Decreasing the burden of treating skin and soft tissue infections is critical to improving care and reducing the costs that SSTIs place on health care facilities, according to a study published in Hospital Practice.

“Despite expert panel recommendations and treatment guidelines, there is no widely accepted classification system for grading SSTIs to outcomes,” wrote the study’s lead author, Kristin E. Linder, PharmD, of Hartford (Conn.) Hospital. “This leads to a considerable variation in treatment approach on initial presentation when deciding which patients should be admitted to receive intravenous (IV) antibiotic therapy or treated as outpatients.”

Dr. Linder and her coinvestigators conducted a single-center retrospective cohort study with the primary objective of determining rates of admission and re-presentation, along with average length-of-stay (LOS) and cost of care for both inpatients and outpatients with SSTIs. Patients aged 18 years and older who received a primary diagnosis of an SSTI during May and June of 2015 at Hartford Hospital were screened; 446 were deemed eligible, with 357 ultimately selected for inclusion (Hosp Pract. 2017 Jan 5. doi: 10.1080/21548331.2017.1279519).

Courtesy U.S. National Institute of Allergy and Infectious Diseases

[email protected]

Decreasing the burden of treating skin and soft tissue infections is critical to improving care and reducing the costs that SSTIs place on health care facilities, according to a study published in Hospital Practice.

“Despite expert panel recommendations and treatment guidelines, there is no widely accepted classification system for grading SSTIs to outcomes,” wrote the study’s lead author, Kristin E. Linder, PharmD, of Hartford (Conn.) Hospital. “This leads to a considerable variation in treatment approach on initial presentation when deciding which patients should be admitted to receive intravenous (IV) antibiotic therapy or treated as outpatients.”

Dr. Linder and her coinvestigators conducted a single-center retrospective cohort study with the primary objective of determining rates of admission and re-presentation, along with average length-of-stay (LOS) and cost of care for both inpatients and outpatients with SSTIs. Patients aged 18 years and older who received a primary diagnosis of an SSTI during May and June of 2015 at Hartford Hospital were screened; 446 were deemed eligible, with 357 ultimately selected for inclusion (Hosp Pract. 2017 Jan 5. doi: 10.1080/21548331.2017.1279519).

Courtesy U.S. National Institute of Allergy and Infectious Diseases

[email protected]

Decreasing the burden of treating skin and soft tissue infections is critical to improving care and reducing the costs that SSTIs place on health care facilities, according to a study published in Hospital Practice.

“Despite expert panel recommendations and treatment guidelines, there is no widely accepted classification system for grading SSTIs to outcomes,” wrote the study’s lead author, Kristin E. Linder, PharmD, of Hartford (Conn.) Hospital. “This leads to a considerable variation in treatment approach on initial presentation when deciding which patients should be admitted to receive intravenous (IV) antibiotic therapy or treated as outpatients.”

Dr. Linder and her coinvestigators conducted a single-center retrospective cohort study with the primary objective of determining rates of admission and re-presentation, along with average length-of-stay (LOS) and cost of care for both inpatients and outpatients with SSTIs. Patients aged 18 years and older who received a primary diagnosis of an SSTI during May and June of 2015 at Hartford Hospital were screened; 446 were deemed eligible, with 357 ultimately selected for inclusion (Hosp Pract. 2017 Jan 5. doi: 10.1080/21548331.2017.1279519).

Courtesy U.S. National Institute of Allergy and Infectious Diseases

[email protected]

Nailfold videocapillaroscopy can help to predict which patients with systemic sclerosis may develop serious cardiopulmonary complications, according to findings from a Dutch cross-sectional study.

While individual autoantibodies seen in systemic sclerosis (SSc) are known to be associated with greater or lesser risk of cardiopulmonary involvement, in this study nailfold vascularization patterns independently predicted pulmonary artery hypertension or interstitial lung disease.

ACR Copyright 2017

Nailfold videocapillaroscopy can help to predict which patients with systemic sclerosis may develop serious cardiopulmonary complications, according to findings from a Dutch cross-sectional study.

While individual autoantibodies seen in systemic sclerosis (SSc) are known to be associated with greater or lesser risk of cardiopulmonary involvement, in this study nailfold vascularization patterns independently predicted pulmonary artery hypertension or interstitial lung disease.

ACR Copyright 2017

Nailfold videocapillaroscopy can help to predict which patients with systemic sclerosis may develop serious cardiopulmonary complications, according to findings from a Dutch cross-sectional study.

While individual autoantibodies seen in systemic sclerosis (SSc) are known to be associated with greater or lesser risk of cardiopulmonary involvement, in this study nailfold vascularization patterns independently predicted pulmonary artery hypertension or interstitial lung disease.

ACR Copyright 2017

Once again, there has been another senseless tragedy: a mass murder that leaves us all feeling vulnerable.

Last Friday, a gunman flew from Anchorage, Alaska, to Florida; retrieved a gun from his checked baggage; and opened fire on total strangers in the baggage claim area of the Fort Lauderdale airport, killing five people and wounding eight others. Why? The media always find a few facts that leave the public to piece together a theory that may or may not hold true.

I heard about the shooting while I was on vacation: The suspected gunman reportedly had visited ISIS websites and was killed at the scene. Later, I saw that he was not a terrorist and was not killed but had been taken into custody without a struggle.

The next reports noted that the 26-year-old man is a former soldier who had served in Iraq, and had come back traumatized and with psychological issues, according to his brother – or, according to what the media say his brother said, since the facts are sometimes selectively reported.

It was then announced that the gunman had gone to the FBI and reported that he was having concerns that U.S. intelligence agencies were infiltrating his brain and commanding him to look at ISIS websites. The FBI sent him for a psychiatric evaluation. His gun was taken by police; he spent a few days in the hospital, and had been released. Soon after, his firearm was returned, and he used it to commit a mass shooting.

Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Care,” which was released last fall (Baltimore: Johns Hopkins University Press).

Once again, there has been another senseless tragedy: a mass murder that leaves us all feeling vulnerable.

Last Friday, a gunman flew from Anchorage, Alaska, to Florida; retrieved a gun from his checked baggage; and opened fire on total strangers in the baggage claim area of the Fort Lauderdale airport, killing five people and wounding eight others. Why? The media always find a few facts that leave the public to piece together a theory that may or may not hold true.

I heard about the shooting while I was on vacation: The suspected gunman reportedly had visited ISIS websites and was killed at the scene. Later, I saw that he was not a terrorist and was not killed but had been taken into custody without a struggle.

The next reports noted that the 26-year-old man is a former soldier who had served in Iraq, and had come back traumatized and with psychological issues, according to his brother – or, according to what the media say his brother said, since the facts are sometimes selectively reported.

It was then announced that the gunman had gone to the FBI and reported that he was having concerns that U.S. intelligence agencies were infiltrating his brain and commanding him to look at ISIS websites. The FBI sent him for a psychiatric evaluation. His gun was taken by police; he spent a few days in the hospital, and had been released. Soon after, his firearm was returned, and he used it to commit a mass shooting.

Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Care,” which was released last fall (Baltimore: Johns Hopkins University Press).

Once again, there has been another senseless tragedy: a mass murder that leaves us all feeling vulnerable.

Last Friday, a gunman flew from Anchorage, Alaska, to Florida; retrieved a gun from his checked baggage; and opened fire on total strangers in the baggage claim area of the Fort Lauderdale airport, killing five people and wounding eight others. Why? The media always find a few facts that leave the public to piece together a theory that may or may not hold true.

I heard about the shooting while I was on vacation: The suspected gunman reportedly had visited ISIS websites and was killed at the scene. Later, I saw that he was not a terrorist and was not killed but had been taken into custody without a struggle.

The next reports noted that the 26-year-old man is a former soldier who had served in Iraq, and had come back traumatized and with psychological issues, according to his brother – or, according to what the media say his brother said, since the facts are sometimes selectively reported.

It was then announced that the gunman had gone to the FBI and reported that he was having concerns that U.S. intelligence agencies were infiltrating his brain and commanding him to look at ISIS websites. The FBI sent him for a psychiatric evaluation. His gun was taken by police; he spent a few days in the hospital, and had been released. Soon after, his firearm was returned, and he used it to commit a mass shooting.

Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Care,” which was released last fall (Baltimore: Johns Hopkins University Press).

Clinical question: Is fecal microbiota transplantation (FMT) an efficacious and safe treatment approach for patients with recurrent Clostridium difficile infection (CDI)?

Background: FMT restores the normal composition of gut microbiota and is recommended when antibiotics fail to clear CDI. To date, only case series and open-labeled clinical trials support the use of FMT.

Study design: Randomized, controlled, double-blinded clinical trial.


Setting: Academic medical centers.

The primary endpoint was resolution of diarrhea without anti-CDI therapy after 8 weeks of follow-up. In the donor FMT group, 90.9% achieved clinical cure, compared with 62.5% in the autologous group. Patients who developed recurrent CDI were free of further disease after subsequent donor FMT.

The study included only patients who experienced three or more recurrences but excluded immunocompromised and older patients (older than 75 years of age).

Bottom line: Donor stool administered via colonoscopy was more effective than autologous FMT in preventing further CDI episodes.

Citation: Kelly CR, Khoruts A, Staley C, et al. Effect of fecal microbiota transplantation on recurrence in multiply recurrent Clostridium difficile infection: a randomized trial. Ann Intern Med. 2016;165(9):609-616.

Dr. Fernandez de la Vara is an instructor at the University of Miami Miller School of Medicine and chief medical resident at the University of Miami Hospital.

