leg 2 years prior and had slowly progressed. He was not currently taking any medications and did not participate in intense physical activity. Multiple biopsies had previously been performed by an outside physician, the most recent one demonstrating an interface and superficial perivascular lymphocytic infiltrate with extravasated red blood cells consistent with pigmented purpura. He did not respond to treatment with intralesional corticosteroids, high-potency topical steroids, or high-dose oral prednisone.

Clinical examination revealed multiple annular purpuric patches on the abdomen, buttocks, and legs that covered approximately 20% of the body surface area (Figure 1). Over several follow-up visits, a few of the lesions evolved from patches to thin plaques. There was no adenopathy or hepatosplenomegaly. Three additional biopsies taken over the next 4 months demonstrated a mixture of small mature lymphocytes with some atypical lymphocytes in the dermis and epidermis exhibiting diminished CD7 staining and lymphocytes lining up at the dermoepidermal junction. T-cell receptor g gene rearrangements demonstrated the same clonal population in all 3 specimens. The patient was diagnosed with stage IB mycosis fungoides (MF) of the pigmented purpura–like variant. Marked improvement of the lesions was noted after 6 weeks of psoralen plus UVA therapy 3 times weekly (Figure 2). Treatment was continued for 6 months but was discontinued due to the international shortage of methoxsalen. Two months after discontinuation, most of the lesions had completely resolved (Figure 3).

Figure 1. Multiple annular purpuric patches on the abdomen, anterior thighs (A), and right leg (B).

Comment

Mycoses fungoides is a rare cutaneous lymphoma that affects approximately 2000 patients in the United States.¹ Only 5% of all cases are known to occur in the first 2 decades of life,² and even fewer cases pre-sent with pigmented purpura, usually of the lichenoid variant.³ Although the patches and plaques of MF can masquerade as many other dermatoses (eg, dermatophytosis, psoriasis, dermatitis), there have been few reports of patients presenting with lesions with the clinical appearance of pigmented purpuric dermatosis (PPD).⁴ As with the many cases of early MF, which are histologically indistinguishable from dermatitis, the pigmented purpura–like variant of MF initially may have the histologic appearance of pigmented purpura and generally evolves to the histologic appearance of MF over time.

Similar to our case, there have been reports of clinical and histologic diagnosis of PPD preceding the histologic diagnosis of MF. In a small cohort study of 3 young men, Barnhill and Braverman⁵ first demonstrated the progression of PPD to MF over a 12-year period. The age of onset ranged from 14 to 30 years, with a mean age of 24.3 years. Biopsies in all 3 patients were consistent with PPD for many years prior to the diagnosis of MF, with an average length of time to diagnosis of 8.4 years. Atypical from most cases of PPD, the patients in this study demonstrated extensive involvement of the trunk, arms, and legs.⁵ It has been suggested that atypical PPD is a variant of PPD that evolves into MF over many years; however, we believe that PPD is a variant of MF, similar to the way an indolent dermatitis may evolve to classical MF over time. If characterized by a T-cell clone, this period preceding the diagnosis of cutaneous T-cell lymphoma could be characterized as a cutaneous T-cell lymphoid dyscrasia.

Guitart and Magro⁶ noted multiple chronic conditions that are associated with T-cell clones, including PPD. These conditions occurred without a known trigger, were unresponsive to topical therapies, and often did not meet diagnostic criteria for MF. The investigators felt the criteria that may indicate a cutaneous T-cell lymphoid dyscrasia include widespread distribution, lymphocytic infiltrate, diminished CD7 and CD62L expression, and clonality. Lymphocytes may be small without notable atypia.⁶

In a study of 43 patients with PPD, Magro et al³ found monoclonality and diminished CD7 expression in 18 participants, correlating with large surface area involvement. Approximately 40% of patients had histologic findings consistent with MF, suggesting that T-cell gene rearrangement studies should be obtained for prognostic evaluation in patients with widespread disease.³

Figure 2. Marked improvement of the lesions was noted after 6 weeks of psoralen plus UVA therapy 3 times weekly.

Figure 3. After 6 months of psoralen plus UVA therapy, most of the lesions had completely resolved.

To facilitate proper patient care, histopathology and molecular markers should be evaluated in conjunction with the clinical picture. A considerable increase in the size of the body surface area affected by purpuric patches combined with the presence of poikilodermatous changes and pruritus as well as disease lasting longer than 1 year should prompt an increased clinical suspicion of MF in patients with PPD.^4,5 Histologically, the presence of Pautrier microabscesses, large cerebriform lymphocytes, and intraepidermal lymphocytic atypia extending beyond the dermis also would support a diagnosis of MF.³ Given the morphologic appearance and distribution of the lesions in our patient combined with epidermotropism, diminished CD7 expression, and monoclonality seen on pathology, we favored a diagnosis of MF. It would not be unreasonable to call this clonal variant of PPD a T-cell lymphoid dyscrasia. We appreciate that both PPD and MF will respond to phototherapy.⁷

Conclusion

We propose that there is a spectrum of disease presenting as PPD or MF sitting at either end of that spectrum and an intermediate stage, where not all criteria for cutaneous lymphoma are met, characterized as cutaneous T-cell lymphoid dyscrasia. Until the potential for evolution of PPD to malignant disease is better understood, patients with unusual presentations of pigmented purpura should be further evaluated for MF.

Case Report

A healthy 17-year-old adolescent boy with an unremarkable medical history presented with an asymptomatic fixed rash on the abdomen, buttocks, and legs. The rash initially developed in a small area on the right leg 2 years prior and had slowly progressed. He was not currently taking any medications and did not participate in intense physical activity. Multiple biopsies had previously been performed by an outside physician, the most recent one demonstrating an interface and superficial perivascular lymphocytic infiltrate with extravasated red blood cells consistent with pigmented purpura. He did not respond to treatment with intralesional corticosteroids, high-potency topical steroids, or high-dose oral prednisone.

Clinical examination revealed multiple annular purpuric patches on the abdomen, buttocks, and legs that covered approximately 20% of the body surface area (Figure 1). Over several follow-up visits, a few of the lesions evolved from patches to thin plaques. There was no adenopathy or hepatosplenomegaly. Three additional biopsies taken over the next 4 months demonstrated a mixture of small mature lymphocytes with some atypical lymphocytes in the dermis and epidermis exhibiting diminished CD7 staining and lymphocytes lining up at the dermoepidermal junction. T-cell receptor g gene rearrangements demonstrated the same clonal population in all 3 specimens. The patient was diagnosed with stage IB mycosis fungoides (MF) of the pigmented purpura–like variant. Marked improvement of the lesions was noted after 6 weeks of psoralen plus UVA therapy 3 times weekly (Figure 2). Treatment was continued for 6 months but was discontinued due to the international shortage of methoxsalen. Two months after discontinuation, most of the lesions had completely resolved (Figure 3).

Figure 1. Multiple annular purpuric patches on the abdomen, anterior thighs (A), and right leg (B).

Comment

Mycoses fungoides is a rare cutaneous lymphoma that affects approximately 2000 patients in the United States.¹ Only 5% of all cases are known to occur in the first 2 decades of life,² and even fewer cases pre-sent with pigmented purpura, usually of the lichenoid variant.³ Although the patches and plaques of MF can masquerade as many other dermatoses (eg, dermatophytosis, psoriasis, dermatitis), there have been few reports of patients presenting with lesions with the clinical appearance of pigmented purpuric dermatosis (PPD).⁴ As with the many cases of early MF, which are histologically indistinguishable from dermatitis, the pigmented purpura–like variant of MF initially may have the histologic appearance of pigmented purpura and generally evolves to the histologic appearance of MF over time.

Similar to our case, there have been reports of clinical and histologic diagnosis of PPD preceding the histologic diagnosis of MF. In a small cohort study of 3 young men, Barnhill and Braverman⁵ first demonstrated the progression of PPD to MF over a 12-year period. The age of onset ranged from 14 to 30 years, with a mean age of 24.3 years. Biopsies in all 3 patients were consistent with PPD for many years prior to the diagnosis of MF, with an average length of time to diagnosis of 8.4 years. Atypical from most cases of PPD, the patients in this study demonstrated extensive involvement of the trunk, arms, and legs.⁵ It has been suggested that atypical PPD is a variant of PPD that evolves into MF over many years; however, we believe that PPD is a variant of MF, similar to the way an indolent dermatitis may evolve to classical MF over time. If characterized by a T-cell clone, this period preceding the diagnosis of cutaneous T-cell lymphoma could be characterized as a cutaneous T-cell lymphoid dyscrasia.

Guitart and Magro⁶ noted multiple chronic conditions that are associated with T-cell clones, including PPD. These conditions occurred without a known trigger, were unresponsive to topical therapies, and often did not meet diagnostic criteria for MF. The investigators felt the criteria that may indicate a cutaneous T-cell lymphoid dyscrasia include widespread distribution, lymphocytic infiltrate, diminished CD7 and CD62L expression, and clonality. Lymphocytes may be small without notable atypia.⁶

In a study of 43 patients with PPD, Magro et al³ found monoclonality and diminished CD7 expression in 18 participants, correlating with large surface area involvement. Approximately 40% of patients had histologic findings consistent with MF, suggesting that T-cell gene rearrangement studies should be obtained for prognostic evaluation in patients with widespread disease.³

Figure 2. Marked improvement of the lesions was noted after 6 weeks of psoralen plus UVA therapy 3 times weekly.

Figure 3. After 6 months of psoralen plus UVA therapy, most of the lesions had completely resolved.

To facilitate proper patient care, histopathology and molecular markers should be evaluated in conjunction with the clinical picture. A considerable increase in the size of the body surface area affected by purpuric patches combined with the presence of poikilodermatous changes and pruritus as well as disease lasting longer than 1 year should prompt an increased clinical suspicion of MF in patients with PPD.^4,5 Histologically, the presence of Pautrier microabscesses, large cerebriform lymphocytes, and intraepidermal lymphocytic atypia extending beyond the dermis also would support a diagnosis of MF.³ Given the morphologic appearance and distribution of the lesions in our patient combined with epidermotropism, diminished CD7 expression, and monoclonality seen on pathology, we favored a diagnosis of MF. It would not be unreasonable to call this clonal variant of PPD a T-cell lymphoid dyscrasia. We appreciate that both PPD and MF will respond to phototherapy.⁷

Conclusion

We propose that there is a spectrum of disease presenting as PPD or MF sitting at either end of that spectrum and an intermediate stage, where not all criteria for cutaneous lymphoma are met, characterized as cutaneous T-cell lymphoid dyscrasia. Until the potential for evolution of PPD to malignant disease is better understood, patients with unusual presentations of pigmented purpura should be further evaluated for MF.

Last year, there were five predictions made that appeared to be on the money – but there is more to the story!

1. The approach to diagnosis and treatment of influenza was essential knowledge for clinicians. Last year, we started seeing influenza activity early – with disease confirmed in mid-November, peaking during the week ending December 28, 2013 and trending downward in early January 2014. Hospitalizations were most common in young and middle aged adults and the 2009 H1N1 virus predominated.

This year, again we are seeing influenza early – with nearly all states reporting at least sporadic and local activity, and several states (Alaska, Florida, Louisiana, Massachusetts, and Texas) reporting regional activity as of the week ending November 24, 2014. At my institution, we’ve already tested over 500 children and over 100 were positive – influenza A (H3N2) strains are predominating. That may be important for the two reasons you’ll read below.

2. Invasive staphylococcal disease caused by methicillin-susceptible Staphylococcus aureus (MSSA) was more common than methicillin-resistant Staphylococcus aureus (MRSA), as the national burden of MRSA disease decreased (JAMA 2014;311:1438-9). The rates of clindamycin resistance continue to be pretty steady at approximately 15%-18%, but higher for MSSA than for MRSA – a point that is important to consider when empirically treating suspected invasive staphylococcal infection.

3. Multidrug resistant uropathogens took an increasingly prominent role in 2014, requiring careful approach to diagnosis (every child treated for urinary tract infection should have an appropriately obtained urine culture with an identified pathogen) and treatment (the drug used should be based on antibiotic susceptibility testing results). Particularly concerning is the emergence of carbapenem-resistant Enterobacteriaceae, which cause infection more commonly in hospitalized patients, those with indwelling devices, and those who have received long courses of antibiotics.

4. It was an outbreak year for parechovirus (HPeV), a viral pathogen causing meningitis in very young infants. Such infants present with signs and symptoms of meningitis but rarely show CSF pleocytosis. Diagnosis relies on the detection of the virus by polymerase chain reaction testing in CSF – a test which is not routinely available in many laboratories. At my institution this season, we saw nearly as many cases of parechovirus meningitis (n = 43) as we saw cases of enterovirus meningitis (n = 63). The parechovirus virus we detected was HPeV type 3, which can cause particularly severe disease in neonates.

5. Data confirmed that making human papillomavirus (HPV) vaccine a standard recommendation increased vaccine uptake and coverage. In February of 2014, a “Dear Colleague” letter that was endorsed by six leading medical organizations encouraged providers to promote HPV vaccination by giving a strong recommendation, citing data based on research conducted by the Centers for Disease Control and Prevention. We still have a long way to go as HPV vaccine coverage for teens remains at 35% for the three-dose series while meningococcal and Tdap vaccine (both vaccines that generally receive a standard recommendation by physicians) coverage is at nearly 90%.

So for 2015, I’ll start the discussion by saying there are five major developments I did not see coming for this past year, but that will remain relevant for the year 2015!

1. In June of 2014, live attenuated influenza vaccine (LAIV) was announced by the Advisory Committee on Immunization Practices to be the preferred vaccine in children aged 2-8 years. The American Academy of Pediatrics followed with a recommendation that either inactivated influenza vaccine (IIV) or LAIV be used for children, including children aged 2-8 years – the key being to give the vaccine as soon as one had it available. What was not known then and I did not predict was that newer data would confirm that in children aged 2-8 years who received LAIV last year when 2009 H1N1 strains predominated, there was essentially no coverage against 2009 H1N1 virus. This was in contrast to data from the prior 2 years and is as yet unexplained. The AAP continues to recommend that either vaccine be given and all children be immunized. That may be especially important this year as the influenza season started early. Disease will likely have been widespread by Christmas in many parts of the United States, and it looks like influenza A H3N2 strains will be most commonly noted. So the good news for young children who received LAIV is that 2009 H1N1 strains so far have not been seen this year. The bad news is that there are two H3N2 strains circulating, and potentially only one will be covered by the 2014-2015 seasonal vaccine. Staffing your office and hospital for a likely high census respiratory viral season is going to be essential.

2. The largest U.S. outbreak ever of enterovirus (EV) D-68 respiratory infection occurred between August and October of 2014. This virus – which had been identified in 1962 but was rarely described over the next 36 years except in small clusters of disease – was reported in nearly every state and characterized by unusually severe respiratory tract infection. Many, but not all children, had a history of asthma or prior wheezing, and the clinical presentation was that of severe bronchospasm that was generally resistant to standard bronchodilator therapy. The spectrum of infection likely ranged from mild upper respiratory infection to severe bronchospasm with respiratory failure, and the burden of disease resulting in hospitalization was substantial at many children’s hospitals. The big question now is what will enterovirus season 2015 bring us? The good news here is that we now have a test to rapidly diagnose EV D-68, which will allow us to more clearly understand the burden of disease – and potentially to define antiviral treatment (none of the current antivirals is effective) and prevention (there is no vaccine against EV D-68).

3. The etiology of the neurologic illness, which appeared to mimic polio and presented during the same time frame during which EV D-68 was circulating, is as yet unknown. As of Nov. 26, 2014, the CDC has received reports of 90 children in 32 states who meet a case definition consistent with acute flaccid myelitis. While certain viruses – including West Nile virus, herpes virus, adenovirus, and certain enterovirus types (for example, enterovirus 71, and the classic being polio) – may cause acute flaccid paralysis and can be confirmed by detecting the virus in cerebrospinal fluid and stool, to date virus testing for all viruses, including EV D-68, has been negative in all of the patients reported. Hopefully, 2015 will be the year that will allow us to more clearly understand this neurologic illness – and this is important because so far most children have shown minimal recovery of function.

