Immunology

LAS VEGAS – In the treatment of eczema, the gap between evidence and practice can be broad.

Dermatologists who treat atopic dermatitis confront many challenges – patients may be severely atopic, have a hard time being compliant with therapies, and have frequent recurrences, Dr. Robert Sidbury said at the Skin Disease Education Foundation’s annual Las Vegas dermatology seminar. “It just is not easy,” he said.

However, even for challenging patients, physicians should be mindful of evidence-supported treatments and be attentive to practice gaps, said Dr. Sidbury, chief of the division of dermatology at the University of Washington’s Seattle Children’s Hospital.

Though the field is rapidly changing, the American Academy of Dermatology has issued practice guidelines that can help guide clinical treatment decisions, said Dr. Sidbury, who helped develop the AAD guidelines. He noted that prescribers may eventually feel the pain of the practice gap if AMA-driven performance measures are enforced.

At the meeting, Dr. Sidbury discussed areas in which many clinicians may have a practice gap in the treatment of eczema. Topping the list of non–evidence-based eczema care are overuse of steroids, oral antibiotics, and nonsedating antihistamines.

Practice gap: Many clinicians believe that topical steroids are more effective for atopic dermatitis when used twice daily.

Reality: “Randomized, controlled trials and a systematic review suggest that there is no benefit to twice-daily use of steroids,” over once-daily use, Dr. Sidbury said, though he admitted that he’s having a hard time breaking his own longstanding practice habit of prescribing twice- rather than once-daily dosing of topical corticosteroids. He pointed out that Dr. Hywel Williams, the director of the University of Nottingham’s Center of Evidence-Based Dermatology, England, calls this the “lowest-hanging fruit” in terms of cost savings, safety, and convenience to patients.

Practice gap: Unnecessary skin cultures can lead to overuse of systemic antibiotics in atopic dermatitis.

Reality: Colonization with Staphylococcus aureus occurs in more than 90% of adults with atopic dermatitis, but the vast majority of these patients are not infected. “Except for bleach baths in concert with intranasal mupirocin, no topical antistaphylococcal treatment has been shown to be clinically helpful in patients with atopic dermatitis,” Dr. Sidbury said.

“How do we know when eczema is infected? We know it when we see it. You are best served by using your clinical gestalt,” he added. Eczematous skin presents along a continuum, ranging from erythema, scaling, and crusting, to a frankly purulent appearance with clear infection, and clinical presentation and judgment should guide treatment. Barring frank infection, the evidence doesn’t support use of systemic antibiotics (Br J Dermatol. 2010 Jul;163 [1]:12-26).

Practice gap: Many patients with atopic dermatitis receive nonsedating antihistamines for itching.

Reality: There is no evidence that nonsedating antihistamines are beneficial unless the patient has concurrent rhinoconjunctivitis, so data don’t support their use “for the actual itch of eczema,” Dr. Sidbury said. In fact, the AMA-sponsored Physician Consortium for Performance Improvement nearly passed an overuse measure that would have penalized the prescription of nonsedating antihistamines in this setting, he said.

Practice gap: Systemic immunomodulatory therapy is used for pediatric atopic dermatitis, despite the lack of data that provide clear guidance.

Reality: The landscape here is a little more complicated, according to Dr. Sidbury. Among the systemic immunosuppressants, cyclosporine, methotrexate, azathioprine, and mycophenolate have the most evidence backing their use. However, there remains a lack of comparative studies and a lack of studies evaluating these therapies in the pediatric population, he said.

In general, Dr. Sidbury said that systemic therapy for atopic dermatitis is indicated only when control is inadequate despite truly optimized topical care, and the condition is having a “significant negative physical, psychological, or social impact” on the patient. Before beginning these potent systemic therapies, it’s important to assess that the patient and family are truly adherent to the topical treatment regime, and that adjunctive treatments like wet wraps and strict allergen avoidance are being followed. The Food and Drug Administration is beginning to include pediatric patients in clinical trials of systemic therapy for atopic dermatitis, so the quality of data should improve.

If systemic therapy is initiated, some clinical pearls can guide use, he said. Cyclosporine has the quickest onset of action and can be dosed at 3-6 mg/kg per day, divided into twice daily dosing. The maximum dose is 300 mg/day, and the microemulsion form is preferred. Overall, mycophenolate is the best-tolerated immunosuppressive. If methotrexate is chosen, it should be dosed at 0.2-0.7 mg/kg per week; liver function should be checked at 5-7 days after dosing, since methotrexate can cause a transient transaminitis. There are no standard recommendations to guide if or when to do liver biopsy recommendations in children receiving methotrexate. (J Am Acad Dermatol. 2014 Aug;71[2]:327-49).

Practice gap: Eczema appointments may only last 10-20 minutes.

Reality: “Proper eczema education takes much longer,” Dr. Sidbury said. Among patients and clinicians, there is still “rampant misinformation,” with persistence of fundamental knowledge gaps. “Studies repeatedly validate the role of education” in providing optimal care for eczema sufferers and their families, he emphasized (Pediatr Allergy Immunol. 2015 Jan 23. doi: 10.1111/pai.12338).

How is a busy physician to integrate all of these recommendations into practice and make sure patients are getting proper education? “Don’t reinvent the wheel – Google it!” Dr. Sidbury said. Resources from the National Eczema Association, among others, can help guide care. Eczema action plans that can be downloaded provide a roadmap for shared decision making; food allergy clinical practice guidelines help patients avoid allergens, and patients can further their knowledge when directed to reputable websites like the National Eczema Association and resources like www.eczemacenter.org, at Rady Children’s Hospital–San Diego.

Dr. Sidbury disclosed that he was a site principal investigator for an Anacor Pharmaceuticals–sponsored trial of a new topical anti-inflammatory agent for allergic dermatitis, and that he is on the Scientific Advisory Committee of the National Eczema Association.

SDEF and this news organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

LAS VEGAS – In the treatment of eczema, the gap between evidence and practice can be broad.

Dermatologists who treat atopic dermatitis confront many challenges – patients may be severely atopic, have a hard time being compliant with therapies, and have frequent recurrences, Dr. Robert Sidbury said at the Skin Disease Education Foundation’s annual Las Vegas dermatology seminar. “It just is not easy,” he said.

However, even for challenging patients, physicians should be mindful of evidence-supported treatments and be attentive to practice gaps, said Dr. Sidbury, chief of the division of dermatology at the University of Washington’s Seattle Children’s Hospital.

Though the field is rapidly changing, the American Academy of Dermatology has issued practice guidelines that can help guide clinical treatment decisions, said Dr. Sidbury, who helped develop the AAD guidelines. He noted that prescribers may eventually feel the pain of the practice gap if AMA-driven performance measures are enforced.

At the meeting, Dr. Sidbury discussed areas in which many clinicians may have a practice gap in the treatment of eczema. Topping the list of non–evidence-based eczema care are overuse of steroids, oral antibiotics, and nonsedating antihistamines.

Practice gap: Many clinicians believe that topical steroids are more effective for atopic dermatitis when used twice daily.

Reality: “Randomized, controlled trials and a systematic review suggest that there is no benefit to twice-daily use of steroids,” over once-daily use, Dr. Sidbury said, though he admitted that he’s having a hard time breaking his own longstanding practice habit of prescribing twice- rather than once-daily dosing of topical corticosteroids. He pointed out that Dr. Hywel Williams, the director of the University of Nottingham’s Center of Evidence-Based Dermatology, England, calls this the “lowest-hanging fruit” in terms of cost savings, safety, and convenience to patients.

Practice gap: Unnecessary skin cultures can lead to overuse of systemic antibiotics in atopic dermatitis.

Reality: Colonization with Staphylococcus aureus occurs in more than 90% of adults with atopic dermatitis, but the vast majority of these patients are not infected. “Except for bleach baths in concert with intranasal mupirocin, no topical antistaphylococcal treatment has been shown to be clinically helpful in patients with atopic dermatitis,” Dr. Sidbury said.