Clinical question: Is fecal microbiota transplantation (FMT) an efficacious and safe treatment approach for patients with recurrent Clostridium difficile infection (CDI)?

Background: FMT restores the normal composition of gut microbiota and is recommended when antibiotics fail to clear CDI. To date, only case series and open-labeled clinical trials support the use of FMT.

Study design: Randomized, controlled, double-blinded clinical trial.


Setting: Academic medical centers.

The primary endpoint was resolution of diarrhea without anti-CDI therapy after 8 weeks of follow-up. In the donor FMT group, 90.9% achieved clinical cure, compared with 62.5% in the autologous group. Patients who developed recurrent CDI were free of further disease after subsequent donor FMT.

The study included only patients who experienced three or more recurrences but excluded immunocompromised and older patients (older than 75 years of age).

Bottom line: Donor stool administered via colonoscopy was more effective than autologous FMT in preventing further CDI episodes.

Citation: Kelly CR, Khoruts A, Staley C, et al. Effect of fecal microbiota transplantation on recurrence in multiply recurrent Clostridium difficile infection: a randomized trial. Ann Intern Med. 2016;165(9):609-616.

Dr. Fernandez de la Vara is an instructor at the University of Miami Miller School of Medicine and chief medical resident at the University of Miami Hospital.

Clinical question: Is fecal microbiota transplantation (FMT) an efficacious and safe treatment approach for patients with recurrent Clostridium difficile infection (CDI)?

Background: FMT restores the normal composition of gut microbiota and is recommended when antibiotics fail to clear CDI. To date, only case series and open-labeled clinical trials support the use of FMT.

Study design: Randomized, controlled, double-blinded clinical trial.


Setting: Academic medical centers.

The primary endpoint was resolution of diarrhea without anti-CDI therapy after 8 weeks of follow-up. In the donor FMT group, 90.9% achieved clinical cure, compared with 62.5% in the autologous group. Patients who developed recurrent CDI were free of further disease after subsequent donor FMT.

The study included only patients who experienced three or more recurrences but excluded immunocompromised and older patients (older than 75 years of age).

Bottom line: Donor stool administered via colonoscopy was more effective than autologous FMT in preventing further CDI episodes.

Citation: Kelly CR, Khoruts A, Staley C, et al. Effect of fecal microbiota transplantation on recurrence in multiply recurrent Clostridium difficile infection: a randomized trial. Ann Intern Med. 2016;165(9):609-616.

Dr. Fernandez de la Vara is an instructor at the University of Miami Miller School of Medicine and chief medical resident at the University of Miami Hospital.

To the Editor:

A 52-year-old woman with a history of arthralgia, rhinitis, sinusitis, and episodic epistaxis was admitted to the hospital with multiple nonhealing severe leg ulcerations. She noticed subcutaneous nodules on the legs 6 months prior to the development of ulcers. The lesions progressed from subcutaneous nodules to red-black skin discoloration, blister formation, and eventually ulceration. Over a period of months, the ulcers were treated with several courses of antibiotics and wound care including a single surgical debridement of one of the ulcers on the dorsum of the right foot. These interventions did not make a remarkable impact on ulcer healing.

On physical examination, the patient had scattered 4- to 5-mm palpable purpura on the knees, elbows, and feet bilaterally. She had multiple 1- to 8-cm indurated purple ulcerations with friable surfaces and raised irregular borders on the feet, toes, and lower legs bilaterally (Figure, A–C). One notably larger ulcer was found on the anterior aspect of the left thigh (Figure, A). Scattered 5- to 15-mm eschars were present on the legs bilaterally. She also had multiple large, firm, nonerythematous dermal plaques on the thighs bilaterally that measured several centimeters. There were no oral mucosal lesions and no ulcerations above the waist.

Magnetic resonance imaging of the foot showed some surrounding cellulitis but no osteomyelitis. Chest radiograph and computed tomography revealed bilateral apical nodules. Proteinase 3–antineutrophil cytoplasmic antibody (PR3-ANCA) testing was positive. Serum complement levels were normal. An antinuclear antibody test and rheumatoid factor were both negative. Skin biopsies were obtained from the thigh ulcer, foot ulcer, and purpuric lesions on the right knee. The results demonstrated leukocytoclastic vasculitis and neutrophilic small vessel vasculitis with necrotizing neutrophilic dermatitis and panniculitis. Granulomatosis with polyangiitis (GPA) was diagnosed based on these findings.

Initial inpatient treatment included intravenous methylprednisolone (100 mg every 8 hours for 3 doses), followed by oral prednisone 60 mg daily. Two weeks later the ulcers were reevaluated and only mild improvement had occurred with the steroids. Therefore, rituximab (RTX) was initiated at 375 mg/m² (700 mg) intravenously once weekly for 4 weeks. After 3 doses of RTX, the ulcerations were healing dramatically and the treatment was well tolerated. A rapid prednisone taper was started, and the patient received her fourth and final dose of RTX. Two months after the initial infusion, the thigh ulcer and most of the ulcerations on the feet and lower legs had almost completely resolved. Photographs were taken 5 months after initial RTX infusion (Figure, D–F). A chest radiograph 4 months after initial RTX infusion showed resolution of lung nodules. Two months after RTX induction therapy, azathioprine was added for maintenance but was stopped due to poor tolerance. Oral methotrexate 17.5 mg once weekly was added 5 months after RTX for maintenance and was well tolerated. At that time the prednisone dose was 10 mg daily and was successfully tapered to 5 mg by 9 months after RTX induction therapy.

Granulomatosis with polyangiitis (Wegener granulomatosis) is a granulomatous small- and medium-sized vessel vasculitis that traditionally affects the upper and lower respiratory tract and kidneys.¹ Skin lesions also are quite common and include palpable purpura, ulcers, vesicles, papules, and subcutaneous nodules. Patients with active GPA also tend to have ANCAs directed against proteinase 3 (PR3-ANCA). Although GPA was once considered a fatal disease, treatment with cyclophosphamide combined with corticosteroids has been shown to substantially improve outcomes.¹ Rituximab, a chimeric monoclonal anti-CD20 antibody, works by depleting B lymphocytes and has been used with success to treat diseases such as lymphoma and rheumatoid arthritis.^2,3 The US Food and Drug Administration approved RTX for GPA and microscopic polyangiitis in 2011, with a number of trials supporting its efficacy.⁴

The success of RTX in treating GPA has been documented in case reports as well as several trials with extended follow-up. A single-center observational study of 53 patients showed that RTX was safe and effective for induction and maintenance of remission in patients with refractory GPA. This study also uncovered the potential for predicting relapse based on following B cell and ANCA levels and preventing relapse by initializing further treatment.⁵ Other small studies and case reports have shown similar success using RTX for refractory GPA.^6-10 These studies included various combinations of concurrent therapies and various follow-up intervals. The Rituximab in ANCA-Associated Vasculitis (RAVE) trial compared RTX versus cyclophosphamide for ANCA-positive vasculitis.¹¹ This multicenter, randomized, double-blind study found that RTX was as efficacious as cyclophosphamide for induction of remission in severe GPA.The data also suggested that RTX may be superior for relapsing disease.¹¹ Another multicenter, open-label, randomized trial (RITUXVAS) compared RTX to cyclophosphamide in ANCA-associated renal vasculitis. This trial also found the 2 treatments to be similar in both efficacy in inducing remission and adverse events.¹²

Some conflicting reports have appeared on the effectiveness of using RTX for the granulomatous versus vasculitic manifestations of GPA. Aires et al¹³ showed failure of improvement in most patients with granulomatous manifestations of GPA in a study of 8 patients. A retrospective study including 59 patients who were treated with RTX also showed that complete remission was more common in patients with primarily vasculitic manifestations, not granulomatous manifestations.¹⁴ However, some case series that included patients with refractory ophthalmic GPA, a primarily granulomatous manifestation, have found success using RTX.^15,16 More studies are needed to determine if there truly is a difference and whether this difference has an effect on when to use RTX. The skin lesions our patient demonstrated were due to the vasculitic component of the disease, and consequently, the rapid and complete response we observed would be consistent with the premise that the therapy works best for vasculitis.

Most of the trials assessing the efficacy of RTX utilize a tool such as the Wegener granulomatosis-specific Birmingham Vasculitis Activity Score.¹⁷ This measure of treatment response does include a skin item, but it is part of the composite response score. Consequently, a specific statement regarding skin improvement cannot be made. Additionally, little is reported pertaining to the treatment of skin-related findings in GPA. One report did specifically address the treatment of dermatologic manifestations of GPA utilizing systemic tacrolimus with oral prednisone successfully in 1 patient with GPA and a history of recurrent lower extremity nodules and ulcers.¹⁸ The efficacy of RTX in limited GPA was good in a small study of 8 patients. However, the study had only 1 patient with purpura and 1 patient with a subcutaneous nodule.¹⁹ Several other case series and studies have included patients with various cutaneous findings associated with GPA.^5-7,9,11 However, they did not comment specifically on skin response to treatment, and the focus appeared to be on other organ system involvement. One case series did report improvement of lower extremity gangrene with RTX therapy for ANCA-associated vasculitis.⁸ Our report demonstrates a case of severe skin disease that responded well to RTX. It is common to have various skin findings in GPA, and our patient presented with notable skin disease. Although skin findings may not be the more life-threatening manifestations of the disease, they can be quite debilitating, as shown in our case report.