4. If you see a child (or adult) who recently traveled to the Caribbean and returns with fever, rash, and joint pain, especially with severe pain of the hands and feet, think chikungunya virus infection. As of the end of October 2014, local transmission had been identified in 37 countries or territories in the Caribbean (including Puerto Rico and the U.S. Virgin Islands), with a total of 780,206 suspected cases and over 15,000 confirmed cases reported from these areas. Consider this in contrast to the numbers from 2006 through 2011, when 117 cases of chikungunya fever were reported in returning travelers. As of Dec. 2, a total of 1,911 chikungunya virus disease cases have been reported to ArboNET from U.S. states. The mosquito that transmits chikungunya virus can bite in day and night, and prevention relies on appropriate use of mosquito repellents. Physicians should be prepared to discuss the risks of this virus with travelers who plan a trip to the Caribbean, especially those at high risk, including those with underlying medical conditions, preexisting arthritis diagnoses, and pregnant women (because of the potential risk to newborns whose mothers develop intrapartum infection).

5. And lastly, Ebola. While there were reports that Ebola virus disease had emerged in West Africa as early as December of 2013, the scope of the outbreak and extent of loss of human life has been unbelievably huge. Dr. Carrie Byington, who is the current chair of the AAP Committee on Infectious Diseases, wrote an article in AAP News in October 2014 describing the needs of children who have been impacted by Ebola virus disease (EVD). She noted that UNICEF estimated there were at that time, over 4,000 Ebola orphans in the countries most affected by EVD, including Sierra Leone, Liberia, and Guinea, and that these countries urgently needed medical infrastructure for treatment and prevention of this disease. It appears that at least two Ebola vaccines will be deployed in West Africa in 2015, and it is not a moment too soon. While cases in Liberia seemed to be decreasing, it looks like Sierra Leone cases continue to mount.

Dr. Jackson is chief of pediatric infectious diseases at Children’s Mercy Hospital, Kansas City, Mo., and professor of pediatrics at the University of Missouri–Kansas City. Dr. Jackson was a member of the AAP Committee on Infectious Diseases who wrote the AAP clinical report entitled “Guidance on Management of Asymptomatic Neonates Born to Women With Active Genital Herpes Lesions,” but said she had no other conflicts of interest to disclose. E-mail her at [email protected].

Last year, there were five predictions made that appeared to be on the money – but there is more to the story!

1. The approach to diagnosis and treatment of influenza was essential knowledge for clinicians. Last year, we started seeing influenza activity early – with disease confirmed in mid-November, peaking during the week ending December 28, 2013 and trending downward in early January 2014. Hospitalizations were most common in young and middle aged adults and the 2009 H1N1 virus predominated.

This year, again we are seeing influenza early – with nearly all states reporting at least sporadic and local activity, and several states (Alaska, Florida, Louisiana, Massachusetts, and Texas) reporting regional activity as of the week ending November 24, 2014. At my institution, we’ve already tested over 500 children and over 100 were positive – influenza A (H3N2) strains are predominating. That may be important for the two reasons you’ll read below.

2. Invasive staphylococcal disease caused by methicillin-susceptible Staphylococcus aureus (MSSA) was more common than methicillin-resistant Staphylococcus aureus (MRSA), as the national burden of MRSA disease decreased (JAMA 2014;311:1438-9). The rates of clindamycin resistance continue to be pretty steady at approximately 15%-18%, but higher for MSSA than for MRSA – a point that is important to consider when empirically treating suspected invasive staphylococcal infection.

3. Multidrug resistant uropathogens took an increasingly prominent role in 2014, requiring careful approach to diagnosis (every child treated for urinary tract infection should have an appropriately obtained urine culture with an identified pathogen) and treatment (the drug used should be based on antibiotic susceptibility testing results). Particularly concerning is the emergence of carbapenem-resistant Enterobacteriaceae, which cause infection more commonly in hospitalized patients, those with indwelling devices, and those who have received long courses of antibiotics.

4. It was an outbreak year for parechovirus (HPeV), a viral pathogen causing meningitis in very young infants. Such infants present with signs and symptoms of meningitis but rarely show CSF pleocytosis. Diagnosis relies on the detection of the virus by polymerase chain reaction testing in CSF – a test which is not routinely available in many laboratories. At my institution this season, we saw nearly as many cases of parechovirus meningitis (n = 43) as we saw cases of enterovirus meningitis (n = 63). The parechovirus virus we detected was HPeV type 3, which can cause particularly severe disease in neonates.

5. Data confirmed that making human papillomavirus (HPV) vaccine a standard recommendation increased vaccine uptake and coverage. In February of 2014, a “Dear Colleague” letter that was endorsed by six leading medical organizations encouraged providers to promote HPV vaccination by giving a strong recommendation, citing data based on research conducted by the Centers for Disease Control and Prevention. We still have a long way to go as HPV vaccine coverage for teens remains at 35% for the three-dose series while meningococcal and Tdap vaccine (both vaccines that generally receive a standard recommendation by physicians) coverage is at nearly 90%.

So for 2015, I’ll start the discussion by saying there are five major developments I did not see coming for this past year, but that will remain relevant for the year 2015!

1. In June of 2014, live attenuated influenza vaccine (LAIV) was announced by the Advisory Committee on Immunization Practices to be the preferred vaccine in children aged 2-8 years. The American Academy of Pediatrics followed with a recommendation that either inactivated influenza vaccine (IIV) or LAIV be used for children, including children aged 2-8 years – the key being to give the vaccine as soon as one had it available. What was not known then and I did not predict was that newer data would confirm that in children aged 2-8 years who received LAIV last year when 2009 H1N1 strains predominated, there was essentially no coverage against 2009 H1N1 virus. This was in contrast to data from the prior 2 years and is as yet unexplained. The AAP continues to recommend that either vaccine be given and all children be immunized. That may be especially important this year as the influenza season started early. Disease will likely have been widespread by Christmas in many parts of the United States, and it looks like influenza A H3N2 strains will be most commonly noted. So the good news for young children who received LAIV is that 2009 H1N1 strains so far have not been seen this year. The bad news is that there are two H3N2 strains circulating, and potentially only one will be covered by the 2014-2015 seasonal vaccine. Staffing your office and hospital for a likely high census respiratory viral season is going to be essential.

2. The largest U.S. outbreak ever of enterovirus (EV) D-68 respiratory infection occurred between August and October of 2014. This virus – which had been identified in 1962 but was rarely described over the next 36 years except in small clusters of disease – was reported in nearly every state and characterized by unusually severe respiratory tract infection. Many, but not all children, had a history of asthma or prior wheezing, and the clinical presentation was that of severe bronchospasm that was generally resistant to standard bronchodilator therapy. The spectrum of infection likely ranged from mild upper respiratory infection to severe bronchospasm with respiratory failure, and the burden of disease resulting in hospitalization was substantial at many children’s hospitals. The big question now is what will enterovirus season 2015 bring us? The good news here is that we now have a test to rapidly diagnose EV D-68, which will allow us to more clearly understand the burden of disease – and potentially to define antiviral treatment (none of the current antivirals is effective) and prevention (there is no vaccine against EV D-68).

3. The etiology of the neurologic illness, which appeared to mimic polio and presented during the same time frame during which EV D-68 was circulating, is as yet unknown. As of Nov. 26, 2014, the CDC has received reports of 90 children in 32 states who meet a case definition consistent with acute flaccid myelitis. While certain viruses – including West Nile virus, herpes virus, adenovirus, and certain enterovirus types (for example, enterovirus 71, and the classic being polio) – may cause acute flaccid paralysis and can be confirmed by detecting the virus in cerebrospinal fluid and stool, to date virus testing for all viruses, including EV D-68, has been negative in all of the patients reported. Hopefully, 2015 will be the year that will allow us to more clearly understand this neurologic illness – and this is important because so far most children have shown minimal recovery of function.

4. If you see a child (or adult) who recently traveled to the Caribbean and returns with fever, rash, and joint pain, especially with severe pain of the hands and feet, think chikungunya virus infection. As of the end of October 2014, local transmission had been identified in 37 countries or territories in the Caribbean (including Puerto Rico and the U.S. Virgin Islands), with a total of 780,206 suspected cases and over 15,000 confirmed cases reported from these areas. Consider this in contrast to the numbers from 2006 through 2011, when 117 cases of chikungunya fever were reported in returning travelers. As of Dec. 2, a total of 1,911 chikungunya virus disease cases have been reported to ArboNET from U.S. states. The mosquito that transmits chikungunya virus can bite in day and night, and prevention relies on appropriate use of mosquito repellents. Physicians should be prepared to discuss the risks of this virus with travelers who plan a trip to the Caribbean, especially those at high risk, including those with underlying medical conditions, preexisting arthritis diagnoses, and pregnant women (because of the potential risk to newborns whose mothers develop intrapartum infection).

5. And lastly, Ebola. While there were reports that Ebola virus disease had emerged in West Africa as early as December of 2013, the scope of the outbreak and extent of loss of human life has been unbelievably huge. Dr. Carrie Byington, who is the current chair of the AAP Committee on Infectious Diseases, wrote an article in AAP News in October 2014 describing the needs of children who have been impacted by Ebola virus disease (EVD). She noted that UNICEF estimated there were at that time, over 4,000 Ebola orphans in the countries most affected by EVD, including Sierra Leone, Liberia, and Guinea, and that these countries urgently needed medical infrastructure for treatment and prevention of this disease. It appears that at least two Ebola vaccines will be deployed in West Africa in 2015, and it is not a moment too soon. While cases in Liberia seemed to be decreasing, it looks like Sierra Leone cases continue to mount.

Dr. Jackson is chief of pediatric infectious diseases at Children’s Mercy Hospital, Kansas City, Mo., and professor of pediatrics at the University of Missouri–Kansas City. Dr. Jackson was a member of the AAP Committee on Infectious Diseases who wrote the AAP clinical report entitled “Guidance on Management of Asymptomatic Neonates Born to Women With Active Genital Herpes Lesions,” but said she had no other conflicts of interest to disclose. E-mail her at [email protected].

Last year, there were five predictions made that appeared to be on the money – but there is more to the story!

1. The approach to diagnosis and treatment of influenza was essential knowledge for clinicians. Last year, we started seeing influenza activity early – with disease confirmed in mid-November, peaking during the week ending December 28, 2013 and trending downward in early January 2014. Hospitalizations were most common in young and middle aged adults and the 2009 H1N1 virus predominated.

This year, again we are seeing influenza early – with nearly all states reporting at least sporadic and local activity, and several states (Alaska, Florida, Louisiana, Massachusetts, and Texas) reporting regional activity as of the week ending November 24, 2014. At my institution, we’ve already tested over 500 children and over 100 were positive – influenza A (H3N2) strains are predominating. That may be important for the two reasons you’ll read below.

2. Invasive staphylococcal disease caused by methicillin-susceptible Staphylococcus aureus (MSSA) was more common than methicillin-resistant Staphylococcus aureus (MRSA), as the national burden of MRSA disease decreased (JAMA 2014;311:1438-9). The rates of clindamycin resistance continue to be pretty steady at approximately 15%-18%, but higher for MSSA than for MRSA – a point that is important to consider when empirically treating suspected invasive staphylococcal infection.

3. Multidrug resistant uropathogens took an increasingly prominent role in 2014, requiring careful approach to diagnosis (every child treated for urinary tract infection should have an appropriately obtained urine culture with an identified pathogen) and treatment (the drug used should be based on antibiotic susceptibility testing results). Particularly concerning is the emergence of carbapenem-resistant Enterobacteriaceae, which cause infection more commonly in hospitalized patients, those with indwelling devices, and those who have received long courses of antibiotics.

4. It was an outbreak year for parechovirus (HPeV), a viral pathogen causing meningitis in very young infants. Such infants present with signs and symptoms of meningitis but rarely show CSF pleocytosis. Diagnosis relies on the detection of the virus by polymerase chain reaction testing in CSF – a test which is not routinely available in many laboratories. At my institution this season, we saw nearly as many cases of parechovirus meningitis (n = 43) as we saw cases of enterovirus meningitis (n = 63). The parechovirus virus we detected was HPeV type 3, which can cause particularly severe disease in neonates.

5. Data confirmed that making human papillomavirus (HPV) vaccine a standard recommendation increased vaccine uptake and coverage. In February of 2014, a “Dear Colleague” letter that was endorsed by six leading medical organizations encouraged providers to promote HPV vaccination by giving a strong recommendation, citing data based on research conducted by the Centers for Disease Control and Prevention. We still have a long way to go as HPV vaccine coverage for teens remains at 35% for the three-dose series while meningococcal and Tdap vaccine (both vaccines that generally receive a standard recommendation by physicians) coverage is at nearly 90%.

So for 2015, I’ll start the discussion by saying there are five major developments I did not see coming for this past year, but that will remain relevant for the year 2015!

1. In June of 2014, live attenuated influenza vaccine (LAIV) was announced by the Advisory Committee on Immunization Practices to be the preferred vaccine in children aged 2-8 years. The American Academy of Pediatrics followed with a recommendation that either inactivated influenza vaccine (IIV) or LAIV be used for children, including children aged 2-8 years – the key being to give the vaccine as soon as one had it available. What was not known then and I did not predict was that newer data would confirm that in children aged 2-8 years who received LAIV last year when 2009 H1N1 strains predominated, there was essentially no coverage against 2009 H1N1 virus. This was in contrast to data from the prior 2 years and is as yet unexplained. The AAP continues to recommend that either vaccine be given and all children be immunized. That may be especially important this year as the influenza season started early. Disease will likely have been widespread by Christmas in many parts of the United States, and it looks like influenza A H3N2 strains will be most commonly noted. So the good news for young children who received LAIV is that 2009 H1N1 strains so far have not been seen this year. The bad news is that there are two H3N2 strains circulating, and potentially only one will be covered by the 2014-2015 seasonal vaccine. Staffing your office and hospital for a likely high census respiratory viral season is going to be essential.

2. The largest U.S. outbreak ever of enterovirus (EV) D-68 respiratory infection occurred between August and October of 2014. This virus – which had been identified in 1962 but was rarely described over the next 36 years except in small clusters of disease – was reported in nearly every state and characterized by unusually severe respiratory tract infection. Many, but not all children, had a history of asthma or prior wheezing, and the clinical presentation was that of severe bronchospasm that was generally resistant to standard bronchodilator therapy. The spectrum of infection likely ranged from mild upper respiratory infection to severe bronchospasm with respiratory failure, and the burden of disease resulting in hospitalization was substantial at many children’s hospitals. The big question now is what will enterovirus season 2015 bring us? The good news here is that we now have a test to rapidly diagnose EV D-68, which will allow us to more clearly understand the burden of disease – and potentially to define antiviral treatment (none of the current antivirals is effective) and prevention (there is no vaccine against EV D-68).

3. The etiology of the neurologic illness, which appeared to mimic polio and presented during the same time frame during which EV D-68 was circulating, is as yet unknown. As of Nov. 26, 2014, the CDC has received reports of 90 children in 32 states who meet a case definition consistent with acute flaccid myelitis. While certain viruses – including West Nile virus, herpes virus, adenovirus, and certain enterovirus types (for example, enterovirus 71, and the classic being polio) – may cause acute flaccid paralysis and can be confirmed by detecting the virus in cerebrospinal fluid and stool, to date virus testing for all viruses, including EV D-68, has been negative in all of the patients reported. Hopefully, 2015 will be the year that will allow us to more clearly understand this neurologic illness – and this is important because so far most children have shown minimal recovery of function.

4. If you see a child (or adult) who recently traveled to the Caribbean and returns with fever, rash, and joint pain, especially with severe pain of the hands and feet, think chikungunya virus infection. As of the end of October 2014, local transmission had been identified in 37 countries or territories in the Caribbean (including Puerto Rico and the U.S. Virgin Islands), with a total of 780,206 suspected cases and over 15,000 confirmed cases reported from these areas. Consider this in contrast to the numbers from 2006 through 2011, when 117 cases of chikungunya fever were reported in returning travelers. As of Dec. 2, a total of 1,911 chikungunya virus disease cases have been reported to ArboNET from U.S. states. The mosquito that transmits chikungunya virus can bite in day and night, and prevention relies on appropriate use of mosquito repellents. Physicians should be prepared to discuss the risks of this virus with travelers who plan a trip to the Caribbean, especially those at high risk, including those with underlying medical conditions, preexisting arthritis diagnoses, and pregnant women (because of the potential risk to newborns whose mothers develop intrapartum infection).