“How do we know when eczema is infected? We know it when we see it. You are best served by using your clinical gestalt,” he added. Eczematous skin presents along a continuum, ranging from erythema, scaling, and crusting, to a frankly purulent appearance with clear infection, and clinical presentation and judgment should guide treatment. Barring frank infection, the evidence doesn’t support use of systemic antibiotics (Br J Dermatol. 2010 Jul;163 [1]:12-26).

Practice gap: Many patients with atopic dermatitis receive nonsedating antihistamines for itching.

Reality: There is no evidence that nonsedating antihistamines are beneficial unless the patient has concurrent rhinoconjunctivitis, so data don’t support their use “for the actual itch of eczema,” Dr. Sidbury said. In fact, the AMA-sponsored Physician Consortium for Performance Improvement nearly passed an overuse measure that would have penalized the prescription of nonsedating antihistamines in this setting, he said.

Practice gap: Systemic immunomodulatory therapy is used for pediatric atopic dermatitis, despite the lack of data that provide clear guidance.

Reality: The landscape here is a little more complicated, according to Dr. Sidbury. Among the systemic immunosuppressants, cyclosporine, methotrexate, azathioprine, and mycophenolate have the most evidence backing their use. However, there remains a lack of comparative studies and a lack of studies evaluating these therapies in the pediatric population, he said.

In general, Dr. Sidbury said that systemic therapy for atopic dermatitis is indicated only when control is inadequate despite truly optimized topical care, and the condition is having a “significant negative physical, psychological, or social impact” on the patient. Before beginning these potent systemic therapies, it’s important to assess that the patient and family are truly adherent to the topical treatment regime, and that adjunctive treatments like wet wraps and strict allergen avoidance are being followed. The Food and Drug Administration is beginning to include pediatric patients in clinical trials of systemic therapy for atopic dermatitis, so the quality of data should improve.

If systemic therapy is initiated, some clinical pearls can guide use, he said. Cyclosporine has the quickest onset of action and can be dosed at 3-6 mg/kg per day, divided into twice daily dosing. The maximum dose is 300 mg/day, and the microemulsion form is preferred. Overall, mycophenolate is the best-tolerated immunosuppressive. If methotrexate is chosen, it should be dosed at 0.2-0.7 mg/kg per week; liver function should be checked at 5-7 days after dosing, since methotrexate can cause a transient transaminitis. There are no standard recommendations to guide if or when to do liver biopsy recommendations in children receiving methotrexate. (J Am Acad Dermatol. 2014 Aug;71[2]:327-49).

Practice gap: Eczema appointments may only last 10-20 minutes.

Reality: “Proper eczema education takes much longer,” Dr. Sidbury said. Among patients and clinicians, there is still “rampant misinformation,” with persistence of fundamental knowledge gaps. “Studies repeatedly validate the role of education” in providing optimal care for eczema sufferers and their families, he emphasized (Pediatr Allergy Immunol. 2015 Jan 23. doi: 10.1111/pai.12338).

How is a busy physician to integrate all of these recommendations into practice and make sure patients are getting proper education? “Don’t reinvent the wheel – Google it!” Dr. Sidbury said. Resources from the National Eczema Association, among others, can help guide care. Eczema action plans that can be downloaded provide a roadmap for shared decision making; food allergy clinical practice guidelines help patients avoid allergens, and patients can further their knowledge when directed to reputable websites like the National Eczema Association and resources like www.eczemacenter.org, at Rady Children’s Hospital–San Diego.

Dr. Sidbury disclosed that he was a site principal investigator for an Anacor Pharmaceuticals–sponsored trial of a new topical anti-inflammatory agent for allergic dermatitis, and that he is on the Scientific Advisory Committee of the National Eczema Association.

SDEF and this news organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

LAS VEGAS – In the treatment of eczema, the gap between evidence and practice can be broad.

Dermatologists who treat atopic dermatitis confront many challenges – patients may be severely atopic, have a hard time being compliant with therapies, and have frequent recurrences, Dr. Robert Sidbury said at the Skin Disease Education Foundation’s annual Las Vegas dermatology seminar. “It just is not easy,” he said.

However, even for challenging patients, physicians should be mindful of evidence-supported treatments and be attentive to practice gaps, said Dr. Sidbury, chief of the division of dermatology at the University of Washington’s Seattle Children’s Hospital.

Though the field is rapidly changing, the American Academy of Dermatology has issued practice guidelines that can help guide clinical treatment decisions, said Dr. Sidbury, who helped develop the AAD guidelines. He noted that prescribers may eventually feel the pain of the practice gap if AMA-driven performance measures are enforced.

At the meeting, Dr. Sidbury discussed areas in which many clinicians may have a practice gap in the treatment of eczema. Topping the list of non–evidence-based eczema care are overuse of steroids, oral antibiotics, and nonsedating antihistamines.

Practice gap: Many clinicians believe that topical steroids are more effective for atopic dermatitis when used twice daily.

Reality: “Randomized, controlled trials and a systematic review suggest that there is no benefit to twice-daily use of steroids,” over once-daily use, Dr. Sidbury said, though he admitted that he’s having a hard time breaking his own longstanding practice habit of prescribing twice- rather than once-daily dosing of topical corticosteroids. He pointed out that Dr. Hywel Williams, the director of the University of Nottingham’s Center of Evidence-Based Dermatology, England, calls this the “lowest-hanging fruit” in terms of cost savings, safety, and convenience to patients.

Practice gap: Unnecessary skin cultures can lead to overuse of systemic antibiotics in atopic dermatitis.

Reality: Colonization with Staphylococcus aureus occurs in more than 90% of adults with atopic dermatitis, but the vast majority of these patients are not infected. “Except for bleach baths in concert with intranasal mupirocin, no topical antistaphylococcal treatment has been shown to be clinically helpful in patients with atopic dermatitis,” Dr. Sidbury said.

“How do we know when eczema is infected? We know it when we see it. You are best served by using your clinical gestalt,” he added. Eczematous skin presents along a continuum, ranging from erythema, scaling, and crusting, to a frankly purulent appearance with clear infection, and clinical presentation and judgment should guide treatment. Barring frank infection, the evidence doesn’t support use of systemic antibiotics (Br J Dermatol. 2010 Jul;163 [1]:12-26).

Practice gap: Many patients with atopic dermatitis receive nonsedating antihistamines for itching.

Reality: There is no evidence that nonsedating antihistamines are beneficial unless the patient has concurrent rhinoconjunctivitis, so data don’t support their use “for the actual itch of eczema,” Dr. Sidbury said. In fact, the AMA-sponsored Physician Consortium for Performance Improvement nearly passed an overuse measure that would have penalized the prescription of nonsedating antihistamines in this setting, he said.

Practice gap: Systemic immunomodulatory therapy is used for pediatric atopic dermatitis, despite the lack of data that provide clear guidance.

Reality: The landscape here is a little more complicated, according to Dr. Sidbury. Among the systemic immunosuppressants, cyclosporine, methotrexate, azathioprine, and mycophenolate have the most evidence backing their use. However, there remains a lack of comparative studies and a lack of studies evaluating these therapies in the pediatric population, he said.

In general, Dr. Sidbury said that systemic therapy for atopic dermatitis is indicated only when control is inadequate despite truly optimized topical care, and the condition is having a “significant negative physical, psychological, or social impact” on the patient. Before beginning these potent systemic therapies, it’s important to assess that the patient and family are truly adherent to the topical treatment regime, and that adjunctive treatments like wet wraps and strict allergen avoidance are being followed. The Food and Drug Administration is beginning to include pediatric patients in clinical trials of systemic therapy for atopic dermatitis, so the quality of data should improve.