Our patient with notable leg ulcerations required hospitalization due to GPA and received RTX in addition to corticosteroids for treatment. We observed a rapid and dramatic improvement in the skin findings, which seemed to exceed expectations from steroids alone. The other manifestations of the disease including lung nodules also improved. Although cyclophosphamide and corticosteroids have been quite successful in induction of remission, cyclophosphamide is not without serious adverse effects. There also are some patients who have contraindications to cyclophosphamide or do not see successful results. In our brief review of the literature, RTX, a B cell–depleting antibody, has shown to have success in treating refractory and severe GPA. There is little reported specifically about treating the skin manifestations of GPA. A few studies and case reports mention skin findings but do not comment on the success of RTX in treating them. Although the severity of other organ involvement in GPA may take precedence, the skin findings can be quite debilitating, as in our patient. Patients with GPA and notable skin findings may benefit from RTX, and it would be beneficial to include these results in future studies using RTX to treat GPA.

To the Editor:

A 52-year-old woman with a history of arthralgia, rhinitis, sinusitis, and episodic epistaxis was admitted to the hospital with multiple nonhealing severe leg ulcerations. She noticed subcutaneous nodules on the legs 6 months prior to the development of ulcers. The lesions progressed from subcutaneous nodules to red-black skin discoloration, blister formation, and eventually ulceration. Over a period of months, the ulcers were treated with several courses of antibiotics and wound care including a single surgical debridement of one of the ulcers on the dorsum of the right foot. These interventions did not make a remarkable impact on ulcer healing.

On physical examination, the patient had scattered 4- to 5-mm palpable purpura on the knees, elbows, and feet bilaterally. She had multiple 1- to 8-cm indurated purple ulcerations with friable surfaces and raised irregular borders on the feet, toes, and lower legs bilaterally (Figure, A–C). One notably larger ulcer was found on the anterior aspect of the left thigh (Figure, A). Scattered 5- to 15-mm eschars were present on the legs bilaterally. She also had multiple large, firm, nonerythematous dermal plaques on the thighs bilaterally that measured several centimeters. There were no oral mucosal lesions and no ulcerations above the waist.

Magnetic resonance imaging of the foot showed some surrounding cellulitis but no osteomyelitis. Chest radiograph and computed tomography revealed bilateral apical nodules. Proteinase 3–antineutrophil cytoplasmic antibody (PR3-ANCA) testing was positive. Serum complement levels were normal. An antinuclear antibody test and rheumatoid factor were both negative. Skin biopsies were obtained from the thigh ulcer, foot ulcer, and purpuric lesions on the right knee. The results demonstrated leukocytoclastic vasculitis and neutrophilic small vessel vasculitis with necrotizing neutrophilic dermatitis and panniculitis. Granulomatosis with polyangiitis (GPA) was diagnosed based on these findings.

Initial inpatient treatment included intravenous methylprednisolone (100 mg every 8 hours for 3 doses), followed by oral prednisone 60 mg daily. Two weeks later the ulcers were reevaluated and only mild improvement had occurred with the steroids. Therefore, rituximab (RTX) was initiated at 375 mg/m² (700 mg) intravenously once weekly for 4 weeks. After 3 doses of RTX, the ulcerations were healing dramatically and the treatment was well tolerated. A rapid prednisone taper was started, and the patient received her fourth and final dose of RTX. Two months after the initial infusion, the thigh ulcer and most of the ulcerations on the feet and lower legs had almost completely resolved. Photographs were taken 5 months after initial RTX infusion (Figure, D–F). A chest radiograph 4 months after initial RTX infusion showed resolution of lung nodules. Two months after RTX induction therapy, azathioprine was added for maintenance but was stopped due to poor tolerance. Oral methotrexate 17.5 mg once weekly was added 5 months after RTX for maintenance and was well tolerated. At that time the prednisone dose was 10 mg daily and was successfully tapered to 5 mg by 9 months after RTX induction therapy.

Granulomatosis with polyangiitis (Wegener granulomatosis) is a granulomatous small- and medium-sized vessel vasculitis that traditionally affects the upper and lower respiratory tract and kidneys.¹ Skin lesions also are quite common and include palpable purpura, ulcers, vesicles, papules, and subcutaneous nodules. Patients with active GPA also tend to have ANCAs directed against proteinase 3 (PR3-ANCA). Although GPA was once considered a fatal disease, treatment with cyclophosphamide combined with corticosteroids has been shown to substantially improve outcomes.¹ Rituximab, a chimeric monoclonal anti-CD20 antibody, works by depleting B lymphocytes and has been used with success to treat diseases such as lymphoma and rheumatoid arthritis.^2,3 The US Food and Drug Administration approved RTX for GPA and microscopic polyangiitis in 2011, with a number of trials supporting its efficacy.⁴

The success of RTX in treating GPA has been documented in case reports as well as several trials with extended follow-up. A single-center observational study of 53 patients showed that RTX was safe and effective for induction and maintenance of remission in patients with refractory GPA. This study also uncovered the potential for predicting relapse based on following B cell and ANCA levels and preventing relapse by initializing further treatment.⁵ Other small studies and case reports have shown similar success using RTX for refractory GPA.^6-10 These studies included various combinations of concurrent therapies and various follow-up intervals. The Rituximab in ANCA-Associated Vasculitis (RAVE) trial compared RTX versus cyclophosphamide for ANCA-positive vasculitis.¹¹ This multicenter, randomized, double-blind study found that RTX was as efficacious as cyclophosphamide for induction of remission in severe GPA.The data also suggested that RTX may be superior for relapsing disease.¹¹ Another multicenter, open-label, randomized trial (RITUXVAS) compared RTX to cyclophosphamide in ANCA-associated renal vasculitis. This trial also found the 2 treatments to be similar in both efficacy in inducing remission and adverse events.¹²

Some conflicting reports have appeared on the effectiveness of using RTX for the granulomatous versus vasculitic manifestations of GPA. Aires et al¹³ showed failure of improvement in most patients with granulomatous manifestations of GPA in a study of 8 patients. A retrospective study including 59 patients who were treated with RTX also showed that complete remission was more common in patients with primarily vasculitic manifestations, not granulomatous manifestations.¹⁴ However, some case series that included patients with refractory ophthalmic GPA, a primarily granulomatous manifestation, have found success using RTX.^15,16 More studies are needed to determine if there truly is a difference and whether this difference has an effect on when to use RTX. The skin lesions our patient demonstrated were due to the vasculitic component of the disease, and consequently, the rapid and complete response we observed would be consistent with the premise that the therapy works best for vasculitis.

Most of the trials assessing the efficacy of RTX utilize a tool such as the Wegener granulomatosis-specific Birmingham Vasculitis Activity Score.¹⁷ This measure of treatment response does include a skin item, but it is part of the composite response score. Consequently, a specific statement regarding skin improvement cannot be made. Additionally, little is reported pertaining to the treatment of skin-related findings in GPA. One report did specifically address the treatment of dermatologic manifestations of GPA utilizing systemic tacrolimus with oral prednisone successfully in 1 patient with GPA and a history of recurrent lower extremity nodules and ulcers.¹⁸ The efficacy of RTX in limited GPA was good in a small study of 8 patients. However, the study had only 1 patient with purpura and 1 patient with a subcutaneous nodule.¹⁹ Several other case series and studies have included patients with various cutaneous findings associated with GPA.^5-7,9,11 However, they did not comment specifically on skin response to treatment, and the focus appeared to be on other organ system involvement. One case series did report improvement of lower extremity gangrene with RTX therapy for ANCA-associated vasculitis.⁸ Our report demonstrates a case of severe skin disease that responded well to RTX. It is common to have various skin findings in GPA, and our patient presented with notable skin disease. Although skin findings may not be the more life-threatening manifestations of the disease, they can be quite debilitating, as shown in our case report.

Our patient with notable leg ulcerations required hospitalization due to GPA and received RTX in addition to corticosteroids for treatment. We observed a rapid and dramatic improvement in the skin findings, which seemed to exceed expectations from steroids alone. The other manifestations of the disease including lung nodules also improved. Although cyclophosphamide and corticosteroids have been quite successful in induction of remission, cyclophosphamide is not without serious adverse effects. There also are some patients who have contraindications to cyclophosphamide or do not see successful results. In our brief review of the literature, RTX, a B cell–depleting antibody, has shown to have success in treating refractory and severe GPA. There is little reported specifically about treating the skin manifestations of GPA. A few studies and case reports mention skin findings but do not comment on the success of RTX in treating them. Although the severity of other organ involvement in GPA may take precedence, the skin findings can be quite debilitating, as in our patient. Patients with GPA and notable skin findings may benefit from RTX, and it would be beneficial to include these results in future studies using RTX to treat GPA.

To the Editor:

A 52-year-old woman with a history of arthralgia, rhinitis, sinusitis, and episodic epistaxis was admitted to the hospital with multiple nonhealing severe leg ulcerations. She noticed subcutaneous nodules on the legs 6 months prior to the development of ulcers. The lesions progressed from subcutaneous nodules to red-black skin discoloration, blister formation, and eventually ulceration. Over a period of months, the ulcers were treated with several courses of antibiotics and wound care including a single surgical debridement of one of the ulcers on the dorsum of the right foot. These interventions did not make a remarkable impact on ulcer healing.