5. And lastly, Ebola. While there were reports that Ebola virus disease had emerged in West Africa as early as December of 2013, the scope of the outbreak and extent of loss of human life has been unbelievably huge. Dr. Carrie Byington, who is the current chair of the AAP Committee on Infectious Diseases, wrote an article in AAP News in October 2014 describing the needs of children who have been impacted by Ebola virus disease (EVD). She noted that UNICEF estimated there were at that time, over 4,000 Ebola orphans in the countries most affected by EVD, including Sierra Leone, Liberia, and Guinea, and that these countries urgently needed medical infrastructure for treatment and prevention of this disease. It appears that at least two Ebola vaccines will be deployed in West Africa in 2015, and it is not a moment too soon. While cases in Liberia seemed to be decreasing, it looks like Sierra Leone cases continue to mount.

Dr. Jackson is chief of pediatric infectious diseases at Children’s Mercy Hospital, Kansas City, Mo., and professor of pediatrics at the University of Missouri–Kansas City. Dr. Jackson was a member of the AAP Committee on Infectious Diseases who wrote the AAP clinical report entitled “Guidance on Management of Asymptomatic Neonates Born to Women With Active Genital Herpes Lesions,” but said she had no other conflicts of interest to disclose. E-mail her at [email protected].

CHICAGO – Cardiologists certainly have their work cut out in order to bring their patients into concordance with the 2013 American College of Cardiology/American Heart Association cholesterol guidelines, according to Dr. Thomas M. Maddox.

An analysis of nearly 1.2 million patients in U.S. outpatient cardiology practices showed that one in three who appeared to have an indication for statin therapy under the latest guidelines weren’t on a statin as of 2012. That constitutes a sizable “statin gap” that cardiologists need to address, he said at the American Heart Association scientific sessions.

Dr. Maddox presented an analysis of 1,174,535 adult patients under cardiologists’ care during 2008-2012 in more than 100 U.S. outpatient cardiology practices participating in the voluntary National Cardiovascular Data Registry’s Practice Innovation and Clinical Excellence Registry (NCDR PINNACLE). Under this national office-based quality improvement program sponsored by the ACC, patient electronic medical record (EMR) data gets uploaded to the registry nightly.

The 2013 ACC/AHA cholesterol guidelines in some ways greatly simplified patient management. The guidelines redefined the risk groups warranting treatment: basically, patients with known atherosclerotic cardiovascular disease (ASCVD), diabetes, an off-treatment LDL of 190 mg/dL or more, or a 10-year ASCVD risk of 7.5% or greater using the risk calculator incorporated in the guidelines (Circulation 2014; 129:S1-45). Also, physicians were advised to use fixed-dose statins and no longer to treat to an LDL target, thereby making repeated LDL testing unnecessary.

The purposes of this new NCDR PINNACLE study were to evaluate the potential impact of the new guidelines on current cardiology practice through an assessment of current treatment and testing patterns, and to make a determination of the scope of changes necessary under the 2013 guidelines, explained Dr. Maddox, a cardiologist at the Veterans Affairs Eastern Colorado Health Care System and the University of Colorado at Denver.

Under the new guidelines, 1,129,205 adult cardiology patients, or 96% of the study population, appeared to be candidates for statin therapy, most often because they had known ASCVD, as was the case in 88%, or diabetes without known ASCVD, accounting for another 6%.

Among the statin-eligible patients, 29% were not on any lipid-lowering therapy, and another 3% were on nonstatin lipid-lowering agents only, which is not recommended in the guidelines. Thus, 32% of the cardiologists’ patients for whom statin therapy appeared to be indicated under the 2013 guidelines weren’t on it.

In addition, 29% of statin-eligible patients were on combined lipid-lowering therapy with a statin plus a nonstatin, such as niacin, a fibrate, or ezetimibe. The guidelines don’t recommend the use of nonstatins because of the lack of evidence of clinical benefit, so cardiologists will want to reconsider their use of combination therapy in this sizable group. The major caveat here is that the guidelines are likely to be revised to embrace the selective use of a moderate-intensity statin plus ezetimibe on the basis of the positive findings of the IMPROVE-IT trial, also presented at the AHA meeting, Dr. Maddox noted.

The registry analysis also pointed to a need to reduce repeated LDL testing, which the guidelines characterize as costly, inconvenient, and unnecessary. Nearly 21% of subjects had at least two LDL assessments during the 4-year period, and 7% had more than four. And those figures probably underestimate the true rate of LDL testing, since many patients may have also had LDL measurements taken in primary care settings.

Several audience members rose to decry the one-in-three-patient statin gap as evidence of widespread substandard care by cardiologists, especially given that 28% of the patients with known ASCVD and 36% with diabetes were not receiving any lipid-lowering therapy, contrary to recommendations both in the current ACC/AHA guidelines and the guidelines in place in 2012. There is good evidence to show that putting such patients on statin therapy would result in roughly a 25% reduction in cardiovascular events.

But Dr. Maddox took a more sanguine view of the statin gap. Although it’s likely there is some heterogeneity in clinical practice that needs to be corrected, he cautioned that the limitations of an analysis based upon EMR data must be borne in mind. Some cardiologists probably didn’t record the use of statins at every visit, and they may not have always reliably documented patients’ intolerance of statins in the EMR.

The NCDR PINNACLE Registry is supported by the American College of Cardiology Foundation. Dr. Maddox reported having no relevant financial conflicts of interest.

[email protected]

CHICAGO – Cardiologists certainly have their work cut out in order to bring their patients into concordance with the 2013 American College of Cardiology/American Heart Association cholesterol guidelines, according to Dr. Thomas M. Maddox.

An analysis of nearly 1.2 million patients in U.S. outpatient cardiology practices showed that one in three who appeared to have an indication for statin therapy under the latest guidelines weren’t on a statin as of 2012. That constitutes a sizable “statin gap” that cardiologists need to address, he said at the American Heart Association scientific sessions.

Dr. Maddox presented an analysis of 1,174,535 adult patients under cardiologists’ care during 2008-2012 in more than 100 U.S. outpatient cardiology practices participating in the voluntary National Cardiovascular Data Registry’s Practice Innovation and Clinical Excellence Registry (NCDR PINNACLE). Under this national office-based quality improvement program sponsored by the ACC, patient electronic medical record (EMR) data gets uploaded to the registry nightly.

The 2013 ACC/AHA cholesterol guidelines in some ways greatly simplified patient management. The guidelines redefined the risk groups warranting treatment: basically, patients with known atherosclerotic cardiovascular disease (ASCVD), diabetes, an off-treatment LDL of 190 mg/dL or more, or a 10-year ASCVD risk of 7.5% or greater using the risk calculator incorporated in the guidelines (Circulation 2014; 129:S1-45). Also, physicians were advised to use fixed-dose statins and no longer to treat to an LDL target, thereby making repeated LDL testing unnecessary.

The purposes of this new NCDR PINNACLE study were to evaluate the potential impact of the new guidelines on current cardiology practice through an assessment of current treatment and testing patterns, and to make a determination of the scope of changes necessary under the 2013 guidelines, explained Dr. Maddox, a cardiologist at the Veterans Affairs Eastern Colorado Health Care System and the University of Colorado at Denver.

Under the new guidelines, 1,129,205 adult cardiology patients, or 96% of the study population, appeared to be candidates for statin therapy, most often because they had known ASCVD, as was the case in 88%, or diabetes without known ASCVD, accounting for another 6%.

Among the statin-eligible patients, 29% were not on any lipid-lowering therapy, and another 3% were on nonstatin lipid-lowering agents only, which is not recommended in the guidelines. Thus, 32% of the cardiologists’ patients for whom statin therapy appeared to be indicated under the 2013 guidelines weren’t on it.

In addition, 29% of statin-eligible patients were on combined lipid-lowering therapy with a statin plus a nonstatin, such as niacin, a fibrate, or ezetimibe. The guidelines don’t recommend the use of nonstatins because of the lack of evidence of clinical benefit, so cardiologists will want to reconsider their use of combination therapy in this sizable group. The major caveat here is that the guidelines are likely to be revised to embrace the selective use of a moderate-intensity statin plus ezetimibe on the basis of the positive findings of the IMPROVE-IT trial, also presented at the AHA meeting, Dr. Maddox noted.

The registry analysis also pointed to a need to reduce repeated LDL testing, which the guidelines characterize as costly, inconvenient, and unnecessary. Nearly 21% of subjects had at least two LDL assessments during the 4-year period, and 7% had more than four. And those figures probably underestimate the true rate of LDL testing, since many patients may have also had LDL measurements taken in primary care settings.

Several audience members rose to decry the one-in-three-patient statin gap as evidence of widespread substandard care by cardiologists, especially given that 28% of the patients with known ASCVD and 36% with diabetes were not receiving any lipid-lowering therapy, contrary to recommendations both in the current ACC/AHA guidelines and the guidelines in place in 2012. There is good evidence to show that putting such patients on statin therapy would result in roughly a 25% reduction in cardiovascular events.

But Dr. Maddox took a more sanguine view of the statin gap. Although it’s likely there is some heterogeneity in clinical practice that needs to be corrected, he cautioned that the limitations of an analysis based upon EMR data must be borne in mind. Some cardiologists probably didn’t record the use of statins at every visit, and they may not have always reliably documented patients’ intolerance of statins in the EMR.

The NCDR PINNACLE Registry is supported by the American College of Cardiology Foundation. Dr. Maddox reported having no relevant financial conflicts of interest.

[email protected]

CHICAGO – Cardiologists certainly have their work cut out in order to bring their patients into concordance with the 2013 American College of Cardiology/American Heart Association cholesterol guidelines, according to Dr. Thomas M. Maddox.

An analysis of nearly 1.2 million patients in U.S. outpatient cardiology practices showed that one in three who appeared to have an indication for statin therapy under the latest guidelines weren’t on a statin as of 2012. That constitutes a sizable “statin gap” that cardiologists need to address, he said at the American Heart Association scientific sessions.

Dr. Maddox presented an analysis of 1,174,535 adult patients under cardiologists’ care during 2008-2012 in more than 100 U.S. outpatient cardiology practices participating in the voluntary National Cardiovascular Data Registry’s Practice Innovation and Clinical Excellence Registry (NCDR PINNACLE). Under this national office-based quality improvement program sponsored by the ACC, patient electronic medical record (EMR) data gets uploaded to the registry nightly.

The 2013 ACC/AHA cholesterol guidelines in some ways greatly simplified patient management. The guidelines redefined the risk groups warranting treatment: basically, patients with known atherosclerotic cardiovascular disease (ASCVD), diabetes, an off-treatment LDL of 190 mg/dL or more, or a 10-year ASCVD risk of 7.5% or greater using the risk calculator incorporated in the guidelines (Circulation 2014; 129:S1-45). Also, physicians were advised to use fixed-dose statins and no longer to treat to an LDL target, thereby making repeated LDL testing unnecessary.

The purposes of this new NCDR PINNACLE study were to evaluate the potential impact of the new guidelines on current cardiology practice through an assessment of current treatment and testing patterns, and to make a determination of the scope of changes necessary under the 2013 guidelines, explained Dr. Maddox, a cardiologist at the Veterans Affairs Eastern Colorado Health Care System and the University of Colorado at Denver.

Under the new guidelines, 1,129,205 adult cardiology patients, or 96% of the study population, appeared to be candidates for statin therapy, most often because they had known ASCVD, as was the case in 88%, or diabetes without known ASCVD, accounting for another 6%.

Among the statin-eligible patients, 29% were not on any lipid-lowering therapy, and another 3% were on nonstatin lipid-lowering agents only, which is not recommended in the guidelines. Thus, 32% of the cardiologists’ patients for whom statin therapy appeared to be indicated under the 2013 guidelines weren’t on it.

In addition, 29% of statin-eligible patients were on combined lipid-lowering therapy with a statin plus a nonstatin, such as niacin, a fibrate, or ezetimibe. The guidelines don’t recommend the use of nonstatins because of the lack of evidence of clinical benefit, so cardiologists will want to reconsider their use of combination therapy in this sizable group. The major caveat here is that the guidelines are likely to be revised to embrace the selective use of a moderate-intensity statin plus ezetimibe on the basis of the positive findings of the IMPROVE-IT trial, also presented at the AHA meeting, Dr. Maddox noted.

The registry analysis also pointed to a need to reduce repeated LDL testing, which the guidelines characterize as costly, inconvenient, and unnecessary. Nearly 21% of subjects had at least two LDL assessments during the 4-year period, and 7% had more than four. And those figures probably underestimate the true rate of LDL testing, since many patients may have also had LDL measurements taken in primary care settings.

Several audience members rose to decry the one-in-three-patient statin gap as evidence of widespread substandard care by cardiologists, especially given that 28% of the patients with known ASCVD and 36% with diabetes were not receiving any lipid-lowering therapy, contrary to recommendations both in the current ACC/AHA guidelines and the guidelines in place in 2012. There is good evidence to show that putting such patients on statin therapy would result in roughly a 25% reduction in cardiovascular events.

But Dr. Maddox took a more sanguine view of the statin gap. Although it’s likely there is some heterogeneity in clinical practice that needs to be corrected, he cautioned that the limitations of an analysis based upon EMR data must be borne in mind. Some cardiologists probably didn’t record the use of statins at every visit, and they may not have always reliably documented patients’ intolerance of statins in the EMR.

The NCDR PINNACLE Registry is supported by the American College of Cardiology Foundation. Dr. Maddox reported having no relevant financial conflicts of interest.

[email protected]

For patients presenting with early septic shock, does early goal-directed therapy reduce mortality?

Bottom line

As compared with usual resuscitation care, early goal-directed therapy (EGDT) using central venous monitoring does not improve mortality in patients presenting to the emergency department with septic shock.

Reference

ARISE Investigators; ANZICS Clinical Trials Group, Peake SL, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med 2014;371(16):1496-1506.

Study design

Randomized controlled trial (nonblinded); (LOE: 1b)

Setting

Inpatient (ICU only)

Synopsis

A recent trial showed that protocolized care using EGDT for the treatment of septic shock does not decrease mortality (N Engl J Med 2014;370:1683-1693). The current study supports these findings. Using concealed allocation, investigators randomized patients presenting to the emergency department with evidence of septic shock to either EGDT or usual care. For the EGDT group (n = 793), clinicians followed a 6-hour resuscitation protocol with central venous hemodynamic monitoring to guide the use of fluids, vasopressors, inotropes, and transfusions. For the usual care group (n = 798), care was at the discretion of the treating physicians, but central venous monitoring was not permitted during the 6-hour intervention. Analysis was by intention to treat and the 2 groups were similar at baseline. Additionally, adherence to the EGDT protocol was high and loss to follow-up was low. During the 6-hour resuscitation, patients in the EGDT group received a greater volume of intravenous fluids and were more likely to have received vasopressors (67% vs 58%), transfusions (14% vs 7%), or dobutamine (15% vs 3%). For the primary outcome of 90-day mortality, however, there was no significant difference detected between the 2 groups. Furthermore, there were no significant differences in the use of renal replacement therapy, in-hospital mortality, or length of hospital stay.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

For patients presenting with early septic shock, does early goal-directed therapy reduce mortality?

Bottom line

As compared with usual resuscitation care, early goal-directed therapy (EGDT) using central venous monitoring does not improve mortality in patients presenting to the emergency department with septic shock.

Reference

ARISE Investigators; ANZICS Clinical Trials Group, Peake SL, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med 2014;371(16):1496-1506.

Study design

Randomized controlled trial (nonblinded); (LOE: 1b)

Setting

Inpatient (ICU only)

Synopsis

A recent trial showed that protocolized care using EGDT for the treatment of septic shock does not decrease mortality (N Engl J Med 2014;370:1683-1693). The current study supports these findings. Using concealed allocation, investigators randomized patients presenting to the emergency department with evidence of septic shock to either EGDT or usual care. For the EGDT group (n = 793), clinicians followed a 6-hour resuscitation protocol with central venous hemodynamic monitoring to guide the use of fluids, vasopressors, inotropes, and transfusions. For the usual care group (n = 798), care was at the discretion of the treating physicians, but central venous monitoring was not permitted during the 6-hour intervention. Analysis was by intention to treat and the 2 groups were similar at baseline. Additionally, adherence to the EGDT protocol was high and loss to follow-up was low. During the 6-hour resuscitation, patients in the EGDT group received a greater volume of intravenous fluids and were more likely to have received vasopressors (67% vs 58%), transfusions (14% vs 7%), or dobutamine (15% vs 3%). For the primary outcome of 90-day mortality, however, there was no significant difference detected between the 2 groups. Furthermore, there were no significant differences in the use of renal replacement therapy, in-hospital mortality, or length of hospital stay.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

For patients presenting with early septic shock, does early goal-directed therapy reduce mortality?