If systemic therapy is initiated, some clinical pearls can guide use, he said. Cyclosporine has the quickest onset of action and can be dosed at 3-6 mg/kg per day, divided into twice daily dosing. The maximum dose is 300 mg/day, and the microemulsion form is preferred. Overall, mycophenolate is the best-tolerated immunosuppressive. If methotrexate is chosen, it should be dosed at 0.2-0.7 mg/kg per week; liver function should be checked at 5-7 days after dosing, since methotrexate can cause a transient transaminitis. There are no standard recommendations to guide if or when to do liver biopsy recommendations in children receiving methotrexate. (J Am Acad Dermatol. 2014 Aug;71[2]:327-49).

Practice gap: Eczema appointments may only last 10-20 minutes.

Reality: “Proper eczema education takes much longer,” Dr. Sidbury said. Among patients and clinicians, there is still “rampant misinformation,” with persistence of fundamental knowledge gaps. “Studies repeatedly validate the role of education” in providing optimal care for eczema sufferers and their families, he emphasized (Pediatr Allergy Immunol. 2015 Jan 23. doi: 10.1111/pai.12338).

How is a busy physician to integrate all of these recommendations into practice and make sure patients are getting proper education? “Don’t reinvent the wheel – Google it!” Dr. Sidbury said. Resources from the National Eczema Association, among others, can help guide care. Eczema action plans that can be downloaded provide a roadmap for shared decision making; food allergy clinical practice guidelines help patients avoid allergens, and patients can further their knowledge when directed to reputable websites like the National Eczema Association and resources like www.eczemacenter.org, at Rady Children’s Hospital–San Diego.

Dr. Sidbury disclosed that he was a site principal investigator for an Anacor Pharmaceuticals–sponsored trial of a new topical anti-inflammatory agent for allergic dermatitis, and that he is on the Scientific Advisory Committee of the National Eczema Association.

SDEF and this news organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

Nucala (mepolizumab) has been approved for use with other asthma medicines as maintenance therapy for patients aged 12 years and older with a history of asthma exacerbations despite adherence with their current asthma medicines, the U.S. Food and Drug Administration announced Nov. 4.

“This approval offers patients with severe asthma an additional therapy when current treatments cannot maintain adequate control of their asthma,” Dr. Badrul Chowdhury, director of the Division of Pulmonary, Allergy, and Rheumatology Products in the FDA’s Center for Drug Evaluation and Research, said in a press release.

Nucala is a humanized interleukin-5 antagonist monoclonal antibody that limits severe asthma attacks by reducing the levels of blood eosinophils. Nucala is administered subcutaneously once every 4 weeks by a health care professional.

This innovation in precision medicine is the first and only approved, biologic therapy specifically developed for people with severe asthma with an eosinophilic phenotype, according to a statement from GlaxoSmithKline, the maker of Nucala.

The safety and efficacy of Nucala were established in three double-blind, randomized, placebo‑controlled trials in patients with severe asthma on currently available therapies. Nucala or a placebo was administered to patients every 4 weeks as an add-on asthma treatment. Compared with placebo, patients with severe asthma receiving Nucala had fewer exacerbations requiring hospitalization or emergency department visits, and a longer time to their first exacerbation. In addition, patients with severe asthma receiving Nucala experienced greater reductions in their daily maintenance oral corticosteroid dose, while maintaining asthma control, compared with patients receiving placebo. Treatment with mepolizumab did not result in a significant improvement in lung function, as measured by the volume of air exhaled by patients in 1 second, the FDA said in their statement.

The most common side effects of Nucala include headache, injection site reactions, back pain, and weakness. Hypersensitivity reactions can occur within hours or days of receiving Nucala.

Nucala (mepolizumab) has been approved for use with other asthma medicines as maintenance therapy for patients aged 12 years and older with a history of asthma exacerbations despite adherence with their current asthma medicines, the U.S. Food and Drug Administration announced Nov. 4.

“This approval offers patients with severe asthma an additional therapy when current treatments cannot maintain adequate control of their asthma,” Dr. Badrul Chowdhury, director of the Division of Pulmonary, Allergy, and Rheumatology Products in the FDA’s Center for Drug Evaluation and Research, said in a press release.

Nucala is a humanized interleukin-5 antagonist monoclonal antibody that limits severe asthma attacks by reducing the levels of blood eosinophils. Nucala is administered subcutaneously once every 4 weeks by a health care professional.

This innovation in precision medicine is the first and only approved, biologic therapy specifically developed for people with severe asthma with an eosinophilic phenotype, according to a statement from GlaxoSmithKline, the maker of Nucala.

The safety and efficacy of Nucala were established in three double-blind, randomized, placebo‑controlled trials in patients with severe asthma on currently available therapies. Nucala or a placebo was administered to patients every 4 weeks as an add-on asthma treatment. Compared with placebo, patients with severe asthma receiving Nucala had fewer exacerbations requiring hospitalization or emergency department visits, and a longer time to their first exacerbation. In addition, patients with severe asthma receiving Nucala experienced greater reductions in their daily maintenance oral corticosteroid dose, while maintaining asthma control, compared with patients receiving placebo. Treatment with mepolizumab did not result in a significant improvement in lung function, as measured by the volume of air exhaled by patients in 1 second, the FDA said in their statement.

The most common side effects of Nucala include headache, injection site reactions, back pain, and weakness. Hypersensitivity reactions can occur within hours or days of receiving Nucala.

Nucala (mepolizumab) has been approved for use with other asthma medicines as maintenance therapy for patients aged 12 years and older with a history of asthma exacerbations despite adherence with their current asthma medicines, the U.S. Food and Drug Administration announced Nov. 4.

“This approval offers patients with severe asthma an additional therapy when current treatments cannot maintain adequate control of their asthma,” Dr. Badrul Chowdhury, director of the Division of Pulmonary, Allergy, and Rheumatology Products in the FDA’s Center for Drug Evaluation and Research, said in a press release.

Nucala is a humanized interleukin-5 antagonist monoclonal antibody that limits severe asthma attacks by reducing the levels of blood eosinophils. Nucala is administered subcutaneously once every 4 weeks by a health care professional.

This innovation in precision medicine is the first and only approved, biologic therapy specifically developed for people with severe asthma with an eosinophilic phenotype, according to a statement from GlaxoSmithKline, the maker of Nucala.

The safety and efficacy of Nucala were established in three double-blind, randomized, placebo‑controlled trials in patients with severe asthma on currently available therapies. Nucala or a placebo was administered to patients every 4 weeks as an add-on asthma treatment. Compared with placebo, patients with severe asthma receiving Nucala had fewer exacerbations requiring hospitalization or emergency department visits, and a longer time to their first exacerbation. In addition, patients with severe asthma receiving Nucala experienced greater reductions in their daily maintenance oral corticosteroid dose, while maintaining asthma control, compared with patients receiving placebo. Treatment with mepolizumab did not result in a significant improvement in lung function, as measured by the volume of air exhaled by patients in 1 second, the FDA said in their statement.

The most common side effects of Nucala include headache, injection site reactions, back pain, and weakness. Hypersensitivity reactions can occur within hours or days of receiving Nucala.

WASHINGTON – Most parents know whether they want to vaccinate their child before the child is even conceived, a study showed.

“Is giving [vaccine] information out at … well-child visits in the pediatrician’s office too late? I think we’re still too early [in our research] to say if that’s the case,” said James N. Yarnall, a fourth-year medical student at the University of North Carolina at Chapel Hill.

The study grew out of talking to parents about their hesitancy toward the hepatitis B vaccine, recommended just after birth, said Mr. Yarnall, whose mentor, pediatrician Jacob Lohr of University of North Carolina Health Care, began asking parents why they were turning down the vaccine.

© javi_indy/ Thinkstock.com

“For a lot of them, they said, ‘We’ve known for a long time,’ ” Mr. Yarnall said.

The two gave surveys to 171 parents (56% of the 304 they asked) who had given birth to a child between February and April 2015 at the University of North Carolina Women’s Hospital in Chapel Hill. The parents answered the question, “When did you develop your preferences for all/certain vaccines for your new baby?”