On physical examination, the patient had scattered 4- to 5-mm palpable purpura on the knees, elbows, and feet bilaterally. She had multiple 1- to 8-cm indurated purple ulcerations with friable surfaces and raised irregular borders on the feet, toes, and lower legs bilaterally (Figure, A–C). One notably larger ulcer was found on the anterior aspect of the left thigh (Figure, A). Scattered 5- to 15-mm eschars were present on the legs bilaterally. She also had multiple large, firm, nonerythematous dermal plaques on the thighs bilaterally that measured several centimeters. There were no oral mucosal lesions and no ulcerations above the waist.

Magnetic resonance imaging of the foot showed some surrounding cellulitis but no osteomyelitis. Chest radiograph and computed tomography revealed bilateral apical nodules. Proteinase 3–antineutrophil cytoplasmic antibody (PR3-ANCA) testing was positive. Serum complement levels were normal. An antinuclear antibody test and rheumatoid factor were both negative. Skin biopsies were obtained from the thigh ulcer, foot ulcer, and purpuric lesions on the right knee. The results demonstrated leukocytoclastic vasculitis and neutrophilic small vessel vasculitis with necrotizing neutrophilic dermatitis and panniculitis. Granulomatosis with polyangiitis (GPA) was diagnosed based on these findings.

Initial inpatient treatment included intravenous methylprednisolone (100 mg every 8 hours for 3 doses), followed by oral prednisone 60 mg daily. Two weeks later the ulcers were reevaluated and only mild improvement had occurred with the steroids. Therefore, rituximab (RTX) was initiated at 375 mg/m² (700 mg) intravenously once weekly for 4 weeks. After 3 doses of RTX, the ulcerations were healing dramatically and the treatment was well tolerated. A rapid prednisone taper was started, and the patient received her fourth and final dose of RTX. Two months after the initial infusion, the thigh ulcer and most of the ulcerations on the feet and lower legs had almost completely resolved. Photographs were taken 5 months after initial RTX infusion (Figure, D–F). A chest radiograph 4 months after initial RTX infusion showed resolution of lung nodules. Two months after RTX induction therapy, azathioprine was added for maintenance but was stopped due to poor tolerance. Oral methotrexate 17.5 mg once weekly was added 5 months after RTX for maintenance and was well tolerated. At that time the prednisone dose was 10 mg daily and was successfully tapered to 5 mg by 9 months after RTX induction therapy.

Granulomatosis with polyangiitis (Wegener granulomatosis) is a granulomatous small- and medium-sized vessel vasculitis that traditionally affects the upper and lower respiratory tract and kidneys.¹ Skin lesions also are quite common and include palpable purpura, ulcers, vesicles, papules, and subcutaneous nodules. Patients with active GPA also tend to have ANCAs directed against proteinase 3 (PR3-ANCA). Although GPA was once considered a fatal disease, treatment with cyclophosphamide combined with corticosteroids has been shown to substantially improve outcomes.¹ Rituximab, a chimeric monoclonal anti-CD20 antibody, works by depleting B lymphocytes and has been used with success to treat diseases such as lymphoma and rheumatoid arthritis.^2,3 The US Food and Drug Administration approved RTX for GPA and microscopic polyangiitis in 2011, with a number of trials supporting its efficacy.⁴

The success of RTX in treating GPA has been documented in case reports as well as several trials with extended follow-up. A single-center observational study of 53 patients showed that RTX was safe and effective for induction and maintenance of remission in patients with refractory GPA. This study also uncovered the potential for predicting relapse based on following B cell and ANCA levels and preventing relapse by initializing further treatment.⁵ Other small studies and case reports have shown similar success using RTX for refractory GPA.^6-10 These studies included various combinations of concurrent therapies and various follow-up intervals. The Rituximab in ANCA-Associated Vasculitis (RAVE) trial compared RTX versus cyclophosphamide for ANCA-positive vasculitis.¹¹ This multicenter, randomized, double-blind study found that RTX was as efficacious as cyclophosphamide for induction of remission in severe GPA.The data also suggested that RTX may be superior for relapsing disease.¹¹ Another multicenter, open-label, randomized trial (RITUXVAS) compared RTX to cyclophosphamide in ANCA-associated renal vasculitis. This trial also found the 2 treatments to be similar in both efficacy in inducing remission and adverse events.¹²

Some conflicting reports have appeared on the effectiveness of using RTX for the granulomatous versus vasculitic manifestations of GPA. Aires et al¹³ showed failure of improvement in most patients with granulomatous manifestations of GPA in a study of 8 patients. A retrospective study including 59 patients who were treated with RTX also showed that complete remission was more common in patients with primarily vasculitic manifestations, not granulomatous manifestations.¹⁴ However, some case series that included patients with refractory ophthalmic GPA, a primarily granulomatous manifestation, have found success using RTX.^15,16 More studies are needed to determine if there truly is a difference and whether this difference has an effect on when to use RTX. The skin lesions our patient demonstrated were due to the vasculitic component of the disease, and consequently, the rapid and complete response we observed would be consistent with the premise that the therapy works best for vasculitis.

Most of the trials assessing the efficacy of RTX utilize a tool such as the Wegener granulomatosis-specific Birmingham Vasculitis Activity Score.¹⁷ This measure of treatment response does include a skin item, but it is part of the composite response score. Consequently, a specific statement regarding skin improvement cannot be made. Additionally, little is reported pertaining to the treatment of skin-related findings in GPA. One report did specifically address the treatment of dermatologic manifestations of GPA utilizing systemic tacrolimus with oral prednisone successfully in 1 patient with GPA and a history of recurrent lower extremity nodules and ulcers.¹⁸ The efficacy of RTX in limited GPA was good in a small study of 8 patients. However, the study had only 1 patient with purpura and 1 patient with a subcutaneous nodule.¹⁹ Several other case series and studies have included patients with various cutaneous findings associated with GPA.^5-7,9,11 However, they did not comment specifically on skin response to treatment, and the focus appeared to be on other organ system involvement. One case series did report improvement of lower extremity gangrene with RTX therapy for ANCA-associated vasculitis.⁸ Our report demonstrates a case of severe skin disease that responded well to RTX. It is common to have various skin findings in GPA, and our patient presented with notable skin disease. Although skin findings may not be the more life-threatening manifestations of the disease, they can be quite debilitating, as shown in our case report.

Our patient with notable leg ulcerations required hospitalization due to GPA and received RTX in addition to corticosteroids for treatment. We observed a rapid and dramatic improvement in the skin findings, which seemed to exceed expectations from steroids alone. The other manifestations of the disease including lung nodules also improved. Although cyclophosphamide and corticosteroids have been quite successful in induction of remission, cyclophosphamide is not without serious adverse effects. There also are some patients who have contraindications to cyclophosphamide or do not see successful results. In our brief review of the literature, RTX, a B cell–depleting antibody, has shown to have success in treating refractory and severe GPA. There is little reported specifically about treating the skin manifestations of GPA. A few studies and case reports mention skin findings but do not comment on the success of RTX in treating them. Although the severity of other organ involvement in GPA may take precedence, the skin findings can be quite debilitating, as in our patient. Patients with GPA and notable skin findings may benefit from RTX, and it would be beneficial to include these results in future studies using RTX to treat GPA.

SAN FRANCISCO – Clinicians and parents should capitalize on a variety of resources and new technologies that help keep teen drivers safe behind the wheel, according to Dr. Joseph O’Neil, a pediatrician at the Riley Hospital for Children in Indianapolis.

“As I like to share with parents, this is the one developmental milestone that parents really want their kids to have that is potentially lethal. This could really kill them,” he said at the annual meeting of the American Academy of Pediatrics. “Believe me, that’s a conversation stopper; they sort of look at you funny. But it’s true.”

Risk factors

Numerous factors increase the risk of crashes and deaths for teen drivers, beginning with their developmental stage, according to Dr. O’Neil. Youth are characterized by their striving for autonomy, impulsivity, risk taking, and greater susceptibility to peer influences, compounded by poor judgment of hazards.

“We know that their executive function is still improving, still maturing, They really don’t start getting to adult levels, if they ever do, until about 25,” he commented humorously.

Other risk factors include speeding, drinking and substance use, sleep deprivation, and distractions that range from cell phones, to eating and grooming, to all the gizmos on the dashboard today. Not wearing seat belts also plays a role, as teens are the age group least likely to buckle up, and risk rises with the number of young passengers in the vehicle.

The rate of fatal crashes among young drivers is more than twice as high at night, compared with during the day, with the hours of 9 p.m. to midnight being most hazardous. And the riskiest meteorologic conditions are, not surprisingly, snow and ice – something that parents should take into account in their typical rush to get driver’s education out of the way in the summer months, he said.

“Most of the evidence points to inexperience as probably the single most important risk factor because with inexperience, you’re going to use cell phones, you’re going to be distracted, you’re not going to be paying attention because you don’t have the experience to know that you should,” Dr. O’Neil said.

Graduated driver’s licenses

A key resource in addressing teen drivers’ inexperience and the fact that their crash rate is highest in their first year of driving are graduated driver licenses (GDLs). These licenses start with a learner’s permit mandating supervision and having many restrictions on conditions such as times when driving is permitted and number of passengers, and if there are no infractions, slowly lift these restrictions as the teen gains more driving experience, until he or she receives a full driver’s license.

©Thinkstock.com

High-tech tools

Clinicians also should also be aware of a host of new high-tech tools designed to make teen drivers safer, often by extending parents’ supervisory role, Dr. O’Neil advised. “Your parents in your practices are going to ask you about these,” he said.