Bottom line

As compared with usual resuscitation care, early goal-directed therapy (EGDT) using central venous monitoring does not improve mortality in patients presenting to the emergency department with septic shock.

Reference

ARISE Investigators; ANZICS Clinical Trials Group, Peake SL, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med 2014;371(16):1496-1506.

Study design

Randomized controlled trial (nonblinded); (LOE: 1b)

Setting

Inpatient (ICU only)

Synopsis

A recent trial showed that protocolized care using EGDT for the treatment of septic shock does not decrease mortality (N Engl J Med 2014;370:1683-1693). The current study supports these findings. Using concealed allocation, investigators randomized patients presenting to the emergency department with evidence of septic shock to either EGDT or usual care. For the EGDT group (n = 793), clinicians followed a 6-hour resuscitation protocol with central venous hemodynamic monitoring to guide the use of fluids, vasopressors, inotropes, and transfusions. For the usual care group (n = 798), care was at the discretion of the treating physicians, but central venous monitoring was not permitted during the 6-hour intervention. Analysis was by intention to treat and the 2 groups were similar at baseline. Additionally, adherence to the EGDT protocol was high and loss to follow-up was low. During the 6-hour resuscitation, patients in the EGDT group received a greater volume of intravenous fluids and were more likely to have received vasopressors (67% vs 58%), transfusions (14% vs 7%), or dobutamine (15% vs 3%). For the primary outcome of 90-day mortality, however, there was no significant difference detected between the 2 groups. Furthermore, there were no significant differences in the use of renal replacement therapy, in-hospital mortality, or length of hospital stay.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Skin diseases are highly prevalent in the United States, affecting an estimated 1 in 3 Americans at any given time.^1,2 In 2009 the direct medical costs associated with skin-related diseases, including health services and prescriptions, was approximately $22 billion; the annual total economic burden was estimated to be closer to $96 billion when factoring in the cost of lost productivity and pay for symptom relief.^3,4 Effective and efficient management of skin disease is essential to minimizing cost and morbidity. Nondermatologists traditionally have diagnosed the majority of skin diseases.^5,6 In particular, primary care physicians commonly manage dermatologic conditions and often are the first health care providers to encounter patients presenting with skin problems. A predicted shortage of dermatologists will likely contribute to an increase in this trend.^7,8 Therefore, it is important to adequately prepare nondermatologists to evaluate and treat the skin conditions that they are most likely to encounter in their scope of practice.

Residents, particularly in primary care specialties, often have opportunities to spend 2 to 4 weeks with a dermatologist to learn about skin diseases; however, the skin conditions most often encountered by dermatologists may differ from those most often encountered by physicians in other specialties. For instance, one study demonstrated a disparity between the most common skin problems seen by dermatologists and internists.⁹ These dissimilarities should be recognized and addressed in curriculum content. The purpose of this study was to identify and compare the 20 most common dermatologic conditions reported by dermatologists versus those reported by nondermatologists (ie, internists, pediatricians, family physicians, emergency medicine physicians, general surgeons, otolaryngologists) from 2001 to 2010. Data also were analyzed to determine the top 20 conditions referred to dermatologists by nondermatologists as a potential indicator for areas of further improvement within medical education. With this knowledge, we hope educational curricula and self-study can be modified to reflect the current epidemiology of cutaneous diseases, thereby improving patient care.

Methods

Data from 2001 to 2010 were extracted from the National Ambulatory Medical Care Survey (NAMCS), which is an ongoing survey conducted by the National Center for Health Statistics. The NAMCS collects descriptive data regarding ambulatory visits to nonfederal office-based physicians in the United States. Participating physicians are instructed to record information about patient visits for a 1-week period, including patient demographics, insurance status, reason for visit, diagnoses, procedures, therapeutics, and referrals made at that time. Data collected for the NAMCS are entered into a multistage probability sample to produce national estimates. Within dermatology, an average of 118 dermatologists are sampled each year, and over the last 10 years, participation rates have ranged from 47% to 77%.

International Classification of Diseases, Ninth Revision, Clinical Modification codes were identified to determine the diagnoses that could be classified as dermatologic conditions. Select infectious and neoplastic disorders of the skin and mucous membrane conditions were included as well as the codes for skin diseases. Nondermatologic diagnoses and V codes were not included in the study. Data for all providers were studied to identify outpatient visits associated with the primary diagnosis of a dermatologic condition. Minor diagnoses that were considered to be subsets of major diagnoses were combined to allow better analysis of the data. For example, all tinea infections (ie, dermatophytosis of various sites, dermatomycosis unspecified) were combined into 1 diagnosis referred to as tinea because the recognition and treatment of this disease does not vary tremendously by anatomic location. Visits to dermatologists that listed nonspecific diagnoses and codes (eg, other postsurgical status [V45.89], neoplasm of uncertain behavior site unspecified [238.9]) were assumed to be for dermatologic problems.

Sampling weights were applied to obtain estimates for the number of each diagnosis made nationally. All data analyses were performed using SAS software and linear regression models were generated using SAS PROC SURVEYREG.

Data were analyzed to determine the dermatologic conditions most commonly encountered by dermatologists and nondermatologists in emergency medicine, family medicine, general surgery, internal medicine, otolaryngology, and pediatrics; these specialties include physicians who are known to commonly diagnose and treat skin diseases.¹⁰ Data also were analyzed to determine the most common conditions referred to dermatologists for treatment by nondermatologists from the selected specialties. Permission to conduct this study was obtained from the Wake Forest University institutional review board (Winston-Salem, North Carolina).

Results

From 2001 to 2010, more than 700 million outpatient visits for skin-related problems were identified, with 676.3 million visits to dermatologists, emergency medicine physicians, family practitioners, general surgeons, internists, otolaryngologists, and pediatricians. More than half (52.9%) of all skin-related visits were addressed by nondermatologists during this time. Among nondermatologists, family practitioners encountered the greatest number of skin diseases (20.5%), followed by pediatricians (11.3%), internists (9.2%), general surgeons (3.4%), otolaryngologists (1.0%), and emergency medicine physicians (0.2%)(Table 1).

Benign tumors and acne were the most common cutaneous conditions referred to dermatologists by nondermatologists (10.6% and 10.1% of all dermatology referrals, respectively), followed by nonmelanoma skin cancers (9.7%), contact dermatitis (8.8%), and actinic keratosis (7.8%)(Table 2). The top 20 conditions referred to dermatologists accounted for 83.7% of all outpatient referrals to dermatologists.

Among the diseases most frequently reported by nondermatologists, contact dermatitis was the most common (12.0%), with twice the number of visits to nondermatologists for contact dermatitis than to dermatologists (51.6 million vs 25.3 million). In terms of disease categories, infectious skin diseases (ie, bacterial [cellulitis/abscess], viral [warts, herpesvirus], fungal [tinea] and yeast [candida] etiologies) were the most common dermatologic conditions reported by nondermatologists (Table 2).

The top 20 dermatologic conditions reported by dermatologists accounted for 85.4% of all diagnoses made by dermatologists. Diseases that were among the top 20 conditions encountered by dermatologists but were not among the top 20 for nondermatologists included actinic keratosis, seborrheic keratosis, atopic dermatitis, psoriasis, alopecia, rosacea, dyschromia, seborrheic dermatitis, follicular disease, and neoplasm of uncertain behavior of skin. Additionally, 5 of the top 20 conditions encountered by dermatologists also were among the top 20 for only 1 individual nondermatologic specialty; these included atopic dermatitis (pediatrics), seborrheic dermatitis (pediatrics), psoriasis (internal medicine), rosacea (otolaryngology), and keratoderma (general surgery). Seborrheic dermatitis, psoriasis, and rosacea also were among the top 20 conditions most commonly referred to dermatologists for treatment by nondermatologists. Table 3 shows the top 20 dermatologic conditions encountered by nondermatologists by comparison.

Comment

According to NAMCS data from 2001 to 2010, visits to nondermatologists accounted for more than half of total outpatient visits for cutaneous diseases in the United States, whereas visits to dermatologists accounted for 47.1%. These findings are consistent with historical data indicating that 30% to 40% of skin-related visits are to dermatologists, and the majority of patients with skin disease are diagnosed by nondermatologists.^5,6

Past data indicate that most visits to dermatologists were for evaluation of acne, infections, psoriasis, and neoplasms, whereas most visits to nondermatologists were for evaluation of epidermoid cysts, impetigo, plant dermatitis, cellulitis, and diaper rash.⁹ Over the last 10 years, acne has been more commonly encountered by nondermatologists, especially pediatricians. Additionally, infectious etiologies have been seen in larger volume by nondermatologists.⁹ Together, infectious cutaneous conditions make up nearly one-fourth of dermatologic encounters by emergency medicine physicians, internists, and family practitioners but are not within the top 20 diagnoses referred to dermatologists, which suggests that uncomplicated cases of cellulitis, herpes zoster, and other skin-related infections are largely managed by nondermatologists.^5,6 Contact dermatitis, often caused by specific allergens such as detergents, solvents, and topical products, was one of the most common reported dermatologic encounters among dermatologists and nondermatologists and also was the fourth most common condition referred to dermatologists by nondermatologists for treatment; however, there may be an element of overuse of the International Classification of Diseases, Ninth Revision code, as any presumed contact dermatitis of unspecified cause can be reported under 692.9 defined as contact dermatitis and other eczema, unspecified cause. The high rate of referrals to dermatologists by nondermatologists may be for patch testing and further management. Additionally, there are no specific codes for allergic or irritant dermatitis, thus these diseases may be lumped together.

Although nearly half of all dermatologic encounters were seen by nondermatologists, dermatologists see a much larger proportion of patients with skin disease than nondermatologists and nondermatologists often have limited exposure to the field of dermatology during residency training. Studies have demonstrated differences in the abilities of dermatologists and nondermatologists to correctly diagnose common cutaneous diseases, which unsurprisingly revealed greater diagnostic accuracy demonstrated by dermatologists.^11-16 The increase in acne and skin-related infections reported by nondermatologists is consistent with possible efforts to increase formal training in frequently encountered skin diseases. In one study evaluating the impact of a formal 3-week dermatology curriculum on an internal medicine department, internists demonstrated 100% accuracy in the diagnosis of acne and herpes zoster in contrast to 29% for tinea and 12% for lichen planus.^5,6

The current Accreditation Council for Graduate Medical Education guidelines place little emphasis on exposure to dermatology training during residency for internists and pediatricians, as this training is not a required component of these programs.¹⁷ Two core problems with current training regarding the evaluation and management of cutaneous disease are minimal exposure to dermatologic conditions in medical school and residency and lack of consensus on the core topics that should be taught to nondermatologists.¹⁸ Exposure to dermatologic conditions through rotations in medical school has been shown to increase residents’ self-reported confidence in diagnosing and treating alopecia, cutaneous drug eruptions, warts, acne, rosacea, nonmelanoma skin cancers, sun damage, psoriasis, seborrhea, atopic dermatitis, and contact dermatitis; however, the majority of primary care residents surveyed still felt that this exposure in medical school was inadequate.¹⁹

In creating a core curriculum for dermatology training for nondermatologists, it is important to consider the dermatologic conditions that are most frequently encountered by these specialties. Our study revealed that the most commonly encountered dermatologic conditions differ among dermatologists and nondermatologists, with a fair degree of variation even among individual specialties. Failure to recognize these discrepancies has likely contributed to the challenges faced by nondermatologists in the diagnosis and management of dermatologic disease. In this study, contact dermatitis, epidermoid cysts, and skin infections were the most common dermatologic conditions encountered by nondermatologists and also were among the top skin diseases referred to dermatologists by nondermatologists. This finding suggests that nondermatologists are able to identify these conditions but have a tendency to refer approximately 10% of these patients to dermatology for further management. Clinical evaluation and medical management of these cutaneous diseases may be an important area of focus for medical school curricula, as the treatment of these diseases is within the capabilities of the nondermatologist. For example, initial management of dermatitis requires determination of the type of dermatitis (ie, essential, contact, atopic, seborrheic, stasis) and selection of an appropriate topical steroid, with referral to a dermatologist needed for questionable or refractory cases. Although a curriculum cannot be built solely on a list of the top 20 diagnoses provided here, these data may serve as a preliminary platform for medical school dermatology curriculum design. The curriculum also should include serious skin diseases, such as melanoma and severe drug eruptions. Although these conditions are less commonly encountered by nondermatologists, missed diagnosis and/or improper management can be life threatening.

The use of NAMCS data presents a few limitations. For instance, these data only represent outpatient management of skin disease. There is the potential for misdiagnosis and coding errors by the reporting physicians. The volume of data (ie, billions of office visits) prevents verification of diagnostic accuracy. The coding system requires physicians to give a diagnosis but does not provide any means by which to determine the physician’s confidence in that diagnosis. There is no code for “uncertain” or “diagnosis not determined.” Additionally, an “unspecified” diagnosis may reflect uncertainty or may simply imply that no other code accurately described the condition. Despite these limitations, the NAMCS database is a large, nationally representative survey of actual patient visits and represents some of the best data available for a study such as ours.

Conclusion

This study provides an important analysis of the most common outpatient dermatologic conditions encountered by dermatologists and nondermatologists of various specialties and offers a foundation from which to construct curricula for dermatology training tailored to individual specialties based on their needs. In the future, identification of the most common inpatient dermatologic conditions managed by each specialty also may benefit curriculum design.

Skin diseases are highly prevalent in the United States, affecting an estimated 1 in 3 Americans at any given time.^1,2 In 2009 the direct medical costs associated with skin-related diseases, including health services and prescriptions, was approximately $22 billion; the annual total economic burden was estimated to be closer to $96 billion when factoring in the cost of lost productivity and pay for symptom relief.^3,4 Effective and efficient management of skin disease is essential to minimizing cost and morbidity. Nondermatologists traditionally have diagnosed the majority of skin diseases.^5,6 In particular, primary care physicians commonly manage dermatologic conditions and often are the first health care providers to encounter patients presenting with skin problems. A predicted shortage of dermatologists will likely contribute to an increase in this trend.^7,8 Therefore, it is important to adequately prepare nondermatologists to evaluate and treat the skin conditions that they are most likely to encounter in their scope of practice.

Residents, particularly in primary care specialties, often have opportunities to spend 2 to 4 weeks with a dermatologist to learn about skin diseases; however, the skin conditions most often encountered by dermatologists may differ from those most often encountered by physicians in other specialties. For instance, one study demonstrated a disparity between the most common skin problems seen by dermatologists and internists.⁹ These dissimilarities should be recognized and addressed in curriculum content. The purpose of this study was to identify and compare the 20 most common dermatologic conditions reported by dermatologists versus those reported by nondermatologists (ie, internists, pediatricians, family physicians, emergency medicine physicians, general surgeons, otolaryngologists) from 2001 to 2010. Data also were analyzed to determine the top 20 conditions referred to dermatologists by nondermatologists as a potential indicator for areas of further improvement within medical education. With this knowledge, we hope educational curricula and self-study can be modified to reflect the current epidemiology of cutaneous diseases, thereby improving patient care.

Methods

Data from 2001 to 2010 were extracted from the National Ambulatory Medical Care Survey (NAMCS), which is an ongoing survey conducted by the National Center for Health Statistics. The NAMCS collects descriptive data regarding ambulatory visits to nonfederal office-based physicians in the United States. Participating physicians are instructed to record information about patient visits for a 1-week period, including patient demographics, insurance status, reason for visit, diagnoses, procedures, therapeutics, and referrals made at that time. Data collected for the NAMCS are entered into a multistage probability sample to produce national estimates. Within dermatology, an average of 118 dermatologists are sampled each year, and over the last 10 years, participation rates have ranged from 47% to 77%.

International Classification of Diseases, Ninth Revision, Clinical Modification codes were identified to determine the diagnoses that could be classified as dermatologic conditions. Select infectious and neoplastic disorders of the skin and mucous membrane conditions were included as well as the codes for skin diseases. Nondermatologic diagnoses and V codes were not included in the study. Data for all providers were studied to identify outpatient visits associated with the primary diagnosis of a dermatologic condition. Minor diagnoses that were considered to be subsets of major diagnoses were combined to allow better analysis of the data. For example, all tinea infections (ie, dermatophytosis of various sites, dermatomycosis unspecified) were combined into 1 diagnosis referred to as tinea because the recognition and treatment of this disease does not vary tremendously by anatomic location. Visits to dermatologists that listed nonspecific diagnoses and codes (eg, other postsurgical status [V45.89], neoplasm of uncertain behavior site unspecified [238.9]) were assumed to be for dermatologic problems.