Among all the parents, 72% said they had developed their vaccination preferences for their newborn before the child had been conceived. The parents reported that friends and family, medical staff, and government agencies such as the Centers for Disease Control and Prevention, played a role in their decisions about vaccines.

Two thirds (66%) of first-time parents reported developing immunization preferences before conception, while 77% of parents with previous children said they had, although the difference was not significant (P = .12). Fathers trended toward being slightly more likely than mothers to have decided their vaccine preferences preconception, but that finding was not significant and weakened further after demographic differences were accounted for.

Parents who had discussed vaccines with one another and who had higher levels of education also were more likely to have decided before conception whether they would vaccinate their newborn. Those who made their vaccine decisions before conception were significantly more likely to plan to vaccinate their children than to decline some or all vaccines (P = .01). Again, this finding was no longer significant following adjustment for demographic covariates.

Although these findings suggest that discussions about vaccines in the pediatrician’s office are coming long past the time when most parents have made up their minds, it’s less clear where to go from here, Mr. Yarnall said.

He and Dr. Lohr are working on a larger study with multiple sites through the Better Outcomes Through Research in Newborns (BORN) network to confirm these findings and determine what the next steps might be.

“We want to make sure the results from this pilot study are reproducible with more national sites,” Mr. Yarnall said. “Once we get those results, we can take it from there.”

WASHINGTON – Most parents know whether they want to vaccinate their child before the child is even conceived, a study showed.

“Is giving [vaccine] information out at … well-child visits in the pediatrician’s office too late? I think we’re still too early [in our research] to say if that’s the case,” said James N. Yarnall, a fourth-year medical student at the University of North Carolina at Chapel Hill.

The study grew out of talking to parents about their hesitancy toward the hepatitis B vaccine, recommended just after birth, said Mr. Yarnall, whose mentor, pediatrician Jacob Lohr of University of North Carolina Health Care, began asking parents why they were turning down the vaccine.

© javi_indy/ Thinkstock.com

“For a lot of them, they said, ‘We’ve known for a long time,’ ” Mr. Yarnall said.

The two gave surveys to 171 parents (56% of the 304 they asked) who had given birth to a child between February and April 2015 at the University of North Carolina Women’s Hospital in Chapel Hill. The parents answered the question, “When did you develop your preferences for all/certain vaccines for your new baby?”

Among all the parents, 72% said they had developed their vaccination preferences for their newborn before the child had been conceived. The parents reported that friends and family, medical staff, and government agencies such as the Centers for Disease Control and Prevention, played a role in their decisions about vaccines.

Two thirds (66%) of first-time parents reported developing immunization preferences before conception, while 77% of parents with previous children said they had, although the difference was not significant (P = .12). Fathers trended toward being slightly more likely than mothers to have decided their vaccine preferences preconception, but that finding was not significant and weakened further after demographic differences were accounted for.

Parents who had discussed vaccines with one another and who had higher levels of education also were more likely to have decided before conception whether they would vaccinate their newborn. Those who made their vaccine decisions before conception were significantly more likely to plan to vaccinate their children than to decline some or all vaccines (P = .01). Again, this finding was no longer significant following adjustment for demographic covariates.

Although these findings suggest that discussions about vaccines in the pediatrician’s office are coming long past the time when most parents have made up their minds, it’s less clear where to go from here, Mr. Yarnall said.

He and Dr. Lohr are working on a larger study with multiple sites through the Better Outcomes Through Research in Newborns (BORN) network to confirm these findings and determine what the next steps might be.

“We want to make sure the results from this pilot study are reproducible with more national sites,” Mr. Yarnall said. “Once we get those results, we can take it from there.”

WASHINGTON – Most parents know whether they want to vaccinate their child before the child is even conceived, a study showed.

“Is giving [vaccine] information out at … well-child visits in the pediatrician’s office too late? I think we’re still too early [in our research] to say if that’s the case,” said James N. Yarnall, a fourth-year medical student at the University of North Carolina at Chapel Hill.

The study grew out of talking to parents about their hesitancy toward the hepatitis B vaccine, recommended just after birth, said Mr. Yarnall, whose mentor, pediatrician Jacob Lohr of University of North Carolina Health Care, began asking parents why they were turning down the vaccine.

© javi_indy/ Thinkstock.com

“For a lot of them, they said, ‘We’ve known for a long time,’ ” Mr. Yarnall said.

The two gave surveys to 171 parents (56% of the 304 they asked) who had given birth to a child between February and April 2015 at the University of North Carolina Women’s Hospital in Chapel Hill. The parents answered the question, “When did you develop your preferences for all/certain vaccines for your new baby?”

Among all the parents, 72% said they had developed their vaccination preferences for their newborn before the child had been conceived. The parents reported that friends and family, medical staff, and government agencies such as the Centers for Disease Control and Prevention, played a role in their decisions about vaccines.

Two thirds (66%) of first-time parents reported developing immunization preferences before conception, while 77% of parents with previous children said they had, although the difference was not significant (P = .12). Fathers trended toward being slightly more likely than mothers to have decided their vaccine preferences preconception, but that finding was not significant and weakened further after demographic differences were accounted for.

Parents who had discussed vaccines with one another and who had higher levels of education also were more likely to have decided before conception whether they would vaccinate their newborn. Those who made their vaccine decisions before conception were significantly more likely to plan to vaccinate their children than to decline some or all vaccines (P = .01). Again, this finding was no longer significant following adjustment for demographic covariates.

Although these findings suggest that discussions about vaccines in the pediatrician’s office are coming long past the time when most parents have made up their minds, it’s less clear where to go from here, Mr. Yarnall said.

He and Dr. Lohr are working on a larger study with multiple sites through the Better Outcomes Through Research in Newborns (BORN) network to confirm these findings and determine what the next steps might be.

“We want to make sure the results from this pilot study are reproducible with more national sites,” Mr. Yarnall said. “Once we get those results, we can take it from there.”

A quadrivalent human papillomavirus vaccine was effective at removing therapy-resistant warts from children aged 9-11 years, according to Dr. Dietrich Abeck in private practice in Munich and Dr. Regina Fölster-Holst of the University Kiel, Lübeck, Germany.

The study group of six children had therapy-resistant warts for at least 2 years, with topical salicylic acid, duct tape occlusion therapy, and cryotherapy failing for all patients either alone or in combination. Patients received three doses of vaccines, with one patient becoming wart-free after the first treatment, four patients becoming disease-free after the second treatment, and the last patient becoming disease-free shortly after receiving the third vaccination.

The only reported side effect was temporary local swelling. The treatment with quadrivalent vaccine seemed to only work with young children, as only three of six patients aged 14-17 years saw results from the treatment, and three out of four adults saw no benefit from the vaccination.

“The rapid response observed shows that vaccination with the quadrivalent HPV vaccine has the ability to become an elegant, well-tolerated therapy for recalcitrant warts in children,” the investigators concluded.

Find the full study in Acta Dermato-Venereologica (doi: 10.2340/00015555-2111).

A quadrivalent human papillomavirus vaccine was effective at removing therapy-resistant warts from children aged 9-11 years, according to Dr. Dietrich Abeck in private practice in Munich and Dr. Regina Fölster-Holst of the University Kiel, Lübeck, Germany.

The study group of six children had therapy-resistant warts for at least 2 years, with topical salicylic acid, duct tape occlusion therapy, and cryotherapy failing for all patients either alone or in combination. Patients received three doses of vaccines, with one patient becoming wart-free after the first treatment, four patients becoming disease-free after the second treatment, and the last patient becoming disease-free shortly after receiving the third vaccination.

The only reported side effect was temporary local swelling. The treatment with quadrivalent vaccine seemed to only work with young children, as only three of six patients aged 14-17 years saw results from the treatment, and three out of four adults saw no benefit from the vaccination.