So-called black boxes on vehicles collect a wealth of data about driving and conditions inside the vehicle that can be made available to parents. If black boxes are used correctly, they can enable parents to give feedback to the young driver and reduce overall crash risk, he said.

New GPS monitors will track a vehicle’s speed and range, with an optional feature called geofencing whereby parents can prespecify geographic limits on where their teen driver can go. If the teen ventures outside those limits, the monitor sends a notification.

Video monitoring systems now on the market will record footage both inside and outside of the car. Some record continuously, whereas others capture only events. Parents can obtain a summary report, generally through a monthly subscription, delivered by telephone or email to see how their teen is driving when solo.

Other in-vehicle monitoring technologies include direct-feedback systems, such as the tones that sound when the driver fails to fasten his or her seat belt, changes lanes, or gets too close to another car. Some systems can be configured to send a text or email when these alerts are engaged.

Parents who want to be more proactive can, for certain vehicles, invest in smart keys that are programmed to control vehicle parameters, such as the vehicle speed or the volume on the radio, according to Dr. O’Neil.

Finally, downloadable apps for cell phones will block the user’s ability to call (except in an emergency), text, surf, and take selfies while driving. “This doesn’t mean the child won’t be able to use someone else’s phone, but it does do a nice job for that particular installation,” he commented.

Parent-teen driving agreements

“We’ve talked about a lot of neat things that are out there, but what it all boils down to in the end are the parents – mom and dad. Parents truly are the gatekeepers of the keys,” Dr. O’Neil asserted. “We know that they can have an influence on their teens’ behavior. Parents can set restrictions and regulations on driving, and make sure [teens] follow all the traffic laws and set limits on high-risk driving situations.”

However, parents often underestimate the risks that their teens take behind the wheel. “Everyone always thinks that it’s the other kid who’s going to be driving wildly,” he said. “It’s okay for us to say, ‘I know he’s a great kid, but it’s not the bad kids who get into crashes. All kids get into crashes,’” he said. “It’s important to remind parents that all kids are at risk.

“One of the most valuable things that we can do as physicians to help parents navigate these crazy waters is talk about parent-teen driving agreements or contracts,” Dr. O’Neil said. “This has been shown time and time again to have a positive effect on driving behavior.”

These agreements list rules and expectations, and consequences for breaking the rules. “Both mom and dad, and the teen sign it. You put your name on the line, and that’s important because that really means something. This is probably the first contract this kid will ever sign, and it’s probably the most important one that [the teen] will ever sign.” He recommended that a paper version of the agreement be placed in a prominent location, such as on the refrigerator door, for maximal effectiveness.

A variety of parent-teen driving agreements are available online through initiatives such as the Checkpoints Program, Parents Are the Key to Safe Teen Drivers, I Drive Safely, and the AAP’s Parent-Teen Driving Agreement. Overall, their use has been shown to reduce the risks of traffic violations and crashes by 40%-50%.

Of note, these contracts complement rather than replace GDLs. Additionally, “the law of the land doesn’t trump the law of reality and the law of physics,” Dr. O’Neil pointed out. “We know that the laws in our states are not really always best practice, so as we advocate for best practice laws, what we can do is let the parents set better limits on the teen’s driving.”

Anticipatory guidance

“I usually start talking [with families] about driving when the child is 12 or 13,” Dr. O’Neil said. “Anticipatory guidance does work. We know that for a lot of other things that we do, but parents often need help in trying to figure out what to do.”

He recommended the AAP’s Healthy Children website as a source of good information and resources, including a Young Driver Tool for parents. “This has been vetted through the PROS [Pediatric Research in Office Settings] network, and it has been shown that parents do use it, parents do like it,” he noted. “And really it makes your job easier, because it takes time to talk about all these risk factors, and you can say, ‘Hey, I want you to go look at this website for teen driving. This will help.’ ”

Clinicians should generally cover with families the various risk factors, limit setting, use of GDLs, and parent-teen driving agreements. “Talk to parents about all these things. Talk to the teen; the teen will listen to you; you are an authority figure,” and “use interventional motivational techniques,” he said.

As parents control the vehicle their child drives, they should be counseled to give their teen the family’s safest car, preferably a newer, mid- to full-size vehicle with a small engine and modern safety features, according to Dr. O’Neil. “And we really do try to discourage teens buying their own cars because that sort of limits the parents’ leverage over them when they are starting to drive.”

Clinicians also should familiarize themselves with the driver’s education and similar resources in their community, including safe-driving initiatives spearheaded by groups such as Mothers Against Drunk Driving (MADD). They also should work with schools and the police to support “risky driving” prevention efforts.

Special anticipatory guidance is warranted when the new teen driver has a relevant condition such as attention-deficit/hyperactivity disorder. These youth are two to four times more likely to have a motor vehicle accident than typical teen drivers.

They may benefit from extended-release ADHD medication or a booster dose of their medication to keep them covered while driving, according to Dr. O’Neil.

“You may want to talk to them about holding off. Maybe their brain hasn’t matured enough yet, and you want to delay their driving. You may want to do a longer period of supervised driving or consider other things we’ve talked about – electronic resources or using a bigger, safer vehicle,” he suggested. “And always, always, always encourage limiting of distractions while driving.”

Dr. O’Neil said he had no relevant conflicts of interest.

[email protected]

SAN FRANCISCO – Clinicians and parents should capitalize on a variety of resources and new technologies that help keep teen drivers safe behind the wheel, according to Dr. Joseph O’Neil, a pediatrician at the Riley Hospital for Children in Indianapolis.

“As I like to share with parents, this is the one developmental milestone that parents really want their kids to have that is potentially lethal. This could really kill them,” he said at the annual meeting of the American Academy of Pediatrics. “Believe me, that’s a conversation stopper; they sort of look at you funny. But it’s true.”

Risk factors

Numerous factors increase the risk of crashes and deaths for teen drivers, beginning with their developmental stage, according to Dr. O’Neil. Youth are characterized by their striving for autonomy, impulsivity, risk taking, and greater susceptibility to peer influences, compounded by poor judgment of hazards.

“We know that their executive function is still improving, still maturing, They really don’t start getting to adult levels, if they ever do, until about 25,” he commented humorously.

Other risk factors include speeding, drinking and substance use, sleep deprivation, and distractions that range from cell phones, to eating and grooming, to all the gizmos on the dashboard today. Not wearing seat belts also plays a role, as teens are the age group least likely to buckle up, and risk rises with the number of young passengers in the vehicle.

The rate of fatal crashes among young drivers is more than twice as high at night, compared with during the day, with the hours of 9 p.m. to midnight being most hazardous. And the riskiest meteorologic conditions are, not surprisingly, snow and ice – something that parents should take into account in their typical rush to get driver’s education out of the way in the summer months, he said.

“Most of the evidence points to inexperience as probably the single most important risk factor because with inexperience, you’re going to use cell phones, you’re going to be distracted, you’re not going to be paying attention because you don’t have the experience to know that you should,” Dr. O’Neil said.

Graduated driver’s licenses

A key resource in addressing teen drivers’ inexperience and the fact that their crash rate is highest in their first year of driving are graduated driver licenses (GDLs). These licenses start with a learner’s permit mandating supervision and having many restrictions on conditions such as times when driving is permitted and number of passengers, and if there are no infractions, slowly lift these restrictions as the teen gains more driving experience, until he or she receives a full driver’s license.

©Thinkstock.com

High-tech tools

Clinicians also should also be aware of a host of new high-tech tools designed to make teen drivers safer, often by extending parents’ supervisory role, Dr. O’Neil advised. “Your parents in your practices are going to ask you about these,” he said.

So-called black boxes on vehicles collect a wealth of data about driving and conditions inside the vehicle that can be made available to parents. If black boxes are used correctly, they can enable parents to give feedback to the young driver and reduce overall crash risk, he said.

New GPS monitors will track a vehicle’s speed and range, with an optional feature called geofencing whereby parents can prespecify geographic limits on where their teen driver can go. If the teen ventures outside those limits, the monitor sends a notification.

Video monitoring systems now on the market will record footage both inside and outside of the car. Some record continuously, whereas others capture only events. Parents can obtain a summary report, generally through a monthly subscription, delivered by telephone or email to see how their teen is driving when solo.

Other in-vehicle monitoring technologies include direct-feedback systems, such as the tones that sound when the driver fails to fasten his or her seat belt, changes lanes, or gets too close to another car. Some systems can be configured to send a text or email when these alerts are engaged.

Parents who want to be more proactive can, for certain vehicles, invest in smart keys that are programmed to control vehicle parameters, such as the vehicle speed or the volume on the radio, according to Dr. O’Neil.

Finally, downloadable apps for cell phones will block the user’s ability to call (except in an emergency), text, surf, and take selfies while driving. “This doesn’t mean the child won’t be able to use someone else’s phone, but it does do a nice job for that particular installation,” he commented.

Parent-teen driving agreements

“We’ve talked about a lot of neat things that are out there, but what it all boils down to in the end are the parents – mom and dad. Parents truly are the gatekeepers of the keys,” Dr. O’Neil asserted. “We know that they can have an influence on their teens’ behavior. Parents can set restrictions and regulations on driving, and make sure [teens] follow all the traffic laws and set limits on high-risk driving situations.”

However, parents often underestimate the risks that their teens take behind the wheel. “Everyone always thinks that it’s the other kid who’s going to be driving wildly,” he said. “It’s okay for us to say, ‘I know he’s a great kid, but it’s not the bad kids who get into crashes. All kids get into crashes,’” he said. “It’s important to remind parents that all kids are at risk.