Sampling weights were applied to obtain estimates for the number of each diagnosis made nationally. All data analyses were performed using SAS software and linear regression models were generated using SAS PROC SURVEYREG.

Data were analyzed to determine the dermatologic conditions most commonly encountered by dermatologists and nondermatologists in emergency medicine, family medicine, general surgery, internal medicine, otolaryngology, and pediatrics; these specialties include physicians who are known to commonly diagnose and treat skin diseases.¹⁰ Data also were analyzed to determine the most common conditions referred to dermatologists for treatment by nondermatologists from the selected specialties. Permission to conduct this study was obtained from the Wake Forest University institutional review board (Winston-Salem, North Carolina).

Results

From 2001 to 2010, more than 700 million outpatient visits for skin-related problems were identified, with 676.3 million visits to dermatologists, emergency medicine physicians, family practitioners, general surgeons, internists, otolaryngologists, and pediatricians. More than half (52.9%) of all skin-related visits were addressed by nondermatologists during this time. Among nondermatologists, family practitioners encountered the greatest number of skin diseases (20.5%), followed by pediatricians (11.3%), internists (9.2%), general surgeons (3.4%), otolaryngologists (1.0%), and emergency medicine physicians (0.2%)(Table 1).

Benign tumors and acne were the most common cutaneous conditions referred to dermatologists by nondermatologists (10.6% and 10.1% of all dermatology referrals, respectively), followed by nonmelanoma skin cancers (9.7%), contact dermatitis (8.8%), and actinic keratosis (7.8%)(Table 2). The top 20 conditions referred to dermatologists accounted for 83.7% of all outpatient referrals to dermatologists.

Among the diseases most frequently reported by nondermatologists, contact dermatitis was the most common (12.0%), with twice the number of visits to nondermatologists for contact dermatitis than to dermatologists (51.6 million vs 25.3 million). In terms of disease categories, infectious skin diseases (ie, bacterial [cellulitis/abscess], viral [warts, herpesvirus], fungal [tinea] and yeast [candida] etiologies) were the most common dermatologic conditions reported by nondermatologists (Table 2).

The top 20 dermatologic conditions reported by dermatologists accounted for 85.4% of all diagnoses made by dermatologists. Diseases that were among the top 20 conditions encountered by dermatologists but were not among the top 20 for nondermatologists included actinic keratosis, seborrheic keratosis, atopic dermatitis, psoriasis, alopecia, rosacea, dyschromia, seborrheic dermatitis, follicular disease, and neoplasm of uncertain behavior of skin. Additionally, 5 of the top 20 conditions encountered by dermatologists also were among the top 20 for only 1 individual nondermatologic specialty; these included atopic dermatitis (pediatrics), seborrheic dermatitis (pediatrics), psoriasis (internal medicine), rosacea (otolaryngology), and keratoderma (general surgery). Seborrheic dermatitis, psoriasis, and rosacea also were among the top 20 conditions most commonly referred to dermatologists for treatment by nondermatologists. Table 3 shows the top 20 dermatologic conditions encountered by nondermatologists by comparison.

Comment

According to NAMCS data from 2001 to 2010, visits to nondermatologists accounted for more than half of total outpatient visits for cutaneous diseases in the United States, whereas visits to dermatologists accounted for 47.1%. These findings are consistent with historical data indicating that 30% to 40% of skin-related visits are to dermatologists, and the majority of patients with skin disease are diagnosed by nondermatologists.^5,6

Past data indicate that most visits to dermatologists were for evaluation of acne, infections, psoriasis, and neoplasms, whereas most visits to nondermatologists were for evaluation of epidermoid cysts, impetigo, plant dermatitis, cellulitis, and diaper rash.⁹ Over the last 10 years, acne has been more commonly encountered by nondermatologists, especially pediatricians. Additionally, infectious etiologies have been seen in larger volume by nondermatologists.⁹ Together, infectious cutaneous conditions make up nearly one-fourth of dermatologic encounters by emergency medicine physicians, internists, and family practitioners but are not within the top 20 diagnoses referred to dermatologists, which suggests that uncomplicated cases of cellulitis, herpes zoster, and other skin-related infections are largely managed by nondermatologists.^5,6 Contact dermatitis, often caused by specific allergens such as detergents, solvents, and topical products, was one of the most common reported dermatologic encounters among dermatologists and nondermatologists and also was the fourth most common condition referred to dermatologists by nondermatologists for treatment; however, there may be an element of overuse of the International Classification of Diseases, Ninth Revision code, as any presumed contact dermatitis of unspecified cause can be reported under 692.9 defined as contact dermatitis and other eczema, unspecified cause. The high rate of referrals to dermatologists by nondermatologists may be for patch testing and further management. Additionally, there are no specific codes for allergic or irritant dermatitis, thus these diseases may be lumped together.

Although nearly half of all dermatologic encounters were seen by nondermatologists, dermatologists see a much larger proportion of patients with skin disease than nondermatologists and nondermatologists often have limited exposure to the field of dermatology during residency training. Studies have demonstrated differences in the abilities of dermatologists and nondermatologists to correctly diagnose common cutaneous diseases, which unsurprisingly revealed greater diagnostic accuracy demonstrated by dermatologists.^11-16 The increase in acne and skin-related infections reported by nondermatologists is consistent with possible efforts to increase formal training in frequently encountered skin diseases. In one study evaluating the impact of a formal 3-week dermatology curriculum on an internal medicine department, internists demonstrated 100% accuracy in the diagnosis of acne and herpes zoster in contrast to 29% for tinea and 12% for lichen planus.^5,6

The current Accreditation Council for Graduate Medical Education guidelines place little emphasis on exposure to dermatology training during residency for internists and pediatricians, as this training is not a required component of these programs.¹⁷ Two core problems with current training regarding the evaluation and management of cutaneous disease are minimal exposure to dermatologic conditions in medical school and residency and lack of consensus on the core topics that should be taught to nondermatologists.¹⁸ Exposure to dermatologic conditions through rotations in medical school has been shown to increase residents’ self-reported confidence in diagnosing and treating alopecia, cutaneous drug eruptions, warts, acne, rosacea, nonmelanoma skin cancers, sun damage, psoriasis, seborrhea, atopic dermatitis, and contact dermatitis; however, the majority of primary care residents surveyed still felt that this exposure in medical school was inadequate.¹⁹

In creating a core curriculum for dermatology training for nondermatologists, it is important to consider the dermatologic conditions that are most frequently encountered by these specialties. Our study revealed that the most commonly encountered dermatologic conditions differ among dermatologists and nondermatologists, with a fair degree of variation even among individual specialties. Failure to recognize these discrepancies has likely contributed to the challenges faced by nondermatologists in the diagnosis and management of dermatologic disease. In this study, contact dermatitis, epidermoid cysts, and skin infections were the most common dermatologic conditions encountered by nondermatologists and also were among the top skin diseases referred to dermatologists by nondermatologists. This finding suggests that nondermatologists are able to identify these conditions but have a tendency to refer approximately 10% of these patients to dermatology for further management. Clinical evaluation and medical management of these cutaneous diseases may be an important area of focus for medical school curricula, as the treatment of these diseases is within the capabilities of the nondermatologist. For example, initial management of dermatitis requires determination of the type of dermatitis (ie, essential, contact, atopic, seborrheic, stasis) and selection of an appropriate topical steroid, with referral to a dermatologist needed for questionable or refractory cases. Although a curriculum cannot be built solely on a list of the top 20 diagnoses provided here, these data may serve as a preliminary platform for medical school dermatology curriculum design. The curriculum also should include serious skin diseases, such as melanoma and severe drug eruptions. Although these conditions are less commonly encountered by nondermatologists, missed diagnosis and/or improper management can be life threatening.

The use of NAMCS data presents a few limitations. For instance, these data only represent outpatient management of skin disease. There is the potential for misdiagnosis and coding errors by the reporting physicians. The volume of data (ie, billions of office visits) prevents verification of diagnostic accuracy. The coding system requires physicians to give a diagnosis but does not provide any means by which to determine the physician’s confidence in that diagnosis. There is no code for “uncertain” or “diagnosis not determined.” Additionally, an “unspecified” diagnosis may reflect uncertainty or may simply imply that no other code accurately described the condition. Despite these limitations, the NAMCS database is a large, nationally representative survey of actual patient visits and represents some of the best data available for a study such as ours.

Conclusion

This study provides an important analysis of the most common outpatient dermatologic conditions encountered by dermatologists and nondermatologists of various specialties and offers a foundation from which to construct curricula for dermatology training tailored to individual specialties based on their needs. In the future, identification of the most common inpatient dermatologic conditions managed by each specialty also may benefit curriculum design.

Skin diseases are highly prevalent in the United States, affecting an estimated 1 in 3 Americans at any given time.^1,2 In 2009 the direct medical costs associated with skin-related diseases, including health services and prescriptions, was approximately $22 billion; the annual total economic burden was estimated to be closer to $96 billion when factoring in the cost of lost productivity and pay for symptom relief.^3,4 Effective and efficient management of skin disease is essential to minimizing cost and morbidity. Nondermatologists traditionally have diagnosed the majority of skin diseases.^5,6 In particular, primary care physicians commonly manage dermatologic conditions and often are the first health care providers to encounter patients presenting with skin problems. A predicted shortage of dermatologists will likely contribute to an increase in this trend.^7,8 Therefore, it is important to adequately prepare nondermatologists to evaluate and treat the skin conditions that they are most likely to encounter in their scope of practice.

Residents, particularly in primary care specialties, often have opportunities to spend 2 to 4 weeks with a dermatologist to learn about skin diseases; however, the skin conditions most often encountered by dermatologists may differ from those most often encountered by physicians in other specialties. For instance, one study demonstrated a disparity between the most common skin problems seen by dermatologists and internists.⁹ These dissimilarities should be recognized and addressed in curriculum content. The purpose of this study was to identify and compare the 20 most common dermatologic conditions reported by dermatologists versus those reported by nondermatologists (ie, internists, pediatricians, family physicians, emergency medicine physicians, general surgeons, otolaryngologists) from 2001 to 2010. Data also were analyzed to determine the top 20 conditions referred to dermatologists by nondermatologists as a potential indicator for areas of further improvement within medical education. With this knowledge, we hope educational curricula and self-study can be modified to reflect the current epidemiology of cutaneous diseases, thereby improving patient care.

Methods

Data from 2001 to 2010 were extracted from the National Ambulatory Medical Care Survey (NAMCS), which is an ongoing survey conducted by the National Center for Health Statistics. The NAMCS collects descriptive data regarding ambulatory visits to nonfederal office-based physicians in the United States. Participating physicians are instructed to record information about patient visits for a 1-week period, including patient demographics, insurance status, reason for visit, diagnoses, procedures, therapeutics, and referrals made at that time. Data collected for the NAMCS are entered into a multistage probability sample to produce national estimates. Within dermatology, an average of 118 dermatologists are sampled each year, and over the last 10 years, participation rates have ranged from 47% to 77%.

International Classification of Diseases, Ninth Revision, Clinical Modification codes were identified to determine the diagnoses that could be classified as dermatologic conditions. Select infectious and neoplastic disorders of the skin and mucous membrane conditions were included as well as the codes for skin diseases. Nondermatologic diagnoses and V codes were not included in the study. Data for all providers were studied to identify outpatient visits associated with the primary diagnosis of a dermatologic condition. Minor diagnoses that were considered to be subsets of major diagnoses were combined to allow better analysis of the data. For example, all tinea infections (ie, dermatophytosis of various sites, dermatomycosis unspecified) were combined into 1 diagnosis referred to as tinea because the recognition and treatment of this disease does not vary tremendously by anatomic location. Visits to dermatologists that listed nonspecific diagnoses and codes (eg, other postsurgical status [V45.89], neoplasm of uncertain behavior site unspecified [238.9]) were assumed to be for dermatologic problems.

Sampling weights were applied to obtain estimates for the number of each diagnosis made nationally. All data analyses were performed using SAS software and linear regression models were generated using SAS PROC SURVEYREG.

Data were analyzed to determine the dermatologic conditions most commonly encountered by dermatologists and nondermatologists in emergency medicine, family medicine, general surgery, internal medicine, otolaryngology, and pediatrics; these specialties include physicians who are known to commonly diagnose and treat skin diseases.¹⁰ Data also were analyzed to determine the most common conditions referred to dermatologists for treatment by nondermatologists from the selected specialties. Permission to conduct this study was obtained from the Wake Forest University institutional review board (Winston-Salem, North Carolina).

Results

From 2001 to 2010, more than 700 million outpatient visits for skin-related problems were identified, with 676.3 million visits to dermatologists, emergency medicine physicians, family practitioners, general surgeons, internists, otolaryngologists, and pediatricians. More than half (52.9%) of all skin-related visits were addressed by nondermatologists during this time. Among nondermatologists, family practitioners encountered the greatest number of skin diseases (20.5%), followed by pediatricians (11.3%), internists (9.2%), general surgeons (3.4%), otolaryngologists (1.0%), and emergency medicine physicians (0.2%)(Table 1).

Benign tumors and acne were the most common cutaneous conditions referred to dermatologists by nondermatologists (10.6% and 10.1% of all dermatology referrals, respectively), followed by nonmelanoma skin cancers (9.7%), contact dermatitis (8.8%), and actinic keratosis (7.8%)(Table 2). The top 20 conditions referred to dermatologists accounted for 83.7% of all outpatient referrals to dermatologists.

Among the diseases most frequently reported by nondermatologists, contact dermatitis was the most common (12.0%), with twice the number of visits to nondermatologists for contact dermatitis than to dermatologists (51.6 million vs 25.3 million). In terms of disease categories, infectious skin diseases (ie, bacterial [cellulitis/abscess], viral [warts, herpesvirus], fungal [tinea] and yeast [candida] etiologies) were the most common dermatologic conditions reported by nondermatologists (Table 2).

The top 20 dermatologic conditions reported by dermatologists accounted for 85.4% of all diagnoses made by dermatologists. Diseases that were among the top 20 conditions encountered by dermatologists but were not among the top 20 for nondermatologists included actinic keratosis, seborrheic keratosis, atopic dermatitis, psoriasis, alopecia, rosacea, dyschromia, seborrheic dermatitis, follicular disease, and neoplasm of uncertain behavior of skin. Additionally, 5 of the top 20 conditions encountered by dermatologists also were among the top 20 for only 1 individual nondermatologic specialty; these included atopic dermatitis (pediatrics), seborrheic dermatitis (pediatrics), psoriasis (internal medicine), rosacea (otolaryngology), and keratoderma (general surgery). Seborrheic dermatitis, psoriasis, and rosacea also were among the top 20 conditions most commonly referred to dermatologists for treatment by nondermatologists. Table 3 shows the top 20 dermatologic conditions encountered by nondermatologists by comparison.

Comment

According to NAMCS data from 2001 to 2010, visits to nondermatologists accounted for more than half of total outpatient visits for cutaneous diseases in the United States, whereas visits to dermatologists accounted for 47.1%. These findings are consistent with historical data indicating that 30% to 40% of skin-related visits are to dermatologists, and the majority of patients with skin disease are diagnosed by nondermatologists.^5,6

Past data indicate that most visits to dermatologists were for evaluation of acne, infections, psoriasis, and neoplasms, whereas most visits to nondermatologists were for evaluation of epidermoid cysts, impetigo, plant dermatitis, cellulitis, and diaper rash.⁹ Over the last 10 years, acne has been more commonly encountered by nondermatologists, especially pediatricians. Additionally, infectious etiologies have been seen in larger volume by nondermatologists.⁹ Together, infectious cutaneous conditions make up nearly one-fourth of dermatologic encounters by emergency medicine physicians, internists, and family practitioners but are not within the top 20 diagnoses referred to dermatologists, which suggests that uncomplicated cases of cellulitis, herpes zoster, and other skin-related infections are largely managed by nondermatologists.^5,6 Contact dermatitis, often caused by specific allergens such as detergents, solvents, and topical products, was one of the most common reported dermatologic encounters among dermatologists and nondermatologists and also was the fourth most common condition referred to dermatologists by nondermatologists for treatment; however, there may be an element of overuse of the International Classification of Diseases, Ninth Revision code, as any presumed contact dermatitis of unspecified cause can be reported under 692.9 defined as contact dermatitis and other eczema, unspecified cause. The high rate of referrals to dermatologists by nondermatologists may be for patch testing and further management. Additionally, there are no specific codes for allergic or irritant dermatitis, thus these diseases may be lumped together.