“The rapid response observed shows that vaccination with the quadrivalent HPV vaccine has the ability to become an elegant, well-tolerated therapy for recalcitrant warts in children,” the investigators concluded.

Find the full study in Acta Dermato-Venereologica (doi: 10.2340/00015555-2111).

A quadrivalent human papillomavirus vaccine was effective at removing therapy-resistant warts from children aged 9-11 years, according to Dr. Dietrich Abeck in private practice in Munich and Dr. Regina Fölster-Holst of the University Kiel, Lübeck, Germany.

The study group of six children had therapy-resistant warts for at least 2 years, with topical salicylic acid, duct tape occlusion therapy, and cryotherapy failing for all patients either alone or in combination. Patients received three doses of vaccines, with one patient becoming wart-free after the first treatment, four patients becoming disease-free after the second treatment, and the last patient becoming disease-free shortly after receiving the third vaccination.

The only reported side effect was temporary local swelling. The treatment with quadrivalent vaccine seemed to only work with young children, as only three of six patients aged 14-17 years saw results from the treatment, and three out of four adults saw no benefit from the vaccination.

“The rapid response observed shows that vaccination with the quadrivalent HPV vaccine has the ability to become an elegant, well-tolerated therapy for recalcitrant warts in children,” the investigators concluded.

Find the full study in Acta Dermato-Venereologica (doi: 10.2340/00015555-2111).

MONTREAL – The immunosuppressant mycophenolate mofetil worked as effectively as cyclophosphamide for treating scleroderma-related interstitial lung disease while being better tolerated and causing fewer adverse effects in a multicenter, head-to-head comparison with 142 randomized patients.

“The findings support the increasingly common clinical practice of prescribing MMF [mycophenolate mofetil] for this disease,” said Dr. Donald P. Tashkin at the annual meeting of the American College of Chest Physicians.

Mitchel L. Zoler/Frontline Medical News

Another limitation of cyclophosphamide is that it is usually not used for more than 1 year because of concerns that longer use substantially increases a patient’s risk for developing malignancy. That’s another reason why there is a “strong need for longer and safer immunosuppressive treatment with a drug like MMF,” said Dr. Tashkin, a pulmonologist at the University of California, Los Angeles.

When used in this trial on patients with scleroderma, as defined by the American College of Rheumatology and with a baseline forced vital capacity of no more than 80% of predicted, “MMF was effective at reducing the rate of decline in vital capacity, improving symptoms such as dyspnea – the cardinal symptom of interstitial lung disease, and reducing lung fibrosis seen on CT scans, and MMF was better tolerated” than cyclophosphamide, Dr. Tashkin said in an interview. Cyclophosphamide treatment in this new trial “was associated with more toxicity, especially hematologic toxicity, an was not nearly as well tolerated, with more patients withdrawing because of side effects or a perceived lack of benefit.”

“Cyclophosphamide has a lot of side effects. MMF is just now coming into increased use. I think we’ll see it being used more for first-line treatment because the side effects with cyclophosphamide are so bad,” commented Dr. Thomas Fuhrman, chief of anesthesiology at the Bay Pines (Fla.) VA Healthcare System.

Dr. Tashkin and his associates conceived the Scleroderma Lung Study II (SLSII) as a follow-up to the first SLS run about a decade ago that compared cyclosphosphamide against placebo for controlling progression of interstitial lung disease in scleroderma patients. The results from the first SLS trial established cyclosphosphamide as a treatment that could preserve forced vital capacity percent predicted in patients with scleroderma-induced interstitial lung disease (N Engl J Med. 2006 Jun 22;354[25]:2655-666).

For the new study they enrolled patients who averaged 52 years old, with an average scleroderma duration of almost 3 years. Their average percent predicted forced vital capacity was 67%, and their baseline dyspnea index was 7.1.

Patients received either a target oral MMF dosage of 1.5 g b.i.d. for 2 years, or a target cyclophosphamide dosage of 2 mg/kg/day for up to 1 year, followed by a year of placebo. Cyclophosphamide treatment was capped at 1 year to protect against causing malignancy. Among the 73 patients randomized to the cyclophosphamide arm, 58 had data available after 12 months with 48 patients continuing on cyclophosphamide, and 53 had data available out to 2 years, with 37 patients remaining on their assigned regimen. Among 69 patients randomized to MMF 58 had data available after 12 months with 53 continuing on MMF, and 53 patients had data available through 24 months with 49 remaining on their MMF regimen.

After 24 months, the average percent predicted forced vital capacity, the study’s primary endpoint, had increased by 3.3% among patients on MMF and 3.0% among those in the cyclophosphamide arm in an intention-to-treat analysis, a nonsignificant difference. After 24 months 72% of patients in the MMF arm and 65% in the cyclophosphamide arm had a positive change, compared with baseline, in their percent predicted forced vital capacity, Dr. Tashkin reported.

MMF also showed a superior overall safety profile. Patients on cyclophosphamide had a significantly increased rate of withdrawal from the study medication. Drug discontinuations occurred in 36 of the cyclophosphamide patients and in 20 of those on MMF. Serious adverse events attributable to study medication occurred in eight patients on cyclophosphamide and three patients on MMF. The most frequent protocol-defined adverse event was leukopenia, which occurred in 30 patients on cyclophosphamide and four patients on MMF.

[email protected]

On Twitter @mitchelzoler

MONTREAL – The immunosuppressant mycophenolate mofetil worked as effectively as cyclophosphamide for treating scleroderma-related interstitial lung disease while being better tolerated and causing fewer adverse effects in a multicenter, head-to-head comparison with 142 randomized patients.

“The findings support the increasingly common clinical practice of prescribing MMF [mycophenolate mofetil] for this disease,” said Dr. Donald P. Tashkin at the annual meeting of the American College of Chest Physicians.

Mitchel L. Zoler/Frontline Medical News

Another limitation of cyclophosphamide is that it is usually not used for more than 1 year because of concerns that longer use substantially increases a patient’s risk for developing malignancy. That’s another reason why there is a “strong need for longer and safer immunosuppressive treatment with a drug like MMF,” said Dr. Tashkin, a pulmonologist at the University of California, Los Angeles.

When used in this trial on patients with scleroderma, as defined by the American College of Rheumatology and with a baseline forced vital capacity of no more than 80% of predicted, “MMF was effective at reducing the rate of decline in vital capacity, improving symptoms such as dyspnea – the cardinal symptom of interstitial lung disease, and reducing lung fibrosis seen on CT scans, and MMF was better tolerated” than cyclophosphamide, Dr. Tashkin said in an interview. Cyclophosphamide treatment in this new trial “was associated with more toxicity, especially hematologic toxicity, an was not nearly as well tolerated, with more patients withdrawing because of side effects or a perceived lack of benefit.”

“Cyclophosphamide has a lot of side effects. MMF is just now coming into increased use. I think we’ll see it being used more for first-line treatment because the side effects with cyclophosphamide are so bad,” commented Dr. Thomas Fuhrman, chief of anesthesiology at the Bay Pines (Fla.) VA Healthcare System.

Dr. Tashkin and his associates conceived the Scleroderma Lung Study II (SLSII) as a follow-up to the first SLS run about a decade ago that compared cyclosphosphamide against placebo for controlling progression of interstitial lung disease in scleroderma patients. The results from the first SLS trial established cyclosphosphamide as a treatment that could preserve forced vital capacity percent predicted in patients with scleroderma-induced interstitial lung disease (N Engl J Med. 2006 Jun 22;354[25]:2655-666).

For the new study they enrolled patients who averaged 52 years old, with an average scleroderma duration of almost 3 years. Their average percent predicted forced vital capacity was 67%, and their baseline dyspnea index was 7.1.