“One of the most valuable things that we can do as physicians to help parents navigate these crazy waters is talk about parent-teen driving agreements or contracts,” Dr. O’Neil said. “This has been shown time and time again to have a positive effect on driving behavior.”

These agreements list rules and expectations, and consequences for breaking the rules. “Both mom and dad, and the teen sign it. You put your name on the line, and that’s important because that really means something. This is probably the first contract this kid will ever sign, and it’s probably the most important one that [the teen] will ever sign.” He recommended that a paper version of the agreement be placed in a prominent location, such as on the refrigerator door, for maximal effectiveness.

A variety of parent-teen driving agreements are available online through initiatives such as the Checkpoints Program, Parents Are the Key to Safe Teen Drivers, I Drive Safely, and the AAP’s Parent-Teen Driving Agreement. Overall, their use has been shown to reduce the risks of traffic violations and crashes by 40%-50%.

Of note, these contracts complement rather than replace GDLs. Additionally, “the law of the land doesn’t trump the law of reality and the law of physics,” Dr. O’Neil pointed out. “We know that the laws in our states are not really always best practice, so as we advocate for best practice laws, what we can do is let the parents set better limits on the teen’s driving.”

Anticipatory guidance

“I usually start talking [with families] about driving when the child is 12 or 13,” Dr. O’Neil said. “Anticipatory guidance does work. We know that for a lot of other things that we do, but parents often need help in trying to figure out what to do.”

He recommended the AAP’s Healthy Children website as a source of good information and resources, including a Young Driver Tool for parents. “This has been vetted through the PROS [Pediatric Research in Office Settings] network, and it has been shown that parents do use it, parents do like it,” he noted. “And really it makes your job easier, because it takes time to talk about all these risk factors, and you can say, ‘Hey, I want you to go look at this website for teen driving. This will help.’ ”

Clinicians should generally cover with families the various risk factors, limit setting, use of GDLs, and parent-teen driving agreements. “Talk to parents about all these things. Talk to the teen; the teen will listen to you; you are an authority figure,” and “use interventional motivational techniques,” he said.

As parents control the vehicle their child drives, they should be counseled to give their teen the family’s safest car, preferably a newer, mid- to full-size vehicle with a small engine and modern safety features, according to Dr. O’Neil. “And we really do try to discourage teens buying their own cars because that sort of limits the parents’ leverage over them when they are starting to drive.”

Clinicians also should familiarize themselves with the driver’s education and similar resources in their community, including safe-driving initiatives spearheaded by groups such as Mothers Against Drunk Driving (MADD). They also should work with schools and the police to support “risky driving” prevention efforts.

Special anticipatory guidance is warranted when the new teen driver has a relevant condition such as attention-deficit/hyperactivity disorder. These youth are two to four times more likely to have a motor vehicle accident than typical teen drivers.

They may benefit from extended-release ADHD medication or a booster dose of their medication to keep them covered while driving, according to Dr. O’Neil.

“You may want to talk to them about holding off. Maybe their brain hasn’t matured enough yet, and you want to delay their driving. You may want to do a longer period of supervised driving or consider other things we’ve talked about – electronic resources or using a bigger, safer vehicle,” he suggested. “And always, always, always encourage limiting of distractions while driving.”

Dr. O’Neil said he had no relevant conflicts of interest.

[email protected]

SAN FRANCISCO – Clinicians and parents should capitalize on a variety of resources and new technologies that help keep teen drivers safe behind the wheel, according to Dr. Joseph O’Neil, a pediatrician at the Riley Hospital for Children in Indianapolis.

“As I like to share with parents, this is the one developmental milestone that parents really want their kids to have that is potentially lethal. This could really kill them,” he said at the annual meeting of the American Academy of Pediatrics. “Believe me, that’s a conversation stopper; they sort of look at you funny. But it’s true.”

Risk factors

Numerous factors increase the risk of crashes and deaths for teen drivers, beginning with their developmental stage, according to Dr. O’Neil. Youth are characterized by their striving for autonomy, impulsivity, risk taking, and greater susceptibility to peer influences, compounded by poor judgment of hazards.

“We know that their executive function is still improving, still maturing, They really don’t start getting to adult levels, if they ever do, until about 25,” he commented humorously.

Other risk factors include speeding, drinking and substance use, sleep deprivation, and distractions that range from cell phones, to eating and grooming, to all the gizmos on the dashboard today. Not wearing seat belts also plays a role, as teens are the age group least likely to buckle up, and risk rises with the number of young passengers in the vehicle.

The rate of fatal crashes among young drivers is more than twice as high at night, compared with during the day, with the hours of 9 p.m. to midnight being most hazardous. And the riskiest meteorologic conditions are, not surprisingly, snow and ice – something that parents should take into account in their typical rush to get driver’s education out of the way in the summer months, he said.

“Most of the evidence points to inexperience as probably the single most important risk factor because with inexperience, you’re going to use cell phones, you’re going to be distracted, you’re not going to be paying attention because you don’t have the experience to know that you should,” Dr. O’Neil said.

Graduated driver’s licenses

A key resource in addressing teen drivers’ inexperience and the fact that their crash rate is highest in their first year of driving are graduated driver licenses (GDLs). These licenses start with a learner’s permit mandating supervision and having many restrictions on conditions such as times when driving is permitted and number of passengers, and if there are no infractions, slowly lift these restrictions as the teen gains more driving experience, until he or she receives a full driver’s license.

©Thinkstock.com

High-tech tools

Clinicians also should also be aware of a host of new high-tech tools designed to make teen drivers safer, often by extending parents’ supervisory role, Dr. O’Neil advised. “Your parents in your practices are going to ask you about these,” he said.

So-called black boxes on vehicles collect a wealth of data about driving and conditions inside the vehicle that can be made available to parents. If black boxes are used correctly, they can enable parents to give feedback to the young driver and reduce overall crash risk, he said.

New GPS monitors will track a vehicle’s speed and range, with an optional feature called geofencing whereby parents can prespecify geographic limits on where their teen driver can go. If the teen ventures outside those limits, the monitor sends a notification.

Video monitoring systems now on the market will record footage both inside and outside of the car. Some record continuously, whereas others capture only events. Parents can obtain a summary report, generally through a monthly subscription, delivered by telephone or email to see how their teen is driving when solo.

Other in-vehicle monitoring technologies include direct-feedback systems, such as the tones that sound when the driver fails to fasten his or her seat belt, changes lanes, or gets too close to another car. Some systems can be configured to send a text or email when these alerts are engaged.

Parents who want to be more proactive can, for certain vehicles, invest in smart keys that are programmed to control vehicle parameters, such as the vehicle speed or the volume on the radio, according to Dr. O’Neil.

Finally, downloadable apps for cell phones will block the user’s ability to call (except in an emergency), text, surf, and take selfies while driving. “This doesn’t mean the child won’t be able to use someone else’s phone, but it does do a nice job for that particular installation,” he commented.

Parent-teen driving agreements

“We’ve talked about a lot of neat things that are out there, but what it all boils down to in the end are the parents – mom and dad. Parents truly are the gatekeepers of the keys,” Dr. O’Neil asserted. “We know that they can have an influence on their teens’ behavior. Parents can set restrictions and regulations on driving, and make sure [teens] follow all the traffic laws and set limits on high-risk driving situations.”

However, parents often underestimate the risks that their teens take behind the wheel. “Everyone always thinks that it’s the other kid who’s going to be driving wildly,” he said. “It’s okay for us to say, ‘I know he’s a great kid, but it’s not the bad kids who get into crashes. All kids get into crashes,’” he said. “It’s important to remind parents that all kids are at risk.

“One of the most valuable things that we can do as physicians to help parents navigate these crazy waters is talk about parent-teen driving agreements or contracts,” Dr. O’Neil said. “This has been shown time and time again to have a positive effect on driving behavior.”

These agreements list rules and expectations, and consequences for breaking the rules. “Both mom and dad, and the teen sign it. You put your name on the line, and that’s important because that really means something. This is probably the first contract this kid will ever sign, and it’s probably the most important one that [the teen] will ever sign.” He recommended that a paper version of the agreement be placed in a prominent location, such as on the refrigerator door, for maximal effectiveness.

A variety of parent-teen driving agreements are available online through initiatives such as the Checkpoints Program, Parents Are the Key to Safe Teen Drivers, I Drive Safely, and the AAP’s Parent-Teen Driving Agreement. Overall, their use has been shown to reduce the risks of traffic violations and crashes by 40%-50%.

Of note, these contracts complement rather than replace GDLs. Additionally, “the law of the land doesn’t trump the law of reality and the law of physics,” Dr. O’Neil pointed out. “We know that the laws in our states are not really always best practice, so as we advocate for best practice laws, what we can do is let the parents set better limits on the teen’s driving.”

Anticipatory guidance

“I usually start talking [with families] about driving when the child is 12 or 13,” Dr. O’Neil said. “Anticipatory guidance does work. We know that for a lot of other things that we do, but parents often need help in trying to figure out what to do.”

He recommended the AAP’s Healthy Children website as a source of good information and resources, including a Young Driver Tool for parents. “This has been vetted through the PROS [Pediatric Research in Office Settings] network, and it has been shown that parents do use it, parents do like it,” he noted. “And really it makes your job easier, because it takes time to talk about all these risk factors, and you can say, ‘Hey, I want you to go look at this website for teen driving. This will help.’ ”

Clinicians should generally cover with families the various risk factors, limit setting, use of GDLs, and parent-teen driving agreements. “Talk to parents about all these things. Talk to the teen; the teen will listen to you; you are an authority figure,” and “use interventional motivational techniques,” he said.