Although nearly half of all dermatologic encounters were seen by nondermatologists, dermatologists see a much larger proportion of patients with skin disease than nondermatologists and nondermatologists often have limited exposure to the field of dermatology during residency training. Studies have demonstrated differences in the abilities of dermatologists and nondermatologists to correctly diagnose common cutaneous diseases, which unsurprisingly revealed greater diagnostic accuracy demonstrated by dermatologists.^11-16 The increase in acne and skin-related infections reported by nondermatologists is consistent with possible efforts to increase formal training in frequently encountered skin diseases. In one study evaluating the impact of a formal 3-week dermatology curriculum on an internal medicine department, internists demonstrated 100% accuracy in the diagnosis of acne and herpes zoster in contrast to 29% for tinea and 12% for lichen planus.^5,6

The current Accreditation Council for Graduate Medical Education guidelines place little emphasis on exposure to dermatology training during residency for internists and pediatricians, as this training is not a required component of these programs.¹⁷ Two core problems with current training regarding the evaluation and management of cutaneous disease are minimal exposure to dermatologic conditions in medical school and residency and lack of consensus on the core topics that should be taught to nondermatologists.¹⁸ Exposure to dermatologic conditions through rotations in medical school has been shown to increase residents’ self-reported confidence in diagnosing and treating alopecia, cutaneous drug eruptions, warts, acne, rosacea, nonmelanoma skin cancers, sun damage, psoriasis, seborrhea, atopic dermatitis, and contact dermatitis; however, the majority of primary care residents surveyed still felt that this exposure in medical school was inadequate.¹⁹

In creating a core curriculum for dermatology training for nondermatologists, it is important to consider the dermatologic conditions that are most frequently encountered by these specialties. Our study revealed that the most commonly encountered dermatologic conditions differ among dermatologists and nondermatologists, with a fair degree of variation even among individual specialties. Failure to recognize these discrepancies has likely contributed to the challenges faced by nondermatologists in the diagnosis and management of dermatologic disease. In this study, contact dermatitis, epidermoid cysts, and skin infections were the most common dermatologic conditions encountered by nondermatologists and also were among the top skin diseases referred to dermatologists by nondermatologists. This finding suggests that nondermatologists are able to identify these conditions but have a tendency to refer approximately 10% of these patients to dermatology for further management. Clinical evaluation and medical management of these cutaneous diseases may be an important area of focus for medical school curricula, as the treatment of these diseases is within the capabilities of the nondermatologist. For example, initial management of dermatitis requires determination of the type of dermatitis (ie, essential, contact, atopic, seborrheic, stasis) and selection of an appropriate topical steroid, with referral to a dermatologist needed for questionable or refractory cases. Although a curriculum cannot be built solely on a list of the top 20 diagnoses provided here, these data may serve as a preliminary platform for medical school dermatology curriculum design. The curriculum also should include serious skin diseases, such as melanoma and severe drug eruptions. Although these conditions are less commonly encountered by nondermatologists, missed diagnosis and/or improper management can be life threatening.

The use of NAMCS data presents a few limitations. For instance, these data only represent outpatient management of skin disease. There is the potential for misdiagnosis and coding errors by the reporting physicians. The volume of data (ie, billions of office visits) prevents verification of diagnostic accuracy. The coding system requires physicians to give a diagnosis but does not provide any means by which to determine the physician’s confidence in that diagnosis. There is no code for “uncertain” or “diagnosis not determined.” Additionally, an “unspecified” diagnosis may reflect uncertainty or may simply imply that no other code accurately described the condition. Despite these limitations, the NAMCS database is a large, nationally representative survey of actual patient visits and represents some of the best data available for a study such as ours.

Conclusion

This study provides an important analysis of the most common outpatient dermatologic conditions encountered by dermatologists and nondermatologists of various specialties and offers a foundation from which to construct curricula for dermatology training tailored to individual specialties based on their needs. In the future, identification of the most common inpatient dermatologic conditions managed by each specialty also may benefit curriculum design.

Clinical question

Does a lower transfusion threshold for critically ill patients with septic shock affect outcomes?

Bottom line

Using a lower threshold for transfusion for patients with septic shock in the intensive care unit (ICU) decreases the number of transfusions received without affecting mortality.

Reference

Holst LB, Haase N, Wetterslev J, et al. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med 2014;371(15):1381-1391.

Study design

Randomized controlled trial (nonblinded); (LOE: 1b)

Setting

Inpatient (ICU only)

Synopsis

Using partial blinding and concealed allocation, these investigators randomized ICU patients with septic shock and a hemoglobin level of less than 9 g/dL to receive red blood cell transfusions at either a higher threshold (< 9 g/dL) or a lower threshold (< 7 g/dL). The intervention continued for the entire ICU stay, to a maximum of 90 days. The 2 groups were similar at baseline with an average age of 67 years and a median Sepsis-Related Organ Failure Assessment (SOFA) score of 10 out of 24. Analysis was by intention to treat. Not suprisingly, patients in the higher threshold group received twice as many transfusions as those in the lower threshold group (3088 transfusions vs 1545; P < .001). Notably, one third of the patients in the lower-threshold group required no transfusions at all compared with only 1% in the higher-threshold group (P < .001). For the primary outcome of death at 90 days, there was no significant difference detected between the 2 groups. The per-protocol analysis, which excluded patients with major protocol violations, also showed the same result. Secondary outcomes, including the use of life support and the number of ischemic events in the ICU (eg, acute myocardial or cerebral ischemia), were also similar in the 2 groups.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Does a lower transfusion threshold for critically ill patients with septic shock affect outcomes?

Bottom line

Using a lower threshold for transfusion for patients with septic shock in the intensive care unit (ICU) decreases the number of transfusions received without affecting mortality.

Reference

Holst LB, Haase N, Wetterslev J, et al. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med 2014;371(15):1381-1391.

Study design

Randomized controlled trial (nonblinded); (LOE: 1b)

Setting

Inpatient (ICU only)

Synopsis

Using partial blinding and concealed allocation, these investigators randomized ICU patients with septic shock and a hemoglobin level of less than 9 g/dL to receive red blood cell transfusions at either a higher threshold (< 9 g/dL) or a lower threshold (< 7 g/dL). The intervention continued for the entire ICU stay, to a maximum of 90 days. The 2 groups were similar at baseline with an average age of 67 years and a median Sepsis-Related Organ Failure Assessment (SOFA) score of 10 out of 24. Analysis was by intention to treat. Not suprisingly, patients in the higher threshold group received twice as many transfusions as those in the lower threshold group (3088 transfusions vs 1545; P < .001). Notably, one third of the patients in the lower-threshold group required no transfusions at all compared with only 1% in the higher-threshold group (P < .001). For the primary outcome of death at 90 days, there was no significant difference detected between the 2 groups. The per-protocol analysis, which excluded patients with major protocol violations, also showed the same result. Secondary outcomes, including the use of life support and the number of ischemic events in the ICU (eg, acute myocardial or cerebral ischemia), were also similar in the 2 groups.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Does a lower transfusion threshold for critically ill patients with septic shock affect outcomes?

Bottom line

Using a lower threshold for transfusion for patients with septic shock in the intensive care unit (ICU) decreases the number of transfusions received without affecting mortality.

Reference

Holst LB, Haase N, Wetterslev J, et al. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med 2014;371(15):1381-1391.

Study design

Randomized controlled trial (nonblinded); (LOE: 1b)

Setting

Inpatient (ICU only)

Synopsis

Using partial blinding and concealed allocation, these investigators randomized ICU patients with septic shock and a hemoglobin level of less than 9 g/dL to receive red blood cell transfusions at either a higher threshold (< 9 g/dL) or a lower threshold (< 7 g/dL). The intervention continued for the entire ICU stay, to a maximum of 90 days. The 2 groups were similar at baseline with an average age of 67 years and a median Sepsis-Related Organ Failure Assessment (SOFA) score of 10 out of 24. Analysis was by intention to treat. Not suprisingly, patients in the higher threshold group received twice as many transfusions as those in the lower threshold group (3088 transfusions vs 1545; P < .001). Notably, one third of the patients in the lower-threshold group required no transfusions at all compared with only 1% in the higher-threshold group (P < .001). For the primary outcome of death at 90 days, there was no significant difference detected between the 2 groups. The per-protocol analysis, which excluded patients with major protocol violations, also showed the same result. Secondary outcomes, including the use of life support and the number of ischemic events in the ICU (eg, acute myocardial or cerebral ischemia), were also similar in the 2 groups.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

This presentation by Adrian Wiestner, MD, PhD, from the 2014 AVAHO Meeting in Portland, Oregon, provides an overview of new insights into the pathogenesis and treatment of CLL, how to interpret molecular targets during treatment, and the advantages and disadvantages of these treatment options for patients.

"The standard of care today is really chemo-immunotherapy," Wiestner said. "Ideally, we would like to have a more disease-directed therapy that is tolerable and active."

This presentation by Adrian Wiestner, MD, PhD, from the 2014 AVAHO Meeting in Portland, Oregon, provides an overview of new insights into the pathogenesis and treatment of CLL, how to interpret molecular targets during treatment, and the advantages and disadvantages of these treatment options for patients.

"The standard of care today is really chemo-immunotherapy," Wiestner said. "Ideally, we would like to have a more disease-directed therapy that is tolerable and active."

This presentation by Adrian Wiestner, MD, PhD, from the 2014 AVAHO Meeting in Portland, Oregon, provides an overview of new insights into the pathogenesis and treatment of CLL, how to interpret molecular targets during treatment, and the advantages and disadvantages of these treatment options for patients.

"The standard of care today is really chemo-immunotherapy," Wiestner said. "Ideally, we would like to have a more disease-directed therapy that is tolerable and active."

Surgeons who treat patients in rural areas are a unique group, distinct from other surgeons because of scope of practice, environment, and resources. These surgeons address a vast range of surgical problems, work in relative professional isolation, and have fewer resources available to get the job done. Nevertheless, these physicians play critical roles in their profession and are irreplaceable assets in their communities.

Although poorly defined, often misunderstood, arguably unfairly characterized, and inadequately documented, surgery has a long distinguished history and tradition in rural communities.

What are the main challenges faced by rural surgeons and what can be done to strengthen their practices, professional lives, and longevity in the field? Rural patients are more likely than urban patients to be elderly and poor and have chronic illnesses (J. Am Coll. Surg. 2014;219:814-8). The average age of rural surgeons suggests that many will retire in the coming decade. Who will replace them and care for 60 million citizens who reside in rural America? How will the gradual decline of residents choosing general surgery and rural practice affect patient care?

This new monthly column, Rural Surgeons Speak, focuses on these questions and searches for answers. Rural Surgeons Speak will introduce to all readers the voices, concerns, questions, and opinions of surgeons practicing in the small towns and rural regions of the United States. Although many of the challenges faced by rural surgeons are unique to this group, there is overlap with issues encountered by urban surgeons and those in academic settings. In spite of problems ranging from a shift from independent practice to hospital employment and to treating the poor with pronounced chronic illnesses, rural surgeons are dedicated and committed. Although these matters are common to all surgeons, rural surgeons’ experiences tend to be singular because of the high percentages of such patients and fewer institutional resources.

I have practiced surgery in small and large rural locations for 37 years. Rural surgery is not a specialty. My case log, filled with endoscopies, laparoscopies, laparotomies, and breast operations, may be even more varied than the logs of urban colleagues. In my early years of practice, I did orthopaedic surgery and gynecology. As a conscious choice, I practiced surgery where I wanted, and how I wanted. My choice was not by default. When I started, I sought a location that would allow me to “have a more complete life with less tension, excellent schools, opportunity for economical living,” and a fulfilling surgery practice. Unknown to me, Dr. Edwin F. Cave, ACS president, made those statements about rural surgery in the Daily Clinical Bulletin for the 37th Annual Clinical Congress decades before I started.

Like other rural surgeons, I wanted to embrace and be embraced by my community. I also saw opportunities for personal advancement (involvement with ACS), and for the development of my surgical talents (lasers, laparoscopies, endoscopies). I live just a mile from the hospital. I know my patients by their first names. They speak to me on the telephone. My number is in the book. When they meet me in church or at the grocery store, I am “Doc.” Occasionally a PEx is performed in such locations. It is personal. It is comfortable. There is a real sense of community and of belonging. I am involved. I provide an invaluable service “right at home,” where my patients want to be treated. In return, I am valued and supported.

After becoming a FACS in 1979, I involved myself in many activities of the ACS. Most recently, I participated in the rural surgery renaissance from its beginning. As part of my participation, I routinely contacted rural surgeons around the United States and gained intimate and detailed knowledge about their practices, successes, and concerns. I bring insights from my background to the writing of this column.

While glamour is at a minimum in rural America, personal satisfaction for many of these surgeons is at a maximum. Unfortunately, isolation is a given in most rural practices, and therein lies the problem. In spite of offering much to their patients and, in turn, to the profession, rural surgeons are easy targets of negative assessments, ill-conceived policy changes, and misunderstandings.

Despite their vital role in treating patients, rural surgeons often regard themselves as unrecognized and unappreciated by their peers. There is a subtle bias in the profession against a surgeon who would choose this life of relative isolation, alleged nonspecialized surgery, and overwork in communities with fewer cultural resources and fewer employment options for spouses. Yet their work is essential to the health of millions of people who live in rural areas. Thankfully, the profession as a whole has stopped ignoring rural surgery in recent years as the ACS leadership has stepped in and begun to increase support for rural surgeons.

In May 2011, during the 5th Annual Rural Surgery Symposium and Workshop, I presented a talk, “The ACS and the Rural Surgeon.” Past President Dr. LaMar McGinnis acknowledged the educational value of the presentation, which then went on to wider distribution. The Board of Regents received another talk about rural surgery in February 2012: “Us vs. Them.” Based on the talk and because of their keen insights, the Regents formed the Advisory Council on Rural Surgery – the first new advisory council in 50 years. Subsequently, a College-developed rural listserv became the most highly successful communications program in ACS history and led to the creation of the rural surgery community. In the following 2 years, rural surgeons exchanged 9 million emails on numerous, varied topics. An article in the July 2014 ACS Bulletin describes the program (http://bulletin.facs.org/2014/07/acs-rural-listserv-an-underdog-success-story/). Finally, in his inaugural address at the 2012 Clinical Congress, Dr. Brent Eastman identified rural surgery as one of the four fundamental components of surgery for the next 100 years (http://bulletin.facs.org/2012/12/presidential-address/). Recognition of rural surgery obviously has increased.

My experience of moderating the rural listserv with nearly 1,000 subscribers has revealed the amazing diversity, passion, commitment, and perseverance of rural surgeons who have united in a true community. Their perspectives on their professional lives and the lives of their patients are well worth closer acquaintance by surgeons from all sectors. They have a lot to teach us all. To learn about rural surgery will be to learn about all surgery. Understand rural surgery in 2014 and, consequently, understand all surgery. Recognize the benefits of rural surgery and then instill them in all practices. Supporting rural surgery today supports all surgery.

The column aims to offer commentary on diverse topics confronting rural surgeons today. Opinions, editorials, letters, economics, and clinical matters, all from the rural perspective, will be included. Over 60 individual “threads” appeared on the listserv this year and the subjects of many of these threads could be covered in future columns. Uncommon subjects such as YKYAARSI (“You know you are a rural surgeon if…”) should be entertaining and informative. Guest authors who are experts on varying subjects will contribute articles.

While its roots are in the rural surgery community, the column’s scope will touch all surgical practices. Rural surgery will be better defined, positively characterized, and documented. In partnership with the ACS to achieve the general goal of supporting rural surgery, Rural Surgeons Speak aims to enable all ACS Fellows to realize that they belong to a community of all surgeons, regardless of location or practice type.

Dr. Caropreso is a general surgeon at Keokuk (Iowa) Area Hospital and Clinical Professor of Surgery at the University of Iowa Carver College of Medicine. He has practiced surgery in the rural communities of Mason City, Iowa; Keokuk, Iowa; and Carthage, Ill., for 37 years.

Surgeons who treat patients in rural areas are a unique group, distinct from other surgeons because of scope of practice, environment, and resources. These surgeons address a vast range of surgical problems, work in relative professional isolation, and have fewer resources available to get the job done. Nevertheless, these physicians play critical roles in their profession and are irreplaceable assets in their communities.