Patients received either a target oral MMF dosage of 1.5 g b.i.d. for 2 years, or a target cyclophosphamide dosage of 2 mg/kg/day for up to 1 year, followed by a year of placebo. Cyclophosphamide treatment was capped at 1 year to protect against causing malignancy. Among the 73 patients randomized to the cyclophosphamide arm, 58 had data available after 12 months with 48 patients continuing on cyclophosphamide, and 53 had data available out to 2 years, with 37 patients remaining on their assigned regimen. Among 69 patients randomized to MMF 58 had data available after 12 months with 53 continuing on MMF, and 53 patients had data available through 24 months with 49 remaining on their MMF regimen.

After 24 months, the average percent predicted forced vital capacity, the study’s primary endpoint, had increased by 3.3% among patients on MMF and 3.0% among those in the cyclophosphamide arm in an intention-to-treat analysis, a nonsignificant difference. After 24 months 72% of patients in the MMF arm and 65% in the cyclophosphamide arm had a positive change, compared with baseline, in their percent predicted forced vital capacity, Dr. Tashkin reported.

MMF also showed a superior overall safety profile. Patients on cyclophosphamide had a significantly increased rate of withdrawal from the study medication. Drug discontinuations occurred in 36 of the cyclophosphamide patients and in 20 of those on MMF. Serious adverse events attributable to study medication occurred in eight patients on cyclophosphamide and three patients on MMF. The most frequent protocol-defined adverse event was leukopenia, which occurred in 30 patients on cyclophosphamide and four patients on MMF.

[email protected]

On Twitter @mitchelzoler

MONTREAL – The immunosuppressant mycophenolate mofetil worked as effectively as cyclophosphamide for treating scleroderma-related interstitial lung disease while being better tolerated and causing fewer adverse effects in a multicenter, head-to-head comparison with 142 randomized patients.

“The findings support the increasingly common clinical practice of prescribing MMF [mycophenolate mofetil] for this disease,” said Dr. Donald P. Tashkin at the annual meeting of the American College of Chest Physicians.

Mitchel L. Zoler/Frontline Medical News

Another limitation of cyclophosphamide is that it is usually not used for more than 1 year because of concerns that longer use substantially increases a patient’s risk for developing malignancy. That’s another reason why there is a “strong need for longer and safer immunosuppressive treatment with a drug like MMF,” said Dr. Tashkin, a pulmonologist at the University of California, Los Angeles.

When used in this trial on patients with scleroderma, as defined by the American College of Rheumatology and with a baseline forced vital capacity of no more than 80% of predicted, “MMF was effective at reducing the rate of decline in vital capacity, improving symptoms such as dyspnea – the cardinal symptom of interstitial lung disease, and reducing lung fibrosis seen on CT scans, and MMF was better tolerated” than cyclophosphamide, Dr. Tashkin said in an interview. Cyclophosphamide treatment in this new trial “was associated with more toxicity, especially hematologic toxicity, an was not nearly as well tolerated, with more patients withdrawing because of side effects or a perceived lack of benefit.”

“Cyclophosphamide has a lot of side effects. MMF is just now coming into increased use. I think we’ll see it being used more for first-line treatment because the side effects with cyclophosphamide are so bad,” commented Dr. Thomas Fuhrman, chief of anesthesiology at the Bay Pines (Fla.) VA Healthcare System.

Dr. Tashkin and his associates conceived the Scleroderma Lung Study II (SLSII) as a follow-up to the first SLS run about a decade ago that compared cyclosphosphamide against placebo for controlling progression of interstitial lung disease in scleroderma patients. The results from the first SLS trial established cyclosphosphamide as a treatment that could preserve forced vital capacity percent predicted in patients with scleroderma-induced interstitial lung disease (N Engl J Med. 2006 Jun 22;354[25]:2655-666).

For the new study they enrolled patients who averaged 52 years old, with an average scleroderma duration of almost 3 years. Their average percent predicted forced vital capacity was 67%, and their baseline dyspnea index was 7.1.

Patients received either a target oral MMF dosage of 1.5 g b.i.d. for 2 years, or a target cyclophosphamide dosage of 2 mg/kg/day for up to 1 year, followed by a year of placebo. Cyclophosphamide treatment was capped at 1 year to protect against causing malignancy. Among the 73 patients randomized to the cyclophosphamide arm, 58 had data available after 12 months with 48 patients continuing on cyclophosphamide, and 53 had data available out to 2 years, with 37 patients remaining on their assigned regimen. Among 69 patients randomized to MMF 58 had data available after 12 months with 53 continuing on MMF, and 53 patients had data available through 24 months with 49 remaining on their MMF regimen.

After 24 months, the average percent predicted forced vital capacity, the study’s primary endpoint, had increased by 3.3% among patients on MMF and 3.0% among those in the cyclophosphamide arm in an intention-to-treat analysis, a nonsignificant difference. After 24 months 72% of patients in the MMF arm and 65% in the cyclophosphamide arm had a positive change, compared with baseline, in their percent predicted forced vital capacity, Dr. Tashkin reported.

MMF also showed a superior overall safety profile. Patients on cyclophosphamide had a significantly increased rate of withdrawal from the study medication. Drug discontinuations occurred in 36 of the cyclophosphamide patients and in 20 of those on MMF. Serious adverse events attributable to study medication occurred in eight patients on cyclophosphamide and three patients on MMF. The most frequent protocol-defined adverse event was leukopenia, which occurred in 30 patients on cyclophosphamide and four patients on MMF.

[email protected]

On Twitter @mitchelzoler

Off-label prescribing of drugs is common and very likely to cause adverse events, particularly when no strong scientific evidence supports the off-label use, according to a report published online Nov. 2 in JAMA Internal Medicine.

No systematic investigation of the off-label use of prescription drugs has been done to date, in part because physicians aren’t required to document intended indications. But recent innovations in electronic health records provided an opportunity to track off-label prescribing and its influence on adverse drug events in the Canadian province of Quebec, which provides health insurance for all 8.5 million residents. There, physicians must provide the indication(s) for every new prescription, the reason(s) for any dose changes or drug discontinuation, and the nature of any adverse events, said Dr. Tewodros Eguale of the department of epidemiology, biostatistics, and occupational health at McGill University, Montreal, and his associates.

istockphoto.com

In what they described as the first large study of its kind, the investigators analyzed the prescribing information in electronic medical records of 46,021 adults (mean age 58 years) given 151,305 new prescriptions during a 5-year period. Physicians reported off-label use in 17,847 (11.8%) of these prescriptions, and that off-label use lacked strong scientific evidence in the great majority of cases (80.9%). The median follow-up time for use of prescribed medications was 386 days (range, 1 day to 6 years).

Prescribed drugs were discontinued because of adverse events in 3,484 cases. The incidence of adverse events was 44% higher for off-label use (19.7 per 10,000 person-months) than for on-label use (12.5 per 10,000 person-months). Moreover, the incidence of adverse events was 54% higher for off-label use unsupported by strong scientific evidence (21.7 per 10,000 person-months) than for off-label use supported by strong scientific evidence (13.2 per 10,000 person-months), the investigators said (JAMA Intern Med. 2015 Nov 2. doi:10.1001/jamainternmed.2015.6058).

The class of drugs with the highest rate of adverse effects was anti-infective agents (66.2 per 10,000 person-months), followed by central nervous system drugs such as antidepressants, anxiolytics, and antimigraine medicine (18.1 per 10,000); cardiovascular drugs (15.9 per 10,000); hormonal agents (12.7); autonomic drugs including albuterol and terbutaline (8.4); gastrointestinal drugs (6.1); ear, nose, and throat medications (2.8); and “other” agents such as antihistamines, blood thinners, and antineoplastics (1.3).

“Selected examples of adverse events associated with the most frequently used off-label drugs include akathisia resulting from the use of gabapentin for neurogenic pain; agitation associated with the use of amitriptyline hydrochloride for migraine; hallucinations with the use of trazodone hydrochloride for insomnia; QT interval prolongation with the use of quetiapine fumarate for depression; and weight gain with the use of olanzapine for depression,” the authors added.