As parents control the vehicle their child drives, they should be counseled to give their teen the family’s safest car, preferably a newer, mid- to full-size vehicle with a small engine and modern safety features, according to Dr. O’Neil. “And we really do try to discourage teens buying their own cars because that sort of limits the parents’ leverage over them when they are starting to drive.”

Clinicians also should familiarize themselves with the driver’s education and similar resources in their community, including safe-driving initiatives spearheaded by groups such as Mothers Against Drunk Driving (MADD). They also should work with schools and the police to support “risky driving” prevention efforts.

Special anticipatory guidance is warranted when the new teen driver has a relevant condition such as attention-deficit/hyperactivity disorder. These youth are two to four times more likely to have a motor vehicle accident than typical teen drivers.

They may benefit from extended-release ADHD medication or a booster dose of their medication to keep them covered while driving, according to Dr. O’Neil.

“You may want to talk to them about holding off. Maybe their brain hasn’t matured enough yet, and you want to delay their driving. You may want to do a longer period of supervised driving or consider other things we’ve talked about – electronic resources or using a bigger, safer vehicle,” he suggested. “And always, always, always encourage limiting of distractions while driving.”

Dr. O’Neil said he had no relevant conflicts of interest.

[email protected]

Exposure to statins can significantly increase the odds of developing herpes zoster (HZ), according to a study published in the British Journal of Dermatology.

“The mechanisms by which statins may increase the risk of HZ are not established. As statins are commonly prescribed worldwide, any adverse effects may have substantial public health implications,” wrote Anthony Matthews of the London School of Hygiene and Tropical Medicine, and his colleagues. “An increased risk of HZ would not only have an impact on the quality of life of affected patients, but could also add to the burden on health services, given the high cost of treatment for PHN [postherpetic neuralgia].”

copyright clsgraphics/iStockphoto.com

[email protected]

Exposure to statins can significantly increase the odds of developing herpes zoster (HZ), according to a study published in the British Journal of Dermatology.

“The mechanisms by which statins may increase the risk of HZ are not established. As statins are commonly prescribed worldwide, any adverse effects may have substantial public health implications,” wrote Anthony Matthews of the London School of Hygiene and Tropical Medicine, and his colleagues. “An increased risk of HZ would not only have an impact on the quality of life of affected patients, but could also add to the burden on health services, given the high cost of treatment for PHN [postherpetic neuralgia].”

copyright clsgraphics/iStockphoto.com

[email protected]

Exposure to statins can significantly increase the odds of developing herpes zoster (HZ), according to a study published in the British Journal of Dermatology.

“The mechanisms by which statins may increase the risk of HZ are not established. As statins are commonly prescribed worldwide, any adverse effects may have substantial public health implications,” wrote Anthony Matthews of the London School of Hygiene and Tropical Medicine, and his colleagues. “An increased risk of HZ would not only have an impact on the quality of life of affected patients, but could also add to the burden on health services, given the high cost of treatment for PHN [postherpetic neuralgia].”

copyright clsgraphics/iStockphoto.com

[email protected]

The addition of the catechol-O-methyltransferase inhibitor entacapone to levodopa-carbidopa intestinal gel provided adequate levodopa exposure at a lower dose than with levodopa-carbidopa intestinal gel alone in a small, open-label randomized, crossover study of patients with advanced Parkinson’s disease.

Over 2 consecutive days, Marina Senek and her associates randomized 11 patients who were on stable levodopa-carbidopa intestinal gel (LCIG; Duodopa) therapy to receive 14-hour infusions of new LCIG formulation with entacapone (LECIG) followed by LCIG alone the next day or vice versa. Five patients received LECIG morning doses that corresponded to 80% of their individual morning dose of LCIG and six received 90% of their individual morning dose. They received maintenance doses that were equal to 80% of the LCIG maintenance dose and extra doses that were equal to 80% of extra LCIG doses.

Dose-adjusted levodopa exposure was significantly higher during LECIG treatment, with 9 of 11 patients exceeding the 20% increase in levodopa exposure targeted. Systemic levodopa exposure did not differ significantly between treatment types.

Sixteen adverse events were reported: 6 by two patients during LCIG treatment, and 10 by five patients during LECIG treatment. Headache was the most common adverse event, experienced by one patient in the LCIG group and by three in the LECIG group. Other adverse events related to treatment were nausea, diarrhea, and dizziness. No serious adverse events were reported.

By blocking the second-largest metabolic pathway for levodopa, the administration of entacapone leads to less levodopa conversion to 3-O-methyldopa and thereby increases the levodopa plasma concentration, the investigators said.

“Because of the short treatment time, conclusions have to be drawn with caution, and long-term comparative efficacy studies are needed to confirm the results and investigate the possible long-term side effects with the addition of entacapone,” the investigators noted.

Read the full study in Movement Disorders (doi: 10.1002/mds.26855).

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The addition of the catechol-O-methyltransferase inhibitor entacapone to levodopa-carbidopa intestinal gel provided adequate levodopa exposure at a lower dose than with levodopa-carbidopa intestinal gel alone in a small, open-label randomized, crossover study of patients with advanced Parkinson’s disease.

Over 2 consecutive days, Marina Senek and her associates randomized 11 patients who were on stable levodopa-carbidopa intestinal gel (LCIG; Duodopa) therapy to receive 14-hour infusions of new LCIG formulation with entacapone (LECIG) followed by LCIG alone the next day or vice versa. Five patients received LECIG morning doses that corresponded to 80% of their individual morning dose of LCIG and six received 90% of their individual morning dose. They received maintenance doses that were equal to 80% of the LCIG maintenance dose and extra doses that were equal to 80% of extra LCIG doses.

Dose-adjusted levodopa exposure was significantly higher during LECIG treatment, with 9 of 11 patients exceeding the 20% increase in levodopa exposure targeted. Systemic levodopa exposure did not differ significantly between treatment types.

Sixteen adverse events were reported: 6 by two patients during LCIG treatment, and 10 by five patients during LECIG treatment. Headache was the most common adverse event, experienced by one patient in the LCIG group and by three in the LECIG group. Other adverse events related to treatment were nausea, diarrhea, and dizziness. No serious adverse events were reported.

By blocking the second-largest metabolic pathway for levodopa, the administration of entacapone leads to less levodopa conversion to 3-O-methyldopa and thereby increases the levodopa plasma concentration, the investigators said.

“Because of the short treatment time, conclusions have to be drawn with caution, and long-term comparative efficacy studies are needed to confirm the results and investigate the possible long-term side effects with the addition of entacapone,” the investigators noted.

Read the full study in Movement Disorders (doi: 10.1002/mds.26855).

[email protected]

The addition of the catechol-O-methyltransferase inhibitor entacapone to levodopa-carbidopa intestinal gel provided adequate levodopa exposure at a lower dose than with levodopa-carbidopa intestinal gel alone in a small, open-label randomized, crossover study of patients with advanced Parkinson’s disease.

Over 2 consecutive days, Marina Senek and her associates randomized 11 patients who were on stable levodopa-carbidopa intestinal gel (LCIG; Duodopa) therapy to receive 14-hour infusions of new LCIG formulation with entacapone (LECIG) followed by LCIG alone the next day or vice versa. Five patients received LECIG morning doses that corresponded to 80% of their individual morning dose of LCIG and six received 90% of their individual morning dose. They received maintenance doses that were equal to 80% of the LCIG maintenance dose and extra doses that were equal to 80% of extra LCIG doses.

Dose-adjusted levodopa exposure was significantly higher during LECIG treatment, with 9 of 11 patients exceeding the 20% increase in levodopa exposure targeted. Systemic levodopa exposure did not differ significantly between treatment types.

Sixteen adverse events were reported: 6 by two patients during LCIG treatment, and 10 by five patients during LECIG treatment. Headache was the most common adverse event, experienced by one patient in the LCIG group and by three in the LECIG group. Other adverse events related to treatment were nausea, diarrhea, and dizziness. No serious adverse events were reported.

By blocking the second-largest metabolic pathway for levodopa, the administration of entacapone leads to less levodopa conversion to 3-O-methyldopa and thereby increases the levodopa plasma concentration, the investigators said.

“Because of the short treatment time, conclusions have to be drawn with caution, and long-term comparative efficacy studies are needed to confirm the results and investigate the possible long-term side effects with the addition of entacapone,” the investigators noted.

Read the full study in Movement Disorders (doi: 10.1002/mds.26855).

[email protected]

Procalcitonin (PCT) testing on the first day of ICU admission for adult patients with sepsis is associated with reduced length of stay, less antibiotic exposure, and reduced hospital and pharmacy costs, Robert A. Balk, MD, and his associates reported.

The researchers analyzed data on more than 15 million patients in the Premier Research Database; of those, more than 730,000 had a potential diagnosis of sepsis, systemic inflammatory response syndrome (SIRS), septicemia, or a shock-related diagnosis on ICU admission or discharge (CHEST. 2017;151[1]:23-33).

After propensity matching to reduce potential bias, a total of 33,569 patients who had received PCT testing on ICU day 1 were identified; a control group of 98,543 non-PCT tested patients were identified as well. Hospital costs were $2,759 lower for PCT-tested patients ($30,454 vs. $33,213), ICU costs were $1,310 lower ($20,155 vs. $21,465), and pharmacy costs were $331 lower ($4,238 vs. $4,568). PCT-tested patients also were more commonly discharged to home (44.1% vs. 41.3%).