Although poorly defined, often misunderstood, arguably unfairly characterized, and inadequately documented, surgery has a long distinguished history and tradition in rural communities.

What are the main challenges faced by rural surgeons and what can be done to strengthen their practices, professional lives, and longevity in the field? Rural patients are more likely than urban patients to be elderly and poor and have chronic illnesses (J. Am Coll. Surg. 2014;219:814-8). The average age of rural surgeons suggests that many will retire in the coming decade. Who will replace them and care for 60 million citizens who reside in rural America? How will the gradual decline of residents choosing general surgery and rural practice affect patient care?

This new monthly column, Rural Surgeons Speak, focuses on these questions and searches for answers. Rural Surgeons Speak will introduce to all readers the voices, concerns, questions, and opinions of surgeons practicing in the small towns and rural regions of the United States. Although many of the challenges faced by rural surgeons are unique to this group, there is overlap with issues encountered by urban surgeons and those in academic settings. In spite of problems ranging from a shift from independent practice to hospital employment and to treating the poor with pronounced chronic illnesses, rural surgeons are dedicated and committed. Although these matters are common to all surgeons, rural surgeons’ experiences tend to be singular because of the high percentages of such patients and fewer institutional resources.

I have practiced surgery in small and large rural locations for 37 years. Rural surgery is not a specialty. My case log, filled with endoscopies, laparoscopies, laparotomies, and breast operations, may be even more varied than the logs of urban colleagues. In my early years of practice, I did orthopaedic surgery and gynecology. As a conscious choice, I practiced surgery where I wanted, and how I wanted. My choice was not by default. When I started, I sought a location that would allow me to “have a more complete life with less tension, excellent schools, opportunity for economical living,” and a fulfilling surgery practice. Unknown to me, Dr. Edwin F. Cave, ACS president, made those statements about rural surgery in the Daily Clinical Bulletin for the 37th Annual Clinical Congress decades before I started.

Like other rural surgeons, I wanted to embrace and be embraced by my community. I also saw opportunities for personal advancement (involvement with ACS), and for the development of my surgical talents (lasers, laparoscopies, endoscopies). I live just a mile from the hospital. I know my patients by their first names. They speak to me on the telephone. My number is in the book. When they meet me in church or at the grocery store, I am “Doc.” Occasionally a PEx is performed in such locations. It is personal. It is comfortable. There is a real sense of community and of belonging. I am involved. I provide an invaluable service “right at home,” where my patients want to be treated. In return, I am valued and supported.

After becoming a FACS in 1979, I involved myself in many activities of the ACS. Most recently, I participated in the rural surgery renaissance from its beginning. As part of my participation, I routinely contacted rural surgeons around the United States and gained intimate and detailed knowledge about their practices, successes, and concerns. I bring insights from my background to the writing of this column.

While glamour is at a minimum in rural America, personal satisfaction for many of these surgeons is at a maximum. Unfortunately, isolation is a given in most rural practices, and therein lies the problem. In spite of offering much to their patients and, in turn, to the profession, rural surgeons are easy targets of negative assessments, ill-conceived policy changes, and misunderstandings.

Despite their vital role in treating patients, rural surgeons often regard themselves as unrecognized and unappreciated by their peers. There is a subtle bias in the profession against a surgeon who would choose this life of relative isolation, alleged nonspecialized surgery, and overwork in communities with fewer cultural resources and fewer employment options for spouses. Yet their work is essential to the health of millions of people who live in rural areas. Thankfully, the profession as a whole has stopped ignoring rural surgery in recent years as the ACS leadership has stepped in and begun to increase support for rural surgeons.

In May 2011, during the 5th Annual Rural Surgery Symposium and Workshop, I presented a talk, “The ACS and the Rural Surgeon.” Past President Dr. LaMar McGinnis acknowledged the educational value of the presentation, which then went on to wider distribution. The Board of Regents received another talk about rural surgery in February 2012: “Us vs. Them.” Based on the talk and because of their keen insights, the Regents formed the Advisory Council on Rural Surgery – the first new advisory council in 50 years. Subsequently, a College-developed rural listserv became the most highly successful communications program in ACS history and led to the creation of the rural surgery community. In the following 2 years, rural surgeons exchanged 9 million emails on numerous, varied topics. An article in the July 2014 ACS Bulletin describes the program (http://bulletin.facs.org/2014/07/acs-rural-listserv-an-underdog-success-story/). Finally, in his inaugural address at the 2012 Clinical Congress, Dr. Brent Eastman identified rural surgery as one of the four fundamental components of surgery for the next 100 years (http://bulletin.facs.org/2012/12/presidential-address/). Recognition of rural surgery obviously has increased.

My experience of moderating the rural listserv with nearly 1,000 subscribers has revealed the amazing diversity, passion, commitment, and perseverance of rural surgeons who have united in a true community. Their perspectives on their professional lives and the lives of their patients are well worth closer acquaintance by surgeons from all sectors. They have a lot to teach us all. To learn about rural surgery will be to learn about all surgery. Understand rural surgery in 2014 and, consequently, understand all surgery. Recognize the benefits of rural surgery and then instill them in all practices. Supporting rural surgery today supports all surgery.

The column aims to offer commentary on diverse topics confronting rural surgeons today. Opinions, editorials, letters, economics, and clinical matters, all from the rural perspective, will be included. Over 60 individual “threads” appeared on the listserv this year and the subjects of many of these threads could be covered in future columns. Uncommon subjects such as YKYAARSI (“You know you are a rural surgeon if…”) should be entertaining and informative. Guest authors who are experts on varying subjects will contribute articles.

While its roots are in the rural surgery community, the column’s scope will touch all surgical practices. Rural surgery will be better defined, positively characterized, and documented. In partnership with the ACS to achieve the general goal of supporting rural surgery, Rural Surgeons Speak aims to enable all ACS Fellows to realize that they belong to a community of all surgeons, regardless of location or practice type.

Dr. Caropreso is a general surgeon at Keokuk (Iowa) Area Hospital and Clinical Professor of Surgery at the University of Iowa Carver College of Medicine. He has practiced surgery in the rural communities of Mason City, Iowa; Keokuk, Iowa; and Carthage, Ill., for 37 years.

Surgeons who treat patients in rural areas are a unique group, distinct from other surgeons because of scope of practice, environment, and resources. These surgeons address a vast range of surgical problems, work in relative professional isolation, and have fewer resources available to get the job done. Nevertheless, these physicians play critical roles in their profession and are irreplaceable assets in their communities.

Although poorly defined, often misunderstood, arguably unfairly characterized, and inadequately documented, surgery has a long distinguished history and tradition in rural communities.

What are the main challenges faced by rural surgeons and what can be done to strengthen their practices, professional lives, and longevity in the field? Rural patients are more likely than urban patients to be elderly and poor and have chronic illnesses (J. Am Coll. Surg. 2014;219:814-8). The average age of rural surgeons suggests that many will retire in the coming decade. Who will replace them and care for 60 million citizens who reside in rural America? How will the gradual decline of residents choosing general surgery and rural practice affect patient care?

This new monthly column, Rural Surgeons Speak, focuses on these questions and searches for answers. Rural Surgeons Speak will introduce to all readers the voices, concerns, questions, and opinions of surgeons practicing in the small towns and rural regions of the United States. Although many of the challenges faced by rural surgeons are unique to this group, there is overlap with issues encountered by urban surgeons and those in academic settings. In spite of problems ranging from a shift from independent practice to hospital employment and to treating the poor with pronounced chronic illnesses, rural surgeons are dedicated and committed. Although these matters are common to all surgeons, rural surgeons’ experiences tend to be singular because of the high percentages of such patients and fewer institutional resources.

I have practiced surgery in small and large rural locations for 37 years. Rural surgery is not a specialty. My case log, filled with endoscopies, laparoscopies, laparotomies, and breast operations, may be even more varied than the logs of urban colleagues. In my early years of practice, I did orthopaedic surgery and gynecology. As a conscious choice, I practiced surgery where I wanted, and how I wanted. My choice was not by default. When I started, I sought a location that would allow me to “have a more complete life with less tension, excellent schools, opportunity for economical living,” and a fulfilling surgery practice. Unknown to me, Dr. Edwin F. Cave, ACS president, made those statements about rural surgery in the Daily Clinical Bulletin for the 37th Annual Clinical Congress decades before I started.

Like other rural surgeons, I wanted to embrace and be embraced by my community. I also saw opportunities for personal advancement (involvement with ACS), and for the development of my surgical talents (lasers, laparoscopies, endoscopies). I live just a mile from the hospital. I know my patients by their first names. They speak to me on the telephone. My number is in the book. When they meet me in church or at the grocery store, I am “Doc.” Occasionally a PEx is performed in such locations. It is personal. It is comfortable. There is a real sense of community and of belonging. I am involved. I provide an invaluable service “right at home,” where my patients want to be treated. In return, I am valued and supported.

After becoming a FACS in 1979, I involved myself in many activities of the ACS. Most recently, I participated in the rural surgery renaissance from its beginning. As part of my participation, I routinely contacted rural surgeons around the United States and gained intimate and detailed knowledge about their practices, successes, and concerns. I bring insights from my background to the writing of this column.

While glamour is at a minimum in rural America, personal satisfaction for many of these surgeons is at a maximum. Unfortunately, isolation is a given in most rural practices, and therein lies the problem. In spite of offering much to their patients and, in turn, to the profession, rural surgeons are easy targets of negative assessments, ill-conceived policy changes, and misunderstandings.

Despite their vital role in treating patients, rural surgeons often regard themselves as unrecognized and unappreciated by their peers. There is a subtle bias in the profession against a surgeon who would choose this life of relative isolation, alleged nonspecialized surgery, and overwork in communities with fewer cultural resources and fewer employment options for spouses. Yet their work is essential to the health of millions of people who live in rural areas. Thankfully, the profession as a whole has stopped ignoring rural surgery in recent years as the ACS leadership has stepped in and begun to increase support for rural surgeons.

In May 2011, during the 5th Annual Rural Surgery Symposium and Workshop, I presented a talk, “The ACS and the Rural Surgeon.” Past President Dr. LaMar McGinnis acknowledged the educational value of the presentation, which then went on to wider distribution. The Board of Regents received another talk about rural surgery in February 2012: “Us vs. Them.” Based on the talk and because of their keen insights, the Regents formed the Advisory Council on Rural Surgery – the first new advisory council in 50 years. Subsequently, a College-developed rural listserv became the most highly successful communications program in ACS history and led to the creation of the rural surgery community. In the following 2 years, rural surgeons exchanged 9 million emails on numerous, varied topics. An article in the July 2014 ACS Bulletin describes the program (http://bulletin.facs.org/2014/07/acs-rural-listserv-an-underdog-success-story/). Finally, in his inaugural address at the 2012 Clinical Congress, Dr. Brent Eastman identified rural surgery as one of the four fundamental components of surgery for the next 100 years (http://bulletin.facs.org/2012/12/presidential-address/). Recognition of rural surgery obviously has increased.

My experience of moderating the rural listserv with nearly 1,000 subscribers has revealed the amazing diversity, passion, commitment, and perseverance of rural surgeons who have united in a true community. Their perspectives on their professional lives and the lives of their patients are well worth closer acquaintance by surgeons from all sectors. They have a lot to teach us all. To learn about rural surgery will be to learn about all surgery. Understand rural surgery in 2014 and, consequently, understand all surgery. Recognize the benefits of rural surgery and then instill them in all practices. Supporting rural surgery today supports all surgery.

The column aims to offer commentary on diverse topics confronting rural surgeons today. Opinions, editorials, letters, economics, and clinical matters, all from the rural perspective, will be included. Over 60 individual “threads” appeared on the listserv this year and the subjects of many of these threads could be covered in future columns. Uncommon subjects such as YKYAARSI (“You know you are a rural surgeon if…”) should be entertaining and informative. Guest authors who are experts on varying subjects will contribute articles.

While its roots are in the rural surgery community, the column’s scope will touch all surgical practices. Rural surgery will be better defined, positively characterized, and documented. In partnership with the ACS to achieve the general goal of supporting rural surgery, Rural Surgeons Speak aims to enable all ACS Fellows to realize that they belong to a community of all surgeons, regardless of location or practice type.

Dr. Caropreso is a general surgeon at Keokuk (Iowa) Area Hospital and Clinical Professor of Surgery at the University of Iowa Carver College of Medicine. He has practiced surgery in the rural communities of Mason City, Iowa; Keokuk, Iowa; and Carthage, Ill., for 37 years.

Attendees at ASH 2014

Photo courtesy of ASH

SAN FRANCISCO—Results regarding daunorubicin escalation in induction for patients with acute myeloid leukemia (AML) have varied among different studies.

And a 90 mg/m² dose has been shown to be more effective than 45. Now, results of the UK NCRI AML17 trial have added yet another dimension to the discussion—the use of 60 mg/m² compared to 90.

Alan K. Burnett, MD, of Cardiff University in the UK, presented the data as abstract 7 at the 2014 ASH Annual Meeting.

He explained that ECOG E1900 had demonstrated superior remission and overall survival for a 90-mg dose of daunorubicin compared to a 45-mg dose in adults younger than 60.

The HOVON trial showed superior remission but no difference in overall survival for the higher dose of daunorubicin in patients older than 60.

The Korean trial demonstrated superior remission and survival rates for the 90-mg dose in patients younger than 60.

And in the GOELAMS trial, investigators found no difference between a 90-mg and a 60-mg dose level.

So the UK AML Study Group undertook to clarify the issue by comparing 90 mg to 60 mg in induction.

The investigators randomized 1206 patients younger than 60 with de novo or secondary AML or high-risk myelodysplastic syndromes (MDS) to receive 90 or 60 mg of daunorubicin on days 1, 3, and 5 of their first induction course, followed by 50 mg/m² on days 1, 3, and 5 in course 2.

All patients received ara-C during courses 1 and 2. Patients had to have LVEF of 45% or greater to be included in the trial.

The median follow-up was 29 months. Patient characteristics were comparable between the 2 groups.

The median age was 53 in both groups (range, 16-72 years), and slightly more than half of patients were male. Eighty-five percent and 84% had de novo AML in the 60-mg and 90-mg arms, respectively. Ten percent in each group had secondary AML. And 5% and 6%, respectively, had high-risk MDS.

Eleven percent in the 60-mg arm had favorable cytogenetics, compared with 9% in the 90-mg arm. Eighteen percent in each arm had mutant FLT3-ITD, and 40% in each arm were poor risk.

The investigators found no significant difference in response between the two arms—84% in the 60-mg arm and 81% in the 90-mg arm.

However, they observed a trend for increased 30-day mortality in the 90-mg arm and a significant difference in the 60-day mortality rate, which was 5% in the 60-mg arm and 10% in the 90-mg arm (P=0.001).

Twenty-nine people died by day 60 in the 60-mg arm compared with 58 in the 90-mg arm.

The main reasons for 60-day mortality in the 60-mg and 90-mg dose groups, respectively, included infection (11 vs 25 deaths), hemorrhage (3 vs 5 deaths), infection plus hemorrhage (3 vs 1 death), and resistant disease (2 vs 14 deaths), among other causes.

At 24 months, overall survival between the 2 groups was comparable, at 60% in the 60-mg arm and 59% in the 90-mg arm.

The cumulative incidence of relapse at 24 months from complete response was 41% in the 60-mg arm and 37% in the 90-mg arm.

One hundred ninety-seven patients in the 60-mg arm and 169 patients in the 90-mg arm went on to receive a stem cell transplant.

When survival was censored at transplant, there was also no difference between the arms, at 60% for the 90-mg group and 61% for the 60-mg group.

The investigators conducted subgroup analyses and found no significant benefit for 90 mg/m² in any subgroup. Dr Burnett noted, however, that there could be a potential late benefit for FLT3-ITD mutated patients who receive a 90-mg dose.

FLT3 mutated patients had a non-significant survival benefit (HR 0.74 [0.47-1.17] P=0.2) with a 90-mg dose.  However, survival was significantly worse for FLT3 wild type patients receiving 90 mg (HR 1.31 [1.03-1.67] P=0.03).

Otherwise, the group found that there is no evidence to suggest that 90 mg is superior to 60 mg.

Attendees at ASH 2014

Photo courtesy of ASH

SAN FRANCISCO—Results regarding daunorubicin escalation in induction for patients with acute myeloid leukemia (AML) have varied among different studies.

And a 90 mg/m² dose has been shown to be more effective than 45. Now, results of the UK NCRI AML17 trial have added yet another dimension to the discussion—the use of 60 mg/m² compared to 90.