“Off-label use may be clinically appropriate given the complexity of the patient’s condition, the lack of alternative effective drugs, or after exhausting approved drugs.” However, previous research has shown that physicians’ lack of knowledge of approved treatment indications was one important factor contributing to off-label prescribing. And one study showed that physicians are finding it difficult to keep up with rapidly changing medication information, and this lack of knowledge is affecting treatment, Dr. Eguale and his associates said.

That knowledge gap could be filled by supplying clinicians with information regarding drug approval status and the quality of supporting scientific evidence at the point of care, when they write prescriptions into patients’ electronic health records, the investigators noted. This would have the added advantage of facilitating communication among physicians, pharmacists, and patients, and could reduce medication errors such as those caused by giving drugs to the wrong patients or by giving patients sound-alike or look-alike drugs.

No sponsors were identified for this study. Dr. Tewodros Eguale and his associates reported having no relevant financial disclosures.

Off-label prescribing of drugs is common and very likely to cause adverse events, particularly when no strong scientific evidence supports the off-label use, according to a report published online Nov. 2 in JAMA Internal Medicine.

No systematic investigation of the off-label use of prescription drugs has been done to date, in part because physicians aren’t required to document intended indications. But recent innovations in electronic health records provided an opportunity to track off-label prescribing and its influence on adverse drug events in the Canadian province of Quebec, which provides health insurance for all 8.5 million residents. There, physicians must provide the indication(s) for every new prescription, the reason(s) for any dose changes or drug discontinuation, and the nature of any adverse events, said Dr. Tewodros Eguale of the department of epidemiology, biostatistics, and occupational health at McGill University, Montreal, and his associates.

istockphoto.com

In what they described as the first large study of its kind, the investigators analyzed the prescribing information in electronic medical records of 46,021 adults (mean age 58 years) given 151,305 new prescriptions during a 5-year period. Physicians reported off-label use in 17,847 (11.8%) of these prescriptions, and that off-label use lacked strong scientific evidence in the great majority of cases (80.9%). The median follow-up time for use of prescribed medications was 386 days (range, 1 day to 6 years).

Prescribed drugs were discontinued because of adverse events in 3,484 cases. The incidence of adverse events was 44% higher for off-label use (19.7 per 10,000 person-months) than for on-label use (12.5 per 10,000 person-months). Moreover, the incidence of adverse events was 54% higher for off-label use unsupported by strong scientific evidence (21.7 per 10,000 person-months) than for off-label use supported by strong scientific evidence (13.2 per 10,000 person-months), the investigators said (JAMA Intern Med. 2015 Nov 2. doi:10.1001/jamainternmed.2015.6058).

The class of drugs with the highest rate of adverse effects was anti-infective agents (66.2 per 10,000 person-months), followed by central nervous system drugs such as antidepressants, anxiolytics, and antimigraine medicine (18.1 per 10,000); cardiovascular drugs (15.9 per 10,000); hormonal agents (12.7); autonomic drugs including albuterol and terbutaline (8.4); gastrointestinal drugs (6.1); ear, nose, and throat medications (2.8); and “other” agents such as antihistamines, blood thinners, and antineoplastics (1.3).

“Selected examples of adverse events associated with the most frequently used off-label drugs include akathisia resulting from the use of gabapentin for neurogenic pain; agitation associated with the use of amitriptyline hydrochloride for migraine; hallucinations with the use of trazodone hydrochloride for insomnia; QT interval prolongation with the use of quetiapine fumarate for depression; and weight gain with the use of olanzapine for depression,” the authors added.

“Off-label use may be clinically appropriate given the complexity of the patient’s condition, the lack of alternative effective drugs, or after exhausting approved drugs.” However, previous research has shown that physicians’ lack of knowledge of approved treatment indications was one important factor contributing to off-label prescribing. And one study showed that physicians are finding it difficult to keep up with rapidly changing medication information, and this lack of knowledge is affecting treatment, Dr. Eguale and his associates said.

That knowledge gap could be filled by supplying clinicians with information regarding drug approval status and the quality of supporting scientific evidence at the point of care, when they write prescriptions into patients’ electronic health records, the investigators noted. This would have the added advantage of facilitating communication among physicians, pharmacists, and patients, and could reduce medication errors such as those caused by giving drugs to the wrong patients or by giving patients sound-alike or look-alike drugs.

No sponsors were identified for this study. Dr. Tewodros Eguale and his associates reported having no relevant financial disclosures.

Off-label prescribing of drugs is common and very likely to cause adverse events, particularly when no strong scientific evidence supports the off-label use, according to a report published online Nov. 2 in JAMA Internal Medicine.

No systematic investigation of the off-label use of prescription drugs has been done to date, in part because physicians aren’t required to document intended indications. But recent innovations in electronic health records provided an opportunity to track off-label prescribing and its influence on adverse drug events in the Canadian province of Quebec, which provides health insurance for all 8.5 million residents. There, physicians must provide the indication(s) for every new prescription, the reason(s) for any dose changes or drug discontinuation, and the nature of any adverse events, said Dr. Tewodros Eguale of the department of epidemiology, biostatistics, and occupational health at McGill University, Montreal, and his associates.

istockphoto.com

In what they described as the first large study of its kind, the investigators analyzed the prescribing information in electronic medical records of 46,021 adults (mean age 58 years) given 151,305 new prescriptions during a 5-year period. Physicians reported off-label use in 17,847 (11.8%) of these prescriptions, and that off-label use lacked strong scientific evidence in the great majority of cases (80.9%). The median follow-up time for use of prescribed medications was 386 days (range, 1 day to 6 years).

Prescribed drugs were discontinued because of adverse events in 3,484 cases. The incidence of adverse events was 44% higher for off-label use (19.7 per 10,000 person-months) than for on-label use (12.5 per 10,000 person-months). Moreover, the incidence of adverse events was 54% higher for off-label use unsupported by strong scientific evidence (21.7 per 10,000 person-months) than for off-label use supported by strong scientific evidence (13.2 per 10,000 person-months), the investigators said (JAMA Intern Med. 2015 Nov 2. doi:10.1001/jamainternmed.2015.6058).

The class of drugs with the highest rate of adverse effects was anti-infective agents (66.2 per 10,000 person-months), followed by central nervous system drugs such as antidepressants, anxiolytics, and antimigraine medicine (18.1 per 10,000); cardiovascular drugs (15.9 per 10,000); hormonal agents (12.7); autonomic drugs including albuterol and terbutaline (8.4); gastrointestinal drugs (6.1); ear, nose, and throat medications (2.8); and “other” agents such as antihistamines, blood thinners, and antineoplastics (1.3).

“Selected examples of adverse events associated with the most frequently used off-label drugs include akathisia resulting from the use of gabapentin for neurogenic pain; agitation associated with the use of amitriptyline hydrochloride for migraine; hallucinations with the use of trazodone hydrochloride for insomnia; QT interval prolongation with the use of quetiapine fumarate for depression; and weight gain with the use of olanzapine for depression,” the authors added.

“Off-label use may be clinically appropriate given the complexity of the patient’s condition, the lack of alternative effective drugs, or after exhausting approved drugs.” However, previous research has shown that physicians’ lack of knowledge of approved treatment indications was one important factor contributing to off-label prescribing. And one study showed that physicians are finding it difficult to keep up with rapidly changing medication information, and this lack of knowledge is affecting treatment, Dr. Eguale and his associates said.

That knowledge gap could be filled by supplying clinicians with information regarding drug approval status and the quality of supporting scientific evidence at the point of care, when they write prescriptions into patients’ electronic health records, the investigators noted. This would have the added advantage of facilitating communication among physicians, pharmacists, and patients, and could reduce medication errors such as those caused by giving drugs to the wrong patients or by giving patients sound-alike or look-alike drugs.

No sponsors were identified for this study. Dr. Tewodros Eguale and his associates reported having no relevant financial disclosures.