The PCT-tested patients had less total antibiotic exposure, (16.2 days vs. 16.9 days) but higher laboratory costs, according to Dr. Balk, director of the division of pulmonary and critical care medicine at Rush Medical College, Chicago, and his colleagues. Laboratory costs of the PCT-tested patients were $81 greater ($1,807 vs. $1,726).

While PCT testing is cleared by the Food and Drug Administration to assist in identifying patients who are highly likely to develop sepsis, there is no approved sepsis test, Dr. Balk and his colleagues noted.

“This study is important in the validation of the ability of PCT testing to favorably impact the outcome of critically ill patients when used according to the FDA cleared guidelines,” the investigators said. “The cost savings were real and consequential, exceeding the potential increased costs of laboratory testing associated with PCT testing on ICU admission.”

All-patient analysis showed a statistically significant, but slightly increased (0.7%) risk of mortality in PCT-tested patients; however, the finding was not seen in an enhanced risk-adjusted analysis of 96% of patients, the investigators pointed out. This finding is consistent with other large prospective studies showing no difference in mortality or other clinical outcomes using PCT guidances.

PCT testing has not been uniformly adopted despite its inclusion in the 2012 Surviving Sepsis Guidelines, in part, due to cost. The lack of a “gold standard” sepsis test has resulted in diagnostic dilemmas, delayed treatment, and poor outcomes, Dr. Balk and colleagues noted.

Because patients were not randomized to PCT testing or non-PCT testing groups, additional variables could have over- or underestimated the effect of PCT on patient outcomes, the researchers added.

Dr. Balk has received advisory board fees from bioMerieux USA, Roche Diagnostics, and ThermoFisher Scientific; Zhun Cao, PhD, Craig Lipkin, MS, and Scott B. Robinson MA, MPH, are employees of Premier Research Services, in Charlotte. Samuel Bozzette is an employee of bioMerieux, which provided funding for the study.

Procalcitonin (PCT) testing on the first day of ICU admission for adult patients with sepsis is associated with reduced length of stay, less antibiotic exposure, and reduced hospital and pharmacy costs, Robert A. Balk, MD, and his associates reported.

The researchers analyzed data on more than 15 million patients in the Premier Research Database; of those, more than 730,000 had a potential diagnosis of sepsis, systemic inflammatory response syndrome (SIRS), septicemia, or a shock-related diagnosis on ICU admission or discharge (CHEST. 2017;151[1]:23-33).

After propensity matching to reduce potential bias, a total of 33,569 patients who had received PCT testing on ICU day 1 were identified; a control group of 98,543 non-PCT tested patients were identified as well. Hospital costs were $2,759 lower for PCT-tested patients ($30,454 vs. $33,213), ICU costs were $1,310 lower ($20,155 vs. $21,465), and pharmacy costs were $331 lower ($4,238 vs. $4,568). PCT-tested patients also were more commonly discharged to home (44.1% vs. 41.3%).

The PCT-tested patients had less total antibiotic exposure, (16.2 days vs. 16.9 days) but higher laboratory costs, according to Dr. Balk, director of the division of pulmonary and critical care medicine at Rush Medical College, Chicago, and his colleagues. Laboratory costs of the PCT-tested patients were $81 greater ($1,807 vs. $1,726).

While PCT testing is cleared by the Food and Drug Administration to assist in identifying patients who are highly likely to develop sepsis, there is no approved sepsis test, Dr. Balk and his colleagues noted.

“This study is important in the validation of the ability of PCT testing to favorably impact the outcome of critically ill patients when used according to the FDA cleared guidelines,” the investigators said. “The cost savings were real and consequential, exceeding the potential increased costs of laboratory testing associated with PCT testing on ICU admission.”

All-patient analysis showed a statistically significant, but slightly increased (0.7%) risk of mortality in PCT-tested patients; however, the finding was not seen in an enhanced risk-adjusted analysis of 96% of patients, the investigators pointed out. This finding is consistent with other large prospective studies showing no difference in mortality or other clinical outcomes using PCT guidances.

PCT testing has not been uniformly adopted despite its inclusion in the 2012 Surviving Sepsis Guidelines, in part, due to cost. The lack of a “gold standard” sepsis test has resulted in diagnostic dilemmas, delayed treatment, and poor outcomes, Dr. Balk and colleagues noted.

Because patients were not randomized to PCT testing or non-PCT testing groups, additional variables could have over- or underestimated the effect of PCT on patient outcomes, the researchers added.

Dr. Balk has received advisory board fees from bioMerieux USA, Roche Diagnostics, and ThermoFisher Scientific; Zhun Cao, PhD, Craig Lipkin, MS, and Scott B. Robinson MA, MPH, are employees of Premier Research Services, in Charlotte. Samuel Bozzette is an employee of bioMerieux, which provided funding for the study.

Procalcitonin (PCT) testing on the first day of ICU admission for adult patients with sepsis is associated with reduced length of stay, less antibiotic exposure, and reduced hospital and pharmacy costs, Robert A. Balk, MD, and his associates reported.

The researchers analyzed data on more than 15 million patients in the Premier Research Database; of those, more than 730,000 had a potential diagnosis of sepsis, systemic inflammatory response syndrome (SIRS), septicemia, or a shock-related diagnosis on ICU admission or discharge (CHEST. 2017;151[1]:23-33).

After propensity matching to reduce potential bias, a total of 33,569 patients who had received PCT testing on ICU day 1 were identified; a control group of 98,543 non-PCT tested patients were identified as well. Hospital costs were $2,759 lower for PCT-tested patients ($30,454 vs. $33,213), ICU costs were $1,310 lower ($20,155 vs. $21,465), and pharmacy costs were $331 lower ($4,238 vs. $4,568). PCT-tested patients also were more commonly discharged to home (44.1% vs. 41.3%).

The PCT-tested patients had less total antibiotic exposure, (16.2 days vs. 16.9 days) but higher laboratory costs, according to Dr. Balk, director of the division of pulmonary and critical care medicine at Rush Medical College, Chicago, and his colleagues. Laboratory costs of the PCT-tested patients were $81 greater ($1,807 vs. $1,726).

While PCT testing is cleared by the Food and Drug Administration to assist in identifying patients who are highly likely to develop sepsis, there is no approved sepsis test, Dr. Balk and his colleagues noted.

“This study is important in the validation of the ability of PCT testing to favorably impact the outcome of critically ill patients when used according to the FDA cleared guidelines,” the investigators said. “The cost savings were real and consequential, exceeding the potential increased costs of laboratory testing associated with PCT testing on ICU admission.”

All-patient analysis showed a statistically significant, but slightly increased (0.7%) risk of mortality in PCT-tested patients; however, the finding was not seen in an enhanced risk-adjusted analysis of 96% of patients, the investigators pointed out. This finding is consistent with other large prospective studies showing no difference in mortality or other clinical outcomes using PCT guidances.

PCT testing has not been uniformly adopted despite its inclusion in the 2012 Surviving Sepsis Guidelines, in part, due to cost. The lack of a “gold standard” sepsis test has resulted in diagnostic dilemmas, delayed treatment, and poor outcomes, Dr. Balk and colleagues noted.

Because patients were not randomized to PCT testing or non-PCT testing groups, additional variables could have over- or underestimated the effect of PCT on patient outcomes, the researchers added.

Dr. Balk has received advisory board fees from bioMerieux USA, Roche Diagnostics, and ThermoFisher Scientific; Zhun Cao, PhD, Craig Lipkin, MS, and Scott B. Robinson MA, MPH, are employees of Premier Research Services, in Charlotte. Samuel Bozzette is an employee of bioMerieux, which provided funding for the study.

Every current guideline and consensus statement regarding systemic glucocorticoid therapy in rheumatoid arthritis falls short of offering clinicians practical, evidence-based guidance, according to a systematic review of all 15 such documents published in 2011-2015 in English, French, German, and Spanish.

Despite the abundant and convincing evidence that systemic glucocorticoids are very beneficial and despite their widespread use for rheumatoid arthritis (RA), fewer than half of the existing guidelines explicitly recommend these agents. Even fewer specify the optimal treatment duration, and about one-third don’t even provide dosage recommendations.

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Every current guideline and consensus statement regarding systemic glucocorticoid therapy in rheumatoid arthritis falls short of offering clinicians practical, evidence-based guidance, according to a systematic review of all 15 such documents published in 2011-2015 in English, French, German, and Spanish.

Despite the abundant and convincing evidence that systemic glucocorticoids are very beneficial and despite their widespread use for rheumatoid arthritis (RA), fewer than half of the existing guidelines explicitly recommend these agents. Even fewer specify the optimal treatment duration, and about one-third don’t even provide dosage recommendations.

copyright kgtoh/Thinkstock

[email protected]

Every current guideline and consensus statement regarding systemic glucocorticoid therapy in rheumatoid arthritis falls short of offering clinicians practical, evidence-based guidance, according to a systematic review of all 15 such documents published in 2011-2015 in English, French, German, and Spanish.

Despite the abundant and convincing evidence that systemic glucocorticoids are very beneficial and despite their widespread use for rheumatoid arthritis (RA), fewer than half of the existing guidelines explicitly recommend these agents. Even fewer specify the optimal treatment duration, and about one-third don’t even provide dosage recommendations.

copyright kgtoh/Thinkstock

[email protected]