Alan K. Burnett, MD, of Cardiff University in the UK, presented the data as abstract 7 at the 2014 ASH Annual Meeting.

He explained that ECOG E1900 had demonstrated superior remission and overall survival for a 90-mg dose of daunorubicin compared to a 45-mg dose in adults younger than 60.

The HOVON trial showed superior remission but no difference in overall survival for the higher dose of daunorubicin in patients older than 60.

The Korean trial demonstrated superior remission and survival rates for the 90-mg dose in patients younger than 60.

And in the GOELAMS trial, investigators found no difference between a 90-mg and a 60-mg dose level.

So the UK AML Study Group undertook to clarify the issue by comparing 90 mg to 60 mg in induction.

The investigators randomized 1206 patients younger than 60 with de novo or secondary AML or high-risk myelodysplastic syndromes (MDS) to receive 90 or 60 mg of daunorubicin on days 1, 3, and 5 of their first induction course, followed by 50 mg/m² on days 1, 3, and 5 in course 2.

All patients received ara-C during courses 1 and 2. Patients had to have LVEF of 45% or greater to be included in the trial.

The median follow-up was 29 months. Patient characteristics were comparable between the 2 groups.

The median age was 53 in both groups (range, 16-72 years), and slightly more than half of patients were male. Eighty-five percent and 84% had de novo AML in the 60-mg and 90-mg arms, respectively. Ten percent in each group had secondary AML. And 5% and 6%, respectively, had high-risk MDS.

Eleven percent in the 60-mg arm had favorable cytogenetics, compared with 9% in the 90-mg arm. Eighteen percent in each arm had mutant FLT3-ITD, and 40% in each arm were poor risk.

The investigators found no significant difference in response between the two arms—84% in the 60-mg arm and 81% in the 90-mg arm.

However, they observed a trend for increased 30-day mortality in the 90-mg arm and a significant difference in the 60-day mortality rate, which was 5% in the 60-mg arm and 10% in the 90-mg arm (P=0.001).

Twenty-nine people died by day 60 in the 60-mg arm compared with 58 in the 90-mg arm.

The main reasons for 60-day mortality in the 60-mg and 90-mg dose groups, respectively, included infection (11 vs 25 deaths), hemorrhage (3 vs 5 deaths), infection plus hemorrhage (3 vs 1 death), and resistant disease (2 vs 14 deaths), among other causes.

At 24 months, overall survival between the 2 groups was comparable, at 60% in the 60-mg arm and 59% in the 90-mg arm.

The cumulative incidence of relapse at 24 months from complete response was 41% in the 60-mg arm and 37% in the 90-mg arm.

One hundred ninety-seven patients in the 60-mg arm and 169 patients in the 90-mg arm went on to receive a stem cell transplant.

When survival was censored at transplant, there was also no difference between the arms, at 60% for the 90-mg group and 61% for the 60-mg group.

The investigators conducted subgroup analyses and found no significant benefit for 90 mg/m² in any subgroup. Dr Burnett noted, however, that there could be a potential late benefit for FLT3-ITD mutated patients who receive a 90-mg dose.

FLT3 mutated patients had a non-significant survival benefit (HR 0.74 [0.47-1.17] P=0.2) with a 90-mg dose.  However, survival was significantly worse for FLT3 wild type patients receiving 90 mg (HR 1.31 [1.03-1.67] P=0.03).

Otherwise, the group found that there is no evidence to suggest that 90 mg is superior to 60 mg.

Attendees at ASH 2014

Photo courtesy of ASH

SAN FRANCISCO—Results regarding daunorubicin escalation in induction for patients with acute myeloid leukemia (AML) have varied among different studies.

And a 90 mg/m² dose has been shown to be more effective than 45. Now, results of the UK NCRI AML17 trial have added yet another dimension to the discussion—the use of 60 mg/m² compared to 90.

Alan K. Burnett, MD, of Cardiff University in the UK, presented the data as abstract 7 at the 2014 ASH Annual Meeting.

He explained that ECOG E1900 had demonstrated superior remission and overall survival for a 90-mg dose of daunorubicin compared to a 45-mg dose in adults younger than 60.

The HOVON trial showed superior remission but no difference in overall survival for the higher dose of daunorubicin in patients older than 60.

The Korean trial demonstrated superior remission and survival rates for the 90-mg dose in patients younger than 60.

And in the GOELAMS trial, investigators found no difference between a 90-mg and a 60-mg dose level.

So the UK AML Study Group undertook to clarify the issue by comparing 90 mg to 60 mg in induction.

The investigators randomized 1206 patients younger than 60 with de novo or secondary AML or high-risk myelodysplastic syndromes (MDS) to receive 90 or 60 mg of daunorubicin on days 1, 3, and 5 of their first induction course, followed by 50 mg/m² on days 1, 3, and 5 in course 2.

All patients received ara-C during courses 1 and 2. Patients had to have LVEF of 45% or greater to be included in the trial.

The median follow-up was 29 months. Patient characteristics were comparable between the 2 groups.

The median age was 53 in both groups (range, 16-72 years), and slightly more than half of patients were male. Eighty-five percent and 84% had de novo AML in the 60-mg and 90-mg arms, respectively. Ten percent in each group had secondary AML. And 5% and 6%, respectively, had high-risk MDS.

Eleven percent in the 60-mg arm had favorable cytogenetics, compared with 9% in the 90-mg arm. Eighteen percent in each arm had mutant FLT3-ITD, and 40% in each arm were poor risk.

The investigators found no significant difference in response between the two arms—84% in the 60-mg arm and 81% in the 90-mg arm.

However, they observed a trend for increased 30-day mortality in the 90-mg arm and a significant difference in the 60-day mortality rate, which was 5% in the 60-mg arm and 10% in the 90-mg arm (P=0.001).

Twenty-nine people died by day 60 in the 60-mg arm compared with 58 in the 90-mg arm.

The main reasons for 60-day mortality in the 60-mg and 90-mg dose groups, respectively, included infection (11 vs 25 deaths), hemorrhage (3 vs 5 deaths), infection plus hemorrhage (3 vs 1 death), and resistant disease (2 vs 14 deaths), among other causes.

At 24 months, overall survival between the 2 groups was comparable, at 60% in the 60-mg arm and 59% in the 90-mg arm.

The cumulative incidence of relapse at 24 months from complete response was 41% in the 60-mg arm and 37% in the 90-mg arm.

One hundred ninety-seven patients in the 60-mg arm and 169 patients in the 90-mg arm went on to receive a stem cell transplant.

When survival was censored at transplant, there was also no difference between the arms, at 60% for the 90-mg group and 61% for the 60-mg group.

The investigators conducted subgroup analyses and found no significant benefit for 90 mg/m² in any subgroup. Dr Burnett noted, however, that there could be a potential late benefit for FLT3-ITD mutated patients who receive a 90-mg dose.

FLT3 mutated patients had a non-significant survival benefit (HR 0.74 [0.47-1.17] P=0.2) with a 90-mg dose.  However, survival was significantly worse for FLT3 wild type patients receiving 90 mg (HR 1.31 [1.03-1.67] P=0.03).

Otherwise, the group found that there is no evidence to suggest that 90 mg is superior to 60 mg.

Piglet

Credit: USDA

VIENNA—Encapsulating the anthracycline doxorubicin in a liposome can reduce the risk of developing heart damage, according to a study presented at EuroEcho-Imaging 2014.

Researchers administered doxorubicin encased in a liposome to a small group of pigs and compared cardiac outcomes to those in pigs that received unmanipulated doxorubicin or epirubicin.

Pigs that received encapsulated doxorubicin still developed cardiotoxicity, but at lower rates than pigs that received traditional doxorubicin.

Pigs that received epirubicin were excluded due to low survival rates.

“[M]any chemotherapies—in particular, anthracyclines—cause cardiac side effects that can lead to cardiomyopathy and severe heart failure,” said study investigator Jutta Bergler-Klein, MD, of the Medical University of Vienna in Austria. “Cardiotoxicity can occur acutely or up to 30 years after chemotherapy and is the second most common cause of death in cancer patients, after secondary malignancy in childhood cancer survivors.”

“Liposomal encapsulation is a new technique which wraps the chemotherapy drug in a fatty cover called a liposome. More of the drug reaches the cancer cells because there is less degradation, and there are fewer side effects on healthy cells because the fat cover acts as a barrier.”

“The drug stays in the bloodstream longer, allowing higher cumulative doses to be given. We tested whether non-pegylated liposome encapsulation of the anthracycline doxorubicin (called Myocet) could decrease its cardiotoxicity compared to conventional doxorubicin or epirubicin, another anthracycline.”

The study included 24 pigs that were randomized to receive the human dose-equivalent of Myocet, conventional doxorubicin, or epirubicin in 3 cycles. The epirubicin group was excluded from the final analyses because of low survival levels.

The researchers assessed cardiac function by echocardiography and MRI at baseline and follow-up (after about 3 months). Laboratory follow-up included hematology, renal function, and measurement of the cardiac enzymes troponin and BNP.

“The dose, imaging methodology, and blood parameters simulate the monitoring that patients on this treatment would receive and produces valuable translational data,” Dr Bergler-Klein said.

The researchers found that the group receiving Myocet had better diastolic and systolic function in the left and right ventricles, compared to conventional doxorubicin. The Myocet group also had less fibrosis in the myocardium, as shown by MRI and histology staining.

“Our study shows that doxorubicin encapsulated in a liposome had fewer cardiac side effects than doxorubicin given in the conventional way,” Dr Bergler-Klein said.

“We did find cardiac toxicity in the Myocet group as well, despite the fact that the pigs were young, healthy, and received anthracyclines for only a short period. This emphasizes how important it is for all cancer patients taking anthracyclines to receive cardiac monitoring using echocardiography and biomarkers, and MRI where indicated.”

“Many patients who recover after chemotherapy have asymptomatic heart damage, which can become symptomatic as they get older. When heart problems are picked up early, patients can be given preventive treatment, including ACE inhibitors, angiotensin receptor blockers, or beta-blockers, to prevent the progression to overt heart failure.”

The researchers are now conducting gene-expression profiling on the histology samples, hoping to explain the better outcome and cardiac function after Myocet therapy. They have found differences in the expression of genes that control energy use and the metabolic state, with better regulation in the Myocet group.

Piglet

Credit: USDA

VIENNA—Encapsulating the anthracycline doxorubicin in a liposome can reduce the risk of developing heart damage, according to a study presented at EuroEcho-Imaging 2014.

Researchers administered doxorubicin encased in a liposome to a small group of pigs and compared cardiac outcomes to those in pigs that received unmanipulated doxorubicin or epirubicin.

Pigs that received encapsulated doxorubicin still developed cardiotoxicity, but at lower rates than pigs that received traditional doxorubicin.

Pigs that received epirubicin were excluded due to low survival rates.

“[M]any chemotherapies—in particular, anthracyclines—cause cardiac side effects that can lead to cardiomyopathy and severe heart failure,” said study investigator Jutta Bergler-Klein, MD, of the Medical University of Vienna in Austria. “Cardiotoxicity can occur acutely or up to 30 years after chemotherapy and is the second most common cause of death in cancer patients, after secondary malignancy in childhood cancer survivors.”

“Liposomal encapsulation is a new technique which wraps the chemotherapy drug in a fatty cover called a liposome. More of the drug reaches the cancer cells because there is less degradation, and there are fewer side effects on healthy cells because the fat cover acts as a barrier.”

“The drug stays in the bloodstream longer, allowing higher cumulative doses to be given. We tested whether non-pegylated liposome encapsulation of the anthracycline doxorubicin (called Myocet) could decrease its cardiotoxicity compared to conventional doxorubicin or epirubicin, another anthracycline.”

The study included 24 pigs that were randomized to receive the human dose-equivalent of Myocet, conventional doxorubicin, or epirubicin in 3 cycles. The epirubicin group was excluded from the final analyses because of low survival levels.

The researchers assessed cardiac function by echocardiography and MRI at baseline and follow-up (after about 3 months). Laboratory follow-up included hematology, renal function, and measurement of the cardiac enzymes troponin and BNP.

“The dose, imaging methodology, and blood parameters simulate the monitoring that patients on this treatment would receive and produces valuable translational data,” Dr Bergler-Klein said.

The researchers found that the group receiving Myocet had better diastolic and systolic function in the left and right ventricles, compared to conventional doxorubicin. The Myocet group also had less fibrosis in the myocardium, as shown by MRI and histology staining.

“Our study shows that doxorubicin encapsulated in a liposome had fewer cardiac side effects than doxorubicin given in the conventional way,” Dr Bergler-Klein said.

“We did find cardiac toxicity in the Myocet group as well, despite the fact that the pigs were young, healthy, and received anthracyclines for only a short period. This emphasizes how important it is for all cancer patients taking anthracyclines to receive cardiac monitoring using echocardiography and biomarkers, and MRI where indicated.”

“Many patients who recover after chemotherapy have asymptomatic heart damage, which can become symptomatic as they get older. When heart problems are picked up early, patients can be given preventive treatment, including ACE inhibitors, angiotensin receptor blockers, or beta-blockers, to prevent the progression to overt heart failure.”

The researchers are now conducting gene-expression profiling on the histology samples, hoping to explain the better outcome and cardiac function after Myocet therapy. They have found differences in the expression of genes that control energy use and the metabolic state, with better regulation in the Myocet group.

Piglet

Credit: USDA

VIENNA—Encapsulating the anthracycline doxorubicin in a liposome can reduce the risk of developing heart damage, according to a study presented at EuroEcho-Imaging 2014.

Researchers administered doxorubicin encased in a liposome to a small group of pigs and compared cardiac outcomes to those in pigs that received unmanipulated doxorubicin or epirubicin.

Pigs that received encapsulated doxorubicin still developed cardiotoxicity, but at lower rates than pigs that received traditional doxorubicin.

Pigs that received epirubicin were excluded due to low survival rates.

“[M]any chemotherapies—in particular, anthracyclines—cause cardiac side effects that can lead to cardiomyopathy and severe heart failure,” said study investigator Jutta Bergler-Klein, MD, of the Medical University of Vienna in Austria. “Cardiotoxicity can occur acutely or up to 30 years after chemotherapy and is the second most common cause of death in cancer patients, after secondary malignancy in childhood cancer survivors.”

“Liposomal encapsulation is a new technique which wraps the chemotherapy drug in a fatty cover called a liposome. More of the drug reaches the cancer cells because there is less degradation, and there are fewer side effects on healthy cells because the fat cover acts as a barrier.”

“The drug stays in the bloodstream longer, allowing higher cumulative doses to be given. We tested whether non-pegylated liposome encapsulation of the anthracycline doxorubicin (called Myocet) could decrease its cardiotoxicity compared to conventional doxorubicin or epirubicin, another anthracycline.”

The study included 24 pigs that were randomized to receive the human dose-equivalent of Myocet, conventional doxorubicin, or epirubicin in 3 cycles. The epirubicin group was excluded from the final analyses because of low survival levels.

The researchers assessed cardiac function by echocardiography and MRI at baseline and follow-up (after about 3 months). Laboratory follow-up included hematology, renal function, and measurement of the cardiac enzymes troponin and BNP.

“The dose, imaging methodology, and blood parameters simulate the monitoring that patients on this treatment would receive and produces valuable translational data,” Dr Bergler-Klein said.

The researchers found that the group receiving Myocet had better diastolic and systolic function in the left and right ventricles, compared to conventional doxorubicin. The Myocet group also had less fibrosis in the myocardium, as shown by MRI and histology staining.

“Our study shows that doxorubicin encapsulated in a liposome had fewer cardiac side effects than doxorubicin given in the conventional way,” Dr Bergler-Klein said.

“We did find cardiac toxicity in the Myocet group as well, despite the fact that the pigs were young, healthy, and received anthracyclines for only a short period. This emphasizes how important it is for all cancer patients taking anthracyclines to receive cardiac monitoring using echocardiography and biomarkers, and MRI where indicated.”

“Many patients who recover after chemotherapy have asymptomatic heart damage, which can become symptomatic as they get older. When heart problems are picked up early, patients can be given preventive treatment, including ACE inhibitors, angiotensin receptor blockers, or beta-blockers, to prevent the progression to overt heart failure.”

The researchers are now conducting gene-expression profiling on the histology samples, hoping to explain the better outcome and cardiac function after Myocet therapy. They have found differences in the expression of genes that control energy use and the metabolic state, with better regulation in the Myocet group.