Most pediatricians and family physicians reported having some families refuse vaccines, and 21% of pediatricians reported dismissal of these families from their practices, findings of a recent survey showed.

Vaccine preventable outbreaks and vaccine refusal continue to be a concern. Despite discouragement by the Centers for Disease Control and Prevention and the American Academy of Pediatrics (AAP), some physicians have started to dismiss families from their practices for refusing vaccines for their children.

CDC/Amanda Mills

Dr. Sean T. O’Leary of The Adult and Child Center for Outcomes Research and Delivery Sciences, University of Colorado, Aurora, and colleagues set out to study the prevalence of parents refusing one or more infant vaccines, physician response, and the association of dismissal to state exemption laws, and practice and provider characteristics.

They conducted a nationally representative survey of family physicians (FPs) and pediatricians with multivariable analysis. Their results were published online in Pediatrics (2015, Nov. 2. doi: 10.1542/peds.2015-2086).

The response rate was 61% (252) for FPs, 70% (282) for pediatricians, and 66% overall (534/815). Of those who responded, data from 83 were excluded because they reported not administering vaccines to children less than 2 years old.

Most respondents (83%) reported at least some parents refusing vaccines in a typical month. In states where philosophical exemptions are not allowed, pediatricians reported no refusals in a typical month more often than in states where exemptions are allowed (17% versus 8%, P = .03); family physicians did not report this difference. Vaccine refusal in 1%-4% of parents was reported by 63% of respondents, with 15% reporting a refusal rate of 5%-9%, and 5% reporting refusal by 10% or more. Likewise, 11% of the respondents reported an increase in vaccine refusal compared with the prior 12 months, whereas 23% reported a decrease and 66% reported a similar frequency.

Overall, 51% of respondents noted always or often requiring parents to sign a form after vaccine refusal (pediatricians 64% versus FPs 29%, P less than .0001).

Fourteen percent of the respondents reported always or often dismissing a family for refusing one or more infant vaccines (pediatricians 21% versus FPs 4%, P less than .0001).

In states without philosophical exemptions, 34% of pediatricians reported dismissal of families for vaccine refusal, versus 9% in states that allow exemptions (P less than .0001).

Finally, pediatrician respondents who reported dismissing patients were more often located in the South, in a state without philosophical exemptions for vaccines, and in private practice.

The authors noted that there are still many aspects of vaccine refusal that are not well understood. “Because many [pediatricians] still dismiss families despite recommendations to the contrary, this practice should be better explored and understood both for its causes and its intended and unintended consequences,” they wrote.

This study was funded by the CDC administered through the Rocky Mountain Prevention Research Center, University of Colorado, Aurora (grant). The authors report no financial disclosures.

Most pediatricians and family physicians reported having some families refuse vaccines, and 21% of pediatricians reported dismissal of these families from their practices, findings of a recent survey showed.

Vaccine preventable outbreaks and vaccine refusal continue to be a concern. Despite discouragement by the Centers for Disease Control and Prevention and the American Academy of Pediatrics (AAP), some physicians have started to dismiss families from their practices for refusing vaccines for their children.

CDC/Amanda Mills

Dr. Sean T. O’Leary of The Adult and Child Center for Outcomes Research and Delivery Sciences, University of Colorado, Aurora, and colleagues set out to study the prevalence of parents refusing one or more infant vaccines, physician response, and the association of dismissal to state exemption laws, and practice and provider characteristics.

They conducted a nationally representative survey of family physicians (FPs) and pediatricians with multivariable analysis. Their results were published online in Pediatrics (2015, Nov. 2. doi: 10.1542/peds.2015-2086).

The response rate was 61% (252) for FPs, 70% (282) for pediatricians, and 66% overall (534/815). Of those who responded, data from 83 were excluded because they reported not administering vaccines to children less than 2 years old.

Most respondents (83%) reported at least some parents refusing vaccines in a typical month. In states where philosophical exemptions are not allowed, pediatricians reported no refusals in a typical month more often than in states where exemptions are allowed (17% versus 8%, P = .03); family physicians did not report this difference. Vaccine refusal in 1%-4% of parents was reported by 63% of respondents, with 15% reporting a refusal rate of 5%-9%, and 5% reporting refusal by 10% or more. Likewise, 11% of the respondents reported an increase in vaccine refusal compared with the prior 12 months, whereas 23% reported a decrease and 66% reported a similar frequency.

Overall, 51% of respondents noted always or often requiring parents to sign a form after vaccine refusal (pediatricians 64% versus FPs 29%, P less than .0001).

Fourteen percent of the respondents reported always or often dismissing a family for refusing one or more infant vaccines (pediatricians 21% versus FPs 4%, P less than .0001).

In states without philosophical exemptions, 34% of pediatricians reported dismissal of families for vaccine refusal, versus 9% in states that allow exemptions (P less than .0001).

Finally, pediatrician respondents who reported dismissing patients were more often located in the South, in a state without philosophical exemptions for vaccines, and in private practice.

The authors noted that there are still many aspects of vaccine refusal that are not well understood. “Because many [pediatricians] still dismiss families despite recommendations to the contrary, this practice should be better explored and understood both for its causes and its intended and unintended consequences,” they wrote.

This study was funded by the CDC administered through the Rocky Mountain Prevention Research Center, University of Colorado, Aurora (grant). The authors report no financial disclosures.

Most pediatricians and family physicians reported having some families refuse vaccines, and 21% of pediatricians reported dismissal of these families from their practices, findings of a recent survey showed.

Vaccine preventable outbreaks and vaccine refusal continue to be a concern. Despite discouragement by the Centers for Disease Control and Prevention and the American Academy of Pediatrics (AAP), some physicians have started to dismiss families from their practices for refusing vaccines for their children.

CDC/Amanda Mills

Dr. Sean T. O’Leary of The Adult and Child Center for Outcomes Research and Delivery Sciences, University of Colorado, Aurora, and colleagues set out to study the prevalence of parents refusing one or more infant vaccines, physician response, and the association of dismissal to state exemption laws, and practice and provider characteristics.

They conducted a nationally representative survey of family physicians (FPs) and pediatricians with multivariable analysis. Their results were published online in Pediatrics (2015, Nov. 2. doi: 10.1542/peds.2015-2086).

The response rate was 61% (252) for FPs, 70% (282) for pediatricians, and 66% overall (534/815). Of those who responded, data from 83 were excluded because they reported not administering vaccines to children less than 2 years old.

Most respondents (83%) reported at least some parents refusing vaccines in a typical month. In states where philosophical exemptions are not allowed, pediatricians reported no refusals in a typical month more often than in states where exemptions are allowed (17% versus 8%, P = .03); family physicians did not report this difference. Vaccine refusal in 1%-4% of parents was reported by 63% of respondents, with 15% reporting a refusal rate of 5%-9%, and 5% reporting refusal by 10% or more. Likewise, 11% of the respondents reported an increase in vaccine refusal compared with the prior 12 months, whereas 23% reported a decrease and 66% reported a similar frequency.

Overall, 51% of respondents noted always or often requiring parents to sign a form after vaccine refusal (pediatricians 64% versus FPs 29%, P less than .0001).

Fourteen percent of the respondents reported always or often dismissing a family for refusing one or more infant vaccines (pediatricians 21% versus FPs 4%, P less than .0001).

In states without philosophical exemptions, 34% of pediatricians reported dismissal of families for vaccine refusal, versus 9% in states that allow exemptions (P less than .0001).

Finally, pediatrician respondents who reported dismissing patients were more often located in the South, in a state without philosophical exemptions for vaccines, and in private practice.

The authors noted that there are still many aspects of vaccine refusal that are not well understood. “Because many [pediatricians] still dismiss families despite recommendations to the contrary, this practice should be better explored and understood both for its causes and its intended and unintended consequences,” they wrote.

This study was funded by the CDC administered through the Rocky Mountain Prevention Research Center, University of Colorado, Aurora (grant). The authors report no financial disclosures.